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2K views915 pages

Essentials of Veterinary Ophthalmology 4th Edition

Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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Essentials of Veterinary Ophthalmology

Essentials of Veterinary Ophthalmology

Fourth Edition

Kirk N. Gelatt, VMD


Diplomate, American College of Veterinary Ophthalmologists
Emeritus Distinguished Professor of Comparative Ophthalmology
Department of Small Animal Clinical Sciences
College of Veterinary Medicine
University of Florida
Gainesville, FL, USA

Caryn E. Plummer, DVM


Diplomate, American College of Veterinary Ophthalmologists
Professor of Comparative Ophthalmology
Departments of Small and Large Animal Clinical Sciences
College of Veterinary Medicine
University of Florida
Gainesville, FL, USA
This fourth edition first published 2022
2022 John Wiley & Sons, Inc.

Edition History
Lippincott, Williams, and Wilkins (1e, 2001); Blackwell Publishing (2e, 2008); John Wiley and Sons Inc (3e, 2014)

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Library of Congress Cataloging-­in-­Publication Data Applied for


Paperback ISBN: 9781119801320

Cover Design: Wiley


Cover Image: Courtesy of Caryn E. Plummer

Set in 9.5/12.5pt STIXTwoText by Straive, Pondicherry, India


v

Contents

Preface vii
Acknowledgments ix
About the Companion Website xi

Section 1 Basics for Clinical Veterinary Ophthalmology 1

1 Development and Morphology of the Eye and Adnexa 3


Section I: Development of the Eye and Adnexa 3
Section II: Morphology of the Eye and Adnexa 13

2 Ophthalmic Physiology and Vision 59


Section I: Physiology of the Eye 59

­  3 Ocular Pharmacology and Therapeutics 114


Section I: Ocular Drug Delivery 114

Section 2 Ocular Exam and Imaging 161

4 Eye Examination and Diagnostics 163

­Section 3 Canine Ophthalmology 217

5 Canine Orbit: Disease and Surgery 219

6 Canine Eyelids: Disease and Surgery 239

7 Canine Nasolacrimal and Lacrimal Systems: Disease and Surgery 270


Section I: Nasolacrimal Duct System 270

8 Canine Conjunctivae and Nictitating Membrane: Disease and Surgery 290

9 Canine Cornea and Sclera: Diseases and Surgery 310


vi Contents

10 The Canine Glaucomas 355

11 Canine Anterior Uvea: Diseases and Surgery 394

12 Canine Cataracts, Lens Luxations, and Surgery 426


Section I: Cataracts – Clinical Findings 426
Section II: Cataract Surgery 455

13 Diseases and Surgery of the Canine Posterior Segment 469


­Section I: Diseases and Surgery of the Canine Vitreous 469
­Section II: Diseases of the Canine Ocular Fundus 478
Section III: Surgery of the Canine Posterior Segment 515
­Section IV: Optic Nerve 525

Section 4 Special Species 539

14 Feline Ophthalmology 541

15 Equine Ophthalmology 604

16 Food and Fiber Animal Ophthalmology 665

17 Exotic Animals: Ophthalmic Diseases and Surgery 716

­Section 5 Ophthalmic and Systemic Diseases 761

18 Neuro-­ophthalmology 763

19 Ocular Manifestations of Systemic Disease 784


Section I: Dogs 784
Section II: Cats 812
Section III: Horses 831
Section IV: Food Animals 840

Glossary 845

Appendix A Inherited Ophthalmic Diseases in the Dog 851

Appendix B Inherited Eye Diseases in the Cat 853

Appendix C Inherited Eye Diseases in the Horse 854

Appendix D Inherited Eye Diseases in Production Animals 855

Appendix E Lysosomal Storage Diseases in the Dog, Cat, and Food Animals 856

Index 858
vii

Preface

The sixth edition of Veterinary Ophthalmology, This fourth edition of the Essentials pre-
released in March 2021, serves as the preemi- sents the most frequently encountered eye
nent clinical and visual science text and diseases of domestic animals along with
reference in the world in this field and has their treatment and prognosis. This book
been referred as the “gold standard” and the also provides critical information for a busy
“blue bible.” The sixth edition was expanded general, small animal and mixed animal
from 2170 pages to 2700 pages and divided practitioner who needs a single ophthalmol-
into two volumes of about the same number ogy text that covers their needs. When there
of pages to accommodate the continued is more time, and if the reader seeks addi-
expansion in knowledge and progression of tional information on an ophthalmic disor-
this discipline. This textbook serves as the der, the comprehensive sixth edition of
base for the fourth edition of the Essentials of Veterinary Ophthalmology and other refer-
Veterinary Ophthalmology, and distills all of ences may be consulted.
this information down to the Essentials. Relevant chapters from the sixth edition
The information base is targeted to the vet- have been distilled or revised into this
erinary medical student and general practi- “Essentials.” Since the ophthalmic structures
tioner. This text is primarily a clinical reference, are, for the most part, examined under direct
presented similarly to the widely used ophthal- observation, and often supplemented with
mology curricula of most colleges of veterinary magnification and special illumination, a
medicine worldwide. Hence, we start with working knowledge of ocular development
those subjects encountered in the veterinary and morphology is important. As most oph-
students’ freshmen year on vision sciences thalmic diseases can easily be visualized and
(embryology, anatomy, and physiology), then photographed, most of the illustrations are in
the sophomore year with pharmacology and color, facilitating transfer of this information
therapeutics, then clinical ophthalmology to the clinical patient! Often photographs of
divided by species (offered in the second and/ clinical conditions are more easily remem-
or third years), and then for the clinical oph- bered rather than the text information!
thalmology clerkships and the subsequent Algorithms have been included when possible
“real world.” The entire text and its associated to speed the clinical problem-­solving process!
photographs are available as text (hard copy) The appendices, positioned in the different
and on the internet. chapters, include the available DNA tests for
viii Preface

eye diseases in animals (continuously updated veterinary ophthalmology, sometimes with


on their websites) and inherited eye conditions adaptations to animals.
(presented in the different chapters) of the dog, We hope you benefit from and build upon
cat, horse, and production animals. these “Essentials of Veterinary Ophthalmology.”
Ophthalmology has a unique vocabulary
(based on Greek rather than Latin since the Kirk N. Gelatt, VMD and Caryn E. Plummer,
early development of ophthalmology paral- DVM, Professors of Veterinary and Comparative
leled the evolution of medicine), and this often Ophthalmology, and Diplomats of the American
presents a challenge to the learner. As a result, College of Veterinary Ophthalmologists, College
a brief glossary is included summarizing those of Veterinary Medicine, University of Florida,
ophthalmic words used most frequently in Gainesville, FL, USA.
ix

Acknowledgments

Selected chapters from the sixth edition of Chapter 11: Ophthalmic Genetics and DNA
Veterinary Ophthalmology (2021) were used in Testing (Simon M. Peterson-­Jones)
the preparation of the chapters for this fourth Chapter 14: Diseases and Surgery of the
edition of the Essentials. These chapters and Canine Orbit (Simon A. Pot, Katrin Voelter,
their authors are listed below: and Patrick Kircher)
Chapter 15: Diseases and Surgery of the
Chapter 1: Ocular Embryology and Congenital
Canine Eyelids (Frans C. Stades and
Malformations (Cynthia S. Cook)
Alexandra Van der Woerdt)
Chapter 2: Ophthalmic Anatomy (Jessica
Chapter 16: Diseases and Surgery of the
M. Meekins, Amy J. Rankin, and Don
Canine Nasolacrimal System (Lynne
A. Samuelson)
S. Sandmeyer and Bruce H. Grahn)
Chapter 3: Physiology of the Eye (Diane
Chapter 17: Disease and Surgery of the Canine
V.H. Hendrix, Sara M. Thomasy, and
Lacrimal Secretory System (Elizabeth
Glenwood G. Gum)
A. Giuliano)
Chapter 4: Optics and Physiology of Vision
Chapter 18: Diseases and Surgery of the
(Ron Ofri and Björn Ekesten)
Canine Conjunctiva and Nictitating
Chapter 5: Fundamentals of Animal Vision
Membrane (Claudia Hartley and Diane
(Björn Ekesten and Ron Ofri)
V.H. Hendrix)
Chapter 8: Clinical Pharmacology and
Chapter 19: Canine Cornea and Sclera –
Therapeutics (Alain Regnier, Alison Clode,
Diseases and Surgery (R. David Whitley and
Erin M. Scott, Amy J. Rankin, Ian P. Herring,
Ralph E. Hamor)
and Caryn E. Plummer)
Chapter 20: The Canine Glaucomas (Caryn
Chapter 10: Ophthalmic Examination and
E. Plummer, András M. Komáromy, and
Diagnostics
Kirk N. Gelatt)
Part 1: The Eye Examination and Diagnostic
Chapter 21: Diseases and Surgery of the
Procedures (Heidi I. Featherstone and
Canine Anterior Uvea (Diane V.H. Hendrix)
Christine L. Heinrich)
Chapter 22: Diseases of the Lens and Cataract
Part 2: Ocular Imaging (David Donaldson
Formation (Marta Leiva and Teresa Peña)
and Claudia Hartley)
Chapter 23: Surgery of the Lens (Tammy
Part 3: Diagnostic Ophthalmic Ultrasound
Miller Michau)
(Ellison Bentley, Stefano Pizzirani, and
Chapter 24: Diseases and Surgery of the
Kenneth R. Waller, III)
Canine Vitreous (Michael H. Boevé and
Part 4: Clinical Electrodiagnostic Evaluation
Frans C. Stades)
of the Visual System (Gil Ben-­Shiomo)
x Acknowledgments

Chapter 25: Diseases of the Canine Ocular Chapter 31: Avian Ophthalmology (Lucien
Fundus (Simon M. Petersen-­Jones and V. Vallone and Thomas J. Kern)
Freya Mowat) Chapter 32: Ophthalmology of the New World
Chapter 26: Surgery of the Canine Posterior Camelids (Juliet R. Gionfriddo and Ralph
Segment (Allison R. Hoffman, Joseph E. Hamor)
C. Wolfer, Samuel J. Vainisi, and András Chapter 33: Laboratory Animal Ophthalmology
M. Komáromy) (Seth Eaton)
Chapter 27: Disease of the Canine Optic Nerve Chapter 34: Small Mammal Ophthalmology
(Gillian J. McLellan) (David L. Williams)
Chapter 28: Feline Ophthalmology (Mary Belle Chapter 35: Exotic Animal Ophthalmology
Glaze, David J. Maggs, and Caryn (Thomas J. Kern)
E. Plummer) Chapter 36: Neuro-­Ophthalmology (Aubrey
Chapter 29: Equine Ophthalmology (Caryn A. Webb and Cheryl L. Cullen)
E. Plummer) Chapter 37: Ocular Manifestations of Systemic
Chapter 30: Food and Fiber Animal Disease (Aubrey A. Webb and Cheryl
Ophthalmology (Bianca C. Martins) L. Cullen)
xi

About the Companion Website

This book is accompanied by a website containing:

www.wiley.com/go/gelatt/essentials4e

Figures from the book as PowerPoint slides


1

Section 1

Basics for Clinical Veterinary Ophthalmology


3

Development and Morphology of the Eye and Adnexa


Revised from 6th edition of Veterinary Ophthalmology, Chapter 1: Ocular Embryology and Congenital Malformations, by Cynthia
S. Cook; and Chapter 2: Ophthalmic Anatomy, by Jessica M. Meekins, Amy J. Rankin, and Don A. Samuelson

Section I: Development of the Eye divides the blastocyst space into the amniotic
and Adnexa cavity (adjacent to epiblast) and the yolk sac
(adjacent to hypoblast).
Ocular development has been investigated in Gastrulation (formation of the mesodermal
some detail in rodents, the dog, and the cow, germ layer) begins during day 10 of gestation in
and demonstrates that the sequence of devel- the dog (day 7 in the mouse; days 15–20 in the
opmental events is very similar across species. human). The primitive streak forms as a longitudi-
When comparing these studies, one should nal groove within the epiblast (i.e., future
consider differences in duration of gestation, e­ctoderm). Epiblast cells migrate toward the prim-
differences in anatomical end point (e.g., pres- itive streak, where they invaginate to form the
ence of a tapetum, macula, or Schlemm’s mesoderm. This forms the three classic germ lay-
canal), and when eyelid fusion breaks (during ers: ectoderm, mesoderm, and endoderm.
the sixth month of gestation in the human ver- Gastrulation proceeds in a cranial-­to-­caudal pro-
sus two weeks postnatal in the dog and cow) gression; simultaneously, the cranial surface ecto-
(Tables 1.1 and 1.2). derm proliferates, forming bilateral elevations
called the neural folds (i.e., future brain). The
columnar surface ectoderm in this area now
­Gastrulation and Neurulation becomes known as the neural ectoderm.
As the neural folds elevate and approach
Cellular mitosis following fertilization results each other, a specialized population of mesen-
in transformation of the single-­cell zygote into chymal cells, the neural crest, emigrates from
a cluster of 12–16 cells. With continued cellu- the neural ectoderm at its junction with the
lar proliferation, this morula becomes a blasto- surface ectoderm. Migration and differentia-
cyst, containing a fluid-­filled cavity. The cells tion of the neural crest cells are influenced by
of the blastocyst will form both the embryo the hyaluronic acid-­rich extracellular matrix.
proper and the extraembryonic tissues (i.e., This acellular matrix is secreted by the surface
amnion and chorion). At this early stage, the epithelium as well as by the crest cells, and it
embryo is a bilaminar disc, consisting of hypo- forms a space through which the crest cells
blast and epiblast. This embryonic tissue migrate. The neural crest cells migrate

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
4 Development and Morphology of the Eye and Adnexa

Table 1.1 Sequence of ocular development in human, mouse, and dog.

Mouse (day Dog (day


Human (approximate post-­ post-­ post-­fertilization or
fertilization age) fertilization) P = postnatal day) Developmental events

Month Week Day

1 3 22 8 13 Optic sulci present in forebrain


4 24 9 15 Optic sulci convert into optic
vesicles
10 17 Optic vesicle contacts surface
epithelium
Lens placode begins to thicken
26 Optic vesicle surrounded by neural
crest mesenchyme
2 5 28 10.5 Optic vesicle begins to invaginate,
forming optic cup
Lens pit forms as lens placode
invaginates
Retinal primordium thickens,
marginal zone present
32 11 19 Optic vesicle invaginated to form
optic cup
Optic fissure delineated
Retinal primordium consists of
external limiting membrane,
proliferative zone, primitive zone,
marginal zone, and internal
limiting membrane
Oculomotor nerve present
33 11.5 25 Pigment in outer layer of optic
cup
Hyaloid artery enters through the
optic cup
Lens vesicle separated from surface
ectoderm
Retina: inner marginal and outer
nuclear zones
11.5 29 Basement membrane of surface
ectoderm intact
Primary lens fibers form
Trochlear and abducens nerves
appear
Lid fold present
6 37 12 Edges of optic fissure in contact
12 30 TVL present
Lens vesicle cavity obliterated
Ciliary ganglion present
­Gastrulation and Neurulatio  5

Table 1.1 (Continued)

Mouse (day Dog (day


Human (approximate post-­ post-­ post-­fertilization or
fertilization age) fertilization) P = postnatal day) Developmental events

41 12 32 Posterior retina consists of nerve fiber


layer, inner neuroblastic layer,
transient fiber layer of Chievitz,
proliferative zone, outer neuroblastic
layer, and external limiting
membrane
17 32 Eyelids fuse (dog)
7 Anterior chamber beginning to
form
12.5 40 Secondary lens fibers present
48 14 32 Corneal endothelium differentiated
8 51 Optic nerve fibers reach the brain
Optic stalk cavity is obliterated
Lens sutures appear
Acellular corneal stroma present
54 30–35 Scleral condensation present
9 57 17 40 First indication of ciliary processes
and iris
—­ EOMs visible
Eyelids fuse (occurs earlier in the dog)
10 45 Pigment visible in iris stroma
Ciliary processes touch lens equator
Rudimentary rods and cones
appear
45–1P Hyaloid artery begins to atrophy to
the disc
3 12 —­ Branches of the central retinal
artery form
4 51 Pupillary sphincter differentiates
Retinal vessels present
—­ 56 Ciliary muscle appears
—­ Tapetum present (dog)
5 40 Layers of the choroid are complete
with pigmentation
6 —­ Eyelids begin to open, light perception
1P Pupillary dilator muscle present
7 1–14P Pupillary membrane atrophies
1–16P Rod and cone inner and outer
segments present in posterior retina
10–13P Pars plana distinct
9 16–40P Retinal layers developed
14P Regression of pupillary membrane,
TVL, and hyaloid artery nearly
complete
Lacrimal duct canalized
6 Development and Morphology of the Eye and Adnexa

Table 1.2 Sequence of ocular development in the cow.

Gestational Gestational
Ocular part or event size (mm) Ocular part or event size (mm)

Lens Nerve fiber layer 20


Optic vesicle 6 Optic nerve well formed 24
Lens placode 6 Inner/outer neuroblastic layers 14
Optic cup and lens placode 10 Transient layer of Chievitz 14
Separation of lens vesicle from 10 Inner plexiform layer 180
surface ectoderm Retinal vessels 180
Primary lens fibers 15 Tapetal cells 410
Lens vesicle cavity disappears 24
Completion of lens capsule 50
Table 1.3 Embryonic origins of ocular tissues.
Secondary lens fibers 58
Perilenticular vascular mesoderm
Neural ectoderm Neural crest
Extension of primary vitreous 15
(hyaloid artery) to lens
Neural retina Stroma of iris, ciliary
TVL 33 body, choroid, and sclera
Disappearance of posterior 410 RPE Ciliary muscles
lenticular vascular network Posterior iris Corneal stroma and
Disappearance of TVL 410 epithelium endothelium
Iris Pupillary Perivascular connective
Major arterial circle of iris 90 sphincter and tissue and smooth muscle
dilator muscle cells
Iris reaches front of lens 200 (except in avian Striated muscles of iris
Pigment in stroma 200 species) (avian species only)
Sphincter muscle 410 Bilayered ciliary Meninges of optic nerve
Dilator muscle 410 epithelium Orbital cartilage and bone
Ciliary body Connective tissue of the
Ciliary processes 125 extrinsic ocular muscles
Ciliary processes touch lens 230 Endothelium of
equator trabecular meshwork
Pars plana (distinct) 200 Surface ectoderm Mesoderm
Pars plana fully developed 410
Lens Extraocular myoblasts
Choroid
Corneal and Vascular endothelium
Choroidal net in posterior pole 33
conjunctival
Choroidal net throughout 50 epithelium
Outermost large choroidal 40 Lacrimal gland Schlemm’s canal (human)
vessels
Posterior sclera (?)
Choriocapillaris 90
Pigmentation of choroid 90
Retina – posterior third peripherally beneath the surface ectoderm to
Inner and outer nucleated zones 10
spread throughout the embryo, populating the
region around the optic vesicle and ultimately
Multilayer outer cup of optic 20
vesicle forms single cells giving rise to nearly all the connective tissue
structures of the eye (Table 1.3).
­Formation of the Optic Vesicle and Optic Cu  7

It is important to note that mesenchyme is a The optic vesicle enlarges and, covered by its
general term for any embryonic connective tis- own basal lamina, approaches the basal lamina
sue. Mesenchymal cells generally appear stel- underlying the surface ectoderm. The optic
late and are actively migrating populations with vesicle appears to play a significant role in the
extensive extracellular space. In contrast, the induction and size determination of the palpe-
term mesoderm refers specifically to the middle bral fissure and of the orbital and periocular
embryonic germ layer. In the eye, mesoderm structure. An external bulge indicating the
probably gives rise only to the striated myocytes presence of the enlarging optic vesicle can be
of the extraocular muscles (EOMs) and vascular seen at approximately day 17 in the dog.
endothelium. Most of the craniofacial mesen- The optic vesicle and optic stalk invaginate
chymal tissue comes from neural crest cell. through differential growth and infolding.
Local apical contraction and physiological cell
death have been identified during invagina-
tion. The surface ectoderm in contact with the
­ ormation of the Optic Vesicle
F optic vesicle thickens to form the lens placode,
and Optic Cup which then invaginates with the underlying
neural ectoderm. The invaginating neural ecto-
The optic sulci are visible as paired evagina- derm folds onto itself as the space within the
tions of the forebrain neural ectoderm on day optic vesicle collapses, thus creating a double
13 of gestation in the dog (Figure 1.1). The layer of neural ectoderm, the optic cup.
transformation from optic sulcus to optic vesi- This process of optic vesicle/lens placode
cle is considered to occur concurrent with the invagination progresses from inferior to supe-
closure of the neural tube (day 15 in the dog). rior, so the sides of the optic cup and stalk meet
inferiorly in an area called the optic (choroid/
retinal) fissure. Mesenchymal tissue (of primar-
Anterior
neuropore ily neural crest origin) surrounds and fills the
Optic sulci
Forebrain
optic cup, and by day 25 in the dog, the hyaloid
Future lens artery develops from mesenchyme in the optic
placode
Midbrain
fissure. This artery courses from the optic stalk
1st and 2nd
(i.e., the region of the future optic nerve) to the
pharyngeal developing lens. The two edges of the optic fis-
pouches
sure meet and initially fuse anterior to the
optic stalk, with fusion then progressing ante-
Pericardial
bulge Hindbrain riorly and posteriorly. This process is mediated
by glycosaminoglycan (GAG)-­induced adhe-
Somite sion between the two edges of the fissure.
Cut edge Apoptosis has been identified in the inferior
of amnion
optic cup prior to formation of the optic fissure
and, transiently, associated with its closure.
Yolk Failure of this fissure to close normally may
sac result in inferiorly located defects
(i.e., co­lobomas) in the iris, choroid, or optic
Figure 1.1 Development of the optic sulci, which nerve. Colobomas other than those in the
are the first sign of eye development. Optic sulci “t­ypical” six-­o’clock location may occur
on the inside of the forebrain vesicles consisting through a different mechanism and are
of neural ectoderm (shaded cells). The optic sulci
d­iscussed later. Closure of the optic cup
evaginate toward the surface ectoderm as the
forebrain vesicles simultaneously rotate inward through fusion of the optic fissure allows
to fuse. intraocular pressure (IOP) to be established.
8 Development and Morphology of the Eye and Adnexa

­Lens Formation vesicle is determined by the contact area of the


optic vesicle with the surface ectoderm and by
Before contact with the optic vesicle, the sur- the ability of the latter tissue to respond to
face ectoderm first becomes competent to induction. Aplasia may result from failure of
respond to lens inducers. Inductive signals lens induction or through later involutions of
from the anterior neural plate give this area of the lens vesicle, either before or after separa-
ectoderm a “lens-­forming bias.” Signals from tion from the surface ectoderm.
the optic vesicle are required for complete lens Lens vesicle detachment is the initial event
differentiation, and inhibitory signals from the leading to formation of the chambers of the
cranial neural crest may suppress any residual ocular anterior segment. This process is accom-
lens-­forming bias in head ectoderm adjacent to panied by active migration of epithelial cells
the lens. Adhesion between the optic vesicle out of the keratolenticular stalk, cellular necro-
and surface ectoderm exists, but there is no sis, apoptosis, and basement membrane break-
direct cell contact. The basement membranes down. Induction of a small lens vesicle that
of the optic vesicle and the surface ectoderm fails to undergo normal separation from the
remain separate and intact throughout the surface ectoderm is one of the characteristics
contact period. of the teratogen-­induced anterior segment dys-
Thickening of the lens placode can be seen genesis described in animal models.
on day 17 in the dog. A tight, extracellular Following detachment from the surface
matrix-­mediated adhesion between the optic ectoderm (day 25 in the dog), the lens vesicle is
vesicle and the surface ectoderm has been lined by a monolayer of cuboidal cells sur-
described. This anchoring effect on the mitoti- rounded by a basal lamina, the future lens cap-
cally active ectoderm results in cell crowding sule. The primitive retina promotes primary
and elongation and in formation of a thick- lens fiber formation in the adjacent lens epi-
ened placode. This adhesion between the optic thelial cells. Thus, while the retina develops
vesicle and lens placode also assures alignment independently of the lens, the lens appears to
of the lens and retina in the visual axis. be dependent on the retinal primordium for its
The lens placode invaginates, forming a hol- differentiation. The primitive lens filled with
low sphere, now referred to as a lens vesicle primary lens fibers is the embryonic lens
(Figures 1.2 and 1.3). The size of the lens nucleus. In the adult, the embryonic nucleus is

Surface ectoderm

Optic cup Collapsing optic


vesicle
Neurosensory
retina
Optic stalk RPE

Lens placode

Lens vesicle
Optic (choroidal) fissure

(a) (b)

Figure 1.2 Formation of the lens vesicle and optic cup. Note that the optic fissure is present, because the
optic cup is not yet fused inferiorly. (a) Formation of lens vesicle and optic cup with inferior choroidal or
optic fissure. Mesenchyme (M) surrounds the invaginating lens vesicle. (b) Surface ectoderm forms the lens
vesicle with a hollow interior. Note that the optic cup and optic stalk are of surface ectoderm origin.
­Vascular Developmen  9

Optic cup Intraretinal space

Neurosensory retina
Surface
ectoderm RPE

Neural ectoderm

Lens
vesicle

Optic stalk
Primary Hyaloid
vitreous vessels Optic fissure

Figure 1.3 Cross section through optic cup and optic fissure. The lens vesicle is separated from the
surface ectoderm. Mesenchyme (M) surrounds the developing lens vesicle, and the hyaloid artery is seen
within the optic fissure.

the central sphere inside the “Y” sutures; there anteriorly to anastomose with the network of
are no sutures within the embryonal nucleus. vessels in the pupillary membrane (Figure 1.4).
At birth, the lens consists almost entirely of The pupillary membrane consists of vessels and
lens nucleus, with minimal lens cortex. Lens mesenchyme overlying the anterior lens cap-
cortex continues to develop from the anterior sule. This hyaloid vascular network that forms
cuboidal epithelial cells, which remain mitotic around the lens is called the anterior and poste-
throughout life. Differentiation of epithelial cells rior TVL. The hyaloid artery and associated TVL
into secondary lens fibers occurs at the lens provide nutrition to the lens and anterior seg-
equator (i.e., lens bow). Lens fiber elongation is ment during its period of rapid differentiation.
accompanied by a corresponding increase in cell Venous drainage occurs via a network near the
volume and a decrease in intercellular space equatorial lens, in the area where the ciliary
within the lens. body will eventually develop. There is no dis-
The zonule fibers are termed the tertiary vit- crete hyaloid vein.
reous, but their origin remains uncertain. The Once the ciliary body begins actively produc-
zonules may form from the developing ciliary ing aqueous humor, which circulates and
epithelium or the endothelium of the posterior nourishes the lens, the hyaloid system is no
tunica vasculosa lentis (TVL). longer needed. The hyaloid vasculature and
TVL reach their maximal development by day
45 in the dog and then begin to regress.
­Vascular Development As the peripheral hyaloid vasculature
regresses, the retinal vessels develop. Spindle-­
The hyaloid artery is the termination of the shaped mesenchymal cells from the wall of the
primitive ophthalmic artery, a branch of the hyaloid artery at the optic disc form buds
internal ophthalmic artery, and it remains (angiogenesis) that invade the nerve fiber layer.
within the optic cup following closure of the Branches of the hyaloid artery become sporadi-
optic fissure. The hyaloid artery branches cally occluded by macrophages prior to their
around the posterior lens capsule and continues gradual atrophy. Placental growth factor and
10 Development and Morphology of the Eye and Adnexa

Primary vitreous

Lid bud
Secondary
vitreous

Cornea
Hyaloid artery

Anterior
chamber
lens

Optic nerve
Pupillary
membrane

Muscle

Tunica vasculosa lentis

Figure 1.4 The hyaloid vascular system and TVL.

vascular endothelial growth factor appear to be detachment (day 25 in the dog). The surface
involved in hyaloid regression. Proximal arteri- ectoderm overlying the optic cup (i.e., the pre-
olar vasoconstriction at birth precedes regression sumptive corneal epithelium) secretes a thick
of the major hyaloid vasculature. Atrophy of the matrix, the primary stroma. Mesenchymal neu-
pupillary membrane, TVL, and hyaloid artery ral crest cells migrate between the surface ecto-
occurs initially through apoptosis and later derm and the optic cup, using the basal lamina
through cellular necrosis, and is usually complete of the lens vesicle as a substrate. This loosely
by the time of eyelid opening 14 days postnatally. arranged mesenchyme fills the future anterior
The clinical lens anomaly known as Mittendorf’s chamber and gives rise to the corneal endothe-
dot is a small (1 mm) area of fibrosis on the poste- lium and stroma, anterior iris stroma, ciliary
rior lens capsule, and it is a manifestation of muscle, and most structures of the iridocorneal
incomplete regression of the hyaloid artery where angle (ICA). The presence of an adjacent lens
it was attached to the posterior lens capsule. vesicle is required for induction of corneal
Bergmeister’s papilla represents a remnant of the endothelium, identified by their production of
hyaloid vasculature consisting of a small, fibrous the cell adhesion molecule, N-­cadherin.
glial tuft of tissue emanating from the center of Patches of endothelium become confluent and
the optic nerve. Both are frequently observed as develop zonulae occludentes during days
incidental clinical findings. 30–35 in the dog, and during this period,
Descemet’s membrane also forms.
Neural crest migration anterior to the lens
­ evelopment of the Cornea
D forms the corneal stroma and iris stroma also
and Anterior Chamber results in formation of a solid sheet of mesenchy-
mal tissue, which ultimately remodels to form
The anterior margins of the optic cup advance the anterior chamber. The portion of this sheet
beneath the surface ectoderm and adjacent that bridges the future pupil is called the pupil-
neural crest mesenchyme after lens vesicle lary membrane. Vessels within the pupillary
­Retina and Optic Nerve Developmen  11

membrane form the TVL, which surrounds and and they represent the only mammalian muscles
nourishes the lens. These vessels are continuous of neural ectodermal origin. In avian species,
with those of the primary vitreous (i.e., hyaloid). however, the skeletal muscle cells in the iris are
The vascular endothelium is the only intraocular of neural crest origin, with a possible small con-
tissue of mesodermal origin; even the vascular tribution of mesoderm to the ventral portion.
smooth muscle cells and pericytes, which origi- Differential growth of the optic cup epithe-
nate from mesoderm in the rest of the body, are lial layers results in folding of the inner layer,
of neural crest origin. In the dog, atrophy of the representing early, anterior ciliary processes.
pupillary membrane begins by day 45 of gesta- The ciliary body epithelium develops from the
tion and continues during the first two postnatal neuroectoderm of the anterior optic cup, and
weeks. Separation of the corneal mesenchyme the underlying mesenchyme differentiates into
(neural crest cell origin) from the lens (surface the ciliary muscles. Extracellular matrix
ectoderm origin) results in formation of the ante- secreted by the ciliary epithelium becomes the
rior chamber. tertiary vitreous and, ultimately, develops into
lens zonules.
The three phases of iridocorneal angle (ICA)
­ evelopment of the Iris, Ciliary
D maturation include (i) the separation of ante-
rior mesenchyme into corneoscleral and irido-
Body, and Iridocorneal Angle
ciliary regions (i.e., trabecular primordium
formation), followed by differentiation of cili-
The two layers of the optic cup (neuroectoderm
ary muscle and folding of the neural ectoderm
origin) consist of an inner, nonpigmented layer
into ciliary processes; (ii) the enlargement of
and an outer, pigmented layer. Both the pig-
the corneal trabeculae and development of
mented and nonpigmented epithelia of the iris
clefts in the area of the trabecular meshwork;
and the ciliary body develop from the anterior
and (iii) the postnatal remodeling of the drain-
aspect of the optic cup; the retina develops from
age angle, associated with cellular necrosis and
the posterior optic cup. The optic vesicle is
phagocytosis by macrophages, resulting in
organized with all cell apices directed to the
opening of clefts in the trabecular meshwork
center of the vesicle. During optic cup invagina-
and outflow pathways.
tion, the apices of the inner and outer epithelial
In species born with congenitally fused eye-
layers become adjacent. Thus, the cells of the
lids (i.e., dog and cat), development of the
optic cup are oriented apex to apex.
anterior chamber continues during this post-
A thin, periodic acid–Schiff (PAS)-­positive
natal period before eyelid opening. At birth,
basal lamina lines the inner aspect (i.e., vitreous
the peripheral iris and cornea are in contact
side) of the nonpigmented epithelium and ret-
with maturation of pectinate ligaments by
ina (i.e., inner limiting membrane). By approxi-
three weeks and rarefaction of the uveal and
mately day 40 of gestation in the dog, both the
corneoscleral trabecular meshworks to their
pigmented and nonpigmented epithelial cells
adult state during the first eight weeks
show apical cilia that project into the intercellu-
after birth.
lar space. These changes probably represent the
first production of aqueous humor.
The iris stroma develops from the anterior
segment mesenchymal tissue (neural crest cell ­ etina and Optic Nerve
R
origin), and the iris pigmented and nonpig- Development
mented epithelia originate from the neural ecto-
derm of the optic cup. The smooth muscle of the Infolding of the neuroectodermal optic vesicle
pupillary sphincter and dilator muscles ulti- results in a bilayered optic cup with the apices
mately differentiate from these epithelial layers, of these two cell layers in direct contact.
12 Development and Morphology of the Eye and Adnexa

Primitive optic vesicle cells are columnar, but ­Sclera, Choroid, and Tapetum
by 20 days of gestation in the dog, they form a
cuboidal layer containing the first melanin These neural crest-­derived tissues are all
granules in the developing embryo. The neuro- induced by the outer layer of the optic cup
sensory retina develops from the inner nonpig- (future RPE). Normal RPE differentiation is a
mented layer of the optic cup and the retinal prerequisite for normal development of the
pigment epithelium (RPE) originates from the sclera and choroid. The choroid and sclera are
outer, pigmented layer. Bruch’s membrane (the relatively differentiated at birth, but the tape-
basal lamina of the RPE) is first seen during tum in dogs and cats continues to develop and
this time, and becomes well developed over the mature during the first four months postnatally.
next week, when the choriocapillaris is devel-
oping. By day 45, the RPE cells take on a hex-
agonal cross-­sectional shape and develop
microvilli that interdigitate with projections ­Vitreous
from photoreceptors of the nonpigmented
(inner) layer of the optic cup. The primary vitreous forms posteriorly,
At the time of lens placode induction, the between the primitive lens and the inner layer
retinal primordium consists of an outer, of the optic cup. In addition to the vessels of
nuclear zone and an inner, marginal (anu- the hyaloid system, the primary vitreous also
clear) zone. This process forms the inner and contains mesenchymal cells, collagenous
outer neuroblastic layers, separated by their fibrillar material, and macrophages. Primitive
cell processes that make up the transient fiber hyalocytes produce collagen fibrils that expand
layer of Chievitz. Cellular differentiation pro- the volume of the secondary vitreous.
gresses from inner to outer layers and, region- The tertiary vitreous forms as a thick accu-
ally, from central to peripheral locations. mulation of collagen fibers between the lens
Peripheral retinal differentiation may lag equator and the optic cup. These fibers are
behind that occurring in the central retina by called the marginal bundle of Drualt, or
three to eight days in the dog. Retinal ganglion Drualt’s bundle. Drualt’s bundle has a strong
cells develop first within the inner neuroblas- attachment to the inner layer of the optic cup,
tic layer, and axons of the ganglion cells col- and it is the precursor to the vitreous base and
lectively form the optic nerve. Cell bodies of lens zonules. The early lens zonular fibers
the Müller and amacrine cells differentiate in appear to be continuous with the inner, limit-
the inner portion of the outer neuroblastic ing membrane of the nonpigmented epithelial
layer. Horizontal cells are found in the middle layer covering the ciliary muscle. Atrophy of
of this layer; the bipolar cells and photorecep- the primary vitreous and hyaloid leaves a
tors mature last, in the outermost zone of clear, narrow central zone, which is called
the retina. Cloquet’s canal.
Significant retinal differentiation continues
postnatally, particularly in species born with
fused eyelids. At birth, the canine retina has ­Optic Nerve
reached a stage of development equivalent to
the human at three to four months of gesta- Axons from the developing ganglion cells pass
tion. In the kitten, all ganglion cells and central through vacuolated cells from the inner wall of
retinal cells are present at birth with continued the optic stalk. A glial sheath forms around the
proliferation in the peripheral retina continu- hyaloid artery. As the hyaloid artery regresses,
ing during the first two to three postnatal the space between the hyaloid artery and the
weeks in dogs and cats. glial sheath enlarges. Bergmeister’s papilla
­Orbi  13

represents a remnant of these glial cells around Section II: Morphology of the Eye
the hyaloid artery. Glial cells migrate into the and Adnexa
optic nerve and form the primitive optic disc.
The glial cells around the optic nerve and the
­Introduction
glial part of the lamina cribrosa come from the
inner layer of the optic stalk, which is of neural
A thorough understanding of normal ophthal-
ectoderm origin. Later, a mesenchymal (neural
mic anatomy is an integral part of the founda-
crest origin) portion of the lamina cribrosa
tional knowledge for diagnosis and treatment of
develops. Myelinization of the optic nerve
ophthalmic diseases as the majority of the ocu-
begins at the chiasm, progresses toward the
lar tissues can be visualized directly. The veteri-
eye, and reaches the optic disc after birth.
narian can examine eyes from a wide variety of
animal species, and fortunately the eye has
largely retained the same basic components, but
­Eyelids important and clinically relevant differences do
exist. This chapter will primarily present the
The eyelids develop from surface ectoderm,
ophthalmic anatomy of dogs, cats, horses, live-
which gives rise to the epidermis, cilia, and
stock species, and occasional birds, and relates
conjunctival epithelium. Neural crest mesen-
information important to the clinician. More
chyme gives rise to deeper structures, includ-
detailed anatomical information is available in
ing the dermis and tarsus. The eyelid muscles
the standard veterinary and comparative anat-
(i.e., orbicularis and levator) are derived from
omy texts.
craniofacial condensations of mesoderm called
somitomeres. The upper eyelid develops from
the frontonasal process; the lower eyelid devel- ­Orbit
ops from the maxillary process. The lid folds
grow together and elongate to cover the devel- The orbit is the bony fossa that surrounds and
oping eye. The upper and lower lids fuse on protects the eye while separating it from the
day 32 of gestation in the dog. Separation cranial cavity. Through numerous foramina,
occurs two weeks postnatally. the orbit also provides pathways for various
blood vessels and nerves involved in the func-
tion of the eye and nearby structures. The size,
­Extraocular Muscles shape, and position of the orbit differ by spe-
cies and are closely associated with time of
The extraocular muscles (EOM) arise from visual activity and feeding behavior (Table 1.5).
mesoderm in somitomeres (i.e., preoptic meso- In domestic carnivores such as the cat and dog,
dermal condensations). Spatial organization of the orbital axes are set rostrolaterally, approxi-
developing eye muscles is initiated before they mately 10° and 20° from midline, respectively,
interact with the neural crest mesenchyme. to enhance binocular vision and predatory
From studies of chick embryos, it has been feeding behavior.
shown that the oculomotor-­innervated mus- In horses and ruminants, the orbits are posi-
cles originate from the first and second somi- tioned more laterally than carnivores, being
tomeres, the superior oblique muscle from the approximately 40° (i.e., horses) and 50° (i.e.,
third somitomere, and the lateral rectus mus- cattle) from midline. Monocular vision in these
cle from the fourth somitomere. The entire and other ungulate species is enhanced, pro-
length of these muscles appears to develop viding a strong panoramic line of vision, which
spontaneously rather than from the orbital allows for scanning the horizon to search for
apex anteriorly. potential predators.
14 Development and Morphology of the Eye and Adnexa

In the rabbit, the axis of each eye extends as In the feline orbit, the processes of the
much as 85° from the midline; this orbit place- fr­ontal and zygomatic bones extend a great
ment also occurs among the majority of liz- deal more toward one another, resulting in a
ards, some snakes, and in certain fish. In these sh­ortened supraorbital ligament (Figure 1.5b).
latter instances where binocular vision has There is limited orbital space in cats. In
become greatly reduced, there is a tendency for a­nimals with enclosed orbits, closure of the
the eyes to protrude so that the visual axis of temporal side of the orbit is accomplished by
the eye can expand what the optic axis of the union of the zygomatic process of the frontal
skull provides. bone with the frontal process of the zygomatic
All vertebrate orbits are one of two kinds: (i) bone. In the horse, the zygomatic process of
the enclosed orbit, which is completely encom- the temporal bone intervenes between these
passed by bone; or (ii) the open or incomplete two and completes the orbital rim (Figure 1.6).
orbit, which is only partially surrounded by Within the orbit, various foramina and fis-
bone (Figure 1.5a and b). Among domestic ani- sures provide osseous pathways for blood ves-
mals, horses, sheep, cattle, and goats have sels and nerves to pass from the cranial cavity
enclosed orbits. Pigs and carnivores (i.e., dogs and alar canal into the orbital region
and cats) have open orbits. The enclosed orbit (Table 1.5). Those foramina of rather constant
of large herbivorous prey species is theorized position in domestic animals are the rostral
to be essential for protection (and sometimes alar, ethmoidal, lacrimal, orbital, ovale, optic,
horns), whereas the open orbit gives carni- rotundum, and supraorbital. Other foramina
vores the ability to open their jaws widely dur- closely related to the orbital structures are
ing consumption of prey. within the pterygopalatine region, and these
The bony orbit typically consists of five to are the maxillary, caudal palatine, and spheno-
seven bones, depending on the species (see palatine. The orbital foramen is elongated in
Table 1.4). The canine orbit is composed of five, most domestic animals, except the horse;
and sometimes six, bones, the su­praorbital liga- therefore, it is referred to as the orbital fissure.
ment that extends from the frontal to the zygo- In cattle, the orbital fissure and foramen rotun-
matic bone, and the periosteum (Figure 1.5a). dum are typically fused to form the foramen
The orbital rim is formed by the frontal, lacri- orbitorotundum.
mal, and zygomatic bones. Laterally, the orbit is
formed by the supraorbital ligament that is con-
Orbital Fascia
tiguous with a fibroelastic connective tissue
sheath for much of the floor of the orbit. The The orbital fascia consists of a thin, tough con-
orbital floor is incomplete, being partially nective tissue lining that envelops all the struc-
formed by the sphenoid and palatine bones. tures within the orbit, including the bony fossa
Therefore, surgical entry into the deeper orbit itself. This fascia consists of three anatomical
is from the dorsal but primarily the lateral wall. components: the periorbita, Tenon’s capsule or

Table 1.4 Orbital dimensions.

Dimension Feline (mm) Canine (mm) Bovine (mm) Equine (mm)

Width 24 29 65 62
Height 26 28 64 59
Depth —­ 49 120 98
Distance between orbits 23 36 151 173
­Orbi  15

(a) (b)

Figure 1.5 (a) Canine orbit. (b) Feline orbit. Bones of the orbit: frontal (F), lacrimal (L), maxilla (M),
sphenoid (S), temporal (T), and zygomatic (Z). Orbital foramina: rostral alar (A), ethmoidal (E), optic (Op), and
orbital fissure (Or).

Figure 1.6 Equine orbit. Bones of


the orbit: frontal (F), lacrimal (L),
sphenoid (S), temporal (T), and
zygomatic (Z). Orbital foramina:
rostral alar (A), ethmoidal (E), optic
(Op), orbital fissure (Or), and
supraorbital (So).

fascia bulbi, and the EOM fascial sheaths wall, the periorbita is thicker laterally next to
(Figure 1.7). Orbital surgery is usually con- the orbital ligament. Anteriorly, in the dorso-
fined within these fascial tissues or beneath it. lateral part of the orbit, the periorbita sepa-
The periorbita is a conically shaped, fibrous rates and surrounds the lacrimal gland. At the
membrane that lines the orbit and encloses orbital rim, it divides into one part becoming
the globe, EOMs, blood vessels, and nerves. continuous with the periosteum of the facial
The apex of the periorbita is located where the bones and the other, that is, the septum orbit-
optic nerve exits the orbit and continuous with ale, merging with the eyelids and becoming
the dural sheath of the optic nerve. In the orbit, continuous with the tarsal plates (the fibrous
it is thin, attaches firmly to the orbital bones, sheet in the eyelids). Within the periorbital tis-
and forms their periosteum. In the dog, the sue of carnivores (dogs and cats), smooth mus-
periorbita does not always fuse with the perios- cle has been observed along the lateral wall of
teum of the frontal and the sphenoid bones. In the orbit, portions of the roof and floor of the
animals with an incomplete lateral orbital orbit, and next to the periosteal lining of orbital
16 Development and Morphology of the Eye and Adnexa

Table 1.5 Foramina and associated nerves and blood vessels.

Foramen or fissure Species Associated nerves and vessels

Alar, rostral Canine, equine, feline Maxillary artery and nerve


Ethmoidal (one or more) All species Ethmoidal vessels and nerve
Orbital Canine, equine, feline Abducens, oculomotor, ophthalmic,
and trochlear nerves
Orbitorotundum Bovine Cranial nerves III–IV, retinal and
internal maxillary arteries
Optic All species Optic nerve, internal ophthalmic artery
Rotundum Canine, equine, feline Maxillary nerve
Supraorbital Bovine, canine, equine Supraorbital vessels and nerve
(feline variable)
Caudal palatine All species Major palatine vessels and nerve
Maxillary All species Infraorbital vessels and nerve
Sphenopalatine All species Sphenopalatine vessels and
pterygopalatine nerve

Periorbita

Orbital
septum Tenon’s
capsule

Cornea

Muscle
fascia

Figure 1.7 Divisions of orbital fascia: muscle fascia, periorbita, orbital septum, and Tenon’s capsule.

bones, and contraction of the muscle has been by a narrow, cleft-­like space filled with loose
produced by stimulation of the cervical sympa- connective tissue, Tenon’s space. Tenon’s cap-
thetic nerve trunk and results in forward sule is attached to the sclera near the corneo-
movement of the globe. scleral junction (i.e., limbus), and it becomes
Tenon’s capsule (fascia bulbi) is connective continuous with the fascia surrounding the
tissue on the outer aspect of the sclera. EOMs. The fascial sheaths of the EOMs are
Tenon’s capsule is separated from the sclera dense, fibrous membranes loosely attached to
­Orbi  17

the muscles with fine trabeculae of connec- 7 mm dorsally, and 9 mm laterally (Figures 1.8
tive tissue. These sheaths are continuous and 1.9). They move the eye in the direction of
with, or reflections of, Tenon’s capsule, but their names. The dorsal (superior) oblique
they are not always considered part of it. originates from the medial orbital apex, con-
tinuing forward dorsomedially to pass through
a trochlea located near the medial canthus
Extraocular Muscles
and pulls the dorsal aspect of the globe medi-
and Orbital Fat
ally and ventrally (intorsion). The ventral
Three sheets of orbital fascia are separated by (inferior) oblique originates from the antero-
orbital fat. Orbital fat fills the dead space in the lateral margin of the palatine bone on the
orbit and acts as a protective cushion for the medial orbital wall and passes beneath the
eye. The amount of orbital fat varies between eye, crossing the ventral rectus tendon. The
individuals and to a greater extent between muscle divides as it reaches the lateral rectus,
species. The color of orbital fat ranges from with the anterior portion covering the inser-
white to yellow. Some animals, including birds tion of the lateral rectus and the posterior por-
and many reptiles, have very little orbital fat. tion inserting beneath the rectus. The ventral
When the retractor oculi muscle contracts, oblique moves the globe medially and dorsally
orbital fat can displace the glandular tissue (extorsion).
associated with the nictitating membrane The retractor oculi (retractor bulbi) muscle
(NM), resulting in its passive movement over originates at the orbital apex and continues
the cornea. forward to form a cone surrounding the optic
The EOMs suspend the globe in the orbit nerve, and inserting posterior and deep to the
and provide ocular motility (Table 1.6). There recti muscles. The retractor oculi muscle
are four rectus muscles: the dorsal, ventral, retracts the globe into the orbit. The retractor
medial, and lateral recti. They originate from oculi muscle is ubiquitous among mammals,
the orbital apex (i.e., annulus of Zinn) and but it is absent in various nonmammalian
insert, in the dog, approximately 5 mm poste- groups, including birds and snakes. The dorsal,
rior to the limbus medially, 6 mm ventrally, ventral, and medial recti as well as the ventral

Table 1.6 Muscles of the eye and eyelids.

Muscle Function Nerve supply

Dorsal (superior) rectus Rotates globe upward Oculomotor


Ventral (inferior) rectus Rotates globe downward Oculomotor
Medial rectus Rotates globe medially Oculomotor
Lateral rectus Rotates globe laterally Abducens
Dorsal (superior) oblique Rotates dorsal part of globe medially Trochlear
and ventrally
Ventral (inferior) oblique Rotates ventral part of globe medially Oculomotor
and dorsally
Retractor oculi (bulbi) Retracts globe Abducens
Levator palpebrae superioris Raises upper eyelid Oculomotor
Orbicularis oculi Closes palpebral fissure Facial
Retractor anguli oculi Lengthens lateral palpebral fissure Facial
18 Development and Morphology of the Eye and Adnexa

Dorsal
Medial rectus
rectus Trochlea
Annulus
of Zinn
Dorsal
oblique

Lateral
rectus Ventral
oblique
Retractor
bulbi
attachments Ventral
rectus

Figure 1.8 Arrangement of the orbital muscles of domestic animals. Annulus of Zinn, ventral oblique
muscle, ventral rectus muscle, lateral rectus muscle, retractor bulbi muscle tendon attachments, medial
rectus muscle, dorsal oblique muscle, and dorsal rectus muscle.

Dorsal rectus muscle

Ophthalmic
artery vein

Oculomotor nerve

Trachlear nerve
Abducens nerve

Levator palpebrae
muscle
Dorsal oblique muscle
Ophthalmic branch
Medial rectus muscle of cranial nerve V
Optic nerve
Orbital vein
Optic foramen

Ventral rectus muscle


Anastomotic artery
Lateral rectus muscle
Retractor bulbi muscle Orbital fissure

Figure 1.9 Orbital apex of the dog, illustrating structures passing through the optic foramen and orbital
fissure as well as the EOM attachments.
­Eyelid  19

oblique muscles are innervated by the oculo- formed by the upper and lower eyelids is the
motor nerve (CN III), whereas the lateral rec- palpebral fissure. This fissure is prevented from
tus and retractor oculi muscles are innervated assuming a circular shape by the medial (nasal)
by the abducens nerve (CN VI), and the dorsal and lateral (temporal) palpebral ligaments that
oblique muscle is innervated by the trochlear attach each canthus to the respective orbital
nerve (CN IV). wall. The medial ligament inserts into the peri-
osteum of the nasal bones, whereas the lateral
ligament inserts into the temporal fascia and
­Eyelids bones associated with the lateral orbit. In the
dog, the lateral ligament is essentially replaced
The eyelids, or palpebrae, are thin folds of skin by the retractor anguli oculi muscle and its ten-
continuous with the facial skin (Figures 1.10 don; this in large breeds of dogs results often in
and 1.11). The upper (superior) and lower entropion. Closure of the eyelids is achieved by
(inferior) eyelids meet to form the lateral and contraction of the orbicularis oculi muscle
medial canthi (singular canthus). The opening located deep in the eyelids. Opening the eyelids

Figure 1.10 Canine eye. Medial canthus (A), lateral canthus (B), cilia (C), NM (D), ciliary zone of iris (E),
pupillary zone of iris (F), and collarette (G). Inset: Arrows indicate meibomian gland openings.

(a) (b)

Figure 1.11 Equine eye. (a) Medial canthus (A), lateral canthus (B), cilia (C), NM (D), lacrimal caruncle (E),
ciliary zone of iris (F), pupillary zone of iris (G), and granula iridica (H). (b) Arrows indicate vibrissae.
20 Development and Morphology of the Eye and Adnexa

is accomplished by relaxation of the orbicularis upper eyelid but absent on the lower eyelid.
oculi muscle and contraction of the levator pal- The facial hair is sparse adjacent to the lower
pebrae superioris muscle, which inserts into eyelid margins at both the medial and lateral
the upper tarsus. canthi and often at the medial upper eyelid.
The upper eyelid has two to four rows of eye- Horizontal folds are present in both the upper
lashes (i.e., cilia) that usually begin near the and lower eyelids. Vibrissae (long, specialized
medial quarter or third and either extend across tactile hairs) are present on the base of the
to the lateral canthus or end shortly before the lower eyelid and on the medial aspect of the
canthus (Figure 1.12). The lower eyelid has no upper eyelid.
cilia and has a hairless region approximately The eyelids protect the eyes from light, pro-
2 mm wide adjacent to the eyelid margin duce part of the tear film, spread the tear film
extending the length of the lower eyelid and across the cornea, and remove debris from the
around the lateral canthus. The medial can- cornea and conjunctival surfaces. Through clo-
thus, unlike the lateral canthus, has variable sure in a “zipper-­like” fashion from lateral to
amounts of facial hair. medial, the eyelids also direct the preocular
In the cat, neither lid has cilia, but the lead- tear film toward the nasolacrimal drain-
ing row of hair from the medial third laterally age system.
on the upper eyelid is distinct enough in most Histologically, the eyelids consist of four
cats to be considered cilia (accessory cilia or parts: (i) the outermost layer contiguous with
eyelashes). adjacent skin, (ii) the subjacent orbicularis
In the horse, a protuberance of variable size oculi muscle layer, (iii) followed internally by a
and pigmentation (i.e., the lacrimal caruncle) tarsus and stromal layer, and lastly (iv) the
is present at the medial canthus. The lateral innermost layer, the palpebral conjunctiva (see
canthus is more rounded than that of the dog, Figure 1.12).
and small amounts of bulbar conjunctiva and The outer layer of the eyelid is skin covered
sclera are visible both medially and laterally. by a dense coat of hairs with associated seba-
The exposed lateral conjunctiva is often pig- ceous and tubular glands. In dogs and cats, the
mented. The cilia are well developed on the hair follicles might be compound. Tactile hairs

Figure 1.12 Photomicrograph of the eyelid of a dog. Hair follicle (HF), cilia follicle (CF), palpebral
conjunctiva (PC), tarsal gland (TG), skin (S), and orbicularis oculi muscle fibers (O).
­Conjunctiv  21

(pili supraorbitales), similar to the eyebrows of the glands of Krause and Wolfring. In domestic
humans, may be present on or near the upper species, these accessory glands are most com-
eyelids. Bundles of smooth muscle fibers, monly located in the conjunctiva and have
arrectores ciliorum, extend from the follicles of been referred to as conjunctival glands. Their
the eyelashes toward the tarsus. These muscle contribution to the volume of tear film in cats
bundles are absent in carnivores and humans, is negligible.
but they are common in ruminants. The roots
of the large cilia are in close association with
prominent sebaceous glands (glands of Zeis) ­Conjunctiva
and modified apocrine sweat glands (glands of
Moll, ciliary glands). These apocrine glands The conjunctiva is a thin mucous membrane
may provide host defense at the margin of the that lines the inner aspect of the eyelids, the
eyelids and possibly in the tears. anterior and posterior surfaces of the NM, and
Deep to the eyelid skin, there is dense colla- the exposed sclera. The conjunctiva consists of
genous stroma and bundles of striated muscle a thin layer of loose connective tissue beneath
fibers that comprise the orbicularis oculi mus- a simple to stratified epithelium that becomes
cle. The orbicularis oculi muscle is arranged in consistently stratified squamous toward the
parallel rows that extend nearly the full length eyelid margin, and provides the primary surgi-
of each eyelid. In the upper eyelid, the levator cal source of tissues to cover deep and pro-
palpebrae superioris muscle, which originates gressing corneal ulcerations (Figure 1.13). The
from the orbital apex, fans out along the dorsal palpebral conjunctiva lines the inner aspect of
half of the mid-­stroma. The muscle extends the eyelids and the anterior portion of the
toward the inner connective tissue boundary NM. As the conjunctiva reflects onto the globe,
of the orbicularis oculi muscle ending in indi- it is called the bulbar conjunctiva and becomes
vidual small tendons. The eyelid muscles are continuous with the limbal and corneal epithe-
separated from the posterior epithelial lining lium. The bulbar conjunctiva also lines the
of the eyelids (i.e., the palpebral conjunctiva) posterior portion of the NM. The junction
by a narrow layer of dense connective tissue. between the palpebral and bulbar conjunctiva
In most veterinary species, it is less developed is the conjunctival fornix, and the epithelial
(fibrous rather than cartilaginous tissue) and lining in this region varies according to spe-
referred to as the tarsus. cies, ranging from pseudostratified columnar
The meibomian (tarsal) glands are located in to stratified cuboidal.
the distal portion of the tarsus near the eyelid Ventrally, an additional fold is formed by
margins and contribute to the outer, oily com- reflection of the conjunctiva over the NM. The
ponent of the preocular tear film. There are reflections at the conjunctival fornix and NM
typically 20–40 glands present in each eyelid in form the conjunctival sac. All parts of the con-
the dog, and they are usually more developed junctiva are continuous, but for descriptive pur-
in the upper eyelid, especially in cats. These poses, it is divided into the palpebral, bulbar,
holocrine, modified sebaceous glands form and fornix conjunctiva and further referenced
parallel rows of lobules, which have their duct to specific eyelids. The distribution of goblet
openings on the eyelid margins. The nerve fib- cells in the conjunctiva is heterogeneous in the
ers, which are largely parasympathetic in ori- dog. The highest densities occur along the lower
gin, closely appose the basement membrane of nasal and middle fornix, and the lower tarsal
each acinus. portion of the palpebral conjunctiva; this infor-
In addition to the meibomian glands, there mation is important when performing conjunc-
are accessory lacrimal glands associated with tival biopsies. In cats, the conjunctival goblet
the eyelids. In humans, they are referred to as cell density varies widely by region but is
22 Development and Morphology of the Eye and Adnexa

Figure 1.13 Bulbar conjunctiva of a porcine eyelid is externally lined by a stratified to pseudostratified
columnar epithelium possessing numerous goblet cells (GC) near the fornix.

highest in the anterior surface of the NM and the fornix is very thin and translucent, and it
the conjunctival fornices. Additionally, in most lies loosely on the underlying connective tis-
domestic species, the bulbar conjunctiva has sue. In the domestic carnivore, approximately
been reported to either essentially lack goblet 3 mm from the limbus, the bulbar conjunctiva,
cells or have a much lower population of these Tenon’s capsule, and sclera become closely
mucus-­forming cells. The substantia propria of united. The connective tissue is much more
the conjunctiva is composed of two layers: a abundant in this location in the dog than in
superficial adenoid layer, which in the dog and humans and other species. The primary func-
cat contains a variable presence of lymphatic tions of the conjunctiva are to prevent desicca-
follicles and glands; and a deep, fibrous layer tion of the cornea, to allow mobility of the
that contains the conjunctival nerves and ves- eyelids and the globe, and to provide a physical
sels. The arteries of the conjunctiva arise from and physiological barrier against microorgan-
the anterior ciliary arteries, which are branches isms and foreign bodies.
of the external ophthalmic artery, and from
branches of the superior and inferior palpebral
and malar arteries. ­Nictitating Membrane
The lymphatics of the conjunctiva, called
the conjunctiva-­associated lymphatic tissue The NM (membrana nictitans, third eyelid, or
(CALT), are arranged in two plexuses: a super- plica semilunaris) protrudes from the medial
ficial and a deep system. CALT is generally dif- canthus in the ventromedial anterior orbit. It
fuse with intermittent nodules or follicles. contains a cartilaginous, T-­shaped plate, the
Often, the diffuse component of CALT infil- horizontal part of which is parallel to the free
trates and is adjacent to tear-­secreting glands, or leading edge of the membrane (Figures 1.14
especially those associated with the and 1.15). In many species, its free edge is pig-
NM. Variations in the size and distribution of mented. The stroma consists of loose to dense
nodules occur between the upper and lower connective tissue that supports glandular and
eyelids and are influenced by exposure to vari- lymphoid tissue. The distal portion of the
ous foreign substances, including potentially anterior (i.e., palpebral) and posterior (i.e.,
infectious microorganisms. The conjunctiva at bulbar) surfaces is usually covered with
­Nictitating Membran  23

Palpebral surface
A
Bulbar surface
Lymphoid tissue

B Cartilage of the
nictitating membrane
A
Gland of the
nictitating membrane

Figure 1.14 Drawing of a histological section of the mammalian NM.

L
BS

C
C

(a) (b)

Figure 1.15 NM of the horse contains both glandular (G) and lymphoid (L) tissues, with the latter being
superficially located within the stroma next to the bulbar surface (BS). C, cartilage. (Original
magnification, 10×.)

nonkeratinized stratified squamous epithe- horizontal portion of the T cartilage appears


lium. The NM possesses a prominent acces- as a reverse S shape in the cat, a crescent
sory lacrimal gland often referred to as the NM shape in the dog, and a hook shape in the
gland (nictitans gland) or gland of the horse. This cartilage is important when plac-
NM. This gland is serous in horses and cats, ing sutures around it for maximal holding of
mixed (seromucous) in cattle and dogs, and the nictitans flaps.
mostly mucous in pigs. The Harderian gland (Harder’s gland), when
The cartilage of the NM is predominately present, is usually located posterior to the NM,
elastic in the horses, cats, and pigs and hya- and appears grossly and histologically to be an
line in ruminants and dogs. The three-­ extension of the NM gland. This glandular tis-
dimensional shape of the cartilage varies sue in some animals can be considerably larger
considerably among domestic species. The than the NM gland. The anatomical presence
24 Development and Morphology of the Eye and Adnexa

of the Harderian gland among mammals has the NM (35.2%). This layer delivers oxygen and
been found mostly in rodents, with only the other nutrients to the avascular cornea and
Mongolian gerbil having the nictitating gland provides a volume of fluid to “flush” the ocular
as well. In mammals, the secretory cells of the surface and remove debris. The innermost
Harderian glands are columnar and lined by layer is the mucin layer and is produced pre-
myoepithelium. Most importantly, their secre- dominately by the conjunctival goblet cells.
tions contain unusual compounds, including The glycocalyx, produced by the corneal epi-
porphyrins and melatonin. thelial cells, also contributes to the mucin
Harderian glands contain autonomically layer. This layer provides a hydrophilic surface
controlled nerves and are also under the con- over which the aqueous tear fluid spreads
trol of gonadal, thyroid, and pituitary hor- evenly and lubricates the corneal and conjunc-
mones. The functions of this gland remain tival surfaces.
speculative, but they may include immunolog- Excess lacrimal fluid collects by gravity in the
ical defense and photoprotection. In most lower conjunctival sac and is mechanically
domestic animals, the movement of the NM is “pumped” through the upper and lower lacrimal
indirect, resulting from contraction of the puncta located approximately 1–2 mm inside the
retractor oculi muscle, which retracts the globe margin of the medial eyelid (Figure 1.16). Each
into the orbital space and causes passive eleva- lacrimal punctum is surrounded by smooth mus-
tion of the NM, but in the domestic cat, small cle that works in coordination with eyelid blink-
bundles of smooth muscle have been found in ing to remove excess lacrimal fluid and prevent
the NM that most likely contribute to its more its backflow. These puncta continue as the upper
rapid movements. and lower canaliculi, which pass slightly verti-
cally away from the eyelid margins and turn
toward the medial canthus, pass through the
­Lacrimal and Nasolacrimal System periorbita, and meet at a dilation, the lacrimal
sac, located in the lacrimal fossa of the lacrimal
An adequate precorneal tear film (PTF) is nec- bone. This sac empties into the nasolacrimal
essary for optical integrity, maintenance of the duct, which passes through a short, bony canal
cornea, and normal ocular function. The PTF (hence, its smallest diameter and the frequent
serves several functions, including site of obstructions) and opens into the nasal cav-
maintenance of an optically uniform corneal ity, where it continues as a duct until it reaches
surface, removal of foreign material and debris an opening at the floor of the nostril approxi-
from the cornea and conjunctival sac, an oxy- mately 1 cm from the end of the nares.
gen source to the outer avascular cornea, and Approximately 40% of dogs have an accessory
lastly presence of antimicrobial substances opening in the canal as it passes by the root of the
(see Chapter 2, Figure 2.1). upper canine tooth.
The PTF is trilaminar, although all three lay- The lacrimal gland is a diamond-­shaped
ers are intricately mingled, and can be visual- structure in the dorsolateral aspect of the orbit
ized clinically with slit lamp biomicroscopy. underneath the orbital ligament. The mean
The outer, thin, oily layer is produced by the length, width, thickness, and weight of the rel-
meibomian glands and sebaceous glands of atively flat lacrimal gland in three different
Zeis. This layer reduces evaporation of the breeds of dogs were ~17 ± 0.7 mm, ~13 ± 0.4 mm,
underlying aqueous layer and forms a barrier ~3 ± 0.1 mm, and ~316 ± 21 mg, respectively.
along the lid margins that prevents tear overflow. Fifteen to twenty small ductules drain into the
The middle layer is the aqueous layer and is superior conjunctival fornix. Histologically, the
secreted by the orbital lacrimal gland (61.7%), gland is a tubuloalveolar type. The innervation
the accessory glands (3.1%), and the gland of to the lacrimal gland is not fully understood,
­Glob  25

Figure 1.16 The nasolacrimal


Lacrimal gland
system: lacrimal puncta, canaliculi,
lacrimal sac, nasolacrimal duct,
lacrimal gland, and lacrimal ducts. Lacrimal puncta

Lacrimal
ducts Canaliculi

Lacrimal
sac

Nasolacrimal
duct

Figure 1.17 Diagram of the three Sclera


tunics that comprise the mammalian
Choroid
globe. Outermost fibrous tunic (light Ciliary
and dark purple), consisting of the body
cornea and sclera; the middle tunic
called the uvea (light orange),
consisting of the iris, ciliary body,
and choroid; and the nervous tunic Retina Optic
(dark orange) consisting of the retina Cornea nerve
and optic nerve.

Iris

Ciliary
body

but the lacrimal branch of cranial nerve V, and transparent, thus enabling light to pass
sympathetic and parasympathetic nerves are through, and is shaped in a manner that makes
all involved in its function. Clinically, certain it a powerful lens that refracts light rays cen-
cholinergic drugs (e.g., pilocarpine) stimulate trally, toward the visual axis of the eye.
tear secretion, whereas other drugs (i.e., The middle layer is the vascular tunic, called
anticholinergics) decrease tear secretion. the uvea (meaning “grape”). The uvea is fur-
ther divided into the iris, ciliary body, and cho-
roid, and is heavily pigmented and vascularized.
­Globe It functions to restrict the amount of light
entering the eye and to provide nourishment
Components
and remove waste products.
The globe is composed of three basic layers or The innermost layer is the nervous tunic,
coats (Figure 1.17). The outer layer is the which consists of the retina and optic nerve.
fibrous tunic, which is further divided into the The three tunics embrace the large, inner,
cornea and sclera. The fibrous tunic provides transparent media of the eye: the aqueous
shape to the eye. In addition, the anterior humor, lens, and vitreous humor, which col-
­portion of the fibrous tunic (i.e., the cornea) is lectively function to transmit and refract light
26 Development and Morphology of the Eye and Adnexa

to the retina and provide an internal pressure (~7 dorsally and ~5 ventrally). The posterior
that keeps the globe firmly distended. ciliary nerves pursue a long intrascleral course
(up to 12 mm) at the 9-­and 3-­o’clock positions
before entering the suprachoroidal space to
Size, Shape, and Topography reach the iris, ciliary body, and limbus. In the
The eyes in domestic animals are quite varia- dog, the long posterior ciliary arteries enter the
ble in size, but their shapes are comparatively sclera approximately 3–5 mm from the optic
uniform, being spherical in most instances, in nerve in the horizontal meridian. In the cat,
which the three axes of the globe (anteroposte- these arteries can enter the sclera immediately
rior, horizontal or transverse, and vertical) are adjacent to the optic nerve. Recurrent vascular
nearly identical in dimensions (Table 1.7). branches enter the choroid, but the main ves-
Some of the larger ungulates, including the sel trunk continues to be the major supply to
cow and horse, possess globes that are rela- the iris. A variable number of vortex veins
tively flattened in the anteroposterior axis. Two (usually four) emerge from the sclera posterior
principal planes, the equatorial and meridi- to the equator; typically, two vortex veins are
onal, are traditionally used in references to the present dorsally and two ventrally.
three axes. The equatorial plane bisects the
anterior and posterior poles,
and is perpendicular to the meridional plane. ­Cornea
Any plane that runs parallel to the equatorial
plane is called the frontal, coronal, radial, or The cornea is the transparent, anterior portion
transverse plane. The meridional plane moves of the fibrous tunic of the globe. Like the lens,
along the anteroposterior axis of the eye, verti- the cornea is normally clear, and transmits and
cally dividing it into medial and lateral halves, refracts light (40–42 diopters in dogs). The
even though meridional planes can be hori- avascular cornea relies on both the aqueous
zontal or oblique. Planes that run parallel to humor and tear film for nourishment and on
the meridional plane are described as sagit- the eyelids and NM for protection from the
tal planes. external environment. The cornea is elliptical
The optic nerve in most domestic animals in shape, with a horizontal diameter greater
lies inferior and lateral to the posterior pole than the vertical (Table 1.8). In the dog and the
(Figure 1.18a and b). Surrounding the optic cat, the difference between these diameters is
nerve are many ciliary nerves and short poste- small (<1–2 mm), thus making their corneas
rior ciliary arteries. In normal dogs, the mean appear almost circular. In most ungulates, this
number of short posterior ciliary arteries is 12 difference is much more pronounced, allowing

Table 1.7 External globe dimensions (mm).

Meridional anteroposterior Equatorial Horizontal, Ratio


Animal axis of the eye, A (mm) axis, V (mm) T (mm) of A/V/T Ratio of V/T

Horse 43.68 47.63 48.45 1:1.09:1.10 1:1.10


Cow 35.34 40.82 41.90 1:1.15:1.18 1:1.02
Sheep 26.85 30.02 30.86 1:1.11:1.15 1:1.02
Pig 24.60 26.53 26.23 1:1.08:1.06 1:0.99
Dog 21.73 21.34 21.17 1:0.98:0.97 1:0.99
Cat 21.30 20.60 20.55 1:0.97:0.96 1:0.99
­Corne  27

(a) (b)

Figure 1.18 (a) Lateral view of the equine globe. Note the marked flattening in the anteroposterior axis
and the marked ventral exit of the optic nerve from the posterior pole. (b) Posterior view of a canine globe.
LP, long posterior ciliary artery; ON, optic nerve.

Table 1.8 Width and height (mm) of the cornea cornea is innervated by the long ciliary nerves,
measured in a straight line. which are derived from the ophthalmic branch
of the trigeminal nerve. The epithelial cell layers
Ratio of height are richly innervated, and these nerve endings
Animal Width Height to width
are unsheathed among the epithelia. Use of
Horse 34.0 26.5 1:1.28 immunohistochemical localization of neuro-
peptides associated with the ciliary ganglion in
33.1 25.8
the dog has revealed the presence of a well-­
Cow 30.5 23.2 1:1.29
developed pattern of epithelial innervation
Sheep 22.4 15.4 1:1.45
consisting of numerous horizontally oriented
Pig 17.7 14.7 1:1.20 leash formations at the level of the epithelial
Dog 16.3 15.25 1:1.07 basal cells, but the stromal innervations, which
Cat 17.0 16.0 1:1.07 exist superficially, consist of main bundles that
repetitively branch in a dichotomous manner
to create elaborate axonal arborizations. In gen-
for a remarkable horizontal field of view that is eral, the most superficial layers are primarily
further complemented by the lateral position- innervated with pain receptors, whereas more
ing of the orbits, and greater protection from pressure receptors are found in the stroma.
predators. This explains why a superficial corneal injury is
Corneal thickness varies between species, often more painful than a deeper wound.
breeds, individuals, and location (i.e., central The cornea comprises four (sometimes five)
versus peripheral cornea). In most domestic layers. From superficial to deep, the layers are
animals, it is less than 1 mm thick. Corneal the epithelium, Bowman’s layer (in some spe-
thickness is also influenced by age and time of cies), stroma, Descemet’s membrane, and
day. Corneal thickness increases significantly endothelium (Figure 1.19). The transparency
with age in the dog, cat, and horse. of the cornea results from lack of blood vessels,
The cornea is richly supplied with sensory nonkeratinized surface epithelium maintained
nerves, particularly pain receptors, and this by a PTF, relative dehydration (deturgescence),
sensitivity provides protection to the cornea and the size and organization of stromal colla-
and helps maintain its transparency. The gen fibrils.
28 Development and Morphology of the Eye and Adnexa

Figure 1.19 Histological view of the


four layers in the equine cornea:
anterior epithelium (AE), stroma (S),
Descemet’s membrane (DM), and
endothelium (E). Inset: Basal cells (B),
wing cells (W), and squamous cells (S).

Corneal Epithelium
microplicae and microvillae that considerably
The corneal epithelium is a nonkeratinized, expand the cells’ surface area enable move-
stratified squamous epithelium that covers the ment of oxygen, potential nutrients, and vari-
anterior corneal surface. The epithelium is ous metabolic products across the exposed cell
approximately 25–40 μm thick in the domestic membranes of the outermost squamous epi-
carnivore and two to four times thicker in the thelial cells. Also more likely, the microprojec-
ungulate. In the dog, cat, and birds, the ante- tions of the squamous epithelial cells, which
rior epithelium consists of a single layer of can be sometimes intricate in their patterns,
basal cells that lie on a thin basement mem- allow mucin of the PTF to adhere firmly to the
brane (Figure 1.20a and b), two or three layers anterior epithelium, which aids in stabilizing
of polyhedral (i.e., wing) cells, and two or three the tear film on the corneal surface.
layers of nonkeratinized squamous cells. In Beneath the epithelium is a basement mem-
larger animals, the layers of polyhedral and brane, which stains positively with PAS (see
squamous cells are more numerous. The cells Figure 1.20). The basal cells are firmly attached
are arranged to provide orderly replacement of to the basal lamina of the basement membrane
the surface cells during desquamation. (i.e., anterior limiting lamina) by hemides-
There are several layers of outer flattened mosomes, anchoring collagen fibrils, and the
superficial squamous cells. The cells appear to glycoprotein laminin. Ultrastructurally, the
be flat and polygonal with straight borders on basement membrane consists of a 30–55 nm
scanning electron microscopy (SEM) thick osmiophilic layer that is separated from
(Figure 1.21). Both light and dark cell types the basal cell plasma membrane by a 25 nm
can be identified. The light cells contain more wide, electron-­lucent zone (see Figure 1.15b).
microvillae and microplicae. These numerous Hemidesmosomes attach the basal cells to the
projections scatter electrons and, as a result, basement membrane, which in turn anchors
produce a lighter appearance of the cell. The the epithelium to the stroma. The arrangement
darker cells are older and are occasionally seen of hemidesmosomes varies among different
to be desquamating (see Figure 1.15b). Cells in animals, being linear among mammals and
the central cornea have more projections (i.e., amphibians, in rosettes among birds and rep-
microplicae and microvillae) than those in the tiles, and punctate without arrangement, or
periphery. It has been proposed that the fine completely absent, among fish. The epithelial
­Corne  29

(a) (b)

Figure 1.20 Basement membrane (arrows) of the anterior epithelium of the canine cornea viewed light
microscopically with the aid of PAS stain (a) and ultrastructurally (b). AE, anterior epithelium; HD,
hemidesmosomes. (Original magnification, 18 000×.)

Figure 1.21 SEM shows the surface


of the anterior epithelium of a
bovine cornea. The surface cells can
be light or dark. Note the round
bulges, where the nuclei lie within
each cell. Note also that some cells
appear to be desquamating.
(Original magnification, 400×.)

Stroma
cells have strong regenerative abilities (basal
cell turnover time is approximately seven The corneal stroma (i.e., the substantia propria)
days), but after removal of the basal lamina, constitutes 90% of the corneal thickness. It con-
weeks to months may be necessary for it to sists of transparent lamellae of collagenous tis-
completely reestablish. sue, and these lamellae lie in sheets and
30 Development and Morphology of the Eye and Adnexa

Superficial
squamous cells
Wing cells
Basal cells
Basal lamina
Corneal nerve Basement
membrane

Anterior stroma

Figure 1.22 The corneal epithelium and anterior stroma. Nonkeratinized squamous cells (two to three
layers), wing cells (two to three layers), basal cells (single layer), basal lamina, and corneal nerves.

separate easily into planes (Figure 1.22). osteoglycin, and decorin. The collagen in the
Between the lamella are fixed cells and infre- human cornea has a periodicity of 100 nm. This
quent wandering cells. The fixed cells are fibro- special arrangement of the collagen in the
cytes, which are called keratocytes, and their stroma is believed to permit 99% of the light
extensions contribute to the formation and entering the cornea to pass without scatter.
maintenance of the stromal lamellae. The When the corneal stroma is replaced, this
keratocytes have thin nuclei, ill-­defined bor- orderly lamellar organization is absent!
ders, and delicate cell membranes (Figure 1.23a Collagen fibrils, along with the proteoglycans
and b). Similar to lens fibers, these cells possess and their associated GAGs and glycoproteins,
crystallins, which are believed to facilitate tis- constitute 15–25% of the stroma, and they are
sue transparency. Keratocytes can transform the principal support structure of the cornea.
into myofibroblasts when deep corneal injury These collagen fibrils form the matrix for a spe-
occurs, and they can form scar tissue that is not cialized population of proteoglycans within the
transparent. While healing (re-­epithelization) corneal stroma. The cornea is 75–85% water,
of the corneal epithelium is relative fast and it is relatively dehydrated compared to
(7–10 days for the complete corneal surface), other body tissues. This state of dehydration is
replacement of large stromal defects may termed deturgescence and is, in part, a function
require weeks, even months! of the endothelium and epithelium. These cells
The lamellae are parallel bundles of collagen move water out of the stroma via energy-­
fibrils, with each lamella running the entire dependent Na+/K+ adenosine triphosphatase
diameter of the cornea. All the collagen fibrils (ATPase) pumps, being most active in the
within a lamella are parallel, but between lamel- endothelium. Other “pumps” for deturges-
lae, they vary greatly in direction. The lamellae cence might also exist, including carbonic
of the posterior stroma are more regular in anhydrase. These cells pump Na+ and HCO3−
arrangement than those of the anterior third of ions outward, into the aqueous humor and
the stroma. The anterior lamellae are more tears. An osmotic gradient is established, and
oblique to the surface, and they have more water flows down the gradient from the corneal
branching and interweaving. The precise organ- stroma into the aqueous humor. Experimentally,
ization of the corneal stroma is the most impor- removal of the epithelium produces an increase
tant factor in maintaining corneal clarity, which of 200% in corneal thickness after 24 h because
involves the select integration of collagen and of the influx of water. Removal of the endothe-
amorphous ground matrix, consisting of select lium produces an increase of 500% or more in
proteoglycans such as lumican, keratocan, thickness as the permeability increases sixfold,
­Corne  31

(a) (b)

Figure 1.23 (a) SEM of corneal stroma in the dog. (b) TEM of corneal stroma in the horse consists of layers
or lamellae (L) of collagen, which are sparsely interspersed with keratocytes (K). (Original magnification: a,
7400×; b, 10 000×.)

so the endothelium appears to be more uniform than those of the stroma. Bowman’s
important in maintenance of corneal deturges- layer is not elastic, and when damaged it is
cence. Figure 1.24 illustrates the primary roles replaced with scar tissue. Bowman’s layers of
the endothelium plays, both as a pump and as a the land-­based species share similarities in
barrier. The barrier component is provided by size, morphology, and histochemistry, differ-
the tight junctions occurring apically along the ing substantially from that of marine mam-
lateral faces of adjoining cells next to the ante- mals, which may reflect a variation of roles
rior chamber. These tight junctions are sensi- that this structure plays.
tive to calcium exposure, and they break down
when excess free Ca2+ exists in the aqueous
Descemet’s Membrane
humor. The Na+/K+ ATPase pump is located
along the lateral membranes of neighboring Descemet’s membrane is a PAS-­positive homo-
cells. A breakdown of the pump, the barrier, or geneous, acellular membrane that is actually
both will result in rapid movement of water the basement membrane of the posterior
into the highly hydrophilic stroma, causing cor- endothelium. Descemet’s membrane is pro-
neal edema to develop. duced throughout life, thus forming a thicker
The anteriormost stroma has a thin, cell-­free membrane as individuals age. Clinically, the
zone corresponding in location with the membrane shows elasticity, but it contains
anterior-­limiting membrane, also known as only fine collagen fibrils. Descemet’s mem-
Bowman’s layer (anterior lamina), in humans brane is normally under some tension and
and nonhuman primates. Bowman’s layer is when ruptured it tends to curl like a scroll.
also present in birds, giraffes, dolphins, some Descemet’s membrane ends at the apex of the
whales, and large herbivores. In avian and trabecular meshwork in the limbal region. To
human corneas, Bowman’s layer is 10–15 μm some degree, its composition is similar to that
thick, relatively acellular, and composed of of the trabeculae of the ICA. Ultrastructurally,
collagen fibrils of various types. Bowman’s Descemet’s membrane is distinctly layered in
layer fibrils are smaller in diameter and less most animals, usually having a relatively thin
32 Development and Morphology of the Eye and Adnexa

(a) (b)

Figure 1.24 SEM of a four-­year-­old canine corneal endothelium reveals occasional variability in cell size
(a) and the lateral surface interdigitations (arrows) between cells (b). The most prominent feature of the
endothelial cell is the nucleus (N), which bulges slightly into the anterior chamber. (Original magnification:
a, 960×; b, 3500×.)

anterior, unbanded zone next to the stroma, interdigitations between adjacent cells in the
followed by a broad-­banded zone and then by dog. The cell junctions, including zonulae
another broad, posterior unbanded zone occludentes and maculae adherentes, are
located next to the endothelium. Healing and located at the lateral cell margins. The abun-
replacement of Descemet’s membrane can dance of mitochondria, smooth and rough
result in duplication of this structure. endoplasmic reticulum, and a variety of vesi-
cles indicates that these cells are metabolically
active. There is gradual loss of the hexagonal
Corneal Endothelium
shape in older animals due to a gradual decrease
The corneal endothelium is a single layer of in the overall cell density of the endothelium.
flattened cells lining the inner (posterior) cor- In young dogs, endothelial density is greater
nea (see Figure 1.24). The regenerative ability than 3000 cells/mm2 with approximately
of the endothelium varies with species and 3600 cells/mm2 in dogs less than one year old.
age. In most species, active mitosis of the As animals age, endothelial density can gradu-
endothelium occurs primarily in only imma- ally decrease to 50% or less of that number.
ture animals. Specular microscopy and SEM of With a smaller population of cells, the
adult eyes reveal that the cells are usually hex- endothelial cells spread out and produce more
agonally shaped. Closer inspection by SEM pump sites to compensate for increasing leak-
reveals that the surface is spotted with small age. An age-­related decrease in the density of
microvillae and pores, and that the lateral corneal endothelial cells results in little change
edges of one cell interdigitate with another. In in overall corneal thickness, but if the cell den-
young canines (i.e., one to four weeks of age), sity continues to decrease, however, the cells
many of the cells do not have the typical hex- become too attenuated, resulting in the pumps
agonal shape. Pronounced pleomorphism has being unable to withstand the increasing leak-
also been observed in kittens and rabbits. age with concomitant corneal thickening and
Transmission electron microscopy (TEM) loss of optical clarity. This point is known as
reveals the extensive, lateral, convoluted corneal decompensation, and it usually occurs
­Scler  33

when the endothelial cell density decreases to variably connected with the choroidal venous
between 500 and 800 cells/mm2. system, the vortex system. The intrascleral
plexus is variable in size and depth within the
sclera. In rabbits and primates, the plexus is
­Sclera formed on the outer side of circumferentially
coursing canals, and it is composed of its small
The sclera comprises the remainder of the vessels deep in the sclera. In carnivores, the
fibrous tunic of the globe. Anteriorly, it merges intrascleral plexus is prominent and composed
with the peripheral cornea and the bulbar con- of two to four large, anastomosing vessels in
junctiva to form a transition zone, the limbus the mid-­sclera. The intrascleral plexus also
(Figure 1.25a and b). The limbus and now the receives afferent channels superficially via the
peripheral cornea are the main entry sites for episcleral network at the limbus. In the horse,
incisions into the anterior chamber (as for cat- the plexus, which is less prominent,
aract surgery). At the limbus, the sclera is vari- co­llateralizes entirely with the anterior vortex
ably pigmented, and the overlying epithelium system, because it is oriented radially to
is thicker, with pigmented epithelial cells (see fa­cilitate u­nidirectional flow outward from the
Figure 1.25b). The stroma loses the regular angle region toward the vortex veins (posterior
arrangement characteristic of the cornea and or uveoscleral aqueous humor outflow).
takes on a less organized appearance of irregu- The color of the sclera depends on the thick-
lar, dense connective tissue. Numerous blood ness of its stroma, appearing blue when thin
vessels (i.e., the anastomosing branches of the (less than 0.2 mm) or yellow with increased fat
anterior ciliary arteries) terminate in the loops content (carotenoids). The inner surface, which
of the marginal plexus, and then drain back is referred to as the “lamina fusca,” is brown
into the conjunctival venules. Any incision in because of the adherent suprachoroidal pig-
the sclera will result in profuse hemorrhage! ment. The sclera contains elastic fibers that are
Along the outer portion of the anterior scle- interlaced among the collagen fibers, as are mel-
ral stroma is an interconnecting network of anocytes (anteriorly) and fibrocytes (the sclera is
veins, the intrascleral plexus, which receives probably more elastic than the cornea). The
aqueous humor from the veins that drain the collagen fibers, fibrocytes, and occasional mel-
angular aqueous plexus (AAP) (Figure 1.26). anocytes are arranged meridionally, obliquely,
In domestic animals, the intrascleral plexus is and radially in an irregular fashion. The most

(a) (b)

Figure 1.25 Photomicrographs of canine limbus. (a) The irregular connective tissue of the sclera (S)
merges with the highly organized connective tissue of the cornea (C). (b) Close-­up of the outer limbus
reveals an anterior epithelium that is markedly thickened, and contains small blood vessels (BV) and
melanocytes. (Original magnification, 250×.)
34 Development and Morphology of the Eye and Adnexa

conjunctiva and attaches to Tenon’s capsule.


Tenon’s capsule consists of small, compact
bundles of collagen that lie parallel to the sur-
face of the episclera.
Besides dense connective tissue, the sclera can
be largely composed of cartilage in some species,
as in fish, lizards, chelonians, some amphibians,
and birds. When cartilage is found in the sclera,
it usually forms a complete cup that extends to
the margin of the cornea or, in birds and lizards,
to a ring of bony plates or ossicles. Scleral ossi-
cles are located external to the ciliary body
(Figure 1.27a and b). Ossicles are believed to
have evolved for retaining ocular rigidity. The
number of ossicles that comprise a ring can vary
within the same species; in individual eyes with
fewer ossicles, the single ossicle area increases,
resulting in a constant scleral ring area, which
must be avoided when this area is incised.
Figure 1.26 The intrascleral plexus (ISP) of a dog Between the inner sclera and outer uveal tis-
is located within the mid-­sclera (S), and is sues is the sclerociliary/sclerochoroidal space,
interconnected to the AAP by aqueous veins (AV). which is the exit pathway for the posterior uve-
ESV, episcleral veins. (Original magnification, 125×.)
oscleral aqueous humor drainage; this extends
all the way to the optic nerve head.
notable emissaria accommodate the optic nerve,
long and short ciliary nerves, long posterior cili-
ary arteries, vortex veins, and anterior ciliary ­Uvea
vessels and represent weak areas in the sclera
and can enlarge and protrude (called staphylo- The iris, ciliary body, and choroid form the
mas) when IOP is chronically elevated. uvea. Unlike the fibrous coat, the uveal coat is
The episclera is a collagenous, vascular, and highly vascular and usually pigmented. The cili-
elastic tissue that is between the sclera and the ary body and choroid are loosely attached to the

(a) (b)

Figure 1.27 Scleral ossicles (SO) in birds vary in size and shape. (a) Screech owl with large intraosseous
spaces. (Original magnification, 40×.) (b) Chicken with smaller scleral ossicles and considerable overlap
between adjacent ossicles. (Original magnification, 100×.) CM, ciliary body musculature (Crampton’s muscle);
TM, trabecular meshwork.
­Uve  35

Figure 1.28 SEM of the canine anterior uvea. Cornea (C), ciliary processes (CP), ciliary body musculature
(CM), iris (I), and sclera (S). (Original magnification, 25×.)

internal surface of the sclera (Figure 1.28). The that augment the effectiveness of horizontal
iris originates from the anterior portion of the pupillary constriction. Eyes of animals with
ciliary body, and it extends centrally to form a pupils that constrict to a slit are believed, in
diaphragm (the pupil) anterior to the lens. The most instances, to be more sensitive to light
iris and ciliary body are collectively the anterior than those with circular pupils.
uvea, and the choroid is the posterior uvea. The iris has a central pupillary zone (the most
active with pupillary changes) and a peripheral
ciliary zone. The demarcation between these
Iris
two zones is the collarette, which is best demon-
The iris is a diaphragm that extends centrally strated clinically with moderate pupillary con-
from the ciliary body to cover the anterior striction. The portion of the pupillary zone
s­urface of the lens, except for a central open- adjacent to the pupil is sometimes more pig-
ing, the pupil. It divides the anterior ocular mented than the rest of the iris.
compartment into anterior and posterior The function of the iris is to control the
chambers, which communicate through the quantity of light entering the posterior seg-
pupil. The shape of the pupil varies widely ment through a central pupil. Constriction of
among species. Among mammals, it is round the pupil reduces the amount of light entering
in primates, canines, most large felines (c­ougar, the eye. Narrowing the pupil also eliminates
leopard, lion, and tiger), and pigs; it is vertical the peripheral portion of the refractive system,
when constricted in the smaller felines (b­obcat, which diminishes lenticular spherical and
lynx, and domestic cat); and it is oval in a chromatic aberrations. During periods of
h­orizontal plane in herbivores (horses, cattle, reduced light, the pupil dilates allowing maxi-
sheep, and goats). In herbivores, along the mal stimulation of photoreceptor cells.
upper and lower margins of the pupil are The iris is composed of an anterior border
s­everal round dark brown “masses” referred to layer, stroma and sphincter muscle, and poste-
as granula iridica (corpora nigra; Figure 1.29). rior epithelial layers. The anterior border layer
The camelid species have a prominent pupil- consists of two cell types: fibroblasts and mel-
lary ruff along the dorsal and ventral pupillary anocytes. The anterior cells, which lack a base-
margins. These pigmented masses are exten- ment membrane, form an almost continuous
sions of the posterior pigmented epithelium layer with their cellular processes, but frequent
36 Development and Morphology of the Eye and Adnexa

ovoid in the horse. In addition to the scattered


melanocytes in the anterior stroma of most
dog irides, a dense band of melanocytes can be
PE present in the ciliary zone anterior to the dila-
tor muscle, extending centrally to the sphinc-
ter muscle. The granules are generally smaller
and more rod-­like than the pigmented gran-
ules of the posterior epithelium. Particularly in
the horse and the dog, large cells containing
pigment are associated with capillaries and
venules near the sphincter muscle. The iris
I stroma is composed of fine collagenous fibers,
chromatophores, and fibroblasts. The stroma
is loosely arranged except around blood vessels
and nerves, where it can form dense sheaths.
Iridal color varies considerably among indi-
viduals, breeds, and species. The variation of
iridal color results from the amount and type of
pigmentation present. The coloration of irides
in most domestic animals is dark brown, golden
brown, gold, blue, or blue-­green. Several avian
species have brightly colored irides. Historically,
CB
these bright colors were thought to result from
the presence of carotenoids; however, purines
and pteridines may be the major iridal pig-
ments in a variety of avian species, including
Figure 1.29 Equine iris (I) and anterior ciliary doves and great-­horned owls. Combinations of
body (CB). The arrow points to the granula iridica, purines, pteridines, and carotenoids probably
which continues posteriorly as the posterior occur in the irides of avian species.
pigment epithelium (PE). The major arterial circle is located at the
peripheral iris root or the anterior ciliary body
small openings with large intercellular spaces (Figure 1.30a and b), and generally avoided
and extension of underlying melanocyte pro- during intraocular surgeries. The arteries enter
cesses break this continuity. This anterior at the 9-­ and 3-­o’clock positions of the iris as
fibrocytic layer can be exquisitely thin and eas- terminations of the medial and lateral branches
ily overlooked histologically. Particles measur- of the long posterior ciliary arteries. Each
ing up to 200 μm in diameter can diffuse into artery branches dorsally and ventrally to pass
the iris stroma through the anterior portion of circumferentially toward the opposite artery
the iris. For the most part, the melanocytes are and forms an incomplete arterial circle in most
oriented parallel to the iris surface, and their species. In primates, the major arterial circle
processes intermingle with other melanocytes forms a completely enclosed ring. The arteries
and anterior fibroblasts with no intercellular radial to the pupil are tortuous in most animals
junctions. The shape of the melanin granules to accommodate changes in the iridal stroma
in the stroma varies between species and with during pupillary changes. A capillary network
the maturity of the granules. The pigment near the pupillary margin connects the termi-
granules in the cat and dog are lanceolate to nal arterioles with the venules, which pass to
ovoid in shape, whereas they are round to the base of the iris behind the arterioles in the
­Uve  37

(a) (b)

Figure 1.30 (a) In many canine irides, melanocytes are concentrated in a wide band anterior to the dilator
muscle (DM), as seen in the lower half of this iris. MAC, major arterial circle. (Original magnification, 100×.)
(b) Photograph of a cat demonstrating the MAC in the peripheral iris.

posterior stroma. The capillary endothelium is forms the dilator muscle, is continuous with
not fenestrated (hence more permeable), but the pigmented epithelium of the ciliary body,
the type of intercellular junctions varies with whereas the posterior layer, which is densely
species. Venous drainage of the iris occurs pigmented, is continuous with the nonpig-
through tortuous, radial vessels that empty mented epithelium of the ciliary body.
directly into the anterior choroidal veins and The iridal dilator muscle is a single layer of
out the vortex veins. These vessels typically smooth muscle fibers in the posterior iridal
number four in humans, pigs, and cats, but stroma extending from the iris sphincter to the
may vary in other species. In horses, a unique iris periphery. These muscle fibers apically
variation of iridal venous drainage exists where (i.e., posteriorly) contain pigment around their
branches of the intrascleral venous plexus nuclei and are innervated by sympathetic
empty into the bases of the iridal veins, which nerve fibers. The basal regions of each cell,
in turn empty into the anterior choroidal which contain the myofilaments, overlap one
venous circulation. another in a shingle-­like fashion. The basal
The iridal sphincter muscle, which is a flat aspect of the posterior epithelium of the iris
band of thin, circular bundles of smooth mus- faces the posterior chamber and has numerous
cle fibers in mammals and striated muscle fib- surface projections.
ers in nonmammalian species, is located in the The apical portion of the cells of the anterior
iris stroma near the pupil. In the dog and cat, it epithelium (iris dilator muscle) contains the
lies in the posterior stroma, separated from the nucleus and is located adjacent to the apical
pigmented epithelium and subjacent dilator portion of the posterior epithelium. Melanin
muscle by a thin layer of connective tissue granules are predominately present in the api-
(Figures 1.31a and b and 1.32a and b). In the cal portion of the cell. The myoepithelial
horse, the sphincter occupies the main portion (basal) portion has scattered melanin granules,
of the central stroma and is capped by the gran- forms irregular projections into the stroma,
ular iridica when present. The shape of the and is covered by a basement membrane.
sphincter muscle varies among species accord- In avian species and other lower vertebrates,
ing to the pupillary shape (see Figure 1.32). The the iris muscles are striated. In addition to con-
sphincter muscle is innervated primarily by trolling the amount of light that enters the
parasympathetic nerve fibers. back of the eye, the iris of birds is thought to
The posterior iridal surface is covered by two contribute to lenticular accommodation.
layers of epithelium. The anterior layer, which Changes in the pupil diameters of chickens
38 Development and Morphology of the Eye and Adnexa

Figure 1.31 Sphincter muscle (SM) location in the dog (a) and in the horse (b). The sphincter muscle in the
horse is capped by the granula iridica (GI), which is a proliferation of the posterior epithelium (PE). (Original
magnification, 200×.)

(a) (b) (c)

Figure 1.32 (a) Iris sphincter muscles that create a slit pupil when the pupil is constricted as found in
domestic cats, bobcats, and lynx. (b) The circular iris sphincter muscle as found in primates, birds, dogs, and
pigs. (c) Iris sphincter muscle in an ungulate with a horizontal pupil.

and pigeons result in changes in the position- Ciliary Body


ing of their lenses.
The ciliary body is a heavily pigmented struc-
The iris contains numerous myelinated and
ture that provides nourishment and removes
nonmyelinated nerves for autonomic innerva-
wastes for the cornea and lens, and participates
tion. The myelinated fibers do not specifically
in lens accommodation. The ciliary body is
follow the iris vessels, but they have a similar
divided into the anterior pars plicata (corona
pattern as they follow the collagen fibers of the
ciliaris) and the posterior pars plana. The pars
stroma. Upon entering the iris, each long cili-
plicata consists of a ring of 70–100 ciliary pro-
ary nerve forms a dorsal and a ventral branch,
cesses, depending on the species, with inter-
to form a circular nerve in the ciliary zone and
vening valleys (Figure 1.33). The processes are
also to meet their counterparts from the oppo-
generally more prominent and numerous in
site side dorsally and ventrally. The belief that
animals with larger anterior chambers (the
reflex constriction of the mammalian pupil in
cow and horse have 100 and 102 processes,
response to light depends exclusively on neural
respectively) than in animals with smaller
pathways between the eye and central nervous
anterior chambers (carnivores and primates
system may not be true.
­Uve  39

Figure 1.33 Inner surface of the ciliary body of a dog treated with α-­chymotrypsin to remove the lenticular
zonules. Note the thin ciliary processes (CP), which posteriorly give rise to smaller secondary folds (small
arrows). These folds flatten and disappear in the region called the pars plana (PP), which ends posteriorly at the
adjoining retina, forming a line known as the ora ciliaris retinae (arrowheads). (Original magnification, 18×.)

Figure 1.34 SEM (sagittal view) of the inner ciliary body of a dog reveals numerous zonular fibers
attached along the epithelial surface. (Original magnification, 130×.)

have 74–76 processes). Ciliary body processes ciliary body processes varies among species
are often absent in lower vertebrates (most (Figure 1.35). In carnivores, the processes are
fish, lizards, and snakes). In anurans, birds, thin and bladelike, with rounded tips that are
and some reptiles, the ciliary body processes invested with zonular fibers.
are attached to the lens and participate directly Each ciliary process consists of a central core
in accommodation. In mammals, the ciliary of stroma and blood vessels covered by a double
body processes are attached to the lenticular layer of epithelium: an inner, nonpigmented,
zonules, which connect to the lens equator cuboidal epithelium and an outer, pigmented,
(Figure 1.34). The appearance of individual cuboidal epithelium (Figure 1.36a and b).
40 Development and Morphology of the Eye and Adnexa

In ungulates, the double-­layered epithelium is


more columnar than cuboidal. The nonpig-
mented ciliary body epithelium is confluent
posteriorly with the neurosensory retina at the
ora ciliaris retinae and anteriorly with the pos-
terior pigmented epithelium of the iris. The
nonpigmented epithelium most likely produces
the GAGs of the vitreous humor. The enzyme
carbonic anhydrase has been cytochemically
localized at or in the nonpigmented epithe-
lium. The types of cellular junctions between
the nonpigmented and pigmented epithelia of
the ciliary processes consist of many gap junc-
tions interspersed with desmosomes and unu-
sual junctions termed puncta adherentes. The
apical ends possess gap junctions, zonula adhe-
rens, and zonula occludens, which represent
the anatomical site of the blood–aqueous bar-
rier (Figure 1.37). There are also dilated por-
Figure 1.35 SEM of the ciliary processes and
zonular fibers in a horse. Ciliary process (A). Arrows tions of the apical intercellular spaces with
point in the direction of the lens equator as well as villous cytoplasmic processes protruding into
to the horizontal fiber network joining adjacent them. These dilations are termed ciliary chan-
process (B). Zonular fibers in valleys between
nels, and they are usually near the apical termi-
processes (C). Note also the zonular fiber
ensheathment of the ciliary processes (black nation of two adjacent cells.
arrows). (Original magnification, 41×.) The ciliary process pigmented epithelium
is confluent with the retinal pigmented

(a) (b)

Figure 1.36 The bilayered ciliary epithelium that lines the ciliary processes and intervening valleys. The
outer layer is pigmented; the inner layer is nonpigmented. (a) Feline ciliary processes. Inset: Cross section of
ciliary processes. The bilayered epithelium, which is cuboidal, lines blood vessels (BV), which together form
a blood–aqueous barrier. (b) Longitudinal section of an equine ciliary epithelium at the base of a process.
Both layers are considerably more columnar than those in the dog and cat. (Original magnification, 400×).
­Uve  41

A thin layer or core of loose connective


t­issue with blood vessels and nerves lies under
the ciliary epithelium, separating the ciliary
body epithelium from the underlying ciliary
body musculature. The vascular plexus within
the stroma of the ciliary process is leaky, being
lined with a fenestrated endothelium. Fibrocytes
and melanocytes are sparsely populated within
the stroma, being more concentrated near the
ciliary body muscle.
The pars plana is the flat, posterior portion
of the ciliary body that extends from the poste-
rior termination of the processes to the retina
(ora ciliaris retinae) and an important area to
access surgically the vitreous space and poste-
rior segment (see Chapter 13, Section III). The
width of the pars plana varies because the ret-
ina extends more anteriorly in the inferior and
medial quadrants in most species, enhancing
Figure 1.37 Apical junctions of nonpigmented peripheral vision. Therefore, the pars plana is
(NPE) and pigmented (PE) ciliary epithelium in a usually widest superiorly and laterally.
cat. The nonpigmented epithelial nuclei are
located apically; the wide intercellular spaces and
villi can be seen in the basilar aspect of the Ciliary Body Musculature
intercellular spaces of the nonpigmented
epithelium. The apical aspect of the nonpigmented The ciliary body muscle is comprised of smooth
intercellular space is the anatomical site of the muscle fibers in mammals. Contraction of the
blood–aqueous barrier and contains a fascia ciliary body muscle draws the ciliary processes
occludens (small arrow) and fascia adherens (large
arrow). The apical cell surfaces contain a fascia and body both forward and inward, thus relax-
adherens, gap junctions (open arrows), and ing the lenticular zonules (suspensory ligament
arch-­shaped gap junctions (curved arrows). The of the lens) and altering the shape and refrac-
basement membrane (B) of the pigmented tion of the lens. This muscle is often weakly
epithelium. (Original magnification, 9800×.)
developed in many nonprimate species and, as
a result, offers poor accommodative ability. On
epithelium. Anteriorly, it continues as the the basis of ciliary body musculature develop-
anterior pigmented epithelial layer of the iris, ment, the placental mammalian ICA has been
which forms the dilator muscle. The pig- categorized into three main groups, the herbiv-
mented epithelium is generally cuboidal and orous, the carnivorous, and the anthropoid,
heavily laden with round-­to-­oval melanin and seems based primarily on the lens rather
granules. The basal aspect of the pigmented than aqueous humor outflow (Figure 1.38).
epithelium faces the ciliary body stroma and The herbivorous type has been characterized
is covered by a basement membrane. The as the most common and primitive in orders of
nuclei of both pigmented and nonpigmented mammals up to and including ungulates. This
epithelia are located apically. The cytoplasm type of angle consists of an inner layer of
of the pigmented epithelium contains mela- connective tissue that forms a baseplate of the
nin granules, rough endoplasmic reticulum, ciliary body and extends from the root of the iris
smooth endoplasmic reticulum, free ribo- to the ora ciliaris retinae. It also consists of an
somes (polysomes), and mitochondria. outer layer of smooth muscle that presses against
42 Development and Morphology of the Eye and Adnexa

and carnivorous types, the ciliary cleft offers


little support to properly anchor the iris.
CC Compensation for wide and deep ciliary clefts
is provided by a series of pectinate ligaments
attaching the anterior iridal root and inner
(a) ciliary baseplate to the limbal cornea.
The ciliary body musculature of primates is
believed to be the most highly developed
CC among mammals. The muscle, which has
three components (i.e., radial, meridional, and
circular), forms a large, anterior pyramidal
(b)
structure that provides a strong baseplate for
iridal attachment. The anterior portion of the
ciliary body muscle has replaced both the cili-
CC
ary cleft, which barely exists in the anthropoid
angle, and the pectinate ligaments, which ves-
(c) tigially consist of scattered iridal processes in
primates, including humans.
Figure 1.38 Degree of development of the ciliary
body musculature among mammalian ICAs in the In birds and other nonmammalian species, the
ungulate (a), carnivore (b), and ape (c). The ciliary ciliary body muscle consists of skeletal muscle
body musculature is most pronounced in primates cells that are primarily meridional. At least two
and least developed in ungulates. The size of the distinct muscle bundles are located in this region
ICA and its cilioscleral cleft or sinus (CC) is inversely
large or most pronounced in the ungulate. of the avian eye: an anterior bundle, which is
known as the muscle of Crampton, arises near
the corneal margin; and a posterior bundle,
the sclera externally and runs meridionally from which is known as Brücke’s muscle. Contraction
the corneoscleral junction toward the ora ciliaris of Brücke’s muscle causes the ciliary body to
retinae. The two layers are often referred to as push against or compress the lens, thus deform-
“leaves” that separate anteriorly forming the cili- ing it, while contraction of Crampton’s muscle
ary cleft. The ciliary cleft is then a triangular area alters the shape of the cornea by shortening its
that varies in both depth (i.e., length) and height, radius of curvature.
and functionally may be considered a posterolat-
eral extension of the anterior chamber into the
Ciliary Body Vasculature
ciliary body. Historically, this region was initially
called the cilioscleral sinus, but the term cilio- The extensive blood supply of the ciliary body
scleral sinus has been replaced with ciliary cleft. is derived from the two long posterior ciliary
The ciliary cleft is an area containing wide arteries and the anterior ciliary arteries. As the
spaces filled with aqueous humor and inter- long posterior arteries pass into the supracho-
spersed with cell-­lined cords of connective tissue. roidal space equatorially along the laterome-
The spaces between the fibrous cords were ini- dial horizontal plane, they undergo several
tially described in cattle and horses, and they divisions. These divisions anastomose anteri-
have been often referred to as Fontana’s spaces. orly with branches of the anterior ciliary arter-
The carnivorous type possesses a bi-­leaflet ies to form the major arterial circle, which is
configuration as well, but the fibrous inner leaf located either in the base of the iris or in the
or layer is usually replaced by meridionally anterior ciliary body. The anterior ciliary arter-
oriented smooth muscle and some radially ori- ies, which arise from branches of the ophthal-
ented muscle fibers. In both the herbivorous mic artery, typically enter the globe at the
­Uve  43

attachment sites for the recti muscles and help The pectinate ligaments consist of long
to supply the ciliary muscles. The major arterial strands anchoring the anterior base of the iris
circle is the primary vasculature supply of the to the inner peripheral cornea (Figures 1.39
ciliary processes. and 1.40). In the dog and cat, these strands are
Numerous anatomical variations of this vascula- usually slender and widely separated from each
ture have been found among mammals. The other, thus making it difficult to visualize histo-
m­ammalian ciliary body muscle is supplied by logically an intact pectinate ligament fiber for
p­arasympathetic fibers from the oculomotor nerve its entire length. In contrast, most ungulates
and by sympathetic nerve fibers. The parasympa- possess moderately broad to very stout pecti-
thetic fibers leave the oculomotor nerve, penetrate nate ligaments. The pectinate ligaments are
the ventral oblique muscle, and synapse in the entirely lined by cells that are confluent with
ci­liary ganglion. From the ciliary ganglion, short the anterior surface of the iris. Posteriorly, the
ciliary nerves penetrate the sclera around the optic pectinate ligament anastomoses with anterior
nerve to pass into the sclera and suprachoroidal beams of the trabecular meshwork that is
space innervating the ciliary muscle and iris divided into the uveal trabecular meshwork,
m­uscles. The sympathetic fibers arrive via the long which in most animals comprises most of the
ciliary nerves from the dorsal or superior cervical inner ICA area, thus forming the ciliary cleft,
ganglia in a similar manner. and the corneoscleral trabecular meshwork,
which is similar in construction to the uveal
meshwork but smaller in size of both the tra-
Iridocorneal Angle
becular beams and the channels or spaces
Aqueous humor is produced by the ciliary between the cell-­lined beams (the main area of
body epithelium and enters the posterior resistance to the outflow of aqueous humor
chamber before flowing through the pupil into outflow). The uveal meshwork interconnects
the anterior chamber. In the conventional out- the inner, anterior ciliary body muscle with the
flow pathway, aqueous humor exits the eye pri- pectinate ligament.
marily through the corneoscleral trabecular
(pressure sensitive) meshwork.
The anatomy of the aqueous humor outflow
system has been extensively studied in humans,
nonhuman primates, dogs, cats, rabbits, horses,
and other ungulate species. This system pri-
marily consists of the ICA, which is bounded
anteriorly by the peripheral cornea and per-
ilimbal sclera, and posteriorly by the peripheral
iris and anterior ciliary body muscle. From
amphibians to higher mammals, the ICA con-
sists of an irregular, reticular network of con-
nective tissue beams called trabeculae that are
lined partially or entirely by a single layer of
cells. The size of the ICA varies among species.
In dogs of different ages and breeds that had
undergone cataract surgeries, the size of the
ICA as determined by the angle opening dis-
Figure 1.39 Gonioscopic view of the anterior
tance (the distance between the internal limbus
ciliary body shows the fibrous strands, known as
and the base of the iris) using ultrasound the pectinate ligaments, that attach the anterior
biomicroscopy was found to vary considerably. base of the iris to the limbus.
44 Development and Morphology of the Eye and Adnexa

Figure 1.40 Frontal view SEM of the canine ICA. Fibrous pillars that attach the iris (I) to the limbus form
the pectinate ligaments (PL). Arrows indicate smaller fibrous connections between these pillars and uveal
trabeculae located behind the pectinate ligament. (Original magnification, 160×.)

The corneoscleral trabecular meshworks of much of the nonfiltering portion of the ante-
domestic animals are characterized mainly by rior trabecular meshwork (Figure 1.41).
small trabeculae separated by small intertra- The external boundary of the corneoscle-
becular spaces. In carnivores, these trabeculae ral trabecular meshwork is formed by the
are incompletely lined by trabecular cells. sclera and a plexus of aqueous humor collec-
Composition of the trabeculae varies very little tor vessels. In mammals and most lower
among species. The core, or center, of each v­ertebrates, the aqueous humor chiefly exits
beam is made up of circularly and me­ridionally the eye through the trabecular meshworks
oriented collagen fibers interspersed with a into these vessels. In most mammals, these
modified elastin. The core is usually en­veloped ve­ssels consist of a small network of veins
by a cortical zone consisting of am­orphous, collectively termed the AAP. These vessels
granular material surrounded by basement have radially oriented lumens, differing from
membrane-­like material. Trabecular cells are the circumferentially coursing canal of
similar across species, being fibroblast-­like Schlemm in primates. The plexiform nature
with slender cell processes that attach to adja- of the drainage vessels in most mammals
cent cells and their processes. These processes allows removal of a substantial amount of
allow the corneoscleral trabecular meshwork aqueous humor.
to act as a sieve, thus reducing the size of the The size of the individual collector vessels
particles that can move into the meshwork. (i.e., trabecular veins) and the tissue immedi-
The trabecular cell also has the ability to ingest ately adjacent to the AAP varies considerably
a wide variety of particles, which can range among mammals. The trabecular veins in cattle,
greatly in size. The phagocytic-­like quality of sheep, and water buffalo are large and exten-
the trabecular cell provides the ICA with an sive. Those associated with dogs, cats, pigs, and
indigenous clearance mechanism for debris, horses are less prominent but are still extensive.
thus reducing possibilities for an inflammatory The manner by which aqueous humor flows
response. An operculum is located within the into the trabecular veins of the AAP or canal of
canine trabecular meshwork, and comprises Schlemm is not completely understood. Most
­Uve  45

Figure 1.41 Cells associated with the operculum in the dog form clusters and can be linearly arranged
(Schwalbe’s line cells [SLC]) within the anteriormost regions of the corneoscleral trabecular meshwork. O,
operculum. (Original magnification, 9800×.)

of the aqueous humor is thought to move C


through large, vacuole-­like structures of the
inner endothelial cells.
The area adjacent to the trabecular veins typi- AC
cally consists of a zone of cellular elements
APP
intermixed with irregularly arranged elastin, I
collagen, and basement membrane-­like mate-
US PC
rial. In some species, including dogs, rats, rab-
bits, and humans, smooth muscle-­like cells Lens
(myofibroblastic cells) have been observed in the
trabecular meshwork, especially adjacent to V
the aqueous humor outflow channels and along
the distal or outer walls of the AAP and Figure 1.42 The majority of aqueous humor flows
Schlemm’s canal. In the dog, the presence of from the posterior chamber (PC) into the anterior
myofibroblastic cells within the ICA suggests chamber (AC), where it is removed via the ICA by
that these cells and the smooth muscle cells of the trabecular meshwork and AAP. Other drainage
routes include exchange across the vitreous face
the ciliary body along the same plane of orienta- (V), iris vessels (I), and corneal endothelium (C), and
tion function to facilitate the removal of aqueous via the uveoscleral (US) pathway.
humor and are likely to be influenced by vascu-
lar mediators.
adjacent sclera (Figure 1.42). The lattermost
Uveoscleral Outflow pathway is called the uveoscleral, or uncon-
Aqueous humor is not entirely removed by a ventional, outflow pathway (not sensitive to
plexus of collector vessels via the ICA. Some changes in intraocular ocular pressure). The
aqueous drains posteriorly into the vitreous degree of uveoscleral outflow varies remarka-
humor, anteriorly within the iridal stroma and bly between species, with cats experiencing the
across the cornea, or exteroposteriorly along a least drainage (3%), followed by humans
supraciliary–suprachoroidal space into the (4–14%), rabbits (13%), dogs (15%), and
46 Development and Morphology of the Eye and Adnexa

nonhuman primates (30–65%). In the horse, the anterior margin of the choroid joins the
the uveoscleral pathway may be just as impor- ciliary body along a regular, non-­serrated junc-
tant as the conventional route for aqueous tion called the ora ciliaris retinae. In primates,
humor removal (Figure 1.43). the junction is irregular and serrated and
termed the ora serrata. The choroid tends to
thicken along the posterior pole, becoming
Innervation
thinner toward the globe equator.
As mentioned previously, the ciliary muscula- For morphological discussions, the choroid
ture is innervated both sympathetically and is divided externally to internally, into the
parasympathetically. Cholinergic and adrener- suprachoroidea, the large-­vessel layer, the
gic nerve endings have been observed in the medium-­sized vessel and tapetum layer, and
various components of the ciliary body, includ- the choriocapillaris (Figure 1.45). The tapetal
ing the trabecular meshwork and within the layer varies among species, and it is absent in
ICA. In the dog, cholinergic activity is most pigs, squirrels, rodents, kangaroos, llamas,
intense in the musculature, ciliary processes, alpacas, and many nonhuman primates. The
and epithelium. suprachoroidea consists of elastic, heavily pig-
mented connective tissue that forms a transi-
tion between the sclera and the choroid, and
Choroid
functions as the posterior component for uveo-
The choroid is the posterior portion of the scleral outflow. Aqueous humor that has
uveal coat. It is composed primarily of blood moved along this narrow junction of the sclera
vessels (mainly thin-­walled veins) and pig- and choroid diffuses into the sclera and, subse-
mented support tissues (Figure 1.44a and b). It quently, the systemic circulation. The layers of
is the main source of nutrition for the outer melanocytes and fibrocytes and the interspers-
layers of the retina. In most domestic animals, ing collagen and elastic fibers may produce

Figure 1.43 Located between the ciliary body meshwork and the sclera (i.e., supraciliary space), the
supraciliary meshwork likely represents a major pathway for aqueous humor drainage in the horse via
uveoscleral outflow. SCT, supraciliary trabecula; TC, trabecular cell. (Original magnification, 3500×.) Inset:
Light micrograph of the meshwork. S, sclera. (Original magnification, 200×.)
­Uve  47

100 μm
(a) (b)

Figure 1.44 (a) The canine choroid (C) consists of the suprachoroidea (1), large-­vessel layer (2), medium-­
sized vessel and tapetum layer (3), and choriocapillaris (4). R, retina; BV, blood vessel. Asterisk denotes a
nerve within the sclera. (b) SEM shows a close-­up view of the outer choroid, where the suprachoroidea (Su)
forms fine collagenous attachments (arrows) with lamina fusca of the sclera (S). (Original
magnification, 850×.)

resistance to uveoscleral drainage, even though


a cellular barrier has not been found. The long
posterior ciliary nerves and arteries course
their way anteriorly in the suprachoroidea
along the horizontal meridian.
Immediately internal to the suprachoroidea
or the large vessel layer is a vascular plexus
embedded in loose connective tissue contain-
ing melanocytes and fibrocytes. This plexus is
composed mostly of large veins and scattered
arteries. Four or more prominent vortex veins
are located obliquely near the globe equator
between the horizontal and vertical meridians.
In cross section, the veins are cavern-­like,
occupying 50% or more of the total volume of
the choroid. The large arteries, which are
much fewer in number, are mostly branches of
the short posterior ciliary arteries, which enter
the globe in the vicinity of the optic nerve and
supply the retina, optic nerve, and choroid.
Figure 1.45 SEM of the posterior canine eye In addition to providing the major source of
shows that the choroid (C) is composed mostly of oxygen and nutrients for the retina, the large
large, cavernous veins (V) that drain the
choriocapillaris (arrow), which nourishes the outer vessels may act as a “cooling system,” dissipat-
retina (R). S, sclera. (Original magnification, 25×.) ing the heat produced from light absorption.
48 Development and Morphology of the Eye and Adnexa

The osmotic pressure created by high levels of passed through the retina and thus restimu-
plasma proteins in the choroidal tissue fluid lates the photoreceptor cells. The tapetum
might also assist in keeping the retina attached lucidum is responsible both for the “eye-
to the RPE, by allowing retinal fluids to pass shine” seen at night when the eye is illumi-
into the choroid, and then subsequently into the nated and for the variable background color
suprachoroidea, sclera, and episcleral tissues. of the ocular fundus when viewed ophthal-
A small layer of medium-­sized vessels and moscopically during fundic examination.
pigmented reticular connective tissue lies inter- Animals without a tapetum lucidum have
nal to the large-­vessel layer. These vessels are diurnal habits and red or orange to pale gray
emissaries between a single sheet of capillaries (depending on the amount of choroidal pig-
and the layer of large blood vessels. The mentation) fundic reflections. The tapetal
medium-­sized vessels, especially the arteries, layer is composed of regularly arranged col-
dichotomously branch, radiating slightly inward lagenous fibers in herbivores (i.e., the tape-
in a fanlike manner from the larger vessels. tum fibrosum in horses, cattle, sheep, and
In most domestic animals, the dorsal por- goats) and of specific polyhedral cells, or iri-
tion of the choroid at the medium-­sized ves- docytes, containing reflecting crystals in car-
sel layer contains a layer of reflective tissue nivores (i.e., the tapetum cellulosum in the
called the tapetum lucidum. The tapetum is dog and cat). Histologically, the tapetum cel-
roughly triangular in shape when viewed lulosum is composed of rectangular-­shaped
funduscopically, and it varies in color cells with a species-­dependent variability in
(Figure 1.46a and b). It reflects light that has number of cell layers. The tapetal layer is
thickest centrally and thins toward the
periphery until the tapetum cellulosum is
replaced by regular choroidal stroma. From
the underlying choroidal stroma, numerous
small vessels penetrate the tapetal layer to
form a single-­layered capillary bed, known as
the choriocapillaris network, on the inner
TL surface of the tapetum.
In ungulates, closely and regularly arranged
collagen fibers comprise the tapetum, which is
often referred to as a fibrous tapetum. The
(a)
fibrous tapetum is basically acellular, except
for an occasional fibrocyte. The collagen fibrils
are organized into well-­ordered lamellae that
branch and interconnect with adjacent lamel-
TL lae at the same level, parallel to the retinal
surface.
Small blood vessels, typically capillaries, pen-
etrate the tapetum at right angles to the long axis
of the iridocytes in carnivores, and to the colla-
gen lamellae in herbivores, directly intercon-
(b) necting the medium-­sized blood vessels with the
choriocapillaris. When observed ophthalmo-
Figure 1.46 The carnivorous tapetum lucidum
scopically, these end-­on vessels are sometimes
consists of layers of cells, called iridocytes, which
vary in number, size, and composition. (a) The dog. called the “stars of Winslow.” The choriocapilla-
(b) The cat. (Original magnification: all, 200×.) ris is the innermost layer of choroidal vessels,
­Len  49

forming a thin layer of capillaries separated from axis, with 10 mm equatorial diameter. The
the RPE by a basement membrane complex ratio of lens volume to entire globe volume
known as Bruch’s membrane. ranges from 1:8 to 1:10. The equine lens, on
the other hand, has a volume of approximately
3 ml, 12–15 mm average anteroposterior axis
­Lens thickness, approximately 21 mm equatorial
diameter, and a lens–globe ratio of 1:20. Lens
The crystalline lens is a transparent, avascular volumes of sheep, cattle, and pigs fall between
structure that focuses light onto the retina. It is these volumes, thicknesses, and diameters.
suspended within the eye by zonules arising The lens consists of an enveloping basement
from the ciliary body epithelium (i.e., pars pli- membrane called the lens capsule, an anterior
cata) and attaching circumferentially to the epithelium, and lens fibers occupying two
lens capsule at the lens equator. The lens is also main zones: the nucleus and the cortex
held in place posteriorly within a shallow (Figure 1.47).
depression in the anterior vitreous (i.e., the
patella fossa), and the iris rests against it anteri-
Lens Capsule
orly. In many mammals, birds, and reptiles, the
lens is biconvex; the degree of convexity (i.e., The lens fibers are completely enclosed within
shape) changes during accommodation due to a thick, PAS-­positive capsule, which is the
the elasticity of the capsule and the pliability of exaggerated basement membrane of the lens
the lens fibers. In young mammals, the lens is
quite soft, with only a small, central, denser
Anterior capsule
nucleus. The lens grows throughout life, with
newly formed fibers added continuously to the Cortex
outermost cortex, causing compression of the
central, older zone of lens fibers. This results in
Adult nucleus
a hardening of the central nucleus (i.e., nuclear
sclerosis), which reduces accommodation abil- Fetal
zf nucleus
ity as the lens ages.
The refractive power of the lens is less than Embryonal
nucleus
the cornea because the change of refractive
index is much greater at the air–cornea inter-
face than at the aqueous–lens and lens–vitre-
ous interfaces. Contraction of the ciliary body
muscle reduces tension on the lenticular
zonules, changing the shape of the lens and
resulting in an alteration of the dioptric power.
Posterior capsule
Of the roughly 60 diopters of total refractive
power of the eye, the lens contributes approxi- Figure 1.47 Composite drawing of the lens,
mately 13–16 diopters in humans. In dogs, the capsule, attachments, and nuclear zones. The lens
epithelial cells line the anterior capsule. At the
dioptric power of the lens contributes approxi-
equator, these dividing cells elongate to form lens
mately 40 diopters. The remaining refraction is cortical cells (fibers). As they elongate anteriorly
provided by the cornea. and posteriorly toward the sutures, their nuclei
The lens is proportionately larger in domes- migrate somewhat anterior to the equator and
form the lens bow. Zonular fibers (zf) attach to the
tic animals than in humans. The dog lens has
anterior and posterior lens capsule and to the
a volume of approximately 0.5 ml and aver- equatorial capsule, forming pericapsular or zonular
ages 7 mm in thickness at the anteroposterior lamellae of the lens.
50 Development and Morphology of the Eye and Adnexa

epithelium. It has elastic properties but no


elastic fibers. The thickness of the capsule var-
ies by region, with the thinnest being the pos-
terior pole. The canine lens capsule thickness
is 8–12 μm at the equator, 50–70 μm anteriorly,
and only 2–4 μm posteriorly.

Anterior Epithelium
Lining the anterior capsule is a monolayer of lens
epithelial cells that continuously produce new
basement membrane (i.e., capsule material). The
cells are cuboidal to squamous axially at the ante-
rior pole of the lens, become columnar near the
equator, and then elongate into slender hexago-
Figure 1.48 Young horse lens near the equator.
nal lens fibers. Nuclei are lost as lens fibers (a) Lens capsule. (b) Columnar lens epithelium at
mature and move centrally. The lens epithelium equator. Arrows delineate the formation of the lens
lines only the interior aspect of the anterior sur- bow by the nuclei of the newly formed fibers. Open
arrow points rostrally. (Original
face of the capsule postnatally. The cell apices
magnification, 500×.)
face the outer lens fibers, being attached to the
underlying cortical fibers by tight junctions
(zonula occludens) and macula adherens. The beneath the epithelium and the basal portion
posterior lens epithelium forms the embryonic posteriorly along the capsule. As these cells
primary lens fibers and, thus, is absent under the transform into lens fibers, small ball-­and-­socket
posterior lens capsule later in life. interdigitations begin to develop and the lens
Mature lens fibers become dependent on the fibers become roughly hexagonal in shape. The
anterior epithelium for maintaining a critical ball-­and-­socket junctions, which are present
level of dehydration, which allows the soluble along the length of the fibers, are formed only at
proteins to be functionally effective, and for the six angular regions; in this way, any particu-
providing a healthy level of reduced glu- lar lens fiber is tightly coupled to six other lens
tathione. The lens epithelium is highly suscep- fibers, including two older fibers, two of the
tible to damage caused by factors such as same generation, and two younger fibers.
changes in local oxygen concentration, expo- The lens fibers elongate toward the anterior
sure to toxins, X-­ray irradiation, and ultraviolet and posterior poles, forming a U-­shaped cell. The
light damage. fibers do not reach the full distance from one
pole to the next, much less the entire circumfer-
ence of the lens; rather, they meet fibers from
Lens Fibers
the opposite side to form the clinically visible
Immediately anterior to the lens equator is a anterior and posterior lens sutures. The sutures
proliferative zone within the epithelium, are simply the junctions from opposite fibers at a
referred to as the lens bow (Figure 1.48a and b). given level in the lens. They vary in configuration
The cells within this zone begin to mitose at among species and at different levels within the
approximately the same time the primary lens lens. The sutures usually form a Y-­shaped pattern
fibers form during early fetal development. This near the center of the lens, but in older eyes, they
zone of mitosis continues throughout life. The become more complex, with branching arms in
most recently formed cells elongate, with the the more superficial layers (Figure 1.49). The
apical portion of the cell extending forward suture patterns extend throughout the depth of
­Len  51

Figure 1.49 Drawing of the embryonal lens (i.e., nucleus) shows the anterior (a) Y suture, posterior (p) Y suture,
and arrangement of the lens cells. The lens cells are depicted as wide, shaded bands. Those that attach to the
tips of the Y sutures at one pole of the lens (a) attach to the fork of the Y at the opposite pole (p).

the lens, but they are apparent in vivo only at mid-­equatorial region of the lens, while the
optical interfaces. The sutures in the anterior half peripheral edge of the iris presses against the
are typically in an upright Y-­shaped pattern, anterior equatorial surface. As an evolutionary
whereas those on the posterior half are in an adaptation to this activity, the avian lens has an
inverted Y-­shaped pattern. annular pad (i.e., “ringwulst”), which consists
The mammalian adult lens consists of lens of lens fibers that are relatively enlarged and
fibers formed chronologically throughout life. arranged radially instead of concentrically. The
The oldest portion, formed during embryonic size of the annular pad appears to relate directly
development, is in the center of the lens and to the degree of accommodative ability.
known as the embryonic nucleus. It is a small,
dark, lucent zone. Extending outwardly, the fetal
Zonular Attachment
nucleus, adult nucleus, and cortex are, respec-
tively, encountered. These portions are fre- The lens is circumferentially suspended from
quently subdivided clinically into anterior and the ciliary body by fibers called zonules.
posterior divisions to further localize lesions. Zonular attachment is achieved by a complex
To a greater extent than in mammals, lentic- arrangement of fibers that insert onto the lens
ular accommodation in birds depends on the capsule in a zone encompassing the equator
ability of the lens to change shape. The avian and a short distance both anterior and poste-
lens is generally softer and more flexible than rior to the equator (Figure 1.50a and b). Each
the mammalian lens, and consequently is more zonular fiber is made of numerous small
readily deformed during contraction of the cili- fibrils, which are visible under SEM as they
ary body and peripheral iris musculature. As attach to the lens capsule. The zonular fibers
the anterior uveal muscles contract, it is theo- spread out near the equator and terminate into
rized that the ciliary body pushes against the smaller bundles. Each of these bundles also
52 Development and Morphology of the Eye and Adnexa

(a) (b)

(c)

Figure 1.50 Zonular attachments to the lens in a dog. (a) SEM shows that zonules (Z) extend from the
ciliary body onto the equator of the lens (L) in a ringlike manner, covering each ciliary process. (Original
magnification, 30×.) (b) SEM shows that each zonule consists of bundles (arrows) of fibrils, which are most
apparent next to the lens (L). (Original magnification, 78×.) (c) SEM shows termination of zonular fibrils,
which unravel to form a dense meshwork over the capsule that greatly increases the surface area of
attachment. A, zonular fiber. (Original magnification, 1600×.)

fans out and forms a network that ramifies the vitreous abuts the neurosensory retina. As
over the surface of the lens capsule, approxi- a result, the vitreous functions to transmit
mately 1.5–2.0 mm away from the lens equator. light, to maintain the shape of the eye, and to
help maintain the normal position of the lens
and retina.
­Vitreous Embryologically, the vitreous is composed of
three components: (i) primary vitreous (con-
The vitreous humor is a transparent hydrogel taining the hyaloid artery system); (ii) second-
that comprises a portion of the clear ocular ary (definitive, or adult) vitreous; and (iii)
media and accounts for up to two-­thirds of tertiary vitreous (lens zonules) (Figure 1.51).
globe volume. Anteriorly, the vitreous provides The primary, or primitive, vitreous develops
support for the lens as it rests in a shallow con- first, as the hyaloid artery system courses
cavity (i.e., the patella fossa), while posteriorly, through it to provide a blood supply to the
­Retin  53

Cortical vitreous
Hyaloideocapsular ligament Posterior hyaloid membrane*
Central vitreous
(Intermediate zone
of vitreous)
Dorsal plica

Primary
vitreous
Optic
Tertiary nerve
vitreous

Optic
disc
Anterior
Cloquet’s canal
hyaloid
membrane* Berger’s space
Vitreous Cortical vitreous
base Ventral
plica

Figure 1.51 Schematic illustrating the various components of and spaces within the vitreous. The
secondary, or adult, vitreous is composed of the cortical and central (intermediate zone) components.
Asterisk denotes not a true “membrane.”

avascular developing lens. The secondary vit- nerve and the optic tracts (Figure 1.52). The
reous then forms around the primary vitreous, rods and cones, the primary retinal photore-
leaving the primary vitreous at the central core ceptors, comprise a complex layer of special-
of the vitreal compartment. The secondary vit- ized cells, which contain photopigments that
reous becomes the definitive, or adult, vitre- convert light energy into a series of biochemi-
ous. Within the adult vitreous exist several cal events. The RPE furnishes important
anatomical structures, potential spaces, and metabolites to the photoreceptors; it also
connection points between the vitreous and actively phagocytizes the outermost photore-
adjacent tissues. The core of the primary vitre- ceptor segments as they are shed during nor-
ous around which the adult vitreous develops mal outer segment renewal. The retina has one
is occupied by Cloquet’s canal (i.e., the hyaloid of the highest rates of metabolism of any tissue
canal), and the remnant of the anterior inser- in the body and receives almost all its nutrition
tion of the hyaloid artery appears as a dense, from the retinal and choroidal capillaries.
white, small dot (i.e., Mittendorf’s dot) with a The function of the retina is to turn light
variable “corkscrew” tail extending from the stimuli from the external environment into
posterior pole of the lens. nervous impulses and transmit this informa-
tion accurately to the brain, where it is then
interpreted as vision. Once photoreceptors are
­Retina stimulated by light, their release of a neuro-
transmitter is altered and this response is then
The retina and optic nerve are derivatives of received and modified by cells whose nuclei
the forebrain; consequently, their morphology are in the inner nuclear layer (i.e., amacrine
and physiology are similar to those of the cells, bipolar cells, and horizontal cells). The
brain. The nine layers of the neurosensory ret- modified message is then transferred to gan-
ina are connected to the brain by the optic glion cells, whose axons form the nerve fiber
54 Development and Morphology of the Eye and Adnexa

Ganglion
cell

Amacrine
cell
Cone
Rod bipolar
bipolar cell
Horizontal
cell cell

Spherule

Pedicle

Rod
Cone

Retinal
pigmented
epithelium

Figure 1.52 Relationship between different neuronal cells within the retina. The amacrine cell has a
reciprocal inhibitory response onto the bipolar cell from which the information originated and acts to
adjust the sensitivity of the ganglion cell synapse after receiving a signal. Horizontal cells interconnect
laterally to integrate and regulate input from multiple photoreceptors.

layer and extend through the optic nerve to tar- (ix) nerve fiber layer; and (x) inner limiting
gets in brain (including the lateral geniculate membrane (Figure 1.53).
nucleus and occipital cortex) (see Chapter 2).
Recent studies indicate that a considerable
Retinal Pigment Epithelium
amount of processing of visual impulses occurs
within the retina. Classically, 10 layers are The RPE is a monolayer of flat, polygonal cells
described in retinal histology. The neurosen- that forms the outermost layer of the retina. It
sory retina contains nine, and the supportive is the continuation of the outer pigmented epi-
pigmented epithelium is the tenth layer. thelial layer of the ciliary body. The RPE is
Remember that the retina develops from both more adherent to the choroid than to the rest of
inner (which invaginates) and outer optic the retinal tissue, and it serves an important
cups. Hence, light and images must pass role in nutrient transport from the choriocapil-
through the entire neurosensory retina to laris to the outer layers of the retina. Each cell
reach the photoreceptors. The 10 identifiable sends cytoplasmic processes inward to sur-
layers are considered, sclerad to vitread, in the round the photoreceptor outer segments, which
following order: (i) RPE; (ii) photoreceptor help to filter out excessive amounts of light and
layer (rod and cone layer); (iii) outer limiting increase the photoreceptors’ individual sensi-
membrane; (iv) outer nuclear layer; (v) outer tivity. They also phagocytize the outer segments
plexiform layer; (vi) inner nuclear layer; (vii) of photoreceptors as they are continuously
inner plexiform layer; (viii) ganglion cell layer; shed. The RPE cells are usually densely
­Retin  55

Figure 1.53 The retina consists of nine discrete


layers and a supportive pigmented epithelium that
forms an outer, tenth layer, as demonstrated by light
microscopy in the dog. G, ganglion cell; 1, RPE; 2,
Figure 1.54 The photoreceptor layer of the pig
photoreceptor layer; 3, outer limiting membrane; 4,
contains many cones (C) among the rods (R)
outer nuclear layer; 5, outer plexiform layer; 6, inner
within the area centralis, making this animal well
nuclear layer; 7, inner plexiform layer; 8, ganglion
suited for day vision. Note that the rods are
cell layer; 9, nerve fiber layer; 10, inner limiting
uniform in width throughout their length.
membrane. The outer and inner limiting
(Original magnification, 400×.)
membranes are denoted by dashed lines.

pigmented, but there is variability in the inten- visual acuity and color sensitivity. Primates and
sity of pigmentation among individual animals. many avian and reptilian species possess cone-­
rich regions completely free of rods; these are
called foveae (i.e., fovea centralis) and are
Neurosensory Retina
responsible for the perception of different hues
The neurosensory retina varies in thickness, of color, high resolution, binocular fixation,
being thickest near the optic disc and tapering and depth perception. Domestic animals do not
toward the ora ciliaris retinae. Ophthalmo­ have foveal pits, but dogs have been shown to
scopically it is clear, and any disease usually have a small fovea-­like structure, a fovea plana.
results in increases in its transparency! The width Other domestic animals instead possess an area
of all layers decreases toward its periphery from of high cone density called the area centralis.
the optic nerve head, but the nerve fiber layer The area centralis, which surrounds the fovea
contributes most to the variation in thickness. plana, frequently occurs in a location 1.5 mm
Most domestic animals have a central retina of temporal and 0.6 mm superior to the optic disc
approximately 200–240 μm and a peripheral ret- in the dog. The visual streak is a region of the
ina of 100–190 μm. In animals with poorly vascu- retina with increased ganglion cell density that
larized or avascular retinas, retinal thickness occurs in a horizontal band, dorsal to the optic
rarely exceeds 140 μm, which is the proposed disc. The area centralis resides within the visual
oxygen diffusion maximum for retinal tissue. streak, and these terms are sometimes used
The retinal photoreceptors are the primary synonymously. The photoreceptor layer con-
visual cells of the eye and are the first-­order tains only the outer parts of the photoreceptor
neurons (Figure 1.54). Rods function in dim or cells known as the inner and outer segments
reduced illumination, and cones function in (Figure 1.55); the photoreceptor nuclei are con-
bright light. The rods allow detection of shapes tained in the outer nuclear layer. These seg-
and motion, while the cones provide sharp ments are cylindrically to conically shaped and
56 Development and Morphology of the Eye and Adnexa

The axons of the photoreceptors and their


synaptic connections are the two components
of the outer plexiform layer. The photoreceptors
of the outer nuclear layer form connections
with the horizontal and bipolar cells of the
inner nuclear layer. Two distinct types of syn-
apses occur in the outer plexiform layer, and
each is specific to the rod spherule or the cone
pedicle. The invagination of each rod spherule
synaptic expansion contains two deeply
inserted, horizontal cell processes laterally and
one or more bipolar cell process centrally.
The inner nuclear layer is composed of the
somas of horizontal, bipolar, amacrine, inter-
plexiform (in some retinas), and Müller cells.
The neurons in this layer maintain connections
between the photoreceptor layer and the gan-
Figure 1.55 Tip of the outer segment discs in a rod glion cell layer and are involved in modification
of a young dog. Note that the discs or lamellae are
and integration of the neural responses elicited
separated from each other as well from as the
plasma membrane (PM). The intralamellar space is by the stimuli. Specifically, horizontal and
slightly dilated at their periphery (arrow). Apical villi bipolar cells are second-­order neurons that
(AV) of pigmented epithelium are found between connect with photoreceptors (first-­order neu-
outer segments. (Original magnification, 54 000×.)
rons) and ganglion cells (third-­order neurons).
The inner plexiform layer comprises the cell
closely packed together, with a radial orienta- processes of the inner nuclear and ganglion cell
tion parallel to incoming light as it passes layers, at which synapses between bipolar,
through the pupil. amacrine, and ganglion cells occur. The bipolar
An extremely thin limiting membrane com- cells synapse in ribbon synapses with two post-
posed of the junctional complexes between synaptic elements, and hence are termed a dyad.
Müller cells, as well as between Müller and The ganglion cell layer contains different
photoreceptor cells, forms a lateral, intercellu- types of ganglion cells, neuroglial cells, and
lar border between the inner segments of the retinal blood vessels. It is the innermost cell
photoreceptor layer and their nuclei. The func- layer of the retina and consists of a single layer
tion of the outer limiting membrane is some- of cells, except in the area centralis and visual
what speculative. streak, where it can be two or three cell layers
The somas, or cell bodies, of the photorecep- thick. Three basic forms of ganglion cells
tors are contained within outer nuclear layer. have been described in the cat, and extensive
The number of rows of nuclei varies greatly research has related the morphology of these
according to species and location within the ret- cells to their neurophysiology (see Chapter 2).
ina. In the central retina, the dog and cat possess α-­, β-­, and γ-­ganglion cells have been identified
the greatest depth of rows (10–15 and 12–18, in the retina on the basis of dendritic fields,
respectively), whereas ungulates have fewer and these morphological types correspond
rows (5 in the horse and pig, 10 in the cow). The with the three physiological types of ganglion
rod and cone connecting fibers link the photore- cells (Y, X, and W). The size of the dendritic
ceptor nuclei to their respective inner segments, fields for each of the three morphological types
while the axons of the rod and cone nuclei varies with location in the retinal field.
extend into the outer plexiform layer to synapse The nerve fiber layer consists of the axons of
with horizontal and bipolar cells. ganglion cells gathered in the nerve fiber layer,
­Retin  57

converging to turn at right angles and coursing holangiotic pattern, in which the majority of
to the posterior pole at which the optic nerve the neurosensory retina receives a direct blood
exits the globe. The nerve fiber layer increases supply. The merangiotic pattern consists of
in thickness as it approaches the optic disc. To blood vessels localized to a region of the retina
maintain transparency of the retina, the axons medial and lateral to the optic disc. Examples
lack myelin sheaths. Large retinal vessels of animals with this retinal vascular pattern
occur in the nerve fiber layer as well as in the are lagomorphs (rabbits and pika). In the pau-
ganglion cell and inner plexiform layers. The rangiotic pattern, blood vessels within the ret-
axons are of various sizes, and the large axons ina occur only circumferentially near the optic
originate from the large ganglion cells (Y or disc (peripapillarily). This pattern is seen in
α-­cells). certain ungulates, such as horses, elephants,
The inner limiting membrane is a true base- and rhinoceroses, and in some marsupials
ment membrane formed by the fused termina- such as kangaroos. The anangiotic pattern is
tions of Müller cells. Vitreal fibrils insert into characterized by an absence of any vasculature
the membrane, effectively establishing a within the ne­urosensory retina, and it occurs
“fusion” between the neurosensory retina and in sugar gliders, guinea pigs, chinchillas, and
the vitreous body. nonmammalian species such as birds
(Figure 1.56a and b). In birds, a structure called
pectin (pectin oculi) lies vitread to the optic
Retinal Vasculature
nerve head. It is pigmented and pleated struc-
Classically, variations in the retinal vascula- ture, and contains a rich plexus of blood
ture have been categorized into four basic pat- v­essels. In general, the retinal arterial supply
terns: holangiotic, merangiotic, paurangiotic, in domestic animals comes from the short
and anangiotic. Most mammals possess the p­osterior ciliary arteries, which are termed

(a) (b)

Figure 1.56 (a) The avian pecten, as seen here in the chicken, consists of a pleated vascular plexus that
lies vitread atop the optic nerve head (ON). (Original magnification, 50×.) (b) Close-­up of the base of the
pecten as it internally lines the nerve fibers (NF) that form the optic nerve head. BV, blood vessels of the
pecten. (Original magnification, 250×.)
58 Development and Morphology of the Eye and Adnexa

cilioretinal arteries, rather than via a central


retinal artery origin as in higher primates, rats,
and mice.

­Optic Nerve

Retinal ganglion cell axons leave the nerve


fiber layer and form the optic disc. From this
area, they pass through the choroid and sclera
and into the orbit as the optic nerve. In addi-
tion to ganglion cell axons, the optic nerve is
composed of glial cells and septae, which arise
from the pia mater. The visual axons synapse
in the lateral geniculate nucleus, whereas the
pupillomotor fibers synapse in the nucleus of
CN III. The optic nerve extends from the globe
Figure 1.57 The optic nerve head and bulbar
to the optic chiasm, and it consists of four
optic nerve of a dog. Arrows indicate lamina
regions: intraocular, intraorbital, intracanalic- cribrosa; note the number of astrocytes anterior to
ular, and intracranial (Figure 1.57). Because of it. C, choroid; CMK, central meniscus of Kuhnt
similar anatomical properties, the optic nerve (accumulation of astrocytes in physiological cup);
CRV, central retinal vein; RV, retinal veins; S, sclera;
is considered to be more of a nerve fiber tract
PS, pial septa. (Original magnification, 720×.)
of the brain than a peripheral nerve. The
intraocular optic nerve consists of retinal, cho-
roidal, and scleral portions. ­Vasculature of the Eye and Orbit
The terms optic disc, papilla, and optic nerve
head are interchangeable and include the reti- Among domestic animals, the main supply of
nal and choroidal portions of the optic nerve. blood to the eye and orbit is via the internal
Optic papilla refers to an elevation of the nerve maxillary artery (a branch of the external
head, and its presence and development vary carotid artery), which after passing through
among and within species. Within the optic the alar canal branches to give rise to the exter-
papilla is a central depression called the physi- nal ophthalmic artery. By comparison, in pri-
ologic cup. The cup is lined by a plaque of mates, the entire microcirculation of the eye
astrocytes known as the central supporting tis- and most of the orbital circulation are supplied
sue meniscus of Kuhnt. An exaggeration of via the internal carotid artery, which gives rise
this tissue is Bergmeister’s papilla, which is the to the internal ophthalmic artery.
remnant of the hyaloid artery on the disc’s Domestic species possess both internal and
surface. external ophthalmic arteries, but the external
The number of optic nerve fibers, and their ophthalmic artery provides most of the circula-
density and size vary considerably among spe- tion to the eye. Both the long and short poste-
cies. Animals with poorly developed eyes, rior ciliary arteries as well as the lacrimal,
such as mole rats, contain approximately muscular, and supraorbital arteries derive
900–1800 nerve fibers, whereas those with from the external ophthalmic artery. The inter-
highly developed eyes, such as various pri- nal ophthalmic artery, which is relatively
mates, have 100–150 times that number. small, provides the blood supply for the optic
Interestingly, the size of the eye often does not nerve and anastomoses with the external oph-
correlate with the total number of nerve fibers thalmic artery or one of its branches; this anas-
within the optic nerve. tomosis is especially prominent in the dog.
59

Ophthalmic Physiology and Vision


Revised from the 6th edition of Veterinary Ophthalmology, Chapter 3: Physiology of the Eye, by Diane V.H. Hendrix, Sara M. Thomasy,
and Glenwood G. Gum; Chapter 4: Optics and Physiology of Vision, by Ron Ofri and Björn Ekesten; and Chapter 5: Vision, by Björn
Ekesten and Ron Ofri

­ ection I: Physiology
S the precorneal tear film (PTF). The conjunctiva
of the Eye lines the inside of the eyelids and reflects onto
Functional knowledge of ocular physiology in the globe contains goblet cells that contribute
animal species provides a critical foundation the mucin to the PTF; accessory lacrimal glands
for clinicians practicing comparative and vet- are also present in some species. The normal
erinary ophthalmology. This chapter presents blinking of the eyelids maintains the physiolog-
the physiology of the eye, especially regarding ical thickness of the preocular tear film, aids
the adnexa, anterior segment, ocular circula- movement of the tears both to and within the
tion, aqueous humor (AH) dynamics, lens, and nasolacrimal system, and helps eliminate small
vitreous; optics; and vision. particles from the corneal and conjunctival sur-
The rate at which both relatively simple and faces. Reflex closure of the eyelids protects the
complex ocular physiological mechanisms are anterior segment from external trauma.
being studied is incredible. This chapter The eyelids determine the shape and width of
presents the essential physiological phenomena the palpebral fissure, along with the associated
of the eye, optics, and vision required by the medial and lateral canthal ligamentous and
clinical veterinary ophthalmologist. muscle attachments. For example, a wide,
round palpebral fissure is normal among brach-
ycephalic breeds, and a narrow, almond-­shaped
palpebral fissure is normal among dolichoce-
­Anterior Eye Structures phalic breeds. The shape of the palpebral fissure
also depends on the relationship of the globe to
Eyelids
the orbit. A small globe in a deep orbit allows a
The eyelids of domestic animals protect the eye, narrow palpebral fissure; the opposite occurs
particularly the cornea. All domestic animal with a large globe in a shallow orbit. The NM
species have a superior (upper) and an inferior aids in protection of the conjunctiva and cornea
(lower) eyelid; most have a nictitating mem- by moving, either passively or actively, over the
brane (NM, third eyelid). The eyelids contain cornea when the globe is retracted.
the meibomian glands; these are large seba- Eyelid closure is mediated by the efferent fib-
ceous glands that secrete the outer, oily layer of ers of the facial nerve (CN VII) and their effects

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
60 Ophthalmic Physiology and Vision

on the orbicularis oculi muscles. The oculomo- present immediately following birth or eyelid
tor nerve (CN III) innervates the levator palpe- opening. In contrast, the menace response is
bral superioris, which is responsible for opening cortically mediated and is initiated by a threat-
the upper eyelids. Eyelid closure is the end ening gesture or loud sounds.
result of two eyelid reflexes, the corneal and pal- Blinking and blink rates have been studied in
pebral reflexes, and the menace response many species under varying circumstances and
(Table 2.1). The corneal and palpebral reflexes methodologies, making comparisons and gen-
are primitive reflexes with a purely subcortical eralized statements difficult (Table 2.2).
course. Both are elicited by touch, with the Blinking does not occur randomly, and blinks
afferent pathway being the ophthalmic branch are often associated with gaze shifts and sac-
of the trigeminal nerve (corneal) or the ophthal- cades. One of the theories for this timing is that
mic and maxillary branches of the trigeminal blinking temporarily blocks visual information,
nerve (palpebral). The efferent pathway of these and blinking during gaze shifts and saccades
two reflexes as well as the menace response is takes advantage of blocking vision when the
the facial nerve stimulating the orbicularis oculi images are already degraded from movement.
muscles, resulting in a blink. These reflexes are Diurnal nonhuman primates and birds have

Table 2.1 Reflexes involving the blink response.

Cornea reflex Palpebral reflex Menace responsea Dazzle reflex

Stimulus Corneal touch Eyelid touch Menacing gesture Bright light


Receptors Somesthetic Somesthetic Photoreceptors Photoreceptors
Afferent Trigeminal nerve Trigeminal nerve Optic nerve Optic nerve
pathway (ophthalmic) (ophthalmic and
maxillary)
Interneuron Subcortical Subcortical Cortical, cerebellum Subcortical
Efferent Facial nerve Facial nerve Facial nerve, VI, IX Facial nerve
pathway
Effectors Orbicularis oculi Orbicularis oculi Orbicularis oculi muscle, Orbicularis
muscle muscle retractor bulbi muscle oculi muscle
Response Blink Blink Blink, retract globeb Blink
a
If sufficient cortex of one cerebral hemisphere is damaged, the menace reaction cannot be elicited in the
contralateral eye of the dog. Pathology of the cerebellar cortex can also affect the menace reaction.
b
The menace response can also involve turning the head or moving away from the stimulus.

Table 2.2 Blinking rates of domestic animals.

Species Blinks/min Interblink period Concurrent blinks (%)

Dog 3–5 20–30 sa 85


Cat 1–5 per 5 min 18.5 s 70
Horse 19 77
Cattle 5 60
Pigs 10 90
a
Dogs have partial blinks every few seconds between complete blinks.
­Anterior Eye Structure  61

higher blink rates than nocturnal nonhuman Other Species


primates and birds, and in general, larger mam- Horse
mals and primates blink more often than In horses, the cilia are long and numerous on the
smaller mammals. Blink rates and evaporation upper eyelid, except near the medial canthus.
of the PTF can affect topical drug activity. Horses blink at about 19 blinks/min, approxi-
mately one-­third of which are minimal incom-
Eyelids in the Dog plete, one-­third of which are moderate
In dogs, the larger upper eyelid, which con- incomplete, and one-­third of which are com-
tains the cilia or eyelashes, is more mobile plete, with only 6% of the blinks having a com-
than the lower eyelid. When the eyelids are plete squeeze. Lid closure is approximately twice
closed, most of the ambient light is prevented as rapid as lid opening. Eyelids are open at birth.
from entering the eyes. Restrained dogs blink Also, long tactile hairs, or vibrissae, are present
10–20 times/min in comparison to unre- on both the dorsal brow and lower eyelid. The
strained dogs. Some 50% of dogs’ blinks are vibrissae are long, stout, single shafts of hair that
incomplete. Puppies normally open their eye- are usually thicker than adjacent skin hair; they
lids between 10 and 15 days of age. may provide additional sensation for the eyelids.

Eyelids in the Cat Cattle, Sheep, and Pigs


In cats, both eyelids lack cilia. The eyelids of In cattle, sheep, and pigs, the upper eyelid is the
pigmented cats allow no more than 5% of light most mobile, largest, and has the majority of
at longer wavelengths to be transmitted. cilia. Pigs, rabbits, rodents, and some rumi-
Kittens normally open their eyelids between 10 nants have a deeper separate structure, the
and 15 days of age; however, both eyes do not Harder’s gland or harderian gland, in addition
always open on the same day. to the superficial gland of the NM. This gland
The NM of the feline species is large and secretes lipids, porphyrins, indoles, and growth
active, but in most other species it moves pas- factors, and is thus also important for lubrica-
sively. In cats, it actively covers most of the cor- tion of the eye. In the pig, the meibomian
nea; it can extend at least two-­thirds of the way glands are poorly developed, and the primary
across the cornea and contains nine smooth eyelid glands are sweat glands. Eyelids are open
muscles that lead to active retraction or protru- at birth in these species.
sion. These smooth muscles draw the mem-
brane into the medial canthus and are Birds and Reptiles
innervated exclusively by postganglionic adr- In birds and certain reptiles, the lower eyelid is
energic sympathetic nerve fibers, with cell bod- larger and more mobile than the upper eyelid.
ies located in the anterior cervical ganglion. There are no feathers corresponding to eye-
Their axons follow the oculomotor nerve. lashes on the lids. The superciliary line refers to
Normally, the NM shows no spontaneous activ- feathers that correspond to the eyebrow and are
ity in most species, because the smooth muscle often of different colors than surrounding
lacks tight junctions like those of the visceral feathers. The superciliary or supraorbital ridge
smooth muscle. Each muscle cell is innervated refers to the unfeathered bony protuberance
by one or more axons, thus confirming that just dorsal to the orbital rim that is seen in
activation of the smooth muscle in the NM is many raptors, such as eagles and hawks. The
neurogenic and that the myogenic conduction ridge is thought to provide shade to the eye.
normally found in visceral smooth muscles Birds may blink with both eyelids or the NM
does not occur. Thus, cats are the only common alone. In contrast to mammals, the thin nearly
domestic animal in which sympathetic stimu- transparent NM of birds is under direct skeletal
lation will cause the NM to move. muscular control with two muscles extraneous
62 Ophthalmic Physiology and Vision

to the lid that can pull the NM over the entire blinking, since the rate of blinking is faster
cornea as many as 15–20 times/min, even with than the development of these dry spots. Actual
the other eyelids closed. Blinks in peacocks are tear flow rates are difficult to measure in most
strongly associated with gaze shifts. The NM species; however, in the horse, the tear flow rate
also contains a superficial tear gland, and some has been estimated to be 34 μl/min with a tear
species have a deeper harderian gland. Chicks volume of 234 μl, which indicates a turnover of
hatch with their eyes open. the tear volume in approximately 7 minutes. By
comparison, tear turnover and tear evaporation
rates in humans are ~1 ± 0.4 and 0.14 ± 0.07 μl/
­Tear Production and Drainage min, respectively.
In all species studied, the PTF can be loosely
Both the optical and normal functions of the divided into three layers that intermix
cornea depend on the integrity of the lacrimal (Figure 2.1). The outer oily layer (~0.1 μm) is
system. The PTF maintains an optically uni- very thin and forms a reversible, noncollapsi-
form corneal surface by smoothing out minor ble, multilayer film with the primary purpose
irregularities, removing foreign matter from of stabilizing the air–tear interface (and pre-
the cornea and conjunctiva, lubricating the venting evaporation). The primary constituent
conjunctiva and cornea, providing nutrients to of this lipid layer is the meibomian gland secre-
the avascular cornea, and controlling the local tion (MGS), or meibum, a composite lipid-­rich
bacterial flora. The PTF also undergoes con- mixture. Up to 22 wt% comprises nonlipid com-
stant evaporation and formation of transient ponents (proteins, salts, and polysaccharides).
“dry spots.” Hence, the rate of tear evaporation The main lipid classes found in canine MGS are
appears to be directly related to the rate of very long chain cholesteryl esters, wax esters,

Lacrimal gland

Microvilli with Goblet cells


200 nm 1 µm
associated glycocalyx Conjunctival epithelium
3–7 µm
Limbus

Lens

Corneal epithelium
Tear film
Lipid layer
Meibomian gland
Aqueous layer Mucin-gel layer
Superficial
(containing mucin and
epithelial cell
other soluble proteins)

Figure 2.1 The tear film is a complex multilayered fluid phase. This figure represents the classic three-­
layered model, composed of a mucin-­gel layer adjacent to the epithelial surface, an aqueous layer
containing mucin and other soluble proteins, and a thin lipid film on the outermost surface.
­Tear Production and Drainag  63

(O-­acyl)-­omega-­hydroxy fatty acids (OAHFAs), whereas the highest density in chinchillas and
and cholesteryl esters of OAHFAs. Dogs have a guinea pigs is in the palpebral conjunctiva. All
relatively larger proportion of OAHFAs than species have lower concentrations of goblet cells
humans, which could be related to a higher tear in the bulbar conjunctiva. Mucin is produced by
film stability and lower blink rate in dogs ver- goblet cells in response to mechanical, immune,
sus humans. The same types of molecules are histamine, antigenic, or (direct or indirect) neu-
found in the MGS of cattle, rodents, and marsu- ral stimulation. The glycocalyx comprises poly-
pials. This outer lipid layer prevents not only saccharides that are produced by the stratified
evaporation of the underlying layers but also squamous epithelial cells of the cornea and con-
the overflow of tear film onto the eyelids, junctiva and project from the surface microvilli
spreads over the aqueous subphase, imparts of those cells. Mucins play a critical role in lubri-
stability to the tear film, thickens the aqueous cating the corneal surface, thus making its
subphase, provides a smooth optical surface for hydrophobic surface more hydrophilic (to per-
the cornea, constitutes a barrier against foreign mit spreading), and in stabilizing the PTF. The
particles, provides some antimicrobial activity, mucin layer as well as the integrity of the outer-
and seals the lid margins during prolonged clo- most layer of corneal epithelium is necessary for
sure. Additionally, it prevents maceration of retention of the tear film on the cornea.
the lid skin by the tears. Tears are a clear and slightly alkaline solu-
The middle aqueous layer (∼7 μm) is the tion, with a mean pH of 8.3, 8.1, and 7.8 in cat-
thickest (>60% of the total tear film thickness) tle, dogs, and horses, respectively. In humans,
and performs the primary nutritional functions horses, cattle, and rabbits, tear electrolyte con-
of the tear film. This layer is composed of ~98% centration is similar to that in plasma, except for
water and ~2% solids, comprising predomi- potassium, which is three to six times more
nantly proteins. The aqueous layer contains abundant in tears, thus indicating an active
inorganic salts, glucose, urea, proteins, glyco- transport mechanism. Tear film osmolarity/
proteins, and soluble mucins. The lacrimal osmolality is influenced by the rate of tear secre-
gland, gland of the NM, harderian gland, and tion, evaporation, and composition. It is simi-
accessory lacrimal glands in the conjunctiva all lar in cats (329 mOsm/l), dogs (356 mOsm/l),
contribute to its formation. Destruction or exci- and rabbits (376 mmol/kg), whereas humans
sion of the canine lacrimal gland or NM gland (283 mmol/kg) and horses (284 mmol/kg) have
results in a variable reduction in aqueous tear a lower osmolarity.
production, and indicates that approximately The PTF contains both nonspecific and spe-
two-­thirds of the aqueous tear production is cific antimicrobial substances. Nonspecific
produced by the lacrimal gland, approximately substances include lysozyme, lactoferrin, α-­
one-­third by the gland of the third eyelid, and a lysine, and complement. Specific antimicrobial
very minor amount by the accessory lacrimal substances include secretory immunoglobulins
glands in the conjunctiva. The aqueous portion A, G, and M. Toll-­like receptors that play a role
is evaluated clinically primarily through use of in the defense against many types of microbial
the Schirmer tear test (STT) I; the phenol red infections are expressed by the corneal and con-
thread test can be used in very small animals. junctival epithelial cells in humans and horses.
The deep, or mucin, layer (∼1 μm) is com- Protein concentrations in canine tears average
posed of tear mucins produced by the apocrine 0.35 g/dl, with 93% globulin, 4% albumin, and
conjunctival goblet cells, as well as an underly- 3% lysozyme, which is a ubiquitous antibacte-
ing glycocalyx that is associated with the corneal rial enzyme that hydrolyzes bacterial cell walls.
and conjunctival microvilli. The distribution of Lysozyme is produced by the conjunctival gob-
goblet cells varies among species, but the fornix let cells and has antibacterial and antifungal
is rich in goblet cells in dogs, cats, and horses, properties; its concentration increases with
64 Ophthalmic Physiology and Vision

conjunctivitis. Relative to humans and nonhu- The nasolacrimal drainage system elimi-
man primates, domestic animals have very low nates used tear film and any excessive tears.
amounts of lysozyme (e.g., the horse has one-­ The PTF accumulates along the palpebral mar-
half to one-­fourth that of human tears) and the gin of each eyelid and is forced by blinking to
cat has none. Lysozyme activity has not been move medially into the upper and primarily
detected in cattle, but it has been detected in the lower lacrimal puncta. When the tears are
sheep and goats. Lactoferrin has been identified in the lacrimal pool and the facial muscles
in the PTF of humans, dogs, cats, cattle, and relax, the tears flow into the lacrimal canaliculi
other mammals, and reversibly binds the iron by capillary action. Normal breathing move-
that is available for bacterial metabolism and ments also facilitate this flow into the canali-
growth. Immunoglobulin A (IgA) contributes to culi. Reflex blinking of the eyelids closes the
ocular defense by coating bacterial and viral lacrimal sac, which acts as a passive pump.
microorganisms, leading to agglutination, neu- Pseudoperistaltic motion of the nasolacrimal
tralization, and lysis. IgA is present in greater duct allows movement of the tears into the
concentrations in the PTF than immunoglobu- nasal cavity. Autoregulation of the lacrimal
lins G and M. Cat tears have a 6.6 mg/ml total system with receptors in the excretory portion
protein concentration with 9.7% IgA. has been suggested in studies of human tear
The lacrimal nerve, a branch of the trigemi- flow. Evaluation of canalicular function in
nal nerve, is primarily sensory but also provides humans suggests that destruction of either
the lacrimal gland with its parasympathetic canaliculus alone does not affect excretion of
(release acetylcholine and vasoactive intestinal tears; in domestic animals, the lower canalicu-
peptide neurotransmitters) and sympathetic lus is considered to be the primary site for tear
(release norepinephrine and neuropeptide Y drainage.
neurotransmitters) innervation. Both adrener-
gic and cholinergic distribution patterns around
the acini and blood vessels of the canine lacri-
mal gland are similar; however, the cholinergic
­Cornea
fibers appear to be greater in number than the
The clear cornea serves as a window for the eye
adrenergic fibers.
with two critical optical properties, transpar-
Lacrimation is stimulated by painful irri-
ency and refractive power, both of which are
tants, eye diseases, mechanical or olfactory
essential for vision. The cornea, with the sclera,
stimuli of the nasal mucous membranes, and
protects the inner components of the eye from
sinus diseases. Tear production as assessed
injury through its exquisite structure, biome-
with the external ocular surfaces anesthetized
chanics, and sensitivity.
and the lower conjunctival fornix dried by
Dacron swabs (STT II) measures ~50% of that
measured without manipulation (STT II) in
Transparency
the cat and dog. Larger dogs also have greater
wetting per minute than smaller dogs as meas- The cornea serves as the most powerful refrac-
ured with STT I. Additionally, canine neonates tive structure of the eye. Corneal clarity or trans-
have lower tear production than adults. parency is a result of the lattice-­like organization
Clinical estimation of the rate of evaporation of the stromal collagen fibrils as well as the
(and, indirectly, of the mucus component of transparency of the cells within the cornea
the PTF) is performed through determining (Figure 2.2). The state of relative dehydration,
the time (in seconds) for the tear film using hypocellularity, unmyelinated nerve fibers, a
topical fluorescein to break up (development nonkeratinized epithelium, and absence of
of “dry spots”). blood vessels and pigment also contribute to
­Corne  65

t
ligh
ible nm
20 nm Vis –700
0
39

25 nm

(a) (b)

Figure 2.2 In the normal cornea (a), a cross section of the corneal fibrils demonstrates a nearly perfect
lattice arrangement, with equidistant collagen fibrils permitting light transmission and concomitant
transparency. In contrast, swelling of the cornea with edema (b) disrupts this highly ordered arrangement,
resulting in light diffraction and an opaque, bluish cornea.

corneal transparency. The corneal stroma com- short-­range order results in corneal transpar-
prises the bulk of the cornea and is responsible ency via destructive interference.
for 90% of its thickness. It is predominantly com- Quiescent keratocytes lie between collagen-
posed of water that is stabilized by an organized ous lamellae to form a closed, exquisitely struc-
network of collagens, glycosaminoglycans tured syncytium. These three-­dimensional,
(GAGs), and glycoproteins. The GAGs are stellate-­shaped cells comprise a cell body with
important for maintaining the regular spacing multiple, extensive dendritic processes that
between fibrils. The uniform thickness, small interact with other keratocytes. Abundant cor-
collagen fibrils arrange into parallel lamellae neal crystallins (~25–30% of the intracellular
running at oblique angles to each other, and are soluble protein), such as aldehyde dehydroge-
separated by less than a wavelength of light nase and transketolase, minimize refractive dif-
(Figure 2.3). This formation results in a highly ferences in the keratocyte cytoplasm, thus
ordered, lattice-­like arrangement whereby ensuring transparency of these cells.
66 Ophthalmic Physiology and Vision

Epithelium
Cornea
Anterior Basement
Membrane

Stroma
(interwoven)

Anterior Banded
Layer

Stroma
(parallel)

Posterior Nonbanded
Layer

Descemet’s
Membrane

Endothelium

Figure 2.3 Schematic of collagen fiber organization in the canine cornea. The epithelium produces an
anterior basement membrane with a complex surface topography consisting of a meshwork of fibers and
holes. The anterior 10% of the cornea comprises unidirectional, interwoven collagen lamellae, while the
posterior 90% consists of unidirectional, nonwoven collagen lamellae with a random orientation.
Descemet’s membrane, the specialized basement membrane of the endothelium, can be divided into the
anterior banded and posterior nonbanded layers. The anterior banded layer is dominated by collagen VIII,
which appears as a hexagonal network en face and parallel bands in transverse section. The surface
topography posterior nonbanded layer has a rich network of intertwined fibers, but with a smaller pore size
in comparison to the anterior basement membrane.

Upon corneal wounding, transformation of increase in light scatter. Corneal scarring is


keratocytes to activated fibroblasts and thought to be due to alterations in the light
myofibroblasts results in a dramatic increase scattering properties of keratocytes, in addi-
in cell volume and subsequent dilution of tion to changes to the extracellular
corneal crystallins, with a concomitant matrix (ECM).
­Corne  67

The epithelium and endothelium are respon- Biomechanics


sible for maintaining the cornea in a relatively
The cornea is a thick-­walled, pressurized, par-
dehydrated state. Specifically, loss of the cor-
tially intertwined, unidirectionally fibril-­
neal epithelium or endothelium results in a
reinforced laminate biocomposite, which
200% or 500% increase in corneal thickness,
imparts stiffness, strength, and extensibility to
respectively, due to stromal edema. Anatomical
withstand both inner and outer forces that may
integrity of the epithelium and endothelium
alter its shape or integrity. A soft, fibrous con-
provides two-­way physical barriers against the
nective tissue, like the cornea, usually is much
influx of tears and AH, respectively. However,
stronger in the parallel versus perpendicular
the multiple-­layered epithelium provides a rel-
direction to the collagen fibrils. Consequently,
atively impermeable barrier versus the leaky,
the collagen fibrils are arranged into complex
single-­layered endothelium. The endothelium
hierarchic structures, which give the cornea its
primarily maintains stromal deturgescence via
anisotropic mechanical properties. The colla-
active transport that is energetically main-
gen lamellar architecture of the cornea varies
tained by sodium–potassium-­activated adeno-
dramatically between vertebrate species, with
sine triphosphatases (Na+–K+-­ATPases).
nonmammalian vertebrates exhibiting an
orthogonal-­rotation arrangement with a
Metabolism marked increase in lamellar branching in spe-
cies such that birds >> reptiles > amphibi-
Steady-­state hydration in the cornea occurs
ans > fish; in contrast, the mammalian species
when the endothelial leak and pump rates
exhibit a random pattern.
are equivalent; this process is termed the
Tissues are biomechanically characterized
“pump–leak” mechanism. The leaky barrier
by measuring the elastic modulus, a property
function of the endothelium may at first
that defines a material’s ability to resist defor-
seem counterintuitive, but most nutrients for
mation under an applied stress, which approx-
the cornea, except oxygen, come from the
imates its stiffness. The elastic moduli of the
AH. Thus, leakiness of the endothelium is
corneal layers as measured by atomic force
essential to providing bulk fluid flow through
microscopy have been reported in the human
a tissue that lacks blood and lymphatic ves-
and the rabbit (Table 2.3); all layers of the
sels. Glucose transporters are found on both
human cornea were stiffer than those of the
the apical and basolateral endothelial cell
rabbit. This variability in corneal collagen fiber
membranes that face the AH and stroma,
organization and matrix properties between
respectively, to ensure transcellular glucose
species likely contributes to their diverse
flux. The corneal epithelium converts glucose
mechanical properties, and may influence
to glucose 6-­phosphate, where it is subse-
indentation tonometry (estimation of intraoc-
quently metabolized to pyruvate via glycoly-
ular pressure [IOP]).
sis. Most of this pyruvate is then metabolized
into lactate, but some is diverted into the tri-
carboxylic acid cycle to produce ATP. Glucose
Sensitivity and Innervation
is also stored in the epithelium as glycogen,
which can be used for energy under stressful The cornea is an exquisitely sensitive tissue, and
conditions such as corneal injury. The cor- this sensitivity provides a critical protective
neal epithelium and keratocytes in the ante- function. Upon stimulation of the cornea, invol-
rior stroma obtain oxygen for aerobic untary blinking occurs via intermediate relays
glycolysis from the PTF, while the endothe- from the ophthalmic branch of the trigeminal
lium and keratocytes in the posterior stroma nerve to orbicularis oculi innervation from the
receive their oxygen from the AH. facial nerve – a fundamental reaction termed
68 Ophthalmic Physiology and Vision

Table 2.3 Elastic moduli of layers of the cornea as determined by atomic force microscopy in rabbits
and humans.

Corneal layer Elastic modulus (kPa)

Rabbit (Thomasy et al., 2014) Human (Last et al., 2009, 2012)

Epithelium 0.6 ± 0.3 Not assessed


Anterior basement membrane 4.5 ± 1.2 7.5 ± 4.2
Bowman’s layer Absent 110 ± 13
Stroma 1.1 ± 0.6 (anterior) 33 ± 6 (anterior)
0.4 ± 0.2 (posterior)
Descemet’s membrane 12 ± 7.4 50 ± 18
Endothelium 4.1 ± 1.7 Not assessed

the corneal or blink reflex. Concomitant with bundles, a dense highly anastomotic subepithe-
the blink reflex is reflex tearing from parasym- lial plexus, and a richly innervated epithelium
pathetic innervation to the lacrimal gland. (Figure 2.4). In the dog, corneal innervation
During extreme pain, the corneal reflex is exag- arises from the corneal limbal plexus, which
gerated, and blepharospasm sometimes occurs comprises a 0.8–1 mm wide, ring-­like band,
such that the eyelids cannot be opened volun- surrounding the peripheral cornea.
tarily. Corneal sensitivity varies by species, The majority of sensory fibers that innervate
region of the cornea, and, in the dog and cat, the cornea are activated by a variety of exoge-
skull conformation. For example, corneal sensi- nous mechanical, chemical, and thermal stim-
tivity in dogs, as measured by the Cochet– uli, as well as endogenous factors released by
Bonnet esthesiometer and histology of the tissue injury, and are thus termed polymodal
corneal nerves, was highest, intermediate, and nociceptors. The remainder of the sensory fib-
lowest in the dolichocephalic, mesaticephalic, ers innervating the cornea comprise mechano-­
and brachycephalic skull types, respectively. nociceptors and cold thermal receptors, which
Similarly, the central cornea is less sensitive in are only activated in response to mechanical
brachycephalic cats than domestic shorthair forces or changes in temperature, respectively.
cats. Corneal sensitivity is greatest in the central In addition to their contributions to corneal
cornea and lower in the peripheral cornea. protection via the blink reflex and reflex tear-
The cornea is one of the most richly inner- ing, corneal nerves maintain corneal epithelial
vated tissues in the body. Most corneal nerve health through the secretion of trophic factors
fibers are sensory in origin and respond to and maintenance of basal tear secretions.
mechanical, chemical, and thermal stimuli via
the ophthalmic branch of the trigeminal nerve.
However, a small proportion of nerves are sym- ­Iris and Pupil
pathetic or parasympathetic in origin and
derive from the superior cervical ganglion or Pupillary functions include regulating light
ciliary ganglion, respectively. Corneal nerve entering the posterior segment of the eye,
organization is similar across mammalian spe- increasing the depth of focus for near vision,
cies, with only minor interspecies differences. and minimizing optical aberrations by the lens.
All mammalian corneas contain a dense limbal The iris muscles consist of a constrictor
plexus, multiple radially directed stromal nerve (sphincter) that encircles the pupil and radial
­Iris and Pupi  69

Anterior
Subepithelial Basement
Membrane
Descemet’s Plexus Subbasal
Membrane Plexus
Intraepithelial
Intraepithelial Stroma
Nerve Terminals
Nerve Terminals
Endothelium
Subbasal Epithelium Epithelium
Plexus

Descemet’s
Anterior Membrane
Basement
Membrane Subepithelial Stromal
Nerve Stromal
Limbal Plexus Nerve
Stroma
Plexus

Figure 2.4 Schematic of corneal innervation. The limbal plexus is a ring-­like band of predominantly
myelinated fibers in the sclera adjacent to the cornea. From the limbal plexus, nerve fibers enter into the
corneal stroma as nerve bundles and lose their myelin as they traverse to the central cornea. The
subepithelial plexus is a dense, anastomosing network of thin axons immediately underlying the anterior
basement membrane. The subepithelial plexus gives rise to the subbasal plexus, a whorl-­shaped network of
axons between the anterior basement membrane and basal epithelium where nerve fibers run horizontally
as long parallel nerves, termed leashes. The axons of the subbasal plexus then vertically ascend to
terminate in various layers of the epithelium.

dilator muscles to expand the pupil. The light decreases pupil size. The sympathetic
sphincter muscle is an annular band of smooth activity in the iridal dilator muscle and ciliary
muscles near the pupillary margin of the iris body musculature (discussed later) is mediated
and is derived from neural ectoderm. The dila- by a combination of β-­receptors (β1 and β2) and
tor muscle, also derived from neural ectoderm, α-­receptors (α1 and α2). Components of the
consists of a series of myoepithelial cells that pupillary light reflex are listed in Table 2.4.
extend from near the pupillary margin to the Species differences of the α-­ and β-­receptors
base of the iris and are contiguous posteriorly have been demonstrated among humans, rab-
with the pigmented epithelium (PE) of the cili- bits, nonhuman primates, cats, and dogs, and
ary body. Pupil size varies on the basis of the they are summarized in Table 2.5. These recep-
balance between these two muscle groups. The tors alter the effects of drugs on the eye. For
constrictor muscle, which is the stronger of the example, feline pupils constrict with the use of
two, is innervated by the oculomotor nerve (CN timolol, a nonselective β-­adrenergic antago-
III) and provides primarily parasympathetic nist, because the feline iris sphincter muscle
control; in contrast, the dilator muscle is inner- has primarily β-­adrenergic nerve fiber. Because
vated primarily by sympathetic nerves. The β-­adrenergic nerve fibers are inhibitory to the
constrictor muscle causes miosis, and the dila- sphincter muscle, the miosis in response to
tor muscle is responsible for mydriasis. Bright topically applied timolol is suspected to be the
70 Ophthalmic Physiology and Vision

Table 2.4 Components of the pupillary Pupil shape also varies among species.
light reflex. Vertical pupils are most commonly seen in ter-
restrial mammals and reptiles that are ambush
Stimulus Illumination of the retina predators, and are diurnal. Prey species tend to
have horizontally elongated pupils. These
Receptors Photoreceptors (rods and cones)
respective variations are thought to keep images
Afferent Optic nerve–optic tract to
on the vertical and horizontal contours sharp.
pathway pretectal area (ipsi-­and
contralateral via posterior In domesticated cats, the constricted pupil is a
commissure) vertical slit, whereas in the larger, wild felines, it
Efferent Pretectal area to the is circular. On dilation, the vertical sides of the
pathway parasympathetic nucleus of CN domestic feline pupil expand to produce a circu-
III (ipsi-­and contralateral), and lar pupil. The constrictor muscle fibers are verti-
then parasympathetic fibers to
ciliary ganglion (via CN III) cally oriented, and therefore contraction leads
to a vertically oriented slit pupil.
Postganglionic fibers to the iris
In young horses, the pupil is more circular
Effector Sphincter muscle of the iris
than in adults. Under illumination, the ends of
Response Miosis (constriction of the pupil the oval pupil of mature horses do not constrict,
both direct and consensual reflex)
but the dorsal and ventral borders do. In bright
daylight, the superior granula iridica occludes
result of its antagonism of inhibitory input to the central papillary opening, resulting in two
the sphincter muscle. Most synapses in the cili- apertures and assisting with focusing through
ary ganglion are involved in relaying impulses the creation of Scheiner’s disc phenomenon.
that result in accommodation; the remainder With very low illumination or administration of
are concerned with constriction of the pupil. a mydriatic, the dorsal and ventral borders of the
Endogenous prostaglandin F2α appears to be pupil dilate, thereby forming a circular pupil.
involved in maintaining muscle tone in the The avian pupil is circular and highly motile.
sphincter muscle of the iris. Prostaglandins The consensual pupillary reflex is usually
most likely act directly on these muscles, and absent (because of total decussation of nerve
they appear to act to a lesser extent on the dila- fibers at the optic chiasm), but occasionally a
tor muscles of the canine iris. Exogenous pros- strong beam of light may traverse the posterior
taglandin analogues cause miosis in cats, dogs, ocular layers and the thin medial orbital bones
and horses, and the receptors have been to stimulate the opposite retina. As the con-
detected in the iris and ciliary body of several strictor and dilator muscles are mainly striated
mammals. Iris color, or the amount of mela- with varying amounts of nonstriated fibers,
nin, influences the effects of many drugs, as the avian pupil is not affected by traditional
melanin can bind drugs, increasing or prolong- mydriatic agents, but it can be dilated variably
ing their time to onset and duration. by various neuromuscular-­blocking drugs.

Table 2.5 Adrenergic receptors in the iris and ciliary body.

Species Iris sphincter Iris dilator Ciliary muscles

Human α and β equally Mainly α, very few or no β Mainly β, very few α


Rabbit Mainly β, few α Mainly α, few β Mainly α, few β
Monkey Mainly α, perhaps β Mainly α, few β Only β, no α
Cat Mainly β, some α Mainly α, some β Mainly β, some α
Dog α and β α and β ?
­Ocular Circulatio  71

­Nutrition of Intraocular Tissues of the blood all influence the blood flow
through all tissues, including the eye. The
While allowing light transmission through the pressure head for blood flow (i.e., perfusion
eye, nutrients are provided and waste is pressure) in most tissues is the difference in
removed by two systems of blood vessels (i.e., pressure between the arteries and the veins.
retinal vessels and uveal vessels), the forma- However, in the eye, the IOP approximates
tion and egress of AH, and the vitreous body. the venous pressure, so the perfusion pres-
Intraocular tissues lack a typical lymphatic sure is the difference in pressure between the
system, and the uveal tract (i.e., iris, ciliary small arteries entering the eye and the
body, and choroid) provides this function. IOP. Of clinical importance is that the per-
fusion pressure to the eye is reduced by low-
ering the blood pressure or raising the IOP, as
­Ocular Circulation occurs in glaucoma. Studies of hemodynam-
ics in the rabbit ophthalmic artery demon-
The choroid, ciliary body, and iris are supplied strate that autoregulation maintains normal
primarily by the uveal vessels. The outer retina blood velocity and resistance when the IOP is
in some animals (e.g., dogs, cats, ruminants, below 40 mmHg. However, at higher pres-
and pigs) and almost all or the entire retina in sures the autoregulatory capacity is limited.
others (e.g., horses and guinea pigs) is nour- As a result, an IOP of about 15–17 mmHg is
ished by diffusion from the choroidal vessels. related to episcleral venous pressure of about
The inner retina is supplied by retinal vessels in 10–12 mmHg and about 5–7 mmHg of resist-
many species. Blood vessels supplying the cor- ance from passage through the AH pathways!
nea and lens in the embryo regress before birth
or shortly thereafter, leaving the AH as the pri- Anterior Uveal Blood Flow
mary source of nutrients for the cornea
and lens. In most species, the major arterial circle of the
Birds have a unique structure, the pecten iris is formed by the nasal and temporal long
oculi, which is a heavily pigmented, highly vas- posterior ciliary arteries. The iris and ciliary
cularized, and usually fanlike structure pro- body receive approximately 1% and 10%,
jecting from the surface of the optic nerve into respectively, of the total ocular blood flow. In
the vitreous. A similar structure occurs in rep- humans and rabbits, additional iridal blood
tiles, termed the conus papillaris. The avian flow occurs from the anterior ciliary arteries
pecten likely functions as an important source via the extraocular muscles (EOMs). Blood
of nutrients for the inner retina. This assump- flow to the ciliary body in most species that
tion is based on the observations that the avian have been studied is provided by the iridal
retina is thicker than oxygen could perfuse major arterial circle, branches of the anterior
from the choroid and that the pectinate artery ciliary arteries, and branches of the long pos-
resistive and pulsatility indices are low. Several terior ciliary arteries. The cat and monkey iris
marine mammals, the bottlenose dolphin and ciliary body have autoregulation of their
(Tursiops truncatus), spotted seal (Phoca lar- blood flow. Carbon dioxide dilates the ante-
gha), and California sea lion (Zalophus califor- rior uveal vessels, and sympathetic α-­
nianus), have an ophthalmic rete from which adrenergic receptors cause vasoconstriction in
the retinal and choroidal arteries are derived. the anterior uvea. Parasympathetic mus-
carinic receptors and prostaglandins, how-
ever, cause vasodilation. Prostaglandins E1
Ocular Blood Flow
and F2α appear to cause a two-­ to threefold
The vascular pressure promoting flow, the increase in blood flow to the anterior uvea
resistance of blood vessels, and the viscosity when applied topically.
72 Ophthalmic Physiology and Vision

Choroidal Blood Flow Retinal Blood Flow


The outer retina (and the entire retina in some The retina receives 4% of the ocular blood flow
species) depends heavily on choroidal blood in the monkey. In cats, 20% of the oxygen con-
flow for nutrients and waste removal. In the ani- sumed by the retina is delivered through the
mal species studied, most of the blood supply to retinal circulation and the remaining 80% is
the choroid is supplied by the short posterior delivered via the choroidal circulation. Similar
ciliary arteries, but some of the peripheral cho- data are not available for other domestic ani-
roid receives blood from the major arterial circle mals. Blood flow in the innermost retina is
of the iris. The choroidal capillaries are fenes- practically unaffected by moderate changes in
trated and large (diameter 15–50 μm). These ves- perfusion pressure. Autoregulation of retinal
sels are highly permeable and permit glucose, blood flow is extensive in the cat, monkey, and
proteins, and other substances (including fluo- pig, and protects the retinal circulation from
rescein) of the blood to enter the choroid. large variations in perfusion pressure. Both
Within the choroid, these proteins create a metabolic and myogenous autoregulation are
high osmotic pressure gradient that assists in present in the eye. Metabolic control of retinal
removal of fluids from the retina. The short blood flow is similar to that of blood flow to the
posterior ciliary arteries appear to supply well-­ brain. In the cat, maximum retinal vasodila-
defined territories within the choroid. As a tion occurs with an increased PCO2 of
result, these “watershed zones” can develop 75–80 mmHg, so as to increase flow from 15 to
with marked elevations of IOP (often 50 ml/min. Neural control of retinal blood flow
>50 mmHg), and appear in the dog and non- is limited to those vessels indirectly affecting
human primate as pyramidal-­shaped areas of retinal blood flow. Retinal vessels have α-­
choroidal and retinal degeneration extending adrenergic binding sites that, when stimulated,
from the optic nerve head. cause vasoconstriction, thus increasing retinal
The rate of uveal blood flow is rapid (1.2 ml/ vascular resistance. Retinal arteries most likely
min in the cat), with a mean combined retinal autoregulate through a myogenic mechanism,
and choroidal circulation time of 3–4 s. In which is activated based on stretch. During
monkeys, 95% of the ocular blood flows sympathetic stimulation, myogenic autoregu-
through the uveal tract, of which 85% is latory responses appear to increase. Opening
through the choroid. With this high rate of and closing of capillary beds in many tissues
blood flow, oxygen extraction from each mil- occur with varying metabolic needs. The vas-
limeter of blood is low (∼5–10%). The oxygen cular endothelial cells may produce nitric
content of choroidal venous blood is 95% of oxide, endothelins, prostaglandins, and renin–
that in arterial blood. Reduced flow rates angiotensin products in response to chemical
result in higher oxygen extraction, so that stimuli (e.g., acetylcholine and bradykinin),
total extraction is reached. This protects the changes in blood pressure and blood vessel
oxygen supply to the retina, and it also pro- wall stress, changes in local oxygen levels, and
tects the eye from light-­generated thermal other stimuli. As the mechanisms of local
damage. Choroidal vessels have little to no autoregulation become better understood,
autoregulatory mechanisms, but carbon diox- pharmacological modulation of these pro-
ide is a potent vasodilator of choroidal ves- cesses may become possible. The theoretical
sels. Choroidal vessels are under the strong oxygen diffusion maximum of 143 μm plays a
influence of sympathetic stimulation, which significant role in animal species with avascu-
can result in a 60% reduction of choroidal lar retinas; as a result, avascular retinas are
blood flow. The α-­adrenergic drugs cause usually very thin, and have short photorecep-
vasoconstriction of choroidal vessels, but β-­ tors, no tapeta, high glycogen levels in the
adrenergic drugs have no effect. Müller cells, and no retinal taper.
­Ocular Barrier  73

Blood Flow of the Optic endothelial cells prevents bulk flow of AH into
Nerve Head the corneal stroma but allows moderate diffu-
sion of small nutrients and water.
Blood flow of the optic nerve head is usually pro-
vided primarily by branches from the short poste-
rior ciliary arteries. In humans, cats, and rabbits, Blood–Aqueous Barrier
optic nerve head blood flow possesses autoregula-
tion over a wide range of IOPs (∼30–75 mmHg), The BAB depends primarily on the tight junc-
but in humans, this autoregulation is most effi- tions in the nonpigmented ciliary body epithe-
cient when IOP is 6–30 mmHg. Ocular perfusion lium, the nonfenestrated iris capillaries, and
pressure, the relationship between systemic blood the posterior iris epithelium. The anterior BAB
pressure and IOP, determines blood flow in the in the iris allows transcellular transport by
optic nerve head. The autoregulatory capacity of means of vesicles. Paracellular transport is
optic nerve head blood flow is more susceptible to controlled by tight junction extensions. The
an ocular perfusion pressure decrease induced by anterior surface of the iris does not serve as a
lowering the blood pressure, compared with that barrier as it does not have a continuous cellular
induced by increasing the IOP. Studies of blood layer. The epithelial portion of the BAB is the
flow in the optic nerve head have been limited by inner, nonpigmented ciliary epithelium, and it
the small tissue mass involved. The optic nerve controls the flow of fluid into the posterior
head is subjected to several different pressures as chamber. The BAB is less effective than the
well as to the tissue stress at the different levels of retinal epithelial barrier, because protein can
the scleral lamina cribrosa. pass into the AH through leakage in other
parts of the anterior uvea. Both the ciliary body
and choroidal blood vessels are highly fenes-
­Ocular Barriers trated and thus leak most of their plasma com-
ponents, including protein, into the stroma. No
Blood–ocular barriers contain endothelial and barrier is present between the AH and the vit-
epithelial tight junctions with varying degrees reous humor, which allows the diffusion of sol-
of “leakiness.” These barriers prevent nearly utes from the posterior aqueous into the
all protein movement and are effective against vitreous humor, or between the anterior uvea
low molecular weight solutes such as fluores- and the sclera. Breakdown of the BAB is seen
cein and sucrose. The complexities of these clinically as an “aqueous flare” in anterior uve-
structures differ between the various vascular itis or secondary to loss of AH, as in anterior
beds, which allow movement of some sub- chamber paracentesis.
stances from one compartment to the other.
The two primary barriers within the eye are
Blood–Retinal Barrier
the blood–aqueous barrier (BAB) and the
blood–retinal barrier (BRB). With inflamma- The tight junctions between the retinal pig-
tion, these barriers may be compromised, and mented epithelial cells comprise the bulk of
allow fibrin and other proteins into the ocular the epithelial portion of the BRB. The nonfen-
tissues and space. Other minor barriers of the estrated retinal capillary endothelium with
eye exist as well. The zonula occludens of the tight junctions between the cells comprises the
corneal epithelium prevents the movement of endothelial portion of the BRB. The most per-
ions and therefore fluid from the tears into the meable point of the BRB is the optic nerve
stroma, prevents some evaporation, and pro- head, at which substances from the choroid
tects the cornea from pathogens. The partial can pass into the nerve. The choroidal capillar-
obliteration of the intercellular spaces pro- ies are highly permeable to permit passage of
vided by the macula occludens of the corneal all low molecular weight compounds and
74 Ophthalmic Physiology and Vision

proteins. Thus, nutrients from the choroidal Aqueous Humor Formation


blood supply pass readily into the retinal pig-
The ciliary body has several critical functions,
ment epithelium, where numerous transport
including production of AH by active secre-
systems account for the selectivity of the bar-
tion, ultrafiltration, and diffusion; generation
rier and elaborate transcellular pathways exist
of IOP through the aqueous dynamic process;
to pass them on into the retina. This high pro-
influencing through its musculature the con-
tein permeability of the choroidal vessels also
ventional (i.e., corneoscleral trabecular mesh-
elevates osmotic pressure, which helps fluid to
work [TM] or pressure-­sensitive) AH outflow;
pass out of the retina. The transport of water
provision of blood and nerve supplies for the
from the retina to the choroid is driven by the
anterior segment; control of accommodation
active transport of chloride to prevent water
via its musculature; formation of the BAB; and
accumulation in the subretinal space. No sig-
provision of the entry for nonconventional
nificant barrier exists between the vitreous
(i.e., uveoscleral or pressure-­insensitive) AH
body and the retina.
outflow. Furthermore, the ciliary body is also
rich in antioxidant systems, with significant
concentrations of catalase, superoxide dis-
­Aqueous Humor mutase, and glutathione peroxidase types I and
and Intraocular Pressure II. In addition, the ciliary body is the major
drug detoxification center in the eye, with its
In the normal eye, IOP is generated by flow of microsomes containing the cytochrome P450
AH against resistance, and is necessary to proteins, which catalyze many drugs.
maintain the appropriate shape and optical The bilayered ciliary epithelium, consisting
properties of the globe. AH is a clear, colorless of the outer PE and inner nonpigmented epi-
liquid that fills the anterior and posterior cham- thelium (NPE), is the site for AH secretion. At
bers as well as the pupil. It has a refractive their apical borders, the PE and NPE connect
index of 1.335, which is slightly denser than via gap junctions to form an intricate network
water, and is a critical constituent of the eye’s (Figure 2.5). Adjacent NPE cells are joined by
optical system. As AH is formed by the ciliary tight junctions to form a barrier that inhibits
body processes, it enters the posterior chamber paracellular diffusion.
and flows through the pupil into the anterior AH is formed by three basic mechanisms:
chamber, where it leaves the eye through the (i) diffusion, (ii) ultrafiltration, and (iii)
corneoscleral trabecular and uveoscleral out- active secretion by the NPE. The processes of
flow pathways. The rate of AH formation diffusion and ultrafiltration form the “reser-
equals the outflow, so the IOP is maintained voir” of the plasma ultrafiltrate in the stroma
relatively constant, and the refractive surfaces of the ciliary body, from which the AH is
of the eye are kept in a normal position. derived via active secretion by the ciliary epi-
This continuous flow of AH supplies the thelium. Energy-­dependent active transport
avascular cornea and lens with nutrients and is required to secrete solutes against a con-
also removes their waste products. A convec- centration gradient across the basolateral
tion current exists within the anterior chamber membrane of the NPE; it is the most impor-
whereby warm AH circulates from the pupil tant factor in AH formation. Two enzymes
downward adjacent to the air-­cooled cornea critical in this process, Na+–K+-­ATPase and
and upward near the lens where the tempera- carbonic anhydrase (CA), are abundantly
ture is warmer. This thermal circulation is present in the NPE. The Na+–K+-­ATPase is
responsible for the deposition of cellular membrane bound and is found in the highest
material – termed keratic precipitates – on the concentrations along the basolateral inter-
inferior aspect of the corneal endothelium. digitation of these cells. Inhibition of the
­Aqueous Humor and Intraocular Pressur  75

tight
junctions
basolateral apical basolateral
membrane membrane
membrane

gap
HCO3– junctions Na+
Cl–
Na+ nucleus
CA melanosome 2K+
3 Na+ ATPase
CA
Cl–

Aqueous Humor
CA
Na+ Cl–
Stroma

CO2
2 Cl–
HCO3–
K+
CA CA
H2O H2O CO2 HCO3– HCO3– CO2 K+
H 2 O H+ H+ H2O
Na+ H2O
H+

PE NPE Aqueous Humor

Protein
200x
Plasma

Ascorbate
20x

Urea 1.4x
Lactate
1.5x
Glucose 1.4x

Figure 2.5 Schematic of AH production across the PE and NPE of the ciliary body. Note the position of the
critical enzyme Na+–K+-­ATPase on the basolateral enzyme of the NPE. CA, also critical to AH formation, is
abundant in the cytoplasm of both the NPE and PE. Ion transporters and channels facilitate transfer of Na+,
K+, chloride (Cl−) and bicarbonate (HCO3−) into, between, and out of the NPE and PE, while aquaporins
enable water movement. Relative solute concentrations that most markedly differ between aqueous humor
and plasma can be found at the bottom.

Na+–K+-­ATPase with cardiac glycosides (e.g., and a passive transporter exchanges bicarbo-
ouabain) or vanadate causes a marked nate for chloride.
decrease in aqueous formation. CA is abundant in the cytoplasm and on the
Due to the primary active secretion of basal and lateral membranes of the NPE and
sodium, other molecules and ions cross over PE and catalyzes the following reaction:
the epithelium by secondary active transport.
As a consequence, increased concentrations of CO2 H 2O HCO3 H .

ascorbate, amino acids, and chloride are
observed in AH relative to plasma in most Formation of bicarbonate by CA is essential
mammalian species. Electroneutrality is main- for secretion of AH, such that inhibition of CA
tained by anions accompanying the actively results in decreased active transport of sodium
transported sodium; channels allow passage of by the NPE; it is unclear how this process
chloride on the basolateral NPE membrane occurs, although several hypotheses exist.
76 Ophthalmic Physiology and Vision

Topical and systemic CA inhibitors substan- observation clinically known as “aqueous


tially decrease AH production, therefore flare.” With the addition of proteins, the aque-
reducing IOP, and are thus useful in the man- ous composition closely approximates that of
agement of glaucoma in animals and humans. plasma and is termed plasmoid aqueous.
Plasmoid aqueous in domestic animals forms
fibrin clots easily due to high concentrations of
the glycoprotein fibrinogen. Unless treated
Aqueous Humor Composition
pharmacologically, these fibrin clots can cause
As an ultrafiltrate of plasma, the compositions numerous complications, including anterior
of AH and plasma are similar, with a few nota- and/or posterior synechiae or adhesions
ble exceptions: a low protein concentration, between the iris and the cornea and/or lens.
high ascorbate and lactate concentrations, and In addition to protein and ascorbate, other
reduced amounts of urea, glucose, and non- organic compounds constitute the AH, and
protein nitrogen occur within AH versus their concentrations vary relative to plasma. In
plasma (Figure 2.6). Thus, breakdown of the most mammalian species, the concentration of
BAB modifies the composition of the AH, pri- amino acids in the AH is higher than that in
marily by the addition of proteins and prosta- the plasma, suggesting that active transport of
glandins, and increases light scattering. The amino acids is occurring across the ciliary epi-
resultant Tyndall effects makes a slit-­lamp thelium. In the dog, however, amino acid con-
beam evident within the anterior chamber, an centrations are less in AH than in plasma.

ea
rn Anterior Chamber
Co

Iris

AAP
SVP

Ciliary Body Lens

Vitreous

Figure 2.6 AH drainage occurs via the traditional and uveoscleral outflow pathways in the iridocorneal
angle of the dog. The ciliary body epithelium produces AH, which flows from the posterior chamber,
through the pupil, and into the anterior chamber. Then, AH drains through the pectinate ligament to enter
the TM. In the traditional outflow pathway, AH enters the AAP to drain anteriorly to the episcleral and
conjunctival veins or posteriorly into the scleral venous plexus (SVP) and vortex veins. With uveoscleral
outflow, AH flows through the ciliary muscle interstitium to the supraciliary and suprachoroidal spaces to
diffuse out the sclera.
­Aqueous Humor and Intraocular Pressur  77

In this species, the vitreous may act as a “sink” influence of parasympathetic drugs such as
for some of the amino acids, thus causing the pilocarpine is relatively minor in AH forma-
deficiency. tion and that their efficacy in decreasing IOP is
The major cations in the AH are sodium, likely due to increased AH outflow.
potassium, calcium, and magnesium, with
sodium comprising 95% of the total cation con-
centration. Sodium enters the AH via active Aqueous Humor Outflow
transport, with a net flow of water into the pos-
AH dynamics involve the balance between
terior chamber. The major anions in AH are
production (i.e., active secretion) and outflow
chloride, bicarbonate, phosphate, ascorbate,
via the conventional and nonconventional
and lactate. The chloride and bicarbonate ions
routes (Figure 2.7). Conventional outflow con-
enter with sodium, but their concentrations
sists of AH flow through the corneoscleral TM,
vary among species.
while the nonconventional route involves uve-
oscleral outflow. Depending on the species,
Aqueous Humor Regulation ~50–95% of AH drains through the TM via con-
ventional outflow (Table 2.6).
The rate of aqueous formation by the ciliary
epithelium is influenced by sympathetic and
parasympathetic innervation as well as Structural and
humoral mechanisms to maintain a steady-­ Biomechanical Attributes
state IOP. Adrenergic regulation of AH forma-
The TM is a complex, three-­dimensional struc-
tion is complex and the role of some receptor
ture comprising cells supported by an intricate
subtypes remains unclear. The β-­adrenergic
ECM. The TM can be divided into three
antagonists, such as timolol, lower IOP by
decreasing AH production. During sleep, AH
formation decreases ~50% via modulation of
the β-­arrestin/cAMP signaling pathway by β-­
adrenergic receptors in humans and reducing Water 99.9% 66%
Na+ 144 20
the ocular hypotensive effects of timolol when Cl– 110 18
instilled at night. Thus, IOP exhibits a circa- K+ 4.5
Ca++ 1.7
125
0.4
dian rhythm, which varies depending on Glucose 6.0 1.0
Lactic acid 7.4 14.0
whether animals are nocturnal or diurnal. For Glutathione 0 S 12.0
Ascorbic acid 5 0.6
example, diurnal species such as dogs and Inositol 0.10 5.9
nonhuman primates exhibit the greatest IOP Amino acids 5 25 AA + AA + RNA

during the early day, while in nocturnal spe- Protein 0.04% 33% S
cies such as cats and rats IOP peaks at night.
Cholinergic regulation of AH formation and
composition is similarly ambiguous. For exam-
Active Transport (Pump)
ple, parasympathomimetic nerve stimulation Diffusion (Leak)
or drugs have been demonstrated to increase, S Synthesis

decrease, or not change the rate of AH produc-


Figure 2.7 Chemical composition of the aqueous
tion; these differences are likely due to species humor and lens. Water and protein are expressed
and technique-­related effects. Cholinergic as percentages of lens weight. Na+, Cl−, K+, and Ca2+
agents may regulate amino acid transport from ions are expressed in microequivalent per milliliter
of lens water. Other compounds are expressed in
the blood to the AH as well as modulate inor-
micromole per gram of lens weight or micromole
ganic ion concentrations within the AH. In per milliliter of aqueous humor. AA, amino acid;
aggregate, these studies suggest that the RNA, ribonucleic acid.
78 Ophthalmic Physiology and Vision

Table 2.6 Estimates of aqueous humor dynamics in selected species.

Dog Cat Rabbit Cow Horse Nonhuman primate

Estimated normal IOP (mmHg) 15–18 17–19 15–20 20–30 17–28 13–15
“C” outflow (μl/mmHg/min by 0.24–0.30 0.27–0.32 0.22–0.28 —­ 0.90 0.24–0.28
tonography)
Uveoscleral outflow (μl/min) 15% 3% 13% —­ —­ 30–65%
Episcleral venous pressure (mmHg) 10–12 8 9 —­ —­ 10–11
Aqueous formation (μl/min) 5.22 6.00–7.00 1.84 —­ —­ 2.75

portions: uveal, the innermost portion; corneo- generating IOP. Steady-­state IOP occurs when
scleral, the middle region; and the juxtacanali- the rates of AH inflow and outflow are equiva-
cular zone, the outermost section nearest the lent. The AH exits the eye by passive bulk flow
sclera (probably the site of greatest outflow via two routes in the ICA:
resistance). The pore size of each TM zone
decreases progressively from inward to out- 1) The traditional or conventional pathway,
ward, resulting in progressive increases in out- which involves passage through the TM,
flow resistance to the passage of AH. The AAP, scleral venous plexus, veins of the
juxtacanalicular zone consists of several episclera and conjunctiva (anterior) or vor-
endothelial cell layers that produce a matrix tex veins (posterior), and systemic venous
comprising GAGs, collagen, fibronectin, and circulation.
other glycoproteins in which these cells are 2) The uveoscleral or nonconventional path-
embedded. Thus, the juxtacanalicular zone, way, which involves passage through the
which is immediately adjacent to Schlemm’s iris root, anterior face of the ciliary body
canal in primates or the angular aqueous muscle, supraciliary or suprachoroidal
plexus (AAP) in most domestic animals, is space, and out through the sclera (and per-
thought to be the major site of aqueous out- haps the optic nerve head).
flow resistance.
The traditional pathway is dependent on
Other studies suggest that the main site of
IOP, while the uveoscleral pathway is not as
resistance to outflow is the endothelial lining
long, since IOP is greater than 7–10 mmHg. At
of the AAP and its ECM. However, the site of
very low IOP, the net pressure gradient across
filtration may be different from the site of flow
the nonconventional pathway declines, so that
resistance. AH transport through the endothe-
uveoscleral outflow subsequently decreases. It
lium of the AAP (or Schlemm’s canal in non-
is unknown why uveoscleral outflow is largely
human primates and domestic chickens) is
independent of IOP, but it may relate to com-
thought to occur via transcellular pores, large
plex relationships between pressure and resist-
vacuoles, or pinocytotic vesicles. However, par-
ance between the fluid compartments and the
acellular routes between the endothelial cells
soft tissues that comprise this route. For exam-
of Schlemm’s canal have also been proposed
ple, the pressure gradient between the anterior
and may be pressure sensitive, particularly at
chamber and suprachoroid is independent of
higher IOPs.
IOP; thus, fluid flow between these compart-
ments is also IOP independent. Uveoscleral
outflow is primarily impacted by the state of
Fluid Dynamics
the ciliary body and by the hydrostatic pres-
As the ciliary body produces AH, the tissues sure difference between the anterior chamber
comprising the ICA resist AH outflow, thus and the suprachoroidal space. Contraction of
­Aqueous Humor and Intraocular Pressur  79

Table 2.7 Aqueous humor dynamics formulas. determines IOP. While minor anatomical var-
iations in the venous system exist between
I Fin = Fat + Fuf species, results of pressure studies in humans,
F = flow (μl/min) nonhuman primates, rabbits, and dogs reveal
Fin = total AH inflow episcleral venous pressure to be between 8
Fat = inflow from active transport and 12 mmHg. Arteriovenous anastomoses
Fuf = inflow from ultrafiltration within the episcleral vasculature have been
demonstrated in the rabbit, dog, owl monkey,
II Fout = Ftrab + Fuveo
and cynomolgus monkey. These vascular
Fout = total AH outflow
shunts may function in rabbits and dogs,
Ftrab = outflow via the TM
where the episcleral vasculature appears to
Fuveo = outflow via the uveoscleral pathway lack a capillary system, and in the monkey
III Ctotal = Ctrab + Cuv + Cpseudo species as an emergency system to elevate
C = facility or conductance of flow (μl/ IOP after globe perforation or to retrogradely
min/mmHg) flush the outflow channel. Episcleral venous
Ctotal = total AH outflow facility pressure can be measured by direct cannula-
Ctrab = facility of outflow via the TM tion (using very fine glass pipettes) or indirect
Cuv = facility of outflow via the partial to complete compression schemes
uveoscleral pathway (using a string-­gauge system or a fluid-­filled
Cpseudo = pseudofacility chamber). Results of limited studies indicate
III At steady state, F = Fin = Fout that the volume of the anterior chamber
IV F = Ctrab (Pi − Pe) (Goldmann equation) directly relates to the rate of aqueous outflow,
so that animals with large eyes have faster
P = pressure (mmHg)
outflow rates per minute. The resistance to
Pi = IOP
aqueous outflow may be inversely propor-
Pe = episcleral venous pressure tional to the facility of outflow (Ctotal).
V Fin = Ctrab(Pi − Pe) + Fuveo
VI Pi = Pe + (Fin − Fuveo)/Ctrab

Regulation of Outflow
the ciliary body musculature decreases uncon- Cholinergic agonists such as pilocarpine
ventional outflow, possibly by reducing the decrease outflow resistance by contraction of
extracellular spaces; in turn, relaxation the ciliary muscle and subsequent spreading
increases outflow via this route. Thus, pilocar- of the TM. This effect is rapid, such that intra-
pine, a parasympathomimetic drug, and atro- venous administration of pilocarpine to vervet
pine, a parasympatholytic drug, will decrease monkeys results in a near-­instantaneous
and increase uveoscleral outflow by contract- decrease in outflow resistance, suggesting that
ing and relaxing the ciliary body musculature, the effect may be mediated by a structure per-
respectively. Because of general venous pres- fused by arteries. Ciliary muscle disinsertion
sure, IOP in the eye under general anesthesia and removal of the iris in nonhuman primates
will decrease to only 10–12 mmHg. obliterate this acute response to pilocarpine,
Formulas can be used to describe the for- suggesting that it is mediated completely by
mation and drainage of AH (Table 2.7). ciliary muscle contraction rather than a direct
Episcleral venous pressure or the “backpres- effect on the TM. The M3 subtype of the mus-
sure” created by the venous portion of the carinic receptor is strongly expressed in the
conventional pathway in the AAP or ciliary muscle and thought to mediate the
Schlemm’s canal constitutes approximately changes in outflow facility in response to
50–75% of the resistance (10–12 mmHg) that cholinergic agonists. Because the effect of
80 Ophthalmic Physiology and Vision

cholinergic agonists on trabecular outflow Table 2.8 Methods to investigate aqueous humor
(increase) is greater than that on uveoscleral dynamics.
outflow (decrease), the net effect is an increase
I Techniques to investigate the formation
in AH outflow and concomitant decrease in
of aqueous humor
IOP. As expected, cholinergic antagonists,
Cannulation of anterior chamber: constant
such as atropine, decrease traditional outflow rate/constant pressure perfusion
and increase nontraditional outflow by similar
Direct view/measurement of newly formed
mechanisms. aqueous humor
Many other influences on the rate of AH Use of markers in aqueous humor
formation and regulation of IOP have been (radioactive, fluorescein, para-­
proposed. For example, a center in the feline aminohippuric acid). Measure the decay rate
diencephalon has been found that, when stim- of intracamerally injected isotopes.
Fluorophotometry, a noninvasive method, is
ulated, causes alterations in the IOP. Central primarily used today
nervous system (CNS) regulation of IOP is
II Procedures to investigate the exit of
poorly understood, however, and hormonal aqueous humor
control of AH production may be involved.
Ocular perfusion to lower IOP
Perilimbic suction cup
Tonography (conventional outflow/pressure
Methods to Measure
sensitive)
Aqueous Dynamics
Use of markers (fluorescein,
Both invasive and noninvasive methods are nitrotetrazolium, latex spheres, radioactive
tracers). Both conventional and uveoscleral
used to investigate AH dynamics, and norma-
outflow routes are measured
tive values have been described in domestic and
III Methods to measure the episcleral
laboratory animal species (Table 2.8). Invasive venous pressure
studies are more difficult to study in animals as
Partial to complete collapse of the episcleral
the uveal tissues quickly respond to these “inva- veins to affect alteration in the blood flow
sions” and can reduce the study objectives, but
Torsion balance
these early methods were essential and formed
Pressure chamber (filled with air or saline)
the basis for later noninvasive methods. They
Air jet
usually measured the dilution of intracamerally
injected substances over short time periods. Ocular compression
With the AH volume within the anterior and Direct cannulation and measurement by
posterior chambers measured and the amount transducer
of dilution of the tracer estimated, the total
amount of AH produced per unit of time could
be determined. Knowledge of anterior and pos- extensively in humans, nonhuman primates,
terior chamber volumes is critical to determin- rabbits, cats, dogs, and, most recently, the red-­
ing the rate of AH production (Table 2.9). tailed hawk. This tool can also be used to assess
Fluorophotometry is a noninvasive method permeability coefficients of the BAB involved
for studying AH flow dynamics, for evaluating in health and disease, determine the effects of
ocular pharmaceutical agents used to treat selected drugs on the BAB, and mechanisms
glaucoma, and for determining iris permeabil- by which drugs affect the AH dynamics.
ity in both normal and disease states. To determine AH outflow invasively, perfu-
Fluorophotometry of the anterior chamber sion of the anterior chamber of in vivo and
and vitreous can noninvasively assess the per- ex vivo eyes has been performed in numerous
meability of the BRB in the normal and dis- species. The constant pressure perfusion tech-
eased eye. Fluorophotometry has been used nique is the most frequently used. It involves
­Aqueous Humor and Intraocular Pressur  81

Table 2.9 Comparative volumes of the chambers and select structures of the eye.

Species Anterior chamber (ml) Posterior chamber (ml) Lens volume (ml) Vitreous volume (ml)

Human 0.2 0.06 0.2 3.9


Rabbit 0.3 0.06 0.2 1.5
Pig 0.3 —­ —­ 3.0
Dog 0.8 0.2 0.5 3.2
Cat 0.8 0.3 0.3 2.8
Cow 1.7 1.5 2.2 20.9
Horse 2.4 1.6 3.1 28.2

maintaining a constant level of IOP with peri- endothelium and wandering macrophages to
odic, intermittent, or continuous minivolumes phagocytize particulate material within the out-
of perfusate. In the perfusion decay test, either flow pathways. An alternative method to esti-
a preselected volume of perfusate is injected or mate the amount of uveoscleral outflow (either
a preselected IOP is achieved. Once the perfu- as μl or %) is by using radioactive isotopes
sate has been injected, the time for the IOP to injected into the anterior chamber; the time,
regain the baseline or preexisting measurement amount of the isotope, or both are standardized.
is obtained. In many ways, the perfusion tech- At the conclusion of perfusion, either the ocular
niques are similar to the noninvasive tonogra- tissues are dissected into the different sections
phy methods (and yield similar results). and analyzed for radioactivity or the entire
The percentages reported for normal uveo- globe is sectioned and the radioactivity of each
scleral outflow range from 30% to 65% in non- area is measured by scintillation counters.
human primates, 15% in dogs, 13% in rabbits,
4–14% in humans, and 3% in cats. The horse
Ocular Rigidity
appears to have an extensive uveoscleral out-
flow system, but the volume and percentage of Another key concept in the measurement of
the total outflow system have not been reported. IOP is ocular rigidity (k), or the resistance
Often uveoscleral outflow is now calculated as offered by the fibrous tunics of the eye (i.e.,
the difference between applanation tonography sclera and cornea) to a change in intraocular
and the results from fluorophotometry. volume. Ocular rigidity may also be defined as
Uveoscleral outflow pathway has been dem- the change in IOP per incremental change in
onstrated using observable tracers measuring the intraocular volume; this resistance mani-
from 10.0 nm to 1.0 μm in diameter. As one fests as a change in IOP. Ocular rigidity is
would anticipate, the smaller-­diameter (i.e., determined by Schiotz indentation tonometry,
pore) tracers penetrate into the different tissues and it estimates the change in volume (open
to greater extents. After perfusion at different manometer system) when the instrument is
IOPs and for different time intervals, the eyes placed on the cornea as well as after injections
(especially the root of the iris, entire ciliary of exact volumes or preselected elevations in
body, suprachoroidal space, and choroid, even IOP. With applanation tonometry, ocular rigid-
as far posterior as the optic nerve) are examined ity is not a factor! This logarithmic relationship
by light microscopy, scanning electron micros- between IOP and volume of the globe is
copy, and transmission electron microscopy for
these markers. These same methods have also
log P2 / P1 k V2 V1 .
demonstrated the ability of the trabecular 
82 Ophthalmic Physiology and Vision

Table 2.10 IOPs in select animal species.

IOP results

Species Mean ± SD Tonometer Investigator

Alligator 23.7 ± 2.1 TonoPen Whittaker et al. (1995)


Cat 22.6 ± 4.0 Mackay-­Marg Miller et al. (1991b)
19.7 ± 5.6 TonoPen
Cow 28.2 ± 4.6 Mackay-­Marg Gum (1990)
26.9 ± 6.7 TonoPen XL
Chinchilla 3.0 ± 1.8 TonoVet-­D Müller et al. (2010)
9.7 ± 2.5 TonoVet-­D Snyder et al. (2018)
Dog 15.7 ± 4.2 Mackay-­Marg Miller et al. (1991a)
16.7 ± 4.0 TonoPen
17.8 ± 0.9 (pm) Mackay-­Marg Gelatt et al. (1981)
21.5 ± 0.8 (am)
Ferret 22.8 ± 5.5 TonoPen Sapienza et al. (1991)
15.4 ± 1.1 TonoPen Vet Di Girolamo et al. (2013)
14.1 ± 0.4 TonoVet
Frog (White’s tree frogs) 16.8 ± 3.9 TonoLab-­R Hausmann et al. (2017)
14.7 ± 1.6 TonoVet-­D
Goat (pygmy) 11.8 ± 1.5 TonoVet-­D Broadwater et al. (2007)
10.8 ± 1.7 TonoPen XL
Guinea pig 18.3 ± 4.6 TonoPen Vet Coster et al. (2008)
6.1 ± 2.2 TonoVet
Horse 25.5 ± 4.0 Mackay-­Marg Cohen & Reinke (1970)
23.5 ± 6.1 Mackay-­Marg Miller et al. (1990)
23.3 ± 6.9 TonoPen
Mouse (no anesthetic) 14.6 ± 0.5 TonoLab Ding et al. (2011)
Nonhuman primate 14.9 ± 2.1 Pneumatonograph Bito et al. (1979)
Rhesus (ketamine)
15.4 ± 2.6 TonoPen XL Komaromy et al. (1998)
Tibetan monkey 29.3 ± 0.9 TonoVet-­P Liu et al. (2011)
Rabbit 19.5 ± 1.8 Pneumatonograph Vareilles et al. (1977a, 1977b)
17.9 ± 2.1 Smith & Gregory (1989)
9.5 ± 2.6 TonoVet Pereira et al. (2011)
15.4 ± 2.2 TonoPen Avia
Raptor
Red-­tailed hawk 20.6 ± 3.4 TonoPen Stiles et al. (1994)
Golden eagle 21.5 ± 3.0
Great horned owl 10.8 ± 3.6
White-­tailed sea eagle 26.9 ± 5.8 TonoVet Reuter et al. (2011)
Northern goshawk 18.3 ± 3.8
­Aqueous Humor and Intraocular Pressur  83

Table 2.10 (Continued)

IOP results

Species Mean ± SD Tonometer Investigator

Red kite 13.0 ± 5.5


Eurasian 15.5 ± 2.5
sparrowhawk
Buzzard, common 26.9 ± 7.0
Kestrel, common 9.8 ± 2.5
Falcon, peregrine 12.7 ± 5.8
Owl, tawny 9.4 ± 4.1
Owl, long-­eared 7.8 ± 3.2
Owl, barn 10.8 ± 3.8
Rat 17.3 ± 5.3 TonoPen Mermoud et al. (1994)
21.4 ± 1.0 TonoPen Sappington et al. (2010)
Sheep 10.6 ± 1.4 Perkins Gerometta et al. (2009)

Table 2.11 Factors that cause short-­and long-­term fluctuations in IOP.

Short-­term fluctuations Long-­term fluctuations

Diurnal changes Aging


Forced eyelid closure Race/breed
Contraction of retractor bulbi muscles Hormones
Coughing/Valsalva maneuver Glucocorticoids
Abrupt changes in blood pressure Growth hormone
Pulse Estrogen
Struggling/electroshock Progesterone
Changes in body/head position Obesity
Succinylcholine Myopia
Acidosis Gender
Season

Ocular rigidity is a constant characteristic Intraocular Pressure


of each eye, but it also depends on IOP. Hence,
In many species, IOPs as measured with
the distensibility of each globe varies among
applanation tonometry in normal animals
individuals as well as with the IOP. Dogs and
have been reported (Table 2.10). In humans
cats have greater scleral elasticity than
and animals, short-­ and long-­term fluctua-
humans, so less resistance is offered with
tions in IOP occur for a variety of reasons
indentation tonometry, and buphthalmia
(Table 2.11). Diurnal IOP variations generally
occurs more readily with prolonged,
occur in most species; in humans and dogs,
increased IOP.
the highest pressure occurs in the morning
84 Ophthalmic Physiology and Vision

and the lowest in the afternoon. In contrast, inorganic ions, carbohydrates, ascorbic acid,
the greatest IOPs occur during the day and the glutathione, and amino acids.
lowest IOPs are documented at night in the The protein content of the lens is very high
rabbit, cat, horse, and nonhuman primate. In in comparison to other body organs. Protein
glaucomatous canine patients, diurnal IOP synthesis ceases with formation of the lens
fluctuations (as measured by tonometry) are fiber cells, and all the protein changes that
typically much greater in comparison to nor- occur after this stage are posttranslational
mal dogs. Consequently, antiglaucoma medi- modifications. Lens proteins are divided into
cations administered once daily to dogs should water-­soluble proteins and water-­insoluble
be given in the evening to mitigate IOP spikes proteins. Crystallins comprise 80–90% of the
in the morning, when pressures are typically water-­soluble lens proteins. Most of the insolu-
the greatest. ble proteins occur in the lens nucleus, whereas
the soluble proteins are concentrated in the
lens cortex. The insoluble proteins are associ-
­Lens ated primarily with membranes of the lens fib-
ers; the soluble proteins comprise the bulk of
The second most powerful refracting structure the refractive fibers of the lens. With aging,
in the eye is the lens. Like the cornea, the lens is water-­soluble proteins coalesce to make high
a transparent tissue without a direct blood sup- molecular weight aggregates and their hydro-
ply. The lens depends primarily on AH for its philicity diminishes. Additionally, when the
metabolic needs. Most of the lens proteins are lens becomes cataractous, the level of water-­
soluble, with a small amount of glycoproteins, insoluble proteins increases.
whereas the cornea consists mostly of insoluble The lens epithelium is the major site of
collagen and a relatively large amount of glyco- energy production in the lens. Energy is used
proteins. The lens considerations are important for active transport of inorganic ions and
to the veterinary ophthalmologists when con- amino acids and for protein synthesis.
sidering cataract surgery in animals, and Osmoregulation occurs through active trans-
attempts using intraocular lenses (IOLs) to re-­ port and involves the action of Na+–K+-­ATPase
establish the best possible visual acuity. Lens to maintain high K+ and amino acid concen-
metabolism is also important as the second larg- trations and low Na+, Cl−, and water concen-
est group of dogs having cataract surgery are trations within the lens. The movement of
those with diabetes mellitus. water is passive and occurs with the active
Lens epithelial cells are the progenitors of cation transport. As the Na+ ion is transported
the lens fibers and transition into lens fiber from the lens, K+ is transported into the lens
cells of the cortex at the equator. This process (see Figure 2.7) in a manner similar to that in
is characterized by distinct biochemical and red blood cells.
morphological changes, such as the synthesis The lens capsule functions as a semiperme-
of crystallin proteins, cell elongation, loss of able membrane. It prevents direct contact
cellular organelles, and disintegration of the between the lens and the surrounding ocular
nucleus. environment and protects the lens from the
Transparency of the lens depends primarily invasion of pathogens. However, the capsule
on the highly ordered lens cell arrangement, as allows water, small solutes, many proteins, and
well as on the solubility and physical arrange- waste to pass, thereby enabling the lens to
ments of its proteins. The lens behaves as a cell grow and perform metabolic functions. Its
syncytium both biochemically and electrically. mechanical functions include maintaining the
The lens consists of approximately 68% water, shape of the lens in association with accom-
38% protein, and small amounts of lipids, modating and providing for the attachment of
­Vitreou  85

the zonules. Because the lens capsules sur- fibers are filled with hyaluronic acid (HA),
round the developing lens before the fetus’s which provides viscoelasticity to the vitreous.
immune system develops, leakage of lens cells An increase in the collagen content of the vitre-
and material causes lens-­induced uveitis in ous makes it more solid, or gel-­like, while a
later life (a major cause for lower cataract sur- decrease in the collagen content makes its con-
gery success results in the long term). sistency more fluid. Species differ in the colla-
The primary source of energy for the lens is gen content of their vitreous, which accounts
glucose, which diffuses from the AH. Energy is for variability in its consistency. Generally, the
derived from anaerobic glycolysis and is used for cortical areas of the vitreous contain more col-
active cation transport and protein synthesis. lagen, so they are more rigid than other por-
Oxygen is not necessary for normal lens metabo- tions. The vitreous contains few cells, termed
lism, though a small percentage of glucose is hyalocytes. Hyalocytes belong to the monocyte/
metabolized through the Krebs cycle. The hex- macrophage lineage and derive from bone mar-
ose monophosphate (i.e., pentose) shunt and the row. Their origin is not from glial cells or retinal
sorbitol pathway are other pathways of glucose pigment epithelial cells, as previously thought.
metabolism in the lens. The major end product Hyalocytes are important for ECM synthesis,
of glucose metabolism in the lens is lactic acid, vitreous cavity immunology regulation, and
which diffuses into the AH. The rate of glycoly- modulation of inflammation.
sis is controlled by the amount of hexokinase The embryonic vitreous is very dense and
enzyme and the rate of entrance of glucose into therefore translucent. As an individual matures,
the lens. With high concentrations of glucose however, important structural changes occur in
(>175 mg/dl), the level of glucose 6-­phosphate the vitreous. The axial length of the vitreous
increases, which inhibits hexokinase and limits increases, which is critical for growth of the eye
the rate of glycolysis. This process prevents (discussed later). The overall collagen content
excessive buildup of lactic acid in the lens, which remains unchanged in the adult, but the HA
would lower the pH and activate the lens pro- concentration undergoes a fourfold increase in
teases. With very high blood and AH glucose both cattle and humans. This change in the
concentrations, as occur in diabetes mellitus, the HA-­to-­collagen ratio contributes to greater dis-
enzyme aldose reductase is activated as an alter- persal of the collagen fibrils, because the newly
native route of glucose metabolism in the lens. synthesized HA molecules push the collagen
The result is an accumulation of sorbitol in the fibril bundles further apart, thus increasing the
lens cells, which causes swelling associated with optical clarity of the vitreous. These changes in
the increased osmotic pressure. The outcome is HA–collagen interactions as well as in the GAG
the intumescent diabetic cataract. contents of the vitreous do not cease upon
reaching adulthood. Rather, these alterations
continue throughout life, and they are believed
to be responsible for the vitreal liquefaction
­Vitreous
observed as part of the aging process in several
species. In humans, rheological (i.e., the gel–
Vitreal Structure and Aging
liquid state of the vitreous) changes begin in
Physically, the vitreous is a hydrogel that con- the central vitreous at five years of age and con-
sists of >98% water and fills the large posterior tinue throughout life, so that in the geriatric
cavity of the eye. Collagen comprises the frame- patient, more than 50% of the vitreous is even-
work of the vitreous and provides its plasticity. tually liquefied. As liquefaction progresses, the
Despite the low protein content, a diverse array collagen bundles are packed into the remaining
of >1200 soluble proteins have been identified gel fraction, whereas HA molecules are redis-
in the vitreous. Spaces between the collagen tributed to the liquid fraction. A common
86 Ophthalmic Physiology and Vision

complication of this progressive liquefaction is The optical transparency of the vitreous is


separation of the posterior vitreous cortex from primarily due to a low concentration of struc-
the retinal inner limiting membrane (posterior tural macromolecules (0.2%, w/v) and soluble
vitreal detachment). This detachment can pre- proteins. Additionally, the configuration of
dispose to retinal tears, and has been impli- highly hydrated GAG chains separating small-­
cated as a risk factor in rhegmatogenous retinal diameter collagen fibers aids in the passage of
detachment in dogs. light with minimal scattering. Another impor-
tant factor in optical clarity is the blood–
vitreous barrier; HA is thought to act as a
Vitreous Functions
barrier that prevents diffusion of macromole-
The vitreous is the largest structure in the eye, cules and cells into the vitreous, except in cases
occupying approximately 80% of the globe. It of trauma or cortex disruption. Inflammatory
contributes to the development, optics, struc- responses, neovascularization, and collagenase
ture, physiology, and metabolism of the eye. activity are likewise suppressed in the vitreous.
The vitreous plays an important role in the As a result of these anatomical and physiologi-
growth of the eye by contributing to the increase cal properties, the vitreous transmits 90% of
in globe size. Inserting a drainage tube into the light at wavelengths between 300 and 1400 nm.
vitreous cavity of chicken embryos lowers intra- In addition to its refractive role, the vitreous
vitreal pressure and effectively stops the growth appears to have additional functions in the
of the eye, and vitrectomy of rabbit eyes has a process of accommodation. In both humans
similar inhibitory effect. In contrast, vitreal and monkeys, imaging has revealed that the
elongation will cause an increase in the axial vitreous bows posteriorly as the ciliary body
length of the globe. This lengthens the path of contracts. This movement is in proportion to
the incoming light, thus providing for greater the accommodative amplitude. The vitreous
light refraction. In some aquatic species, such as also plays an important role in ocular metabo-
goldfish, this increased vitreal refractivity is a lism. It serves as a storage site for retinal
physiological mechanism that compensates for metabolites, including glycogen, amino acids,
the loss of refractive power when the cornea is and potassium. Retinal and lenticular waste
submerged in water. In terrestrial species, the products, including lactic acid and free radi-
increased refraction by the vitreous leads to cals, are absorbed by the vitreous, which thus
myopia. Vitreal elongation resulting in axial serves to protect the lens and retina from toxic
myopia has been induced through visual depri- compounds. In cattle, these molecules (and
vation in a number of species, including nonhu- water) can diffuse across the vitreous through
man primates, chickens, and cats. This pores that are 400 nm in diameter. HA serves
elongation of the vitreous is affected by the syn- as a barrier to this diffusion process; therefore,
thesis of collagen. Synthesis, molecular recon- molecule size and HA concentration are two of
figuration, and hydration of HA molecules the primary factors affecting the diffusion of
likewise change the volume of the vitreous and, molecules through the vitreous. A decrease in
hence, of the eye. HA concentration, which results in vitreous
Diffusion is slow and bulk flow is limited in a liquefaction, will thus lead to an increase in
gel such as the vitreous. Therefore, topically particle diffusion through the vitreous.
administered substances are prevented from Therefore, pathological or aging processes
reaching the retina and optic nerve and systemi- leading to a decreased HA concentration and
cally administered antimicrobials are unable to vitreal liquefaction will affect the nutrient sup-
reach the center of the vitreous. This slow ply, waste removal, and drug delivery in the
change of substance concentrations has been posterior segment of the eye.
used in humans to determine time of death and The vitreous also provides some mechanical
aid in postmortem diagnosis in manatees. and structural support to the lens and retina.
­Ocular Mobilit  87

Furthermore, its viscoelastic properties protect ventrally. These muscles keep vision horizon-
the internal eye structures from trauma and tally level irrespective of eye position in the
stress, especially during rapid eye movement orbit. The retractor bulbi, which is present in
(REM). Concentrations of collagen and HA, as most species other than primates and birds, is
well as the nature of their cross-­links, contrib- innervated by CN VI and pulls the globe deeper
ute to this viscoelasticity. For example, in within the orbit. The EOMs contain both fast
humans, the concentration of vitreal HA and (~85%) and slow (~15%) fibers; however, in
collagen is twice as high as in the pig, and this contrast to noncranial skeletal muscles, they
corresponds to a 60% increase in the spring exhibit both very fast contractility and extreme
constant of human versus porcine vitreous. fatigue resistance. Even among the EOMs there
Woodpecker vitreous differs from human vit- is great variation in the composition of each
reous in that it does not have vitreoretinal muscle in regard to the myosin heavy chain iso-
attachments. This lack of coupling of the vitre- forms that assist with the dynamic physiologi-
ous to the posterior pole, as well as the orienta- cal properties and CNS control of eye
tion of the eye with respect to the axis of movements. The EOMs are highly aerobic as
striking, is thought to reduce relative shearing well as resistant to injury and oxidative stress,
motions that would be expected to result in with only cardiac muscle having a higher blood
ocular trauma from the woodpecker’s rapid flow rate. Additionally, normal EOMs undergo
acceleration–deceleration movements. myonuclear addition and subtraction through-
out life while maintaining overall size and
function, which is not observed in any other
­Ocular Mobility noncranial muscle. A motor axon innervates
5–10 muscle fibers in the extrinsic eye muscles,
Higher-­resolution vision is subserved by a whereas thousands may be innervated by a sin-
small section of the retina termed the area cen- gle axon in skeletal muscles, thus allowing for
tralis in animals. Visual acuity and other finer control of eye muscles by the CNS.
parameters of vision (e.g., color perception) The EOMs of the eyes of birds are generally
decrease rapidly in the more peripheral retina similar to those of mammals, other than the
outside the area centralis. To keep an object of lack of a retractor bulbi muscle. In addition,
interest in the center of the visual field, so that the rectus muscles are much less robust than
its image will stimulate the area centralis (or in mammals. Globe shape varies considerably
fovea in birds and primates), vertebrates rely on among avian species, but the globes are rela-
the actions of six or seven EOMs. Domestic spe- tively large, such that the two eyes weigh
cies have four rectus EOMs – dorsal (or supe- nearly as much as the brain. The globe shape
rior), ventral (inferior), nasal (medial), and and tight fit within the orbit impede globe
temporal (lateral) – all of which move the eye movement, thus leading to the less robust rec-
in those respective directions (see Chapter 1). tus muscles. Birds compensate for this
The oculomotor nerve (CN III) innervates the restricted globe mobility through movement of
dorsal, ventral, and medial rectus muscles, and upper body and neck muscles to obtain a spa-
the abducens nerve (CN VI) innervates the lat- tial perspective on objects.
eral rectus muscle. Two oblique muscles that Simplistically, two fundamental laws govern
work in conjunction with the rectus muscles eye movements. The first, formulated by
are also present. The ventral oblique, which is Sherrington, states that antagonistic muscles
innervated by the oculomotor nerve, rotates the (in the same eye) have reciprocal innervation.
ventral aspect of the eyeball both nasally and In other words, stimulation of an agonistic
dorsally; the dorsal oblique, which is inner- muscle (e.g., medial rectus) occurs concur-
vated by the trochlear nerve (CN IV), rotates rently with inhibition of the antagonistic mus-
the dorsal aspect of the eyeball both nasally and cle (e.g., lateral rectus) in the same eye. The
88 Ophthalmic Physiology and Vision

second governs innervation of yoked muscle otherwise might result in a disparity between
pairs (i.e., the two muscles responsible for the retinal images of the two eyes.
moving both eyes in the same direction). In The afferent stimulus for all these eye move-
mammals, yoked muscle pairs are always ments is the visualized object. If the head is
equally innervated; therefore, a lateral move- moving, however, eye movement is controlled
ment of the left eye will be accompanied by an by a different afferent limb, which allows for a
identical, medial movement of the right eye. faster tracking response. In this case, the stim-
Additionally, several EOM pulley systems have ulus is the acceleration of the head. Linear
been hypothesized but not proven. acceleration stimulates the otoliths of the ves-
The seven EOMs are responsible for numer- tibular apparatus, and angular acceleration
ous types of eye movements. Saccadic eye stimulates the hair cells of the semicircular
movements are very rapid (up to 1000°/s) and canals. These organs provide the afferent input
very brief (<0.1 s). They are intended for fast for the vestibulo-­ocular reflex (VOR), the neu-
correction of eye position to rapidly bring the ronal pathways of which are discussed in detail
image of interest onto the area centralis. Thus, in Chapter 18. The reflex produces immediate,
saccadic movements are used mostly when but slow, eye movements, which compensate
tracking a fast-­moving object or to begin pur- for movement of the head and help stabilize
suit of a formerly stationary object. the image on the area centralis. Thus, if the
Once the image of the object has been “cap- head moves up, the VOR moves the eyes down,
tured” by the area centralis, smooth pursuit and if the head moves to the left, the VOR
eye movements are used to match the speed of moves the eyes to the right. It appears that the
the object and to maintain its image in the area cat makes greater use of the VOR arc than the
centralis. Required minor corrections and dog to follow moving objects. Comparison of
adjustments are, again, executed by saccadic the dog and cat when visually following a
movements. This combination of alternating bouncing ball is most dramatic.
rapid and slow eye movements is called optoki- Nystagmus is usually characterized by an
netic nystagmus (discussed later), which can REM in one direction and a slow movement in
be used to track objects moving at speeds the opposite direction. Nystagmus can be
<100° as well as the determination of visual either horizontal or vertical. The types of
acuity in nonvocal individuals and animals. nystagmus are categorized on the basis of
Saccades and smooth pursuit constitute the their causes, and they include optokinetic,
two types of conjugate (or version) eye move- rotatory, postrotatory, ocular, caloric, galvanic,
ments, in which the two eyes move together anesthetic, brain stem, cerebellar, and vestibu-
without changing the angle between them. lar. In optokinetic nystagmus, the eyelids must
Vergence eye movements, in contrast, be open, and the fast phase is opposite in
change the angle of intersection between the direction to the movement of the visual stim-
two eyes. These can be either convergent (i.e., uli. However, the visual stimuli can be moving
increasing the angle between the visual axes to with the head stationary, or the head and body
focus on a near target) or divergent (i.e., can be moving with the visual stimuli station-
decreasing the angle between the visual axes to ary. In the latter case, the fast phase is in the
focus on a far target). Vergence movements are same direction as the movement of the head.
usually slow (<21°/s) and they have two roles. This can be used as an objective means of
The first is to aid in visualizing nearby objects, detecting vision in animals. Optokinetic nys-
which is a process that combines convergent tagmus usually occurs in the horizontal plane
eye movement, accommodation, and miosis. and is less well substantiated in the vertical
The second is to resolve any small misalign- plane. In rotatory nystagmus, the fast phase is
ments between the two visual axes that in the same direction as the rotation of the
­Introductio  89

head. In postrotatory nystagmus, which is ­Oculocardiac Reflex


seen after rotation stops, the fast phase is
opposite to the direction of the rotation of the The oculocardiac reflex can cause reflexive
head. Postrotatory nystagmus lasts approxi- slowing of the heart and can be stimulated by
mately 10 s after rotation stops. In rotatory and pressure on the globe, tension on the EOMs or
postrotatory nystagmus, the stimuli are accel- iris, or increased intraorbital pressure caused
eration and deceleration, respectively. At a by injection, hemorrhage, or a foreign body.
constant rate of rotation, nystagmus does not The most common effect of the reflex is brady-
occur if the lids are closed. Optokinetic nys- cardia, but other clinically significant effects
tagmus occurs if the eyelids are open. Ocular are cardiac arrest and ventricular fibrillation.
nystagmus is associated with congenital blind- The oculocardiac reflex has been reported in
ness and has a wandering or searching move- humans, dogs, cats, horses, rabbits, mice, and a
ment of the eyes rather than the distinct fast cockatiel. The afferent arc of the oculocardiac
and slow phases (see Chapter 18 for more reflex begins with the long and short ciliary
details). nerves to the ciliary ganglion. The ophthalmic
There are several other types of eye move- division of the trigeminal nerve (CN V) contin-
ments. During certain stages of sleep, REM ues to the trigeminal ganglion to its sensory
occurs, usually in bursts lasting from 5 to nucleus. The afferent arc continues along short
60 min. Numerous REM bursts, which are tra- internuncial fibers in the reticular formation to
ditionally associated with dreaming, may connect with the efferent pathway in the motor
occur during a single sleep. Sleep patterns vary nucleus of the vagus nerve (CN X) to the myo-
with age, however. Discrete eye movement cardium. Sensory stimulation of the eye and
bursts during certain stages of sleep are infre- orbital areas results in stimulation of the vagal
quent in newborn kittens, but after three weeks nucleus in the brain stem, thus causing a reflex-
of age adult patterns of sleep develop. ive slowing of the heart. Conscious, healthy
Another important class of movements, micro- rabbits and dogs do not show clinically signifi-
saccades or micronystagmus, are those that cant decreases in heart rate with globe com-
maintain eye position while gazing at a station- pression of 1 min. Endotracheal intubation can
ary target. These movements are required to cause vagal stimulation as well, resulting in
maintain fixation on the object even when both similar reflexive cardiac alterations. In the dog,
the observer and the target are immobile. Though as the IOP increases, the heart rate may also
slow drifts are also used for this purpose, position increase, thus indicating the possibility of an
maintenance movements are usually character- intraocular-­sympathetic-­cardiac reflex as well
ized by their low magnitude (several minutes/ as a trigeminovagal reflex.
arc) and high frequency (1–50/s).
Kittens are born with a divergent strabismus
that is evident following eyelid opening at Section II: Optics and Physiology
approximately 12–14 days postnatally. Normal of Vision
interocular alignment, which depends on vis-
ual stimuli, develops during the second post- ­Introduction
natal month. Crossed eyes (i.e., convergent
strabismus), which are commonly seen in The goal of this section is to describe the physi-
adult Siamese cats and certain albino mam- cal, anatomical, and physiological aspects of the
mals, result from a genetic neuroanatomical process of vision, and it has been divided into
defect in the primary visual pathway that two parts. The first part is devoted to light and
involves the retinogeniculate and geniculocor- vision and the different refractive structures of
tical projections. the eye. It covers the physical changes that light
90 Ophthalmic Physiology and Vision

undergoes during its passage from the cornea, water, a wave of light has two principal charac-
through the various structures of the eye, until teristics (Figure 2.8). Its amplitude, A, is the
it reaches the retina. The second part is devoted maximum value of the field generated by the
to the visual processing and describes what hap- propagating wave; it determines the wave’s
pens once light reaches the retina. This part is intensity. The wavelength, λ, is the distance
dedicated to the neuronal processes of vision between adjacent wave crests; it determines
and describes the generation, processing, and the wave’s location in the electromagnetic
propagation of the visual signal in the retina, spectrum. Light, which is the visible portion of
the visual pathways, and the cortex. Both these the electromagnetic spectrum, occupies a
parts lay the foundations for understanding small fraction of that spectrum, which ranges
how optical and neuronal processes enable the from cosmic and gamma rays (λ < 10−10 m) to
detection of movement, details, and color that radio transmission (λ > 103 m). In humans, vis-
create the rich experience of vision described in ible light normally ranges in wavelength from
last section of this chapter. 380 nm (i.e., deep blue) to 780 nm (i.e., deep
red). However, additional wavelengths, outside
the 380–780 nm spectrum, can be seen by other
­Visual Optics species. Many nonmammalian species, and
some mammals, possess ultraviolet (UV)
Physical Optics vision that allows them to detect light with a
wavelength shorter than 380 nm, enabling
Light them to see hues that are not perceived by
Light has alternately been described as a wave humans; this capability is used in both forag-
or as photon particles. However, these descrip- ing and courting behavior. The cat retina has
tions are not mutually exclusive. Both models also been shown to respond to infrared (IR)
also are applicable in the eye: the wave theory light (826–875 nm), though the functional and
explains the physical changes light undergoes behavioral implications of this capability are
during its passage through the eye, and the not clear. This is not to be confused with the IR
particle theory explains the energy transforma- “vision” of snakes, which relies on the heat
tion that occurs when light strikes the outer detection properties of the pit organs.
segments of the photoreceptors. Hence, the At the same time, light also possesses the prop-
first part of this chapter discusses light as a erties of particles, termed photons, which repre-
wave, while the second part discusses it as a sent quanta of energy that can be emitted (at the
particle. light source) or absorbed (e.g., by retinal photore-
Light behaves as a wave as it passes through ceptors). The amount of energy in a given photon
transparent media such as air, vacuum, or the is inversely proportional to its wavelength;
visual axis of the eye. Much like a wave of ­therefore, blue light possesses more energy than

Figure 2.8 Representation of light as a wave, which is characterized by two parameters. Its amplitude (A)
is the maximum value the wave obtains as it propagates. Its wavelength (λ) is the distance between two
consecutive peaks.
­Visual Optic  91

red light, which has a longer wavelength. An Table 2.12 Luminances of natural and artificial
example of the particle nature of light is seen in light sources.a
the use of cobalt blue light to highlight fluores-
cein staining of corneal ulcers. Fluorescein Source Luminance (cd/m2)
sodium molecules absorb photons of blue light
Sun 109
and reemit photons with lower energy content,
Car light 107
in the yellow-­green portion of the spectrum, in a
process known as fluorescence. Incandescent tungsten lamp 106–107
As light strikes the photoreceptor outer seg- Fluorescent lamp 104–105
ments, it is absorbed by a visual photopigment. Clear sky at noon 104
The function of this two-­part molecule reflects Full moon 103
the principles of quantum physics, as it utilizes Street lamp 0.1–1.0
both the wave properties and the particle prop- Moonless night sky 10−3 to 10−6
erties of light. The first part of the molecule,
a
the opsin, determines the wavelength of the In general, only the photopic system is active at a
luminance >3 cd/m2; at a luminance <0.03 cd/m2, the
light that the photopigment will absorb, thus scotopic system functions alone. Both systems are
determining color vision. The second part of active at intermediate luminance values, which are
the molecule, the visual chromophore or reti- defined as mesopic vision.
nal, uses the energy of the photon to undergo
isomerization (from 11-­cis-­retinal into all-­trans
Luminance is measured using photometers,
retinal in the case of rhodopsin), thereby initi-
which are divided into two major classes. Visual
ating conversion of a light stimulus into an
photometers provide a subjective reading,
electric signal. This process, the phototrans-
because the observer compares the illumination
duction process, which is discussed in detail
of the measured light with that of a standard
later in this chapter, is the first step in the prop-
light. Photoelectric photometers convert the
agation of a visual signal.
measured light into an electric current, which is
displayed by the instrument. Photometry meas-
Photometry
urements are extremely important in electrore-
Photometry is the quantitative measurement
tinographic (ERG) recordings because they are
of visible light. Photometry measures a num-
used to describe such variables as threshold,
ber of interrelated properties of light, using a
ambient light, and stimulus parameters.
basic unit called a candela. Two important
characteristics of light are its luminous inten-
sity, which describes the intensity of a light
Transmission and Reflection
source (as measured in candela), and its lumi-
nance, which describes its brightness reflected Human vision is limited to a wavelength range
from a surface (as measured in foot-­lamberts of 380–780 nm. This limitation is a result of
or cd/m2). These two properties are related, but two factors: the first is the absorption spectrum
they are not necessarily proportional. A hand- of the opsin component of the visual photopig-
held transilluminator is a bright source of ment, and the second limiting factor is the
light, but it possesses low intensity and there- transmission, reflection, and attenuation of
fore cannot be used to illuminate a football sta- the various wavelengths by the ocular media.
dium. On the other hand, a streetlight provides In humans, radiation wavelengths of
high-­intensity light, which illuminates a large 300–2500 nm are transmitted through the cor-
area, but it is not bright and does not provide nea. Not all wavelengths, however, are trans-
enough illumination to conduct cataract sur- mitted through the cornea equally, as
gery (Table 2.12). transmission is directly related to wavelength.
92 Ophthalmic Physiology and Vision

In the rabbit, the cornea transmits 89–93% of new medium. Most of the reflection that takes
the light at 370–500 nm, falling to 50% transmit- place in the eye occurs as incoming light strikes
tance at 310 nm and a mere 2% at wavelengths the cornea because of the large difference in
below 290 nm. refraction indices between the cornea and air.
Additional attenuation of transmission Reflection that occurs at the cornea–air inter-
occurs inside the eye. Even though light with face affects not only incoming light but also
wavelengths of up to 2500 nm passes the cornea, outgoing light.
there is barely any transmission of wavelengths Light that is not transmitted and not reflected
greater than 1950 nm through the AH, and in can be either scattered in the eye or absorbed
humans, the lens only transmits wavelengths by pigments. Foremost among these pigments
between 390 and 1400 nm. A similar range of are the photopigments of the photoreceptor
wavelengths is transmitted through the pig eye. outer segments, which absorb photons and
The implication of these numbers is that the thus initiate the visual process. Additional
aqueous and lens act as color filters, preventing absorption processes in the eye may have clini-
UV and IR light with very short and very long cal implications. Cyclophotocoagulation in
wavelengths (which has passed the cornea) glaucoma patients is based on the preferential
from reaching the retina. The UV filtering by absorbance of 810 and 1064 nm radiation of
the lens is of particular importance, as UV light the diode and Nd:YAG lasers, respectively, by
is a risk factor in a number of retinal diseases. melanin-­containing tissues.
Therefore, the current IOLs are coated with UV
filters to restore this protection in pseudophakic
Geometric Optics
patients. In this context, it is noteworthy that
aphakic humans can detect UV radiation fol- Refraction
lowing lens extraction, because the lens serves In vacuum, light travels at a constant speed (c)
as a filter, blocking out light of shorter wave- of approximately 3 × 108 m/s. As it strikes
lengths. In other words, human opsin is capable denser media, light undergoes three changes:
of absorbing UV light, but these wavelengths do (i) its velocity is reduced; (ii) its wavelength
not reach the retina of phakic subjects. shortens; and lastly (iii) it is bent (unless it
Additional ocular structures, such as tear film struck the surface of the medium at a 90° angle).
and eyelids, also act as color filters, causing sig-
nificant attenuation of short-­wavelength light. Vergence
Thus, when cumulative transmittances are calcu- An object that bends (or refracts) light is called
lated for the successive components of the eye, a a lens. When a single ray of light strikes a lens,
maximal transmittance rate in humans of 84% is the ray undergoes simple refraction, as depicted
obtained for light between 650 and 850 nm, while in Figure 2.9. Most objects or images, however,
in rabbits the transmittance rate to light between generate a pencil of light rays rather than a sin-
370 and 500 nm is 90%. Obviously, transmission gle ray. When a pencil of rays strikes a lens, they
will be further reduced by ocular opacities. Age is spread apart (i.e., diverge) or come together
another factor affecting transmittance. (i.e., converge). Convergence, or positive ver-
Transmission of light at 480 nm through the gence, occurs when light strikes a convex lens
human lens decreases by 72% from the age of (Figure 2.10a–c). Such a lens has a positive
10 years to the age of 80 years, thus affecting color power, indicating that it forms a real image,
perception of the elderly. which means that incoming rays from the object
Ocular surfaces can also reflect back incom- are converged and focused on the other side of
ing light, depending on the angle of incidence. the lens (see Figure 2.10a and b). On the other
Light that strikes a surface at an oblique angle hand, divergence, or negative vergence, occurs
is reflected back; it is not transmitted into the when light strikes a concave lens (see
­Visual Optic  93

θi

ni (a)

nr
(b)

θr

ni ∙ sin θi = nr ∙ sin θr

Figure 2.9 Refraction of light as it passes from one


medium to another is governed by Snell’s law, (c)
summarized in the formula below the diagram. The
angle of refraction (θr) is a function of the angle of Figure 2.10 Refraction of light through various
incidence (θi) and the refractive indices of the two lenses. (a) A spherical convex lens with a power of
media. In this representation, ni < nr; therefore, θi > θr. 10 D focuses parallel light rays at a distance of
0.1 m. (b) A flatter, less spherical convex lens with a
power of 5 D focuses parallel rays at a distance of
Figure 2.10c). The negative power of the con- 0.2 m. (c) Parallel rays passing through a concave
cave lens indicates that it forms a virtual or aer- spherical lens diverge. A virtual image is formed by
ial image, which means that the diverging rays tracing back (dashed lines) the diverging rays.
are traced, using imaginary extensions, back-
ward to a “focused” virtual image “located” on
the same side of the lens as the object (dashed, eye. This is due to the large difference in refrac-
“imaginary” lines). The vergence power (i.e., tive indices as light passes from air, which has a
amount of bending) of a lens is measured in refractive index of almost 1, into the tear film,
units called diopters. One diopter (D) is the ver- which has a refractive index of 1.337.
gence power of a lens with a focal length (f) of The cornea is the next tissue through which
1 m when in air. incoming light passes. The human corneal stroma
has a refractive index of 1.376. Because this value
is slightly higher than the refractive index of the
Visual Optics
tear film, passage of light from the tear film into
Refractive Structures of the Eye the anterior layers of the cornea results in an
Precorneal Tear Film and Cornea additional 5 D of refractive power. However, these
As mentioned, light is successively refracted by 5 D are “lost” when light passes from the poste-
the various ocular structures as it passes rior cornea into the AH, which has a refractive
through the eye on its way to the retina. index nearly identical to that of the tears. When
Table 2.13 lists the refractive indices and pow- combined, the PTF and the cornea of humans
ers of various ocular surfaces in humans. The contribute a net refractive power of 43 D.
most anterior optical surface of the eye is the Another factor affecting the refractive power
PTF. By strict definition, it could be argued that of the cornea, besides the refractive index, is its
the tear film is the most refractive layer of the curvature. Because the cornea converges light,
94 Ophthalmic Physiology and Vision

Table 2.13 Refraction constants in the human eye.

Structure Refractive index Refractive power (D) Reference

Tears 1.336 43.0a Montes-­Mico et al. (2004)


Cornea 1.376 42.3a Duke-­Elder (1970); Naeser et al. (2016)
Anterior surface 1.401 48.2 Patel et al. (1995)
Posterior surface 1.373 −5.9 Patel et al. (1995)
Lens 1.41 21.9 Duke-­Elder (1970); Chang et al. (2017)
Anterior surface 8.4 Millodot (1982)
Posterior surface 14.0 Millodot (1982)
Vitreous/aqueous 1.336 Duke-­Elder (1970)
Retina 1.363 Millodot (1982)
a
The refractive power of the cornea and tears is not additive. Rather, that of the former arises from the latter, and
from its interface with air. The net power of the tears and the anterior and posterior cornea is 43 D.

it acts as a convex lens. As stated earlier, the spherical in fish and aquatic mammals, while it
refractive power of such a lens depends to a is more discoid (i.e., less spherical) in terrestrial
large extent on its curvature radius. Therefore, species. Therefore, the lens will have a higher
in large eyes, which are characterized by flat refractive power in the former compared to the
corneas, the refractive power of the cornea is latter (Table 2.14). The reason for the increased
reduced. Conversely, in small eyes with spheri- refractive index and lens curvature in aquatic
cal corneas, its power is increased. species is the loss of corneal refractive power
underwater. Of course, the curvature (and,
Lens hence, the refractive power) of the lens can also
As noted, the refraction that occurs as light be changed actively through a process termed
passes from the cornea into the AH and during accommodation.
its passage through the aqueous has little overall
significance. Therefore, the next significant Vitreous
refractive structure through which light passes The next refractive tissue is the vitreous.
after the cornea is the lens. As in the case of the Though there is little refraction as light passes
cornea, the refractive power of the lens is deter- from the lens into the vitreous (due to their
mined by both its refractive index and its curva- similar refractive indices), the vitreous plays
ture. In humans and in many nonaquatic species, an important role in refractive development of
the refractive index of the lens nucleus is about the eye. Vitreous elongation increases the axial
1.41; it decreases gradually toward the cortex, length of the eye, thereby increasing the refrac-
forming a bell-­shaped refractive index curve tive path of light and inducing myopia, or
known as the gradient index. In humans, the cal- nearsightedness (Figure 2.11). In certain fish,
culated refractive power of the lens is approxi- this mechanism serves to increase ocular
mately 22 D. refraction and compensate for loss of corneal
The second factor determining lenticular refractive power. In different goldfish strains,
refractivity, the lens curvature, also differs for example, the vitreous body can contribute
between aquatic and nonaquatic species. anywhere from 37% to 70% of the total axial
Generally, it can be said that the lens is length of the eye.
­Visual Optic  95

Table 2.14 Eye size (ascending order) and corneal power (descending order) in selected animal species.

Species Axial length (mm) Corneal power (D) References

Goldfish 4.2 129 (in air) Hughes (1977)


Rat 6.3 112.7 Hughes (1977)
Chicken 8.9 108 Cohen et al. (2008)
Guinea pig 8.9 83.9 Howlett & McFadden (2007)
Sea otter 14.0 59.2 Murphy et al. (1990)
Rhesus monkey 16.3 56 Qiao-­Grider et al. (2010)
(4 months)
Rabbit 18.0 44.6 Hughes (1977); Wang et al. (2014)
Cat 21.3 43.0 Habib et al. (1995)
Dog 19.5–21.9 37.8–43.2a Gaiddon et al. (1991); Nelms et al.
(1994); Rosolen et al. (1995)
Ostrich 38/0 25.3 Martin et al. (2001)
Elephant 38.8 21.3 Murphy et al. (1992a)
Horse 39.2 16.5 McMullen & Gilger (2006)
43.7 15.7–19.5 Farrall & Handscombe (1990);
Miller & Murphy (2017)
a
The range of values in the dog probably reflects a breed difference, because larger breeds have flatter corneas.

Accommodation the ciliary body muscle, which in turn leads to


Accommodation is a rapid change in the stretching of the lens zonule. The increased
refractive power of the eye, which is intended tension of the zonules results in a greater pull
to bring the images of objects at different dis- on the lens capsule, thus causing the lens to
tances into focus on the retina. The stimulus become more discoid and decreasing its overall
for the accommodative response is a blurred, axial thickness and refractive power in a pro-
or defocused, retinal image. In vertebrates, cess of disaccommodation. To accommodate
eyes accommodate by one or more of the fol- for near objects, the reverse process takes
lowing mechanisms: (i) changing the curva- place. Parasympathetic input induces contrac-
ture or position of the lens; (ii) changing the tion of the ciliary body muscles, leading to
corneal curvature; (iii) changing the distance relaxation of the zonular fibers and reduced
between the cornea and retina; or (iv) having tension on the lens capsule. In turn, this liber-
two or more separate optical pathways of dif- ates the inherent elasticity of the lens, result-
ferent refractive powers. Accommodation is ing in a more spherical lens possessing greater
most commonly measured using IR photoreti- axial thickness and refractive power.
noscopy, which uses reflection of IR light from Consequently, anterior chamber depth
the fundus to measure dynamic changes in the decreases and increases during accommoda-
refractive error. Since mammalian accommo- tion and disaccommodation, respectively.
dation is mediated by contraction of the Unlike mammals, chickens (and possibly liz-
smooth ciliary muscle, it can be stimulated by ards) also accommodate by changing the cor-
pilocarpine. Humans and other primates neal curvature. Corneal accommodation is
accommodate by changing the curvature of mediated by the anterior ciliary muscle.
the lens (Figure 2.12). To view distant objects, Contraction of Crampton’s muscle, which orig-
sympathetic innervation induces relaxation of inates in the sclera and inserts in the cornea,
96 Ophthalmic Physiology and Vision

illumination, as mydriasis also decreases the


depth of focus of the eye. This means that as
the pupil dilates, the range of distances at
which objects remain in focus decreases.

Abnormal Refractive States


and Optical Errors
Emmetropia and Ametropia
(a) The “purpose” of refraction and the accommo-
dative processes described in the previous sec-
tions is to focus an image on the outer segments
of the photoreceptors. An emmetropic eye is
one in which parallel light rays (from a distant
object) are focused on the outer segments when
the eye is disaccommodated. A nonemme-
Focal tropic, or ametropic, eye is one in which the
Plane focused image (from a distant object) falls ante-
rior to the retina (i.e., nearsighted or myopic
(b) eye) or posterior to it (i.e., farsighted, hyperopic
Figure 2.11 The effect of vitreous elongation on or hypermetropic eye) (see Figure 2.12).
ocular refraction. (a) A focused emmetropic eye. (b) Retinoscopy is the most commonly used
The refractive power of the eye has not changed, clinical method to determine the refractive
and the light is focused on the same spot as in
state of the eye in young children and animals.
panel (a). However, due to vitreous elongation, the
retina has moved posteriorly, and therefore the It is based on two assumptions: first, that light
light is now focused in front of the retina. As a emerging from the eye (i.e., emergent rays) fol-
result, the eye is now nearsighted or myopic. lows the same optical path as light entering the
eye; and second, that the fundus reflex origi-
flattens the peripheral cornea and increases the nates at the level of the outer segments. If
curvature of the central cornea. Corneal accom- those two assumptions hold, then emergent
modation is reported to play an important role rays exit an emmetropic eye as parallel rays, a
in chicken accommodation, contributing 8–9 hypermetropic eye as diverging rays, and a
D. Thus, the reported combined (corneal and myopic eye as converging rays. Therefore, the
lenticular) accommodative power of the eye in location of the focal point formed by the emer-
young chicks is 25 D, compared with a maximal gent rays can be used to determine the refrac-
power of 15 D in children. tive state of the eye. Table 2.15 lists refractive
errors in select species. Most of these values
have been determined using streak retinoscopy,
Pupil
though autorefractors have also been used in
The pupillary aperture is not considered to be a veterinary medicine. A large survey found
classic refractive structure as it has no refrac- that, on average, dogs are indeed emmetropic,
tive index, but it does make an important con- with a mean refractive error of −0.05 D. Nine
tribution to the resolving power of the eye. As dog breeds, including English Springer Spaniel,
the pupil dilates in dim light, the number of German Shepherd, Golden Retriever, Siberian
photons entering the eye increases, resulting Husky, Shetland Sheepdog, Labrador Retriever,
in increased retinal illumination. However, Border Collie, Samoyed, and “other” terriers
there is “a price to be paid” for this increased were found to be emmetropic (defined as
­Visual Optic  97

demonstrating a significant effect of age. It is


interesting to note that myopia decreases with
age in cats, but in horses and in some dog
breeds, notably the English Springer Spaniel
and Beagle, it increases with age.
Several large studies have shown horses to
be overall emmetropic. However, only 48–68%
of horses are emmetropic in both eyes, with
hyperopia and myopia reported in equal pro-
(a)
portions in the ametropic horses, with errors
of up to ±3 D. Age and breed may affect the
refractive error in horses.
A large range of retinoscopy values is
reported in species with small eyes. For exam-
ple, values range from +20 to −13 D in the rat,
and from −0.7 to +13.7 D in C57BL/6J mice.

Aphakic Eyes and Intraocular Lenses


(b) Because of the significant refractive role of the
lens, cataract surgery (or any surgical lens
extraction) resulting in aphakia leaves the eye
severely hypermetropic. The aphakic eye lacks
the refractive contribution of the lens; therefore,
light is not sufficiently refracted, resulting in
image formation “behind” the retina. Since the
early 1980s, veterinary ophthalmologists have
sought to alleviate this problem by implanting
IOLs in dogs’ eyes following cataract extraction.
The purpose of these implants is to compensate
(c)
for loss of refraction by the lens, thereby return-
Figure 2.12 (a) In emmetropia, parallel light rays ing the eye to an emmetropic state. Following
are focused on the retina. (b) In a farsighted the results of studies involving large numbers of
(hypermetropic or hyperopic) eye, light rays are dogs of various breeds, it has been determined
focused behind the retina. (c) In a nearsighted, or
myopic, eye, the light is focused in front of that the canine IOL should have a power of
the retina. 40.0–41.5 D. The 1.5 D range of recommended
values probably results from breed differences.
having a mean refractive error <0.5 D in either Use of 41 D IOLs in 60 dogs resulted in an aver-
direction). The same study also found that 8% age refractive error of 1.2 D. However, it is
of all dogs were hypermetropic, with a refrac- important to note that though 41 D IOLs are
tive error of up to +3.25 D. Three breeds used to bring aphakic dogs to emmetropia, this
(Australian Shepherd, Alaskan Malamute, and does not mean that aphakic dogs suffer from
Bouvier des Flandres) were found to have a hypermetropia of 41 D.
mean refractive error that was hypermetropic. While canine IOLs are widely used by veteri-
A study in cats reported that kittens nary ophthalmologists, their development and
( 4 months) are myopic, with a mean error of use in other species is lagging behind. A study
−2.45 D, while adult cats are close to emmetro- in horses concluded that an IOL of 25–30 D
pia, with a mean error of −0.39 D, thus overcorrects the aphakic equine eye, even
98 Ophthalmic Physiology and Vision

Table 2.15 Refractive errors in selected animal species.a

Species Refractive value (D) References

Cat by habitat Belkin et al. (1977)


Street cat −0.8
Laboratory cats 1.4
Cat by age Konrade et al. (2012)
Kitten ( 4 months) −2.45
Adult (>1 year) −0.39
Cat by coat length Konrade et al. (2012)
DSH −1.02
DLH −0.13
Dog – mean value −0.05 to −0.39 Murphy et al. (1992b); Gaiddon et al. (1996);
Kubai et al. (2008); Groth et al. (2012)
Dog by habitat Gaiddon et al. (1996)
Indoor dogs −0.64
Outdoor dogs 0.17
Dog by breed −1.87 to +0.98 For specific breeds, see Mutti et al. (1999),
Black et al. (2008), Kubai et al. (2008),
Williams et al. (2011), and Kubai et al. (2013)
Horse −0.17 to +0.33 Harman et al. (1999); Rull-­Cotrina et al.
(2013); Bracun et al. (2014)
Horizontal meridian −0.06 to +0.41 Grinninger et al. (2010); McMullen et al.
(2014)
Vertical meridian 0.25–0.34 McMullen et al. (2014)
Rabbit (New Zealand 1.7 Herse (2005)
White)
Chicken (Cornell-­K) 4.1, 3.7 (4 and 17 weeks old, Wahl et al. (2015)
respectively)
Guinea pig (pigmented) 0.7 Howlett & McFadden (2007)
Rat (Norway brown) 4.7, 14.2 (infant and adult, Guggenheim et al. (2004)
respectively)
Mouse (CBL75/6) −1.5, 4.0 (10 and 102 days old, Zhou et al. (2008)
respectively)
a
See reference list for additional refractive studies in wildlife and aquatic species.
DSH, domestic shorthair; DLH, domestic longhair.

though preliminary calculations showed a the- difference between the canine and feline IOL
oretical power of up to 30 D. Subsequent stud- values stems from differences in the anterior
ies, supported by a calculated IOL power of chamber depth of the dog and cat.
15.4 D, have shown that a 14 D IOL brought
5/6 horse eyes to within 0.4 D of emmetropia. Astigmatism
Studies in the cat indicate that IOLs for this Astigmatism is a state of unequal refraction
species should have a power of 52–53 D. The of light along the different meridians of the
­Visual Optic  99

eye. Normally, a given refractive structure of Spherical and Chromatic Aberrations


the eye (e.g., the cornea or lens) has a con-
Spherical Aberrations
stant curvature radius in all its meridians
The eye is not a perfect optical system. Two of
(though the cornea may flatten toward the
the most significant optical problems that
limbus). Astigmatism occurs when the hori-
affect the eye are spherical and chromatic
zontal and vertical meridians of the cornea
aberrations. Positive spherical aberrations
or lens have different curvature radii.
occur because in both the cornea and the lens,
Because of these differing curvatures, light
rays passing through the periphery are
entering the eye through the vertical merid-
refracted more than rays passing through the
ian may be refracted more (i.e., direct, or
center. Therefore, rays passing through the
with-­the-­rule, astigmatism) or less (i.e., indi-
periphery are focused closer to the cornea (or
rect, or against-­the-­rule, astigmatism) than
lens) than rays passing through its center.
light entering through the horizontal merid-
Obviously, as the image is not uniformly
ian. Astigmatism is diagnosed by refracting
focused on the retina, the aberration causes
the eye in both the horizontal and vertical
blurred vision. A comparative study found sig-
meridians. A difference of 0.5 D or more in
nificant degrees of spherical aberrations in the
the refractive power of the horizontal and
lenses of dogs, cats, and rats, but minimal len-
vertical meridians in the same eye is defined
ticular aberrations in cows, sheep, and pigs.
as astigmatism.

Static Accommodation Emmetropia and Accommodation Underwater


Several avian and reptilian species possess In aquatic species, the cornea is in contact with
lower-­f ield myopia. The eyes of these animals water rather than air. Because of the very small
are emmetropic along the horizontal and in (∼0.003) difference between the refractive
the upper visual field, but they become pro- indices of the cornea and water, the cornea of
gressively myopic below the horizontal. In these species has virtually no refractive power.
other words, different parts of the eye have a In fact, because the anterior corneal surface
different refractive power because the shape has lower curvature than the posterior surface,
of the eye is more like a flattened circle, so under water the cornea acts as a weak diver-
that the posterior focal length differs for dif- gent lens. Fish are forced to compensate for the
ferent meridians. This adaptation can be absence of corneal refraction by increasing the
regarded as a static accommodation mecha- refractive power of other ocular structures,
nism. Hence, the animal shifts its gaze to see usually the lens. For this reason, as noted ear-
the object with the appropriate refractive lier, the lenses of fish eyes are very spherical.
power, and can match the average viewing Their increased curvature results in signifi-
distances of different areas of the visual cantly larger refractive power.
field. This allows the animal to keep the The problem of refraction under water is fur-
ground in focus with relaxed accommoda- ther complicated in species that move in and out
tion while foraging for food and, at the same of water because it is physically impossible for
time, monitor the sky for predators while an eye to be emmetropic both in air and under
focused at infinity. The same principle is also water. Eyes that are emmetropic in the air will be
found in eyes of pinnipeds, where regional hypermetropic under water because the refrac-
changes in the refractive powers of different tive power of the cornea is lost due to its submer-
parts of the cornea allow these animals to sion in water. Therefore, species that live and
maintain high-­resolution vision in both function in both habitats must “choose” whether
water and air. they will be emmetropic in the air or under water.
100 Ophthalmic Physiology and Vision

­ isual Processing: Photoreceptors


V of the retina, connecting, directly or indirectly,
to Cortex the first-­order (photoreceptors) and third-­order
neurons (RGCs).
Retina
Other INL Cells
The optical part of the visual process ends The INL is populated by three more types of
with photons striking the outer segments of cells, in addition to some displaced RGCs.
the photoreceptors. The neuronal part of the Little is known about the interplexiform cells,
visual process begins with the capture of which are neurons with processes in both the
these photons and absorption of their energy outer plexiform layer (OPL) and IPL. In the
by the photopigments in the outer segments OPL, they are presynaptic to bipolar cells. In
of the cones and rods, where a chain of bio- the IPL, they are pre-­ and postsynaptic to
chemical reactions starts. In addition to amacrine cells, and presynaptic to bipolar
these sensory neurons, the retina also con- cells. Thus, it is believed that they may modu-
tains secondary and higher order neurons late the synaptic gain between photoreceptors
and an intricate neural circuitry that per- and their second-­order neurons. Müller cells
forms the initial stages of image processing are another class of cells found in the INL, and
before trains of electrical impulses are trans- are the main glial cells of the retina. Müller
ferred through the axons of the retinal gan- cells are ependymoglial cells, meaning they
glion cells (RGCs) to areas in the brain have both a structural support and a meta-
where secondary processing and eventually bolic role.
visual perception occur. A schematic repre-
sentation of the retina is shown in Ganglion Cells
Figure 2.13. All information processed by the retina even-
tually converges on the RGCs, the innermost
Photoreceptors cell layer in the retina, and its third-­order, final
The outermost cells in the neural retina are the output neuron. Though much signal process-
photoreceptors, which are divided into two ing has already occurred in the vertical (photo-
classes: rods and cones. Rods and cones differ receptor to bipolar to RGC) and in the lateral
from each other in their morphology, function, (photoreceptor to horizontal cell to bipolar to
and retinal distribution. Functionally, cone amacrine to RGC) pathways, the RGCs are the
systems are characterized by high resolution of most complex information processing cells in
fine details, rapid responses, color perception, the retina.
and low sensitivity to small fluctuations in
light intensity. Rod systems are characterized Optic Nerve
by poor visual resolution and no color percep- RGC axons constitute the optic nerve fibers.
tion, but they are extremely sensitive to minute These axons converge at the optic disc, where
changes in light levels and detection of motion. they are joined in bundles to form the nerve.
Therefore, cones are particularly suitable for As the nerve contains RGC axons but no other
daylight photopic vision, whereas rods contrib- neuronal cell body, it can be considered a pure
ute mostly to dim-­light scotopic vision white matter tract. However, the nerve does
(Figure 2.14). contain several important glial cell popula-
tions. These include oligodendrocytes, which
Horizontal and Bipolar Cells contribute to its myelin sheath and formation
The somas of both the horizontal and bipolar of nodes of Ranvier, and astrocytes, which
cells are located in the inner nuclear layer have several functions including K+ homeo-
(INL). Both cells serve as second-­order neurons stasis and transportation and storage of
­Visual Processing: Photoreceptors to Corte  101

Ch
PE

OS

OLM
R
C
ONL

H
OPL

As
M
B
Mi
INL

IPL
GCL
As
G
Mi BV
NFL
ILM

Figure 2.13 Schematic drawing of the mammalian retina with part of the choroid (Ch) on top. Below the
retinal pigment epithelium (PE) are the layers of the neuroretina: the outer segments of the photoreceptors
(OS), the outer limiting membrane (OLM), the outer nuclear layer with nuclei of cones (C) and rods (R), the
neuropil of the OPL, the INL with nuclei of horizontal (H), bipolar (B), and amacrine (A) cells, the inner
plexiform layer with synapses in strata, the ganglion cell layer (G), their axons in the nerve fiber layer, and
finally the inner limiting membrane (ILM) facing the vitreous. The glial elements of the retina, Müller cells
(M) and microglia (Mi), as well as astrocytes (As) embracing retinal blood vessels, are shown.

metabolites (mainly glycogen) used by the Optic Chiasm and Optic Tract
axons. RGCs (and some subtypes of amacrine As the optic nerve approaches the optic chi-
cells) are the only retinal neurons that gener- asm, the location of fibers within the nerve
ate action potentials. Unlike the graded hyper- gradually shifts in preparation for decussation
polarizing or depolarizing responses of other at the optic chiasm. Generally, fibers from the
retinal neurons, action potentials are all-­or-­ temporal retina remain in the ipsilateral hemi-
nothing spikes of electrical activity. This sphere, and fibers from the nasal retina cross
means that all of the neuronal processing of over to the contralateral side. The amount of
the visual signal that has taken place in the decussation varies between species, perhaps
retina so far, including information about representing a broad evolutionary scale. Birds,
stimulus size, contrast, color, movement, and as well as many amphibian and reptilian spe-
location, is coded as alterations in the firing cies, have complete crossover of fibers to the
pattern (e.g., short bursts or sustained epi- contralateral side. A greater proportion of fib-
sodes of firing) and firing rates of the RGCs. ers remain on the ipsilateral side in mammals
102 Ophthalmic Physiology and Vision

Spherule Pedicle

Outer plexi-
Inner form layer
fiber

Müller
cell
Nucleus
Outer nuclear
layer
Outer
fiber External
limiting
membrane
Myoid Inner
segment

Ellipsoid
Cilium
Cilium Photo-
receptor
layer
Outer segment

(a)
Rod bipolars Midget bipolar Flat bipolar

Horizontal
cell

Rod spherules Cone pedicles


(b)

Figure 2.14 (a) The discs of the outer segments (facing the retinal pigment epithelium) of the
photoreceptors contain the photopigment required for vision. The photoreceptors’ inner segments contain
the mitochondria, and together with the outer segments constitute the photoreceptor layer. The rod
spherule and cone pedicle are synaptic expansions where their axons synapse with dendrites of bipolar and
horizontal cells in the OPL. Portions of Müller’s cells (dotted lines) are shown adjoining the rods and cones.
(b) Rod and cone bipolar cells show extensive contacts. Horizontal cells also make synapses with both rods
and cones. Interconnections are shown between spherules and pedicles.
­Scotopic and Photopic Visio  103

that have developed binocular vision. In the cortex, extending from the crown of the lateral
horse, 15% of the fibers stay on the ipsilateral gyrus on the dorsal surface to the superior bank
side, as do 25% in the dog and 33% in the cat. In of the splenial sulcus on the medial surface. In
humans, only half of the fibers cross over. the dog, it is located at the junction of the mar-
The optic tract runs from the optic chiasm to ginal and endomarginal gyri. The striate cortex
the lateral geniculate nucleus (LGN). Because of has also been identified in the horse.
decussation at the chiasm, fibers of the optic tract
conduct information from the opposite visual
field of both eyes. In humans, where roughly 50% Section III: Vision
of the axons decussate in the chiasm, the left
optic tract relays the right visual hemifield of Ability to detect light is, of course, fundamen-
both eyes, and the right optic tract relays both left tal for vision, but other aspects, such as detec-
visual hemifields. In animals, where a greater tion of motion and determining other qualities
percentage of fibers cross over, the left optic tract of an object, such as shape and details, color,
will relay a greater proportion of the right visual size, and distance, help to form our visual per-
field from the right eye and a smaller proportion cept. The processing of the output from the
of the right visual field from the left eye. photoreceptors starts in the retina (Figure 2.15),
but countless neurons in the brain finally
Lateral Geniculate Nucleus shape and interpret the image of the world
For most RGC axons, the first synapse occurs around us. Animal visual perception is a sub-
in the LGN, which is one of about 10 targets of ject of great fascination to researchers, clini-
RGCs in the thalamus. The axons maintain cians and animal owners. Unfortunately, we
their retinotopic arrangement through the can neither tell exactly what an animal sees
optic nerves, chiasm, and tracts and as they because they usually cannot tell, nor do we
enter the LGN. Here, the RGC axons synapse know precisely what there is to see because of
with dendrites of LGN interneurons (which the limitations of our own visual system.
provide for signal processing) and projecting
cells in synaptic glomeruli. In the LGN, RGC
axons segregate by eye and functional group, ­Scotopic and Photopic Vision
usually forming layers where they terminate in
discrete clusters, generating a retinotopic map Photoreceptors can respond to changes in lev-
of the contralateral visual hemifield (with els of background luminance by processes of
receptive fields similar in size and response adaptation and this results in an extended oper-
properties to the retinal receptive fields). ating range, allowing the eye optimal perfor-
mance at a given illumination level. A decrease
in background illumination to below 0.03 cd/
Primary Visual Cortex
m2 will deactivate the cone system, resulting in
Brodmann demonstrated that the primary visual increased light sensitivity (i.e., lower threshold)
cortex (i.e., area 17) receiving the input from the and scotopic rod vision. An increase in back-
LGN is located in the posterior part of the occipital ground illumination, to 0.03–3 cd/m2, will lead
lobe in a number of species. This area is now usu- to mesopic vision in which both the rod and
ally called V1 (visual area 1) or the striate cortex, cone systems are active, for example, before
after the striae of Gennari. In contrast, all other dawn or after sunset. Further increase in back-
visual areas in the cortex lacking the stria (which ground illumination above 3 cd/m2, to photopic
is a myelinated stripe where the LGN axons enter levels, will result in rod saturation. In such an
the gray matter of the V1) are termed extrastriate. environment, cones will continue to function,
V1 has been mapped in several species. In the albeit with a higher threshold, or with lower
cat, it occupies the posteromedial portion of the sensitivity.
(a) P P P P

Voltage
B
Time

(b)
B B B B B
Voltage

Time

Periphery Center
(c) Global
Firing rate

B B B B B B

Local

Time
Global A
G
motion
Local motion

(d)Approaching motion Lateral motion on off on off on off


B B B B B B

A A A

(e) Image ∆t ∆t ∆t
appearance on off on off on off
B B B B B B

G
Time

(f) on off
B B

A1

A2

Figure 2.15 A considerable amount of processing of data from the photoreceptors is performed already in the
neuroretina. Left-­hand panels briefly describe the purpose of the computations performed, and the right-­hand
column illustrates important elements of the underlying circuits schematically (triangle – neuron; A – amacrine
cell; B – bipolar cell; G – RGC; P – photoreceptor; rectangle – temporal filter function; oval – instantaneous rectifier;
closed/open circle – sign-­preserving/sign-­inverting synapse. (a) The rod-­to-­rod pathway detects single photons.
The output of each rod (noisy tracings) is sent through a bandpass temporal filter followed by a thresholding
operation. Signals from several rods are then pooled to and summed by one rod bipolar cell, which shows distinct
activations (tracings without noise). (b) The Y-­RGC is activated by texture motion in either direction over its
receptive field (red circle). Each movement elicits either transient ON or OFF responses in the bipolar cells, but only
the depolarized bipolar cells signal to the ganglion cell that fires transiently to each shift in the grating. (c) An RGC
sensitive to local motion fires when the object in its central receptive field moves in different direction that from
the background, thus detecting differential motion. This RGC is silent when the object in the center moves in the
same direction as the background because the excitatory input in the center is counteracted by inhibitory input
from the surround via the amacrine cell. (d) A RGC responds strongly (several spikes) to an approaching dark object,
but only weakly to lateral motion. More OFF bipolar cells are excited when a larger part of the receptive field is
dark. When the object only moves laterally, the RGC receives both excitatory signals from the OFF bipolar cells and
inhibitory signals from amacrine cells activated by ON bipolar cells. (e) Specific RGCs use differences in spike
latencies to rapidly encode the structure of an image. RGCs with receptive fields (circles) in the dark part of the
image have short latencies, and those in the light part have long latencies. RGCs with receptive fields containing
both dark and light areas fire in between, thus indicating the position of the border. Here, signals from both ON and
OFF bipolar cells are individually rectified, and the timing difference follows from a delay (Δt) in the ON pathway.
(f) Wide-­field amacrine cells (A1) are activated during rapid shifts of the image in the retinal periphery, which
suppresses the OFF bipolar cell signal and disinhibits the ON bipolar cell through a local amacrine cell (A2). Hence,
this circuit acts like a switch, in this case enabling a signal in the more central part of the retina.
­Scotopic and Photopic Visio  105

Scotopic Vision Globe Size


The dimensions of the ocular tissues also con-
Rods and Rod Pathways
tribute to improved scotopic sensitivity in
Cones are inactive in scotopic conditions, and
many species. For example, the mean diameter
in such an environment our fovea becomes a
of the cornea in cats and humans is 16.5 and
relative blind spot. Instead, scotopic vision is
11.7 mm, respectively. Consequently, much
possible because of the molecular and anatom-
more light enters the cat’s eye. Next, light must
ical characteristics of both rods and the rod
pass through the pupil. The diameter of a
pathway. The unique features make an indi-
mydriatic pupil in cats and humans is about 12
vidual rod more sensitive than an individual
and 8 mm, respectively, translating into a
cone. Another important feature that enables
pupillary aperture of 113 and 50 mm2, respec-
sensitive scotopic vision is the converging
tively. As a result, far more light passes through
nature of the rod pathways. In cats, it has been
the cornea and pupil to reach the feline retina
estimated that in the peripheral retina, the out-
at night, when the pupil is fully dilated. Indeed,
put of approximately 75 000 rod photorecep-
it has been calculated that a fully dilated pupil
tors converges on about 5000 rod bipolar cells,
increases the amount of light reaching the ret-
which output to 250 amacrine cells, that con-
ina by 135-­fold in the cat, compared to an 80-­
verge on one ganglion cell.
fold increase in humans.
In many animal species, increased number
and density of rods enhance scotopic vision. It
Dark Adaptation
can be appreciated that dogs have a higher max-
Dark adaptation is a process in which sensitiv-
imal rod concentration than cats, even though
ity of photoreceptors increases, and their
most people associate the latter with greater
threshold decreases. It takes place in darkness
scotopic sensitivity. This discrepancy may be
following prolonged exposure to bright light,
explained by the structure of the tapetum,
which causes bleaching of a substantial por-
which is less reflective in dogs than in cats.
tion of the photopigment and includes several
processes. One mechanism of dark adaptation
Tapetum is biochemical and revolves around the re-­
One of the most fascinating adaptations for synthesis of rhodopsin from free opsin and
enhanced scotopic vision is the evolution of a from recycled (or newly available) 11-­cis-­retinal
reflective tapetum in the choroid. Light pho- (Figure 2.16).
tons striking this layer bounce back onto the
retina, thus giving them a second chance to be
Photopic Vision
absorbed by the photoreceptors. This second
opportunity is not significant in daytime, as Light Adaptation
cones absorb enough photons during their Light adaptation is a process in which cone
“first pass” through the retina. In fact, the (and rod) sensitivity decreases, and threshold
tapetum has a detrimental effect on visual increases, in response to increased background
acuity in broad daylight, as the light is reflected light intensity and the resulting increased pho-
onto a photoreceptor different from the one in topigment bleaching. This is a much faster pro-
the original trajectory. However, at night this cess than dark adaptation. Our eyes begin light
detrimental effect on visual resolution is adaptation within seconds to a sudden increase
insignificant as cones are inactive. Instead, the in background light intensity, such as that
retina benefits from the increased probability experienced when exiting a dark room. Indeed,
that rods will absorb the few photons entering it is suggested that the reason for the initial
the eye in a dim environment, thus enhancing photophobia exhibited when exiting a dark
scotopic vision. room is an attempt by the eye to preserve the
106 Ophthalmic Physiology and Vision

dark-­adapted state of the retina. Several mech- (and often the inferior pupil also) border of
anisms account for light adaptation. One is the the iris in some species provides additional
increased activity of phosphodiesterase, result- protection as it decreases the amount of light
ing in shorter turnover time for cGMP and entering the eye from the superior visual
accelerating the response kinetics of cones. field (where the Sun is located), further
reducing glare and improving vision in bright
Pupil light. Moreover, because a miotic slit pupil
As with scotopic vision, the pupil also con- can block light more efficiently than a miotic
tributes to photopic vision because miosis circular one, it is suggested that slit pupils
protects the retina from excessive and harm- have evolved in nocturnal or crepuscular spe-
ful amounts of light. It is proposed that the cies such as cats and geckos that need to
large corpora nigra found on the superior function in daytime.

190.0

180.0

170.0

160.0

150.0

140.0

130.0

120.0

110.0

100.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0.0

–10.0 100.0
50.0 150.0

Figure 2.16 In a comprehensive canine ERG protocol, following preparation of the animal in ambient light,
the light is turned off. During the next 20 min, the retina is stimulated with a dim flash every 4 min, thus
generating a dark adaptation curve. In a normal animal, signal amplitude will increase from one flash to the
next as the retina dark adapts (black, red, green, pink, and yellow traces represent the respective responses
recorded after 4, 8, 12, 16, and 20 min in the dark). Failure of the signal to increase with time in the dark
may be an early sign of rod dysfunction.
­Visual Fields, Binocular Vision, and Depth Perceptio  107

­Flicker Detection for a large visual field, virtually 360° in some


species, and for stereopsis, or depth perception.
Temporal responsiveness of the retina has two However, no more than two eyes are required
aspects: motion detection and flicker detection. to achieve these aims.
The retina responds to flashes of light as long as
there is sufficient interval between two consecu-
Visual Fields
tive flashes, allowing the retina to recover from
one response before the next flash is presented. The extent of the visual field depends largely
However, as the frequency of these flashes on placement of the orbits within the skull
increases, a point is reached at which the retina (Figure 2.17). Many mammalian prey, avian,
does not have enough time to recover between and fish species have lateral eyes, providing
flashes and therefore it can no longer distinguish almost 360° field of view. These animals have a
the individual flashes. At this point, which is small, frontal binocular field; two large periph-
termed the critical flicker frequency (CFF) or eral monocular fields; and a small blind spot
flicker fusion frequency, the eye perceives a behind their head.
steady light even though this light is made up of On the other hand, most primate and preda-
numerous flickers. There are separate CFFs for tor species have frontal eyes. In these species,
rod-­driven responses and signals generated from most of the frontal visual field is covered by a
the different cone types, just as there are sepa- binocular vision; there are two small, periph-
rate adaptation mechanisms for the rod and eral monocular fields and a large blind spot
cone systems. behind the skull. Therefore, enucleation will
cause a cat, for example, to lose approximately
30° of one visual field, while in a horse the
­Motion Perception same procedure will cause a loss of about 145°.
Large (monocular) visual fields are typically
Moving through the environment produces a associated with prey species that need to detect
flow of images projected onto the photorecep- predators. This is why these species usually
tors, resulting in huge amounts of visual infor- have a pupil and a visual streak whose shapes
mation necessary for navigating through a are aligned with the horizon, allowing them to
complex environment. Perception of motion is identify predators and conspecifics.
required for both directing visual attention to a
certain location in the visual field and segment-
ing moving objects from their background. Stereopsis
Psychophysically, there are various ways of dis- Many associate stereopsis with predatory
cerning motion: (i) movement can be perceived behavior, as depth vision is required to pounce
if an object is moving across our visual field while on prey with precision. However, stereopsis is
our eyes and head are stationary; and (ii) motion just as important for the prey that uses it to
can also be perceived when either the head or the distinguish between a camouflaged predator
eyes are moved to pursue a moving object. and its surroundings. Though monocular ste-
reopsis is possible thanks to various visual
cues including grain, texture, brightness, con-
­ isual Fields, Binocular Vision,
V tour, size, and relative motion, in most cases
and Depth Perception stereopsis is the result of binocular vision, and
the extent to which the visual fields of the two
It is rather extraordinary to note that all verte- eyes overlap. In addition, optimal stereopsis
brate species, and many invertebrates, have requires normal visual function and refrac-
two eyes. Having more than one eye is required tion, oculomotor control to maintain fixation,
108 Ophthalmic Physiology and Vision

CULAR VISIO
BINO N
65°

UNIOCU AR VISION

UNI
OCULA
146°

146°
L

R VISION

B LI N D A R E A

(a)

CULAR VISIO CULAR VISIO


BINO N BINO N
140° 60°
UNIOCU AR VISION

UNI

UNI
UNIOCU AR VISION
OCULA

OCULA
90°

90°
30°

30°
L

L
R VISION

R VISION
160° 120°
B LIN D A R E A B LI N D A R E A

(b) (c)

Figure 2.17 (a) The visual field of the horse showing a frontal binocular field (65°) comparable to that of
a dog but with much larger panoramic monocular fields (each spanning 146°) and a very small posterior
blind area (3°). (b) Visual field of a cat showing a large frontal binocular field (140°) with relatively small
monocular fields (each 30°) and a relatively large posterior blind area (160°). (c) Monocular and binocular
visual fields in a typical mesocephalic dog. The dog has a modest frontal binocular visual field (60°) with
relatively large monocular visual fields (each 90°) and a posterior blind area of approximately 120°.

and sensory and neuronal mechanisms to eye, resulting in disparate images. The visual
extract and process important visual cues. angle can serve as a “range finder.” An object
is deemed close if the projection lines from
Geometry and Retinal Disparity both eyes intersect before the plane of fixa-
If an object is located in the plane of fixation tion, thus triggering a converging oculomo-
of both eyes, it is viewed with the same angle tor response; for a distant object, the
by both eyes (Figure 2.18). However, objects projection lines intersect beyond the plane
outside the binocular plane of fixation are of fixation, serving as an oculomotor stimu-
viewed with a slightly different angle by each lus for divergence.
­Color Visio  109

binocular input and act as disparity detectors.


The disparity-­sensitive neurons of the occip-
ital cortex act as “low-­level” detectors of spa-
tial disparity and process stereopsis;
additional neurons in the parietal lobe, infer-
otemporal cortex, and other cortical areas
α2
process “high-­level” cues such as texture,
shading, and motion to construct a three-­
dimensional image of the visual field.

Stereoacuity
α1
Stereoacuity is the measurement of the small-
est detectable stereoscopic depth. Just like vis-
ual acuity, it is measured in arc minutes or arc
seconds (see the following section on visual
acuity). It is largely determined by the distance
of the object, as obviously smaller disparities
can be detected for nearby objects than for dis-
tant objects. For example, at a distance of
fv fv 25 cm some humans can detect a depth of
25 μm! Of course, such fine discrimination is
Figure 2.18 Binocular disparity and the
perception of stereoscopic depth. The green not possible for objects 100 m away. However,
diamond is on the plane of fixation of both eyes. It stereoacuity is also determined by other stimu-
is therefore seen at the same angle by both eyes lus parameters such as color, contrast, orienta-
and projected onto both foveas (fv). Both the
tion, size, duration of exposure, location
purple circle and red square are outside the plane
of fixation. Therefore, they are viewed at different (central or peripheral), and luminance.
angles by both eyes, and projected onto disparate
(but corresponding) retinal regions. The purple
circle is closer than the object of fixation (the
green diamond) and therefore the projection lines
­Color Vision
from both eyes intersect before the plane of
fixation. The red square is further away, and the Prerequisites for color vision are that the retina
projection lines from both eyes intersect after the has both photoreceptors with different spectral
plane of fixation. The α angles of these projection
sensitivities that are active under the same
lines, and their intersection, serve as range finders
in stereoscopic depth detection. background light conditions and circuits where
signals from the different photoreceptors are
Processing Retinal Disparity compared. In most mammals, two or three
Retinal disparity is resolved in the visual cor- types of cones with different opsins provide the
tex that has the unenviable task of recon- first step in color vision in daylight, but some
structing a three-­dimensional image from amphibians have more than one type of rod
the projection of this image on two two-­ and are therefore likely to distinguish between
dimensional retinas. The segregation hues at night too. The central part of the absorp-
between the outputs of the two eyes is still tion curve of a photopigment is bell shaped and
maintained at the first cortical synapse, that the overlap of different photopigments’ absorp-
is, the simple cells populating layer 4 of the tion curves will allow perception of intermedi-
striate cortex. Binocular interaction begins ate hues. Photopigments are the most common
when these cells output to adjacent layers of opsin molecules of cones, such as L-­, M-­, and
the striate cortex and to extrastriate visual S-­opsins, most sensitive to either long
areas, where many of the neurons receive (∼560 nm, greenish-­yellow light, but by
110 Ophthalmic Physiology and Vision

convention called the L-­or red opsin), medium retina will not be able to distinguish this wave-
(∼530 nm, green light), and short (∼420 nm, length from an achromatic stimulus. This neu-
blue light) wavelengths, respectively. This tral point is reported at about 505 nm in the cat,
means that even though peak absorbance (or and 480 nm in the dog and horse. Despite hav-
maximum sensitivity) occurs at a primary ing fewer cones than humans and being dichro-
wavelength, the photoreceptor can also be mats, color vision cues seem to be important
hyperpolarized by a relatively broad range of during daylight conditions for dogs, and it is
wavelengths. likely that other mammalian species also take
Humans and Old World primates possess advantage of their ability to discriminate
three opsins, thus allowing them trichromatic between different wavelengths to enhance their
vision. The green photopigment is the most daily lives, and particularly their sexual and
abundant in the human retina, while the blue is feeding behavior.
the scarcest. Total color blindness, which is very Some dichromats, including many rodents,
rare, usually refers to rod monochromacy (or such as the mouse, rat, gerbil, and Siberian
achromatopsia) where the patient has no cones hamster, have a specialized short-­wavelength
at all and no color vision. Cone monochromats opsin that peaks in the UV range of the spec-
potentially have limited color vision under trum rather than in the blue. Hence, they have
lighting conditions where both the rods and extended the spectral range of the electromag-
their single type of cones are active. Most color netic radiation that they can perceive.
vision-­deficient human subjects have dichro- Furthermore, some dichromats that have “reg-
matic vision, either missing or having a mutated ular” S-­ and M/L-­cone pigments, such as the
form of the red (protanopia or protanomaly, reindeer and dog (and most likely the cat, too),
most frequent), green (deuteranopia or deuter- have lenses transmitting UV light, which ena-
anomaly), or blue opsin (tritanopia or tritanom- bles them to see in the UV part of the spectrum
aly, least frequent). Hence, they perceive colors using their regular cone pigments.
but, for example, a protanope will perceive red Many modern-­day reptilian, avian, and fish
and green objects to have very similar color, but species still have all four ancestral photopig-
will readily discriminate between isoluminant ments, including an additional short-­
blue and green (or red) objects. wavelength opsin with peak absorbance in the
Some species are monochromats. Rod mon- UV or violet range (355–450 nm) that humans
ochromacy is mainly found in some fish spe- and most domestic mammals have lost, and
cies, whereas marine mammal species and a have thus tetrachromatic vision.
few terrestrial mammalian species, including Birds have developed additional unique
the owl monkey, are cone monochromats. mechanisms for color vision. Their double
Most mammals, including cats, dogs, horses, cones are used for fine spatial discrimination
cattle, goats, sheep, and swine, are dichromats, (visual acuity), while single cones are used for
just like human protanopes or deuteranopes. color vision. Oil droplets found in the cones of
Horses, for example, have cone opsins with birds contribute to color perception by filtering
peak absorbance in the blue and green parts of out different wavelengths of incoming light
the spectrum, making their color vision compa- and shifting the wavelength sensitivity of the
rable to human protanopes. Dogs (and cats), on photoreceptor.
the other hand, have cone opsins most sensitive
to blue and greenish-­yellow, making their color
Visual Acuity
vision more similar to that of human deuteran-
opes (Figure 2.19). When light stimulates the Visual acuity is the minimal detection power
two opsins in a dichromat equally (a monochro- of the eye, or the minimal angle that can be
matic light of a wavelength that coincides with resolved by the eye. There are a number of
the intersection of the absorption curves), the ways to express visual acuity, but the best
­Color Visio  111

(a) (b)

(c) (d)

(e) (f)

Figure 2.19 A colorful dog, as seen by a normal trichromat (a). In (b), the color information from the
photograph has been extracted. The photograph has been filtered to mimic how a protanope (c), a
deuteranope (d), a tritanope (e), and a cone monochromat (f) would perceive the same scene. The protanope
and deuteranope can distinguish between short and long wavelengths, whereas the tritanope can
subdivide the middle-­to-­long wavelengths into different hues.

known method is based on the Snellen chart. discrimination tests, by electrophysiological


This is determined by the size of letters that recordings to determine the smallest pattern
a subject can read at a distance of 20 ft, or that elicits an ERG or cortical response, or
6 m. Obviously, determination of Snellen by pursuit (i.e., optokinetic) eye responses
acuity requires verbal cooperation by the to determine the smallest stimulus that elic-
test subject and therefore is not applicable its a tracking eye movement. Acuity is also
in veterinary medicine. In animals, visual often determined by theoretical calculations
acuity can be determined using behavioral based on cone or RGC density (Table 2.16).
Table 2.16 Visual acuity in select species.a

Spatial
frequency
(cycles/
Species Snellen resolutionb degree)b Methodc References

Eagle (Aquila audax) 20/4 140 Behavioral and anatomical Reymond (1985)
Falcon (Falco berigora) 20/8 73 Behavioral and anatomical Reymond (1987)
Macaque monkey 20/16 38 Behavioral Merigan & Katz (1990)
Human 20/20 30 Ravikumar et al. (2011)
Horse 20/26 23 Behavioral Timney & Keil (1992)
20/36 16.5 Anatomical Harman et al. (1999)
King penguin Anatomical Coimbra et al. (2012)
Underwater 20/30 20.4
In air 20/40 15.3
Alpaca 20/45 13.4 Anatomical Wang et al. (2015)
Sheep 20/51–20/43 11.7–14 Behavioral Sugnaseelan et al. (2013)
20/86–20/60 7–10 Anatomical Hughes (1977)
Camel 20/60 10 Anatomical Harman et al. (2001)
Dog 20/140–20/52 4.3–11.6 Electrophysiology Odom et al. (1983); Ofri et al. (1993);
Murphy et al. (1997)
20/110–20/31 5.5–19.5 Behavioral Lind et al. (2017)
Cat 20/190 3.2 Behavioral Jarvis & Wathes (2007)
20/90 6.5 Electrophysiology Berkley & Watkins (1971)
20/33 18 Anatomical Steinberg et al. (1973); Clark & Clark
(2013)
Barn owl Behavioral Orlowski et al. (2012)
20/190 3.2 (Mesopic)
20/500 1.2 (Scotopic)

0005300029.INDD 112 04-26-2022 18:10:13


Rabbit 20/200 3 Electrophysiology Pak (1984)
Cow 20/460–20/230 1.3–2.6 Behavioral Rehkämper et al. (1998, 2000)
Rat Behavioral Prusky et al. (2002)
pigmented 20/600–20/400 1–1.5
albino 20/1200 0.5
Mouse 20/1000 0.58 Behavioral Lehmann et al. (2012)
20/1500 0.39 Optokinetics Lehmann et al. (2012)
a
This table mostly contains data for species commonly seen by veterinary ophthalmologists in clinical and research settings. Avian species have been included to
demonstrate their high acuity (eagle, falcon) or the effects of aquatic vision (penguin) and light conditions (owl). The scientific literature reports visual acuity values for
numerous other species such as giraffes, elephants, rhinoceros and marsupials that are beyond the scope of this book.
b
Most articles report visual acuity in cycles/degree. These values have been converted to Snellen units by the author (R.O.) as most readers are more familiar with this latter
scale. Values for Snellen acuity <20/200 have been rounded.
c
Anatomical methods of assessment include counting the density or cones and/or RGCs; electrophysiological methods are based on recordings of the pattern
electroretinogram or pattern visual evoked potentials.

0005300029.INDD 113 04-26-2022 18:10:13


114

Ocular Pharmacology and Therapeutics


Revised from 6th edition of Veterinary Ophthalmology, Chapter 7: Sections 1, 2, 3, 4, and 5 – Clinical Pharmacology and Therapeutics,
by Alain Regnier, Alison Clode, Erin M. Scott, Amy Rankin, Ian P. Herring, and Caryn E. Plummer

Section I: Ocular Drug Delivery


major problem for all drug therapy, frequency
In veterinary ophthalmic pharmacology and of drug administrations is an important limit-
therapeutics, those drugs of importance as pri- ing factor, especially for long-­term drug ther-
mary front-­line drugs are presented for the apy and chronic eye diseases.
treatment of ophthalmic diseases. Often by Hence, dosage regimen and route of admin-
understanding the different disease processes, istration should also be adapted to clinical
as well as the strengths and weaknesses of the management of the patient in order to maxi-
selected drugs, critical windows for therapy mize owner compliance.
can be identified for the maximum effects of The bulk of ophthalmic drugs are adminis-
these drugs. Critical factors in ocular pharma- tered locally as drops or ointments. While this
cology are reducing the significant barriers for tends to limit systemic side effects, local
drug entry at the corneal surface, the blood– administration has its own set of restrictions
aqueous barrier (BAB) at the ciliary body epi- because the eye is a unique organ with several
thelium, and the blood–retinal barrier for the functional and structural protective mecha-
posterior segment. These barriers can also be nisms, such as blinking, permanent lacrima-
changed in certain diseases, so investigations tion, and lacrimal drainage, which are
of drug delivery and pharmacokinetics must necessary to preserve visual acuity, but favor
be conducted in both normal and diseased rapid removal of drugs topically applied to the
eyes. The fact that in the drug development ocular. For drugs periocularly or systemically
process animals are used to understand the administered, the sclera and the blood ocular
drug properties, and then drugs are tested in barriers, which are critical for maintaining
clinical trials in humans facilitates drug the delicate homoeostasis of the transparent
development and access in veterinary oph- media, act as major obstacles for the access of
thalmology. Also, as a drug is exposed to multi- xenobiotics to intraocular target tissues.
ple species, a greater appreciation of the drug’s Increasing knowledge of drug absorption and
effect and usefulness becomes evident. Future disposition combined with advances in drug
drug development will emphasize not only the delivery system technology has provided
drug’s effectiveness, but also its toxicity and newer approaches for optimal bioavailability,
their ability to target specific areas of a disease prolonged action, and improved safety of ocu-
process more effectively. As compliance is a larly delivered drugs.

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
­Barriers to Ocular Drug Deliver  115

­ arriers to Ocular
B Conjunctiva and Sclera
Drug Delivery Membrane Barriers
Penetration across the conjunctiva, and then
Compared with drug delivery to other organs sclera, contributes significantly to the intraoc-
of the body, ocular drug delivery is a major ular penetration of certain topically applied
challenge because the ocular barriers refer to drugs. The conjunctiva is more permeable
anatomical and physiological ocular structures (2–30 times higher) than the cornea through a
that have protective functions for maintaining significant paracellular route, which makes its
ocular homeostasis and represent natural permeability to molecules of varying physico-
defense mechanisms against the entry of xeno- chemical characteristics, such as beta-­blockers,
biotics into the eye. hydrophilic macromolecules, and [3H]
mannitol.
Corneal Barriers The sclera may represent a barrier to intraoc-
ular transfer of either topically applied drugs
For topically applied drugs, the corneal route that are absorbed via the conjunctiva/scleral
has been assumed to be the major route of entry route of entry or those that are injected perio-
into the eye. The cornea consists of three pri- cularly. Scleral permeability was found to be
mary layers, the epithelium, stroma, and approximately 10 times higher than that of the
endothelium, representing distinct barriers to cornea with a direct relationship between the
absorption organized as an aqueous phase ability of a drug to penetrate sclera and both
(stroma) sandwiched by two lipid layers (epi- the thickness and total surface area of this
thelium and endothelium). Drug passage tunic. Studies in rabbits suggest the molecular
through the corneal epithelium can occur both radius is a better predictor of scleral permeabil-
across the cells (transcellular route) and ity than is the molecular weight. The primary
between the cells (paracellular route). The para- route for solute transport through the sclera is
cellular route is blocked by one type of special- by passive diffusion through the interfibrillar
ized intercellular junction, the tight junction or aqueous media of the gel-­like proteoglycans.
zonula occludens characterized by multiple sites
of fusion between the plasma membrane of
adjoining cells, which completely surround and Blood–Ocular Barriers
seal the superficial epithelial cells of the cornea Following systemic administration, penetra-
to all but the smallest hydrophilic molecules. As tion of drugs into the eye is limited by the
a consequence, the transcellular route across endothelial cells of iridial and retinal vessels
the lipid cell membrane will contribute to the and epithelial cells of the ciliary body and reti-
epithelial transfer of lipophilic drugs, while very nal pigment epithelium (RPE). In these barri-
low molecular weight hydrophilic (polar) com- ers, the paracellular route is blocked because
pounds will diffuse through the intercellular the clefts between the endothelial or epithelial
space, which represents the aqueous pore path- cells are sealed by impermeable tight junction
ways of the corneal epithelium. complexes that prevent the entry of solutes
The corneal stroma with its 78% water con- into the ocular environment (i.e., aqueous
tent allows the free passage of compounds humor [AH] and vitreous body). In the ante-
possessing high aqueous solubility and acts rior segment of the eye, the permeabilities of
as a barrier to lipophilic molecules. The the ciliary body and iris vasculature and epi-
endothelium does not provide significant thelium are remarkably different (Figure 3.1).
resistance to lipophilic and hydrophilic oph- In the stroma of the ciliary processes, circulat-
thalmic drugs. ing macromolecules escape through the
116 Ocular Pharmacology and Therapeutics

the endothelial cells of the vessels represent


IRIS CROSS SECTION
the other anatomical location of the BAB
ABL Stroma PE because they lack fenestrae and are joined by
tight junctions, which prevents movement of
macromolecules from the lumen of the iridial
vessels into the iris stroma, and then into the
anterior chamber.
In the posterior segment, the two barriers to
penetration include the endothelial cells of the
retinal vessels (also referred to as the inner
blood–retinal barrier) and the cells of the RPE
(sometimes termed the outer blood–retinal bar-
Tight junctions rier). The retinal vessels are nonfenestrated and
Iridial vessel
endothelial cell
have tight junctions, creating an obstruction to
movement of substances from plasma into the
retina and vitreous. The outer blood–retinal
barrier is produced by the tight junctions
CILIARY PROCESS CROSS SECTION
between the RPE cells, so that substances leak-
PL NPL ing out from the extremely permeable capillar-
ies of the choriocapillaris encounter this barrier
of junctional complexes between RPE cells.

­Topical Administration

Topical administration is the most common


route of administration for ophthalmic drugs
because of its advantages, including simplicity
of application and convenience to reach both
extra-­and intraocular tissue targets (Figure 3.2).
Stroma

Tight
junctions
The pharmacokinetic profile of topically applied
ophthalmic drugs is influenced by precorneal
Ciliary vessel factors (i.e., lacrimation and drainage) and the
PL NPL
endothelial cell Fenestrae
Ciliary epithelium specific characteristics of the formulation itself
that can influence the amount of drug penetrat-
Figure 3.1 The BAB in the anterior segment ing the eye.
consists of the endothelial cells of the iris blood
vessels and the nonpigmented cell layer of the
ciliary epithelium and their tight junctions. ABL, Ophthalmic Solutions
anterior border layer; NPL, nonpigmented layer of and Suspensions
the ciliary epithelium; PE, posterior epithelium;
and PL, pigmented layer of the ciliary epithelium. Eye drops represent the pharmaceutical for-
mulations most widely used in veterinary oph-
capillary walls but their transfer to the poste- thalmology and consist of solutions and
rior chamber is blocked by the tight junctions suspensions. Ophthalmic solutions are formu-
that interconnect the apices of the nonpig- lations in which the drug is totally dissolved in a
mented ciliary epithelium. However, in the iris given solvent. Typically, they are low-­viscosity,
­Topical Administratio  117

Anterior
Corneal Aqueous
segment
absorption humor
disposition

Lacrimal fluid
Topical
drug Conjunctival Iris–Ciliary
Sclera
administration absorption body Posterior
segment
disposition
Nasolacrimal General
drainage circulation

Drug loss

Figure 3.2 Disposition of ophthalmic drugs after instillation to the eye. Only a small portion of topically
applied drug may reach the posterior segment.

aqueous solutions mixable with the aqueous size, and micronized to prevent irritation of
tear film. Thus, the drug must be, at least to the ocular surface.
some degree, water soluble. To minimize irrita- All multidose eye preparations must include
tion of the eye, ophthalmic solutions must ide- a bacteriostatic preservative (i.e., benzalkonium
ally have an osmolality (tonicity) of about chloride, benzethonium chloride, methylpara-
300 mOsm/kg, which is the tonicity of normal ben, propylparaben, mercurial compounds, and
tears. However, various studies have shown that thimerosal) to prevent or inhibit microbial
the eye can tolerate solutions with an osmolality growth during clinical use. Of primary concern
in the range of 200–600 mOsm/kg, or 0.2–2.0% with their frequent or prolonged use in humans
in NaCl equivalents. To improve stability and is their potential toxicity to the ocular surface
sterility, ophthalmic solutions are formulated epithelium, disruption of tear film stability, and
with appropriate vehicles that may contain buff- hypersensitivity reactions. As benzalkonium
ers, organic or inorganic carriers, emulsifiers, chloride is used in most antiglaucoma agents, it
and wetting agents. Most agents are well toler- is presently assumed that the similar inflamma-
ated, cause little discomfort, and do not affect tory ocular surface changes induced during
vision. When frequent applications of ophthal- long-­term treatment in humans directly influ-
mic solutions are required in animals, especially ence the outcome of filtering surgery by increas-
horses (i.e., in the treatment of severe corneal ing the risk of bleb encapsulation.
infections), a continuous or intermit irrigation Unpreserved eye drops are supplied in unit
system, such as a subpalpebral lavage system or dose containers or multidose bottles, but the
a nasolacrimal cannula, is necessary to provide range is still limited, so they cannot be used in
frequent instillations with minimum handling. all cases.
Pharmaceutical derivatives of low aqueous
solubility, such as acetates and alcohols used as
Drug Disposition After Eye
topical corticoids, require formulations as oph-
Drop Application
thalmic suspensions. A suspension consists of
particles of active ingredient in a saturated As indicated in Figure 3.3, an ophthalmic drug
aqueous vehicle that includes dispersing and topically applied to the eye is distributed in
suspending agents designed to be instilled into three ways. It is drained by the nasolacrimal
the eye. The drug particles contained in sus- apparatus, may penetrate into the eye through
pension must be less than 10 μm, uniform in the corneal and/or noncorneal routes, and is
118 Ocular Pharmacology and Therapeutics

Sites of systemic absorption after topical instillation

Lacrimal drainage Conjunctiva Inner eye after


system • Relative leakiness of corneal absorption
the epithelium
• Venous blood flow of
• Rich blood flow the anterior uvea
Lacrimal • Fenestrated capillary wall • Aqueous humor outflow
Nasopharynx
ducts • Large surface area
• Same
• Vascularized
permeability
lining
as conjunctiva
• Surrounding
cavernous • Large surface
body area
(man, rabbit)

Transfer to the general circulation

Clinical relevance of the systemic absorption


• Systemic adverse effects of topical ophthalmic agents
• Systemic delivery of drugs through ocular route

Figure 3.3 Topically applied medications can enter the systemic circulation though the conjunctival
absorption, drainage via the nasolacrimal system, and absorption through the nasopharyngeal mucosa. After
transcorneal penetration, minor routes of systemic drug transfer involve AH outflow and diffusion into the iris.

absorbed into the systemic circulation via the tear flow dynamics. Within the cul-­de-­sac, the
conjunctiva and nasopharynx. drainage rate of an instilled volume has been
shown to be proportional to the volume of the
Nasolacrimal Drainage drop that is above the normal lacrimal fluid vol-
and Tear Washout ume. The larger the volume instilled, the more
When eye drops are administered to the ocular rapidly it is drained through the nasolacri-
surface, they first mix with the tear film com- mal system.
partment, the volume of which is about 7–10 μl As an instilled drop is removed in about
(with 1 μl covering the cornea and about 3–4 μl 10 min, dosage guidelines therefore recom-
residing in each conjunctival sac), as estimated mend that at least 10 min elapse between the
in humans and rabbits. The drop volume deliv- instillation of drops of different medications.
ered by many ophthalmic dropper bottles is
about 40 μl on average. Since the palpebral fis- Penetration Across the Cornea
sure is capable of holding only 25–30 μl of After topical ocular application, drugs may be
fluid, the volume of most ophthalmic drops absorbed into the inner eye through the cor-
largely exceeds the volume of the cul-­de-­sac, neal or conjunctival–scleral route. The rate
so complete retention of this drop volume is and extent of absorption through one route or
unlikely to occur. The tear volume and tear the other are dependent both on transport
flow rate in horses have been reported to be characteristics of the cornea, conjunctiva, and
230 μl and 33 μl/min, respectively. sclera and on the physicochemical properties
of the drug itself.
Factors Influencing the Drainage Rate Transfer through the epithelium is the rate-­
The rate at which the instilled drug is elimi- limiting step for absorption for hydrophilic com-
nated from the ocular surface due to drainage pounds, whereas transfer through the stroma is
by the nasolacrimal system is influenced by rate limiting for lipophilic compounds. Thus, in
three main factors: the size of the drop deliv- order for an ophthalmic drug to penetrate the
ered to the eye, the blinking frequency, and the cornea, it must exhibit intermediate solubility
­Topical Administratio  119

characteristics, being soluble to some degree in Penetration via the Conjunctiva/


both oil and water to penetrate the epithelium Scleral Route
and stroma. For moderately lipophilic drugs In the two last decades, studies have shown
such as timolol and dexamethasone, the corneal that the conjunctival–scleral absorption of
epithelium contributes 50% to the total resist- ocularly applied drugs contributes to the ocu-
ance to transport, while the stroma and endothe- lar absorption known as noncorneal absorp-
lium each contribute 25%. For hydrophilic drugs tion. The noncorneal absorption route through
such as epinephrine and pilocarpine, the cor- conjunctiva and sclera is important mostly for
neal epithelium contributes more to the total very hydrophilic and large molecules that are
resistance. A very lipophilic drug, such as cyclo- not able to penetrate through the corneal bar-
sporine (CSA), will penetrate the epithelium rier (examples include topical carbonic anhy-
readily, but the stroma will be rate determining. drase inhibitors [CAIs]).
Conversely, very hydrophilic drugs such as gen- Once the drug penetrates the conjunctiva,
tamicin, tobramycin, prednisolone sodium there are two different possibilities for it to reach
phosphate, dexamethasone sodium phosphate, the intraocular target tissues. Drug entry directly
cromolyn, and idoxuridine will penetrate the into the anterior chamber can result from lateral
epithelium slowly or not at all because the para- diffusion into the sclera and then the cornea, or
cellular pathway predominates. it enters the scleral blood vessels that supply the
uvea, particularly the anterior ciliary arteries,
Factors Influencing Corneal Absorption and deposits within the ciliary body.
In the case of ionizable drugs, the pH of the
ophthalmic preparation and that of the tear Systemic Absorption
fluid affect ocular drug penetration by influ- Mechanisms and Consequences
encing the ratio of the ionized (dissociated) A large part from each drop applied to any eye
and unionized (nondissociated) forms of the is drained through the nasolacrimal system,
molecule in equilibrium. The degree of ioniza- where the vascularized lining of the nasolacri-
tion of a drug in solution, and hence its capac- mal duct and nasopharyngeal mucosa is avail-
ity to diffuse across cellular barriers, is able for systemic absorption.
determined by its dissociation constant (pKa) Systemic drug absorption also results from
and the solvent’s pH. uptake by fenestrated blood vessels located in the
Protein binding of topical drugs is known to conjunctiva/episclera and must also be consid-
occur in the precorneal tear film, rendering the ered. This seems the case for the ophthalmic beta-­
bound fraction no longer available for absorp- blockers, which show an extremely low drug
tion. As local inflammation increases tear pro- concentration in plasma after corneal application
tein content, drug loss by this route may gain compared to conjunctival and scleral applica-
significance during topical treatment. tions. The significance of circulatory system
Hydrophilic drugs that penetrate poorly access by topical agents is that these medications
through the intact epithelium reach very high entering the systemic circulation through the
levels in the cornea when the epithelium is dam- nasolacrimal mucosa bypass the primary metabo-
aged or inflamed. In the case of a corneal ulcer, lism in the liver in this way. The administration of
drug is further retained by the craterlike effect of eye drops has therefore been compared with a
irregular tissue margins. Experimentally, it has slow intravenous injection, which can account for
been shown that penetration into the cornea and the systemic toxicity of some topically applied
anterior chamber of a topically applied hydro- ophthalmic preparations such as beta-­blockers.
philic antifungal agent is increased up to nine- After topical drug application in one eye, sig-
fold when 25–50% of the surface area of the nificant contralateral effects may sometimes be
corneal epithelium is removed. observed. It is generally postulated that drugs
120 Ocular Pharmacology and Therapeutics

can enter the fellow eye by way of the systemic For topically applied drugs that penetrate
circulation after absorption across the conjunc- the eye via the noncorneal route of entry,
tiva of the treated eye or the epithelial lining of higher peak concentrations may be observed
the nasolacrimal duct. Changes in intraocular in the iris–ciliary body before the AH, because
pressure (IOP) in the contralateral eye have scleral penetration permits the drug to reach
been noted with topical application of various the target tissue first without entering the AH.
antiglaucoma agents but have been particularly
documented for beta-­blockers in humans and Drug Elimination
animals. Topical atropine in one eye in the dog Aqueous outflow is presumed to be the pri-
can lower Schirmer tear test (STT) I levels in mary route of drug elimination from the eye,
both eyes. Topical timolol in one eye of cats or although loss of drug may occur by additional
dogs lowers IOP in treated and nontreated eyes. pathways (i.e., retinal blood flow) or processes
such as metabolism and drug binding to dis-
Systemic Drug Delivery Through Ocular Route tinctive tissues. Once drugs are absorbed into
Since part of the instilled drugs is absorbed the anterior chamber, they are eliminated
systemically, the technique to deliver drugs mostly by AH turnover, which was estimated
into systemic circulation via ocular route has to be 1.5–5 μl/min in humans and about 5 μl/
been studied. The delivery of systemic insulin min in dogs. In dogs, the clearance rate of mar-
through the ocular route in healthy cats and bofloxacin from AH (5 μl/min) was found to be
dogs, and diabetic dogs indicates that systemic very close to that reported for AH turnover.
absorption of insulin may occur subsequently
to topical ocular administration. Drug Binding
One established form of binding is the affinity of
Topical Drug Delivery to the Posterior drugs to melanin present in different ocular tis-
Eye Segment sues. The iris and ciliary body have a heavily pig-
Pharmacological effects after topical instilla- mented layer of epithelial cells, which can
tion of drugs indicate improvement of an ade- influence the pharmacological effect of instilled
quate blood flow to the retina or optic nerve ophthalmic drugs, because accumulation of drug
head with antiglaucoma agents. Significant in this pigmented tissue by melanin binding
intraocular distribution occurs after topical decreases the free drug concentration available
application of various drugs such as brimoni- for target tissues. The higher the amount of mel-
dine, betaxolol, dorzolamide, nepafenac, and anin in the eye, the smaller is the initial mydriatic
dexamethasone–cyclodextrin. effect of atropine. Topical pilocarpine accumu-
lates up to 10 times more in the pigmented rabbit
eyes than in the albino anterior uvea and its
Inside the Globe
miotic effects are significantly prolonged in the
Drug Distribution pigmented rabbit eyes compared to albino ones.
Following intraocular penetration of topically This effect also occurs in blue eyes of horses,
applied drugs, their subsequent distribution dogs, and cats, but has not been quantified.
and retention at the target site are critical to
their therapeutic success. Those drugs that dif- Drug Metabolism
fuse through the cornea enter the AH first and Although many oxidoreductase, hydrolytic,
then are distributed to the iris–ciliary body, and conjugating enzymes that exist in systemic
lens, and vitreous. The peak aqueous concen- tissues are expressed in various ocular tissues,
tration occurs from 0.5 to 3 h after instillation, little is known about the extent of local metab-
and was estimated in humans to be about a olism. Ocular drug metabolism is still evolv-
150 000 dilution of the drop for a hydrophilic ing, and is being investigated in prodrugs and
drug and a 1500 dilution for a lipophilic one. soft drug analogues. Esterase activity is the
­Topical Administratio  121

highest in the iris–ciliary body, followed by of irrigating fluid to the eye is used in humans
the cornea and then the AH. Depending on the for the treatment of acute chemical burn. The
nature of the drug, these enzymes contribute Morgan lens is a convenient device for continu-
to either an inactivating or activating effect. ous ocular irrigation in human patients.
Esterases are responsible for inactivating pilo- Continuous ocular treatment was also pro-
carpine and idoxuridine. posed for horses to reduce labor of treatment
and improve its pharmacological effects; the
feasibility and potential usefulness of a sub-
Drug Delivery Kinetics
conjunctivally implanted micro-­osmotic pump
and Ocular Bioavailability
and a continuous infusion pump connected to
Drugs topically applied to the eye do not obey a subpalpebral lavage system have been evalu-
the classic pharmacokinetics based on systemic ated. The nonbiodegradable micro-­osmotic
absorption, because unique factors affect drug pumps implanted subconjunctivally were well
absorption across the ocular surface mem- tolerated by the horses and allowed effective
branes. As most of the instilled volume is rap- delivery of atropine during the seven days they
idly lost from the preocular area, ophthalmic were in place. Subpalpebral systems in horses
solutions exhibit a fast drug pulse delivery with can also be used with intermittent drug admin-
an initially high concentration that rapidly istrations. They ensure drug delivery to the eye
declines to a concentration below the therapeu- and reduce the difficulty associated with topi-
tic range (Figure 3.4). The disappearance of a cal drug administrations in horses.
drug from ophthalmic solution follows first-­
order kinetics in which the instilled drug avail- Ophthalmic Ointments
able for target tissues declines exponentially as Ointments can achieve prolonged delivery, but
the medication is lost through the nasolacrimal can blur vision. The thick, oleaginous bases of
system and is washed away by the tear turnover. ophthalmic ointments are primarily mixtures
It is generally considered that for ophthal- of white petrolatum and mineral oil, with or
mic drugs, less than 1% to no more than 10% of without a water-­miscible agent such as lanolin.
the dose topically applied enters the eye. Hydrophilic drugs are dispersed in the base as
Increasing the frequency of drug administra- particles, as in suspensions, while lipid-­soluble
tions can directly influence drug concentra- drugs are dissolved in the ointment base.
tions in the target ocular tissues. Ophthalmic ointments must contain preserva-
tives in order to prevent bacterial contamina-
tion during use, and effects of pH and tonicity
Improvement of Ocular
should be controlled as previously discussed
Bioavailability
for ophthalmic solutions and suspensions.
Because only a very small fraction of the drug
applied to the eye can be absorbed into the Mucoadhesive and Viscosity-­Enhancing Polymers
inner eye, many schemes have been developed Drug–eye contact time can be improved in
to improve ocular bioavailability of medica- part by increasing the viscosity of the vehicle
tions delivered to the eye. with the addition of methylcellulose, a hydro-
philic polymer. These research efforts led to a
Improvement of Precorneal Retention significant body of literature demonstrating
Continuous Infusion of Topical Drugs that these polymers can prolong precorneal
Subcutaneous abdominal pumps, lacrimal duct residence time and improve ocular bioavaila-
cannulation and external infusion pumps for bility of hydrophilic drugs. Experimentally, it
delivery of topical pilocarpine as an antiglau- was determined that the improvement in ocu-
coma agent or artificial tears for dry eye have lar drug delivery reached a maximum level at
been reported in humans. Continuous delivery a viscosity of about 12–15 cps and that higher
122 Ocular Pharmacology and Therapeutics

Eyedrop instillation Figure 3.4 The differences between


the drug levels between single eyedrop
instillations, and an ophthalmic insert.
The goal is to try and maintain drug
therapeutic levels as high as possible.
Dose Dose Dose
Drug Concentration

Time
FIRST ORDER KINETIC

Ophthalmic insert
Drug Concentration

Dose

Time
ZERO ORDER KINETIC

viscosity formulations caused ocular irrita- bilayers separated by aqueous compartments


tion with an increase in reflex tears and blinks containing aqueous core, which have been
leading to rapid elimination of the widely exploited in ocular drug delivery.
instilled drug. The potential use of nanoparticles as an oph-
thalmic drug delivery system has been exten-
Colloidal Carriers sively evaluated for various hydrophilic and
Applications of nanotechnology currently rep- hydrophobic drugs, including pilocarpine,
resent a very exciting field of research for devel- amikacin, betaxolol, carteolol, CSA, and indo-
opment of new delivery drug systems to the methacin, loaded into or on nanospheres of
eye. The main focus has been given to colloidal different polymers.
systems consisting of micro/nanoparticles,
micro/nanoemulsions, nanosuspensions, and Solid Polymeric Devices
liposomes. Liposomes are vesicles (0.01–10 μm) Soft contact lenses used for the treatment of a
composed of one or more phospholipid variety of corneal diseases as a support bandage
­Periocular Administratio  123

can also serve as nonerodible vehicles for pro- properties of the drug through prodrug deri-
gressive drug release in the tear pool. Soft con- vatization, and the second is to increase tran-
tact lenses are typically composed of siently the permeability of the corneal
nonbiodegradable hydrophilic polymers, such epithelium.
as polyhydroxyethylmethacrylate or hydroxy-
ethylmethacrylate, and 50–75% water, and Ophthalmic Prodrugs
when soaked in a drug solution, they absorb To overcome the resistance to transport of
the drug, which is then released slowly in the hydrophilic drugs across the corneal epithe-
tear film when the lens is placed on the cornea. lium, a prodrug approach can be considered.
Although some studies demonstrated the Prodrugs are defined as pharmacologically
improved delivery of certain medications via inactive derivatives of drug molecules that are
presoaked contact lenses, these devices still chemically or enzymatically converted to the
represent “pulse-­dose” drug delivery system. active parent drugs. An ideal ocular prodrug
An alternative to contact lenses as a drug should be stable and soluble in aqueous solu-
vehicle is the use of collagen corneal shields, tions to enable formulation, sufficiently lipo-
originally developed for use as corneal band- philic to pass the corneal barrier, well tolerated,
ages. The shield is currently fabricated from and capable of releasing the active moiety
porcine scleral tissue or bovine dermal collagen. within the eye at a rate corresponding to the
The shield undergoes hydrolysis while in place therapeutic need.
on the cornea, within 12, 24, 48, or 72 h depend- Steroids were perhaps the first class of oph-
ing on the degree of collagen cross-­linking thalmic drugs to which prodrug concept was
determined by titrating the exposure to ultravio- applied, since the acetate prodrugs of dexa-
let radiation during the manufacturing process. methasone and prednisolone were designed to
Ophthalmic inserts are solid or semisolid improve corneal absorption and were found to
devices, the size and shape of which are increase the anti-­inflammatory efficiency by a
designed for application in the lower fornix. factor of 1.5–2.0 compared to their parent drugs.
They have been classified as biodegradable (sol- Dipivalyl epinephrine (or dipivefrin), devel-
uble) or nonbiodegradable (insoluble) inserts. oped as an epinephrine prodrug in the late
The best known nondegradable ocular insert is 1970s, is formed by esterification of the
the Ocusert® Pilo (Alza Corp., USA), a diffu- hydroxyl groups of the epinephrine molecule.
sional system designed for controlled release of The major advantage of dipivefrin is that a
pilocarpine for seven days. A nonbiodegradable 10-­fold lower dose has a therapeutic effect
ophthalmic insert containing 5.4 mg phenyle- comparable to that produced by epinephrine,
phrine and 0.28 mg tropicamide (Mydriasert®, with a significant lowering of systemic side
Zeiss-­Meditec, France), which is equivalent to effects and reduction of dose. Topical latano-
one 10% phenylephrine and 0.5% tropicamide prost, travoprost, and bimatoprost are all prod-
drop, is currently available in Europe to induce rugs of prostaglandin F2α (PGF2α).
mydriasis in human patients prior to cataract
surgery. A preliminary evaluation in dogs indi-
cates that mydriasis develops more slowly with ­Periocular Administration
Mydriasert than with topical application of the
corresponding drugs formulated as eye drops. The periocular routes include the subconjunc-
tival, sub-­Tenon’s, peribulbar, and retrobulbar
Improvement of Corneal Penetration routes that are used to improve the delivery of
There are two main approaches for enhancing drugs to intraocular structures. Their selection
corneal transfer of topically applied drugs. The depends on the inability of a drug to penetrate
first approach is to modify the physicochemical the ocular surface, and/or the location of the
124 Ocular Pharmacology and Therapeutics

target site. Among those, subconjunctival capsule and adjacent to the scleral surface,
injection is the most commonly used in veteri- where little resistance to the diffusion of
nary patients. It can provide high local concen- hydrophilic drugs is thought to occur. Anterior
trations for prolonged periods of time, and sub-­Tenon’s injections are associated with a
deliver drugs to both the anterior and posterior higher risk of scleral perforation compared to
structures of the eye. the subconjunctival injection. Posterior sub-­
Tenon’s injection of corticosteroids is indi-
cated in human patients with chronic
Subconjunctival Injection
equatorial and posterior uveitis, and those
Subconjunctival administration may be indi- with cystoid macular edema after cataract sur-
cated for infectious or inflammatory condi- gery or diabetic macular edema.
tions of the cornea and anterior segment
because of the expected high and/or sustained
Retrobulbar
drug levels that can be achieved in these ocular
and Peribulbar Injections
structures (Figure 3.5). This route of adminis-
tration provides therapeutic drug levels for Retrobulbar and peribulbar injections are used
8–12 h after a single injection of a water-­soluble to introduce a drug into the orbital cavity. The
drug and for up to two to three weeks with drug then diffuses rapidly through the orbital
drugs in suspension, such as the acetate for- tissues and the back of the eye. Several tech-
mulations of corticosteroids. niques have been proposed for the dog and
They are used (i) to supplement topical drug evaluated in terms of the consistency with
delivery; (ii) to replace topical drug when they which each technique deposits the drug within
cannot be used; and (iii) to provide a sustained the retrobulbar cone.
level of drugs for several days. Retrobulbar or peribulbar injection is used
primarily for regional anesthesia as an adjunc-
tive procedure in ocular surgery to reduce
Sub-­Tenon’s Injection
nystagmus and enophthalmos. Potential com-
In a sub-­Tenon’s injection, the Tenon’s capsule plications of retrobulbar block include globe
is elevated from the sclera with a needle or perforation, optic nerve injury, extraocular
cannula to place the drug underneath Tenon’s muscle injury, and orbital hemorrhage.

Injected drug

SUBCONJUNCTIVAL SITE

Leakage through Absorption by


Transscleral penetration
conjunctival puncture subconjunctival
blood vessels
Cornea Vitreous chamber Tear film
Aqueous humor General circulation
Anterior uvea
Transcorneal intraocular Return to the eye
penetration via hematogenous
route

Figure 3.5 Routes of drug distribution after subconjunctival injection.


­Other Methods of Ocular Drug Deliver  125

­Intraocular Administration cavity, with the advantage of bypassing the ocu-


lar permeability barriers.
Intracameral and Intravitreal
Injections
Intraocular Implants
Intracameral administration involves delivering
Polymeric implants have been specifically
a drug directly onto the anterior chamber of the
developed for the treatment of human diseases
eye. Most commonly, injection or irrigation of
affecting both anterior and posterior segments
the anterior chamber is realized to control iris
of the eye, which are not readily accessible by
hemorrhage or pupil size with viscoelastic sub-
the conventional methods and require pro-
stances and/or epinephrine during intraocular
longed therapeutic drug levels. This approach
surgery. Tissue plasminogen activator and car-
has been employed in veterinary ophthalmol-
bachol can also be administered intracamerally
ogy for the long-­term control of equine recur-
at the completion of cataract surgery in the dog.
rent uveitis (ERU) using a sustained-­release
Intracameral injection poses a significant risk
system of CSA. Nonbiodegradable devices
for local drug toxicity because local intolerance
include reservoir-­type devices, and implant-­
may result in corneal endothelial damage with
type devices such as intravitreal pellets or
corneal edema and damage to the iris and lens.
sclera and punctal plugs, which are able to
The direct administration of a drug solution
release drug over a span of weeks or months.
or suspension into the vitreous cavity is the
most efficacious method to provide effective
concentrations at the target site and is gener-
ally required in threatening posterior segment ­Systemic Administration
diseases. However, the potential hazards of the
procedure have actually limited its use to the In veterinary ophthalmology, systemically
chemical ablation of the ciliary epithelium in administered drugs are used for the treatment
end-­stage glaucomatous eyes and less fre- of eyelid diseases (i.e., bacterial blepharitis)
quently to the treatment of infectious endoph- and orbital infections (i.e., orbital cellulitis or
thalmitis. The safety of the drug, its vehicle, abscess), and can also be used for intraocular
and its concentration reaching the retina must conditions, such as bacterial endophthalmitis.
be taken into account to avoid toxicity. However, as discussed previously, diffusion of
drugs present in the systemic circulation to
anterior segment and posterior segment is cur-
­ ustained Drug Delivery
S tailed by the BAB and blood–retinal barrier,
to Intraocular Tissues respectively. Factors affecting the permeability
of these barriers include the drug lipophilicity,
The relatively short half-­life of many intraocu- drug molecular weight, plasma drug levels,
larly administered drugs necessitates re-­ and inflammation of the intraocular structures.
injections to maintain therapeutic drug
concentrations, which predispose to side effects
such retinal detachment, vitreous hemorrhage, ­ ther Methods of Ocular
O
and bacterial endophthalmitis. As an alternative Drug Delivery
to multiple injections, delivery systems such as
polymeric implants or colloidal carriers have the Ocular iontophoresis, microneedle, and
benefit of providing prolonged activity with con- ultrasound-­based ocular drug delivery are non-
trolled drug release within the eye, with a single invasive methods designed to deliver drugs to
administration. They can be injected or or thorough the fibrous tunic and intraocular
implanted in the anterior chamber or vitreous tissues.
126 Ocular Pharmacology and Therapeutics

­ ntibacterial, Antifungal,
A effects should be considered. Often antibiotics
and Antiviral Agents used commonly topically are not first choice
for systemic antibiotics, and hopefully reduce
General Principles of Antibacterial the likelihood of antibiotic resistance.
Therapy
Drugs That Inhibit Bacterial Cell
Antibacterial agents are essential in the suc- Wall Synthesis
cessful management of ocular diseases, and Drugs that inhibit bacterial cell wall synthesis
used in either a prophylactic or a therapeutic include the penicillins, cephalosporins, baci-
manner. When used prophylactically, selection tracin, and vancomycin.
of antibiotics and factors such as general spec-
trum of activity, the potential development of Penicillins
resistant organisms, and adverse reactions or Penicillins may be broadly classified as effec-
toxicities are important. When used therapeu- tive against Gram-­positive bacteria, resistant to
tically, the most effective antibiotic agent avail- penicillinases, exhibiting extended spectra of
able is most important. Because of the activity, or effective against Pseudomonas spp.
transcorneal, blood–aqueous, and blood– The two primary members of this group are
r­etinal barriers, the antibacterial agents’ possi- penicillin G (inactivated by gastric acid and
ble routes of administration are also important, thus administered parenterally) and penicillin
and often combined. Lastly, drug-­to-­drug V (orally administered). Unfortunately, these
interactions should be considered. When drugs are highly susceptible to organisms that
selecting an antibiotic, bactericidal drugs produce β-­lactamases, including most strains
should be used in patients with impaired of Staphylococcus aureus and S. epidermidis.
defenses, as bacteriostatic drugs depend more Relating to treatment of ocular diseases, the
upon interaction with the natural defenses of low lipophilicity of penicillin G restricts its
the host for maximal efficacy (Box 3.1). When passage through the blood–ocular barriers,
administering a combination of antibiotics, thereby limiting its efficacy for intraocular
the potential for synergistic or antagonistic infections. Because of the limits of most sys-
temic antibiotics for food animals, the penicil-
lins are used in cattle; administration of
Box 3.1 Classification of Antibiotics Used
penicillin G topically or subconjunctivally,
in Veterinary Ophthalmology
with or without added procaine, achieves ther-
Bacteriostatic Chloramphenicol apeutic ocular surface or tear film drug levels,
Macrolides sustained for up to 67 h. The penicillinase-­
resistant drugs, including methicillin, oxacil-
Sulfonamides
lin, cloxacillin, dicloxacillin, and nafcillin, are
Tetracyclines able to resist bacterial β-­lactamases due to
Trimethoprim alterations to their chemical structures, thus
Bactericidal Aminoglycosides making them effective against S. aureus and
Bacitracin S. epidermidis infections. In cattle, topical
administration of benzathine cloxacillin is
Cephalosporins
reportedly effective in the treatment of experi-
Fluoroquinolones mental Moraxella bovis infections.
(FQNs)
Gramicidin Extended-­Spectrum Penicillins
Penicillins Ampicillin and amoxicillin are the two mem-
bers of this group, whose spectrum extends
Polymyxin B
beyond Gram-­positive organisms to include
Vancomycin
Gram-­negative rods. They are inactivated by
­Antibacterial, Antifungal, and Antiviral Agent  127

β-lactamases; however, addition of sulbactam to in vitro activity versus β-­hemolytic Streptococcus,


ampicillin and clavulanic acid to amoxicillin with no efficacy versus P. aeruginosa.
imparts resistance to β-­lactamases by irreversi-
bly binding the bacterial enzymes, making Second-­Generation Cephalosporins
these two combinations more effective in the Cefaclor, cefuroxime, cefoxitin, and cefotetan
treatment of S. aureus and S. epidermidis infec- are second-­generation cephalosporins, which
tions. In horse with bacterial keratitis and ulcer- have increased Gram-­negative activity relative
ations, 50–100% of Streptococcus equi isolates to the first generation. Among dogs and cats
from horses with bacterial keratitis were sus- with orbital disease, 73% and 100% of isolates,
ceptible to ampicillin (Table 3.1). In ocular sur- respectively, were susceptible to cefoxitin.
face of older dogs, increasing resistance to both
cloxacillin and amoxicillin–clavulanic acid Third-­Generation Cephalosporins
among Staphylococcus intermedius but not Ceftiofur, cefotaxime, ceftriaxone, and ceftazi-
S. aureus isolates has been noted. In cats, orally dime are third-­generation cephalosporins with
administered clavulanic acid–amoxicillin was increased activity versus enteric Gram-­
as clinically effective as orally administered dox- negative bacteria. Aerobic bacterial isolates
ycycline for the treatment of experimentally from dogs with orbital disease identified 100%
induced chlamydial conjunctivitis. Of aerobic susceptibility of isolates to ceftiofur.
bacterial isolates from dogs and cats with orbital
disease, 78% and 100%, respectively, were sus- Fourth-­Generation Cephalosporins
ceptible to amoxicillin–clavulanic acid. Cefepime has a broad spectrum versus both
Gram-­positive and Gram-­negative organisms,
Antipseudomonal Penicillins with good demonstrated efficacy versus P. aer-
Carbenicillin, mezlocillin, piperacillin, and uginosa isolates from canine dermatological
ticarcillin are effective against Pseudomonas diseases.
aeruginosa and some Proteus and Enterobacter
species, Gram-­negative organisms that are Bacitracin
resistant to most other penicillins. Ticarcillin Bacitracin inhibits bacterial cell wall synthesis
has demonstrated in vitro efficacy versus by inhibiting the movement of a peptidoglycan
Gram-­positive bacterial isolates from equine precursor from the cytoplasm through the cell
eyes with bacterial keratitis, as well as aerobic membrane. Its spectrum of action is primarily
bacterial isolates from dogs and cats with Gram-­positive, with good activity versus
orbital disease. S. intermedius isolates from dogs with bacterial
keratitis and β-­hemolytic S. equi isolates from
Cephalosporins dogs and horses with bacterial keratitis.
Cephalosporin antibiotics are composed of a Bacitracin is a common component of triple
dihydrothiazine and a β-­lactam ring connected antibiotic ophthalmic ointments, as it is unsta-
to a side chain. The division of cephalosporins ble in solution. Its combination with neomycin
into generations is based upon the spectrum of and polymyxin B (both having greater Gram-­
activity conferred by various side chains. negative efficacy) produces a good broad-­
spectrum preparation commonly used for
First-­Generation Cephalosporins prophylaxis (corneal ulcerations) or therapy
Cephalexin, cefadroxil, cefazolin, cephalothin, (nonspecific ocular surface infections).
and cephradine are first-­generation cephalo- Bacitracin has no appreciable transcorneal
sporins, all with good efficacy versus Gram-­ penetration in intact corneas, and therefore is
positive organisms and only marginal efficacy of limited value in deep corneal or intraocular
versus Gram-­negative organisms. Evaluating infections. The primary side effect of bacitracin
isolates from dogs and horses with bacterial that is a potential concern is a local hypersensi-
keratitis, cephalothin demonstrates good tivity reaction,
128 Ocular Pharmacology and Therapeutics

Vancomycin administered topically or parenterally due to


Vancomycin inhibits bacterial cell wall syn- poor oral absorption. In general, the spectrum
thesis by inhibiting incorporation of the pep- of activity is strong versus Gram-­negative organ-
tidoglycan into the cell wall. It is effective isms (P. aeruginosa, Proteus, Escherichia coli,
versus Gram-­positive organisms, particularly Enterobacter, etc.), while efficacy versus Gram-­
Staphylococcus spp. (including MRSA) and positive organisms is restricted to S. aureus.
Streptococcus spp., as well as Clostridium dif-
ficile. Due to its spectrum of activity and the Neomycin
development of resistance among organisms Neomycin, a component of common ophthal-
highly resistant to other antibiotics, it is mic triple-­antibiotic preparations, is primarily
imperative to exercise extreme caution in the used for prophylaxis in superficial corneal ulcer-
use of vancomycin in veterinary patients. ation, or for nonspecific treatment of ocular sur-
Ophthalmic use of vancomycin has included face infections. Its primary side effect is contact
topical administration for infectious keratitis hypersensitivity. It has limited to no corneal pen-
and intraocular administration for bacterial etration in the presence of an intact corneal epi-
endophthalmitis. thelium. Consistent with general aminoglycoside
susceptibility patterns, S. intermedius isolates
Drugs That Disrupt the Bacterial from dogs with bacterial keratitis are highly sus-
Cell Membrane ceptible to neomycin, Pseudomonas isolates
As bacterial and mammalian cell membranes demonstrate good susceptibility, but β-­hemolytic
are quite similar, few antibiotics are able to Streptococcus isolates are highly resistant.
selectively and effectively target this cellular
component without inducing patient toxicity. Gentamicin
Polymyxin B and gramicidin are the two most Gentamicin, administered topically or subcon-
readily used. Polymyxin B disrupts bacterial junctivally, is used in the treatment of infec-
cell membrane phospholipids, increasing cell tious keratitis, particularly that caused by
permeability and leading to cell death. Its spec- P. aeruginosa. The commercially available con-
trum is limited to Gram-­negative organisms, centration (3 mg/ml) or fortified solutions
with good activity versus P. aeruginosa isolates (13.6 mg/ml) may be utilized in the presence of
from horses and dogs with bacterial keratitis. infection. The ability of gentamicin to provide
Its penetration through an intact corneal epi- prophylactic protection is limited due to its
thelium is poor. Gram-­negative spectrum of activity. In canine
corneal epithelial cell cultures, gentamicin in
Gramicidin various concentrations adversely affected
Gramicidin also alters cell membrane permea- wound healing. Gentamicin achieves limited
bility, and its spectrum is directed toward transcorneal penetration in normal corneas;
Gram-­positive organisms. Its stability in solu- however, therapeutic levels are more readily
tion enables its substitution for bacitracin in reached in the presence of inflammation.
triple antibiotic ophthalmic preparations. Reports vary significantly regarding develop-
ment of resistance to gentamicin, indicating
Drugs That Affect Bacterial Protein no change to increased resistance of P. aerugi-
Synthesis nosa and S. equi isolates from horses with
This group of antibiotics includes aminoglyco- infectious keratitis (see Table 3.1). Isolates
sides, tetracyclines, and macrolides, as well as from dogs with bacterial keratitis showed no
chloramphenicol. overall increase in resistance between 1993
and 2003; however, as would be expected,
Aminoglycosides β-hemolytic Streptococcus strains were more
Aminoglycosides inhibit the 30S bacterial ribo- likely to be resistant to gentamicin than were
some translation of mRNA into protein, and are S. intermedius or Pseudomonas strains.
Table 3.1 Recommended ophthalmic antibiotic choices based on in vitro susceptibility of organisms isolated from clinical bacterial keratitis cases. Antibiotic
(# resistant/total # isolates evaluated, % resistant in reference indicated).

Canine Equine

Ledbetter
Organism Tolar et al. (2006) et al. (2007a) LoPinto et al. (2015) Brooks et al. (2000)a Sauer et al.(2003)a Keller & Hendrix (2005)

Staphylococcus Bacitracin (0/30, 0%) N/A N/A N/A N/A N/A


intermedius Chloramphenicol
(1/34, 3%)
Ciprofloxacin (0/9, 0%)
Neomycin (2/31, 6%)
Polymyxin (1/31, 3%)
Tobramycin (3/31, 10%)
Methicillin-­resistant N/A N/A Amikacin (0/17, 0%) N/A N/A N/A
Staphylococcus spp. Chloramphenicol
(0/17, 0%)
Gentamicin (0/17, 0%)
Neomycin (5/17, 29%)
Streptococcus spp. Bacitracin (0/19, 0%) N/A N/A Bacitracin (0/11, 0%) Bacitracin (0/12, 0%) Chloramphenicol (0/17,
Chloramphenicol Chloramphenicol Chloramphenicol 0%)
(0/19, 0%) (0/11, 0%) (0/13, 0%) Ciprofloxacin (0/5, 0%)
Ciprofloxacin (0/3, 0%) Enrofloxacin (2/13, Erythromycin (1/17, 6%)
15%) Gentamicin (3/17, 18%)
Tetracycline (2/17, 12%)
Pseudomonas Ciprofloxacin (1/15, Ciprofloxacin (0/27, 0%) N/A N/A Polymyxin (0/14, 0%) Ciprofloxacin (0/6, 0%)
aeruginosa 7%) Ofloxacin (2/27, 7%) Neomycin (4/14, Gentamicin (0/6, 0%)
Gentamicin (0/25, 0%) Levofloxacin (0/27, 0%) 29%) Neomycin (0/3, 0%)
Neomycin (3/22, 14%) Gatifloxacin (1/27, 4%) Enrofloxacin (0/14, Polymyxin (0/2, 0%)
Polymyxin (0/22, 0%) Moxifloxacin (3/27, 11%) 0%) Tobramycin (0/2, 0%)
Tobramycin (0/22, 0%)
a
Fluoroquinolones available as ophthalmic preparations were not evaluated.

0005300332.INDD 129 04-26-2022 11:31:32


130 Ocular Pharmacology and Therapeutics

Tobramycin administration beneficial for organisms that


The spectrum of activity and indications for sequester in nonocular sites (Chlamydophila
use of tobramycin are similar to those of gen- felis or Mycoplasma spp. in cats, M. bovis in
tamicin; however, a recent study indicates its cattle), as well as for administration to large
efficacy versus Pseudomonas isolates from populations of cattle. With the exception of
horses with bacterial keratitis has declined, doxycycline, orally administered tetracyclines
while Pseudomonas isolates from dogs with are generally poorly absorbed from the gastro-
bacterial keratitis were uniformly susceptible. intestinal tract. Additional pharmacological
As would be expected, efficacy versus benefit provided by the tetracyclines is their
Streptococcus isolates is very poor, while effi- ability to inhibit matrix metalloproteinases
cacy versus S. intermedius isolates is good. (MMPs) and other mediators of inflammation
that digest corneal proteins leading to “melt-
Kanamycin ing” ulcers. In cats, oral doxycycline (5 mg/kg
Kanamycin has been used to treat infectious p.o. q 12 h or 10 mg/kg p.o. q 24 h) has been
bovine keratoconjunctivitis caused by M. bovis. shown to more effectively control chlamydio-
sis than topical administration of chlortetracy-
Amikacin cline. In cattle, an intramuscular injection was
Amikacin is not available as a topical ophthal- clinically successful in treating M. bovis ocular
mic preparation; however, its administration disease, while therapeutic tear film drug levels
topically has led to therapeutic corneal levels were maintained for up to 72 h following a sin-
that may be useful in treating patients with gle subconjunctival injection of a long-­acting
ocular infections caused by Gram-­negative oxytetracycline formulation. Tetracyclines are
bacilli that are resistant to gentamicin or known to induce photosensitivity reactions,
tobramycin. gastrointestinal upset, and discoloration of
teeth during development.
Tetracyclines
Like the aminoglycosides, tetracyclines inter- Macrolides and Lincosamides
act with the 30S ribosomal subunit to inhibit Erythromycin, azithromycin, and clarithromy-
bacterial mRNA translation. They may be cin are macrolide antibiotics that bind the 50S
cl­assified as short-­acting (tetracycline, oxytetra- bacterial ribosomal subunit, preventing elonga-
cycline), intermediate-­acting (demeclocycline), tion of the peptide chain in bacterial mRNA
or long-­acting (doxycycline, minocycline). While translation. They are primarily effective versus
they have a broad spectrum of bacterial cover- Gram-­positive bacteria; however, their ability to
age, their clinically relevant spectrum of activ- accumulate intracellularly makes them effec-
ity is relatively narrow, due in part to tive treatments for Chlamydophila, Mycoplasma,
development of efflux mechanisms within bac- and Bartonella infections. Organisms pertinent
teria that actively pump drug out of the cells, to veterinary ophthalmology effectively treated
creating resistant strains. Activity versus rick- with erythromycin include Mycoplasma spp.
ettsial organisms, Borrelia burgdorferi, and Chlamydophila spp. Isolates of S. equi from
Mycoplasma spp., Chlamydophila spp., and horses with bacterial keratitis were highly sus-
Moraxella spp. is consistently strong, while ceptible to erythromycin. In contrast, various
Staphylococcus spp. and Streptococcus spp. aerobic bacteria species isolated from dogs and
may be developing increased resistance. P. aer- cats with orbital disease identified only 40%
uginosa is generally considered resistant to susceptibility in dogs (9 of 22 isolates) and 0%
tetracyclines, which has been supported by a susceptibility in cats (0 of 3 isolates).
recent evaluation of isolates from horses with
bacterial keratitis. Tetracyclines may be Azithromycin
administered topically, orally, or parenterally Azithromycin is a newer derivative of erythro-
in patients with ocular disease, with oral mycin that is rapidly absorbed following oral
­Antibacterial, Antifungal, and Antiviral Agent  131

administration and has an increased spectrum functions. The spectrum of activity generally
of activity toward Gram-­negative organisms, in includes Gram-­positive organisms with some
particular B. burgdorferi and Bartonella henselae, Gram-­negative organisms; however, resistance
relative to that of erythromycin. Unfortunately, mechanisms acquired by bacteria are numer-
emerging information indicates that its clinical ous. The activity of trimethoprim-­sulfonamide
efficacy in veterinary medicine is relatively poor. combinations versus Streptococcus isolates
from horses with ocular disease is good; how-
Clindamycin ever, Pseudomonas isolates have been docu-
Clindamycin is a lincosamide antibiotic, which mented to be 100% resistant. Systemic reactions
also has inhibitory effects on the 50S ribosomal may occur with the use of sulfonamides,
subunit of susceptible bacteria. It has good effect including gastrointestinal disturbances, aller-
in the treatment of cats infected with Toxoplasma gic skin reactions, renal complications, and
gondii and has been shown to prevent repeat blood dyscrasias, as may local reactions such
shedding of oocysts in experimentally infected as irritation and dermatitis. In dogs, multiple
cats, even under conditions of immunosuppres- sulfonamides are known to cause keratocon-
sion. Of aerobic bacterial isolates from dogs and junctivitis sicca (KCS), postulated to be associ-
cats with orbital disease, 50% (6/12) and 0% ated with a direct toxic effect on lacrimal acinar
(0/2), respectively, were sensitive to clindamycin. cells by the nitrogen-­containing pyridine and
pyrimidine rings. This reaction may occur in a
Chloramphenicol dose-­dependent or idiosyncratic manner, and
Chloramphenicol also inhibits the 50S bacterial is reproducible experimentally by structurally
ribosomal subunit. It is broad-­spectrum, with similar salicylic acid compounds.
activity versus Rickettsia, Chlamydophila, and
Mycoplasma, as well as Gram-­positive and Drugs That Affect Bacterial
Gram-­negative agents, with the exception of DNA Synthesis
P. aeruginosa. Consistent with these general pat- Nalidixic acid and related FQNs inhibit DNA
terns, Staphylococcus and Streptococcus isolates gyrase (topoisomerase II) and/or topoisomer-
from dogs with bacterial keratitis were suscepti- ase IV, enzymes specific to bacteria that main-
ble to chloramphenicol, while Pseudomonas tain the bacterial DNA superhelix during
isolates were resistant, with the same trends in replication, thus exerting bactericidal effects.
horses with bacterial keratitis (see Table 3.1) . The spectrum of activity of FQNs varies with
Topically administered chloramphenicol pene- generation (first, second, third, or fourth,
trates poorly through the cornea in eyes with although the classification scheme is not
intact corneal epithelium, with the ointment standardized), with newer generations gener-
formulation providing greater corneal and AH ally providing greater Gram-­positive efficacy
drug levels. The primary restriction to its use of through greater inhibition of topoisomerase IV.
chloramphenicol is the development of two
variants of hematopoietic disorders, which have First-­Generation Fluoroquinolones
occurred after both systemic and topical ocular Nalidixic acid is considered the first-­generation
administration of the drug. FQN and has moderate Gram-­negative and
Gram-­positive activity, with weak activity ver-
Drugs That Alter Bacterial sus P. aeruginosa.
Folate Metabolism
These antibiotics include sulfonamides, Second-­Generation Fluoroquinolones
pyrimethamine, and trimethoprim, and are Second-­generation FQNs generally include
frequently combined with one another due to lomefloxacin, norfloxacin, enrofloxacin, cipro-
additive effects. A bacteriostatic effect is floxacin, and ofloxacin. Their spectrum of
achieved through inhibition of bacterial folate activity is strong toward P. aeruginosa and
production, a necessary cofactor for cellular some Gram-­positive organisms; however,
132 Ocular Pharmacology and Therapeutics

increasing resistance is developing, particu- Antifungal Agents


larly by Streptococcus spp. and Pseudomonas
General Principles of Therapy
spp. in human ophthalmology. In dogs with
Medically significant fungi exist as yeasts (sin-
bacterial keratitis, 100% of Staphylococcus spp.
gle cells, reproduce by budding), molds (cylin-
and Streptococcus spp. isolates were suscepti-
drical hyphae, reproduce by branching and
ble to ciprofloxacin and enrofloxacin, while
apical extension, form multicellular filamen-
85% of Streptococcus spp. isolates from horses
tous mass in culture called mycelium), or
with bacterial keratitis were susceptible to
dimorphic forms (yeast phase in host tissues,
enrofloxacin. Susceptibility of Pseudomonas
mycelial phase in culture media). Fungal
isolates from dogs with bacterial keratitis to
organisms are more complex and share more
ciprofloxacin ranged from 93% to 100%, with
structural commonalities with mammalian
100% susceptible to norfloxacin, 93% suscepti-
cells, making selective pharmacological target-
ble to ofloxacin, and 87% susceptible to enro-
ing more difficult. As a result, antifungal medi-
floxacin. Pseudomonas isolates from horses
cations are generally indicated only in the
were 100% susceptible to enrofloxacin.
presence of confirmed infection (Table 3.2). Of
the different fungal infections in animals, sys-
Third-­Generation Fluoroquinolones
temic fungal infections occur mainly in small
Third-­generation FQNs include sparfloxacin,
animals, while fungal infections are localized
gemifloxacin, and levofloxacin. P. aeruginosa
in the horse cornea. Antifungal drugs fall into
isolates from dogs with bacterial keratitis were
one of four classes – polyenes, pyrimidines,
100% susceptible to levofloxacin.
azoles, or echinocandins – all of which act pri-
marily on the fungal cell wall, with the goal
Fourth-­Generation Fluoroquinolones
being greater selectivity for the fungal organ-
Fourth-­generation FQNs include gatifloxacin,
ism versus the host.
moxifloxacin, and besifloxacin. Their Gram-­
positive spectrum is increased relative to that of
earlier FQNs; however, their efficacy versus Polyenes
Pseudomonas spp. may be limited. Of 27 The polyenes (amphotericin B, natamycin, and
P. aeruginosa isolates from dogs with bacterial nystatin) target the fungal cell membrane com-
keratitis, 1 and 3 were resistant to gatifloxacin ponent ergosterol, binding to it and forming a
and moxifloxacin, respectively. It is currently rec- polyene–sterol complex, which ultimately
ommended that use of these agents be restricted induces leakage of vital intracellular constitu-
to serious ocular surface bacterial infections. ents (i.e., K+). Their action is concentration
Ciprofloxacin, ofloxacin, and norfloxacin dependent, with the likelihood of fungicidal
have been shown to be cytotoxic and have activity present at higher concentrations.
antiproliferative effects on stromal kerato-
cytes. Parenteral enrofloxacin may cause irre- Amphotericin B
versible generalized retinal degeneration in Amphotericin B is a broad-­spectrum antifungal
cats when administered at dosages higher agent that exhibits strong in vitro activity versus
than 5 mg/kg once daily. When administered most fungal organisms responsible for invasive
at the recommended dose of 2.5–7.5 mg/kg, systemic disease processes (i.e., Aspergillus spp.,
orbifloxacin does not produce the same Blastomyces spp., Candida spp., Coccidioides
effects; however, subtle changes were noted spp., and Cryptococcus spp.); however, other
in cats receiving 45 and 75 mg/kg once daily strains are poorly susceptible (Trichosporon
for 30 days. Marbofloxacin at 20 times the rec- spp., Geotrichum spp., Scedosporium spp.).
ommended dose did not produce retinal Although topically administered amphotericin
degeneration. B has been effective in the treatment of fungal
Table 3.2 Antifungal medications used to treat keratomycosis.

Drug Spectruma Concentration/dose Route Complications Other

b
Amphotericin B Good versus yeast 0.15%–0.3% Topical Corneal toxicity Limited corneal penetration
Good versus filamentous 0.5% Subconjunctival (every Local irritation
48 h × three doses) Discomfort
Natamycin Good versus filamentous 5% Topical Minimal Limited corneal penetration
Kétoconazole Poor versus filamentous l%–5%b Topical Minimal Slower onset
Good corneal penetration
Miconazole Good versus filamentous l%–5%b Topical Minimal Good corneal penetration
Fluconazole Good versus yeast 2 mg/mlb Topical Minimal Good corneal penetration
Poor versus filamentous 14mg/kg once, followed by 5 mg/kg Oral Good intraocular penetration
every 24 hours
Itraconazole Good versus filamentous 1%> in 30% dimethyl sulfoxideb Topical Minimal Good corneal tissue levels
(except Fusarium) 5 mg/kg every 24 hours Oral Poor corneal penetration
Poor intraocular penetration
Voriconazole Good versus yeast 1%b Topical Minimal Good corneal penetration
Good versus filamentous 3–4 mg/kg every 12–24 hours Oral Good precorneal tear film
Topical levels
Caspofungin Good versus yeast 0.5%–0.7%b Minimal Good corneal penetration
with
Good versus filamentous epithelial defect
(except Fusarium)
a
In relation to organisms relevant to keratomycosis in veterinary patients.
b
Not commercially available as an ophthalmic preparation.

0005300332.INDD 133 04-26-2022 11:31:33


134 Ocular Pharmacology and Therapeutics

conjunctivitis, scleritis, and keratitis, corneal Azoles


penetration is limited in the presence of an The azoles are antifungal agents with fungio-
intact corneal epithelium, and ocular surface static activity that, like polyenes, target the
irritation and discomfort are potential side fungal cell membrane component ergosterol.
effects. Reports of the clinical use of ampho- Rather than binding to ergosterol, however,
tericin B to treat surface ocular fungal infections they inhibit its synthesis through inhibition
in veterinary ophthalmology have been limited of the cytochrome P450-­dependent enzyme
to horses. 14α-­sterol demethylase, which leads to accu-
mulation of toxic sterol precursors, inhibits
Natamycin fungal growth, and increases membrane per-
As the only approved topical ophthalmic anti- meability. Ketoconazole and miconazole are
fungal agent (5% suspension), natamycin has an azoles based on the imidazole parent ring
improved spectrum of action relative to that of structure. Relative to other azoles, ketocona-
amphotericin B, with better coverage versus fila- zole has a more limited spectrum, greater
mentous organisms common in keratomycosis risk for systemic toxicities, and slower onset
(i.e., Fusarium, Aspergillus, Curvularia, and of clinical effect, somewhat limiting its ther-
Acremonium). It is well tolerated and induces apeutic usefulness. It is well absorbed when
fewer ocular toxicities following topical applica- administered systemically; however, topical
tion; however, it has historically poor ophthalmic formulations are not available.
transcorneal penetration, limiting its use in deep When administered topically as a com-
corneal or intraocular infections. Natamycin is pounded preparation, it has good corneal
frequently used in the treatment of equine fun- and intraocular penetration and minimal
gal keratitis and has demonstrated strong in vitro toxicity.
activity versus isolates from horses with clinical Topical ketoconazole in the treatment of
disease, particularly Fusarium and Candida, equine keratomycosis demonstrates consist-
with generally lesser but still potentially thera- ently inferior activity relative to polyenes and
peutic efficacy versus Aspergillus. other azoles. In an in vitro comparison of
ketoconazole, voriconazole, miconazole, flu-
Nystatin conazole, itraconazole, and natamycin versus
Nystatin is a polyene with relatively broad-­ Aspergillus and Fusarium isolates from horses
spectrum fungistatic activity; however, its use in the midwestern and southern United
in the treatment of keratomycosis is somewhat States, ketoconazole was consistently the least
limited, considering minimal corneal penetra- effective. For isolates from horses in the
tion when administered topically, as well as northeastern United States, only fluconazole
local toxicity. was less effective versus filamentous organ-
isms, with 56% of isolates (35 of 62) suscepti-
Pyrimidines ble to ketoconazole.
Flucytosine (5-­fluorocytosine, 5-­FC) is a cyto- In dogs with ocular manifestations of blas-
sine analogue that exerts antifungal activity tomycosis, systemically administered keto-
following uptake and conversion by fungal conazole in combination with amphotericin
cells. Flucytosine has greatest effect versus B was as effective as achieving clinical
yeasts such as Candida and Cryptococcus; improvement as itraconazole alone. A side
however, intrinsic resistance may be signifi- effect of oral ketoconazole administration in
cant, and resistance may also develop during dogs for the treatment of Coccidioides immitis
the course of therapy. In naturally occurring infections is the development of cataracts,
keratomycosis in horses, flucytosine indicates which occur with long-­term (up to 37 months)
lesser efficacy relative to other more com- therapy, at dosages ranging from 6 to
monly administered antifungal agents. 30 mg/kg/day.
­Antibacterial, Antifungal, and Antiviral Agent  135

Miconazole limited due to its narrow spectrum of activity.


Miconazole is a broad-­spectrum azole fre- Isolates of filamentous organisms from horses
quently administered topically as a 1% com- with keratomycosis in the northeastern United
pounded suspension or as the 2% dermatological States demonstrated 87% resistance to flucona-
or 2% vaginal creams. Topical application and zole, versus 14% resistance for yeast organisms.
subconjunctival injection of miconazole reach
measurable and potentially therapeutic corneal
and intraocular levels in rabbits. Miconazole Itraconazole
has been used frequently in the treatment of Itraconazole has a broader spectrum of activity
equine keratomycosis, either as the com- than does fluconazole, particularly toward fila-
pounded preparation or as a topical cream, in mentous fungal organisms; however, Fusarium
part due to availability and comparative ease of species isolated from human cases of ocular
ocular administration. Miconazole demon- disease are more resistant to itraconazole than
strated good in vitro activity when compared to other azoles. Due to its lipophilic nature and
with other antifungal drugs versus Aspergillus high degree of protein binding, itraconazole is
and Fusarium isolates from horses with ocular well absorbed following oral administration
disease in the midwestern and southern United and concentrates well in lipid-­rich tissues;
States; however, efficacy was considerably however, its intraocular penetration is poor.
lower versus both filamentous and yeast These pharmacokinetic parameters have been
organisms from horses in the northeastern supported in horses, in whom bioavailability
United States. following oral administration is high, with
more consistent absorption following oral
Triazoles administration of the commercially available
Fluconazole, itraconazole, voriconazole, posa- solution than capsules dissolved in corn syrup.
conazole, and ravuconazole are examples of Although oral absorption is high, no drug was
azoles based on the triazole parent ring detected in the AH of normal horses without
structure. ocular inflammation following a single dose of
5 mg/kg itraconazole. Topical administration
Fluconazole of 1% itraconazole compounded in 30% dime-
Fluconazole has a spectrum of activity limited thyl sulfoxide (DMSO) to normal horses
primarily to yeast, such as Candida and resulted in significantly greater corneal tissue
Cryptococcus, with minimal efficacy versus fil- levels than those achieved with 1% itracona-
amentous fungal organisms. While its spec- zole without DMSO, while neither formulation
trum is more limited than that of most other produced detectable AH levels. Consistent
azoles, fluconazole exhibits an excellent phar- with its expected spectrum of activity, itracon-
macokinetic profile, as following oral adminis- azole demonstrated reasonable in vitro activity
tration to rabbits, fluconazole was detectable versus fungal isolates from horses with ocular
in the cornea, AH, vitreous, and choroid and disease in the northeastern United States, with
retina, while following topical administration overall resistance of 28% of filamentous organ-
to rabbits with and without corneal epithelial isms (11 of 40) and 11% of yeast organisms.
debridement, relatively high concentrations Importantly, of the six Fusarium isolates evalu-
were identified in both the cornea and AH. Use ated, five were resistant and one demonstrated
of fluconazole in the treatment of equine ker- intermediate susceptibility. Similarly,
atomycosis is supported by its strong pharma- Fusarium isolates from horses in the midwest-
cokinetic profile, with AH levels of ern and southern United States were signifi-
11.39 ± 2.83 μg/ml following oral administra- cantly more susceptible to natamycin than
tion (14 mg/kg once, and then 5 mg/kg q itraconazole, with Aspergillus isolates demon-
24 h × 10 days) to normal horses; however it is strating stronger susceptibility to itraconazole.
136 Ocular Pharmacology and Therapeutics

Voriconazole or RNA contained within a protein coat (cap-


Voriconazole is a newer derivative of flucona- sid), with or without a surrounding lipid enve-
zole that has a significantly improved spectrum lope. Following infection of the host cell, viral
of activity and is used to treat invasive fungal DNA or RNA replication occurs through use of
infections (i.e., candidiasis, aspergillosis). Its either virus-­specific or host cell enzymes, ulti-
in vitro activity is comparable to that of ampho- mately resulting in abundant copying of the
tericin B versus filamentous and yeast isolates viral genome. Antiviral agents pharmacologi-
from cases of human ocular disease. When cally target this viral replication cycle within
administered orally in people, it is highly bioa- the host cell, resulting in a virostatic, rather
vailable (90%). Pharmacokinetic studies of than virocidal, effect. Drugs currently used in
voriconazole in horses indicate good bioavaila- veterinary ophthalmology are nucleoside ana-
bility, with a single oral (4 mg/kg) or i.v. (1 mg/ logues, which mimic either the pyrimidine
kg) dose well tolerated and resulting in poten- (cytidine, thymidine) or purine (adenosine,
tially therapeutic maximal serum concentra- guanosine) nucleic acid building blocks to dis-
tions within 3 h of administration. Potentially rupt viral genome synthesis. Additionally,
therapeutic plasma levels were reached within l-­lysine may decrease viral replication, while
10 min following a 10 mg/kg i.v. dose and interferons (IFNs) may be used to stimulate the
within 20 min following a 10 mg/kg oral dose, host immune response targeting the virus. The
and were maintained for up to 24 h. primary indication for antiviral therapy in vet-
Additionally, likely therapeutic precorneal tear erinary ophthalmology is the treatment of feline
film levels were reached following twice daily herpesvirus-­1 (FHV-­1)-­associated ocular dis-
administration of 3 mg/kg orally for 10 days. eases (Table 3.3). Also, equine herpesvirus-­
Evaluation of in vitro activity of voriconazole ver- associated ocular diseases and more recently
sus fungal isolates from cases of equine ocular canine herpesvirus-­associated ocular disease
disease confirms the significantly greater activity may benefit from antiviral therapy. It is impor-
of voriconazole relative to that of the other tant to emphasize that the virostatic nature of
azoles. Fusarium and Aspergillus isolates from current antiviral medications as well as the abil-
horses in the midwestern and southern United ity of herpesviruses to establish latency indicates
States were consistently significantly more sus- that eradication of viral infections is not possible.
ceptible to voriconazole than to any of the azoles,
and only natamycin surpassed voriconazole in
Specific Antiviral Agents
efficacy versus Fusarium isolates. Clinical effi-
cacy has been reported with its topical adminis- Pyrimidine (Thymidine) Analogues
tration in dogs and cats with keratomycosis, and Drugs in this class include idoxuridine and tri-
with oral administration in cats with orbital fluridine, both of which are thymidine ana-
aspergillosis; however, the cats experienced logues. Following intracellular phosphorylation,
treatment-­limiting side effects (lethargy, inappe- idoxuridine competitively inhibits incorpora-
tence, azotemia, cutaneous reaction). tion of thymidine into viral DNA, resulting in a
virus that cannot effectively replicate.
Trifluridine is also phosphorylated intracellu-
larly, allowing it to inhibit thymidylate syn-
­Antiviral Agents thase, an enzyme necessary for DNA synthesis.
Both of these medications lack sufficient speci-
General Principles
ficity for viral versus host enzymes, rendering
Although the sizes and morphologies of viruses them too toxic for systemic use, and topical
are highly variable, the common basic struc- administration is generally necessary four to
ture is that of single-­ or double-­stranded DNA six times daily. While no longer commercially
­Antiviral Agent  137

Table 3.3 Summary of Selected Topically Administered Antiviral Drugs for Treatment of Feline Herpesvirus.

Antiviral drug ED50 (μM)a Formulation Other

Trifluridine 0.67 1% solution 4–6 times daily dosing Variably well


tolerated by cats
Idoxuridine 4.3–6.8 0.5% solutionb 4–6 times daily dosing Poor intraocular
penetration Well tolerated by cats
Vidarabine 21.4 3% ointment 4–6 times daily dosing No clinical trials in
cats
a
ED50, effective dose50, the in vitro concentration that effectively suppresses 50% of viral growth relative to
untreated control wells.
b
Not commercially available as an ophthalmic preparation in the United States.

available in the United States, idoxuridine can Purine Nucleoside Analogues


be compounded as a 0.1% solution, or up to a Acyclovir and its prodrug valacyclovir, ganciclo-
0.5% ointment, and is generally well tolerated vir, and penciclovir and its prodrug famciclovir
for topical administration to cats, although no are acyclic nucleoside guanosine analogues that
clinical trials in cats have been performed (see require three phosphorylation steps to become
Table 3.3). Trifluridine also has good in vitro active. While acyclovir is a valuable medication
specificity for FHV-­1, and is reported to have in the treatment of human herpetic diseases, it
good ocular bioavailability in the presence of demonstrates low in vitro efficacy versus FHV-­1
disease. and poor bioavailability following oral adminis-
tration in the cat. Repeated administration of
Pyrimidine (Cytosine) Analogue both medications was associated with systemic
Cidofovir is a cytosine analogue that requires toxicity, however, manifesting as hepatic and
two (rather than three) phosphorylation steps, renal necrosis, as well as bone marrow suppres-
both of which are catalyzed by host rather than sion. Taken together, the poor efficacy, low bio-
viral enzymes. The phosphorylated form then availability, and potential for systemic toxicities
demonstrates relatively high specificity for indicate that acyclovir and valacyclovir are of
subsequent inhibition of viral DNA polymer- limited use as systemically administered antivi-
ase. It has demonstrated strong activity versus rals in cats, and valacyclovir in particular should
FHV-­1 in vitro. A significant advantage of cido- never be used in cats.
fovir over the thymidine analogues is its clini-
cal efficacy, necessitating only twice daily Interferons
topical administration of a 0.5% solution, IFNs are glycoprotein cytokines released by
which is thought to be due to the long intracel- infected cells in response to pathogen invasion
lular half-­life of the active metabolite. that subsequently influence neighboring,
Evaluation of this twice-­daily dosing regimen uninfected cells to induce an antiviral state.
in cats experimentally infected with FHV-­1 Type I IFNs (primarily IFN-­α, IFN-­β, and IFN-ω)
demonstrated significantly reduced viral shed- share structural homology, are produced by
ding and severity of clinical signs. Cidofovir most cells in response to viral infection, and
diluted with normal saline to 0.5% solution in bind the same cell surface IFN receptor
solutions and stored in glass or plastic for up to (IFNAR1/2). Type II IFN (IFN-­γ) is considered
six months at 4, −20, or −80 °C demonstrated a more powerful immunomodulatory cytokine,
no loss in virus inhibitory activity in vitro. as it is produced by natural killer, CD4+ helper,
138 Ocular Pharmacology and Therapeutics

and CD8+ cytotoxic cells, and binds its own Endogenous PGs play an important role in the
receptor (IFNGR1/2). Type III IFNs (IFN-­λ1, initiation and maintenance of intraocular
IFN-­λ2, and IFN-­λ3) are recently classified and inflammation. PGs comprise a group of oxygen-
appear to contribute significantly to antiviral ated fatty acids with a wide range of biological
defense. IFNs influence antiviral effects within activity. PGs have several effects in the eye,
cells through inducing gene transcription, the including miosis, an initial increase and then a
products of which inhibit viral genome trans- decrease in IOP, disruption of the BAB, vasodila-
lation, lead to degradation of viral nucleic tion, iris neovascularization, and possibly cor-
acids, and stimulate innate cellular immunity. neal neovascularization. PGs are synthesized in
In vivo evaluation of the biological response the iris and ciliary body.
to rFeIFN-­ω has been evaluated utilizing
expression of Mx protein, an antiviral cellular
protein induced in response to exposure to
­Anti-­inflammatory Agents
type I IFNs. Following oral administration of
200–20 000 U rFeIFN-­ω, Mx protein was not
Corticosteroids
detected in conjunctival cells, but was detected
in white blood cells in a dose-­dependent man- Mechanism of Action
ner for 3–42 days. Corticosteroids bind to specific receptors in the
cytoplasm of cells in the iris, choroid, sclera,
L-­Lysine cornea, conjunctiva, and retina within the eye.
The amino acid l-­lysine has been demonstrated The effectiveness of corticosteroids is medi-
to interfere with viral replication, presumptively ated through their impact on both the cycloox-
through antagonism of l-­arginine, an essential ygenase and lipoxygenase pathways (Table 3.4).
component of replication. In vitro support for
this is evidenced by a study in which, following Routes of Administration
inoculation with FHV-­1, CRFK cell cultures Topical Ocular Administration
demonstrated a significant (approximately 80% Topical administration of corticosteroids is indi-
relative to control) reduction in virus titer when cated to treat anterior segment disease due to
incubated with 200 or 300 μg/ml of lysine, pro- ease of application and decreased systemic side
vided that arginine levels were restricted to 0 or effects. Selection of a particular topical steroid
2.5 μg/ml. In vivo, administration of 500 mg l-­ and the frequency of administration vary with
lysine orally twice daily to a group of random-­ the severity and location of the inflammation.
source cats, beginning 6 h prior to experimental Several factors limit the therapeutic effect of a
inoculation with FHV-­1 and continuing for the topical corticosteroid ophthalmic preparation,
subsequent three weeks, significantly lessened including corneal permeability, degree of ster-
but did not eliminate clinical signs of disease oid receptor binding, extent of ocular metabo-
relative to untreated control cats. Other studies lism of the drug, and the effect of the drug on
reveal conflicting evidence regarding the effi- the target cell. The lipophilic acetate and alco-
cacy of l-­lysine. hol corticosteroid preparations penetrate the
cornea more readily than sodium salts of the
steroid phosphate. The water-­soluble salts are
Anti-­inflammatory
generally formulated as solutions, and the more
and Immunosuppressant Drugs
lipid-­soluble derivatives are available as suspen-
Ocular inflammatory responses are mediated by sions and ointments. Prednisolone acetate 1% or
several compounds, including PGs, leukot- dexamethasone alcohol 0.1% have superior
rienes, platelet-­activating factor, neuropeptides intraocular penetration and are generally rec-
like calcitonin gene-­related peptide and sub- ommended as therapy for anterior segment
stance P, interleukins (ILs), and bradykinin. inflammation.
­Anti-­inflammatory Agent  139

Table 3.4 Corticosteroids for veterinary ophthalmology.

A. Topical Corticosteroids
Eyelid/nasolacrimal/ 1.5% hydrocortisone and 0.25–05% prednisolone recommended
conjunctival diseases Use often as antibiotic/corticosteroid combinations
Administer 2–4 times daily
Cornea/iris/ciliary body Generally stronger steroids and those with good corneal
diseases penetration recommended: 1% prednisolone acetate; 0.1%
dexamethasone alcohol; and 0.1% betamethasone
Administer 4–6 times daily
Retina/choroid/optic nerve Systemic route most important
diseases Prednisolone usually used:
Dogs: 0.5–1.0 mg/kg orally one daily (anti-­inflammatory dose);
2.2 mg/kg orally once daily (immunosuppressant)
Cats: 0.5–2.0 mg/kg orally once daily (anti-­inflammatory);
2.2–6.6 mg/kg orally once daily (immunosuppressant)
Horses: 0.5–1.0 mg/kg orally or IM once daily

B. Depot Glucocorticoids for Subconjunctival Administration

Dosage (mg/eye)

Small and
Drug Cats medium dogs Large dogs Horses
Methylprednisolone acetate 4 4–8 8–12 40
Triamcinolone acetonide 4 4–8 8–12 40
Betamethasone sodium 0.75 0.75–1.5 2 15
phosphate plus acetate
Dexamethasone acetate 0.75 0.75–1.5 2 15

Subconjunctival Injection macular edema, and proliferative diabetic


Subconjunctival injections of corticosteroids can retinopathy. In veterinary medicine, intravit-
be used as a supplement to topical and systemic real injections of corticosteroids are not com-
administration of steroids in cases of severe monly used. In a recent pilot study, there was
inflammation and in uncooperative patients. no evidence of overt toxicity from intravitreal
Corticosteroids injected into the subconjunctival vehicle-­free triamcinolone acetonide injec-
space should be well tolerated in the subconjunc- tions of 10, 20, or 40 mg in normal equine eyes
tival space as well as on the ocular surface and there were sustained drug ocular concen-
because a portion of the injected material will trations for at least three weeks after the
regurgitate through the conjunctival hole and injection.
mix with the preocular tear film. Dexamethasone’s
duration of effect is approximately one to two Systemic Administration
days while triamcinolone and betamethasone act Inflammation of the adnexa, posterior seg-
as repositol preparations and have duration of ment, optic nerve, or orbit usually requires sys-
effect up to two to three weeks (Figure 3.5). temic administration of corticosteroids in
veterinary medicine once an infectious etiology
Intravitreal Injection has been ruled out. Systemic corticosteroids
Intravitreal injections of corticosteroids are may also be used to treat anterior uveitis in con-
used in humans to treat chronic uveitis, junction with topical corticosteroid therapy.
140 Ocular Pharmacology and Therapeutics

Indications for Ocular Disease sodium phosphate suspension, or in combina-


Corticosteroids are beneficial in treating various tion with neomycin and polymyxin B or
inflammatory disorders of the adnexa and tobramycin, as either a suspension or ointment.
globe. For treatment of superficial external ocu-
lar inflammatory conditions, such as blephari- Hydrocortisone
tis, conjunctivitis, episcleritis, and nonulcerative Hydrocortisone is available in combination
keratitis, formulations of topical medications with neomycin/polymyxin B/bacitracin oph-
that do not penetrate the cornea well may be thalmic ointment. Since it does not penetrate
preferred such as topical dexamethasone the cornea well, it is appropriate and useful for
sodium phosphate 0.1%, prednisolone sodium treatment of mild ocular and eyelid surface
phosphate 1%, or hydrocortisone. When treat- inflammatory conditions.
ing intraocular inflammation, preparations that
easily penetrate the cornea are preferred such as Fluorometholone, Rimexolone,
topical prednisolone acetate 1% or dexametha- and Loteprednol
sone alcohol 0.1%. The frequency of medication A number of glucocorticoids (fluorometholone,
application should be dictated by the severity of rimexolone, and loteprednol) have been devel-
the disease condition being treated. Subcon- oped and marketed that have a lower propen-
junctival corticosteroid injections may be used sity to increase IOP than prednisolone and
for the treatment of noninfectious keratocon- dexamethasone in humans. There are no
junctivitis, anterior episcleritis or scleritis, and reports of the efficacy of these medications in
anterior uveitis. Systemic corticosteroid admin- veterinary species.
istration may be combined with either topical or
subconjunctival corticosteroids for the therapy
Side Effects
of anterior uveitis or used alone for the treat-
of Ophthalmic Corticosteroids
ment of blepharitis, extraocular polymyositis,
chorioretinitis, optic neuritis, or noninfectious Effect on Ocular Infection
orbital inflammation. Corticosteroids decrease leukocyte migration
and depress macrophage phagocytosis of
microbes. Corticosteroids can potentially acti-
Ophthalmic Corticosteroids
vate or exacerbate ocular bacterial, viral, or
Prednisolone fungal infections and are generally considered
Prednisolone is an effective anti-­inflammatory contraindicated in most ocular infections. The
agent in patients with external as well as intraoc- administration of subconjunctival betametha-
ular inflammatory conditions. It is commercially sone has been shown to cause FHV-­1-­
formulated as a 1% and 0.12% acetate suspension associated stromal keratitis in cats that have
and 1% phosphate solution. It is also available in been experimentally infected. In horses with
combination with several antibiotics. Compared fungal keratitis or stromal abscesses, the use of
with other topical ocular steroids, 1% predniso- topical corticosteroids is generally contraindi-
lone acetate is generally considered the most cated. Previous corticosteroid use was identi-
preferred and effective anti-­inflammatory agent fied in 76% of 53 equine eyes with fungal
for anterior segment inflammations. keratitis.

Dexamethasone Effects on Corneal Wound Healing


Dexamethasone has been reported to be 10-­ In vitro studies demonstrate that corticoster-
fold more potent than prednisolone. The dif- oids increase the lytic action of corneal colla-
ference in potency between dexamethasone genase, which can lead to rapid stromal
and prednisolone is somewhat obviated by the melting of corneal ulcers. As a result, topical
commercial formulations of these medica- corticosteroids are generally considered con-
tions. Dexamethasone is available as a 0.1% traindicated in the presence of corneal
­Anti-­inflammatory Agent  141

ulceration. However, systemic corticosteroids in adrenal suppression as well as histopatholog-


have little effect on the corneal healing pro- ical changes in the liver. Subconjunctival
cesses and may be used in patients with an administration of two doses of 10 mg of methyl-
active corneal ulcer and an intense anterior prednisolone acetate at an interval of 21 days
uveitis. caused suppression of adrenocorticotropic
Topical corticosteroids are routinely used hormone-­stimulated cortisol. Administration of
after intraocular surgery to reduce postopera- topical 0.1% dexamethasone ophthalmic oint-
tive inflammation. Experimental data suggest ment four times daily to one eye of adult horses
that topical corticosteroids may delay corneal resulted in detectable levels of corticosteroids in
healing by affecting corneal epithelial heal- the urine and serum.
ing rates.
Other Side Effects
Cataract Formation In humans, calcific band keratopathy has been
Steroid-­induced cataract formation, although associated with the use of topical ophthalmic
not well documented in small animals, has corticosteroids. Although this condition is not
been produced experimentally in cats by topi- reported in the veterinary literature, lipid kera-
cal administration of dexamethasone or pred- topathy is a clinically recognized condition in
nisolone. The cataracts were subcapsular small animal patients treated in the long term
opacities that occurred after at least 40 days of with topical corticosteroids. The lipid keratopa-
corticosteroid therapy. thy does not resolve after cessation of the topical
steroids. In calves receiving parenteral adminis-
Ocular Hypertension tration of dexamethasone (30 mg/kg subcutane-
Corticosteroids have been documented to ously twice daily) for an experimental purpose,
produce an increase in IOP in normal bilateral exophthalmos was observed after
humans and in patients with glaucoma. approximately 28 days of treatment. Protrusion
Human corticosteroid-­induced ocular hyper- of the globes was the result of adipose tissue
tension appears to have a genetic basis and is deposition in the retrobulbar space area.
related to a decrease in outflow facility result-
ing from an accumulation of extracellular
Nonsteroidal Anti-­inflammatory
material, resembling basement membranes,
Drugs
in the trabecular meshwork. The hyperten-
sive effect of corticosteroids has recently Mechanism of Action
been documented in Beagles with primary Nonsteroidal anti-­inflammatory drugs (NSAIDs)
open-­angle glaucoma, and in normal cats and have been widely used for their analgesic, anti-
cattle. Healthy cats treated with topical 0.1% pyretic, and anti-­inflammatory properties in
dexamethasone or 1.0% prednisolone acetate, humans and veterinary patients (Table 3.5).
as well as normal cows receiving topical 1% NSAIDs inhibit PG synthesis by inhibiting the
prednisolone acetate, manifested a signifi- cyclooxygenase enzyme that converts arachi-
cant increase in IOP within two to three donic acid to PGs (PGE2, PGD2, PGF2α, and
weeks of treatment. PGI2) and thromboxane A2. Aspirin, indo-
methacin, flurbiprofen, and possibly flunixin
Systemic Effects meglumine cause irreversible inactivation of
Suppression of the hypothalamic–hypophyseal– the enzyme, while interaction with ibuprofen
adrenal axis has been noted in dogs following is reversible. Many common NSAIDs such as
application of topical prednisolone acetate 1% aspirin, indomethacin, diclofenac, flurbipro-
four times daily for two weeks. Topical applica- fen, ketorolac, and ibuprofen are considered
tion of dexamethasone suspension 0.1% four to be nonselective COX inhibitors, which
times daily to both eyes in Beagles (average dose mean they inhibit both COX-­1 and COX-­2.
of 0.03 mg/kg of body weight/day) also resulted Deracoxib, firocoxib, meloxicam, etodolac,
142 Ocular Pharmacology and Therapeutics

Table 3.5 Nonsteroidal anti-inflammatory drugs (NSAIDS) in Veterinary Ophthalmology.

Route/agent Indications/dose

Topical: Anti-­inflammatory effects/promote pupil dilation


0.03% flurbiprofen To prevent synthesis of prostaglandins
0.1% diclofenac and breakdown of the blood-­aqueous barrier
1.0% indomethacin To prevent miosis and/or maintain mydriasis after anterior
0.5% ketorolacromethamine paracentesis and chamber during intraocular surgery
1.0% suprofen Can slow or prevent corneal vascularization

Systemic: Anti-­inflammatory effects


Flunixin megumine Dog only: 0.2 mg/kg IV immediately before cataract surgery
Horse: 0.25–1.0 mg/kg orally twice a day. Also administer
gastric protectant (Gastrogard®) 4 mg/kg
PO once daily or 2 mg/kg once daily (low dose)
Carprofen Dog only: 0.5 mg/kg orally twice a day
Phenylbutazone Horse only: 1 g IV or orally twice a day
Aspirin Horse only: 25 mg/kg orally twice a day

and carprofen are classified as selective sometimes systemic anti-­PG therapies are nec-
COX-­2 inhibitors. essary for mydriasis to occur.

Indications for Ocular Disease Ophthalmic Nonsteroidal


Topical NSAIDs have been developed to improve Anti-­inflammatory Drugs
the ocular bioavailability of these compounds Presently available topical ophthalmic NSAIDs in
and to decrease their systemic side effects. In the United States include 0.09% bromfenac, 0.1%
veterinary medicine, topical NSAIDs are most diclofenac, 0.03% flurbiprofen, 0.4% and 0.5%
commonly used to decrease intraocular inflam- ketorolac, and 0.1% nepafenac. Topical formula-
mation and to prevent intraoperative miosis dur- tions of indomethacin are commercially available
ing cataract surgery in dogs and horses. Topical only outside the United States at this time.
NSAIDs are often used in combination with
topical corticosteroids to reduce intraocular Side Effects of Ophthalmic NSAIDs
inflammation and they may allow less frequent The most common adverse effect with topical
application of topical steroids. Topical NSAIDs ophthalmic NSAIDs is transient ocular irrita-
have been demonstrated to increase IOP in dogs tion after administration of the medication.
and should be used with caution in animals that This is generally characterized by epiphora,
have ocular hypertension. blepharospasm, and conjunctival hyperemia.
Occasionally in dogs with intense iridocycli-
tis (usually after lens removal), the small pupil Effects on Ocular Infection
appears unresponsive to intensive anticholin- Topical NSAIDs should not be considered as
ergic agents (usually topical 1% atropine); this ideal substitutes for topical corticosteroids in
has been termed mydriatic-­resistant miosis, cases of infectious keratitis because of their
frozen pupil, or other terms. The massive potential negative effects on ocular inflamma-
release of endogenous PGs from within the iris tions. Corneal complications after topical NSAID
and ciliary body tissues is thought to be respon- use are relatively uncommon. In humans, super-
sible for the miosis. Intensive topical and ficial punctate keratitis, corneal infiltrates, and
­Anti-­inflammatory Agent  143

epithelial defects have been reported after use of The most common use of CSA in veterinary
these agents. Corneal neovascularization in ophthalmology medicine is for the treatment
horses with corneal ulcerations appears delayed of canine KCS, which is a presumed immune-­
or inhibited by topical NSAIDs. mediated disease of the lacrimal glands. CSA
typically increases tear production within two
Ocular Hypertension to three weeks of therapy, and after its discon-
Topical NSAIDs have not been reported to tinuation tear production can decrease within
increase IOP in humans; however, in veterinary 12–24 h. Topical CSA has been extended to
species, they have been demonstrated to increase treatment of other canine immune-­mediated
IOP in both dogs and cats. The increased IOP ophthalmic diseases, including chronic super-
associated with the use of topical NSAIDs may ficial keratitis in dogs and nictitans plasma-
be due to a reduction of AH outflow. cytic conjunctivitis. Some forms of equine
keratitis and immune-­mediated keratitis/kera-
Systemic NSAIDs touveitis have been reported to respond favora-
Systemically administered NSAIDs are used com- bly to topical CSA. Devices for sustained
monly in veterinary medicine to pretreat cataract release of CSA into intraocular tissues have
patients to inhibit intraoperative inflammation. been developed for long-­term control of
Orally administered NSAIDs are often used post- ERU. The most recent CSA slow-­release device
operatively for their analgesic and anti-­ is implanted into the suprachoroidal space
inflammatory properties after intraocular surgery. (avoiding entry into the eye) allowing constant
Side effects of systemic NSAID administration long-­term release of CSA to the uveal tissue,
include renal disease, gastrointestinal irritation while not invading the eye.
and ulceration, and inhibition of platelet func- Horses with implants had significantly fewer
tion. Recently, oral administration of etodolac in episodes of inflammation after surgery (mean
dogs has been associated with the development of 0.09 flares/month) compared to the frequency
severe KCS. In cats, systemic NSAIDs have been rate of uveitis episodes reported prior to surgery
associated with gastrointestinal ulceration, bone (0.54 uveitis episodes/month) (see Chapter 15).
marrow suppression, acute renal failure, hemor- It takes about 30–45 days after implantation of
rhage, vomiting, and diarrhea. the CSA device to obtain adequate ocular drug
levels and the duration of medication delivery is
approximately 36 months.
Immunosuppressant Drugs
Tacrolimus can be compounded into a 0.02%
CSA, tacrolimus, pimecrolimus, and rapamycin or 0.03% oil or aqueous solution or as an oint-
(sirolimus) are immunosuppressant drugs that ment. A 0.03% tacrolimus solution in olive oil
inhibit specific signal transduction pathways that applied twice daily for 14 days was safe in nor-
lead to T lymphocyte activation. CSA, a 1.2-­kDa mal dogs and gave clinical results similar to
cyclic polypeptide, was isolated from the fungus those observed with topical 2% CSA in KCS-­
Tolypocladium inflatum in 1972. Tacrolimus and affected dogs. Topical tacrolimus may be a
rapamycin are macrolide antibiotics isolated promising alternative to CSA for treatment of
from Steptomyces tsukubaensis and Streptomyces presumed autoimmune-­mediated canine KCS
hygroscopicus, respectively. CSA is currently and may be beneficial in patients that do not
available as a commercial 0.2% ophthalmic oint- respond adequately to topical CSA. Topical
ment or compounded solutions in oil at different pimecrolimus was evaluated in a pilot study
concentrations (usually 1% or 2%) for topical use. with 14 dogs with either KCS or chronic super-
In humans, a 0.05% ophthalmic emulsion, ficial keratitis (pannus). Topical treatment
Restasis®, has been approved for the treatment of with 1% pimecrolimus was effective in 10/14
chronic dry eye. Episcleral and suprachoroidal dogs in that study.
(deep scleral lamellar) CSA implants have been Superficial corneal squamous cell carcinoma
used in horses and dogs. has recently been described in 26 dogs with
144 Ocular Pharmacology and Therapeutics

chronic keratitis treated in the long term with factors, most notably the desired duration of
topical CSA. There may be a potential associa- mydriasis and whether or not cycloplegia is
tion between chronic corneal inflammation required (Table 3.6). While cycloplegia is
and topical immunosuppressive therapy in the important to refraction in humans and pri-
development of corneal squamous cell carci- mates, refraction by retinoscopy is reportedly
nomas in dogs. unaffected by cycloplegia in dogs.
Mydriatic agents achieve pupillary dilation by
either paralysis of the pupillary sphincter (e.g.,
­ ydriatics/Cycloplegics,
M cholinergic antagonists) or stimulation of the
Anesthetics, and Tear iris dilator muscle (e.g., sympathomimetics).
The iridal sphincter muscle is generally consid-
Substitutes and Stimulators
ered stronger that the dilator muscles. Generally
speaking, drugs that induce pupillary sphincter
Mydriatics/Cycloplegics
paralysis also provide some variable degree of
Pharmacological agents used to achieve pupil- cycloplegia, while those that stimulate the iris
lary dilation and/or relieve ciliary spasm have dilator musculature do not.
a variety of ophthalmic diagnostic and thera- With regard to speed of onset, completeness
peutic applications. The agent of choice for of effect, and duration of action, the
any given situation is dictated by a number of effects of the available mydriatic/cycloplegic

Table 3.6 A summary of the reported mydriatic effects of some commonly utilized mydriatic/cycloplegics
in dogs, cats, and horses.

Time until maximal Duration of


Drug Species dilation (hours) action (hours) Extent of dilation

1% tropicamide Dog 0.5 12 Maximal


Cat 0.75 8–9 Maximal
Horse 5 12 Maximal
1% atropine Dog 1 96–120 Maximal
Cat 1 60 Maximal
Horse 10–48 132 Maximal
2% homatropine Dog 0.75 48 Moderate
Cat 0.75 7 Moderate
Horse 3 8 Moderate
1% cyclopentolate Dog 0.75 60 Maximal
Cat 0.5 66 Maximal
Horse 12 96 Maximal
0.25% scopalamine Dog 0.75 96–120 Maximal
a
Cat NA NA NA
Horse 4 108 Maximal
10% phenylephrine Dog 2 12–18 Maximal
b
Cat —­ – –
Horse —­ – –
a
Information not available.
b
Indicates no significant effect.
­Mydriatics/Cycloplegics, Anesthetics, and Tear Substitutes and Stimulator  145

Table 3.7 Commercially available corticosteroid Salivation is seen frequently in cats, puppies,
agents for subconjunctival injection. and foals and vomiting occasionally following
topical administration of anticholinergics, par-
Drug Suggested dose (mg) ticularly in cats, presumably due to their bitter
taste. Systemic gastrointestinal side effects are
Betamethasone 1–3
a particular concern in horses, due to their
Dexamethasone 0.5–1
potential for inducing colic.
Methylprednisolone 4–8
acetate
Tropicamide
Triamcinolone acetonide 4–12
Tropicamide is available as a 0.5% and 1.0%
solution. Due to its rapid onset, completeness
of mydriasis, and relatively short duration of
medications vary by species (Table 3.7). In action, it is well suited for diagnostic mydria-
addition, ophthalmic disease states (e.g., uvei- sis. In the dog, complete mydriasis is produced
tis) generally prolong onset and shorten dura- within 30 min and effects may begin to wane as
tion of mydriatics. soon as 2 h following application. In cats,
mydriasis from a single application of 0.5%
Cholinergic Antagonists tropicamide begins within 15 min, becomes
Cholinergic antagonists act through a reversi- maximal within 1–2 h, and begins to decline
ble blockade of cholinergic receptors in smooth within 4 h. In the horse, 0.5–1% tropicamide
muscle and secretory glands. Cholinergic has a similar rapid onset, with reasonably com-
antagonists are used clinically to facilitate lens plete mydriasis occurring within 15–30 min,
and posterior segment visualization during maximal mydriasis within 1–5 h, and effects
ophthalmic examination and intraocular sur- lasting 5–12 h. Pupillary dilation in the horse
gery. They also have therapeutic indications in affects more of the dorsal and ventral iris than
the management of iridocyclitis. The two most the nasal and temporal iris. A single instilla-
frequently used cholinergic antagonist mydri- tion of tropicamide does not cause a reduction
atics are tropicamide (0.5% and 1.0%) for the in STT values in normal nor fellow nontreated
ophthalmic exam and atropine (usually 1%). eyes dogs, but causes a transient STT decline in
Other available but infrequently used choliner- cats and horses.
gic mydriatics are homatropine, scopolamine,
and cyclopentolate. Atropine
Mydriatic agents should be avoided in pri- Atropine sulfate is available as a 0.5–2.0% solu-
mary glaucoma cases, where pupillary dilation tion and a 1% ointment for nearly a century.
may cause a severe rise in IOP. Statistically sig- Due to its potent mydriatic and cycloplegic
nificant IOP elevations have been documented effects and long duration of action, atropine is
in cats following topical anticholinergic appli- often the iridoplegic and cycloplegic agent of
cation. Studies in dogs and horses have choice in cases of iridocyclitis. Onset and dura-
reported variable IOP effects related to topical tion of action vary somewhat by species and
mydriatic application. Dilation of the pupil iridal melanin binding. Blue irides are most
may allow an unstable lens to migrate anteri- sensitive to topical atropine but show a shorter
orly, potentially resulting in pupillary block duration of its effect. Topical atropine in cats,
glaucoma. Topical application of some anticho- dogs, and foals are common and include pro-
linergic agents can occasionally induce a fuse salivation and occasional vomiting (asso-
reduction in IOP by substantial reduction in ciated with the bitter taste of the drug).
aqueous tear production, increasing uveoscle- Delirium has been noted occasionally in older
ral or nonconventional aqueous outflow. dogs, where it is usually manifest as
146 Ocular Pharmacology and Therapeutics

compulsive circling and resolves when the mydriatic in the cat. Intracameral epinephrine is
drug is discontinued. commonly used to help achieve maximal pupil-
lary dilation during intraocular surgery, where it
Sympathomimetics is instilled by itself as a dilute solution (1:10 000)
Sympathomimetic effects on the iris include or added to irrigating fluids (1:1 000 000).
direct stimulation of alpha-­adrenergic recep-
tors in the iris dilator musculature. Indirect-­Acting Sympathomimetics
Sympathomimetics are useful in potentiating Cocaine and hydroxyamphetamine are
the effects of other mydriatic medications in indirect-­acting sympathomimetic agents with
some species and to provide adjunct mydriasis clinical utility predominantly related to the
and vasoconstriction during ocular surgery. localization of nerve lesions causing ocular
Because their induced mydriasis is only par- sympathetic denervation (Horner’s syndrome).
tial, they are not used as the sole mydriatic in Cocaine exerts sympathomimetic activity by
animals. Adrenergic agents of low concentra- preventing norepinephrine reuptake at the
tions are also useful in the diagnosis and lesion nerve terminus, resulting in a buildup of nor-
localization of ocular sympathetic denervation epinephrine at the synapse.
(Horner’s syndrome).
Side effects following ophthalmic applica-
Local and Regional Anesthetics
tion of sympathomimetic medications are rare.
Arterial hypertension and cardiac arrhythmia Pertinent routes of administration include top-
have been described in clinical cases of dogs ical application and intracameral, intravenous,
and cats receiving topical ophthalmic phenyle- and regional injection (Table 3.8) . All local
phrine in preparation for ocular surgery. anesthetics act by temporarily impeding
Topical administration of 10% phenylephrine sodium ion entrance to the axon interior,
in research dogs elicited a dose-­dependent thereby preventing nerve depolarization.
arterial hypertensive response and associated
bradycardia. Topical
Topical anesthetics facilitate many veterinary
Phenylephrine ophthalmic diagnostic and therapeutic proce-
Ophthalmic phenylephrine hydrochloride is dures, including tonometry, corneal and con-
available in 2.5% and 10% solutions. A direct-­ junctival scrapings, corneal suture and foreign
acting alpha-­1 adrenergic agonist, phenyle- body removal, nasolacrimal canalicular
phrine, causes local ocular effects of moderate manipulations, and intracameral injection.
mydriasis and conjunctival vasoconstriction Topical anesthetics are sometimes employed in
following topical ophthalmic administration. a modification of STT I to investigate basal tear
It is commonly used in conjunction with other production (STT II), wherein the anesthetic
cholinergic medications to maximize pupillary causes a substantial reduction in total (basal
dilation for diagnostic and therapeutic pur- and reflex) STT values. Due to their toxic
poses and alone to help localize and treat the effects on corneal epithelium, topical anesthet-
site of sympathetic denervation in Horner’s ics should not ever be used as therapeutic
syndrome. agents. Topical anesthetics have demonstrated
antimicrobial (preservatives) activity, so, where
Epinephrine applicable, corneoconjunctival cultures should
Applied topically, 0.1% epinephrine is an ineffec- be obtained prior to applying these agents.
tive mydriatic, but at 1–2% concentrations Intracameral anesthetics without preservatives
incomplete mydriasis of short duration occurs. have been used prior to cataract surgery in
Topical 2% epinephrine is an ineffective humans and animals.
­Mydriatics/Cycloplegics, Anesthetics, and Tear Substitutes and Stimulator  147

Table 3.8 Topical and local/injectable anesthetics induced by topical ophthalmic proparacaine is
for veterinary ophthalmology. approximately 25 min.

Topical: Administer 1 to 2 drops /eye.


Tetracaine
Produce surface anesthesia of the conjunctiva and
cornea within 10-­20 seconds and for a duration
Tetracaine is available as an ophthalmic oint-
15-­20 minutes. Multiple drops may increase ment and solution and is an effective topical
duration but not depth within the ocular tissues. anesthetic. It tends to be more irritating com-
Less effective in inflamed eyes probably because of pared to topical proparacaine. Ocular sensitiv-
edema and limited penetration.
ity manifest by symptoms of acute conjunctival
May cause local irritation, corneal epithelial
toxicity, and reduce short-­term tear production by hyperemia, chemosis, and nictitans protrusion
up to 50%. Generally avoid before bacterial has been reported in dogs following topical
culturing of the cornea and conjunctiva, if possible. application, but a recent report suggests that
Use only for diagnostics. Not to be used for topical ophthalmic tetracaine is well tolerated
therapeutic analgesia as they may delay corneal in the horse. It is useful when cannulating the
wound healing.
distal nasolacrimal duct in horses.
Tetracaine (0.5%) More irritating (usually
conjunctival hyperemia) than proparacaine.
Proparacaine (0.5%) Intracameral
Oxybuprocaine (0.4%) – also called benoxinate Intracameral anesthetics are now commonly
(may be found in combined with fluorescein employed as an adjunct method of pain con-
sodium) trol in humans undergoing cataract extraction
Local/injectable: Use for auriculopalpebral [1 ml surgery, with an additional benefit of provision
(small animals) to 5 ml (horse and cow)] and
retrobulbar nerve blocks (10-­30 ml for horse and of mydriasis. In dogs, intracameral administra-
cow). Take care to calculate and avoid toxic doses, tion of 0.1 ml 1% and 2% preservative-­free lido-
particularly in small or susceptible patients (e.g. caine caused no clinically detectable adverse
cats). effects on corneal endothelial density or mor-
The addition of 1:200,000 epinephrine prolongs phology, corneal thickness, or IOP.
anesthetic action. Addition of hyaluronidase
(15,000 IU/100 ml) increases local tissue infiltration
by the local anesthetic. Regional Injection
Lidocaine Regional injection of anesthetic agents may be
Mepivacaine applied to achieve eyelid akinesia (via auricu-
Bupivacaine (longer acting) lopalpebral nerve block), local analgesia
through local infiltration/line blocks, or globe
akinesia and analgesia via peribulbar/retrobul-
Proparacaine bar injection. The local anesthetic agents with
Available as a 0.5% solution, proparacaine the widest ophthalmic application include
hydrochloride is a well-­tolerated and effective lidocaine and bupivacaine. Lidocaine 2%
topical ophthalmic anesthetic. In multiple-­dose appears to be the most popular local anesthetic
droptainers, proparacaine should be refrigerated used for auriculopalpebral nerve block in ani-
after its initial use. In dogs, using Cochet–Bonnet mals. In domestic animal species, retrobulbar
esthesiometry as a measurement tool, a single anesthetic block techniques have been
application of topical proparacaine results in a described in cattle, horses, and dogs.
significant anesthetic effect lasting 45 min, with Complications of retrobulbar nerve block are
maximal effect lasting approximately 15 min. uncommonly reported in companion animals.
Application of a second drop can extend the
detectable duration of effect to 55 min, but not Intravenous
the depth within the tissues. In cats and horses, Intravenous lidocaine has been examined as an
the duration of measurable corneal anesthesia adjunct to general anesthesia for veterinary
148 Ocular Pharmacology and Therapeutics

ophthalmic application, where systemic than dogs with STT values of 0–2 mm/min,
­lidocaine infusion has been shown to be as effec- presumably due to more extensive and
tive as morphine in provision of intraoperative ­irreversible lacrimal acinar destruction in the
analgesia during phacoemulsification in dogs. latter group. The primary side effect of topical
CSA administration is ocular irritation, which
occurs in a proportion of treated dogs and
Tear Substitutes and Stimulators
often improves with continued treatment and
Tear Substitutes resolution of disease. Often topical antibiotics
Tear replacement solutions and ointments are or antibiotics combined with corticosteroids
widely used in the management of quantita- (usually hydrocortisone) are also administered
tive and qualitative tear film disorders in ani- for the concurrent secondary bacterial
mals and humans, the most common of these infection.
being canine immune-­mediated KCS. Tear While topical CSA has long been the treat-
substitutes serve a host of purposes in these ment of choice for dogs with immune-­mediated
diseases, the most important being provision KCS, other calcineurin inhibitors have been
of lubrication and improving comfort levels in documented as effective therapeutic agents.
affected animals. The recommended frequency Topical 0.02% tacrolimus has been shown to sig-
of application depends upon the agent used nificantly increase tear production and improve
and severity of disease. Common agents clinical signs in dogs with naturally occurring
included in tear replacement solutions include KCS, including some animals that were nonre-
polyvinyl alcohol, cellulose polymers (e.g., sponsive to topical CSA treatment. While clini-
methylcellulose, carboxymethylcellulose, and cal use of pimecrolimus does not appear as
hydroxypropyl methylcellulose), polyethylene widespread as that of tacrolimus as a CSA alter-
glycol, dextran, polyvinylpyrrolidone, and native, two studies evaluating it for the treat-
hyaluronate. ment of canine KCS have been reported. Topical
calcineurin inhibitors are indispensable in the
Tear Stimulators management of canine KCS and other corneal
Calcineurin Inhibitors – Cyclosporine, Tacrolimus, diseases, but some concerns exist regarding
and Pimecrolimus their carcinogenic potential.
CSA, a naturally occurring fungal metabolite,
exhibits immunosuppressive mechanisms Pilocarpine
related to the binding of nuclear proteins Topical and oral pilocarpine, a muscarinic cho-
required for initiation of T-­cell activation, pre- linergic agonist, have long been recommended
venting T-­cell production of specific inflam- for the management of neurogenic KCS, but
matory cytokines such as IL-­2 and IL-­4 and controlled studies involving KCS-­affected ani-
thereby disrupting immune-­mediated pro- mals are lacking. Applied topically, pilocarpine
cesses. Because of its highly specific inhibition produces limited to no detectable effect on tear
of T-­cell activation, CSA has been used to treat production in normal dogs; the miotic effect
a number of immune-­mediated ocular disor- can also decrease vision if the cornea is
ders in animals, including KCS. pigmented.
Early studies using a 1–2% solution of CSA Oral pilocarpine has been described as effi-
in an oil base and later studies using the 0.2% cacious in a case series of normal and KCS-­
commercial ointment demonstrated signifi- affected animals, but signs of systemic toxicity
cant improvement in aqueous tear production (e.g., salivation, vomiting inappropriate defe-
and clinical signs in dogs with KCS. Increased cation, or diarrhea) are common with this
aqueous tear production is more likely to result route of administration. If oral pilocarpine
in dogs with initial STT values >2 mm/min therapy is considered, the pilocarpine dose
­Mydriatics/Cycloplegics, Anesthetics, and Tear Substitutes and Stimulator  149

should be adjusted to cause limited salivation Therapy for the glaucomas in humans has
but increased tear formation. Pilocarpine changed in the past 50+ years as new drugs
remains the most viable treatment in dogs with became available with greater reductions in
neurogenic KCS wherein loss of parasympa- IOP and fewer side effects. In the 1960s, the
thetic innervation is the presumed cause of antiglaucoma treatments included topical
impaired lacrimal secretion. miotics (most often pilocarpine), epinephrine
supplements, and systemic CAIs. In the 1970s,
topical timolol and other beta-­blockers became
Drugs That Affect Aqueous Humor
available, but caused infrequent cardiac and
Dynamics and Intraocular Pressure
pulmonary side effects, Because of infrequent
The primary and secondary glaucomas in ani- but serious systemic side effects, in the 1980s
mals represent a group of ocular diseases in and 1990s, topical CAIs replaced the systemic
which the major risk factors are altered AH CIAs. Then in the 1990s and into the next cen-
dynamics and elevated IOP. The changes sec- tury, topical PGs with their greater reductions
ondary to the altered AH dynamics and elevated in IOP, no miosis, and fewer side effects
IOP affect the entire globe and its tissues, but replaced the miotics nearly completely. Today,
tend to target the vital retinal ganglion cells, human glaucoma patients are usually treated
optic nerve head, and subsequently vision. This with sole or combinations of PGs, topical CAI,
group of drugs consists of several classes, each and beta-­blockers.
acting in specific mechanisms, and includes the It is important to note the predominant type
parasympathomimetics or cholinomimetics, of glaucoma in humans in most of the world is
CAIs (Table 3.9), and the intravenous and oral primary open-­angle glaucoma; in Asian coun-
osmotic agents (also called hyperosmotic tries in humans and in dogs in the entire world,
agents) (Table 3.10). As the primary glaucomas the most frequent type of primary glaucoma is
tend to progress in humans and animals, single primary angle closure glaucoma, which is
drug regimens eventually become combina- more difficult to control and often refractory to
tions of these drugs. most medical therapies.

Table 3.9 Systemic carbonic anhydrase inhibitors (mg/kg): Single-­dose studies in dogs.

Effects on Intraocular Pressure (h)

Recommended dosage Mean onset Maximum Decrease Duration

Acetazolamide
10 1 7 1 8+
Dichlophenamide
5 1 8 15 8+
10 1 3 24 8
Ethoxzolamide
5 1 5 17 8
7.5 1 2 20 8+
Methazolamide
5 1 6 28 8+
7.5 1 7 29 8+
150 Ocular Pharmacology and Therapeutics

Table 3.10 Hyperosmotics for veterinary there is the potential for modulation of outflow
ophthalmology. facility by the cholinergic nervous system.

Mannitol 1–2 g/kg IV over 10–20 min


In the dog the IOP begins to
decrease 0.5 h post
Direct-­Acting Parasympathomimetics
administration and lasts for at Pilocarpine is a natural alkaloid obtained from
least 5.5 h Considerable diuresis the leaves of South African shrubs of the genus
may result Pilocarpus. The drug is used as a nitrate or a
Caution or avoid in older hydrochloride and is available in concentrations
patients with cardiovascular
diseases of 0.5–8%, in methylcellulose or polyvinyl alco-
hol vehicles. Most commercial pilocarpine eye
Glycerin 1–2 g/kg PO
drops are in solutions with a pH range of 4.5–5.5,
In the dog the IOP begins to
decline 1.0 h post ingestion and to preserve the drug from hydrolysis, but cause
remains low for 10 h Frequently the drug to be irritating immediately after instil-
vomiting post administration lation. When the topical pilocarpine’s vehicle is
(solution’s taste, temperature,
adjusted at pH 7, drug concentrations at 0.25%
and dose are important) Avoid in
diabetic patients as increases and 0.5% are as effective in lowering IOP as pilo-
blood glucose levels Limited carpine concentrations of 2% and 4% without
diuresis local irritation. Pilocarpine hydrochloride 4% in
a high-­viscosity acrylic gel has been introduced
to prolong drug–eye contact time. Studies in
Parasympathomimetics or
glaucomatous (open-­angle) and normotensive
Cholinomimetics
Beagles indicate that a single instillation of
Parasympathomimetics or cholinomimetics 0.5–8.0% pilocarpine hydrochloride reduces IOP
produce biological responses similar to those of by 30–40% for at least 6 h. In these animals, a
acetylcholine; these agents are divided accord- single drop instillation of pilocarpine (1%, 2%, or
ing their mechanism of action as direct acting 4%) increased the coefficient of tonographic out-
and indirect acting. Drugs in the former class flow facility from 0.33 μl/min/mmHg prior to
stimulate cholinergic receptors directly, while treatment up to 0. 61 μl/min/mmHg after treat-
drugs in the latter class are inhibitors of acetyl- ment in normal eyes and from 0.15 μl/min/
cholinesterase, permitting acetylcholine to mmHg prior to treatment up to 0.38 μl/min/
accumulate at the cholinoreceptive sites. Topical mmHg after treatment in glaucomatous eyes.
application of a parasympathomimetic com- The combination of 1% epinephrine and pilocar-
pound on the eye results in miosis and lowering pine hydrochloride (1%, 2%, 3%, 4%, and 6%)
of IOP. In human and nonhuman primate eyes, produced a significant IOP-­lowering effect in
contraction of the longitudinal fibers of the cili- glaucomatous (open-­angle) and normotensive
ary muscle with widening of the scleral spur is Beagles. Following a single instillation of these
the likely mechanism by which parasympatho- combinations, the drop in IOP lasted for at least
mimetics decrease resistance of AH passage 8 h and was not dose related.
through the conventional outflow pathways. In In normotensive mares, once-­daily or twice-­
small animals, the contribution that contraction daily topical application of 2% pilocarpine
of ciliary muscle makes on aqueous removal hydrochloride was not associated with signifi-
has not been determined, but is probably the cant decrease in both IOP and vertical pupil
same. Nevertheless, a cholinergic activity has size. The lack of pharmacological effect of
been identified in the ciliary body musculature ­pilocarpine on IOP was attributed most likely
of the canine eye (decreased tonometric and by a decrease in uveoscleral (nonconventional)
tonographic measurements), indicating that outflow resulting from ciliary muscle
­Mydriatics/Cycloplegics, Anesthetics, and Tear Substitutes and Stimulator  151

contraction as well as the dilution of the drug Clinical Use


in the large equine tear volume. The parasympathomimetic drugs have been
Carbachol is the carbamyl ester of choline. largely replaced by the PGs for the long-­term
Because the drug is not lipid soluble at any pH treatment of open-­angle glaucoma in the dog in
and penetrates the intact corneal epithelium the last decade. Parasympathomimetic agents
poorly, it must be combined with a surfactant, should be avoided in secondary glaucoma asso-
such as benzalkonium chloride, to facilitate its ciated with iridocyclitis, and used with caution
penetration through the corneal epithelium. in dogs with subluxated or luxated lens, because
Carbachol is stable in solution and is available the miosis predisposes to synechia formation
for topical use in concentrations of 0.75–3%. It and may induce a pupillary block, respectively.
was been investigated in dogs, but, as in In a study to determine the ability of prophy-
humans, not frequently used in animals. In lactic antiglaucoma treatment to prevent or
one report, 0.01% solution injected into the delay onset of primary glaucoma in the second
anterior chamber of dogs at the end of cataract eye of dogs with unilateral closed-­angle glau-
surgery was found to prevent the postoperative coma, a combination of 0.25% demecarium
increase in IOP associated with phacoemulsifi- bromide and a topical corticosteroid (DB/GB)
cation, but further confirmed by an investiga- was compared to topical 0.5% betaxolol in a
tion in dogs treated with intracameral multicenter clinical trial. Untreated control
administration of 0.3 ml of 0.01% carbachol eyes developed glaucoma significantly sooner
immediately after phacoemulsification. (median eight months) than eyes treated with
either betaxolol (median 30.7 months) or DB/
Indirect-­Acting Parasympathomimetics GB (median 31 months). Although both treat-
The anticholinesterases are divided into the car- ment protocols similarly delayed the onset of
bamate inhibitors, which bind to the acetylcho- glaucoma in the fellow eye, DB/GB would be
linesterase in a reversible manner, and the preferable to betaxolol in preventing closed-­
organophosphorus inhibitors, which irreversi- angle glaucoma because of less frequent dosing.
bly inhibit the enzyme by forming a stable com-
plex. Demecarium bromide is a potent carbamate Side Effects
inhibitor, no longer commercially available, Because of the low pH (4.5–5.5) of its ophthal-
which can be compounded in 0.125% and 0.25% mic solutions, pilocarpine may cause local irri-
solutions for veterinary use. Investigations using tation manifested by blepharospasm, prolapsed
single-­drop application of either 0.125% or 0.25% nictitans, epiphora, and conjunctival hypere-
topical demecarium bromide and conducted in mia, which are observed within the first 15 min
normal and glaucomatous (open-­angle) Beagles and may last for up to 6 h. Use of a special
revealed that both formulations induce long-­ droptainer with a buffer system in its tip to
term miosis (up to 77 h) and IOP-­lowering effect adjust the pH of the pilocarpine solution to a
that lasts up to 55 h. level close to the physiological pH in 1% and 2%
Echothiophate iodide (or phospholine pilocarpine solutions showed excellent phar-
iodide) is another long-­acting organophospho- macological effects determined by miosis and
rus compound, available in 0.03%, 0.125%, and ocular hypotension, and were well tolerated.
0.25% solutions. The refrigerated solution An experimental investigation in dogs dem-
remains stable for at least one month after onstrated that miosis and increased flare
reconstitution. Instillation of one drop of caused by topical pilocarpine were inhibited by
echothiophate iodide 0.125% or 0.25% results both proparacaine and NSAIDs, such as flurbi-
in decrease in IOP of about 10 and 13 mmHg in profen, suprofen, and diclofenac, while IOP
normotensive and glaucomatous (open-­angle) was decreased only in proparacaine-­treated
Beagle eyes, respectively. eyes and increased in NSAID-­treated eyes.
152 Ocular Pharmacology and Therapeutics

Drugs Acting on Adrenoceptors apraclonidine-­treated eyes showed mean IOP


Drugs that stimulate or block the activity of the decrease of 4.8 mmHg (24%) 6 h after treat-
ocular sympathetic nervous system may be ment. Mydriasis occurred in 29% of the treated
used to lower IOP (Table 3.8). canine eyes and at the opposite pupillary diam-
eter was reduced a mean 46% in the treated
Epinephrine and Dipivefrin feline eyes. Reduction in heart rate was more
Epinephrine, or adrenaline, is classified as a non- marked in cats than in dogs and undesirable
specific adrenergic agonist that stimulates α and gastrointestinal effects, such as salivation and
β types of membrane receptors. Dipivefrin, or vomiting, occurred in most cats. Thus, it
dipivalyl epinephrine, is an epinephrine prodrug appears that apraclonidine is not a first-­line
produced by the addition of two pivalic acid antiglaucomatous agent in the dog and is too
groups to the parent compound. The lipophilic toxic to be used in the cat.
prodrug penetrates the corneal epithelium bar- Brimonidine tartrate, a highly selective α2-­
rier, where it is converted by esterases (acetylcho- agonist, has been introduced for treating acute
linesterase, cholinesterase, and arylesterase) to and chronic elevations of IOP in humans.
its parent drug, epinephrine, which is absorbed Current data indicate that brimonidine reduces
in the anterior segment. Epinephrine is believed IOP in human eyes by a dual mechanism,
to lower IOP by a reduction in the formation of decreasing aqueous inflow and increasing uve-
AH and an increase in aqueous outflow. oscleral outflow. Ocular effects of single and
Concentrations of 1% and 2% topical epineph- multiple doses of topical 0.2% brimonidine in
rine were effective in reducing IOP in glaucoma- glaucomatous Beagles indicated that a trend to
tous (open-­angle) and normotensive Beagles. In reduction in IOP was observed but not at statis-
these animals, the 0.5% solution of dipivefrin tical significance. As a result, the authors
manifested hypotensive and mydriatic effects advised to use brimonidine as additive therapy
similar to those of the 2% solution of epineph- and not as monotherapy in glaucomatous
rine. Topical epinephrine or dipivefrin, alone or dogs. Side effects observed with brimonidine
in combination with other antiglaucomatous treatment in dogs include miosis and decrease
drugs such as direct-­acting parasympathomimet- in heart.
ics, β-­blockers, and CAIs, has its main indication
in the management of open-­angle glaucoma. Beta-­Adrenergic Antagonists (Beta-­Blockers)
Topical β-­blockers are one of the most widely
α2-­Adrenergic Agonists used medications for the control of ocular
The mechanism by which α2-­adrenergic ago- hypertension in humans, but have limited IOP
nists lower IOP is not fully understood. It effects in animals necessitating their use in
appears that α2-­adrenergic agonists most likely combination with other drugs. Since the timo-
decrease AH formation by interfering with lol was first marketed in 1978, levobunolol,
presynaptic (nerves) and postsynaptic (non- betaxolol, metipranolol, and more recently
pigmented epithelial cells) α2-­adrenoceptors at carteolol have also been released as antiglau-
the sympathetic nerve–ciliary body junction. coma medications. All but betaxolol are non-
Apraclonidine (p-­aminoclonidine), a deriva- specific β-­blocking agents (i.e., they block both
tive of clonidine with comparable IOP-­ β1 and β2 receptors). Betaxolol is a β1-­selective
lowering effect and minimal cardiovascular ophthalmic β-­blocker. Many investigations
effects, has been developed for use in humans. have convincingly demonstrated that topical
It is available as a topical 0.5% solution. Single β-­blockers reduce IOP by decreasing formation
topical administration of 0.5% apraclonidine in of AH. In cat eyes, the rate of AH formation is
canine eyes resulted in a 3.0 mmHg (16%) IOP reduced 28%, 56%, and 71% by 0.005%, 0.025%,
decrease 8 h after treatment. In the cat, and 0.15% intracamerally injected timolol
­Mydriatics/Cycloplegics, Anesthetics, and Tear Substitutes and Stimulator  153

solution, respectively. Topical timolol is availa- the introduction of acetazolamide. Methazola-


ble as a 0.25% and 0.50% solution of the maleate mide and dichlorphenamide were released
salt. In the United States, the drug is also sup- subsequently. These agents have been widely
plied as 0.25% and 0.50% hemihydrate salts, used ever since, but as their clinical usefulness
which have an ocular hypotensive effect simi- is limited by frequent various systemic side
lar to that of the maleate salt in humans. In effects, topical CAIs have been developed (Fig-
1993, timolol maleate became also available in ure 3.6 and Table 3.9).
an anionic heteropolysaccharide gellan gum
(Gelrite), which gels in contact with the cati- Mechanism of Action
ons in the tear fluid. Diverging results have The nonpigmented ciliary body epithelium
been obtained in normotensive dogs after sin- contains enzyme systems, such as Na,
gle and repeated instillation of 0.5% timolol K-­ATPase and carbonic anhydrase, that are
maleate. In an early investigation, a mean involved in AH formation. Carbonic anhydrase
reduction in IOP of 2.5 mmHg (16%) was is a ubiquitous enzyme for which seven isoen-
observed within 2–4 h postdosing, while in two zymes have been identified. CA I, CA II, and
other reports the 0.25% and 0.5% timolol for- CA III are located in the cytosol, CA IV is
mulations were found ineffective at reducing membrane bound, CA V is present in mito-
IOP in normal dogs. The effect of topical appli- chondria, and CA VI and CA VII are only
cation of timolol on IOP has been evaluated in found in salivary glands. Only CA II, CA III,
mares with normotensive eyes. A significant and CA IV are present in significant amounts
mean decrease of approximately 4–5 mmHg in pigmented and nonpigmented ciliary body
was observed 8 h after single-­dose application, epithelial cells to catalyze the reversible hydra-
and the pressure-­lowering effect was present tion of carbon dioxide. AH formation depends
throughout the five-­day multiple-­dose study on the production of bicarbonate (HCO3−)
with a maximum reduction in IOP of 27%. from CA II, the isoenzyme found in the non-
In people, topical β-­blockers are contraindi- pigmented ciliary body epithelium (Figure 3.5).
cated in patients with severe heart failure and Competition of the sulfonamide group with
bronchial asthma due to their potential cardio- carbonic acid for its site on carbonic
pulmonary adverse effects resulting from sys-
temic absorption. Significant decrease in pulse Pigmented Cell Unpigmented Cell
rate was observed in normotensive and glauco-
Carbonic anhydrase
matous Beagles treated with topical timolol at
H+ H+ + HCO3– ↔ H2O + CO2
concentrations ranging from 2% to 8%. A con-
Na+ Na+
tralateral effect on IOP and pupillary diameter
K+
was also identified in the nontreated eyes Cl–

when timolol was topically given to dogs and


cats. To prevent occurrence of deleterious car- Ultrafiltrate Cl–
Na+
diovascular effects secondary to systemic HCO3–
absorption, use of 0.25% timolol in cats as well
as dogs weighting less than 20 lb and 0.5% tim- Osmotic
olol in dogs with body weight above 25 lb is water
flux
recommended.

Carbonic Anhydrase Inhibitors


CAIs that belong to the class of nonbacterio-
Figure 3.6 Contribution of carbonic anhydrase to
static sulfonamide-­related compounds were AH formation in the pigmented and nonpigmented
used in ophthalmology as early as 1954 with ciliary epithelium.
154 Ocular Pharmacology and Therapeutics

anhydrase, to make it inactive, is the basis of IOP was accounted for by a mean 28% reduc-
the pharmacological action of these drugs. It is tion in AH formation. In a study of the sys-
known that 98% inhibition of CA II must be temic CAIs in normal and glaucomatous dogs,
achieved in ciliary body epithelium by sys- results suggested that methazolamide
temic or topical inhibitors for full IOP decreases IOP at dosage levels lower than
reduction. acetazolamide, dichlorphenamide, and ethox-
Although systemic CAIs are diuretics, it is zolamide. In glaucomatous dogs, the IOP-­
believed that their ocular hypotensive effect lowering effect of oral methazolamide (5 mg/
does not depend on diuresis. There is, how- kg twice daily) was comparable to that achieved
ever, some indication that the systemic acido- with topical dorzolamide instilled twice of
sis induced by these agents also inhibits AH three times daily. Systemic CAIs in cats are
formation and enhances their pressure-­ generally poorly tolerated and usually used in
lowering effect. In addition to their IOP-­ the short term (a few days).
lowering effect, CAIs have also been shown to
affect the ocular circulation. Topical Carbonic Anhydrase Inhibitors
Systemic complications associated with
Systemic Carbonic Anhydrase Inhibitors chronic use of oral CAIs in humans inspired
Acetazolamide, the first drug in this group to many attempts at developing formulations that
be synthesized, can be administered either would allow for topical administration of
orally or intravenously. It is supplied in tablets CAIs. Dorzolamide was the first of these drugs
of 125 and 500 mg as well as in time-­release to be marketed in 1995, and brinzolamide was
capsules of 500 mg. A single oral administra- launched on the market a few years later.
tion of a dose ranging from 10 to 75 mg/kg sig- Dorzolamide and brinzolamide are most
nificantly lowers IOP in normotensive and potent against CA II, with less activity against
glaucomatous Beagles for at least 8 h. A dosage CA IV. Experimental data in rabbits indicate
of 4–8 mg/kg two to three times daily is usually that topical dorzolamide and brinzolamide
recommended for treatment of canine glau- readily penetrate the eye by both the corneal
coma. In the cat, doses ranging from 10 to and scleral routes. In healthy dogs, administra-
25 mg/kg are effective in lowering the IOP in tion of a single dose of 2% dorzolamide was
glaucomatous animals. The hypotensive effect associated with a mean reduction in IOP of
lasts about 5 h. Intravenous acetazolamide at a 3.1 mmHg (18%) from 30 min to 6 h after treat-
dose of 5–10 mg/kg is useful as adjunctive ther- ment. Mean aqueous flow rate decreased from
apy in the management of acute glaucoma. 43% in treated eyes. In a short-­term study in
Dichlorphenamide has been withdrawn from normal dogs, a maximum decrease in IOP of
the market, but is available as generic forms in about 6 mmHg was reached after five days of
the United States. The oral dose rate in the dog treatment at 8-­h intervals, suggesting several
ranges from 2 to 4 mg/kg, two to three times days of medication may be necessary for maxi-
daily. Single oral administration of dichlorphen- mum effect.
amide in the cat in doses ranges from 0.5 to Topical dorzolamide was also found to lower
2 mg/kg significantly reduced IOP for 4 h. IOP when applied to normotensive feline eyes
Methazolamide is supplied in 50 mg tablets. every 12 h. The amplitude of IOP decrease
After oral administration of 25 or 50 mg meth- observed in cats after twice daily applications
azolamide to healthy Beagle dogs, a significant of dorzolamide was almost the same as that
IOP decrease of 18–21% was observed 3–6 h observed previously in dogs with three times
after administration depending on the dose, daily applications. Topical dorzolamide seems
but thereafter IOP increased to levels above the to influence IOP in horses less than it does in
control baseline values. The lowering effect on small animals, since its twice-­daily application
­Mydriatics/Cycloplegics, Anesthetics, and Tear Substitutes and Stimulator  155

to normotensive equine eyes only reduced IOP dorzolamide three times daily. After four days
by an average of 2 mmHg. of treatment, the mean reduction in IOP was
The effect of topical administration of 1% –7.50, −3.75, and –8.40 mmHg for the dorzola-
brinzolamide on the IOP has been evaluated in mide, timolol, and combination products,
small and large animals. In a preliminary study respectively.
in healthy dogs, 1% brinzolamide instilled
twice a day (i.e., every 12 h) significantly Adverse Effects
reduced IOP with the peak effect observed No ocular side effects have been described in
between 5 and 6 h after medication. The ampli- relation to the systemic administration of
tude of the IOP reduction was similar to that CAIs, but acute overdosage or long-­term ther-
induced by topical dorzolamide, but lower apy may result in a variety of clinical and bio-
than that resulting from oral administration of chemical disorders. The side effects of the
5 mg/kg methazolamide. Contrary to dorzola- various agents of this class are similar, with
mide, brinzolamide topically applied every dichlorphenamide appearing to cause the few-
12 h was unable to significantly influence IOP est and being considered as the drug of choice
of normotensive feline eyes. for prolonged treatment in dogs. Common
transient side effects associated with oral or
Clinical Use parenteral CAIs include increased diuresis,
Because they diminish AH formation, CAIs gastrointestinal disturbances (anorexia, vomit-
can be employed in the treatment of practically ing, diarrhea), and possibly increased respira-
all types of glaucoma. Short-­term administra- tory rate secondary to metabolic acidosis. Cats
tion of systemic or topical CAIs may be effec- appear to be more susceptible to these drugs
tive in the management of acute increases in and should be observed very closely. With
IOP resulting from primary or secondary glau- availability of systemic CAIs greatly limited,
coma. On the basis of findings in normal and this class of drugs is now used primarily as the
glaucomatous dogs, combined administration topical forms.
of topical and systemic CAI has no additional
IOP-­lowering effects over dorzolamide or brin- Prostaglandin Analogues
zolamide alone that would warrant its use in Background History and Chemistry
dogs with acute glaucoma. Theoretically, CAIs The PGs are a family of biologically active lipids
can be used in combination with other with a wide spectrum of possible pharmacologi-
antiglaucoma agents as their effect is usually cal activity. Since early studies showed that low
additive, reducing IOP more than any single doses of PGF2α can decrease IOP, it has been
agent. In the dog, the combined use of dorzola- established that most of the naturally occurring
mide and latanoprost may be appropriate for PGs, as well as some of their analogues and
the management of chronic glaucoma, since esters, are potent ocular hypotensive agents in
dorzolamide given every 8 h and latanoprost both animals and humans, but individual spe-
instilled once in the morning were demon- cies differences have been reported in the dog,
strated to have an additive effect on decreasing cat, and horse (Table 3.9). The PG derivatives
IOP. The additivity of topical CAIs to topical currently approved for the reduction of IOP in
β-­blockers regarding the decrease in AH out- humans and animals were all developed
flow has also been documented in normoten- through chemical modification of PGF2α.
sive human eyes, and a fixed combination of Latanoprost and isopropyl unoprostone first
2% dorzolamide and 0.5% timolol is available emerged as a result of active screening pro-
commercially. In glaucomatous Beagles, the grams. Unoprostone was available in Japan in
combination product has been compared with 1994, and was marketed in 2000 in the United
monotherapy with either 0.5% timolol or 2% States. Latanoprost was marketed in 1996, and
156 Ocular Pharmacology and Therapeutics

then two other PG analogues, travoprost and conventional outflow pathway as measured by
bimatoprost, were approved for use in 2001 in tonography. The mechanisms by which activa-
humans. All the commercially available PG tion of FP receptors leads to an increased uveo-
analogues used for their IOP-­lowering activity scleral outflow are still under investigation, but
are esterified prodrugs of the PGF2α, more lipo- there is scientific evidence that MMP-­mediated
philic, and designed to facilitate penetration remodeling of the extracellular matrix of the
through the ocular barriers. These drugs are ciliary body muscle contributes to this pharma-
now available as generics and their costs have cological effect. The amount of myocilin, an
been decreased, making their availability higher intra-­ and extracellular protein of the ciliary
for animal patients. body muscle that may contribute to outflow
resistance, is also reduced after topical PGF2α
Mechanism of Action treatment. Experiments in humans, monkeys,
The biologically active forms of latanoprost, and rabbits indicate that in addition to its IOP-­
bimatoprost, travoprost, and unoprostone reducing effect, latanoprost increases blood
exhibit high affinity and selectivity for the velocity in the optic nerve head or dilates the
prostanoid FP receptors, and the IOP-­lowering vessels supplying the optic nerve head, because
action of these PG derivatives is mediated of its pharmacological effect on the vessels.
through the binding of their free acid (the
active molecule) to FP receptors in humans Clinical Pharmacology
and presumably in dogs. Despite their differ- Experimental studies have demonstrated that
ences in potency at the FP receptor, the free topical application of 0.005% latanoprost sig-
acids of latanoprost, travoprost, and bimato- nificantly reduces IOP in normotensive and
prost fully activate the receptor relative to the glaucomatous canine eyes. In normotensive
naturally occurring PGF2α. The pivotal role of canine eyes, 0.005% latanoprost instilled in the
FP receptors in the ocular hypotensive effects evening, morning, and twice daily induced an
of the PGF2α analogues has also been demon- average decline in IOP of about 25%, while in
strated with the use of FP receptor-­deficient glaucomatous eyes it produced a mean decline
mice. The IOP-­lowering action of PGs in the in IOP of about 50%. In glaucomatous dogs, a
feline species reportedly works through EP1 comparable IOP-­lowering action was observed
receptors and not FP types. In the dog, EP with once-­ or twice-­daily application of 0.03%
receptors mediating PGE2 action also can alter bimatoprost and 0.004% travoprost (Figure 3.7).
AH dynamics as demonstrated with a potent The potential of 0.005% latanoprost for lower-
and selective EP4-­PGE2 agonist that was able ing IOP has also been evaluated in normoten-
to lower IOP by 5–7 mmHg in healthy Beagles sive equine eyes. In clinically normal horse, a
when given topically. The mechanism by once-­daily application of 0.005% latanoprost
which this EP4 receptor agonist lowers IOP is resulted in a mean decrease in IOP of 1.03 mmHg
currently unknown but may involve trabecular or about 5% in males, and 3.01 mmHg or about
outflow and not uveoscleral outflow. 17% in females. The reason for the gender effect
In humans and animal species studied so far, in the response of the equine eye to topical
it has been well established that increase in 0.005% latanoprost has not been determined.
uveoscleral outflow is the primary mechanism
by which PGs reduce IOP. Increased uveoscle- Clinical Use
ral outflow has been reported in humans, mon- PG derivatives have reached extensive clini-
keys, rabbits, and dogs treated with PGF2α or its cal use in human beings with ocular hyper-
analogues, and in cats treated with PGA2. tension and primary open-­angle glaucoma
However, data in the current literature indicate because of the magnitude of the IOP decrease
that latanoprost, bimatoprost, and unopros- and single-­daily instillation schedule (in the
tone also affect the pressure-­dependent evening). In patients with either ocular
­Mydriatics/Cycloplegics, Anesthetics, and Tear Substitutes and Stimulator  157

60
Evening Instillation
Opposite Eye (Control)

50
Intraocular Pressure (mmHg)

40

30

20

Day 1 Day 2 Day 3 Day 4 Day 5


Control Drug Instilled Drug Instilled Drug Instilled Drug Instilled
10
Day / Time
(a)
60
Morning and Evening Instillation
Opposite Eye (Control)

50
Intraocular Pressure (mmHg)

40

30

20

Day 1 Day 2 Day 3 Day 4 Day 5


Control Drug Instilled Drug Instilled Drug Instilled Drug Instilled
10

Day / Time
(b)

Figure 3.7 Effect on IOP of 0.005% latanoprost in the Beagle with primary open-­angle glaucoma after
(a) evening and (b) q 12 h dosing.

hypertension or primary open-­angle glau- their use as monotherapy, PGF2α-­related


coma, latanoprost, bimatoprost, and travo- drugs became first-­line prescriptions as com-
prost administered once daily in the evening bination therapies in humans, because about
induce a higher reduction in IOP than 0.5% half of the patients require more than one
timolol applied twice daily. Latanoprost twice antiglaucoma agent for IOP reduction. Beta-­
daily is less effective than once daily in blockers, topical CAIs, and alpha-­adrenergic
human glaucoma patients. In addition to agonists are the most common antiglaucoma
158 Ocular Pharmacology and Therapeutics

agents used in addition to PG analogues in occurrence of miosis reflects the sensitivity of


glaucomatous humans. the canine iridal sphincter muscle to the PGF2α
In the dog, the PG derivatives are mostly that appears to act directly rather than through
indicated for the treatment of the primary glau- the release of adrenergic neurotransmitters.
comas, and may replace mannitol and/or aceta- Reports have also described miosis in cats and
zolamide as first-­line drugs in the emergency horses receiving latanoprost, and cats treated
management of acute closed-­angle primary with bimatoprost. A consequence of the miotic
glaucoma. High-­resolution imaging of the effect of PG derivatives in companion animals is
anterior segment of dogs with primary glau- their contraindication in glaucoma secondary to
coma suggests that latanoprost may rapidly subluxation or anterior luxation of the lens,
lower IOP in primary closed-­angle glaucoma by because of the potential pupillary block that
inducing miosis that breaks the pupillary block, may result from vitreous entrapment. PGs at
and by opening the collapsed ciliary cleft in pri- high concentrations are well known to induce
mary open-­angle glaucoma. Topically applied breakdown of the BAB. Because most horses
to normotensive canine eye, the latanoprost with secondary glaucoma appear to be at risk
0.005%–timolol 0.5% fixed combination caused for recurrent uveitis, PG analogues are consid-
the IOP to decrease by 1–2 mmHg more than ered to have the potential to exacerbate the
the decrease for latanoprost alone, while no inflammatory process and should be used with
ocular hypotensive effect was observed with caution in these animals.
0.5% timolol alone. Although latanoprost,
bimatoprost, and travoprost are instilled once Osmotic Agents
daily in humans, experimental data in glauco- Osmotic agents are another important class of
matous dogs suggest that twice-­daily instilla- antiglaucoma drugs. They are almost always
tion of these drugs should be recommended in used in combination with other drugs and usu-
the dog to result in less daily IOP fluctuations. ally for very short term. They are most often
For secondary glaucoma from iridocyclitis, administered in the therapy of high-­pressure
ophthalmic anti-­inflammatory drugs some- glaucoma when an animal is initially pre-
times are administered concurrently to sented (Table 3.10).
antiglaucoma agents. Topical prednisolone and
flurbiprofen were shown to significantly inhibit Mechanism of Action
the IOP-­lowering effect of latanoprost in dogs. After oral or intravenous administration,
osmotic agents (also called hyperosmotic
Side Effects agents) are distributed in the extracellular flu-
Side effects most commonly encountered in ids (primarily plasma), thereby contributing to
glaucomatous human eyes treated with PG2α a substantial increase in their osmolality. This
analogues include conjunctival hyperemia, iris increase creates an osmotic gradient in which
darkening, and eyelash changes. The second- the extracellular fluids are hypertonic to
ary effects of elongation and thickening of the intraocular fluids (i.e., aqueous and vitreous
human eyelashes after latanoprost therapy humors), from which they are separated by sem-
have resulted in a new commercial use for this ipermeable membranes (i.e., blood–aqueous
drug in humans. As reported in humans, con- and blood–vitreous barriers). This osmotic gra-
junctival hyperemia has been observed in dogs dient favors the diffusion of water from the
treated with latanoprost, which also induced intraocular fluids back into the plasma. This
epiphora, blepharospasm, and blepharedema fluid shift has two effects on the eye. First, it
when instilled in equine eyes. A moderate to inhibits the ultrafiltration process that contrib-
marked miosis is usually present in dogs utes to AH formation, and second, it reduces
treated with the PGF2α derivatives, and the the volume of the vitreous body. Shrinkage of
pupillary constriction is more limited when the vitreous displaces the iris–lens plane poste-
the drug is instilled only in the evening. The riorly and subsequently opens the iridocorneal
­Mydriatics/Cycloplegics, Anesthetics, and Tear Substitutes and Stimulator  159

angle, allowing for better drainage. As a final Isosorbide is a dihydric alcohol that resembles
result, IOP is reduced. For the pharmacologi- mannitol in chemical structure and can be
cal effects of osmotic agents to occur, they given orally. It is available as a 45% flavored
should not cross the blood–aqueous and solution. Unlike glycerin, it is totally inert and
blood–vitreous barriers; in ocular inflamma- does not produce elevated blood glucose. A
tion, the osmotic agent may leak in the intraoc- daily dose of 1.5 g/kg is recommended in the
ular fluids, and the extent of ocular hypotension dog, although there is currently no published
is reduced. Because of its large molecular study documenting its effect on IOP in this
weight, mannitol penetrates in the eye less species.
than other osmotic agents in the presence of
ocular inflammation. Clinical Use
Osmotic agents are used mainly in the emer-
Products Available gency treatment of acute glaucoma. These
Mannitol, a six‑carbon sugar, is poorly absorbed compounds are employed for short-­term con-
from the gastrointestinal tract and must, there- trol of IOP since they are not practical for pro-
fore, be administered intravenously. It is available longed therapy. Rapid reduction of IOP is
in concentrations of 5–25%, but the 20% solution usually achieved with mannitol rather than
is most often used in ophthalmology. The dose with glycerin. Osmotic agents are also indi-
for the lowering of IOP in dogs ranges from 1 to cated to reduce IOP in patients with hyphema,
2 g/kg, infused over a period of 20–30 min. but their value in facilitating the resorption of
Following intravenous administration of 1.5 g/kg anterior chamber hemorrhage is not clearly
mannitol, IOP of normal canine eyes decreases established. Mannitol may be employed preop-
from baseline values in times ranging from 0.25 eratively or intraoperatively to lower IOP and
to 5.5 h. A mean maximal depression of 9 mmHg reduce vitreous volume.
occurs 1.5 h after administration. If mannitol is
infused during surgery, bladder catheterization is Side Effects and Contraindications
advisable to prevent uncontrolled urination dur- The major potential toxicity of intravenous
ing the recovery period. osmotic agents is related to their effect on the
Glycerin, or glycerol, is a trihydric alcohol volume and distribution of body fluids.
that is rapidly absorbed from the gastrointesti- Mannitol may quickly expand extracellular
nal tract after oral administration. The drug is fluid volume and subsequently overload the
marketed as flavored commercial preparations cardiovascular system. This acute expansion of
of 50% and 75% glycerin. Glycerin USP, which extracellular fluid volume may precipitate pul-
contains approximately 1.25 g of glycerin/ml, monary edema in patients with cardiac failure
may also be used and mixed in milk or syrup to or who are under general anesthesia. Deaths
improve palatability. Glycerin is administered due to pulmonary edema occurred in a few
perorally or in food in a daily dose of 1–2 g/kg. dogs and cats that underwent ophthalmic sur-
Occasionally, animals may experience nausea gery and were given mannitol while anesthe-
or vomiting after ingestion of the drug. The tized with methoxyflurane in oxygen. Mannitol
incidence of vomiting appears to be dose does not cross the blood–brain barrier and thus
dependent, occurring most frequently with extracts water from cerebral fluid and tissue.
doses higher than 2 g/kg. Administrations of Cerebral dehydration induced during the
1.44 g/kg glycerin in healthy dogs led to a sig- phase of maximal plasma hyperosmolization
nificant ocular hypotensive effect, occurring has been found in association with side effects
within 1 h and lasting about 10 h. Glycerin is such as nausea, vomiting, and changed con-
metabolized into glucose, so hyperglycemia sciousness. Shrinking the brain could also pro-
and glycosuria may ensue. As this agent is mote subdural hematoma formation. Mannitol
readily metabolized, it induces less diuresis should be avoided in patients with renal
than mannitol. failure.
161

Section 2

Ocular Exam and Imaging


163

Eye Examination and Diagnostics


Revised from 6th edition of Veterinary Ophthalmology, Chapter 10: Part 10.1 – Ophthalmic Examination and Diagnostics, by Heidi
I. Featherstone and Christine L. Heinrich; Part 10.2 – Ocular Imaging, by David Donoldson and Claudia Hartley; Part 10.3 – Diagnostic
Ophthalmic Ultrasound, by Ellison Bentley, Stefana Pizzirani, and Kenneyh R. Waller; and Part 10.4 – Clinical Electrodiagnostic
Evaluation of the Visual System, by Gil Ben-­Shiomo; and Chapter 11: Ophthalmic Genetics and DNA Testing, by Simon M. Peterson-­Jones

An ophthalmic diagnosis is often made at the information that may be helpful includes travel
time of the examination, more often than in history, vaccination, and deworming history,
most systems, because most ocular structures and whether other animals in the vicinity are
can be visualized either directly or indirectly. similarly affected. More specific information
Furthermore, the eye lends itself to numerous pertaining to the eye includes the owners’
simple and efficient noninvasive diagnostic interpretation of vision, pain, and whether one
procedures, many of which can be performed or both eyes are involved. Further information
during a routine examination. This chapter may be required depending on the primary
describes examination techniques and diag- presenting problem.
nostic procedures available to veterinarians, Signalment can provide an important clue to
and those often employed by veterinary the cause of many ophthalmic conditions;
ophthalmologists. these clues include conditions that are specific
to a particular species (e.g., corneal sequestrum
in the cat), those that are associated with a par-
­History ticular coat color (e.g., multiple ocular anoma-
lies in the homozygous merle dog), those with
A thorough history, when combined with clini- strong breed predispositions (e.g., keratocon-
cal findings, will support appropriate case junctivitis sicca [KCS] in the West Highland
management. In taking a history, the same White Terrier), and others known to be heredi-
considerations apply as to other body systems tary (e.g., cataract in the Morgan horse).
and include signalment, use of the animal, Primary complaints from the owner usually
environment, diet, characterization of the pri- include ocular discharge, change in appear-
mary complaint (onset, initial clinical signs, ance of the eye (size, color, pupil), or reduced
progression, duration), treatment (response vision or blindness. The role of concurrent dis-
and current treatment), and nonophthalmic ease or secondary complaints should not be
disease (previous and concurrent). Additional underestimated. Concurrent systemic disease

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
164 Eye Examination and Diagnostics

may also affect treatment; for example, timo-


Box 4.1 Diagnostic Sequence for the
lol, a topical β-­blocker, should be avoided in
Basic Eye Examination
cats with both asthma and glaucoma. Intensive
therapy with topical atropine can induce ●● History: signalment, primary complaint,
mydriasis for several days up to 14 days in the concurrent disease, and treatment
horse. Questions should be directed toward ●● Examination in ambient light
vision in different situations: photopic and sco- –– Distance examination
topic conditions, i.e., hemeralopia (day blind- ○○ Observation of animal’s demeanor,

ness) versus nyctalopia (night blindness); and confidence, and movement within
stationary and moving objects, i.e., central ver- its environment
sus peripheral retinal disease. Owners are ○○ Symmetry, ocular discharge

often poor judges of ocular pain. They may ○○ Globe (position, size, movement)

notice classic signs of ophthalmic pain – –– “Hands-­on” examination


watery discharge (increased lacrimation), ○○ Neuro-­ ophthalmic testing: menace
closed or small eye (blepharospasm), and pho- response, dazzle, reflex, PLR, corneal
tophobia, but do not interpret them as such. reflex, VOR
○○ Tear tests, corneal esthesiometry

–– Close examination of adnexa and globe


­General Ocular Examination ●● Examination after topical anesthesia
–– Tonometry
The ocular examination should proceed in a –– Gonioscopy
logical and systematic manner. The general –– Posterior segment/ocular fundus
order of steps is listed in Box 4.1, but the ●● Mydriasis
method will vary according to personal prefer- –– Anterior segment after pupil dila-
ence, available equipment, and the individual tion (lens)
case. However, certain diagnostic tests and –– Posterior segment after pupil dilation
observations must precede others to avoid (vitreous humor and fundoscopy)
interference with results and interpretation. ●● Additional diagnostic tests: corneocon-
Important tests influenced by previous diag- junctival culture and cytology, ophthal-
nostics include the Schirmer tear test (STT), mic dyes, nasolacrimal flush, conjunctival
the evaluation of pupillary light reflexes biopsy, aqueous and vitreous paracente-
(PLRs), instillation of topical anesthetics, and sis, imaging modalities, photography, ERG
tonometry before the administration of mydri- Abbreviations: ERG, electroretinography; PLR, pupil-
atic agents. lary light reflex; VOR, vestibulo-­ocular reflex.
The place of the ophthalmic examination
varies with the species, but the illumination
must be dark enough to prevent undue corneal time. Small animals can usually be examined
reflection but not too dark to cause risk to the on a table in a closed room; large animals
examiner and assistants! Regardless of the spe- require more specialized facilities, e.g., stocks
cies, it is essential to have a well-­lit area for the or stalls for horses, and chutes or stanchions
initial examination and the option to darken for cattle.
the environment for subsequent steps. The
examination area should also be quiet and
Restraint
away from major distractions. An appropriate
examination area minimizes animal and exam- The best method of restraint for any given situ-
iner stress, which in turn maximizes coopera- ation varies with the species involved, the
tion levels and helps to reduce examination patient’s temperament, and the desired effect.
­General Ocular Examinatio  165

Generally, however, the least amount of Dairy cattle can usually be adequately
restraint possible is best for the ophthalmic restrained in a stanchion, with the head pulled
examination. Most dogs and cats require only laterally by an assistant using a nose lead. Beef
gentle manual restraint for an ophthalmic cattle may be more difficult to restrain, and
examination. Fractious animals may require squeeze chutes with special head restraints are
additional restraint. Muzzles can be employed often necessary. Sheep and goats can usually be
with aggressive or fearful dogs, but their use is restrained manually with the help of an assis-
limited in brachycephalic breeds. A large towel tant. Goats can be examined standing, and
or blanket or a cat bag can “wrap up” a frac- sheep can be examined seated on their rumps
tious cat and is a minimally invasive way to to avoid excessive movements. Llamas and
avoid claw injuries to the examiner or owner. alpacas may need to be supported in a chute or
When sedation or general anesthesia is nec- a sling. Rodents, rabbits, birds, and small exotic
essary, there can be side effects. Many anes- species can usually be restrained manually.
thetic agents and sedatives decrease tear Rabbits are usually adequately restrained on a
production, or alter intraocular pressure (IOP) table with a handler supporting the hind limbs
in most dogs; deep sedation and general anes- with one hand and the back or neck with the
thesia frequently make the ophthalmic exami- other. Most small-­ to medium-­sized birds can
nation more difficult because the eyes tend to be examined safely when properly restrained
roll downward (infraversion) and the nictitat- with a hand about the neck and feet, with wings
ing membrane tends to protrude. Ketamine tucked in or wrapped within a towel. Leather
with or without diazepam in cats results in a working gloves facilitate handling of raptors
loss of the blink reflex, which can lead to cor- and other large birds. Ferrets are usually simply
neal drying and mydriasis, which alters the and sufficiently restrained by suspension from
PLRs. Ketamine can cause nystagmus and, in the neck scruff with legs dangling free.
some species, will elevate IOP. Acepromazine
may cause nictitans protrusion, which obscures Eyelid Akinesia
the globe during evaluation. Opioids may alter The orbicularis oculi muscle closes the eyelids
pupil size, reactivity, and IOP. Specifically, opi- and thus can impair or even prevent ocular
oids tend to produce mydriasis in those species examination, especially in large animals.
that exhibit central nervous system (CNS) exci- Akinesia of this muscle is routine in the horse,
tation and miosis in those that become sedated occasionally required in cattle, and only rarely
after opioid administration. performed in small animals. Most horses
Although eye exams in horses can be accom- require an auriculopalpebral block for a thor-
plished without chemical restraint, these drugs ough ocular examination, especially if the eye
markedly facilitate the complete eye examina- is painful or if the structural integrity of the
tion without undue stress on the horse and with globe (usually the cornea) is compromised.
greater protection for the owner and examiner. The palpebral nerve, which arises from the
Detomidine hydrochloride 0.02–0.04 mg/kg i.v. auriculopalpebral branch of the facial nerve
is the chemical agent of choice as it provides (cranial nerve VII), innervates the orbicularis
rapid onset of tranquilization without an excita- oculi muscle. These motor fibers may be
tory phase, and a steady and low head position blocked at any point between the origin of the
without movement. Xylazine, 0.5–1.0 mg/kg i.v., auriculopalpebral nerve and the palpebral
has also been recommended to facilitate equine nerve branch, but blocks administered closer
ocular examination; it may be necessary to add to the origin of the nerve are most effective.
butorphanol 0.01–0.02 mg/kg i.v. or aceproma- There are three main points at which the auric-
zine 0.02–0.04 mg/kg i.v. for painful procedures ulopalpebral or palpebral nerves can be
or additional restraint. blocked in the horse (Figure 4.1).
166 Eye Examination and Diagnostics

Figure 4.1 Horse skull depicting sites for the auriculopalpebral (a and b), palpebral (c), frontal/supraorbital
(d), lacrimal (e), zygomatic (f), and infratrochlear (g) nerve blocks.

Akinesia can be achieved in a similar fash- single drop of 0.5% proxymetacaine resulted in
ion in cattle. The auriculopalpebral nerve can the loss of sensation for 55 min, with a maxi-
sometimes be palpated as it passes over a pal- mal effect of 15 min, while the application of a
pable notch in the zygomatic arch at the level second drop of the drug increased the maximal
of the temporomandibular joint. If the nerve duration of corneal sensation loss to 25 min.
cannot be palpated, anesthetic may be injected The use of a 1% tetracaine and 0.4% oxybupro-
subcutaneously along the zygomatic arch, caine preparation showed a fast onset of maxi-
starting at the supraorbital process and con- mum corneal anesthesia within 1 min and a
tinuing approximately 3.75 cm caudally. The significant loss of sensation for a duration of
auriculopalpebral nerve block is usually neces- 45 min; however, it can be irritating to some
sary with other retrobulbar nerve blocks in cat- individuals. In the horse, maximal corneal sen-
tle for enucleations. sation loss is noted 5 min following the appli-
In the dog, the auriculopalpebral nerve can cation of a single drop of 0.5% proxymetacaine
be located and blocked along the most lateral and the duration is approximately 25 min;
part of the zygomatic arch, at the midpoint of however, full loss of corneal sensation is not
the caudal third of the bone. Alternatively, ter- achieved.
minal palpebral nerve fibers may be blocked as Several different sensory blocks may be
they pass over the orbital rim. employed in large animals depending on the
location of the eyelid lesion to be addressed
(see Figure 4.1) (the anesthetic agents used are
Regional Anesthesia/Analgesia
the same as those described earlier for induc-
The most commonly applied form of anesthe-
tion of eyelid akinesia):
sia for the eye is the application of topical anes-
thetic to the cornea, which is routinely used 1) The central two-­thirds of the upper eyelid
during ocular examination, specifically to are innervated by the frontal or supraorbital
facilitate the assessment of painful eyes, the nerve, which is blocked by injecting 2 ml of
measuring of IOP, and for obtaining of labora- 2% lidocaine under the skin immediately
tory samples. In the dog, the application of a above the supraorbital foramen.
­General Ocular Examinatio  167

2) The lateral upper eyelid and lateral canthus is then positioned at the ventral orbital rim and
are innervated by the lacrimal nerve and inserted through the lower lid at the junction of
can be blocked either by injecting 1 ml of its middle and lateral thirds. The needle is
local anesthetic agent adjacent to the lacri- advanced until a slight “popping” sensation is
mal notch (a depression that can be pal- detected, indicating that the orbital fascia has
pated on the dorsolateral bony orbital rim) been pierced. The needle is then directed
or with a line block along the lateral third of slightly dorsally and medially toward the apex
the dorsal orbital rim. of the orbit and advanced approximately
3) A block of the zygomatic nerve will anes- 1–2 cm. Then, 1–2 ml of a suitable local anes-
thetize the lateral lower lid and is achieved thetic (e.g., lidocaine, bupivacaine, mepiv-
with a line block along and adjacent to the acaine, or ropivacaine) is injected after gentle
ventrolateral orbital rim. aspiration to check for blood to avoid intravas-
The medial canthal region is innervated by cular injection. In the cat, a dorsomedial
the infratrochlear nerve and is desensitized approach for retrobulbar anesthesia has been
by injecting anesthetic agent through the shown to be more reliable than the inferotem-
bony trochlear notch on the dorsal rim of poral approach recommended for dogs. In cats,
the orbit near the medial canthus the available retrobulbar space for an intraorbi-
tal injection is very limited. With the cat in ster-
Retrobulbar anesthesia aims to block cranial nal recumbency, a 1.5-­in. (38-­mm) spinal needle
nerves III, IV, V, and VI and the ciliary ganglion, is bent at the midpoint to achieve an angle of
and therefore provides loss of sensation to the approximately 20°. The needle is then inserted
globe and eyelids as well as extraocular muscle through the superior eyelid at the medial region
akinesis. In the horse, retrobulbar blocks are of the orbit (at the junction between the medial
commonly used to allow surgical manipulation and middle third of the eyelid) and advanced
of the eye and adnexa in order to avoid general approximately three-­quarters of its length
anesthesia. The use of combined sedation and (30 mm) toward the caudal pole of the globe,
retrobulbar block is well established for enucle- but in close proximity to the orbital wall.
ation in the standing horse. The retrobulbar In the horse, several methods have been
block has been shown to prevent heart rate described:
decrease associated with the oculocardiac reflex
during enucleation. Retrobulbar blocks are also 1) The four-­point block: 5–10 ml of anesthetic
used in equine patients undergoing general agent is placed in each of four sites (dorsal,
anesthesia to provide extraocular muscle akine- lateral, ventral, and medial) with a 20-­
sia during cataract surgery, thereby reducing gauge, 3-­in. spinal needle through either
the need for nondepolarizing neuromuscular skin or bulbar conjunctiva, following the
blocking agents (NMBAs) and ventilation. In curve of the globe posteriorly into the
small animals, retrobulbar injections are most extraocular muscles and orbit.
commonly used to augment analgesia for enu- 2) Direct injection into the orbital cone through
cleation procedures, and to replace the need for the supraorbital fossa: a 22-­gauge, 2.5-­in. spi-
NMBAs to provide immobilization and optimal nal needle is directed through the skin, per-
exposure during intraocular surgery. pendicular to the skull and into the orbital
Various techniques have been described for fossa, just posterior to the posterior aspect of
achieving retrobulbar anesthesia. In the dog, the dorsal orbital rim. When the needle is
the most commonly employed approach is the advanced, the eye will show a slight dorsal
inferior temporal technique in which an approx- movement as the needle passes through the
imate 20° angle is created by bending a 2-­gauge, fascia of the dorsal retrobulbar cone into the
1.5-­in. spinal needle at its midpoint. The needle retrobulbar space. The needle is advanced
168 Eye Examination and Diagnostics

until it enters the cone, evidenced by the vision. Conformation of the orbit and periocu-
slight “popping” sensation as the eye is lar region, and the size, position, and move-
released into its normal position. After aspi- ment of the eyes should be assessed with
ration, 10–12 ml of 2% lidocaine, mepiv- particular note of asymmetry. Abnormalities
acaine, or bupivacaine is injected into the in globe size (e.g., microphthalmia), buphthal-
space so that the globe is pushed forward. mos from changes in globe position (e.g.,
enophthalmos and exophthalmos), and any
More recently, alternatives to retrobulbar
type of ocular discharge should be noted.
anesthesia, including peribulbar injection and
sub-­Tenon’s methods, have been explored for
veterinary patients. In peribulbar anesthesia, Vision Assessment and
the needle is introduced into the extraconal Neuro-­ophthalmic Examination
space (i.e., outside the extraocular muscle
The cranial nerve examination is an inherent
cone), thereby limiting risk of injury to intra-
and essential part of any thorough ocular
conal structures, especially the optic nerve and
examination. Specifically, cranial nerves II–VIII
major blood vessels supplying the globe. The
are assessed via the menace response, daz-
injectate spreads throughout much of the
zle, pupillary light, palpebral, corneal, and
orbit, including the intraconal space. Sub-­
vestibulo-­ocular reflexes (VORs). Vision can be
Tenon’s anesthesia in the dog and horse is
assessed by the menace response, tracking
described via the mediodorsal area of the bul-
reflex (cotton ball test), visual placing reflex
bar conjunctiva, which is incised with ophthal-
(for small animals), and maze test (in photopic
mic scissors 5 mm from the limbus. Closed
and scotopic conditions).
scissors are introduced through the created
aperture and the sclera is exposed by blunt dis-
Menace Response
section through Tenon’s capsule. A human,
The menace response is part of a routine oph-
curved, blunt 19-­gauge, 25-­mm sub-­Tenon’s
thalmic examination. A menacing movement
cannula is inserted along the equator of the
toward the eye results in closure of the ipsilat-
globe until it reaches the posterior sub-­Tenon’s
eral eyelids, and possibly globe retraction or an
space, where the local anesthetic is infused.
avoidance head movement. The menacing ges-
ture should be directed toward different visual
fields to gather information about partial vis-
­ phthalmic Examination
O ual deficits. The menace response is an
in Ambient Lighting acquired protective cortical response. It is
absent in puppies and kittens, and should be
Initial examination is performed in ambient acquired by approximately 12 weeks of age in
lighting and without instruments. This is an these species. In foals, the menace response
important stage because it can be very inform- should be acquired by 2 weeks of age, although
ative. Examination is started from a distance, some reports have described a positive menace
before handling the animal, and is followed by response between 5 days and 19.5 weeks, and
close examination. by 9 days. The menace response is inconsistent
in cats, birds, and some exotic species.
Distance Examination
Pupillary Light Reflex
The animal’s attitude, general body condition, The resting pupil size should first be observed
and ability to navigate in an unfamiliar envi- in normal light and then in a darkened room.
ronment are carefully evaluated to provide Pupil size and asymmetry can be accurately
some information about its general health and assessed by distant direct or indirect
­Ophthalmic Examination in Ambient Lightin  169

ophthalmoscopy; the PLR, tested by shining a reflex is unknown, but the retina, cranial nerve
bright focal light source at the eye, results in II, rostral colliculus, and/or supraoptic nuclei
constriction of the ipsilateral pupil (direct of the hypothalamus, and cranial nerve VII
PLR), and in some species, constriction of the (innervating the orbicularis oculi) are involved.
contralateral pupil (indirect or consensual Being a subcortical reflex, in contrast to the cor-
PLR). The PLR evaluates the retina, cranial tical menace response, the dazzle reflex is pre-
nerve II, midbrain, and cranial nerve III (para- sent from birth. Sufficient brightness of the
sympathetic fibers). An animal with cortical light source is crucial for this test to be per-
blindness can have a normal PLR because the formed reliably. The dazzle reflex is especially
pupillomotor fibers branch from the optic tract helpful to evaluate retina and optic nerve func-
before the visual fibers. The equine PLR is tion when the PLR cannot be assessed (e.g.,
biphasic, i.e., an initial brisk but small reaction hyphema and severe corneal edema).
followed by a slower complete constriction.
The direct PLR is difficult to assess in birds Palpebral Reflex
because intermittent dynamic anisocoria can The palpebral reflex (blink reflex), tested by
be a normal feature; this results from (pre- lightly touching the lateral and medial canthi,
sumptive) voluntary control of the striated results in eyelid closure. The afferent arm of
component of the iris musculature and the the palpebral reflex is the ophthalmic branch
bird’s emotional state. The indirect PLR is only of cranial nerve V, and the efferent arm is cra-
present in species with partial decussation of nial nerve VII. As for the menace response, the
the optic nerve fibers at the optic chiasm (e.g., palpebral reflex should be performed before
33% in the cat, 75% in the dog, and 85% in the sedation or eyelid akinesia.
horse). In species with more than 50% decussa-
tion, the indirect PLR is weaker than the direct Corneal Reflex
PLR because more efferent pupillomotor fibers The corneal reflex is one of the most sensitive
return to the ipsilateral side of the brain reflexes in the body and its purpose is to pro-
(dynamic contraction anisocoria). tect the eye. The corneal reflex, tested by touch-
The “swinging flashlight test” is a modifica- ing the peripheral cornea with a sterile swab
tion of the PLR. A focal light source is passed tip or wisp of cotton wool, results in retraction
repeatedly from one eye to the other, causing of the globe and closure of the eyelids
the pupil under direct illumination to constrict (Figure 4.2). The afferent arm of the corneal
slightly more than the contralateral pupil. A reflex is the ophthalmic branch of cranial
unilateral prechiasmal lesion (i.e., involving the
retina and/or optic nerve) will result in a pupil
constricting when the fellow eye is illuminated,
but subsequently dilating under direct illumina-
tion (a Marcus–Gunn pupil). It is, however,
important to note that pupillary escape, a slight
dilation that follows constriction under direct
light stimulation, is normal in many species.

Dazzle Reflex
The dazzle reflex is a subcortical reflex in which
a bright focal light source shone quickly into
the eye results in closure of the ipsilateral and,
Figure 4.2 Corneal reflex. Corneal sensation is
to a lesser extent, contralateral eyelids. The tested by means of a wisp of cotton wool
complete anatomical pathway for the dazzle contacting the peripheral cornea.
170 Eye Examination and Diagnostics

nerve V, and the efferent arm is mediated by the globe through the closed upper eyelid.
cranial nerves VI (globe retraction) and VII A more detailed assessment of the orbit
(eyelid closure). Veterinary ophthalmologists includes manipulation of the mandible and
can quantify corneal sensitivity using the cor- oral examination (this can be deferred to mini-
neal esthesiometer. mize stress in the early stages). As the coronoid
process of the vertical ramus of the mandible is
Vestibulo-­ocular Reflex (Oculocephalic Reflex) closely associated with the floor of the orbit,
The VOR assesses eye movement in relation to jaw opening may cause pain or resistance if
changes within the vestibular apparatus. It orbital disease is present. A careful examina-
thereby indirectly assesses the three cranial tion of the oral cavity should follow.
nerves (III, IV, and VI) that innervate the Eyelids should be examined in more detail in
extraocular muscles, and cranial nerve VIII terms of position, mobility and conformation,
and the medial longitudinal fasciculus that and skin lesions. In some animals, it is impor-
coordinate movement. The animal’s head is tant to assess eyelid conformation with the
moved from side to side and up and down. head in different positions. Close inspection of
During head movement, the eyes will attempt the eyelid margins allows observation of the
to maintain the last eye direction, i.e., where cilia (eyelashes) and meibomian gland open-
the animal was looking at the start of the test. ings. The eyelids differ greatly between spe-
This results in a slow movement of the eyes cies. The upper eyelid is more mobile in
away from the direction of head movement. As mammals, whereas the lower eyelid is more
the head continues to be moved, the extraocu- mobile in birds and many lower vertebrates.
lar muscles, influenced by the vestibular sys- Birds have a tarsal plate in the lower eyelid and
tem, move the eyes quickly in the same a well-­developed, almost transparent third eye-
direction as the head movement. The eyes lid. Complete fusion of the upper and lower
should move in unison and should stop mov- eyelid forms the spectacle in snakes and geckos.
ing when head movement is stopped. The VOR The eyelids, conjunctiva, and third eyelid
is more difficult to perform in large animals. should be examined in one almost continuous
movement: the upper eyelid is retracted to
examine the dorsal bulbar conjunctiva; the
Tear Tests
eyelid margin is everted to examine the upper
At this point in the examination, or even before palpebral conjunctiva and the upper nasolacri-
some of the neuro-­ophthalmic tests, tear pro- mal punctum; and the third eyelid is protruded
duction should be measured using STT I. This by applying gentle pressure through the upper
is to avoid falsely high values from excessive eyelid to retropulse the globe and enable exam-
manipulation of the eye and/or eyelids (induc- ination of the anterior surface, leading edge,
ing reflex tear production) and/or the adminis- and alignment of the third eyelid. Finally, the
tration of any topical agents (e.g., stains, lower eyelid is retracted to aid visualization of
anesthetic agents, and mydriatic agents). the lower conjunctival fornix and nasolacrimal
punctum. The leading edge of the third eyelid
is usually pigmented. The lacrimal caruncle
Close Examination of the Adnexa
lies just inside the medial canthus; it appears
and Globe
as a small mound covered with conjunctiva
Following initial distance examination, the and, in some animals, fine hairs. It is more
animal can be handled gently, with minimal prominent in ungulates than in carnivores.
manipulation of adnexal tissues. The orbit A preliminary assessment of the nasolacri-
should be examined by palpation of the bony mal system is made at this stage. Tear overflow
orbital rim and indirectly by retropulsion of (epiphora) is noted and can represent either
­Ophthalmic Examination in Ambient Lightin  171

increased tear production or decreased tear mammals and should appear as a transparent,
drainage. Increased tear production is typically smooth, convex structure. Evaluation of the
caused by ocular surface irritation (e.g., ectopic resting pupil size, shape, and mobility of the
cilia) or pain (e.g., anterior uveitis) and can be pupil, and appearance of the anterior chamber
objectively quantified by STT I. Tear drainage structures should follow. In the horse, the
may be reduced or absent as a result of partial insertion of the pectinate ligaments onto
or complete obstruction of the nasolacrimal Descemet’s membrane (i.e., “gray line”) can be
drainage system. The drainage apparatus is observed laterally and medially, enabling
evaluated by examining the proximal upper direct observation of the iridocorneal drainage
and lower lacrimal puncta, and the distal nasal angle. Direct observation of the drainage angle
punctum; the latter is only really practical in is also possible in the cat because of its deep
the horse because it is large and easy to iden- anterior chamber and marked corneal
tify on the ventrolateral floor of the nasal vesti- curvature.
bule. The lacrimal puncta are slit-­like openings The cornea is examined next. Most mamma-
in most species, but are round in the cat. In the lian corneas are oval, with a greater horizontal
dog, the lacrimal puncta are 1 mm long and than vertical diameter. The normal cornea is
0.3 mm wide and are located 2–5 mm lateral to an avascular, nonpigmented, convex structure.
the medial canthus, on the palpebral conjunc- The presence of surface irregularities, blood
tiva, where the line of meibomian glands ends. vessels, pigment, or other opacities indicates
In the horse, the 2-­mm slit-­like lacrimal puncta disease. Corneal integrity is most readily eval-
are located 8–9 mm lateral to the medial can- uated with fluorescein dye. Fluorescein dye is
thus. The rabbit has a single lower lacrimal hydrophilic and binds readily to exposed cor-
punctum and the pig has a single upper punc- neal stroma if an ulcer is present. The dye will
tum Abnormalities in size, position, shape, not bind to intact healthy corneal epithelium
and ocular discharge should be noted. The area nor to Descemet’s membrane and the
ventral to the medial canthus should be evalu- endothelium.
ated for abnormalities (e.g., swelling) as the Corneal sensation may be demonstrated by
underlying lacrimal sac, the small dilation at touching the cornea gently with a thin wisp of
the confluence of the upper and lower canali- cotton while holding the eyelids open. When
culi, is a common site for foreign bodies. A touched from the periphery to avoid a menace
more detailed assessment of the nasolacrimal response, the normal corneal reflex is retrac-
system can be made with the application of tion of the globe, with protraction of the nicti-
fluorescein dye (Jones test), irrigation (see the tating membrane. This corneal reflex tests
“Nasolacrimal Flush” section), and imaging. cranial nerves V, VI, and VII. The degree of cor-
Gross examination of the ocular surface neal sensation can be semi-­quantified in differ-
includes assessment of the tear film and cor- ent areas of the cornea using an esthesiometer,
nea. The specular reflection of the cornea discussed later in “Advanced Ophthalmic
(Purkinje image) appears as a focal reflection Diagnostics.” Slit-­lamp biomicroscopy by the
of light from a window or artificial light in the veterinary ophthalmologist may be useful in
examination area. The specular reflection pro- characterizing the microscopic details and
vides information about the optical smooth- exact depth of corneal lesions. Additional tests
ness of the ocular surface and thereby the for corneal disease include culture, cytology,
quality and quantity of the tear film and cor- tear tests, and use of other ophthalmic dyes,
neal regularity. Gross examination of the lim- e.g., Rose Bengal. The anterior chamber is
bus, cornea, anterior chamber, anterior iris, observed for transparency and depth. Anterior
pupil, and anterior lens is performed at this chamber depth shows more variation in exotic
stage. The cornea is slightly oval in most species than in domestic animals. The anterior
172 Eye Examination and Diagnostics

chamber depth may decrease because of intu- The iris is evaluated for color, consistency,
mescent cataract, iris bombé, or a mass within pupillary membrane strands, pupil size and
or behind the iris. It may appear unusually shape, and stability. Multiple colors within an
deep in eyes without lens support in cases of iris may occur congenitally, as with hetero-
aphakia or pseudophakia, reabsorbing cataract, chromia irides, or may be acquired, as with
or lens luxation. A slit beam, as may be found chronic inflammation or neoplasia. Blue irides
on many direct ophthalmoscopes and slit-­lamp occur in some lightly pigmented breeds,
biomicroscopes, may be useful in evaluating whereas albino animals have pink-­to-­white iri-
the depth of the anterior chamber. The aqueous des. Iris darkening or thickening (or both) may
humor of the anterior chamber should be occur with chronic inflammation and neopla-
transparent and therefore free of blood (i.e., sia. Hypoplastic and atrophic irides are thin,
hyphema), protein (i.e., aqueous flare), cells, and usually transilluminate; focal holes may
fibrin, cysts, parasites, tumors, and foreign be present as well, especially near the pupil
material. Aqueous flare can be detected with a margin. The major arterial circle of the iris is
slit beam. In a dark room, a slit or tiny circular often visible (especially in iridal heterochro-
beam is focused on the cornea and viewed from mia) as an elevated, wavy line near the iris base.
an angle perpendicular to the beam. As it con- The pupil may be abnormally dilated with
tains only 10–50 mg/dl of protein, the normal iris atrophy, iris coloboma, glaucoma, and reti-
aqueous humor is clear. With inflammation, nal or optic nerve disease, or it may be abnor-
however, this protein content can reach 5–7 g/ mally small in microphthalmic eyes with
dl, which is a condition called plasmoid aque- congenital hypoplasia of the iris sphincter
ous. Under these conditions, both protein and with Horner’s syndrome or with anterior uvei-
cells suspended in the aqueous humor reflect tis. Abnormalities of pupil shape may occur
the focused beam, creating the Tyndall effect. with lens luxations, anterior and posterior
If the anterior chamber cannot be visualized synechiae, iris neoplasia, trauma, or iris atro-
because of corneal opacification, B-­scan ultra- phy. The pupil is round in dogs, a vertical slit
sonography may prove useful for evaluating in cats, and a horizontal ellipse in horses and
chamber depth and consistency. Aqueous par- cattle. Most ungulate species have nodular
acentesis, described under the “Advanced extensions of the posterior pigmented epithe-
Ophthalmic Diagnostics” section, may provide lium of the iris (i.e., granula iridica or corpora
useful information via culture, serology, or nigra), which protrude along the dorsal and
cytology. Laser cell fluorophotometry or ventral pupillary margins. In alpacas and lla-
flaremetry can measure protein and cellular mas, the dorsal iris is extended in “radial
debris levels in the aqueous humor and is folds” protruding above the pupil, similar to
extensively used in pharmacological testing. the granula iridica in the horse. Similar struc-
Because of the presence of the scleral shelf, tures are not typically seen in small animals.
the canine iridocorneal angle (ICA) and open- Iris masses in small animals should be retroil-
ing of the ciliary cleft (CC) cannot be visualized luminated to determine whether they are hol-
without special lenses. The direct goniolens low (i.e., cystic) or solid (i.e., neoplastic).
and indirect gonioprism allow observation of Details of iris lesions may be seen through an
the entrance into the ICA for congenital defects, otoscope head or, preferably, with the slit-­
abnormal narrowing, peripheral anterior syne- lamp biomicroscope. A slit beam can be used
chiae, extension of iris or limbal neoplasms, to determine whether an iris lesion is elevated
and foreign bodies. Though still limited in use, or, less commonly, depressed. Further diag-
ultrasonic biomicroscopy using probes from 40 nostic procedures include transillumination,
to 60 MHz permits high-­resolution imaging of retroillumination, gonioscopy, ultrasonogra-
the aqueous outflow pathways. phy, brush cytology, and biopsy.
­Ophthalmic Examination Technique  173

Intraocular Pressure Measurement animals, the hyaloid artery extends from the
and Pupil Dilation center of the optic disc to the axial posterior
lens capsule. In very young animals, and espe-
IOP is assessed in all patients presented for com-
cially ruminants, a persistent hyaloid artery
plete ophthalmic examination; the applanation
may be visible postnatally for several weeks.
or rebound tonometer is preferred by the veteri-
Abnormalities of the anterior vitreous may be
nary ophthalmologist as these instruments are
observed with direct illumination and prefera-
most accurate. IOP measurement should ini-
bly the slit-­lamp biomicroscope. The vitreous
tially be always carried out prior to the applica-
should be examined for extensions of uveal or
tion of mydriatics. In the absence of glaucoma
retinal hemorrhage, neoplasia, parasites, reti-
and lens luxation, pupils are pharmacologically
nal detachment, infection, and inflammation.
dilated. Tropicamide (1%) is preferred in most
Ultrasonic examination of the vitreous as well
mammals because of its rapid onset (10–20 min)
as vitreous paracentesis (i.e., hyalocentesis) is
and relatively short duration (6–8 h in dogs and
an additional diagnostic.
8–12 h in horses). Complete mydriasis is essen-
Successful examination of the ocular fundus
tial for thorough lens evaluation, as well as for
requires intimate knowledge of the normal
peripheral fundic examination.
variations within each species. Structures or
areas to be evaluated include the optic nerve
Anterior Segment Examination After head (i.e., optic disc or optic papilla: shape,
Pupil Dilation: Lens Examination color, and topography), retinal vasculature
The lens is evaluated with both direct illumina- (number and size), tapetal fundus in species
tion and retroillumination for its position, size, with a tapetum (reflectivity, pigmentation,
shape, surface irregularities, and transparency. depigmentation, hemorrhage, exudates), and
The size and shape of the lens in different species nontapetal fundus (pigment loss, hemor-
vary tremendously. A slit beam and the biomicro- rhages, exudates). Diagnostic procedures to
scope are preferred by the veterinary ophthal- evaluate the ocular fundus include both direct
mologist to characterize cataracts. While and indirect ophthalmoscopy, slit-­lamp biomi-
directing the beam onto the lens and looking croscopy with a condensing lens, fluorescein
from an oblique angle, the examiner observes a angiography (FA), electroretinography (ERG;
cross section of the lens. Cataracts should be clas- i.e., flash and pattern), ultrasonography,
sified both anatomically and by stage of maturity. biopsy, scanning laser tomography, and optical
Nuclear sclerosis, which is an aging change that coherence tomography (OCT). Direct and indi-
leads to a hazy, gray-­blue appearance in the rect ophthalmoscopy are the primary means to
center of the lens, must be distinguished from visualize and evaluate the ocular fundus.
senile cataract. The lens may appear to be cata-
ractous at a glance, but retroillumination and
ophthalmoscopy demonstrate that nuclear scle- ­ phthalmic Examination
O
rosis does not actually obstruct the passage of Techniques
light or prevent visualization of the ocular fun-
dus. Other methods of lens evaluation include Slit-­Lamp Biomicroscopy
both A-­and B-­scan ultrasonography.
The slit-­lamp biomicroscope is the most versa-
tile and important diagnostic tool for the vet-
Posterior Segment Examination
erinary ophthalmologist, allowing magnified,
The normal vitreous is a clear and homogene- three-­dimensional examination of the adnexa,
ous gel that fills the space between the poste- cornea, anterior chamber, lens, and vitreous.
rior lens capsule and the retina. In prenatal With the help of specifically designed
174 Eye Examination and Diagnostics

condensing lenses, even the ocular fundus can technology, and photographic and video adapt-
be inspected with the slit-­lamp biomicroscope. ers have also become available for some of the
The first slit-­lamp biomicroscope, which handheld slit-­lamp biomicroscope models.
combined a corneal microscope with a slit-­ Portable slit-­lamp biomicroscopes are less
lamp biomicroscope that used a magnesium expensive, and can be used in any position,
oxide light, was developed in 1911. Since then, and are thus are useful for laboratory, compan-
numerous refinements and modifications have ion, and large animals.
been made, and the slit-­lamp biomicroscope Simplified handheld units or headpieces for
was introduced into veterinary medicine in the direct ophthalmoscope handle combine a
1953. With the introduction of the portable slit-­ bright light source that can be used with both a
lamp biomicroscope in the 1960s (to accommo- diffuse (approximately 3–5-­mm circle) or a slit
date bedridden and anesthetized human (0.3–4 mm) setting with a magnifying lens of
patients and children), veterinary ophthalmol- 6× magnification at a 25–35° fixed angle. These
ogists quickly changed from the cumbersome instruments have obvious limitations when
table units to the smaller portable scopes! compared to the more versatile handheld slit-­
The slit-­lamp biomicroscope is the combina- lamp biomicroscopes described earlier, but can
tion of a binocular microscope with a highly still be useful for depth estimation of lesions in
versatile source of illumination. The micro- the anterior segment and lens, as well as with
scope and light source are copivotal (i.e., they the detection of aqueous flare.
swing on the same axis), confocal (i.e., they The aim of slit-­lamp biomicroscope exami-
focus on the same point), and isocentric (i.e., nation is to serially examine the eye under
they center on the same plane) (Figure 4.3). magnification with as many forms of illumina-
The strong white focal halogen, xenon, or tion as possible, to identify any pathology and
light-­emitting diode (LED) light can be modi- to create a mental, complete composite of the
fied by a series of diaphragms and filters that eye, including both detail and context. The
adjust the light shape (diffuse or focused light beam used during the slit-­lamp biomi-
beam), light intensity, and light-­beam width, croscopy can be diffuse or focal. Diffuse forms
length, orientation, and color (neutral density, of lighting are useful to examine a large area
cobalt blue, or red-­free). Returning light is for gross abnormalities and to obtain an initial
focused through the objective lenses of the bin- overview of the adnexa, cornea, anterior cham-
ocular microscope, and magnification can be ber, and iris. However, to gain more detailed
adjusted from 5× to 40× (10–20× in portable information and highlight subtle lesions, more
units), depending on the model. Digital focal forms of illumination are required. The
concept of slit-­lamp biomicroscopy with a
focal light is the creation of an optical section
of the transparent tissues of the eye (cornea,
anterior chamber, and lens). This is achieved
by projecting a narrowly delineated, sharply
focused, and bright slab of light onto the eye.
The optical section of the structures visible to
the examiner through the adjacent nonillumi-
nated tissues can be likened to a histological
section. Portable slit-­lamp biomicroscopes
offer slit beam width options varying from 0.1
to 1.6 mm. With the use of a broad slit beam
Figure 4.3 Use of a handheld slit-­lamp (>0.5 mm), transparent ocular structures such
biomicroscope in a dog. as the cornea become visible as a parallel-­piped
­Ophthalmic Examination Technique  175

“block of tissue.” The usually tall or long slit


Box 4.2 Advantages and Limitations
beam used for optical sectioning can be
of Direct Ophthalmoscopy
reduced to a minimum height or even a pin-
Advantages Greater magnification
point (1–2 mm) to allow checking for the
Tyndall effect, indicating any deviations of the Can be performed through a
small pupil
composition of the normally optically clear
Availability of options such as
AH.Both direct illumination and retroillumi- the slit and graticule
nation are utilized during ocular slit-­lamp
Ability to alter the dioptric
biomicroscopy. With direct illumination, the power of the ophthalmoscope
structure to be examined is illuminated by the Limitations Small field of view
light source itself, while in retroillumination, Short working distance
the structure of interest is illuminated by light between examiner and
reflected from a neighboring tissue. The same patient
opacity within the clear ocular media may Lack of stereopsis
appear bright in direct illumination and dark Difficulty in examining the
on indirect illumination. For this purpose, cor- peripheral fundus
neal changes are mostly examined by retroillu- Eye movements can be
mination from the iris, while iris and lens distracting
changes are routinely examined with the help Greater distortion when the
cornea and lens are not
of light reflected from the fundus. Iris transil-
transparent
lumination can be achieved when the fundus is
illuminated through a small pupil only and will
highlight defects in iris pigmentation or tissue. Examiner Mirror Patient

Direct Ophthalmoscopy
Ophthalmoscopy is a technique that requires
extensive practice before it becomes a valuable
and rapid diagnostic tool for the clinician. This
is not only because of the actual difficulty of
performing the procedure (with a moving eye),
but also because of the huge variation in fun- Figure 4.4 Optics of direct ophthalmoscopy. The
direct ophthalmoscope allows alignment of the
dic appearance both between and within dif-
observer’s visual axis with a light beam, which is
ferent species. The direct ophthalmoscope is reflected via a mirror to illuminate the patient’s
the most fundamental diagnostic instrument fundus. Light rays emanating from the patient’s eye
for the ophthalmologist! As the veterinary oto- form a real image on the observer’s retina.
scope and ophthalmoscope are often a combi-
nation set for the veterinarian, direct prism into the patient’s eye and is reflected
ophthalmoscopy is best first mastered before back through a lens in the ophthalmoscope to
other types of ophthalmoscopes are attempted. the examiner. To focus clearly on the animal’s
Direct ophthalmoscopy is the classic form of ocular fundus, the direct ophthalmoscope is
ophthalmoscopy with which most clinicians influenced by the combined refractive power
are familiar because the direct ophthalmo- of the patient’s cornea and lens, as well as the
scope is commonly available as part of a set refractive errors of the examiner. Refractive
with an otoscope (Box 4.2). The direct ophthal- errors for most animals appear to be reasona-
moscope consists of a power source and a halo- bly static with the exceptions of the nonhuman
gen or xenon coaxial optical system primate and the cat, in which some accommo-
(Figure 4.4). Light is directed via a mirror or dation may occur. Most fundi are in focus at
176 Eye Examination and Diagnostics

Table 4.1 Fundus magnification with direct


ophthalmoscopy in animals.a

Fundus Millimeter equivalent


Animal magnification per diopter change

Cat 19.5 0.22


Dog 17.2 0.28
Cow 10.6 0.74
Horse 7.9 1.33
Sheep 13.9 0.43
Rabbit 25.3 0.13 Figure 4.5 Close direct ophthalmoscopy. The
examiner must be as close as possible to obtain an
a
Change in millimeters with 1-­D change in focus by optimal image with direct ophthalmoscopy. To
direct ophthalmoscopy. achieve this, the examiner ideally should use the
right eye to examine the patient’s right eye, and
vice versa.
0–2 D if the examiner is emmetropic. The
resultant image is real, erect, and magnified
several times depending on the species being orderly fashion. It is important for each exam-
evaluated (Table 4.1). The size of the eye being iner to establish an order or pattern for the fun-
examined, and therefore the working distance dic examination to ensure that no features are
between the examiner and the lesion of inter- missed. The optic nerve is typically identified
est, can affect magnification. and examined first. Afterward, the remainder
To perform direct ophthalmoscopy, animals of the fundus is thoroughly examined in quad-
must be either reasonably cooperative or ade- rants, making sure that the tapetal regions of
quately restrained. Most small animals can be the fundus, the atapetal regions of the fundus,
gently restrained on the examination table by the fundic periphery, and the retinal vascula-
the owner or an assistant; some fractious ani- ture are closely examined.
mals or large animals require some form of A circular dial on the direct ophthalmoscope
sedation and/or an auriculopalpebral nerve holds a series of concave and convex lenses
block. Before examination, the pupils are usu- that can be rotated through the viewing aper-
ally dilated with a short-­acting mydriatic such ture (Figure 4.6). Green or black numbers on
as 0.5–1% tropicamide. the circular dial represent convex or converg-
To initiate direct ophthalmoscopy, the ing lenses (positive), while red numbers repre-
patient’s fundic reflex is identified approxi- sent concave or diverging lenses (negative).
mately an arm’s length away from the patient’s These lenses are selected so that the focus of
eye. Ideally, the examiner’s right eye should be the patient’s eye is obtained. A separate dial or
used to examine the patient’s right eye, and switch adjusts the size, shape, and color of the
vice versa. Once the fundic reflex is identified, light beam (Table 4.2).
the examiner moves toward the patient to a The direct ophthalmoscope can also be used
point approximately 2–3 cm from the eye – the to pick up any central opacities in the clear
closer the examiner is to the patient’s eye, the media anterior to the fundus by retroillumina-
wider the angle of view (Figure 4.5). In the dog tion. Once the fundic reflex is identified by the
and nonhuman primate, the patient’s eye is examiner looking through the ophthalmo-
intermittently moving and often the desired scope at a distance (“distant direct ophthal-
area of the ocular fundus is only occasionally moscopy”), a dark spot detected against the
viewed. Once the fundus is visualized, oph- fundus reflection indicates that an opacity is
thalmoscopy should proceed in a timely and blocking the return of light to the observer.
­Ophthalmic Examination Technique  177

(a) (b)

Figure 4.6 Direct ophthalmoscope head. (a) Observer’s side with viewing aperture, lens dial, quick lens
switch, and diopter indicator. (b) Patient side with viewing hole and switches/dials allowing selection of
beam size and shape, as well as light filters.

Table 4.2 Light beam selections for direct


ophthalmoscopy. Box 4.3 Advantages and Limitations
of Indirect Ophthalmoscopy
Small spot Use with pinpoint pupil Advantages Larger (and often safer) working
distance from the patient
Medium spot Use with pupil in a darkened Larger field of view
room
Stereopsis
Large spot Use in a pupil dilated by
Can be used with limited
mydriatics
corneal/lens translucency
Red-­free light To evaluate retinal vessels and Limitations A dilated pupil is necessary
the nerve fiber layer
More difficult to master
Graticule Grid (often of 16 squares) to
estimate size of fundic lesions Lower magnification

Slit beam Helps estimate fundic


elevations/depressions
Blue light Helps detect fluorescence

Indirect Ophthalmoscopy
Indirect ophthalmoscopy, in contrast to direct
ophthalmoscopy, allows the clinician to view a
larger portion of the fundus (larger field of
view) at one time and to do so from a greater
and safer working distance from the patient
(Box 4.3 and Figure 4.7). Because much less Figure 4.7 Binocular indirect ophthalmoscopy with the
Keeler Vantage head-­mounted indirect ophthalmoscope
magnification of the image is perceived with
in the dog. In this technique, the observer has not only
indirect ophthalmoscopy than with direct oph- stereopsis, but also one hand free to hold the patient’s
thalmoscopy, a better overview of the fundus head and eyelids.
178 Eye Examination and Diagnostics

(a) (b) (c)

(d) (e) (f)

Figure 4.8 Comparison of direct (a and d), panoptic (b and e), and indirect ophthalmoscopy (c and f). These
photographs illustrate the different appearances in terms of magnification and orientation of the canine
and equine ocular fundus with each of the three methods of ophthalmoscopy.

can be achieved (Figure 4.8a–f). Direct and reflected light so that it can be directed into
indirect methods complement each other, par- both of the examiner’s eyes, thereby permit-
ticularly if a lesion detected with the indirect ting stereopsis (Figure 4.9). Most binocular
method is then examined more closely, at indirect ophthalmoscopes have interchangea-
greater magnification, with the direct method. ble apertures and filters, as well as permanent
The direct method is most useful when exam- or detachable teaching mirrors for students,
ining the optic disc and surrounding retinal clients, or others, and are also available with
vasculature. video cameras. Commercial indirect ophthal-
The necessary components of indirect oph- moscopes cost in excess of US$1000.
thalmoscopy are a strong, focal light source Monocular indirect ophthalmoscopy can
and a converging lens. Indirect ophthalmos- also be performed using a bright, handheld
copy has additional advantages over direct light source (e.g., a transilluminator, direct
ophthalmoscopy when a binocular indirect ophthalmoscope or strong otoscope, fiberoptic
ophthalmoscope is utilized, including stereop- bundle, and penlight) and a handheld lens
sis and the ability to use both hands for patient (Figure 4.10). This method does not provide
manipulation. Binocular indirect ophthalmos- stereopsis and requires an assistant to restrain
copy uses a halogen, xenon, or LED light the patient and position the head, but nonethe-
source, a mirror to direct light into the patient’s less gives an overall view of the fundus.
eye, a handheld converging lens to magnify the To perform the fundic examination follow-
reflected image, and two prisms to split the ing induction of mydriasis, the examiner
­Ophthalmic Examination Technique  179

E xa m in e r Aerial image of retina Condenser Patient

Figure 4.9 The optics of binocular indirect ophthalmoscope allow the light from the indirect
ophthalmoscope to illuminate the patient’s ocular fundus. The image is split with a prism into both
examiner’s eyes, permitting stereopsis. The patient’s fundus image is virtual and inverted.

reflection, as in distant direct ophthalmoscopy.


Examination of the fundus with indirect oph-
thalmoscopy should proceed in an orderly fash-
ion, as with direct ophthalmoscopy, taking care
to examine the optic nerve, retinal vasculature,
tapetal and nontapetal fundus, and periphery.
The extreme peripheral retina at the ora ciliaris
can be visualized with practice and good mydri-
asis, especially ventrally and temporally.
Figure 4.10 Monocular indirect ophthalmoscopy. There are many different lenses available for
The technique can be carried out with minimal use with indirect ophthalmoscopy, ranging in
equipment, but stereopsis is lost and the observer diopter strength from +5.5 to +90 D. The
relies on the help of an assistant to stabilize the
patient’s head. choice of lens will vary depending on the
required magnification, field of view, stereop-
grasps the patient’s muzzle with one hand and sis, and the size of the patient’s pupil. Various
stabilizes the head. The other hand is used models of binocular indirect ophthalmoscopes
both to hold the eyelids open and to position are available from Heine, Keeler, Propper,
the lens (with the strongest convex surface fac- Topcon, Xonix, and Zeiss. Camera and video
ing the examiner) 2–4 cm in front of the attachments are available for some models,
patient’s cornea. From a distance of approxi- thus allowing the examiner to display and
mately 0.50–0.75 m (at arm’s length), the exam- record findings for teaching and research pur-
iner then directs the light into the patient’s eye poses. Commercial monocular indirect oph-
and identifies the fundic reflex. thalmoscopes are manufactured by Reichert
Once the fundic reflex is identified, opacities and the American optical Corporation. These
of the cornea, lens, and vitreous can be seen as instruments use an internal lens to magnify
dark areas highlighted against the fundic the reflected fundic image.
180 Eye Examination and Diagnostics

Indirect ophthalmoscopy can also be used to human ophthalmology and optometry, this
semi-­qualify the refractive error of an animal. technique has also found use in veterinary
By slowly withdrawing the handheld lens from ophthalmology, particularly to define the nor-
the eye and observing any change in magnifi- mal, pathological, and surgically induced
cation of the image, the clinician can roughly refractive state of eyes, and in the evaluation
estimate the refractive power of the patient. If and improvement of intraocular lens implants.
the fundic image becomes larger, then the ani- When light rays are projected onto an eye from
mal is somewhat myopic; if it becomes smaller, infinity, they emerge from an emmetropic eye
then the patient is hyperopic; and if the size of as parallel rays, from a myopic eye as converg-
the image remains static, then the animal is ing rays, and from a hyperopic eye as diverging
emmetropic. rays. The location at which these emergent
light rays form a focal point or plane is called
Pan-­Retinal Ophthalmoscope the far point. The far point is at infinity, in
The recently introduced 2.2 pan-­retinal oph- front of infinity, and beyond infinity for the
thalmoscope is the most versatile instrument emmetropic, myopic, and hyperopic eyes,
for the clinician who wishes to only purchase respectively. The procedure of retinoscopy uti-
one scope, as it provides the best compromise lizes a lens placed in front of the eye to modify
between magnification and field of view, but the image produced (Figure 4.12). The power
does not provide dioptric readings. The focus is of the lens that corrects the image, or neutral-
adjusted to zero, the fundic reflex is located, izes the movement of the fundic reflex, permits
and the instrument is positioned about 2–3 cm an estimation of the dioptric power of the
from the cornea. In many ways, the pan-­retinal patient’s eye and its difference from emmetro-
ophthalmoscope is easier to master than the pia. Retinoscopy allows veterinary ophthal-
direct ophthalmoscope (Figure 4.11). mologists to quantitatively determine the
refractive error of the eye to within 0.25–0.50 D
Retinoscopy of its true refractive state. Retinoscopy has
Retinoscopy, also known as skiascopy, is the become a firmly established procedure in clini-
objective determination of the dioptric state or cal veterinary ophthalmology. However, con-
refractive error of the eye. Commonly used in siderable practice is necessary to produce
consistent results with retinoscopy in animals.
For that reason, model eyes are available for
teaching and practice. With increased use, reti-
noscopy will not only continue to improve our

Figure 4.11 The panoptic ophthalmoscope is a


good compromise between the direct and indirect
methods of ophthalmoscopy proving a real image Figure 4.12 Retinoscopy carried out in a dog.
(neither inverted or reversed) and is intermediate Note the working distance of 67 cm between
in magnifications between the two. (Courtesy of examiner and patient. The skiascopy bar or rack is
Franck J. Ollivier, Centre Veterinaire DMV, Montreal, positioned in front of the dog’s eye; it contains a
Quebec, Canada.) series of plus and minus.
­Ophthalmic Examination Technique  181

selection of intraocular lens implants for positions to examine the entire 360°. The
patients undergoing cataract surgery, but also Koeppe and Lovac–Barkan lenses are both
assist with evaluating performance problems direct gonioscopy lenses, which are commonly
associated with ametropia in working animals. used in the dog. The Koeppe lens is held in
place by a combination of the vacuum created
Gonioscopy by pressing the lens onto the anesthetized cor-
Gonioscopy describes the technique that neal surface and the small “flange” placed into
allows examination of the anterior face of the the conjunctival fornices, whereas the Lovac–
ICA and opening of the CC. The clinical exam- Barkan lens is held in place by a vacuum cre-
ination of this region is an integral part of the ated via a syringe and a silicone tube
evaluation of the aqueous outflow pathways attachment (Figure 4.14). Indirect gonioscopy
and may provide insight into the pathways of lenses use single or multiple mirrors or prisms
aqueous humor outflow and the pathogenesis that reflect the light rays emanating from the
of a glaucomatous state. In 1936, Troncoso and ICA through a planoanterior contact lens,
Castroviejo published the comparative gonio- ensuring that the critical angle is not reached.
scopic anatomy of the rabbit, pig, cat, dog, and Indirect lenses allow the ICA and opening of
nonhuman primate. Gonioscopy was reported the CC to be visualized from directly in front of
in dogs in the 1960s. the patient.
The ICA of most animals and humans can-
not be directly visualized because it is obscured
by the scleral shelf. The application of a con-
tact lens to the eye can overcome this problem
by removing the cornea–air interface and cre-
ating a new contact lens–air interface instead
(Figure 4.13). Many different designs of gonio-
lens are available commercially, but all fall into
one of two categories: direct or indirect. Direct
goniolenses are very convex to avoid the criti-
cal angle being reached and allow the exam-
iner to look obliquely across the anterior
chamber to the opposite ICA segment. The
Figure 4.14 Koeppe lens in situ. The lens is
image in direct gonioscopy is real and magni- retained by suction on the corneal surface, freeing
fied 1.5–3×, but the examiner must change the examiner’s hands.

(a) (b)

Mirror

Figure 4.13 Gonioscopy lenses can be divided into direct and indirect. (a) Direct gonioscopy lenses allow
examination of the ICA opposite to the viewing position of the examiner, and create a real image (b).
182 Eye Examination and Diagnostics

Practical Application management of glaucoma and to distinguish


Gonioscopy can usually be performed in the between open-­ and closed-­angle glaucoma.
conscious patient following topical anesthesia; Canine patients presenting with unilateral
sedation is only required in a few uncoopera- glaucoma often have marked corneal pathol-
tive patients. Restraint of the patient’s head ogy in the affected eye because of the elevated
should ideally be provided by a trained assis- IOP and it may not be possible to visualize the
tant as the examiner will require both hands face of the ICA. Gonioscopic evaluation of the
for the procedure. Both sitting and lateral entrance to the ICA in the fellow eye is used in
recumbent positions have been described for this situation to extrapolate information about
canine gonioscopy. the etiology of the glaucoma in the affected eye.
A portable slit-­lamp biomicroscope is ideal
for providing illumination, magnification, and
stereopsis, but a handheld fundus camera can
Ophthalmic
also provide good magnification and will allow
photodocumentation of the ICA entrance.
Diagnostic Procedures
Some examiners traditionally use an otoscope
Corneal Esthesiometry
with the speculum removed, which obviously
affords less magnification. With direct gonios- The corneal reflex is one of the most sensitive
copy lenses, the examiner must look into the reflexes in the body and its purpose is to protect
lens from all four quadrants to obtain a com- the eye. When tested subjectively by touching
plete image of the ICA, with the dorsal and lat- the peripheral cornea with a sterile swab tip or
eral quadrants being the least accessible in the wisp of cotton wool, the corneal reflex results in
awake and upright patient. The entire ICA and globe retraction (indicated by protrusion of the
opening of the CC are systematically evaluated, third eyelid) and eyelid closure (a blink). The
with special attention given to angle width and stimulus is applied to the peripheral cornea to
pectinate ligament conformation (Figure 4.15). avoid eliciting a menace response. The afferent
Gonioscopy is most commonly performed arm of the corneal reflex is the ophthalmic
in the dog as an essential tool in the branch of cranial nerve V, and the efferent arm

Cornea

Light (limbal)
pigment band
Dark pigment band
Pectinate ligament
fibers

Iris

Pupil

Figure 4.15 Normal ICA in a Flat-­Coated Retriever. (Courtesy of Stuart Ellis, Riverbank Veterinary Centre,
Ashton, Lancashire, UK.)
Ophthalmic Diagnostic Procedures  183

is mediated by cranial nerves VI (globe retrac- shortened by 0.5 cm decrements. The CTT in
tion) and VII (eyelid closure). centimeters is converted to pressure in milli-
Corneal esthesiometry uses the corneal grams per 0.0113 mm2 sectional area of the fil-
reflex to quantitatively evaluate corneal sensi- ament (S) and grams per square millimeter
tivity, and thereby indirectly assess corneal using the conversion table provided by the
innervation. Different types of corneal esthesi- esthesiometer manufacturer. Sensitivity can be
ometers include Cochet–Bonnet, Larson– assessed in different regions, e.g., the central,
Millodot, and noncontact air jet esthesiometers. dorsal, temporal, ventral, and nasal regions.
The Cochet–Bonnet esthesiometer is the most
commonly used in veterinary ophthalmology.
Corneal and Conjunctival Cultures
It consists of a nylon filament that is 0.12 mm
and Cytology
in diameter and has a variable length of
0.5–6 cm. (The filament is platinum in the Corneal and conjunctival cultures and cytology
Larson–Millodot esthesiometer.) A change in can aid in the diagnosis and determination of
filament length relates to a change in pressure appropriate antimicrobial therapy in many ocu-
exerted on the cornea by the filament tip; lar diseases, and are presented in both basic and
shorter filament lengths apply more pressure advanced diagnostics. The technique is quick
to the cornea, and vice versa. The pressure and straightforward, and is tolerated without
ranges from 5 to 180 mg/0.0113 mm (0.4–15.9 g/ topical anesthesia in most compliant animals.
mm). The instrument is held perpendicular to If, however, the eye is very painful, sedation and
the cornea with the filament extended to its regional nerve blocks may be necessary, particu-
maximum length, and advanced until the fila- larly in the horse. Corneal cultures and cytology
ment contacts the cornea, creating a slight are more difficult to perform, especially when
bend in the fiber (Figure 4.16). The corneal an animal is painful, and care should be used
touch threshold (CTT) is the degree of corneal when sampling a fragile corneal wound. These
stimulation that is required to elicit a blink diagnostic techniques are routinely employed
reflex. Corneal sensitivity and CTT are by the veterinary ophthalmologist.
inversely proportional. The CTT is defined as Ideally, a sample for culture should be taken
the pressure at which the majority of touch before solutions are applied to the eye. Topical
stimuli elicit a blink – this is quantified in most anesthetics can hinder the growth of microbes.
studies. For example, when more than 50% of If a sample can be achieved safely and without
attempts result in a blink reflex, the filament is undue discomfort to the animal without topi-
cal anesthetics, the sample is less likely to
become adulterated. However, if the wound is
fragile or the animal fractious or painful, topi-
cal anesthesia may be applied prior to sample
collection. Topical anesthesia is requisite prior
to the collection of cells for cytology.
To obtain a sample using a swab, the swab is
gently rubbed or rolled over the lesion; for a
conjunctival sample, the swab is rolled in the
lower conjunctival sac anterior to the third
eyelid (facilitated by retropulsion to protrude
the third eyelid) (Figure 4.17a and b). To obtain
Figure 4.16 Corneal sensation can be assessed
deeper corneal material by scraping, the blunt
quantitatively by a Cochet–Bonnet esthesiometer.
(Courtesy of UW Madison Ophthalmology Service, end of a sterile surgical blade or a Kimura
Madison, WI, USA.) spatula is used in a scraping motion, ideally in
184 Eye Examination and Diagnostics

(a) staining characteristics (Gram-­positive or


Gram-­negative), number, and location (intra-
cellular/extracellular).
The swab is the least traumatic method to
the eye for sample collection and is most fre-
quently used to collect samples for microbiol-
ogy. Swabs preserve cellular integrity, but the
number of cells collected is often too low to
make a diagnosis. Samples should be gently
rolled (not rubbed) onto glass slides to mini-
mize cell damage. Swabs are more commonly
(b)
used for collection of samples for microbiology
than for cytology.
The Kimura spatula provides a more precise
method of collecting cells from specific areas,
and greater numbers of deeper cells are usually
obtained, compared to the swab methods. This
technique remains the standard in diagnostic
veterinary ophthalmology. However, this
method may lead to greater damage to both the
Figure 4.17 (a) To obtain a conjunctival sample, sample (overlapping cells and crushing arti-
for either microbiology or cytology, the swab is
gently rolled in the lower conjunctival sac anterior fact) and the eye. The cytobrush has proved to
to the third eyelid. This is facilitated by be superior for all cytological parameters stud-
retropulsion to protrude the third eyelid. Care must ied when compared with cotton-­tipped swabs
be taken to ensure that the swab touches only the and two different spatulas in dogs, cats, sheep,
area of interest to avoid contamination from
nearby structures, e.g., eyelids. (b) Instruments for goats, cattle, and horses. The advantages of this
corneoconjunctival cytology include the Kimura technique include an increase in sample cellu-
spatula (top), cytobrush (middle), and scalpel larity acquisition of cells from deeper layers
blade (bottom). with less intervention, and improved morpho-
logical appearance of each cell because of
one direction to create a “pile of cells.” The reduced cell overlap (i.e., a good monolayer).
material is then transferred onto a sterile swab Impression cytology relies on cells that exfoli-
tip. Conjunctival scrapings can be performed ate easily and is therefore most readily applied
in the same way, but are less commonly done to the investigation of superficial conjunctival
because the conjunctiva is freely moveable. disease. It can be performed with a clean glass
Corneoconjunctival cytology is a convenient slide, cellulose acetate strip, Biopore membrane
method to characterize, and in some cases device, or asymmetric strips of Millipore paper.
diagnose, the disease process involving the Impression cytology provides a good number of
ocular surface. It can be used either alone or in cells, but cell clumping is common. It has
combination with culture to provide rapid received some use in KCS research, but does
results that may influence the immediate not provide clinically relevant advantages over
course of therapy. Although less sensitive than scrapings and cytobrush samples, both of
culture, exfoliative cytology is a very rewarding which tend to collect more cells from
tool in clinical ophthalmology. It can identify deeper layers.
organisms (e.g., bacteria, fungal hyphae, and The material on the slide needs to be fixed
yeast bodies), and provide information in immediately to prevent cellular degeneration.
terms of morphology (e.g., rods/cocci), A simple practical method for rapid fixation is
Ophthalmic Diagnostic Procedures  185

to apply heat from a hairdryer to the underside tear tests are available, but are mainly used by
of the slide. A special cytological fixative spray the veterinary ophthalmologist and are pre-
can also be applied immediately, while the sented briefly in the “Advanced Ophthalmic
sample is wet. Rapid staining kits (e.g., Diff-­ Diagnostics” section. Commercial standard-
Quick) have a fixative incorporated into the ized strips have a millimeter scale and may be
staining process. If possible, several slides with impregnated with blue dye at the 5 mm point
adequate sample material should be prepared to highlight tear fluid migration. The use of a
to permit the use of different stains if needed. modified strip has been described in the dog;
Commonly used stains include the Gram the strip is 5 mm wide for the first 10 mm and
stain and various Romanowsky-­type stains then 7 mm wide beyond this.
(e.g., Diff-­Quick and modified Wright– Despite criticism of its poor repeatability
Giemsa stain). and inconsistencies, the STT remains the
standard method for quantifying aqueous tear
production in veterinary ophthalmology. It has
Additional Tests
been used extensively to establish normal val-
Additional tests that can be performed on cor- ues in domestic and nondomestic species.
neal and conjunctival samples include poly- The STT should be performed early in the
merase chain reaction (PCR) and ophthalmic examination to minimize the effect
immunofluorescent antibody (IFA) tests for of reflex tearing from eyelid manipulation and
Chlamydophila felis, feline herpesvirus before any topical agents are applied to the eye.
(FHV-­1), equine herpesvirus (EHV-­1, EHV-­2, The strip should be bent slightly at the notch
EHV-­4), and fungal DNA. In PCR testing (the before removal from the pack and placed in the
detection of organism DNA or RNA), nucleic lateral half of the lower conjunctival sac so that
acid can be affected by heat, ultraviolet light, the notch is at the level of the lid margin and the
and enzymes from damaged tissue. Any type strip is in contact with the cornea (Figure 4.18).
of swab can be used for sample collection, The eyelids can be open or held closed, although
unlike for microbiology (designated microbiol- the latter may help to stop the premature loss of
ogy swab). the strip. The strip is left in place for 1 min and
tears are measured immediately upon removal.
STT I values in the normal adult dog vary from
Tear Tests
The tear film can be assessed in quantitative
and qualitative terms. Three quantitative tests
are described in this section: the STT, the phe-
nol red thread (PRT) tear test, and the most
recent endodontic absorbent paper point test
(EAPTT). The tear film breakup time (TBUT),
a qualitative test, is described under the
“External Ophthalmic Stains” section.

Schirmer Tear Test I


The tear film can be assessed in quantitative
and qualitative terms, and thus is described in Figure 4.18 Aqueous tear production can be
both the basic and advanced diagnostics sec- accessed by the Schirmer tear test. The short folded
end of the paper strip is placed in the lateral half of
tions. The most frequently used quantitative
the lower conjunctival sac so that it is in direct
test is STT I, which measures both the reflex contact with the cornea, in order to measure both
and basal aqueous tear formation rates. Other basal and reflex tear reproduction.
186 Eye Examination and Diagnostics

18.64 ± 4.47 to 23.90 ± 5.12 mm/min. In the dog, end. The folded end is placed in the lower con-
values of less than 5 mm/min are considered to junctival fornix for 15 s. As the slightly alkaline
be diagnostic for KCS, and values of less than tears wick along the thread, the pale yellow
10 mm/min are suspicious if combined with thread turns orange. The PRT tear test values
characteristic clinical signs. STT I values in the are 34.15 ± 4.45 and 23.04 ± 2.23 mm in the dog
normal adult cat vary from 14.3 ± 4.7 to and cat, respectively. A recent study provided
16.92 ± 5.73 mm/min. Low STT values in the cat PRT tear test values of 30.22 ± 0.99 and
must be carefully interpreted together with the 31.00 ± 1.4 mm in the Arabian and
clinical signs, because the range of values in Thoroughbred horses, respectively. The main
normal cats is wide; in one study of 76 cats, STT advantage of the PRT tear test in veterinary oph-
II values ranged from 1 to 33 mm/min. Tear pro- thalmology is that it can be used in small eyes
duction in the horse is greater than in the dog and is therefore appropriate for many nondo-
and cat and may overwhelm commercial strips mestic species. Recent techniques have included
in less than the standard 1-­min period. STT I meniscometry (indirect assessment of tear vol-
values in the normal adult horse, using a stand- ume by measurement of the tear meniscus
ard 5 × 35-­mm test strip, vary from 20.6 ± 6.5 to radius), interferometry (assessment of tear film
24.8 ± 4.8 mm/min. thickness and analysis of the lipid layer), and
meibometry (quantification of the amount of
Schirmer Tear Test II meibomian lipid on the lid margin).
STT II quantifies basal production of the aque-
ous component of the tear film, and can be per- Endodontic Absorbent Paper Point Test
formed after completion of STT I. Commercial The EAPPT was first reported in marmosets by
strips have a millimeter scale and may be Lange in 2012. Like the STT and the PRT test,
impregnated with blue dye at the 5 mm point to the EAPPT quantifies the aqueous portion of
highlight tear fluid migration. STT II is used to tears. Like the PRT test, the EAPTT is particu-
determine the relative contributions of aque- larly suitable for eyes with very low tear produc-
ous tears from the lacrimal and nictitans tion and/or for very small eyes. The suitability
glands, and to assess the influence of different for small eyes is highlighted by results from a
factors such as signalment, environment, and seed finch weighing 20 g with a palpebral length
drugs on tear production. The STT II test is of 4.46 ± 0.09 mm (the width of a standard STT
used more widely in humans where high reflex strip is 5 mm). The strip is used in dentistry and
tear production may mask low basal tear pro- is highly absorptive and sterile. The standard
duction. One drop of topical anesthetic is length is 28 mm and the diameter of the conical
applied to the eye and the excess is blotted away tip varies from 0.15 to 0.80 mm, making it highly
with a swab or cotton-­tipped applicator; a few applicable to species with small eyes. The Lange
minutes are allowed to elapse. The test is then marmoset study used a 0.3 mm tip (Sterile
performed as for STT I. Reported STT II values Roeko Top Color, size 30, Roeko, Langenau,
in the normal adult dog are 6.2 ± 3.1, 9.52 ± 4.55, Germany). The strip is pin the lower conjuncti-
and 11.6 ± 6.1 mm/min. The STT II value in the val fornix for 1 min. After removal, the length of
normal adult cat is 13.2 ± 3.4 mm/min, which is wetting is measured in millimeters.
approximately 80% of the STT I result.
External Ophthalmic Stains
Phenol Red Thread Tear Test
A recently described tear test, the PRT tear test, External ophthalmic dyes are routinely used in
also quantifies production of the aqueous com- veterinary medicine to aid the diagnosis of cor-
ponent of the tear film. The standardized cotton neal, conjunctival, lacrimal, and nasolacrimal
thread is 75 mm long with a fold 3 mm from one diseases. The most commonly used dye is
Ophthalmic Diagnostic Procedures  187

Table 4.3 Topical stains for veterinary (a)


ophthalmology.

Stain Effect Indications

Fluorescein Intercellular Corneal ulcers


spaces and
nasolacrimal
patency (b)
Rose Bengal Mucin KCS, and
covering cells degenerating
Mucus corneal and
conjunctival
cells
Alcian blue Mucus KCS and
conjunctivitis
Trypan blue Mucus KCS and
Dead and conjunctivitis
degenerating
cells
Figure 4.19 Ophthalmic stains. A. Fluorescein dye
Methylene Mucus
is available as a sterile impregnated paper strip
blue Dead and and can be made into a solution by mixing with
degenerating sterile water, saline, or eyewash. B. Fluorescein dye
cells stains the exposed hydrophilic corneal stroma in a
large superficial ulcer in a cat.

fluorescein, but Rose Bengal and Trypan blue


are also used by veterinary ophthalmologists absorbed light to emitted fluorescent light with
(Table 4.3). a peak wavelength of 520 nm (i.e., green light).
Fluorescence is most intense at alkaline pH
Fluorescein Dye (e.g., saline solution or the tear film); at acid
The most common use for topical sodium fluo- pH, sodium fluorescein appears yellow or
rescein is in the detection of corneal ulceration orange. Fluorescein is available as a 2.0% alka-
(Figure 4.19). It is also used to detect conjunc- line solution or as an impregnated paper strip.
tival epithelial defects, aqueous humor leakage Only disposable sources (e.g., impregnated
(Seidel test), qualitative tear film abnormalities paper strips and single-­dose vials) should be
(TBUT), and to assess physiological flow of the used for topical application, because multidose
nasolacrimal system (Jones test). Less com- solutions have been associated with bacterial
mon but still important uses include some contamination. Viruses can also survive in flu-
methods of applanation tonometry, fluoropho- orescein solution: feline calicivirus (a nonen-
tometry (e.g., determination of aqueous humor veloped virus) remained viable in a multidose
flow rate, determination of tear flow, and FA), bottle of fluorescein for up to seven days. In the
tear film studies, and pharmacology studies same study, two enveloped viruses, EHV-­4 and
(e.g., as a topical ophthalmic drug delivery FHV-­1, were not detected at 1 h.
device in the horse). Sodium fluorescein is a In small animals, the strip should be mois-
water-­soluble, weak dibasic acid of the xan- tened with sterile normal saline or eyewash
thene group that is detectable in solution at and gently touched once on the dorsal bulbar
concentrations as low as 1 ppm. Its absorption conjunctiva (Figure 4.20). In large animals, e.g.,
spectrum peaks at 490 nm (i.e., blue light). horses, the easiest method of application is to
Sodium fluorescein converts almost 100% of squirt fluorescein solution directly from a 3-­ml
188 Eye Examination and Diagnostics

epithelium (conjunctival and corneal), but


adheres to, and is absorbed by, any exposed
stroma. It also stains intercellular spaces,
because of exposed hydrophilic substance, and
therefore assists in the detection of corneal
erosions (which by definition do not penetrate
the basement membrane of the epithelium).
Fluorescein does not stain Descemet’s mem-
brane. The use of magnification and/or an
ultraviolet or blue light, usually available on a
direct ophthalmoscope or a slit-­lamp biomicro-
Figure 4.20 Application of fluorescein dye. The
scope, improves visualization of the dye, but is
fluorescein impregnated strip is moistened with, for
example, sterile saline or eyewash, and then gently not usually necessary.
touched once to the dorsal bulbar conjunctiva, with
the upper lid retracted. The eyelids are then closed
Jones Test (Nasolacrimal Drainage)
or the animal allowed to blink to distribute the
fluorescein across the ocular surface. The fluorescein drainage test (Jones test)
assesses the entire mechanism of tear drainage
syringe through the hub of a 25-­gauge needle by determining both the anatomical and the
that has been manually broken off. After appli- physiological patency of the nasolacrimal sys-
cation, regardless of the method used, the eye- tem. It is an essential part of both basic and
lids should be closed or the animal allowed to advanced eye examinations. It does so without
blink to distribute the fluorescein across the altering the natural state of the nasolacrimal
ocular surface. The eye is then irrigated (if tol- system, in contrast to nasolacrimal flushing
erated) with additional saline or eyewash to (see later). Fluorescein is applied to the eye as
remove excess dye from the ocular surface. This described previously, but without subsequent
important step reduces the potential for a false-­ rinsing.
positive diagnosis of a corneal ulcer. The Jones test is the timing of the passage of
Fluorescein is highly lipophobic and hydro- fluorescein through the system to the ipsilat-
philic. Thus, when applied to the surface of the eral nares. The test is performed on both eyes
eye, it does not remain in contact with the and the times compared (Figure 4.21). The
lipid-­containing cell membranes of the reported values for normal passage times in

(a) (b)

Figure 4.21 Jones test (fluorescein dye passage test) in a one-year-old Labrador Retriever with a swelling
ventral to the medial canthus of the right eye. (a) Fluorescein dye flows onto the skin at the medial canthus
of the right eye. (b) As viewed at the nostrils, the right nasolacrimal apparatus is occluded but the left
nasolacrimal system is patent.
Ophthalmic Diagnostic Procedures  189

(orthograde; from the lacrimal puncta) or ret-


rograde (from the nasal punctum) direction;
the choice depends on the species and the clin-
ical signs. Normograde irrigation is routine in
most species because identification and can-
nulation of the small nasal punctum are diffi-
cult; the exception is the horse, as the horse
distal nasal punctum is large, easy to identify,
and readily cannulated. The level of restraint
required varies between species and individu-
als. The technique can be performed conscious
in many dogs, rabbits, and cattle, whereas
Figure 4.22 A positive Jones result at the right horses usually require sedation and cats
nostril in a horse. require general anesthesia (because the lacri-
mal puncta are very small and difficult to can-
different species are highly variable. In dogs nulate). With the aid of illumination and
and cats, the following values have been magnification (depending on the species), the
reported: 30–60 s in dogs; 30 s to 5 min in dogs upper and lower lacrimal puncta are identified.
and 15 s to 1 min in cats; within 5 min in dogs The lacrimal puncta are slit-­like openings in
and cats; and up to 5–10 min in clinically nor- most species, but are round in the cat. In the
mal dogs. In the horse, the normal passage dog, the slit-­like lacrimal puncta are 1 mm long
time is less than 5 min, but may be up to 20 min and 0.3 mm wide and are located 2–5 mm lat-
(Figure 4.22). The test was not considered to be eral to the medial canthus, on the palpebral
clinically useful in brachycephalic dogs. A neg- conjunctiva, where the line of meibomian
ative result is only suggestive of a problem glands ends. In the horse, the 2-­mm slit-­like
because there are several reasons for a false-­ lacrimal puncta are located 8–9 mm lateral to
negative result. the medial canthus. The rabbit has a single
Despite its inherent problems, the Jones test lower lacrimal punctum, and the pig has a sin-
is a quick and simple diagnostic procedure, gle upper lacrimal punctum. It is recom-
and is the most common test for nasolacrimal mended that the upper lacrimal punctum is
patency. If the Jones test is negative and the first cannulated to avoid damage to the lower
clinical signs suggest a problem with tear punctum (which is responsible for the major-
drainage, further investigations are indicated, ity of tear drainage and obstructions) and
usually in the form of a nasolacrimal flush and because it is usually easier in terms of manual
imaging techniques (computed tomography dexterity.
[CT] and dacryocystorhinography [DCRG]). A metal or Portex lacrimal cannula or intrave-
nous catheter (without metal stylet) is appropri-
Nasolacrimal Flush ate for irrigation in the rabbit, cat (24–25 gauge),
Nasolacrimal flush is the manual irrigation of and dog (22–24 gauge) (Figure 4.23). A 2–5-­ml
the nasolacrimal system to determine anatom- syringe of sterile saline or eyewash is attached
ical patency. Indications include delayed or to the cannula prior to cannulation. With the
absent fluorescein passage from the eye to the upper lid everted to expose the upper lacrimal
ipsilateral distal punctum (negative Jones test), punctum, the cannula is inserted in a ventrome-
epiphora without an identified cause, mucopu- dial direction, following the line of the upper
rulent ocular or nasal punctal discharge (latter canaliculus (Figure 4.24). Fluid is slowly irri-
in the horse), and dacryohemorrhea. The flush gated until it exits the lower lacrimal punctum.
can be performed in either a normograde This establishes patency of the upper and lower
190 Eye Examination and Diagnostics

Expelled debris may be collected for cytology


and culture, and sensitivity if indicated. The dif-
ferent fluorescein passage times for selected
species are provided in the basic diagnostics
section.

Seidel Test
Fluorescein may also be used to detect the leak-
age of aqueous humor through the cornea
(Seidel test). To perform the Seidel test, fluores-
cein is applied to the cornea without subsequent
flushing. The resulting high concentration of
dye causes it to fluoresce at wavelengths closer
to the yellow and orange spectra. If the corneal
Figure 4.23 Selection of plastic and metal integrity is compromised, aqueous humor leak-
lacrimal cannulas suitable for performing a age locally dilutes the fluorescein as it exits the
nasolacrimal flush in a small animal, e.g., dog and
corneal defect, and makes the dye appear green.
cat. Entry into the lacrimal puncta can be
facilitated by cutting the end short and at an A positive Seidel test is most easily observed
oblique angle. with some form of magnification, e.g., slit-­lamp
biomicroscope. The aforementioned descrip-
tion is theoretically correct, but a more practical
description is as follows: a positive Seidel test
typically appears as a dark area, representing an
exiting wave of aqueous humor that rapidly
increases in size and flows downward over the
cornea as the leak continues, pushing the fluo-
rescein solution away as an advancing green
band (Figure 4.25).

Tear Film Breakup Time


Fluorescein is used to evaluate the stability of
the tear film by measurement of the TBUT. The
TBUT indirectly evaluates the mucin and/or
Figure 4.24 Nasolacrimal flush in a dog. With a
2–5-­ml syringe of sterile saline or eyewash
attached to the cannula, and the upper lid everted
to expose the upper punctum, the cannula is
inserted into the dorsal punctum in a ventromedial
direction, following the line of the upper canaliculus.

lacrimal puncta, upper and lower canaliculi,


and lacrimal sac. Digital pressure is then applied
to occlude the lower punctum, diverting the
irrigating fluid into the nasolacrimal duct. Fluid
exiting from the ipsilateral nasal punctum
establishes patency of the nasolacrimal duct.
The muzzle should be directed ventrally to min- Figure 4.25 Positive Seidel test depicts a leaking
imize fluid draining into the nasopharynx. corneal wound at 12 o’clock.
Ophthalmic Diagnostic Procedures  191

lipid layers of the tear film by measuring the Other Ophthalmic Dyes
time it takes for fluorescein dye, and hence the Lissamine green is an organic acid dye. It is
tear film, to dissociate from the corneal sur- used widely in human ophthalmology, but its
face. It is a provocative test in so far as fluores- use in veterinary ophthalmology is mostly lim-
cein shortens the normal TBUT. To perform ited to those countries in which Rose Bengal is
this test, fluorescein solution is applied to the not available. It has been characterized as a
eye, the animal is allowed to blink, and the true vital dye because it does not stain healthy
eyelids are then held open until the tear film cells, even in the absence of the tear film.
begins to dissociate from the corneal surface. Despite this difference, Lissamine green has a
Dissociation results in the formation of a dry similar staining pattern to Rose Bengal and has
spot, which appears as a dark round area been used in cases of KCS. At concentrations
within the fluorescent tear film. Observation is of 0.5% and 1%, Lissamine green is less toxic
facilitated by slit-­lamp biomicroscopy using a than Rose Bengal and is less irritant.
cobalt blue filter. In the dog, the mean TBUT Trypan blue, an azo dye, has been used
ranges from 19.7 ± 5 to 21.53 ± 7.42 s. Values extensively in human cataract surgery over the
for the mean TBUT in the cat are 16.7 ± 4.5 s in last decade, and its utilization has been
the juvenile cat and 21 ± 12 s in the adult cat. extended to other anterior segment surgeries,
including trabeculectomy and corneal trans-
Rose Bengal plantation. Trypan blue stains the anterior lens
Rose Bengal is used in veterinary medicine to capsule and thus aids in its visualization dur-
aid in the diagnosis of tear film disorders and ing capsulorrhexis; it is used by many veteri-
superficial corneal epithelial abnormalities. nary ophthalmologists for this purpose. Trypan
Rose Bengal is not a vital dye. It is toxic to nor- blue is also used in research in both human
mal healthy corneal epithelial cells in a dose-­ and veterinary fields. Two recent studies have
dependent manner, which includes routine involved work on the equine cornea: an in vitro
concentrations. Negative stain uptake is a model for corneal scarring and a novel method
result of normal tear film components, such as of gene delivery.
mucin and albumin, which protect the epithe- Topical ophthalmic dyes can interfere with
lial cells from the dye; positive stain uptake the detection of infectious agents by culture
therefore represents a tear film abnormality. and PCR, and, more specifically, fluorescein
This differs from the previous belief that Rose can cause false-­positive results in IFA testing.
Bengal simply stains dead and degenerating In contrast to fluorescein, which can support
cells and mucus. It is available as a solution bacterial growth and virus viability, Rose
and as an impregnated paper strip. Use of the Bengal and Lissamine green are bactericidal
5% or lower concentrations can reduce the irri- and virucidal. Although fluorescein did not
tancy associated with the 1.0% solution. The interfere with the PCR assay for C. felis and
dye is applied to the ocular surface in the same FHV-­1 (an in vitro study), Rose Bengal and
way as that described for fluorescein. It can be Lissamine green inhibited the detection of her-
applied before or after fluorescein application, pes simplex virus by PCR. In summary, sample
or even at the same time because the stain collection for infectious agents should ideally
properties are unaffected by mixing. In addi- be performed prior to the topical application of
tion to its use in tear film assessment, Rose ophthalmic dyes if possible.
Bengal can demonstrate superficial corneal
erosions or early ulcers that may not stain with Tonometry
fluorescein, e.g., punctate keratitis, herpetic Tonometry is the measurement of IOP and is
keratitis (cat, horse, and dog), and early an essential diagnostic procedure for a thor-
keratomycosis. ough ophthalmic examination. Instrumental
192 Eye Examination and Diagnostics

tonometry is an essential part of the advanced Table 4.4 Normal IOP reported in animals.
ophthalmic diagnostics, and may or may not
be available for the basic eye exanimation. IOP results
Direct tonometry via a manometer is the most Species Tonometer (mean/SD)
accurate method, but it is invasive and there-
Dog Mackay–Marg 15.7 ± 4.2
fore impractical for clinical use. Indirect
TonoPen 16.7 ± 4.0
tonometry, the measurement of corneal ten-
sion, is the technique used to determine IOP in Mackay–Marg 17.8 ± 0.9 PM
clinical ophthalmology. It is a quick, simple, 21.5 ± 0.8 AM
and noninvasive procedure that can be per- Cat Mackay–Marg 22.6 ± 4.0
formed with minimal discomfort to the patient, TonoPen 19.7 ± 5.6
and the results determine not only the diagno- Rabbit Pneumatonograph 19.5 ± 1.84
sis, but also the prognosis and treatment 17.9 ± 2.11
options. Tonometry is part of the complete
Horse Mackay–Marg 25.5 ± 4.0
ophthalmic examination by the veterinary
Mackay–Marg 28.6 ± 4.8
ophthalmologist. Although tonometry in the
outpatient clinic provides only a “snapshot” TonoPen 29.6 ± 6.2
measurement of IOP, repeat tonometry is Mackay–Marg 17.1 ± 3.9
(left eye)
invaluable for effective monitoring of the dis-
ease itself and response to therapy. The normal 18.4 ± 2.2
(right eye)
IOP in most animals is somewhere between 15
Mackay–Marg 23.5 ± 6.1
and 25 mmHg because of the conservation
between species (Table 4.4). The mean IOP TonoPen 23.3 ± 6.9
and range for an individual species vary with Mackay–Marg 23.5 ± 4.5
different studies, but general values in com- Mackay–Marg 20.6 ± 4.7
mon domestic species are 15–18 mmHg in the Cow Mackay–Marg 29.5 ± 5.0
dog, 17–19 mmHg in the cat, 15–20 mmHg in 23.4 ± 5.9
the rabbit, and 17–28 mmHg in the horse. The Raptors
highest mean IOP recorded in any species is
Hawks TonoPen 20.6 ± 3.4
32.1 ± 10.4 mmHg in the rhesus monkey, and
Eagle 21.5 ± 3.0
the lowest is 3 mmHg in the chinchilla.
Generally, the difference in IOP between fel- Owl 10.8 ± 3.6
low eyes should be less than 4-­8 mmHg.

Digital Tonometry applied with a weighted plunger to the anes-


Digital tonometry is the estimation of IOP by thetized cornea. The instrument measures the
digital palpation. It was reported as early as amount of corneal indentation produced by a
pre-­Hippocratic times, but generally is consid- given weight; the degree of corneal indenta-
ered unreliable. Its use in humans and animals tion is inversely proportional to the IOP. Various
is generally limited to patients that do not have models are available, but the fundamental
access to specialized eye care, such as in rural design comprises three parts: footplate,
areas or underdeveloped countries. plunger, and handle (holding bracket and
recording scale) (Figure 4.26a and b). The
Indentation Tonometry greater the weight applied to the eye at a given
Indentation tonometry is exemplified by the IOP, the greater the indentation of the rod. The
Schiötz tonometer, which was developed in conversion table is for humans and has been
1905. In this method, a standard force is revised several times to improve the accuracy
Ophthalmic Diagnostic Procedures  193

(a) (b)

Figure 4.26 Indentation tonometry. (a) Schiotz tonometer with 7.5 and 10.0 g weights. (b) Schiotz
tonometer use in a cat.

of its measurements. This type of tonometer is applanation tonometer based on the Mackay–
no longer recommended for veterinary oph- Marg tonometer (Reichert, Buffalo, NY)
thalmologists, and its estimates of IOP are (Figure 4.27a–d). It is battery operated, com-
unreliable. pletely portable, and highly accurate with an
experienced user. The footplate of the instru-
Applanation Tonometry ment contains a central, pressure-­sensitive tip,
Applanation tonometers measure the force which protrudes from and is surrounded by an
required to flatten, or applanate, a constant insensitive ring. When the tip makes contact
area of cornea (pressure = force/area). with the cornea, the tip applanates or flattens
Applanation tonometry works on the principle the predetermined area of cornea: the point of
of Goldmann’s Imbert–Fick law: “The pressure applanation is read electronically (amplified,
in a sphere filled with liquid and surrounded digitized, and passed through a single-­chip
by an infinitely thin membrane is measured by microprocessor). The tip is covered by a dispos-
the counterpressure that just flattens the mem- able latex membrane that protects the sensitive
brane.” The force required to flatten a known plunger and prevents disease transmission.
area of cornea provides an estimate of the Following topical anesthesia, the eyelids are
IOP. Applanation tonometers include the gently retracted with the nondominant hand,
Goldmann, Draeger, Perkins, Halberg, taking care to avoid pressure on the globe.
Maklakoff, Mackay–Marg, TonoPen, and pneu- Using the dominant hand, the instrument is
matonograph. The Goldmann, Draeger, held perpendicular to the cornea so that the
Perkins, and Halberg applanation tonometers flat tip is parallel to the cornea. The tip is
estimate IOP by aligning a corneal contact tapped very lightly multiple times on the cen-
prism with a hand dial or small motor to calcu- tral cornea without causing visible indenta-
late the force of applanation. The electronic tion. Readings taken from the central
applanation tonometers are handheld instru- two-­thirds of the cornea are most accurate.
ments. The TonoPen is a digital handheld The mean IOP is then displayed along with the
194 Eye Examination and Diagnostics

(a) (d)

(b) (c)

Figure 4.27 Applanation tonometry. (a) TonoPen Vet. (b) The footplate contains a central pressure-­sensitive
tip that protrudes from and is surrounded by an insensitive ring. (c) The tip is covered by a disposable latex
membrane that protects the sensitive plunger and prevents disease transmission. (d) TonoPen Vet use in a dog.

coefficient of variance (i.e., 5%, 10%, 20%, or


more than 20%). If the coefficient of variance is
more than 5%, the tonometry should be
repeated. Because of its ease of use, portability,
reliability, and low cost, the TonoPen has
become the most popular tonometer among
veterinary ophthalmologists. The design has
been modified over the years. The most recent
model, TonoPen AVIA (Reichert, Buffalo, NY),
has not been evaluated clinically in the differ-
ent species.
Figure 4.28 Rebound tonometry with the TonoVet
The pneumatonograph is an applanation
in a dog.
tonometer–tonographer that measures IOP via
a gas-­suspended plunger, and has the advantage
of being able to measure both IOP and the con- Rebound Tonometry
ventional (pressure-­sensitive) trabecular aque- Rebound (impact or dynamic) tonometry uses
ous humor outflow (tonography). Compressed a different mechanical principle to measure
air is directed into a sensor housing that con- IOP. A small probe (such as a metal pin with a
tains a hollow, metal plunger with a silicone rounded end) is rapidly and electromagneti-
sensor membrane at its tip that gently presses cally propelled, from a fixed distance from the
the sensor against the cornea during applana- cornea, to contact the cornea before returning
tion. For pneumatonography, the eye needs to (rebounding) to the instrument (Figure 4.28).
be still for 2–4 min. The instrument assesses the rebound
Ophthalmic Diagnostic Procedures  195

characteristics (probe deceleration): eyes with (Figure 4.29). Ocular paracentesis should ide-
a higher IOP cause a more rapid deceleration ally be performed by a veterinary ophthalmol-
of the probe and shorter return time to the ogist in most instances.
instrument than those with a lower IOP. The
technique is affected by ocular surface tension Aqueous Paracentesis
and should ideally be performed before the Aqueous paracentesis is the aspiration of a
application of any topical medications, includ- small amount of aqueous humor from the ante-
ing topical anesthetics. Despite this recom- rior chamber for both diagnostic and therapeu-
mendation, two studies found that the IOP tic purposes (see Figure 4.29a). The procedure
results were unaffected by topical anesthesia. can be performed either with sedation and topi-
Advantages of the rebound tonometer are as cal anesthesia or under short-­acting general
follows: topical anesthesia is not necessary; a anesthesia. If performed in the standing horse
very small probe tip (1.3–1.8 mm) makes it under sedation, retrobulbar and auriculopalpe-
suitable for very small eyes, as in many exotic bral nerve blocks should also be performed.
species, and in the presence of significant cor- Some clinicians perform aqueous paracentesis
neal disease; and the tip is disposable. One dis- with only topical anesthesia, but the risk of
advantage is that the instrument must be held complications is then greater. The conjunctival
upright during measurement so that the probe sac, and most importantly the bulbar conjunc-
is propelled horizontally; this may make its use tiva, should be cleaned with a dilute (5%) povi-
difficult in recalcitrant or recumbent patients. done–iodine solution followed by sterile saline
The TonoVet rebound tonometer (Icare solution or eyewash. The hypodermic needle is
Finland, Helsinki, Finland) is becoming usually inserted through the peripheral cornea
increasingly popular in veterinary ophthal- in the dorsolateral quadrant as this allows great-
mology. A strong linear correlation between est exposure and is more comfortable hand
rebound tonometry and direct manometry has placement. Furthermore, in large herbivores
been demonstrated in the dog, cat, and horse. such as the horse, the dorsal-­to-­dorsolateral
In contrast, rebound tonometry underesti- limbus is preferred to take advantage of the scle-
mated the IOP by 37–60% in enucleated rabbit ral extension beyond the iris base. The bulbar
eyes and by 17–63% in enucleated porcine eyes, conjunctiva is grasped with small forceps near
as compared to direct manometry. When com- the site of entry and a 27–30-­gauge needle is
pared to the TonoPen Vet, rebound tonometry inserted (bevel up) through the clear cornea
underestimated the IOP by an average of immediately adjacent to the limbus or the sub-
2 mmHg in the dog, and overestimated the IOP conjunctival limbus. The needle must enter the
by 2–3-­mmHg in the cat and by 1 mmHg in the anterior chamber anterior to the iris and be
horse. These differences do not appear signifi- directed parallel to the iris.
cant in the clinical environment! The volume of the anterior chamber varies
between species: 0.3 ml (rabbit), 0.4–0.77 ml
(dog), 0.6 ml (cat), and 2.4–3 ml (horse). A
Ophthalmic Paracentesis
small volume (0.1–0.25 ml) of aqueous humor
Paracentesis, the aspiration of fluid from a can be removed by one of several methods.
body cavity using a needle, can be performed Possible complications of aqueous paracente-
on the eye for both diagnostic and therapeutic sis include hyphema, anterior lens capsule
purposes. Aqueous and vitreous paracentesis rupture with subsequent phacoclastic uveitis,
requires some expertise and familiarity with corneal edema associated with endothelial
ocular anatomy, and should only be used damage, anterior uveitis, endophthalmitis,
where its potential contribution to the man- choroidal edema, and hemorrhage. The tech-
agement of the case is clearly appreciated nique is more challenging if the cornea is
196 Eye Examination and Diagnostics

(a) (b)
10 mm (horse)
5–7 mm (dog)

Figure 4.29 Paracentesis. (a) Aqueous paracentesis. The hypodermic needle is inserted (bevel up) through
the clear cornea immediately adjacent to the limbus or the subconjunctival limbus. A tunneling motion
facilitates passage through the sclera or cornea. The needle must enter the anterior chamber anterior to
the iris and be directed parallel to the iris. (b) Vitreous paracentesis. The hypodermic needle is inserted
posterior to the limbus (5–7 mm in the dog and 10–12 mm in the horse) and firmly tunneled through the
sclera and pars plana of the ciliary body. The needle must be directed toward the posterior pole to avoid
the lens. (Courtesy of Simon Scurrell, Willow Referral Service, Shirley, West Midlands, UK.)

opaque and in the presence of iris thickening recommendation is 5–7 mm posterior to the
or displacement (e.g., iris bombé). Diagnostic limbus, but the distance varies with the ocular
tests for aqueous humor samples obtained by quadrant and globe size. These sites are likely
aqueous paracentesis include cytology, culture to be more posterior in larger dogs with larger
and sensitivity, protein measurement, PCR, eyes. In the horse, the recommended site is
and antibody titers (e.g., Leptospira spp., 10–12 mm posterior to the limbus in the dorso-
Toxoplasma gondii, and Bartonella spp.). lateral quadrant. The needle size varies from
26 gauge (dog and cat) to 23 gauge (horse). The
Vitreous Paracentesis globe is stabilized by grasping the bulbar con-
Vitreous paracentesis (hyalocentesis) is the junctiva with forceps adjacent to the site of
aspiration of small amounts of vitreous humor needle entry. The needle is gently but firmly
for both diagnostic and therapeutic purposes tunneled through the sclera and pars plana of
(see Figure 4.29b). Vitreous paracentesis is the ciliary body, directed toward the posterior
usually performed with the patient under pole to avoid the lens. Using a syringe attached
short-­acting general anesthesia or heavy seda- to the needle, 0.1–0.3 ml of fluid is slowly aspi-
tion. Preparation is the same as for aqueous rated (sometimes more in the end-­stage glau-
paracentesis in terms of aseptic preparation of comatous eye). Although the volume of the
the ocular surface and placement of an eyelid vitreous varies between species and is quite
speculum. Visualization of the posterior seg- large (1.5 ml [rabbit], 1.7–3.2 ml [dog], 2.8 ml
ment is aided by the head-­mounted indirect [cat], and 26–28.8 ml [horse]), only 0.1–0.2 ml
ophthalmoscope and drug-­induced mydriasis. of liquid vitreous is aspirated.
The site of needle entry is very important and Possible complications of vitreous paracentesis
varies with species. In the dog, the general include intraocular hemorrhage, retinal tear or
Ocular Imaging: Basic and Advanced Diagnostics  197

detachment, lens subluxation, cataract forma-


tion, uveitis, and endophthalmitis. The incidence
of lens damage in humans is very low; 0.009%
(2 of 21 653) when the technique is performed by
experienced personnel. As for the aqueous
humor, diagnostic tests for vitreous humor sam-
ples obtained by paracentesis include cytology,
culture and sensitivity, protein measurement,
PCR, and antibody titers (e.g., Leptospira spp.).
Vitreous paracentesis is also used extensively in
research to determine drug levels in the vitreous
humor and drug pharmacokinetics.

Figure 4.30 Reformatted sagittal CT images of a


Ocular Imaging: Basic and normal feline globe seen in the soft tissue window
Advanced Diagnostics (W 426, L 55). (Courtesy of Paul Mahoney, Willows
Veterinary Centre & Referral Service, Solihull, UK.)

There have been progressive changes in the


information can be obtained with conventional
noninvasive methodologies in both human
radiographs. Conventional radiography helps
and veterinary ophthalmology, as these imag-
evaluate the bony orbit for evidence of osteoly-
ing schemes have improved diagnostic results,
sis, bone remodeling, or fracture; assess the
enhanced understanding of many eye diseases,
nasal cavity, frontal sinuses, and maxillary den-
and, most importantly, increased the quality of
tal arcades for pathology; and assist identifica-
clinical management of patients. In this sec-
tion of radiodense foreign bodies. Conventional
tion, the different imaging systems will be
radiography may be superior to cross-­sectional
divided into those utilized by the solo or group
imaging techniques in some situations such as
general practitioner, large and comprehensive
trauma with bony fracture and dental disease.
referral centers, and those possibly offered by
When an orbital or ocular malignancy is sus-
the veterinary ophthalmologist. Some of these
pected, survey radiology of the thorax and abdo-
imaging systems are still in development and
men, as well as abdominal ultrasound, is often
being implemented in specialty practices and
performed at the time of orbital imaging, to help
institutions. These noninvasive imaging sys-
rule out metastatic disease.
tems represent the future!
Selection of Appropriate Radiographic Views
Basic Imaging Systems A series of views is necessary to thoroughly
assess the dorsal, medial, and lateral bony mar-
Radiography gins of the canine orbit. Both orbits are always
In veterinary ophthalmology, the relative econ- imaged so that a comparison can be made of
omy and availability of routine radiography the two sides. A routine study should include
when compared to cross-­sectional imaging tech- lateral and dorsoventral (DV) radiographs and
niques (CT and magnetic resonance imaging sometimes a DV intraoral radiograph, which
[MRI]) ensures an ongoing role for this tech- provides finer detail of the nasal cavity, maxil-
nique in the investigation of many cases of lary recess, and medial orbital wall.
orbital and neuro-­ophthalmic disease
(Figure 4.30). Although the complex nature of Interpretation of Radiographs
the skull, the superimposition of tissues, and the The bilateral symmetry of the skull allows
poor ability to differentiate orbital soft tissues all direct comparison of the right and left sides on
impair radiographic assessment, important ventrodorsal/DV projections for differences in
198 Eye Examination and Diagnostics

structure or opacity. The main aim of radio- differentiate orbital soft tissue structures com-
graphic assessment of orbital disease is to iden- pared to standard radiographs, and potentially
tify bony pathology, including fractures, delineate tumors or inflammatory lesions.
osteolysis, and osteoproliferative lesions. It is These techniques have not become established
important to note that although bone lysis is for the routine investigation of orbital disease
highly suggestive of malignancy in dogs and and in the modern era they have been largely
cats, a tissue diagnosis is still required to rule supplanted by the cross-­sectional imaging
out infectious processes, in particular fungal techniques.
disease. Furthermore, orbital radiography may
not be highly sensitive in detecting orbital Zygomatic Sialography
bone pathology as compared to MRI. Zygomatic sialography is the only contrast
Diseases of structures adjacent to the orbit, radiographic technique that is still utilized
including the sinuses, nasal cavity, and maxil- occasionally for the evaluation of orbital dis-
lary premolar and molar teeth, may be radio- ease in dogs. Zygomatic sialography involves
graphically apparent. Other pathology, the retrograde instillation of a nonionic iodi-
including orbital and periorbital emphysema nated contrast medium into the zygomatic sali-
and calcification of soft tissues, may also be vary gland duct. Lateral and DV radiographs
identified. Orbital emphysema may follow are obtained to ensure correct exposures prior
infection or trauma, or be a complication of to contrast instillation. The sialoadenogram
enucleation. Calcification of the ocular and reveals the zygomatic salivary gland to be
orbital tissues may be dystrophic or metastatic. large, single lobed, and positioned ventral to
Conventional radiographs may be used to the rostral end of the zygomatic arch.
screen for radiodense foreign bodies. For accu- Radiographic abnormalities may include fill-
rate localization, two orthogonal views are ing defects, enlargement of the nasolacrimal
needed. Screening of patients to rule out duct, formation of fistulas, and displacement
intraorbital metallic foreign bodies prior to of the gland.
MRI may be indicated in some cases.
Dacryocystorhinography
DCRG is a contrast radiographic procedure
Advanced Imaging Systems
that may be used to assess diseases affecting
Many of the advanced imaging systems are any level of the nasolacrimal system. DCRG is
often available at nearby specialty clinics, com- performed with the patient under general
prehensive specialty practices and institutions, anesthesia. Lateral and DV radiographs are
and most academic centers. Veterinary oph- obtained to ensure correct exposures prior to
thalmologists use these special imaging sys- contrast instillation. After a nasolacrimal flush
tems to diagnose and manage their patients with 0.9% saline performed through the upper
with improved results. Some, but not all, of punctum, an iodinated contrast medium agent
these imaging systems are presented next. is injected via the upper punctum while digital
pressure or forceps occlude the lower punc-
Contrast Radiography tum. The volume of contrast medium needed
for Orbital Disease for DCRG varies from 0.5 to 1.0 ml in the dog,
Contrast radiographic techniques described cat, and rabbit, to 3.0–5.0 ml in the horse, cow,
for the investigation of orbital disease have and llama. The contrast medium is injected
included zygomatic sialography, positive and continuously until a few drops appear at the
negative contrast orbitography, venography, external nares or reflux occurs from the upper
angiography, and optic thecography. The aim punctum around the cannula, at which stage
of these techniques is to improve the ability to the radiograph is taken. Gross anatomical
Ocular Imaging: Basic and Advanced Diagnostics  199

(a) (b)

Figure 4.31 (a) Dacryocystorhinogram of the normal nasolacrimal duct system of a nine-­year-­old West
Highland White Terrier. The cannula placed via the upper punctum into the lacrimal sac is visible (small
arrow). Contrast medium is present at the nares and refluxing into the nasal cavity (large arrow). Note that
the metallic pulse oximetry device is superimposed over the rostral nares and maxillary region. (b)
Dacryocystorhinogram of a three-­year-­old Labrador Retriever with chronic dacryocystitis affecting the right
side. Obstruction of contrast is evident at the level of the third upper premolar tooth (arrow). Proximal to
the obstruction there is an irregular cystic dilation of the duct. No contrast is visible distal (rostral) to the
obstruction.

studies and DCRG have been used to study the indications, and contraindications of the spe-
normal anatomy of the nasolacrimal system in cific imaging modality, and the specific
the dog, cat, horse, llama, sheep, goat, one sequences used in neuro-­ophthalmic and
humped camel, and rabbit (Figure 4.31a). orbital imaging. Furthermore, discussion with
Demonstrated congenital nasolacrimal system imaging colleagues regarding the reason for
anomalies include nasolacrimal duct atresia in imaging the patient and the suspected nature
the alpaca, llama, horse, and cattle; anomalous and location of pathology will allow selection
nasolacrimal duct openings and dysplastic lac- of the most appropriate imaging study.
rimal puncta in cattle; and congenital lacrimal The advantages of MRI over CT include the
gland cyst (dacryops) in the dog (Figure 4.31b). absence of ionizing radiation, direct multipla-
Primary or secondary nasolacrimal duct nar imaging that does not require changing
pathology due to trauma, neoplastic, or inflam- the position of the patient in the gantry,
matory diseases may be recognized on DCRG enhanced anatomical detail, and soft tissue
as complete or partial obstruction, deviation, characterization (Figure 4.32a and b). MRI is
cystic dilatation, and/or irregularities of the considered superior to CT for most neuro-­
nasolacrimal duct. ophthalmic indications with better assess-
ment of both the intra-­ and extraorbital optic
Cross-­sectional Imaging Techniques: nerve. The advantages of CT over MRI include
Computed Tomography and Magnetic shorter data acquisition time, decreased slice
Resonance Imaging thickness and greater special resolution, more
The cross-­sectional imaging techniques of CT precise imaging of cortical bone and soft tis-
and MRI have greatly improved the diagnosis sue mineralization, acute hemorrhage, and
and management of a diverse range of ocular, the ability to image when magnetic foreign
orbital, and neuro-­ophthalmic conditions. In bodies are present. MRI and CT are therefore
order to maximize the information gained complementary and when combined often
from an imaging study, it is important for the provide a more complete picture of the nature
clinician to understand the basic mechanics, of disease.
200 Eye Examination and Diagnostics

(a) (b)

Figure 4.32 The appearance of the normal canine globe and orbit on (a) dorsal T1-­and (b) T2-­weighted
MRI. (a) The dorsal T1 image shows hyperintense retrobulbar fat, lens capsule, iris, and ciliary body. The
aqueous humor and vitreous humor have a slightly lower signal when compared with muscle, and the
normal lens has low signal characteristics. (Courtesy of Paul Mahoney, Willows Veterinary Centre & Referral
Service, Solihull, UK.)

CT-­Guided Percutaneous Biopsy MRI improves visualization of blood vessels,


The ability of CT to provide excellent imaging breakdown of the blood–brain barrier, tumors,
of orbital and skull topography, and detailed or inflammation. Generally, the use of contrast
delineation of orbital tumor location and enhancement is recommended for cases of
boundaries makes it a valuable technique for orbital or neuro-­ophthalmic disease, but it may
aspiration biopsy guidance. The technique for not be necessary for acute hemorrhage
CT-­guided percutaneous biopsy of orbital or trauma.
pathology in dogs has been described. It is rec-
ommended for lesions judged to be inaccessi-
Pachymetry
ble (due to location or poor resolution) using
other imaging techniques for guidance, includ- Ex vivo measurements of corneal thickness are
ing ultrasonography and fluoroscopy, or when subject to inaccuracy due to postmortem/post-
CT is needed to provide additional information surgical swelling of the tissue, especially if
regarding diagnosis, staging, or therapy immersed in storage medium or fixative, and
planning. are therefore of limited value in the clinical
setting. Various technologies are available to
Magnetic Resonance Imaging provide measurement of in vivo corneal thick-
MRI is a technique for creating cross-­sectional ness, including ultrasound pachymetry, in vivo
images of the body based on the magnetic reso- confocal microscopy, optical biometry with a
nance (MR) of atomic nuclei. Many pathological Scheimpflug camera, OCT, and optical coher-
processes in the brain are associated with ence pachymetry. Most of these systems have
increased tissue fluid content and/or increased been investigated in animals, and several
tissue vascularity. MR scanning with intrave- reported in clinical patients. Those optical-­
nous paramagnetic agent contrast agents, such based systems (optical pachymetry, specular
as gadolinium-­diethylenetriamine pentaacetic microscopy, and OCT) require clear corneal
acid (Gd-­DTPA), may be used to enhance the reflections and are therefore of limited use in
appearance of these changes. Contrast-­enhanced cases of corneal edema, fibrosis, or infiltrates.
Ocular Imaging: Basic and Advanced Diagnostics  201

In contrast, ultrasound pachymetry uses ultra- for greater patient comfort. Specular micros-
sound energy reflected from interfaces of dif- copy is used clinically to assess corneal
fering refractive indices to measure corneal endothelial cell density, rate of polymegathism
thickness; probes can vary from 20 to 65 MHz (or coefficient of variation in cell size, i.e.,
and measure from the anterior tear film to the objective measure of cellular morphology vari-
posterior surface of the endothelium. The dis- ation), and pleomorphism (variation in cell
tance between reflections is then calculated shape, i.e., subjective assessment of cell mor-
based on the speed of ultrasound through the phology differences).
cornea (1550–1639 m/s, depending on species).
This technology can be used in the face of con-
Scanning Laser Polarimetry
current corneal opacity.
The retinal nerve fiber layer (RNFL) has bire-
fringent properties due to retinal ganglion cell
Specular Microscopy
(RGC) axon microtubules and neurofilaments
Specular microscopy is an imaging modality being highly ordered and parallel. Polarized
that allows morphological analysis of the cor- light is composed of two orthogonal compo-
neal endothelium (in addition to corneal thick- nents; these components travel at different
ness), although the technology can be applied velocities when they pass through a birefrin-
to image the corneal epithelium and stroma, as gent tissue, which creates a relative phase shift.
well as the lens (Figure 4.33a and b). This pro- The phase shift is termed “retardation,” and
cedure also requires a reasonably clear cornea the amount of phase shift or retardation is pro-
as corneal opacity or edema increases light portional to the thickness of the RNFL. This
scatter and reduces the specular reflex and modality has been shown to correlate well
image quality. Original specular microscopes with histopathological measurements
were contact microscopes, where the objective of RNFL.
lens was placed directly against the corneal
epithelium, therefore requiring topical anes-
Optical Coherence Tomography
thetic (and a compliant patient). Noncontact
specular microscopes were later developed, OCT was originally developed to image the
utilizing automatic focusing technology, which retina and optic nerve head with micron-­scale
generally have a smaller field of view but allow resolution. In vivo use was expanded in 1994 to

(a) (b)

Figure 4.33 (a) Noncontact specular microscopy being undertaken on an anesthetized Beagle cross-­bred
dog. (b) Specular microscopy image of the central corneal endothelium of a normal nine-­month-­old
cross-­bred dog. (Courtesy of Matthew Chandler, Animal Eye Clinic of North Florida, Jacksonville, FL, USA.)
202 Eye Examination and Diagnostics

of quantifying blood–aqueous barrier break-


down by the passage of a tracer substance
(injected intravenously) across the barrier. The
ratio of the aqueous to plasma level of the
tracer indicates the permeability of the blood–
aqueous barrier to this tracer. Sodium fluores-
cein is a small molecule and therefore readily
passes through an intact blood–aqueous bar-
rier. Laser flare-­cell photometry can objectively,
and noninvasively, monitor intraocular inflam-
mation by quantifying aqueous flare and cells.
To quantitatively measure protein (flare), the
Figure 4.34 OCT with 3D reconstruction images machine records the amount of scattered light
of the fundus of a normal, 15-­week-­old domestic
shorthair kitten fundus. (Courtesy of Laurence
(usually a helium–neon beam) detected by a
Occelli and Simon Petersen-­Jones, Michigan State photomultiplier in a set volume of aqueous.
University, East Lansing, MI, USA.)

Fluorescein Angiography
include imaging of the anterior segment of the
human eye. The ability to measure retinal layer FA provides a means of examining the vascu-
and optic nerve head thickness allows in vivo lar components of the fundus as well as the
assessment of the progression of a number of anterior uvea (iris vasculature, iritis in nonpig-
ophthalmic and neurological diseases mented animals, iridal tumors, and vascular
(Figure 4.34). Quantification of the RNFL anomalies). Sodium fluorescein is injected
thickness also provides an indirect measure of intravenously and the retina is illuminated
axonal and neuronal loss in the inner retina. In with blue light (490 nm) using a barrier filter,
veterinary patients, OCT is performed under which excites the fluorescein as it travels
general anesthesia to reduce eye movement. through the choroidal and retinal vasculature.
Ultrahigh-­resolution OCT retinal imaging was Baseline photographs or digital images as well
first demonstrated in 2001; it can achieve axial as videos are taken prior to fluorescein injec-
resolutions of approximately 3 μm, in compari- tion to identify (and thereby exclude in inter-
son to commercially available OCT instru- pretations) autofluorescence of retinal
ments with axial resolutions of approximately structures. Images are recorded after fluores-
10 μm. These images compare favorably with cein injections to chart the stages of retinal cir-
histological studies and allow the identifica- culation from the choroid to retinal vessels,
tion of individual retinal layers, including the and recirculation when present (Figure 4.35).
photoreceptor layer. Ceroid lipofuscinosis autofluorescence in dogs
and sheep (animal models for the human neu-
Laser Fluorophotometry and Laser ronal ceroid lipofuscinosis disease) has been
Flare Cell Meters objectively quantified using a digital radiome-
Laser fluorophotometry provides a means of ter and FA, and compared to age-­matched con-
assessing aqueous production and outflow, and trols. FA is usually performed under deep
is used extensively in research to indirectly sedation or anesthesia in veterinary species, to
assess the blood–aqueous barrier. An increase avoid eye movements disrupting photographic
in aqueous concentration of a plasma protein, sequences. General anesthesia is sometimes
indicating blood–aqueous barrier breakdown, avoided due to the downward deviation of the
can be identified by paracentesis, but this pro- globe, making fundus photography more prob-
cedure itself will induce blood–aqueous barrier lematic. Abnormalities in an FA are broadly
breakdown. Laser fluorophotometry is a means categorized into hypofluorescence and
Ophthalmic Imaging by Ultrasonography  203

is more compressible than a solid medium; for


example, sound waves pass through vitreous
much more slowly than through the lens. This
medium-­specific resistance to sound propaga-
tion is called the acoustic impedance, which is
the product of density and sound velocity
within this medium. If the sound waves strike
an acoustic interface, which is the junction of
two ocular media with different acoustic
impedances (e.g., lens–vitreous, vitreous–retina),
an echo occurs and part of the wave is reflected
Figure 4.35 Normal equine fluorescent antibody back to the transducer. This process of emit-
image with maximal fluorescence (retinal arterial
and venous phase). ting and receiving sound waves as an echo is
repeated thousands of times per second, and
referred to as “real-­time” echography.
hyperfluorescence, and also by location and
Structures within the cornea, anterior cham-
size of the abnormality.
ber, and iris cannot be depicted with great
detail with the standard 10–12-­MHz probes.

Ophthalmic Imaging Echoes


by Ultrasonography If the ultrasound beam strikes a smooth sur-
face (e.g., lens capsule) perpendicularly, the
Ultrasonography is a noninvasive imaging tech- majority of the wave is reflected back to the
nique that is used for the qualitative and quanti- transducer and a maximal echo is produced on
tative evaluation of intraocular and orbital the screen. The greater the angle at which the
structures and lesions. It is a safe and rapid sound wave hits the interface, the more of the
method, relatively easy to learn, and can be per- sound energy is diverted away and the return-
formed in an awake animal. Ultrasonography is ing echoes are much weaker as a result.
indicated in eyes with opaque ocular media Ultrasound energy is gradually absorbed, as
when an ophthalmic examination can no longer the ultrasound waves propagate through tis-
be performed (corneal edema, hyphema, cata- sue. Depth of sound wave penetration in tissue
ract, vitreous hemorrhage), and in eyes with is directly proportional to the wavelength. For
ocular trauma or suspected orbital disease. example, the ultrasound waves of a low-­
Other indications involve biometric measure- frequency 7.5-­MHz ultrasound transducer pro-
ments of intraocular and orbital structures, and vide poor ocular near-­field visualization, but
determination of axial eye length for artificial better tissue penetration. Therefore, this type
lens power calculations. of transducer is best used for examination of
the orbit and retrobulbar area. On the other
hand, high-­frequency ultrasound waves
Physics and Basic Principles
(20–50 MHz) only penetrate a few millimeters
The ultrasonic beam is a series of acoustic into tissue and, therefore, allow excellent
waves with a frequency of greater than 20 kHz imaging and resolution of the more anterior
(20 000 oscillations/s) and, therefore, inaudi- located structures of the eye.
ble by humans. Ultrasound frequencies used
in ocular diagnostics usually range from 7.5 to A-­Mode
50 MHz. Travel velocity of ultrasound in a A-­mode (amplitude modulation) is the most
medium depends on the density and com- original of all ultrasound methods. Echoes
pressibility of that medium. A liquid medium received by the transducer are displayed
204 Eye Examination and Diagnostics

one-­dimensionally in time-­dependent man- water-­f illed glove placed between the closed
ner as vertical spikes (amplitudes) from a eyelids and the transducer.
baseline. The height of the spike reflects the
intensity of the echo. The distance between Examination Technique
individual spikes depends on the time required
for the ultrasound waves to reach a given The ultrasound transducer is placed directly
acoustic interface and for their echo to return onto the cornea after a topical anesthetic
to the transducer. Spacing of spikes on the (e.g., tetracaine or proparacaine) has been
horizontal baseline also reflects the spatial instilled into the eye. The corneal contact
distribution of the structures being examined. method is the preferred examination tech-
Diagnostic A-­mode was first used in human nique and allows the best possible imaging
ophthalmology in 1956 and now has been of the globe and orbit. Scanning of the eye
replaced by ophthalmic ultrasound machines through the closed lids is less desirable due
incorporating a vector A-­scan within the to sound attenuation produced by the lid tis-
B-­mode picture. sues, but is the recommended examination
technique in case of a corneal injury, ocular
B-­Mode trauma, or after intraocular surgery to avoid
In B-­mode (brightness modulation) ultra- further damage to the cornea. It is very
sound, echoes are displayed two-­ important to use a large amount of coupling
dimensionally as light dots of different gel, such as methylcellulose on the cornea or
intensity and brightness on the screen. The lids to decrease near-­f ield reverberation arti-
coalescence of multiple dots forms a picture facts. Ultrasound examination is performed
that reassembles a histological “slice” of the in vertical and horizontal planes and initially
examined tissue. The quality of the B-­mode in an axial direction, with the lens being a
picture largely depends on the technical char- landmark for orientation within the globe
acteristics of the ultrasound machine, such as (Figures 4.36a and b and 4.37). Since in many
signal processing, gray scale, and speed of animal species the lateral or dorsolateral
transducer oscillation. Most B-­mode trans- orbital wall consists of only fibrous and mus-
ducers are real-­time sector scanners with a cle tissues, ultrasonography can be per-
very fast frame rate of 10–60 frames/s, allow- formed through this area to view the deeper
ing visualization of movement during the orbital tissues.
scanning process.
B-­scan ultrasonography is the most com-
Standard (10–12 MHz)
monly used echographic method for evalua-
Ultrasonographic Imaging
tion of intraocular and orbital lesions in
veterinary ophthalmology. A standard 10-­ The eye is ideal for an ultrasound examination
MHz transducer with a focal range of 3–4 cm due to pronounced acoustic interfaces that
is the most suitable ophthalmic transducer, reflect strong echoes. Structures in the globe
allowing visualization of anterior and poste- and orbit are described as hyperechoic, hypo-
rior segment abnormalities, as well as orbital echoic, or anechoic, depending on the pres-
lesions. However, structures very close to the ence and strength of the returning echo. In a
transducer tip (cornea, anterior chamber, normal eye and by using a 10-­MHz sector scan-
iris) are more difficult to image with a 10-­ ner, the most prominent echoes are received
MHz transducer due to near-­field reverbera- from the posterior lens capsule and the poste-
tion artifacts. For an improved examination rior eye wall.
of the anterior segment, a “water-­bath tech- Those echoes appear as vertical spikes on the
nique” is helpful and may consist of a A-­mode axis or as bright, reflective lines on
Ophthalmic Imaging by Ultrasonography  205

(a) (b)

Figure 4.36 (a) Standardized diagnostic A-­mode probe with tissue model for calibration. (b) Ocular
ultrasound probes. Top: Diagnostic 10-­MHz probe. The white marker on the probe designates the upper
portion of the echogram. Middle: High-­frequency (20-­MHz) B-­mode probe. Bottom: Standardized diagnostic
8-­MHz A-­mode probe.

bordered posteriorly by the posterior eye wall


echo. This strong echo is composed of retina,
choroid, and sclera, which can echographically
not be differentiated from each other. The adja-
cent orbital soft tissue, comprised of fat, connec-
tive tissue, nerves, and blood vessels, is depicted
as a highly reflective and heterogeneous area on
B-­mode, and represented by a series of multiple,
gradually declining echoes of different heights
on A-­mode. The optic nerve can be visualized as
a cone-­shaped, elongated hyporeflective area in
the medioventral part of the orbit. Retrobulbar
muscles are recognized as thin, elongated hypo-
Figure 4.37 Vertical axial scan. The white marker echoic structures with attachments at the globe.
on the probe points dorsally.
Anterior Segment Lesions
Neoplasia
B-­mode (Figure 4.38). With a water-­bath tech- Neoplastic lesions in the anterior segment typ-
nique, the cornea, anterior chamber, and ante- ically present as circumscribed, echodense,
rior lens capsule can be identified, with cornea mass-­like structures. They usually arise from
and anterior lens capsule appearing as bright, the iris or ciliary body and may invade the
reflective echoes, and the anterior chamber as anterior chamber or vitreous, causing lens lux-
an anechoic, black area on B-­mode. The iris may ation or subluxation (Figure 4.39). These
be more difficult to visualize in dogs and cats, tumors usually arise as a densely pigmented
but iris and corpora nigra are easily recognized structure from the iris surface and require dif-
in the horse, especially when using a linear scan ferentiation from iris cysts.
head. The normal lens is translucent, and the
posterior lens capsule can usually be visualized Lens Abnormalities
as a highly reflective, concave line on B-­mode. Nucleus sclerosis or cataract formation
The normal vitreous is clear and anechoic, and increases the internal reflectivity of the lens,
appears as a homogeneous black area on B-­mode which is normally an anechoic structure.
or a horizontal line on A-­mode. The vitreous is Depending on the distribution, density, and
206 Eye Examination and Diagnostics

12.00

6.00

Figure 4.38 Normal B-­mode/vector A-­scan echogram of the canine eye. The integrated vector A-­scan is
displayed in the bottom half of the echogram. Echoes appear as bright lines or dots of different intensities
on B-­mode, and as vertical spikes from a horizontal baseline on the A-­scan vector. In axial vertical direction
(white marker points dorsally), the posterior lens capsule produces a strong echo A-­mode and B-­mode
(arrows). The strong posterior eye wall echo contrasts against the acoustically empty vitreous.

Figure 4.39 Ciliary body tumor (T)


invading the vitreous and causing a
lens subluxation (arrow).

maturity of the cataract, single or multiple ech- Posterior Segment Lesions


oes may be received from within the lens, and Posterior segment lesions will appear as point-­
the equatorial regions of the lens become like, membrane-­like, or mass-­like structures on
clearly outlined. Ocular ultrasound is an B-­mode. The vitreous is acoustically empty in
important part of the preoperative evaluation the normal eye and recognized as a homogene-
process for cataract surgery and lens anoma- ous, black area on B-­mode, or as a horizontal
lies, embryonal remnants in the vitreous, vitre- flat line on A-­mode. Pathological changes in
ous degeneration, or retinal detachment may the vitreous include hemorrhage, inflamma-
be detected prior to surgery (Figure 4.40). In an tion, membrane formation, degeneration, and
anterior or posterior lens luxation, the lens can embryologic remnants. Diagnosis of a complete
be visualized as a spherical structure with retinal detachment is facilitated by its typical
smooth, very highly reflective borders. appearance on ultrasound. The detached retina
Ophthalmic Imaging by Ultrasonography  207

Figure 4.40 B-­mode ultrasound of a


long-­standing retinal detachment,
which appears as a T-­shaped
membrane (closed funnel).

Figure 4.41 B-­mode/vector A-­scan


echogram of a retrobulbar abscess in
a Miniature Schnauzer. The abscess
(A) is anechoic in the center and
surrounded by a thick, highly
reflective wall. It can be clearly
distinguished from the surrounding A
orbital tissues. The corresponding
vector A-­scan shows the low
echogenicity within the cystic abscess
and the high posterior wall echo
(arrows).

is seen as a highly reflective, continuous, linear Advanced Ultrasound Imaging


structure with attachments at the optic disc (20–100 MHz)
posteriorly and ora ciliaris retina anteriorly,
Biometric A-­scan is commonly used for axial
resembling the wings of a seagull.
eye length measurements in both human and
Orbital Lesions veterinary ophthalmology, and requires a spe-
Most orbital lesions (neoplasia, abscesses) cial biometric A-­mode transducer. It is the
have a more homogeneous composition than method of choice for in vivo measurement of
normal orbital tissue and, if large enough to intraocular distances, such as anterior cham-
produce clinical symptoms, can be easily ber depth, axial lens thickness, vitreous body,
detected. Depending on the type of lesion, the and axial globe length. Measurements of the
affected area may exhibit higher or lower anteroposterior axial globe length for calcula-
reflectivity. An abscess can be identified as a tion of intraocular lens dioptric strength have
cyst-­like, well-­circumscribed area of very low been performed in dogs, cats, and horses.
internal reflectivity (Figure 4.41), whereas an Within continued development, higher fre-
orbital neoplasia is characterized by increased quency ultrasound probes can enhance resolu-
reflectivity and a more invasive growth pattern. tion of the images, but with loss of tissue
208 Eye Examination and Diagnostics

penetration. Ocular ultrasound probes with cornea, sclera, anterior chamber, iris, ICA, CC,
higher frequencies between 20–35 MHz (high-­ and ciliary processes is comparable to a low-­
frequency ultrasound) and 50–100 MHz (ultra- power histopathological section. The layers of
sound biomicroscopy [UBM]) allow a the cornea (epithelium, stroma, Descemet’s
specialized and highly magnified examination membrane, and endothelium) can be easily
of the cornea, sclera, anterior chamber, iris, differentiated.
ICA, ciliary body, and anterior lens capsule. In human ophthalmology, UBM is extremely
With high-­frequency ultrasound, tissue resolu- useful in the diagnosis of pupillary block glau-
tions between 20 and 80 μm can be achieved coma, pigment dispersion syndrome, lens-­
with pictures comparable to a low-­power induced glaucomas, iris plateau syndrome, and
microscopic view of ocular structures. the visualization of iris and ciliary body tumors.
Furthermore, it is possible to evaluate the func-
High-­Frequency Ultrasound Biomicroscopy tional status of glaucoma-­filtering devices, and
The pioneering work of Charles Pavlin and the position of intraocular lenses. UBM has also
Stuart Foster led to the development of UBM, been very helpful in the quantitative evaluation
which allows the observation of living tissue at of the ICA dimensions and iris position in the
microscopic resolution. With the use of polyvi- normal human eye, especially in regard to glau-
nylidene fluoride in the late 1990s, transducer coma evaluation and prevention. This is facili-
membranes could be made sufficiently thin to tated through the integrated UBM measurement
support higher frequencies of 35 MHz and software. The angle opening distance is one of
above. The UBM imaging technique is similar to the most important measurement landmarks in
conventional B-­scan ultrasonography, but uses the evaluation of the ICA. This is referred to as
frequencies between 50 and 100 MHz, thereby the distance between the posterior corneal sur-
increasing tissue resolution by approximately 10 face and the anterior iris surface measured on a
times compared with a 10-­MHz probe. This cor- line perpendicular to the trabecular meshwork,
responds to a lateral tissue resolution between 250–500 μm from the sclera spur. As most ani-
20 and 50 μm compared to 500–600 μm achieved mals’ outflow pathways also include the CC,
with a 10-­MHz probe. The trade-­off for the UBM permits their examination (Figure 4.42).
higher resolution is a decreased tissue penetra- UBM is expected to provide important insight
tion of only 4–5 mm. Ocular imaging of the into the glaucomas at different stages in animals.

Figure 4.42 UBM (50 MHz) of the


ICA of a dog. A, cornea; B, sclera; C,
basal iris; D, pectinate ligaments;
and E, CC.

E
C
Ophthalmic Imaging by Ultrasonography  209

Color Doppler Ultrasound has a high peak systolic velocity (PSV) and a
low end-­diastolic velocity (EDV). The resistive
Color Doppler imaging (CDI) combines con-
index (RI) or Pourcelot ratio is a measurement
ventional B-­mode ultrasound with a color
to interpret the shape of the waveform or a ves-
Doppler instrument and allows the simultane-
sel, and can be calculated as follows:
ous evaluation of vascular velocity pattern.
RI = (PSV – EDV)/PSV. The RI ranges from 0%
The technique of the Doppler instrument is
to 100%, with 0% representing no resistance
based on the Doppler principle, which is a
and 100% representing highest resistance. A
change in the perceived frequency of the sound
high RI correlates with increased distal vascu-
emitted by a moving echo source. The greater
lar resistance and decreased perfusion.
the velocity of the blood cells in the blood ves-
Determination of the RI helps to evaluate the
sels, the greater is the Doppler shift, e.g., the
functional variables of the orbital vascular bed,
difference between the reflected and emitted
such as blood flow velocities and vascular
frequencies. Doppler color flow imaging allows
resistance patterns, which may be altered dur-
visualization of blood vessels and their flow
ing the course of ocular disorders in humans
characteristics within the eye and orbit. The
and animals. CDI has been reported in normal
best resolution is achieved for evaluation of
Beagle dogs. The external and internal oph-
blood vessels of greater than 200 μm in diame-
thalmic artery and vein, external ethmoid
ter. By definition, blood flow toward the trans-
artery, dorsal and ventral external ophthalmic
ducer appears red, and blood flow away from
veins, long posterior ciliary arteries, major reti-
the transducer appears blue. Spectral analysis
nal artery, and short posterior ciliary arteries
can be used to quantify the velocity of the
can consistently be imaged (Figure 4.43).
blood flow. The velocity waveform of an artery

(a) (b)

30
20

/s /s

30 20

Figure 4.43 Color Doppler images (top) and pulse waves (bottom) of the short posterior ciliary arteries
(SPCA; arrows) of a (a) normal and (b) glaucomatous Beagle. Comparisons of the normal to the glaucomatous
Beagle’s SPCA Doppler blood flow parameter indicated decreased EDVs and increased RIs compared to the
normal dogs. (Courtesy of Kathleen Gelatt-­Nickolson, North Florida Radiology, Gainesville, FL, USA.)
210 Eye Examination and Diagnostics

When compared to values obtained from electrooculogram is used to assess the function
Beagles with primary open-­angle glaucoma, of the retinal pigment epithelium in human
significant differences in blood flow velocities patients. Combining different electrodiagnos-
and RIs were detected in several arteries, even tic tests is a powerful way to both assess func-
before IOP was elevated. Hypervascularity on tion and localize where in the visual system
CDI was detected in two dogs and a cat with the dysfunction occurs.
acute proptosis, in a dog with orbital cellulitis,
and in two dogs with iris neoplasia. A hypovas-
Flash Electroretinogram
cular CDI pattern was observed in a dog with
acute head trauma and periorbital swelling, in The flash ERG (FERG) provides an opportu-
a dog with chronic glaucoma and buphthal- nity to assess the function of a part of the CNS,
mos, and in two cats with traumatic proptosis. the retina, which can easily be visualized by
ophthalmoscopy. It is an electrical mass
response of the retina to light stimulation,
­ lectrodiagnostic Evaluation
E which reflects the function and integrity of the
of Vision photoreceptors and the retinal cell layers they
contact, the inner nuclear layer and, if a spe-
Electrodiagnostic testing provides unique, cial recording technique is used, the retinal
noninvasive opportunities to probe the visual pigment epithelium (Figure 4.44). The electri-
system from the retina to the visual cortex in cal responses of the different cell types are
virtually any animal species. Unlike psycho- superimposed in the ERG, which makes the
physics that establishes relationships between interpretation of the results more challenging.
the physical properties of stimuli and the sub- In clinical veterinary ophthalmology, the
jective sensations they produce, electrodiag- FERG has been used to diagnose patients with
nostic tests measure the electrical potentials acquired or inherited retinal diseases, assess
generated in various parts of the visual system. retinal function in patients with opaque ocular
Therefore, electrodiagnostic testing should not media, such as cataracts, and exclude an outer
be considered a measure of vision per se. The retinal component in patients with RGC or
ERG is still the most widely used electrodiag- postretinal dysfunction. The FERG provides
nostic test in veterinary ophthalmology. It is a more objective results than ophthalmoscopy
complex response of different cells within the and characterizes the function of specific cell
retina, which is often used to diagnose outer types in the retina. Furthermore, the FERG
retinal disease. usually allows much earlier diagnosis of outer
The visual evoked potential (VEP), which is retinal disease than an ophthalmoscopic or
a cortical response, is less commonly tested. behavioral examination.
VEPs are particularly helpful in diagnosing
visual impairment of postretinal origin. OP
Additionally, the VEP has been used to predict
subjective psychophysical contrast sensitivity b-wave
or limits of spatial resolution. There are other
electrodiagnostic tests that are not commonly
used in veterinary ophthalmology; they
include (i) the pattern electroretinogram, a-wave
which can be used to evaluate RGC function;
Figure 4.44 A dark-­adapted canine ERG in
(ii) the multifocal ERG, which is a technique
response to a brief, bright flash. Both rod and cone
for recording local cone ERGs in multiple areas photoreceptors drive this response. OP, oscillatory
in the central retina; and (iii) the potential.
­Electrodiagnostic Evaluation of Visio  211

Equipment for Recording equipment meets the safety standards


and Light Stimulation imposed on equipment used for human clini-
The electrical changes produced by light cal ERGs.
stimulation of the retina are usually recorded
using an active electrode touching the cor- Photostimulator
nea and a reference (passive) electrode either A light stimulus, such as a strobe flash or an
in contact with the eyelid margin (as in bipo- LED, does not provide a uniform illumination
lar contact lens electrodes) or subcutane- of the entire retina. A full-­field (Ganzfeld in
ously at least 2 cm aboral to the lateral German) dome with built-­in photostimulator
canthus in the cat and dog (Figure 4.45a and b). and adapting (background) light source will
A ground electrode is normally placed in an minimize the problem of uneven retinal illu-
indifferent location, such as the top portion mination and is strongly advocated
of the skull. (Figure 4.46). Full-­field stimulators have been
The electrical signals generated by the retina used successfully in several animal species,
are small in amplitude (often less than 10−1 mV including the dog.
and certainly less than 10 mV) and need to be A xenon strobe flash, a halogen, tungsten, or
amplified approximately 104 times to be prop- xenon arc lamp fitted with a mechanical shut-
erly visualized. Hence, FERG amplitudes are ter or LEDs, can provide an appropriate light
normally presented in microvolts. Signal aver- stimulus in the full-­field dome. The duration
aging will reduce the impact of noise on the of the stimulus should not exceed 50 ms.
ERG signal and bandpass filters will attenuate According to international guidelines, the
frequencies that do not contribute substan- brightest light stimulus in the standard proto-
tially to the ERG. col should be 2–3 cd/m2/s, whereas the stimu-
Recording the FERG does not necessarily lus for the dark-­adapted rod tests should be 102
require very sophisticated equipment. Today, times dimmer, i.e., 0.02–0.03 cd/m2/s.
computerized data acquisition systems are
most commonly used. They are generally Patient Preparation
reliable, easy to use, reasonably priced, and Topical mydriatics should be instilled ahead of
provide excellent opportunities to store wave- the ERG so that the pupils are fully dilated
forms. It is recommended that the recording throughout the examination. To make sure

(a) (b)

Figure 4.45 (a) The corkscrew-­, needle-­, and button-­type electrodes are reliable and easy to use as
reference and ground electrodes, as well as active electrodes for VEPs in animals. The JET electrode is a
monopolar corneal contact lens electrode that can be used in many species, such as the cat and dog. (b)
The gold foil electrode can be used as an active electrode for recording the equine ERG. The plastic foil is
bent over the rim of the lower eyelid so the gold-­coated side touches the corneal surface.
212 Eye Examination and Diagnostics

(a) (b)

Figure 4.46 Two types of stimulators for FERGs and flash VEPs. (a) Both the stimulus and background light
intensities need to be measured to ensure that a known amount of light is delivered to the patient’s eye.
The detector of the photometer is positioned at the level of the eye of a patient. A xenon flash and a
halogen bulb, used for steady adapting light, are built into the aluminum housing on top of this full-­field
(Ganzfeld) stimulator. (b) A handheld stimulator (“mini-­Ganzfeld”) is easy and convenient to use in large
animals, but can also be used in small animals. The stimulator should be held close to the eye without
disturbing the corneal electrode.

that aberration from normal is not caused by ERG Results


reduced retinal illumination due to incomplete
The ERG is usually reported by providing val-
dilation of the pupils, it is recommended that
ues for the implicit times and amplitudes for
pupil size be checked immediately before and
the a-­and b-­waves. Rods and cones contribute
after the examination. The visual field of the
their signals to the FERG independently.
patient should not be blocked by a protruded
Taking advantage of the inherent, physiologi-
third eyelid or equipment, which can interfere
cal differences of the two systems allows sepa-
with the light stimulus.
ration of rod-­ and cone-­driven responses in a
Anesthetic Protocol number of ways (Figure 4.47). A dim stimulus
The FERG can readily be recorded in conscious, will be relatively more effective in stimulating
cooperative human patients. Brief protocols, to the rods than the cones. Dim stimuli under
test whether the retina is capable of producing a dark-­adapted (scotopic) conditions will bring
light-­driven response, can be performed in out the rod-­driven responses, whereas the
sedated or occasionally awake animals. cone-­driven response will be insignificant
However, for most animals, general anesthesia because the cones will be too poorly stimu-
is recommended for more comprehensive ERG lated. A bright background light, mimicking
testing, in order to maintain proper fixation and daylight conditions, will bleach the rhodopsin
stable position of electrodes, as well as minimiz- and saturate the rods, making them unable to
ing movement artifacts and patient stress. The respond to light stimuli. Using bright stimuli
most common effects of general anesthesia are under light-­adapted (photopic) conditions will
decreased response amplitudes and increased give responses almost exclusively driven by the
implicit times for both rod-­ and cone-­driven cone system. Flickering stimuli presented at
responses to the FERG. 30 Hz or higher will produce pure cone-­driven
­Ophthalmic Genetics and DNA Testin  213

20 µV
(a)
20 ms

(b)

(c)

(d)

Figure 4.47 Four ERG responses from a normal dog. (a) A mixed, dark-­adapted rod–cone response. The
small positive deflection just below the letter is a stimulus artifact, which shows when a brief, white flash
(3.0 cd/m2/s) is delivered. The response has a conspicuous, negative a-­wave followed by the large, positive
b-­wave. Superimposed on the ascending limb are a few oscillatory potentials (open arrow). The peak of the
b-­wave is bipartite where the later peak reflects the slower rod b-­wave (black arrow). (b) A dark-­adapted,
mainly rod-­driven ERG in response to a dim white flash (0.03 cd/m2/s). Note that there is no obvious a-­wave
and that the implicit time of the b-­wave is similar to the rod-­driven peak in (a). (c) A cone response to a
bright, white flash (3.0 cd/m2/s) presented on a rod-­saturating background (40 cd/m2). The amplitude is
considerably smaller than that of the dark-­adapted responses, but both an a-­wave and a b-­wave can be
seen. (d) A cone-­driven response to a bright, white flickering stimulus (30 Hz) in the presence of the steady,
adapting light.

responses in cats and dogs, too. Given that includes physical traits as well as pathological
canine (and feline) cones can follow frequen- conditions. Some pathological conditions are
cies of up to 70 Hz or higher, it is possible to straightforward inherited conditions, such
employ even higher stimulus frequencies to that if the gene mutation causal for the condi-
test retinal function driven by the cones. tion is present, the individual will develop the
However, technical limitations usually force condition. However, other factors such as
the examiner to use stimulus frequencies far interactions of other genes can alter the dis-
below the cone-­driven flicker fusion frequen- ease phenotype. For example, these factors
cies in these species. Flicker photometry has might influence age of onset, rate of progres-
proven to be useful in assessing the spectral sion, or even whether the trait is expressed at
sensitivity of the two classes of cones in some all (thus contributing toward variable pene-
companion and farm animal species. trance of some genetic traits). This is often
described as “background genetic effects.”
Some hereditary conditions are under the
­ phthalmic Genetics and
O influence of several genes and are described as
DNA Testing having polygenic inheritance. Other genetic
variation confers susceptibility or resistance to
There is a complex interaction between the disease, for example, resistance to infection or
genetics of an individual and the environ- predisposition to cancer formation. Thus, a
ment, both of which combine to result in genetic predisposition for a condition may be
the individual’s phenotype. The phenotype present, but unless there is an environmental
214 Eye Examination and Diagnostics

influence, the condition may not develop, or complex conditions where there may be more
may be less severe. than one locus involved. For example, the cone
rod dystrophy type 1 (CORD1) form of PRA
originally associated with an RPGRIP1 inser-
Tests for Genetic Disease
tion mutation appears to require the presence
There are a rapidly increasing number of DNA-­ of a variation in the MAP9 gene and probably
based genetic tests available as more gene an additional unknown locus for the pheno-
mutations underlying hereditary diseases are type to develop. The RPGRIP1 insertion has
identified (for a list of ophthalmic conditions been detected in several breeds of dog but does
for which DNA tests are available, please refer not appear to always be associated with retinal
to the ECVO Hereditary Eye Diseases Manual degeneration. In some breeds, there is a high
on the ECVO website: http://ECVO.org, and incidence of the RPGRIP insertion and yet a
Appendix T). It is important to appreciate and low incidence of PRA. For this reason, the
explain to clients the information that the tests results of DNA tests for the RPGRIP1 insertion
actually provide. When designed to identify a should be interpreted with care.
specific gene mutation, the test will do only
that. This means that a test for progressive reti-
Sample Collection
nal atrophy (PRA) will only identify whether
an animal is affected or is not affected by (or in To carry out a genetic (DNA-­based) test, a DNA
the case of recessive PRA, is a carrier for) that sample is required. This is commonly isolated
specific type of PRA. Some breeds of dogs have from a blood sample, cheek swab or hair folli-
multiple forms of PRA, each caused by a differ- cle. The instructions from the laboratory con-
ent genetic mutation. Each test will only iden- ducting the test should be followed. Care must
tify one of those forms. To use the Golden be taken to ensure that the sample is not con-
Retriever as an example, it is known that at taminated (e.g., with DNA from another ani-
least three forms of PRA are segregating within mal or person) and is clearly labeled. When
the breed. Dogs could have the PRCD form of samples from multiple animals are being col-
PRA (which is common across several breeds lected, particular care should be taken with
of dog), or they could have PRA caused by a identification of the animal, and the sample
mutation in the SLC4A3 gene, or the TTC8 should be clearly and accurately labeled imme-
gene. In the Papillon, about 70% of PRA was diately after it is collected.
shown to be caused by a mutation in CNGB1,
meaning that PRA in the breed can also result
Breeding from Carriers
from one or more additional gene mutations.
for Recessive Disease
Thus, a Papillon could be clear of the CNGB1
form of PRA and yet still develop PRA (caused Breeding from carriers of recessive disease
by a non-­CNGB1 form of PRA). DNA-­based where the underlying gene mutation is known
tests are completely specific for the one form of can be performed without risk of producing
hereditary disease they were designed to iden- affected offspring, so long as carriers are mated
tify, and they should also be very accurate, if with genetically clear animals. In some cir-
they are well designed. Obviously, there is still cumstances, use of carrier animals in breeding
opportunity for human errors to be made, for programs can be important. If a recessive dis-
example, if samples are mislabeled, which is ease is present in a breed at a high incidence,
probably more of a risk if multiple dogs are avoiding breeding from all affected and carrier
being sampled at the same time. animals can considerably limit the available
The interpretation of tests can be compli- gene pool for breeding. Use of only a small pro-
cated in some situations such as with more portion of available animals for breeding could
­Ophthalmic Genetics and DNA Testin  215

run the risk of bringing out other “back- be sensible to use the animal in breeding pro-
ground” hereditary diseases that are in the grams (avoiding mating with another carrier
population at low levels. It may also run the animal). Then by selective breeding over a few
risk of losing some desirable characteristics generations, the desirable characteristics can
from the breed. If there is a particularly good be separated from the disease genotype (i.e.,
specimen that happens to be a carrier for a separating the “good genes” from the “bad
recessive disease that can be tested for, it may genes”).
217

Section 3

Canine Ophthalmology
219

Canine Orbit: Disease and Surgery


Revised from 6th edition of Veterinary Ophthalmology, Chapter 14: Diseases and Surgery of the Canine Orbit, by Simon A. Pot, Katrin
Voelter, and Patrick Kircher

Orbital diseases are not uncommon in the dog. artery, the an­astomotic branch of the exter-
The close vicinity of the oral and nasal cavity, nal ophthalmic artery, and the extensive
tooth roots, and paranasal sinuses renders orbital venous plexus. The extraconal space
orbital structures susceptible to disease pro- is enclosed by the periorbita, which is a fas-
cesses extending from any of these cavities cial layer co­vering the periosteum and soft
through the orbital wall. The dog has an incom- tissue walls of the orbit. The concentration
plete bony orbit. The orbital rim consists of of blood vessels and nerves that cross the
bone for approximately four-­fifths of its cir- caudal orbital floor is of major significance
cumference and is completed laterally by the and is to be avoided during surgery; they
orbital ligament. The rest of the orbit is enclosed include the maxillary artery and nerve, the
by bone only; hence, surgical entry into the pt­erygopalatine ganglion, and the associated
orbital space is either through the palpebral fis- pa­rasympathetic, sympathetic, and somatic
sure or through its fibrous and muscular caudal ne­rves. Throughout the orbit, space-­f illing
dorsolateral wall. The roof, floor, and the lateral fatty tissues cushion the globe and other
wall of the orbit are formed by the periorbita susceptible intraorbital structures, and accom-
and temporal, masseter, and medial pterygoid modate globe movements.
muscles of mastication, and by the zygomatic
salivary gland. Also, through these surround-
ing soft tissues, the orbital contents are rela- ­Clinical Signs/Examination
tively susceptible to penetrating trauma
(Figure 5.1). Clinical signs of orbital disease are relatively
The orbit can be divided into an intraconal nonspecific with regard to etiology. Orbital dis-
and an extraconal space, separated from eases result in (i) altered orbital volume, (ii)
each other by the fascial sheets (septum impaired function of orbital structures, or
orbitale, periorbita, and epibulbar fascia) (iii) both.
that envelop the extraocular muscles and
fuse with Tenon’s capsule anteriorly, and
Exophthalmia Versus Enophthalmia
with the periorbita around the annulus of
Zinn at the orbital apex. The intraconal Changes in orbital volume manifest as exoph-
space contains the rectus and retrobulbar thalmos or enophthalmos, depending on
muscles, CN II–VI, the internal ophthalmic whether the orbital volume has increased or

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
220 Canine Orbit: Disease and Surgery

Palpation of Orbital Structures


Some of the orbital contents can be palpated
both caudal to the orbital ligament and from
the oral cavity through the pterygoid muscle.
The immediate retrobulbar tissues can be pal-
pated by retropulsion of the globe. In normal
mesaticephalic and dolichocephalic dogs but
not in brachycephalic breeds, the globe can be
displaced caudally for some distance. In the
presence of space-­occupying orbital lesions,
Figure 5.1 Canine skull demonstrating the lack of retropulsion of the globe will be restricted or
an osseous orbital floor, rendering the orbital impossible, and may be painful.
contents susceptible to penetrating trauma The bony rim of the orbit and the walls of
through the roof of the mouth.
the nasal cavity and paranasal sinuses should
be carefully palpated and evaluated for any
decreased respectively, and are influenced by
asymmetry.
the specific location of tissue changes within
Percussion of the paranasal sinuses can be
the orbit. Diffuse orbital volume increases, or
helpful to determine the presence of sinus
mass lesions located inside the muscle cone
occupying inflammatory or neoplastic mate-
behind the globe, typically displace the globe
rial. The presence of a symmetric flow of air
directly forward. Focal lesions outside the
through both nostrils should be evaluated, as
muscle cone in a more nasal, temporal, infe-
sinonasal tumors can cause tumor invasion of
rior, or superior position in relation to the
the orbit.
globe will displace or rotate the globe off-­axis
The oral cavity is routinely inspected, because
into a direction opposite to the mass lesion.
disease processes from the oral cavity or teeth
These often subtle changes can help localize
may adversely affect the orbit and its contents.
the lesion within the orbit and assist planning
Conversely, orbital diseases may affect, or be
an approach for biopsy acquisition and/or sur-
visualized through observation of, adjacent
gical exploration.
structures, such as the oral cavity, e.g., swelling
The degree of exophthalmos or enophthal-
behind the last upper molar tooth. Restrictive
mos is usually estimated by determining the
myopathies, like masticatory muscle myositis
position of the axial cornea relative to the
(MMM), can cause restrictions or even an ina-
orbital ligament and other eye, both from a
bility to open the mouth.
distance and from above. Exophthalmos can
be measured directly with a Luedde or Hertel
exophthalmometer, but these instruments
Clinical Signs
have not been utilized in veterinary ophthal-
mology. Nictitating membrane protraction in Inflammatory changes within the orbit are
the dog results from contraction of the usually accompanied by pain, especially upon
retractor oculi muscles with the resultant for- globe retropulsion and when opening the
ward displacement of orbital fat to push its mouth. Movement of the vertical ramus of the
base outward. A most passive nictitating mandible into the orbital space upon opening
membrane protrusion can accompany the mouth increases pressure on the orbital
increased orbital volume. Conversely, with contents. Most dogs with orbital pain will
any decrease in volume or/and orbital fibro- therefore display difficulties with, or will vocal-
sis, passive nictitans protrusion occurs due ize during, some activities requiring jaw move-
to enophthalmos. ment: chewing and eating (especially dry food,
­Ancillary Diagnostic Test  221

rawhides, and bones), playing with balls and


sticks, barking, or yawning. Inflammatory
changes in the orbit (cellulitis, abscess forma-
tion), which cause tissue edema, can be accom-
panied by conjunctival hyperemia and
chemosis, and periocular swelling.

Other Clinical Signs


Impaired function of orbital structures can
also manifest as reduced ocular motility, stra-
bismus, abnormal globe position, anisocoria,
blindness, and increased or reduced tear pro-
duction. These clinical signs can be caused by
mechanical entrapment, pressure atrophy and Figure 5.2 Ultrasonography of an orbital
loss of nerve function, and neural stimulation neoplasm (meningioma) in a 10-­year-­old Collie.
There is marked indentation of the
of affected tissues. Congestion of episcleral
caudonasal globe.
vessels is caused by a decreased venous return,
which is due to an increased orbital tissue and
Auscultation
intravenous pressure.
In more extreme cases of exophthalmos, In rare cases of pulsating or intermittent
associated with orbital cellulitis, trauma, and exophthalmos associated with arteriovenous
advanced masses, lagophthalmos can ensue fistula or varix, auscultation of the orbit may
due to a decreased ability to close the eyelids. reveal systolic murmur (“bruit”).
This quickly results in exposure keratitis,
ulceration, and potential loss of the eye.
­Ancillary Diagnostic Tests
Ophthalmoscopy
Because the entire orbit cannot be visualized
Posterior indentation of the globe can be directly, a combination of diagnostic imaging
observed by ultrasound or ophthalmoscopi- and cytology/biopsy sample acquisition may be
cally as an area of fundus elevation and necessary. Standard radiography, however, is
altered reflectivity due to the altered angles rarely of diagnostic value due to the poor con-
of incident and reflected light (Figure 5.2). trast resolution of orbital soft tissues and conse-
This indented fundus area should be observed quential poor delineation of lesions, as well as
during spontaneous eye movements. The the superimposition of bony structures. Those
indentation will not change position if it is lesions causing osseous proliferation or destruc-
caused by a mass attached to the globe, tion, or containing radiopaque material (such as
whereas unattached masses will cause an metallic foreign bodies) can be visualized.
indentation that shifts position during globe Contrast radiography of orbital tissues, such as
movement. Even with marked deformation pneumo-­orbitography, orbitography, orbital
of the globe, intraocular pressure usually arteriography, venography, optic nerve thecogra-
remains within normal range. However, in phy, and sialography, has been largely replaced
dogs with a relatively short palpebral fissure, by the newer cross-­sectional diagnostic imaging
the globe can be pressed against the lids by a techniques, including orbital ultrasonography,
space-­occupying lesion, slightly elevating the color Doppler imaging, computed tomography
intraocular pressure. (CT), and magnetic resonance imaging (MRI).
222 Canine Orbit: Disease and Surgery

Diagnostic Ultrasound dogs with cystic lesions and orbital abscesses,


but are also identified in more than 10% of neo-
The basic principles of diagnostic ultrasound
plasms. When the suspicion for a retrobulbar
have been described in Chapter 4. The portals
abscess or cellulitis is high and the presence of
for placement of the ultrasound probe include
a foreign body needs to be determined, ultra-
the following: (i) on the anesthetized corneo-
sound seems to be a relatively sensitive diag-
conjunctival surface for a direct corneocon-
nostic tool. CT or MRI studies are indicated for
junctival contact approach; (ii) on the upper
an evaluation of the size, number, and exact
eyelid skin with the eyelids closed for a
localization of retrobulbar foreign bodies.
transpalpebral approach, which can decrease
Neoplastic lesions were most commonly hypo-
patient discomfort; (iii) caudal to the orbital
echoic and homogeneous, and globe indenta-
ligament for a temporal approach, which
tion was identified more often than with
allows visualization of the deeper orbital struc-
inflammatory lesions. However, these features
tures, including the optic canal and orbital fis-
are by no means distinctive. Orbital bone
sure; and (iv) on the oral mucosa behind the
defects and tissue mineralization were almost
last upper molar, directed toward the orbit, for
exclusively seen in neoplastic lesions.
a transoral approach (Figure 5.3), which is use-
ful for fine needle aspirate (FNA) guidance
and foreign body searches in retrobulbar Computed Tomography
abscess or cellulitis. and Magnetic Resonance Imaging
Ultrasound is a useful technique to image the
In many respects, advanced orbital imaging
orbit, especially for an initial screening for the
techniques are superior to the traditional tech-
presence of lesions. The normal orbit is charac-
niques of radiography and ultrasonography, due
terized by a relative hypoechogenicity of the
to their superior tissue contrast resolution, abil-
extraocular muscles and optic nerve, compared
ity to image the entire skull, including the adja-
to the orbital fat. The bony orbital wall presents
cent nasosinal and cranial cavities, and their 3D
as a reflecting interface, which can be scanned
reconstruction capabilities (also see Chapter 4).
for surface irregularities and defects. In cases of
Due to the natural contrast between bone,
cellulitis, either a generalized loss of contrast
soft tissues, air, and fat, CT has superior con-
between the orbital contents or no ultrasono-
trast resolution qualities, enabling excellent
graphic abnormalities are observed. Cavitary
visualization of orbital structures, especially
lesions with a fluctuant center are found in
bone. MRI provides better soft tissue contrast
resolution compared to CT. MRI scans are
therefore superior to CT scans in cases in
which an exact evaluation of soft tissue tumor
extension into the surrounding soft tissues,
including intracranial extension, is needed.
Cysts and abscesses are also more easily identi-
fied with MRI.

Fine Needle Aspiration


and Tissue Biopsy
Biopsy specimens can be obtained via the oral
cavity, through bulbar conjunctiva, or through
Figure 5.3 Ultrasound probe placement for a the skin caudal to the orbital ligament, with or
transoral approach to the orbit. without the use of ultrasound or CT guidance.
­Acquired Orbital Disease  223

With the advent of modern imaging tech- Vascular Anomalies


niques, diagnostic orbitotomies have become
Orbital varices and arteriovenous fistulas are
almost obsolete. Available data on the diagnos-
very rare orbital anomalies with few reported
tic sensitivity of FNAs and tissue biopsies show
cases. Varices can be congenital as well as
that an FNA yields diagnostic results in
acquired. Dogs usually present with a non-
approximately 50% of the cases, whereas tissue
painful, pulsating or intermittent exophthal-
biopsies provide a definitive diagnosis in
mos. A decrease in venous return from the
approximately 75% of the cases.
head can influence the extent of exophthalmos
if an orbital varix is present, with the exoph-
­Congenital Anomalies thalmos worsening when the head is kept low
of the Orbit and Globe or pressure applied to the jugular vein region.
In arteriovenous fistula cases, not varices, a
Anophthalmos systolic murmur (“bruit”) can be auscultated
in the orbital region. Treatment is difficult in
Complete absence of the eye, or anophthalmos, all cases, and the prognosis is grave. In one
is very rare. In most cases, some remnants of case, attempted ligation of orbital vessels
ocular tissue can be identified histologically. caused massive hemorrhage as well as subse-
quent enucleation of the globe and ligation of
Cystic Eye, Microphthalmia, the common carotid artery. Orbital exentera-
and Nanophthalmia tion and careful hemostasis should be curative.
If remnants of ocular tissue are present histo-
logically, a diagnosis of either a cystic eye or
microphthalmia can be made. In true microph-
­Exophthalmos
thalmia, the globe contains evidence of the pres-
Table 5.1 lists the most important differential
ence of surface ectoderm (lens), neural crest
diagnoses for exophthalmos.
migration, and neuroectodermal differentiation.
Microphthalmia therefore presents as an abnor-
mally small globe, with various other ocular Orbital Cysts
anomalies involving the cornea, lens, uvea, vit-
Orbital cysts are rare in the dog. A retrobulbar
reous, and retina. Vision may be normal,
dermoid cyst in a Dachshund, containing a yel-
reduced, or absent. In contrast, a small but oth-
lowish, viscous fluid and long black hair, has
erwise normal globe is called nanophthalmia. In
been described. On histopathological examina-
the Doberman Pinscher, microphthalmia is
tion, the cyst wall consisted of a keratinized
associated with anterior segment and retinal
squamous epithelium. Surgical excision is
dysplasia. In the homologous merle Australian
recommended.
Shepherd and other breeds, the microphthalmia
is associated with equatorial staphylomas, per-
sistent pupillary membranes, and retinal dyspla-
sia, and an excessively white hair coat. Poorly
­Acquired Orbital Diseases
pigmented animals (>90% white) are most
Inflammatory Lesions: Orbital
affected. Collies and Shetland Sheepdogs with
Cellulitis/Abscess
Collie eye anomaly often exhibit variable degrees
of microphthalmia; this is especially true for In contrast to large animals, orbital inflamma-
merles (see Appendix A or access http://Optigen. tory diseases are rather common in the dog.
com for the most recent information on DNA According to most studies, dogs presenting with
tests for canine eye diseases). non-­neoplastic orbital diseases are significantly
224 Canine Orbit: Disease and Surgery

Table 5.1 Differential diagnoses Foreign bodies may enter the orbit from the
for exophthalmos in dogs. oral cavity, percutaneously or through the con-
junctival sac (Figure 5.4a–c). Hematogenous
Vascular anomalies
infection of orbital tissues is possible with the
Orbital varix microorganisms invading from the oral cavity,
Orbital arteriovenous fistula sinuses, or tooth roots. Infections of the zygo-
Cystic lesions matic gland may present as orbital cellulitis or
Salivary retention cyst and mucocele abscess, and in these cases a swollen excretory
Inflammatory lesions duct may be seen lateral to the second molar
Abscess tooth. Significant inflammatory diseases of the
globe itself (panophthalmitis, scleritis) can
Cellulitis
also cause orbital cellulitis.
Granuloma
Extension from adjacent structures, exoge-
Extraocular muscle myositis
nous trauma, and foreign bodies were the most
MMM
common causes of infectious orbital disease.
Neoplasia Staphylococcus spp. were isolated in 25%,
Primary orbital Escherichia coli in 16.7%, Pasteurella multocida
Metastatic or primary multifocal in 8.3%, and anaerobic bacteria (mostly
Locally invasive tumor invading orbit Bacteroides and Clostridium spp.) in 30.5% of
Traumatic causes the canine patients in this study. In another
Orbital fracture
study, Pasteurella spp. were the most common
isolates from orbital abscesses. Fungal organ-
Hematoma
isms are an uncommon cause of orbital dis-
Emphysema
ease. Onchocerciasis occurs in the
Miscellaneous southwestern United States and south-­central
Craniomandibular osteopathy Europe, and in chronic cases, the live and dead
worms are incorporated in subconjunctival,
episcleral, and orbital granulomas causing cor-
younger than dogs presenting with neoplastic responding clinical signs. Treatment consists
diseases (orbital abscesses at 4 years of age on of surgical excision and the postoperative use
average and mean age of tumor patients at of microfilaricidal drugs.
9.5 years). Ultrasonography is a cost-­effective method
Typically, dogs present with acute, unilateral to determine the presence of a drainable ret-
exophthalmos, protrusion of the nictitating robulbar abscess and to screen for the presence
membrane, conjunctival hyperemia and che- of a foreign body. The type of foreign body
mosis, episcleral venous congestion, periocu- material dictates which imaging modality is
lar swelling, serous to mucopurulent ocular most useful for identification. Most foreign
discharge, and pain. The globe itself is usually bodies are not recognized on plain radiographs,
normal and normotensive. Affected dogs are but metallic foreign bodies are easily demon-
usually febrile and inappetent. The white strated. MRI scans are contraindicated when a
blood cell count is often elevated with a suspicion for a metallic foreign body exists,
neutrophilia. due to the risk of foreign body displacement
The cause often remains unidentified. under the influence of the strong magnetic
Foreign material is sometimes encountered field. A CT scan can directly pick up foreign
with porcupine quills not infrequent. The bodies that are sufficiently dense (metal, glass,
point of entry for both foreign bodies and gun- bone). Foreign bodies of lower density (plant
shot pellets is not always easily identified. material, wood, plastic, porcupine quills) may
­Acquired Orbital Disease  225

(a) (b)

(c) (d)

Figure 5.4 Orbital foreign body in a six-­year-­old dog. (a) Dog at initial presentation with chronic purulent
discharge. (b) Fistulous tract in the dorsal conjunctival fornix. (c) Surgical exploration of the fistulous tract.
(d) Foreign material (wood) retrieved from the orbit.

be identified in postcontrast studies as a filling [e.g., amoxycillin–clavulanic acid], and carbap-


defect with a contrast-­enhancing rim of reac- enems) is indicated pending the results of bacte-
tive tissue. Obtaining samples for cytology and rial culture and sensitivity testing. Additionally,
culture and sensitivity assays is an important if no contraindications exist, these patients are
step in the diagnostic process. FNAs and tissue usually treated with nonsteroidal anti-­
biopsies can be used for these purposes. inflammatory drugs. Hot packs also are benefi-
The first and most important step in treating cial and well tolerated by most dogs.
an orbital abscess is drainage (Box 5.1 and The globe itself must be treated symptomati-
Figure 5.5). The oral mucosa behind the last cally. In cases of lagophthalmos, lubrication of
upper molar tooth, which may show a fluctuat- the ocular surface is important. In most cases,
ing swelling, is incised. A closed hemostat is application of an antibiotic ointment three to
advanced through the pterygoid muscle and four times daily is sufficient. The degree of
then opened and withdrawn without closing. exophthalmos often increases temporarily after
Irrigation of the retrobulbar area is a controver- drainage, and a temporary tarsorrhaphy may be
sial issue; however, irrigation with crystalline necessary. Soft food should be offered until the
penicillin has been recommended. Systemic globe is back in its normal position. The prog-
antibiotic therapy using broad-­spectrum antibi- nosis is usually good. Once diagnosed and
otics (cephalosporins, extended-­spectrum peni- treated with the appropriate systemic antibiot-
cillins [e.g., ticarcillin], potentiated penicillins ics, clinical signs often begin to regress within
226 Canine Orbit: Disease and Surgery

Box 5.1 Treatment of Orbital Cellulitis in the Dog


Drainage Incise oral mucosa behind the last upper molar tooth. Insert closed
hemostat, and then slightly open and withdraw. Blood and purulent
material usually drain from the affected orbit. Area richly supplied
by blood vessels and nerves, but complications are rarely
encountered (damage to the optic nerve and ciliary nerves)
Irrigation Irrigation of the retrobulbar area is controversial. Irrigation with
crystalline penicillin reported
Systemic antibiotics Use broad-­spectrum antibiotics pending culture/sensitivity results.
Administer for 5–7 days
Hot packs Promote healing/comfort
Topical antibiotics Reduce conjunctival inflammation and lubricate the corneas

the mass effect created by the volume of


the cyst.
Mucoceles (or sialoceles) usually result from
trauma to the head, with or without skull frac-
tures. In a mucocele, leakage of saliva from the
zygomatic gland or its excretory duct causes
inflammation and tissue fibrosis, resulting in a
thick fibrous capsule, but no true epithelium,
surrounding the cavitary lesion. Mucoceles
must be distinguished from salivary retention
cysts (which are lined with a true epithelium)
caused by inflammation and ulceration of the
oral mucosa and obstruction of salivary out-
flow with subsequent cyst formation.
Figure 5.5 Image illustrating transoral abscess In zygomatic gland mucoceles, the distended
drainage technique. excretory duct of the zygomatic gland can some-
times be seen through the oral mucosa. The
48 h. In a series of 17 cases, 15 healed within a clinical signs suggest a fluctuating swelling with
week, 1 healed after one recurrence, and 1 was a variable position within the orbit and possible
lost to follow-­up. In most cases, the exophthal- conjunctival or oral presentation. Exophthalmos
mos regresses within 36–48 h, and the general and protrusion of the nictitating membrane are
condition of the animal markedly improves. usually present, and pain on opening the mouth
or palpation of the globe is variable but usually
minimal. The diagnosis is made on the basis of
Salivary Retention Cysts
clinical signs and results of orbital ultrasonogra-
and Mucoceles (Sialoceles)
phy, CT, and/or MR imaging. Aspiration of a
Cystic structures in the orbit or periorbital tis- yellowish and slightly tenacious fluid with vari-
sues can arise from any glandular or epithelial able amounts of blood is typical for mucoceles.
tissue, including lacrimal, third eyelid, and True cysts usually yield clear to mucoid fluid.
salivary glands, and conjunctival or paranasal Mucoceles are best treated by surgical excision
sinus mucosa. The main clinical signs relate to of the cystic cavity and associated gland. The
­Acquired Orbital Disease  227

prognosis appears to be favorable. In most In acute myositis, a leukocytosis with periph-


reported cases, healing occurs within a short eral eosinophilia, elevated serum levels of cre-
time following surgical and medical therapy. atine phosphokinase, and a positive 2M
antibody test are typically present. Affected
muscles are dark orange in color during biopsy,
Myositis
and histopathology of temporal muscle biop-
Because of the absence of a bony orbital wall sies reveals degeneration of muscle fibers as
laterally, swelling or atrophy of the muscles of well as neutrophilic and eosinophilic infiltra-
mastication as well as the extraocular muscles tion. The digastricus muscle does not contain
can displace the globe. type 2M fibers, which likely explains the
results of a recent study, describing the CT
Eosinophilic Myositis/Masticatory findings in dogs with MMM. Swelling, atrophy,
Muscle Myositis or both were identified in the temporalis, mas-
Eosinophilic myositis of the muscles of mastica- seter, and pterygoid muscles of mastication,
tion, or MMM, predominantly affects young but not in the digastricus muscle.
German Shepherds and Weimaraners, but has MMM is usually an acute disease accompa-
also been described in Labrador Retrievers and nied by fever, lethargy, anorexia, and weight
Golden Retrievers (Figure 5.6). MMM is an loss. Pain and swelling of the masseter and
immune-­mediated inflammatory myopathy tar- temporal and pterygoid muscles causes pain-
geting the temporalis, masseter, and pterygoid ful and restricted jaw movements and exoph-
muscles of mastication. Affected muscles con- thalmos, respectively. Optic neuritis and
tain type 2M myofibers, which are composed of subsequent blindness have been described.
myosin heavy and light chains unique to the Despite the fact that this is usually a bilateral
masticatory muscles. Type 2M fiber-­specific disease, symptoms of bilateral muscle involve-
autoantibodies against masticatory muscle ment are not always appreciable clinically.
myosin heavy and light chains are routinely Without treatment, inflammatory episodes
found in dogs with MMM, but not in dogs with persist for one to three weeks. Acute myositis
polymyositis, using immunoblotting and ELISA. must be differentiated from orbital cellulitis

Figure 5.6 MMM in a German


Shepherd. There is marked swelling
of the masticatory muscles and
bilateral exophthalmos, which is
more marked in the right eye.
(Courtesy of I. Walde.)
228 Canine Orbit: Disease and Surgery

or abscesses, temporomandibular joint disease, strabismus. Ultrasonography (Figure 5.7b), CT,


and (extraocular) polymyositis. or MR images will reveal swollen extraocular
Repeated bouts of MMM can result in muscles in cases of extraocular polymyositis.
marked fibrosis of the muscles of mastica-
tion and muscle atrophy, enophthalmos, and Restrictive Strabismus
an inability to open the mouth in chronic Restrictive nasoventral strabismus has been
cases. Difficulties in opening the mouth can described as a uni-­ or bilateral, progressive
handicap a dog and negatively impact its esotropia in young dogs often of the large
quality of life. Severe enophthalmos causes breeds, which can lead to blindness within a
secondary entropion and may impair vision few weeks. Extraocular muscle fibrosis was
in combination with nictitans protrusion. In histologically diagnosed in all specimens in
some cases, muscle fibrosis and atrophy one report, and in most cases signs of either
occur without clinically detectable anteced- acute or chronic lymphocytic inflammation
ent inflammation. (extraocular muscle myositis) were present.
Radical surgical transection of the affected
Extraocular Polymyositis muscles resulted in a central eye position in
Extraocular polymyositis occurs mainly in about 80% treated eyes, although most eyes
females and in the Golden Retriever breed remain enophthalmic.
(Figure 5.7a). Young dogs are typically affected. In the acute stages, myositides respond well
Bilateral exophthalmos with anterior globe dis- to immunosuppressive doses of oral corticos-
placement and very limited ocular mobility, teroids over three to four weeks. Azathioprine
retraction of the upper eyelid without protru- can be given at a dose of 1–2 mg/kg body
sion of the nictitating membrane, and conges- weight for 10–14 days and then slowly tapered
tion of episcleral vessels are often presenting off. The prognosis is guarded. Recurrence rates
signs. A predominantly CD3+ lymphocytic have traditionally been reported to be quite
infiltrate dominates the muscle histopathology. low, but relapses have been described.
In chronic cases, fibrosis of the extraocular Uncontrolled myositis will invariably lead to
muscles can cause mild enophthalmos and atrophy of the affected muscles.

(a) (b)

Figure 5.7 (a) Bilateral extraocular polymyositis in an eight-­month-­old Golden Retriever. (b)
Ultrasonographic image of swollen rectus muscles (outlined by asterisks) in a five-­year-­old Great Dane with
extraocular polymyositis.
­Acquired Orbital Disease  229

Orbital Neoplasia of all orbital tumors are malignant, thereby


resulting in a guarded to poor prognosis in
Tumors represent the most common group of
most patients.
orbital diseases in older dogs. Primary tumors
Depending on the localization, orbital
can arise from any orbital tissue, and second-
tumors cause slowly progressive, unilateral
ary neoplasms either invade the orbit from
exophthalmos or enophthalmos, with variable
adjacent structures or metastasize to the orbit
displacement and indentation of the globe
from distant sites (Box 5.2). In general, orbital
(Figure 5.8). Nictitans protrusion is present
neoplasms occur in older animals. About 90%
and retropulsion of the globe is decreased or
impossible. Bilateral orbital neoplasia appears
to be extremely rare. In contrast to orbital
Box 5.2 Tissue Origins of Orbital inflammatory diseases, neoplasms tend not to
Neoplasms in the Dog be painful. However, a diagnosis of orbital neo-
plasia cannot reliably be made based on clini-
1) Tumors of mesenchymal origin cal signs alone. Vision can be retained even in
(osteosarcoma, fibrosarcoma, chronic cases, depending on the level of pres-
multilobular osteochondrosarcoma). sure or pull on the optic nerve, but tumors aris-
About 25–40% of all orbital tumorsa ing from the optic nerve or its meninges will
2) Tumors of epithelial origin (mostly cause blindness at an early stage. Orbital
adenocarcinoma, among which primary extensions by nasosinal tumors can cause
nasosinal tumors are common). About epistaxis, altered percussion tones and pain
40–50% of all orbital massesa upon palpation and/or percussion of the
3) Miscellaneous (peripheral nerve sheath nasosinal cavities, and a decreased or absent
tumor, orbital meningioma, mastocytoma)a airflow through the nose.
Most of these tumors are of primary In patient workups for possible orbital masses,
orbital origin, with the exception of a complete general physical examination,
nasal and paranasal sinus tumors (about including evaluation of regional and distant
10–15% of all orbital tumors) lymph nodes, and a search for possible metasta-
a ses via thoracic and abdominal imaging are
Mbtsalignant.
important. After localization of the lesion, an

Figure 5.8 A 12 year-old mixed breed dog with exophthalmos and dorsolateral stribimus secondary to an
orbital osteosarcoma.
230 Canine Orbit: Disease and Surgery

FNA or tissue biopsy is obtained. Unfortunately, may increase the risk of further hemorrhages.
many orbital neoplasms are discovered in an Topical application of atropine sulfate is con-
advanced stage at which euthanasia or palliative troversial, because secondary glaucoma may
surgery are the only options. Osteolysis is a poor be a complication of marked hyphema.
prognostic indicator and is associated with a sig- Small, nondisplaced fractures stabilize spon-
nificant decrease in survival time. Localized taneously and do not require surgical reduc-
neoplasms without evident distant metastasis tion and fixation. Small, displaced and
may be surgically removed while preserving the offending bone fragments need to be removed
globe and, possibly, the animal’s vision. If pres- surgically and large, unstable fractures may
ervation of the globe is not possible, exenteration require internal fixation.
of the globe or radical orbitectomy must be con-
sidered (for reference, see the “Orbitotomy” and
Orbital Emphysema
“Orbitectomy” sections). Surgical management
Orbital emphysema is usually a complication
of orbital neoplasia can be combined with radia-
of enucleation. Brachycephalic dogs appear to
tion therapy, chemotherapy, or both. For some
be predisposed. This may result from
tumor types, including nasosinal tumors, irradi-
increased pressure in the nasal cavity of such
ation yields favorable results when used as
dogs during expiration (coughing and sneez-
monotherapy.
ing). The soft swelling of an orbital emphy-
sema often reveals crepitus when palpated. If
Traumatic Lesions clinical signs are equivocal, plain radiographs
will show air in the orbit and, at the same
Orbital Fractures and Hematomas
time, may demonstrate orbital fractures.
Orbital fractures and hematomas usually result
Orbital emphysema resolves spontaneously in
from road accidents. The frontal, temporal, and
most cases.
zygomatic bones are most commonly involved,
If an emphysema persists after enucleation,
and clinical signs include skin lacerations,
the proximal end of the nasolacrimal duct
pain, facial asymmetry, lacrimation, exophthal-
must be identified and ligated. In brachyce-
mos or enophthalmos, strabismus, proptosis,
phalic breeds, prophylactic ligation of the
lagophthalmos, and secondary xerophthalmia.
nasolacrimal duct at the time of enucleation
Contusions of the globe are often associated
could be considered.
with lens luxation, intraocular hemorrhage,
and retinal detachment. In severe cases, scleral
ruptures, usually extending from the lamina Traumatic Proptosis
cribrosa, may occur. CT is by far the most com- Traumatic proptosis results from a sudden, for-
prehensive imaging modality when dealing ward displacement of the globe with simulta-
with trauma patients: an exact evaluation of neous entrapment of the eyelids behind the
fracture topography, a reliable assessment of equator. This eyelid entrapment prohibits
globe integrity, and a complete evaluation of spontaneous repositioning of the globe
the entire head are possible. (Figures 5.9 and 5.10). Proptosis must be dif-
Animals with orbital fractures should be ferentiated from exophthalmos, in which the
kept quiet to prevent further swelling and lid margins remain in a physiological position.
hemorrhage, and cold compresses should be Proptosis of the globe is a true ophthalmic
administered. The eye must be cleansed imme- emergency, which requires rapid assessment
diately and kept moist. Local and systemic of the situation as well as immediate medical
antibiotics and systemic corticosteroids should and surgical therapy.
be given. Topical steroids are administered if The prognosis for vision is guarded to poor
the corneal epithelium is intact. Nonsteroidals in general and depends on the extent of (peri)
­Acquired Orbital Disease  231

ocular tissue damage (Table 5.2). As an approx-


imation, about 20% of proptosed globes regain
some functional vision. Hence, prognosis
refers to the possibility of salvaging the globe
for cosmetic purposes, as opposed to blindness
and enucleation.
The amount of proptosis may provide some
idea regarding the amount of extraocular mus-
cle damage. Usually, the shorter medial rectus
muscle is the first to be avulsed. If more than
two rectus muscles are avulsed, the vascular
supply and innervation to the anterior segment
Figure 5.9 Proptosis of the right globe in a young are compromised due to the extensive tissue
Golden Retriever. There is entrapment of the trauma, and the globe should be enucleated
eyelids as well as severe swelling and hyperemia (see Figure 5.11). Scleral ruptures are often
of the bulbar conjunctiva. The cornea has already
associated with intraocular hemorrhage and
been protected with an ointment.
loss of shape and turgor of the globe.
Enucleation is recommended in these cases.
Globes with intraocular hemorrhage, espe-
cially if combined with avulsion of more than
one extraocular muscle, have a guarded prog-
nosis. Such eyes may still be repositioned. If an
acceptable status does not result, enucleation
can be performed at a later date.
Keratitis sicca and neurogenic keratitis due
to corneal desensitization are common seque-
lae and may be difficult to manage. The long-­
term prognosis must be discussed with the
owner in such cases. Some owners may prefer
enucleation rather than a blind eye that is sal-
vaged but requires constant attention for many
Figure 5.10 Severe proptosis with avulsion of the
optic nerve and several extraocular muscles in a years. Optic nerve damage with later atrophy
Cocker Spaniel. Despite the clear and intact can occur and are often detected a few months
anterior segment, enucleation was inevitable. after traumatic proptosis.

Table 5.2 Recommended treatment and prognosis for traumatic proptosis in dogs.

Clinical sign Possible prognosis Treatment

Positive direct pupil reflex Guarded to good Replacement


Medial rectus muscle avulsion Guarded Monitor/reattach
Two or more rectus muscle avulsions Poor Enucleation
Corneal/scleral rupture(s) Guarded to poor Repair/enucleation
Massive intraocular hemorrhage Poor Repair/possible enucleation later
Optic nerve transection Poor Enucleation
232 Canine Orbit: Disease and Surgery

(a) (b)

(c) (d)

(e)

(f)

Figure 5.11 Enucleation: subconjunctival approach. (a) Incision of the bulbar conjunctiva. (b) After
transection of the extraocular muscles close to their scleral attachments, the optic nerve is clamped and
severed. (c) The orbit is packed with a gauze sponge and the nictitating membrane resected. (d) Excision of
the lid margins. (e and f) Closure of the periorbital and deep fascial layers with a continuous suture pattern,
after removal of the gauze sponge. Skin closure with simple interrupted or continuous sutures.
­Acquired Orbital Disease  233

Therapy for Traumatic Proptosis muscle, the shortest of the four rectus mus-
The different components for medical and sur- cles. Globe position often returns to near nor-
gical therapy for traumatic proptosis in the dog mal over the course of several months (and
are summarized in Box 5.3. Depending on the the globe is unable to move laterally).
amount of orbital swelling and degree of Bilateral medial or lateral canthoplasty in
exophthalmos, all eyelid sutures should remain order to shorten the palpebral fissure in the
in place for at least one week and are then brachycephalic breeds, and thus prevent
removed one at a time, starting medially, on future proptosis, should be discussed with
subsequent clinical visits, once an effective the owner at the time of repositioning the
blink reflex is reestablished. proptosed globe.

Complications After Traumatic Proptosis


Miscellaneous Lesions
Long-­term sequelae of proptosis include
blindness, strabismus (usually exotropia), Orbital Fat Prolapse
mild exophthalmos, lagophthalmos, sensory Prolapse of orbital fat is uncommon in dogs;
deficits of the cornea, keratoconjunctivitis only a few cases have been described. Orbital
sicca, exposure keratitis, glaucoma, and fat is separated from the subconjunctival space
phthisis bulbi. Exotropia is a common sequel by Tenon’s capsule. The cause of orbital fat
resulting from avulsion of the medial rectus prolapse in the dog is unknown. Prolapsed fat
presents as a subconjunctival swelling. The
swelling is easily movable and usually nonpro-
Box 5.3 Treatment Steps for
gressive, but enophthalmos and protrusion of
Proptosed Globes
the nictitating membrane can be present. FNA
1) Keep moist with an antibiotic ointment is typically diagnostic. If necessary, orbital fat
2) Cleanse external eye with NaCl solution prolapse can be treated surgically, by excision
3) Engage eyelids with strabismus of the prolapsed fatty tissue and suturing the
hooks and pull lids over the globe conjunctiva to the episcleral tissue to prevent
4) Lateral canthotomy may be needed recurrences.
to increase palpebral fissure
Craniomandibular Osteopathy
5) Temporary tarsorrhaphy with two to three
horizontal mattress sutures with stent Craniomandibular osteopathy is a non-­
(3-­0 to 5-­0 monofilament nonabsorbable neoplastic, proliferative bone disease that pre-
suture) material. Two or three are usually dominantly affects Scottish Terriers and West
required. Leave small opening at medial Highland White Terriers at the age of three to
canthus for medications six months. Affected pups are often lethargic,
6) Systemic antibiotic and possible inappetent, and slightly febrile. The mandibu-
corticosteroid therapy is instituted for lar lymph nodes are enlarged, and the tempo-
7–10 days ral muscles may be atrophied. Because of their
7) Topical therapy includes atropine inability to open the mouth, affected dogs sali-
sulfate and antibiotic drops vate profusely, have difficulty eating and drink-
8) Warm compresses are applied twice ing, and are often dehydrated and emaciated.
daily The orbit is rarely involved, but exophthalmos
can occur. The etiology is unknown, but hered-
9) Remove lid sutures (only one suture/
visit), starting with the medial itary factors are suspected to play a role. The
sutures once an effective blink reflex disease is self-­limiting. However, supportive
can be demonstrated therapy during the active stage of the disease is
important.
234 Canine Orbit: Disease and Surgery

­Surgery of the Globe and Orbit for aseptic surgery in a routine manner. The
ocular surface and conjunctival sac are copi-
Orbital surgeries include (i) enucleation ously flushed with sterile saline solution; a
(removal of the globe); (ii) exenteration half-­strength povidone–iodine aqueous solu-
(removal of the conjunctiva, periorbita, tion can also be used as part of the chemical
extraocular muscles, and globe); (iii) orbital preparation of the eye for surgery. A preoper-
prosthesis (implantation of silicone or methyl ative retrobulbar block with a sodium chan-
methacrylate spheres into the orbit [extrascle- nel blocker (bupivacaine, lidocaine, etc.),
ral] or eviscerated [intrascleral] globe); and (iv) with or without epinephrine, can be used to
orbitotomy and orbitectomy (used to explore improve perioperative analgesia and reduce
the orbit, biopsy, and excise orbital masses). Of the need for additional postoperative analge-
these orbital surgeries, the enucleation proce- sics. The inferotemporal palpebral route has
dure is most frequently used by the small ani- been shown to give the most consistent intra-
mal and general practitioner. The other conal drug placement. A successful nerve
surgeries are more difficult and generally per- block is indicated by no resistance to globe
formed by the veterinary ophthalmologist. movement and the eye should move forward
slightly and rotate centrally while the pupil
Enucleation dilates.

Enucleation is the most common orbital sur- Subconjunctival Enucleation Technique


gery performed in animals. Removal of the The most commonly used surgical technique
globe is indicated in any case involving blind, is the subconjunctival approach (Figure 5.11).
painful eyes (e.g., uncontrollable glaucoma, The main objectives are to remove the globe,
endophthalmitis, and severe ocular trauma nictitating membrane, conjunctival sac, and
with hemorrhage). It is also indicated for lid margins while leaving as much soft tissue
treatment of intraocular tumors not amena- behind as possible to minimize depression of
ble to other forms of surgical or medical skin over the orbit. A lateral canthotomy is
treatment. performed to facilitate exposure of the globe,
Three different enucleation techniques and a lid retractor or speculum is inserted.
have been described: (i) the most common Beginning in the dorsal quadrant, the bulbar
procedure for small animals is the subcon- conjunctiva is incised approximately 5 mm
junctival procedure where the primary inci- posterior to the limbus. The conjunctiva and
sion starts just posterior to the limbal bulbar Tenon’s capsule are bluntly dissected from the
conjunctiva; (ii) the second most common globe, and the extraocular muscles are
enucleation technique is the subpalpebral id­entified and transected close to their scleral
approach that is used often in large animals; in­sertion. Incision of the extraocular muscles’
and (iii) the third approach is a modified lat- insertions allows the globe to be mobilized
eral or subbulbar technique. Both the lateral fu­rther and displaced in an anterior direction.
and transpalpebral approaches have the The retractor bulbi muscles’ insertions to the
advantage of minimizing intraoperative expo- posterior globe are identified and transected.
sure of the orbit to contaminants from the Medial rotation of the globe will expose the
ocular surface, and used in patients with optic nerve, which is clamped with curved
active ocular surface infections. hemostats and then transected approximately
5 mm behind the globe. The surgeon must
Surgical Site Preparation avoid tension on the optic nerve, to not dam-
For all orbital surgeries, the periorbital skin age contralateral optic nerve fibers at the
and eyelids are clipped, shaved, and prepared crossover point in the optic chiasm. Blunt
­Surgery of the Globe and Orbi  235

dissection of soft tissue and transection of the performed. The outer layers of the lids are first
muscles as close as possible to the sclera will clamped with curved hemostats and then tran-
minimize hemorrhage. Once the globe is sected approximately 3 mm from the margin.
removed, the orbit is packed with gauze The lid margins are then joined with Allis tis-
sponges to control diffuse hemorrhage, and sue forceps and the globe rotated medially. The
the nictitating membrane is grasped with for- lateral canthal ligament is cut, and the sclera
ceps and dissected at its base (to include the and extraocular muscles are exposed by blunt
gland of the third eyelid). The lacrimal gland dissection. Further dissection exposes the
is usually not removed. In addition, 3–5 mm of retractor oculi muscle and the optic nerve. The
eyelid margin is removed with scissors. The lateral part of the retractor oculi muscle is sev-
conjunctival sac is removed as thoroughly as ered, and the optic nerve (with remaining
possible. After removal of the gauze package, muscle) is clamped with a curved hemostat.
the periorbital/deep fascial layers and subcu- The optic nerve is then severed immediately
tis are sutured with 4-­0 absorbable suture behind the globe. Remaining tissue attach-
material in a continuous pattern. The skin is ments at the medial canthus are cut, and the
closed with simple continuous or interrupted globe is removed with the nictitating mem-
sutures using 4-­0 nonabsorbable monofila- brane within the conjunctival sac. Wound clo-
ment suture material. Postoperative care is sure is the same as with the subconjunctival
symptomatic, and sutures are removed after enucleation.
10–14 days. Owners should be informed that
serosanguinous secretions from the ipsilateral
Postoperative Complications
nostril may occur over the first few postopera-
The most common postoperative complication
tive days until the nasolacrimal duct is
is hemorrhage within the first few hours after
obliterated.
surgery, which results in swelling of the surgi-
cal site and serous discharge from the suture
Transpalpebral Enucleation Technique
line. Cold compresses, pressure bandages, and
In the transpalpebral approach in which the
sedation of the patient are usually sufficient to
eyelids are sutured together in a continuous
control hemorrhage. Icing the wound between
suture pattern or clamped together with tissue
wound closure and recovery may help to
or towel forceps, two elliptical incisions
reduce swelling. Warm compresses applied to
approximately 5 mm behind the lid margins
the orbit during the days following surgery can
are joined near the medial and lateral canthi.
also help to reduce swelling.
Deep dissection will identify the bulbar con-
Draining fistulas from the orbit can result
junctiva. After transection of the medial and
from incomplete removal of the caruncle at the
lateral canthal ligaments, forward traction of
medial canthus or of the remaining secretory
the eyelids will help with dissection of the con-
tissues (e.g., conjunctival goblet cells and third
junctiva, until the sclera is encountered at the
eyelid gland) within the orbit. Postoperative
limbus. Further dissection, globe removal, and
orbital infection is a rare complication. In
wound closure are the same as for the subcon-
brachycephalic breeds, orbital emphysema
junctival approach. The globe, conjunctival
may also be a complication of enucleation.
sac, nictitans, and lid margins are removed
“en bloc.”
Exenteration
Lateral Enucleation Technique
After the lateral canthotomy, a lateral-­to-­ Exenteration involves removal of the conjunc-
medial blunt cleavage of the outer layers of the tiva, periorbita, extraocular muscles, and globe
eyelids from the palpebral conjunctiva is (all of the orbital contents). In case of an orbital
236 Canine Orbit: Disease and Surgery

tumor, exenteration may be extended to involve neoplasia or infection in the orbit, or extraorbi-
all orbital contents, including the periosteum. tal sources of a systemic bacteremia.
A transpalpebral approach is used, in which
the eyelids are sutured together in a continu-
ous pattern. An incision is made around the
Evisceration and Implantation
palpebral fissure and approximately 5 mm
of Intrascleral
from the lid margins. Dissection is then
(Intraocular) Prostheses
advanced caudally through the orbicularis
oculi and orbital fascia toward the orbital rim, Blind and painful eyes of an approximately
involving all extraocular muscles, the globe, normal size, without septic endophthalmitis or
conjunctiva, nictitating membrane, and lacri- intraocular neoplasia, are candidates for evis-
mal gland. If necessary, the remaining orbital ceration and implantation of a silicone pros-
connective tissues and fat can be excised. thesis. A blind eye with early phthisis bulbi can
Closure of the subcutis and skin is routine, as be fitted with an intrascleral prosthesis to pre-
described for enucleation. vent further globe shrinkage and secondary
The orbital depression is more marked fol- adnexal problems. Evisceration involves
lowing exenteration than following enuclea- replacing the intraocular contents with an
tion because of the entire loss of orbital tissues. appropriately sized silicone sphere, leaving
As a result, Prolene or Dacron mesh can be only the fibrous tunic. The diameter of the sili-
anchored to the orbital rim to avoid an cone sphere should equal the horizontal diam-
unsightly depression. eter of the opposite healthy cornea, or be
1–2 mm larger.
Animals are premedicated with systemic flu-
Orbital Prosthesis
nixin meglumine and antibiotics. After the lat-
To improve the cosmetic appearance of enu- eral canthotomy is performed, a 5–8 mm, 120°,
cleation or exenteration surgery, silicone or limbal-­based flap of bulbar conjunctiva and
methyl methacrylate spheres may be Tenon’s capsule or, alternatively, a fornix-­based
implanted. This reduces the depression of skin flap of equal size is then prepared. The sclera is
over the anterior orbit, commonly seen after incised parallel to and 5 mm behind the limbus
enucleation surgery. Silicone spheres are most with a #64 Beaver blade over a length of
commonly used today by veterinary ophthal- 2–3 mm. A cyclodialysis spatula is then
mologists. The size of the implant is selected inserted between the uvea and sclera and care-
according to the size of the orbital space to be fully advanced into the anterior chamber. The
filled; the diameters in dogs vary between 12 scleral incision is enlarged with scissors to a
and 28 mm. These implants are placed into the length 1–2 mm larger than the diameter of the
orbit after hemostasis has been achieved. To prosthesis, and the uveal tract is then grasped
improve the cosmetic appearance and avoid with forceps and removed in one piece by slow,
rotation of the implant, the anterior quarter of gentle, continuous traction. The lens, vitreous,
the sphere is removed using scalpel. and retina are also removed. The premeasured
Postoperative care is the same as for enuclea- prosthesis is inserted into the globe using a
tion and exenteration. Possible complications special sphere introducer. The scleral incision
include (i) traumatic dislocation and rotation and limbal-­based conjunctival flap apposed.
of the implant; (ii) orbital seroma formation; The canthotomy is closed with 4-­0 nonabsorb-
and (iii) infection. The latter can result in able suture material. Because of the large lim-
wound dehiscence and extrusion of the bal incision, the cornea is protected for several
implant. Contraindications to the placement days postoperatively by a temporary complete
of an orbital prosthesis include the presence of tarsorrhaphy.
­Surgery of the Globe and Orbi  237

Complications, including regrowth of uni- anterior to the equator of the globe. (ii) Lateral
dentified intraocular neoplasms, scleral wound approach, with or without transection of the
dehiscence, and postoperative intrascleral lateral orbital ligament. If deep orbital struc-
infections, have been reported to occur in 10% tures such as the zygomatic salivary gland
of cases. Corneal erosions and septic keratitis must be accessed, a portion of the zygomatic
were identified as the most common postoper- arch can be removed with a rongeur. (iii)
ative complications in 9/20 patients in a recent Lateral orbitotomy with resection of the zygo-
retrospective study. This same method may be matic arch as required for removal of localized
used to salvage globes with corneal lacerations. orbital neoplasms resulting in adequate access
The cosmetic results are usually acceptable to the ventral and caudal aspects of the orbit.
(Figure 5.12a and b). In a retrospective study, This technique can retain both the globe and
most clients were satisfied with the result. vision. (iv) A modification of this technique,
the orbital ligament is transected and the
zygomatic arch deflected ventrally after oste-
Extrascleral Prosthesis otomy. Extensive tissue dissection of the tem-
Extrascleral prostheses are more commonly used poral muscle is prevented, thus decreasing
in horses than in small animals. Such devices are closure time and sparing and safeguarding the
acrylic or porcelain shells designed to fit into the dorsal buccal branch of the facial nerve.
conjunctival sac and cover a noninfected blind This last modified lateral orbitotomy cur-
and phthisical eye, an orbital implant, or an rently seems to be the most widely used tech-
empty socket. Species-­related problems are with nique to gain access to the orbit. Possible
hygiene and potential self-­trauma. complications of orbitotomies include hemor-
rhage, transient lagophthalmos, postoperative
swelling and infection, enophthalmos, and
Orbitotomy strabismus.

Exploratory orbitotomy is indicated to evalu-


Orbitectomy
ate and biopsy space-­occupying lesions.
Several approaches to the orbit are possible, In cases with local extraorbital tumor exten-
depending on the localization of the lesion, sion and/or bone involvement, and extensive
and include the following: (i) Transconjunctival and aggressive tumor resection, partial or
approach, which provides access to lesions total orbitectomy may be indicated. These are

(a) (b)

Figure 5.12 (a) Dog with intrascleral prostheses in both eyes. (b) Close-­up of right eye showing mild
corneal neovascularization, pigmentation, and fibrosis of the cornea.
238 Canine Orbit: Disease and Surgery

invasive surgical procedures that involve maxillary bone including last molar(s), zygo-
opening of the (para)nasal sinuses, calvar- matic arch, etc.). When partial orbitectomy is
ium, and/or oral cavity, up to complete resec- performed, the globe is sacrificed if a neoplas-
tion of the orbit, including its osseous tic process involves the globe or structures
delineation (orbital rim, frontal bone, that are critical to globe survival.
239

Canine Eyelids: Disease and Surgery


Revised from 6th edition of Veterinary Ophthalmology, Chapter 14: Diseases and Surgery of the Canine Eyelids, by Frans C. Stades and
Alexandra Van der Woerdt

­Introduction mucosa connecting to the corneal limbus and


allowing movements of the globe behind
Diseases of the eyelids of the dog represent the lids.
another large clinical population that will con- Eyelid diseases can be divided into
front the veterinarian. With nearly 250 differ- co­ngenital–developmental and hereditary,
ent canine breeds, the size and shape of these trauma, inflammatory, immune-­mediated and
dogs’ heads can predispose to certain eyelid others, and neoplastic disorders. Clinical
diseases. In contrast to other ophthalmic struc- m­anagement of most of the eyelid diseases,
tures, diseases of the canine eyelids are treated except for the inflammatory and immune
frequently with one or more of about 30 differ- mediated types, is mostly surgical. The selec-
ent types of surgeries. Some of these surgeries tion of the surgical technique for a particular
can be performed by the general and small ani- condition may be influenced not only by the
mal practitioners, but others require the exper- most effective procedure, but also by the expe-
tise and advanced training by veterinary rience of the surgeon, and other factors. In this
ophthalmologists. The main goals of eyelid chapter, the eyelid diseases and surgeries of
surgery are to provide continued protection of the dog are presented; fundamental eyelid sur-
the eye, relieve or prevent pain, and restore gical techniques are emphasized.
cosmesis as much as possible.
The primary function of the eyelids is the
protection of the globe; they cover the orbit ­Structure and Function
and globe, and surround the palpebral fissure
through which the globe contacts the environ- The eyelids are composed of outer skin, inner
ment. It is normal for the lateral limbus and palpebral conjunctiva, and collagen, muscle,
sclera to be exposed in the dog, and when the and glandular tissue (Figure 6.1). They are
globe is deviated laterally, the medial sclera is divided into the larger, 2–5 mm longer, and
seen. The hairless margins of the eyelids more mobile dorsal, superior, or upper eye-
should be well aligned to the curvature of the lid; and the ventral, inferior, or lower eyelid.
cornea and should move smoothly across the The circular muscle surrounding the
globe. The inside of the lids is lined by very pa­lpebral fissure is the orbicularis oculi
loose (except the area over the meibomian m­uscle. The eyelids do not close by circular
glands–tarsal plate) palpebral conjunctival c­ontraction, but because of the subcutaneous

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
240 Canine Eyelids: Disease and Surgery

tear surplus to the lacrimal puncta. The levator


palpebrae muscle (innervated by the oculomo-
tor nerve), levator anguli oculi medialis muscle
(Müller’s muscle), and other superficial facial
8 muscles help open the upper eyelid and the
9 5 malaris muscle opens the lower eyelid
1
(Figure 6.2) to maintain the precorneal or pre-
ocular tear film.

2 3
Skin and Cilia
The eyelids are thin pliable skin, enabling
blinking and following the corneal surface
smoothly. Fine and short hairs normally cover
the eyelid skin. The transition of the “eyelash”
6 hairs and regular hairs in the upper lid begins
4 about 1 mm away from the free lid margin. In
the lower lid, hairs start about 2 mm away from
7
the free margin. This transition is important as
it represents the site to position the eyelid
Figure 6.1 Cross section through the canine lid: sutures to rotate outward the lid margin (as to
(1) eyelash-­like hair on the lateral part of the correct entropion). Cilia or eyelashes occur pri-
upper lid; (2) Zeis/Moll glands; (3) meibomian marily on the lateral part of the upper eyelid,
gland; (4) mucus cells conjunctiva; (5) fornix; usually in two or four irregular rows. These
(6) scleral conjunctiva; (7) nictitating
membrane gland; (8) orbicularis oculi muscle; cilia are usually the same color as the adjacent
and (9) tarsal plate. eyelid hair coat. Long tactile hairs (pili supraor­
bitales or vibrissae) appear as a tuft along the
dorsomedial orbital margin.
tissues and a ligament in the medial canthus
attached to the nasal bones and the retractor
anguli lateralis muscle plus a lateral palpe-
bral ligament at the lateral canthus, it nar- 6
rows to a horizontal slit. The lateral ligament 5
may contribute to eyelid distortion, particu-
larly in mesocephalic breeds. The average
length of the palpebral fissure when stretched 2
3
by calipers is approximately 33 mm in most
medium to large breeds of dogs. In breeds
with distinct lack of contact of the lower lid
to the globe, the palpebral fissure length 1
4
measures often <39 mm.
With its base anchored at the medial can-
thus, the orbicularis oculi muscle enables the Figure 6.2 Muscles of the lids of the left eye of
closing phase of blinking, a movement in the dog: (1) orbicular oculi muscle; (2) lateral
palpebral ligament or retractor anguli oculi lateralis;
which the upper eyelid plays the most impor-
(3) medial palpebral ligament; (4) malaris muscle;
tant part. During closure, there is a lateral-­to-­ (5) levator palpebrae muscle; and (6) levator anguli
medial zipper-­like movement, bringing the oculi medialis muscle.
­Structure and Functio  241

Eyelid Margin muscle, but contributes to lateral canthal


instability and eyelid abnormalities in medium
The free margins (margo intermarginales) of
and large breeds of dogs.
the eyelids are generally pigmented (usually
nonpigmented if the skin around the eye is
nonpigmented, e.g., in the area of a white spot Lid Sensation and Innervation
around the eye), and they are hairless.
The main sensation of the canine eyelids is
Furthermore, the margins are smooth, glossy,
provided by several branches of the trigeminal
and fatty, but dry. Thirty to forty orifices of the
(V) nerve. Sensation of the lateral two-­thirds of
meibomian glands open into the posterior free
the upper eyelids is provided by the ophthal-
lid margin in a fine groove, also named the
mic branch of the trigeminal nerve. The sensa-
“gray line,” an important surgical landmark
tion for the entire lower eyelid is provided by
used to appose the lid margins.
the maxillary division of the trigeminal nerve.
Below the palpebral conjunctival surface
The palpebral branch of the facial (VII) nerve
starting at the eyelid margin, the meibomian
innervates the majority of the muscles (e.g.,
glands are visible, below the palpebral con-
orbicularis oculi) that control the palpebral fis-
junctiva, as 3–4 mm long, whitish yellow lines
sure size, except for the levator palpebral supe­
running perpendicular to the margin. Just out-
rioris muscle, which is innervated by the
side the groove are the even smaller orifices of
oculomotor (III) cranial nerve. The levator
the glands of Zeis and Moll (modified sweat
anguli oculi medialis is under sympathetic con-
glands). The oily material secreted by these
trol. Loss of sympathetic innervation results in
glands coats the margin of the lid with a lipid
ptosis of the medial upper lid.
layer, preventing the tear fluid from flowing
across it and forms the outer lipid component
of the precorneal film. Meibometers have Blood Supply
become available to measure the delivery rate and Lymphatic Drainage
of lipids on the lid margin, but their usefulness
The blood supply to the eyelids primarily origi-
in dogs is still under investigation. The tarsal
nates from the medial and lateral palpebral
layer in humans consists of a distinct cartilagi-
arteries. Additional blood supply to the lateral
nous plate that provides internal support for
canthus and upper and lower eyelids is derived
the eyelids, but in dogs this tarsal plate consists
from branches from the external ethmoidal
of a thinner and more flexible fibrous tarsus
artery. The medial aspects of the canine eyelids
resulting in a less rigid lid structure.
are also supplied by branches of the malaris
artery, a branch of the infraorbital artery,
which anastomose with the inferior palpebral
Canthus
and transverse facial arteries and branches of
Both canthi are composed of the lid margins the external ophthalmic artery. Limited blood
converging together in the medial canthus, supply to the eyelids originates from the deeper
leaving 3–5 mm of skin, which continues into orbital blood vessels. The extensive blood sup-
the conjunctiva in a minor eminence at the ply to the eyelids provides nearly absolute pro-
base of the nictitating membrane, called tection and eliminates the need for surgical
the “lacrimal caruncle.” The hair growth removal after traumatic injuries.
from the area is short and soft; excessive hair The lymphatic drainage from the eyelids
length promotes “wicking” and escape of tears converges at both the medial and lateral can-
onto the medial canthal surface. The lateral thal areas. Lymphatic drainage is mainly to the
canthal ligament is relatively weak. It is sup- parotid lymph node. Some of the same areas
plemented by the retractor anguli lateralis also drain to the mandibular lymph nodes.
242 Canine Eyelids: Disease and Surgery

­Diagnostics for Eyelids Preparation of the Operative Field


The lid skin is usually shaved or clipped by very
There are several tests that can evaluate the small hair clippers. The last row of eyelash
eyelids and their functions (Box 6.1). These hairs may be cut by scissors with some oint-
diagnostics are used in the preoperative evalua- ment on the blades so that the cut hairs will
tion, ophthalmic exam, and in the neuro-­ stick to the ointment. Afterward, the conjuncti-
ophthalmologic evaluations. In the preoperative val sac and the skin are washed copiously with
evaluations before the different entropion, hand-­warm saline. Diluted baby shampoo
ectropion, and other lid deformities, the divi- (1 part diluted with 20 parts water) can be used
sion of the real lid deformity from the addi- to clean the eyelids. The preferred method pre-
tional effects of pain is critical to prevent the pares the eyelid surface with 1:50 aqueous povi-
overcorrection of the lid defect. done–iodine solution, which is not toxic if
corneoconjunctival contact occurs. If the stand-
ard alcohol-­based surgical povidone–iodine
­Principles of Lid Surgery solution is used, the solution should not con-
tact the conjunctival sac or the other eye.
Anesthesia
Positioning
In general, sedation and local anesthesia are
insufficient for lid surgery, especially because For lid surgery, the palpebral fissure has to be
there should be sufficient muscle relaxation positioned more or less horizontally and the
for the correct estimation of, e.g., the lid fissure medial canthus lower than the forehead. The
length, the amount of tissue to be removed, or positioning of the head is best carried out by
the amount of correction necessary. using a vacuum pillow. In lid surgery, the

Box 6.1 Diagnostic Tests for the Eyelids


●● Use of some magnification (2–10×) and a spot or slit illumination
●● Palpebral or blink reflex: touch different areas of both eyelids and canthi and expect a rapid
and rigorous blink. Use either a wisp of cotton or esthesiometer. Cranial nerves tested include
afferent path (trigeminal nerve of either cornea or lid surface) and efferent path (abducens
nerve and facial nerve)
●● Corneal reflex: touch different areas of the cornea and expect a rapid and rigorous blink. Use
either a wisp of cotton or esthesiometer. Cranial nerves tested include afferent path (trigem-
inal nerve of cornea surface) and efferent path (abducens nerve and facial nerve). Different
areas of the cornea have different sensitivities
●● To differentiate entropion into its structural and secondary pain components, measure the
total entropion, and then instill topical anesthetic
●● Dazzle reflex: a subcortical reflex with pathways including afferent (retinal and optic nerves,
and subcortical brain) and efferent (facial nerve). Use a bright focal light directed at the eye;
a rigorous blink or rapid blink should occur
●● Topical fluorescein and/or rose Bengal instilled on the cornea to evaluate the corneal sur-
face in contact with entropion, distichia, or ectopic cilia. These stains can indicate epithelial
damage from the trichiasis
●● Consider neurotropic and neuroparalytic keratitis in any diagnosis
­Principles of Lid Surger  243

surgeon works in a sitting position, at the ven- soft suture material such as silk is advised, but
tral side of the head, with the hands resting, should be removed in 7–10 days. If strength is
as much as possible, on the animal’s head, or important, 5-­0 or 6-­0 monofilament nylon can
special adjustable arms on the surgeon’s chair, be used. For difficult-­to-­handle animals,
thus reducing the risk of uncontrolled absorbable material, such as polyglactin 910 or
movements. polyglycol acid, can be used, eliminating the
need for suture removal.
Draping
Suturing
Special ocular drapes with an opening for the
eye, or disposable drapes with a pre-­existing Wound edges must be closed very precisely.
hole or a hole cut during surgery, are used. The Suture ends are left long to allow easy removal
drapes may be fixed by towel clamps. Any trac- and thus hang downward, or else they are gath-
tion of these drapes during surgery should be ered together in the upper lid or canthi
avoided. (Figure 6.3); short ends may “brush-­irritate” the
cornea. If wounds are unequal in length (e.g., in
Celsus–Hotz or Stades procedures), the longer
Magnification and Illumination
wound edge has to be “smuggled” away over the
Magnification (3–5×) is sufficient in most sur- total, thus preventing folding on either side of
geries. Powerful, well-­focused operating lights, the wound. Special attention is necessary to
a head-­mounted light, or operating microscope appose the edges of eyelid margin defects.
lights are essential.
Hemostasis
Surgical Instruments
Hemostasis is usually achieved by direct pres-
The ophthalmic instruments for eyelid surgery sure. Excessive hemorrhage can also be
are not numerous, and may include the Kalt, stopped by (bipolar) electrocoagulation. For
Arruga, strong modified (teeth shortened to hemorrhages of very fine vessels, special oph-
0.3 mm) Castroviejo’s forceps, calipers, oph- thalmic (battery) disposable microcautery
thalmic needle holder, eye scissors for sutures, units are available. Cautery of vessels will
and chalazion or eyelid clamps. A source of cause a local area of necrosis, and for this rea-
cautery (Perma Tweez electroepilator™; most son, cauterization should not be done too
small animal cautery units result in excessive quickly or excessively. Good hemostasis should
cauterization) and cryotherapy are also useful. be achieved to prevent excessive lid swelling
Cutting using a pointed scalpel blade from the and distortions before the final closure of the
inside to the outside provides a more precise wound, or a small drain must be placed, espe-
incision; however, cutting by scissors causes cially following extensive blepharoplasties.
crushing of the tissues and nonperpendicular
incisions edges.
Cryosurgery
In cryosurgery, the destructive effect of freezing
Suture Material
the intracellular water ruptures the cell mem-
For eye (lid) surgery, atraumatic suture needles brane in unwanted tissues. In general, two
are always used. For lid skin, 10–16 mm, cycles of rapid freezing and slow, spontaneous
3/8–1/2 circle, extra-­sharp-­pointed round, thawing are used. The tissues are frozen to at
micropointed, or extra-­fine-­cutting needles are least −25 °C by the use of carbon dioxide or
used. To avoid any corneal contact and injury, nitrous oxide. Cryosurgery is used for the
244 Canine Eyelids: Disease and Surgery

Figure 6.3 The ends of upper lid or lateral


canthus sutures can be caught or linked
together in an outer-­placed suture to
prevent irritation of the cornea.

destruction of hair follicles (as in distichia), the may be the earliest indication of the later sepa-
destruction of reactive granulation, or several ration. This period of natural ankyloblepharon
types of neoplasia (especially in large animals). is required in the dog because of the relative
The main advantage of cryosurgery is the rela- immaturity of the ocular and adnexal tissues at
tive simplicity and repeatability of the method. parturition. The bridge of tissue in the palpe-
Potential disadvantages are severe postoperative bral fissure between the already developed
swelling; depigmentation, which may be per- margins of the eyelid normally regresses at
manent; and the unwanted loss of normal tissue. 10–14 days postpartum. Premature opening of
the palpebral fissure is usually accompanied
by exposure keratoconjunctivitis and severe
Postoperative Care
corneal ulceration; globe perforation and
During recovery from general anesthesia or u­veitis are possible complications. In such
later during uncontrolled moments, the patient cases, wetting ointments or gels must be used
may loosen or lose stitches, or worse, tissues. to protect the ocular surfaces. On occasion,
Routine use of an Elizabethan or E-­collar may temporary tarsorrhaphy with long and adjust-
prevent such complications; these collars able sutures may be necessary, particularly if
should be long enough to prevent dogs from the palpebral fissure opens within the first few
rubbing the surgical sites on the rugs or the days postpartum.
floor, and should be in place as long as lid
swelling and sutures are present. Ankyloblepharon: Pathological
Ankyloblepharon is delayed or complete failure
of opening of the palpebral fissure. The anom-
­ ongenital and Presumed
C aly occurs infrequently and is usually bilateral.
Heredity Conjunctivitis or ophthalmia neonatorum
must be considered in the differential diagno-
Structural Abnormalities
sis, but in this condition, the closed eyelids will
bulge as a result of the inflammatory exudate
Ankyloblepharon: Physiological
that accumulates behind the adhered eyelids.
The canine palpebral fissure is sealed at birth. This often staphylococcal keratoconjunctivitis
A pinhole-­sized patency at the medial canthus may result from an intrauterine infection or
­Congenital and Presumed Heredity Structural Abnormalitie  245

from the dam’s genital tract during partum. cataract, retinal dysplasia, and optic nerve head
The bacteria enter the conjunctival sac, pre- colobomata.
sumably via the patent opening in the medial
canthus (the nasolacrimal apparatus) resulting
Dermoids and Dysplasia Palpebrae
in a bead of purulent material at the medial
canthus and the bulging lids (Figure 6.4). The Dermoids or choristomas of the lids are ectopic
lid fissure should be carefully opened without and abnormally developed islands of skin in or
delay; otherwise, the lacrimal gland, cornea, at the margin of the eyelid, frequently associ-
and even the whole globe can be irreversibly ated with some dysplastic deformities of the
damaged. The prognosis is usually favorable. adjacent conjunctiva. They are rare, possibly
There are no known means of preventing this hereditary, anomalies, usually of the lower lid
condition. near the lateral canthus. Genetic predisposition
exists in the German Shepherd, Dalmatian, and
Saint Bernard, with the latter breed demonstrat-
Eyelid Aplasia or Coloboma
ing a familial relationship between lower eyelid
In aplasia palpebrae or lid agenesis, the lid coloboma and dermoid formation. An island or
margin and the lid itself are completely or fold of skin often disrupts the lid margin and is
partly undeveloped. This rare anomaly is con- continuous with the conjunctiva. Blinking is
genital, possibly hereditary, usually bilateral, abnormal, and long coarse hairs generally grow
and in the canine affecting the lateral part of toward the cornea, causing chronic irritation
the lower eyelid; the condition is not infrequent and resulting in edema, neovascularization, and
in cats. Aplasia palpebrae is often associated pigmentation. Treatment consists of removal of
with other congenital anomalies such as micro- the abnormal parts of the eyelid and conjunc-
phthalmia, persistent pupillary membrane, tiva (especially the hair follicles).

Figure 6.4 Pathological


ankyloblepharon. Delayed eyelid
opening in a puppy has resulted in
ophthalmic neonatorum with
purulent exudate from the medial
canthus.
246 Canine Eyelids: Disease and Surgery

­Distichiasis
and Conjunctival
Ectopic Cilia

Distichiasis refers to single or multiple hairs


arising from the free lid margin. They usually
arise singly or with two or more hairs from the 2
meibomian duct openings (Figure 6.5). In
ectopic cilia, the follicle is located 4–6 mm
behind the margin of the upper lid in the pos-
terior distal tarsal plate, in or near the base of
the meibomian glands. Most ectopic cilia affect 1
the central upper eyelid. Meibomian glands
are modified hair follicles, and distichia can
develop from undifferentiated gland tissue.
In dogs affected with soft distichia, directed
away from the cornea, the condition appears to
have limited clinical significance. However, 4
3
stiff hairs that rub the cornea can irritate and
cause injury. Irritation leads to increased lacri- Figure 6.5 Distichiasis (hairs in or on the lid
margin) emerging from the meibomian (1), Zeis, or
mation, blepharospasm, and epiphora. In more
Moll (2) gland openings; (3) tear film; and
severe cases, corneal pigmentation, neovascu- (4) cornea.
larization, and even ulceration can result.
Primary or secondary (from pain) entropion
oxide) specific probes produce a −25 °C freeze,
may be present, and distichia may cause severe
which can destroy the follicles but spare the
irritation, resulting in a vicious circle.
adjacent eyelid tissue. Because temperatures
below −30 °C will easily produce necrosis and
Treatment of Distichiasis
eyelid distortion, the use of thermocouple nee-
The simplest treatment is manual epilation dles may ensure that tissue temperature does
by rounded-­tip epilation forceps at regular not fall below −25 °C. The immediate postop-
intervals (four to five weeks). The advantages erative effect is considerable swelling of the
of this method are that it determines the irri- cryosurgery site, sometimes so much that
tation is caused by the hairs, it needs no gen- blinking is impaired. As a result, preoperative
eral anesthesia, and if there are only a few systemic nonsteroidals or postoperative topical
hairs, it can also be performed by skillful treatment with corticosteroid–antibiotic eye
owners themselves. ointment is helpful. The swelling usually lasts
For permanent treatment, the distichia hair no more than two to four days. Depigmentation
follicle is destructed, removed, or redirected of the frozen areas occurs within 72 h.
(Table 6.1) and the eyelid margin remains Repigmentation usually takes up to six months
intact. Cryosurgery is the most popular tech- to complete. Permanent depigmentation, scar-
nique and it is performed through the conjunc- ring, and distortion are possible complications.
tival surface directly over the follicle, 3–4 mm
behind the free margin of the lid. The lid mar-
Ectopic Cilia
gin is stabilized and everted, using a Von Graefe
forceps or Desmarres eyelid clamp (Figure 6.6). Dogs with distichiasis are also predisposed to
A double freeze–thaw cycle using (nitrous having ectopic cilia. The cilia emerge through
­Distichiasis and Conjunctival Ectopic Cili  247

Table 6.1 Methods to treat distichiasis in the dog.

Method Indications/results

Mechanical epilation For few distichia; regrowth common (four to seven weeks). Can be
used to confirm diagnosis
Celsus–Hotz resection Produces mild ectropion and rotates the distichia from the
conjunctival and/or corneal surface(s). Used when the entire eyelid
is affected
Electrolysis Limited to few distichia
Diathermy/electrocautery Limited to few distichia
Eyelid splits More difficult/for few distichia/use partial thickness technique
Partial resection of the distal More difficult/for few distichia
tarsal plate
Transpalpebral conjunctival More difficult/for few distichia
dissection
Cryotherapy More swelling post freezing; lid margin depigmentation
usually temporary. Because of its repeatability, has become most
popular

(a) (b)

Figure 6.6. (a) Cryodestruction of multiple distichiae in the conjunctiva–tarsal plate in a dog (b) Lid
margin damage after distichiasis hair removal with excessive energy from electrocautery.

the dorsal palpebral conjunctiva and impinge everted to detect these cilia). Predisposed
directly on the cornea, causing severe corneal breeds are Flat-­Coated Retriever, Pekingese,
irritation. They are usually pigmented in the Shih Tzu, Cavalier King Charles Spaniel,
same color as the rest of the hairs of the dog Boxer, English Bulldog, Poodle, and Jack
and located in a small, pigmented spot of mid Russell Terrier. The condition is usually in the
dorsal conjunctiva several mm posterior to young dog, accompanied by acute, intense
the eyelid margin (the upper lid must be blepharospasm and lacrimation, and may
248 Canine Eyelids: Disease and Surgery

resemble a foreign body. It easily results in a Table 6.2 Site of entropion in selected breeds.
superficial, rounded (no scratch) corneal
defect, without undermined edges, and is Position of
accompanied by vessels. entropion Breeds affected

Entire lower lid Chow Chow, Shar Pei,


Therapy (lid often shorter) Bouvier des Flandres,
The lid is everted by Von Graefe’s forceps, a Rottweiler
chalazion, or an eyelid clamp. From the palpe- Lateral 3/4 lower Hunting breeds; German
bral conjunctival surface, the assumed follicle lid Pointer, Labrador Retriever,
area is excised “en bloc” by scalpel, dermal Golden Retriever
biopsy punch, or destroyed by cryosurgery. Lateral 1/2 lower Great Dane, Saint Bernard,
Aftercare consists of topical antibiotic oint- lid and lateral Leonberger
canthus (lid may
ment four times daily for seven days. be too long)
Upper lid Bloodhound, Chow Chow,
Shar Pei, and older English
­Entropion Cocker Spaniel and Basset
Hound
Entropion is the inversion of all or part of the Medial lower lid Toy and Miniature Poodle,
margin of the eyelid such that the outer skin Pekingese, Pug, Shih Tzu,
English Bulldog, and Cavalier
contacts the conjunctival or corneal surface, or King Charles Spaniel
both, and is the most frequent eyelid abnor-
mality in the dog. Entropion may be lateral,
medial, angular, or total, and may affect the the looseness of the circumorbital skin, the
lower or upper lid, or both. Entropion can be presence of loose facial folds, and the long and
divided into categories: primary, such as con- heavy ears contribute to upper lid distortion.
genital or developmental entropion, and sec- Not all patients with entropion require sur-
ondary or acquired, such as spastic and gical correction. Entropion may be secondary
cicatricial entropion. Entropion is influenced as a result of severe (corneal) pain, such as
by multiple conditions such as the length of that occurs in primary corneal ulceration. It
the lid fissure, conformation of the skull, the can also be secondary to a loss of lid support
orbital anatomy, gender, and the extensiveness (e.g., in microphthalmos, phthisis bulbi, ret-
of folds of the facial skin around the eyes. robulbar fat resorption, or muscle atrophy
secondary to chronic myositis). However, in
rare cases, conjunctival and skin scarring
Epidemiology
(caused by wounds or surgery) may cause
Primary, congenital, or developmental entro- traction to the lid margin and cause second-
pion is the most common lid disease in pure- ary cicatricial entropion, trichiasis, or both,
bred dogs. In most cases, it is because of a and require surgery.
hereditary defect, but the genetic basis is not
well understood. In many breeds of dogs, the
Clinical Signs
entropion has been demonstrated to affect spe-
cific areas of the eyelids (Table 6.2). Severe The inverted position of the lid margin against
entropion of the entire lower lid often results in the palpebral conjunctiva of the nictitating
surgical correction, especially with secondary membrane and the bulbar conjunctiva and
corneal ulceration, neovascularization, and cornea results in irritation, excessive lacrima-
pigmentation develop. In certain breeds, entro- tion, mucopurulent discharge, conjunctival
pion is complicated further by the presence of hyperemia, and blepharospasm. Signs of
­Entropio  249

chronic irritation of the cornea include edema, Therapy


neovascularization, granulation, pigmenta-
In mild entropion, the cornea may be protected
tion, and even ulceration. Injury of the corneal
by a topical lubricant. It is usually best to post-
surface in the area of the trichiasis from the
pone surgical correction until the head has
entropion can be demonstrated with faint topi-
grown to full size (1.5–2 years of age). However,
cal fluorescein and/or rose Bengal retention.
if there are signs of distinct conjunctival or
Because of the trigeminal irritation, the patient
corneal irritation, surgical intervention is indi-
will be in constant pain, resulting in excessive
cated, but may need repeating when the ani-
lacrimation, enophthalmos, a loss of support
mal reaches maturity.
of the lid margin, and subsequently a further
increase of the entropion.
Tacking Lids or Stay Sutures
In puppies (mainly Shar Pei and Chow Chow)
less than 12 weeks old (when the general anes-
Diagnosis
thesia risk is relatively high) with severe entro-
Diagnosis is based on clinical signs, history, and pion, temporary retraction sutures (Figure 6.7)
breed. The patient should be observed without can be placed to gather up the skin of the lid
restraint to determine the degree of entropion. and thereby evert the lid, thus preventing cor-
After the evaluation has been done at a dis- neal lesions. Alternative staple or skin-­crushing
tance, during closer examination, the animal methods are considered unpredictable, irritat-
should not be held too tightly by the nape of the ing, and animal-­unfriendly methods. Usually
neck because the traction on the skin may evert two to four, 4-­0 to 5-­0 nonabsorbable tacking
the entropion. In dogs with single or multiple sutures are placed adjacent to the involved lid
skin folds and/or long and heavy ears, elevating margin. Simple, interrupted (needle direction:
these areas can influence the extent of the away from the cornea, thus less risk for corneal
entropion and suggest more extensive surgery. trauma) mattress sutures or interrupted, verti-
Instillation of topical anesthetics is another cal mattress sutures are placed in the lower and
diagnostic method to differentiate the struc- less frequently in the upper eyelids. The “bites”
tural component from the secondary spastic or are about 5 mm long to ensure adequate retrac-
pain contribution of the entropion. tion and tissue holding occur. Often, the sutures

(b)
(a)

Figure 6.7 Entropion correction by retraction sutures (tacking). The sutures can be maintained for at least
two to three weeks. The scar tissue “tube” formed around the suture material may result in moderate
permanent correction. (a) Simple, interrupted sutures. (b) U-­figure suture, with the disadvantage that the
needle points in the direction of the cornea during suturing.
250 Canine Eyelids: Disease and Surgery

are left long to permit multiple adjustments. Table 6.3 Surgical procedures for canine
When the sutures are removed (two to four entropion.
weeks) or lost, the surrounding “scar tunnel”
will remain, thus still causing correcting trac- Surgical
procedure Type of entropion treated
tion on the lid margin. In some cases, the entro-
pion will not require further correction. Eyelid Puppy entropion; holds lid open
Persistent entropion requires additional “tacking” to avoid conjunctiva and/or
surgery. corneal contact (pain)
Quickert– Puppies; young dogs with lower
Quickert–Rathbun Procedure Rathbun entropion
The Quickert–Rathbun technique can be used Celsus–Hotz Most cases of entropion involving
in dogs for lower lid entropion using fornix-­ lower, upper, medial, and lateral
canthus. Can be easily modified
based sutures. This technique may be an
Wyman For central lower entropion.
alternate procedure to the tacking method in
pedicle Pedicle used with Celsus–Hotz
young puppies (especially those that recur modification
after tacking) or may be employed in older “Y” to “V” Mild central lower entropion
dogs. In this procedure, double-­ended 4-­0 plasty
absorbable suture is positioned from the deep (Wharton–
fornix to exit externally 1–2 mm from the eye- Jones)
lid margin, everting the lid margin and Celsus–Hotz For medial entropion and
entropion. modified secondary epiphora in toy and
small breeds. A variable sized
triangle of skin is excised.
Alternatives: cryotherapy or
Surgical Procedures electrocautery, and secondary
Many methods and variations are available for fibrosis
the correction of the different types of entro- Arrowhead Modified Celsus–Hotz for lateral
canthal entropion. Can be
pion (Table 6.3). Complicated entropion cases,
modified for micro-­and
such as combinations of upper and lower lid macroblepharon
entropion, medial entropion, and combina- Wyman For 1/2 upper entropion and
tions with severe corneal lesions (e.g., ulcer, lateral lower ectropion combined with
corneal pigmentation), require more surgical canthoplasty lateral canthal entropion in large
skills and experience, and are best referred to a and giant breeds. Celsus–Hotz
combined with myopedicle for
veterinary ophthalmologist. new lateral canthus stability
The Celsus–Hotz procedure and its modifi-
Robertson Lateral lower lid and canthal
cations are currently the basic surgical tech- entropion in large and giant
niques for the treatment of most types of breeds. Transection of the lateral
entropion (Figure 6.8), and the most frequently canthal ligament in lower lid
performed entropion surgery worldwide. This Gutbrod– Lateral canthoplasty for lateral
procedure and its modifications provide con- Tietz canthal entropion and
macroblepharon in large and
sistent and beneficial results. Lid procedures in giant breeds. Shortens both
dogs must consider that this species lacks a tar- eyelids
sal plate and a well-­developed lateral canthal
ligament that are present in humans. Often the
presence of enophthalmos can further compli- The Celsus–Hotz procedure and its modifi-
cate the correction of entropion, as eyelid–cor- cations have several characteristics that require
nea contact in the dog seems essential for lid consideration (Box 6.2). Surgical correction
function and shape. should be close to the eyelid margin to achieve
­Entropio  251

(a)
(c)

1 4

3
(d)
5

(b) 5

(e)

Figure 6.8 The Celsus–Hotz procedure for the correction of severe lower lid entropion with corneal
ulceration. (a) The skin is incised at about 2.5 mm (as near as possible to the margin for better prediction of
the entropion correction but with enough space for skin suturing) from and parallel to the lid margin (b).
(c) The skin and orbicularis muscle are excised (not deeper: canaliculus and [sub]conjunctival tissues
should not be damaged). The lid margin should no longer show spontaneous intention of inward rolling.
(d) The skin is sutured with material not exceeding 5-­0 (e.g., nonabsorbable silk or absorbable, especially in
difficult-­to-­handle animals, mono-­or polyfilament), using a fine, round-­body needle with or without a
micropoint. Continuous sutures alone are not used because of the risk of rupture of the suture material
when rubbed, resulting in dehiscence of the entire wound. The first sutures are placed at the medial and
lateral ends, and the rest of the wound is closed by halving the intervals in the following order: 1, 2, 3, 4,
and so on. The distance between sutures is 2–2.5 mm. Alternatively, the intervals of the simple interrupted
sutures can be made at about 4 mm and thereafter the remaining wound intervals closed by a continuous
suture. (e) Secondary upper eyelid trichiasis to the lower, caused by postoperative lower lid conjunctival
swelling, can be prevented by tacking of the upper lid (5).

the outer rotation of the eyelid margin so that than anticipated. Overcorrection may cause
the squamous transition of the outer lid mar- ectropion, which may result in additional sur-
gin ceases to contact the cornea. This remain- gery. To estimate the size of the surgical wound
ing strip of eyelid margin must be wide enough (and amount of correction of the entropion), a
to accommodate the sutures that secure appo- simple rule-­of-­thumb technique is performed
sition of the surgical wound. If the first inci- by placing digital pressure on the lid skin adja-
sion is too far from the margin, the lid will not cent to the entropic margin and pulling down
evert sufficiently, and the result will be less until the free lid margin is exposed. The second
252 Canine Eyelids: Disease and Surgery

Box 6.2 Key Components of the Hotz–Celsus Procedure for Entropion in the Dog
●● Slight undercorrection as postoperative wound contraction will further evert the eyelid
margin
●● Initial skin incision parallel to and 2–3 mm from the eyelid margin (just enough for sutures)
●● Section of skin and orbicularis oculi muscle excised approximates entropion defect and can
vary markedly based on the extent of entropion
●● Excision of the section of skin–orbicularis oculi muscle with scissors or scalpel. Partial exci-
sion of the muscle thickness is essential, especially in large and giant breeds (with thick lids).
Do not penetrate the tarsal layer and palpebral conjunctiva
●● Initial suture placement starts in the middle of the wound to ensure accurate coaptation of
the different lengths of the upper and lower skin incisions
●● Anticipate some postoperative lid swelling. Treat topically with antibiotics and corticoster-
oids to “control” swelling. If corneal ulcer is present, avoid topical steroids. To avoid
self-­trauma, maintain Elizabethan collar until all lid sutures are removed (usually 10–12 days
postoperatively)

skin incision is made in an elliptical fashion Continuous sutures are not recommended
joining the two ends of the primary incision. because of the risk of dehiscence of the entire
The skin incision opposite from the lid margin wound when it is rubbed. Placement of the
incision mirrors the amount and shape of the sutures must accommodate the shorter eyelid
desired correction. Hence, some Celsus–Hotz margin wound and the longer distal incision.
procedures have elliptical wounds; others sem- The first sutures are placed at the medial and
ielliptical shape, and even nearly separate cir- lateral ends, and then the rest of the wound is
cles near both canthi. closed by halving. Some postoperative swelling
The part of the skin around which the inci- of the conjunctiva is normal and even desira-
sions have been made is further excised with a ble because it keeps the eyelid margin off the
scalpel or with scissors (“fold” method), cornea, which is often still painful, thus allow-
including a superficial strip of the orbicularis ing the cornea to heal quickly.
muscle (approximately one-­half lid thickness)
so as to avoid perforation of the palpebral con- Other Entropion Surgeries
junctiva. After removal, the remaining lid mar- As indicated in Box 6.3, there are several sur-
gin should conform to the corneal surface and gical techniques to treat the different types of
not tend to invert. Hemorrhage is usually the breed-­related entropion. Each procedure
minor and occurs from both the lateral and has certain advantages and limitations.
medial ends of the incisions. Direct digital Treatment of lateral canthal entropion in
pressure or temporary clamping of the larger large breeds of dogs is complicated by exces-
blood vessels by hemostats (not usually ligated) sive facial skin folds as well as large and
is usually sufficient. heavy ears that distort the palpebral fissures,
The wound is closed with simple interrupted eyelids, and lateral canthi. A relatively unsta-
sutures of material that effectively reappose ble lateral canthus weakened by a poorly
the wound edges and should be 5-­0 or smaller developed lateral canthal ligament and small
(e.g., nonabsorbable silk or absorbable mono-­ retractor anguli lateralis muscle decrease the
or polyfilament), using a fine, round-­body nee- success of the surgeries in this area.
dle with or without a micropoint. The sutures Development of a viable lateral canthal liga-
are placed at intervals of not more than 2 mm. ment using preserved fibrous tissue or the
­Entropio  253

Box 6.3 Surgical Procedures to Reduce Palpebral Fissure Size by Shortening Upper and/or
Lower Eyelids
●● Lateral reduction canthoplasty or lateral full-­thickness permanent tarsorrhaphy
●● Medial reduction canthoplasty
●● Roberts–Jensen pocket technique for medial canthus, best in brachycephalic breeds
●● Modified Roberts–Jensen pocket technique for lateral canthus
●● Modified Fuchs lateral canthoplasty
●● Lateral canthoplasty (Bedford): a modification of the Kühnt–Szymanowski procedure
●● Gutbrod–Tietz procedure: shortens lower lid and lateral canthus
●● Bigelbach procedure: for upper and lower lid shortening, and lateral lower entropion
●● Grussendorf procedure: shortening both upper and lower lids and stabilization (suture) of
lateral canthus
●● Stades (Diabolo procedure): shortens upper and lower lids and lateral canthus

host tissue will be an important step to resting on the dog’s cornea over a distance of
improving surgical corrections in this area. 1–10 mm or more, a funnel or sac is formed in
the lower eyelid. The lids, blink reflex, and
tears cannot perform their normal function of
Ectropion and Oversized Palpebral
cleaning, shielding, and lubricating the eye.
Fissure (Macro-­or Euryblepharon)
The conjunctival sac becomes chronically
Ectropion is an eversion of the lid margin, usu- inflamed as a result of its permanent exposure
ally of the lower eyelid (Figure 6.9), but cicatri- to air, dust, bacteria, and stagnant tears.
cial eversion of the upper lid may be occur Most forms of ectropion and oversized pal-
following trauma and chronic inflammation. pebral fissure are primary or congenital and
In an oversized fissure, the lid margin is dis- breed-­related or presumed hereditary. The
tinctly longer (stretched 5–15 mm) than the breeds of dogs frequently affected with lower
normal 33–35 mm necessary to cover the sclera lid ectropion include the Bloodhound, Saint
in the opened eye. When the lower eyelid is not Bernard, Great Dane, Newfoundland, Mastiff,

Figure 6.9 Pronounced macroblepharon–


ectropion (diamond-­shaped fissure) in a
Bloodhound. The stretched fissure length
was 48 mm. There is also some medial and
lateral entropion and a notch or kink in the
lower lid margin. Note that the lower lid
hangs in the middle about 15 mm away
from the third eyelid–cornea and is not
really everted in an ectropion position. This
results in chronic exposure and secondary
conjunctivitis.
254 Canine Eyelids: Disease and Surgery

and several spaniel and French hunting breeds. Because the medial canthus is relatively fixed
Some owners, dog fanciers, and breeders and more complicated by the presence of the
believe ectropion and oversized palpebral fis- lacrimal ducts and the nictitating membrane,
sure to be normal, and some even encourage most surgical procedures for ectropion and
the “diamond”-­appearing palpebral fissures macroblepharon involve the lateral lower eye-
and the everted lower eyelids (which gives the lid and canthus. In general, the Blaskovic or
dog a “devoted and sad expression”). Excessive similar procedures are used for moderate to
facial skin folds, heavy ears, long eyelids (espe- severe ectropion of the lower lids, and the
cially the lower lid), and unstable lateral can- simple lid fissure reduction permanent tarsor-
thus result in a sagging lower lid and an rhaphy procedures for distinct, oversized pal-
inverted upper and lower lateral canthus. pebral fissures.

Clinical Signs
Ectropion–Macroblepharon
Signs of ectropion or oversized palpebral fis-
Correction Procedures to Shorten
sure are as follows: the lower lid margin is
the Lower Lid Margin
rotated outward (the openings of the meibo-
mian glands are visible in the free margin); the In most instances of ectropion, the lower eye-
fissure is often diamond-­ or pagoda-­shaped; lid margin or both the upper and lower eyelid
and the conjunctiva is red, swollen, and folded, margins are oversized. Methods aimed at
resulting in increased tear and mucus produc- reduction either around the defect in the mar-
tion and purulent exudate. There is a slight gin or at the lateral canthus yield the best
enophthalmos, which increases the distance results. Before surgery, the lid fissure is
between the lid margin and the globe. When stretched and measured by calipers. The fis-
the animal is more active than usual, as at dog sure should be shortened to approximately
shows or on the veterinarian’s examination 33–35 mm. When the lower lid overlength is
table, and whenever it is held tightly by the not excessive, procedures for shortening only
nape of the neck, the ectropion or oversized the lower lid may be sufficient. These proce-
palpebral fissure may almost disappear, but dures effectively shorten the lower eyelid, give
then too much sclera will be visible on the lat- some support of the lateral lower lid by the
eral side. scar tissue between the double layers, and
cause moderate traction laterally.
Therapy
If the defect is slight, no treatment is required
Kühnt–Szymanowski Blaskovic’s
apart from irrigating the eyes upon returning
Modification (Further Modified by
from walks and applying a neutral, lubricating
Fox and Smith): Procedure for
ophthalmic ointment or solution, particularly
Oversized Lower Lid Margin
in young dogs whose heads have not yet
and Ectropion
reached adult size. Surgical correction of ectro-
pion is recommended when chronic or severe In this procedure, the skin incision is made
secondary ophthalmic disease results. Surgery 2–2.5 mm from and parallel to the margin of
should attempt to provide a relatively normal the lid, starting a few mm medial of the worst
lower eyelid length and an adequate apposi- area of ectropion and ending 5–10 mm lateral
tion to the cornea. Overcorrection should be to the lateral canthus and from there down-
avoided. Because in most dogs there is a com- ward (Figure 6.10). The entire skin–orbicular
bination of ectropion and an oversized lid oculi flap is loosened. A wedge-­shaped part of
fissure, the different ectropion surgical proce- the tarsoconjunctiva is excised in the worst
dures primarily shorten and strengthen the lid. area of ectropion. A similarly sized wedge of
­Entropio  255

(a) (c)

(d)
(b)

Figure 6.10 The Kühnt–Szymanowski procedure, modified by Blaskovic and further by Fox and Smith for
ectropion–macroblepharon to avoid splitting the lid margin. Use in the dog was first described by Munger
and Carter. (a and b) The skin incision is 2–2.5 mm below the eyelid margin and extends 5–10 mm beyond
the lateral canthus. The skin flap is dissected from its deeper muscle layers. All bleeding has to be arrested.
(c and d) Equal-­sized wedges, one of lid margin conjunctiva and one of skin, are excised by scissors. The lid
margin is apposed by a figure-­of-­8 or U-­figure 5-­0 to 6-­0 suture. If desired, the conjunctival wound can be
sutured by a subconjunctival, simple, continuous, 8-­0 absorbable suture. The skin defect is apposed by
simple, interrupted, 5-­0 to 6-­0 sutures. Advantage: staggering wound, less damaging to the lid margin.
Disadvantage: shortens only the lower lid.

skin–orbicular oculi is excised laterally, thus trichiasis. In these breeds, the palpebral fissure
shortening the flap. This method shortens the measures some millimeters longer than the
eyelid margin to the desired length and draws average 33 mm, thus easily allowing the globe
it upward and laterally. The double-­layered, to luxate but preventing spontaneous reposi-
staggered wound prevents leakage and wound tioning. Therefore, slight lid shortening com-
dehiscence. bined with a canthoplasty in the medial
canthus is indicated (see also trichiasis of the
medial canthus).
Macroblepharon–Ectropion
Correction, Reducing Lower
and Upper Lid Length Permanent Lateral Palpebral
Fissure Reduction Plasty (Modified
Because the medial canthus is relatively fixed
Roberts–Jensen Pocket Procedure)
and more complicated by the presence of the
lacrimal ducts and the nictitating membrane, The original procedure can be used for both
surgical procedures just to change the size of the medial canthus and the lateral canthus.
the palpebral fissure usually involve the lateral The medial canthal procedure starts with the
canthus. Surgical reduction of the medial can- removal of the medial or lateral upper lid mar-
thus is usually restricted to the smaller breeds, gin and the inside margin plus meibomian
such as the Pekingese and Shih Tzu, with glands, as described in the simple palpebral fis-
medial entropion, nasal folds, and caruncle sure reduction tarsorrhaphy (Figure 6.11).
256 Canine Eyelids: Disease and Surgery

If performed in the medial canthus, the upper


punctum is lost during the procedure. A flap of
upper conjunctiva is pulled downward into the
pocket in the lower lid between the conjunc-
tiva and muscle–skin layers and anchored. The
method is simple, provides a double-­layered,
staggered wound, and prevents leakage and
wound dehiscence.
The medial canthal procedure results in
loss of the upper lacrimal punctum, but has
the advantage of concurrent correction of
(a) medial lower entropion and protection from
nasal folds in Pekingese, Shih Tzu, Pug, and
similar breeds. It has the disadvantage of
being more complicated and the loss of the
upper punctum.

Postoperative Treatment
Therapy after ectropion-­oversized lid fissure
procedures consists of applying topical anti-
biotic ointment (more lubricating than drops)
four times daily for 14 days. Systemic antibi-
otics may be indicated for the extensive pro-
(b) cedures. An Elizabethan or E-­collar is used
routinely to prevent the patient from rubbing
the surgical site and producing local irrita-
tion and even suture loss. The sutures are
removed 10–14 days after surgery. The end
result can be judged only after cicatrization,
about six to eight weeks after surgery.

Microblepharon, Blepharophimosis,
or Blepharostenosis

(c) An abnormally small or narrowed palpebral


fissure, which is referred to as microblepha-
Figure 6.11 The Roberts–Jensen pocket method ron, blepharophimosis, or blepharostenosis,
for lid fissure length reduction by permanent
is seen particularly in miniature breeds like
medial or lateral tarsorrhaphy. (a) The procedure
starts with the removal of the outside lid margin the Miniature Pinscher and Shetland
and the inside margin plus meibomian glands. If Sheepdog, but also in larger breeds such as
performed in the medial canthus, the upper the English Bull Terrier, Chow Chow, Kerry
lacrimal punctum is incised in the procedure.
Blue Terrier, and both Rough and Smooth
(b) Flap of upper conjunctiva is pulled downward
into the pocket in the lower lid between the Collies. Correction is achieved by a lateral
conjunctiva and muscle–skin layers and anchored augmentation canthoplasty that increases
through the muscle–skin by a simple, interrupted, the functional length of the palpebral fis-
5-­0 suture. (c) Apposition of the new lateral or
sure. A 5–10 mm long lateral canthotomy is
medial canthus by a figure-­of-­8, 5-­0 to 6-­0 suture
and further closure by simple interrupted sutures. created using tenotomy scissors. Two small
­Entropio  257

arrowhead skin resections will achieve a Removal of part (upper) or all of the nasal
more gradual transition to the newly created folds is usually beneficial although corneal
lid “margin.” pigmentation often persists. Removing the
medial canthus and caruncle hairs, reposition-
ing the medial canthus more laterally, and
Trichiasis
reducing the normal or suboversized palpebral
Trichiasis is the presence of normally located fissures may be indicated in the brachycephalic
but abnormally directed hairs that irritate breeds with nasal fold trichiasis and exoph-
the globe, conjunctiva, or both. The chronic thalmia, such as the Pekingese, Shih Tzu, and
corneal irritation results in extra lacrima- Lhasa Apso.
tion, blepharospasm, and mucopurulent
conjunctival discharge. When hairs contact
Removal of Nasal Folds
the cornea, corneal disease is common.
Trichiasis is usually corrected surgically, Nasal folds (partial upper or complete) can
although cryotherapy and cautery can be simply be removed. In this operation, the fold
used to destroy the hair follicle and cause is lifted and excised with large scissors, and the
fibrous to alter the eyelid surface. Trichiasis wound is closed with 5-­0 absorbable sutures
occurs mainly in nasal folds and in brachyce- (Figure 6.12). However, this operation does not
phalic breeds with exophthalmia, such as the correct the associated medial entropion, the
Pekingese, Shih Tzu, and Lhasa Apso. Also, caruncle trichiasis, and does not reduce the
caruncle hairs may also irritate the globe and palpebral fissure length.
contribute to epiphora
Trichomegaly
Nasal Fold Trichiasis
Because of breed standards and fashions that dis- Trichomegaly refers to abnormally elongated
regard the animals’ health but are nevertheless eyelid cilia and is most commonly observed in
supported by breeders, judges, and buyers alike, American Cocker Spaniels. It has no clinical
almost all eyes of prominent-­eyed breeds significance as long as the hairs do not touch
(e.g., Pekingese, Shih Tzu, and Lhasa Apso) are the conjunctiva or cornea.
chronically irritated, have corneal disease
(u­sually pi­gmentation), and are predisposed to
Redundant Skin Folds
pr­optosis or luxation. In most patients, it is found
Around the Eye
in co­mbination with medial entropion, caruncle
tr­ichiasis, a slightly oversized lid fissure, and Redundant skin folds around the eye, compli-
lagophthalmos. These breeds often develop cated by heavy ears, usually do not directly irri-
recurrent mediocentral corneal neovasculariza- tate the eye but cause pressure on the lid
tion and, in severe cases, corneal ulcerations. The margins and canthi, resulting in medial and
blink reflex may be weak and incomplete, result- upper lid entropion and trichiasis. In breeds
ing in a thin precorneal tear film at the center of such as the Bloodhound, Chow Chow, and Shar
the cornea and increased risk of epithelial loss. Pei, the elderly English Cocker Spaniel, Basset
In cases of minor corneal disease, therapy Hound, English Bulldog, and Pug, the wrinkles
can be started with antibiotic and lubricating may cause serious eye problems. In
ointments, q 6 h. If the corneal defects have the Bloodhound and English Cocker
healed after 10 days, the cornea may be pro- Spaniel, the problem is worsened by the heavy
tected by oil or a neutral ointment two to four weight of the ear pinnae when the head is
times daily, adhering the hairs together, but turned toward the ground. The palpebral fis-
this alone seldom resolves the problem. sure droops and masks the globe affecting sight.
258 Canine Eyelids: Disease and Surgery

Figure 6.12 For the treatment of nasal fold


trichiasis, the nasal folds can be excised.
(a) The nasal folds are clamped and carefully
excised by curved Mayo scissors. (b) The
wound edges are apposed with simple,
interrupted, 5-­0 to 6-­0 sutures. The first
sutures are placed at the upper and lower
ends and at the medial canthus, and then
the rest of the wounds are closed by halving
the intervals.

(a)

(b)

There is usually entropion of both the upper four times daily, but this measure alone sel-
and lower eyelids at the lateral canthus as well dom resolves the problem. A simple
as ectropion of the central part of the lower eye- Celsus–Hotz entropion correction is seldom
lid. The nictitating membrane and the lower sufficient. In breeds such as the Pekingese,
palpebral conjunctiva are exposed, and there is Shih Tzu, English Bulldog, and Pug, the removal
impaired tear film drainage and ocular surface of the nasal folds will relieve pressure on the
disease. The irritation results in extra lacrima- medial canthus, but in most patients, surgical
tion and blepharospasm, which may worsen correction by medial canthoplasty of the medial
the situation. The hairs on the upper eyelid are canthus is much more likely to produce an
dark and moist, and the upper lid margin is effective and durable result, and such correction
entropic. The conjunctiva is red and swol- should be attempted as the first option.
len, and the corneal epithelium is damaged,
re­sulting in ulceration, mainly of the upper
la­teral part of the cornea, and in rare cases, the ­Lid Trauma
condition also leads to perforation. Finally, it
often results in scarring and pigmentation. Eyelid lacerations are frequent in young small
In cases of minor irritation, the cornea may dogs and require surgical repair. Eyelid lacera-
be protected from the trichiasis by an indiffer- tions may be divided into partial and full thick-
ent topical ointment, oil, or petrolatum two to ness, marginal and nonmarginal, and may
­Inflammation  259

include the lacrimal puncta and canaliculi. the wound. Some clinicians avoid topical ther-
Eyelid and conjunctival sac wounds are often apy and administer antibiotics only parenter-
right-­angled. Because eyelids are highly vascu- ally, and some do both. If contamination is
lar, they will usually bleed heavily, but this pro- evident and concern about bacterial infection
tects against tissue ischemia and necrosis. If is present, culture and sensitivity tests are indi-
the lid edge is transected, the defect will cated. The progression of healing should be
enlarge spontaneously in the lid via contrac- evaluated and treatment modified as necessary.
tion of the orbicularis oculi muscle. Lid heal-
ing by secondary intention can result in
considerable fibrosis and distortion of the eye- ­Inflammations
lids and lid margin, which may eventually
require surgical correction. Inflammation of the eyelids may be restricted
Wounds in the eyelid should therefore to one eye or both or may be associated with a
always be sutured directly, even if they are generalized dermatological disease. They may
more than 8 h old. Hair along the wound edges involve only certain glands of the eyelids or
can be clipped. Both the wound in the lid and involve the entire lid surfaces
the wound in the conjunctival sac must be very
thoroughly irrigated. Mechanical wound
Generalized Blepharitis
debridement should be avoided or kept to a
minimum. Loose parts (over 1 mm), especially Blepharitis covers a number of inflammatory
of lid margin, should not be excised but used to conditions of the eyelid, often the primary
fill the defect. Reapposition of severely trau- cause being masked to some extent by possible
matized eyelids usually yields better postoper- secondary complications. The inflammation
ative results than the excision of still attached may be focal or diffuse with variable involve-
but lacerated lid tissues and subsequent recon- ment of both eyelids of one or both eyes. Pain
structive blepharoplastic surgical procedures. is indicated by blepharospasm and excessive
Sutures at the eyelid margin should have lacrimation with epiphora, which may be
their knots external to the free rim of the lid worsened by self-­induced trauma. In addition,
margin to avoid contact with the cornea. Two there may be exudate, evidence of self-­trauma,
layers of sutures may be used in sterile wounds. alopecia, erosion, and scaliness.
The deeper palpebral conjunctiva and tarsus Chronic inflammation can lead to eyelid dis-
can be closed by simple, continuous, 6-­0 to 8-­0 tortion with both entropion and ectropion
absorbable suture. resulting from cicatrix formation and second-
Knots should be avoided or placed beneath ary corneal and conjunctival diseases. The
the conjunctiva. The wound in the eyelid mar- causes for generalized blepharitis include
gin must be apposed very precisely with a sebaceous overproduction, bacteria, parasites
figure-­of-­8 or mattress (only in thick lid mar- (especially demodex and scabies), leishmania,
gins) suture. The skin, together with the fungi, flies, and ticks.
orbicularis oculi muscle, is closed using sim-
ple, interrupted, 5-­0 to 6-­0 nonabsorbable
Bacterial Blepharitis
monofilament sutures. Absorbable material is
used in aggressive or anesthesia-­risk patients. In puppies, a purulent blepharitis occurs as
part of juvenile pyoderma or puppy “stran-
gles.” The entire skin of the head may be
Aftercare
involved with multiple abscesses usually
After surgical repair, the aftercare consists of caused by Staphylococcus spp. Pain and com-
topical antibiotic ointment onto the eye and plicating self-­trauma to the face may require
260 Canine Eyelids: Disease and Surgery

an Elizabethan collar. Systemic antibiotics and develop. Abscessation and impaction of the
steroids usually resolve the condition and meibomian glands may also occur. Systemic
should be based on culture and sensitivity. and topical ophthalmic antibiotics (applied
Topical broad-­spectrum antibiotics are used to directly to the eyelid skin) are based on culture
help lubricate and protect the cornea. and sensitivity.
In adult dogs, Staphylococcus and Strepto­ Staphylococcal infections may also involve
coccus spp. are most commonly involved in the deeper parts of the lids and present as sin-
bacterial blepharitis, which is often bilateral gle or multiple pyogranulomas (Figure 6.14).
(Figure 6.13). Bacterial blepharitis may be pre- Diagnosis is established by histopathological
sented as a diffuse superficial lid inflamma- examination, which reveals microabscesses.
tion, pyogranulomas of the lid subcutaneous Pyogranulomatous blepharitis is treated with
tissues, and as meibomianitis. Acute diffuse systemic and intralesional antibiotics. Because
blepharitis is characterized by hyperemia, lid staphylococcal toxins may have a necrotizing
swelling, and crusting. Over several weeks, effect, topical corticosteroids may be benefi-
ulceration of the eyelid skin and margins, alo- cial. Autogenous vaccine can be effective in
pecia, and fibrosis with the development of chronic and seemingly resistant staphylococ-
entropion, ectropion, or a combination of both cal infections.

Figure 6.13 Chronic staphylococcal


blepharitis in an adult dog. (Courtesy
KN Gelatt.)

Figure 6.14 Eyelid pyogranulomas of


the upper lid and lateral canthus in a
Miniature Poodle. (Courtesy KN Gelatt.)
­Inflammation  261

Mycotic Blepharitis probably enters the conjunctiva or lid surface;


wounds can facilitate penetration. Larva
Blepharomycosis is uncommon, but infection
requires about four weeks to develop with
with Microsporum and Trichophyton spp. is
black cuticular spines, often within a thick-­
seen as part of a generalized problem in young
walled abscess and an identifying entry hole.
dogs. Expanding alopecia, scaling, and hyper-
Therapy is larva removal, and topical and sys-
emia are the clinical features, and diagnosis is
temic antibiotics.
confirmed by staining skin scrapings with
either Gram or Giemsa stain or culturing the
organisms on Sabouraud’s agar. Effective anti-
Leishmania Blepharitis
fungal therapy may include povidone–iodine
cleansing together with topical miconazole Systemic leishmaniasis, a chronic and poten-
nitrate. Clotrimazole creams are effective for tially fatal disease, is endemic in countries
superficial infection, but care should be taken around the Mediterranean Sea as well in India
to avoid corneal contact. and Central and South America. In the
Mediterranean region, the protozoan
Leishmania infantum is carried by the sand
Parasitic Blepharitis flies (Phlebotomus spp.). The clinical signs of
leishmaniasis are quite variable, but the eye-
Both demodectic and sarcoptic mange can
lids are frequently involved. In one report, one-­
include the eyelids, the lesions being charac-
fourth of all leishmania cases had ocular or
terized by hyperemia, alopecia, and pruritus
periocular disease. The eyelid lesions may vary
and often complicated by secondary bacterial
from a dry dermatitis with alopecia, diffuse
infection and self-­trauma. Demodex canis is
edema, and cutaneous ulcerations to discrete
considered to be a normal inhabitant of hair
nodular granuloma formations.
follicles, sebaceous glands, and sweat glands,
Diagnosis is by cytological or histopathologi-
and disease may develop only when large
cal examination, serology, or polymerase chain
numbers of the parasite are present in the pres-
reaction testing. Antileishmania therapy
ence of immunosuppression or possible inher-
includes subcutaneous N-­methylglucamine
ited T-­cell deficiency. In young dogs, the
antimoniate (80 mg/kg daily for a minimum of
disease tends to be restricted to the face, and
30 days) and allopurinol orally (10 mg/kg every
eyelid involvement is common. Spontaneous
12 h for 6–12 months). Local treatment often
regression is expected, but topical rotenone
includes antibiotics and corticosteroids.
ointment or isofluorophate ophthalmic oint-
ment can be used to good effect. In older dogs,
a more generalized disease is seen, which often
Immune-­Mediated Blepharitis
proves resistant to treatment.
Sarcoptes scabiei var. canis infection causes Several autoimmune and immune-­mediated
intense pruritus, several parts of the body phenomena can involve the canine eyelid,
being classically involved in addition to the either in isolation or in association with sys-
eyelids. Treatment routinely involves the use temic clinical features, but are fortunately rare
of sulfur dips, while amitraz is currently prov- diseases. In all types of pemphigus, the lesions
ing to be very effective as a potential first-­line seen are the result of autoantibody production
therapy. against the intercellular matrix of the epider-
Cuterebra infestation has been reported in mis, but in bullous pemphigoid, it is autoanti-
the conjunctiva of a puppy. Cuterebra sp., order body against epidermal basement membrane
Diptera, family Cuterebridae, is a larva of the that is responsible for clinical signs indistin-
rabbit or rodent bot fly. Larva involving the lid guishable from pemphigus vulgaris. These
262 Canine Eyelids: Disease and Surgery

autoantibodies cause separation of the corni- ophthalmologists. Often, the loss of pigmenta-
fied from the uncornified epithelial cell layers. tion of the nose and eyelids is the primary clin-
The treatment of this disease complex requires ical sign recognized by the owner and is the
long-­term systemic and topical corticosteroid basis for the initial examination. Breed predis-
therapy with additional immune suppression position may be important; affected breeds
through the use of cyclophosphamide or aza- include Akita, Siberian Husky, Golden
thioprine for refractory cases. Occasionally, the Retriever, Samoyed, Rottweiler, Chow Chow,
cicatricial entropion from these diseases may Shetland Sheepdog, and others. For treatment
require corrective blepharoplasty. of this condition, see Chapters 11 and 19.
Medial canthal ulcerative blepharitis repre-
sents a juxtapalpebral disorder, usually affect-
Chalazion
ing the medial canthus (Figure 6.15). Breeds
most often affected include the German Chalazion is a firm, nonpainful swelling of the
Shepherd, Long-­Haired Dachshund, and Toy meibomian gland caused by accumulation of
and Miniature Poodle. In German Shepherds, secretion that results in chronic inflammation
the medial canthal blepharitis may be concur- and a granulomatous reaction. The inflamma-
rent with pannus (chronic superficial kerati- tion may predispose to a staphylococcal infec-
tis) and the immune-­mediated plasma cell tion and thus hordeolum formation. Treatment
infiltration (plasmacytoma) of the nictitating is by scalpel incision along the granuloma with
membrane. Biopsy reveals both lymphocytic curettage. Topical antibiotic ointment is
and plasma cell infiltration; sebaceous glan- administered for 7 to 10 days after curettage.
dular hyperplasia may also be present.
Epithelial cell antibodies have been demon-
Hordeolum or Stye
strated in selected cases and may suggest a
relation to pemphigus. The condition usually An external hordeolum or stye is caused by
responds to topical ophthalmic corticosteroids suppurative infection of the Zeis or Moll glands
and/or cyclosporine. and manifests itself as either single or multiple
Vogt–Koyanagi–Harada (VKH), or uveoder- abscess formation along the anterior aspect of
matological syndrome, is another immune-­ the eyelid. External hordeolum affects mainly
mediated disease that can affect the eyelids young dogs; an individual dog may exhibit
and can be presented to veterinary these lesions over several weeks. Affected lids

Figure 6.15 Immune-­mediated


medial canthal blepharitis in an adult
mongrel German hunting dog. The dog
also has bilateral chronic superficial
keratitis.
­Eyelid Masses and Neoplasi  263

are usually swollen and painful; focal abscesses An allergic blepharitis is usually character-
occur on the eyelid surface. Treatment consists ized by an acute onset edema and hyperemia
of hot compresses and topical and systemic and may be caused by local exposure to a con-
antibiotics. During therapy, these abscesses tact allergen or may occur as part of a general-
usually rupture. Focal abscesses can be opened ized response. Swelling of the eyelids and
by scalpel incision along the swelling with muzzle will be seen following insect bites
curettage. (ants, ticks, fleas) and as postvaccinal reaction.
In the hordeolum internum, the eyelid is Topically applied drugs may be responsible for
also swollen and painful. The localized infec- contact allergy, with neomycin being most
tion can be directly observed within the tarsal commonly involved. Identification of the spe-
plate, distending the palpebral conjunctiva cific allergen and desensitization are rarely
when the eyelid is everted. Treatment is by possible, with treatment relying upon the use
scalpel incision along the swelling, parallel to of topical and systemic corticosteroids and
the margin of the lid, with curettage. antihistamines.
Food allergies and systemic drug reactions
can cause periocular dermatitis and blephari-
Focal Blepharitis, Blepharitis tis, with the avoidance of the allergen or the
Adenomatosa, Meibomianitis, cessation of the drug therapy being the obvious
and External Hordeolum lines of treatment.
Meibomianitis is inflammation of the meibo-
mian glands; either or both eyelids can be
involved, and the condition may be unilateral ­Eyelid Masses
or bilateral. The lid is usually swollen and and Neoplasia
somewhat painful with blepharospasm.
Eversion of the affected eyelid permits direct Masses of the canine eyelids are divided into
observation of the swollen and often enlarged those of inflammatory origin and neoplasms,
meibomian glands. Pressure on the inflamed with the latter being more common, especially
glands often causes expression of exudate from in older animals. Sometimes, only biopsy
the gland’s ducts along the eyelid margin. With results can differentiate the two conditions.
persistent meibomianitis, bacterial culture and
cytological examination may guide the optimal Inflammatory Masses
choice of topical and systemic antibiotics.
Chronic meibomianitis may result in thick- Inflammatory masses or pseudotumors of the
ened and fibrotic eyelids with either entropion eyelids are infrequent in dogs and tend to
or ectropion that may require surgical occur in certain breeds. Eosinophilic granu-
correction. loma may present as slow progressing granu-
lomatous nodules or plaques, sometimes with
yellow-­white detritus on it. It is mostly local-
Other Eyelid Diseases
ized in the oral cavity but also at the lid mar-
Marginal meibomian cysts are single to multi- gin, or in cats, on the cornea. Complete
ple small cystic structures, which may develop remission usually can be achieved with topical
along the eyelid margin. These cysts may occur glucocorticoid eye ointment or oral glucocorti-
more frequently in older than in younger dogs coid treatment.
and may or may not be associated with meibo- Histiocytosis of the Bernese Mountain Dog
mian tumor formation. Therapy consists of is a systemic and familial disorder that affects
manual rupture and topical antibiotics and males more often than females; the condition
steroids for five to seven days. also affects the Rottweiler, Golden Retriever,
264 Canine Eyelids: Disease and Surgery

Labrador Retriever, and Flat-­Coated Retriever. Table 6.4 Histologic classification and frequency
This disease manifests in two different forms: of canine eyelid neoplasms.
(i) a generally slow, cutaneous form and (ii)
an aggressive or malignant cutaneous form. Tumor Classification N = 202 (%) N = 200 (%)
The eyelids are often involved and present as
Sebaceous adenoma 28.7 60
recurrent or persistent nodules, papules, or
Squamous papilloma 17.3 10.6
plaques of upper and lower eyelids. Their sur-
face may be alopecic to ulcerated, and subse- Sebaceous 15.3 2.0
adenocarcinoma
quent recurrences tend to be more severe.
Benign melanoma 12.9 17.6
Biopsy of the masses is usually diagnostic.
This disease is unfortunately progressive Malignant melanoma 7.9 2.8
and fatal. Histiocytoma 3.5 1.6
Nodular fasciitis occurs rarely in the dog and Mastocytoma 2.5 1
is most frequent in the Collie and related Basal cell carcinoma 2.5 1.2
breeds. In Collies, the condition affects the Squamous cell 2 1
eyelids, conjunctiva, episclera, and peripheral carcinoma
cornea. Microscopically, the lesions are charac- Fibroma 2.1 –
terized as a subcutaneous mass with abundant Fibropapilloma 1 –
fibroblasts, variable ground substance, and
Lipoma 1 –
fiber formation. Inflammatory cells consist of
All others (less than 3 1
lymphocytes and mononuclear cells with occa- 1% individually)
sional giant cells. Therapy consists of surgical
Undetermined 0.5 1.2
excision, cryotherapy, and for dogs heavier
Benign 73.3 87.8
than 10 kg, oral administration of niacinamide
(500 mg q 8 h) and tetracycline (500 mg q 8 h) Malignant 26.7 8.2
with therapy gradually tapered. Source: Data from Krehbiel & Langham (1975) and
Roberts et al. (1986).

Eyelid Neoplasia
The dog eyelids exhibit a large number of dif- slightly more often than the lower lid. Breeds
ferent neoplasms that are fortunately, for the reported as having increased prevalence of lid
most part, locally minimally invasive and tumors include the Beagle, Siberian Husky, and
respond to fairly conservative surgical proce- English Setter in one report, while Bedford in
dures. Distinct metastasis from eyelid neo- England reports the Toy and Miniature Poodle,
plasms in dogs has not been reported. Eyelid Labrador Retriever, and Golden Retrievers are
tumors are different from conjunctival neo- overrepresented.
plasms, which tend to be locally invasive and The largest group of neoplasia arising from
often recur after attempts of surgical excision the meibomian glands are the adenomas and
and may even metastasize. adenocarcinomas. These tumors are first
Two reports on canine eyelid neoplasms indi- noticed erupting though the eyelid margin or
cate similar results (Table 6.4). Benign neo- the palpebral conjunctiva just behind the
plasms outnumber malignant tumors by a ratio eyelid margin (Figure 6.16a and b). They may
of 3:1. The epithelial tumors outnumber the be pink or have varying degrees of pigmenta-
mesenchymal tumors by a ratio of about 5:1. tion and may appear as multiple lobes. With
Most eyelid tumors occur primarily in dogs exposure, advanced meibomian adenomas or
over 10 years old, and no gender predisposition adenocarcinomas may ulcerate and even
has been reported. The upper lid is affected hemorrhage, and cause local irritation
­Eyelid Masses and Neoplasi  265

(a) (b)

Figure 6.16 Preoperative (a) and postoperative (b) appearance of an adenoma in the lateral upper eyelid
in a nine-year Dalmation.

resulting in blepharospasm, epiphora, con- tumors may also spontaneously regress over a
junctival hyperemia, corneal neovasculariza- few weeks.
tion, and pigmentation. Papillomas represent about 10–20% of the lid
Lid melanomas are the second-­largest tumors, and if combined with oral papilloma-
group of tumors and appear as either involv- tosis, affect young dogs. These tumors may
ing the eyelid skin and usually a single or have a viral origin, but autogenous vaccines
multiple pigmented mass (which can usually have been of limited value. These lid tumors
be excised with low recurrence rates) or aris- often regress with time and are removed only
ing from the pigmented eyelid margin and when tumor-­induced corneal contact and irri-
tend to expand to both directions. These tation result. Surgical excision followed by
tumors are more aggressive locally, and their cryosurgery decreases recurrence.
removal involves the eyelid margin, which
must then be restored. These melanomas
Therapy
behave more aggressively locally but appear
more benign than melanomas in the mouth Therapies for the canine lid tumors include
or other sites. They can be treated success- surgical excision, cryosurgery, or a combina-
fully by one or more attempts at surgical exci- tion of both. Most veterinary ophthalmolo-
sion. Often the surgery site is treated by gists prefer surgery. Recurrence rates after
cryosurgery following the excisional surgi- surgery (15%) and cryosurgery (11%) were not
cal biopsy. significantly different in one study, but the
Fibromas and fibrosarcomas are less preva- time for recurrence after surgery was
lent but can be locally invasive. They appear as 28.3 months compared to 7.4 months after
gradually enlarging subcutaneous masses. cryosurgery.
Other masses affecting the lid subcutaneous Surgical procedures depend on the size and
tissues are mastocytoma, or mast cell sarcoma, site of the eyelid mass and the involvement of
and lipomas. the lid margin (Box 6.4). Canine eyelid neo-
Squamous cell carcinoma rarely affects the plasms are best removed early, when the result-
canine eyelid; they appear as either a surface ant surgical defect is small and more
proliferative or ulcerative lesion. Histiocytomas manageable. Larger masses result in more
affect mainly young dogs, appearing often as extensive defects that require greater recon-
rapidly proliferative masses. These same struction, and usually an attempt to replace the
266 Canine Eyelids: Disease and Surgery

meibomian glands obliquely) or four-­sided


Box 6.4 Blepharoplastic Procedures
(house-­shape – cutting the lid margin in a
Reported in the Dog
rectangular-­shaped excision) wedge excision is
●● Wedge excision for small eyelid mar- performed by scissors and/or scalpel and
gin masses should be at least 1 mm beyond the tumor mar-
●● Four-­sided excision for masses less than gins. Closure is by one or two layers. The
1/4 of the eyelid margin deeper tarsoconjunctival layer can be apposed
●● Four-­sided excision combined with lat- by simple, continuous, 6-­0 to 8-­0 absorbable
eral canthotomy for masses less than 1/3 sutures with the knots buried. The eyelid mar-
of the eyelid margin gin is apposed with a figure-­of-­8 or U-­figure
●● H-­plasty or sliding skin graft for masses suture, using a 5-­0 to 6-­0 monofilament nylon
>1/2 of the eyelid margin or polyfilament silk material, sometimes
●● Sliding “Z”-­plasty; used for lateral can- including the upper eyelid for extra support.
thal masses involving both upper and The lid margin is most important because the
lower lids greatest tension occurs at this single suture.
●● Tarsoconjunctival grafts; used to line the The remaining muscle–skin lid is apposed
inner surface of skin grafts with simple, interrupted, 5-­0 to 6-­0 nonabsorb-
●● Whole eyelid grafts; often termed the able monofilament or silk sutures. The four-­
Beard–Cutler technique sided wedge technique offers the advantage of
●● Pedicle skin grafts; from face or cheek accommodating a larger surgical approach,
●● Buccal and conjunctival mucosa graft; and all of the muscle–skin sutures share
island or pedicle equally in the wound tension and prevent an
●● Mustardé technique (semicircular obvious notch postoperatively.
procedure) The usual postoperative treatment after the
excision of small lid masses is topical antibiot-
ics, eventually combined with topical corticos-
eyelid margin. Lid masses removed at surgery teroids. The Elizabethan collar or other
should be submitted for histopathological protective devices (e.g., Optivizor) are useful to
examination and the surgical margins closely prevent the patient from rubbing and possibly
examined for the possible tumor. Masses that interrupting the surgical wound. The most fre-
involve the medial and lateral canthi or are quent result after these procedures is the devel-
near the lacrimal puncta involve greater opment of an obvious “V” notch at the eyelid
difficulty. margin. This can usually be avoided by use of
Hyperthermia, cryotherapy, and carbon the four-­sided procedure.
dioxide laser therapy have been reported for
canine lid tumors. Cryosurgery is best moni-
tored with thermal couples within and adja- ­ econstructive
R
cent to the mass to measure the extent of Blepharoplasty
freezing. Laser ablation can successfully treat
meibomian gland adenomas, but because lid When the surgical defect approaches or exceeds
margin loss occurs often, apposition of the 50% of the upper eyelid, a semicircular skin flap
wound post laser is recommended. can be constructed to permit medial movement
Depending on the lid laxity, eyelid masses to increase the size of the resultant palpebral fis-
involving up to 25% of the eyelid length may be sure. When 60–90% of the eyelid is involved with
excised by scalpel or scissors as a wedge of full-­ neoplasia, more extensive blepharoplastic proce-
thickness lid shaped either as a V or a four-­ dures are required for successful treatment (see
sided defect. The V (thus cutting some Box 6.4). Reconstructive blepharoplasty includes
­Other Eyelid Procedure  267

the different surgical procedures to restore the Lid flaps and grafts should be handled mini-
lids after extensive defects resulting from con- mally during surgery because they rapidly
genital defects or abnormalities, trauma, or the swell. They tend to contract postoperatively,
removal of scar tissues and neoplasia. The limits and should always be constructed slightly
of these surgical procedures depend on the skill larger than the defect to allow for shrinkage.
and imagination of the surgeon. All of these pro- Immediate postoperative dressings can be
cedures, with occasional modifications, are used to apply limited pressure to fresh grafts
applicable to all animal species. and reduce the swelling, hemorrhage, and
These procedures have several general prin- serum accumulation. An E-­collar is necessary
ciples. The upper lid is more mobile than the as long as eyelid dressings and sutures are in
lower lid and is the most important lid to cover place to prevent self-­damage to the surgical
the cornea and in the blink reflex. The upper lid site. Most blepharoplastic procedures can
is also larger than the lower lid and a potential restore adequate lid function following large
donor of autogenous tarsoconjunctiva, myocu- congenital, traumatic, and surgery defects, but
taneous, or full-­thickness lid tissues. Only the they may not completely restore the lid appear-
lateral upper lid margin of the dog contains ance to normalcy.
eyelashes or cilia; transplantation of these cilia
follicles from the same or fellow upper eyelid
has not been described but is technologically ­Other Eyelid Procedures
simple with insertion of a strip of cilia follicles
into a V-­shaped furrow about 5 mm deep in the In the tarsorrhaphy procedures, portions of or
recipient upper lid. Lid surgeries involving the the entire eyelids are apposed, either temporar-
medial canthus must consider the upper and ily or permanently. In the partial procedures,
lower lacrimal puncta; if a punctum is to be only part (medial, central, or lateral) of the pal-
sacrificed, the lower one carries the majority of pebral fissure is closed, thereby permitting
the tears into the nasolacrimal system and vision by the patient, daily inspections by the
should be spared if possible. The lid margin is veterinarian, and topical medication of the eye
the most important in blepharoplasty and as well as keeping the eye in its orbit and pro-
sometimes the most difficult area to restore. tecting the cornea in the absence of an effective
Fibrotic eyelid margins can cause considerable blink reflex. If the indication was traumatic
corneal and conjunctival discomfort and dam- proptosis in brachycephalic breeds, a tempo-
age. The posterior aspects of the skin graft may rary complete tarsorrhaphy is used for 7–14 days
be lined by conjunctival cells spontaneously, as part of its treatment, while later a permanent
possibly with more scarring, or can be lined medial canthoplasty (tarsorrhaphy) may be
with mucosa from adjacent palpebral conjunc- considered as a preventive measure for the
tiva, buccal mucosa, or an island graft from bul- lagophthalmos. In permanent tarsorrhaphy
bar conjunctiva of the opposite eye. However, procedures, all or parts of the eyelid margins of
these methods are more time consuming and the upper and lower eyelids are excised; they
may result in traction bands (also in the area grow together and remain sealed for extended
where the graft is harvested) and secondary periods of time or indefinitely. Partial perma-
leading-­edge entropion. The lower conjunctival nent tarsorrhaphies are indicated to treat long-­
fornix is critical to tear collection and move- term ocular disorders, such as neuroparalytic
ment to the lacrimal punctum. Adequate blunt keratitis, neurotropic keratitis, lagophthalmos,
dissection and tissue undermining is important and chronic proptosis and exposure keratitis.
to reduce tension on sutures but should be min- Complete permanent tarsorrhaphies are part of
imized to reduce trauma, postoperative tissue the enucleation and exenteration procedures
swelling, and comprised blood supply to the lid. after removal of the eye and the orbital contents.
268 Canine Eyelids: Disease and Surgery

Temporary Tarsorrhaphy After days or weeks, the sutures are removed


(the medial first, if proptosis was the indica-
The partial temporary tarsorrhaphy is used fre-
tion; if there is still an apparent tendency to
quently after conjunctival and corneal surgery
luxation, the remaining sutures are left in
to reduce the eyelid trauma to the surgical site
place for a longer period). The suture ends in
and provide some contact and pressure to fresh
the temporary tarsorrhaphies may be left long
grafts or to keep contact lenses in place. The
to facilitate occasional adjustment of the
complete temporary tarsorrhaphy is also indi-
suture pressure (as the eyelid edema and swell-
cated for the treatment of traumatic proptosis,
ing disappear) as well as occasional loosening
after most orbitotomies, after many extensive
to open the tarsorrhaphy and inspect the eye.
eyelid procedures, after nictitating membrane
flaps, after extensive conjunctival surgery, to
treat premature opening of the eyelids, to help Permanent Tarsorrhaphy
maintain collagen shields or soft contact
In permanent tarsorrhaphy procedures, all or
lenses, and for the treatment of recurrent cor-
parts of the eyelid margins of the upper and
neal erosions and other selected superficial
lower eyelids are excised, and after apposition
corneal disorders. Complete temporary tarsor-
by sutures, the “eyelids” grow together and
rhaphies are also indicated when upper eyelid
remain sealed for extended periods of time or
function is impaired and the development of
indefinitely. Medial or lateral partial, perma-
exposure keratitis is imminent.
nent tarsorrhaphies are indicated for diseases
A temporary tarsorrhaphy is performed by
such as trichiasis, chronic exposure keratitis,
placing one to three horizontal mattress
and recurrent central corneal ulceration in the
sutures (4-­0 or 5-­0, cutting, micropoint, or
brachycephalic breeds.
round-­body needle) on the required area,
Aftercare consists of administration of an
using, for example, silicone or infusion tubing
appropriate antibiotic ointment for 10 days.
to prevent the suture from cutting into the skin
The wounds close spontaneously. Complete,
(Figure 6.17). Mattress sutures are used to
temporary tarsorrhaphy constitutes a barrier
close the lid fissure. Sutures placed too far
to topical mediation of an eye, but subpalpe-
from the lid margin can cause entropion.
bral systems can be inserted in the conjuncti-
Sutures placed through the conjunctiva may
val fornix at the conclusion of surgery to
result in an “egg slicing” effect to the cornea.
ensure delivery of ophthalmic solutions. The

Figure 6.17 Temporary tarsorrhaphy.


(a) After, for example, a canthotomy
and repositioning of a luxated or
proptosed globe, a temporary
tarsorrhaphy can be performed.
(b) The lid fissure is closed by two or
three U-­figure sutures, prevented
from cutting into the skin by, for
example, infusion tubing.

(a) (b)
­Other Eyelid Procedure  269

apposed eyelids may also retain the topical should be examined daily or every other day. If
solutions in contact with the cornea for longer the sutures become too tight, local eyelid
periods of time, thereby increasing their necrosis and irritation result. If the sutures
effectiveness. become too loose, “egg slicing” suture contact
to the cornea may occur. Routine use of a pro-
tective E-­collar postoperatively in small ani-
Postoperative Care
mals is important and effectively prevents
and Complications
self-­trauma to the surgical site.
After Tarsorrhaphy
The most frequent postoperative complica-
The most frequent complications immediately tions after permanent tarsorrhaphy are related
after temporary tarsorrhaphy techniques are to excessive tension on the lid sutures for the
variable swelling of the eyelids and suture con- short term and wound failure for the long term.
tact with the cornea (if the sutures are placed Chronic tension may result in gradual weaken-
full thickness of the eyelids). Thus, patients ing and atrophy of the surgical a­ pposition site.
270

Canine Nasolacrimal and Lacrimal Systems: Disease


and Surgery
Revised from 6th edition of Veterinary Ophthalmology, Chapter 12: Diseases and Surgery of the Canine Nasolacrimal System, by Bruce
H. Grahn and Lynne S. Sandmeyer; and Chapter 13: Disease and Surgery of the Canine Lacrimal Secretory System, by Elizabeth A. Giuliano

Section I: Nasolacrimal end of this cord develops two buds, which grow
Duct System into the upper and lower eyelids near the medial
­canthus (Figure 7.2c) and develop into the
The nasolacrimal duct system of the dog is superior and inferior canaliculi and puncta. The
similar to that of most domestic mammals. It is cord becomes a duct through a process of
a walled conduit that drains the tear film from canalization and normally is patent at birth.
the eye into the nasal passages. The first sec-
tion of this chapter reviews the embryology,
anatomy, physiology, and diagnostic proce- ­Anatomy
dures as well as the clinical manifestations for
both congenital, developmental, and acquired The superior and inferior lacrimal puncta are
diseases and their appropriate medical and oval-­to-­slit-­like openings that measure approxi-
surgical management (Figure 7.1). mately 1 mm by 0.3 mm, with their long axis par-
allel to the lid margin. They are located on the
palpebral conjunctiva at the edge of the upper
­Embryology and lower eyelids 2–5 mm from the medial can-
thus, approximately where the tarsal glands end
The nasolacrimal duct system develops from (Figure 7.3a). The lacrimal puncta open into the
surface ectoderm within the nasolacrimal superior and inferior canaliculi. The canaliculi
groove (i.e., furrow), which separates the lateral are approximately 4–7 mm in length and
nasal fold and the maxillary process (Figure 7.2a). 0.5–1.0 mm in diameter. They extend through
Ectodermal cells grow along this groove, sink the orbicularis oculi muscle, and they join
into mesenchyme, and become buried. These together ventral to the medial canthus to form
cells form a cord as the maxillary process fuses the lacrimal sac, which lies within a slight
with the lateral nasal fold between days 22 and depression (i.e., the lacrimal fossa) in the lacri-
26 of gestation in the dog (Figure 7.2b). The ecto- mal bone. The lacrimal sac is simply a slight
dermal cords grow toward the nasal cavity and dilation at the beginning of the nasolacrimal
the eye, and eventually, they extend from the duct, not a distinct sac. The proximal nasolacri-
eyelid to the inferior nasal passage. The upper mal duct itself is constricted as it traverses the

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
­Physiolog  271

Tear overflow at medial canthus

Epiphora Lacrimation (pain generated)


(Schirmer tear test: 10–25 mm/min) (Schirmer tear test values: >30 mm/min)

Fluorescein passage Fluorescein passage to nares

Absent at nares: Nasolacrimal flush Examine eyelids (entropion, distichia, etc.)


Examine conjunctiva, cornea, and
intraocular tissues
If negative: Lacrimal punctum atresia
surgery
Treat primary disorder

If positive:
Medial lower entropion
Lacrimal punctum obstruction:
inflammatory
Lacrimal micropunctum/displacement
Dacryocystitis
Nasolacrimal duct obstruction

Treatment of inciting condition

* Character of the ocular discharge is mainly serous or seromucus. If the ocular


disharge is mucopurulent or purulent, see Chapter 10.

Figure 7.1 Strategy and procedures for diagnosis and treatment of nasolacrimal (drainage) disease.

lacrimal bone, and the most frequent site for ­Physiology


retention of foreign bodies and development of
dacryocystitis in the dog. The duct, then enlarged The sole purpose of the nasolacrimal duct system
in diameter, passes through a canal on the is to drain tears from the surface of the eye to the
medial surface of the maxillary bone, and it ends nasal passages. Evaporation, which varies with
in a nasal punctum. The nasal puncta are usu- environmental conditions and whether the eye-
ally located in the ventral lateral nasal meatus, lids are open or not, removes a significant portion
opening approximately 1 cm inside the external (approximately 25%) of tears from the ocular sur-
nares (Figure 7.3b). They can be accessed with face. Most (60%) of the tear volume is normally
the dog under general anesthesia and the nares drained through the inferior puncta and canali-
dilated. In approximately 50% of dogs, the nasol- culi. Tears flow ventrally in response to gravity,
acrimal duct has a second opening in the oral and they are pulled into the canaliculi during
mucosa of the central hard palate, behind the eyelid closure because of reduced intracanalicu-
incisors at the level of the canine teeth. The lar pressure. This reduced pressure develops as
nasolacrimal duct is approximately 1 mm in these thin-­walled ducts are compressed by con-
diameter, and the length varies considerably traction of the orbicularis oculi muscle. Capillary
between brachycephalic, mesocephalic, and action and siphon effect from the lacrimal sac
dolichocephalic dogs. Brachycephalic breeds pull tears through the canaliculi and duct.
often have very short nasolacrimal ducts, and Mucosa-­associated lymphoid tissue (MALT)
they often drain the tears into the pharynx. has been reported in human nasolacrimal
272 Canine Nasolacrimal and Lacrimal Systems: Disease and Surgery

drainage systems. This lacrimal drainage-­


associated lymphoid tissue is part of the com-
mon mucosal immune system, and T cells, B
cells, and plasma cells were confirmed with
immunohistochemistry within the walls of the
Lateral nasal fold
nasolacrimal ducts and canaliculi. MALT and
Maxillary process production of natural peptide antibiotics have
not been reported in the dog, but they are likely
present in animals.

(a)
­Clinical Manifestations
of Nasolacrimal Disease

Disorders of the nasolacrimal duct system in the


dog may be congenital, developmental, or
acquired, and they are limited to a lack of
Nasolacrimal groove patency or inflammation. The clinical manifes-
tations of nasolacrimal system disease include
epiphora; mucopurulent punctal, conjunctival,
and nasal discharge; swelling of the ventral
(b) medial canthal region; punctal foreign bodies;
and draining fistula in the medial canthal region.

Epiphora
Epiphora is the most common clinical manifes-
tation. Epiphora develops secondary to obstruc-
tions of tear flow through the nasolacrimal
Nasolacrimal duct
duct system or to an overproduction of tears
(i.e., lacrimation – usually in response to ocular
pain), in which the tear volume overwhelms
the normal drainage system. Mucopurulent
punctal and ocular discharge, conjunctivitis,
and draining fistulas from the duct system may
(c) develop secondary to nasolacrimal sac inflam-
mation (i.e., dacryocystitis).
Figure 7.2 Embryologic development of the canine
nasolacrimal system. (a) Note the nasolacrimal groove
between the lateral nasal fold and the maxillary
process at approximately day 21 of development in
the dog. (b) The lateral nasal fold fuses with the
­Diagnostic Procedures
maxillary process between days 22 and 26. This fusion
buries the surface ectoderm cells, which will grow and Several diagnostic procedures allow clinicians
form the nasolacrimal duct system. (c) The ectodermal to establish an accurate diagnosis of obstruction
cells form a cord with two proximal processes that
or inflammation of the nasolacrimal duct sys-
extend toward the medial upper and lower eyelids,
whereas the distal end grows toward the nostril. This tem or epiphora secondary to increased
ectodermal cord canalizes and becomes a duct and la­crimation. These include the Schirmer tear
canaliculi shortly after birth. test (STT), cytology and microbial culture,
­Diagnostic Procedure  273

Canaliculi

Puncta

Lacrimal
sac

(a)

Nasolacrimal duct
Nasal puncta

(b)

Figure 7.3 A, B. Gross anatomy of the canine nasolacrimal duct system. Note the relationship of the
eyelids, puncta, canaliculi, lacrimal sac, nasolacrimal duct, and nasal puncta.

fluorescein dye passage test, normograde punc- Cytology and Microbial Cultures
tal and canalicular cannulation and lavage,
Cytology as well as both aerobic and anaerobic
nasal punctal cannulation and retrograde flush-
bacterial and fungal culture reveals inflamma-
ing, dacryocystorhinography, ultrasonography,
tory cells, foreign bodies, and microbial con-
computed tomography (CT), magnetic reso-
tent of mucopurulent ocular discharge. These
nance imaging (MRI), and lacrimal scintigra-
laboratory evaluations may be completed on
phy (see Chapter 4).
the discharge expressed from puncta, canali-
culi, and skin fistulae, or on that flushed from
the nasolacrimal duct system of dogs with
Schirmer Tear Test
dacryocystitis, before application of topical
The STT should be the first diagnostic test com- anesthetics or stains. Bacterial opportunists,
pleted during examination of a dog with epi- including Staphylococcus sp., Streptococcus sp.,
phora. It estimates total reflex aqueous tear Proteus sp., and Escherichia sp., are often cul-
production; volumes from dogs in excess of tured from the nasolacrimal duct system (and
25 mm per minute are consistent with the diag- the conjunctiva) of dogs with dacryocystitis.
nosis of stimulated lacrimation. Lacrimation
may overwhelm a functional nasolacrimal duct
Fluorescein Dye Passage
and result in epiphora. The causes of increased
lacrimation vary, and they relate to diseases that Fluorescein dye passage (i.e., Jones test) is the
cause red eye (e.g., conjunctivitis, keratitis, scle- primary clinical test of patency. It involves
ritis, uveitis, glaucoma, and orbital cellulitis). placing liquid fluorescein dye on the cornea
274 Canine Nasolacrimal and Lacrimal Systems: Disease and Surgery

and conjunctiva, and after several minutes Results of dacryocystorhinography will


have elapsed, both the nasal area and pharynx c­ onfirm nasolacrimal duct patency. This radio-
are examined with cobalt-­filtered or ultraviolet graphic contrast study involves injection of
light to confirm dye passage and duct patency. approximately 1 ml of a viscous, radiopaque dye
In a study evaluating fluorescein nasolacrimal through the cannulated canaliculi. Radiographs
transit times in normal dogs, transit times were are obtained as the dye passes through the nasol-
highly variable, ranging from 2 to 840 s, with acrimal duct system. Perforations, blockages,
cephalic conformation, snout length, and and deviations of the nasolacrimal duct are read-
reproductive status affecting the result. The ily detected on these images.
test was found not to be of clinical use in Advanced imaging studies (i.e., ultrasonog-
brachycephalic dogs as most of these dogs did raphy, CT, MRI, and scintigraphy) are also
not show dye passage at the 30-­min test cutoff. useful to confirm compression and occlusion
Failure of passage to the nares may be an indi- of the nasolacrimal duct system. In addition,
cation of physiological or functional inade- they are useful to determine the extent of pri-
quacy of the nasolacrimal duct system. mary disease in the nose and orbit. CT dacry-
ocystography and lacrimal scintigraphy are
utilized by ophthalmologists to facilitate
Nasolacrimal Flushing
diagnosis of nasolacrimal drainage disorders
A 24-­gauge intravenous catheter or nasolacri- with increased frequency.
mal cannula is preplaced on a 3-­ml syringe
containing a commercial eye wash, and a drop
of topical anesthetic is applied to the conjunc- ­Congenital Diseases
tiva. The lacrimal punctum and canaliculus
(usually the lower) are cannulated, and a small Reported congenital anomalies of the nasolac-
volume of eye wash is injected while observing rimal duct system include punctal atresia and
the contralateral punctum. When fluid passes micropuncta, canalicular and nasal lacrimal
through the opposite lacrimal punctum, it is duct atresia, misplacement of the punctum
gently occluded with finger pressure, and con- and canaliculus, displacement of the punctum
tinued injection into a normal nasolacrimal secondary to medial ventral entropion, dacry-
duct system will produce eye wash at the nos- ops, and canaliculops. Of these anomalies, lac-
trils or induced swallowing as the solution rimal punctal atresia is presented.
flows into the pharynx.
Retrograde nasolacrimal duct flushing is
Lacrimal Punctal Atresia
performed when a normograde flush is not
successful. In most dogs, general anesthesia is Punctal atresia is the most frequently diag-
required before cannulation of the nasal punc- nosed congenital anomaly. It may affect the
tum and retrograde flushing can be completed. superior, inferior, or both puncta, and it may be
either unilateral or bilateral (Figure 7.4). It
occurs in numerous breeds and is commonly
Radiographic and Other
seen in American Cocker Spaniels, Bedlington
Imaging Examinations
Terriers, Golden Retrievers, Miniature and Toy
Lateral and ventrodorsal open-­mouth nasal Poodles, and Samoyeds.
radiographs are useful in evaluation of the The diagnosis is confirmed by biomicro-
nasal bones along which the nasolacrimal duct scopic examination and normograde or retro-
passes. The nasolacrimal ducts are vulnerable grade nasolacrimal duct flushing. Superior
to traumatic laceration, erosion, or compres- punctal atresia is usually asymptomatic and
sion by infectious processes or nasal tumors. is diagnosed incidentally during routine
­Congenital Disease  275

Figure 7.4 Twelve-­week-­old Papillon puppy with


bilateral inferior punctal atresia, resulting in
marked epiphora.

biomicroscopic examinations. When inferior (a)


punctal atresia is present, epiphora is usually
present in puppies, and nasolacrimal flush-
ing is warranted. The conjunctiva over the
punctum will bulge during flushing. Ventral
punctal atresia is treated by surgical excision
of the ballooning conjunctiva (Figure 7.5a
and b). The affected eye is then treated with
topical antibiotic and corticosteroid solutions (b)
four times a day for 7–10 days until the punc-
tum is patent and epiphora is absent. Figure 7.5 Ventral punctal atresia. Note the
ballooning of the conjunctiva over the aplastic
punctum (a) during a normograde nasolacrimal
Micropunctum flush through the superior punctum. The
ballooning conjunctiva is excised with scissors
Incomplete development (i.e., micropunctum) (b) to create a new punctum.
or strictures of the ventral punctum causing
epiphora may be enlarged with a punctal dila- present, and the diagnosis is confirmed with a
tor, or the 1-­2-­3 snip technique and catheteri- dacryocystorhinograph. Therapeutic options
zation. Punctal strictures in humans have also are limited to surgery, and include conjunctival
been treated successfully with cauterization rhinostomy, conjunctival-­maxillary sinusot-
and the punctal pucker technique. omy, or conjunctival buccostomy. These proce-
dures attempt to create a permanent fistula
from the conjunctiva directly to the nasal turbi-
Atresia of the Canaliculus, nates, maxillary sinus, or mouth, respectively.
Nasolacrimal Sac,
and Nasolacrimal Duct
Congenital Puncta
Atresias of the canaliculus, nasolacrimal sac, or
and Canaliculi Misplacement
duct are rare. Congenital anomalies of the
nasolacrimal duct have been reported in cattle Congenital puncta and canaliculi misplace-
and the horse, but not in the dog. When the ment is often asymptomatic in dogs. When
ventral canaliculus, nasolacrimal sac, or nasol- chronic epiphora is present and relates to the
acrimal duct is missing, epiphora will be position of the ventral punctum, surgical
276 Canine Nasolacrimal and Lacrimal Systems: Disease and Surgery

repositioning is indicated. This procedure (Figure 7.6). This displacement is integral to


should be completed with the aid of an oper- the tear-­staining syndrome, commonly seen in
ating microscope. After routine presurgical the toy and brachycephalic breeds. The lacri-
preparation and positioning, the affected mal puncta are usually normal in these dogs,
punctum and canaliculus are cannulated with and the clinical signs relate to multiple factors,
a sterile, 24-­gauge intravenous catheter or including displacement of the ventral lacrimal
monofilament suture. This allows the oph- puncta and compression of the canaliculi by
thalmic surgeon to accurately microdissect the medioventral entropion. In addition, tight
the punctum and thin-­walled canaliculus and medial canthal ligaments displace the medial
move them through a conjunctival incision to canthus ventrally and, in combination with
the eyelid margin approximately 3 mm from medial canthal trichiasis and eyelid trichiasis,
the medial canthus. exacerbate tear spillage in these dogs. Oral tet-
racycline and metronidazole have been
reported as a therapy for tear staining, but nei-
­Developmental Disorders ther has any appreciable effect on tear produc-
tion or excretion. Their success relates to
Many brachycephalic and toy dogs have epi- reduced staining of the medial canthal region
phora related to multiple anomalies of the by bacteria rather than to control of the epi-
medial canthal region and inferior lacrimal phora. Therefore, they are used infrequently as
punctum. These anomalies are inherited as therapy today.
part of the facial development in these breeds The treatment of choice for this condition is
of dogs, and epiphora usually manifests in the a Hotz–Celsus repair of the medial ventral
first year of life. The inferior lacrimal puncta entropion in which a triangular piece of skin is
and canaliculi are commonly displaced inward excised with the apex of the triangle opposite
and ventrally by a subtle, medioventral entro- the lower lacrimal punctum or, preferably, a
pion, which rolls the medial eyelid margin into bilateral medial canthoplasty to correct the
the cornea and partially obstructs the lacrimal caruncular trichiasis and tight medial canthal
puncta and narrows the canalicular lumen ligaments.

Figure 7.6 Anomalies of the medial canthus of small breed of dogs that predispose to epiphora and pigmentary
keratitis. Note the caruncular trichiasis, the tight medial canthal ligaments that create a medial canthal trough,
and the medial ventral entropion that compresses the ventral lacrimal punctum and canaliculus.
­Developmental Disorder  277

Acquired Diseases
Acquired nasolacrimal disorders of the dog
include traumatic lacerations, dacryocystitis
and obstruction with foreign bodies, and inva-
sion or compression by neoplasms.

Lacerations
Facial trauma may result in lacerations of the
lacrimal puncta, canaliculi, medial canthus,
and eyelids. Lacerations of the canaliculi are
diagnosed with use of biomicroscopic examina-
tion and the bubble test, which involves cannu-
lation of both lacrimal puncta and injection of
air. The resultant bubbling allows the surgeon
to detect and cannulate the lacerated canalicu-
lar ends with a silastic tube. The lacerated eyelid
surfaces are then repaired by microsurgical
apposition of the tissues around the cannulated
duct. The eye is treated with topical antibiotic
Figure 7.7 A superior punctal and canalicular
solutions four times a day until the cannula is foreign body that caused dacryocystitis in a
removed (at approximately three weeks). These two-­year-­old Lhasa Apso. Note the mucopurulent
surgeries require the operation microscope and ocular discharge and conjunctivitis.
are best left to the specialist.
lavage, or they may be removed via a dacryo-
cystotomy. The skin incision for a dacryocysto-
Dacryocystitis and Foreign Bodies
tomy is ventral to the medial canthus over the
Dacryocystitis, with or without foreign bodies, lacrimal fossa. After removal of the foreign
occurs infrequently in the dog, and must be dif- body, the nasolacrimal duct system is then
ferentiated from abscesses secondary to the cannulated with a silastic tube and treated
canine carnassial tooth. Clinical manifestations with topical broad-­spectrum antibiotics while
of dacryocystitis and nasolacrimal duct foreign catheterized for approximately three weeks
bodies include epiphora, purulent conjunctival postoperatively.
discharge, punctal foreign bodies (Figure 7.7),
and late developing draining skin fistulas ven-
Neoplasia of the Nasolacrimal Duct
tral to the medial canthus. These foreign bodies
must be removed for effective therapy. Primary neoplasia of the nasolacrimal duct is
The diagnosis of dacryocystitis is confirmed rare in all species. Lymphoma is reported to
by (i) the nasolacrimal flush performed have invaded the lacrimal sac and to have
through the upper lacrimal punctum, (ii) the induced dacryocystitis. Pseudotumors of the
dacryocystorhinography, and (iii) cytological lacrimal canaliculus have been reported in a
examination of the contents from a nasolacri- dog. Tumors of nasal turbinates and the maxil-
mal lavage or from biopsies from tissues lary sinus, however, may compress or invade the
excised during surgical exploration. Foreign nasolacrimal ducts and spread into the orbit via
bodies may be flushed from the nasolacrimal the nasolacrimal foramen and cause epiphora,
duct system by retrograde or normograde mucopurulent, or serosanguineous ocular and
278 Canine Nasolacrimal and Lacrimal Systems: Disease and Surgery

nasal discharge, masses ventral to the medial The lacrimal glands of the orbit and the nicti-
canthus, and orbital signs, including prolapse of tating membrane are tubuloacinar and histo-
the third eyelid, enophthalmos, and conjuncti- logically similar. Ductules from these glands
val hyperemia. The diagnosis of nasal neoplasia deliver aqueous tear secretions into the con-
with involvement of the nasolacrimal duct sys- junctival fornices. In the dog, three to five duct-
tem is established by clinical examination, plain ules from the orbital lacrimal gland open into
and contrast radiography, and advanced multi- the dorsolateral conjunctival fornix, whereas
sectional imaging, and it is confirmed through the nictitans gland delivers aqueous tears onto
light microscopic evaluation of nasal biopsies. the corneal surface through multiple ducts
opening between lymphoid follicles on the pos-
terocentral (bulbar) third eyelid (Figure 7.8).
Section II: Lacrimal Secretory The relative contributions by each of the main
System: Disease and Surgery lacrimal glands to reflex tear secretion have been
investigated in the dog by surgical removal of
The “headwater” of the tear system is the lacri- either one or both glands and measurement of
mal glands, located dorsolateral of the globe the resulting tear production. Removal of both
and within the nictitating membrane. Tear glands resulted in near-­total absence of secre-
abnormalities are among the most common tions, thereby suggesting that accessory con-
causes of canine ocular surface disease. junctival glands may not be present in the dog,
Medical and surgical procedures for treatment or that they play an inconsequential role in
of tear-­deficient ocular surface diseases are fre- aqueous secretions. The role of each gland (i.e.,
quently performed in both general and small orbital or nictitans glands) in the production of
animal practices as well as in veterinary oph- basal secretions versus reflex tear secretions in
thalmology clinics. the dog has been investigated using the STTs I
and II. Surgical removal of either the lacrimal or
the tear gland of the nictitans does not signifi-
­ ormation and Dynamics
F cantly lower STT I measurements (total tear pro-
of Tear Components duction), but reduces by about 50% of the basal
tear measurements (STT II).
The precorneal tear film (PTF) is crucial for
the maintenance of ocular surface health and
clear vision, as it is the first refractive surface
of the eye. Its functions include primary oxy-
gen source to the avascular cornea, lubricant
between the lids and ocular surface, source of
protective antimicrobial proteins, and removal
of debris and exfoliated cells through drainage.
The PTF is classically described as a superim-
position of three structurally and functionally
unique layers consisting of lipid, aqueous, and
mucin components and, in some references, a
fourth innermost layer of glycocalyx extending
from the superficial layer of the ocular surface
epithelia (see Chapters 1 and 2). Tear film Figure 7.8 Scanning electron micrograph of the
thickness is a key variable in the study of nor- bulbar surface of the canine third eyelid
mal tears and dry eye diseases. In humans, cur- (nictitating membrane). A nictitans ductile
openings onto the posterocentral surface of the
rently accepted PTF thickness is estimated to third eyelid is well visualized. (Original
be 3.4 ± 2.6 μm. magnification, 800×.)
­Pathogenesis of Tear Film Diseas  279

The tear film, lacrimal glands, and eyelids act colonize affected eyes, thereby resulting in
together with the ocular surface as a functional increased incidence of ocular surface infections.
unit to preserve the quality of the refractive sur- Whatever the underlying cause of tear film dis-
face of the eye and to protect the globe from ease, ocular surface inflammation results, which
injury. Important to any discussion of the home- in turn becomes the cause and consequence of
ostasis of this functional unit is the mucosal cell damage, creating a self-­perpetuating cycle of
immune system. The conjunctiva forms a con- external ocular tissue deterioration.
tinuous mucosal surface from the eyelid margin
to the cornea and continuously contacts air-
Causes of Aqueous Tear Deficiency
borne antigens as well as those on adjacent eye-
lid skin and in the PTF. Conjunctival lymphoid Absence or reduction of lacrimal secretions may
follicles, routinely identified on the bulbar sur- result from a single disease process or a combi-
face of the nictitans in dogs, will undergo hyper- nation of conditions affecting the orbital and
plasia upon stimulation by a variety of nictitans glands (Box 7.1). The most frequent
pathogens. In addition to innate defense mecha- cause of keratoconjunctivitis sicca (KCS) is the
nisms, an increasing body of evidence supports immune-­mediated dacryoadenitis and subse-
the role of conjunctival lymphoid cells in the quent dacryoadenopathy in the adult dog. Drug-­
normal homeostasis of the ocular surface as part induced KCS may occur in the dog following
of the body’s larger MALT. systemic sulfonamide therapy or administration
of topical atropine. Systemically administered
sulfonamides causing KCS in dogs include
­ athogenesis of Tear
P phenazopyridine, sulfadiazine, sulfasalazine,
Film Disease and trimethoprim–sulfonamide combinations.
The mechanism for toxicity is not completely
Ocular surface health is ensured by a close rela- understood, but may be due to a T-­cell mediated
tionship between the PTF and normal adnexal response to proteins haptenated by oxidative
conformation and function. Normal tear sulfonamide metabolites. Certain nonsteroidal
p­roduction in dogs fluctuates slightly during the anti-­inflammatory drugs have also been associ-
day (differences of less than 2 mm/min) in a ated with KCS in dogs; oral administration of
p­redominantly nocturnal acrophase and etodolac (EtoGesic®, Fort Dodge Animal Health,
decreases with age. Tear production in puppies Fort Dodge, IA) for less than six months prior to
reaches normal levels by 9–10 weeks of age. the diagnosis of KCS was 4.2 times more likely to
Abnormalities in either the quantity or quality experience complete resolution of KCS than
of any tear component (lipid, aqueous, mucus) dogs that were treated for six months or longer.
may alter tear fluid dynamics and compromise Atropine administered as a preanesthetic
tear function. Hypertonicity and dehydration of agent transiently decreases tear production;
conjunctival and corneal epithelia are initial this effect is most noticeable in dogs with low
pathophysiological events associated with tear Schirmer’s values before drug administration.
deficiency. Hypoxia of the corneal epithelium Topically applied atropine, which is often
and subepithelial corneal stroma also occurs used empirically to treat anterior uveitis asso-
early in the course of tear film disease. Lack of ciated with ulcerative keratitis, may signifi-
appropriate lubrication results in frictional irri- cantly decrease tear production bilaterally in
tation of the ocular surface by the eyelids and the dog. Before prescribing topical atropine in
third eyelid. Potentially toxic tissue metabolites cases of ulcerative keratitis, it is important to
(i.e., lactic acid, desquamated cells, denatured document adequate aqueous tear production
mucus, and other “micro” debris) may accumu- with STTs in both eyes. Single dose 1% tropi-
late on the ocular surface as well. In tear-­ camide does not significantly lower tear pro-
deficient patients, microorganisms more readily duction rates as measured by the STT in
280 Canine Nasolacrimal and Lacrimal Systems: Disease and Surgery

Box 7.1 Causes of KCS in the Dog


Immune-­mediated dacryoadenitis/dacryoadenopathy
Canine distemper virus
Chronic blepharoconjunctivitis
Congenital acinar hypoplasia (i.e., congenital alacrima)
Drug-­induced KCS may occur in the dog following:
Short term:
Topical and general anesthetics
Topical and systemic atropine
Long-­term:
Systemic sulfonamide therapy (phenazopyridine, sulfadiazine, sulfasalazine, and trimethoprim–
sulfonamide combinations)
Nonsteroidals (Etodolac™)
Removal of nictitans gland and/or corrected nictitans gland prolapse
Uncorrected nictitans gland prolapse
Traumatic or inflammatory orbital diseases
Loss of parasympathetic innervation to lacrimal glands (cranial nerve VII)
Loss of sensory innervation (i.e., sensation) to the ocular surface (cranial nerve V)
Local irradiation of head neoplasms
Systemic metabolic diseases (hypothyroidism, diabetes mellitus, and Cushing’s disease)

normal dogs. Several breeds are dispropor- stromal malacia, descemetocele formation with
tionately affected by acquired KCS, thus sug- resultant staphyloma, and iris prolapse
gesting a genetic predisposition to this most (Figure 7.9). In most cases, however, onset of KCS
frequent immune-­mediated disease (Box 7.2). is more gradual, with increasing severity over a
period of several weeks. In the early stage of KCS,
affected eyes initially appear to be red and
Clinical Findings in KCS
inflamed, with intermittent mucoid or mucopu-
Clinical signs of KCS will vary depending on the rulent discharge. KCS may be misdiagnosed as an
period of time since onset and the extent of dry- irritant or primary bacterial conjunctivitis
ness. A very acute, severe form of KCS is some- (Figure 7.10). As the severity of the KCS increases,
times seen, in which the eye becomes acutely however, the ocular surface becomes lackluster,
painful in association with axial corneal ulcera- the conjunctiva appears to be extremely hypere-
tion. In such cases, suppurative inflammation mic, and persistent tenacious mucopurulent ocu-
may result in progressive corneal disease with lar discharge is observed (Figure 7.11). Progressive
keratitis characterized by extensive corneal vascu-
larization and pigmentation with or without
Box 7.2 Breeds at Highest Risk to KCS
ulceration may occur (Figure 7.12). The severe
English Bulldog pigmentary keratitis may be refractory to medical
West Highland White Terrier and surgical therapy.
Pug
Yorkshire Terrier
American Cocker Spaniel Diagnosis of Aqueous Tear Deficiency
Pekingese
The diagnosis of KCS is made on the basis of
Miniature Schnauzer
typical clinical signs, positive ocular staining
English Springer Spaniel
using vital stains, and reduced quantitative
­Qualitative Abnormalitie  281

Figure 7.12 Six-­year-­old male castrated


mixed-­breed dog with chronic KCS. Note the
Figure 7.9 Acute onset KCS in a five-­year-­old female marked conjunctival hyperemia, lackluster
Pug with mucopurulent discharge, hyperemic appearance to the corneal surface, and superficial
conjunctiva, and an infected axial corneal ulcer, stromal corneal neovascularization.
malacia, diffuse corneal edema, and ciliary flush.
tear readings. The STT I remains the standard
means for quantifying aqueous tear produc-
tion (see Chapter 4). STTs may be performed
either without (i.e., STT I) or with (i.e., STT II)
use of topical anesthetic. STT I measures the
ability of the eye to produce reflex tears in
addition to basal secretions, and is the most
commonly performed test, whereas STT II esti-
mates only basal tear secretion. In the clinical
setting, STT I readings in dogs are generally
interpreted as follows:

Figure 7.10 Four-­year-­old Boston Terrier with early 15 mm/min = normal production;
KCS. Note the mucoid ocular discharge, moderate 11–14 mm/min = early or subclinical KCS;
conjunctival hyperemia, and mild chemosis. This eye 6–10 mm/min = moderate or mild KCS; and
had an STT I measurement of 8 mm wetting/min.
5 mm/min = severe KCS.

­Qualitative Abnormalities

Problematic cases of KCS can occur in which


aqueous tear volume appears to be adequate
and other recognized causes of surface disease
(e.g., infection, frictional irritation, and inef-
fectual blinking) have been excluded. In such
instances, qualitative tear deficiency from an
abnormality of either the lipid or the mucin
tear components may be a primary (or a con-
Figure 7.11 Dog with early KCS. Note the intense
tributing) cause of the surface disease. These
conjunctival hyperemia, thick mucopurulent
discharge, and chronic keratitis characteristic of a variants of KCS are infrequent and require
subacute or chronic tear deficiency. additional diagnostics, including evaluation of
282 Canine Nasolacrimal and Lacrimal Systems: Disease and Surgery

the meibomian glands and their secretions, from conjunctival biopsy specimens provides an
and the preocular mucin with diffuse conjunc- indirect measure of mucin production.
tival inflammatory cell infiltrates may reduce
or eliminate goblet cells. Loss of conjunctival
goblet cells results in an unstable tear film, as ­ reatment of Tear
T
manifested by rapid breakup of the PTF, lack- Film Deficiencies
luster appearance of the ocular surface, and
corneal desiccation. Medical Treatment
Medical therapy is the primary means of treat-
Diagnosis of Qualitative ing tear-­deficient ocular surface disease, as
Tear Deficiencies selected drugs often stimulate sufficient levels
of tears to restore corneoconjunctival health.
Making the diagnosis of lipid tear abnormalities Specific treatment regimens are tailored to
depends on findings from a detailed examina- individual patients and are influenced by the
tion using a focused light and a magnifying underlying pathogenesis, disease severity, and
source. Swollen, rounded eyelid margins indi- owner’s ability to comply with recommended
cate acute or subacute marginal blepharitis. treatment schedules. Treatment generally
Hyperemia of the mucocutaneous junction, consists of some combination of the following:
with dry, crusty, porphyrin-­stained exudates on tear stimulation, tear replacement, topical
the lid margins, is also indicative of marginal and/or oral antimicrobial agents, mucinolyt-
blepharitis. The clinical diagnosis of canine ics, and anti-­inflammatory therapy (Box 7.3).
ocular mucin deficiency may be supported by
the results of a tear film breakup time (TBUT) Lacrimostimulants
test (Figure 7.13). The diagnosis may also be Lacrimostimulants, which are drugs adminis-
confirmed by the results of conjunctival biopsy tered to promote tear secretion, include two
and quantification of epithelial goblet cells. The
tear breakup time evaluates the ability of the
corneal surface to retain a homogeneous tear Box 7.3 Selected Drugs for the Treatment
covering. Determination of goblet cell numbers of Canine KCS
Topical antimicrobial agents
Mucinolytics – with excessive ocular
discharge
Anti-­inflammatory therapy (avoid in acute
KCS; need frequent exams)
Lacrimominics (see Chapter 3):
For aqueous deficiency: methylcellulose-
­and polyvinyl-­based preparations
For lipid deficiency: dextran-­and
viscoelastic-­based preparations
For mucin deficiency: lanolin-­, petrola-
Figure 7.13 TBUT test can be performed in the dog tum-­, and mineral oil-­based preparations
with some difficulty. Immediately after instillation of Lacrimostimulants:
one drop of topical fluorescein stain, the eyelids are
digitally held open, and the dispersion of fluorescein Immunomodulating: topical cyclosporine
is observed with a portable slit lamp biomicroscope (0.02–2%), tacrolimus (0.03–0.2%), and
using a cobalt blue filter. The TBUT is the mean time pimecrolimus (1%)
for the development of dark (dry) spots in the Cholinergic: oral pilocarpine
precorneal film.
­Treatment of Tear Film Deficiencie  283

categories of therapeutic agents: cholinergics preventing graft rejection after organ trans-
and immunomodulators. plantation. Although structurally nonho-
mologous, the mechanism of action of both
Cholinergic Agents CsA and tacrolimus is similar: T-­cell prolif-
The lacrimal gland is innervated by both the eration and activation are altered by the
parasympathetic and sympathetic branches of inhibition of interleukin (IL)-­2 gene expres-
the autonomic nervous system. The parasym- sion in CD4+ T helper lymphocytes. IL-­2
pathetic innervation of lacrimal gland has ena- transcription blockage leads to impaired T
bled cholinergic drugs to be used to stimulate helper and T cytotoxic proliferation. When
tear secretions in select neural deficiency administered systemically as an immuno-
cases. Ophthalmic pilocarpine solution has suppressive agent to humans with normal
been administered, either topically or orally, as tear flow, CsA stimulates lacrimal secretions.
a tear stimulant. The use of pilocarpine for dry The ability of topical CsA to stimulate tear
eye is indicated in cases of KCS resulting from production in the dog is well documented.
parasympathetic denervation of the lacrimal Most cases of canine KCS are presumed
glands and will only be effective if some func- immune-­mediated. CsA has been the primary
tional lacrimal gland remains. Oral adminis- treatment for KCS in the dog for over three dec-
tration consists of applying 1–2% ophthalmic ades and has now been approved for topical use
solution to the food; a safe initial oral dosage is in people with dry eye. Before the commercial
one drop of 2% topical pilocarpine per 10 kg of availability of CsA for ophthalmic use, 1–2%
body weight twice daily. oil-­based solutions were compounded from
10% oral CsA solution using a vegetable oil (i.e.,
Immunomodulating Agents olive or corn oil) solvent. Currently, either the
Cyclosporine A (CsA), a derivative of the 0.2% commercial ointment (Optimmune®;
fungus Tolypocladium inflatum, and tacroli- Schering-­Plough) is prescribed or different for-
mus (formally FK 506), a macrolide antibi- mulations (e.g., aqueous-­based; higher concen-
otic produced by Streptomyces tsukubaensis, trations of CsA) are obtained through
are both T-­cell activation inhibitors initially compounding pharmacies. Tacrolimus and
developed for their systemic uses in pimecrolimus (both calcineurin inhibitors)

(a) (b)

Figure 7.14 (a) Ten-­year-­old male castrated Shih Tzu with chronic KCS. The condition had been treated
intermittently with topical antibiotics and corticosteroids and twice-­daily topical cyclosporine therapy for four
years. (b) Same dog after substituting topical 0.02% tacrolimus ointment for the cyclosporine therapy. Patient
exhibited marked improvement with less mucopurulent ocular discharge and increased ocular comfort.
284 Canine Nasolacrimal and Lacrimal Systems: Disease and Surgery

have both been shown to improve tear produc- Antibacterials


tion in dogs (Figure 7.14a and b). In a recent Antibiotics with broad-­spectrum activity, such
study comparing the efficacy of topical tacroli- as triple antibiotic ointment or solution, are
mus compared to cyclosporine for treating KCS commonly administered to control secondary
in dogs, both drugs were found to significantly bacterial infections that occur in KCS cases
increase STT values in affected dogs over time. because of inadequate cleansing of the ocular
Further, tacrolimus was effective in increasing surface.
the STT values in four dogs nonresponsive to
cyclosporine. Investigations into new agents for
Mucinolytic–Anticollagenase Agents
the treatment of canine KCS are ongoing.
Good ocular hygiene (i.e., frequent cleansing of
A number of other presumed immune-­
discharges) is essential to minimize the accu-
mediated keratopathies have been treated
mulation of debris with degradative enzymes
successfully with topical immunomodulating
that contribute to ocular surface inflammation
therapy, including chronic superficial keratitis
and ulceration. To facilitate removal of copious
(pannus), plasmacytic conjunctivitis, eosino-
exudates and mucoid debris that may accom-
philic keratoconjunctivitis, superficial punc-
pany KCS, a 5–10% solution of acetylcysteine
tuate keratitis, and nodular granulomatous
may be applied topically two to four times daily.
episclerokeratitis. Although topical CsA ther-
In addition, the anticollagenase properties of
apy has been widely used for over three dec-
acetylcysteine may aid in preventing enzymatic
ades and appears relatively free of undesirable
degradation of surface tissues and may be use-
side effects, it does reach the systemic circula-
ful in treatment of corneal ulceration.
tion in both dogs and people. Chronic KCS
treated with topical immunosuppressive
therapy may also be a risk factor for develop- Anti-­inflammatory Therapy
ing primary corneal squamous cell carcinoma Anti-­inflammatory therapy may be a valuable
in dogs. adjunct to other medical therapy in improving
clinical signs of KCS. Topical corticosteroids are
Tear Substitutes (Lacrimomimetics) commonly administered to minimize conjunc-
Tear substitutes contain ingredients, or combi- tivitis, to alleviate discomfort, and to reduce cor-
nations of ingredients, to replace deficiencies neal opacities associated with chronic keratitis.
in one or more of the three primary tear com- Triple-­antibiotic ointment in combination with
ponents (i.e., aqueous, mucin, and lipid). Many dexamethasone is beneficial in many KCS
ophthalmic solutions and ointments are com- patients. Caution must be exercised, however,
mercially available for tear replacement ther- when administering topical corticosteroids,
apy (Box 7.4) and new products frequently because their use may significantly complicate
emerge on the market. Aqueous tear replace- healing of an ulcerated cornea.
ments are initially applied four to six times In addition to its marked lacrimostimulant
daily to affected eyes and are generally used effects, topical CsA also has beneficial anti-­
concurrently with other topical therapeutic inflammatory properties (e.g., reducing corneal
agents. Although more frequent applications inflammatory infiltrates). Use of CsA appears
(i.e., q 1 or 2 h) are often desirable, this treat- to be safe in the presence of corneal ulceration,
ment regime is rarely possible or practical for and CsA does not alter the ocular surface
the pet owner to accomplish. Despite their flora. CsA and other immunomodulators (e.g.,
limitations, lacrimomimetics are warranted in tacrolimus and pimecrolimus) may also be
the treatment of qualitative tear film abnor- beneficial in reducing corneal vascularization
malities and as an adjunct to lacrimostimulant in dogs with chronic keratitis from causes
therapy for quantitative tear film deficiencies. other than KCS.
­Treatment of Tear Film Deficiencie  285

Box 7.4 Tear Substitutesa

Viscosity agents/
Product concentration(s) Preservative Source

Polyvinyl alcohol solutions


AKWA tears PVA 1.4% BAC Akorn
Artificial tears PVA 1.4% BAC Many
LiquiTears PVA 1.4% BAC Major
Cellulose-­based
solutions
Refresh celluvisc CMC 1% None Allergan
Genteal mild HPMC 0.2% None Alcon
Genteal mild to HPMC 0.3% None Alcon
Moderate HPMC 0.3% None Alcon
Genteal moderate to CMC 0.25%
Severe
Gonak HPMC 2.5% BAC Akorn
Goniovisc HPMC 2.5% BAC Contacare
Bion tears HPMC 0.3% None Alcon
Isopto tears plain HPMC 0.5% BAC Alcon
Refresh tears CMC 0.5% None Allergan
Refresh plus CMC 0.5% None Allergan
Retaine CMC 0.5% None Ocusoft
Polymer combinations
GenTeal mild DEX-­70 0.1%, HPMC POLYQUAD or PF Alcon
lubricant 0.3%
Natural balance tears DEX-­70 0.1%, HPMC BAC Major
0.3%
Nature’s tears DEX-­70 0.1%, HPMC BAC Rugby
0.3%
GenTeal moderate DEX-­70 0.1%, Glycerin None Alcon
0.2%, HPMC 0.3%
Tears naturale forte DEX-­70 0.1%, Glycerin POLYQUAD Alcon
0.2%, HPMC 0.3%
Optixcare Carbomer, Sorbitol EDTA, Cetrimide CLC Medica
Clear eyes natural PVA 0.5%, Povidone BAC Meditech
0.6%
Tears Povidone 2%, PVA 2.7% POLYQUAD Focus
FreshKote lubricant PEG-­400 1%, PVA 1% BAC Alcon
Hypo tears HPMC 0.3%, DEX-­70 0.1% None Novartis
Bion tears Glycerin 0.3%, BAC Bausch &
Propylene glycol 1% Lomb
286 Canine Nasolacrimal and Lacrimal Systems: Disease and Surgery

Viscosity agents/
Product concentration(s) Preservative Source

Moisture eyes DEX-­70 0.1%, HPMC 0.8% BAC or PF Bausch & Lomb
Moisture eyes liquid PVA 1.4%, Povidone None Allergan
gel 0.6%
Refresh classic CMC 0.5%, Glycerin None Allergan
0.9%
Refresh optive CMC 0.5%, Glycerin 1%, None Allergan
PSB 0.5%
Refresh optive PEG-­400 0.4%, None Rugby
advanced Propylene glycol 0.3%
Lubricant eye drops PEG-­400 0.4%, POLYQUAD or PF Alcon
Propylene glycol 0.3%
Systane lubricant Glycerin 0.2%, HPMC BAC McNeil
0.2%, PEG-­400 1%
Visine dry eye relief Glycerin 0.2%, HPMC None McNeil
0.2%, PEG-­400 1%
Visine pure tears portables
Viscoelastic products
i-­drop vet gel Hyaluronate 0.3%, None I-­Med Pharma
Glycerin
i-­drop vet plus Hyaluronate 0.25% None I-­Med Pharma
Remend drops 0.4% Hyasent-­S None Bayer
Remend gel 0.75% Hyasent-­S None Bayer
Glycerin, propylene glycol, and PEG Products
Clear eyes pure relief Glycerin 0.25% None Meditech
Systane Propylene glycol 0.6% POLYQUAD Alcon
Opti-­free balance Propylene glycol 0.6% POLYQUAD Alcon
Moisture eyes Propylene glycol 0.95% None Bausch &
Lomb
Blink tears PEG-­400 0.25% Sodium Chlorite Abbott
Ointments
AKWA tears ointment White petrolatum 83%, None Akorn
MO 15%, lanolin 2%
Soothe night time White petrolatum 80%, None Bausch &
MO 20% Lomb
Refresh PM White petrolatum None Allergan
57.3%, MO 42.5%
Stye sterile lubricant White petrolatum None Meditech
57.7%, MO 31.9%
Puralube White petrolatum 85%, None Paddock
MO 15%
GenTeal nighttime PM White petrolatum 85%, None Novartis
MO 15%
Sterilube nighttie White petrolatum 85%, None FERA
MO 15%
­Treatment of Tear Film Deficiencie  287

Viscosity agents/
Product concentration(s) Preservative Source

Artificial tears White petrolatum 57.3, None Rugby


MO 42.5%
Systane nighttime White petrolatum 94%, None Alcon
MO 3%
Tears naturale PM White petrolatum 94%, None Alcon
MO 3%
Refresh lacri-­lube White petrolatum Chlorobutanol Allergan
56.8%, MO 42.5%
Advanced eye relief White petrolatum 80%, None Bausch &
nighttime MO 20% Lomb

BAC, benzalkonium chloride; CMC, carboxymethyl cellulose; DEX, dextran; EDTA, ethylenediaminetetraacetic acid;
GEL, gelatin; HEC, hydroxyethyl cellulose; HPMC, hydroxypropyl methylcellulose; MC, methylcellulose; MO, mineral
oil; PEG, polyethylene glycol; POLYQUAD, polyquaternium-­1; PSB, polysorbate 80; PVA, polyvinyl alcohol; PF,
preservative free.
a
Percentage composition given where information available.Compiled December 1, 2017, courtesy of Brandon
Haake, PharmD

Other Considerations in Aqueous which reduces exposure and enhances blinking.


Tear Deficiency Nasolacrimal puncta occlusion is commonly
used in humans as a tear-­conserving procedure
Cases of acute KCS may present with corneal
by blocking tear drainage; unfortunately in dogs
stromal ulceration requiring aggressive medical
the very low levels of tear production in canine
or surgical therapy (or both). Because opportun-
KCS do not benefit from this therapy.
istic infections may contribute to rapid degrada-
tion of ulcerated cornea, bacterial culture of the
Parotid Duct Transposition
ulcer margins with subsequent sensitivity test-
Physiological similarities between saliva and
ing is indicated. When corneal ulceration occurs
tear fluid, including similar osmolarity and pH,
as a sequela to KCS, local atropine administra-
led to the supposition that saliva might serve as
tion should be used judiciously and only for as
a substitute for tears. PDT surgery was subse-
long as is necessary to treat the concurrent uvei-
quently developed for humans to provide symp-
tis (and miosis), because surface drying will be
tomatic relief in cases of refractory KCS. From
exacerbated by its application. In cases of deep
the mid-­1960s to mid-­1980s, before CsA was
stromal ulceration or descemetocele formation,
available, this surgery was also being performed
reconstructive corneal surgery (i.e., conjuncti-
successfully in dogs affected with KCS nonre-
val grafting) may be necessary to stabilize the
sponsive to medical therapy. Following the
cornea and to stimulate fibrovascular resolution
introduction of CsA in 1987, the percentage of
of the ulceration.
KCS cases treated by PDT declined dramati-
cally. Nonetheless, the few dogs with persistent
absolute sicca (STT I, 0 mm/min) after several
Surgical Treatment of Chronic and/
weeks of medical treatment remain candidates
or Medical Refractory Tear
for PDT.
Deficiencies
The parotid gland is located at the junction
Surgical procedures indicated for treatment of of the head and neck, near the base of the ear
selected KCS cases are parotid duct transposi- canal. From a lateral perspective, the parotid
tion (PDT), which provides saliva as a substitute gland is a “V”-­shaped structure, with the apex
for tears, and permanent partial tarsorrhaphy, of the gland directed ventrally. The main duct
288 Canine Nasolacrimal and Lacrimal Systems: Disease and Surgery

is formed by the convergence of two or three


small branches arising from the ventral ante-
rior border of the gland and uniting over the
masseter muscle, several millimeters from the
gland. The duct extends subcutaneously over
the surface of the masseter muscle, courses
forward across the face, and opens into the
buccal cavity at a single papilla slightly poste-
rior and lateral to the fourth upper premolar
tooth and rostral to the zygomatic papilla.
Access to the parotid duct is by either the open
approach (through the skin) or the closed pro-
cedure (through the mouth and buccal
mucosa). Duct size and length vary depending
Figure 7.15 Seven-­year-­old female spayed
on the breed, with mesocephalic breeds having Yorkshire Terrier three months after PDT, showing
a diameter of approximately 1.5 mm and a precipitates on the ocular surface and eyelids.
length of approximately 6 cm.

alter the pH and mineral content of saliva; a


Complications, Sequelae,
number of anecdotal improvements have been
and Postoperative Considerations
discussed in various non-­peer-­reviewed forums,
Various postoperative complications have been
including oral supplementation with tomato
reported following PDT surgery. Intraoperative
juice, vitamin C, calcium carbonate, buttermilk,
twisting, laceration, or trauma to the parotid
and systemic carbonic anhydrase inhibitors.
duct may occur with either the closed or the
Continued use of topical CsA or similar agent
open PDT procedure. Some surgeons indicate
also appears to be helpful in reducing irritation
a greater chance of twisting and damaging the
from mineral deposits, probably by virtue of its
duct with the closed approach; potential diffi-
lubricant, mucinogenic, and anti-­inflammatory
culties associated with the open PDT proce-
properties. Surgical remedies include (i) partial
dure include trauma associated with dissection
duct ligation – ligation of one to three accessory
of the highly vascular and innervated facial tis-
branches at the beginning of the duct just
sues, increased postoperative swelling, and
beneath the parotid gland (this is the most prom-
potential discomfort from the extensive surgi-
ising technique), (ii) reversal of the surgery, and
cal dissection. Causes for delayed failure in
(iii) enucleation. Following PDT, the bacterial
PDT surgery include retraction of the papilla
flora of the eyes changes significantly and will
into the subcutaneous space, fibrous closure of
consist of large numbers of mixed bacteria gen-
the conjunctival opening, occlusion of the duct
era, with many uncommon isolates and some
by sialoliths, and acute or chronic sialadenitis.
potential pathogens.
Saliva contains higher concentrations of
minerals (especially at high rates of flow) as com-
pared to tears and owners should be advised that Partial Tarsorrhaphy
mineral deposits are considered a normal sequel A partial permanent tarsorrhaphy, or lateral or
on the cornea and eyelid margins after PDT sur- medial canthoplasty may be beneficial in dogs
gery (Figure 7.15). Medical treatments of this not with KCS, especially among brachycephalic
infrequent complications include (i) instillation breeds, to afford greater corneal protection and
of a chelating solution containing 1–2% EDTA to conserve existing tears. Lateral canthoplasty
(ethylenediaminetetraacetic acid), (ii) oral doxy- is easier to perform, but medial canthoplasty
cycline as a chelating agent, and (iii) attempts to provides additional protection from medial
­Cysts and Neoplasms of the Lacrimal Secretory Syste  289

canthal trichiasis, especially in brachycephalic Depending on the site of origin, cysts may
breeds (see Chapter 6). distend the conjunctiva and protrude into the
palpebral fissure, expand within the orbit and
Replacement of Prolapsed cause displacement of the globe, or both.
Nictitans Gland Possible causes include developmental defects,
Removing a prolapsed nictitans gland or allow- blunt trauma, foreign body injury, or inflam-
ing chronic prolapse without treatment may mation affecting the ducts. Basset Hounds and
predispose an affected eye to KCS. Repair of a Labrador Retrievers may be predisposed. As a
prolapsed nictitans gland using an appropriate fibrosing agent, intralesional tetracycline has
replacement procedure may prevent the sequela been used to treat periocular cysts involving
of KCS. A number of replacement techniques the zygomatic salivary gland. However, given
have been described, and the reader is referred the necrotizing potential of injectable tetracy-
to elsewhere in this text for more discussion of clines and concern about possible conjunctival
this topic (see Chapter 8). necrosis and severe periocular inflammation,
this technique is not routinely recommended
for treatment of lacrimal gland cysts.
­ ysts and Neoplasms of the
C Although lacrimal neoplasms are also
Lacrimal Secretory System uncommon in the dog, primary adenomas
and adenocarcinomas of the orbital and nicti-
Cysts involving lacrimal tissue, though uncom- tans glands have been reported. These tumors
mon, have been reported and may originate tend to be locally invasive and have a guarded
from either the orbital or the nictitans glands. prognosis.
290

Canine Conjunctivae and Nictitating Membrane: Disease


and Surgery
Revised from 6th edition of Veterinary Ophthalmology, Chapter 18: Diseases and Surgery of the Canine Conjunctiva and Nictitating
Membrane, by Claudia Hartley and Diane V.H. Hendrix

­Conjunctiva epidermis of the eyelid, just as the bulbar con-


junctiva is continuous with the corneal epithe-
The conjunctiva is associated with many lium. Medially, the conjunctiva covers both the
adnexal and bulbar diseases because of its palpebral (outer) and bulbar (deep) surfaces of
exposure and close proximity to ocular struc- the nictitating membrane (NM).
tures. Thorough physical and ocular examina-
tions should be performed on dogs with signs
of conjunctival disease because some of these ­Microscopic Anatomy
diseases can be an indication of systemic and/
or severe ocular disease. The cause of conjunc- The conjunctiva is composed of nonkerati-
tival disease can often be determined solely on nized, stratified squamous epithelium and an
the basis of history and complete ophthalmic underlying substantia propria. The substantia
examination. propria is divided into superficial and deep lay-
ers. The superficial layer contains many lym-
phoid nodules that are the major components
­Functional Anatomy of the conjunctiva-­associated lymphoid tissue
and Physiology (CALT). The purpose of CALT is to receive
antigen and to present it to circulating mono-
The conjunctiva, a mucous membrane, plays a nuclear cells. The lymphatics that drain this
role in tear dynamics, immunological protec- area represent the only known lymphatic
tion of the eye, ocular movement, and corneal drainage of the canine eye. The deeper layer of
healing. The conjunctiva lines the inside of the the substantia propria is fibrous and contains
eyelids, beginning at the eyelid margin and the conjunctival vessels and nerves. M cells
extending deep toward the orbit to create a for- have been reported in the nictitans, but not in
nix (conjunctival sac), at which it reverses direc- the remaining conjunctiva.
tion and extends over the globe to the limbus. Goblet cells are also present in the epithelial
These three major areas are referred to as the layer of the conjunctiva. These cells produce a
palpebral conjunctiva, the fornix (i.e., “cul-­de-­sac”), gel-­like mucin, which forms the deepest of the
and the bulbar conjunctiva, respectively. The three layers of the preocular (i.e., precorneal)
palpebral conjunctiva is continuous with the tear film and protects the ocular surface by

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
­Normal Bacterial and Fungal Flor  291

trapping both debris and bacteria and by pro- aerobes are the most commonly cultured, with
viding a medium for adherence of immuno- Staphylococcus spp., Bacillus spp., Corynebac-
globulins (i.e., immunoglobulin A) and terium spp., and Streptococcus spp. predomi-
microbicidal lysozymes. For biopsy, the areas nating. Gram-­negative bacteria have been
of highest goblet cell density in the dog are the recovered from the conjunctival sac in 7–8% of
lower nasal fornix, lower middle fornix, and normal dogs. Anaerobes are rarely isolated.
lower nasal tarsal regions. While fungi are rare, the most commonly cul-
tured are Cladosporium oxysporum, Curvu-
laria lunata, and Malassezia pachydermatis.
­ ascular Supply
V The normal conjunctival flora appears to vary
and Innervation with the season.

The vascular supply of the conjunctiva is


Conjunctival Cytology
extensive. Branches of the dorsal and ventral
palpebral and malar arteries, as well as ter- Cytological examination of scrapings from
minal branches from the anterior ciliary normal conjunctiva reveals sheets of epithelial
arteries, provide the conjunctiva with its cells with large, round, homogeneous nuclei
blood supply. Innervation is provided by and abundant cytoplasm. Keratinized epithe-
branches of the long ciliary, zygomaticofa- lial cells are uncommon. Bacteria are occa-
cial, zygomaticotemporal, infratrochlear, sionally seen and leukocytes are rare.
and frontal nerves. Cytological samples are easy to obtain from
the dorsal and ventral conjunctiva. After
administration of a topical anesthetic, a cyto-
­ ormal Bacterial
N brush, the blunt end of a scalpel blade, or even
and Fungal Flora an impression using a membrane filter can be
effective for obtaining cells. After infection,
Bacteria can be cultured from the conjunctival injury, or other insults, the conjunctival cytol-
sac in 46–90% of normal dogs. Gram-­positive ogy changes (Table 8.1).

Table 8.1 Summary of cytology in conjunctivitis.

Cause cells Conjunctival cells Inflammatory Mucin Organisms

Normal Few nonkeratinized sheets Few neutrophils Limited Few bacteria


Bacterial More nonkeratinized; Mainly neutrophils Moderate Frequent
keratinized – later
Viral Early – more nonkeratinized Mainly lymphocytes Moderate Possible
Distemper Late – more keratinized Mainly neutrophils Heavy Usually no
inclusions
Parasitic More keratinized Mainly eosinophils and Moderate Possible
Thelazia lymphocytes
Fungus Mainly neutrophils Variable
Allergy Variable Mainly eosinophils, plasma cells, Little
and lymphocytes
KCS pigment Keratinization Neutrophils, goblet cells Variable Variable
cells bacteria
292 Canine Conjunctivae and Nictitating Membrane: Disease and Surgery

­ eneral Response
G KCS, anterior uveitis, glaucoma, orbital dis-
to Disease ease, and toxic or septic shock. Conjunctival
hyperemia should be differentiated from epis-
The conjunctiva responds to insult with a lim- cleral injection and ciliary flush, which occur
ited number of mechanisms. Chemosis, hypere- with glaucoma and anterior uveitis. Generally,
mia, blepharospasm, and cellular exudation the conjunctival vessels are smaller in diame-
characterize acute conjunctivitis (Figure 8.1). ter, have a branching pattern, blanch quickly
The loose arrangement of the conjunctival with topical application of 1–2% epinephrine,
stroma permits extensive edema to develop rap- and are mobile. Episcleral vessels are larger in
idly after trauma or exposure to allergens or tox- diameter, do not branch, do not blanch
ins, and the vast blood supply as well as the quickly with topical application of epineph-
lymphoid tissue allows acute development of rine, and are not mobile. While the vessels
hyperemia and a cellular response. Goblet cell associated with ciliary flush form a branching
proliferation occurs with keratoconjunctivitis network near the limbus, the vessels’ other
sicca (KCS), chronic conjunctivitis, and vitamin characteristics are similar to those seen with
A deficiency. Conjunctival flora is altered in dogs episcleral vessels.
with various diseases. Bacteria are more likely to
be isolated from the conjunctiva of dogs with
ulcerative keratitis than from dogs with healthy ­Infectious Conjunctivitis
eyes. Cytological and culture differences
between the conjunctiva of dogs with atopic der- Infectious conjunctivitis indicates the associa-
matitis and normal dogs found that affected tion with specific pathogens and is uncommon
dogs had significantly more bacteria, keratinized in the dog.
and nonkeratinized epithelial cells, eosinophils,
and lymphocytes, and had more positive cul- Bacterial Conjunctivitis
tures regardless of clinical parameters.
Ocular redness, which can result from Primary bacterial conjunctivitis is an uncom-
­conjunctival hyperemia or episcleral conges- mon disease in the dog. In most cases, bacterial
tion, occurs with many diseases, including conjunctivitis develops secondary to eyelid
ab­normal eyelid conformation, abnormal abnormalities or KCS. Bacterial conjunctivitis
cilia, allergic conjunctivitis, corneal disease, is usually caused by Staphylococcus spp. and
other Gram-­positive organisms. Cytological
examination of conjunctival scrapings from
dogs with bacterial conjunctivitis can help to
confirm the diagnosis. Neutrophils with few
mononuclear cells, many bacteria, and
de­generating epithelial cells are present in
acute infections (Figure 8.2). In chronic
d­isease, neutrophils remain the predominant
cell type, but there are many more mononu-
clear cells. Additionally, degenerate or
ke­ratinized epithelial cells are seen with the
presence of bacteria being variable. Pending
culture results, topical chloramphenicol,
Figure 8.1 Neutrophils, cocci, and conjunctival
erythromycin or bacitracin, neomycin, and
epithelial cells in a cytological specimen from a
dog with bacterial conjunctivitis. (Diff Quik; original polymyxin B can be used for Gram-­positive
magnification, 330×.) bacteria conjunctivitis, and tobramycin,
­Infectious Conjunctiviti  293

Conjunctival hyperemia, chemosis, and exudate

Schirmer tear test

Reduced levels (<10 mm/min) Normal or elevated levels (20+ mm wetting/min)

Suspect keratoconjunctivitis sicca (KCS) Stain with fluorescein (observe any cornea, or conjunctiva
retention, and nasolacrimal passage)

Treat: artifical tears, antibiotics,


corticosteroids, and cyclosporine Nasolacrimal passage No nasolacrimal passage
Periodic examinations

Evaluate eyelids: entropion, Nasolacrimal flush


distichia, ectropion, etc.
Evaluate cornea and
inner eye Treat with antibiotics:
Evaluate globe position: corticosteroids.
Enophthalmia, etc. Re-examination

Evaluate conjunctival surfaces and exudates


Surfaces:
Diffuse hyperemia: bacterial and viral causes
Focal hyperemia: foreign body
Pigmentation: any chronic inflammation, KCS
Follicles: chronic inflammation, allergic and parasitic
causes
Exudates:
Serous to mucus: allergic; limited to no bacterial involvement
Mucus: early keratoconjunctivitis sicca; early bacterial involvement
Mucopurulent: bacterial involvement
Purulent: bacterial involvement

Conjunctival cytology

Eliminate any predisposing disorder


Treat any primary conjunctivitis

Figure 8.2 Clinical strategy for the diagnosis and treatment of conjunctivitis of the dog.

gentamicin, or topical bacitracin, neomycin, Of 30 dogs with clinical conjunctivitis, 5 were


and polymyxin B can be used for bacterial con- positive for CHV-­1 and 2 for canine adenovi-
junctivitis caused by Gram-­negative bacteria. rus-­2. An outbreak of CHV-­1 in a closed colony
of Beagles caused conjunctivitis and keratitis
in all dogs, ulcers in 26% of dogs (punctate,
Viral Conjunctivitis
dendritic, or geographic), and nonulcerative
Viral conjunctivitis has been most commonly keratitis in 19% of dogs. All dogs tested were
associated with canine distemper virus; how- positive for CHV-­1 on PCR and virus isolation.
ever, a recent virological survey and other The conjunctivitis began to decrease in sever-
research added canine herpesvirus-­1 (CHV-­1). ity over the following 15 days and returned to
294 Canine Conjunctivae and Nictitating Membrane: Disease and Surgery

antigens can be detected using direct immu-


nofluorescence and PCR. Cytoplasmic inclu-
sion bodies may be found in the conjunctival
epithelial cells after six days of infection and
are seen more frequently in cells acquired
from the NM; however, these inclusions are
scarce and infrequently seen.

Fungal Conjunctivitis
Fungal conjunctivitis is very rare in the dog.
Infection with Blastomyces dermatitidis can
cause nodule formation in the inferior con-
junctiva. The diagnosis can be made on the
Figure 8.3 Dog with experimentally induced basis of cytology or biopsy results. Treatment
recurrent CHV-­1 conjunctivitis in a dog. (Photo with systemic itraconazole may resolve the
courtesy of Dr Eric Ledbetter.)
condition.

normal by day 35 (Figure 8.3). No dogs devel-


Rickettsial Conjunctivitis
oped keratitis or signs of systemic disease.
Ocular viral shedding was detected in all Infection with Rickettsia rickettsii is frequently
infected dogs between days 3 and 10 after associated with ocular lesions of the conjunc-
infection. All infected dogs also developed tiva, uvea, and retina. Evidence of conjunctivi-
CHV-­1 serum neutralizing antibody titers, tis usually begins with the onset of fever and
beginning at 7 days after inoculation and peak- includes conjunctival hyperemia, chemosis,
ing on day 21. petechial hemorrhages, and a mucopurulent
Recrudescent CHV-­1 disease has been to purulent ocular discharge. Canine ehrlichi-
induced in dogs with latent CHV-­1 infection by osis can cause conjunctival hyperemia, serous
administration of an immunosuppressive dos- ocular discharge, conjunctival hemorrhages,
age of prednisolone for seven days. Bilateral anterior uveitis, and retinal hemorrhages.
mild-­to-­moderate conjunctivitis, characterized
by intermittent blepharospasm, conjunctival Parasitic Conjunctivitis
hyperemia, chemosis, and mucoid-­to-­ Ocular thelaziasis occurs in the western United
mucopurulent ocular discharge or keratitis, States, Europe, and Southeast Asia. Thelazia is
was detected in 83% of dogs between days 3 a nematode that can be found under the NM
and 18 after initiating the prednisolone. and in the conjunctival sac and nasolacrimal
Canine distemper virus is associated with duct. Both Thelazia callipaeda and Thelazia
conjunctivitis, chorioretinitis, KCS, and optic californiensis infect the dog. The milky-­white
neuritis. Conjunctivitis generally occurs with worms are approximately 10–14 mm long. The
the rhinitis and tracheobronchitis that accom- lateral serrations of the cuticle of the nema-
panies the initial febrile episode; the neuro- todes cause mechanical damage to the con-
logical and ocular signs occur about a week junctiva and cornea leading to lacrimal
later. A mucopurulent discharge is often secretions upon which nonbiting diptera feed.
p­resent. Initially, mononuclear cells are seen The adult nematodes live under the eyelids or
on cytology. Later, the number of neutrophils behind the nictitans.
increases, and plasma cells, goblet cells, and Musca autumnalis in North America and
cellular debris are seen. Distemper viral Phortica variegata in Asia are known
­Noninfectious Conjunctiviti  295

intermediate hosts. Foxes and wolves may be


important in the spread and maintenance of
disease. The parasitic infection causes a uni-
lateral or bilateral purulent conjunctivitis
with blepharospasm, epiphora, conjunctivi-
tis, keratitis, and intense lacrimal secretion.
Topical moxidectin (1% aqueous solution)
and tetramisole (0.5% solution), spot-­on imi-
dacloprid (10%) and moxidectin (2.5%), and
physical removal of the nematodes are effec-
tive treatments.
Figure 8.4 Chemosis in a dog associated with a
bee sting.

­Noninfectious Conjunctivitis
by histamine and immunoglobulin E after food
absorption; drug administration; and enveno-
Allergic Conjunctivitis
mation by ant, bee, wasp, or hornet stings as
Allergic conjunctivitis occurs frequently in the well as spider bites (Figure 8.4). The chemosis
dog and is often a component of atopic derma- is often bilateral, and the actual area of trauma
titis. Atopy is a type 1 hypersensitivity reaction. (if caused by an insect) is rarely identified and
The common allergens are pollens, molds, and may be distant from the eyes. These cases usu-
dust mites. Clinical signs include conjunctival ally respond rapidly to intravenous or intra-
hyperemia, chemosis, facial pruritis, periocu- muscular short-­acting corticosteroids and an
lar alopecia, and ocular discharge. With antihistamine with or without topical corticos-
chronic antigenic stimulation, conjunctival teroid ophthalmic ointments.
lymphoid follicles develop. History, physical
examination, and intradermal skin testing are
Follicular Conjunctivitis
used to make the diagnosis of atopy in the dog.
Results of cytology and histopathology indi- Follicular conjunctivitis develops secondary to
cate eosinophils (even a single one) on cyto- chronic antigenic stimulation. There is no evi-
logical examinations of conjunctival scrapings dence to link follicle formation to a viral or
are considered to be diagnostic for an allergic bacterial cause. Semitransparent follicles form
process; however, plasma cells and lympho- primarily on the bulbar surface of the NM, but
cytes are more commonly seen with allergic they may also form elsewhere on the conjunc-
responses in the dog. tiva (Figure 8.5). The follicles on the bulbar
Avoidance of the offending allergen, hypo- surface of the NM that are present with this
sensitization, and pharmacological modifica- disease greatly outnumber those normally
tion of the clinical signs are the primary forms seen, and they can be significantly larger.
of treatment. Intermittent use of a topical oph- Frequently, hyperemia of the conjunctiva and
thalmic hydrocortisone or dexamethasone a mucoid ocular discharge are present concur-
may be necessary to relieve clinical signs. rently. This condition occurs most frequently
Topical antihistamines, such as naphazoline, in dogs younger than 18 months of age. The
and mast cell stabilizers may have some bene- diagnosis is made on the basis of characteris-
fit, but studies on their efficacy in the dog have tic clinical signs. Cytological results of con-
not been reported. junctival scrapings will confirm the diagnosis
Intense chemosis and blepharedema may by revealing the lymphoid nature of the folli-
occur as an immediate-­type reaction mediated cles. Most cases respond to treatment with
296 Canine Conjunctivae and Nictitating Membrane: Disease and Surgery

­ onjunctivitis Associated
C
with Tear Deficiencies

KCS is a frequent cause of conjunctivitis in the


dog, and it is the most common cause of sec-
ondary bacterial conjunctivitis. Thus, the
Schirmer tear test (STT) should be performed
on all dogs with conjunctivitis. Cytological
examination of conjunctival scrapings from
dogs with chronic KCS reveals increased
Figure 8.5 Follicular conjunctivitis involving the mucus, goblet cells, and keratinization; cytol-
bulbar conjunctiva of the NM. ogy from dogs with acute KCS reveals bacteria,
neutrophils, mucus, and debris. Treatment of
KCS with cyclosporine has been shown to
saline irrigation and symptomatic use of oph- result in greater intraepithelial mucin quanti-
thalmic dexamethasone administered three to ties in vivo and to promote goblet cell differen-
four times daily. tiation in vitro. Treatment with cyclosporine,
tacrolimus, or pimecrolimus decreases the
Environmental Irritants conjunctival inflammation and mucous dis-
and Contact Hypersensitivity charge associated with KCS.

Over 60% of the dogs deployed to assist in relief


efforts at the World Trade Center site following ­Ligneous Conjunctivitis
the terrorist attacks developed acute conjuncti-
val irritation characterized by severe conjunc- Ligneous conjunctivitis is a rare disorder in
tival hyperemia, tearing, squinting, and face dogs that results in thickened, hyperemic pal-
rubbing. Conjunctival irritation and fatigue pebral conjunctivae with proliferative, opaque
were the most common health problems to membranes. It has been reported in four
affect the dogs. The irritation was secondary to Doberman Pinschers, a Golden Retriever, and
exposure to toxic chemicals, smoke, and mas- a Yorkshire Terrier. There are varying degrees
sive amounts of particulate matter. Affected of concurrent systemic illness. Histologically,
animals were treated by means of gentle irriga- the affected conjunctiva has a thick, amor-
tion of the conjunctival fornices with eye phous, eosinophilic, hyaline-­like material in
solution. the substantia propria, with a moderate mono-
Ophthalmic medications can occasionally nuclear infiltrate. Topical therapies have
lead to contact hypersensitivity reactions, included corticosteroids, heparin, and cyclo-
which are exhibited by blepharitis and con- sporine or tacrolimus. Systemic treatment with
junctivitis. Neomycin, thimerosal, and benza- prednisone, azathioprine, fresh frozen plasma,
lkonium chloride are the most likely drugs danazol, and diethylstilbestrol has been
used in canine ophthalmology that can cause attempted but generally yields poor results.
this reaction. Diagnosis and treatment involve
cessation of all medications for one week.
While any medication can be irritating in cer- ­Conjunctival Neoplasia
tain individuals, some medications such as
topical pilocarpine (pH 4–5) are notorious for Melanomas, squamous cell carcinomas, angi-
causing immediate conjunctival hyperemia oendotheliomatosis, mast cell tumors, heman-
and chemosis. giomas, hemangiosarcomas, angiokeratomas,
­Non-­neoplastic Conjunctival Masse  297

papillomas, lymphosarcomas, histiocytomas,


and transmissible venereal tumors all may
affect the canine conjunctiva. The paucity of
large studies and case reports, however, sup-
ports the clinical impression that conjunctival
neoplasia occurs infrequently in the dog.
Melanomas of the conjunctiva most com-
monly involve the NM, but they have also been
reported to originate from the upper palpebral
conjunctiva. These tumors tend to be malig-
nant, and recurrences and metastasis are com-
Figure 8.6 Multiple papillomas on the skin and
mon. Combined excision and cryotherapy bulbar conjunctiva. (Photo courtesy of Dr Nancy
appear to be the most effective treatment. McLean.)
Mast cell tumors can arise from the bulbar or
palpebral conjunctiva or the NM. Some dogs
may have a history of intermittent swelling and canine oral papillomavirus DNA. While most
redness of the conjunctiva. These tumors are lesions in young dogs regress spontaneously,
easily diagnosed via fine needle aspirate. Surgical excision is curative and may be necessary if the
excision is usually curative. Conjunctival mast lesion is irritating.
cell tumors have a low risk of recurrence and are Lymphosarcoma can infiltrate the conjunc-
unlikely to metastasize regardless of tumor tiva causing thickening. Cytology of a con-
grade or having incomplete surgical margins. junctival scraping may be diagnostic for
Squamous cell carcinoma of the perilimbal area lymphosarcoma, but in one known case of
is seen infrequently. These tumors are white to lymphosarcoma, a scraping revealed only reac-
pink, elevated, and papillomatous. Conjunctival tive lymphoid hyperplasia. While conjunctival
hemangiomas and hemangiosarcomas tend to lymphosarcoma is usually considered to be
occur at the nonpigmented, leading edge of the associated with systemic lymphosarcoma,
NM, and at the temporal bulbar conjunctiva. apparent ocular extranodal presentation has
Hemangiosarcomas of the conjunctiva can been reported with a T-­cell phenotype.
encroach on the cornea, thereby causing corneal Canine lobular orbital adenomas can appear
edema and vascularization. There is also a linear as a subconjunctival mass, eyelid swelling, or
trend showing an increased risk of tumor exophthalmos. The masses are either nodular
de­velopment with increased UV exposure, and or solid and extend into the orbit. These can be
there is a statistically significant risk for bilateral and commonly recur after excision.
c­onjunctival hemangiosarcoma development, Histopathology reveals well-­differentiated,
compared to hemangioma, with increased UV lobulated, glandular tissue resembling either
levels. Resection appears to be curative in most lacrimal or zygomatic salivary gland with a
cases, but recurrences are possible. Metastasis mucoserous secretory pattern and a complete
has not been confirmed. lack of ductular structures.
Papillomatosis occurs on the palpebral and
bulbar conjunctivae as well as the NM. The
lesions are well demarcated, rough, and papil- ­ on-­neoplastic
N
lary or sessile (Figure 8.6). Histopathology Conjunctival Masses
shows various degrees of epithelial hyperpla-
sia, acanthosis, hyperkeratosis with koilocyto- Non-­neoplastic conjunctival masses can be
sis, and vascular and connective tissue cores. inflammatory nodules, dermoids, displaced
Some lesions are positive for gene fragments of orbital fat, or cysts. Specific inflammatory
298 Canine Conjunctivae and Nictitating Membrane: Disease and Surgery

diseases of the sclera, including episcleritis weeks. Cryotherapy or intralesional triamci-


and scleritis, cause conjunctival hyperemia nolone at 4–12 mg per eye, with higher dosages
and swelling; they are described in the corneal for larger dogs, can also be used. Ocular nodu-
Chapter 9. lar fasciitis, which may be a different disease
syndrome, usually causes subconjunctival,
scleral, corneal, nictitans, limbal, and eyelid
Inflammatory Masses
masses. Histopathologically, fibroblasts and
Nodular granulomatous episclerokeratitis, abundant reticulin formation are the primary
fibrous histiocytoma, and recurrent prolifera- changes, with lesser numbers of lymphocytes,
tive keratoconjunctivitis are thought to repre- plasma cells, and histiocytes. Excision of the
sent very similar diseases, or even an identical lesions, even when incomplete, is curative.
disease syndrome. Collies appear to be predis-
posed, but the disease occurs in many breeds.
Dermoids
This group of non-­neoplastic diseases primar-
ily affecting the cornea, limbus, episclera, and Dermoids are benign congenital masses of ecto-
nictitans often presents as a subconjunctival dermal and mesodermal origin usually affecting
mass. Limbal masses infiltrate the corneal the lateral limbal region, but they can also
stroma causing vascularization and edema involve the cornea, sclera, conjunctiva, eyelid,
(Figure 8.7). Histopathologically, the lesions or NM (Figure 8.8). Frequently, the presence of
are primarily granulomatous with lympho- a dermoid is not appreciated until long, coarse
cytes, plasma cells, histiocytes, fibroblasts, and hair extends from the surface and causes irrita-
reticulin formation. The lesions tend to recur tion. Histopathologically, the tumor resembles
when excised, but excision with adjunctive normal haired skin, and excision is curative.
cryotherapy is reported to be a successful mode
of therapy. Some lesions will respond to 1%
Subconjunctival Fat Prolapse
ophthalmic prednisolone acetate with treat-
ment initiated q.i.d. and very gradually tapered Subconjunctival prolapse of orbital fat is seen
to the lowest effective dose. Additionally, aza- as a nonpainful, movable light pink mass at
thioprine, with or without topical corticoster-
the limbus. Cytological examination reveals
oids, can be used to induce resolution of the
lesions. Dogs should be monitored for hepato- multiple lipid droplets and few mononuclear
toxicity and myelosuppression every four to six cells. Surgical removal, while curative,
should not be overzealous as enophthalmia

Figure 8.7 Nodular fasciitis on the temporal


aspect of the globe. An immature cataract is also Figure 8.8 Conjunctival dermoid with hair at the
present. temporal aspect of the globe.
­Foreign Bodie  299

can result. Onchocerciasis causes bean-­sized ­Conjunctival Hemorrhages


masses in the conjunctiva, nictitans, and
sclera (Figure 8.9). Conjunctival and subconjunctival hemor-
rhages occur commonly in the dog and most
frequently result from trauma. When this
Parasitic Granulomas condition is caused by trauma, no treatment
The surface of the masses is generally irregular is necessary if the remaining ophthalmic
with nodular thickenings caused by the coiled and physical examinations are normal
adult worms. Histopathologically, a pyogranu- (Figure 8.10). If there is no history or evi-
lomatous or granulomatous reaction with dence of trauma, a coagulopathy or vasculi-
eosinophils is associated with the presence of tis must be considered as the possible cause.
adult worms. Treatment includes surgical Specifically, conjunctival hemorrhage has
removal of the masses followed by medical been reported with angiostrongylosis and
therapy. Medical therapy includes predniso- von Willebrand factor deficiency. No treat-
lone 0.5 mg/kg p.o. b.i.d. for three to four weeks ment is needed specifically for the conjunc-
and doxycycline 5 mg/kg p.o. b.i.d. for six to tival hemorrhages.
eight weeks. One week after surgery, 2.5 mg/kg
of melarsomine is given i.m. twice within 24 h,
followed by ivermectin 50 μg/kg s.c. and melar- ­Foreign Bodies
somine one month after surgery.
Physical irritation caused by foreign bodies
Cysts lodged within the conjunctiva or NM can
cause a severe reaction, including blepharos-
Multiple causes of cyst formation in the pasm, mucoid discharge, hyperemia, and cor-
conjunctiva have been described, but all neal ulceration. Grass awns and other plant
occur only rarely in the dog. Conjunctival material are the most common culprits. Most
epithelial inclusion cysts, cystic neoplasms, foreign bodies can be removed with forceps
parasitic cysts, lacrimal cysts (i.e., dacry- after administration of a topical ophthalmic
ops), orbital cysts with conjunctival fistula anesthetic.
formation, and cysts of the lacrimal canali-
culi can occur.

Figure 8.10 Conjunctival hemorrhage secondary


Figure 8.9 Onchocerca granuloma in the ventral to trauma in a dog. Note the miosis indicating
bulbar conjunctiva. (Photo courtesy of Dr Nancy anterior uveitis, which is also a result from
McLean.) the trauma.
300 Canine Conjunctivae and Nictitating Membrane: Disease and Surgery

­Orbital Disease with deep orbits, enophthalmia, narrow skulls,


slight entropion, and inadequate tear drainage.
The conjunctiva is frequently affected by It has been reported in the Afghan Hound,
orbital disease. The redundancy and elasticity Doberman Pinscher, Golden Retriever, Gordon
of the conjunctiva allow it to be the path of Setter, Great Dane, Great Pyrenees, Ibizan
least resistance; therefore, it may be the first Hound, Labrador Retriever, Newfoundland,
tissue to show swelling or displacement Standard Poodle, Rottweiler, Samoyed, and
(Figure 8.11). Conjunctival hyperemia also Weimaraner. This enophthalmia then creates a
occurs commonly with orbital disease. “pocket” in the ventral conjunctival fornix that
Zygomatic mucoceles can cause protrusion collects dust, dirt, and other foreign material.
of the conjunctiva beyond the palpebral fissure The conjunctivitis occurs secondary to the irri-
in addition to causing exophthalmos, prolapse tation and poor tear drainage, and it is poorly
of the NM, and periorbital swelling. Orbital cel- responsive to medical therapy (frequent flush-
lulitis can be localized or associated with sinus ing of debris from the ventral fornix with eye
disease. Infectious organisms include bacteria, wash may help).
fungi such as Blastomyces and Aspergillus, and
parasites such as Toxocara canis. Occasionally,
periapical abscesses, slab fractures of the fourth Medial Aberrant Dermis
maxillary premolar, and extraction or fracture (Caruncular Trichiasis)
of the first or second maxillary molars can Aberrant dermis derived from the facial skin
cause the same clinical signs. may continue past the intermarginal space in
the medial canthus and onto the conjunctiva
and caruncle. When this occurs, irritation from
­Anatomical Abnormalities the hair, which can grow very long, can cause
keratitis, epiphora, or both. The condition has
Conjunctival disease can develop secondary to been observed in the Pekingese, Shih Tzu, and
anatomical defects that cause inadequate tear Lhasa Apso. Surgical treatment with the
drainage, chronic exposure, and other changes. medial pocket canthoplasty or removal of the
aberrant dermis using conjunctiva and
Medial Canthal Pocket Syndrome the medial palpebral ligament for closure can
be done.
Medial canthal pocket syndrome refers to the
chronic conjunctivitis occurring in large dogs

­ onjunctival Manifestations
C
of Systemic Disease

Many systemic diseases cause conjunctival


manifestations (Box 8.1). Some diseases, such
as canine distemper, may cause a primary con-
junctivitis, while others cause anterior uveitis,
which leads to a ciliary flush or episcleral
injection that is often misinterpreted as con-
junctivitis. Several diseases that commonly
cause conjunctival manifestations are men-
Figure 8.11 Severe conjunctivitis associated with tioned here; for further discussion, see
systemic and retrobulbar blastomycosis. Chapter 11.
­Effects of Radiatio  301

Box 8.1 Systemic Diseases that May


Cause Conjunctival Diseases

Conjunctival hyperemia/ Leishmaniasis


conjunctivitis
Generalized Listeria
monocytogenes
Hepatozoonosis
Tyrosinemia
Multiple myeloma
Systemic Figure 8.12 Petechial and ecchymotic
histiocytosis hemorrhages are present on the conjunctiva of the
Other conjunctival Severe anemia: NM in a dog with thrombocytopenia.
changes pallor
Polycythemia: “brick
red” mucous with systemic histiocytosis; other ocular and
membranes orbital tissues were also involved.
Clotting deficiencies: Severe anemia can cause pallor of the con-
subconjunctival
junctiva and other mucous membranes as well
hemorrhages
as lightness of the retinal vessels. Polycythemia
Jaundice
can cause “brick red” mucous membranes.
Clotting deficiencies can cause periocular
hemorrhages but more commonly cause
intraocular hemorrhages (Figure 8.12).
Leishmaniasis caused by Leishmania infan- Jaundice is most easily seen in the dog in the
tum can manifest with conjunctivitis, kerati- mucous membranes, sclera, and skin. Jaundice
tis, blepharitis, retinitis, anterior uveitis, is an indication of hemolysis, hepatic disease,
lymphadenomegaly, cutaneous signs, or biliary tract obstruction.
cachexia, abnormal locomotion, and other
clinical signs.
Dogs experimentally inoculated with
Leptospira kirschneri serovar grippotyphosa ­Effects of Radiation
developed clinical signs including conjunctivitis
with a thick ocular discharge, lethargy, diar- Because of the close proximity of the globe
rhea, dehydration, vomiting, and icterus. and adnexa to the nasal and paranasal
Conjunctivitis along with dermatological sinuses, the globe is frequently within the
signs, anorexia, lethargy, fever, and vomiting field of irradiation used in treatment of sinus
has been reported in dogs with Babesia gibsoni neoplasia. Mild to severe conjunctivitis is the
infection. Rapid improvement was seen with most frequently occurring early ocular com-
treatment with imidocarb dipropionate. plication, and this conjunctivitis is usually
Dogs with multiple myeloma can develop poorly responsive to medical therapy. The
congested conjunctival blood vessels in conjunctival disease results from a direct
­association with anterior uveitis and retinal effect of radiation on the basal epithelial
changes. stem cell layer. KCS can occur as an early or a
A thickened and hyperemic conjunctiva late complication; therefore, an STT should
infiltrated perivascularly with histiocytes, lym- be performed on all dogs that develop this
phocytes, and plasma cells occurred in a dog condition.
302 Canine Conjunctivae and Nictitating Membrane: Disease and Surgery

­Surgical Procedures conjunctiva of the other eye or from the buc-


cal mucosa.
The conjunctiva is an invaluable tissue to
ophthalmic surgeons. Because of its redun- Conjunctival Autografts
dancy and rather loose bulbar adhesions, the to the Cornea
bulbar conjunctiva can be easily resected
and relocated. Conjunctival grafts created by Conjunctival autografts are used to treat deep
incising the conjunctiva and relocating a corneal ulcers for several reasons. They pre-
part of it to the cornea are used to deliver a serve corneal and ocular integrity, replace lost
focal blood supply to an otherwise avascular corneal tissue, and supply vascularization
cornea in the face of progressive infection or (Figure 8.13). Many types of grafts have been
deep corneal defects. Conjunctival grafts can described. Selection of the conjunctival graft in
be used alone for the treatment of deep a clinical situation depends on the ulcer size,
ulcers or can be used to cover tectonic cor- depth, and position; the presence of infection;
neal grafts and porcine small intestinal sub- the surgeon’s abilities; and the available instru-
mucosa used for the repair of full-­thickness mentation. The surgeries for these different
corneal defects (for additional information, grafts are described in Chapter 9.
see Chapter 9). Treatment for a corneal ulcer after conjunc-
tival graft placement includes topical ophthal-
mic antibiotics and parasympatholytic drugs.
Laceration Repair Because a blood supply is created, systemic
antibiotics will be able to reach the corneal
Small lacerations of the conjunctiva (<1 cm)
ulcer and therefore are frequently initiated.
can be allowed to heal by secondary intention.
Serum, which is frequently used for its anticol-
Large lacerations should be carefully cleansed,
lagenase and antiproteinase properties, is not
but debridement should be kept to a mini-
necessary, as the graft will supply this therapy.
mum. Any foreign material is removed. Severe
Generally, the base of the graft is severed from
conjunctival lacerations are rare and may be
the limbus five to eight weeks postoperatively.
associated with intraocular damage, and the
Conjunctival grafts are a highly successful
sclera underlying the conjunctival defect
should be carefully evaluated for damage,
especially if hyphema is present. After the area
has been cleansed and explored, simple, inter-
rupted, 5-­0 to 7-­0 absorbable sutures are used
to appose the edges.

Surgical Repair of Conjunctival


Defects
Conjunctival defects smaller than 1 cm in
diameter can be either allowed to heal by sec-
ond intention or closed with 5-­0 to 7-­0 polyg- Figure 8.13 Pedicle bulbar conjunctival graft. A
lactin 910 suture in a simple interrupted or viable conjunctival graft two weeks postsurgery.
simple continuous pattern. Burying the knots Multiple vessels are seen extending to the edges
of the graft. The polyglactin 910 sutures are still
decreases postoperative irritation. Repair of
present. The remaining corneal edema resolved
defects larger than 1 cm in diameter usually and the corneal vessels regressed with time. While
involves autografts from the bulbar not visible in this image, the pupil was mydriatic.
­Anatomy, Histology, and Functio  303

treatment modality (about ≥90%) for deep and present between the anterior and posterior
perforated corneal ulcers in the dog. Graft fail- conjunctival surfaces. Numerous lymphoid
ure has been associated with incorrect corneal aggregates populate the posterior subconjunc-
graft-­bed preparation or suturing, incomplete tiva of the NM, and goblet cells are found
covering of keratomalacia, aqueous leakage, a between the lymphatic nodules and epithe-
graft direction of more than 45% from the ver- lium. Movement of the canine NM is accom-
tical, and excessive stretching of the graft plished passively when the globe is retracted,
between opposite sutures. which displaces orbital fat and thereby pushes
the NM across the cornea. The NM sweeps
over the cornea from inferonasal to
­Nictitating Membrane superotemporal.
Some individual animals have an encircling
The NM, which is also called the membrana NM in which the free margin continues cir-
nictitans, third eyelid, or haw, is a thin sheet of cumferentially around the eye posterior to the
tissue found in the medial canthus of most limbus (Figure 8.14). This is especially com-
domestic animal species; the analogue in mon in American Cocker Spaniels but does not
humans is called the semilunar fold. The pri- result in ocular pathology.
mary purpose of the NM is physical protection A tubuloacinar gland surrounds the ventral
of the cornea. Its gland also contributes signifi- portion of the cartilage shaft. When the NM is
cantly to normal tear production. The NM is in its normal position, the gland is deeply
affected by a number of inflammatory and seated posterior to the orbital rim and is not
neoplastic conditions as well as anatomical visible. Histochemical studies have shown that
malformations that require surgical correction. in the canine NM gland, the tubular cells are
primarily serous, the acinar cells are primarily
mucus, and the principal mucous secretory
­ natomy, Histology,
A product is sialomucin. Lipid-­secreting acini
and Function similar to those in the Harder’s gland, which is
present in many animals but not the dog, have
The basic shape of the canine NM is defined by been identified in the canine NM gland, with
a T-­shaped piece of hyaline cartilage (see the function of the Harder’s gland presumably
Chapter 1). The “arm” of the T parallels the having been incorporated into the NM gland in
free margin of the NM, and the “shaft” is per- dogs. The NM gland contributes a significant
pendicular to the free edge. The shaft of the proportion (~30%) of the aqueous tear film as
NM cartilage is cone shaped at the basal end
and terminates to form a triangular plate. The
cartilage is of hyaline material with some elas-
tic fibers detectable only in the neighboring
connective tissue. The ventral extent of the
shaft originates from the periorbital connec-
tive tissue associated with the inferonasal
aspect of the globe.
The conjunctival mucosa on the posterior
surface is contiguous with the bulbar conjunc-
tiva mucosa; the conjunctiva mucosa on the
anterior surface is contiguous with the palpe-
bral conjunctiva mucosa. In addition to the Figure 8.14 Completely encircling NM in an
cartilage, a fibrous connective tissue stroma is American Cocker Spaniel.
304 Canine Conjunctivae and Nictitating Membrane: Disease and Surgery

measured by the STT (STT I without topical as an anterior folding of the leading edge of the
anesthesia; STT II with topical anesthesia and NM with exposure of the posterior aspect. The
drying of the lower conjunctival sac). result is chronic conjunctivitis and ocular dis-
The blood supply of the NM is supplied by charge. The most popular surgical correction is
the malar artery. As the artery enters the base simple excision of the folded portion of the
of the NM, it divides into smaller branches that NM cartilage.
cross almost the entire length superficially to
the free border before ramifying deeply toward
­Prolapse of the Gland
an inner segmental level.
Prolapse of the NM gland (or “cherry eye”) is
the most common primary disorder of the NM
­ nomalous, Congenital, and
A (Figure 8.16). The pathogenesis of this disor-
der has not been determined; however, it is
Developmental Disorders
thought to result from weakness in the connec-
tive tissue attachment between the NM ven-
Bent Cartilage
trum and the periorbital tissues. This weakness
Eversion of the shaft of the NM cartilage is a allows the gland, which normally is located
commonly occurring anomaly in large breeds ventrally, to flip up dorsally to protrude above
and may be hereditary in German Shorthaired the leading edge of the NM, where it then
Pointers (Figure 8.15). It is thought to result becomes enlarged and inflamed from chronic
from more rapid growth of the posterior por- exposure. Prolapse of the NM gland can be
tion of the cartilage compared with that of the either unilateral or bilateral, and it generally
anterior portion. The everted cartilage appears occurs before two years of age. Prolapse of the
NM gland is common in the American Cocker
Spaniel, Lhasa Apso, Pekingese, Beagle, and

Figure 8.15 Eversion of the cartilage of the NM Figure 8.16 Prolapse of the gland of the NM
in a Great Dane. (“cherry eye”) in an English Bulldog.
­Protrusio  305

English Bulldog. The prolapsed gland appears surface of the NM. The Morgan technique
as a smooth, red mass protruding from behind may be the most commonly used pocket tech-
the leading edge of the NM. If uncorrected, nique. The choice of repositioning technique
chronic conjunctivitis and ocular dis- is a matter of personal preference. The pocket
charge occur. techniques of Moore and Morgan may be the
easiest to learn, but the anchoring techniques,
once mastered, are simple and quick to per-
Surgical Repositioning
form. No systematic studies have compared
When the importance of the NM gland in tear effects on tear production and reprolapse
production became apparent, surgical reposi- rates among all the described techniques.
tioning of the gland, rather than partial exci- Tear production following both anchoring
sion, became widely recommended (Table 8.2). and pocket techniques, however, is superior
While many modifications of repositioning to that following gland excision, and neither
techniques have been published, the surgical posterior pocket techniques alter tear produc-
techniques can be divided into methods that tion or morphology of the NM gland excretory
anchor the gland and methods that create a ductules. While surgical repositioning is rec-
pocket for the gland. In anchoring techniques, ommended, it should not be assumed that
the prolapsed gland is sutured to the inferior retention of the gland guarantees that dry eye
episcleral tissue, to the inferior sclera, to the will not develop, since many breeds that com-
origin of the ventral oblique muscle (cats), and monly develop prolapsed NM glands are also
to the periosteum of the ventral orbital rim predisposed to KCS.
using an anterior approach, and in a recently
report the gland is anchored to the cartilage of
the NM allowing mobility. ­Protrusion
Rather than anchoring the gland, some
advocate burying it in a pocket created by Primary protrusion of the NM without pro-
conjunctiva on the anterior or posterior lapse of the gland can occur in the dog
(Figure 8.17). Though principally a cosmetic
problem, the protrusion sometimes causes
Table 8.2 Surgical techniques to replace
the prolapsed nictitating membrane gland.
conjunctivitis and epiphora. The NM can be
shortened surgically to return it to a more
Reinforce gland Imbrication or mucosa normal position. Protrusion can also occur
envelope: scarification and secondary to enophthalmos, microphthal-
cover with adjacent mos, and space-­occupying retrobulbar
conjunctival mucosa.
lesions. Protrusion may also occur in Horner’s
Envelope or mucosa pocket: syndrome, dysautonomia, cannabis intoxica-
cover with adjacent mucosa
tion, tetanus, and rabies.
Anchoring or tacking
methods:
Posterior To ventral oblique muscle ­Neoplasia
techniquesa
Neoplasia of the NM, like neoplasia in the
To ventral equatorial sclera
rest of the conjunctiva, is uncommon in the
To ventral periorbital fascia
dog. Melanomas, adenocarcinomas, squa-
Anterior To ventral periorbital rim/ mous cell carcinomas, mastocytomas, papil-
techniquea periosteum
lomas, hemangiomas, hemangiosarcomas,
Within nictitans Intranictitans technique
angiokeratomas, and lymphosarcoma have
a
Prevents nictitans movements. all been reported. Results of one study
306 Canine Conjunctivae and Nictitating Membrane: Disease and Surgery

Protrusion of nictitans

Closely observe for focal abnormalities

Curled outwardleading margins-eversion of the nictitans cartilage-

Treat byexcision of the curled portion of the cartilage.

Pinkmass from posterior nictitans in young dog-”cherry eye”=

Treat by repositioning gland (envelope or anchoring procedure).


Pinkmass from behind the nictitans in old dogs-possible adenocarcinoma of the
nictitans gland.

Treat by total excision of the nictitans

Focal mass(s)on anterior nictitans surface-consider several types of tumors-

Treat by local excision or cryosurgery

Generalized enlargement of the nictitans

Plasma cell infiltration-gradualloss of pigment; German Shepherd predisposed-


Treatment-Biopsy and topical corticosteroid/cyclosporin.

Nodular granulomatous epikeratitis-nictitans thickened and inflamed. Mainly


Collies.Usually other areas involved including cornea, episclera, and
bulbar conjunctiva.

Biopsy and treat withcorticosteroids/localexcision/systemic azathioprine.

Ocualr nodular fasciitis-similar to granulomatous epikeratitis. Other breeds.


Treat-Biopsy. Local excision and topical corticosteroids.
Lymphosarcoma and other systemic neoplasms-bilateral involvement; biopsy.

Protrusion with few or no abnormalities

Inflamed and medial corneal ulcer-foreign body. Treat-remove foreign body.

Topical antibiotics/mydriatics.

Primary condition in large breeds-bilateral. Generally no treatment.

Secondary to pain-closely exam conjunctiva, cornea and inner eye.

Horner’s syndrome-observe for miosis, ptosis, enophthalmia. Test with topical

1-2% epinephrine or 2.5% phenylephrine to determinesite of sympathetic


denervation.
Secondary to orbital diseases-cellulitis, tumors,masticatory myositis.
With systemic diseases-tetanus, rabies, etc.

Figure 8.17 Strategy for diagnosis and treatment of protrusion of the NM.
­Inflammatory Condition  307

revealed adenocarcinomas (several varie- ­Inflammatory Conditions


ties), papillomas, and malignant melanomas
to be the most common primary tumors of Nodular
the third eyelid. Granulomatous Episclerokeratitis
Nodular granulomatous episclerokeratitis is an
Adenocarcinoma inflammatory disease that most commonly
Adenocarcinomas of the NM gland generally arises from the temporal limbus, but it may
are localized, firm, smooth, pink swellings that involve the NM as well. Collies are predis-
appear to involve the gland, and occur mainly posed. Clinically, the affected NM is hypere-
in older dogs. Removal of the entire third eye- mic, depigmented, and edematous, with
lid is currently the recommended treatment. multiple, smooth, tubular-­shaped thickenings
With recurrence, surgery in conjunction with involving the palpebral surfaces. The disease
external beam radiation therapy can be suc- process is generally controllable with use of
cessful. Adenomas of the NM gland also occur systemic prednisone and azathioprine, but oral
(Figure 8.18). doxycycline and niacinamide have also been
used successfully.

Other Neoplasms Plasma Cell


Squamous cell carcinoma has been reported Infiltration (Plasmoma)
to arise from both the palpebral and bulbar Plasma cell infiltration of the NM, or “plas-
surfaces of the NM, and it may appear dark in moma,” can cause thickening, depigmenta-
color. Excision of the third eyelid is curative. tion, and follicle formation (Figure 8.19).
When extensive, squamous cell carcinoma of Pannus (i.e., chronic superficial keratitis) is
the NM may invade the orbit. In one case often associated with this condition. German
of a mastocytoma, the mass was very firm, Shepherds appear to be predisposed, and
and local excision appeared to be curative. plasmoma has bilateral potential in the
Hemangiomas, hemangiosarcomas, and Belgian Sheepdog, Borzoi, Doberman
angiokeratomas of the NM appear as red, pro- Pinscher, English Springer Spaniel, and
liferative, protruding masses. Local surgical German Shepherd breeds. Histopathology
excision tends to be curative. Bilateral lym- reveals a subconjunctival epithelial inflam-
phosarcoma of the NMs was reported in a matory infiltrate consisting primarily of
German Shepherd.

Figure 8.19 Plasma cell infiltration of the NM,


Figure 8.18 Adenoma of the gland of the NM. plasmoma, in a German Shepherd.
308 Canine Conjunctivae and Nictitating Membrane: Disease and Surgery

plasma cells, with fewer lymphocytes and forceps following instillation of a topical
stromal pigmentary incontinence. Treatment anesthetic. Generally, topical ophthalmic
generally consists of topical ophthalmic dex- antibiotic should be used after removal of
amethasone four times daily initially or sub- the foreign body, especially if the cornea is
conjunctival or systemic corticosteroids. ulcerated.
Topical ophthalmic cyclosporine ointment
or drops or 1% pimecrolimus administered
two to three times daily is also effective. ­ ictitating
N
Once there is resolution, medication admin- Membrane Surgery
istration is slowly decreased to the lowest
effective frequency. The NM can be used as a corneal shield in select
cases of corneal ulceration. These NM “flaps”
aid in the healing of idiopathic bullous keratop-
Follicular Conjunctivitis
athy in the cat. They have also been used in con-
Follicular conjunctivitis most frequently junction with frozen lamellar corneal grafts to
involves the bulbar aspect of the NM, but the protect the graft from blinking movements and
follicles can be present anywhere on the con- to help maintain pressure on the graft’s surface.
junctiva (see Figure 8.5). A small area of lym- Nictitans flaps for the treatment of corneal
phoid follicles is normally present on the ulcers have been largely replaced with conjunc-
bulbar side of the NM, closely associated with tival grafts of different types.
the NM gland. With follicular conjunctivitis,
the follicles are more numerous and larger Nictitating Membrane Flaps
than normal in size, and conjunctival hypere-
Several types of flaps have been described. In
mia as well as mucoid discharges commonly is
the most widely advocated technique, the free
present.
margin of the NM is sutured to the temporal
as­pect of the superior eyelid (Figure 8.20a and b).
Another technique temporary attaches the NM
­ rauma, Reconstruction,
T to the dorsolateral episclera. Two to three hori-
and Foreign Bodies zontal mattress sutures of 3-­0 monofilament
nonabsorbable material are placed between the
Trauma to the medial canthal area may free edge of the NM and the lateral aspect of the
result in lacerations of the NM. Small lesions superior lid. The lid sutures should be placed
heal spontaneously, but larger lesions should well within the superior cul-­de-­sac, and the NM
be sutured with 6-­0 braided, absorbable sutures should be approximately 2 mm from the
suture material, taking care not to leave free edge, incorporating cartilage into the center
sutures or knots where they could abrade the suture. Alternatively, a single mattress suture
cornea. If the NM has been removed because can be placed between the superior lid and the
of neoplasia or extensive areas were lost midpoint of the cartilage shaft. The surgeon
because of trauma, it may be reconstructed must be careful to seat the NM margin as deeply
from labial mucosa. Foreign bodies lodged as possible in the superior conjunctival fornix.
either within or behind the NM can cause When an NM flap is sutured to the superior lid,
persistent corneal ulceration as well as movements of the globe cause the cornea to rub
inflammation of the NM. The foreign bodies, against the posterior aspect of the NM, theoreti-
which are commonly grass awns, seeds, or cally exacerbating corneal disease; however,
other plant material, usually are loosely serious consequences of the superior lid tech-
embedded and can be removed using thumb nique are rare.
­Nictitating Membrane Surger  309

(a) (b)

Figure 8.20 The NM flap may be temporarily attached to either (a) the dorsolateral conjunctival fornix
(most frequently used) or (b) the dorsolateral episclera (permits movement with the NM and globe, but
penetration of the globe with sutures is a danger).

Complications of NM flaps include necrosis these flaps obscure visualization of the cornea
of the upper lid if sutures are placed too tightly and intraocular structures. These flaps also do
in the NM-­to-­superior-­lid technique and inad- not deliver a blood supply or give as much sup-
vertent penetration of the globe in the NM-­to-­ port as a conjunctival pedicle graft. They also
episclera technique. The sutures are generally may inhibit topical medications from reaching
left in place for one to two weeks, but with the the cornea. To allow visualization of the cor-
NM-­to-­episclera technique, sutures may pull nea, the suture ends can be left long so that the
free prematurely. It should be remembered flap can be released and retied.
310

Canine Cornea and Sclera: Diseases and Surgery


Revised from 6th edition of Veterinary Ophthalmology, Chapter 19: Diseases and Surgery of the Canine Cornea and Sclera, by
R. David Whitley and Ralph E. Hamor

The cornea is a unique portion of the outer selected to induce as little trauma as possible.
fibrous tunic of the eye. It is transparent and Minimizing corneal trauma reduces the likeli-
serves a major refractive function while main- hood and severity of scarring, and maintains
taining an impermeable physical barrier maximal corneal transparency.
between the ophthalmic structures and the envi- This chapter provides an overview of the
ronment. The transparency of the cornea ena- most common corneal and scleral disorders in
bles it to perform two main functions: to refract the canine eye and their clinical management.
light and to allow sufficient quantity and quality
of light into the eye to form an image on the ret-
ina. In spite of its exposure to environmental ­Corneal Anatomy
hazards, the cornea can maintain a smooth
and Pathophysiology
outer surface necessary for retinal image forma-
tion by the continuous replacement of the sur-
Corneal Anatomy
face epithelium and a healthy preocular tear
film. Since most pathological corneal responses The fibrous tunics of the canine eye consist of the
are associated with changes in transparency, sclera and the cornea, and the limbus is the tran-
many different corneal disorders can lead to sition zone between the cornea anteriorly and
opacification and loss of vision. the sclera posteriorly. The canine cornea consists
Fortunately, most corneal pathology is obvi- of the corneal epithelium externally, the corneal
ous to the animal caregiver and usually ame- stroma, Descemet’s membrane, and corneal
nable to medical or surgical therapy. The most endothelial cells (Figure 9.1) (also see Chapter 1).
important goals of corneal treatment are to Descemet’s membrane, the basement membrane
preserve or improve the quantity and quality of underlying endothelial cells, becomes thicker
light entering the eye (even in the presence of with age as it is continuously produced. Canine
corneal opacities, e.g., eyes with scarring or endothelial cells are hexagonally shaped with a
dystrophy) and to promote corneal healing normal density of approximately 2500–3175 cells/
(e.g., eyes with ulceration or neoplasms). To mm2. These cells decrease in number with age,
achieve these goals, damage to normal corneal with the number of cells in older dogs being
tissues should be avoided and therapies frequently below 2100 cells/mm2, resulting in an

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
­Corneal Anatomy and Pathophysiolog  311

Tear film
Corneal epithelium

Corneal stroma

Descemet’s membrane
Endothelium

Figure 9.1 The canine cornea consists of the corneal epithelium externally, the corneal stroma, Descemet’s
membrane, and corneal endothelial cells.

increased diameter per endothelial cell to com- The corneal stroma consists primarily of col-
pensate for the reduced number. lagen fibrils, keratocytes, nerves, and glycosa-
The peripheral cornea is thicker on average minoglycans. Corneal collagen fibrils exist in
than the central cornea. In neonatal puppies, broad belts called lamellae that run approxi-
there is a decrease in corneal thickness until mately parallel to the corneal surface. Keratan
approximately six weeks of age; then it increases sulfate, chondroitin sulfate, and dermatan sul-
with age until approximately 30 weeks. In adult fate are the predominant glycosaminoglycans
dogs, corneal thickness increases gradually with in the cornea. In the equine cornea, chondroi-
age. Mean corneal thickness, as measured by tin 4-­sulfate is more concentrated in the deep
ultrasonic pachymetry (USP) and in vivo confo- central, peripheral, and middle central layers of
cal microscopy, is 562 ± 6.2 and 585 ± 79 μm, the cornea compared to chondroitin 6-­sulfate.
respectively. Spectral-­domain optical coherence The canine cornea is highly innervated by an
tomography in normal dogs demonstrated that average of 11.5 large “trunks” of the trigeminal
the epithelial thickness was 72.3 ± 4.6 μm, none- nerve (cranial nerve V) that enter the midstro-
pithelial thickness was 538.9 ± 42.5 μm, and cen- mal region circumferentially at the limbus.
tral corneal thickness (CCT) was 611.2 ± 40.3 μm. These trunks course radially to the central cor-
A diurnal variation in CCT measured by USP nea forming anterior and posterior nerve plexi
was found in normal dog corneas with CCT val- in the anterior stroma. Subepithelial plexus for-
ues significantly lower in the evening. mation and extensions into the basal epithelium
312 Canine Cornea and Sclera: Diseases and Surgery

with free nerve endings extending to the epithe- to remove and transport fluid from the corneal
lial wing layers also occur. Axons from the sub- stroma into the anterior chamber. In this way,
epithelial plexus give rise to the subbasal nerve the corneal endothelium regulates hydration
plexus after penetrating the epithelial basal lam- of the corneal stromal collagen matrix, which
ina. The nerve fiber density of the central subep- provides mechanical strength.
ithelial nerve plexus, as determined by in vivo Sclera is composed of collagen fibrils with
confocal microscopy, was 12.39 ± 5.25 mm/mm2 various diameters ranging from 25 to 230 nm.
in mesocephalic dogs and 10.34 ± 4.71 mm/mm2 Scleral collagen fibrils are arranged in irregu-
in brachycephalic dogs. The nerve fiber density lar, nonparallel bundles that vary in width and
of the central subbasal nerve plexus was thickness, intertwine with each other, and
14.87 ± 3.08 mm/mm2 in mesocephalic dogs and branch extensively
11.80 ± 3.73 mm/mm2 in brachycephalic dogs.
Corneal sensitivity, or corneal touch thresh-
Corneal Wound Healing
old (the minimum stimulation of the corneal
surface by a Cochet–Bonnet esthesiometer to The different stages of corneal healing are sum-
elicit a blink reflex), is higher in dogs with doli- marized in Table 9.1 as the outer epithelium
chocephalic skull types compared with dogs bridges the defect to months later as the
with mesaticephalic or brachycephalic (which endothelium recovers. Fortunately, these events
had the least sensitive cornea) skull types. In can be observed directly.
general, the central corneal region was most
sensitive, followed by the nasal, temporal, dor- Epithelial Healing
sal, and then ventral corneal regions. Dogs The corneal epithelium is maintained by a
with diabetes mellitus have reduced corneal constant cycle of proliferation of cells in the
sensitivity in all corneal regions. basal layer and shedding of cells at the surface.
Renewal of basal cells also occurs by centripe-
tal migration of stem cells from the limbus.
Corneal Clarity
An epithelial defect of the cornea heals rap-
Factors supporting transparency of the normal idly (in the absence of sepsis) by epithelial slid-
canine cornea include the absence of blood ves- ing and mitosis. After a short lag period of
sels and pigment, the absence of keratinization approximately 1 h, the normal epithelium at
of the anterior surface epithelium, a well-­ the edge of the defect flattens, retracts, thick-
organized stromal collagen lattice, and the small ens, and loses its hemidesmosomal attach-
diameter of the collagen fibrils. The collagen ments to the basement membrane.
fibrils that comprise the corneal stroma are com- Limbal stem cells appear to play an important
posed of parallel arrays of long collagen mole- role in the maintenance of corneal epithelial
cules held together by intermolecular bonds. health and corneal clarity. The limbal epithe-
The collagen fibrils in the cornea have a uniform lium has been studied in multiple species
diameter of approximately 25 nm. Some nonfi- searching for stem cell crypts found in humans.
brillar collagens are also found in the corneal While the limbal epithelium demonstrated
stroma, types VI and XII being the most notable. invagination similar to humans, no crypt-­like
Studies suggest that corneal clarity may not be structures were found in dogs. Canine corneal
dependent only on the absolute size of the stro- epithelial stem cells appear to reside in the lim-
mal collagen or spacing of the fibrils, but also bus and give rise to proliferative cells in response
the fibril volume fraction (i.e., the proportion of to stimulation.
the stroma that is occupied by hydrated collagen
fibrils) may also be a major factor in clarity. Stromal Healing
The corneal endothelium uses physiological Epithelial sliding and stromal replacement
pumps (i.e., water and ion transport systems) mainly accomplish healing of corneal defects
­Corneal Anatomy and Pathophysiolog  313

Table 9.1 Dynamics of corneal healing after corneal ulcerations.

Tissue Healing starts Time to replace Clinical monitoring

Epithelium 1h 48–72 h Very faint retention of fluorescein (new


cell layer)
14 days No fluorescein retention (multiple layers)
Corneal epithelial Several weeks Firm bond (epithelium cannot be
dislodged) basement membrane
Corneal stroma One to two days Days to weeks Stromal replacement requires local
fibroblasts; occasional vasculature
Occurs under the healing epithelium
Descemet’s Regeneration depends on the endothelium
membrane (limited to very young animals)
Endothelium Regeneration in young animals only

that involve the epithelium and anterior stroma. clinically. The hexagonally shaped canine
Stromal replacement requires synthesis and endothelial cells tend to enlarge in size and
cross-­linking of collagen, proteoglycan synthe- decrease in number with age. In the young dog,
sis, and gradual wound remodeling, which the number of endothelial cells averages
requires several weeks. The stroma adjacent to 2500–3175 per mm2. Injury to endothelial cells
the defect exhibits edema early, followed by an results in decreased cell density in dogs, suggest-
influx of neutrophils from the tear film (via the ing a limited capacity for mitosis in the canine
lacrimal gland and conjunctival blood vessels) adult. Phacoemulsification, radiofrequency
within 1–2 h of injury. Regional keratocytes hyperthermia, and CO2 photokeratotomy and
transform into fibroblasts that proliferate and intraocular surgery usually result in damage to
rapidly synthesize collagen and other compo- endothelial cells in dogs, but intraocular irriga-
nents of the extracellular matrix (ECM). Stromal tion with various saline solutions, low doses of
fibroblasts produce fibronectin, an ECM glyco- tissue plasminogen activator (25 μg/100 μl), and
protein that stimulates cell adhesion, cell migra- transcorneal diode laser iridal photocoagulation
tion, and protein synthesis. Shortly thereafter, did not appear to damage the cornea endothelium
fibroblastic proliferation begins in the stroma.
Fibroblasts also arise from the stromal histio- Repair of Full-­Thickness Corneal
cytes, and as the fibrous reaction continues, the Laceration or Perforation
epithelium is displaced anteriorly to its normal Healing of a full-­thickness corneal laceration
surface level. New collagen fibers and lamellae may be divided into approximately six phases
are produced, but disorganized arrangement (Box 9.1). This is about the most severe injury
may result in opacity or corneal scarring. The that the cornea can exhibit, and potentially
main cell type involved in the corneal fibrosis recover from with vision.
and scarring is the myofibroblast.
Role of Proteases in Corneal
Endothelial Healing Wound Healing
The endothelial cell monolayer is the inner limit- Healing of corneal wounds is a complex process
ing layer of the cornea. Endothelial cells nor- involving the integrated actions of proteinases,
mally form a hexagonal, mosaic pattern on growth factors, and cytokines produced by epi-
Descemet’s membrane that can be visualized thelial cells, stromal keratocytes, inflammatory
314 Canine Cornea and Sclera: Diseases and Surgery

Box 9.1 Phases of the Healing of Full-­Thickness Corneal Lacerations


1) Mechanical factors, the fibrin plug, and corneal stromal edema. When fibrinogen in the
inflamed aqueous humor contacts the wound edges, fibrin forms a plug that may seal the
wound and act as a scaffold for the fibroblastic reparative processes
2) Thirty minutes to 5 h later, the leukocytic or polymorphonuclear leukocytes migrate into
the corneal wound. They arrive via conjunctival blood vessels and the tears, as well as
within the aqueous humor, and with chronicity, from the perilimbal blood vessels
3) This epithelial phase appears to begin 1 h after injury. By the process of sliding and mitosis,
the epithelium begins to cover the anterior part of the wound during this phase. This seems
to be an important moderator for healing of the underlying stroma
4) This fibroblastic phase begins 12 h after injury. Fibroblasts are formed mainly from kerato-
cytes and, initially, from the keratocytes closest to the wound margin. Fibroblasts may also
form from mononuclear cells that have migrated to the cornea from the tears, or perhaps
from perilimbal vessels. The fibroblasts enlarge, multiply, and form an active fibroblastic
tissue that elaborates collagen and ground substance composed of glycosaminoglycans
5) This endothelial phase of corneal healing begins 24 h after the injury. The endothelium
appears to heal mainly by endothelial sliding or amitotic multiplication. The endothelial
cells produce a new Descemet’s membrane after a few weeks
6) This last phase begins seven days after injury. Cellularity in the cornea slowly diminishes,
and nuclei in the fibers reorient themselves parallel to the corneal surface. The fibroblastic
tissue decreases in size and becomes less cellular, and a thin scar is formed. Corneal inci-
sions heal to sufficient tensile strength for sutures to be removed in 19 days

cells, and the lacrimal glands (Table 9.2). is prevented by natural proteinase inhibitors in
Multiple autocrine and paracrine interactions the PTF and cornea, such as α1-­proteinase
occur between epithelial cells, activated stromal inhibitor, α2-­macroglobulin, and tissue inhibi-
fibroblasts, and the exocrine actions of factors tors of metalloproteinases.
secreted by lacrimal gland cells into the However, pathological degradation of cor-
precorneal tear film (PTF). Various proteinases, neal stromal collagen and proteoglycans occurs
proteinase inhibitors, growth factors, and when the balance between proteinases and pro-
cytokines in the tear film and aqueous humor teinase inhibitors favors the proteinases. The
play a role in the natural turnover of the corneal rapid degradation of the corneal stroma associ-
cells and corneal wound healing. As a result of ated with some severe corneal ulcers is caused
these discoveries, therapy of corneal ulcerations by proteolytic enzymes acting on the collagen,
is now also directed at controlling these pro- proteoglycans, and other components of the
teases as well as the antibacterial therapies. stromal ECM and is referred to as keratomala-
cia or “corneal melting” (Figure 9.2).
Proteinases and Proteinase Inhibitors
Maintenance and repair of the corneal stromal Major Proteinases in the Cornea and Their Origin
ECM require a tightly coordinated balance of Microorganisms, inflammatory cells (e.g., poly-
ECM synthesis, degradation, and remodeling. morphonuclear leukocytes and macrophages),
Proteolytic enzymes (proteinases) perform corneal epithelial cells, and fibroblasts produce
physiological functions in the slow turnover and release proteolytic enzymes. Endogenous
and remodeling of the corneal stroma. proteinases are produced by host cells.
Excessive degradation of normal healthy tissue Exogenous proteinases are secreted by
­Corneal Anatomy and Pathophysiolog  315

Table 9.2 Types of corneal ulcerations in the dog.

Clinical diagnosis Corneal layers lost Outcome

Superficial ulcer Epithelium/basement Uncomplicated/progressive


membrane (BM) variable
Corneal erosion Epithelium/BM Refractory/recurrent
Shallow ulcer Epithelium/BM/¼ – ⅓ stroma Uncomplicated/progressive
Moderate ulcer Epithelium/BM/ ½ stroma Uncomplicated/progressive
Deep ulcer Epithelium/BM/⅔ – ¾ stroma Uncomplicated/progressive
Descemetocele Epithelium/BM/stroma Complicated/progressive
Iris prolapse Epithelium/BM/stroma/ Complicated/progressive
Descemet’s membrane/
endothelium

and macrophages. It degrades native III and IV


collagen as well as corneal ECM compounds
such as laminin and fibronectin. Two MMPs
(MMP-­2 and MMP-­9) are of major importance
in the remodeling and degradation of corneal
stromal collagen. MMP-­2 and MMP-­9 were
identified by immunohistochemistry in both
healthy and ulcerated corneas of humans, dogs,
and a variety of other animal species. In most
species, MMP-­2 is constitutively present in the
unwounded corneal epithelium and stroma and
is upregulated after wounding, while MMP-­9 is
found only in the wounded cornea.
Figure 9.2 Keratomalacia in a dog with bacterial
keratitis.
Proteolytic Activity in Healthy
and Diseased Corneas
infectious organisms. Examples of exogenous In damaged corneas, proteinase activity
proteinases include the variety of proteases pro- increases in the tear film and is considered an
duced by Pseudomonas aeruginosa (e.g., alka- important fundamental response of the mam-
line protease, elastases A and B, protease IV, malian eye to corneal injury. If infection is
modified elastase, P. aeruginosa small protease), present, proteinases secreted by infectious
and serine proteinase production by Aspergillus organisms further contribute to corneal damage.
and Fusarium spp. Extracellular enzymes of In dogs with traumatic keratoconjunctivitis, PTF
bacterial or fungal origin also contribute indi- levels of MMP-­9 were significantly increased
rectly to corneal proteolytic activity by activat- compared to clinically normal dogs. In dogs with
ing endogenous proteinases. P. aeruginosa ulcerative keratitis, PTF concentra-
Two important families of enzymes that affect tions of MMP-­2 and MMP-­9 were significantly
the cornea are the matrix metalloproteinases higher than contralateral unaffected eyes and
(MMPs) and serine proteases. Neutrophil clinically normal dogs. Protease levels subse-
elastase, an abundant serine proteinase in tears, quently decreased as corneal healing progressed
is synthesized by polymorphonuclear leukocytes following medical or surgical therapy.
316 Canine Cornea and Sclera: Diseases and Surgery

Corneal Pigmentation specifically identified a high prevalence in this


breed, with approximately 70–82% of examined
Corneal pigmentation is most commonly asso-
dogs affected. Both studies also identified a high
ciated with chronic inflammation. Corneal
prevalence of ocular comorbidities, including
pigmentation is found in disorders such as
disorders of the lacrimal system and eyelids.
chronic superficial keratitis (CSK) (i.e., pan-
A statistical association between KCS (kerato-
nus) in the German Shepherd; the pigmentary
conjunctivitis sicca) and SCP (superficial cor-
keratitis syndrome in brachycephalic breeds
neal pigmentation) was reported in one study,
(Figure 9.3); keratoconjunctivitis sicca (KCS);
but it was also noted that SCP developed in the
and scarring with ulcerative keratitis. Corneal
absence of KCS in other dogs. In the other study,
pigmentation results from migration of mel-
the absence of consistently identifiable inflam-
anocytes from the limbal and perilimbal tis-
matory risk factors (ocular adnexal or tear film
sues. Melanin pigment may accumulate within
abnormalities) and the detection of SCP were
corneal epithelial cells, macrophages, and
considered suggestive of a hereditary epithelial
fibroblasts in the dog. Other signs of active
or pigmentary dystrophy in the Pug, or pigmen-
keratitis, such as corneal vascularization, stro-
tary keratopathy. Several other brachycephalic
mal inflammatory cell infiltration, and granu-
dog breeds develop SCP commonly and without
lation tissue formation, usually accompany
an identifiable underlying etiology and include
pigment cell migration. Melanin is transferred
the Boston Terrier, Lhasa Apso, Pekingese, and
to the basilar or suprabasilar cells of the cornea
Shih Tzu.
and the anterior stromal tissue. Once present,
Another less common source of corneal
corneal pigmentation is nearly impossible to
pigmentation is anterior synechiae (often after
eliminate!
corneal perforations) and less common after
Only two previous studies that have investi-
the adherence of anterior uveal cysts to the cor-
gated the histopathology of canine corneal pig-
nea. Cysts of the anterior uvea may be either
ment are available. Corneal epithelial melanin
congenital or acquired (as the result of uveal
deposition usually is usually concurrent with
inflammation or degeneration). The pigmented
presence of blood vessels and inflammatory
cells may arise from the pigment epithelium of
cells. Ocular surface disease and signalment
the ciliary body, iridal stroma, and posterior
certainly play a role in the condition. Recent
iridal epithelium.
studies investigating corneal pigment in Pugs

Corneal Edema
Corneal edema or swelling (i.e., corneal hydra-
tion) may result from imbibition of fluid by the
epithelium or stroma (Figure 9.4). Corneal
transparency depends both on its physical
structure and on mechanisms that prevent
overhydration. The major barriers to edema
are the endothelium and the epithelium.
Removal of the epithelium in rabbits produces
an average increase in corneal thickness of
200% in 24 h, whereas removal of the endothe-
lium produced an increase of 500%.
Figure 9.3 Superficial corneal pigment in a Pug Alterations in endothelial cells (as in iridocy-
with chronic pigmentary keratitis. clitis) result in the cornea absorbing aqueous
­Corneal Anatomy and Pathophysiolog  317

thickened Descemet’s membrane, and


endothelial cell hypocellularity. This condition
is similar to Fuchs dystrophy in humans and is
commonly bilateral (see more information
later in this chapter).
Corneal edema associated with endothelial
changes is commonly seen with anterior uve-
itis in the dog. Intraocular inflammation
results in corneal edema via an increase in
endothelial permeability and a decrease in
Na+/K+-­ATPase pump activity. Infectious
Figure 9.4 Afghan Hound with diffuse corneal
edema after canine adenovirus type 1 vaccination. canine hepatitis, which is an immune-­
mediated, Arthus-­type reaction, develops in
humor and becoming edematous. The the anterior uveal tract and progresses to
endothelium maintains corneal deturgescence destruction of the corneal endothelium with
by an energy-­dependent sodium–potassium resultant corneal edema, thus causing the
transport pump as well as by a physical barrier. “blue eye” appearance. Natural infections or
The barrier function of the endothelium vaccination with modified live canine adeno-
results from tight cellular junctions known as virus type 1 may result in the development of
“zonula occludens.” Traditionally, corneal corneal edema (see Figure 9.4), but current
edema was regarded simply as increased cor- vaccinations with canine adenovirus type 2
neal water content that results in increased decrease the incidence to below 1%.
thickness, increased scattering of light, and Approximately 30% of dogs that develop cor-
decreased transparency; however, corneal neal edema from adenovirus infections do
edema also involves loss of stromal glycosami- not completely resolve.
noglycans and water uptake. When the cornea Traumatic endothelial damage may occur
swells, fluid is not uniformly distributed within with anterior lens luxation. Trauma to the
the corneal stroma with its anterior stroma endothelium may also result from intraocular
most affected. The posterior corneal lamellae surgery, such as phacoemulsification, intraca-
are hydrated to a greater extent, possibly psular lens extraction, and intraocular lens
because of differences in the glycosaminogly- replacement. Irrigation solutions used in
can content between the anterior and posterior phacoemulsification also damage the corneal
stroma or presence of lamellar interweave in endothelium. Results of one study on the
the anterior stroma that limits the extent to response of canine corneal endothelium to
which these lamellae can swell. Corneal intraocular irrigation solutions indicated that
edema in the dog may be associated with a irrigating fluid composition has a less deleteri-
variety of causes, including endothelial dystro- ous effect on the corneal endothelium than the
phy, age-­related degeneration, endothelial volume of fluid and time of irrigation (less
damage associated with persistent pupillary than 100 ml of fluid for less than 20 min had
membranes (PPMs), mechanical trauma, toxic the least damaging effect).
reactions, anterior uveitis, endotheliitis, glau- There are a number of drugs that result pri-
coma, neovascularization, and ulceration. marily in corneal edema in dogs. As an exam-
Endothelial dystrophy occurs in several ple, chlorpromazine accumulates in the
breeds, including Boston Terriers, Chihuahuas, canine posterior corneal stroma, lens, and
Dachshunds, and German Shepherds. Light uveal tract. In addition to causing cataracts, it
microscopic findings have included stroma produces posterior corneal precipitates and
edema, fibrous tissue proliferation on a pigmentation. Chlorpromazine is a phototoxic
318 Canine Cornea and Sclera: Diseases and Surgery

compound, and the cellular damage to


endothelial cells occurs after light exposure.
Bilateral corneal edema occurred in 3 of 12
dogs after long-­term treatment (>3 months)
with tocainide, an antiarrhythmic agent.
Because of the lack of inflammation, this was
presumed to be a direct endothelial toxic effect
of the drug.

Corneal Vascularization
Corneal stromal vascularization is a nonspe-
cific response to corneal injury or inflamma-
tion. The healthy canine cornea is avascular
and the presence of blood vessels within the
Figure 9.5 Superficial corneal vascularization in a
cornea represents pathological change. dog with chronic KCS.
Vascularization is a normal component of the
reparative response after injury in a variety of
tissues; however, in the cornea, this process
can result in disrupted corneal architecture,
opacification, and reduced vision. Superficial
highly branching blood vessels in the anterior
stroma are associated with corneal diseases
(often can be observed connected to conjuncti-
val blood vessels) and the short fine blood ves-
sels deep in the corneal stroma at the limbus
(paintbrush vessels) are associated with ante-
rior uveal diseases.
The avascular state of the cornea is actively
maintained by a balance of antiangiogenic and
angiogenic factors. Corneal vascularization
occurs when this balance is lost and the local
corneal microenvironment favors angiogenic
factors. The presence of vascular endothelial
Figure 9.6 Deep corneal vascularization in a dog
growth factor (VEGF) receptors 1 and 2 has with chronic anterior uveitis.
been demonstrated in normal canine eyes. In
the normal canine cornea, superficial and
basal corneal epithelium, corneal endothe- Superficial vessels arise from conjunctival
lium, and limbal vascular endothelium con- vessels and are bright red, fine, branch repeat-
tained VEGF receptor 1, while VEGF receptor edly, and can be observed to cross the limbus
2 was found in the scleral vascular endothe- (Figure 9.5). Deep corneal vessels are located in
lium. Both VEGF receptors 1 and 2 were the posterior stroma and suggest deep corneal
detected in pathological vascular endothelium or intraocular disease. Deep corneal vessels
and corneal neovascularization. Any corneal arise from anterior ciliary vessels and appear
insult that induces inflammation or hypoxia dark red, straight with few or no branches, and
may result in corneal angiogenesis. do not cross the limbus (Figure 9.6).
­Developmental Abnormalities and Congenital Disease  319

­ evelopmental
D Dermoids
Abnormalities and A dermoid is a choristoma, or normal tissue in
Congenital Diseases an abnormal position. Dermoids occur most
commonly at the temporal limbus and can
Microcornea involve the eyelids, conjunctiva, nictitans, cor-
nea, or a combination of these structures
Microcornea is a small cornea in an other-
(Figure 9.7). Dermoids may contain kerati-
wise normal globe. The appearance in dogs is
nized epithelium, hair, blood vessels, fibrous
a cornea with a horizontal diameter of less
tissue, fat, nerves, glands, smooth muscle, and
than 12 mm. A small cornea may also occur
cartilage. Dermoids are present at birth, but
with ocular or systemic conditions associated
they may not be recognized clinically until the
with multiple ocular anomalies; the most
dog is several weeks old. If they are irritating
common is microphthalmia. Microcornea is
from the long hairs extending from its surface
reported as a feature of merle ocular dysgen-
or obstructing vision, dermoids can be treated
esis in a variety of breeds, including
by surgical removal. The procedure of choice
Australian Shepherds and Dachshunds. The
for corneal dermoids is superficial lamellar
Collie, Miniature and Toy Poodle, Miniature
keratectomy (see the next section). In the
Schnauzer, Old English Sheepdog, Saint
uncommon situation where a dermoid requires
Bernard, and possibly other breeds may be
deep keratectomy, a conjunctival graft may be
predisposed to microcornea and multiple
warranted. Surgical placement of canine amni-
ocular anomalies as well.
otic membrane following excision of large der-
moids is reported to enhance healing and
Megalocornea reduce corneal scarring.
Megalocornea is a cornea of greater than nor-
mal size, normal being approximately Superficial Keratectomy
16–18 mm in horizontal diameter. This is a Superficial keratectomies are the most fre-
rare, congenital anomaly in the dog and is usu- quent corneal surgery in the dog. Other super-
ally concurrent with congenital glaucoma and ficial corneal lesions amenable to superficial
buphthalmos (or megalophthalmos). keratectomy include indolent ulcers, corneal

(a) (b)

Figure 9.7 (a) A dermoid, or choristoma, at the temporal limbus in a young dog. (b) A histological section of
a dermoid after keratectomy. Note the hair follicles and glands that are typical of dermal tissue.
(Hematoxylin and eosin stain.)
320 Canine Cornea and Sclera: Diseases and Surgery

neoplasms, sequestrums, foreign bodies, cor- insertion of the lamellar-­separating device (e.g.,
neal abscesses, inclusion cysts, bacterial and Martinez corneal dissector, microsurgical blade
fungal keratitis (usually in conjunction with a #6400 or #6900, and iris spatula) to be inserted.
conjunctival graft or flap), and corneal degen- Using this separator instrument through the ini-
eration. The specific procedure or method for tial incision, the entire lamellar plane under the
the superficial keratectomy is determined by lesion to be removed is separated, thus under-
the type of lesion. Before performing a superfi- mining the lesion. Corneal section scissors are
cial keratectomy, determining the depth of the then introduced into the initial incision and
lesion using biomicroscopy, high-­frequency used to complete the keratectomy.
ultrasound, confocal microscopy, or optical Following keratectomy, the cornea is treated
coherence tomography is important in plan- much like a corneal ulcer with topical broad-­
ning the surgery. If the resulting corneal spectrum antibiotics to prevent infection and
wound extends deeper than one-­half corneal with topical atropine to decrease ciliary spasm
thickness, use of a conjunctival pedicle flap or and discomfort. A potentially devastating com-
amniotic membrane graft is warranted to pro- plication after keratectomy is corneal perfora-
tect the cornea, to help prevent perforation, tion, which generally results from infection at
and to promote healing. Current observations the surgical site. The potential for infection is
suggest that corneal stromal tissue may not exacerbated by deep, extensive keratectomies
completely regenerate; the number of superfi- but is largely preventable by use of conjuncti-
cial keratectomies that can be performed at the val flaps or other supportive surgeries.
same site is limited to two or three. Reevaluations after surgery (with monitoring
Superficial keratectomy is most commonly of healing by use of fluorescein dye applica-
performed in veterinary medicine using tradi- tion) and use of topical antibiotics should pre-
tional microsurgical instruments; however, it vent most postsurgical complications.
can also be performed using carbon dioxide or
excimer laser ablation. Magnification (e.g., an
Congenital Corneal Opacities
operating microscope) is essential to perform
the surgery, and specialized surgical equipment Corneal opacities are commonly classified by
(e.g., corneal dissector, dermatology punch, the degree of opacity and are described as a
corneal trephine, and micrometer diamond nebula, macula, or leukoma. A nebula is a
knife) greatly facilitates the removal of corneal minor, diffuse, hazy opacity with indistinct
tissue and may improve the clinical outcome. borders. A macula is a moderately dense opac-
There are two common methods to perform a ity with a circumscribed border. A leukoma is a
superficial keratectomy: the complete and the dense, white opacity. When iris tissue adheres
partial incision keratectomy. In the first to the posterior surface of the cornea beneath
method, the complete incision keratectomy, an an area of corneal opacity, the condition is
initial corneal incision is made that surrounds described as an adherent leukoma.
completely the lesion to be removed. The inci-
sion needs to be at appropriate depth to allow Infantile Corneal Dystrophy
complete removal of the lesion. It is made using Infantile corneal dystrophy, or puppy keratop-
a corneal trephine, diamond knife, or micro- athy, is a congenital, subepithelial, geographic
surgical blade (Figure 9.8). corneal opacity that is nonhereditary, tran-
In the second type of superficial keratectomy, sient, and observed in puppies younger than
the partial incision keratectomy, a small corneal 10 weeks. The condition slowly resolves and, in
incision is made adjacent to the lesion that is to most cases, is absent by 12–16 weeks of age.
be removed. This initial incision is made at the There is no interference with functional vision
appropriate depth but only wide enough to allow and treatment is unnecessary.
­Developmental Abnormalities and Congenital Disease  321

(a)

(b)

(c)

(d)

Figure 9.8 Complete incision superficial keratectomy. (a) The initial corneal incision, which may be round,
square, or triangular, should completely surround the lesion to be removed and can be made using a
corneal trephine, diamond knife, or microsurgical blade. (b and c) After the initial incision is made, the edge
of the tissue to be removed is grasped by a forceps, and a corneal dissector (e.g., Martinez corneal dissector,
Beaver #64 microsurgical blade, and iris spatula) is introduced and held parallel to the cornea. The
dissector is used to separate the corneal lamella without penetrating deeper than the original incision. The
cornea is then separated until the opposite incision line, or limbus, is reached. (d) Scissors may be needed
to connect the dissection to the opposite incision or to remove the corneal tissue from the limbus.

Corneal Opacities with Persistent in some. Persistent pupillary tissue strands arise
Pupillary Membranes from the iris collarette and represent failure of
PPMs are congenital lesions that occur in many normal embryonic vasculature structures to
canine breeds and are known to be hereditable completely regress. Corneal and/or anterior lens
322 Canine Cornea and Sclera: Diseases and Surgery

capsule lesions can be associated with adher- Ulcerative Keratitis


ence of PPMs (Figure 9.9). Both focal and diffuse
Corneal ulceration, or ulcerative keratitis, is
corneal opacities occur, but the former is more
one of the most common ocular diseases in the
frequent. Focal lesions appear as punctate, lin-
dog. A corneal ulcer is present when there is a
ear, or round deep corneal opacities that may be
break in the corneal epithelium that exposes
pigmented or unpigmented. Larger, more dif-
the underlying corneal stroma. Clinically, lac-
fuse corneal opacities also affect Descemet’s
rimation, blepharospasm, photophobia, con-
membrane and may result from generalized
junctival hyperemia, corneal edema, and
stromal edema. PPM-­associated leukomas may
possibly miosis and aqueous flare are also pre-
be isolated anomalies or a component of a more
sent. The diagnosis of a corneal ulcer is made
extensive anterior segment dysgenesis.
on the basis of these clinical signs and the
retention of topically applied fluorescein dye
Limbal Colobomas and Staphylomas by the corneal stroma (Figure 9.10). There are
several types of corneal ulcerations (Table 9.2).
Colobomas or staphylomas of the limbus or sclera
Uncomplicated superficial ulcers usually heal
are rare in the dog. The lesions are thin regions of
rapidly, with minimal scar formation. Complicated
the globe’s fibrous tunic lined by uveal tissue and
deep ulcers, such as those with microbial infec-
appear as a tan, gray, or blue raised mass covered
tion, however, may lead to impaired vision because
with conjunctiva. If strabismus is present, vision
of corneal scarring or, when corneal perforation
may not be present! Etiologies include congenital
occurs, to anterior synechia formation. Severe
malformation and secondary to inflammation,
ulcerative keratitis may lead to loss of the eye
glaucoma, neoplasia, trauma, or surgery.
because of endophthalmitis, glaucoma, phthisis
bulbi, or a combination of these. Corneal ulcers
are classified by depth of corneal involvement and
­Inflammatory Keratopathies by their underlying cause.
The first step in treating all corneal ulcers
Corneal diseases may be categorized into
involves identifying and removing the inciting
inflammatory and noninflammatory causes.
cause, which may be eyelid abnormalities (e.g.,
Inflammatory corneal disorders can be further
classified into ulcerative and nonulcerative
keratitis.

Figure 9.10 The diagnosis of a corneal ulcer is


made on the basis of retention of topically applied
Figure 9.9 Dog with PPMs adherent to the posterior fluorescein dye by the corneal stroma as observed
cornea and resulting in a focal corneal opacity. in this superficial corneal ulcer.
­Inflammatory Keratopathie  323

masses, lagophthalmos, distichiasis, ectopic penetrating corneal and lenticular injury. If


cilia), foreign bodies, trauma, and KCS. Chronic, the pellet is ferrous (rather than lead), surgical
infected, or progressive corneal ulcers should removal should be attempted as iron or ferrous
undergo microbiological culture and antibiotic pellets are retinotoxic, and eventually can
susceptibility tests and cytological examination destroy the retina.
of corneal samples. These diagnostic proce-
dures help guide specific antimicrobial therapy. Ulcerative Keratitis: Depth
of Corneal Involvement
Corneal Foreign Bodies Corneal ulcers are classified by the depth of
Epithelial and superficial stromal foreign bodies corneal involvement and by their underlying
are not uncommon and may occur more fre- cause. Depth of corneal involvement is
quently in hunting dogs and in the fall. They reviewed first and includes superficial corneal
may be successfully removed with saline hydro- ulcers, stromal corneal ulcers, descemetoceles,
pulsion, a cytobrush, an ophthalmic spear and perforations (see Table 9.3).
sponge, or a Kimura spatula. This can generally
be performed under topical anesthesia alone Superficial Corneal Ulcers
with excellent success rates. Superficial corneal ulcers are further classified
Stromal or penetrating foreign bodies, with- as uncomplicated, progressive, or refractory.
out lens involvement and without significant For successful management of ulcerative kera-
anterior uveitis, usually require general anes- titis, the inciting cause of the ulcer is identified
thesia for removal but have a good prognosis and removed, the stage and severity of the
for vision retention after surgery. There is a ulcer is determined, and an appropriate thera-
report of a penetrating gunshot injury with peutic modality is selected. Identifying the
lead shot entrapped within the choroid where cause or contributing factors requires a thor-
the dog remained visual for 4.5 years after ough ocular examination. Eyes should always

Table 9.3 Antiproteolytic agents for topical treatment of melting corneal ulcers.

Compound Concentration used Inhibitory activity Inhibitory mechanism

Tetracyclines (doxycycline, 0.1%a MMP inhibitor Chelating agent


oxytetracycline) (Ca2+ and Zn2+)
N-­Acetylcysteine 5–10% MMP inhibitor Chelating agent
(Ca2+ and Zn2+)
Disodium 0.2%b MMP inhibitor Chelating agent
ethylenediaminetetraacetic (Ca2+ and Zn2+)
acid (EDTA)
Ilomostast (Galardin™) 0.1% MMP inhibitor Chelating agent
(Ca2+ and Zn2+)
Serum (α2-­macroglobulin Undilutedc MMP and serine Various entrapment
and α1-­proteinase inhibitor) protease inhibitor of the protease
α1-­Proteinase inhibitor 0.1% Serine protease Entrapment of the
inhibitor protease

MMPs require Ca2+ and Zn2+ as cofactor and stabilizing ion, respectively.
a
Note that doxycycline can also be administered orally (10 mg/kg, s.i.d.).
b
Easily made by the addition of 5 ml of sterile water to a commercial blood collection tube.
c
Serum stored in the refrigerator can be used for up to five to seven days. It should then be discarded because of the
risk of bacterial contamination.
324 Canine Cornea and Sclera: Diseases and Surgery

be evaluated for eyelash abnormalities, eyelid Boxer ulcer and superficial nonhealing ulcera-
structure and function, and preocular tear film tions in old dogs of other breeds.
disorders (e.g., Schirmer tear test, tear breakup Although originally reported as Boxer ulcers
time, and Rose Bengal retention). (due to its predilection for Boxers), subsequent
Uncomplicated superficial ulcers from direct larger studies document occurrence in almost
trauma, shampoos, exposure while under gen- every breed that are affected middle-­to
eral anesthesia, and other factors can resolve advanced aged, overrepresented by the Boxer
with only topical antibiotic therapy applied breed, and exhibit varying degrees of blepha-
three to four times daily to prevent secondary rospasm. The initiating event in dogs with
bacterial infection. Combination ophthalmic SCCEDs is likely superficial corneal trauma.
preparations (e.g., neomycin, bacitracin, and These epithelial defects result in variable
polymyxin B), erythromycin, or oxytetracy- amounts of ocular discomfort along with the
cline are frequently good antimicrobial selec- potential for corneal neovascularization, fibro-
tions that provide broad-­spectrum coverage. sis, and edema. Hallmark clinical and histo-
Stimulation of the abundant sensory recep- logical features of SCCED include a superficial
tors in the superficial cornea by ulceration axial or paraxial corneal ulcer that does not
results in a localized neurogenic reflex anterior extend into the stroma, associated with redun-
uveitis associated with miosis of the pupil, iris dant, nonadherent corneal epithelial borders
hyperemia, and increased protein levels in the that may be associated with an acellular hya-
aqueous humor (i.e., aqueous flare). Therefore, line zone in the anterior stroma, neovasculari-
a mydriatic agent (1% atropine or 1% tropi- zation, and, when not treated adequately, may
camide) is applied topically once or twice daily persist for weeks to months. While the Boxer
to control ciliary muscle spasm, a dilated pupil, breed is overrepresented with this condition,
and the ocular discomfort associated with the comparison and inclusion of other breeds of
secondary uveitis. The ulcer should resolve in older dogs has not determined whether their
two to six days with limited or no scarring; if pathogenesis is the same or different.
not, it should be reevaluated for an undetected,
underlying cause or contributing factor. Diagnosis
Corneal ulcers may be a complication of gen- SCCED should be considered in any middle-­
eral anesthesia for nonophthalmic procedures and advanced aged dog with an erosion that
in dogs, even those whose eyes were lubricated has not healed in one to two weeks. An average
with topical lubricating gel. Evaluation of 199 age of eight to nine years is reported with these
canine eyes lubricated before general anesthe- dogs (the Boxer breed may be younger dogs);
sia demonstrated corneal ulceration in 1 eye therefore, young dogs with nonhealing ero-
and corneal erosion in 25 eyes. sions should be very carefully examined prior
to a diagnosis of SCCED. Often in the Boxer
Spontaneous Chronic Corneal Epithelial Defects breed, both eyes may be affected, but not at the
Spontaneous chronic corneal epithelial defects same time. This condition may be divided into
(SCCEDs) in dogs are chronic superficial (i) the Boxer breed and (ii) aged dogs of any
ulcers that fail to resolve through normal breed. Studies suggest possible defects in the
wound-­healing processes. A variety of other basal epithelium and its basement membrane
terms include indolent erosions or ulcers, and/or defects in the anterior stroma.
canine recurrent erosions, refractory corneal SCCEDs have a typical clinical appearance
ulcers, Boxer ulcers, nonhealing erosions, per- (Figures 9.11 and 9.12). A ring of loose epithe-
sistent corneal erosions, recurrent epithelial lium surrounds a SCCED, resulting in a diffuse
erosions, and idiopathic persistent corneal ero- ring or halo of less intense fluorescein staining
sions. SCCEDs are generally divided into the around the defect as fluorescein diffuses
­Inflammatory Keratopathie  325

Treatment
Most studies for medical treatment for SCCEDs
include epithelial debridement of the loose epi-
thelial lip of epithelium, and medical treatment
leads to healing (Box 9.2). The most common
therapy for the treatment of SCCEDs is epithe-
lial debridement, used alone or in combination
with other medical or surgical therapies. After
application of topical anesthetic, epithelial
debridement is performed using multiple dry
cotton-­tipped applicators, beginning in the
center of the erosion and working out to the
periphery with radial strokes. Normal corneal
Figure 9.11 Large nonvascularized SCCED in a epithelium cannot be removed with a cotton-­
nine-­year-­old Boxer dog. Note the axial location, tipped applicator, so debridement should be
ring of loose epithelium, and the decrease in continued until only firmly adhered epithelium
intensity of the fluorescein staining as it migrates
under the loose epithelium surrounding the defect. remains. Debridement can also be performed
with corneal burrs, excimer laser spatulas,
scalpel blades, spatulas (Kimura and iris), or
forceps. Typically, debridement can be repeated
at 7-­to 14-­day intervals. Success rates and time
to healing vary between studies from 20% in
14 days to 84% in an average of 23 days. The
number of debridements, the time between
procedures and examinations, and the number
treatments suggest the success rates of approxi-
mately 50%. It was noted that adding a soft
contact lens or third eyelid flap increased heal-
ing rates after debridement to 58% and 64%,
respectively. A number of treatment options
have been reported for the treatment of
SCCEDs. With all treatments, prophylactic
Figure 9.12 Vascularized SCCED in a 10-­year-­old
antibiotics should be administered q 6 h to q 8 h
Boxer dog. Note the peripheral location of the erosion,
superficial corneal vascularization, ring of loose to prevent secondary infection of the compro-
epithelium surrounding the defect, and fluorescein mised cornea. A cycloplegic (e.g., atropine) to
leakage under surrounding loose epithelium. improve comfort and Elizabethan collar to pre-
vent self-­trauma are usually indicated.
underneath the poorly attached epithelium. Most studies of topical medications for the
A SCCED is always superficial, with no stromal treatment of SCCEDs consist of small, nonran-
loss. Varying degrees of vascularization occur domized, nonmasked, and/or uncontrolled
in SCCED (determined by the duration of the clinical trials. The lack of controls and small
active ulcer) with studies reporting 58–64% of sample sizes make interpretation of these
lesions exhibiting neovascularization. The results difficult, particularly since statistical
degree of pain demonstrated by blepharospasm power is often too low to detect a meaningful
varies between dogs, but tends to be fairly high difference between treatment groups. A wide
in the early stages of the disease but may variety of medical therapies have been utilized
decrease with chronicity. in the therapy of SCCEDs. Treatment with
326 Canine Cornea and Sclera: Diseases and Surgery

Box 9.2 Clinical Management of Corneal Erosions


Drugs reported to facilitate healing of corneal erosions
●● Polysulfated glycosaminoglycans (PSGAGs)
●● Aprotinin
●● Epidermal growth factor
●● Substance P alone and combined with insulin-­like growth factor
●● Chondroitin sulfate combined with antibiotics
●● Fibronectin
●● Autogenous serum
●● Doxycycline and tetracycline
Recommended approach for “first-­time” patients
●● Topical broad-­spectrum antibiotics (some are mildly epitheliotoxic; administer at low frequency,
i.e., three to four times daily)
●● Topical 1% atropine is indicated as a cycloplegic for acute ocular pain, usually for one to
three days. Avoid if tear formation is significantly decreased
●● Debridement of the nonadherent epithelium using a dry cotton-­tipped applicators. Other
devices to remove loose corneal epithelia include a dull scalpel blade, dull spatula (e.g.,
platinum Kimura spatula, iris spatula), or fine-­toothed forceps. After topically anesthetizing
the cornea, all loose epithelium is removed, usually to a point 1–2 mm beyond the margin of
fluorescein stain retention. Hence, it is not uncommon to have a large area of abnormal
epithelium and to greatly increase the ulcer’s size by debridement. Debridement may need
to be repeated at 7–14-­day intervals, but the amount of loose epithelium should decrease
with each removal as the ulcer heals
For refractory cases (after two or three debridements)
●● Debridement followed with diamond burr keratectomy or grid or punctate keratotomy
recommended
●● Bandage corneal soft contact lenses, collagen shields made from porcine scleral collagen,
and cyanoacrylate tissue adhesives are other possibilities

topical PSGAGs resulted in healing of 82% of (5 mg/kg q 12 h) and topical triple antibiotic
the treated dogs. A separate study evaluated (q 8 h), topical oxytetracycline ophthalmic
aprotinin, with a resulting healing rate of 33%. ointment (q 8 h) and oral cephalexin (22 mg/kg
Treatment with topical substance P alone or q 12 h), or a control group of topical triple anti-
combined with insulin-­like growth factor biotic ointment and oral cephalexin. Dogs
resulted in healing of erosions in 70% and 75% treated with topical oxytetracycline ophthal-
of dogs, respectively. A chondroitin sulfate– mic ointment healed significantly faster (74%
antibiotic combination brought about healing healed within two weeks) than dogs in the con-
in 81% of treated dogs, but treatment had to be trol group (10% healed within two weeks).
continued for four weeks, which is longer than Dogs treated with oral doxycycline healed
many other reported therapies. In a rand- more rapidly than dogs in the control group, but
omized, controlled clinical trial, dogs were the difference was not statistically significant.
treated with manual debridement and grid The effects of topically applied heterologous
keratotomy followed by oral doxycycline serum versus isotonic saline were evaluated in
­Inflammatory Keratopathie  327

41 dogs with SCCEDs. Median time to epitheli- determine the underlying etiology, due to the
alization was not significantly different high likelihood of microbial infection. These
between serum-­or saline-­treated eyes and was diagnostic tests are performed first to maximize
not significantly different between Boxer ver- growth of the organisms on culture and to
sus non-­Boxer breeds. avoid altering surface organisms or cell types.
Topical corticosteroids generally should be Stromal ulcers may be divided into progres-
avoided in SCCEDs because they decrease the sive and nonprogressive types. Nonprogressive
rate of corneal wound healing and inhibit host deep ulcers can be managed medically, similar
defense mechanisms. Some clinicians believe to superficial ulcers, with treatment directed
that SCCEDs with excessive granulation tissue, by the results of culture and susceptibility test-
however, may benefit from judicious use of topi- ing. Surgical intervention is indicated in deep
cal corticosteroids, with the aim of reducing the corneal ulceration (i.e., when depth of the cor-
formation of vision-­obscuring scar tissue. neal lesion is 50% of the corneal thickness or
deeper). Surgical procedures most commonly
Stromal Corneal Ulcers employed in these cases include grafts from
Ulcerative keratitis that extends into the cor- conjunctiva, amniotic membrane, bovine peri-
neal stroma usually involves a secondary cardium, or porcine urinary bladder, cornea, or
microbial infection that initiates or participates synthetic or bioengineered grafts.
in the stromal destruction. Less commonly, Progressive deep stromal ulcers in the dog are
traumatic injuries can result in a wound that potentially vision-­ and globe-­threatening, and
extends into the deeper stroma. Generally, any therapy must be aggressive. Antibiotic selection
visible defect in the corneal surface suggests is frequently made on the basis of cytology, cul-
possible stromal involvement (Figure 9.13), ture, and susceptibility test results. Topical 1%
because most ulcers involving only the epithe- atropine is administered to minimize the dis-
lium are not readily visible (except possibly for comfort from ciliary muscle spasm and to pre-
indolent corneal ulcers) and require fluores- vent synechiae formation. If rapid stromal loss
cein staining for definitive diagnosis. Any ulcer or melting is present, intensive topical antibiotic
with a suspected stromal defect should be therapy (every 1–2 h) is indicated, and bacteri-
cultured and corneal scrapings for cytological cidal antibiotics with a spectrum that includes
examination performed, prior to instillation of Gram-­negative rods, such as P. aeruginosa, and
fluorescein or other topical substances, to Gram-­positive cocci, such as Staphylococcus and
Streptococcus spp., should be empirically selected
while culture results are pending. Monotherapy
with a broad-­spectrum antimicrobial such as a
late-­generation fluoroquinolone (e.g., moxiflox-
acin and gatifloxacin) or combination therapy with
an early-­generation fluoroquinolone (e.g., cipro-
floxacin and ofloxacin) or aminoglycoside (e.g.,
tobramycin), in addition to a first-­generation ceph-
alosporin (e.g., cefazolin) or triple antibiotic, is a
good empirical choice. After culture and suscep-
tibility testing results are received, the antibiotic
regimen can be altered to more specifically target
the infectious agent. Topical anticollagenase–
antiproteinase preparations are also strongly
Figure 9.13 Central, deep stromal corneal ulcer in recommended in cases of progressive ulcera-
a brachycephalic dog. tive keratitis.
328 Canine Cornea and Sclera: Diseases and Surgery

Corneal Tissue Adhesives the lesion. Conjunctival grafts are generally


Corneal tissue adhesives may also be used as a harvested from adjacent bulbar conjunctiva;
nonsurgical therapy for nonhealing corneal however, the tarsal conjunctiva can be used.
ulcers as well as for corneal ulcerations in which The disadvantage of a tarsoconjunctival graft
general anesthesia is not possible.. Isobutyl is that the eyelid is mobile, and some tension
cyanoacrylate tissue adhesive has been used in can be applied to the flap by movement of the
treatment of deep stromal ulcers, descemetoce- eyelids, thereby leading to a possible higher
les, small perforations, lacerations, and refrac- rate of dehiscence. The bulbar conjunctival
tory corneal ulcers in the dog. The procedure flap moves with the eye; thus, no tension is
involves use of topical anesthesia (if general applied to the flap itself.
anesthesia is not used); debridement of the With all types of conjunctival flaps, it is
defect (as necessary and judiciously); drying of important that the corneal graft bed and ulcer
the site with a cotton-­tipped swab, cellulose be properly prepared. The recipient bed for the
sponge, or a warm-­air (i.e., hair) dryer; applica- conjunctival graft is prepared by debriding the
tion of a thin layer of tissue adhesive through a lesion, thereby removing loose epithelium and
25-­to 30-­gauge needle; and prevention of blink- devitalized corneal tissue. Great care should be
ing for 15–60 s while the cyanoacrylate solidi- taken to prevent corneal perforation during
fies. Care must be taken to apply a minimal this debridement.
amount of adhesive.
Total (360°) Conjunctival Flap
Conjunctival Grafts The total or 360° conjunctival flap (Gunderson
The surgical procedure most commonly used for flap) covers the entire cornea and is rarely indi-
chronic, infected, or progressive corneal ulcers is cated now. It has been described in cases when
a conjunctival flap or graft. Conjunctival flaps the ulcerative keratitis or other lesion involves
provide corneal support, provide fibrovascular the entire cornea. The 360° conjunctival graft is
tissue to fill the corneal defects, and bring a blood easy to perform, and it is effective for large cor-
supply (as well as blood-­associated immune neal lesions. It does, however, cover the entire
components, systemic antibiotics, and natural cornea, which decreases vision and prevents
anticollagenases [e.g., α2-­macroglobulin]) to the monitoring of the corneal lesion or inflamma-
lesion. Because partial conjunctival flaps cover tion within the eye and results in a very large,
only a small area of the normal cornea, the clini- probably blinding scar. If the goal is to only sal-
cian can visualize much of the cornea and ante- vage the globe (and not vision), then this graft
rior chamber, which in turn allows continuous should be considered.
examination of these structures to monitor ulcer
progression and possible anterior uveitis. Having Bridge or Bipedicle Graft
only a small portion of the cornea covered may The bridge or bipedicle graft is a linear graft
also allow the animal to continue to be visual. attached to the conjunctiva at two sites. This
This technique has distinct advantages over graft is generally indicated in long, linear
other types of surgical procedures once used for corneal lesions, such as corneal lacerations
corneal ulcers, which are now considered to be that require conjunctival graft covering after
archaic, such as third eyelid flaps. direct suturing or in ulcers that may require
Available types of conjunctival grafts additional vascularization, such as some
include the total or 360° conjunctival graft central corneal lesions. These grafts are
(Gunderson flap), the bridge or bipedicle, the begun by incising the conjunctiva from the
hood, and the pedicle conjunctival graft. limbus for approximately 180° both adjacent
Conjunctival grafts consist of thin conjuncti- and parallel to the linear corneal lesion
val tissue transposed onto the cornea to cover (Figure 9.14).
­Inflammatory Keratopathie  329

(a)

(b)

(c)

(d)

Figure 9.14 Bridge or bipedicle conjunctival graft. (a) The conjunctiva is excised from the limbus for
approximately 180° both adjacent and parallel to the linear corneal lesion. This area is extensively
undermined, and the underlying fibrous tissue is removed. A second conjunctival incision is made 5–8 mm
peripheral and parallel to the original conjunctival incision, thus creating a “bridge” of conjunctiva. (b and c)
The bridge is advanced over the lesion and then sutured, using simple, interrupted sutures into the cornea
around the lesion. (d). The original graft harvesting site is closed by opposing the remaining conjunctiva
with a simple, continuous suture.
330 Canine Cornea and Sclera: Diseases and Surgery

Hood (180°) Conjunctival Flap


The hood or 180° flap is indicated for periph-
eral corneal lesions. The conjunctiva adjacent
to the lesion is cut from the limbus and under-
mined, and the graft is then advanced to cover
the lesion and sutured in place, generally with
simple, interrupted sutures. The combination (a)
of superficial keratectomy and a conjunctival
advancement hood flap has been used success-
fully in the treatment and management of dogs
with bullous keratopathy. (b)

Pedicle Conjunctival Graft


The pedicle or rotational graft is probably the
most useful and versatile conjunctival graft
and usually preferred by a veterinary ophthal-
mologist. The base of the pedicle graft should
be directed toward the area of the limbus
nearest to the lesion. It is probably the most
difficult conjunctival graft to perform, but
also the most rewarding (Figure 9.15).
Conjunctival tissue will adhere to the corneal
lesion and epithelialization surrounding the
graft, but they will not adhere underneath the
conjunctiva where there is normal corneal (c)
epithelium. Four to twelve weeks after place-
ment of the grafts, the blood supply may be Figure 9.15 Pedicle conjunctival graft. (a) The
base of the pedicle flap should be directed toward
interrupted by cutting the base of the pedicle the area of the limbus nearest to the lesion. Once
flap at the limbus. This can usually be per- the location of the base is determined, a site
formed with use of topical anesthesia and 1.0–1.5 cm temporal to the base is located, at
Westcott or Stevens tenotomy scissors which the flap will be initiated. Through a small
slit in the conjunctiva, the entire conjunctival flap
(Figure 9.16). Eliminating the blood supply site is undermined using blunt dissection. Two
will allow the conjunctival graft to recede and parallel cuts are then made to create a strip of
lessen the resulting corneal scar. conjunctiva. (b) The strip of conjunctiva is rotated
to cover the corneal lesion. The flap is sutured to
the cornea with simple, interrupted sutures of 7-­0
Island Conjunctival Graft to 9-­0 polyglactin 910 or nylon. (c) The sutures are
A conjunctival free island graft is a modified placed first at the distal end of the flap and then
conjunctival graft in which the blood supply is 1.0–1.5 mm apart.
severed from the outset. These grafts are essen-
tially a transplant of conjunctival tissue to the Complications
cornea, and their use has been described in The most common complication from any type
deep corneal lesions or corneal perforations. of conjunctival grafting procedure is dehis-
The donor site can be either the tarsal or bul- cence of the graft from the corneal lesion. This
bar conjunctiva. The graft usually becomes may occur because the corneal lesion is pro-
revascularized within three to five days gressing, worsening, and damaging the cornea
depending on the amount of corneal vascula- at the points where sutures secure the graft.
ture present near the lesion before surgery. Excessive tension on the graft or allowing a
­Inflammatory Keratopathie  331

(a) (b)

Figure 9.16 After the corneal ulcer is healed, the blood supply to the conjunctival graft can be trimmed
(a). After installation of topical anesthetic, the scissors can be placed under the pedicle portion of the graft,
which is not adhered to the underlying normal corneal epithelium, and transect it (b).

significant portion of the fibrous Tenon’s cap- lesion occurs, aqueous humor is lost, and iris
sule to remain attached to the graft may result prolapse may occur. Potential contamination of
in premature dehiscence of the graft. the anterior chamber can occur after rupture of
Descemet’s membrane, which may lead to
Amniotic Membranes endophthalmitis and a much poorer prognosis
Amniotic membranes are used for treatment for saving the eye as well as for vision. However,
of corneas after superficial keratectomy and all deep corneal lesions should be considered
bullous keratopathy, for treatment of malacic infected, and preoperative bacterial and fungal
stromal corneal ulcers, and for corneal recon- culture and sensitivity tests should always be
struction after removal of an inclusion cysts performed along with conjunctival cytology
and dermoids. Amniotic membranes have also before surgery to help direct topical and sys-
been used as grafting material after full-­ temic medical therapy after surgery.
thickness keratotomy, both experimentally and Before surgery, the posterior segment of the
clinically. Benefits of amnion include its antifi- affected eye should be assessed (or attempted)
brotic, antiangiogenic, antiprotease, anti-­ to help determine the prognosis for vision.
neoplastic and anti-­inflammatory properties. Posterior segment examination may be possi-
Amniotic membrane may be used as the sole ble in descemetoceles, but it is usually difficult
material for ocular surface reconstruction or it with perforations and iridal prolapses. In those
may be combine with or covered with a con-
junctival graft (thereby providing additional
strength).

Descemetoceles
and Corneal Perforations
A descemetocele is a deep corneal lesion in
which the corneal epithelium and stroma are
completely destroyed, leaving a lesion lined
only by Descemet’s membrane and corneal
endothelium (Figure 9.17). Descemet’s mem-
brane is a tough, elastic membrane, but it is only
3–12 μm thick and thus easily ruptured. Once Figure 9.17 Central corneal descemetocele in a
this final barrier is breached, a full-­thickness dog with chronic corneal disease.
332 Canine Cornea and Sclera: Diseases and Surgery

cases when ophthalmoscopy is not possible, has been replaced with the corneoconjunctival
evaluation of consensual pupillary light reflex graft, which is easier to perform, provides a
and the dazzle reflex as well as ultrasonogra- clearer corneal result, and avoids the hemor-
phy may provide some information regarding rhage as the sclera is incised.
the integrity of the posterior segment. This surgery is similar to the sliding skin
Most small descemetoceles (i.e., less than grafts used in many surgeries, and offers the
3–5 mm in diameter) can be repaired successfully best opportunity for a clear central cornea. After
using conjunctival grafts (described earlier). If a the animal is anesthetized, necrotic cornea is
conjunctival flap is used, however, the corneal debrided using sharp dissection. If the cornea is
lesion will remain fragile, and in many instances, not perforated, great care should be taken dur-
a large stromal scar will develop. Corneal perfo- ing this debridement not to rupture Descemet’s
rations have also been treated successfully with membrane. Following debridement, a micro-
conjunctival flaps and grafts. There is an increas- surgical blade (i.e., Beaver #64) is used to create
ing number of reports describing the use of syn- two diverging, linear, one-­half to three-­quarter
thetic grafting material that temporarily stabilizes corneal thickness incisions that extend from the
an eye and acts as a scaffolding for growth of periphery of the lesion to the limbus. If the eye
fibrous tissue. Bioengineered porcine small intes- is perforated, filling the anterior chamber with a
tinal submucosa and ECM derived from porcine viscoelastic substance (e.g., sodium hyaluro-
urinary bladder have been used for corneal sur- nate) will greatly enhance the ability to create
gery. More recent reports have shown increased corneal incisions and facilitate suture place-
success and fewer complications with these syn- ment. The incisions are then extended over the
thetic materials utilized with or without a con- limbus and into the conjunctiva and sclera. This
junctival graft. is the area from which the graft will be har-
vested. The width of the graft should be slightly
Corneoscleral more than that of the corneal defect. The edge
and Corneoconjunctival Transposition of the lesion at the leading edge of the graft is
Corneoconjunctival transposition is a type of grasped with a forceps and elevated, and the
autologous corneoscleral graft that uses a sliding cornea is split and undermined toward the lim-
pedicle of cornea and attached sclera (or con- bus. A corneal dissector greatly facilitates this
junctiva) to repair corneal defects. It is indicated stromal lamellar dissection; however, microsur-
in central, deep, or perforated corneal lesions gical blades or a flat iris spatula can also be used.
with sufficient peripheral healthy cornea that The undermining should cross over the limbus
can be used for the grafting procedure. In gen- into the sclera. Sufficient dissection should be
eral, the distance from the peripheral edge of the performed so that the graft can be advanced to
lesion to the corneal limbus must be at least cover the lesion without tension.
1 mm longer than the diameter of the corneal The corneal graft tissue is advanced to cover
lesion itself. Because autologous (“self”) tissue is the lesion and is trimmed to fill the corneal
used, corneoscleral transposition eliminates the defect – either square in shape or curved. The
need for corneal tissue donors and minimizes leading edge of the corneal graft should be
immune-­mediated inflammation. This may trimmed, especially if it was traumatized by
decrease corneal scarring and allow a clearer forceps during the dissection phase of the pro-
postoperative cornea than that seen after con- cedure. The graft is sutured to the cornea using
junctival and some other corneal grafts. A disad- simple, interrupted sutures of 8-­0 to 10-­0 pol-
vantage, however, is that corneoconjunctival yglactin 910™ or nylon. The sclera or conjunc-
transposition damages normal, healthy corneal tiva (or both) is then sutured to the cornea at
tissue and may leave a larger scar than other cor- the diverging linear incision with a continuous
neal grafts. The first reported corneoscleral graft suture pattern using the same type of suture
­Inflammatory Keratopathie  333

material used in the corneal graft. As with any ophthalmologists prefer the conjunctival grafts
corneal surgery, sutures should not penetrate because of potential rejection of the graft and
the entire thickness of the cornea but instead many if not most of these ulcerations’ infec-
be placed at a depth of two-­thirds to three-­ tions have not been controlled before grafting.
quarters the depth of the cornea. Autogenous lamellar corneal grafts from adja-
In cases of corneal perforation, the eye must cent cornea can be considered as a compro-
be reinflated following surgery. A 27-­ or 30-­ mise for treating descemetoceles, stromal
gauge needle attached to a tuberculin syringe abscesses, and perforated ulcers. These grafts
filled with balanced salt solution (BSS™) or lac- use adjacent corneal tissue slid to cover the
tated Ringer’s solution is introduced into the eye corneal defect. Advantages of this procedure
at a site opposite to the corneal graft by under- are that autografts are used, thus minimizing
mining the needle for several millimeters adja- graft rejection; that tissue is usually readily
cent to the limbus, then passing it through the available; and that a clear cornea may result
limbus and into the anterior chamber (parallel after surgery. The main disadvantage of this
to the iris). Generally, 0.5–0.8 ml of fluid is suffi- procedure is that an area of normal cornea is
cient to reinflate the eye. The corneal graft weakened. In seven dogs with corneal disease,
should be evaluated carefully for leakage; if six of the seven grafts remained translucent
leakage is present, additional sutures should be and that only one had pigmentation.
placed to create a watertight seal. The surgical procedure is initially similar to
Postoperative management of corneocon- corneoconjunctival transposition, but is limited
junctival transposition is similar to that of con- to only the cornea. Two parallel incisions are
junctival grafts. Topical antibiotics, which are made that extend past the lesion toward the lim-
chosen on the basis of culture, sensitivity, and bus. The distance between the incisions is
cytological results, and medications to control 2–3 mm wider than the diameter of the lesion.
postoperative uveitis and pain (e.g., topical The incisions are then joined by making a per-
atropine, systemic nonsteroidal anti-­ pendicular incision, and a half-­thickness kera-
inflammatory medications, or both) should be tectomy is performed. The graft should be
used. Generally, the corneoconjunctival sliding 0.5–1.0 mm wider and deeper than the lesion.
graft is well adhered to the cornea and cannot The graft is positioned in the graft bed of the
be trimmed, as is typically done with conjunc- lesion and then sutured into place with a con-
tival flaps. In some animals, however, after the tinuous or interrupted suture pattern. A con-
cornea has completely healed (usually in four junctival pedicle flap can be placed over both the
to six weeks), the conjunctiva can be cut, graft and the lesion to help promote healing, to
undermined, and excised. This usually requires bring in blood supply, and to add strength to the
general anesthesia but, in most cases, it is not corneal lesions and graft site. Use of the con-
required because the conjunctiva is on the junctival flap may be especially important with
peripheral cornea and does not significantly infected or rapidly progressing ulcers; however,
obstruct vision. These grafts yield the best increased scarring may subsequently occur.
results after the corneal ulceration has been
sterilized by intensive topical and systemic Fresh or Cryopreserved Corneal Grafts
antibiotic therapy. If the corneal is heavily Other techniques for treatment of descemetoce-
infected, the transposed cornea of the tip of the les and full-­thickness corneal perforations
graft may also become infected and slough! include grafts from using cryopreserved tissue
and corneal transplantation (i.e., penetrating
Autogenous Lamellar Corneal Grafts keratoplasty). Fresh corneal transplantation is
To provide the clearest central cornea, corneal described later in this chapter. Corneal grafting
grafts can yield the best results; however, most using homologous (i.e., from the same species)
334 Canine Cornea and Sclera: Diseases and Surgery

frozen corneal tissue has also been described for Deflation of the anterior chamber, iris prolapse,
treatment of corneal descemetoceles and perfo- hyphema, hypopyon, and significant corneal
rations. In both studies, fresh corneal tissue was edema may prevent a complete ophthalmic
collected at euthanasia of donor animals, placed examination. A consensual pupillary light reflex
in antibiotic solution containing neomycin and and dazzle reflex are positive clinical signs, but
bacitracin, and stored at a temperature of they do not ensure a normal posterior segment.
−30 °C for up to 12 months. When needed, the Ocular ultrasonography, as described previ-
tissue is thawed in sterile, warm water or at ously, can also be used to assess posterior seg-
room temperature. The grafts are cut and placed ment damage with corneal lacerations; however,
over descemetoceles or perforations, and they it is important the ultrasound coupling gel not
are sutured into place with simple, interrupted enter into the wound or anterior chamber. If
sutures. In the studies reported, no attempt was ultrasonography of the injured eye is attempted,
made to limit vascularization until the graft was the animal should be sedated or anesthetized so
completely vascularized and the cornea stains that movement of the animal does not further
fluorescein-­negative. In a series of 19 cases, 84% damage the eye. A standoff pad (e.g., solid-­gel
resulted in vision despite vascularization and standoff pad or water-­filled balloon) should also
scarring of the graft. In a series of 30 cases, 100% be used to separate the globe, gel, and probe. If
were visual at 60 days despite various complica- the lens capsule is ruptured, significant lens-­
tions such as focal dehiscence of the wound induced uveitis and cataractogenesis may occur.
(30%), partial graft necrosis (23%), and graft pig- Phacoemulsification of the lens and implanta-
mentation (13%). tion of a synthetic intraocular lens simultane-
ous with the corneal repair will decrease the
Full-­Thickness Corneal Lacerations postoperative inflammatory response and help
Surgical repair of most corneal lacerations gen- to maintain vision.
erally is not overly challenging, provided proper Full-­thickness corneal lacerations may or
instrumentation, magnification, and suture may not have incarcerated uveal tissue.
materials are used. A successful visual outcome Incarcerated yet viable iris tissue should be
after traumatic corneal laceration (Figure 9.18), repositioned in the anterior chamber when pos-
however, requires a careful, thorough preopera- sible; iris tissue that has been prolapsed for
tive evaluation and selection of the appropriate longer than 6–8 h should be amputated with
surgical procedure. The extent of ocular trauma electrocautery. When removing a prolapsed iris,
must be determined before repairing the cor- gentle traction is placed on the prolapsed por-
nea, and in many cases, this can be difficult. tion, and the fresh uveal tissue is cauterized
near the cornea. Care must be taken not to cau-
terize the cornea. The anterior chamber is irri-
gated with BSS or lactated Ringer’s solution,
and the lens is carefully inspected (as described
earlier). Viscoelastic substances, such as 2.0%
hyaluronic acid, can be used to reinflate the
anterior chamber and to keep it formed while
suturing the cornea. Removal of the viscoelastic
substances by irrigation is recommended before
placement of the final suture, however, to help
prevent ocular hypertension following surgery.
Appropriate suture material for corneal lac-
Figure 9.18 Horizontal full-­thickness corneal erations includes 7-­0 to 10-­0 absorbable or non-
laceration with uveal prolapse and hyphema in a dog. absorbable suture. Choice of suture type
­Inflammatory Keratopathie  335

depends largely on surgeon preference. Nylon is broad-­spectrum topical antibiotic and atropine
easiest to handle and least reactive in the cornea are administered to limit infection and second-
initially, but in most cases, it needs to be ary uveitis. If perforation of the globe has
removed after four to six weeks. Several suture occurred, a systemic antibiotic is needed.
patterns have been described for corneal
wounds, and each has advantages and disad- Ulcerative Keratitis: Cause
vantages. Simple interrupted, simple continu- of Corneal Disease
ous or running, shoelace can be used. Also, a Corneal ulcers are classified by the depth of
tight suture placed slightly oblique to the inci- corneal involvement (as described in the pre-
sion will cause the wound edges to shift along ceding section) and by their underlying etiol-
the entire wound line When corneal sutures are ogy. Common causes of ulcerative keratitis
placed properly, minimal shift of the wound include bacterial, viral, and fungal infections
edges occurs. Following closure of the cornea, and chemical burns. Primary or secondary cor-
the anterior chamber is reformed with BSS or neal ulceration has been associated with
BSS Plus™ via a limbal injection using a 27-­ to snakebite envenomation in dogs.
30-­gauge needle. After wound closure, sterile
fluorescein dye may be applied to the wound to Bacterial Corneal Ulcers
ensure proper wound closure and to detect The intact and healthy canine cornea is highly
leaks (i.e., Seidel test). resistant to bacterial infection. If the anatomi-
cal and physiological defenses of the cornea
Corneal Foreign Bodies are compromised, such as by external trauma
Corneal foreign bodies are divided into two dif- or KCS, bacteria invasion may occur. Bacterial
ferent types: those that adhere to the corneal keratitis is the most common type of corneal
surface or become embedded on the surface of infection encountered in the dog (especially in
the cornea and those that penetrate into the cor- the brachycephalic breeds). Staphylococcus
nea or actually penetrate into the globe. Corneal spp., Streptococcus spp., and P. aeruginosa are
foreign bodies should be removed to reduce the the most frequent etiological agents of canine
potential for infection, limit pain, and prevent bacterial ulcerative keratitis; however, numer-
vascularization and scar formation. ous other Gram-­positive and Gram-­negative
Most small, adherent foreign bodies are aerobic bacteria are isolated from dogs with
removed by hydropropulsion with a fine stream corneal ulcers, including Acinetobacter,
of saline or eye wash directed forcefully at the Bacillus, Corynebacterium, Enterobacter,
corneal surface after application of a topical Enterococcus, Escherichia, Klebsiella,
anesthetic. This procedure is safe only if the cor- Micrococcus, Pantoea, Pasteurella, and Proteus
nea is not weakened, because a stream of fluid spp. Obligate anaerobic bacteria, including
can rupture a descemetocele or other deep ulcer. Actinomyces, Bacteroides, Capnocytophaga,
Penetrating foreign bodies have the potential Clostridium, Fusobacterium, Peptococcus, and
for greater ocular damage and commonly Peptostreptococcus spp., are isolated less fre-
require the expertise of an ophthalmic special- quently from dogs with ulcerative keratitis
ist for removal and management. Foreign bod- (14% of dogs with ulcerative keratitis in one
ies may be removed using a sterile hypodermic study (Figure 9.19).
needle or small ophthalmic forceps. Some pen- The basic pathophysiological steps of bacte-
etrating foreign bodies may require removal by rial keratitis are (i) bacterial adherence to the
an incision (#6500 microsurgical blade) made damaged corneal surface, (ii) bacterial inva-
in the cornea over the long axis of the foreign sion of the corneal epithelium and underlying
body utilizing an operating microscope. After stroma, (iii) bacterial multiplication, (iv) elab-
removal of a corneal foreign body, a oration of bacterial exotoxins, endotoxins, and
336 Canine Cornea and Sclera: Diseases and Surgery

samples. Use of both microbial culture and


cytological evaluation of corneal specimens is
recommended because the combination maxi-
mizes identification of infectious keratitis.

Viral Keratitis
Canine herpesvirus-­1 (CHV-­1) infection may
result in ulcerative or nonulcerative keratitis in
dogs of all ages. Despite the ubiquitous pres-
ence of latent infection in domestic dogs
worldwide, corneal disease associated with
naturally acquired CHV-­1 infection is infre-
quently reported. A variety of clinical manifes-
Figure 9.19 Bacterial keratitis in a dog associated tations are observed in the cornea associated
with extensive keratomalacia. with CHV-­1 infection. CHV-­1 infection may
produce punctate, dendritic, or geographic
corneal ulcers (Figure 9.20). In the absence of
secondary bacterial infection, CHV-­1 corneal
ulcers remain superficial and are not associ-
ated with stromal loss. The corneal lesions are
reported with CHV-­1 infection and appear as a
circumferential ring of superficial corneal vas-
cularization with epithelial and subepithelial
leukocyte infiltrates in the peripheral cornea.
Diagnosis of CHV-­1 keratitis is achieved by
virus isolation or polymerase chain reaction
assay of corneal or conjunctival samples. In
contrast to some other alphaherpesviruses
associated with keratitis in domestic animals,
subclinical ocular shedding of CHV-­1 occurs
uncommonly in mature dogs, and viral detec-
tion in dogs with compatible clinical signs is
Figure 9.20 CHV-­1 dendritic ulcerative keratitis in
a dog receiving systemic immunosuppressive
strongly suggestive of an etiological role.
therapy (cornea stained with fluorescein). In addition to treatment to prevent second-
ary bacterial infection of the compromised cor-
proteases, and (v) influx of leukocytes and sol- neal (topical ocular antibiotic) and improve
uble inflammatory mediators with further tis- comfort (topical ocular atropine), antiviral
sue damage. Progression (i.e., stromal loss and therapy with 0.1% idoxuridine, 1% trifluridine,
ulcer deepening) with bacterial keratitis is and 0.5% cidofovir is used for CHV-­1 keratitis.
often rapid and attributable to both bacterial Idoxuridine and trifluridine are administered
and host-­derived toxins and proteases. Corneal six to eight times daily for the first 48 h and
leukocyte infiltrates and concurrent anterior then four times daily until resolution of active
uveitis (i.e., miosis, aqueous flare, and clinical signs of infection. Cidofovir is admin-
hypopyon) are frequent clinical findings. istered twice daily. This dosage reduced the
Diagnosis of bacterial infection of corneal duration of viral shedding in dogs with experi-
ulcers is made on the basis of cytological exam- mentally induced recurrent CHV-­1 but did
ination and microbiological culture of corneal cause exacerbation of conjunctivitis, marked
­Inflammatory Keratopathie  337

conjunctival pigmentation, and ulcerative antifungal medication commercially available in


blepharitis, as well as increased corneocon- the United States and is effective against
junctival leukocyte infiltrates. Fusarium and Aspergillus. Miconazole has broad
activity against filamentous fungi, yeast, and
Mycotic Keratitis Gram-­positive bacteria; has excellent corneal
Fungal keratitis is the canine has been increas- penetration; and does not retard corneal healing
ingly reported in the literature, and can present or cause pathological changes during corneal
as either ulcerative or nonulcerative lesions. epithelial regeneration. Voriconazole (1%) pene-
Aspergillus spp. are the most common isolates. trates the cornea well, has low toxicity, and has
Other fungi recovered include Acremonium, good activity against Aspergillus and Fusarium.
Alternaria, Aspergillus, Candida, Appropriate topical broad-­spectrum antibi-
Cephalosporium, Chrysosporium, Cladosporium, otic therapy is used concurrently with antifun-
Curvularia, Fusarium, Hormographiella, gal therapy because bacterial coinfection is
Penicillium, Phialemonium, Pseudoallescheria, common and to help prevent bacterial infection
Phialemonium, and Scedosporium spp. Clinical with chronic corneal compromise. Therapy
histories may include long-­term treatment with should generally be continued for 14–21 days,
antibiotic, corticosteroid, or a combination of or until resolution of the keratitis. Superficial
these drugs or previous corneal trauma. keratectomy with or without a conjunctival
Infections with Aspergillus spp. are usually ulcer- graft is required in many cases to resolve the
ative in nature with extensive stromal inflamma- infection, preserve the cornea, and promote
tion and melting (Figure 9.21). Lesions associated healing.
with Candida spp. are often raised yellow-­white
or gray-­white plaques or ulcerated lesions. Chemical-­Induced Corneal Ulcerations
Most cases show evidence of fungal hyphae Chemical burns to the cornea are rarely
and/or yeasts on corneal cytology, validating the reported in the dog. A chemical burn should
importance of this diagnostic modality in evalu- be considered in any dog with unexplained
ating canine ulcerative keratitis. Classes of anti- acute blepharospasm and severe corneal opac-
fungal medications include the polyenes ity (Figure 9.22). There are two general types
(natamycin, nystatin, amphotericin B), imida- of chemical burns to the cornea: acidic and
zoles (miconazole, ketoconazole), triazoles (flu- alkali. Clinical signs for either type may
conazole, itraconazole, voriconazole), and include edema, opacity, loss of corneal epithe-
fluorinated pyrimidines (5-­fluorocytosine). lium, pain, rapid dissolution of the corneal
Natamycin is the only topical ophthalmic stroma, and anterior uveitis. Alkali burns tend

Figure 9.22 Chemical burn or keratitis after mace


Figure 9.21 Mycotic keratitis in a dog. exposure in a dog.
338 Canine Cornea and Sclera: Diseases and Surgery

to be more severe, as the chemical damage is group; rather, they are a complicating component
deeper. Acidic chemicals that may cause burns of corneal ulceration. During normal corneal
to the cornea include sulfuric acid, sulfurous healing, proteases and collagenases are pro-
acid, hydrochloric acid, nitric acid, acetic acid, duced to aid in removal of devitalized cells
chromic acid, and hydrofluoric acid. and debris from the cornea. Corneal epithe-
Automobile batteries, which contain sulfuric lial cells, fibroblasts, polymorphonuclear leu-
acid, are the most common source of acidic kocytes, and some microorganisms produce
burn of the eye in humans. Hydrofluoric acid proteases and collagenases. In some corneal
may be found commonly at home in rust ulcers, these enzymes contribute to the pro-
removers, aluminum brighteners, and heavy-­ gressive breakdown and rapid “melting” of
duty cleaners. the corneal stroma. With keratomalacia, the
Chemical mace has the active ingredient corneal stroma assumes a gelatinous appear-
chloroacetophenone, a severe lacrimation and ance and may be anteriorly displaced from its
irritating substance. In dogs, high levels of normal anatomical boundaries. Acute ulcera-
exposure may produce intense necrotizing ker- tive keratitis with progressive melting requires
atitis, blepharitis, conjunctivitis, and anterior vigorous topical therapy. Appropriate broad-­
uveitis. Treatment for mace exposure is the spectrum antibiotics, antiproteinases, and atro-
same as for other chemical irritants. pine are applied (see earlier discussion).
Acid burns cause protein coagulation in the
corneal epithelium, which limits further pen-
Control of Proteolytic Activity in the
etration and thus further damage to the eye.
Treatment of Ulcerative Keratitis
Thus, these burns usually are nonprogressive
In addition of topical antibiotics, medical con-
and superficial. Alkali substances are lipo-
trol of the ulcers’ proteinases may be critical to
philic. A case series of four dogs with alkaline
success. There is increased proteinase activity
ocular injury has been reported. In all but one
in animal eyes with corneal ulcers and particu-
case, outcomes were poor and affected dogs
larly melting ulcers. Success of medical and
had decreased to no vision. In acute cases,
surgical treatment of corneal ulcers is reflected
treatment should focus on removing the alka-
by the proteolytic activity in tears. Effective
line agent and neutralizing the ocular surface
treatment leads to a rapid reduction in tear
pH. It can take several months for the cornea
film proteolytic activity that corresponds with
to heal and a fully vascularized cornea may
the improvement in the clinical signs of cor-
result in a visual outcome. Treatment for
neal ulceration. Normalizing proteolytic activ-
chemical burns of the cornea starts with copi-
ity in the tear film is an important objective of
ous irrigation. Sterile physiological saline, BSS,
the treatment of corneal ulcers (see Table 9.2).
or eyewash reduces further damage to the eye.
The goal of irrigation is to dilute the chemical,
remove particulate matter, and normalize ocu- Corneal Sequestrum
lar surface pH. Once irrigation is completed, Corneal sequestrum is rarely reported in dogs, but
assessment of the cornea and globe can be per- is rare compared to domestic cats. Brown-­ or
formed. Treatment with anticollagenase medi- black-­discolored corneal stroma associated with
cations, topical antibiotics, mydriatics, nonhealing corneal ulceration was observed clini-
systemic tetracycline, and systemic steroidal or cally. The corneal lesions corresponded micro-
nonsteroidal medication is recommended. scopically with an acellular layer of corneal stroma
surrounded by vascularization and leukocytes
Melting Ulcers (Collagenase-­ without the presence of melanin. Canine corneal
and Protease-­Associated Ulcers) sequestrum appears to be clinically and histo-
Melting ulcers with progressive stromal dis- pathologically similar to feline corneal seques-
solution (i.e., keratomalacia) are not a specific trum. Keratectomy is reported to be curative.
­Inflammatory Keratopathie  339

Nonulcerative Keratitis of nasal folds usually prevents additional


­pigmentation. In brachycephalic breeds, a
Pigmentary Keratitis (Superficial
combination of surgical procedures, which
Pigmentary Keratitis)
usually include removal of aberrant dermis in
Pigmentary keratitis develops secondary to
the medial canthus, correction of lower medial
chronic corneal irritation in the dog
eyelid entropion, and lateral or medial can-
(Figure 9.23). Corneal pigmentation can be a
thoplasty, will often prevent disease progres-
nonspecific response to chronic keratitis in any
sion. Tear production should be evaluated
canine breed; however, some brachycephalic
frequently in these dogs because KCS is a com-
breeds (e.g., Pug, Boston Terrier, Shih Tzu,
mon contributory cause of diffuse pigmentary
Lhasa Apso, and Pekingese) appear prone to
keratitis. Low-­temperature cryotherapy and
marked and rapid corneal pigmentation. The
brachytherapy with strontium-­90 have been
term “pigmentary keratitis” is often used to
reported to be successful as well.
specifically describe this clinical syndrome in
Surgical removal of pigmentary keratitis has
brachycephalic dogs. Focal corneal pigmenta-
been suggested if the inciting causes have been
tion often begins in these dogs in the nasal cor-
corrected. However, frequent recurrence of the
nea and then progresses at a highly variable
pigment and corneal scarring, despite appropri-
rate over the ocular surface. Corneal pigmenta-
ate therapy, generally limits the success of super-
tion results from migration of perilimbal mel-
ficial keratectomy alone. The primary objective
anocytes into the cornea and deposition of
is to maintain a clear central cornea and vision.
melanin granules within corneal epithelial
Topical cyclosporine, corticosteroids, and tac-
cells. The most common causes of pigmentary
rolimus have been administered topically in the
keratitis include chronic irritation from disti-
treatment of pigmentary keratitis.
chiasis, districhiasis, nasal fold trichiasis,
entropion, ectropion, KCS, and chronic expo-
Chronic Superficial Keratitis (Pannus)
sure resulting from macropalpebral fissure
CSK is a progressive, bilateral, inflammatory,
which occurs in many brachycephalic breeds.
and potentially blinding disease of the canine
Treatment, currently, is directed at halting
cornea. It is also known as German Shepherd
the progression of pigmentation and correct-
pannus, Uberreiter’s syndrome, and degenera-
ing the inciting cause. Correction of entropion
tive pannus. Clinically, CSK is manifested ini-
or ectropion, removal of abnormal lashes and
tially at the temporal or inferior temporal
aberrant dermis, and possible partial removal
limbus as a red, vascularized, conjunctival
lesion. Early in the disease, vascularization and
pigmentation occur at the temporal cornea and
progress centrally (Figure 9.24a and b). As the
disease progresses, it spreads as a fleshy, well-­
vascularized lesion that migrates toward the
central cornea. A white, crystalline line or
small white foci often are seen clinically in the
clear corneal stroma, located 1–2 mm in front
of the leading edge of the lesion and advancing
blood vessels. With time, corneal neovasculari-
zation also begins at the nasal limbus and
extends centrally. Eventually, the entire cornea
may become vascularized, pigmented, and
opaque. Some dogs with CSK also develop con-
Figure 9.23 Pigmentary keratitis in a dog with current thickening and pigmentation of the
chronic keratitis. palpebral surface of the nictitating membrane.
340 Canine Cornea and Sclera: Diseases and Surgery

(a) (b)

Figure 9.24 Mild (a) and severe (b) CSK in the German Shepherd breed.

German Shepherds, Shepherd crosses, and with CSK tend to respond more favorably
Greyhounds are most commonly affected dogs and with less intensive topical therapy than ­animals
with CSK, but it can occur in any canine breed with the disease living at higher elevations.
(Table 9.4). Both the incidence and severity The age of onset and breed of the affected
increase at higher altitudes (>4000 ft). In one animal are of prognostic value in this condi-
study, dogs living at altitudes >7000 ft above sea tion. In German Shepherds affected at a fairly
level were 7.75 times more likely to develop young age (i.e., one to five years), the condition
CSK than dogs living at elevations between is usually rapidly progressive and severe. In
3000 and 5000 ft. Dogs from lower elevations those animals first affected later in life (i.e.,
four to six years), however, the lesions appear
be less severe and to progress more slowly.
Table 9.4 Breed predisposition to CSK (pannus)
with age of onset if available. Greyhounds, however, tend to be affected at
younger ages, usually less than two or three
Breed Age of onset (years) years, but exhibit relatively mild lesions.

Airedale Terrier 1–2 Histopathological Features of CSK


Australian Kelpie CSK appears initially as superficial corneal vas-
Belgian Sheepdog 2–5 cularization, with progressive infiltration of
Belgian Tervuren 2–5
granulation tissue into the superficial corneal
stroma. The invading fibrovascular tissue is
Border Collie
accompanied by lymphocytes and plasma cells.
Cattle dogs
Generally, the corneal epithelium remains
Dachshund 2–4 intact, but may be variably hyperplastic or atro-
Dalmatian 2–3 phied. Migration of pigment-­laden cells (i.e.,
English Springer Spaniel 1–3 corneal melanosis) commonly accompanies
German Shepherd Dog 1–6 the fibrovascular inflammatory infiltrate invad-
Greyhound 2–5 ing the anterior stroma. Infiltrating CD4+
Miniature Pinscher 7–8 lymphocytes are the predominant cell types
found in CSK, suggesting an immune-­mediated
Pointer 2–4
pathogenesis. An additional indication that
Siberian Husky 1–3
CSK is an immune-­mediated condition is the
­Inflammatory Keratopathie  341

Table 9.5 Crystalline corneal opacities in the dog.

Composition Breed
Clinical features Associated conditions of opacity predisposition Treatment

Corneal dystrophy
Crystalline Hereditary Cholesterol Beagles Low-­fat diet
Bilateral Phospholipids Siberian Husky Do not breed
Symmetrical or Fatty acids Cavalier KCS
asymmetrical
Superficial or deep Rough Collie
stroma
± Ringlike Shetland
Sheepdog
Airedale
Lipid keratopathy
Unilateral or Cushing’s disease Cholesterol Rottweiler Treat underlying
bilateral cause
Asymmetrical Hypothyroidism Phospholipids Miniature Low-­fat diet
Schnauzer
Superficial stroma Primary Fatty acids
hyperlipoproteinemia
± Perilimbal Diabetes mellitus
High-­fat diet
Corneal
degeneration
Unilateral Keratitis Cholesterol Afghan Hound Treat underlying
cause
Uveitis Cocker Spaniel
German Shepherd
Corneal Episcleritis Phospholipids Golden Retriever Low-­fat diet
vascularization
Superficial stroma Scleritis Fatty acids Great Dane Superficial
keratectomy
Plaque-­like or lacy Chronic lipid Calcium Labrador 1% disodium
(Ca2+) keratopathy Retriever EDTA (Ca2+)
± Blepharospasm Chronic corneal Old English
dystrophy Sheepdog
Gritty (Ca2+) Rough Collie
Epithelial loss Springer Spaniel
(Ca2+)
Boxer

To rule out corneal infiltration from systemic disease (i.e., corneal lipidosis) in cases that are not typical of
hereditary dystrophy, serum chemistry panels may be useful. In addition to cholesterol, high-­density lipoprotein,
low-­density lipoprotein, fasting blood glucose, triglycerides, calcium, and phosphorus levels, it is often useful to
evaluate thyroid and adrenal function.
342 Canine Cornea and Sclera: Diseases and Surgery

clinical observation that CSK can be controlled Neurogenic Keratitis


by topical administration of corticosteroids and Two forms of neurogenic keratitis occur: neu-
cyclosporine. rotrophic keratitis, which is associated with
lack of sensory innervation (trigeminal nerve);
Treatment and neuroparalytic keratitis, which results
CSK can usually be controlled by a variety of from lack of motor innervation (facial nerve)
medical and surgical methods, but it cannot be to the orbicularis oculi muscle of the eyelids,
cured. Owners should be advised of the need with facial paralysis.
for lifelong therapy to control this disease and Neurotrophic keratitis is a form of chronic
that both severity and prognosis depend on ­keratopathy and poor corneal healing resulting
many factors, including age of onset, altitude, from damage to the trigeminal nerve, which pro-
and geographic location. Vision can usually be vides sensory innervation to the cornea. It has a
preserved with medical therapy alone in areas variety of etiologies in the dog, including follow-
of low to medium elevation (i.e., <4000 ft) and ing orbital trauma or with cavernous sinus syn-
in cases of mild lesions occurring in middle-­ drome. This disease leaves the cornea susceptible
aged and older dogs. However, at higher eleva- to injury and decreases reflex tearing.
tions, additional therapies may be required. Clinical features early in the disease process
Initial therapy usually consists of topical corti- may include a roughened corneal surface, rose
costeroid ointments or solutions (i.e., 0.1% dex- Bengal-­positive staining, decreased tear breakup
amethasone or 1.0% prednisolone) three to four time, and punctate fluorescein dye retention.
times daily for three to four weeks, followed by A Cochet–Bonnet esthesiometer can be used to
a reduced maintenance schedule. Dogs on assess corneal sensitivity and assist with early
long-­term corticosteroids should be monitored diagnosis. With increased severity, with or with-
for ocular infection or corneal ulceration, and out chronicity, there may develop a superficial
topical therapy adjusted based on the active dis- corneal ulcer surrounded by a rim of loose epi-
ease. Topical cyclosporine (0.2–2.0%), with or thelium, corneal edema, and a secondary ante-
without concomitant corticosteroids, is often rior uveitis. In some cases, the disease progresses
effective in controlling CSK. Cyclosporine oph- to corneal melting and perforation.
thalmic ointment (0.2%) applied to affected cor- A complete neurologic workup including
neas twice daily was shown to be as effective as cranial nerve examination should be per-
treatment with topical dexamethasone at ame- formed to locate the underlying abnormality
liorating clinical signs. In one study, 1% pime- for neurotrophic keratitis. Treatment is
crolimus given topically three times a day directed at the underlying cause for neuro-
resulted in total or moderate regression of the trophic keratitis. In some cases, a conjunctival
CSK in four of six dogs. In some cases, subcon- or amniotic membrane graft may be required,
junctival injection of corticosteroids in addition especially for those that have progressed to
to topical therapy may also be necessary to con- stage 3. Topical nerve growth factor or other
trol the disease. If topical and subconjunctival neuropeptides may also be considered.
corticosteroids are ineffective or only mini- Neuroparalytic keratitis from loss of eyelid
mally effective, application of beta radiation movement often results in severe exposure
(i.e., strontium-­90β plesiotherapy) may be used ulcerative keratitis and possible vision loss.
concurrent with medical therapy. During the early stages of these diseases, epi-
Superficial keratectomy may be required for thelial degeneration and stromal edema occur.
severe cases in which blindness has resulted As the condition advances, there is corneal
from pigmentation of the central cornea, but drying, vascularization, and opacification. The
recurrence should be expected and repeat ulcerative keratitis may progress to corneal
keratectomies may need to be performed. perforation. Treatment is often symptomatic.
­Inflammatory Keratopathie  343

Temporary tarsorrhaphies may prevent cor- vascularization, stromal granulation tissue,


neal trauma and drying. Animals should also corneal edema, epithelial ulceration, and lim-
be treated with topical lubricants and antibi- bal granulomas. Viable mature Onchocerca
otics to prevent secondary bacterial infection. have been surgically extracted from the canine
If response to therapy is not satisfactory, a cornea. Canine ocular onchocercosis in the United
permanent tarsorrhaphy or enucleation may States has been documented to be caused by
be necessary. Onchocerca lupi.
Toxoplasma gondii keratitis was described in
Corneal Abscessation a dog with KCS and pigmentary keratitis that
A corneal abscess is an accumulation of inflam- presented with a raised, pink, vascular corneal
matory cell debris in the superficial or deep mass. The mass was removed by superficial
stroma, and occurs infrequently in dogs. Affected keratectomy and consisted of suppurative
eyes are intensely painful and have a distinct, inflammation with protozoal organisms.
raised, yellow-­white corneal stromal opacity. Protozoal keratitis and conjunctivitis noted in
Abscesses must be differentiated from a corneal dogs presented with fleshy corneal or conjunc-
epithelial inclusion cyst, which is generally not tival masses. Histological examination revealed
painful. Corneal scrapings are obtained for bac- granulomatous inflammation with intrale-
terial and fungal culture and susceptibility tests sional protozoal organisms: amoeba (2),
and for cytological examination. Therapy con- Toxoplasma gondii (2) or Leishmania mexicana
sists of topical antimicrobials and atropine. (1). All dogs had been treated with topical tac-
Curettage or keratectomy followed by placement rolimus or cyclosporine for at least 1.2 years.
of a conjunctival graft is highly effective. These lesions clinically appeared similar to
nodular episcleritis or squamous cell carci-
Parasitic Keratitis noma emphasizing the importance of biopsy
Leishmania is a genus of protozoal parasites prior to aggressive therapy or enucleation.
transmitted by sandflies. Canine leishmaniasis
is endemic in the Mediterranean basin, but is Superficial Punctate Keratitis
reported in many other regions of the world, Superficial punctate keratitis is seen most com-
including Asia and North, Central, and South monly, but not exclusively, in the Shetland
America. Keratitis occurs frequently in dogs Sheepdog and Longhaired Dachshund.
with leishmaniasis and is usually present con- Clinically, it appears as multiple, punctate or
current with systemic disease and other ocular circular, gray, superficial corneal opacities that
lesions. Corneal lesions associated with leish- may or may not be ulcerated (Figure 9.25). The
maniasis are commonly distributed adjacent to condition is bilateral, and lesions are fre-
the limbus and include regional corneal quently symmetric. When ulcerated, dogs
edema, leukocyte infiltrates, vascularization, demonstrate signs of discomfort (e.g., epiphora
and raised corneal nodules. Granulomatous or and blepharospasm). The corneal ulcers are
lymphoplasmacytic inflammation with typically recurrent, and lesions can progress to
Leishmania organisms are detected microscop- crystalline corneal deposits and diffuse corneal
ically in the cornea of infected dogs. edema, pigmentation, and vision loss.
Onchocerca spp. are filarial nematodes that The pathogenesis of this condition is
most frequently produce periorbital inflamma- unknown, but superficial punctate keratitis
tion or subconjunctival nodules in dogs. Canine has been suggested to be an immune-­
ocular onchocercosis is reported in Europe and mediated or dystrophic corneal disease.
the western United States. Canine ocular Lymphoplasmacytic inflammation is reported
onchocercosis may be associated with concur- in corneal biopsies from Dachshunds with
rent keratitis and peripheral corneal acute disease. Treatment consists of topical
344 Canine Cornea and Sclera: Diseases and Surgery

Box 9.3 Breeds of Dogs Reported


with Corneal Dystrophies
●● Afghan Hound
●● Airedale Terrier
●● Alaskan Malamute
●● Beagle
●● Bearded Collie
●● Bichon Frise
●● Boston Terrier
●● Chihuahua
Figure 9.25 Dachshund with superficial punctate ●● American Cocker Spaniel
keratitis. ●● Collie (Rough)
●● Dachshund
cyclosporine or corticosteroids combined ●● English Toy Spaniel
with a topical antibiotic when ulcerations are ●● German Shepherd
present. The clinical response to therapy is ●● Golden Retriever
typically rapid. Long-­term maintenance ther- ●● Italian Greyhound
apy with cyclosporine may prevent recur- ●● Lhasa Apso
rence of corneal ulcers. ●● Mastiff
Long-­term medical or surgical therapy was ●● Miniature Pinscher
necessary for the resolution clinical signs. ●● Norwich Terrier
Starting antimicrobial therapy was met with a ●● Pembroke Welsh Corgi
pronounced and acute keratitis and anterior ●● Pointer
uveitis in some animals. ●● Poodle (Miniature)
●● Samoyed
●● Shetland Sheepdog
Siberian Husky
­ on-­inflammatory
N ●●

Weimaraner
Keratopathies
●●

●● Whippet
●● Cavalier King Charles Spaniel
Crystalline Corneal Opacities
There are three main clinical groups of corneal
lesions that are associated with crystalline cor- of others, especially the development of
neal opacities (Table 9.5). Many of the clinical degenerative components with chronicity.
features are similar in these diseases, although
the underlying causes of the opacity differ Corneal Dystrophies
(Box 9.3). These groups include the corneal A corneal dystrophy is any primary, bilateral,
dystrophies, lipid keratopathy, and corneal inherited disorder of the cornea not accompa-
degeneration. In general, corneal dystrophies nied by corneal inflammation or systemic dis-
are bilateral and inherited (i.e., observed in ease. Most corneal dystrophies in the dog appear
specific breeds), lipid keratopathy is associated clinically as gray-­white or silver, crystalline or
with systemic lipid abnormalities (e.g., hypo- metallic opacities in the central or paracentral
thyroidism and Cushing’s disease), and degen- cornea. The condition is bilateral and often
eration is secondary to a localized ocular appears as nearly symmetric lesions. Corneal
inflammatory process. These groups are not dystrophy may affect the corneal epithelium,
mutually exclusive and may have components stroma, or endothelium. Variations in both size
­Non-­inflammatory Keratopathie  345

and density may represent different stages of Siberian Husky, Shetland Sheepdog, Cavalier
progression for the dystrophy. Typically, the King Charles Spaniel, Airedale Terrier, and
opacity is oval or circular, with the edge of the Rough Collie. Posterior polymorphous dystro-
lesion well demarcated. The opacity is often in phy is described in the American Cocker
the anterior stroma with intact epithelium. On Spaniel. Endothelial corneal dystrophy is
slit lamp biomicroscopy, a myriad of fine, small observed in several breeds, including the Basset
particles are often seen. These particles may be Hound, Boston Terrier, Boxer, Chihuahua,
present throughout the cornea, but are most Dachshund, Miniature Schnauzer, and Poodle.
commonly subepithelial. Frequently, cholesterol
crystals and clefts are observed as well. In many
Lipid Keratopathy
cases, there are discrete, oval, or round areas of
uniform opacity, though in some animals, the Lipid keratopathy in the dog has been associ-
lesions are oval, ringlike (i.e., doughnut-­shaped) ated with systemic lipid abnormalities, such as
opacities with a clear central zone. Corneal dys- hypothyroidism, pancreatitis, diabetes melli-
trophy is not primarily associated with corneal tus, spontaneous hyperlipoproteinemia, and
vascularization; however, with chronicity, the postprandial (overindulgence) plasma lipid
lipid accumulation may cause cell death and elevations. Lipid keratopathy is characterized
induce inflammation with subsequent develop- by peripheral and central corneal crystalline
ment of corneal vascularization. opacities (Figure 9.26). Clinically, lipid kera-
To rule out corneal infiltration from systemic topathy can be unilateral or bilateral, and the
disease (i.e., corneal lipidosis) in cases that are corneas are nonvascularized, especially early
not typical of hereditary dystrophy, serum chem- in the disease process; however, corneal degen-
istry panels may be useful. In addition to choles- eration commonly occurs with chronicity, and
terol, high-­density lipoprotein, low-­density this is associated with vascularization (see
lipoprotein, fasting blood glucose, triglycerides, more information on corneal degeneration
calcium, and phosphorus levels, it is often useful later in the chapter). All dogs with lipid kera-
to evaluate thyroid and adrenal function. In a topathy should undergo a lipid serum profile
recent study, altered lipid metabolism (i.e., and be screened for thyroid function, pancrea-
hypercholesterolemia, hypertriglyceridemia, titis, and diabetes mellitus (i.e., fasting blood
and abnormal results of serum lipoprotein elec- glucose). Most serum lipid profiles include
trophoresis) was identified in some dogs with
corneal dystrophy, but the pathophysiological
significance of these abnormalities has not been
determined. In general, corneal dystrophies do
not respond to medical treatment and topical
anti-­inflammatory medications may exacerbate
the lesion. Low-­fat diets, such as Hill’s W/D, are
anecdotally suggested to prevent progression of
the disease. The corneal lesions can be removed
by keratectomy if the opacity is obstructing
vision significantly.

Breed-­Predisposed Corneal Dystrophy


Several forms of corneal dystrophy occur in
specific breeds, but detailed descriptions are
available for relatively few of these (see Box 9.3). Figure 9.26 Crystalline corneal dystrophy in the
These include corneal dystrophy in the Beagle, Siberian Husky.
346 Canine Cornea and Sclera: Diseases and Surgery

measurements of serum cholesterol, serum tri- degeneration, not typically seen in primary cor-
glycerides, serum total lipids, and lipoprotein neal dystrophy or lipid keratopathy. Clinically,
electrophoresis. In some cases, serum choles- corneal degeneration has a highly variable
terol esters and phospholipids are also useful. appearance. Lesions may be dense white,
Corneal lipidosis (arcus lipoides corneae) has grayish-­white, and crystalline, with well-­
been reported in the German Shepherd breed. demarcated borders (Figures 9.27 and 9.28).
Lipidosis has been associated with hyperlipo- They can occur in any area of the cornea, but
proteinemia resulting from hypothyroidism generally they are axial or paraxial.
(i.e., thyroid atrophy and lymphocytic thyroidi- Calcium degeneration may occur secondary
tis), and corneal lipidosis has been reported in a to systemic disease or may be spontaneous
dog with bilateral thyroid carcinoma. (i.e., associated with local inflammation).
Treatment of these underlying systemic dis- Hypercalcemia, hyperphosphatemia, hyper-
orders and feeding of a low-­fat diet (e.g., Hill’s adrenocorticism, uremia, and hypervitamino-
W/D) may prevent the corneal opacities from sis D may potentially be accompanied by
progressing and, in some cases, allow them to secondary corneal calcification. Calcium
fade. Topical anti-­inflammatory medications degeneration appears punctate, bright white,
may exacerbate the lesion. The lesions can be irregular, and is usually superficial, while
removed by keratectomy if the opacity is lipids may be present throughout the cornea.
obstructing vision significantly Localized inflammation or injury may pre-
cipitate in situ lipid formation by fibroblasts
Corneal Degeneration and keratinocytes. Alternatively, vasculariza-
Corneal degenerations are crystalline corneal tion of the cornea or anterior segment inflam-
opacities secondary to pathological changes mation may allow hematogenous lipid to be
within the cornea. Degenerations can consist of deposited in the cornea. With inflammation,
lipid, cholesterol, or calcium, and are preceded cells die, become necrotic, and liberate crystal-
by keratitis, vascularization, and possibly mela- line and noncrystalline lipids. Presence of
nosis. Corneal degeneration can occur in lipid, especially noncrystalline and esterified
chronic corneal dystrophy or lipid keratopathy cholesterol, causes additional inflammation,
and are usually unilateral. Vascularization is and subsequently, further degeneration of
the hallmark clinical feature of corneal the cornea. However, keratectomy may be

(a) (b)

Figure 9.27 (a) Dog with Cushing’s disease with focal lipid keratopathy. (b) Dog with perilimbal lipid
keratopathy.
­Non-­inflammatory Keratopathie  347

Boston Terrier, Chihuahua, and Dachshund. It


occurs more frequently in females. The age of
onset in the Boston Terrier breed ranges from
5 to 9 years (mean age, 7.5 years) (Figure 9.29a
and b); the age of onset in the Chihuahua ranges
from 6 to 13 years (mean age, 9.5 years). Four
cases of primary canine corneal endothelial dys-
trophy: were reported in a 12-­year-­old male
Boxer, a 2-­year-­old male Miniature Schnauzer, a
3-­year-­old male Miniature Poodle, and a
12-­year-­old male Boston Terrier. A similar condi-
tion also occurs in the aged Wire-­Haired Fox
Figure 9.28 Diffuse corneal degeneration with a Terrier and the Basset Hound.
dense white plaque and vascularization. Canine endothelial cell dystrophy, in at least
the Boston Terrier breed, may represent a disease
considered if the lesion is progressive and process similar to, and possibly an animal model
vision is compromised. Keratectomy may of, Fuchs’ dystrophy in humans. Fuchs’ dystro-
decrease or stop this cycle of cell death and phy is a progressive, bilateral degeneration of
lipid deposition by removing the necrotic corneal endothelial cells that results in an edem-
tissue. Calcium, which in itself is irritating atous, avascular cornea. It is characterized by a
to the cornea, is also effectively removed by slow, continuous loss of morphologically and
keratectomy. physiologically altered endothelial cells, leading
to corneal edema. Treatment options are pallia-
tive medical therapy or penetrating keratoplasty.
Noncrystalline Cornea Opacities
The endothelium has a decreased number of
Corneal Endothelial Dystrophy cells and exhibits fibrous metaplasia. Descemet’s
Endothelial cell dystrophy is a disease of sponta- membrane is thickened because of fibrillar
neous, progressive corneal edema resulting from deposits and exhibits some guttata. Boston
abnormal dystrophic endothelial cells. In the Terriers with endothelial dystrophy evaluated by
dog, this condition is most prevalent in the in vivo confocal microscopy and Fourier-­domain

(a) (b)

Figure 9.29 (a) Bullous keratopathy in a dog with endothelial dystrophy. (b) Diffuse corneal edema in a
dog with advanced corneal endothelial dystrophy.
348 Canine Cornea and Sclera: Diseases and Surgery

optical coherence tomography had significantly Dogs with persistent bullous keratopathy
decreased corneal endothelial density, signifi- and nonhealing corneal ulcers as a result of
cantly increased CCT, and significantly increased endothelial dystrophy (or degeneration, dis-
endothelium–Descemet’s complex thickness cussed earlier in this chapter) may benefit
compared with age-­matched controls. In dogs from thermokeratoplasty (TKP). In TKP, the
with endothelial dystrophy, the corneal opacity use of multifocal points of superficial thermal
clinically has a blue-­white appearance, with a cautery (Figure 9.30a and b) applied in a circu-
lack of corneal vascularization or conjunctival lar fashion to the exposed corneal stroma
hyperemia. The initial lesion, corneal edema, is results in contraction of the anterior stromal
located temporally and progresses slowly, over collagen fibers. The goal is to develop mild
several months to a few years, to involve the superficial stromal contracture and opacity,
entire cornea. Involvement between fellow eyes and not a focal burn, with the use of minimal
is often initially asymmetric but progresses to probe temperatures. The resulting subepithe-
bilateral, complete corneal opacity. lial scar tissue acts as a partial barrier to the
Palliative therapy is most commonly used for flow of fluid through the cornea and helps to
canine endothelial dystrophy. Most dogs main- reduce the buildup of fluid that results in epi-
tain limited vision with this disease and only thelial bullae. Superficial keratectomy fol-
develop morbidity when corneal ulcers develop lowed by placement of Gundersen conjunctival
following rupture of epithelial bullae. These grafts in a variety of configurations are espe-
ulcers are managed using topical broad-­spectrum cially useful for improving comfort and facili-
antibiotics and topical hyperosmotic medications tating healing of corneal ulcers secondary to
(e.g., 5% sodium chloride). Hyperosmotics may endothelial disease. Penetrating keratoplasty
decrease the extent of epithelial bullae forma- with full thickness corneal transplantation
tion, but significant corneal clearing does not may improve corneal clarity by providing a
occur. Ocular irritation and lacrimation, which healthy donor endothelium. Transplantation
may cause drug dilution and reduce corneal of only the posterior stroma with Descemet’s
contact time, from hyperosmotic preparations membrane and endothelium has been recently
also limit their usefulness. reported and has yielded promising results.

(a) (b)

Figure 9.30 (a) Thermokeratoplasty (thermal cautery) uses multifocal points of superficial thermal cautery.
The goal is to develop mild superficial stromal contracture and opacity, and not a focal burn, with the use
of minimal probe temperatures. (b) Cornea four weeks after TKP. The resulting subepithelial scar tissue acts
as a partial barrier to the flow of fluid through the cornea and helps to reduce the buildup of fluid that
results in epithelial bullae.
­Corneoscleral Masses and Neoplasm  349

Florida Keratopathy and corneal neoplasia. In penetrating kerato-


plasty, all corneal layers are excised and replaced
Corneal opacities, apparently unique to tropi-
by a homologous, full-­thickness corneal graft.
cal and subtropical climates, are described in
Penetrating keratoplasty is indicated when a
the dog and cat. These opacities have been
central corneal opacity obstructs vision. Use of
referred to as Florida keratopathy, Florida
penetrating keratoplasty in veterinary medicine
spots, Florida fungus, and tropical keratopa-
has been rare; however, there are several clinical
thy. Clinically, this condition is characterized
and experimental reports. Corneal endothelial
by multifocal, round, gray to gray-­white, fluffy,
cell decompensation and subsequent corneal
cotton-­like opacities of varying size in the cor-
edema are the most common indications for
neal stroma (Figure 9.31). The condition
this procedure in the dog.
appears to be self-­limiting and does not
respond to topical corticosteroids and/or anti-
fungal drugs. Superficial lamellar keratectomy ­ orneoscleral Masses
C
is reported to be curative, but the need for this
and Neoplasms
procedure is questionable as the corneas are
devoid of evidence of inflammation, the eyes
Corneal, limbal, and corneoscleral masses, in
exhibit no discomfort, and visual compromise
general, are rare in dogs. Masses may include
is generally not appreciable.
nonneoplastic cysts, abscesses, inflammatory
There are essentially two types of keratoplasty
disorders (e.g., nodular granulomatous episcle-
procedures – lamellar keratoplasty and pene-
ritis [NGE]), and neoplasms such as squamous
trating keratoplasty – with both types using
cell carcinoma, melanoma, papilloma, lym-
homologous corneal grafts (i.e., corneal tissue
phoma, and hemangioma/hemangiosarcoma.
from animals of the same species). Lamellar
The immunohistochemical characteristics of
keratoplasty is the excision of corneal epithe-
normal and neoplastic canine eyes have been
lium and stroma with replacement by graft tis-
documented and reviewed allowing for more
sue of equal thickness. With this procedure, the
accurate diagnosis of corneal and other ocu-
Descemet’s membrane remains intact, and
lar masses.
complications of intraocular surgery (e.g.,
intraocular inflammation) are largely avoided.
Indications for lamellar keratoplasty include Corneal Epithelial Inclusion Cysts
corneal degeneration, corneal sequestrations,
Cyst formation in the canine cornea may involve
any of the four layers. Epithelial inclusion cysts
occur as raised, white to pink, corneal masses.
They are typically chronic and nonpainful, but
may impair vision. Inclusion cysts are usually
unilateral and solitary, although dogs with mul-
tiple inclusions cysts are reported. It is postu-
lated that epithelium is deposited traumatically
into deeper cornea, epithelial cells replicate,
and a cyst, with central proteinaceous material
and desquamated cells, is formed. Inclusion
cysts must be differentiated from stromal
abscesses (which are usually associated with
discomfort) or other infectious keratitides.
Treatment consists of a complete superficial
Figure 9.31 Dog with Florida keratopathy. keratectomy, with or without conjunctival or
350 Canine Cornea and Sclera: Diseases and Surgery

other grafting (depending on the depth of the appears as a raised, multilobulated, pink to
resulting lesion after excision). Definitive diag- white mass (Figure 9.33). The corneoscleral
nosis is made by histopathology, where a cyst is limbus may be involved, and superficial vascu-
observed that is lined by nonkeratinizing squa- larization as well as diffuse opalescence of the
mous epithelium. remainder of the cornea is common. The mean
age of dogs at the time of diagnosis was
9.6 years (range 6–14.5 years) in one large
Papillomas
study. Central squamous cell carcinomas have
Papillomas are primary corneal tumors that been associated with long-­term therapy of KCS
occur most commonly in young dogs and eyes. Topical immunosuppressive agents used
resemble the exophytic, arborizing papilloma- for the therapy of chronic keratitis, such as
tous growths in the mouth and eyelids cyclosporine or tacrolimus, are also theorized
(Figure 9.32). Corneal papillomas may result to play a role in tumor development. Topical
from papillomavirus infection or chronic kera- monotherapy with 5-­flurouracil has been
titis. Most papillomas respond well to excision reported as successful in dogs.
by superficial keratectomy. Recurrence may be
decreased by cryosurgery using a double
Corneal Lymphosarcoma
freeze–thaw cycle after the mass has been
removed by superficial keratectomy. Beta irra- Lymphosarcoma may invade the cornea and
diation combined with superficial keratectomy resemble a pink to white cellular infiltrate
may also decrease recurrence. (Figure 9.34a and b). These lesions may be
intrastromal, scleral, or episcleral in location
and usually are not painful unless the cornea
Squamous Cell Carcinoma
becomes ulcerated. The prognosis for these
Primary corneal squamous cell carcinoma is dogs is poor, and treatment is directed at chem-
uncommon but does occur in the dog when the otherapy for the systemic lymphosarcoma.
neoplastic mass arises directly from the cor-
nea. This neoplasm is classified as a corneal
Other Corneal Neoplasms
intraepithelial neoplasia (carcinoma in situ)
because the basement membrane is intact. Several other tumors have been reported in the
Primary corneal squamous cell carcinoma canine cornea, including hemangiomas,

Figure 9.33 Squamous cell carcinoma in the


cornea of a Pug dog with chronic KCS and
Figure 9.32 Corneal papilloma in a dog. pigmentary keratitis.
­Corneoscleral Masses and Neoplasm  351

(a) (b)

Figure 9.34 (a) Bilateral corneal lymphosarcoma in a dog. (b) Closer image of the right cornea.

hemangiosarcomas, melanocytoma, and ade-


nocarcinoma. Corneal hemangiomas and
hemangiosarcomas are uncommon in the dog
and can be primary corneal neoplasms or orig-
inate in the limbus. They appear as raised, red,
irregular masses, and are commonly accompa-
nied by extensive corneal vascularization and
perilesional edema (Figure 9.35).

Limbal Melanomas
Limbal or epibulbar melanomas are typically
benign neoplasms, but they may invade the cor- Figure 9.35 Limbal and corneal hemangioma
nea or intraocular structures (Figure 9.36). in a dog.
These tumors are usually smooth and pig-
mented lesions, but occasionally, they may be
nonpigmented (i.e., amelanotic). Limbal mela-
nomas occur in two age groups among dogs. In
the younger group (i.e., two to four years), the
tumors tend to be invasive, with a history of
rapid growth. In the older group (i.e., 8–11 years),
the tumors are more likely to be stationary or
found incidentally on physical examination;
however, exceptions do occur. The dorsal arc
between the dorsomedial and ventrolateral
limbi is usually the site of origination, and the
German Shepherd, Golden Retriever, and
Labrador Retriever appear predisposed.
Primary limbal melanomas must be differ- Figure 9.36 Limbal or epibulbar melanoma in a
entiated from external extension of intraocular Labrador Retriever with corneal invasion.
uveal melanomas. Complete intraocular exam-
ination, gonioscopy, and high-­resolution ultra- originating from the sclera. In older dogs with
sonography can be performed to differentiate nonprogressive limbal masses, periodic sur-
between primary intraocular tumors and those veillance appears to be adequate.
352 Canine Cornea and Sclera: Diseases and Surgery

Treatment of Limbal Melanoma can be further subdivided into simple episcleri-


Treatment of limbal (i.e., epibulbar) melano- tis and NGE. Simple episcleritis is seen infre-
mas should be considered for dogs in which quently, and it is not associated with systemic
the mass is enlarging and the surgeon is cer- disease. It is usually responsive to topical or cor-
tain the mass is not a scleral extension of an ticosteroid therapy and, in most cases, is self-­
intraocular neoplasm. Treatments of limbal limiting. Secondary episcleritis may result from
melanomas include lamellar or full-­thickness diffuse, severe ocular disorders such as panoph-
excision and replacement with grafting proce- thalmitis, chronic glaucoma, or ocular trauma.
dures (e.g., fresh or frozen homologous corne-
oscleral graft, third eyelid graft, synthetic
implants, porcine small intestinal submucosa,
Nodular Granulomatous Episcleritis
autologous pinnal cartilage), cryotherapy,
strontium-­90β plesiotherapy, and laser photo- The veterinary literature includes several
coagulation. Full-­thickness, corneoscleral accounts of episcleral disorders at the limbus
grafts have been used to maintain a functional resembling corneoscleral fibrous histiocytoma
eye in younger dogs with progressive limbal in humans. Several different names have been
melanomas (Figure 9.37a and b). ascribed to this disorder, including nodular
fasciitis, fibrous histiocytoma, proliferative
keratoconjunctivitis, limbal granuloma, pseu-
­Scleral Diseases
dotumor, and Collie granuloma. When these
Inflammatory diseases that affect the episclera cases are reviewed, however, it appears that
and sclera of the dog are the most common dis- most have a similar basic inflammatory pro-
eases of the canine sclera. Many of these are cess, and a morphological description of NGE
presumed to be immune-­mediated, and most seems to be most appropriate.
are relatively uncommon compared to corneal Ocular findings in NGE include multiple, ele-
diseases. vated, fleshy masses or a single mass arising at
the limbus and infiltrating the adjacent corneal
stroma (Figure 9.38). Nictitating membrane
Episcleritis
involvement is common, and there is a breed
Episcleritis in the dog may be divided into pri- predisposition in the Collie, Cocker Spaniel, and
mary and secondary types. The primary form Shetland Sheepdog. The lesions tend to be

(a) (b)

Figure 9.37 Corneoscleral graft, using cryopreserved tissue, for repair of a full-­thickness excision of a
limbal melanoma. (a) Limbal melanoma, prior to surgery. (b) Corneoscleral graft sutured in place prior to
covering with conjunctiva.
­Corneoscleral Masses and Neoplasm  353

lamellar keratectomy, intralesional corticoster-


oid injections, and beta irradiation (7500 rad
per surgical site) and cryotherapy have
been used.

Scleritis
Inflammatory diseases of the sclera (i.e., scleritis)
can be divided into non-­necrotizing granulomatous
scleritis and necrotizing granulomatous scleritis.
Dogs with scleritis usually present with pink-­tan-­
colored sector lesions arising near, but posterior to,
the limbus. There may be some adjacent corneal
Figure 9.38 Focal nodular granulomatous edema as well (Figure 9.40). Clinical signs include
episclerokeratitis. Note the subconjunctival
ocular pain, photophobia, and excessive lacrima-
swelling, the conjunctival injection, and the
peripheral corneal edema adjacent to the lesion. tion. In some cases, keratitis, anterior uveitis, or
both may be present because the scleral inflamma-
tion extends into these adjacent tissues. Anterior
uveitis, when present, is nongranulomatous.
bilateral in the Collie and to recur following
therapy (Figure 9.39).
Histopathological features of NGE are consist- Non-­necrotizing
ent with those of chronic granulomatous inflam- Granulomatous Scleritis
mation. The predominant cell types are The histopathological characteristics of canine
histiocytes, lymphocytes, and plasma cells. scleritis and nodular episcleritis most resemble
Epithelioid cell accumulations, fibroblastic cells, those of non-­necrotizing form of the disease in
abundant reticulin fiber formation, and neovas- humans. There is little or no tendency for nod-
cularization with perivascular polymorphonu- ule formation. The typical lesion of canine
clear inflammatory cell infiltration also occur. scleritis consists of granulomatous inflamma-
Generally, NGE tends to be benign, with tion and is characterized by the infiltration of
good response to topical administration of lymphocytes, plasma cells, and epithelioid
­corticosteroids with or without the use of oral macrophages. Multinucleated giant cells are
azathioprine treatment or topical or systemic uncommon. The granulomatous response is
cyclosporine. Local surgical excision by seen in the corneal stroma when there is

(a) (b)

Figure 9.39 (a) Diffuse, severe nodular granulomatous episclerokeratitis involving both eyes. (b) In the
right eye, the masses were large and obscured the view of the cornea.
354 Canine Cornea and Sclera: Diseases and Surgery

nongranulomatous choroiditis. Adjacent to the


affected choroid is retinal degeneration, which is
characterized by loss of the outer retinal layers
and hypertrophy and migration of the retinal
pigment epithelium. Systemic corticosteroids,
however, are needed in some cases to provide
maximal regression.

Necrotizing Granulomatous Scleritis


Necrotizing granulomatous scleritis is rare in
Figure 9.40 Severe scleritis, peripheral corneal the dog. It is a bilateral, progressive, granu-
edema, and focal area of corneal degeneration. lomatous, inflammatory disease of the sclera
and cornea that induces significant anterior
anterior extension. When uveitis is present, the uveitis. These cases have a limited response to
uveal infiltrate is nongranulomatous. immunosuppressive therapy, involve both the
When present, the posterior segment lesions anterior and posterior segments, and involve
consist of granulomatous scleritis and adjacent the uveal tract as well.
355

10

The Canine Glaucomas


Revised from 6th edition of Veterinary Ophthalmology, Chapter 20: The Canine Glaucomas, by Caryn E. Plummer,
András M. Komáromy, and Kirk N. Gelatt

The definition of glaucoma in the dog has primary open-­angle glaucoma has its primary
evolved during the past seven decades, reflect- characteristic of a slow increase in IOP and
ing our better understanding of this disease cupping of the optic nerve head (ONH), and
group. William Magrane, who first investigated initial damage to the peripheral RGCs, our
the canine glaucomas in some detail during more common clinical glaucoma in dogs (pri-
the 1950s, wrote, “Glaucoma, whether it be in mary narrow/closed glaucoma) has as its
man or beast, is not in itself a disease entity. It, dominant clinical sign an abrupt and very
rather, consists of a ‘wastebasket’ group of dis- high elevation in IOP and damage to all of the
eases which have as their common feature an retinal layers. As a result, the veterinary defi-
abnormal elevation of intraocular pressure nition of glaucoma for animals is a little dif-
(IOP). This group may be referred to as the ferent, but the major focus is still the RGCs!
glaucomas.” Peter Bedford in 1974 described The different type of IOP elevations (slow
glaucoma as “a disease process of complex eti- progressive IOP elevations over several years
ology, in which elevation of the internal fluid versus acute very high elevation in IOP over
pressure (IOP) of the eye results in destruction hours, days, or a few weeks) may influence
of ocular structures and function.” Recent defi- the ocular tissues differently but eventually
nitions of the glaucomas in humans have result in the loss of vision!
described the glaucomas as “an ocular disorder
characterized by the progressive loss of retinal
ganglion cells (RGC) and their axons, accom- ­ pidemiology of Primary
E
panied by gradual loss of the visual field.” and Secondary Glaucomas
While this description is most appropriate for in the Dog
primary open-­angle glaucoma, it is not so
accurate for the other 25 or so types of primary Martin in 1977 reported the prevalence of the
and secondary glaucomas. In veterinary oph- canine glaucomas as 0.5% using the Veterinary
thalmology, the 20 or so thus recognized differ- Medical Database, and the Canine Eye Registry
ent types of glaucomas in animals always Foundation lists a large number of predisposed
include elevated internal fluid pressure (IOP), breeds. Two studies in 2004 determined that
which have adverse visual effect on the reti- the prevalence of the primary or breed-­related
nal ganglion cells (RGCs), but very high IOP glaucomas and secondary glaucomas in dogs
also affects all of the retinal layers. While presented to the veterinary teaching hospitals

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
356 The Canine Glaucomas

in North America over about four decades has hypertension. The secondary glaucomas asso-
been gradually increasing. Prevalence range ciated with cataract formation and lens-­
for the breed-­related or primary types increased induced uveitis represented 81% of the total
from 0.29% (1964–1973), 0.46% (1974–1983), secondary glaucomas. The prevalences of the
0.76% (1984–1993) to 0.89% (1994–2002). secondary glaucomas from the other causes
Predisposed breeds varied by decade, but the were less: lens luxation (12.0%), postcataract
American Cocker Spaniel, Basset Hound, Wire surgery (5.1%), uveitis of unknown cause
Fox Terrier, and Boston Terrier were constantly (7.1%), hyphema of unknown cause (7.3%),
high from 1964 through 2002. Although 27 and intraocular neoplasms (3.5%). Thus, the
breeds were presented with glaucoma above combined prevalence of the primary or breed-­
the baseline of mixed-­breed dogs (0.71%), related and the secondary glaucomas in the
those breeds with the highest prevalence dur- dog during the past decade was 1.7%, which is
ing 1994 through 2002 were American Cocker comparable to the estimated 1–2% worldwide
Spaniel (5.52%), Basset Hound (5.44%), Chow prevalence of the glaucomas in humans. The
Chow (4.70%), Shar-­Pei (4.40%), Boston Terrier largest series of the canine primary glaucomas
(2.88%), Wire Fox Terrier (2.28%), Norwegian reported is based on the US College of
Elkhound (1.98%), Siberian Husky (1.88%), Veterinary Medicine Teaching Hospitals.
Cairn Terrier (1.82%), and Miniature Poodle Smaller but important epidemiology studies
(1.68%). Gender effect varied among breeds by are available from university-­based patients.
decade, and in some breeds females were more These reports, like those in human medicine
often affected (i.e., American Cocker Spaniel, describing patient populations in small cities,
Basset Hound, Cairn Terrier, English Cocker islands, or countries, provide important infor-
Spaniel, Jack Russell Terrier, Norwegian mation on the prevalence of the specific types
Elkhound, Samoyed, and Siberian Husky). of glaucomas, breeds of dogs predisposed, pos-
Age of presentation with these glaucomas var- sible geographic differences, and other factors.
ied by breed but was generally between 4 and The Vienna study in 1982 published four
10 years. Of the top 27 breeds identified, only reports on the glaucomas in the dog based on
about 8 breeds with possible inherited glau- patients at the Vienna Small Animal Hospital
coma have been investigated in any detail and during 1975–1980, which included a total of
reported in the literature. Studies of the canine 167 dogs. Primary glaucoma affected 51 dogs
glaucomas are very expensive and long dura- (30.5% of the glaucoma dogs; 84 eyes). The
tion; fortunately, with some breeds’ genetic breeds and number of 167 affected dogs
mutations discovered, these tests can be included the Miniature Poodle – 99 (Pudel),
applied rather inexpensively to other breeds. Fox Terrier – 9, Welsh Terrier – 8, Japanese
The prevalence of the secondary glaucomas Terrier – 7, English Cocker Spaniel – 6,
in the dog in North America from 1964 to 2002 Bastard – 6, Dachshund – 5, American Cocker
also varied by decade: 0.25% (1964–1973), Spaniel – 2, Bernhardiner – 2, Deutsche
0.46% (1974–1983), 0.79% (1984–1993), and Schäferhund – 2, Airedale Terrier – 2,
0.80% (1994–2002). The secondary glaucomas Mittelschnauzer – 2, and other breeds – 17.
investigated were not inclusive and focused on The fourth publication of this series included
those associated with cataract formation, lens 116 dogs with secondary glaucomas. Causes
luxation, cataract surgery, uveitis of unknown for the secondary glaucomas included, in part,
cause, hyphema of unknown cause, and cataract, trauma, uveitis, zonular defects and
intraocular neoplasia. To ensure these patients lens displacement, chorioretinitis, intraocular
had secondary glaucoma, the preexisting con- tumor, uveokeratitis, corneal perforation, pro-
dition (e.g., cataract, lens luxation, etc.) was gressive retinal atrophy, aphakia, Collie eye
diagnosed prior to the onset of the ocular anomaly, and retrobulbar tumor.
­Epidemiology of Primary and Secondary Glaucomas in the Do  357

The Utrecht study in 1985 reported on the the secondary glaucomas in the dog occurred
canine and feline glaucoma patients during a in 156 of 2257 (6.9%) animals examined
four-­year period at the University of Utrecht because of ophthalmic disease and affected
based on 421 patients (379 dogs and cats), both eyes in 33 (21.2%) of these dogs at first
which accounted for 8.6% of all of the small presentation. The most common causes of sec-
animal clinic patients. Primary glaucoma ondary glaucoma were nonsurgical anterior
occurred most frequently in the American uveitis (44.9%), anterior uveitis associated with
Cocker Spaniel, Bouvier, Basset Hound and prior phacoemulsification (15.8%), and lens
Basset Artésien Norm, Beagle, Duitse Dog and dislocation (15.2%). Certain breeds were pre-
Duitse Herder, English Cocker Spaniel, and Toy disposed to the secondary glaucoma and
and Miniature Poodle breeds. The secondary included Parson Russell Terriers, Toy and
glaucomas were grouped into those secondary Miniature Poodles, Boston Terriers, American
to lens dislocations, iritis or uveitis, trauma, Cocker Spaniels, Rhodesian Ridgebacks, and
tumor, and post-­lens extraction. Of the second- the Australian Cattle Dogs.
ary glaucomas, 182 had lens dislocations and
were concentrated in the small terrier breeds.
Genetics
Another report was from the University of
Zurich in 2011: 4 congenital, 123 primary, and Based on the specific breed predilection of pri-
217 secondary cases of canine glaucoma were mary glaucomas, a genetic etiology is sus-
documented from a period of 1995 through pected to be responsible, and affected dogs
2009. Primary glaucoma occurred with an over- should be excluded from breeding. Despite the
all male to female ratio (M:F) of 1:1.41, and the high prevalence of primary glaucomas in
age of onset ranged from 0.12 to 18.3 years dogs, genetic etiologies have been studied in
(mean 7.3 ± 3.6 years). Breed predisposition only a relatively small number of breeds.
occurred in the Siberian Husky, Magyar Vizsla, Primary angle-­closure glaucoma (PACG) is
and Newfoundland. The secondary glaucomas the most common form of primary, breed-­
affected dogs ranging in age from 88 days to related canine glaucomas, suggesting a genetic
19 years (mean 7.7 ± 3.6 years), and accounted etiology. Many breeds have been studied, with
for 3.6% of all ophthalmology patients seen at the highest prevalences documented in the
the University of Zurich. Breed predisposition American Cocker Spaniel, Basset Hound,
for the secondary glaucomas occurred in the Chow Chow, Siberian Husky, Shiba Inu, Shih
Cairn Terrier (ocular melanosis), Jack Russell Tzu, Magyar Vizsla, and Newfoundland.
Terrier (lens displacement), and English Because a simple mode of Mendelian inherit-
Cocker Spaniel breeds. Most of those eyes with ance could not be identified in most canine
bilateral disease shared the same risk factor breeds studied, PACG appears to be a complex
(anterior uveitis or lens luxation). Causes iden- trait with multiple suspected genetic and envi-
tified with the secondary glaucomas included ronmental risk factors contributing to the
anterior uveitis (23.0%), lens luxation (22.6%), ­disease. The possible exceptions are Welsh
intraocular surgery (13.4%), intraocular neo- Springer Spaniel with a proposed autosomal
plasia (10.6%), unspecified trauma to the globe dominant trait, as well as Siberian Husky and
(8.3%), ocular melanosis (6.9%), hypermature Basset Hound with suggested autosomal
cataract (6.9%), and hyphema (3.23%). recessive inheritance.
PACG genetics has been investigated most
extensively in the Basset Hound, thanks to the
University of California Study
availability of a closed colony with informative
Finally, a recent five-­year study from the pedigree. Genome-­wide association study
University of California, Davis reported that has revealed three genetic loci as possible
358 The Canine Glaucomas

contributors to the PACG phenotype in this Genetics of Pectinate Ligament


breed with the following three positional can- Dysplasia and Ciliary Cleft Opening
didate genes: COL1A2, RAB22A, and NEB. All in the Dog
three have been shown to be expressed in the Goniodysgenesis or pectinate ligament dyspla-
anterior segment of the eye where they may sia (PLD), combined with the narrowing of the
play a role in aqueous humor outflow. While iridocorneal angle (ICA) and ciliary cleft, is a
COL1A2 (encoding the pro-­alpha 2 chain of well-­recognized risk factor of PACG. The
type I collagen) is a promising PACG candidate inheritance of PLD and the width of the ciliary
gene due to the suspected involvement of col- cleft have been studied in a number of dog
lagen and other extracellular matrix compo- breeds, such as English Springer Spaniel, Flat-­
nents in the PACG pathogenesis, subsequent Coated Retriever, Great Dane, and Samoyed.
studies focused on NEB, which encodes for Quantitative polygenic traits are most likely,
nebulin, a protein that is expressed in the cili- based on the observation that both the severity
ary muscle where it may regulate muscle con- of PLD and narrowing of the ciliary cleft
tractility. It is possible that changes in nebulin worsen with the degree of kinship in PACG-­
and its function may alter muscle function and affected animals. Breeding of only animals
thereby contribute to PACG development. The with normal ICAs led to a reduction in the
disease-­associated NEB allele is commonly presence and degree of ICA abnormalities in
found in the Basset Hound population: 88% of the English Springer Spaniel. The Bouvier des
PACG-­affected Basset Hounds are homozy- Flandres is the only breed to date where a
gous for the NEB risk allele; the remaining 12% recessive inheritance of PLD has been
are heterozygous. Among PACG-­unaffected proposed.
Basset Hounds, 33% and 44% are homozygous Because much remains unknown about the
and heterozygous for the NEB risk allele, link between the presence of PLD and glau-
respectively, while 22% are homozygous for the coma development and the genetics of PLD,
non-­risk allele. The identification of the NEB there is no consensus between veterinary oph-
risk allele in the Basset Hound represents a sig- thalmology organizations regarding the inclu-
nificant progress toward the better under- sion of gonioscopy as part of routine genetic
standing of canine PACG; however, it remains eye screening in order to provide breeding
a complex disease since not all of the homo-­ advice. Furthermore, without the additional
and heterozygous animals develop glaucoma; assessment of the ciliary cleft width by high-­
additional genetic and environmental factors resolution ultrasonography (HRUS) or ultra-
likely contribute. sound biomicroscopy (UBM), gonioscopy
Progress in the understanding of canine alone may not provide a full picture about the
PACG genetics has been made in other breeds status of the aqueous humor outflow path-
as well, and investigations are ongoing. In ways. While the American College of
Shiba Inus and Shih Tzus, SRBD1 was identi- Veterinary Ophthalmologists (ACVO) has not
fied as a PACG risk gene. It encodes for S1 issued recommendations against breeding of
RNA-­binding domain and has been associated PLD-­affected dogs, the European College of
with human forms of primary glaucoma; how- Veterinary Ophthalmologists (ECVO) has
ever, its function remains unknown. In the adopted stricter rules with recommended goni-
Dandie Dinmont Terrier, a 9.5-­megabase oscopy for a number of breeds, including the
region on canine chromosome 8 has been American Cocker Spaniel, all types of Bassets,
identified as susceptibility locus for canine Bouvier des Flandres, English Springer
PACG; no specific disease gene has been Spaniel, Flat-­Coated Retriever, Siberian Husky,
­identified yet. and Samoyed. While dogs with mild degree of
­Epidemiology of Primary and Secondary Glaucomas in the Do  359

PLD (fibrae latae affecting less than 25% of the veterinary ophthalmologist because of pri-
pectinate ligament circumference) are consid- mary lens luxation (PLL) or primary glau-
ered unaffected, a diagnosis of laminae and coma. In our clinical experience, even
occlusion will result in a recommendation ADAMTS10-­mutant Beagles can present with
against breeding. limited PLL, even though this has not been
observed over four decades in the POAG
Genetics of Canine Primary Beagles housed at the University of Florida.
Open-­Angle Glaucoma and Primary Based on these recent genetic discoveries, we
Lens Luxation think it is important for the clinician to con-
Thanks to the monogenic, autosomal recessive sider a POAG component in “classic” PLL
inheritance of all currently known forms of breeds, such as terriers, because of their
canine primary open-­angle glaucoma (POAG) genetic defect in ADAMTS17 (splice donor
and the availability of well-­established POAG site mutation: ADAMTS17c.1473+1 G>A).
Beagle colonies, great advances were made in These canine patients may present with ele-
recent years toward the better understanding vated IOP without lens displacement into the
of canine POAG genetics. All currently known anterior chamber or pupillary block but
canine POAG-­causing mutations have been instead with lens subluxation or posterior
identified in two genes encoding for secreted lens luxation. Furthermore, glaucoma often
matrix metalloproteinases: ADAMTS10 and persists following surgical lens removal. In
ADAMTS17. The first mutations were identi- other words, glaucoma associated with PLL
fied in the ADAMTS10 gene of affected Beagles may not be entirely secondary to anterior lens
(p.G661R missense mutation [glycine to argi- dislocation and vitreous prolapse as generally
nine change at position 661]) and Norwegian perceived; instead, there may be a POAG
Elkhounds (p.A387T missense mutation [ala- component. Like canine POAG, PLL also
nine to threonine amino acid change at posi- appears to be an autosomal recessive trait in
tion 387]), a gene that is strongly expressed in most affected breeds; hence, most heterozy-
the trabecular meshwork (TM). These findings gous dogs that carry an ADAMTS17 mutation
were followed by the discovery of ADAMTS17 remain clinically unaffected. Interestingly,
mutations in POAG-­affected Petit Basset an estimated nearly 5% of heterozygous
Griffon Vendéen (PBGV) dogs (inversion in Miniature Bull Terriers, and a few heterozy-
intron 12), Basset Hounds (19-­bp deletion in gous dogs of other breeds, such as the Parson
exon 2), Basset Fauve de Bretagne dogs Russell Terrier, Chinese Crested Dog, and
(p.G519S missense mutation [glycine to serine Tenterfield Terrier, may develop PLL. This
change at position 519]), and Chinese Shar-­ phenomenon could be attributed to haploin-
Peis (6-­bp deletion in exon 22). Routine genetic sufficiency, a dominant negative effect of the
testing for some of these mutations is availa- mutant ADAMTS17 protein, or additional,
ble. The p.G661R ADAMTS10 missense still unknown mutations in ADAMTS17 or
m­utation responsible for Beagle POAG was elsewhere in the genome. The Animal Health
excluded as a cause of primary glaucoma in the Trust recommends that carriers of ADAMTS17
American Cocker Spaniel, Australian Cattle mutations be regularly screened for signs of
Dog, Chihuahua, Jack Russell Terrier, Jindo, PLL. Diurnal IOP and/or tonography studies
Siberian Husky, Shiba Inu, Shih Tzu, and in these dogs with DNA mutations may help
Yorkshire Terrier. separate those dogs with PLLs (and secondary
It is likely that modifier genes are involved glaucoma) from those dogs with a combina-
in determining whether an ADAMTS10-­ tion of PLL and primary glaucoma that may
or ADAMTS17-­mutant dog presents to the exhibit at different times.
360 The Canine Glaucomas

Because of their important function in micro- ADAMTS17c.1473+1 G>A). These canine


fibril formation, mutations in ADAMTS10 and patients may present with elevated IOP
ADAMTS17 result in not only an ocular pheno- ­without lens displacement into the anterior
type with ectopia lentis/PLL and glaucoma in chamber or pupillary block but instead with
affected human Weill Marchesani syndrome lens subluxation or posterior lens luxation.
(WMS) patients, but also short body stature, Furthermore, glaucoma often persists follow-
fingers, and toes. In contrast, the canine disease ing surgical lens removal. In other words,
phenotype appears to be limited to ocular glaucoma associated with PLL may not be
symptoms. However, there have been specula- entirely secondary to anterior lens dislocation
tions that PLL-­affected, ADAMTS17-­mutant and vitreous prolapse as generally perceived;
dogs may be slightly smaller than unaffected instead, there may be a POAG component.
littermates and that selection toward smaller
body size may have contributed to the higher
frequencies of the disease allele in ­Classification of the Glaucomas
affected breeds.
Canine glaucomas may be classified on the
POAG and PLL in Other Canine Breeds basis of (i) the possible cause (primary,
The division of canine primary glaucoma into se­condary, or congenital), (ii) the gonioscopic
POAG and PLL–primary closed-­angle glau- appearance of the filtration angle (i.e., open,
coma (PCAG) types is still unresolved. Some narrow, or closed iridocorneal angle and open,
breeds may share both types of glaucoma. narrow, or collapsed ciliary cleft), and (iii) the
Unfortunately, there are no detailed clinical duration or stage of the disease (Box 10.1).
descriptions for most of them, only reports of Because no single classification scheme is
the genetic defect in ADAMTS17. In other totally satisfactory, combinations of all three
words, glaucoma associated with PLL may schemes typically are used. There have been
not be entirely secondary to anterior lens dis- recent ­suggestions that the classification
location and vitreous prolapse as currently schemes of animal glaucomas have limited
­perceived; instead, there may be a POAG com- usefulness because of microanatomical differ-
ponent. Tonography has suggested that some ences in the outflow pathways between pri-
Wirehaired Fox Terriers presented with ante- mates and the dog; however, alternate schemes
rior lens luxations and glaucoma in one eye have not emerged nor been recommended. In
and normal IOP in the fellow eye with no the dog, the majority of the filtration angle
­evidence of lens luxations, have decreased (e.g., the corneoscleral meshwork and all of
aqueous outflow in the normotensive eye. the uveal trabecular meshwork) is located in
The relationship between lens luxations and the ciliary cleft, which can only be imaged by
­glaucoma is at best unsettled and requires ≥20 MHz ophthalmic ultrasonography.
investigations.
ADAMTS17 mutations have been discov-
Cause(s) of the Glaucomas
ered in POAG-­affected Basset Hounds (19-­bp
deletion in exon 2), Basset Fauve de Bretagne Primary glaucomas, which are thought inher-
dogs (p.G519S missense mutation [glycine to ited, may result from abnormal biochemical
serine change at position 519]), and Chinese metabolism of the trabecular cells of the out-
Shar-­Peis (6-­bp deletion in exon 22). It is flow system or the physical effects of pupil-
important for the clinician to consider a POAG lary blockage and changes in the iridocorneal
component in “classic” PLL breeds, such as angle and sclerociliary cleft. PLD or the
terriers, because of their genetic defect in ­consolidation of adjacent pectinate liga-
ADAMTS17 (splice donor site mutation: ments into broad sheets (initially termed
­Classification of the Glaucoma  361

Table 10.1 Types of glaucomas reported.


Box 10.1 Types of Glaucoma in Dogs
Primary glaucomas Open angle Closed angle
Open/normal angle (acute/chronic)
Narrow/closed angle (acute/chronic) Beagle Akitaa
Great Danea American
Secondary glaucomas Cocker Spaniel
Uveitis Keeshond Basset Hounda
Lens luxations (subluxations/anterior and
Norwegian Elkhound English Cocker
posterior luxations) Spaniela
Intumescent cataract Poodle (Miniature/Toy) English Springer
Phacolytic/phacoclastic uveitis Spaniela
Hyphema Samoyed Flat-­Coated
Intraocular neoplasia Retrievera
Aphakic/pseudophakic Siberian Huskya Golden Retriever
Malignant/ciliary block Poodles (Miniature/Toy)
Melanocytic/pigmentary proliferation (Cairn
Samoyed
Terrier)
Shiba Inua
Giant retinal tears (Schwartz–Matsuo
syndrome) Shar-­Peia
Anterior chamber silicone oil Welsh Springer Spaniel
Postoperative ocular hypertension a
Pectinate ligament dysplasia.
Congenital glaucoma
Pectinate ligament dysplasia initiate these forms of glaucoma, however,
Goniodysgenesis may be genetically determined in certain
breeds, such as those with cataracts and lens
luxation (i.e., dislocation). The secondary glau-
mesodermal dysgenesis) is common in the comas are divided according to cause as well as
dog, and often described in many primary by an open, narrow, or closed anterior cham-
narrow-­ or closed-­angle glaucomas. In our ber angle and ciliary cleft at gonioscopy. In the
classification scheme, the persistent mesoder- dog, the primary and breed-­related glaucomas
mal bands and PLD-­associated glaucomas in as well as the secondary glaucomas constitute
selected breeds have been classified with the the largest clinical groups.
primary glaucomas because the clinical signs In the congenital glaucomas, the increased
of these glaucomas occur later in life. These IOP is associated with often multiple anterior
anomalies appear to predispose to elevated segment anomalies, and the elevation in IOP
IOP, but their direct role is not known. As the develops soon after birth. Congenital glauco-
basic pathogenesis for all breed-­related glau- mas with overt anterior segment anomalies
comas becomes ­documented, however, these during the first few months of life are rare.
glaucomas could be reclassified into more
specific types (Table 10.1).
Onset and Duration
In the secondary glaucomas, the increase in
IOP is associated with some known antecedent Classification of the canine glaucomas by
or concurrent ocular disease that physically duration (i.e., acute, subacute, and chronic) is
obstructs the aqueous outflow pathways. They useful clinically. Such classification may be
tend to be unilateral conditions and are not misleading, however, regarding the amount of
inherited. Some of the conditions that may damage present and the pet owners’ critical
362 The Canine Glaucomas

observations. Corneal edema, conjunctivitis, gas (now air) with the pneumatonograph. In
and a dilated pupil may be the first clinical the rebound tonometers, a magnetic field is
signs of glaucoma noticed by a pet owner or induced that propels a small magnetized probe
veterinarian. Because an IOP in excess of (plastic tip is 1.4 mm) against the cornea. The
40 mmHg is necessary for corneal endothelial probe “rebounds” at different velocities and
dysfunction to develop, these eyes may not levels of IOP from the cornea causing voltage
truly be at an early or acute stage of the actual changes within the tonometer’s collar, which
disease at presentation. Glaucoma in one eye, are converted into electrical signals that have
with only slight elevation in IOP, is often not been calibrated to different levels of IOP in
noticed by the owner; hence, most dogs are not selected species.
presented to a veterinarian until extensive Currently models used include the TonoPen®
damage or even blindness is present in the first XL, TonoPen Vet™, and TonoPen Avia Vet
eye with the primary glaucomas. In fact, in (Reichert, Buffalo, NY); AccuPen Vet
both the dog and humans, presentation of the (Automated Ophthalmics, Columbia, MD);
initial eye with PACG is associated with TonoVet® Rebound Tonometer (Icare Labs, St
25–50% blindness before examination by a Petersburg, FL; Vedco, St Joseph, MO; and
medical professional. In addition to the dura- TioLat, Helsinki, Finland); and the pneuma-
tion of the IOP elevation, glaucoma is also tonograph model 30 (Reichert, Buffalo, NY). In
influenced by the amount of IOP elevation. An general, tonometric measurements with the
IOP of 35 mmHg is not as damaging as an IOP older TonoPen models underestimate IOP lev-
of 70 mmHg! els starting at about 30 mmHg and above, and
are progressively less accurate as IOP increases
(e.g., 60 mmHg). However, the new TonoPen
­Diagnostics Avia Vet (Reichert, Buffalo, NY) has been
updated and reported by the manufacturer as
The three basic procedures for the diagnosis more accurate at the higher levels of IOP than
and clinical management of glaucomatous its previous models. Clinical and experimental
patients are tonometry, gonioscopy, and impressions suggest that the TonoVet meas-
­ophthalmoscopy. Recently introduced high-­ urements are slightly lower than those from
resolution imaging procedures, such as 20, 35, the TonoPen XL results within the normal
50, or 60 MHz ultrasonography and anterior range of IOP (10–25 mmHg), but perhaps more
segment optical coherence tomography, can accurate when IOP exceeds 40 mmHg.
noninvasively observe the dog’s trabecular With use of only topical anesthesia and the
meshwork and sclerociliary cleft and are dog loosely restrained in a sitting or standing
­beginning to be used for clinical patients. position, applanation tonometry can be per-
formed with the instrument held horizontal
or vertical, and the tonometer tip perpendicu-
Applanation Tonometry
lar to the central cornea. Several reproducible
Reliable tonometry is essential for optimal readings with consistent IOP measurements
clinical management of canine glaucomas. Of should be obtained. With TonoVet rebound
the three types of tonometry (i.e., indentation tonometry no topical anesthesia is necessary,
[Schiotz], applanation, and rebound tonome- but the instrument must be held horizontally.
ters), only the latter two types are recom- Normal IOP for the dog has been estimated
mended in veterinary ophthalmology. Current at 16.7 ± 4.0 mmHg (TonoPen XL) and
tonometers for animals are based on the 15.7 ± 4.2 mmHg (Mackay–Marg®), and in a
Mackay–Marg applanation principle, the larger group at 18.7 ± 5.5 mmHg (TonoPen
rebound magnetic effect, or the exchange of XL) and 18.4 ± 4.7 mmHg (Mackay–Marg),
­Diagnostic  363

and 12.9 ± 2.7 mmHg (TonoPen XL) and anterior sclerociliary cleft morphology (i.e.,
10.8 ± 3.1 mmHg (TonoVet). Body position as open, narrow, and closed filtration angles and
well as manual restraint can also affect tono- sclerociliary clefts) (see Chapter 4) by the veteri-
metric measurements. nary ophthalmologist. Both direct and indirect
Tonometry in the outpatient clinic provides gonioscopic lenses are used, with the former
only an “instant snapshot,” or a single point in type of lenses most popular and less expensive.
time, while multiple measurements of IOP Gonioscopic findings in both primary open-­
over a 24-­h period can be more informative, and narrow-­angle/angle-­closure glaucomas are
because IOP is a biological variable. Acclimation dynamic, changing as the glaucoma and globe
to the clinical environment and multiple IOP enlargement progress. Regardless of the basis
measurements over 24 h can provide a more for these changes, the continual narrowing and
accurate estimation of the actual IOP. Diurnal eventual closure of these outflow pathways
variations in IOP have also been documented indicates that progressively more aggressive
in the dog, with higher levels in the early morn- medical and surgical therapy will be required
ing and the lowest readings in the early even- as the glaucoma progresses.
ing, and may be the most informative clinically. Gonioscopic findings must be compared
In the normal dog, these diurnal variations with tonometric results and clinical findings
span approximately 2–4 mmHg within an eye, because gonioscopic results do not directly cor-
and between fellow eyes. The peak levels of relate to level of IOP or aqueous humor out-
IOP are potentially the most damaging! flow. Gonioscopy observations should include
Tonometry is a critical procedure in both the the following: width of iridocorneal angle;
diagnosis and clinical management of canine depth of the sclerociliary opening and cleft;
glaucomas. As presented later, both “safe” and length and diameter of pectinate ligaments;
“target” IOP levels can be addressed only if any abnormalities – most often PLD; size of
applanation tonometry is routinely performed dysplastic areas; and number of flow holes by
on the glaucomatous patient at every visit. quadrant or degrees (Figure 10.1).
The information gleaned from gonioscopic
examination may be useful for giving breeding
Gonioscopy
advice for breeds predisposed to PLD and glau-
Gonioscopy is the diagnostic examination of coma. Recommendations to examine the ICA
the iridocorneal angle and opening of the cili- by gonioscopy as part of the genetic eye screen-
ary cleft (i.e., the filtration angle), usually per- ing and in giving breeding advice for dogs with
formed by the veterinary ophthalmologist. The PLD differ between the ACVO and the
uveal trabeculae are located immediately pos- ECVO. The ECVO has stricter guidelines
terior to the pectinate ligaments and are visual- regarding the need for gonioscopy and the
ized directly during gonioscopy. Only the exclusion of PLD-­affected animals from breed-
opening of the ciliary cleft, however, can be ing. Gonioscopy is advised by the ECVO in the
visualized at gonioscopy, though the entire following breeds: American Cocker Spaniel, all
cleft can be imaged at HRUS. Gonioscopy has types of Bassets, Bouvier des Flandres, Chow
been documented and performed in the dog Chow, Border Collie, Dandy Dinmont Terrier,
since the 1930s. Because the primary glauco- Rough-­Haired Dutch Shepherd, English
mas represent progressive diseases of the aque- Springer Spaniel, Entlebucher Mountain Dog,
ous humor outflow pathways (both open-­ and Flat-­Coated Retriever, Siberian Husky,
narrow–closed-­angle types), serial gonioscopy Leonberger, Magyar Vizsla, Samoyed, and
in glaucoma patients is most informative. Tatra. PLD is classified by the ECVO, based on
Gonioscopy permits classification of glau- severity, as free, fibrae latae (abnormally broad
coma on the basis of the iridocorneal angle and and thickened pectinate ligament fibers),
364 The Canine Glaucomas

Figure 10.1 Grading by gonioscopy and a schematic of the iridocorneal angle and opening of the
sclerociliary cleft: (from left to right) closed; very narrow; narrow; open (or normal); and more open
than normal.

laminae (solid plates or sheets of pectinate lig- Ophthalmoscopy


ament tissue), and occlusion (persistence of an
As the ocular fundus is directly influenced by
embryonic sheet of ICA tissue and the absence
elevated IOP, clinical management of the
of intraligamentary spaces, except for flow
canine glaucomatous patient requires a combi-
holes). Fibrae latae, laminae, and occlusion are
nation of direct and indirect ophthalmoscopy
associated with a narrow ICA. With fibrae
(Figure 10.2). The direct ophthalmoscope and
latae affecting 50% or less of the pectinate liga-
the small-­pupil indirect ophthalmoscope per-
ment circumference, the animal can still be
mit careful examination of the ONH and retina.
considered unaffected; however, a diagnosis of
The direct method has the higher magnifica-
laminae in more than 50% of circumference is
tion than the indirect method (17.2× lateral
considered severely affected. In addition to
and 405× axial versus 1.7× lateral and 4× axial,
PLD, the ECVO recommendations also include
respectively), which favors detailed ONH
ICA width: open, narrow, or closed. Performing
inspections. The red-­free filter of the direct
a gonioscopy as part of the genetic eye screen-
ophthalmoscope, which results in a green light
ing remains optional according to the ACVO,
source, permits examination of the retinal
despite the recent issue of a special form by the
nerve fiber layer for nerve fiber bundle defects
ACVO Genetics Committee and the Orthopedic
as well as examination of the neuroretinal rim.
Foundation for Animals for information gath-
The panoptic ophthalmoscope provides a little
ering and tracking information related to
less magnification but a larger view of the ocu-
PLD. There are currently no ACVO guidelines
lar fundus.
against the breeding of PLD-­affected dogs. The
Glaucomas with abrupt bouts of marked
less restrictive ACVO recommendations were
elevations in IOP tend to produce progressive
justified by the poor predictive value of
optic nerve degeneration and often “water-
go­nioscopy findings for PCAG development in
shed” areas of retinal degeneration (wedge-­
individual dogs and their offspring. Furthermore,
shaped areas of retinal degeneration adjacent
without the additional assessment of the ciliary
to the optic disc secondary to short ciliary
cleft width by HRUS or UBM, the examination
artery ischemia), while slow and gradual eleva-
of the ICA by gonioscopy alone may not provide
tions of moderate IOP tend to produce a grad-
a complete picture of the status of the aqueous
ual optic disc cupping, gradual loss of myelin,
humor outflow pathways.
and smaller and pigmented optic discs.
­Diagnostic  365

(a) (b)

(c)

Figure 10.2 ONHs in three Beagles. (a) Normal optic disc. (b) Optic disc in early hypertension with
electrophysiological evidence of glaucoma. (c) Optic disc in a moderate stage of POAG with enlargement of
the optic cup.

performed in the early stages of the diseases


High-­Resolution Ultrasonography (and before enucleation is usually possible) by
and Ultrasound Biomicroscopy the veterinary ophthalmologist. Both HRUS
Classification of the canine glaucomas based (20 MHz) and UBM (50–60 MHz) have been
on histopathological examinations of end-­ reported in dogs, with the latter method
stage and advanced glaucomas is of limited requiring sedation or general anesthesia. Both
value and may indicate erroneous assump- methods require a latex rubber sleeve or eye
tions as to the genesis of elevated IOP. With cup as an interface between the ultrasound
these newer noninvasive imaging clinical probe and the eye. Both methods can image
p­rocedures, examination of the anterior the iridocorneal angle, pectinate ligaments,
chamber and outflow pathways can approxi- and sclerociliary cleft (Figure 10.3). As with
mate r­outine histology resolutions and can be any new diagnostic, it may be a few years
366 The Canine Glaucomas

(a) (b)

Figure 10.3 (a) HRUS or UBM of the iridocorneal angle and ciliary cleft in a normal dog, and (b) an
American Cocker Spaniel with iridocorneal angle closure and collapse of the ciliary cleft. (Courtesy of
Ursula Dietrich, North Downs Specialist Referrals, Bletchingley, Surrey, UK.) C, cornea; S, sclera; I, iris; PL,
pectinate ligament; CC, ciliary cleft; and A, iridocorneal angle.

before these imaging procedures become com- anteroposterior dimension of the vitreous
monplace in the clinical management of the body. Results of ultrasonic studies of primary
canine glaucomas. glaucoma in Samoyeds suggest a narrow-­ or
closed-­angle glaucoma pathogenesis with a
narrowed anterior chamber and increased
Other Diagnostics thickness of the axial lens and vitreous body.
Tonography is tonometry expanded over These same findings have been reported in
2–4 min, and it permits quantification of the human PACG in people.
IOP-­sensitive component of the aqueous Electrophysiology studies have received
humor trabecular meshwork outflow, and has limited attention in the canine glaucomas;
had limited use in the investigations of the however, there are reports on normal dog eyes
canine glaucomas. Tonography is the clinical with abruptly increased IOP. Pattern electrore-
procedure that documents the pressure-­ tinography, multifocal electroretinography,
sensitive (trabecular meshwork) aqueous and flash electroretinography with different
humor outflow. It has not been used clinically colors of light stimuli, particularly blue, may
in the canine glaucomas, except in POAG in be useful.
the Beagle. Combined with fluorophotometry,
tonography can reveal, in relative terms, both
the conventional (i.e., pressure-­sensitive cor- ­Provocative Tests
neoscleral–trabecular outflow) and unconven-
tional (i.e., pressure-­insensitive uveoscleral Provocative tests are used traditionally to
outflow) components of the glaucomas. In ­evaluate an eye and its predisposition to
three separate pneumatonographic studies, the both open-­ and narrow-­angle glaucomas in
mean ± SD for conventional outflow for the humans. They can provide insight into the
normal dog was 0.30 ± 0.15, 0.28 ± 0.09, and ­possible mechanism(s) about the increase in
0.35 ± 0.129 μl/min/mmHg. IOP. Provocative tests may not be indicated
A-­scan ultrasonography is important to for the individual patient, but they may be
measure the anteroposterior globe, depth of employed by veterinary ophthalmologists and
the anterior chamber, lens thickness, and vision scientists investigating the pathogenesis
­Clinical and Pathological Effects of Elevated IO  367

Table 10.2 Clinical effects of elevated IOP.

Ocular tissue Changes in the glaucomas

Globe size Enlargement from stretching of cornea and sclera; termed hydrophthalmos, buphthalmia,
megaloglobus, and macrophthalmia. Occurs rapidly in puppies (often reversible)
Cornea Becomes thicker because of stromal edema. Eventually corneal endothelial cell death
occurs. Focal, linear breaks in Descemet’s membrane (i.e., Haab’s striae). Exposure
keratitis later with buphthalmia
Sclera and Sclera is stretched and becomes thinner. Areas of sclera through which the nerves and
lamina blood vessels penetrate may form large staphylomas. Scleral lamina cribrosa is distorted
cribrosa and compressed posteriorly
Iris Mydriasis in most types of glaucoma. With time, the iridal stroma becomes thin, and the
sphincter muscle becomes atrophied
Ciliary body Gradual degeneration with atrophy of the pars plicata and individual ciliary processes.
Both direct cellular damage and ischemia
Anterior Open-­and narrow-­or closed-­angle glaucoma. Secondary changes in the iridocorneal
chamber angle and ciliary cleft of the dog from buphthalmia invariably involve progressive
angle narrowing, and eventual closure, of the iridocorneal angle and collapse of the ciliary cleft
Choroid and Depends on rapidity of onset, duration, and level of the IOP elevation. Areas of
tapetum chorioretinal ischemia and degeneration in the ischemic zones with markedly increased
cellulosum IOP. Tapetal changes include degeneration and thinning
Lens Cataract formation and changes in the lens position within the patella fossa (from
primary zonular disease or secondary to globe enlargement)
Vitreous Liquefaction and formation of vitreal cortical strands
Retina and Progressive degeneration with continued high IOP. Large-­diameter optic nerve axons
ONH appear particularly sensitive. The inner retinal layers, especially the RGC and nerve fiber
layers, as well as the ONH appear to be very sensitive to IOP, and degenerate rapidly. With
high IOP (≥50 mmHg), outer retinal damage (photoreceptors)

of glaucoma or screening IOP-­reducing drugs. Pathology of Canine Glaucoma


The common tests for the POAGs include the in Clinical Patients
water provocative and steroid provocative
Observations on the pathology of glaucoma
tests. The provocative tests for the closed-­angle
globes from clinical patients must be carefully
glaucomas include the mydriatic drug test and
interpreted because these globes are usually
the darkroom test.
from advanced stages of the disease, have irre-
versible blindness, and may have received
treatment with medications and/or surgeries
­ linical and Pathological
C for varying lengths of time. The determination
Effects of Elevated IOP of the underlying cause for the elevation in
IOP is often a challenge, and may or may not
All glaucomas are diseases of constant and always be possible. Possible mechanisms for
progressive change, with decreases in aqueous the development of the secondary glaucomas
humor outflow throughout the disease. In con- included open iridocorneal angle with cili-
trast to most ophthalmic diseases, elevated IOP ary cleft closure; open iridocorneal angle
affects all of the ocular tissues as the disease obstructed by preiridal fibrovascular mem-
progresses (Table 10.2). branes (rubeosis iridis), endothelialization and
368 The Canine Glaucomas

descemetization, lens epithelialization, inflam- duration of the elevation in IOP. As the pri-
matory cells, or red blood cells; open angle mary glaucomas are usually progressive dis-
with pupillary obstruction; closed angle caused eases, the clinical signs of the disease also
by anterior synechia; closed angle secondary to change, and are used to ascertain the relative
lens luxation and pupillary block; and oblitera- stage of the glaucoma. The stage of glaucoma
tion of the outflow structures secondary to may be asymmetric in the fellow eyes of the
neoplasia or necrotizing inflammation. The same dog, with one eye at advanced stages of
intraocular tissues in chronic glaucomas and disease and the other apparently normal or at
those with high IOP often also exhibit inflam- very early stages. In the earliest phase of the
mation probably secondary to direct tissue primary open-­angle and narrow-­angle glauco-
damage as well as ischemia. mas in the dog, the disease is usually insidious,
and the eyes are usually asymptomatic. Cross-­
or mixed-­breed dogs can also develop primary
­Clinical Signs glaucoma with an overall frequency in North
America of about 1%.
Clinical signs of the glaucomas depend on the Early signs range from none, slight mydria-
stage of disease and, to some extent, on the sis, mild but transient corneal edema, variable
type of glaucoma (Table 10.3). Clinical signs episcleral congestion, normal ONH appear-
are also directly related to the level and ance, to IOPs of approximately 25–30 mmHg.
Unless periodic and even diurnal applanation
Table 10.3 Clinical signs of the primary tonometry and careful ophthalmoscopy are
glaucomas in the dog. performed, these early glaucomatous eyes are
not usually presented to the veterinarian for
Stage of ophthalmic examinations until the disease
glaucoma Clinical signs advances to more overt clinical signs.
The clinical signs of moderate glaucoma
Early May be asymptomatic; slight
include more prominent amounts of mydriasis
mydriasis; mild but transient corneal
edema; variable episcleral congestion; (especially in a darkened room), episcleral
normal ONH appearance; IOPs of congestion, variable degrees of corneal edema
approximately 20–30 mmHg; visual. and striae, slight buphthalmia, early lens sub-
Often not detected by owner
luxation, variable retinal and optic disc
Mild/ Variable mydriasis, episcleral changes, and IOPs of 30–40 mmHg. When pri-
moderate congestion, variable degrees of
corneal edema/striae, slight
mary glaucoma is advanced, clinical signs may
buphthalmia, early lens subluxation, include intermittent visual impairment to total
variable retinal and optic disc blindness, persistent mydriasis, corneal edema
changes, and IOPs of 30–40 mmHg; with corneal striae, peripheral anterior syne-
vision to visual impairment. Usually
detected by owner
chiae and angle closure with peripheral cor-
neal edema, buphthalmia, lens displacement
Advanced Persistent mydriasis, corneal edema
with corneal striae, peripheral from the patella fossa, cortical cataract forma-
anterior synechiae and angle closure, tion, vitreous degeneration and syneresis,
buphthalmia, lens displacement from extensive retinal and optic disc degeneration,
the patella fossa, cortical cataract and IOPs of more than 40–50 mmHg.
formation, vitreous degeneration and
syneresis, extensive retinal and optic Occasionally, with IOPs in excess of 50 or
disc degeneration, and IOPs of more 60 mmHg, mild papilledema may be detected
than 40–50 mmHg; intermittent through a less than transparent ocular media.
visual impairment to total blindness. Presumably, the optic nerve fibers within the
Usually detected by owner
prelaminar ONH and peripapillary retina are
­Primary and Breed-­Predisposed Canine Glaucoma  369

enlarged because of impaired axoplasmic Table 10.4 Breeds with primary glaucomas.
transport at the prelamina cribrosa. With very
high elevations in IOP, wedge-­shaped areas of Akita Italian Greyhound
chorioretinal degeneration based at the edge of Alaskan Malamute Lakeland Terrier
the ONH may result, apparently from ischemia Basset Hound Maltese
secondary to infarction of individual short cili- Beagle Miniature Pinscher
ary arteries. ONH cupping is usually slight and Border Collie Miniature Schnauzer
most obvious with advanced atrophy. Loss of
Boston Terrier Norfolk Terrier
myelin within the ONH in glaucoma results in
Bouvier des Flandres Norwegian Elkhound
smaller and round optic discs.
Brittany Spaniel Norwich Terrier
The signs of the secondary glaucomas are
like those of the primary glaucomas, but the Cairn Terrier Poodle Toy/Miniature
cause for the rise in IOP, such as an anterior Cardigan Welsh Corgi Samoyed
uveitis, an intraocular mass, or a lens luxation, Chihuahua Scottish Terrier
is evident. By gonioscopy, the iridocorneal American Cocker Sealyham Terrier
angle and cleft may be open, narrow, or closed Spaniel
dependent on the inciting cause. The congeni- Dachshund Shih Tzu
tal glaucomas affect young puppies, usually Dalmatian Shiba Inu
within the first one to six months of life and, Dandie Dinmont Siberian Husky
compared to the primary and secondary glau- Terrier
comas, are quite rare. Often, the first clinical English Cocker Spaniel Skye Terrier
sign in these animals is rapid onset of buphthal- English Springer Smooth Fox Terrier
mia, inability to completely close the palpebral Spaniel
fissure, and the development of exposure cor- German Shepherd Tibetan Terrier
neal disease. Giant Schnauzer Welsh Springer Spaniel
Greyhound Welsh Terrier
Irish Setter West Highland White
­ rimary and Breed-­Predisposed
P Terrier
Canine Glaucomas Wire Fox Terrier

The primary glaucomas in the dog are divided


into open-­angle and the narrow-­ or closed-­
angle glaucomas, and are often breed-­specific noted. In the United States, primary glaucoma
(Table 10.4). In the veterinary medical litera- in the American Cocker Spaniel appears as a
ture, the association of abnormalities of the narrow-­angle or angle-­closure type, without
pectinate ligaments (goniodysgenesis or more significant amounts of PLD. In the Samoyed
precisely PLD) and the angle-­closure glauco- breed in Sweden, narrow iridocorneal angle
mas in these dogs appears to be more than just width has been recently related to the develop-
coincidence. ment of glaucoma. Dysplasia of the pectinate
ligaments (i.e., solid sheets of pectinate liga-
ments, initially termed mesodermal remnants)
Pectinate Ligament Dysplasia
appears to be common in some breeds, but has
In clinical studies of American and English not been directly related to an increased resist-
Cocker Spaniels as well as of the Basset Hound, ance to the outflow of aqueous humor. It would
narrow iridocorneal angles and sclerociliary appear glaucoma may develop in only the most
clefts were common findings, and in the latter severity affected forms of PLD (well in excess
breed, dysplasia of the pectinate ligaments was of 180° of the iridocorneal angle involved).
370 The Canine Glaucomas

It is important to differentiate the iridocorneal the American Cocker Spaniel, Basset Hound,
anomalies (e.g., persistent mesodermal bands Cairn Terrier, Chow Chow, English Cocker
and PLD) from any inflammatory-­associated Spaniel, Samoyed, and perhaps the Siberian
changes (peripheral anterior synechiae). In Husky. In the American Cocker Spaniel, the
some breeds, i.e., Basset Hound, the extent of females were affected more often than the
the PLD may progress over time and thereby males (percentage male–female, 1:1.93). In the
predispose these dogs to glaucoma at later ages. 1974–1983 interval, the percentage ratios of
females to males were higher in the American
Cocker Spaniel (male–female, 1:1.49), Basset
Breed Predisposition
Hound (1:1.65), English Cocker Spaniel
In the years 1994–2002, 22 different breeds (1:7.44), and Welsh Terrier (1:2.51).
had 1% or higher prevalence of the glaucomas.
The highest prevalence of glaucomas in the
Effect of Age
time period 1994–2002 by breed included
American Cocker Spaniel (5.52%), Basset Age also appears to be an important risk factor
Hound (5.44%), Chow Chow (4.70%), Boston and affects the time for presentation of most of
Terrier (2.88%), Wire Fox Terrier (2.28%), the glaucomas in the purebred dog. In the
Norwegian Elkhound (1.98%), Siberian Husky majority of breeds, the glaucomas are pre-
(1.88%), Cairn Terrier (1.82%), and Miniature sented most often in dogs at an average age of
Poodle (1.68%). Breeds recently introduced to about six years, except in the Siberian Husky,
North America showing higher prevalences of Samoyed, and Welsh Springer Spaniel, which
the glaucomas included the Akita, Australian are usually younger. The other breeds range
Cattle Dog, and Shar-­Pei. Those breeds con- from 7 to 10 years of age, when first presenting
sistently among the most frequent throughout with glaucoma (usually unilateral).
the entire 38 years included American Cocker
Spaniel, Basset Hound, Boston Terrier,
Miniature Poodle, Wire Fox Terrier, and I­ nheritance of the
Siberian Husky. Breeds among the top 20 glau- Canine Glaucomas
coma breeds for three of the four periods of
study (28–30 years) included Standard Poodle, Inherited open-­ and narrow-­angle primary
Pekingese, Norwegian Elkhound, English glaucomas occur bilaterally in purebred dogs.
Cocker Spaniel, Australian Cattle Dog, and Although the primary glaucomas have been
Chow Chow. The prevalence of the glaucomas reported in at least 45 breeds in the United
among other breeds or cross-­bred breeds also States (see Table 10.4), very few breeds have
increased from 0.27% (1964–1973), 0.34% been investigated to date. There is very limited
(1974–1983), 0.67% (1984–1993) to 0.71% information on the mode(s) of inheritance for
(1994–2002). the canine primary glaucomas. POAG in the
Beagle is inherited as an autosomal recessive
trait, and has been associated with the
Effect of Gender
ADAMTS10 mutation. Genetic investigations
The effect of gender appears important in of glaucoma in the American Cocker Spaniel
humans with narrow-­angle-­closure primary and Basset Hound have heretofore failed to
glaucoma with the female affected much more establish the inheritance of this condition in
frequently, especially in the Asian race. Does these breeds. Primary glaucomas in the Welsh
the risk factor of gender also occur in the dog? Springer Spaniel and Great Dane appear to be
Yes! Differences in the ratios of males to inherited as a dominant trait, with variable
females for the glaucomas by gender appear in expression.
­Clinical Stages of the Primary Glaucoma  371

hypertension. In the breeds with POAG, the


Box 10.2 Inherited and Breed
increase in IOP is gradual and progressive,
Predisposition to Lens Luxation in Dogs
and the clinical signs develop from barely
noticeable to advanced over a few (2–4) years.
Inherited Breed predisposed
In the early and moderate stages of the dis-
Border Collie Australian Collie ease, IOP is generally between 25 and
Cairn Terrier Basset Hound 40 mmHg, and there is mydriasis, variable
Jack Russell Terrier Beagle corneal edema, and episcleral congestion.
Lakeland Terrier Chihuahua Vision is present. The dog’s eye is not appreci-
ated as abnormal, and the dog is not usually
Manchester Terrier German Shepherd
presented to the veterinarian. As POAG
Miniature Bull Greyhound
Terrier
advances and the IOP climbs further, globe
enlargement (megaloglobus, buphthalmos)
Norfolk Terrier Miniature Poodle
occurs and lens instability results from the
Norwich Terrier Miniature Schnauzer
damage to the zonules and directly contrib-
Scottish Terrier Norwegian Elkhound utes to abrupt increases in IOP. Episcleral
Skye Terrier Spaniel Breeds congestion, corneal edema, mydriasis, lens
Sealyham Terrier Pembroke Welsh Corgi subluxation or total luxation, optic disc and
Smooth-­Haired Fox Welsh Terrier retinal degeneration, and blindness result.
Terrier Lens instability leads to more variable IOP,
West Highland Toy Poodle with frequent pupillary blockage by lens and/
White Terrier or vitreous abrupt high IOP (50–60 mmHg).
Tibetan Terrier Toy Terrier Often, this is when the dog is first presented
Wirehaired Fox to the veterinary ophthalmologist.
Terrier The clinical stages of the PACG dogs are dif-
ferent and characterized by abrupt increases
in IOP, which are initially transient and self-­
controlled, but eventually the elevation in
Breeds of dogs having secondary glaucoma IOP persists and necessitates presentation to
associated with luxation of the lens include the veterinary ophthalmologist. These abrupt
many terrier breeds (Box 10.2). A mutation of IOP changes are apparently the result of
the ADAMTS17 gene has been associated with pupillary blockage to aqueous humor from
lens luxation in the Jack Russell Terrier, posterior chamber to anterior chamber and
Miniature Bull Dog, and Lancashire Heelers. It the forward displacement of the basal iris
is likely additional breeds will be added to the with narrowing to closure of the iridocorneal
three breeds! However, the association of angle and cleft. These abrupt increases in IOP
the lens displacement and onset of glaucoma initially are in the 30 mmHg or higher range,
in these dogs we believe requires additional but as the angle narrowing and closure
studies! advance, the increase can reach 50 mmHg or
higher and produce clinical signs that merit
presentation to the veterinarian. Eventually
­ linical Stages of the
C (sometimes within days), this appositional
Primary Glaucomas narrowing and closure of the iridocorneal
angle and sclerociliary cleft develops periph-
Both POAG and PACG have different clinical eral anterior synechiae, “zipping” the outflow
stages or phases based on the level of IOP pathways close, and rending the glaucoma
elevation and the duration of the ocular refractory to pressure-­lowering drugs. During
372 The Canine Glaucomas

(a) (b)

Figure 10.4 Narrow-­angle and cleft glaucoma in an American Cocker Spaniel. (a) Both corneal edema
and striae are present, and the IOP is 52 mmHg. (b) Gonioscopy reveals a closed iridocorneal angle
and cleft.

the next decade or so, the PACG breeds will Cocker Spaniel contains few classic clinical
hopefully be characterized further and the signs of glaucoma, but occasional histories
exact genesis of their glaucomas documented. report the presence of conjunctival hyperemia
The stages of canine PACG can be divided and even transient corneal edema. Most
clinically into latent or prodromal; intermit- affected dogs present either with classic clini-
tent glaucoma; acute congestive or high-­ cal signs of unilateral, acute congestive glau-
pressure glaucoma; postcongestive glaucoma; coma of a few days’ duration or with chronic,
and chronic glaucoma. Each stage of PACG advanced glaucoma with buphthalmia, lens
has certain clinical characteristics that can changes, retinal and ONH degeneration, and
determine the stage and serve as a guide for blindness (Figure 10.4a and b).
therapy. Because the acute congestive stage of Both the history and clinical course suggest
PACG is usually the first stage presented to this glaucoma may be a series of acute IOP
the veterinarian, it is not surprising that attacks, with the subsequent magnitude of the
nearly 50% of these eyes are blind and medi- IOP elevation gradually increasing. Tonometry
cal therapy of this stage has limited success of the acute congestive glaucomas often yields
and for a short duration. IOPs as great as 50–70 mmHg, and the corneal
edema that parallels the elevation in IOP after
approximately 40 mmHg usually prevents
Glaucoma in the American
gonioscopy. Gonioscopy of the American
Cocker Spaniel
Cocker Spaniel with ocular hypertension usu-
Prevalence of the glaucomas in the American ally reveals a narrow to closed iridocorneal
Cocker Spaniel varies from 1.39% (1964–1973), angle and reduced ciliary clefts; as the glau-
2.07% (1974–1983), 3.95% (1984–1993) to 5.52% coma progresses, angle closure and ciliary cleft
(the highest for any breed). In the North collapse with peripheral anterior synechial for-
American survey of 1982 glaucomatous cock- mation are common.
ers, 665 were males and 1331 were females Changes of the ocular fundus in the
(1:2). The mean ± SD for affected animals was American Cocker Spaniel may not correlate
6.72 ± 1.13 years. The usual history of PCAG or well with the duration and magnitude of the
narrow-­angle glaucoma in the American elevated IOP because of the wide difference in
­Clinical Stages of the Primary Glaucoma  373

the levels of elevated IOP. Ophthalmoscopically, by the formation of peripheral anterior


the ocular fundus cannot be often visualized synechiae.
until the IOP is lowered and the corneal This form of glaucoma usually presents
edema reduced. The optic nerve and retina clinically as either a unilateral, acute, conges-
may initially appear to be normal, although tive, closed-­angle glaucoma or a chronic
some vascular attenuation may be present. narrow-­angle-­closure glaucoma with
With the IOP maintained within the normal buphthalmia and eventual blindness
range after these acute increases, additional (Figure 10.5a and b). Anterior uveitis can
retinal and ONH degeneration may become accompany Basset glaucoma, with at least
apparent within a few weeks. Because this some of the corneal edema related to this
breed often presents with its first affected eye inflammation, which is unusual among breed-­
with very high IOP and often irreversibly related canine glaucomas. This inflammation
blind, prophylactic therapy of the fellow eye is complicates greatly the medical and surgical
essential for maintenance of vision for as long treatments of this form of glaucoma and
as possible. requires concurrent topical and systemic cor-
ticosteroid therapy. Gonioscopy of Basset
Hounds that eventually develop glaucoma
Glaucoma in the Basset Hound
suggests that the PLD may become more
In the Basset Hound in the recent North extensive over time and with progressive nar-
American survey, 545 glaucomatous dogs were rowing of the iridocorneal angle. Medical
diagnosed with glaucoma; the mean ± SD age treatment of Basset Hound glaucoma is diffi-
was 6.3 ± 1.30 years at first presentation for cult because of the often acute and very high
glaucoma. Prevalence has increased in the elevations of IOP, and the clinical signs of
Bassett Hound from 3.08% (1964–1973) to 5.44% combined angle-­closure glaucoma and irido-
(1994–2002). Prevalence of glaucoma in the cyclitis. Often the first presenting eye is mod-
Basset Hound appears to increase with age. In erately enlarged, the lens is subluxated, the
1994–2002, the glaucoma prevalence was 0.47% ONH is cupped, and vision has been lost.
(2–6 months), 0.37% (6–12 months), 0.36%
(1–2 years), 4.19% (2–4 years), 6.74% (4–7 years),
Glaucoma in the Beagle
6.95% (7–10 years), and 6.81% (10–15 years). The
mean ± SD age of initial presentation with glau- In the 2002 North American survey, the prev-
coma in the Basset Hound was 6.33 ± 1.30 years. alence of glaucoma in the Beagle was 1.01%
The gender ratio differs with more females in 1984–1993 and 1.10% in 1994–2002.
affected than males (1:2.4). Inherited glaucoma in Beagles was first
Narrow-­ and closed-­angle glaucoma with reported in 1971, and a colony of affected
PLD (i.e., mesodermal dysgenesis) has been dogs was established shortly thereafter to
documented in Basset Hounds. Serial gonios- permit long-­term investigation of this spon-
copy of some glaucomatous Basset Hounds taneous disease. In the closed colony of glau-
suggests a gradual increase in the extent of comatous Beagles, the ocular hypertension
PLD with aging, suggesting possible formation begins between one and two years of age but
of peripheral anterior synechiae. Recent becomes first noticeable by owners when sec-
reports in the glaucomatous Basset Hound ondary globe enlargement, mydriasis, and
have classified the disease as a chronic angle-­ lens subluxation develop much later (usually
closure glaucoma animal model. Primary at four to six years of age).
chronic angle-­closure glaucoma in humans is The elevation in IOP becomes apparent at
characterized by positions of the anterior tonometry in Beagles between 8 and 16 months
chamber angle becoming permanently closed of age, but the clinical signs of glaucoma are
374 The Canine Glaucomas

(a) (b)

Figure 10.5 (a) Basset Hound with bilateral advanced glaucoma. (b) At gonioscopy, large, persistent
mesodermal bands, rather than the distinct, individual pectinate ligaments, are often visible. With extensive
involvement, flow holes are present in these dysplastic pectinate ligaments. Because iridocyclitis is often
present, these pectinate ligament anomalies must be differentiated from progressive, peripheral anterior
synechiation of the aqueous outflow pathways in this type of glaucoma.

delayed until two to five years. In some affected


dogs, IOP elevates over 2–4 years and results in
blindness, while in other affected Beagles,
vision is still present at 10 years of age. The
increase in IOP and decline in facility of out-
flow, as measured by Schiotz tonography,
pneumatonography, and constant-­ pressure
perfusion of the anterior chamber, develop
slowly. The iridocorneal angle and sclerocili-
ary cleft are initially open and devoid of any
abnormalities (Figure 10.6). Eventual iridoc-
orneal angle and sclerociliary cleft closure
result in animals from 4 to 6 years to as much
as 8–10 years of age. Lens removal prior to the
onset of ocular hypertension in Beagles bred
for POAG did not delay the onset of glaucoma.
POAG is inherited in Beagles as an autosomal Figure 10.6 Gonioscopic view of the iridocorneal
recessive trait and recently associated with an angle and opening of the ciliary cleft in a Beagle
ADAMTS10 mutation. The ADAMTS10 muta- with early POAG.
tion has been identified not only in this colony
of glaucomatous Beagles but also in clinical reported at different phases of the disease
patients. (pre-­, early, moderate, and late) (Samuelson,
Among the different breeds of dogs with 1989). In the preglaucomatous dogs
POAG, the Beagle glaucoma has the most (1–11 months old), no abnormalities were pre-
documentation. The TM cells, like humans, sent in the TM. In 12-­month-­old dogs, clus-
decline with aging and more so in POAG. The tered basement membrane-­like material was
ultrastructural changes of the aqueous humor scattered throughout the corneoscleral TM. In
outflow pathways of Beagle POAG have been the same region, elastin-­like fibers appeared
­Clinical Stages of the Primary Glaucoma  375

more numerous and arranged less regularly. glaucomatous aqueous humor. However, a
Occasional trabecular cells within the corneo- recent study in POAG dogs found that aqueous
scleral TM possessed small cluster of serrated humor concentrations of active, latent, and
opaque rods within their cytoplasm. In moder- total TGF-­β2 were not significantly increased
ate to advanced POAG, these changes were in ADAMTS10-­mutant dogs compared to age-­
more generalized and affected the entire cor- matched controls. In contrast to reported
neoscleral TM. Narrowing developed with findings in glaucomatous cats and humans,
compression and less organization with a con- elevated levels of TGF-­β2 may not contribute
comitant buildup of extracellular materials. to the development of open-­angle glaucoma in
Intertrabecular spaces were markedly reduced Beagles. Alternatively, TGF-­β2 may be bound
in size in the uveal meshwork and to a lesser within the extracellular matrix rather than free
extent in the corneoscleral TM. A uniform within aqueous humor in the anterior cham-
layer of fibrils, 10–12 nm in diameter, and ber. Preliminary immunohistochemical stud-
amorphous material coated most of the ies to evaluate expression of TGF-­β2 in ocular
endothelial walls along the angular aqueous tissues have characterized patterns of tissue
plexus. Elastin-­like fibers frequently pressed distribution of TGF-­β2 in the eyes of dogs with
against the endothelium of the angular aque- open-­angle glaucoma and indicate there is
ous plexus. increased TGF-­β2 in the ciliary body epithe-
Microfibrils are macromolecular aggregates lium, corneal epithelium, and optic nerve of
located in the extracellular matrix of both elas- affected dogs.
tic and nonelastic tissues that have essential
functions in formation of elastic fibers and
Glaucoma in the Boston Terrier
control of signaling through the transforming
growth factor beta (TGF-­β) family of cytokines. The prevalence of glaucoma is also increasing
Microfibril defects could contribute to glau- in the Boston Terrier breed, ranging from
coma through alterations in biomechanical 0.97% (1964–1973), 1.82% (1974–1983), 2.60%
properties of tissue and/or through effects on (1984–1993) to 2.88% (1994–2002). The preva-
signaling through TGF-­β, which is well estab- lence of the glaucoma in the Boston Terrier
lished to be elevated in the aqueous humor of (n = 255) was consistently in the highest 10
human and feline POAG patients. A role for breeds for the past 38 years. Glaucoma presents
microfibrils in glaucoma is suggested by iden- in the middle-­age and predominately old-­age
tification of risk alleles and mutations in the Boston Terrier, and mean ± SD age of initial
microfibril-­associated genes LOXL1 (for exfo- presentation was 7.02 ± 1.24 years. The male/
liation glaucoma) and LTBP2 (for primary female ratio was 1:1. There is no clinical report
­congenital glaucoma) in humans. Recent iden- on glaucoma in this breed to date, but several
tification of a G661R missense mutation in the papers on inherited cataracts.
ADAMTS10 gene in the dog model of POAG
naturally leads to microfibril hypothesis of
Glaucoma in the Bouvier
glaucoma, which in general states that
des Flandres
de­fective microfibrils may be an underlying
cause of glaucoma. Recent work has shown In the Bouvier des Flandres, two reports of
that ­diseases caused by microfibril defects are PLD and narrow-­angle glaucoma included 35
­associated with increased concentrations of and 36 glaucoma animals. Both reports were
TGF-­β protein and chronic activation of TGF- based on dogs in the Netherlands, where the
β-­mediated signal transduction in humans. breed is the most frequently affected purebred
Defective microfibrils could provide a mecha- dog with glaucoma. In America, the Bouvier
nism for the elevation of TGF-­β2 in des Flandres is a relatively new breed of dog,
376 The Canine Glaucomas

and the number of glaucomatous animals in dogs with a mean age of 9.8 years. The preva-
the survey report was limited to 23 (mean ± SD lence of glaucoma in the English Cocker
age of 5.43 ± 1.70 years). The male:female ratio Spaniel in North America was fairly constant
of affected dogs was 1:1. In addition to PLD (1.16% in 1974–1983, 1.59% in 1984–1993, and
and narrow iridocorneal angle and ciliary cleft, 1.35% in 1994–2002), and primarily affected
histopathology of the affected secondary pec- middle-­aged and older dogs. Bedford reported
tinate ligaments and trabecular meshwork both narrow and closed iridocorneal angles
contained significant amounts of periodic and clefts as well as PLD in this breed.
acid-­Schiff (PAS) material, which may also
affect aqueous humor outflow.
Glaucoma in the English
Springer Spaniel
Glaucoma in the Chow Chow
The prevalence of primary glaucoma in this
In the Chow Chow breed in the prevalence sur-
breed in North America is low (0.48% in
vey in North America, 223 glaucomatous dogs
1974–1983); only 25 dogs were affected (15 males
were recorded with the mean ± SD age of
and 12 females). The prevalence based on age at
6.45 ± 1.07 years on first presentation for glau-
initial diagnosis of primary glaucoma varied
coma. During nearly 40 years in North America,
from 0.48% (2–4 years), 0.28 (4–7 years), 0.72%
glaucoma was diagnosed in the Chow Chow
(7–10 years) to 1.40% (10–15 years). Primary
not infrequently: 2.05% (1984–1993) and 4.70%
glaucoma, characterized as narrow iridocorneal
(1994–2002). Glaucoma in this breed predomi-
angle and PLD, was reported in English Springer
nantly affects the older dog. The mean ± SD age
Spaniels in Norway. While narrowing of the
of initial presentation with glaucoma in the Chow
iridocorneal angle in the hypertensive dogs
Chow was 6.45 ± 1.07 years. The male:female
seemed somewhat constant, the degree of PLD
ratio in primary glaucoma in this breed was
was more variable with affected dogs generally
about 1:2. Primary glaucoma in the Chow
more severely affected, and more frequent in
Chow has been associated with iridocorneal
older dogs. This breed-­related glaucoma appears
angle closure and limited PLD. Most animals
to be inherited because related dogs were
presented with bilateral, acute congestive glau-
affected, and this possibility should be investi-
coma. Results of gonioscopy, when possible,
gated more thoroughly.
revealed narrow to closed iridocorneal angles,
with short, stout pectinate ligaments. PLD,
appearing as focal areas of solid pigmented Glaucoma in the
sheets, was usually quite limited (<1/16 the cir- Flat-­Coated Retriever
cumference of the angle). On the basis of clini-
Primary glaucoma also affects Flat-­Coated
cal observations regarding the extent of PLD,
Retrievers from England, but the condition has
the genesis of this form of primary glaucoma
not been reported among those from the
appears to be of the narrow-­ and closed-­angle
United States. Flat-­Coated Retrievers with the
type. The Chow Chow is another breed with
more extensive forms of PLD are predisposed
primary glaucoma that often retains functional
to glaucoma. Many other aspects of this type of
vision until late in the disease, often with pro-
glaucoma need to be investigated.
found optic disc cupping.

Glaucoma in the English Cocker Spaniel Glaucoma in the Great Dane


Glaucoma in the English Cocker Spaniel may PACG occurs in Great Danes from England.
be more common in the United Kingdom, and Eighteen dogs (11 females and 7 males) have
the single report included 16 glaucomatous been affected, with an age range of one to nine
­Clinical Stages of the Primary Glaucoma  377

years (mean age, 4 years). Most dogs presented Glaucoma in the Toy and Miniature
with unilateral acute congestive glaucoma, Poodles
with 3-­to 24-­month intervals between binocu-
Although the glaucoma is not common in
lar involvement. Gonioscopy of the initially
North American Miniature Poodle (1.49% in
affected eyes, as well as of the opposite, nor-
1984–1993 and 1.68% in 1994–2002) and Toy
motensive eyes, revealed narrow to closed iri-
Poodle (1.06% in 1984–1993 and 1.20% in
docorneal angles with PLD.
1994–2002), the popularity of these two breeds
results in larger numbers of glaucomatous ani-
Glaucoma in the Petit Basset
mals. The prevalences of the glaucomas in
Griffon Vendéen
North America in the Toy and Miniature
POAG was recently reported in the PBGV in
Poodles were combined and involved a large
the United Kingdom based on the examination
number of affected dogs (n = 573). The
of 366 dogs over a six-­year period. Thirty-­eight
mean ± SD age of initial presentation with
dogs were affected with POAG (prevalence
glaucoma in the Miniature Poodles was
10.4%). Clinical signs developed after three
7.31 ± 1.23 years. The glaucomas in the Toy and
years of age with elevated IOP ranging between
Miniature Poodle breeds appeared to be
34 and 48 mmHg at presentation.
increasing slightly. The affected male:female
Initially, the drainage angle appears open
ratio for this breed is 1:1.4.
gonioscopically and the pectinate ligaments
appear normal. In advanced POAG, globe
enlargement, lens subluxation, ONH cupping,
Glaucoma in the Norwegian Elkhound
and impaired to complete loss of vision
occurred. Lens subluxation was prominent in The prevalence of glaucoma in the Norwegian
10 dogs with phacodonesis and/or iridodonesis Elkhound is 2.96% (1974–1983), 2.34%
and aphakic crescents. An inversion mutation (1984–1993), and 1.98% (1994–2002). POAG
in intron 12 of the ADAMTS17 was discovered was originally described in 29 Norwegian
as the cause for POAG (and PLL) in the affected Elkhounds in Norway. The 15 glaucomatous
PBGV dogs. dogs (1 female and 14 males) ranged in age
from 3.9 to 13.0 years (median age, 6.6 years).
The male:female ratio of affected dogs is 1:1.3.
Glaucoma in the Shiba Inu in Japan
The iridocorneal angle and ciliary cleft
The Shiba Inu is a relatively new breed in appeared normal in early affected dogs, with
America and does not have a large number of IOPs ranging from upper 20s to the 30s
registered dogs at this time. However, the (mmHg). PLD was not observed, though occa-
Shiba Inu is a popular breed in Japan and sional “stout” pectinate fibers were noted, with
­demonstrates glaucoma with iridocorneal some narrowing of the ciliary cleft opening.
angle narrowing and thickening of pectinate The ciliary cleft gradually closed as the glau-
ligaments. The thickened pectinate ligaments coma advanced, and the IOP progressively
range from very broad strands, small sheets to increased. Synechial closure of the ciliary cleft
broad solid sheets with or without flow holes. occurred in the advanced cases. Lens subluxa-
Of the primary glaucoma dogs in Japan, the tion and total lens luxation, buphthalmos and
Shiba Inu breed had the highest incidence (42 Haab’s striae, and ONH atrophy and retinal
dogs; 33%), followed by Shih Tzu breed (21 degeneration occurred late in the disease, with
dogs; 16.5%). Most Shiba Inu patients present subsequent loss of vision. This breed is an
with acute high IOP elevations, mydriasis, cor- excellent example of the members that can still
neal edema, scleroconjunctival congestion, see with IOPs in the mid-­30 mmHg, and ONH
pain, and often loss of vision. cupping that involves the entire nerve head.
378 The Canine Glaucomas

Histopathological study of 9 clinically normal glaucoma in humans and some canine breeds.
and 22 glaucoma eyes showed open-­angle and The glaucomatous eyes all had closed iridoc-
closed-­cleft glaucoma with PLD (2 normal and orneal angles. Eyes with narrow iridocorneal
18 glaucoma eyes), ciliary cleft abnormalities angles had anteriorly positioned lenses and a
(hypoplasia or collapse), and linear deposition longer vitreous body.
of PAS-­positive basement material within the
uveal trabecular meshwork (in 19 glaucoma
Glaucoma in the Shar-­Pei
eyes). Transmission electron microscopy
(TEM) demonstrated thickening of uveal tra- A relatively new breed to North America, the
becular beams by poorly staining large colla- Shar-­Pei exhibits primary or breed-­related
gen fibrils and irregular deposition of excess glaucoma (1.53% in 1984–1993 and 4.40% in
basement material. 1994–2002) in later life. The breed has also
been reported with hereditary lens luxation,
and how these two breed-­related diseases
Glaucoma in the Samoyed
inter-­relate remains to be defined. In the glau-
In the Samoyed, the first report of narrow-­ coma study, the male to female ratios were
angle/angle-­closure glaucoma was in Europe about the same, and the prevalence of
and included 12 glaucomatous animals (mean ­glaucoma based on age was 0% (2–6 months),
age ± SD: 6.6 ± 2.8 years) and 179 normoten- 0% (6–12 months), 0% (1–2 years), 1.49%
sive dogs. In the North American survey, (2–4 years), 7.58% (4–7 years), 7.42%
there were 148 glaucomatous dogs with the (7–10 years), and 3.17% (10–15 years). The
age (mean ± SD) at first presentation of male:female ratio of glaucomatous dogs was
6.16 ± 1.39 years. Prevalence in North America 1:0.89. In the dogs with PLLs, the mean age of
is relatively stable (1.43% in 1974–1983, 1.57% affected animals was much lower (4.9 years;
in 1984–1993, and 1.59% in 1994–2002). In the range of 3–6 years). This breed is another
Samoyed breed, glaucoma is presented in example of the members that can still see with
middle-­aged and older dogs, and the mean ± SD IOPs in the mid-­30 mmHg, and ONH cupping
age of initial presentation with glaucoma was that involves the entire nerve head.
6.16 ± 1.39 years. The ratio of males to females
in the breed is 1:2.23.
Glaucoma in the Siberian Husky
Narrow-­ or closed-­angle glaucoma in
Samoyeds has been investigated clinically in The prevalence of glaucoma in the Siberian
Sweden. This breed is an excellent example of Husky (1.13% in 1984–1993 and 1.88% in
the members that can still see with IOPs in the 1994–2002) reflects the increased popularity of
mid-­30 mmHg, and ONH cupping that involves the breed in North America. PLD and progres-
the entire nerve head. Results of gonioscopy sive narrowing of the iridocorneal angle have
indicated PLD to varying degrees in 47 of the been related to this form of ocular hyperten-
210 eyes, and the opening of the ciliary cleft (as sion. PLD was observed more frequently in the
measured from goniophotographs) declined female and in blue irides. In these normoten-
with age. Ultrasonic measurements of the fel- sive dogs, there was no relationship between
low eyes of unilateral glaucomatous Samoyeds the amount of PLD and IOP. Glaucoma in this
revealed a longer axial length; a more shallow breed affects mainly young and middle-­aged
anterior chamber; a thicker, more forward-­ dogs; the mean ± SD age of initial presentation
positioned lens; and a longer (anteroposterior) with glaucoma was 5.27 ± 1.64 years. In the
vitreous body, which are the more frequent Husky, the ratio of affected males to females
observations for primary narrow–closed-­angle is 1:1.88.
­Secondary Glaucoma  379

Glaucoma in the Welsh Springer Spaniel secondary glaucoma in the dog requiring
surgery is lens displacement (subluxation,
Twenty-­eight cases of primary angle closure
anterior luxation, or posterior luxation) and
have been reported in Welsh Springer Spaniels
cataract formation. Chronic anterior uveitis
from England. Females were affected more fre-
is the second most frequent cause of the
quently than males. Age of onset ranged from
­secondary glaucomas. Intraocular tumors
10 weeks to 10 years (mean age, two years and
are also associated with secondary glaucoma,
nine months). Four dogs were affected before
but these tumors develop infrequently in
one year of age. Time from the onset of glau-
the dog.
coma in the first eye to that in the second eye
ranged from six days to three years. Clinical
signs were either those of acute congestive Risk Factors of the Canine
glaucoma with pain, dilated and unresponsive Secondary Glaucomas
pupils, episcleral congestion, corneal edema,
Epidemiology Study of North America
and IOP as high as 80–100 mmHg or those of
In the veterinary schools of North America
chronic angle-­closure glaucoma with enlarged
from 1964 through 2003 in a total population
globes, Haab’s striae, lens subluxation and cat-
of 1 592 831 dogs, secondary glaucoma was
aract formation, and advanced retinal and
diagnosed in 9695 dogs. The secondary glau-
ONH degenerations. Gonioscopy of the
comas had been diagnosed at the same exami-
affected dogs revealed eyes with regions of nar-
nation or after the primary diagnosis has been
row and regions of closed iridocorneal angles
made. Selected glaucomas included those
and ciliary clefts, as well as other eyes with the
associated with cataract formation, lens luxa-
angles totally closed.
tion, cataract surgery, uveitis of unknown
cause, hyphema of unknown cause, and
Other Breeds intraocular neoplasia. Secondary glaucoma
associated with cataract formation repre-
Additional breeds also develop the primary sented 81% of all canine secondary glaucomas.
glaucomas (see Table 10.4), but most breeds Breeds predisposed to secondary glaucoma
have not been investigated. and cataract had an overall prevalence of 0.5%,
but nearly 20% of all cataractous dogs devel-
oped glaucoma in at least one eye. These
­Secondary Glaucomas breeds included the American Cocker Spaniel,
Boston Terrier, Toy and Miniature Poodles,
The secondary glaucomas consist of diseases English Springer Spaniel, Bichon Frise, and
with increased IOP, open to closed iridoc- Labrador Retriever. Other forms of secondary
orneal angles and ciliary clefts, and detecta- glaucoma were less frequent, and included
ble impairment of aqueous humor outflow. glaucomas with lens luxation or displacement
Both the medical and surgical management (12.0%), postcataract surgery (5.1%), uveitis
of secondary glaucomas in the dog have been of unknown cause (7.1%), hyphema from
overshadowed by those of the primary glau- unknown cause (7.3%), and intraocular
comas. Clinical management of these sec- ­neoplasia (3.5%). The prevalence of canine
ondary glaucomas is often more clear-­cut, secondary glaucomas ranged from 0.25%
because the cause of the increased IOP can (1964–1973), 0.46% (1974–1983), 0.79%
usually be ascertained (Box 10.3), and (1984–1993) to 0.80% (1994–2003) and was
the prognosis for the glaucoma progression as frequent as the primary or breed-­related
ascertained. The most frequent cause of glaucoma (0.9%).
380 The Canine Glaucomas

Box 10.3 Treatment for the Secondary Glaucomas in Dogs


Anterior uveitis: Hyphema
Peripheral anterior synechiae Surgical: aspirate/tissue plasminogen
Pupillary obstruction activator
Iris bombé
Melanocytic
Medical: corticosteroids, nonsteroidal anti-­
Surgical: anterior chamber shunts, enucleation
inflammatory agents, mydriatics
Surgical: coreoplasty, iridencleisis Aphakic/pseudophakic (angle/pupil
obstruction)
Lens-­associated:
Surgical: coreoplasty/iridencleisis, anterior
Cataract
vitrectomy
Surgical: lens removal
Displacement: anterior luxation, subluxation, Malignant
posterior luxation Surgical: anterior vitrectomy
Surgical: lens removal, other
Silicone oil
Intraocular neoplasms Surgical: aspirate oil/vitreous
Surgical: iridocyclectomy, enucleation
Rhegmatogenous retinal detachment

­Lens and the Glaucomas causes progressive stretching of the zonules,


which eventually breaks their attachments to
Removal of the lens, though not commonly the equatorial lens capsule or, infrequently,
considered to be a surgical procedure for treat- causes disinsertion of their attachments to the
ment of glaucoma, may be necessary in treat- ciliary body. In the dog with bilateral buphthal-
ment of many of the canine lens-­induced mia and lens subluxation/luxation, it may be
glaucomas in the future. Lens removal by impossible to determine whether the lens luxa-
phacoemulsification with the lens in situ has tions are primary or secondary; the breed, age
higher success rates than if the lens is sublux- of onset, and presence or absence of cataract
ated or luxated anteriorly. Lens removal may development may aid in making this determi-
also be indicated for secondary glaucomas nation. Total luxation with normal-­sized
associated with lens-­induced uveitis and cata- globes is more common in primary luxation
ract resorption, intumescent cataracts, anterior syndromes, with subluxations more commonly
and posterior lens luxations, and subluxations. caused by the buphthalmia from glaucoma.
When the lens is displaced from its patella Lens luxations in terriers are common, and
fossa in a glaucomatous eye, maintenance of these dogs may present with either unilateral
IOP within normal limits by surgical, medical, or bilateral and acute or chronic secondary
or some combination of these treatments may glaucoma. The terrier breeds with apparent
be impossible without lens removal. PLL are usually younger (Jack Russell Terriers
with a mean age of 4.7 years), while secondary
lens luxations in other breeds of dogs with
Subluxated Lenses, and Anterior
inherited cataracts were older (over eight years
and Posterior Lens Luxations
old). The secondary glaucoma in the terriers
Lens luxations are the most frequent cause of may be associated with iridocyclitis from
secondary glaucoma in the dog, but they also microtrauma between the unstable subluxated
occur secondary to buphthalmia in the pri- lens and iris, with resultant increases of aque-
mary glaucoma. Enlargement of the globe ous humor fibrin, proteins, and inflammatory
­Lens and the Glaucoma  381

cells, which can themselves interfere with in turn causes anterior ballooning of the
aqueous drainage, and it also may aid in for- peripheral iris and reduction in the area of
mation of preiridal fibropupillary membranes the iridocorneal angle outflow pathways. Such
as well as anterior and posterior synechiae, movement of the iris also contributes to forma-
which further compromise aqueous humor tion of permanent peripheral anterior syne-
drainage (Figure 10.7a and b). chiae, and posterior synechia that cause a
The completely luxated lens can remain in condition known as iris bombé.
the patella fossa, luxate into the anterior cham- With posterior or vitreal luxation of the lens,
ber, or move posteriorly through the torn ante- the torn anterior vitreal membrane allows both
rior vitreal face and into the vitreous (see liquid and formed (i.e., gel) vitreous access into
Figure 10.8a). Anterior lens luxations can the pupil and the anterior chamber. Formed
mechanically impair passage of aqueous vitreous may cause pupillary blockage and sec-
humor through the pupil, thereby causing ondary glaucoma. It can also adhere to the pos-
increased posterior chamber pressure, which terior cornea and iridocorneal angle. Blockage

(a) (b)

(c)

Figure 10.7 Lens luxations in the dog may produce secondary glaucomas, especially in terriers, or lens
luxation may develop secondary to globe enlargement. (a) and (b) In anterior lens luxation, the ocular
hypertension appears to arise from pupillary obstruction by the cortical vitreous still adherent to the
posterior lens capsule, from compression of the iridocorneal angle and ciliary cleft by the basal iris, or from a
combination of both. (c) In lens subluxation, the cause of the ocular hypertension is less obvious. Intermittent
pupillary obstructions of aqueous humor passage by the unstable lens and formed anterior vitreous, chronic
iridocyclitis, and progressive iridocorneal angle and ciliary cleft closure, however, appear to be important.
382 The Canine Glaucomas

degenerations, small aphakic crescents develop,


and partially liquefied vitreous may protrude
through a defect in the anterior hyaloid mem-
brane and into the pupil. This vitreous may also
display pigment spots. A key difference between
the glaucomas with luxated lens and cataract
formation and those with luxations and clear
lenses is that the ­former also has lens-­induced
uveitis, which further complicates their clinical
management and results in poorer outcomes.
Early removal of displaced lenses, particu-
Figure 10.8 Aphakic glaucomas may develop
larly in terriers, has the highest possibility of
secondary to pupillary occlusion from annular
posterior synechiae (iris to iris, iris to lens capsular/ success for retention of vision and prevention
anterior vitreous adhesions, or both), thus resulting of secondary glaucoma. The primary objective
in iris bombé, as in this eye. Alternatively, they may of lens extraction is to prevent secondary glau-
develop secondary to angle obstruction with
coma, to diminish inflammation, or to treat
inflammatory debris and peripheral anterior
synechiation. the secondary glaucoma. Delayed medical or
surgical treatment of eyes with displaced
lenses can result in secondary glaucoma.
Surgical removal of subluxated lenses, ante-
of the iridocorneal angle with formed vitreous rior luxated lenses, and the posterior luxated
sufficient to increase IOP is infrequent, but (i.e., intravitreal) lenses is accomplished by
blockage of the pupil from vitreous sufficient the extracapsular, phacoemulsification, or
to increase IOP is more common. intracapsular techniques. In contrast to the
high success rate of cataract surgery in dogs by
phacoemulsification, the removal of luxated
Cataractous Versus “Clear” Lens
lenses has a much higher risk of serious post-
Lens luxation may involve normal as well as operative complications, including glaucoma
cataractous lenses, with the mechanism for and retinal detachment. A medical approach
the zonular disinsertions that occur in lux- is long-­term therapy with demecarium bro-
ated lens or cataracts differing. In terriers, mide in those eyes with very little gel vitreous
Tibetan Terriers, and Border Collies, the and posterior luxated lens, often attached to
zonules appear to possess structural malfor- the ventral retina.
mations, and bilateral lenticular displace-
ment occurs in dogs only a few years old
Phacomorphic Glaucoma
having clear lenses. IOP can remain normal
and Intumescent Cataract
or be associated with abrupt elevations. In
contrast, luxations of cataractous and often The intumescent (i.e., swollen) cataract has
hypermature lenses tend to occur with inher- been associated with an acute pupillary block,
ited cataracts in older dogs of the non-­terrier phacomorphic glaucoma in the dog. This phe-
breeds. The zonular degenerations with nomenon occurs most frequently in the dog
advanced cataractous lenses produce subtle with diabetic cataracts, which may also develop
to overt degrees of subluxation/luxation, anterior and equatorial capsular tears. The
and they appear to relate to the capsular changes enlarged lens displaces the iris forward, thus
associated with cataract hypermaturity and increasing the posterior chamber pressure and
lens-­induced uveitis. With focal zonular causing the base of the iris to shift forward.
­Aphakic and Pseudophakic Glaucoma  383

This in turn narrows the iridocorneal angle occur. In a recent report involving 172 dogs fol-
and impinges on the ciliary cleft opening. If iri- lowing phacoemulsification, the frequency of
docyclitis is also present, peripheral anterior glaucoma increased with time during the three
synechia may form. Treatment of this form of months (290 eyes) to one year (200 eyes) of
secondary glaucoma is by phacoemulsification follow-­up examinations, but remained <10%
extraction of the cataract. overall. The Boston Terrier, American Cocker
Spaniel, Cocker Spaniel–Poodle crosses, and
Phacolytic Glaucoma/Resorbing Shih Tzus had increased risks of developing
Hypermature Cataracts glaucoma. Eyes with hypermature cataracts
and Lens-­Induced Uveitis and anterior uveitis were most likely to develop
glaucoma. Another recent report indicated
Chronic inflammations of the anterior uvea are about 15.8% of the patients having phacoemul-
not infrequent causes of secondary glaucoma sification can develop anterior uveitis and
(in contrast to more frequent acute iridocycli- glaucoma later. Periodic ocular examinations
tis). Rupture of the lens capsule from ocular to monitor IOP after cataract surgery in the
trauma, diabetes, and lens-­induced uveitis from dog are important to prevent this complication
resorbing hypermature cataracts can cause the and preserve vision for as long as possible!
phacolytic form of open-­angle glaucoma in the Aphakic and pseudophakic glaucomas prob-
dog. If the lens-­induced uveitis is not carefully ably represent multiple etiologies, with the two
monitored and controlled medically, the filtra- most frequent being occlusion of the pupil
tion angle can eventually become obstructed from inflammatory membranes and closure of
with inflammatory cells, protein-­rich aqueous the iridocorneal angle and ciliary cleft by for-
humor, fibrin, and macrophages filled with mation of preiridal fibrin membranes and
lens-­like material. With chronic lens-­induced peripheral anterior synechia. The aphakic
uveitis, formation of anterior and posterior syn- glaucomas that occur secondary to pupillary
echia, peripheral anterior synechia, and iris blockage in the dog are usually characterized
bombé may cause this phacolytic form of sec- by a small pupil that is either adhered to itself
ondary glaucoma. The definitive treatment for or obstructed by a membrane consisting of
phacolytic glaucoma is cataract extraction to organized fibrin, inflammatory cells and
eliminate the source of the lens protein obstruct- fibrous tissue, anterior capsule remnants, pos-
ing the aqueous outflow pathways. terior capsule, the anterior vitreous, or any
combination of these. There is usually iris
bombé as well (Figure 10.8). The occluded
­ phakic and Pseudophakic
A pupil may be depressed and sometimes barely
Glaucomas visible because of the iris bombé that bulges
into the central and peripheral anterior cham-
The frequency of aphakic and pseudophakic ber. IOP, as measured by applanation tonome-
glaucomas in humans after cataract surgery try, is usually raised to 30 or 40 mmHg, with a
has gradually declined as surgical techniques higher IOP posterior to the iris.
have improved. In the 1950s and 1960s, the
incidence of these glaucomas in humans was
Acute Postoperative Hypertension
reported to be from 0.7% to 7.0%, and even as
high as 12%. With the increased frequency of Increases in IOP during the immediate postop-
phacoemulsification cataract surgery and the erative period after cataract removal have been
intracapsular lensectomy for luxated lens in recognized for several years in both humans
the dog, aphakic and pseudophakic glaucomas and the dogs. In a clinical study involving 88
384 The Canine Glaucomas

dogs that received cataract surgery, the intracapsular cataract, or lens extraction sur-
in­cidence of postoperative hypertension of gery. The pupil is usually of medium size and is
25 mmHg or greater was 49%, of 30 mmHg or obstructed with inflammatory membranes,
greater was 34%, of 40 mmHg or greater was combined with either the posterior lens capsule
20%, and of 50 mmHg or greater was 6%. Other and anterior vitreous face (with extracapsular/
studies have confirmed ocular hypertension phacoemulsification) or the organized anterior
following lens removal: perhaps the most vitreal face or membrane. Rather than remain-
important variables are the times and frequen- ing in the enlarged posterior chamber behind
cies of the postoperative applanation tonome- the iris bombé, the aqueous humor is either
try. The average onset for postoperative misdirected or redirected into the vitreous body
hypertension of 25 mmHg or greater was 4.9 h. through a tear in its anterior face. As aqueous
The incidence of postoperative hypertension humor formation continues and the IOP rises,
was not affected by either extracapsular or the aqueous humor is now misdirected into the
phacoemulsification techniques; however, vitreous body, thereby pushing the organized or
those eyes operated on by phacoemulsification formed vitreous further into the occluded pupil.
demonstrated a more rapid increase in IOP This is a surgical condition in which the imper-
(mean, 3.9 h) than those eyes operated on by meable pupillary membranes are removed by
extracapsular techniques (mean, 8.4 h). incisions with iridal scissors and an anterior
The cause of postoperative hypertension is vitrectomy is performed.
not specifically known, but it may result from
several factors. It is also unknown whether
dogs that develop postoperative ocular hyper- ­Traumatic Glaucomas
tension will, at a future date, develop glaucoma.
Results of computer-­aided morphological anal- Traumatic glaucomas, which occur secondary
ysis indicated the increased IOP immediately to blunt and penetrating trauma, are infre-
after surgery may result from a significant quent in the dog. Complete acute hyphema in
reduction in the ciliary cleft cross-­sectional the dog is usually associated with uveal inflam-
area and width. mation and low IOP; chronic or repeated
Results of both of these studies confirm the intraocular hemorrhage in the dog is more apt
value of tonometric monitoring in the dogs to increase IOP. Traumatic glaucomas in the
undergoing postoperative cataract and lens dog are usually associated with intense irido-
removal. If the IOP exceeds “safe limits,” topi- cyclitis and are best managed clinically, with
cal or systemic carbonic anhydrase inhibitors aggressive treatment of the inflammation, pre-
(CAIs) (or both) or β-­blockers (or some combi- vention of peripheral anterior synechia, and
nation of these) are recommended, because control of the IOP (with CAIs).
they reduce the rate of aqueous humor forma-
tion but do not affect pupil size or increase the
amount of iridocyclitis. ­Uveitic Glaucomas

The iridocyclitides are a frequent group of


­ alignant Glaucoma
M intraocular diseases in the dog, and develop-
(Aqueous Misdirection) ment of inflammatory glaucomas with these
conditions is a serious complication. The
Malignant glaucoma is a variation of pupil- inflammatory glaucomas occur with chronic
lary block aphakic glaucoma, and it may develop iridocyclitis, usually from peripheral anterior
after extracapsular/phacoemulsification, synechia but infrequently from annular
­Ocular Melanosis and Melanocytic Glaucom  385

Treatment of uveitic glaucomas occurring


secondary to peripheral anterior synechia in
phakic eyes is targeted at the underlying
­uveitis and at controlling the IOP; thus, retinal
and ONH damage are minimized. High levels
of topical and systemic corticosteroids and
nonsteroidals are indicated. Because neither
miosis nor mydriasis is desired, short-­term
mydriatics may be used to intermittently move
the inflamed iris and pupil and to discourage
formation of posterior synechiae. Topical and
Figure 10.9 Secondary glaucoma from angle
systemic antibiotics may also be indicated if an
closure and formation of extensive peripheral
anterior synechiae and preiridal rubeosis in an infectious process is present. Topical and sys-
Akita with uveodermatologic syndrome (Vogt– temic CAIs are administered to, hopefully,
Koyanagi–Harada syndrome). Secondary glaucoma maintain the IOP within normal limits.
associated with uveitis is most likely to be
associated with chronic uveal inflammations.

­ cular Melanosis
O
posterior synechia and iris bombé (Figure 10.9). and Melanocytic Glaucoma
The most frequent cause of secondary glau-
coma in the dog in North America is associated Pigmentary glaucoma or melanocytic glau-
with cataract-­induced uveitis and chronic uve- coma in the Cairn Terrier is associated with
itis. The iridocyclitides may be associated with ocular melanosis. Glaucoma in this breed in
localized ocular diseases (e.g., corneal perfora- North America has a prevalence of 1.33%
tion, iris prolapse, and iris bombé) or many (1984–1993) and 1.82% (1994–2002).
systemic infectious diseases (see Chapters 11 This unique glaucoma affects middle-­aged
and 19). Vogt–Koyanagi–Harada-­like syn- to older Cairn Terriers, and it may affect one or
drome, or uveodermatologic syndrome, occurs both eyes (Figure 10.10). It has also been
in several Arctic breeds of dogs, and a recently reported in the Boxer and Labrador Retriever.
discovered pigmentary dispersion and cyst for- In these eyes, large aggregations of melano-
mation in Golden Retrievers and Great Danes cytes and melanophages occur within the fil-
can occur as chronic intraocular inflamma- tration angle, episcleral and subconjunctival
tions. Their serious long-­term complications tissues, tapetal ocular fundus, and even in the
are frequently cataract formation and second- meninges about the ONH. What initiates the
ary glaucoma. Clinical signs of uveitic glau- unchecked proliferations of these melanocytes
coma are a combination of iridocyclitis and is unknown, but the condition may represent a
either acute or chronic glaucoma. The pupil diffuse type of benign iris melanin cell prolif-
may be normal in size, thus representing a eration. Onset of the chronic glaucoma appears
balance between the iridal inflammation and to be slow and to be associated with the accu-
the IOP. Episcleral venous congestion, which mulation of pigmented cells within the filtra-
is often present in the glaucoma, is partially tion angle and scleral venous plexus. Some free
masked by the conjunctival hyperemia (or cili- melanin granules occur and are phagocytized
ary flush) associated with the anterior segment by the wandering macrophages and trabecular
inflammation. Likewise, corneal edema may endothelia within the outflow pathways.
represent a combination of the intensity of the Medical and surgical treatment of this second-
iridocyclitis and the IOP. ary glaucoma has not been successful in the
386 The Canine Glaucomas

Figure 10.10 Glaucoma in the Cairn


Terrier associated with melanocytosis of
the ocular tissues. Note the protruding
pigmented areas beneath the bulbar
conjunctiva.

long term because the proliferating melano- closure by mechanical and inflammatory
cytes and melanophages eventually completely means. Medical and/or surgical treatment of
obstruct any surgical anterior chamber bypass. this syndrome may lower IOP and prolong
vision for a short period of time, but eventu-
ally fails.
­Pigmentary and Cystic Glaucoma

An angle-­closure/occlusion secondary glau- I­ ntraocular Neoplasms


coma has been associated with pigment disper- and Glaucoma
sion, and iris and ciliary body cysts in Golden
Retrievers (see Chapter 11). The mean age of the The most frequently occurring primary
affected dogs is 7.6 years. Affected eyes, early in intraocular neoplasms in the dog are
the disease, demonstrate iridal hyperpigmenta- melanomas and adenomas and adenocar-
tion, pigment deposition on the anterior lens cinomas of the ciliary body and iris. Not
capsule, cataract formation, and web-­like infrequently, the presenting clinical sign
strands of opaque material within the anterior of these anterior ­s egment tumors is sec-
chamber. The clinical syndrome is characterized ondary glaucoma, iridocyclitis, hyphema,
by the formation of thin-­walled cysts within the or some combination of these. Metastatic
posterior chamber, proteinaceous exudation, intraocular neoplasms, which are most
and pigment dispersion, which appears to cause often adenocarcinomas, also frequently
the glaucoma and cataract formation. The time involve the iris and ciliary body.
from diagnosis of the syndrome to glaucoma is Lymphoma or lymphosarcoma may also
about five months. All affected globes had free affect the anterior uvea. Glaucomas
pigment within the trabecular meshwork. ­s econdary to these neoplasms usually
The pigment dispersion seems to cause the result from direct infiltration of the fil-
elevation in IOP. The cysts may compress focally tration angle, obstruction of the angle by
the iridocorneal angle and ciliary cleft, or by tumor-­a ssociated inflammatory products
releasing their own contents cause angle and peripheral anterior synechiae, or
­Congenital Glaucoma  387

secondary preiridal membrane forma- ­Congenital Glaucomas


tion. Rapidly growing neoplasms often
produce ­g laucoma, and tumor-­r elated Extensive goniodysgenesis or trabecular mal-
necrosis may produce a secondary development is rare in the dog. When pre-
iridocyclitis. sent, however, it may be unilateral or
bilateral, and it occurs as an isolated defect or
with other systemic anomalies. When pre-
­ laucomas Secondary
G sent, elevations of IOP occur early in the pup-
to Silicone Oil py’s life (usually three to six months of age),
and the primary complaint is one of rapid
and Rhegmatogenous
and often dramatic globe enlargement
Retinal Detachments (Figure 10.11). This often severe buphthal-
mia occurs because of the abundance of elas-
New glaucomas recently reported or
tin fibers within the immature sclera, and if
observed in the dog are those occurring
the IOP can be rapidly reduced to a normal
secondary to silicone oil in the anterior
level, the globe may return to near-­normal
chamber and secondary to rhegmatoge-
size. The longer the buphthalmia persists,
nous retinal detachments. Silicone oil is
however, the less likely an ­approximately
used in the repair of canine retinal detach-
normal globe size will result. This rapid
ments to tamponade the detached retina
buphthalmia also somewhat protects the
into contact with the retinal pigment epi-
ONH and retina against the elevated
thelium. Shifting of the oil from the vitre-
IOP. Histopathological results of the few
ous into the anterior chamber, which
globes available with canine congenital glau-
occurs frequently in both aphakes and
comas have revealed multiple anterior seg-
pseudophakes, increases the IOP by physi-
ment and aqueous humor pathology
cally obstructing most of the aqueous out-
abnormalities, including the trabecular
flow pathways. Treatment consists of
meshwork.
removing the oil from the anterior
chamber.
The association between rhegmatogenous
retinal detachments and elevated IOP in
humans was described in 1972 and reported
in the dog. Nonrhegmatogenous retinal
detachments in the dog are usually associ-
ated with normal or low IOP (i.e., ocular
hypotony), presumably resulting from
increased uveoscleral aqueous humor out-
flow. Canine rhegmatogenous detachments,
however, especially in those dogs with giant
retinal tears, may release rod and cone outer
segment fragments into the subretinal fluids
and ­vitreous, which eventually enter the
Figure 10.11 Advanced unilateral congenital
anterior chamber. This cellular debris accu- glaucoma in a Parson Russell Terrier puppy. Young
mulates in the aqueous humor outflow path- puppies will often develop marked buphthalmia
ways and elevates the IOP. quickly when IOP is elevated.
388 The Canine Glaucomas

­Medical and Surgical Treatment years. The glaucoma-­related glaucoma blind-


ness in at least one eye was estimated to be 27%
The optimal plan(s) for clinical management and for both eyes 9%. At the time of the diagno-
and preservation of vision for the different sis, 15 of the 295 patients were already blind
forms of the canine glaucomas have not been from POAG. While medical therapy of POAG
developed. In the primary or breed-­related glau- in humans is generally quite successful ini-
comas, the genesis of the disease continues dur- tially, treatment of PACG in humans is far less
ing the medical control of IOP; as a result, the rewarding because, as in the dog, vision is
need to increase the frequency of medications often impaired or lost on the initial presenta-
and/or to combine mediations will occur. The tion to the ophthalmologist.
choice of medical, surgical, or, most frequently,
a combination of both modalities is based on
the absence or presence of vision at initial pres- ­Target, Safe, and Diurnal IOP
entation, interest and ability of the owner to
treat the glaucoma, the projected costs, and the IOP has been firmly established as the ­primary
temperament of the patient (Box 10.4). risk factor for development of glaucomatous
Long-­term vision outcomes in human POAG optic neuropathy in the dog. Other factors are
as well as PACG are infrequently reported in also important, but the higher the IOP, the
the human medical literature, but can provide greater the risk and severity of optic nerve
the veterinary ophthalmologist some useful damage. Establishing a “target” or “safe” IOP
information. In a long-­term study of POAG for each canine eye implies an IOP reduction
patients in the Olmsted County, Minnesota, to levels that reduce the RGC loss from glau-
patients were followed for an average of ≥15 coma to normal, age-­related levels of RGC loss

Box 10.4 IOP Control


Initial (emergency) medical control: reduce CAIs (topical dorzolamide or brinzolamide q
IOP to below 20 mmHg within a few hours 12 h–q 8 h; or systemic methazolamide
Intravenous mannitol (1–2 g/kg i.v.) – if IOP 1–5 mg/kg/day p.o. q 12 h in two
exceeds 30 mmHg divided doses)
Prostaglandins (latanoprost, travoprost, and Neuroprotective drugs – future
bimatoprost q 12 h–q 24 h) Surgery–gonioimplant/laser
CAIs (topical dorzolamide or brinzolamide q
Long-­term control
12 h–q 8 h)
Surgery/laser cyclophotocoagulation
Miotics (2% pilocarpine q 12 h–q 8 h or deme-
Supplement with medical control
carium q 12 h)
Prostaglandins (latanoprost, travoprost, and
Neuroprotective drugs – future
bimatoprost q 12 h–q 24 h)
Short-­term control (one to three months) CAIs (topical dorzolamide or brinzolamide q
Prostaglandins (latanoprost, travoprost, and 12 h–q 8 h; or systemic methazolamide
bimatoprost q 12 h–q 24 h) 1–5 mg/kg p.o. q 12 h in two divided doses)
Miotics (2% pilocarpine q 12 h–q 8 h or Neuroprotective drugs – future
demecarium q 12 h)
­Current Strategies for Surgical Treatment  389

and achieving an IOP that maintains the subluxation, and normal-­appearing optic
threshold number of RGCs necessary for discs. Patients with vision and with IOP that
vision. In the dog setting, the “target IOP pres- is increasing despite maximum levels of med-
sure” at 21 mmHg is reasonable, but with pro- ical therapy are also good candidates. Surgical
gressive loss of vision should be lower. treatments for advanced glaucomas not under
adequate medical control and often without
the possibility of restoration of vision require
different strategies.
­Medical Therapy for IOP Control

Treatment of the different types of canine glau-


coma has, as the paramount purpose, mainte- ­Available Surgical Procedures
nance of vision and IOP within the normal
range after the condition has been diagnosed Surgical procedures for treatment of the primary
and prevention of further damage to the optic glaucomas in the dog are divided into two types:
nerve and retina. Unfortunately, most canine those that construct alternate pathways of drain-
glaucomatous patients present with the condi- age within or to the outside of the eye and those
tion at an advanced stage in at least first eye, that decrease the formation rate of aqueous
and the therapeutic goal may simply be a pain-­ humor by destroying part of the ciliary body. The
free eye that requires little to no medical care. most frequently used procedures are anterior
No single treatment regimen for canine glau- chamber shunts (i.e., gonioimplants) and
coma is possible because of the many different destruction of the ciliary body processes by cryo-
types of glaucoma (see Box 10.4). Medical thermy or laser photocoagulation.
treatment of canine glaucoma is the most
important aspect, because surgical procedures
often still require concurrent medical therapy. ­Preoperative Treatment
Medical therapy for the narrow-­ and closed-­
angle glaucomas is usually short term when Preoperative considerations in treatment of
employed alone, because eventually the out- the primary glaucomas include
flow becomes so impaired that ­drug-­associated 1) preoperative control of IOP to a near-­
changes in formation and outflow are inade- normal level,
quate. Prophylactic ­treatment of fellow eyes in 2) suppression of any concurrent anterior
dogs presenting with ­unilateral primary glau- ­segment inflammation with corticosteroids
coma appears to delay the onset of glaucoma and nonsteroidal agents,
in these eyes for several months or longer, and 3) maintenance of desired pupil size, and
is highly recommended. 4) dehydration and reduction in size of the vit-
reous with osmotic agents.

­ atient Selection
P
for Glaucoma Surgery ­ urrent Strategies
C
for Surgical Treatments
The optimal canine candidates for antiglau-
coma surgery are visual patients with early Two newer treatment modalities, laser trans-
glaucoma, no iridocyclitis or lens scleral cyclophotocoagulation and anterior
390 The Canine Glaucomas

chamber shunts (i.e., gonioimplants), have Postoperative Management


shown promise in the clinical management of General postoperative management includes
canine primary glaucomas. Hence, a treat- the following:
ment strategy for canine primary glaucomas
1) Control and resolution of the iridocyclitis
is evolving that includes initial surgical
with use of topical and systemic corticoster-
implantation of an anterior chamber shunt
oids and nonsteroidal anti-­inflammatory
(i.e., gonioimplant) or laser transscleral cyclo-
agents.
photocoagulation that is supplemented, if
2) Moderate pupillary dilatation and
necessary, with postoperative medical ther-
encouragement of pupil movement with
apy. In our practice, anterior chamber shunts
careful use of mydriatics (e.g., 1%
are reserved for glaucomatous eyes that are
tropicamide).
visual or have the potential for vision. Laser
3) Prevention of infection with use of topical
cyclophotocoagulation, which is less expen-
and systemic antibiotics.
sive, is used in blind glaucomatous eyes to
4) Maintenance of normal IOP levels using
reduce or eliminate the need for topical and
CAIs and, if necessary, β-­b locker adren-
systemic medications and to prevent pain. For
ergics (miotics and prostaglandins may
enlarged blind and buphthalmic glaucoma-
be counterindicated because of their
tous eyes with corneal exposure and repeated
effects on the episcleral fibroblasts and
central corneal ulcerations, intrascleral pros-
increased aqueous humor flare).
thesis, intravitreal gentamycin, or enuclea-
5) Maintenance of a patent anterior chamber
tion is recommended.
tubing and valve system; if IOP increases in
excess of 12–15 mmHg in the first week
postoperatively, the valve mechanism may
Anterior Chamber be plugged with fibrin, and an intracameral
Shunts (Gonioimplants) injection of 25 μg tissue plasminogen acti-
Gonioimplants are divided into those with vator (tPA) usually resolves the problem.
unidirectional valved systems, which are 6) Continued topical medications that may
designed to permit passage of aqueous lower IOP as well as control inflamma-
humor at approximately 10–12 mmHg, and tion may be important postoperatively.
those with bidirectional nonvalved systems, Prednisolone acetate (1%) was recom-
which have no pressure-­regulatory devices mended in one clinical series to reduce any
except for the ­limited resistance in the inflammation and control the fibroblasts
shunt’s tubing. With fibrosis around the within the bleb surrounding the extrascle-
implant, which develops approximately ral implant.
three to six weeks postoperatively, the resist-
ance for aqueous outflow with both types of Complications of Anterior
implants is the same. Chamber Shunts
Failures of anterior chamber shunts may be
Surgical Procedure for Anterior grouped into three types. The immediate postop-
Chamber Shunts erative iridocyclitis can usually be controlled by
The surgical procedures for gonioimplants are the routine anti-­inflammatories; any fibrin or
about the same for all of the episcleral devices blood in the anterior chamber that may occlude
(Figure 10.12). the tubing or valve usually resolves with one or
­Current Strategies for Surgical Treatment  391

Figure 10.12 Surgical placement is similar for all the various anterior chamber shunts. (a) Either the
dorsolateral or dorsolateral quadrant is approached by scissor dissection under a fornix-­based conjunctival
flap. A space adequate to accommodate the episcleral base of the shunt between the dorsal rectus muscle
and either the medial or tissue plasminogen activator. (b) The anterior chamber shunt must be primed with
balanced salt solution before implantation. (c) The anterior chamber shunt is positioned between the
adjacent rectus muscles and, with some implants, under the rectus muscles. It is secured with simple
interrupted nonabsorbable sutures. (d) After limbal puncture with a 20-­to 22-­gauge hypodermic needle and
creation of the proper length and beveled end for the tube, the silicone tubing is inserted into the anterior
chamber. The scleral aspect of this tube should be covered with either autogenous or homologous sclera to
protect the overlying bulbar conjunctiva. (e) Sagittal, postoperative view shows the proper position of the
anterior chamber shunt, with its leading edge approximately 10–14 mm posterior of the limbus.
392 The Canine Glaucomas

two injections of tPA. Long-­term failure of ante- decreasing aqueous humor formation through
rior chamber shunts is usually associated with partial destruction of the ciliary body pro-
development of an impermeable capsule about cesses. Excessive heat, as with diathermy or
the episcleral base of the device. lasers, or extreme cold, as with cryotherapy, is
directed through the overlying sclera to the
ciliary body processes. Proper positioning of
Surgical Results
the cryo-­ and laser probes is critical; these
The success rate for anterior chamber shunts probes must be directly over the ciliary body
has progressively improved with the refine- processes. In the dog, this area is approxi-
ment in the gonioimplant, surgical procedure, mately 5 mm from the limbus in the dorsal
and postoperative clinical management. aspects of the globe.
A larger series of studies in 1993, 1995, and
1998, involving 83 eyes in 65 dogs, compared
three different anterior chamber shunts for Cyclocryothermy
treatment of primary glaucoma. The criteria
Cyclocryothermy is employed primarily in
for success were maintenance of vision and
advanced glaucomatous eyes to reduce IOP in
IOP levels of 20 mmHg or less. The median
the presence of persistent pain or to induce
time at which the IOP began to increase
phthisis bulbi, which may be more cosmetically
postoperatively depended on the shunt and
acceptable than a buphthalmic eye. This tech-
ranged from 4 to 10 to 15 months. The
nique is also used in permanently blind glauco-
median time for vision loss to develop post-
matous eyes that are nonresponsive to intensive
operatively again varied by shunt and ranged
medical treatments. The nitrous oxide or liquid
from four to six to nine months. Fifteen of
nitrogen, 2.0-­ to 3.0-­mm cryoprobe is applied
the 22 eyes with an IOP of 20 mmHg or less
5 mm from the limbus directly onto the dorsal
were still visual at one year. The most prom-
bulbar conjunctiva. Four to eight sites in the
ising shunt was the large Ahmed shunt
dorsal half of the eye are frozen for 120 s, each
attached to a silicone band.
with the temperature of the cryoprobe reaching
More recent reports have combined the
−60 to −80 °C. The 3-­ and 9-­o’clock positions
gonioimplant with cyclophotocoagulation or
are avoided to prevent direct damage to the
cryotherapy. Using a combination of diode
long posterior ciliary blood vessels.
laser cycloablation and the Ahmed gonioim-
plant in 48 dogs (51 eyes), good control of
Transscleral and Endoscopic Laser
IOP was achieved in 39/51 (76%) of the eyes,
Photocoagulation
and IOP was poor or uncontrolled in 12/51
Transscleral cyclophotocoagulation uses
(24%) of the eyes. Twenty of 41 (49%) eyes
energy developed by different types of lasers to
maintained vision after six months, and
destroy the ciliary body and to reduce aqueous
12/29 (41%) of the eyes had vision after
humor formation. Both noncontact and con-
12 months.
tact Nd:YAG and diode lasers have been used
in different animal species and, though costly,
are promising treatments of canine glaucoma.
­Cyclodestructive Techniques Diode endoscopic cyclophotocoagulation has
been recently reported for therapy of the
Several noninvasive cyclodestructive proce- canine glaucomas, and offers highly selective
dures have been developed to treat the differ- laser ablation of the pigmented ciliary body
ent primary glaucomas in small animals by epithelium while under direct observation.
­Treatment of End-­Stage Primary Glaucoma  393

eyes may produce cataract formation directly,


related to the sites lasered.

­ reatment of End-­Stage
T
Primary Glaucomas

Because of the limited success of both medical


and surgical therapies for primary glaucoma in
the dog, salvage procedures to prevent ocular
pain, to reduce the enlarged and blind globe to
near-­normal size to reduce corneal exposure, and
to provide a cosmetically acceptable eye may be
Figure 10.13 For medically refractory and necessary. These procedures include pharmaco-
advanced glaucoma, enucleation may be another logical destruction of the ciliary body with intra-
option to relieve the pain and eliminate any
medical therapy. In this American Cocker Spaniel, vitreal injection of gentamicin; intrascleral or
bilateral enucleations have resulted in a still intraocular prosthesis, in which a silicone ball is
acceptable house pet. placed in an eviscerated globe; and enucleation
(i.e., surgical removal of the globe). Sometimes
Therapy in glaucoma patients is encouraging, enucleation is the only viable option for certain
but patient follow-­ups are limited in both time patients and can even be used bilaterally to pro-
and animal numbers. Endolasering in phakic vide a happy pain-­free house pet (Figure 10.13).
394

11

Canine Anterior Uvea: Diseases and Surgery


Revised from 6th edition of Veterinary Ophthalmology, Chapter 21: Diseases and Surgery of the Canine Anterior Uvea,
by Diane V.H. Hendrix

The uvea includes the iris, ciliary body, and systemic diseases. Intraocular neoplasia is not
choroid. The anterior uvea refers to the iris and unusual in dogs and varies in its appearance. In
ciliary body. The iris, because of its pupil, is addition to inflammatory and neoplastic disor-
responsible for regulating light entering the ders, developmental, degenerative, and trau-
posterior segment, and it is also important for matic disorders can all affect the anterior uvea.
normal esthetics. The ciliary body is contigu- This chapter focuses on diseases that primarily
ous with the choroid at its posterior aspect and involve the iris and ciliary body, but because
is responsible for aqueous production and out- the anterior uvea is contiguous with the cho-
flow, and lens accommodation. The anterior roid (or posterior uvea), several of the diseases
uvea is also the site of the blood–aqueous bar- may concurrently affect the posterior segment.
rier, which normally prevents large, high
molecular weight proteins from entering the
aqueous humor. The rich blood supply and ­Developmental Conditions
immunosensitivity of the anterior uvea con-
tribute to most of the inflammatory responses Developmental abnormalities of the canine
in the eye. anterior uvea include disorders of incomplete
A complete ophthalmic examination, espe- development (e.g., coloboma), maldevelop-
cially with the use of magnification as that pro- ment (e.g., anterior segment dysgenesis), and
vided by a slit-­lamp biomicroscope, can reveal incomplete regression of embryonal tissues
much information in an eye with uveal disease. (e.g., persistent pupillary membranes [PPMs]).
The size of the pupil can vary tremendously, Most anterior uveal anomalies in the dog occur
and abnormalities in its size, shape, color, or sporadically, but some are heritable.
responsiveness may indicate ocular or neuro- Color Variants
logical disease. Diseases such as anterior uvei-
tis, glaucoma, retinal detachment and Subalbinism
degeneration, and lesions along the afferent Subalbinism refers to dilution of ocular pig-
and efferent pupillary neuropathways can alter mentation. In contrast to complete albinism, in
pupil size and function. Inflammations of the which the eye lacks all pigment, subalbinism
anterior uvea, termed anterior uveitis or irido- in the dog occurs as a blue iris with a red fun-
cyclitis, are very common with both ocular and dus reflex. The neuroectodermal layer of the

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
­Developmental Condition  395

iris has normal pigmentation; however, the


overlying stroma lacks pigment. These animals
have a nonpigmented fundus that allows the
visualization of choroidal vessels. Presence of
a tapetum is variable. Complete ocular albi-
nism has not been reported in the dog.

Heterochromia Iridis
Heterochromia iridis refers to different colors
within one iris or between the two fellow iri-
des. In the heterochromic eye, the iris is char-
acterized by at least two distinct, solidly
colored areas or by differently colored patches Figure 11.1 Heterochromia iridis in a mixed-­
or spots (Figure 11.1). Alternatively, each iridis breed dog.
may be a different color. Lay terms for this con-
dition include “watch eye” and “china eye.”
Heterochromia iridis may be the sole mani-
festation of ocular color dilution in many breeds,
including the Old English Sheepdog, Siberian
Husky, American Fox Hound, American Cocker
Spaniel, Malamute, and Shih Tzu. Apart from
the variation in appearance, simple heterochro-
mia iridis has no significance. Heterochromia
iridis can also be a component of ocular merling
and may be accompanied by multiple ocular
anomalies such as dyscoria, corectopia, iris
hypoplasia, PPMs, staphylomas, cataract, and Figure 11.2 An iris coloboma in the nasal aspect
retinal detachment. iris in this Australian Shepherd.

Iridal Changes Associated with Merling segment colobomata (Figure 11.2) and mild to
Multiple ocular anomalies including iris anom- severe PPMs are also common findings in
alies occur in breeds affected by the merle gene merle dogs. While the ocular disease is reces-
when red or blue merles dogs and bitched are sively inherited, the inheritance of merling
bred together. These breeds, in part, include appears to be dominant.
(e.g., Rough and Smooth Collies, Shetland
Sheepdogs, Australian Shepherds, Great Danes,
Persistent Pupillary Membranes
Pembroke Welsh Corgi, and Miniature
Dachshunds). The most severe ocular anoma- The pupillary membrane is a primitive meso-
lies occur in homozygous merles with excessive dermal tissue present during fetal develop-
white hair coat involving the head region. ment that forms a layer on the anterior face of
Affected animals may also have varying degrees the iris. The central vascular arcades of this
of congenital deafness. Anterior uveal manifes- membrane begin to regress, beginning during
tations of the merling gene may include hetero- the sixth week of canine development and the
chromia irides, iris hypoplasia, a black-­rimmed peripheral arcades at the collarette regress last.
pupil from prominent iridal pigmented epithe- This process continues through the final three
lium, and an eccentric pupil (i.e., corectopia). weeks of fetal development and into the imme-
Both typical and atypical iris and posterior diate postnatal period. In most puppies, the
396 Canine Anterior Uvea: Diseases and Surgery

pupillary membranes completely atrophy by Familial PPMs occur in the Pembroke Welsh
six weeks after birth. The rate of pupillary Corgi, Basenji, Chow Chow, and Mastiff
membrane dissolution varies, however, and it breeds; breeding affected animals is not recom-
may not be complete for several months. mended. PPMs and congenital cataracts of
Incomplete resorption of embryonal vascu- varying densities occur in the English Cocker
lature and mesenchymal tissues results in Spaniel. Test matings have not been conclusive
retained iris strands in both juvenile and adult but suggest a complex mode of inheritance.
dogs. These uveal remnants, which are termed PPMs, cataracts, entropion, wandering nystag-
PPMs, attach at the collarette region of the iris mus, microphthalmia, and multifocal retinal
and usually retain the color of the adjacent iris. folds have been observed in a closely inbred
PPMs occur commonly in the dog and are line of Chow Chows.
usually an incidental finding. Iris-­to-­iris Therapy is rarely needed for PPMs. Therapy
strands that bridge over the iris surface or cross may be beneficial in severely affected eyes,
the pupil and remnants with a single iris but the number of options is limited. In cases
attachment that occur as small, free-­floating of diffuse corneal opacities with considerable
tags are benign (Figure 11.3). Forms of PPMs corneal edema, topical instillation of a hyperos-
that can result in significant ocular opacifica- motic agent (i.e., 5% NaCl ointment) may be
tion are iris-­to-­cornea strands and iris-­to-­lens used three times daily for a trial period of three
strands. Resultant corneal or lenticular opaci- to four weeks. If this treatment is helpful, it
ties may compromise vision. Dysplastic pupil- may be continued indefinitely. Mydriasis is
lary membranes should be differentiated from not recommended for dysplastic pupillary
anterior or posterior synechia by observing membrane-­associated opacities because phar-
their origin. macological dilation may induce tension on the
Heritable, clinically significant PPMs occur membrane attachments, thereby aggravating
in the Basenji breed. The incidence of PPMs in the corneal or lens lesions. Surgically, the mem-
this breed is high, and the severity varies con- branes attached to the cornea can be excised
siderably. Such lesions usually have no clinical after entering the anterior chamber, and phaco-
significance, but they do present a problem emulsification can be done for an extensive
regarding genetic control of the disease. anterior capsular or subcapsular cataract.

Peter’s Anomaly
Peter’s anomaly refers to a condition in which
a central corneal leukoma is associated with
iridocorneal or corneolenticular adhesions
that may also be associated with other ocular
and systemic malformations. The more severe
form of PPM in the Basenji, which manifests
as strands of iridal tissue attachments that dis-
rupt the endothelium leading to corneal opaci-
ties, fits the definition of Peter’s anomaly.
Figure 11.3 Persistent (dysplastic) pupillary
membranes are present in this Rottweiler puppy.
The membranes extend from the iris collarette to Aniridia and Iris Hypoplasia
the lens, creating a circular opacity on the anterior
Aniridia, iris hypoplasia, and iris coloboma all
lens capsule. They previously extended to the
cornea, and an endothelial and deep stromal refer to incomplete iris development. Aniridia
opacity remains. is a total absence of iris tissue, and it is
­Degenerative Iridal Change  397

extremely rare in the dog. Partial-­thickness involved. A primary defect in formation of the
hypoplasia (i.e., incomplete iris coloboma) is a neuroectodermal optic cup is suspected as the
defect of one or more, but not all, layers of the cause. The mode of inheritance in Doberman
iris. In cases of full-­thickness hypoplasia, com- Pinschers is thought to be autosomal recessive.
plete iris coloboma, the ciliary body processes, Owners of dogs related to affected Doberman
zonules, and equator of the lens can be visual- Pinschers should be informed about the genetic
ized. A complete iris coloboma is a result of implications of this anomaly.
localized developmental failure of all layers of
the iris. These colobomata may be at the pupil-
lary margin (i.e., notch coloboma), at the base
­Degenerative Iridal Changes
of the iris (e.g., iridodiastasis), or within the
Senile Iris Atrophy
iris body (i.e., pseudopolycoria). Iris coloboma
is a common feature of ocular merling. Spontaneous, progressive thinning of the
stroma or pupillary margin of the iris is a com-
mon finding in older dogs and may occur in
Other Congenital
any breed. Most commonly, the pupillary mar-
Pupillary Abnormalities
gin develops a scalloped, moth-­eaten appear-
Several congenital pupillary abnormalities ance (Figure 11.4). In these animals, atrophy
exist in dogs and may occur as sporadic abnor- of the pupillary muscles often results in dysco-
malities or in conjunction with previously ria and may lead to a reduced or absent pupil-
described anomalies. Polycoria, an iris with lary light responses and increased sensitivity to
more than one pupil with associated muscula- bright light.
ture, is extremely rare. More often, pseudopol- Senile iris atrophy may also initially mani-
ycoria is present. fest as a subtle color change: the natural iris
color fades, and foci of hyperpigmentation
may be noted as stroma is lost and pigmented
Miscellaneous
epithelium exposed. As degeneration pro-
Congenital Abnormalities
gresses, additional thinning may result in loss
Abnormal, lightly pigmented irides occur in of pigmented epithelial layers. With transillu-
Beagles with hereditary tapetal degeneration. mination, affected areas appear as translucent
The melanosomes in the iris stroma and cho- patches or openings within the iris and are
roid of affected dogs are fewer in number than most striking when light is reflected from the
those found in the irides of unaffected beagles. tapetal fundus through the areas of affected iris.
The iris and ciliary body pigmented epithelium
contain melanosome organelles but no normal
melanosomes. The condition may result from a
defect in synthesis of the matrix component of
melanosomes, resulting in absent or abnormal
deposition of melanin and initiating autophagy
of these organelles.
Anterior segment dysgenesis, which is an
anterior chamber–cleavage anomaly syndrome,
has been described in Doberman puppies.
Affected eyes are blind and are characterized
clinically by variable microphthalmia and
opaque corneas. Malformation of mesodermal, Figure 11.4 Iris atrophy at the pupillary margin of
ectodermal, and neuroectodermal tissues is the iris is present in a geriatric dog.
398 Canine Anterior Uvea: Diseases and Surgery

Secondary Iris Atrophy


Glaucoma and chronic uveitis may cause
degenerative changes in the iris resembling
those of senile iris atrophy. Signs of preexisting
disease such as buphthalmia, lens subluxation,
synechiae, or pigment dispersion on the ante-
rior lens capsule may be present, aiding in the
diagnosis.

Uveal Cyst Figure 11.5 A single large pigmented translucent


uveal cyst and several smaller cysts are present in
Uveal cysts are frequently seen in dogs. They the ventral anterior chamber. An immature cataract
may arise either from the posterior pigmented is also visible.
epithelium of the iris or from the inner ciliary
body nonpigmented epithelium, and therefore cause lens or corneal opacities. Reports describ-
are neuroectodermal in origin. The cysts can ing the association with cysts and glaucoma in
be congenital or acquired. They occur most both the Golden Retriever and Great Dane have
commonly in Golden Retrievers, Labrador emerged and are described in the “Pigmentary
Retrievers, and Boston Terriers. Multiple iris and Cystic Glaucoma (Pigmentary Uveitis)” sec-
cysts have also been reported in an English Setter. tion. The condition in these two breeds is much
Cysts may arise most often from the pupillary more serious.
margin, the posterior iris face, or the pars pli- Uveal cysts are usually diagnosed on the
cata of the ciliary body. Examination through a basis of the clinical appearance described.
dilated pupil may facilitate visualization of However, the most definitive diagnostic test is
cysts in the posterior chamber. Potential seque- performed by transilluminating the cysts with
lae of larger cysts include vision impairment, a bright light source. Cysts should transillumi-
corneal endothelial opacities, pigmentation of nate, whereas neoplastic masses will not tran-
the anterior lens capsule, mechanical silluminate. Ocular ultrasound can be used in
in­terference with iris function, and aqueous questionable cases.
outflow obstruction with secondary ocular
hypertension. Uveal Cyst Removal
Uveal cysts are usually benign and are inci- Because most uveal cysts are benign and gen-
dental findings in the dog. Iridal or ciliary cysts erally do not interfere with vision, they usually
can be unilateral or bilateral; single or multiple; do not require treatment. However, attached or
variably sized; and spherical, oval, or elongated free-­floating uveal cysts that occlude the pupil
dark or translucent masses (Figure 11.5). Uveal and compromise vision or multiple cysts that
cysts are usually brown or black, though light may lead to angle closure may be aspirated
brown and amelanotic cysts may occur. They are with a small-­gauge needle or deflated with a
often found free-­floating within the anterior semiconductor diode laser. Because these cysts
chamber or attached in the posterior chamber. generally arise from the posterior iris pigment
Rarely, dislodged uveal cysts can move into the layer, they are darkly pigmented and easily
vitreous if the vitreous is degenerated or visualized. Poorly pigmented cysts may not be
detached. Collapsed uveal cysts may be observed amenable to diode laser therapy. Surgical
as a thin layer of pigment on the ventral corneal removal or aspiration of the cysts may prevent
endothelium or the anterior lens capsule. In progressive angle closure when identified and
most cases, uveal cysts do not obstruct vision or treated early.
­Uveal Inflammatio  399

­Uveal Inflammation evaluating for the most common diseases


based on signalment, historical information
Uveitis or inflammation of the iris (iritis), cili- including travel, ocular and physical exami-
ary body (cyclitis), and choroid (choroiditis), nation findings, and locale.
or some combination, occurs commonly in Many etiologies for uveitis exist in all ani-
conjunction with many intraocular and sys- mal species. Most simply, causes can be
temic diseases. Uveitis is common because of divided into endogenous and exogenous.
the highly vascular nature of the tissue, its Endogenous causes originate from within the
immunosensitivity, and its close proximity to eye or spread to the eye from the bloodstream
other structures. Similar to inflammation else- or from contiguous structures. Endogenous
where, inflammation in the uvea consists of causes account for most cases of uveitis and
three basic events: increased blood supply, include infectious, neoplastic, toxic, meta-
augmented vessel permeability, and white bolic, and autoimmune diseases. Immune-­
blood cell migration to the injury site. Anterior mediated and autoimmune disease is the
uveitis is inflammation of the iris and ciliary most rapidly growing group of diseases
body, posterior uveitis is inflammation of the responsible for endogenous uveitis. Trauma
choroid, and panuveitis is inflammation of all also includes surgical procedures and both
three portions of the uvea. More specifically, perforating and nonperforating injuries with
iritis and cyclitis may be used to describe or without secondary infection. The more
inflammation of the iris and ciliary body, commonly recognized causes of uveitis in
respectively. Anterior uveitis is the term most the dog are listed in Box 11.1.
commonly used, because differentiating
between iritis and cyclitis clinically is very dif- General Uveal Inflammatory
ficult and usually both tissues are inflamed Responses
simultaneously. Posterior uveitis, or choroidi-
tis, can occur independently from anterior Several unique aspects of uveal inflammation
uveitis. A more advanced condition, termed include (i) the blood–aqueous barrier, (ii) the
endophthalmitis, is inflammation involving concentration of ascorbic acid and other
the ocular cavities and adjacent intraocular antioxidants in the aqueous humor, (iii) the
structures. Panophthalmitis is inflammation anterior chamber-­associated immune devia-
of all the intraocular structures, including the tion, and (iv) the lack of an intrinsic lym-
cornea and sclera. phatic system.
The blood–ocular barrier is composed of
the blood–aqueous barrier anteriorly and
Etiopathogenesis of Uveitis
the blood–retinal barrier posteriorly.
Uveitis can occur independently of disease in Morphologically, this barrier consists of tight
other ocular structures, or it can occur junctions (zonulae occludens) between non-
s­econdary to lens, corneal, or scleral disease. pigmented ciliary body epithelial cells, tight
Additionally, uveitis can be associated with junctions and gap junctions in the iris vascu-
primary ocular disease or be secondary to lar endothelium, and nonfenestrated imper-
neoplastic, infectious, or immune-­mediated meable capillaries in the iris. Evolutionary
diseases. Elucidating the etiology of uveitis in divergence in ocular defense mechanisms has
the dog can be difficult. However, because resulted in extreme differences of blood–
uveitis can lead to blindness or be a sign of a aqueous barrier stability among different
potentially fatal disease, attempting to define mammalian species. Destabilization of the
the etiology is always warranted. Uveitis blood–aqueous barrier marks the onset of
should be approached in a systematic fashion anterior uveitis.
400 Canine Anterior Uvea: Diseases and Surgery

Box 11.1 Diseases Proved or Suspected of Causing Uveitis in the Dog

Algal Pigmentary and cystic glaucoma in the


Prototheca sp. Golden Retrievera

Bacterial Radiation therapya

Brucella canis Snake bite (pit vipers) periocular


and ocular
Borrelia burgdorferi
Traumaa
Leptospira sp.
Toxemia of many causes (e.g., pyometra)
Septicemia of any cause
Ulcerative keratitis (any cause)
Fungal
Miscellaneous parasitic
Aspergillus fumigatus
Ophthalmomyiasis interna posterior (OIP)
Blastomyces dermatitidis (Diptera sp.)
Candida albicans Ocular filariasis (Dirofilaria immitis)
Coccidioides immitis (Angiostrongylus vasorum)
Cryptococcus neoformans and C. gattii Ocular larval migrans (Toxocara and
Histoplasma capsulatum Balisascaris sp.)

Immune-­mediated Neoplastic and paraneoplastic disorders

Cataracts (lens-­induced uveitis [LIU]) Histiocytic proliferative disease

Immune-­mediated thrombocytopeniaa Hyperviscosity syndrome (HVS)a

Immune-­mediated vasculitis Granulomatous meningoencephalitis

Lens trauma (phacoclastic uveitis) Primary and secondary neoplasms


(lymphosarcoma most common)a
Uveodermatologic syndrome (UDS)
Protozoan
Metabolic
Leishmania infantum
Diabetes mellitus (particularly diabetic
cataract-­induced uveitis) Toxoplasma gondii

Hyperlipidemiaa Neospora caninum

Systemic hypertensiona Trypanosoma evansi

Miscellaneous Rickettsial

Coagulopathiesa Ehrlichia canis or E. platys

Deep necrotizing or non-­necrotizing scleritis Rickettsia rickettsii

Drug-­induced (particularly miotic and Viral


prostaglandin [PG] agents) Adenovirus infection (including
Idiopathic postvaccinal “blue eye”)

Idiopathic uveitis and exudative retinal Herpesvirus


detachment
a
These etiologies often lead to aqueous flare or hyphema but do not necessarily have an inflammatory
component.
­Uveal Inflammatio  401

Three phases of the ocular inflammatory healing occurs, or there is necrosis, recurrence,
response have been identified: active, suba- or chronicity. If the inflammatory response is
cute, and chronic responses. The acute phase localized, the PMNs and mononuclear phago-
has the five cardinal signs, including redness cytes can resolve the injury and healing is
and heat, which are both caused by increased ­possible with minimal scarring. If the inflam-
rate and volume of blood flow; increased mass mation is profound and uncontrolled, how-
caused by exudation of fluid and cells; and ever, granulation tissue may result in excessive
pain and loss of function, which are both scarring, with subsequent ocular dysfunction.
caused by outpouring of fluid and irritating If healing does not occur because of the ina-
chemicals. Immediately after injury, the arteri- bility to control both acute and subacute
oles contract for approximately 5 min and then inflammatory events, the inability to eliminate
gradually dilate because of histamine release the causative agent, or both, the inflammation
from mast cells and factors released from becomes chronic. Permanent alterations in
plasma (kinin, complement, and clotting uveal vascular structure, permeability, or both
s­ystems). The chemical mediators, which have been implicated as the cause of recurrent
include histamine, serotonin, kinins, plasmin, or chronic episodes of uveitis.
complement, PGs, and peptide growth factors,
increase vascular permeability by causing the
Chemical Mediators of Inflammation
intercellular tight junctions in the vascular
endothelial cells to open, allowing fluid to leak Much effort has been directed toward identifying
into the tissues. Early after injury, various the chemical mediators of ocular inflammation
types of blood cells marginate (polymorphonu- because their recognition has direct therapeutic
clear neutrophils [PMNs]), and then leave the implications. While progress is always being
vessels via emigration (PMNs), emperipolesis made toward understanding inflammation, the
(PMNs, small lymphocytes, macrophages, and variations in species’ responses to inflammation
immature erythrocytes), and diapedesis and the varying ­diseases among species slow the
(mature erythrocytes). Reported mean values progress. Invasive investigative methods can also
for aqueous protein in the noninflamed canine affect ocular inflammations, and hamper serial
eye using different assays range from 21 ± 1.2 to methodologies.
37.4 ± 7.9 mg/dl. In sharp contrast, aqueous PGs are the most widely studied mediators
protein values at various intervals after the of ocular inflammation and are considered to
onset of uveitis range from approximately be primary mediators of ocular inflammation.
1200 mg/dl to as high as 6600 mg/dl in experi- Cyclooxygenase has been identified in all cell
mental and clinical cases, respectively. types, except for mature red blood cells, and
The acute phase of the ocular inflammatory PGs are produced by the irides of all species
response is exudative. There are four types of studied to date. The most notable pathological
exudates: (i) serous exudate is composed pri- ocular effects of PGs include miosis, hypere-
marily of protein; (ii) fibrinous exudate is com- mia, changes in vascular permeability, and
posed primarily of fibrin; (iii) sanguineous alterations in intraocular pressure (IOP)
exudate is composed primarily of erythrocytes; depending on the particular PG and species in
and (iv) purulent exudate is composed primar- question.
ily of PMNs and necrotic products. These Arachidonic acid derivatives also appear to
­exudates are seen clinically as aqueous flare, play a key role in ocular inflammation.
fibrin clot (or plastic aqueous), hyphema, or Arachidonic acid is released from damaged
hypopyon, respectively. The subacute stage has cellular membranes through phospholipases
special significance because during this period acting on cellular phospholipids. It can then
the immunological reactions are initiated, enter one of at least three metabolic pathways:
402 Canine Anterior Uvea: Diseases and Surgery

the cyclooxygenase, lipoxygenase, or oxidation Numerous other chemical mediators also


pathway. The cyclooxygenase pathway pro- have contributory, albeit largely undefined, roles
duces PGs, thromboxane, and prostacyclin, in ocular inflammation. Histamine is important
and the lipoxygenase pathway produces leu- in the initiation of many inflammatory pro-
kotrienes, hydroperoxyeicosatetraenoic acid, cesses, and its release from mast cells leads to
and hydroxyeicosatetraenoic acid. an increase in vascular permeability, but hista-
Leukotrienes are synthesized in the cornea, mine’s role in canine uveal disease is poorly
conjunctiva, anterior uvea, and lens. Species understood. Reactive oxygen metabolites,
variations exist in the extent and duration of angiotensin-­converting enzyme, and basic fibro-
leukotriene production. Leukotrienes are blast growth factor may also play a role in uveitis
potent vasoactive substances and chemoat-
tractants. Their chemotactic, humoral, and cel-
Clinical Manifestations and Diagnosis
lular activities are greater than those of PGs.
Substance P, a unadecapeptide normally pre- The clinical signs of anterior uveitis can be for
sent in sensory nerves, may be important in uveitis, such as aqueous flare and hypopyon,
uveitis, particularly when associated with cor- while others are general ocular responses,
neal irritation. Ulcerative keratitis causes vary- such as blepharospasm and ocular hypere-
ing degrees of uveitis, but it does so through a mia. Anterior uveitis can also be a secondary
poorly understood “axonal reflex.” With cor- ­component of other ocular diseases, such
neal irritation, antidromic impulses mediated as corneal ulceration and glaucoma, demon-
by the trigeminal nerve (ophthalmic branch) strating the need for a complete ophthalmic
reaching the iris and ciliary body are believed examination. The clinical signs of uveitis are
to stimulate release of substance P. This causes listed in Table 11.1.
vascular dilatation and altered permeability as Excessive lacrimation, blepharospasm, and
well as PMN chemotaxis. photophobia are readily observed. These signs

Table 11.1 Clinical signs of uveitis in the dog.

Anterior uveitis Posterior uveitis Additional adverse sequelae

Aqueous flare Vitreous opacity Deep corneal vascularization


Fibrin in anterior chamber Decreased vision Ectropion uvea
Keratic precipitates Chorioretinal granulomas Iris atrophy
Hypopyon Retinal detachment Rubeosis iridis (or PIFM)
Hyphema Retinal hemorrhage Secluded pupil and iris bombé
Miosis Choroidal effusion Secondary glaucoma
Decreased IOP Optic neuritis Cataract
Ciliary flush Lens luxation
Corneal edema Endophthalmitis/panophthalmitis
Iris color change (usually darker) Phthisis bulbi
Iris swelling
Pain
Posterior synechiae
Decreased vision
Conjunctival hyperemia
­Uveal Inflammatio  403

suggest varying degrees of ocular discomfort


not specific to uveitis. Acute uveitis tends to be
more painful than chronic uveitis. The pain is
referred to the ocular and periorbital regions.
Pain and photophobia are caused by ciliary
spasm. Excessive lacrimation is thought to
occur secondary to the photophobia.
Ciliary flush is hyperemia of the deep, per-
ilimbal, or circumcorneal anterior ciliary ves-
sels and is common with deep corneal and
intraocular disease (i.e., uveitis and glaucoma).
Figure 11.6 Severe corneal edema, corneal
Congestion of the conjunctival vessels also
vascularization, and conjunctival hyperemia are
commonly occurs with uveitis, and in severe present in this dog with anterior uveitis secondary
cases, uveitis can even lead to chemosis. to blastomycosis.
Determination of the presence of ciliary flush
is important for diagnostic purposes because it what is described as “brow ache” in humans.
must be distinguished from superficial con- Subtle miosis is often more apparent when
junctival hyperemia, which is commonly seen examining both eyes simultaneously in a dark-
with extraocular disease such as allergic con- ened room using retroillumination with a pen-
junctivitis. Distinguishing between these vas- light or Finoff transilluminator. Iris swelling
cular patterns may be facilitated by topical from edema and cellular infiltrates may also, in
application of a sympathomimetic agent (e.g., conjunction with inflammatory mediators,
1% epinephrine solution). The topical sympa- impede normal pupil mobility. Subclinical
thomimetic agent will have a greater immedi- uveitis often manifests with a pupil that dilates
ate vasoconstrictive effect on the superficial more slowly after short-­acting mydriatic ther-
conjunctival vessels than on the deeper ante- apy (i.e., 1% tropicamide) compared with the
rior ciliary vessels. In addition, conjunctival normal eye.
vessels are noted to move on the surface of the Synechiae formation is one of the more seri-
globe, whereas the anterior ciliary vessels ous complications of anterior uveitis, and it
remain stationary within the sclera during results from inflammatory cells, fibrin, and
movement of the globe. fibroblasts leading to adhesions of the iris to
Corneal edema with an associated increase the lens or peripheral cornea (Figure 11.7).
in corneal thickness develops with anterior
uveitis secondary to both an increase in
endothelial permeability and a decrease in
Na/K-­ATPase pump site density (Figure 11.6).
Severe edema may result in painful bulla for-
mation. Morphologically, edematous endothe-
lial cells with disrupted intercellular junctions
and a normal cell density are seen. Persistent
corneal edema may be followed by peripheral
corneal vascularization. Pupillary constriction,
or miosis, is a very common sign of anterior
uveitis. Miosis occurs in response to PGF2 act-
ing directly on the iris sphincter muscle.
Figure 11.7 Posterior synechiae are the only
Inflammatory mediators also cause painful evidence of previous anterior uveitis in this eye
spasm of the ciliary body musculature, causing that has a hypermature cataract.
404 Canine Anterior Uvea: Diseases and Surgery

Three types of synechiae can develop; they and cellular components accumulate within the
include (i) anterior synechia (iris–posterior anterior chamber after the blood–aqueous bar-
cornea); (ii) posterior synechia (iris–anterior rier has been disrupted. Aqueous flare is visual-
capsule of the lens); and (iii) peripheral ante- ized when light scattering from particles
rior synechia (between the basal iris and ciliary suspended in the anterior chamber causes a
body involving the opening of the ciliary cleft). continuous light reflection throughout the
Peripheral anterior synechiae form because of chamber. This continuous beam effect is called
shallowing of the anterior chamber and the iri- the Tyndall phenomenon, and it is analogous to
docorneal cleft as a result of pupillary block, shining a flashlight within a smoke-­filled room.
secondary to organization of inflammatory Observation of the Tyndall phenomenon is
exudates in the angle with gradual attraction indicative of aqueous flare, and aqueous flare is
of the iris toward the angle structures, and pathognomonic of the breakdown in the blood–
with intense swelling of the root of the iris. aqueous barrier for anterior uveitis. Varying
Posterior synechiae are a consequence of the degrees of aqueous flare are possible, and
central portion of the anterior lens capsule though this scheme is highly subjective, some
extending more anteriorly than the peripheral clinicians attempt to quantitate flare numeri-
lens. With miosis, the iris is in more intimate cally as 1+ to 4+, with higher numerals indicat-
contact with the lens, increasing the surface ing increased severity. The term fibrinous (or
area for synechia formation. Posterior synechia plasmoid) aqueous refers to aqueous humor
can cause occlusion of the pupil, leading to that has an increased level of aqueous protein
loss of sight or seclusion of the pupil, and approximating that of normal plasma. This con-
resulting in iris bombé with subsequent acute dition occurs most commonly in cases of acute,
glaucoma (Figure 11.8). Synechia can result in severe anterior uveitis with sudden onset. Lipid-­
a fixed miotic or midrange pupil. With chronic laden aqueous is also possible if the patient has
synechiae, pigment often migrates from the concurrent hyperlipidemia in which the aque-
surface of the iris onto the anterior lens cap- ous assumes a milky-­white appearance
sule, which is more likely to interfere with (Figure 11.9).
vision if the pupil is miotic. Cells from the inflammatory process pass
Aqueous flare, increased turbidity of aqueous into the aqueous humor either from diffusion
humor, occurs as protein-­rich aqueous humor or from active migration from the uvea. They
either are manufactured locally or egress
through the capillary walls from the blood into
the uveal tissue and into the aqueous humor.

Figure 11.8 Iris bombé secondary to 360° of


posterior synechia has caused the iris to balloon
forward in this dog. Episcleral injection is also Figure 11.9 Lipoid aqueous is visible in the
present. anterior chamber of this Miniature Schnauzer.
­Uveal Inflammatio  405

Keratic precipitates (KPs) are accumulations


of inflammatory cells, fibrin, and pigment
from the iris that are deposited on the corneal
endothelium. KPs are usually located inferi-
orly on the cornea in a triangular shape with
the apex located superiorly. Convection
c­urrents in the anterior chamber cause the
aqueous humor to rise along the warm dorsal
iris, and fall along the cooler dorsal and central
cornea creating its characteristic formation. It
is important to note KPs because their pres-
ence is always indicative of active or previous
Figure 11.11 Hypopyon is present in the ventral
uveitis.
anterior chamber in this dog with lymphosarcoma.
The deposition of red and white blood cells
within the anterior chamber are the most
marked examples of blood–uveal barrier break- Cytological evaluation of aqueous humor,
down and are termed hyphema and hypopyon, bacterial or fungal culture of the aqueous, vit-
respectively (Figure 11.10). In both instances, reous aspirates, or a combination thereof may
cellular components typically gravitate toward be beneficial in determining the cause of uvei-
the ventral anterior chamber and settle in a tis. Aqueous aspiration appears to yield useful
homogeneous layer. If bleeding was initially and positive results, mainly in eyes with visible
extensive or is continuous, complete (i.e., total) exudates or in animals suspected of having
hyphema with filling of the entire anterior lymphosarcoma. Most commonly, aqueous
chamber may occur. Layering in the hyphema aspiration yields nonspecific inflammatory
may indicate rebleeding. Occasionally, iridal cells. Because of the rarity of specific results
hemorrhage may be seen. Hypopyon rarely and the exacerbation of existing uveitis, the
occupies more than a third of the anterior procedure is not recommended in most cases.
chamber and is easily missed because the ven- In patients with concurrent posterior uveal
tral anterior chamber is often obscured by the involvement, vitreous aspiration is more likely
third eyelid (Figure 11.11). Generally, hypopyon to yield positive results than aqueocentesis (see
leaves the eye rapidly through the trabecular Chapter 13).
meshwork when treatment of the inflamma- Preiridal fibrovascular membranes (PIFMs)
tory processes is initiated and effective. arise from the anterior border layer of the
iris and develop secondary to chronic ocular
disease such as uveitis, glaucoma, intraocular
neoplasia, endophthalmitis, and retinal
detachment. The clinical term for this condi-
tion is rubeosis iridis. Clinically, a haphazard
array of very small vessels is seen on the iridal
surface (Figure 11.12). PIFMs are always pre-
ceded by ocular disease, and their develop-
ment can lead to hyphema because of the
fragility of the vessel walls and to glaucoma
because of membrane formation within and
over the iridocorneal angle. In addition to
Figure 11.10 Small KPs are visible on the ventral rubeosis iridis, diffuse iris hyperpigmentation
half of the corneal endothelium. can occur with chronic anterior uveitis. This
406 Canine Anterior Uvea: Diseases and Surgery

changes are not specific and include epithelial


metaplasia or posterior migration and liquefac-
tion, degeneration, or necrosis of lens fibers.
Posterior synechiae can also result in cataract
formation.

Systemic Evaluation
When the diagnosis of uveitis is made, an
attempt should be made to identify the etiology.
Some causes are readily apparent, such as
Figure 11.12 A PIFM is present on the surface of when anterior uveitis occurs in conjunction
this iris. Because this iris was very lightly with a hypermature cataract. Conversely, exten-
pigmented, the membrane can be seen as a fine sive diagnostic testing and evaluation fre-
meshwork of small vessels on the iris. The clinical
term is rubeosis iridis. Areas of posterior synechia quently do not lead to a specific conclusion. A
are also present. complete ophthalmic and physical examina-
tion is always indicated when a diagnosis of
uveitis has been made. Physical examination
condition is more obvious in eyes with lightly
should include evaluation of the skin, looking
pigmented irides and in cats.
for depigmented areas or draining lesions,
Decreased IOP is one of the earliest and
lymph node palpation, auscultation, and
most subtle indications of uveitis. Proposed
abdominal and possibly rectal (especially in
mechanisms for decreased IOP include both
intact male dogs) palpation. A complete blood
decreased aqueous humor production with
count and serum panel is usually indicated.
breakdown of the blood–aqueous barrier and
Selected titers are run based on the endemic
increased uveoscleral flow mediated in part by
diseases in the dog’s location and in areas
PGs. IOP will vary depending on the duration
where the dog may have traveled. Thoracic
and severity of uveitis. In acute or subacute
radiographs are also considered part of the
uveitis, IOP is usually decreased for the previ-
minimal screening protocol when systemic dis-
ously mentioned reasons; in chronic uveitis,
ease is suspected. Radiographs are evaluated
fibrosis or atrophy (or both) of the ciliary body
for evidence of metastatic or fungal diseases.
may contribute to decreased secretory function
Additional serological tests and diagnostics are
with subsequent ocular hypotony. Marked cili-
indicated according to the clinician’s index of
ary body dysfunction and hypotony may result
suspicion. Refer to the section on selected uveal
in phthisis bulbi.
diseases in this chapter as well as to Chapter 19
Secondary glaucoma is a common manifesta-
for further discussion.
tion of severe or protracted uveitis. The causes
of secondary glaucoma include obstruction of
Therapy for Anterior Uveitis
the angle by inflammatory debris, iris bombé
that occurs with formation of annular posterior Topical anti-­inflammatory therapy should be
synechiae, extensive anterior peripheral syne- instituted immediately after the diagnosis of
chia, and formation of PIFMs. An IOP of less anterior uveitis is made, even in those patients
than 10 mmHg is consistent with uveitis. with suspected systemic disease. Topical ther-
Cataracts, especially anterior subcapsular cata- apy alone may suffice for mild anterior uveitis,
racts, occur commonly with chronic anterior but for severe anterior uveitis, posterior uvei-
uveitis. They are thought to arise from inflam- tis, and systemic disease, systemic therapy as
matory mediators in the aqueous humor inter- dictated by the primary disease is also indi-
fering with normal lens metabolism. Lenticular cated (Table 11.2).
­Uveal Inflammatio  407

Table 11.2 Recommended therapies for anterior uveitis in the dog.

Dose Effects/limitations/comments

Corticosteroids
Topical
1% Prednisolone or 4–6× daily Suppress uveal inflammation; decrease
dexamethasone aqueous flare
Systemic
(parenteral/p.o.)
Prednisolone 0.5–1.0 mg/kg Avoid with the mycosis and corneal
q 12 h ulcers. Caution or avoid with diabetes
mellitus
Subconjunctival
Triamcinolone acetonide, 5–10 mg Avoid at potential surgical sites
methylprednisolone,
betamethasone, or
dexamethasone
Nonsteroidal anti-­
inflammatory drugs
Topical
Indomethacin, flurbiprofen, 2–4× daily
suprofen, or diclofenac
Systemic
Carprofen 2 mg/kg orally Hepatotoxicity has been recognized,
b.i.d.–t.i.d. particularly in the Labrador Retriever
Immunosuppressives
Azathioprine Initial dosage is 2 mg/kg/day Frequent blood and platelet counts as
for 3–5 days, then taper based well as liver enzyme determinations
on response because of potential hepatotoxic and
myelosuppressive effects of this drug
Antimicrobials
Topical
Broad spectrum Often combined with corticosteroids
Systemic
Amoxicillin, trimethoprim/ Chosen based on antibacterial activity
sulfadiazine, cephalosporin, and ability to penetrate blood–aqueous
and chloramphenicol barrier
Mydriatics/cycloplegics
Atropine (1%) 2–6× daily Dilate and provide pupil mobility to
decrease posterior synechiae Decrease
“ocular” pain. Stabilize the blood–
aqueous barrier Contraindicated by
elevated IOPs Side effects with atropine
include decreased tear production by
both eyes
Scopolamine (0.3%)/ To effect Very strong mydriatic combination to
phenylephrine (10%) break fibrous adhesions and dilate
pupils that are unresponsive to atropine
408 Canine Anterior Uvea: Diseases and Surgery

Anti-­inflammatory Agents monitored frequently for deterioration and col-


Corticosteroids are the primary therapy for the lagenolysis. Systemic corticosteroids should be
treatment of anterior uveitis (see Chapter 3). avoided in diabetic dogs if possible, and though
Corticosteroids inhibit phospholipase and the topical therapy may alter an animal’s glucose
release of arachidonic acid. Treatment with levels and subsequently its insulin require-
topical corticosteroids can be initiated in all ments, the clinician must weigh the benefits
cases of uveitis pending diagnostics except in against the risks. Therapy with either topical or
those cases with corneal ulceration. systemic therapy is gradually reduced as the
Prednisolone acetate, 1% suspension, is the clinical signs of uveitis resolve and is then
most commonly prescribed ophthalmic corti- maintained at the lowest necessary dose.
costeroid because of its potency and availabil- Many topical nonsteroidal anti-­inflammatory
ity. An initial application frequency of four to drugs (NSAIDs) are available for ophthalmic
six times daily may be required with solutions, use (see Chapter 3). NSAIDs prevent intraop-
compared with three to four times daily as rec- erative miosis, control postoperative pain and
ommended for ointments. Subconjunctival inflammation after intraocular surgery, control
corticosteroids may be administered in select symptoms of allergic conjunctivitis, and allevi-
cases as an adjunct to topical therapy, but they ate signs of uveitis. They can also assist the
are not intended as a substitute. Triamcinolone mydriatics in pupillary dilation (varies by
acetonide and betamethasone are long-­acting country). Most NSAIDs inhibit PG-­mediated
steroids that may be used for subconjunctival inflammation by interrupting the cyclooxyge-
injection. Risks include scleral perforation nase pathway. PGs generated via the cyclooxy-
at the time of injection, granuloma forma- genase pathway appear to have a greater effect
tion, and extraocular muscle atrophy and on the blood–ocular barrier in the dog than do
paralysis. Systemic corticosteroid therapy or leukotrienes or sensory neuropeptides after
treatment with other systemic immunosup- anterior chamber paracentesis. Many ophthal-
pressive drugs should not be initiated until mic NSAIDs are available and include indo-
diagnostics have been completed. Systemic methacin, flurbiprofen, suprofen, and
infectious disease may require treatment diclofenac. A newer ophthalmic NSAID, brom-
with antibiotics or antifungal drugs. fenac, is effective in human patients when
Systemic neoplasia may require treatment dosed once daily, which is in difference to the
with chemotherapeutic agents. Systemic other ophthalmic NSAIDs that are usually
corticosteroids are contraindicated in most dosed q 6 h. Many other systemic NSAIDs are
cases of infectious systemic disease. When available, but their ocular effects have not been
systemic prednisone is indicated, a recom- evaluated. Etodolac (EtoGesic; Fort Dodge
mended initial dosage is 1–2 mg/kg/day in Animal Health, Fort Dodge, IA) has been asso-
divided doses per os, followed by gradual ciated with the development of keratoconjunc-
reduction. tivitis sicca and should be avoided. For years,
Contraindications for the use of topical and aspirin and flunixin meglumine were the
systemic corticosteroids differ. In general, topi- mainstays of systemic NSAID therapy; how-
cal steroids should not be used on eyes with ever, use of these drugs has been replaced with
corneal ulceration because of the inhibition of newer and safer systemic NSAIDs. Systemic
corneal healing and possible potentiation of NSAIDs are not used in conjunction with sys-
infection and collagenolysis. Systemic steroids temic corticosteroids because of the greater
can be used in dogs with simple, superficial, potential for gastrointestinal complications,
noninfected corneal ulcers; however, caution and their use is contraindicated when hyphema
should be used and the corneal ulcer should be or generalized bleeding tendencies are present.
­Uveal Inflammatio  409

Immunosuppressive Agents the most efficacious ophthalmic parasympa-


Immunosuppressive drugs such as azathio- tholytic drug. The two major benefits of
prine can be administered in cases of chronic ­parasympatholytic drugs are mydriasis and
uveitis that are deemed immune-­mediated and cycloplegia. Dilating the pupil decreases con-
are unresponsive to conventional therapy. tact between the iris and lens, thereby mini-
Frequent blood and platelet counts as well as mizing the likelihood of posterior synechiae
liver enzyme determinations are recom- formation. Dilating the pupil also decreases the
mended with this therapy because of potential possibility of occlusion of the pupil resulting in
hepatotoxic and myelosuppressive effects. One vision loss. Parasympatholytic agents paralyze
recommended initial dosage is 2 mg/kg/day for the iris (i.e., iridoplegia) and ciliary body (i.e.,
3–5 days, followed by reduction to 1 mg/kg/day cycloplegia) musculature. Intraocular pain is
for 10 days, and then, if needed, 0.5 mg/kg/day primarily derived from ciliary body muscle
as a maintenance dose. spasm. Atropine also stabilizes the blood–aque-
ous barrier by blocking the effect of acetylcho-
Antimicrobial Agents line, which dilates blood vessels. Atropine is
There are few indications for the use of topical contraindicated when IOPs are elevated, with
antibiotics in the treatment of anterior uveitis the rare exception of early iris bombé, for which
both because the intraocular inflammation is atropine may be beneficial in breaking poste-
rarely bacterial in origin and because the rior synechiae. Atropine ointment or solution is
intraocular penetration of topically adminis- the most commonly used parasympatholytic
tered antibiotics would not be adequate for agent and is given to effect (once mydriasis is
treatment of an intraocular infection without achieved, daily dose can be reduced) with mild
the concurrent use of systemic antibiotics. uveitis requiring therapy once or twice daily
Topical antimicrobial therapy is primarily used and more severe cases requiring more frequent
to prevent bacterial infection of corneal ulcers application (e.g., four to six times daily) ini-
that may be present concurrently with anterior tially. The actively inflamed eye reacts much
uveitis (see Chapter 3). If ulceration occurs more slowly to atropine than does the normal
during topical steroid therapy, treatment with eye, and the effects are shorter lived. If syne-
an ophthalmic antibiotic preparation should chiae are present at examination, repeated
be initiated. drops of atropine may break them down. If the
Systemic antimicrobial therapy for uveitis synechiae have been present longer than a few
may be indicated for treatment of specific sys- days, the continued application of atropine
temic diseases or for prophylaxis against infec- may break them down over several days. The
tion in the case of corneal perforation or addition of 10% phenylephrine may aid in
intraocular surgery. The blood–aqueous bar- breaking the synechiae.
rier is normally impermeable to many antibiot- Side effects of frequent treatment with topi-
ics, but during active uveitis, the blood–aqueous cal atropine may include decreased tear pro-
barrier is compromised and drug permeability duction in both eyes, tachycardia, decreased
enhanced. Therefore, it is assumed that sys- gut motility, and the potential to precipitate
temically administered antibiotics will reach acute glaucoma (especially in the horse). While
the aqueous humor when trauma, infection, or the decrease in tear production is statistically
ocular surgery dictates their use. Fortunately, significant, the levels do not typically drop
bacterial uveitis is extremely rare in the dog. below normal. However, caution should be
used in dogs with borderline tear production
Mydriatics/Cycloplegics and in dogs with ulcerative keratitis.
Parasympatholytic agents are important in Tropicamide (0.5% and 1.0%) is a very weak
therapy for uveitis (see Chapter 3). Atropine is parasympatholytic compared to atropine, but
410 Canine Anterior Uvea: Diseases and Surgery

can be used as a substitute. It can be useful in lymphocytic–plasmacytic uveitis, not unlike


treating cases of anterior uveitis in which the that occurring with most idiopathic uveitides.
IOP is borderline high. Tropicamide can dilate The diagnosis of this type of LIU is presump-
the pupil just enough to prevent synechia and tive, being made on the observation of cata-
tends to alter the IOP less than atropine does. racts and the absence of other ocular or
systemic disease. Phacolytic LIU may develop
more rapidly in young dogs after the onset of
­ veal Manifestations
U cataract. Long-­term success rates of cataract
of Selected Diseases surgery in dogs with LIU may be lower than in
dogs without LIU. LIU also needs to be treated
The following discussion summarizes selected in dogs that are not cataract surgical candi-
diseases that are documented causes of uveitis dates because the uveitis is painful and treat-
in the dog. A complete ophthalmic and physi- ment may delay the onset of secondary
cal examination is necessary in all cases of glaucoma. Granulomatous LIU also occurs in
uveitis. Many ophthalmic and systemic dis- dogs with an intact lens capsule but usually
eases can lead to uveitis, and results from ocu- occurs in older dogs with rapidly progressing
lar and physical examinations in conjunction cataracts, especially Miniature Schnauzers, or
with ancillary diagnostic tests are necessary to long-­standing cataracts. These eyes have severe
confirm or rule out etiologies. Referral to text- uveitis, often with large KPs, and are less
books on internal medicine and infectious dis- responsive to therapy.
eases are recommended for detailed discussions The other type of LIU in dogs is phacoclastic
of specific disorders, diagnostics, and systemic uveitis that occurs after lens capsule rupture,
treatment (also refer to Chapter 19). which causes sudden exposure of intact lens
protein in large amounts sufficient to over-
whelm the normal low-­dose T-­cell tolerance to
Lens-­Induced Uveitis
lens proteins. There may be a history of recent
LIU is a common complication of cataract ocular trauma; however, lens penetration is
­formation in the dog (also see Chapter 12). rarely suspected. Clinically, there is evidence
Historically, LIU was associated with hyper- of corneal penetration, varying degrees of
mature cataracts, but studies using fluoropho- anterior uveitis, and exudate or hemorrhage in
tometry, laser flaremetry, and applanation the anterior chamber. Usually, the corneal
tonometry have shown that dogs with all stages wound has sealed and the anterior chamber
of cataracts have evidence of at least subclini- has reformed.
cal uveitis. Most likely, small amounts of lens Lensectomy using phacoemulsification is the
protein escape the normal lens and induce ideal therapy for lens rupture in the dog. One
T-­cell tolerance. Increased immune system study showed that the average number of days
exposure to lens crystallins by lens trauma, to referral in cases amenable to surgery was 3
spontaneous lens resorption, or cataract extrac- versus 10 in dogs that were not considered sur-
tion may overwhelm this tolerance and induce gical candidates. Medical therapy was not suc-
an intraocular or systemic cell-­mediated and/ cessful in dogs with ruptured lenses, and most
or humoral immune response. Two distinct of those eyes developed phthisis bulbi or
types of LIU are recognized in the dog. required enucleation because of progressive
Phacolytic uveitis occurs in dogs with rapidly anterior uveitis and secondary glaucoma.
developing or hypermature cataracts in which Anterior Uveitis Secondary to Corneal and
soluble lens protein leaks through an intact Scleral Disease
lens capsule. This type of LIU is nongranu- Anterior uveitis occurs commonly second-
lomatous and is characterized by mild ary to corneal ulceration. Miosis is the most
­Uveal Manifestations of Selected Disease  411

common clinical sign of anterior uveitis seen and secondary glaucoma with buphthal-
in dogs with corneal ulceration, but decreased mos occur with chronicity in a high per-
IOP and aqueous flare are also seen. centage of affected dogs. Dermatological
Non-­necrotizing scleritis in dogs is relatively changes usually follow the development of
common and does not typically involve the ocular disease, and include vitiligo of the
anterior and posterior segments of the eye. facial mucocutaneous junctions, nasal pla-
Necrotizing scleritis, however, may cause num, scrotum, and footpads; however, gen-
­anterior uveitis, vitritis, subretinal masses, eralized vitiligo may occur (Figure 11.13).
tapetal degeneration, hemorrhage, and edema. Poliosis may be confined to the facial region
Therapy with immunosuppressive dosages of or be generalized. Alopecia occurs incon-
prednisone and azathioprine is indicated but sistently. General physical examination on
may not be effective in the low term. affected dogs is normal, excluding the der-
mal and ocular changes.
Routine laboratory parameters are normal.
Uveodermatologic Syndrome
Immune function tests and titers for multiple
UDS, or Vogt–Koyanagi–Harada (VKH)-­like syn- infectious diseases have been negative.
drome, is a disease of dogs that causes anterior Histopathologically, the primary ocular change
uveitis, chorioretinitis, poliosis, and vitiligo. The is a granulomatous panuveitis with prominent
syndrome in dogs was initially termed VKH-­like perivascular lymphoid aggregates and melano-
syndrome because of similarities to a disease in phages. Retinal detachment, destruction of the
humans known as VKH syndrome, but the term retinal pigmented epitheliae, subretinal neo-
UDS has also been adopted to further separate vascularization, choroidal scarring, and signs
the disease in dogs from that in humans because consistent with secondary glaucoma are also
of the absence of neurological signs in dogs. The seen frequently.
disease was first reported in Japan in 1977. The Immunosuppressive drugs are the mainstay
pathogenesis of UDS is not completely under- of therapy. Standard therapy for anterior uvei-
stood. VKH syndrome in humans is an autoim- tis with topical steroids and atropine (if the
mune disease directed against melanocytes and IOP is not elevated) is initiated. Oral pred-
is mainly mediated by cellular immune nisone at immunosuppressive doses is also
responses. Experimentally, Akita dogs have been used. Subconjunctival injections of steroids,
immunized with tyrosinase-­related protein, an such as methylprednisolone, are used by some
enzyme involved in melanin formation that is clinicians. Generally, there is a relatively rapid
expressed specifically in melanocytes. The Akitas response to therapy. Unfortunately, many dogs
developed some clinical and histological signs
consistent with UDS, supporting the similarities
between the canine and human diseases. UDS
appears to affect primarily young adult dogs; the
mean age from two reports was three years. UDS
also appears to occur more frequently in the
Akita, Samoyed, Siberian Husky, and Shetland
Sheepdog than in other breeds, but many other
breeds can be affected.
Ocular findings include bilateral progres-
sive anterior uveitis or panuveitis, iris or
choroidal depigmentation, bullous retinal
detachment, and blindness. Cataract, Figure 11.13 This black Labrador Retriever has
extensive posterior synechiae, iris bombé, UDS with generalized poliosis.
412 Canine Anterior Uvea: Diseases and Surgery

have recurrence of clinical signs if the dose of filariasis and ocular larva migrans (OLM).
oral prednisone is decreased but have the Ocular filariasis due to aberrant migration of
undesirable side effects of weight gain, polyu- immature Dirofilaria immitis occurs in dogs
ria, and polydipsia if they are continued. and humans. The condition occurs in dogs
Therefore, other immunosuppressive drugs, with and without concurrent microfilaremia.
such as azothioprine, are often combined with Uveitis and mild to severe corneal opacity are
corticosteroids in the long-­term manage- the predominant signs. Uveitis is commonly
ment of UDS. attributed to direct mechanical trauma or reac-
tion to metabolic waste products of the para-
site. Typically, one 5–10-­cm filaria is seen
Mycoses-­Associated Uveitis
undulating in the anterior chamber; it may
Disseminated mycotic infections with ocular migrate freely between the anterior and poste-
involvement are relatively common among rior chambers and vitreous. Light stimulation
dogs living in endemic areas. Even though may increase motility of the filaria and, subse-
mycotic infections typically involve multiple quently, discomfort to the patient. The progno-
body systems, ocular disease is often the sis is favorable with anti-­inflammatory therapy
­reason for presentation. Common systemic and manual removal of the filaria.
mycoses include blastomycosis, coccidioido- Angiostrongylus vasorum, a metastrongylid
mycosis, histoplasmosis, and cryptococcosis nematode that infects the pulmonary artery
(Table 11.3). Less frequently occurring infec- and right ventricle, has also been found in the
tions are aspergillosis and candidiasis. anterior chamber of dogs. This parasite is pri-
Inhalation is believed to be the primary route marily found in Europe.
of infection for all the major systemic mycoses, OLM generally refers to aberrant ocular
with later hematogenous spread to the eye. migration of Toxocara spp.; Toxocara canis is
Direct animal-­to-­animal or animal-­to-­human suspected to be the most commonly involved.
infection is rare. Ocular involvement may be Toxocara canis is of public health significance
unilateral or bilateral, and infections of the because the nematode causes OLM and vis-
paranasal sinus, orbit, and optic nerve may ceral larval migrans in children. In dogs and
affect the eye secondarily. humans, OLM resulting from Toxocara spp. is
The diagnosis is made on the basis of con- characterized by inflammation primarily of
current clinical signs, which vary between the retina and vitreous. Ophthalmoscopy
mycotic organisms; identification of organ- reveals areas of hyperreflectivity, hyperpig-
isms in ocular or other tissue aspirates; or the mentation, and vascular attenuation.
results of fungal culture, histopathological Onchocerciasis primarily causes pea-­ to
examination, or various serological tests. bean-­sized masses in the conjunctiva, nicti-
The preferred systemic therapy for each type of tans, and sclera. However, it may also cause
mycosis varies. Eyes that are potentially visual anterior and posterior uveitis, periorbital
should be treated topically with corticosteroids swelling, exophthalmos, conjunctival conges-
and atropine if hypotensive or normotensive, tion, protrusion of nictitating membranes,
but a painful, blind eye is best enucleated granuloma formation, and localized corneal
edema. Histopathologically, a pyogranuloma-
tous or granulomatous reaction with eosino-
Parasitic Diseases
phils is associated with the adult worms.
Ocular Nematodiasis There is debate as to whether the organism
Intraocular nematodiasis is reported infre- is Onchocerca lienalis or Onchocerca lupi.
quently in domestic animals. Ocular nemato- Surgical removal may be curative, but medical
diasis includes two distinct conditions: ocular therapy is often needed as well to clear the dog
Table 11.3 Diagnosis and treatment of the systemic mycoses and anterior uveitis in the dog.

Mycosis Uvea affected Diagnosis Treatment

Blastomyces Anterior/posterior Vitreous aspirates Itraconazole (5 mg/kg) orally twice a


dermatitidis Serological tests: agar gel immunodiffusion specificity 90% Cross-­reactivity day for the first 2 weeks, followed by
with H. capsulatum once-­a-­day administration
Parenteral amphotericin B somewhat
effective; potential renal toxicity
Ketoconazole (can also combine with
amphotericin) 10–30 mg/kg/day p.o.
Coccidioides Mainly posterior Serology diagnosis: tube precipitin (IgM antibody levels); IgM both appears Oral ketoconazole at a dosage of
immitis and disappears early 10 mg/kg two times a day
Complement fixation (IgG antibody), which persists longer. Titer of ≥1:8 is
considered to be suspicious; titer of ≥1:16 or greater, disseminated disease
Cryptococcus Mainly posterior Identification or culture organism in ocular or cerebrospinal fluid fluid; Systemic amphotericin B and
neoformans latex agglutination test flucytosine; efficacy unknown
Histoplasma Mainly posterior Cytological identification or culture organism Serology problematic, but Amphotericin and ketoconazole
capsulatum complement fixation used

0005300036.INDD 413 04-26-2022 12:15:30


414 Canine Anterior Uvea: Diseases and Surgery

of all parasites. Postoperative medical therapy include blepharitis, keratoconjunctivitis,


includes prednisolone 0.5 mg/kg p.o. b.i.d. for uveitis, retinitis, and endophthalmitis. Ocu-
at least three to four weeks and doxycycline lar disease may be the only clinical sign in
5 mg/kg p.o. b.i.d. for at least six to eight weeks. some dogs. The anterior segment is usually
Additionally, 2.5 mg/kg of melarsomine is more severely involved than the posterior
given i.m. twice within 24 h one week after sur- segment. Additional signs include lymphad-
gery, followed by ivermectin 50 μg/kg s.c. and enopathy, splenomegaly, hepatomegaly,
melarsomine one month after surgery. renal failure, anemia, thrombocytopenia,
and varying ­dermatological conditions.
Ophthalmomyiasis Treatment usually consists of pentavalent
Ophthalmomyiasis refers to aberrant ocular antimonials and/or allopurinol. However,
migration of fly larvae, most commonly of the organisms are rarely completely elimi-
the order Diptera, but also the sheep nasal nated, the clinical response to therapy is var-
botfly (Oestrus ovis) and the cattle warble iable, and relapses are common.
(Hypoderma bovis). Both intraocular and
extraocular diseases occur in domestic ani- Toxoplasmosis
mals, but the intraocular disease OIP has Toxoplasma gondii is a protozoan-­obligate
been reported most often in dogs, cats, and intracellular parasite that affects most warm-­
humans. As the name implies, OIP is primar- blooded animals. The cat is considered the only
ily a disease of the posterior segment. The definitive host and is therefore integral to trans-
characteristic lesion has roadmap-­like sub- mission of the disease. Dogs may be infected via
retinal tracts that may be active or inactive. congenital transmission or by ingesting sporu-
Active disease may be associated with uveitis, lated oocysts from cat excreta, ingesting tissue
retinal detachment, and hemorrhage. The cysts in infected meats, or ingesting a transport
larva may be visible in active infections; host. Infection is usually subclinical, but clini-
larvae have been identified in the anterior cal signs may include neuromuscular, respira-
segment with concurrent uveitis. Increased tory, gastrointestinal, or ocular disease. Ocular
numbers of migratory tracts in the retina toxoplasmosis has been reported infrequently
may be visualized daily in active infections. in dogs; when it is present, anterior uveitis,
Organophosphates may be administered in an retinochoroiditis, and vitritis are seen.
attempt to kill the larva, but a dead larva may Diagnosis of ocular toxoplasmosis is by clini-
exacerbate inflammation. The larva may also cal signs, serological testing, and histopatho-
spontaneously depart from the globe. logical examination. Serological evaluation is
beneficial but does not always correlate with
clinical disease, as some subclinically affected
Protozoal Diseases
dogs may have high antibody titers. A test that
Leishmaniasis distinguishes IgM and IgG antibodies is neces-
Visceral leishmaniasis is most commonly sary, and convalescent titers should be run.
caused by the flagellate organism Leishma- Granulomatous or nongranulomatous inflam-
nia infantum. The disease is endemic along mation is possible. Clindamycin is the drug of
the Mediterranean shore and in parts of East choice for treating toxoplasmosis.
Africa, India, and Central and South Amer-
ica, but it also rarely occurs in North Amer- Other Protozoal Diseases
ica, especially in foxhounds. Domestic and Neospora caninum was diagnosed in four lit-
wild members of Canidae serve as reservoir ters of puppies from one owner. The most com-
hosts, and the intermediate host is the sand- mon clinical sign was hindlimb paralysis.
fly (Phlebotomus spp). Ocular findings Others had generalized encephalomyelitis.
­Uveal Manifestations of Selected Disease  415

Trypanosoma evansi may cause corneal Rocky Mountain Spotted Fever


opacities, conjunctivitis, and anterior uveitis in Rocky Mountain spotted fever (RMSF) is an
dogs. Therapy with subconjunctival steroids acute infectious disease caused by Rickettsia
and intramuscular diminazene aceturate leads rickettsii and transmitted by ticks of the
to corneal clearing and restoration of vision in Dermacentor spp. Vasculitis is the primary
affected dogs. lesion caused initially by direct infection of the
vascular endothelium and perithelial smooth
muscle, and later by immunological phenom-
Rickettsial Diseases
ena. It is postulated that an Arthus-­type reac-
Ehrlichiosis tion may be involved. Common clinical signs
Ehrlichia canis is an obligate intracellular par- include fever, neurological dysfunction, pol-
asite transmitted by the brown dog tick, Rhipi- yarthritis, thrombocytopenia, nonregenerative
cephalus sanguineus. Pronounced cl­inical and anemia, and ocular disease.
laboratory abnormalities often occur with Ocular lesions are commonly observed
E. canis infections (canine mo­nocytic in dogs with serologically confirmed RMSF.
eh­rlichiosis) and include fever, ly­mpha​denop- Anterior segment findings include subcon-
athy, anemia, leukopenia, thrombocytopenia, junctival hemorrhage, iris stromal petechia-
m­onoclonal or polyclonal gammopathy, tions, anterior uveitis, and hyphema. Posterior
n­eurological signs, and g­eneralized bleeding segment findings include retinitis character-
tendencies. Ocular signs are common, and ized by perivasculitis, focal areas of edema,
dogs may have ocular signs with no other and petechiation. Because ocular disease may
apparent clinical signs. Ocular signs are most be confined to the retina, ophthalmoscopy
commonly bilateral and may occur in both the should always be done in dogs with suspected
acute and chronic forms of natural or experi- RMSF. Generally, the ophthalmic lesions are
mentally induced E. canis infections. mild with RMSF. Doxycycline, tetracycline,
Anterior uveitis and exudative retinal chloramphenicol, enrofloxacin, and trovaflox-
detachment are reported to be the most com- acin are all effective systemic therapies.
mon ophthalmic signs. Other signs include
conjunctivitis, conjunctival or iridal petechia-
Viral Diseases
tions, corneal opacity, corneal ulceration,
necrotic scleritis, low tear production, orbital Infectious Canine Hepatitis
cellulitis, panuveitis often with hyphema, dif- Infectious canine hepatitis (ICH) is caused by
fuse retinitis or vasculitis, retinal hemor- the canine adenovirus-­1 (CAV-­1). Natural
rhage, papilledema, and optic neuritis. infection is most common in unvaccinated
The ocular hemorrhage associated with dogs less than one year of age, in which the dis-
­ehrlichiosis is thought to be related to ease may be fatal. The virus replicates in reticu-
­thrombocytopenia, platelet dysfunction, and/ loendothelial, hepatic parenchymal, and
or hyperviscosity. vascular endothelial cells. Clinical findings
Diagnosis is made on the basis of clinical may include fever, vomiting, diarrhea, abdomi-
signs, hematological abnormalities, and nal tenderness, hepatitis or hepatic necrosis,
­serological testing. Multiple intracytoplasmic hemorrhagic diathesis, tonsillar enlargement,
subunits of E. canis (i.e., morulae) may be pneumonia, glomerulonephritis, and CNS and
seen within monocytes. Serological diagnosis ocular disease. Nongranulomatous anterior
is by indirect immunofluorescence antibody uveitis and secondary corneal edema (so-­called
(IFA) testing. Doxycycline and several other blue eye) are reported in approximately 20%
antibiotics are commonly used for systemic of dogs recovering from natural ICH. This
therapy. ­keratouveitis may be the only abnormality in
416 Canine Anterior Uvea: Diseases and Surgery

otherwise subclinically affected dogs. Persistent complicated and must be continued in the long
corneal edema, secondary glaucoma, and term because of the intracellular nature of the
phthisis bulbi are possible sequelae of severe organism, but successful treatment has been
keratouveitis. reported.
Keratouveitis occurs as a postvaccinal reac- Leptospirosis is caused by a spirochete, a fil-
tion in approximately 0.4% of dogs that receive amentous bacterium belonging to the genus
the CAV-­1 vaccine. An increased susceptibility Leptospira, which includes many species and
of the Afghan hound to postvaccinal keratou- serovars. Leptospira organisms are most com-
veitis has been suggested. The CAV-­2 vaccine is monly transmitted through urine. Vasculitis
thought to cause ocular disease only when and endotheliitis involving the kidneys, liver,
experimentally injected into the anterior spleen, muscles, CNS, and eyes occur. Ocular
chamber. However, anecdotal accounts exist of lesions are infrequently seen but may include
rare keratouveitis following subcutaneous anterior uveitis. The leptospira organisms may
administration of CAV-­2 vaccines. be cultured from the aqueous humor of
Therapy for dogs suffering from systemic some dogs.
disease with ICH is primarily supportive.
Anti-­inflammatory therapy of keratouveitis
in dogs recovering from natural ICH infec- Algal Disease
tion or suffering postvaccinal reaction is Prototheca zopfii and Prototheca wickerhamii
debatable, since some consider the keratou- are algae that lack chlorophyll and are known
veitis self-­limiting. Corticosteroid therapy pathogens in dogs and other animals. The pri-
may be contraindicated and has been impli- mary clinical sign is usually hemorrhagic diar-
cated in prolongation of corneal lesions and rhea; however, dogs may present with
even blindness in dogs ­suffering postvaccinal blindness as the initial sign. Neurological signs
reactions. However, the potential for severe may also occur, and ocular signs may include
sequelae without therapy may be sufficient anterior uveitis, secondary glaucoma, chori-
justification to treat affected eyes. oretinitis, and retinal detachment. Cytology or
culture of vitreal aspirates may be diagnostic.
Bacterial Disease Prototheca sp. are extracellular, round to oval
organisms with thin, unstained walls. Larger
Brucella canis is an aerobic, Gram-­negative cells may contain endospores. Therapy with
coccobacillus that can survive in mononuclear itraconazole has been attempted but has been
cells. Infection is by penetration of the organ- unsuccessful in the long term.
isms through mucous membranes of the oro-
pharynx, genital tract, and conjunctiva. The
concentration of the organism is highest in
­Miscellaneous
semen and vaginal discharge in infected dogs.
Abortion and infertility are common clinical
Hyperlipidemia
signs that occur in breeding dogs, but neutered
dogs may also be affected. Ocular signs occur Dogs with hyperlipidemia resulting from ele-
in ~14% of dogs with brucellosis. The more vations in either cholesterol or triglycerides
common ocular findings include endophthal- may have associated ocular abnormalities.
mitis, chronic uveitis, hyphema, and chorioret- Lipid-­laden aqueous humor was discussed
initis. Diagnosis is made using the slide briefly in the “Uveal Inflammation” section
agglutination test in combination with the as occasionally occurring with anterior uvei-
agar gel immunodiffusion assay (AGID) or by tis (see Figure 11.9). Lipoproteins of dogs
positive culture. Antimicrobial therapy is range in size from 50 to 350 Å in diameter.
­Miscellaneou  417

However, the iridal vascular endothelium Other clinical signs include uveal cysts,
and nonpigmented ciliary body epithelium spiderweb-­like fibrinous debris in the anterior
normally prevent particles greater than 40 Å chamber, cataracts, and posterior synechiae.
from entering the aqueous humor. Breakdown Secondary glaucoma occurs within in a few
of the blood–aqueous barrier (i.e., anterior months in the majority of eyes, and this dis-
uveitis) concurrent with hyperlipidemia can ease is usually bilateral.
result in lipid-­laden aqueous. The syndrome in Great Danes may not be
Additional ocular manifestations of hyper- identical to that in the Golden Retrievers.
lipidemia may include lipid engorgement of Consistent findings in Great Danes with ciliary
retinal vasculature and infiltration of the body cysts include multiple cysts in the ante-
­perilimbal cornea, conditions referred to as rior and posterior chambers and glaucoma.
lipemia retinalis and corneal lipidosis (or The cysts are variable in size, very poorly pig-
arcus lipoides corneae), respectively. Lipid-­ mented, and usually transparent. The entire
laden aqueous and lipemia retinalis are likely posterior chamber is filled with cysts that may
to resolve with resolution of the primary push the iris forward.
disorder.
Solid Intraocular Xanthogranuloma
Pigmentary and Cystic Glaucoma in Miniature Schnauzer Dogs
(Pigmentary Uveitis)
Solid intraocular xanthogranulomas were
Uveal cysts are usually considered to be benign; identified in four globes from three older
however, reports describing an association Miniature Schnauzers that all had a history of
with cysts and glaucoma in both the Golden diabetes mellitus, hyperlipidemia, and bilater-
Retriever and the Great Dane have emerged. A ally severe uveitis with glaucoma that was
syndrome that occurs primarily in Golden believed to be lens-­induced. Grossly, all globes
Retrievers in the United States has been were filled with a heterogeneous tan mass.
referred to as both pigmentary uveitis and pig-
mentary and cystic glaucoma. Pigment disper-
Hyperviscosity Syndrome
sion on the anterior lens capsule in a radial
orientation is the most frequently observed Monoclonal gammopathy associated with
early clinical sign (Figures 11.14 and 11.15). ­lymphoproliferative disorders may result in
HVS. HVS causes clinical signs referable to

Figure 11.14 This Golden Retriever had Figure 11.15 The Golden Retriever has multiple
multifocal iris cysts caudal to the iris and one iris cysts caudual to the iris and one anterior to the
anterior to the iris, which is part of the breed-­ iris, which is part of the breed-­related pigmentary
related pigmentary and cystic glaucoma syndrome. and cystic glaucoma syndrome.
418 Canine Anterior Uvea: Diseases and Surgery

multiple organ systems, including the cardiac, Emergency Management of Acute


renal, hemostatic, ocular, and central nervous Ocular Trauma
systems. In the dog, HVS associated with
Cases of acute ocular trauma must be handled
increased serum concentrations of IgG, IgM,
on an emergency basis. When a dog is pre-
and IgA is reported. HVS secondary to poly-
sented with ocular trauma, the dog should be
cythemia vera has also been reported. Anterior
restrained or sedated as needed to facilitate an
segment findings include conjunctival hypere-
ocular examination. If possible, the clinician
mia, corneal edema, hyphema, and secondary
should determine whether a laceration or rup-
glaucoma, all of which are likely related to con-
ture of the globe is present. Assessment of the
current anterior uveitis. Posterior segment may
extent of globe laceration or rupture is not
include retinal vascular dilatation, tortuosity,
always easy, but it is important as a prognostic
microaneurysms, retinal hemorrhage, retinal
indicator. If the globe is ruptured, further
detachment, chorioretinitis, and papilledema.
examination to assess the degree of rupture
and foreign body examination should be
Sulfonamide Hypersensitivity delayed until the animal has been anesthetized
(Box 11.2).
Multiple clinical abnormalities have been
described in dogs with sulfonamide
hy­persensitivity. General signs include fever, Ancillary Diagnostic Procedures
arthropathy, blood dyscrasias, glomerulone-
phropathy, hepatopathy, skin eruption, Following a thorough ocular examination,
re­tinitis, and keratoconjunctivitis sicca. Uveitis additional diagnostics may be required.
may also occur alone or secondary to intraocu- Radiography of the skull, including oblique
lar bleeding from thrombocytopenia. views of the orbit or orbits, will confirm or rule
out the presence of fractures and establish
whether gunshot injury is involved. B-­scan
­Uveal Trauma ultrasonography is specifically indicated when
the normally transparent ocular media are
Ocular trauma may result in clinical signs that opaque. Integrity of the lens and posterior
vary from mild miosis to disruption of the cor- sclera as well as the position of the lens and
nea or sclera. Often, blunt trauma manifests retina can generally be determined with B-­scan
with flare, fibrin or hyphema, corneal edema, ultrasonography. Computed tomography (CT)
or iridial dialysis, but rarely hypopyon. With and magnetic resonance imaging (MRI) may
sharp trauma or extremely severe blunt be beneficial in assessing trauma, especially
trauma, fibrin, hemorrhage, uveal prolapse, when intraocular foreign bodies (IOFBs) are
and perforation of the cornea or sclera can be suspected. Care should be taken with MRI
seen. Uveal prolapse occurs with globe rupture because metallic foreign bodies can incite
because the sudden decompression of the additional damage.
anterior chamber with aqueous outflow forces
the iris into the wound; plugging it. Intraocular
Treatment of Blunt Injuries
hemorrhage may be in the form of hyphema,
iridal stromal hemorrhage, or hemorrhage Intense pressure exerted on the globe during
around the equator of the lens or in the vitre- blunt trauma may result in vector forces
ous. In all cases of trauma, careful examina- reflecting off the posterior sclera and transfer-
tion with necessary additional diagnostics ring anteriorly, causing a blowout rupture of
should be done to determine the extent of ocu- the perilimbal cornea or anterior sclera. Some
lar and periocular damage. causes of blunt injuries are impacts by golf
­Uveal Traum  419

Box 11.2 Emergency Management of Acute Ocular Trauma


1) Restrain the patient carefully and admin- 5) If the globe is ruptured, determine
ister sedatives if necessary to exam the whether surgical repair is feasible or
eye and associated tissues whether enucleation or implantation of
2) Gently irrigate the ocular surface with an intraocular prosthesis should be
warm physiological saline solution (with- advised. This determination is made on
out preservative) to remove debris or exu- the basis of the extent of intraocular dam-
dates if present age, the likelihood of preserving vision,
3) Determine whether laceration or rupture and cosmetic concerns. Ultrasonography
of the globe has occurred, and if either may be necessary
one is present, attempt to determine 6) Administer systemic antibiotics
its extent. Any globe with hyphema is 7) Temporary tarsorrhaphy may be used to
suspect! protect the eye when transport of the
4) If the globe is intact, apply topical anes- animal to a veterinary ophthalmologist
thetic solution, and inspect the ocular is anticipated or the animal’s general
surfaces, including the conjunctival for- condition (e.g., concurrent head or chest
nices and both sides of the nictitating trauma) necessitates stabilizing
membrane, for foreign bodies the patient

balls and baseball bats; commonly, the owner Most penetrating injuries of the globe result
is not aware that the dog is in such close prox- in uveal prolapse, which appears as a protru-
imity when the accident occurs. sion of darkly pigmented tissue through the
A ruptured globe resulting from blunt cornea or sclera. A grayish, fibrinous mem-
trauma is handled similarly to cases of pene- brane typically covers the prolapsed uvea
trating corneal trauma with uveal prolapse (Figure 11.16). Sometimes the uvea abuts the
(see Chapter 9). When globe rupture has penetrating wound and exudes fibrin, creating
occurred secondary to forceful trauma, retinal a mass of fibrin on the surface of the cornea. A
detachment with vitreal hemorrhage is a com- shallow or absent anterior chamber, pupil loss,
mon complicating factor. Iris bombé, trau- and hyphema may also be present. Traumatic
matic cataract, endophthalmitis, and phthisis uveal prolapse requires surgical repair that
bulbi may also occur. Therefore, the prognosis
following severe blunt trauma to an eye is
guarded to grave.

Treatment of Penetrating Injuries


Focal small punctures of the globe may cause
minimal damage to the cornea and may seal
spontaneously. If the eye is examined within a
few hours of the injury, it may be difficult to
determine whether the cornea was completely
penetrated or determine the extent of intraocu-
Figure 11.16 Uveal prolapse secondary to a
lar damage. Penetrating corneal injuries that
corneal laceration is seen. Fibrin is exuding from
seal spontaneously are treated with topical and the surface and is prominent on the corneal
systemic antibiotics and topical NSAIDs. surface adjacent to the prolapse.
420 Canine Anterior Uvea: Diseases and Surgery

involves replacement or amputation of the certain ceramics and plastics may be difficult
prolapsed uvea. Specific steps in the repair of to see on CT. MRI may be beneficial as well but
corneal perforation with uveal prolapse are should be used only when metallic foreign
covered in Chapter 9. bodies have been ruled out because MRI can
cause metallic foreign bodies to shift, leading
to increased intraocular damage. Ultrasound
Traumatic Uveitis with Lens Rupture
can also be helpful as long as increased trauma
Lens capsule rupture is most commonly caused can be avoided. Method of removal of IOFBs
by a penetrating foreign body or a cat claw depends on the location, depth, size, composi-
injury and may lead to phacoclastic uveitis. tion of the foreign body, extent of associated
Lens capsule rupture allows the release of lens tissue damage, and the amount of uveal
cortex into the anterior chamber, which may inflammation. Immediate referral to a veteri-
precipitate fulminating endophthalmitis. nary ophthalmologist is advised in difficult
Medical therapy of phacoclastic uveitis needs cases to confirm the diagnosis, offer a progno-
to be aggressive with the use of topical and sis, perform any necessary surgery, or treat any
immunosuppressive doses of prednisone and complications, which frequently arise.
topical atropine. Unfortunately, medical ther-
apy is often inadequate, and endophthalmitis
or secondary glaucoma commonly develops. ­Hyphema
Phacoemulsification may be necessary to treat
lens rupture in the dog, and when indicated, it Hyphema, or blood in the anterior chamber,
must be done early in the disease process. For occurs when uveal or retinal vessels are dam-
additional information, see the “Lens-­Induced aged or abnormally formed (Figure 11.17).
Uveitis” section. Causes of hyphema in the dog include
trauma, neoplasia, retinal detachments,
blood dyscrasias, PIFMs, hypertension, infec-
Intraocular Foreign Bodies
tious disease, severe uveitis, and congenital
IOFBs are relatively rare in dogs. IOFBs may anomalies (Box 11.3). Retinal detachment is
be characterized by a range of clinical signs. the disease process most commonly associ-
The variability of presenting signs results from ated with hyphema seen at referral institu-
the type, size, location, point of entry of the tions. Chronic uveitis, chronic glaucoma,
foreign material, and the severity of the initial neoplasia, and retinal detachments may all
trauma. Foreign bodies can cause mechanical
damage, anterior uveitits, endophthalmitis,
and direct toxicity depending upon the compo-
sition of the IOFBs. Organic foreign bodies
such as splinters, thorns, pine needles, cactus
needles, and porcupine quills may be more
likely to cause endophthalmitis than inorganic
foreign bodies. Inorganic foreign bodies such
as lead, glass, and plastic are nonreactive.
However, iron and copper foreign bodies are
reactive and are the most likely metals to cause
direct toxicity to intraocular structures.
Figure 11.17 Hyphema, filling over half the depth
Diagnosing IOFBs can be difficult. CT with
of the anterior chamber, is secondary to systemic
thin cuts is beneficial in the diagnosis and hypertension and retinal detachment in
localization of an IOFB, but fresh wood and this Beagle.
­Hyphem  421

Box 11.3 Causes of Hyphema in the Dog


●● Uveitis: multiple causes
●● Trauma: blunt or penetrating
●● Neoplasia: primary ocular or systemic
●● Systemic hypertension: multiple causes
●● Coagulation factor abnormalities: von
Willebrand, dicoumarin toxicity, liver
disease, disseminated intravascular
­
coagulation
●● Platelet disorders: thrombocytopenia,
thrombopathia
Figure 11.18 Iridal hemorrhages are present on
●● Hyperviscosity syndrome this iris of this dog with immune-­mediated
●● Multiple myeloma thrombocytopenia.
●● Congenital anomalies: Collie eye anom-
aly, vitreoretinal dysplasia, persistent examinations are essential. In young dogs with
hyaloid artery no history of trauma, congenital anomalies
●● Neovascularization: iris or retinal must be considered. Examining the eyes of lit-
●● Retinal detachment/retinal tear termates and reviewing breed predilections to
●● Chronic glaucoma hereditary congenital ocular disease such as
Collie eye anomaly (the initial Collie eye anom-
aly puppies in the 1950s were presented because
lead to the development of PIFMs, which of hyphema and esotropia) or persistent hya-
may result in hyphema. loid artery may also be helpful in making a
The prognosis for hyphema is dependent on diagnosis. Other differential considerations in
the etiology and presence of posterior segment young adult dogs with spontaneous hyphema
damage. Hemorrhage from damaged choroidal but no history of trauma include infections
or retinal vessels frequently moves anteriorly (e.g., ehrlichiosis) (Figure 11.18) and toxic
through to the pupil to manifest as hyphema. bleeding disorders. Neoplasia and systemic
Vitreous, retinal, or choroidal hemorrhages or hypertension are causes that must be consid-
retinal detachment and retinal tears indicate ered in geriatric animals. Regardless of the ani-
severe intraocular disease and a poor visual prog- mal’s age, both genetic and acquired hemostatic
nosis. Also, the cause of hyphema influences diseases should be ruled out. A complete oph-
whether blood clots in the anterior chamber. If thalmic examination including fluorescein
the hyphema is secondary to a blood dyscrasia stain and IOPs is indicated for all cases of
resulting in clotting abnormality, then the hyphema. A complete physical examination
hyphema is unlikely to clot. However, hyphema in association with a diagnostic evaluation,
occurring secondary to trauma or iridocyclitis including appropriate laboratory tests, may be
will usually clot. Hemorrhage resulting from indicated to rule out systemic disease in
neoplastic, retinal detachment or congenital ocu- animals with atraumatic hyphema (see
lar diseases is often recurrent, and the hyphema Chapter 19). In many cases of hyphema, the
in these cases may be clotted or unclotted and most informative ancillary diagnostic proce-
may form multiple purple (ventral) to red (dorsal dure is ocular ultrasonography.
and most recent) layers within the anterior Thoughts on the best medical treatment of
chamber. hyphema vary. Assuming no contraindications,
When hyphema is present, a detailed topical dexamethasone or prednisolone acetate
­history and complete physical and ocular with or without systemic prednisone is typically
422 Canine Anterior Uvea: Diseases and Surgery

used to reduce and control intraocular inflam- choroid, and filtration angle. Often, the iris
mation and to reduce the incidence of rebleed- appears thickened and there is pigment dispersed
ing. Pupilloactive drugs are often used; however, in the aqueous humor. Additionally, patchy pig-
their use is somewhat controversial. Therefore, ment deposition develop around the perilimbal
tonometry should be done regularly to monitor zone of the sclera and progressive pigmentation
for changes in IOP. If an increased IOP is noted of the tapetal fundus and secondary glaucoma
after the initiation of mydriatic treatment, atro- occurs. Affected dogs are poorly responsive to
pine is discontinued immediately and topical long-­term therapy.
timolol and dorzolamide are then initiated (see
Chapter 3) to reduce the IOP. Tropicamide (1%)
may help prevent synechia formation without Iris Freckles and Nevi
having the risk of elevating IOP if used judi-
Non-­neoplastic areas of hyperpigmentation are
ciously. Red blood cells in the anterior chamber
frequently observed on the canine iris. These
generally exit intact through the aqueous humor
are generally referred to as iris freckles or iris
outflow pathways.
nevi. Iris freckles, benign melanosis, or pigment
Tissue plasminogen activator (TPA) is effec-
cell clusters are terms used to describe benign
tive in the treatment of hyphema when large
hyperplasia or increased pigmentation of nor-
blood clots and fibrin are present in the ante-
mal melanocytes. An iris nevus is a proliferation
rior chamber or the IOP is elevated secondary
of melanocytes that forms a well-­circumscribed,
to fibrin blocking the iridocorneal angle. An
slightly elevated mass on the iris face. Nevi tend
injection of TPA into the anterior chamber can
to occur in young dogs, and perhaps in heter-
lead to rapid dissolution of the clot. TPA is most
chromic irides. No treatment is recommended,
effective when injected within 72 h of clot for-
but continued observations are suggested as
mation, but it may also be effective in dissolv-
nevi may undergo malignant transformation.
ing clots of longer duration (perhaps one to two
weeks duration). The recommended dosage for
intracameral injection is 0.1 ml of a 25 mg/100 μl
solution. TPA should not be injected if recur- ­Anterior Uveal Tumors
rent bleeding is likely; however, the risk of
rebleeding is low due to clot specificity. Intraocular tumors are relatively uncommon in
the dog. The tumors may be primary or second-
ary from metastatic disease or local invasion. The
great majority of primary intraocular tumors
­Non-­neoplastic have their origin in the anterior uvea. While
Iridal Proliferations d­istant metastasis from primary intraocular
tumors is rare (~4%), local tissue destruction and
­ cular Melanosis
O secondary glaucoma occur commonly. Tumors
(Pigmentary Glaucoma) must be differentiated from other intraocular
masses, including iris cysts, granulomatous
Abnormal ocular pigment deposition and glau- lesions, and staphylomas.
coma (ocular melanosis or pigmentary glau- Diagnosis is based on findings from complete
coma) has been described primarily in Cairn ophthalmic and physical examinations and
Terriers, but also in the Boxer and Labrador whether the masses are unilateral or bilateral,
Retriever. The disease appears to be familial and singular or multiple, raised or flat, and station-
tends to occur in older dogs. This syndrome has ery or changing in appearance. Most often,
been compared with the pigmentary dispersion these masses are not noticed by most pet own-
syndrome reported in humans. Clinically, hyper- ers, but the complications of these masses, e.g.,
pigmentation involves the iris, ciliary body, iridocyclitis, blindness, secondary glaucoma,
­Anterior Uveal Tumor  423

intraocular hemorrhage, cataract formation,


retinal detachment, cause these dogs to present
to the veterinarian.

Primary Neoplasms
Melanocytic Neoplasms
Melanocytic neoplasia (i.e., melanoma) is the
most common primary intraocular neoplasm
in the dog. In veterinary medicine, benign and
malignant are often used as qualifiers in the
description of a melanoma. The two larger Figure 11.19 Melanocytic neoplasia is present in
the nasal aspect of the iris. The tumor is protruding
studies of canine ocular melanomas classify through the limbus.
canine uveal melanomas as melanocytomas
and (malignant) melanomas. The term mel-
anocytoma refers to benign anterior uveal mel- cysts, staphylomas, and limbal melanocytoma.
anomas, limbal melanomas, and choroidal The use of ultrasound may be helpful when the
melanomas. Benign melanocytomas are differ- cornea or ocular media is opaque, to differenti-
entiated from (malignant) melanoma by ate between cysts and tumors and to help
nuclear pleomorphism, nuclear-­to-­cytoplasmic determine the extent of growth of the tumor.
ratio, and mitotic index. Most canine ocular Gonioscopy may facilitate in differentiating
melanomas arise in the anterior uvea, and between uveal and limbal melanocytomas.
both the iris and the ciliary body are common Uveal melanomas with extraocular extension
sites of origin. With large masses, the tissue of often invade the filtration angle, whereas lim-
origin is often difficult to determine even histo- bal melanocytoma, though extending deep
pathologically. Intraocular melanocytic tumors into the sclera, may compress but will less
are most common in older dogs with a mean commonly invade the angle; still, invasion of
age of around nine years. Inherited iris mela- limbal melanomas into the filtration angle and
noma has been reported in a family of Labrador anterior uvea has been reported. Primary cho-
Retrievers, but the diagnosis was made on the roidal melanoma has been reported rarely in
basis of clinical examinations with no histo- the dog, though anterior uveal melanomas
pathological confirmations. may infiltrate posteriorly into the choroid. In
A color change or mass effect in the dog’s eye humans, the most frequent intraocular mela-
may be the first abnormality observed, or noma is in the choroid! It is important to rule
changes may go unnoticed until secondary uvei- out metastasis from a distant site by doing a
tis or glaucoma develops. Melanomas in dogs thorough physical examination that includes
tend to produce nodular growth rather than dif- examining the oral cavity, foot pads, lungs and
fuse infiltration, as is seen in cats and humans. liver, and nail beds.
At clinical presentation, melanoma may be focal Dogs with malignant melanoma have shorter
and confined to the iris, or it may be extensive. survival times than unaffected dogs and dogs
Large masses will often bulge through the pupil, with melanocytomas. Tumor extension, tumor
displace the iris anteriorly, or cause dyscoria. Iris size, and mitotic index are not specifically
thickening, an irregular pupil, blindness, and related to survival time. The metastatic rate for
ocular pain are the most common clinical signs uveal melanomas in dogs has been reported to
(Figure 11.19). Pigmentation is variable, and be low (4% and 10%).
amelanotic melanomas can occur but are rare. Treatment of an intraocular neoplasm is
Diagnosis is usually made by clinical exami- based on many factors, including the type of
nation. Possible differentials include uveal neoplasia, the overall health of the globe and
424 Canine Anterior Uvea: Diseases and Surgery

the dog, the presence of metastatic disease,


and the financial constraints of the owner.
Treatment options may include temporization,
local excision, enucleation, orbital exentera-
tion, and possibly euthanasia if metastatic
d­isease is present. Given the seemingly benign
biological behavior of most uveal melanomas,
some clinicians elect to simply observe the
mass for progression rather than to hastily
remove a sighted eye. Removal of a mass local-
ized to the iris and not invading the filtration
Figure 11.20 A ciliary body adenoma can be
angle may be attempted by iridectomy. Diode
visualized extending into the pupil in a Labrador
laser photocoagulation of melanomas is an Retriever.
effective, less invasive treatment and may be
used for small iridal melanomas. Transscleral
laser ablation and surgical excision of iris or similar to that of melanoma, and distinguish-
ciliary body adenocarcinoma combined with ing clinically between the two may be difficult.
chemotherapy using 5-­fluorouracil has been
reported. From a practical standpoint, therapy
Medulloepitheliomas
in many instances is limited to enucleation or
exenteration. Medulloepitheliomas arise from the primitive
medullary epithelium or inner layer of the
optic cup, before differentiation into adult tis-
Iridociliary Epithelial Tumors
sues and are therefore classified as congenital
Iridociliary epithelial tumors are the second-­ tumors and diagnosed in young dogs. Although
most common primary intraocular tumor in these tumors are reported rarely in dogs, his-
the dog. These tumors arise from either the torically diagnoses of retinoblastoma, melano-
epithelial cells of the iris or ciliary body. carcinoma, and intraocular ganglioma in the
Primary iridociliary epithelial tumors are dog were reevaluated and believed to actually
identified by having one of the following cri- represent medulloepitheliomas. Usually, a
teria: noninvasive epithelial growth extend- white or gray-­white mass is present in the pupil
ing into the aqueous adjacent to the iris or or extending through the iris. Secondary glau-
ciliary body, pigmented epithelial cells, or coma may be the presenting clinical sign.
thick basement membrane structures on the Tumors typically arise from the ciliary body.
cell surface. Iridociliary epithelial tumors are Treatment is enucleation.
more common in middle-­aged to older dogs
(mean age, 9.0 years). They appear clinically
Miscellaneous Primary Neoplasms
as segmental or nonsegmental, solid or
pa­pillary, and invasive or noninvasive Reports of additional primary intraocular
(Figure 11.20). The incidences of adenoma ­neoplasms are extremely rare. Masses include
(i.e., benign) and adenocarcinoma (i.e., poten- ciliary body hemangioma, iridal hemangiosar-
tially malignant) are approximately equal, coma, iridal leiomyosarcoma, iridal myxoid
and these tumors combined are suggested to leiomyoma, and ocular osteosarcomas. Spindle
have an incidence approximately half that of cell tumors of the anterior uveal tract of dogs
uveal melanoma. Distant metastasis of ciliary present as nodular, nonpigmented masses of
body adenocarcinoma has been reported; the anterior uvea. The majority of affected
however, metastasis appears to be highly unu- dogs have blue irides, and the Siberian Husky
sual. The clinical presentation may appear breed is overrepresented.
­Uveal Surger  425

Secondary Neoplasms Laser Photocoagulation


of Iris Melanoma
Neoplasms may metastasize hematogenously to
Diode laser photocoagulation may be used in
the eye from local or distant sites, or they may
the treatment of presumed iris melanoma in
invade the eye by local extension from the ocu-
dogs. Selection criteria should include lesions
lar adnexa, cornea, orbit, paranasal sinuses, or
isolated to the iris with no evidence of compli-
nasal cavity. Hematogenous spread accounts for
cating factors. The diode laser delivery system
most secondary neoplasms, and of these,
may be used in a continuous mode with either
intraocular lymphosarcoma is the most com-
an operating microscope adapter or a laser
mon in the dog. Other metastatic neoplasms
indirect ophthalmoscope with a 20 D lens.
include hemangiosarcoma, cutaneous and oral
Treatment is discontinued when no further
melanoma, osteosarcoma, malignant histiocy-
shrinkage is observed, and surface changes are
tosis, seminoma, transmissible venereal tumor,
noted over the entire lesion. Some cases may
transitional cell carcinoma of the urinary
need more than one laser treatment.
bl­adder and urethra, and adenocarcinomas of
mammary gland, thyroid gland, parotid salivary
gland, adrenal gland (presumed), nasal, renal, Sphincterotomy, Synechiotomy,
pancreatic, and pulmonary origin. Ocular signs and Pupil Iridotomy
may include anterior uveitis, hyphema, and Occasionally, intraoperative mydriasis is inade-
glaucoma. Hyphema of undetermined etiology quate to allow lens delivery during cataract
may be the presenting sign of a metastatic neo- surgery, or miosis occurs immediately after lens
plasm; in those cases, ocular ultrasound may removal. In those cases, iridotomy of the pupil-
help delineate the mass. lary sphincter (also termed sphincterotomy) may
be necessary. Sphincterotomy is done by incising
1–3 mm of the pupil margin, usually at two to
­Uveal Surgery four positions in quadrants, with iris scissors.
Limited hemorrhage and fibrin formation will
Uveal surgery is indicated most commonly in the follow. After pupil iridotomy, intensive medical
treatment of intraocular neoplasms and in treat- therapy for anterior uveitis is initiated with oph-
ment of pupillary abnormalities secondary to thalmic steroids and atropine. Postoperatively,
inflammation. Two other indications for surgery additional pharmacological mydriasis may fur-
of the anterior uvea are the repair of globe perfo- ther dilate the pupil, thus enhancing the elliptical
rations with prolapsed uveal tissue and the treat- appearance. Unfortunately, the posterior syne-
ment of glaucoma refractory to medical therapy. chiae may recur.

Iridotomy
Mass Removal Procedures
Iridotomies are used for the creation of an
Sector Iridectomy alternative pathway for aqueous flow when flow
Localized masses of the iris may be removed through the pupil is not possible because of exten-
by sector iridectomy although this procedure sive annular posterior synechia. By creating holes
has largely been replaced with laser photoco- in the iris peripheral to the synechiae, aqueous
agulation. This procedure is optimal for flow can bypass the normal route through the
removing well-­defined focal lesions of the iris pupil and go directly from the posterior chamber
that are located axially to the major iris blood to the anterior chamber. The Nd:YAG and
vessels. A sector iridocyclectomy may be indi- diode lasers have been used to treat pigmented
cated when the ciliary body is involved in an irides with iris bombé in the dog; unfortunately,
anterior uveal tumor; however, this surgery is these procedures are not effective in the long
rarely performed. term as these “holes” eventually heal close.
426

12

Canine Cataracts, Lens Luxations, and Surgery


Revised from 6th edition of Veterinary Ophthalmology, Chapter 22: Diseases of the Lens and Cataract Formation, by Marta Leiva and
Teresa Peña; and Chapter 23: Surgery of the Lens, by Tammy Miller Michau

Section I: Cataracts – Clinical make up over 90% of the proteins in the lens,
Findings are specially adapted to contribute to the main-
tenance of transparency by forming soluble,
The lens is the transparent, biconvex, avascular,
high molecular weight aggregates that need to
and highly structured tissue located in the ante-
stay in solution for the duration of an individu-
rior segment of the eye, and is partly responsi-
al’s life. Loss of transparency is the common
ble for the refraction of incoming light rays to a
denominator of all lens diseases. Due to the
point source on the retina. The crystallin lens
high prevalence of heritable cataracts in dogs,
represents a unique tissue in light of its embry-
this is the most common of all intraocular dis-
ologic development, retention of old cells and
eases and a leading cause of vision loss in this
nuclear makeup, transparent nature, immune
species. Cataract surgery is the most frequent
privileged status, and metabolic restrictions. Its
and important intraocular surgery that defines
unique anatomical structure englobes a
veterinary ophthalmology. Advances in cata-
nucleus, cortex, and an external capsule com-
ract removals, such as phacoemulsification
posed of basement membrane, epithelia, and
and implantation of intraocular lenses (IOLs),
differentiated lens fibers (Figure 12.1). The lens
have markedly increased the success rate and
is suspended by many dense zonular ligaments
restoration of vision.
that, by directly connecting the ciliary body
Primary lens displacement (or luxation) is
with the equatorial capsule, induce subtle
the second most common threatening lens
changes in the lens curvature.
condition in dogs as well as the most frequent
Despite this simplistic anatomical structure,
secondary glaucoma. In addition, infrequent
the lens has a highly refined and elegant series
congenital lenticular disorders, as well as lens
of biochemical processes that must function
conditions secondarily to intraocular or sys-
correctly throughout life of the animal to
temic diseases, although less commonly seen,
maintain clarity. This transparency is a crucial
can also affect visual acuity. Breed-­related
property of the lens that is achieved, in part, by
­cataracts in dog are the majority type of lens
the absence of light-­scattering organelles
opacity. This section of the chapter focuses
within the lens fibers. New lens fibers are gen-
on the clinical manifestations of congenital,
erated from the equatorial cells of the lens epi-
developmental, and acquired diseases of the
thelium, which elongate, synthesize crystallins,
lens, and their appropriate medical management.
and finally lose their nuclei as they become
Lens Examination
mature lens fibers. The crystallins, which

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
­Congenital Lens Abnormalitie  427

Anterior capsule the lens. Precise localization of these opacities


can provide important clues as to their genesis
Anterior epithelium and possible cause. Inherited cataracts in
Cortex
many canine breeds affect the same region of
the lens and often with the same relative
Adult age range.

Infantile
Nucleus

Fetal ­Normal Findings by Age


Embryonic Before examining a lens, the examiner should
review the parameters of what is considered
within the “normal limits” in the species, so as
to separate those conditions from true disease
processes. In young animals, the suture lines
of the lens, usually shaped as a “Y” anteriorly
and as an “inverted Y” at the posterior pole,
can often be observed as faint lines when
examined under the biomicroscope. These
Figure 12.1 Schematic optical section of the lines, or arrowhead opacities, often disappear
adult canine lens, showing lens stratification with age and should not be mistaken for con-
(front to back): anterior capsule, anterior cortex,
nucleus (adult, infantile, fetal, and embryonic),
genital cataracts (CCs). In addition, in the very
posterior cortex, and posterior capsule. Note the young dog, a visible nuclear ring can be occa-
significant size of the nucleus when compared to sionally seen and should not be mistaken
the rest of the lens layers. Scheme performed by for CCs.
A. Peña.
Since lens transparency changes with age,
understanding the aging lenticular changes in
the dog is mandatory before issuing a diagno-
Initial lens exams involved pupillary dila- sis, as the majority of cataracts develop in dogs
tion, head loupes, and the otoscope or penlight older than five to seven years. Nuclear sclerosis
to illuminate the lens and permit inspection of is a normal aging feature of the lens due to the
the entire lens. Any opacity can interfere with compression of fibers in the nuclear region.
the light beam and permit both direct and Although it has little or no effect on vision, the
­indirect visualization. The Sanson–Purkinje blue-­gray appearance of the lens may prompt a
images are light reflections from the cornea, misdiagnosis of cataract by inexperienced vet-
anterior lens capsule, and posterior lens cap- erinarians. While cataract results in a black
sule that help identify the thickness of the lens shadow against the reflection from the fundus,
and aid in the localization of opacities within nuclear sclerosis presents no barrier to the fun-
the lens. The otoscope can also provide limited dus reflection.
magnification for the viewer.
In the framework of a complete ophthalmic
examination by the veterinary ophthalmolo- ­ ongenital
C
gist, the complete lens evaluation can be Lens Abnormalities
achieved by slit-­lamp biomicroscopy using dif-
ferent widths of light beams and magnifica- Congenital anomalies of the lens can be
tions to visualize the different regions of the divided into (i) those that involve abnormali-
lens and precisely localize any opacity within ties in the formation and differentiation of the
428 Canine Cataracts, Lens Luxations, and Surgery

lens placode and subsequently the lens epithe-


lial cells (LECs); (ii) those that are associated
with anterior segment dysgenesis; (iii) those
that are associated with abnormalities of
the fetal vasculature; and (iv) those that are
associated with the zonule formation (tertiary
vitreous). The first group includes aphakia,
microphakia, CC, and posterior lenticonus/
lentiglobus. The second group includes a spec-
trum of abnormalities related to incomplete or
late separation of the lens vesicle from the sur-
face ectoderm; most are capsular/subcapsular Figure 12.2 Microphakia and spherophakia with
cataracts associated with dysplastic pupillary elongated ciliary body processes in a terrier-­
membranes (PMs). The third group includes cross dog.
posterior capsular opacities (PCOs), posterior
capsular defects, and retrolental choristoma- Microphakia and Spherophakia
tous plaques (persistent embryonic vascula-
Microphakia and spherophakia are rare
ture). Finally, the last group of congenital
­congenital conditions; the lens may be either
anomalies encompasses lens luxations, lens
too small (microphakia) or spherical
coloboma, spherophakia, and microphakia. In
(spherophakia) when examined in cross sec-
addition, congenital abnormalities affecting
tion (Figure 12.2). The abnormal shape may be
the lens may be caused by genetic and/or exog-
caused by an underdeveloped zonule of Zinn
enous factors. Because proper development
(tertiary vitreous), which does not exert suffi-
of the lens is crucial in the orchestration of
cient force on the lens to make it form the usual
intraocular embryogenesis, eyes with lens
oval shape seen in cross section. In addition,
anomalies often exhibit multiple ocular defects.
microphakia may also be induced by abnormal-
ities in the formation and differentiation of the
Aphakia lens placode. In both presentations, elongated
ciliary processes may be present, and deficient
Congenital aphakia or congenital absence of
lens metabolism may result in either congenital
the lens is an extremely rare anomaly in the
or juvenile cataract. Canine breeds reported to
dog that occurs through failure of contact of
be affected with microphakia/spherophakia
the optic vesicle with the surface ectoderm
include the Beagle, Doberman Pinscher,
during a critical inductive period of embryo-
English Springer Spaniel, Saint Bernard, Great
genesis with subsequent failure of lens placode
Dane, and Miniature Schnauzer. Treatment
formation. In primary aphakia, there is no lens
includes long-­term monitoring, and occasional
induction of the surface ectoderm, while in
medical management using a long-­term miotic
secondary aphakia, lens development takes
agent in order to minimize the risk of complete
place, but later is resorbed or expelled in utero.
lenticular luxation, and/or surgical lens
Embryonic lens tissues have a major influence
removal/replacement.
on the development of the optic cup. As a
result, aphakia has been reported in associa-
tion with multiple ocular defects such as ­Lens Coloboma
microphthalmia, deformities of the anterior
segment (e.g., Peters’ anomaly and acorea), A coloboma of the lens is also a rare congenital
retinal dysplasia, retinal detachment, and condition characterized by equatorial notch-
staphylomas. ing. Like lens spherophakia and microphakia,
­Embryonic Vascular Abnormalitie  429

coloboma is related to problems of zonular demarcated conical projection of the lens cap-
development (local absence or marked defi- sule and cortex, usually axial in localization
ciency of the zonular fibers [zonular aplasia or and of variable size. If biomicroscopy of the
marked hypoplasia]) in a specific region, rather posterior lens is not possible because of cata-
than to an incomplete embryonic fissure clo- ract formation, the condition may also be rec-
sure during development. Thus, when com- ognized ultrasonographically.
pared with other ocular colobomas (iris, optic Posterior lenticonus, first described in the
nerve, scleral, etc.), a lens coloboma is not a Miniature Schnauzer and the Mastiff, may
true coloboma. As such, lens notching can be unilateral or bilateral and may occur in
occur secondary to different etiologies causing conjunction with other ocular anomalies.
focal weakened or deficient zonules. Lenticonus and secondary cataracts have been
Colobomas can be either typical (6-­o’clock primarily reported in the Cavalier King Charles
position) or atypical (other locations), the lat- Spaniel, Akita Inu, and Shih Tzu. In breeds
ter not always being apparently associated such as Doberman Pinscher, Golden Retriever,
with overt lens zonule defects. Based on size, Bouvier des Flandres, Bloodhound, Old English
colobomas can be further classified into focal Sheepdog, Labrador Retriever, Staffordshire
or extensive. Furthermore, lens colobomas Bull Terrier, and American Staffordshire
may be seen alone or associated with other Terrier, lenticonus and/or lentiglobus have
congenital anomalies such as colobomas of the been also associated with retrolental fibrovas-
uvea, MOD (merle ocular dysgenesis), or per- cular plaques, microphthalmia, coloboma,
sistent hyperplastic tunica vasculosa lentis/ retinal dysplasia, optic nerve hypoplasia, and
persistent hyperplastic vitreous (PHTVL/ intraocular hemorrhage. If visual acuity is
PHPV). When alone and focal, they may go affected, phacoemulsification with posterior
unnoticed until cataracts develop, but when continuous capsulorhexis and IOL implanta-
extensive, they may be associated with lens tion is recommended.
displacement.

­ mbryonic Vascular
E
Lenticonus/Lentiglobus
Abnormalities
Lenticonus and lentiglobus are congenital
anomalies in the shape of the lens with either The main vascular supply of the lens, present
anterior or posterior protrusion of the lens in during prenatal development, derives from the
conical or spherical contours, respectively. The intravitreal hyaloid vascular system. At about
deformity occurs in late fetal development fol- day 25 of gestation, the hyaloid artery (HA)
lowing normal formation of the lens nucleus, branches to create a capillary network on the
at the time of primary lens fiber elongation posterior surface of the lens capsule, the tunica
(25th day of gestation in dogs). What is gener- vasculosa lentis (TVL). These capillaries grow
ally accepted is that lenticonus/lentiglobus are toward the equator of the lens, where they
caused by a weakness of the lens capsule, anastomose with a second network of capillar-
which allows the cortex to protrude causing ies, called the PM, which covers the anterior
malformation at the anterior or, most com- surface of the lens. Once the ciliary body
monly, the posterior pole. Rarely, cases may begins actively producing aqueous humor, the
show rupture of the lens capsule with extrusion hyaloid vascular system is no longer needed
of lens cortical material into the vitreous, with and starts to regress. Some remaining parts of
varying degrees of secondary inflammation. the PM–TVL–HA system that are still present
Biomicroscopically, lenticonus is character- by eight weeks after birth will not undergo
ized by a transparent, localized, sharply ­further regression and will persist throughout
430 Canine Cataracts, Lens Luxations, and Surgery

Table 12.1 Breed predisposed to dystrophic PPMs causing secondary anterior polar cataract.

Airedale Terrier (b) Grand, Briquet, and Petit Basset Griffon Vendéen (a1, b)
Akita (b) Great Pyrenees (b)
Alaskan Malamute (b) Havanese (b)
American Pit Bull Terrier (b) Jack Russell Terrier (b)
Australian Shepherd (b) Japanese Chin (Japanese Spaniel) (b)
Basenji (b) Labradoodle (Australian) (b)
Basset Hound (b) Lakeland Terrier (b)
Bearded Collie (b) Leonberger (b)
Belgian Tervuren (b) Lowchen (b)
Bloodhound (a1, b) Mastiff (English) (b)
Border Collie (b) Miniature American and Australian Shepherd (b)
Bouvier des Flandres (b) Miniature Bull terrier (b)
Braque d’Auvergne (a1) Norwegian Elkhound (b)
Bull Terrier (b) Nova Scotia Duck Tolling Retriever (b)
Bullmastiff (b) Old English Sheepdog (a1, b)
Chihuahua (b) Pyrenean Shepherd (a1)
Chinese Crested (b) Pembroke Welsh Corgi (b)
Chow Chow (a1, b) Poodle (b)
Collie (Rough and Smooth) (b) Portuguese Water Dog (b)
Dachshund (b) Puli (b)
Doberman Pinscher (b) Samoyed (b)
Dogue de Bordeaux (a1) Scottish Terrier (b)
English Cocker Spaniel (b) Shetland Sheepdog (b)
English Springer Spaniel (b) Tibetan Terrier (b)
French Bulldog (b) Toy Australian Shepherd (b)
Fox Terrier (Wire and Smooth) (a1, b) West Highland White Terrier (a1, b)
German Pinscher (b) Whippet (b)
German Shorthaired Pointer (b) Wirehaired Vizsla (b)
Golden Retriever (b) Yorkshire Terrier (b)
(a1) Published studies referenced in the “ECVO Manual of Presumed Inherited Eye Diseases,” ECVO Genetics
Committee, 2017. (a2) Nonpublished reports considered in the “ECVO Manual of Presumed Inherited Eye
Diseases,” ECVO Genetics Committee, 2017. (b) Published studies and nonpublished reports referenced in “Ocular
Disorders Presumed to Be Inherited in Purebred Dogs,” ACVO Genetics Committee, 2015.

life, thus the term “persistent.” Sometimes, a predisposition is likely although, unfortu-
short remnant of the HA may be seen as a very nately, its mode on inheritance has not been
small, white, spiral-­shaped strand on the pos- yet elucidated (Table 12.1). Arising from the
terior pole of the lens (Mittendorf’s dot). iris ­collarette, PPMs may show three differ-
Persistent PM (PPM) is a common congenital ent presentations that may affect the lens
ocular anomaly seen sporadically in many (dysplastic PMs): (i) pigmented strands
breeds, presumably as a nonhereditary trait. attached to the anterior lens capsule, inducing
Nevertheless, in breeds with a higher preva- varying degrees of focal or multifocal lenticu-
lence or more severe manifestations of lar opacities (Figure 12.3a); (ii) PPMs may
PPMs (Basenji, Bloodhound, and English appear as multiple, punctate pigment foci on
Cocker Spaniel, among others), a hereditary the central anterior lens capsule, which are a
­Embryonic Vascular Abnormalitie  431

(a)

Figure 12.4 Spherophakia and PHTVL inducing


early immature posterior capsular cataract in a
nine-­months-­old Doberman Pinscher. Note the
reddish coloration of the lens opacification.

and 3.3% in Germany. All the other forms


(grades 2–6) were bilateral and eventually
(b) resulted in progressive cataract and, subse-
quently, severe impairment or loss of vision.
Figure 12.3 Different presentations of PPMs in
the dog. (a) Multiple punctate pigment deposition
Conversely, in the Staffordshire Bull Terrier,
on the axial anterior lens capsule in a nine-­year-­ the condition has been rarely associated with
old Yorkshire Terrier with mature cataract. Capsular progressive secondary cataracts.
pigment deposition is a common incidental finding Although the disease has been suspected to
in dogs (Courtesy of A. Bayón). (b) Multiple
punctate pigment deposits on the axial anterior
be inherited in more than 35 breeds of dogs, its
lens capsule in a nine-­year-­old Yorkshire Terrier mode of inheritance has been elucidated only
with mature cataract (Courtesy of A. Bayón). in 5 breeds (Table 12.2), being considered as an
incomplete autosomal dominant trait in the
common incidental finding in many breeds of Doberman, English Toy Spaniel, and
dogs (Figure 12.3b); and (iii) total PPM cover- Staffordshire Bull Terrier, and suspected to be
ing the entire pupil, which is extremely rare. an autosomal recessive trait in German
PHTVL/PHPV is the most severe congenital Pinscher (Miniature and Standard) and
lesion associated with abnormal development Miniature Schnauzer. Breeding programs in
of the intraocular vasculature leading, in the Doberman breed in the Netherlands have
most cases, to posterior or complete cataract resulted in a decreased incidence of severely
(Figure 12.4). The condition may occur unilat- affected dogs from 5% to 1%.
erally or bilaterally and appear alone or con- The diagnosis of PHTVL/PHPV is based on
currently with microphthalmia or other history, clinical examination with complete
multiple inherited eye anomalies. mydriasis, exclusion of other causes of leuko-
The first canine case was reported in 1969 in coria, and often ocular ultrasonography (US).
a Greyhound and subsequently the Doberman Color Doppler imaging and contrast-­enhanced
breed. Incidence of PHTVL in the Doberman US can be useful to assess the blood flow in the
has been reported to be as high as 42.6% in the vascular remnants and evaluate the likelihood
Netherlands, 14.5% in Norway, 9% in Finland, of surgical complications.
432 Canine Cataracts, Lens Luxations, and Surgery

Table 12.2 Canine breeds affected by PHPV/PHTVL causing lens opacification with possible mode
of inheritance.

Canine breeds affected by PHPV/PHTVL Inheritance

American Staffordshire Terrier Unknown


Australian Cattle Dog Unknown
Basset Hound Unknown
Bouvier des Flandres Not Defined
Boxer Unknown
Braque d’Auvergne Familial predisposition
Bull Terrier Unknown
Cavalier King Charles Spaniel Unknown
Dobermann Presumed dominant, incomplete penetrance
Dutch Partridge Dog Unknown
English Toy Spaniel (King Charles) Presumed dominant/incomplete penetrance
German Pinscher (Standard and Miniature) Presumed Autosomal recessive
German Shorthaired Pointer Unknown
Grand Anglo-­Français, Anglo-­Français de Petite Vénerie Unknown
Great Dane Unknown
Greyhound Unknown
French Pointing Griffon Korthals Unknown
Grand Griffon Vendéen Unknown
Japanese Chin Unknown
Labrador Retriever Unknown
Labradoodle (Australian) Unknown
Leonberger Unknown
Maremma Sheepdog Unknown
Miniature Schnauzer Autosomal recessive
Neapolitan Mastiff Unknown
Newfoundland Unknown
Old English Sheepdog Unknown
Pug Unknown
Pyrenean Shepherd Unknown
Schnauzer (Standard) Unknown
Shih Tzu Unknown
Siberian Husky Unknown
Staffordshire Bull Terrier Autosomal dominant with incomplete penetrance
Sussex Spaniel Unknown
Tibetan Terrier Unknown
Vizsla Unknown
Welsh Terrier Unknown
West Highland White Terrier Unknown
­Embryonic Vascular Abnormalitie  433

Although surgical success rates for


­restoration of vision were low in the pre-­
phacoemulsification era, surgical results have
markedly improved in the recent years.
Combination of phacoemulsification, poste-
rior capsulectomy, and placement of an IOL
has been successfully used.

Congenital Lens Luxation


Lens luxation is the displacement or disloca-
Figure 12.5 Incipient posterior cortical cataract
tion of the lens from its normal position and
in a six-­month-­old German Shepherd with
implies lack or rupture of zonules. Occasionally, concomitant keratoconjunctivitis sicca.
lens luxation may be a congenital condition,
which may occur alone or, more often, associ-
ated with other, usually multiple, congenital source of much speculation and research but,
defects, such as lens coloboma, microphakia, unfortunately, the majority have no identifia-
or spherophakia. There are no reports of inher- ble cause, being usually the result of lens ran-
ited congenital luxations equivalent to congen- dom dysgenesis (primary noninherited CC).
ital ectopia lentis in humans. Clinical and morphological features of CCs
vary among breeds. They may appear as small
nonprogressive or slowly progressive opacities
Congenital Cataract
in the suture lines or in the fetal nucleus or as
CC refers to a lens opacity present at birth or, larger opacities in the posterior lens pole. This
in altricial animal species, when the eyelids latter form may be nonprogressive or progres-
open for the first time. When presented as the sive, leading to complete blindness in some
only clinical sign, cataracts should be diag- cases. To simplify understanding, CCs are
nosed prior to eight weeks of age in order to be grouped according to the dog’s weight/size.
considered as congenital. CCs, whether unilat-
eral or bilateral, have a broad spectrum of Clinical and Morphological Features
causative factors contributing to their forma- of Primary Congenital Cataracts
tion, such as DNA mutations (random or in Small Breeds (<10 kg)
hereditary), infectious diseases of the dam dur- In small dogs, CCs were first reported in the
ing pregnancy, teratogenic drugs, irradiation Miniature Schnauzer. In this breed, CCs are
exposure, metabolic disease, and malnutrition frequently bilateral and involve the nucleus
during gestation. Based on its triggering condi- and, to a lesser extent, the posterior cortex. Its
tion, CC may be classified into primary or sec- progression is variable, but in some dogs may
ondary, depending on whether there is a direct progress to complete cataracts as early as six
or indirect effect to the lens, respectively. weeks of age. Microphthalmia, microphakia,
and lenticonus are commonly associated find-
ings. Nonprogressive cataracts affecting the tips
Primary Congenital Cataract
of the posterior “Y” suture lines occur in West
Primary CCs can be classified into inherited or Highland White Terriers. An autosomal recessive
noninherited, based on the mutation nature mode of inheritance has been postulated for both
(inherited or random, respectively). CCs may of these breeds. In Cavalier King Charles
be an incidental finding in any dog breed Spaniels, CCs affecting the cortex and nucleus
(Figure 12.5). The causes of CCs have been the have been reported; however, although suspected
434 Canine Cataracts, Lens Luxations, and Surgery

to be inherited, the mode of inheritance has not very slowly progressive and do not interfere
been elucidated. In affected animals, a rapid pro- with vision.
gression to complete cataract occurs. Congenital posterior polar cataracts have
been described in German Shepherds, and
Clinical and Morphological Features of Primary Golden and Labrador Retrievers. These are
Congenital Cataracts in Medium Breeds (10–20 kg) generally bilateral and nonprogressive or
CCs in American Cocker Spaniels have a cen- slowly progressive, although occasional unilat-
tral nuclear discoid shape, are bilateral and eral cataracts and extensive progression to
nonprogressive, and may be detected as early complete cataract may be observed. Although
as four weeks of age. The nuclear distribution suspected to be dominant with incomplete
favors the lower proportion of cataractous to penetrance in Labrador Retrievers, the mode
normal lens as the pups mature. Color variants of inheritance for CC has been only defini-
of this breed manifest different and quite var- tively established in German Shepherds, being
ied forms of primary CC with respect to loca- inherited as an autosomal dominant trait.
tion within the lens, even in closely related Conversely, in the German Shepherd breed
dogs, suggesting that the phenotype does not in England, an autosomal recessive trait has
segregate according to familial lines. Similarly, been reported and a severe progression of the
English Cocker Spaniels also have CCs and posterior polar cataract to complete cataract
non-­CCs, but, in this breed, CCs are mainly and vision impairment has been described.
located in the anterior capsule and commonly Concomitant microphthalmia has been
associated with microphthalmia and dysplas- described only in the Golden Retriever. In
tic PMs (secondary CC). addition, cortical CCs have been described
Primary congenital capsular opacities have in Labrador Retrievers with appendicular
also been described in Beagles, although they skeletal growth retardation, persistent hyaloid
seem to represent a transient growth phase var- remnants, and rhegmatogenous retinal
iant, as they gradually disappear by six to eight detachment, as well as in short-­limbed dwarfed
months of age. Conversely, congenital posterior Samoyeds in conjunction with vitreal liquefac-
cortical cataracts, concurrent with multiple tion, hyaloid remnants, and retinal detachment.
dysplastic ocular abnormalities (e.g., microph- Australian Shepherds affected by MOD may
thalmia, lens luxation, dysplastic PM, choroi- also show CC as one of the signs of their clini-
dal hypoplasia, scleral thinning, and atypical cal picture (e.g., microphthalmia, microcornea,
coloboma of the posterior segment), have been colobomas of the iris, retina, choroid, and/or
described in Soft-­Coated Wheaten Terriers, sclera, and retinal dysplasia with or without
English Cocker Spaniels, and Red Cocker detachment). This ocular syndrome is inher-
Spaniels. Although suspected to be inherited, ited as an autosomal recessive trait.
the mode of inheritance has not been yet estab- Nonprogressive congenital nuclear cata-
lished for any of the previously listed breeds. racts, in association with concurrent ocular
signs (e.g., wandering nystagmus, entropion,
Clinical and Morphological Features of Primary microphthalmia, PPM, and multiple retinal
Congenital Cataracts in Large Breeds (>20 kg) folds), have been described in Chow Chows. In
In large dog breeds, CCs may show two distinct addition, CCs have been associated with reti-
phenotypic presentations. The first presentation nal dysplasia in breeds such as the Bedlington
consists of small, white, dense opacities located Terrier, Sealyham Terrier, Akita Inu, Beagle,
in the suture lines, the embryonic or fetal Bloodhound, Samoyed, Old English Sheepdog,
nucleus, or at attachment points of associated and Labrador Retriever.
anomalies (e.g., dysplastic PMs and PHTVL). Finally, an autosomal dominant cataract has
These cataracts are mostly nonprogressive or been reported in Norwegian Buhunds. The
­Embryonic Vascular Abnormalitie  435

cataract appears as small dots in the fetal Based on the degree of opacity and progres-
nucleus, and progresses over four to five sion (probably the most useful), cataracts may be
years to assume a pulverulent (“candy floss”) further classified as incipient (see Figure 12.5),
appearance. immature, mature, hypermature, intumescent,
and Morgagnian (Figures 12.6–12.10). Tapetal
reflection is used as a classifying tool for
Secondary Congenital Cataract
most cataracts. An incipient cataract is the
Secondary CCs can be classified into inherited or ­earliest stage of opacification and does not/
noninherited. The former group encompasses minimally affect the tapetal reflection
all the ocular congenital diseases that induce (<10–15%). In this type of cataract, small lens
secondary cataracts (e.g., PPM and PHTVL/ opacities are often only seen under magnifica-
PHPV). Secondary noninherited cataracts have tion with a dilated pupil, and vision is not
been previously associated with infectious dis- noticeably affected.
eases of the dam during pregnancy, teratogenic A more advanced cataract is described as
drugs, irradiation exposure, metabolic disease, immature, in which the tapetal refection is
and malnutrition during gestation. reduced, but still present. Immature cataracts
can be further categorized into early immature
(affects 15–50% of the tapetal reflection) or late
Acquired Lens Abnormalities
immature (affects 50–99% tapetal reflection)
Acquired lens abnormalities are common in (see Figure 12.6b). When vision no longer
the dog, and include cataracts, lens sclerosis, exists, no tapetal refection is visible, and
and lens displacement as the most commonly inspection of the fundus is no longer possible,
reported conditions. the cataract is then referred to as mature (see
Figure 12.10). Later, the cortex may liquefy
(hypermature cataract) and adopt a crystalline
Cataracts
appearance with wrinkling of the lens capsule.
Acquired cataracts are lens opacifications diag- Limited vision and tapetal reflection may
nosed after the arbitrary cutoff of eight weeks return (especially with mydriasis). In the end
of age in dogs. Nevertheless, an exception can stage, total liquefaction of the cortex allowing
be made for all those cataracts that even diag- the nucleus to sink inferiorly may occur in
nosed after the cutoff show distinct proofs of some middle-­aged/old dogs (Morgagnian cata-
congenital in origin (e.g., associated PPM and ract) (see Figure 12.10d). In some young ani-
PHTVL/PHPV). mals, the liquefied contents escape through
the capsule, resulting in cataract resorption,
which restores partial vision. Spontaneous cat-
Classification of Canine Cataracts
aract resorption is rarely seen in geriatric dogs,
Cataracts are classified according to different cri- but is not uncommon in young dogs (1–3 years
teria: age at onset, anatomical location, degree old). In cases in which the only abnormality is
of maturation, and etiology. Based on the age a cataract, the pupillary light reflexes should
of onset, cataracts can be graded as congenital, remain normal regardless of maturity.
developmental, and senile. Based on location,
cataracts are classified into capsular, subcapsu-
Detailed Description
lar, cortical (these three areas are further divided
of Acquired Cataracts
into anterior and posterior), nuclear (embryonic,
fetal, infantile, or adult), and suture lines. Like CCs, acquired cataracts can be further
Cataracts can also be categorized as axial, par- classified into primary and secondary. Primary
axial, or inferior/superior equatorial. cataracts include lens opacifications induced
436 Canine Cataracts, Lens Luxations, and Surgery

(a) (b)

Figure 12.6 Immature cataracts. (a) Early immature cataract in diffuse illumination. Note the peripheral
vacuole formation. (b) Late immature cataract and lateral lens spherophakia seen with retroillumination.

Figure 12.7 Typical appearance of a mature or Figure 12.8 Hypermature cataract seen in diffuse
complete cataract seen in diffuse illumination. illumination. Note glistening, refractile appearance
Note separation of the fibers and formation of a of lens material, and the beginning of the anterior
cleft along the anterior Y-­suture. capsule wrinkling.

by a lenticular metabolic abnormality (heredi- (developmental cataract), and senile cataract,


tary or not in nature) and those age-­related most commonly seen in dogs older than eight
(senile). Secondary cataracts are those induced to nine years.
by other ocular or systemic conditions, such as
ocular trauma, glaucoma, uveitis, lens luxa- Developmental Cataracts
tion, progressive retinal atrophy (PRA), nutri- Developmental cataracts are defined as a pri-
tional or metabolic disorders, infectious mary opacification of the lens that displays a
diseases, and toxins. variable presentation among breeds but, at the
same time, shows marked intrabreed specific-
Acquired Primary Cataracts ity in their ophthalmoscopic appearance, age
Acquired primary cataracts are further classi- of onset, rate of progression, and degree of bin-
fied into those appearing from eight weeks ocular symmetry, indicating their genetic
of life to middle age, which in the dog is homogeneity within a breed. They are consid-
­considered about six to seven years of age ered nowadays as one of the most important
­Embryonic Vascular Abnormalitie  437

breed, and the expression can be influenced by


other modifying genes or environmental fac-
tors. In many breeds, posterior polar cataract is
the most common manifestation, primarily
affecting the cortex and sparing the nucleus in
the initial stages. Those cataracts might only
progress to a limited extent, rarely affecting the
lens completely. Nevertheless, many different
presentations have been described for develop-
mental cataracts in the dog.

Clinical and Morphological Features of


Developmental Cataracts in Small Breeds (<10 kg)
Figure 12.9 Morgagnian cataract seen in diffuse
illumination. Note the complete liquefaction of the Grossly, developmental cataracts tend to occur
cortex allowing the nucleus to sink inferiorly most frequently in the smaller canine breeds.
(Courtesy of M. Matas). Among the affected breeds, it is worth noting
the Miniature Schnauzer, Standard Poodle,
Bichon Frise, Boston Terrier, and West
Highland White Terrier, of which specific
reports on phenotypic lenticular appearance
and its progression have been described.
In the Miniature Schnauzer, apart from the
well-­known congenital form, a juvenile devel-
opmental cataract has also been described.
This form has an age of onset of six months
and primarily affects the posterior lens cortex,
with no nuclear involvement. Its progression is
variable.
Juvenile cataracts have also been described
Figure 12.10 Nearly complete cataract in the Standard Poodle and Afghan Hound in
reabsorption in a two-­year-­old West Highland
which lens opacification affects the equator
White Terrier. Note the capsular wrinkling and the
crystalline appearance of the lens remnants. and tends to impair vision by 6–18 months of
age. Bichon Frise shows a late-­onset develop-
causes of blindness in purebred dogs, with mental cataract (two to eight years of age) that
more than 180 breeds affected (Table 12.3). In affects the anterior and posterior cortices.
some cases, more than one form of cataract Two distinct types of developmental cata-
occurs in the same breed. racts have been described in Boston and West
Developmental cataracts may be classified Highland White Terriers. In the Boston Terrier,
into early form (juvenile) and late form, accord- the first form, originally described in 1978 by
ing to the age at which it is first diagnosed. Barnett, is bilateral and begins at the suture
Often, cataract changes develop early in life, at lines, affecting the nucleus, as well as the pos-
about 12 months of age. The clinical and mor- terior cortex. Despite its early age of onset
phological features of developmental cataracts (8–12 weeks), it is considered as a developmen-
have been described for many breeds of dogs. It tal cataract and tends to progress to maturity.
should be noted that the phenotypic expression The other form has a late onset (three to four
of heritable cataract in dogs, most notably age years of age), involves the equator and anterior
of onset and progression, can vary within a cortex, and has a very slow progression. In the
438 Canine Cataracts, Lens Luxations, and Surgery

Table 12.3 Canine breeds affected by presumed HCs.

Affenpinscher (a1, b) Dachshund (a1, b) Maltese (a1, b)


Afghan Hound (a1, b) Dalmatian (a1, b) Manchester Terrier (a1)
Airedale Terrier (a2, b) Doberman Pinscher (a2, b) Maremma Sheepdog (a1)
Akbash Dog (a2, b) Dogue de Bordeaux (a1, b) Markiesje (a2)
Akita Inu (a2, b) Dutch Partridge Dog (a2) Mastiff (a2, b)
Alaskan Malamute (a2, b) English Cocker Spaniel (a1, b) Mi-­Ki (a2, b)
American Cocker Spaniel (a1, b) English Pointer (a1, b) Miniature Bull Terrier (b)
American Eskimo Dog (a2, b) English Setter (a1, b) Miniature Pinscher (b)
American Hairless Terrier (b) English Springer Spaniel (a1, b) Münster Spaniel (a1)
American Staffordshire English Toy Spaniel (a1, b) Neapolitan Mastiff (a1, b)
Terrier (a1, b) Entlebucher (a1, b) Newfoundland (a1, b)
American Water Spaniel (a1, b) (Eurasier a1) Norbottenspets (a2, b)
Australian Cattle Dog (a1, b) Field Spaniel (a1, b) Norfolk Terrier (a1)
Australian Kelpie (a2, b) Finnish Lapphund (a2, b) Norwegian Buhund (a1, b)
Australian Shepherd (Standard, Finnish Spitz (b) Norwegian Elkhound (a2, b)
Miniature, and Toy) (a1, b) Flat-­Coated Retriever (a1, b) Norwich Terrier (a1, b)
Australian Terrier (a2, b) Fox Terrier (Wire and Nova Scotia Duck Tolling
Barbet (a1) Smooth) (a1, b) Retriever (a1, b)
Basenji (a2, b) French Bulldog (a1, b) Old English Sheepdog (a1, b)
Basset Artésien Normand (a1) French Shorthair Pointer (a1) Papillon (a1, b)
Basset Hound (a1, b) French Spaniel (a1) Parson Russell Terrier (a1, b)
Beagle (a1, b) French Pointing Griffon Pekingese (a1, b)
Bearded Collie (a1, b) Korthals (a1) Pembroke Welsh Corgi (b)
Bedlington Terrier (a1, b) German Pinscher (a1, b) Petit Basset Griffon
Belgian Malinois (a2, b) German Shepherd Dog (a1, b) Vendéen (a1, b)
Belgian Sheepdog (a2, b) German Shorthaired Pointer (a1, b) Pharaoh Hound (b)
Belgian Tervuren (b) German Wirehaired Pointer (a1, b) Picard Spaniel (a1, b)
Bernese Mountain Dog (a2, b) Giant Schnauzer (a1, b) Polish Lowland Sheepdog
Bichon Frise (a1, b) Glen of Imaal Terrier (a2, b) (a1, b)
Black and Tan Coonhound (a1, b) Golden Retriever (a1, b) Pomeranian (a1, b)
Black Russian Terrier (a2, b) Gordon Setter (a2, b) Poodle (a1, b)
Bloodhound (a1, b) Great Dane (a1, b) Polish Tatra Sheepdog (a1)
Blue de Gascogne (a1) Great Pyrenees (a1, b) Portuguese Water Dog (a1, b)
Bolognese (a1, b) Greater Swiss Mountain Dog (a1, b) Portuguese Pointer (a1)
Border Collie (a1, b) Greyhound (a2, b) Pug (a1, b)
Border Terrier (a2, b) Groenendael (a1) Puli (a1, b)
Borzoi (a1, b) Harrier (b) Pyrenean Shepherd (a1, b)
Boston Terrier (a1, b) Havana Silk Dog (b) Rat Terrier (b)
Bouvier des Flandres (a1, b) Havanese (a1, b) Rhodesian Ridgeback (a1, b)
Boxer (a1, b) Ibizan Hound (a1, b) Rottweiler (a1, b)
Boykin Spaniel (a2, b) Icelandic Sheepdog (a2, b) Saint Bernard (a1, b)
Bracco Italiano (a1, b) Irish Setter (b) Saluki (a1, b)
Braque de l’Ariège (a2) Irish Soft-­Coated Wheaten Terrier Samoyed (a1, b)
Braque d’Auvergne (a1) (a1, b) Saarloos Wolfhound (a1)
Briard (a1, b) Irish Water Spaniel (a1, b) Sarplaninac (a1)
Brittany Spaniel (a1, b) Irish Wolfhound (a1, b) Schapendoes (a1)
Brussels Griffon (a1, b) Italian Greyhound (a1, b) Schipperke (a1, b)
­Embryonic Vascular Abnormalitie  439

Table 12.3 (Continued)

Bull Terrier (a1, b) Jack Russell Terrier (a1, b) Schnauzer Miniature and
Bulldog (a1, b) Japanese Chin (a1, b) Standard (a1, b)
Bullmastiff (a2, b) Jagdterrier (a1) Scottish Deerhound (a1)
Cairn Terrier (a1, b) Karelian Bear Dog (a2) Scottish Terrier (a1, b)
Cane Corso Italiano (a1) Keeshond (a1, b) Sealyham Terrier (a1, b)
Canaan Dog (b) Kerry Blue Terrier (a1, b) Segugio Maremmano (a1)
Cardigan Welsh Corgi (a2, b) Komondor (a1, b) Shar-­Pei (a1, b)
Cavalier King Charles Kuvasz (a1, b) Shetland Sheepdog (a1, b)
Spaniel (a1, b) Labradoodle Australian (b) Shiba Inu (a1, b)
Chesapeake Bay Retriever (a1, b) Labrador Retriever (a1, b) Shih Tzu (a1, b)
Chihuahua (a1, b) Lagotto Romagnolo (a1, b) Siberian Husky (a1, b)
Chinese Crested Dog (a2, b) Lakeland Terrier (a1) Silky Terrier (a1, b)
Chinook (b) Leonberger (a1, b) Skye Terrier (a1)
Chow Chow (a1, b) Lhasa Apso (a1, b) Soft-­Coated Wheaten Terrier (b)
Cirneco dell’Etna (a1) Lowchen (a2, b) Spinone Italiano (a1, b)
Clumber Spaniel (a2, b) Staffordshire Bull Terrier (a1, b)
Collie (a2, b) Sussex Spaniel (a1)
Coton de Tulear (a2, b) Standard Schnauzer (b)
Curly-­Coated Retriever (a1, b) Swedish Vallhund (b)
Tibetan Spaniel (a1, b)
Tibetan Terrier (a1, b)
Vizsla (a1, b)
Volpino Italiano (a1)
Weimaraner (a1, b)
Welsh Corgi Pembroke (a1)
Welsh Springer Spaniel (a1, b)
Welsh Terrier (a1, b)
West Highland White Terrier
(a1, b)
Whippet (a1, b)
Yorkshire Terrier (a1, b)
(a1) Published studies referenced in the “ECVO Manual of Presumed Inherited Eye Diseases,” ECVO Genetics
Committee, 2017. (a2) Nonpublished reports considered in the “ECVO Manual of Presumed Inherited Eye
Diseases,” ECVO Genetics Committee, 2017. (b) Published studies and nonpublished reports referenced in “Ocular
Disorders Presumed to Be Inherited in Purebred Dogs,” ACVO Genetics Committee, 2015.

West Highland White Terrier breed in Sweden, affected breeds include Staffordshire Bull
the two types of developmental cataracts also Terrier, German Pinscher, and American and
clearly differ: one involves the tips of the poste- English Cocker Spaniel.
rior Y-­sutures primarily, and the other affects In Staffordshire Bull Terriers, developmen-
the complete lens structure. tal cataract is described as bilateral and
­symmetrical, located primarily in the nucleus
Clinical and Morphological Features of Developmental and posterior capsule of the lens and
Cataracts in Medium Breeds (10–20 kg) ­progressing to blindness by two to three
Medium breed dogs are also commonly years of age.
affected by developmental cataracts, but stud- German Pinchers in Finland are affected by
ies describing the disease in each breed indi- a late-­onset developmental cataract (nine years
vidually are less common. The most frequently old at diagnosis) that primarily affects the
440 Canine Cataracts, Lens Luxations, and Surgery

posterior and subcapsular area. Conversely, in In the German Shepherd breed in England,
dogs bred in Germany, developmental cata- developmental cataracts have been reported at
racts are seen significantly earlier in life 8–12 weeks of age, as small dot opacities in the
(median age 3.9 years) with a predisposition posterior cortex that can involve the Y-­sutures
for the anterior cortical area followed by the and nucleus. With progression, by one year of
posterior pole. The reason for these significant age, nuclear and cortical cataracts with vision
geographic differences is unknown. impairment can be present. No progression is
The American Cocker Spaniel, apart from noted after one to two years of age.
the previously mentioned CC, also shows a Cataracts in the Norwegian Buhund exhibit
developmental cataract that affects the cortex, moderately large posterior polar cataracts with
with the posterior aspect most commonly occasional extensions around the suture lines,
affected, and the anterior cortex and the equa- as well as occasional vacuoles in the peripheral
tor involved less frequently. They can appear as cortex and rapid progression to blindness. A
early as six months of age and have variable different type of cataract was described in this
progression depending on age of onset. breed in 1995, which was termed pulverulent
Progression tends to be rapid in dogs with early nuclear cataract. The term pulverulent means
onset (<3.5 years of age) and slower in cases of “dust-­like” and is commonly used in human
late onset (>3.5 years of age). Both presenta- ophthalmology. The cataracts may be visible as
tions seem to be genetically distinct. Cortical early as 6.5 weeks of age as small dots parallel
cataracts are also seen secondary to PRA in the to the suture lines behind the nucleus. By the
American Cocker Spaniels. age of 4–5.5 years, the opacities progress to
involve the fetal nucleus that then resembles a
Clinical and Morphological Features of Developmental ball of “candy floss.” The adult nucleus and the
Cataracts in Large Breeds (>20 kg) cortex remain clear.
Large breed dogs are commonly affected by In the Entlebucher Mountain Dog, develop-
developmental cataract, with the posterior mental cataract is the most frequently observed
area the most frequently involved. In the hereditary eye disease with a prevalence of
Golden and Labrador Retriever, apart from the 23.5%. Most of the affected dogs develop bilat-
previously described congenital form, a late-­ eral symmetric opacifications, which are
onset form of developmental cataract has also mostly capsular and subcapsular in the poste-
been described. In these breeds, cataracts are rior polar part of the lens along the suture
cortical, most commonly located in the poste- lines. The first sign of cataracts can be seen at a
rior polar cortex, and viable in progression. In mean age of 5.5 ± 2.6 years and PRA may be
the Labrador Retriever, dogs with posterior concurrent.
polar cataracts produce affected offspring with Nuclear, posterior nuclear, and posterior polar
both focal and diffuse forms of cataract, sug- subcapsular cataracts have been identified in
gesting the two forms cannot be considered closely related Leonbergers in the United
totally separate entities. Kingdom. Similarly, triangular-­shaped polar
Equatorial and posterior subcapsular cata- (anterior and posterior) and complete cataracts
racts occur in the Siberian Husky. These cata- have been described in Rottweilers of different
racts are considered to be juvenile onset, as ages, with the youngest at 10 months of age. In
they appear at 6–18 months of age and are typi- the Welsh Springer Spaniel, a bilateral, symmet-
cally slowly progressive. rical, progressive cataract affecting the nucleus
Developmental cataracts suspected to be and posterior cortex has been described in a
inherited have also been described in the pedigree of three generations. Equatorial cata-
Chesapeake Bay Retriever and Labradoodle, racts can occur as early as four months in the
both showing multiple lens locations without a Afghan Hound. Progression is rapid in this
clear phenotypic predisposition. breed, with visual impairment often present by
­Embryonic Vascular Abnormalitie  441

two years of age. In the Old English Sheepdog, (HC) is probably a genetically complex disor-
developmental cataracts have also been der in most dog breeds, and studies to date
described, with the location of the opacity within have not included the analysis of sufficient
the lens and the age of onset highly variable. numbers of cases and controls to identify DNA
variants associated with the disease. Indeed,
Mode of Inheritance and Affected Genes although presumed HCs have been described
in Hereditary Cataracts The paucity of canine in more than 180 canine breeds, the mode of
cataract mutations reported in the literature, inheritance has been established only in 17
compared to those associated with, for exam- breeds (Table 12.4).
ple, inherited retinal degenerations in the dog, In humans and mice, several mutations in
is testament to the fact that hereditary cataract limited different genes have been linked to

Table 12.4 Canine breeds affected by HCs in which mode of inheritance has been described or a genetic
test has been developed.

Canine breeds affected by HC Inheritance Available genetic tests

Australian Shepherd Autosomal dominant with HSF4-­2


incomplete penetrance
Border Terrier Autosomal recessive HSF4-­1
Boston Terrier Autosomal recessive HSF4-­1 for early onset
presentation
Chesapeake Bay Terrier Autosomal dominant with –
incomplete penetrance
American Cocker Spaniel Autosomal recessive –
Entlebucher Mountain Dog Autosomal recessive –
French Bulldog – HSF4-­1
German Shepherd Dog Congenital: autosomal dominant –
Noncongenital: autosomal recessive
Australian Labradoodle Autosomal dominant with –
incomplete penetrance
Autosomal recessive
Not defined
Labrador Retriever Autosomal dominant with –
incomplete penetrance
Autosomal recessive
Not defined
Miniature Australian Autosomal dominant with HSF4-­2
Shepherd incomplete penetrance
Miniature Schnauzer Autosomal recessive –
Norwegian Buhund Autosomal dominant –
Staffordshire Bull Terrier Autosomal recessive HSF4-­1
Toy Australian Shepherd Autosomal dominant with HSF4-­2
incomplete penetrance
Welsh Springer Spaniel Autosomal recessive –
West Highland White Terrier Autosomal recessive –
442 Canine Cataracts, Lens Luxations, and Surgery

both autosomal dominant and recessive Age-­Related Cataracts


HC. Different studies have evaluated the role Cataracts are commonly seen in the aged dog
of these mutations in the development of HC and are often classified as age-­related cataracts
in the dog. More than 21 candidate genes have (ARCs) or senile cataracts, if no other anteced-
been investigated in several canine breeds, but ent cause is apparent. The age of onset at
to date, only 2 genes, the heat shock transcrip- which a cataract should be considered age-­
tion factor 4 (HSF4) and the Sec1 Family related is arbitrary (often >10 years) and breed-­
Domain Containing 2 (SCFD2), have been related. In fact, different studies show that
associated with the developmental HC in dogs. body size, life expectancy, and ARC incidence
One study demonstrated a nearly complete are interrelated in dogs, body size being nega-
linkage with microsatellites adjacent to exon 9 tively correlated to longevity, and this in turn
of HSF4 of chromosome 5 in Staffordshire Bull positively correlated with the age at which
Terriers, Boston Terriers, and Australian prevalence of cataract is 50% (C50).
Shepherds. The two gene mutations described While the clinical appearance and rate of pro-
in these breeds are predicted to alter the read- gression of ARC can vary, they often are seen
ing frame of the protein transcript and intro- initially as an increase in relucency in the adult
duce a premature stop codon, which results in nucleus of the lens, generally occurring concur-
truncated and aberrant crystalline proteins. rent with or following dense nuclear sclerosis
These abnormal proteins are the common final (Figure 12.11). Cortical cataractous changes
result of two possible HSF4 exon 9 mutations: may also occur to varying extents, either concur-
a 1-­bp insertion seen in Staffordshire Bull rent with or separate from nuclear cataracts. The
Terriers and Boston Terriers (HSF4-­1), and a rate of progression of these classic ARCs in dogs
1-­bp deletion detected in Australian Shepherds is often slow, requiring many months to several
(HSF4-­2). years to result in demonstrable vision loss.
More recently, a mutation in the intron 5 of
the SCFD2 gene on chromosome 13 has been Acquired Secondary Cataracts
associated with bilateral posterior polar cata- Cataracts Associated with Medications and
racts in Australian Shepherd dogs. The SCFD2 Other Toxic Substances
gene encodes a sec1 family domain-­containing Cataracts have been associated with medica-
protein 2, a molecule that may be involved in tions (drug-­induced cataracts), and a number
protein transport, although very little is
reported on its function. Many other genes
causing cataracts in humans have been tested
in different canine breeds with no significant
linkage or association.

Breeding Strategies and Genetic Tests Available


for HC Currently, there are only two DNA-­
based tests available for the diagnosis of HC in
dogs (see Table 12.4): the HSF4-­1 (exon 9 1-­bp
deletion in Border Terrier, Boston Terrier,
French Bulldog, and Staffordshire Bull terrier)
and the HSF4-­2 (exon 9 1-­bp insertion in
Australian Shepherd). The high frequency of
Figure 12.11 Typical ARC in a 13-­year-­old
HSF4 mutations and their significant associa-
Miniature Schnauzer seen in direct illumination.
tion with HC in the above-­mentioned breeds Note denser nuclear cataract with multifocal
call for careful planning of breeding strategies. opacities in the cortices.
­Embryonic Vascular Abnormalitie  443

reductase inhibitors group is atorvastatin


Box 12.1 Drugs Associated
that does not seem to have cataractogenesis
with Cataracts in Dogs
effects in the dog. The hypocholesterolemic
●● Diazoxide (antihypertensive agent) drugs are thought to have a cataractogenic
●● Phenylpiperazine (antihypertensive agents) effect by inhibition of cholesterol synthesis
●● HMG-­CoA reductase inhibitors in the outer cortical regions of the lens,
(cholesterol-­lowering drugs) where cholesterol is critical for the newly
●● Sulfonylurea glimepiride (a hypoglycemic synthesized lens fibers’ cell membranes.
agent) Chronic topical and oral administration of
●● Pefloxacin (a quinolone) dimethyl sulfoxide (DMSO) in dogs (dosage
●● Dinitrophenol (anthelmintic agent) of 2.5–40 g/kg) has been associated with unu-
●● DNCA (a fungicide) sual lens changes with an unexplained patho-
●● Progesterone-­based oral contraceptives genesis. The lens alteration was characterized
●● Ketoconazole by a reduction in the refractive index of newly
●● DMSO synthesized lens fibers in the cortex causing
them to appear optically clear instead of relu-
cent. Cataractogenesis in dogs has also been
associated with the administration of oral
of pharmacological agents have been reported contraceptives and with disophenol.
to produce cataracts in dogs (Box 12.1). As Cataracts Associated with Toxic
this species is commonly used in toxicological Substances. A number of toxic substances are
screenings of new pharmacological agents known to trigger cataract, including acetone,
and chemicals, numerous cataractogenic dinitrophenol, cresol, and paradichlorobenzol,
agents have been noted in the laboratory dog. as well as numerous chemicals and solvents.
Drug-­induced cataracts tend to be bilateral Intraocular foreign bodies containing metals
and dose-­related, and although initially such as iron, copper, lead, mercury, silver, gold,
appear at a variety of locations within the and thallium have been also associated with
lens, often begin in either the anterior and cataractogenesis. Accidental ingestion of an
posterior cortical region near the equator or overdose of xylitol-­containing chewing gum
the Y-­suture regions. This type of secondary (estimated dose 0.7 g/kg) has been associated
cataract is often associated with lens vacuole with acute bilateral cataract, retinal detach-
formation and reported to be reversible if the ment, and hepatotoxicity in a dog (unpub-
drug insult is removed. In laboratory dogs, lished data).
cataracts have been described with the
chronic use of antihypertensive agents such Cataracts Associated with External Agents
as diazoxide and phenylpiperazine. Induced Several external agents have been associated
lens opacities are progressive for phenylpip- with cataracts in human and different animal
erazine, but transient and reversible for species, including radiation, electricity, hypo-
diazoxide. The administration of high dos- thermia, hyperthermia, and pH shifts.
ages of cholesterol-­lowering drugs such Ionizing, nonionizing (microwave), ultravio-
as hydroxymethylglutaryl-­CoA (HMG-­CoA) let, and infrared radiation can cause cataracts
reductase inhibitors or drugs inhibiting oxi- by altering formation of new cells and differ-
dosqualene cyclase have also been described entiation of fibers. The likelihood of develop-
to produce cataracts, seen initially as accen- ment of cataracts following ionizing radiation
tuation of the suture lines that finally pro- is related to the dose and the degree of expo-
gress to anterior and posterior subcapsular sure of the eye to the radiation beam. In dogs,
areas. One exception from the HMG-­CoA cataract was a common late finding
444 Canine Cataracts, Lens Luxations, and Surgery

(>6 months) when given 36–67.5 Gy in frac- Cataracts Associated Systemic Ion Disturbances
tionated doses over four weeks using a 6-­MV Calcium Abnormalities (Hypocalcemia
linear accelerator. and Hypercalcemia). Hypocalcemia, most
Electricity-­induced cataracts have been spo- commonly caused by renal failure or primary
radically reported in both humans and dogs. or secondary hypoparathyroidism in dogs, can
Bilateral anterior subcapsular cataract forma- be associated with characteristic cataracts
tion has been reported in a three-­year-­old dog manifested as multifocal, punctate opacities
after biting an electric cord. or coalescing lamellar cortical opacities (as a
“field of stars”), which are bilaterally symmet-
Cataracts Associated with Other Ocular Diseases ric. The opacities are thought to relate to
Several intraocular diseases can cause sec- hypocalcemia-­associated defects in the active
ondary cataract in the dog. The most clini- cation transport mechanism of the lens epi-
cally relevant type of secondary cataract thelium, causing an increase in sodium con-
is undoubtedly that associated with PRA or tent and a loss of lens potassium. Hypercalemia
other types of retinal degeneration. PRA-­ is rarely reported in dogs, with neoplasia being
induced cataract is presumed to be of an its most common cause, followed by primary
endogenous toxicity nature. Degenerative hyperpara­thyroidism, chronic kidney disease,
rod outer segments may release water-­soluble and hypoadrenocorticism.
dialdehydes from peroxidation of photo­ Cooper Abnormalities (Hypercupremia).
receptor lipid membranes that diffuse A characteristic, sunflower-­shaped anterior
through the vitreous and are toxic to lens cel- subcapsular cataract is seen in humans suffer-
lular membranes. Cataracts are commonly ing from Wilson’s disease, and other noncon-
seen in dogs with moderate to advanced genital disorders causing derangement of
stages of PRA, often obscuring ophthalmo- copper metabolism. Lens opacities have little
scopic detail of the fundus. Typically, the effect on vision and clear after treatment
cataract is accompanied by dilated pupils with penicillamine. A familial copper storage
with poor pupillary light reflexes and, if the disorder, similar to Wilson’s disease, has
retina can be examined, hyperreflectivity been described in Bedlington Terriers, West
from the fundus. Although all the breeds Highland White Terriers, Skye Terriers,
genetically predisposed for PRA may develop Dalmatians, Doberman Pinschers, and
secondary cataracts, some breeds, such as the Labrador Retrievers. Despite this, cataracts
Labrador Retriever, American Cocker have not been described in those animals,
Spaniel, and Miniature and Toy Poodle, have probably because, unlike the disease in
been suggested to most frequently develop humans, serum copper levels are generally
PRA-­induced cataracts. The reported inci- normal, or only transiently elevated during
dence of PRA-­induced cataracts varies hemolytic crises, and also perhaps owing to
between 12.4% (50/404 dogs with cataracts) the relatively short life span of severely
and 27% (66/244). affected dogs.
Cataract formation has also been associated
with other intraocular conditions such as uvei- Cataracts Associated with Metabolic Systemic
tis, glaucoma, and primary lens luxation (PLL). Diseases
Uveitis may have different mechanisms of cat- Inborn Metabolic Diseases A single case report
aractogenesis; among those, posterior syne- of bilateral cataracts, keratitis, and small globes
chia, capsular deposition of inflammatory (possible microphthalmia) associated with
cells, and abnormal lens metabolism associ- congenital tyrosinemia in a German Shepherd
ated with diffusion of toxins into the lens is reported. Ehlers–Danlos syndrome, a con-
should be considered. genital inherited connective tissue disease, has
­Embryonic Vascular Abnormalitie  445

(a)
A

(b) (c)

Figure 12.12 (a) Typical appearance of a mature diabetic cataract. Note the intumescent appearance, the
separation of the fibers, and formation of a cleft along the anterior Y-­suture. (b) Incipient, equatorial
cataracts in a dog with diabetes mellitus. (c) Note lens vacuoles at the equator area characteristic of early
cataractous changes.

been associated with bilateral cataract and lens bilaterally symmetric complete cataract for-
luxation in a dog. Congenital lysosomal stor- mation in dogs, from well-­characterized
age diseases have been rarely associated with alterations in lens metabolic pathways. In
cataracts in dogs. normoglycemic dogs, glucose is primarily
phosphorylated to glucose 6-­phosphate by
Diabetes Mellitus Diabetes mellitus is the hexokinase to enter the glycolytic and pen-
most common cause of metabolic cataracts in tose phosphate pathways. With hyperglyce-
the dog, and the second in number of affected mia, high glucose 6-­phosphate levels inhibit
dogs presented for cataract surgery. Cataracts hexokinase activity to prevent excess produc-
are one of the most prevalent and important tion of lactate. In addition, activity of the
complications of the disease. A study evalu- enzyme aldose reductase is increased, caus-
ating incidence and estimated median time ing shunting toward an alternate energy
to cataract formation in 200 dogs found that metabolism, the sorbitol pathway.
half of the population had developed cata- Accumulation of sorbitol (a polyol or sugar
racts by the 170th day after diagnosis of dia- alcohol) also results, which does not readily
betes mellitus, while 75% and 80% of the diffuse across the lens capsule. Water from
population developed cataracts by 370 and the aqueous humor is imbibed into the lens
470 days, respectively. The disease is com- due to osmotic forces, causing lens architec-
monly associated with rapidly developing, tural changes, including fiber swelling and
446 Canine Cataracts, Lens Luxations, and Surgery

rupture, vacuole formation, and clinically essentials amino acids or an excess of particu-
evident cataract. lar sugars, have been observed in different ani-
Typical early clinical findings in diabetic mal species, with the specific amino acid
cataracts include equatorial vacuoles that pro- implicated varying from species to species. It
gress rapidly (few weeks to months) to a has been postulated that a deficiency of the
mature markedly intumescent cataract with essential amino acids arginine and phenylala-
broad and clearly visible suture lines (“water-­ nine produces cataracts in dog, cat, and wolf
cleft” formation) (Figure 12.12a–c). The early puppies raised on commercial, as well as
presentation of cataracts is rarely reported in experimentally produced, milk replacers.
naturally occurring diabetes mellitus, probably
owing to the rapid onset and progression of Traumatic Cataracts
cataract or to the fact that equatorial vacuole Physical injuries to the eye can be a serious
changes may sometime dissipate following threat, potentially causing devastating damage
insulin therapy. Unfortunately, substantial cat- to the lens and, consequently, to the eye.
aractous changes with canine diabetes are not Traumatic lens injuries can be classified into
reversible with control of hyperglycemia. blunt trauma, sharp penetrating trauma, or
Canine diabetic cataracts are often so rapidly intraocular foreign body penetration. Mild blunt
progressive and osmotically active that intu- injury to the globe rarely causes injury to the
mescence of the lens and phacolytic uveitis lens. Conversely, moderate force blunt injury
commonly ensues. Spontaneous lens capsule may result in cataracts and posterior displace-
rupture, usually equatorial, and subsequent ment of the iris, causing pigment imprinting
varying degrees of phacoclastic uveitis have also on the anterior lens capsule in a fashion ring,
been identified in dogs with diabetic cataracts. commonly known as “Vossius ring.” Blunt
Phacomorphic glaucoma is one of the possible trauma-­induced cataracts result from the coup
clinical scenarios, induced by the large intumes- and contrecoup ocular compressive forces,
cent lens and the shallow anterior chamber. The causing damage to the lens epithelia, and rup-
success of cataract surgery in diabetic dogs is ture and disruption of spacing of lens fiber
similar to the other canine primary cataracts. membranes in the underlying cortex. Variable
degrees of subcapsular cataract formation, gen-
Cataracts Associated with Infectious erally adjacent to the site of injury in the ante-
Diseases Infectious diseases are rarely rior superficial cortex, may ensue.
reported to directly induce cataract formation In sharp trauma-­induced cataract, anterior
in the dog, with most cases secondary to ante- lens capsule disruption is seen most commonly
rior uveitis. Encephalitozoon cuniculi, proto- in young animals from cat claw wounds,
zoan parasite of rabbits, has been described as although a variety of other sources of penetrat-
cataractogenic in rabbits, cats, and dogs. ing injury are possible. Penetrating ocular
Affected dogs showed positive serum antibody injury that perforates the anterior lens capsule
titers against E. cuniculi, and the two that would be expected to invariably cause focal to
underwent cataract removal showed positive diffuse cataract formation, whose size and
polymerase chain reaction (PCR) of the lens severity depend mainly on three factors. The
material. In addition, Aspergillus spp. panoph- first one is the size of the capsular rent, where
thalmitis with intralenticular invasion and lacerations less than 1.5 mm long are associated
cataract has been reported in two dogs. with small focal nonprogressive cataract (and
are self-­sealing), while larger rents often cause
Cataracts Associated with Dietary Deficiencies progressive opacification of the lens and, in the
Nutritional cataracts, resulting from a neona- dog, may be associated with severe phacoclastic
tal deficiency of certain vitamins and uveitis, which results in vision threatening
­Embryonic Vascular Abnormalitie  447

sequel. Conversely, there are some descriptions Visual Consequences of Cataracts


of larger rents that sealed spontaneously with-
There are no reports establishing the conse-
out clinically relevant consequences.
quences of cataracts on vision in dogs. Visual
In foreign body-­induced cataract, lens pene-
deficits vary greatly depending on the severity
tration with a metallic foreign body would be
and location of the cataract, and pupillary size.
expected to result in at least a focal cataract and,
Often, clinically apparent changes in behavior
more commonly, diffuse opacification from sub-
associated with diminished vision go unno-
stantial disruption of fiber cells and lens metab-
ticed until the cataract is 40–50% complete,
olism. The effect of intraocular metallic foreign
and usually not unless both lenses are affected.
bodies not penetrating the lens but within the
Axial cataract would be expected to be associ-
eye is dependent on inertness, position, compo-
ated with earlier and more profound visual
sition, and size of the foreign body. Most shot
deficits (especially with miosis). Interestingly,
pellets are composed of lead, which are usually
those dogs are reported to have more visual
sterile due to high-­velocity entry, and are sur-
difficulties in daylight versus dim lighting
prisingly well tolerated by the globe, as they are
(perhaps from a larger pupillary diameter in
usually covered with an insoluble carbonate that
dim light).
prevents diffusion of chemical reactivity.
Complete, dense cataracts are associated
Lead shot retained within the globe but that
with total loss of visual discrimination and
did not perforate the lens capsule might not be
motion detection but are not necessarily
expected to de facto cause cataract. Gold, silver,
expected to cause total loss of the ability to dis-
glass, and rubber are also relatively inert
criminate photopic from scotopic lighting con-
within the eye. Conversely, copper, zinc, iron,
ditions, being associated with positive dazzle
and brass foreign bodies have moderate oxidiz-
and pupillary light reflexes.
ing potential and often cause panophthalmitis,
and iron and steel are most damaging, causing
severe inflammatory reaction and secondary Complication of Untreated
cataract (siderosis lentis). Intralenticular iron Cataracts in Dogs
foreign bodies cause siderotic deposition, When cataracts are diagnosed but cataract sur-
resulting in slowly progressive, focal red-­ gery is not performed, many canine cataracts
brown or rusty-­appearing lens opacities. will continue to progress, and often result in
intraocular problems such as LIU, glaucoma,
Medical Treatment of Cataracts lens luxation/subluxation, vitreal degenera-
tion, and retinal detachment. Spontaneous
Despite the current availability of some thera- resorption of cataractous lens material occurs
peutic agents that claim to prevent or delay most frequently in dogs less than six years of
cataracts in different species, the only effective age. In those animals, cataract reabsorption
current treatment, once cataract has been diag- may lead, in some cases, to improved vision,
nosed, is the surgical removal of the lens by although the animal is rendered permanently
phacoemulsification and IOL implantation. In hyperopic.
fact, medical therapy may actually decrease
the chance for vision return by allowing the
Lens-­Induced Uveitis
untreated lens-­induced uveitis (LIU) to cause
further damage. In the early stages of cataract, LIU is an inflammatory response of the uvea to
especially if vision is not impaired, the use of lens proteins. Lens material may induce uveitis
mydriatics may allow the animal to see around by two different well-­known mechanisms:
the opacities, providing functional vision until leakage of soluble lens proteins through an
the lens is totally opaque. intact capsule (phacolytic uveitis) or direct
448 Canine Cataracts, Lens Luxations, and Surgery

extrusion of lens content into the anterior


chamber due to capsule disruption (phacoclas-
tic uveitis). Phacolytic uveitis is usually a
chronic condition, characterized by a mild
unspecific lymphocytic–plasmacytic uveitis
that may display scleral injection, mild to mod-
erate ocular discomfort, mild aqueous flare,
and, eventually, darkening of the iris. In addi-
tion, the pupil is usually slightly miotic and
the intraocular pressure (IOP) moderately
reduced. The condition has been described to
accompany both cataract formation and Figure 12.13 Lens sclerosis in a 10-­year-­old
resorption, being usually milder when accom- mixed dog, seen with diffuse illumination. Note the
panying cataract formation. scattering of light induced by nuclear fibers.
In fact, fluorophotometric studies, D-­dimer
detection (a fibrin degradation product) and in the lens nucleus. Dehydration and conden-
prostaglandin E2 concentration in aqueous sation of old nuclear fibers induce light
humor of dogs with cataracts of different ­scattering and thus reduces transparency
degrees of maturation, suggest that a blood– (Figure 12.13). These changes are known as
aqueous barrier breakdown might be present nuclear or lenticular sclerosis and are a con-
in all the eyes with cataract, regardless of sistent finding in dogs greater than seven years
degree of maturity. However, more clinically of age, although transmission of wavelengths
relevant uveitis may be present when hyper- in the UV-­B/UV-­A and visible ranges starts
mature cataract develops. It is worth noting to diminish from four to six years. Indeed,
that phacolytic uveitis may cause a reduction the prevalence of nuclear sclerosis has been
in electroretinogram parameters including a reported as high as 50% in dogs aged
reduction in b-­wave amplitudes and b/a 9.6 ± 2.6 years.
wave ratio.
Unfortunately, the common occurrence of
Lens Luxation
phacolytic uveitis and hypermature cataracts
in dogs may be a diagnostic challenge in distin- The lens is surrounded by three anatomical
guishing primary cataracts from those occur- landmarks: (i) anteriorly, by the posterior sur-
ring secondary to inflammation. Clinical face of the iris, (ii) posteriorly, by the vitreous
history, signalment, anatomical location, and that has rather firm hyaloid-­capsular attach-
the typical mild nature of phacolytic uveitis are ments, and (iii) equatorially, by the zonules,
useful distinguishing features. With LIU pre- which are elastic filamentous structures that
sent with most, if not all, canine eyes with cat- extend from both the anterior and posterior
aracts, selection of candidates for cataract equatorial capsule, to blend with the internal
surgery has shifted from mature or hyperma- limiting membrane of the nonpigmented cili-
ture to beginning mature or even immature ary body epithelium.
(usually blind with miosis). Dislocation of the lens from its normal posi-
tion within the patellar fossa is referred to as
subluxation (partial dislocation) or luxation
Nuclear Sclerosis
(total dislocation) and is related to a pathologi-
The lens continues to grow throughout life, cal alteration in the ciliary zonules from
with progressive lens fiber formation and abnormal development, degeneration, rup-
internal compression of older fibers, especially ture, tearing, or a combination of these factors.
­Embryonic Vascular Abnormalitie  449

Subluxation is the early stage in the process of Primary Lens Luxation


luxation, in which there is partial breakdown PLL is not a disease of the lens itself, but rather
or degeneration of the zonules, with the result an inherited deterioration of the lens suspen-
that the lens, although slightly mobile, remains sory apparatus, the zonule, which is a system
in its grossly normal position. of fibers that suspend the lens from the ciliary
Similar to canine cataracts, lens luxation has body, maintaining it within the visual axis and
been classified according to different schemes, in contact with the anterior surface of the vit-
most commonly based on its etiology (congeni- reous body (Table 12.5). In dogs affected with
tal, primary, and secondary), and the segment PLL, ultrastructural abnormalities of the zonu-
to which the lens has been displaced (anterior lar fibers are already evident at 20 months of
or posterior). age. Lens luxation typically occurs when the

Table 12.5 Canine breeds affected with PLL mode of inheritance and genetic test available.

Canine breeds affected by PLL Inheritance Genetic tests available

American Eskimo Dog Autosomal recessive ADAMTS17


American Hairless Terrier Not defined No
Australian Cattle Dog Autosomal recessive ADAMTS17
Australian Terrier Not defined No
Border Collie Autosomal recessive No
Brittany Not defined No
Brussels Griffon Not defined No
Bull Terrier (Miniature and Autosomal recessive ADAMTS17
Standard)
Cairn Terrier Not defined No
Cardigan Welsh Corgi Not defined No
Chihuahua Not defined No
Chinese Crested Dog Autosomal recessive ADAMTS17
Chow Chow Not defined No
Dutch Partridge Dog Not defined No
English Pointer Not defined No
Brittany Spaniel Not defined No
French Spaniel Not defined No
Fox Terrier (Wire, Toy, and Not defined ADAMTS17
Smooth Haired)
French Bulldog Not defined No
German Pinscher Not defined No
Grand Bleu de Gascogne Not defined No
Greyhound Not defined No
Grand and Petit Not defined No
Basset Griffon Vendéen
Italian Greyhound Not defined No
Jack Russell Terrier Autosomal recessive ADAMTS17
(Continued)
450 Canine Cataracts, Lens Luxations, and Surgery

Table 12.5 (Continued)

Canine breeds affected by PLL Inheritance Genetic tests available

Jagdterrier Autosomal recessive ADAMTS17


Lakeland Terrier Autosomal recessive ADAMTS17
Lancaster Heeler Autosomal recessive ADAMTS17
Leonberger Not defined No
Manchester Terrier Not defined No
Norfolk Terrier Not defined ADAMTS17
Norwich Terrier Not defined ADAMTS17
Parson Russell Terrier Autosomal recessive ADAMTS17
Patterdale Terrier Not defined ADAMTS17
Pekingese Not defined No
Pyrenean Shepherd Not defined No
Rat Terrier Not defined ADAMTS17
Russell Terrier Not defined ADAMTS17
Scottish Terrier Not defined ??
Sealyham Terrier Autosomal recessive ADAMTS17
Shar-­Pei Autosomal recessive ADAMTS17
Siberian Husky Not defined No
Skye Terrier Not defined No
Tibetan spaniel Autosomal recessive No
Tibetan Terrier Autosomal recessive ADAMTS17
Volpino Italiano Autosomal recessive ADAMTS17
Welsh Terrier Not defined ADAMTS17
West Highland White Terrier Not defined No
Yorkshire Terrier Autosomal recessive ADAMTS17

dogs are three to eight years old as a result of Box 12.2 Clinical Findings in Lens
progressive degeneration and breakdown of Luxations
the zonules.
●● Increased lens mobility (phacodonesis or
tremor of the lens with globe movement)
Presentation and Clinical Signs of Primary Lens
●● Iridodonesis (iridal movements due to
Luxation
lack of lens stability)
PLL most commonly manifests as an acute
Asymmetry in the anterior chamber
emergency, although onset and clinical find-
●●

depth (usually due to lens tilting)


ings vary depending on the severity and loca-
Appearance of a lens equator and ciliary
tion of the dislocated lens (Box 12.2). Its
●●

zonule remnants (aphakic crescent)


presentation is mostly bilateral, although not
Degenerative white vitreal strands displaced
necessarily simultaneous. Primary lens dis-
●●

or prolapsed into the anterior chamber


placement is documented most commonly in
Lens luxation into the anterior chamber
3–8-­year-­old dog with the lower mean age
●●

or vitreous
reported to be 4.5 years in terriers and terrier
­Embryonic Vascular Abnormalitie  451

(a) (b)

Figure 12.14 (a) Lens subluxation viewed with optical section from left to right. The margin of the
lens is visible as an aphakic crescent, and early cortical cataract formation is present. Vitreal fibers that
have displaced into the anterior chamber are seen as fin strands with increased relucency. (b) Lens
instability in eight-­year-­old mixed breed dog. Note the presence of pigmented vitreous in the
anterior chamber.

crosses (the terrier breeds with lens luxation (Figure 12.14a and b). Individual subluxated
tend to younger). However, some variation in lenses left without treatment have remained
the age of onset may exists. In primary lens subluxated for up to four years.
instability, an increased mobility of the lens, Pathophysiological changes accompanying
manifested as phacodonesis (lens trembling) lens subluxation or anterior luxation often cul-
or iridodonesis (iris trembling), can be seen as minate in secondary glaucoma from several pos-
early clinical manifestations. A change or sible mechanisms (Figure 12.15). The first one is
asymmetry in the depth of the anterior cham- the occlusion of aqueous humor flow from the
ber may also be evident in early stages, as well posterior chamber through the pupil due to
as the margin of the lens visible if pharmaco- the anterior shift in the lens and/or vitreal face,
logical mydriasis is induced. An inherent causing diversion of aqueous humor posterior
reduction in zonular tension would explain the
tendency for the lens of an affected eye to
assume a slightly more globoid form than nor-
mal, therefore allowing the visualization of the
lens periphery when full dilation. Degenerative
vitreal strands, which appear by biomicros-
copy as fine wispy fibers with increased relu-
cency, are often displaced or prolapsed into the
anterior chamber and may be apparent with
gonioscopy in the iridocorneal angle.
Subluxated lens are generally associated
with signs of mild uveitis, presumably related
to an abnormal physical contact of the lens jos-
tling against the uveal tissue. In the majority of
Figure 12.15 Primary anterior lens luxation in a
cases, the subluxation progresses to luxation
five-­year-­old dog seen with diffuse illumination.
into the anterior chamber (anterior luxation) Note the lens in the anterior chamber inducing
that tends to show acute clinical signs corneal edema and dyscoria.
452 Canine Cataracts, Lens Luxations, and Surgery

(a) (b)

(c)

Figure 12.16 (a) Age-­related posterior lens luxation in an 11-­year-­old mixed breed dog. Note the aphakic
crescent and the late immature cortical cataract. (b) Posterior lens luxation associated with advanced
primary glaucoma in a dog. Note the Haab’s striae and the irregularly shaped aphakic crescent associated
with hypermature cataract. (c) Posterior lens subluxation associated with chronic cataract in a dog. Note the
dorsal aphakic crescent and the zonular stretching.

to the lens or into the vitreous (pupillary block transient or permanent corneal edema, and
glaucoma). The second reported mechanism is mild anterior uveitis.
associated with the substantial amounts of pro- Posterior luxations are less frequently reported
lapsed vitreous that are often seen in the anterior and show a more chronic onset than anterior
chamber and iridocorneal angle that may PLL (Figure 12.16a–c). These are commonly
theoretically cause mechanical obstruction to seen in old dogs with liquefied vitreous (synere-
aqueous outflow. The last mechanism is the sis). In syneresis-­affected dogs, the absence of
obstruction of the filtration angle due to the posterior physical restraint and the disruption of
presence of the lens in the anterior chamber. the anterior hyaloid face predispose posterior
In three retrospective studies on dogs with displacement of the lens. In those cases, lens
secondary glaucoma, lens luxation was the sec- luxations tend to occur ventrally toward the vit-
ond most common cause, with incidences of reous space, lying adjacent to or on the ventral
12% (779/9695), 15.2% (24/156), and 26.2% retina and/or pars plana. Complete posterior
(49/217). Other secondary pathophysiological luxation is more innocuous than anterior luxa-
changes seen in anterior luxated lens include tion, and the complications of glaucoma, uveitis,
­Embryonic Vascular Abnormalitie  453

or corneal edema are less prevalent. As syneresis developing the condition compared to dogs
is necessary for the lens to fully luxate posteri- that are homozygous for the wild-­type allele.
orly, mechanical obstruction glaucoma by vitre-
ous strands is uncommon. Secondary Lens Luxation
Lens dislocation can appear secondary to dam-
Breed Predisposition, Affected Genes, Genetic Tests, age to the suspensory apparatus of the lens,
and Mode of Inheritance which can arise from senility, trauma, or be
The number of canine breeds predisposed to associated with ocular conditions such as
this abnormality has increased significantly, chronic glaucoma, chronic uveitis, mature/
nowadays being identified in nearly 50 differ- hypermature cataract, or intraocular tumors.
ent breeds, including terriers and nonterrier When compared to PLL, secondary lens luxa-
dogs. ADAMTS17, one of the 29 known mam- tion does not usually have such an acute pres-
malian members of the ADAMTS family of entation and the direction of displacement is
gene encoding proteins, interacts with fibril- variable. In a retrospective study of 134 dogs
lin-­1 in some way to contribute to both the with lens luxation, 36% dogs presented with
structural and regulatory roles of zonular secondary lens luxation. The most common
microfibrils. In addition, other proteins of the causes for this condition were glaucoma (58%),
same family, ADAMTS4 and ADAMTS10, have cataract (19%), and trauma (17%).
also been suggested to be involved with forma-
tion or maintenance of the zonule. Age-­Related Lens Luxation
A mutation involving a nucleotide substitu- Lens displacement, in the absence of other ocu-
tion in ADAMTS17 was initially associated lar disease, may also occur in older-­aged dogs
with PLL in Miniature Bull Terriers, Lancashire (>10 years of age), comprising various terrier
Heelers, and Jack Russell Terriers. Subsequently, and nonterrier breeds. Senescent lens displace-
the mutation was identified in other additional ment in terrier breeds may represent a late-­onset
15 canine breeds, mostly terriers or breeds presentation of PLL. Older-­aged dogs presuma-
with terrier coancestry. In addition, a recent bly develop lens displacement from undefined
study reported ADAMTS17 mutation inducing mechanisms that may reflect age-­related degen-
PLL and primary open-­angle glaucoma in erative process occurring in the zonules and/or
Chinese Shar-­Pei dogs. Mutations in anterior vitreous and vitreal base. Fibrillin-­1 is
ADAMTS17 in humans are associated with produced by the nonpigmented epithelium of
short stature and ocular anomalies, and the the ciliary body throughout life, although the
preponderance of PLL in terrier and other rate of production declines with age.
breeds with a miniature or short stature has
led to speculation that selection for this body Traumatic Lens Luxation
phenotype may have inadvertently led to Although lens luxation was historically sug-
­selection of this mutation. gested to commonly result from blunt trauma
Surprisingly, although PLL is suspected to be to the globe, this premise has not been sub-
inherited in more than 50 canine breeds, its stantiated with retrospective case studies.
mode of inheritance has been suggested in Blunt trauma with force sufficient to cause
very few, where it is considered as a simple lens displacement generally would result in
autosomal recessive trait. The great majority of collateral and profound ocular injury.
PLL-­affected dogs are homozygous for the
mutation, but a small minority are heterozy- Glaucoma and Secondary Lens Luxation
gous (5%), leading to speculation that carriers, Lens displacement may be associated with
of some breeds at least (e.g., Miniature Bull chronic glaucoma, in which the high and sus-
Terrier), might be at increased risk of tained pressure will lead ultimately to
454 Canine Cataracts, Lens Luxations, and Surgery

stretching of the ocular tunics and enlarge- relucency highlighted by the aqueous flare.
ment of the globe (hydrophthalmos or Gonioscopy should also routinely be performed,
buphthalmia). As the eye enlarges, the physi- especially if ocular hypertension is documented,
cal stretching of the zonular fibers will eventu- in both the affected (if possible) and unaffected
ally bring about their rupture, most commonly eyes, to attempt to determine any causal rela-
leading to subluxation, but in some cases, lib- tionship. In addition, vitreous strands may also
erating the lens allowing it to move freely. This be obliterating the iridocorneal angle in cases of
may lead to speculate that, in some cases, ocu- severe vitreous displacement.
lar hypertension may precede and actually
cause breakdown of the zonules in some cases Treatment Approaches for PLL
through an undefined mechanism unrelated to Treatment strategy differs greatly between pri-
a change in globe size. Subclinical changes in mary and secondary lens luxations. It is widely
globe size with primary glaucoma may theo- accepted that gold-­standard treatment for pri-
retically account for some of these cases. mary anterior dislocated lenses is surgical
removal by two-­handed phacoemulsification
Cataract-­Induced Lens Luxation (with removal of the lens capsular bag) or
Lens luxation occasionally results from intracapsular lens extraction (ICLE), with or
advanced and chronic cataractogenesis: (i) without sulcus IOL placement.
Lens luxation can be theoretically associated Anteriorly luxated lens may occasionally be
with chronic shrinking of the lens and second- successfully manipulated into the posterior
ary zonular stretching and breakage, or with chamber by transcorneal repositioning or
the increased weight of a mature/hypermature reduction (“couching-­like” technique), a
cataractous lens; and (ii) a zonulolytic effect change in head position, or by directing the
from any associated lens-­induced inflamma- lens posteriorly with a fine hypodermic needle
tion may also contribute. inserted into the anterior chamber. Couching,
as originally described, has not been previ-
Diagnostic Approach and Medical ously reported as therapy for lens instability in
Treatment of Lens Luxation dogs, but a very similar technique, called
Diagnostic Approach for Lens Luxation. “transcorneal reduction,” was successfully
Clinical evaluation of the patient with lens described for the treatment of anterior lens
luxation should include critical ophthalmic luxation in dogs in 2014. The authors per-
examination for any primary cause. Because formed the procedure in sedated or awake ani-
PLL is almost invariably a bilateral disorder, mals positioned in dorsal recumbency with
the contralateral eye should be evaluated ventroflexion of the neck. When combined
biomicroscopically following mydriasis for evi- with long-­term topical 0.005% latanoprost
dence of lens instability, or signs compatible administration every 12 h, transcorneal reduc-
with subluxation. tion provides a nonsurgical alternative to ICLE
Diagnosis of lens luxation is generally straight- or enucleation (nonvisual eyes). This tech-
forward. Biomicroscopy is the gold-­standard nique should be considered in dogs with ques-
diagnostic technique for this purpose. Diffuse tionable vision or at high risk for general
illumination of the eye may reveal phacodonesis anesthesia; however, dogs are still at risk for
or iridodonesis. In subluxated lens, only the very reluxation, retinal detachment, and glaucoma.
peripheral part of the reflected slit-­lamp beam
on the lens may be missing, highlighting an Treatment Approaches for Secondary Lens
aphakic crescent. In lens instability, subluxation Luxations
and posterior luxation, vitreal strands, may Secondary luxations are treated according to
appear as fine wispy fibers with increased the triggering condition, seldom necessitating
­Patient Selectio  455

surgical lens removal. Conversely to PLL, the Signalment in Patient Selection


fellow eye will not be at risk if the primary
1) Age: The age of the dog is important in
cause was trauma, unilateral cataract, or
decisions about whether to perform sur-
tumor; however, if primary glaucoma is pre-
gery or not.
sent, the fellow eye might be predisposed and
2) The breed of dog can also determine intra-
may need to be addressed accordingly.
operative and postoperative complications.
The Labrador Retriever has a significantly
Section II: Cataract Surgery increased risk (33%) of postoperative ocu-
lar hypertension (POH) following cataract
Cataract surgery is the signature procedure surgery compared to 18% in
performed by veterinary ophthalmologists. non-­Labradors.
Marked improvements in cataract surgery 3) General behavior: An aggressive dog is not
started in the late 1960s, including rapid evolu- a good candidate as postoperative therapy
tion of surgical techniques, reduction of ocular may be a major problem.
pharmacology, and success rates of restoring 4) Additional diagnostics used by the veteri-
vision approaching ≥90%. In this section, an nary ophthalmologist in patient selection
overview of cataract surgery as performed cur- include Schirmer tear test 1, gonioscopy,
rently is presented. Cataract surgery requires tonometry, and B-­scan US (Figure 12.17a
considerable training and instrumentation. and b), as well as quantitative electroreti-
nography. They should always be performed
when the fundus cannot be examined clini-
­Patient Selection cally. Both photopic and scotopic values
should be determined.
Selection of the appropriate patient for cata- 5) Other preoperative conditions that usually
ract surgery is perhaps most important stand- require successful medical therapy before
ard in determining the eventual visual patient. considerations for cataract surgery include
Cataract surgery is an elective procedure in the spontaneous lens capsule rupture (usually
majority of cases and many animals can adapt in diabetic dogs); uncontrolled lens-­
well to vision loss. Surgery is indicted in ani- induced uveitis, elevated IOP, and kerato-
mals when impairment is associated with the conjunctivitis sicca.
cataract or in animals with a progressive cata-
ract for which vision loss is imminent. Decision for Surgery, Timing, Prognosis,
and Outcome
The decision to perform cataract surgery at all
History, Systemic Evaluation,
and, in the case of bilateral cataracts, whether
and Ophthalmic Examination
to perform surgery on one or both eyes must
The thorough ophthalmic and systemic history now be made. These decisions are made after
is indicated. The visual history should identify careful communications between the surgeon
when the cataract was first observed and when and owner. With the use of more advanced
vision changes were noted. Vision loss prior to phacoemulsification equipment and tech-
the onset of the cataract or a history suggestive niques, both short-­term and long-­term out-
of nyctalopia are concerning. The ophthalmic comes for canine cataract surgery continue to
examination is of paramount importance. improve. Emmetropia and a clear visual axis
Maze testing in photopic and scotopic condi- are expected. Successful outcomes range from
tions can help determine the degree of visual 70% to 95%, but depend on length of follow-­up,
compromise. stage of the cataract, and diligent postoperative
456 Canine Cataracts, Lens Luxations, and Surgery

(a) (b)

Figure 12.17 (a) An 11-­MHz ultrasound using a linear probe demonstrating a complete retinal
detachment posterior to an advanced hypermature, cataractous lens. (b) An 11-­MHz ultrasound using a
linear probe and color Doppler demonstrating a nonpatent persistent HA posterior to the cataractous lens.
Significant posterior lenticonus is also present.

care. Retrospective studies have documented a Failures included a painful globe, glaucoma,
higher success rate with immature cataracts lens luxation, enucleation/evisceration, and,
compared with those of mature and hyperma- in surgical eyes, loss of vision.
ture cataracts. Retinal detachment, secondary
glaucoma, uveitis, and other complications Perioperative Therapy
may occur days to years following cataract Cataract surgery is commonly facilitated by
surgery. the use of medications before, during, and
Diabetic dogs have similar postsurgical after the surgical procedure. These medica-
­outcomes to nondiabetic dogs, although tions may include antibiotics, corticosteroids,
these eyes are more likely to develop compli- nonsteroidal anti-­inflammatory drugs (NSAIDs),
cating postoperative uveitis that requires and antiglaucoma medications to modulate
more aggressive and prolonged topical anti-­ IOP. Critical pre-­ and intraoperative goals
inflammatory therapy. include mydriasis, suppression of ocular
If the owner elects not to perform cataract inflammation, minimization of ocular micro-
surgery or performs cataract surgery on only bial flora, and akinesia and central fixation of
one eye, the patient must still be monitored in the globe. Postoperative goals include minimi-
the long term for lens-­induced complications zation of inflammation and synechiae forma-
such as LIU, secondary glaucoma, retinal tion, control of IOP, and continued monitoring
detachment, and lens luxation. Possible medi- for signs of infection.
cal and/or surgical intervention in these eyes
may negate any cost savings of performing Mydriasis
cataract surgery on only one eye. In a study of Rapid, adequate, stable mydriasis of limited
44 dogs, eyes receiving no treatment had fail- duration is crucial in cataract surgery. Topical
ure rates 65 and 255 times greater than medi- mydriatics are routinely used and include
cally and surgically managed eyes, respectively, anticholinergic agents, sympathomimetic
indicating that animals that do not undergo agents, or both. The most common topically
phacoemulsification should be managed with applied drugs include 1% atropine, tropicamide,
topical anti-­inflammatories in the long term. and 2.5–10% phenylephrine. While only a
­Spontaneous Lens Capsule Ruptur  457

single dose is generally required 1–2 h prior to study, 57 of 398 samples tested positive for
surgery, some surgeons will choose to use it ­bacterial DNA, but this was not associated
more frequently (e.g., q 30 min for 2 h) or for an with significant postoperative complications.
even longer period of time preoperatively. For Patients over 13 years of age were more likely
atropine, this is not necessary, nor advised to be positive. In veterinary patients, broad-­
because of its effect of reducing tear production spectrum bactericidal topical antibiotics are
in both eyes for several hours or more. administered every 6 h beginning 12–24 h prior
to surgery. Topical povidone–iodine solution is
Anti-­inflammatories routinely used at induction to cleanse the eye
Both corticosteroids and NSAIDs are used and surrounding adnexa.
perioperatively in dogs. They can be adminis-
tered systemically, topically, or intracamerally. Akinesia, Analgesia, and Anesthesia
Topical corticosteroids are used every 6 h start- Most cataract surgeons choose a protocol of
ing at least 12–24 h prior to surgery, and longer general anesthesia using standard premedica-
if LIU is present. The topical corticosteroid tion followed by inhalation anesthesia. To facil-
should be potent and have good corneal pene- itate globe position and decrease external forces
tration. One percent prednisolone acetate is on the globe caused by extraocular muscle
the corticosteroid of choice or 0.1% dexameth- contraction (i.e., akinesia), systemic adminis­
asone can be used as an alternative. tration of a nondepolarizing neuromuscular
NSAIDs have been proven to be a safe and blocking agent to paralyze the patient is rou-
effective alternative to corticosteroids in the tine. These neuromuscular blocking agents, in
topical prevention and management of nonin- addition to akinesia, cause paralysis of respira-
fectious ocular inflammations. NSAIDs both tory muscles, which requires positive-­pressure
suppress inflammation and prevent miosis ventilation and close monitoring of carbon
during surgery. Along with corticosteroids, dioxide levels and respiratory function. These
topical NSAIDs can be administered every agents can be reversed with neostigmine.
30 min starting 1–2 h preoperatively, and a sys-
temic NSAID such as flunixin meglumine
(0.5–1.0 mg/kg i.v.) or carprofen (2.2 mg/kg ­ pontaneous Lens
S
s.q.) can also be administered at or prior to Capsule Rupture
induction, respectively, instead of dexametha-
sone. Topical available NSAIDs include brom- Spontaneous lens capsule rupture is a compli-
fenac, diclofenac, flurbiprofen, ketorolac, and cation that occurs most commonly in associa-
nepafenac. tion with the osmotic component of diabetic
cataracts and rapid intumescence of the lens.
Antibiotic Prophylaxis Most ruptures (>95%) occur equatorially, but
Postoperative endoph­thalmitis is a devastat- posterior capsule ruptures are also reported.
ing inflammatory condition of the eye pre- Clinical signs include an asymmetrically
sumed to be due to an infectious process from shallow anterior chamber, anterior movement
bacteria. Bacteria gain access into the eye dur- of the iris and lens, posterior synechia in the
ing surgery or postoperatively via the incision. location of the rupture, visibility of the edge of
Multiple measures for preventing endophthal- the capsule, signs of anterior uveitis, and sec-
mitis following cataract surgery have been ondary glaucoma (Figures 12.18a and b,
studied. and 12.19a and b). The anterior uveitis is the
Bacterial contamination of the anterior result of phacoanaphylaxis or phacoclastic
chamber has been shown to be a common uveitis. The secondary glaucoma can be caused
occurrence in canine cataract surgery. In one acutely by an angle-­crowding mechanism
458 Canine Cataracts, Lens Luxations, and Surgery

(a) (b)

Figure 12.18 The preoperative right (a) and left (b) eye of a diabetic dog with spontaneous lens capsule
rupture OU. The rupture extends from 12 o’clock to 6 o’clock OS but can only be visualized from 1 to 2 o’clock
due to posterior synechia of the iris in the other clock hours. The rupture extends from 6 o’clock to
12 o’clock OD. The presence of keratic precipitates can be appreciated OD ventrally. IOLs were not placed
and the dog was left aphakic OU.

(a) (b)

Figure 12.19 Spontaneous equatorial lens capsular rupture extending from 10 o’clock to 6 o’clock. (a) The
exposed lens cortex is visible. (b) The red blood cells can be seen within the capsule tracking along the
lens sutures.

when the iris is moved forward by the lens and cases. Aggressive anti-­inflammatory therapy
also by inflammatory cells. Preoperative glau- combined with possible emergent surgical
coma can be alleviated by surgical removal of intervention is indicated. Postoperatively,
the lens and resolution of angle crowding. long-­term anti-­inflammatory therapy may be
The diagnosis of spontaneous capsule rup- required to control inflammation, but long-­
ture is made preoperatively in over 90% of term visual outcome can be good. Depending
­Spontaneous Lens Capsule Ruptur  459

Aspiration Port

Stroke Length

Irrigation Port

Irrigation Sleeve Hub

Silicone Irrigation Sleeve

Handpiece Body

15°

Aspiration
Line
30°

Irrigation
45° Line
Ultrasonic
Power Line

60°

Figure 12.20 Diagram of a routine phacoemulsification handpiece drawing the aspiration port (needle
opening), one of two irrigation ports in the in the silicone sleeve, aspiration line, irrigation line, and power
cord. The stroke length is the length the needle moves forth and backward in longitudinal
phacoemulsification (Courtesy of Brian Wilson).

on the size of the rupture, an IOL can some- There are five different parameters that the
times still be placed inside the lens capsule, surgeon can control with the phacoemulsifica-
with the haptics directed away from the rup- tion machine: (i) power, (ii) evacuation flow
ture. In some large equatorial ruptures, the rate, (iii) vacuum, (iv) vacuum rise time, and
anterior capsule can be removed while leaving (v) bottle height. These parameters are inter-
the posterior capsule intact. twined. The vibrations of the phaco handpiece
(Figure 12.20) converting electrical energy to
mechanical energy, emulsifying the lens, cre-
Surgical Equipment and Devices
ate the ultrasonic power.
Microsurgical instruments, surgical micro-
scopes, phacoemulsification machines, auto-
Surgical Approach
mated irrigation/aspiration (I/A), and
vitrectomy capabilities are considered the cur- Cataracts can be removed by phacoemulsifica-
rent standard of care. Single-­use instrumenta- tion, extracapsular and intracapsular cataract
tion is preferable over multiuse instruments surgeries. Since the 1980s, phacoemulsifica-
(e.g., cannulas, phaco needles, I/A tips, etc.) to tion has become the universal standard for
minimize the risk of endophthalmitis or toxic veterinary ophthalmologists. There are many
anterior segment syndrome (TASS). variations in the surgery as there are persons
460 Canine Cataracts, Lens Luxations, and Surgery

performing the surgery. A lateral canthotomy Phacoemulsification Techniques


is indicated to increase exposure and to relieve Phacoemulsification, automated I/A, and
globe-­deforming forces caused by the eyelids implantation of an IOL to restore emmetropia
and eyelid speculum. It may be unnecessary in are the universal standard of care for cataract
most brachycephalic breeds and can increase surgery in veterinary ophthalmology. At all
the postoperative discomfort. times, the surgeon must look to maximize effi-
An ideal incision should provide adequate ciency, and minimize time and trauma inside
exposure for phacoemulsification and IOL the eye. The four main goals of any cataract
implantation, minimize postoperative astig- surgery are to break the nucleus into frag-
matism, form a watertight seal when closed, ments, emulsify those fragments, aspirate
and have negligible scarring (Figure 12.21a). those fragments, and control surge. These can
The location, number, and length of the cor- be accomplished using a variety of techniques
neal incisions needed are dependent on the that are described in the human and veterinary
technique being performed. Most veterinary literature (Figure 12.21f and g).
ophthalmologists perform biplane two-­step
groove corneal incisions, which serve to facili-
Intraocular Lens
tate a watertight closure. Foldable IOLs require
smaller incisions in contrast to rigid The placement of a 41D IOL and return to
poly(methyl methacrylate) (PMMA) lenses. If “emmetropia” following phacoemulsification
a PMMA IOL is to be implanted, the wound is considered current standard of care in the
will subsequently be enlarged to 7.0–8.0 mm. dog at this time (Figure 12.21h). PMMA was
Foldable acrylic IOLs and their injection car- the first biomaterial used in the manufacture
tridges only require enlarging the incision and implantation of IOLs in humans. The
to 4.0 mm. most common biomaterials used in IOL con-
The anterior chamber is then entered with struction are divided into two major catego-
an angled keratome in the trough of the ini- ries: acrylic and silicone. Acrylic lenses can be
tial incision to create a two-­plane incision further divided into rigid and foldable IOLs.
(Figure 12.21b). Once the anterior chamber is Rigid IOLs are manufactured from PMMA,
entered, intracameral epinephrine (1: 10 000) and foldable IOLs are manufactured from
can be placed at this time to facilitate mydriasis hydrophilic acrylic (hydrogel) and hydropho-
and vasoconstriction. The width of this entry bic acrylic. Foldable IOLs were developed to
incision is critical and corresponds to the width allow for smaller incisions and silicone was
required by the phacoemulsification needle and replaced with acrylic when it was thought to
infusion sleeve. This ranges from 2.8 to 3.2 mm. cause significant intraocular inflammation,
Following placement of a highly viscid solu- although improved versions of silicone IOLs
tion (viscoelastics) to maintain the anterior do not show this. The material, size, shape,
chamber and protect the corneal endothelium, angulation, and other modifications of the IOL
the center of the anterior capsule of the lens impact the degree of PCOs that occur after sur-
must now be opened in order to gain access to gery. Additional advantages of a foldable IOL
the nucleus and cortex during phacoemulsifica- are a smaller incision, ability to implant an
tion. The continuous curvilinear capsulorhexis IOL in instances of capsular tears, expanding
was developed to provide a consistent, regular, vitreous, and some instances of zonular
and reproducible surgical opening that did not instability.
predispose to radial tears (Figure 12.21c–e). The Both hydrophilic and hydrophobic IOLs are
size of the capsulorhexis should be approxi- available. Implantation of silicone IOLs has
mately 1 mm smaller than the diameter of the also been described in the dog. The average
IOL optic to be implanted. canine lens diameter is approximately 12 mm.
(a) (b)

(c) (d)

(e) (f)

Figure 12.21 (a) An anterior-­limbal incision is made using a #64 Beaver blade such that the anterior edge of
the incision is corneal and the posterior edge scleral. (b) The corneal incision is completed and entry into the
anterior chamber facilitated by the use of an angled keratome. (c) Curved Vannas scissors are used to extend
the initial capsule entry clockwise and then counterclockwise. (d) The anterior lens capsule is torn using Utrata
forceps, folding it over and using shearing and ripping forces to create a continuous circular capsulorhexis. (e)
The correct location to start a tangential cut to enlarge the capsulorhexis (white line) compared to an incorrect
perpendicular location (black line). (f) The phacoemulsification needle is advanced bevel up across the lens
sculpting a groove in the lens (white arrow). The needle is retracted to the starting point, and the area
immediately adjacent to the initial groove is engaged and a second groove is cut and then a third (black lines).
(g) The irrigation tip (A) engages the cortex and then is rolled upward toward the pupillary opening as the
cortex is aspirated. (B) Cortex at the 12 o’clock position should be engaged on either side (11–1 o’clock) and
removed first if possible. (h) A foldable acrylic IOL (Acrivet 60-­V™). The dialing hole is visible in the dorsal
haptic. The right side of the capsulorhexis is not as circular in the area where a ripping force was used to
complete the capsulorhexis. (i) A double continuous sawtooth pattern for corneal wound closure following
phacoemulsification. A superficial corneal ulcer is also present two days postoperatively in a diabetic dog.
462 Canine Cataracts, Lens Luxations, and Surgery

(A) (B) (g)

(h) (i)

Figure 12.21 (Continued)

The haptic lengths are 15–17 mm for single-­ section scissors to a size dependent on the type
piece PMMA IOLs and 12–14 mm for acrylic of IOL and technique used. This is approxi-
IOLs in the dog. Most canine IOL optics are mately 8 mm for a 7-­mm PMMA IOL and
7 mm in diameter with a power of 41 D. Dogs 3.5–4 mm or smaller for foldable acrylic IOLs. To
are 14 D hyperopic, if left aphakic after cata- insert a PMMA IOL, the optic is grasped using
ract surgery. Dialing holes in the optic or hap- IOL forceps (e.g., Shepherd forceps). The haptics
tics, which are designed to facilitate insertion are oriented at 6-­and 12-­o’clock sweeping coun-
and manipulation of the lens, or in certain terclockwise with the IOL forceps passing over
instances to attach sutures for fixation, are the 12-­o’clock haptic to grasp the optic. The IOL
available in some designs. is centered in the visual axis and the haptics
A viscoelastic is placed to distend the capsular should be placed at 3-­and 9-­o’clock positions.
bag and anterior chamber to provide space for Foldable IOLs are implanted using IOL fold-
implantation and maneuvering of the IOL. The ing forceps or an injection cartridge. Every IOL
corneal incision is elongated using corneal company has its own injector system with a
­Spontaneous Lens Capsule Ruptur  463

cartridge either fitted to or free from the including wound dehiscence are uncommon
­injector. Some IOLs come preloaded in the but can occur due to many reasons, including
­cartridge. Using the cartridge minimizes incisional weakness, improperly placed
­iatrogenic trauma and incision size. sutures, spike in IOP, and blunt or self-­trauma.
Ulceration of the cornea can occur postopera-
Viscoelastic Removal tively in the dog. One report had an incidence
of 5.68%. A higher incidence of 13% has been
The decision to remove the viscoelastic at reported in a brachycephalic breed (i.e., Pugs)
the end of surgery is based on the type used within three months of surgery (Figure 12.22).
(i.e., cohesive, dispersive, etc.), preoperative Corneal edema can be a short-­term and/or
gonioscopy/breed concerns, need for space a long-­term postoperative complication of
occupation in the postoperative period (e.g., ­cataract surgery (Figure 12.23). Some loss of
tamponade, posterior capsular tear, etc.), and
manipulation and trauma associated with
removal. Removal can be performed following
placement of the IOL using the automated I/A
system or manual irrigation.
Closure of the corneal incision should result
in a watertight seal with minimal astigmatism.
In veterinary surgery, this is still predominantly
accomplished by suturing. The smallest suture
that is strong enough to ensure a successful clo-
sure and result in minimal suture reaction should
be used and this is typically 8-­0 to 10-­0 nonab-
sorbable polypropylene type or absorbable polyg-
lactin 910 (Vicryl™). Polyglactin 910 comes as a Figure 12.22 A bacterial stromal corneal ulcer in
this diabetic dog six weeks following
monofilament (9-­0), the most commonly used, phacoemulsification. Vascularization from the
or braided (8-­0) size (Figure 12.21i). dorsal limbus has occurred in response to the
ulceration. This ulcer is more likely to leave an
opacity in the visual axis once healed.
Intraoperative Complications
The best way to manage intraoperative compli-
cations is take steps ahead of time to minimize
or avoid their occurrence and be prepared when
a setback occurs. Some intraoperative complica-
tions can be anticipated based on the preopera-
tive examination, including shallow anterior
chamber, anterior capsular fibrosis, vitreous in
the anterior chamber, lens instability, synechiae
formation, spontaneous lens capsule rupture,
lens coloboma, lenticonus, and PHPV/PHTV.

Postoperative Complications of
Phacoemulsification and
IOL Implantation
Figure 12.23 Corneal endothelial degeneration
Postoperative complications can be mini- that progressively worsened over 5 years following
mized by adequate therapy and follow-­up phacoemulsification and IOL implantation in a
examinations. The postoperative complications 10-­year-­old Bichon Frise.
464 Canine Cataracts, Lens Luxations, and Surgery

endothelial cells occurs even in the most in which symptoms more commonly develop
­routine of cataract surgeries. This has been two to seven days postoperatively. The etiology
minimized by the continued revolution of the of TASS includes any substance used during
techniques, viscoelastics, and equipment use. or immediately postoperatively in surgery that
POH is a distinct clinical syndrome charac- causes toxic injury to intraocular tissue.
terized by a transient increase in IOP in the Eyes affected with TASS should be treated
acute postoperative period. By definition, the aggressively with topical and oral anti-­
increase in IOP during POH spontaneously inflammatory therapy. Surgical intervention
decreases or responds to pressure-­lowering (e.g., IOL removal and irrigation of the ante-
drugs and resolves in 24–48 h. POH occurs in rior chamber) is indicated as soon as hypopyon
0–100% of cases with the average incidence is noticed.
around 35%.
Hyphema and/or vitreal hemorrhage can Postoperative Therapy
occur in the immediate postoperative period Topical antibiotics and corticosteroids are
but is relatively uncommon. The reported ­routinely continued every 6 h in the imme­
prevalence in dogs is 7–12.3%. It occurs in 9.4% diate postoperative period and subsequently
of patients less than three days postoperatively. weaned. Topical antibiotics are frequently used
Possible causes include hypotony, underlying due to the presence of corneal sutures and
uveitis, underlying coagulopathy, iridociliary ­possible corneal postoperative complications.
cysts, breakdown of iridal synechia during sur- Systemic antibiotics are commonly adminis-
gery, sudden changes in IOP, tension on the tered postoperatively, but their use in prevent-
ciliary processes during surgery, an oversized ing endophthalmitis has not been studied
IOL, unidentified intraocular masses, and reti- in dogs.
nal detachment or tears.
Cataract surgery is now minimally invasive,
Long-­Term Postoperative
decreasing the associated risks. However, it is
Complications
still associated with varying degrees of postop-
erative uveitis. Some level of postoperative Corneal Complications
uveitis is always expected and has been clini- Corneal lipidosis or degeneration was the sec-
cally reported in 29–82% of cases. Control of ond most commonly reported complication
anterior uveitis both preoperatively and post- (19%) after POH in one study, occurring a
operatively is imperative because of the dogs’ median of 135 days postoperatively. Progressive
amplified uveal inflammatory response. and severe degeneration can lead to visual
Intraocular fibrin development can occur compromise.
with uveitis or without other signs of inflam- Corneal stromal abscesses can be seen weeks
mation one to three weeks postoperatively in to months after cataract surgery, predominantly
up to 50% of patients. It can be mild, and in diabetic dogs. β-­Hemolytic Streptococcus sp.,
require no intervention as it resolves with topi- Staphylococcus aureus, Escherichia coli, and
cal therapy, or it can be severe and require fungal organisms have been reported as under-
additional intervention. The incidence in the lying causative organisms.
dog has been reported at 4.55–34%. Epithelial inclusion cysts or epithelial down-
TASS is an intense, anterior segment sterile growth has not been documented in the veteri-
inflammatory reaction usually described nary literature and is a rare complication of
12–48 h following surgery. Clinical signs include human cataract surgery. In humans, epithelial
severe corneal edema, fibrin, and hypopyon. downgrowth can manifest as corneal decom-
The main differential diagnosis is infectious pensation, glaucoma, chronic anterior uveitis,
endophthalmitis. The onset of TASS is typically and a retrocorneal membrane with a demar-
more acute than infectious endophthalmitis cated leading edge.
­Spontaneous Lens Capsule Ruptur  465

Postoperative endophthalmitis after cataract


surgery, although rare, is a devastating sight-­
and globe-­threatening complication. The
recent incidence of endophthalmitis in human
cataract patients is reported between 0.04%
and 0.2% (routine use of topical antibiotics
before and after surgery is infrequent). This
incidence has changed over time, with con-
flicting evidence that it was related to the type
of incision used (clear corneal versus scleral or
limbal based). Prevalence in the canine litera-
ture is higher compared to humans (0.57–1.4%).
Aqueocentesis should be performed in the sus-
picion of endophthalmitis for cytology, culture
and sensitivity, and PCR testing. Antibiotic Figure 12.24 Long-­term complications of chronic
therapy should be commensurate with those uveitis including anterior synechiae (dorsal
temporal and ventral, dyscoria, corneal edema, and
results, but aggressive intervention should be glaucoma 10 months following surgery in a
started immediately. diabetic dog. Topical anti-­inflammatories were
Persistent anterior uveitis and PCO is the most stopped for over a month immediately post op
common long-­term postoperative ­complication due to an infected corneal ulcer.
after phacoemulsification (Figures 12.24
and 12.25). Even with the most careful and
meticulous lens removal, some LECs are always
left behind within the capsule. The development
of capsular opacification involves proliferation,
migration, and differentiation of these LECs.
IOL problems following cataract surgery
were reported in 6.3% of dogs. These issues can
include IOL or haptic dislocation, both in and
out of the bag, as well as IOL decentration
(Figure 12.26). Possible causes of IOL decen-
tration include an excessively large lens cap-
sule (i.e., intumescent diabetic cases), an IOL
that is too small in diameter for the lens cap-
sule, a larger anterior capsulotomy, radial
Figure 12.25 Patient that underwent
tears, and capsule contraction from PCO that phacoemulsification and foldable acrylic IOL
displaces the IOL. implantation. Elschnig’s pearls are visible around
The development of glaucoma postopera- the body of the IOL and under the haptic ventrally.
tively is a significant contributor to failure of
phacoemulsification in dogs. In a study look- factors for glaucoma postoperatively include
ing at eyes enucleated or eviscerated due to breed, age, stage of cataract, aphakia, preexist-
complications from glaucoma, glaucoma ing uveal and retinal abnormalities, intensity
accounted for 76% of those cases. Glaucoma of the lens-­induced uveitis, and intraocular
secondary to cataract was present in 19.3% of hemorrhage. Many breeds have both possible
dogs in a retrospective study over 39 years. inherited primary glaucoma and cataracts.
Glaucoma as a sequela to cataract surgery Retinal detachment is a devastating compli-
occurred in approximately 5.1% of dogs. Risk cation following phacoemulsification.
466 Canine Cataracts, Lens Luxations, and Surgery

(a)

(b) (c)

Figure 12.26 (a) A PMMA IOL two years postoperatively. The axial IOL and capsule remain transparent,
and peripheral anterior capsular fibrosis is evident. (b) 30-­V acrylic (Acrivet Inc.) IOL one year
postoperatively. The IOL and lens capsules remain clear. (c) A 60-­V acrylic (Acrivet Inc.) IOL 18 months
postoperatively. PCO is noted at the edge of the optic, but the central optic remains clear.

Retinal detachment rates in dogs following diabetic dogs have been shown to be more
phacoemulsification, without focusing on likely to develop peripheral neuropathies, such
breed, have been reported to be 1–2%. In the as facial nerve paralysis, Horner’s syndrome,
study with a prevalence of 8.4%, RD was the and neurogenic keratoconjunctivitis sicca, than
most common cause of blindness with an aver- nondiabetic dogs. Corneal complications are
age of one year of follow-­up. Therapy for RD more likely in diabetic dogs as corneal sensitiv-
and/or tears detected following cataract sur- ity is decreased in the first seven days following
gery includes transpupillary barrier retinopexy surgery, and small breed diabetic dogs are more
or pneumatic retinopexy, depending on the likely to have keratoconjunctivitis sicca.
severity of the detachment or tear.
Diabetes causes a wide variety of acute,
Surgery for Lens
chronic, focal, and diffuse neuropathy syn-
Instability (Luxation)
dromes in humans. Tear and epithelial barrier
dysfunction, recurrent epithelial defects and Lens instability can occur as a congenital, pri-
erosions, delayed epithelial wound healing, mary, or secondary abnormality. The decisions
corneal edema, superficial punctate keratitis, about surgical intervention for lens instability
endothelial dysfunction, corneal nerve tortuos- can be difficult. Once the lens is luxated com-
ity, and decreased nerve density have also pletely, intervention depends on whether it is
been documented. After phacoemulsification, located anteriorly or posteriorly, and whether
­Spontaneous Lens Capsule Ruptur  467

glaucoma is present already or not. There is of the vitreous, and surgeon preference.
considerable diversity of opinion among veteri- Surgical techniques for lens extraction include
nary ophthalmologists regarding when unsta- ICLE for lens luxation, two-­handed phacoe-
ble lenses should be removed, and some mulsification (with or without removal of the
individuals avoid surgical intervention for as lens capsular bag), and/or capsular tension
long as possible or completely. It has been advo- rings for mild to severe lens instability. Small
cated that unstable lenses should be removed incision phacoemulsification is the preferred
as soon as the instability is detected. A retro- method of extraction if the lens is stable
spective study comparing the outcome of 23 enough to allow it. This may allow for signifi-
dogs (26 eyes) that were treated medically with cantly improved outcome as compared with
prostaglandin analogues (i.e., latanoprost and large incision ICLE. With improvements in
travoprost) twice daily for lens subluxation viscoelastics, use of two-­handed techniques,
were compared with 26 dogs (29 eyes) that and CTRs, many unstable lenses can now be
underwent phacoemulsification for lens sub- safely removed by phacoemulsification.
luxation on presentation. Results of statistical
analysis demonstrated that there was a signifi- Perioperative Medications in Instability
cant increase in time remaining visual for dogs Most veterinary ophthalmologists, with the
treated surgically compared to those treated exception of mydriasis, use a similar preop-
medically when age was not taken into account. erative medical plan of phacoemulsification.
However, only 30% of medically treated eyes Mydriasis may allow the anteriorly luxated
and 45% of the surgically treated eyes were lens to drop into the vitreous chamber and
reported still visual at the end of the study. should be avoided if surgical removal is
Medical management of unstable lenses offers desired. If the lens still has some zonular
a similar outcome to ICLE, neither of which is attachments, a weak mydriatic such as 1%
very satisfactory. The prognosis for vision after tropicamide or intracameral 1:10 000 epi-
ICLE is poor if glaucoma is present at surgery. nephrine may be used to allow for visualiza-
The posteriorly luxated lens is more difficult tion of the edges and movement forward.
to remove surgically than an anteriorly luxated Manual breakdown of intact zonules can
lens. The lens must be floated anteriorly for cause intraocular hemorrhage or, alterna-
removal, increasing interaction with the tively, they can sometimes be transected with
­vitreous and risk of retinal detachment. Vannas scissors.
Alternatively, a topical prostaglandin analogue
or other miotic can be used as a therapeutic Standard Surgical Approach
approach in managing the luxation without The traditional approach to an ICLE has not
surgery. Potent miosis occurs in dogs, as well substantially changed over time. A 160°, two-­
as a concurrent antiglaucoma effect. Use of thirds depth, corneal groove is made with a #
demecarium bromide 0.25% topically twice 6400 Beaver blade and combined with right
daily showed a median vision retention time of and left corneal section scissors are used to
1313 days. Of the 34 dogs with lens instability extend the incision. The lens is then extracted
managed medically, vision was maintained in by the cryoprobe method or via OVD use. In
80% at one year and 57% at two years. the cryoprobe method, the anterior surface of
the lens should be freed of any vitreous before
Surgical Management of Lens placement and activation of the probe.
Luxations The degree of zonular instability influences
The technique for removal of an unstable lens the need for an ICLE versus attempted phaco-
will depend on the degree of instability, loca- emulsification. Zonular instability during
tion of the lens, equipment availability, health phacoemulsification is associated with an
468 Canine Cataracts, Lens Luxations, and Surgery

increased incidence of intraoperative compli- Secondary Glaucoma


cations and is more technically challenging. Glaucoma is the most common postoperative
The degree of lens instability may preclude complication after ICLE occurring in as high
placement of an intracapsular IOL and other as 81% of cases. Preoperatively, 73% of eyes
options include leaving the patient aphakic or with anterior luxations had secondary glau-
suturing an IOL in place. coma compared to 43% with subluxations and
38% with posterior luxations. Eyes with glau-
Sulcus IOL Fixation coma preoperatively had a lower success rate
Suturing of an IOL into the ciliary sulcus has (66%) than eyes without (82%).
been described in the dog. The standard ab
interno and ab externo approaches to suturing Retinal Detachment
an IOL into the ciliary sulcus have not Retinal detachment following ICLE is the sec-
changed substantially. The location where the ond most common and serious postoperative
suture will exit or enter the sclera is marked, complication after secondary glaucoma and
depending on whether an ab interno or ab has been reported in 38% of cases. This is
externo approach is used, respectively. Small thought to be due to preexisting retinal tears
conjunctival flaps should be made 1.5 mm that enlarge following surgery, and/or disrup-
posterior to the limbus in these marked areas. tion of the anterior hyaloid face may predis-
Both nonfoldable PMMA and foldable acrylic pose eyes to this complication. Performing
IOLs that have an eyelet(s) in the haptic for ICLE soon after the luxation occurs may
attaching the suture are available. decrease the incidence of this complication.
469

13

Diseases and Surgery of the Canine Posterior Segment


Revised from 6th edition of Veterinary Ophthalmology, Chapter 24: Diseases and Surgery of the Canine Vitreous, by Michael H. Boevé
and Frans C. Stades; Chapter 25: Diseases of the Canine Ocular Fundus, by Simon M. Petersen-­Jones and Freya Mowat; Chapter 26:
Surgery of the Canine Posterior Segment, by Allison R. Hoffman, Samuel J. Vainisi, Joseph C. Wolfer, and András M. Komáromy; and
Chapter 27: Diseases of the Canine Optic Nerve, by Gillian J. McLellan

­ ection I: Diseases and Surgery


S optic fissure and grows toward the posterior
of the Canine Vitreous pole of the lens. Just retrolentally, the hya-
loid artery branches, generally into three
The vitreous, also called the vitreous body or cor- main trunks, which subsequently develop
pus vitreum, is a transparent, elastic hydrogel into a vascular network around the primitive
accounting for approximately 80% of the volume lens, thus forming the tunica vasculosa len-
of the canine globe. Posteriorly and about it sides, tis. More proximally in the vitreous space,
the vitreous is bordered by the retina, for which it the hyaloid artery branches into the vasa
provides support, and the optic disc, and at the hyaloidea propria. On the anterior side of the
anterior side by the posterior lens capsule and lens, the primitive vascular system anasto-
the Zinn zonules (i.e., fossa patellaris). moses with the annular vessel at the rim of
the optic cup, which is the location where
the iridal base will later be formed. In the
­Development and Anatomy dog, the hyaloid system is at its maximal
development by day 45. At this stage, the
By days 16–24 of gestation, the lens vesicle hyaloid system has developed into an elabo-
becomes separated from the surface ecto- rate vascular network. After approximately
derm from which it originated, and the ecto- day 45, however, the hyaloid system starts to
dermal and mesodermal fibrillar material regress, and between the second and the
extends into the space between the lens vesi- fourth week after birth, the entire vitreal vas-
cle and presumptive retina, thus forming the cular system has degenerated. Eventually,
primitive vitreous. Later, the primitive vitre- only a small, short, usually corkscrew-­
ous is concentrated centrally, in the optic shaped, rudimentary string of the hyaloid
cup, while the definitive or secondary vitre- artery remains, which is attached retrolen-
ous develops around it. After formation of tally to the posterior lens capsule just ventral
the lens vesicle, the hyaloid artery, which is to the posterior pole between the two ventral
of mesodermal origin, penetrates into the suture lines; the site of attachment to the
primary (or primitive) vitreous through the posterior lens capsule is named Mittendorf’s

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
470 Diseases and Surgery of the Canine Posterior Segment

dot. Remainders of the primitive vitreous In puppies, however, tropicamide may not cause
concentrate around the hyaloid artery. After adequate pupil dilation in all cases; use of 1%
regression of the latter, a channel-­like struc- atropine may be indicated. The part of the oph-
ture (i.e., Cloquet’s channel) remains, but thalmic examination dealing with the posterior
this structure is only barely observable in segment of the globe should be performed in
normal adult canine eyes. twilight conditions.

Focal Light
­Morphology
The eye is both illuminated and inspected from
The vitreous forms one of the refractive media a distance (≈40–60 cm). The light source
of the eye, and it provides the necessary pres- should be powerful and focal, such as a pen-
sure to maintain the neuroretina properly posi- light of good quality, a direct ophthalmoscope,
tioned against the pigment epithelium. The two or an otoscope, to allow any vitreal opacities or
main solid components of the vitreous are hya- condensations to be visualized by both direct
luronic acid and collagen. Approximately 1% of and indirect illumination (i.e., by light reflected
the vitreous consists of a network of polygonal, from the tapetal fundus [tapetum fundus]).
hydrated fibrils of hyaluronic acid and collagen Because opacities will either partly or com-
(type II, with a helical structure of α1(II)3). As pletely block the reflected light, they will be
cellular component, few hyalocytes, which orig- seen as dark structures against a bright tapetal
inated from blood macrophages, are mainly reflectivity. Movement of vitreal structures fol-
located peripherally, near the ciliary body. The lowing motions of the globe or lagging behind
hyalocytes are believed to be responsible for the ocular motions may be determined more easily
production of glycosaminoglycans, especially in this way. As the vitreous becomes more liq-
hyaluronic acid. The remaining 98–99% of the uefied, opacities can appear unstable with the
vitreous consists of water. gel or even settle to the bottom of the vit-
The outer limits of the vitreous do not con- real space.
sist of membranes; rather, they consist of con-
densations of fibrils that are firmly attached to
Slit-­Lamp Biomicroscopy
the ora ciliaris retinae and the pars plana cili-
aris. The anterior portion of the canine vitre- A slit-­lamp biomicroscope is a highly useful
ous is strongly attached to the posterior lens and necessary tool for examination of the vit-
capsule, which has given rise to the confusing reous, even though such inspection using a
term hyaloideocapsular ligament (i.e., Wieger’s slit-­lamp biomicroscope will be limited to the
ligament and Egger’s line). The vitreous is also anterior part. A slit-­lamp biomicroscope is
attached to the region of the ora ciliaris retinae therefore especially useful to evaluate disor-
and to the prepapillary area. The vitreoretinal ders at the lens/vitreous interface, such as
interface consists of outer part of the vitreous, persistence of parts of the tunica vasculosa
anchoring fibrils of the vitreous body and the lentis posterior, persistent hyaloid artery
inner limiting membrane of the neuroretina. (PHA), persistent hyperplastic tunica vascu-
losa lentis (PHTVL)/persistent hyperplastic
primary vitreous (PHPV), and posterior len-
­Diagnostic Procedures tal pathology. Examination of the posterior
vitreous requires the Hruby contact lens with
To completely observe and evaluate the vitreous, slit-­lamp biomicroscopy and can provide
the pupil should be dilated using a short-­acting magnifications from 5× to 50× of the vitreous
mydriatic agent, such as 0.5–1.0% tropicamide. structure.
­Therapeutic Procedure  471

Ophthalmoscopy needle is used to penetrate the sclera, and the


exact location of needle penetration is of great
The direct ophthalmoscope may be used as
importance. The eye should be penetrated via
previously described. By decreasing the dis-
the anterior or medial region of the pars plana
tance between the light source and the eye,
ciliaris. The corresponding external sites in
direct illumination of vitreal structures will
medium-­sized mesocephalic dogs are 7 mm
increase, enabling better visualization of their
(i.e., superotemporal quadrant), 6 mm (i.e.,
morphology. Vitreous liquefaction and floaters
inferotemporal quadrant), 5 mm (i.e., inferona-
may also be visualized with an indirect
sal quadrant), and 4–5 mm (i.e., superonasal
ophthalmoscope.
quadrant) posterior to the limbus. There are
indications that these sites will be more poste-
Diagnostic Imaging rior in larger dogs with larger eyes. Needle
penetration through the pars plicata ciliaris
Ultrasonography, using a high-­resolution will result in considerable intraocular hemor-
ultrasound machine, is a highly useful and rhage, whereas penetration posterior to the
noninvasive means of vitreal examination. pars plana ciliaris will cause punctures of
This is especially true in eyes with opacities of the retina.
the anterior segment of the globe that exclude
visual examination of the vitreous. Only
dense vitreal opacities, however, will be visu-
alized during a B-­mode scan. Examples of
­Therapeutic Procedures
abnormal structures in the vitreal cavity that
Medical Treatment
may be visible ultrasonographically include
hyaloid remnants, vitreal hemorrhage, vitre- Because the vitreous is avascular in adult dogs,
ous degeneration, retinal detachment (RD), penetration of systemically administrated drugs
and intraocular neoplasia. Use of color-­flow is poor. When the blood–aqueous barrier is
Doppler may be useful to indicate blood flow compromised, such as occurs in uveitis, acces-
in suspected structures. Contrast-­enhanced sibility of the vitreous for drugs increases.
ultrasonography has been described to be a Hence, systemic administration of drugs, even
useful tool in the differentiation of RD and though relatively safe, is of limited use in reach-
vitreous membranes in dogs and cats. In ing the vitreous medically. The most direct way
addition, computed tomography (CT) and to achieve high drug concentrations in the vitre-
magnetic resonance imaging (MRI) may con- ous is by intraocular injection. The globe only
tribute to the evaluation of vitreal disease. tolerates rather low doses and volumes, how-
ever, and large doses may produce severe ocular
damage. The latter phenomenon is used by
Hyalocentesis injecting gentamicin into the vitreous as a treat-
In diagnostic vitreal paracentesis (i.e., hyalo- ment in globes with absolute glaucoma and in
centesis), a small amount of liquid vitreous is which enucleation is contraindicated.
aspirated for analysis, most often cytological
examination or microbiological culture.
Surgical Treatment
Hyalocentesis is performed after instillation of
a short-­acting mydriatic agent, preferably Surgical treatment is necessary when the vitre-
under general anesthesia, and after antiseptic ous is displaced within the pupil during ante-
pretreatment of the conjunctival sac (e.g., with rior segment surgeries and in the treatment of
a 0.5% povidone–iodine aqueous ophthalmic RDs. Additional details on vitreous surgery are
solution). A 22-­ to 26-­gauge (0.70–0.45 mm) provided later in this chapter.
472 Diseases and Surgery of the Canine Posterior Segment

Vitrectomy requires considerable experience and spe-


Vitrectomy is generally indicated when vitre- cialized instrumentation. The surgical
ous presentation or protrusion occurs during entrance is where the dorsolateral sclera is
anterior segment surgery. Another indication positioned over the pars plana ciliaris. This
for vitrectomy is during vitreoretinal surgery procedure is commonly included in surgical
for the treatment of RDs and vitreal trac- treatment of complicated RD and vitreal
tion bands. traction bands. Other indications for this
procedure include ophthalmomyiasis interna
Anterior Vitrectomy posterior and uveitis (mainly used in horses
Anterior vitrectomy is indicated when formed with equine recurrent uveitis).
vitreous protrudes into the pupil or the ante-
rior chamber during anterior segment surgery.
In most cases involving dogs, protrusions ­Vitreal Diseases
occur during or directly after intracapsular
lens removal, and during phacoemulsification Developmental Disorders
of hypermature cataracts and placement of
Developmental disorders form a group of rela-
the intraocular lens (IOL). If the posterior lens
tively rare ophthalmic anomalies. Usually,
capsule is perforated during cataract surgery,
these anomalies are part of syndromes associ-
the vitreous may protrude into the capsular
ated with persisting intraocular vasculature or
bag, pupil, anterior chamber, or even into the
with other ocular developmental disorders,
corneal incision. Protrusion of vitreous in the
such as microphthalmia, Collie eye anomaly
pupil or the anterior chamber may physically
(CEA), and retinal dysplasia.
impair or obstruct the flow or drainage of
aqueous, resulting in an increased intraocular
Persistent Hyaloid Artery
pressure. In addition, vitreous touching the
The anomaly PHA results from failure of part
corneal endothelium may cause persistent
or all of the hyaloid artery to regress
corneal edema. Anterior vitrectomy can be
(Figure 13.1). The artery may have persisted as
performed manually, using microsurgical cel-
lulose sponges or vitreous forceps, or it can be
performed using an automated vitrectome.
Left untreated, vitreous protrusions may
cause the development of traction bands, with
the risk of subsequent RD. Anterior vitrectomy
is generally performed through an already
existing corneal or corneoscleral incision or,
seldomly, through a traumatic perforation. A
second corneal incision in a different area
occasionally is necessary for adequate access to
the pupil. In selected cases, a pars plana vitrec-
tomy (PPV) through a newly made surgical
entrance (i.e., pars plana posterior vitrectomy)
may be indicated.

Pars Plana Posterior Vitrectomy


In pars plana posterior vitrectomy, part of
Figure 13.1 PHA in a Golden Retriever. The
the vitreous is removed using an automated hyaloid artery is visible as a white string (arrow)
vitrectome. Successful use of this method (Frans C. Stades).
­Vitreal Disease  473

a string (in some cases containing blood) situ- PHTVL/PHPV generally occurs bilaterally, is
ated in the vitreous space, between the optic inherited (probably because of an incomplete
disc and the lens. In PHA, only a small, dense, dominant gene in the Dobermann), and
white, connective tissue string usually remains hence has a higher prevalence in these breeds
adhered to the posterior lens capsule. The compared with that in others. Signs range
optic disc may have a conical shape (i.e., from very small, retrolentally positioned
Bergmeister’s papilla), and during ocular fibrovascular dots that represent minor rem-
movements, PHA structures lag slightly nants of the tunica vasculosa lentis vascula-
behind and thus may show a “waving” motion. ture (i.e., grade 1) (Figures 13.2 and 13.3).
PHA has been suggested to be hereditary in The differential diagnosis of PHTVL/PHPV
the Sussex Spaniel and the Dobermann. includes cataracts resulting from other causes,
PHA alone rarely requires surgical treatment. microphthalmia alone, and other solitary dys-
If the associated cataract formation leads to vis- plastic disorders of the lens. In severely affected
ual impairment, however, surgery may be indi- blind eyes (i.e., grades 2–6), cataract surgery
cated. In these cases, the risk of complications is with fenestration of the posterior capsule and
slightly higher than that in cases of cataract transection of the hyaloid artery, if applicable,
alone, because in PHA-­related cataracts, central combined with anterior vitrectomy may be
fenestration of the posterior lens capsule and indicated. The prognosis for surgery in severely
anterior vitrectomy are indicated. affected cases of PHTVL/PHPV is less favorable
than that in routine cataract surgery because of
Persistent Tunica Vasculosa Lentis the higher chance of complications.
In persistent tunica vasculosa lentis, there are
fine, white, strand-­like deformities (i.e., “spi- Other Anomalies
derweb”), or parts of vascular structures, The vitreous may be involved in diseases of its
attached to the posterior lens capsule (i.e., bordering structures as well. In CEA, a partial
persistent tunica vasculosa lentis posterior).
These structures are the remainder of the
tunica vasculosa lentis (posterior), retrolen-
tally connected to, or “printed” on, the poste-
rior lens capsule. These structures generally
have no clinical significance, and they may be
observed incidentally during routine ophthal-
mic examinations.

PHTVL/PHPV
In this group of apparently rare and generally
unilateral disorders, parts of the hyaloid sys-
tem and primitive vitreous have become
hyperplastic during early fetal development,
combined with a subsequently incomplete
regression. This anomaly has been described
in several species. In the dog, PHTVL/PHPV
has been described in the Bloodhound,
Bouvier des Flandres, Samoyed, Siberian Figure 13.2 Postnatal persistence of vasculature
belonging to the hyaloid system, including the tunica
Husky, and Spanish Pachon, and studied
vasculosa lentis posterior, as seen in the right eye of a
extensively in the Dobermann in Holland and Dobermann puppy with grade 3 PHTVL/PHPV (Frans
in the Staffordshire Bull Terrier in England. C. Stades).
474 Diseases and Surgery of the Canine Posterior Segment

blood residues, traction bands, and other scars,


and the foreign body itself may still be present
in the vitreous. Less often, blunt trauma causes
vitreal hemorrhage. Dogs that show ophthal-
mic problems of sudden onset that include
signs of trauma such as corneal edema,
hyphema, uveitis, and vitreal hemorrhage
should additionally be examined with diagnos-
tic imaging techniques.
Depending on the severity of the concurrent
uveitis, therapy in such patients consists of
topical antimicrobial treatment/prophylaxis,
mydriatics/cycloplegics (e.g., 1% atropine), and
0.1% dexamethasone (four to six times daily),
as well as systemic prophylactic antimicrobial
and extensive anti-­inflammatory treatment
Figure 13.3 Right eye of a two-­month-­old
Doberman with PHTVL/PHPV. Note the presence of
(e.g., corticosteroids or nonsteroidal anti-­
elongated ciliary processes at the 12-­o’clock to inflammatory drugs). In case of ocular hyper-
2-­o’clock positions (yellow arrows), macrophakia, tension, the intraocular pressure should be
and cataract (blue arrow). reduced as well, in which case use of parasym-
patholytic mydriatics, and especially atropine,
failure of vitreal development, which is only would be contraindicated.
recognizable with use of a slit-­lamp micro-
scope, has been described. Vitreal syneresis, Degenerative Vitreal Disorders
vascular anomalies, hemorrhages, and RD and Reactions
may also be found in CEA. These anomalies The term “vitreous degeneration” is clinically
may include preretinal vascular loops pene- used to indicate vitreous changes that are
trating into the vitreous, and such vessels may consistent with breakdown of the vitreous
easily give rise to vitreal hemorrhage. In case hydrogel (Box 13.1). Signs may comprise
of RD, the neuroretina is partially or totally
detached into the vitreous.
In the focal and geographic forms of retinal Box 13.1 Vitreal Opacities or Floaters
dysplasia, the retina folds slightly into the vit- Young dogs Vascular remnants (PHA,
reous. In severe forms of retinal dysplasia, as PHTVL/PHPV)
has been described for the Bedlington Terrier, Vitreal hemorrhages (trauma,
Yorkshire Terrier, and Labrador Retriever (in RD; CEA, anomalous vessels,
combination with skeletal abnormalities), the penetrating foreign bodies)
retina is partly or totally detached and dislo- Older dogs Cortical opacities with
cated into the vitreal space. liquefaction
Inflammatory and tumor cells

Acquired Disorders Synchysis scintillans


Vitreal hyalosis
Trauma
Vitreal syneresis
Penetrating trauma, such as caused by air-­rifle
or shotgun pellets, easily causes floaters of Vitreal parasites (Dirofilaria
immitis, Toxocara canis,
blood in the vitreous. The penetration tunnel is Echinococcus, Diptera spp.)
usually marked by prolapsed lens material,
­Vitreal Disease  475

liquefaction (syneresis) and opacities (float- Syneresis may predispose to posterior vitre-
ers, asteroid hyalosis, and synchysis scintil- ous detachment. Development of rhegmatoge-
lans). However, in “normal” dogs, a wide nous RD in the Shih Tzu has been suggested to
variety of vitreous gel consistencies can clini- occur through primary retinal degeneration
cally be noticed. Over the last few years, an and secondary vitreous degeneration (synere-
entity called primary vitreous degeneration sis). Dogs older than 10 years often have some
has become an issue in a number of breeds, degree of vitreal syneresis.
such as Brussels Griffon, Chihuahua, Chinese
Crested, Havanese, Italian Greyhound, Vitreous Floaters
Lowchen, Papillon, Shih Tzu, and Whippet. Vitreous floaters, muscae volitantes, or “flying
However, there still is a lack of scientific lit- flies” are larger flakes or streaks in the vitreous
erature concerning this entity in dogs. that may lag behind ocular movements. In the
Small or large opacities that consist of con- past, this was thought to cause the so-­called
glomerates of calcium and lipids, condensa- fly-­biting syndrome, but today, this behavior is
tions of vitreous fibrils, groups of erythrocytes, suspected to result mainly from nonophthal-
or pigment cells (including remnants of the mic causes, such as temporal or occipital lobe
hyaloid system) may persist or develop in the dysfunction. Vitreous floaters are uncommon
vitreous. Such opacities may move as well, fol- and rarely require surgical treatment.
lowing the movements of the eye. In older ani-
mals, further degeneration of the vitreous can Asteroid Hyalosis
lead to liquefaction, in which case the opacities Asteroid hyalosis is characterized by many small
have a greater tendency to lag behind ocular and possibly slightly pigmented particles (i.e.,
movements, whirl about, and then settle to the “asteroid bodies” from 0.03 to 0.10 mm in diam-
vitreous floor. eter) in the vitreous of one or both eyes
(Figure 13.4a and b). These particles move both
Syneresis during and following movements of the globe,
Syneresis is a degenerative breakdown of the but they also return to their initial position. They
vitreous gel that separates its liquid from its generally have no distinct influence on vision by
solid components, resulting in liquefaction their presence alone; however, asteroid hyalosis
and development of fluid-­filled cavities within may be associated with posterior uveal changes
the vitreous. or (progressive) retinal atrophy. Comparisons of

(a) (b)

Figure 13.4 Asteroid hyalosis in a dog. (a) External appearance. (b) Ophthalmoscopic appearance (Frans
C. Stades).
476 Diseases and Surgery of the Canine Posterior Segment

vitreous humor containing asteroid bodies from of the vitreous itself (i.e., hyalitis and vitritis) will
affected dogs indicate that asteroid bodies con- almost always be secondary to inflammatory
tain calcium and phosphorus. reactions of adjacent structures. Floaters of hem-
orrhagic or other exudate in the vitreous, espe-
Synchysis Scintillans cially if diffuse or bilateral, often result from
Synchysis scintillans is characterized by exudative uveitis, chorioretinitis, retinitis, or
numerous cholesterol particles in a more or optic neuritis.
less liquefied vitreous. Especially after eye Free blood in the vitreous is relatively
movements, they can resemble a snow flurry uncommon (Figure 13.5a and b). Hemorrhage
behind the lens, and against bright light, they may result from congenital anomalies, such as
may cause dazzling. With ocular movement, the persistence of fetal vasculature (e.g., PHA
these opacities move within the liquid vitre- and PHTVL/PHPV), CEA, trauma, infection,
ous; when the globe is till, they settle to the or systemic diseases (e.g., coagulopathies, vas-
bottom of the vitreous space. The abnormality culitis, systemic hypertension, and neoplasms).
is rare and seldom causes recognizable prob- Blood in the vitreous has been described to
lems in dogs. have a destructive effect on the gel structure:
vitreous adjacent to a hemorrhage is prone to
Intravitreal Membranes liquefaction. The arrival of macrophages
Intravitreal membranes are associated with induces an inflammatory reaction, which
past and/or current intravitreal hemorrhage. results in the formation of vitreal fibrinous
Additional common findings in that study membranes and traction bands.
included epiretinal membranes, retinal neo- Depending on the geographic location of the
vascularization, preiridal fibrovascular mem- patient, various infectious agents are known to
branes, and glaucoma. induce vitreal exudates. Infections reported to
cause vitreal exudates include blastomycosis,
Vitreal Inflammations cryptococcosis, histoplasmosis, brucellosis,
Because the adult vitreous has no intrinsic vascu- and other diseases. In these cases, therapy
lature nor nerve supply, the possibilities of reac- should be directed primarily at the underly-
tion to noxae are limited. Hence, inflammation ing cause.

(a) (b)

Figure 13.5 Vitreal hemorrhage following trauma in a dog. (a) Limited hemorrhage. (b) More extensive
vitreal hemorrhage.
­Vitreous in Relation to Other Ophthalmic Disorder  477

The prognosis of vitritis strongly depends on retina, choroid, and optic nerve are extremely
the underlying cause. Small amounts of blood rare in the dog, and neoplasms originating
or exudate may be resorbed, but larger amounts from the anterior uvea are relatively uncom-
usually cause visual disturbances, even if the mon in this species. Uveal neoplasms mainly
inflammatory reaction can be controlled. Vitreal comprise malignant melanomas, but other
membranes and traction bands may develop. In neoplasms have been reported. The prognosis
turn, vitreal displacement, prolapse, herniation, for an eye affected by a neoplasm extending
and traction caused by traction bands or mem- into the vitreous depends on both the type of
branes may cause secondary RDs even months neoplasm and its extension, but such a neo-
after the primary disorder has resolved. plasm generally should be considered an indi-
cation for enucleation.
Cysts
Cysts, most likely originating from the pig-
mented epithelial layer of the iris or the cili- ­ itreous in Relation to Other
V
ary body, may extend into the vitreous. These
Ophthalmic Disorders
cysts are much less common than anterior
chamber uveal cysts. Cysts may also be caused
Lens Luxation
by parasites. Vitreal cysts have the appear-
ance of spherical or oval, translucent bodies The lens may dislocate when its suspension
that may be stationary or move slowly in liq- system is compromised by dysplasia, degenera-
uefied vitreous following movement of the tion, and/or rupture of the Zinn zonular fibers.
globe. Depending on their size and location, The zonular fibers may have developed abnor-
they seldom interfere with vision. mally or have degenerated; in exceptional situ-
ations, they can rupture from external trauma.
Parasites If several zonular fibers have ruptured, vitre-
Migrating larvae of Dirofilaria immitis, Toxocara ous may leak into the anterior chamber along
canis, the larvae of flies (i.e., ophthalmomyiasis the lental equator and through the pupil. If the
interna), and Echinococcus sp. may penetrate the fibers have ruptured over a greater area, sub-
vitreous. Living or dead intraocular parasites luxation of the lens will occur. If the lens
may cause local irritation, uveitis, or cyst forma- becomes completely unattached, it may remain
tion. Killing intraocular dirofilaria by medication more or less in its normal position, be dis-
is sometimes possible. However, the intraocular placed toward anterior or posterior, or topple.
presence of a dead parasite generally induces Because of its volume and the strong attach-
severe immunogenic uveitis, with possible sub- ment of the posterior lens capsule to the vitre-
sequent endophthalmitis. Therefore, if the para- ous, a dislocated lens will dislocate part of the
site can be reached without an unacceptable risk, vitreous as well. Subsequently, vitreous may
surgical removal is to be preferred. prolapse or herniate in the pupil, thus impair-
ing, or even blocking, drainage of aqueous
Neoplastic Disease between the posterior surface of the lens and
Intraocular neoplasms generally arise from the anterior surface of the iris (if the lens has
the uvea and may occupy part, or almost all, become dislocated into the anterior chamber)
of the vitreous space. Neoplasms may be pri- or, at the level of the drainage angle, causing
mary, metastatic, or systemic/multicentric. secondary glaucoma in all cases. The earliest
Depending on location and size, a vitreal recognizable sign of a lens luxation is the pres-
tumor may cause more or less displacement ence of slight vitreous protrusions, which are
of the vitreous and lens as well as posterior recognizable on slit-­lamp biomicroscopy as
uveitis and RD. Primary neoplasms of the thin, white clouds along the pupil margin.
478 Diseases and Surgery of the Canine Posterior Segment

often the best available animal model with a


human-­size eye for investigations into their
pathogenesis (looking for therapeutic win-
dows) and possible gene therapy. Examination
of the posterior segment starts with direct and/
or indirect ophthalmoscopy, and with recent
noninvasive diagnostic procedures can be
imaged at very high levels of resolution (often
approaching 10–20 μm).

­Methods of Examination

The ocular fundus is examined with various


direct and indirect noninvasive diagnostic
Figure 13.6 Bullous RD in the left eye of a
methods. Several methods are routinely used
Bernese Mountain dog suffering from systemic clinically, while others are more investigative.
hypertension.

Behavioral Testing
Retinal Detachment
Behavioral testing is relatively simple and can
An RD may occupy part, or almost all, of the be quantified by difficulty of the maze, time to
vitreous space. A small RD is observed as an complete successfully the maze, amount of illu-
indistinctly bordered, grayish blue “cyst” or mination, and other measurable factors. Careful
fold of the retina. Large detachments look more questioning of the owner is usually an impor-
like grayish blue to red, parachute-­shaped, vas- tant source of information about a dog’s visual
cularized bullae positioned either directly performance; however, this information may be
behind the posterior lens capsule or deeper in incomplete or invalid. Furthermore, the ability
the vitreous. Depending on the type of detach- of a visually impaired or blind dog to adapt to
ment, the optic disc may be obscured. Also, familiar surroundings by relying on other senses
dark sheets of blood, pigment, or other inflam- and a memorized image of the environment can
matory signs may be found. The combination mask the signs of impaired vision.
of intraocular (intravitreal) hemorrhage and Vision may also be assessed from the dog’s
RD may be indicative of systemic hypertension response to falling objects (visual tracking) that
(Figure 13.6). Diagnostics should therefore do not create a noise or current of air (e.g., small
include an internistic workup including blood cotton balls). The balls can be dropped both in
pressure measurement. front of the dog and to the sides to get an impres-
sion of central and peripheral vision. The results
should be interpreted with some caution, how-
Section II: Diseases of the ever, because of patient indifference.
Canine Ocular Fundus

Ocular fundus diseases occur frequently in the


Testing Reflexes and Responses
dog. Inherited vitreal and retinal diseases are The pupillary light reflex (PLR) requires a
more frequent in the dog than in any other ani- functional retina but also depends on postreti-
mal species as compared to man. Human and nal transmission of signals. Loss of the PLRs is
canine retinal diseases are often caused by the not a definite sign of retinal dysfunction or
same DNA mutation, and as a result, the dog is even of loss of vision. They can also be
­Structural Visualization of the Fundu  479

partially inhibited in an apprehensive patient fundus in a shorter time. Moreover, it allows


because of an increased sympathetic tone. stereopsis, which is useful in appreciating the
Furthermore, residual PLRs are often present topographical features of the retinal surface
in dogs even with advanced retinal degenera- such as when appraising RDs, colobomas, and
tion, such as in progressive retinal atrophy papillary edema. Different indirect lenses can
(PRA), especially if the inner retina is pre- be selected to allow for a more highly magni-
served. The reason for this phenomenon is that fied view when required. For additional details,
the PLRs are driven by the photoreceptors at see Chapter 4.
low light levels and have been shown in vari-
ous species to be driven by the melanopsin-­
Scanning Laser Ophthalmoscopy
containing ganglion cells at high light intensity
stimulation. The presence of the PLRs is there- Scanning laser ophthalmoscopy (SLO) is a
fore not a guarantee of a healthy retina in dogs diagnostic imaging technique developed for
with opaque media (e.g., preoperatively in very precise and detailed fundus visualiza-
those with dense, extensive cataracts) that pre- tion. Lasers of different wavelengths allow
vents ophthalmoscopic examination. the examiner to obtain information about
specific tissues and layers on the basis of their
reflection and transmission characteristics.
­Structural Visualization of The SLO can also be utilized in an angiogra-
phy mode in order to correlate functional
the Fundus
with morphological aspects in disease pro-
cesses affecting the retinal and/or the choroi-
Ophthalmoscopy
dal vasculature.
Direct and indirect ophthalmoscopy are both
used in veterinary ophthalmology to visualize
Optical Coherence Tomography
the fundus. Three types of ophthalmoscopes are
available: (i) the standard monocular direct During the past decade, an imaging technique
ophthalmoscope; (ii) pan-­ophthalmoscope; and called optical coherence tomography (OCT)
(iii) monocular and binocular indirect ophthal- has been developed and used both in research
moscopes. Each type of ophthalmoscope has and for clinical purposes to evaluate in vivo
advantages and limitations, and can comple- retinal structure. High-­resolution, cross-­
ment each other. sectional images of optical reflectivity are
The ophthalmoscopic examination is per- obtained. The technique is based on the princi-
formed in a darkened room using short-­acting ple of low-­coherence interferometry in which
mydriatics, such as 0.5–1.0% tropicamide distance information concerning various ocu-
(Mydriacyl; Alcon Laboratories, Ft Worth, TX, lar structures is extracted from time delays of
USA). Direct ophthalmoscopy, in general, pro- reflected signals. This in vivo microscopy tech-
vides the observer with a smaller field of view nique gives information about retinal organi-
that is of greater magnification and detail than zation and structural integrity. For example,
that with indirect ophthalmoscopy. The newer photoreceptor layer thickness can be quanti-
pan-­ophthalmoscope has lower magnification fied using OCT. Instrumentation has also been
and a larger viewing field. Direct ophthalmos- developed that utilizes both OCT and SLO
copy is mainly used to examine the central techniques simultaneously.
parts of the fundus, especially the region of the
optic nerve head (ONH), but it is considered
Adaptive Optics
inadequate to examine the peripheral fundus
of domestic animals. Indirect ophthalmoscopy Newer noninvasive imaging techniques are
allows a more complete examination of the under development. Some use adaptive optics
480 Diseases and Surgery of the Canine Posterior Segment

to adjust for the aberrations of the optical neuronal and nonneuronal cells that can be
media allowing for highly magnified examina- recorded as the electroretinogram (ERG). This
tion of the retina in vivo. Individual photore- response is a summation of electrical poten-
ceptors can be imaged using the adaptive tials that result from light-­induced changes in
optics techniques. the movement of ions, mainly sodium and
potassium, within the extracellular space.
Thus, the ERG is an objective, functional test
Ultrasonography
of the retina and is critically dependent on the
Ultrasonography is a valuable aid in detecting function of the photoreceptors (i.e., the rods
and monitoring pathological conditions in the and cones). It has a characteristic waveform
canine posterior segment. In patients with that varies depending on several factors, but
opaque media (e.g., dense cataracts and intraoc- mostly on the type of stimuli used. The inten-
ular hemorrhage), ultrasonography can be used sity, duration, frequency, and wavelength of
to detect, for example, a detached retina or pos- the light stimulus as well as the interval
terior segment neoplasm. Furthermore, ultra- between stimuli, size of the retinal area illu-
sonography can be used to study space-­occupying minated, pupil size, and (very important)
conditions that are difficult to examine because stage of retinal adaptation are variables that
of their location (e.g., neoplasms in the choroid account for alterations in the ERG response.
close to the ciliary body). The ERG is recorded by using an active con-
tact lens electrode, and a reference and a
ground electrode, and the results are displayed
Angiography
on an oscilloscope, ink writer, or computer
Angiography is a helpful adjunct in the diagno- screen (Figure 13.7).
sis of retinal diseases. It is mainly used to evalu-
ate disease processes in which the vasculature Flash Electroretinography
of the eye is involved, such as vascular anoma- In clinical veterinary ophthalmology, the flash
lies, posterior segment neoplasms, hyperten- ERG is used in two broad applications. The
sion, RD, inflammatory processes, diabetic first is to test whether a standard stimulus elic-
retinopathy, and degenerative processes. The its an ERG response. This is useful in assessing
procedure is performed in sedated, anesthe- retinal activity when the fundus is obscured
tized, or conscious dogs, depending on the pref- (e.g., before cataract surgery) and in the dif-
erence and need of the examiner. Fluorescein ferential diagnosis of retinal disease when
sodium solution (Fluoresceine 10%; Faure, ophthalmoscopic lesions are absent. The sec-
France) is given as an intravenous bolus into ond is to specifically test rod and cone func-
the cephalic vein. Fundus photography is then tion in conjunction with research into retinal
performed using a fundus camera connected to disease processes and in the early diagnosis of
a power-­back unit to allow for quick recycling hereditary retinal degenerations and dystro-
of the black-­and-­white or color film, as well as phies. Procedures for standardization of ERG
using the newer digital cameras. procedures have been adopted in human oph-
thalmology. Guidelines have also been devel-
oped for performing dog ERGs.
­Functional Testing of the Retina Pattern ERG
The pattern ERG (PERG) measures a retinal
Electroretinography
response to a phase-­reversing pattern stimulus
When the retina is stimulated by light, a dif- that is focused onto the retina and maintains a
fuse electrical response is generated by constant overall mean luminance. The
­Functional Testing of the Retin  481

Dark adapted

50 µV
–2.0 log cd-s/m2

0.6 log cd-s/m2

Light adapted

20 µV
0.0 log cd-s/m2

30 Hz

50 ms

50 Hz
(a) (b)

Figure 13.7 Bilateral ERG in progress using a protocol for evaluation of rod and cone function and
Ganzfeld (full-­field) stimulation. (a) The dog is under general anesthesia (propofol/isoflurane) in order to
obtain maximally stable recordings. (b) Details of the procedure are shown on the right, which starts with
dark adaptation, whereafter the eye is stimulated by a low and a high intensity of white light. Light
adaptation follows (using 37 cd/m2), and then recordings are obtained using single-­flash and flicker
stimulation with white light as indicated.

response is an electrical potential thought to cortex in response to visual stimulation. These


derive from the retinal ganglion cells (RGCs) responses are of small amplitude (1–40 μV)
and the neighboring inner retinal structures. and are extremely sensitive to stimulus
The main characteristics of a pattern stimulus changes. Therefore, computer averaging is
include overall screen brightness (i.e., mean necessary for their recording, and correct
luminance), brightness contrast of neighbor- placement of electrodes is a necessary factor in
ing bars or checks (i.e., percent contrast), rate achieving correct and reproducible results. The
of pattern reversal (i.e., temporal frequency), VEP reflects the electrical activity of the cen-
and bar or check size (i.e., spatial frequency). tral part of the fundus, because this area has a
Moreover, for measurements to be reliable, the much larger cortical representation than the
refractive error of the patient must be cor- peripheral regions. Thus, in veterinary oph-
rected during the testing so that the stimulus is thalmology, the VEP is a test not only of the
focused on the retina. Other methods to esti- central visual function but also of the optic
mate canine visual acuity include behavioral nerve and the higher visual tracts and visual
testing, assessment of the optokinetic response, cortex. It is useful in patients with normal oph-
and measurement of visually evoked cortical thalmic examination results and a normal ERG.
potentials (VEPs).
Multifocal ERGs and VEPs
Visually Evoked Potentials Regional functional testing procedures have
The VEP, or visually evoked response, is a gross been developed for both ERG and VEP record-
electrical signal generated at the occipital ings in order to obtain precise topographical
482 Diseases and Surgery of the Canine Posterior Segment

mapping of disease. Both techniques allow for and reflective. The size of the tapetal fundus
simultaneous measurements of ERG or VEP varies extensively. Usually, it is large, and it may
activity from many different retinal locations. sometimes surround the ONH in gaze hounds
The former technique utilizes SLOs for laser (i.e., dogs that hunt by sight [e.g., Greyhounds])
stimulation and direct visualization of the pro- and large breeds. It is often poorly developed,
cedure with an additional stimulus in the opti- however, in toy breeds (e.g., Papillons). In the
cal pathway of the SLO by means of a latter case, the tapetal fundus often only occu-
wavelength-­sensitive mirror. pies a small area, usually temporal and dorsal to
the ONH. The retinal blood vessels transverse
the tapetal fundus, and the vessels are more eas-
DNA-­Based Tests for Retinal Dystrophies
ily viewed in the tapetal zone than in the nonta-
Appendix A lists the tests currently available. petal area when ophthalmoscopy is performed.
However, this is a rapidly progressing field and The nontapetal fundus surrounds the entire
the reader is advised to review the current lit- tapetal area and is typically darkly pigmented.
erature and websites of the laboratories offer- In dogs with a merle coat color (e.g., blue
ing genetic tests for the most up-­to-­date merle Collies, Shetland Sheepdogs, Australian
information. Shepherds, and related breeds), the tapetal
fundus may be absent. Occasionally, the tapetal
fundus may also be missing in other dogs, and
­Normal Ocular Fundus in this case, the entire fundus resembles the
nontapetal zone (i.e., dark, dull, and nonreflec-
The canine ocular fundus is a challenge for the tive). The palette of the tapetal fundus includes
examiner because of its enormous variation in hues of yellow, orange, green, and blue. Often,
normal ophthalmoscopic appearance more than one color is present.
(Figure 13.8a–j). Normal ocular fundus varia- Among breeds in which pale blue or hetero-
tions occur by age, breed, iris color, coat color, chromic irides may appear (e.g., merle-­coated
and other factors. The great range of normal Collies, Shetland Sheepdogs, and related
variation in fundic appearance could, perhaps, breeds, harlequin-­coated Great Danes, and
be expected when the diversity in the gross Cardigan Welsh Corgis, which also carry merle
appearance of different canine breeds is con- genes, and some arctic breeds such as Siberian
sidered. The eyes of one individual are often Huskies), a subalbinotic fundus may be found.
mirror images of another, though marked dif- The appearance of the fundus ranges from a
ferences may be seen in some dogs (e.g., one small segment of albinism or subalbinism situ-
eye may have a subalbinotic fundus and one ated randomly in the tapetal or nontapetal fun-
fundus with a brightly colored tapetum and dus to almost complete absence of pigmentation
pigmented nontapetal area in a Collie or in the fundus. The tapetal fundus has a light or
Siberian Husky). dark blue color in young pups up to the age of
five to seven weeks. After this age, the adult
coloration starts to develop.
Tapetal Fundus
The combination of the tapetum lucidum and
Nontapetal Fundus
an absence of pigment in the overlying retinal
pigment epithelium (RPE) is the anatomical The nontapetal fundus comprises the largest
basis for the tapetal fundus. The tapetal fundus area of the ocular fundus in the dog. The junc-
forms an almost triangular area, with a horizon- tion between the tapetal and nontapetal fundi
tal base, in the dorsal half of the fundus. The exhibits a continuous variation, from a distinct
area is usually brightly and beautifully colored, line of demarcation to a gradual transition with
­Normal Ocular Fundu  483

(a) (b) (c) (d)

(e) (f) (g) (h)

(i) (j)

Figure 13.8 Normal appearance of the fundus in different canine breeds. (a) A four-­year-­old Beagle with a large,
mostly yellow tapetal area and a relatively large, round disc at the border of the tapetal and nontapetal areas. (b) A
one-­year-­old Briard with a yellow to orange tapetal fundus and a disc at the border of the tapetal and nontapetal
fundi. (c) A three-­year-­old Irish Wolfhound in which the circular disc is enclosed in the yellow to green tapetal
fundus and the vessels are slightly tortuous. (d) A six-­year-­old Toy Poodle in which the tapetal fundus is extremely
small and the disc is located in the nontapetal fundus. Some large choroidal vessels are visible (light red)
underlying the retinal vessels (dark red). (e) A two-­year-­old Clumber Spaniel with a rather lightly colored
nontapetal fundus, with a reddish coloration in the area caused by the underlying choroid. The border of the
tapetal and nontapetal fundi is uneven, with some scattering of tapetal cells. (f) A six-­year-­old Cavalier King
Charles Spaniel with sparse tapetal cells within the tapetal fundus. The uneven borders of the optic disc are
caused by pronounced myelination. (g) A submelanotic right eye in a one-­year-­old Papillon. The regular striation of
the choroidal vessels is seen against the white sclera, and there are no tapetal cells. The nontapetal fundus is
pigmented. The fellow eye had an orange-­yellow “normal” tapetal and a pigmented nontapetal fundus. (h) A
two-­year-­old blue merle Collie with an amelanotic fundus. There is a lack of tapetal cells and of visible
pigmentation. (i) A four-­year-­old liver-­colored Labrador Retriever with a light brownish coloration of the entire
fundus. No tapetal cells are visible. (j) A seven-­week-­old Collie pup with an immature, blue-­colored fundus.

scattered foci of tapetal cells, which become reddish brown. Sometimes, the choroidal ves-
more and more sparse with increasing distance sels will cause a striped or tigroid appearance
from the center of the tapetal fundus. The non- when viewed through the ophthalmoscope.
tapetal fundus has a nonreflective, usually dark In the dog with a subalbinotic fundus, parts
or grayish brown to black color. In the dog of the nontapetal fundus will be unpigmented,
(regardless of the breed) with a brown, choco- thus showing the choroidal vessels overlying
late, or liver coat color associated with a paler the white sclera. Absence of pigment in the
brown iris, the nontapetal fundus is less heavily entire nontapetal region is common (e.g., in
pigmented and will appear paler brown or blue merle Collies).
484 Diseases and Surgery of the Canine Posterior Segment

Optic Nerve Head consists of arterioles and venules located at the


surface of the retina. The diameter of the ves-
The canine ONH, or the optic disc or papilla,
sels decreases with increasing distance from
also exhibits a wide range of normal variations
the ONH; otherwise, no differences should be
in ophthalmoscopic appearance. It is located in
observed with location.
the center of the fundus, sometimes in the non-
The arterioles (usually 15–20 in number)
tapetal fundus and sometimes in the tapetal
radiate away from their origin close to the
region, depending on the extension of the latter.
periphery of the ONH. They appear slightly
There is an obvious variation in size of the
lighter in color compared with the vessels
ONH between different individuals and differ-
transporting venous blood, and they may be
ent breeds. There is no strict relationship, how-
more tortuous than the venules. The main
ever, between breed or size of the dog and the
veins (usually three or four in number) are
size of the ONH. The extent of myelinization
obviously larger and darker red in color than
affects the shape as well as the size of the
the arterioles. They end in the usually incom-
ONH. In young pups where the myelinization
plete venous circle on the top of the ONH but
is incomplete, the ONH is smaller than that in
may, in part, be covered by the ONH tissue.
the adult dog.
Several smaller venules coalesce with the
The shape of the ONH may be round, oval,
major veins, thereby building a branching tree
triangular, or polygonal, and sometimes the
of vessels over the optic fundus. The area cen-
disc edge may be clearly indented. The edge
tralis is an indistinctly bordered area slightly
may be sharply demarcated to a zone of diffuse
superior and about two optic nerve head diam-
transition at which the medullated nerve fibers
eters temporal to the ONH, which is devoid of
extend into the surrounding fundus, especially
blood vessels but encircled by fine branches.
along the retinal blood vessels. The anterior
surface of the ONH is elevated compared with
the surrounding retina in the adult dog, ­ evelopment of the Canine
D
whereas this topographical difference can be
Ocular Fundus
difficult to detect in very young pups with
poorly myelinated nerves. The anterior surface
The difference between the immature ocular
rarely is perfectly flat, and an obvious, central
fundus of a young pup and the fully devel-
prominence of medullated nerve fibers can be
oped, functional fundus of an adult dog is
seen in some dogs, especially Golden Retrievers
striking (Figure 13.9a–c). The process of
and German Shepherds. In the center of the
development includes both a successive series
ONH, a minute, round depression is usually
of morphological events and a functional
seen, which is the physiological cup. The phys-
maturation of the retina.
iological cup, which usually appears grayish in
color, represents the origin of the hyaloid vas-
culature. The color of the ONH varies from Ophthalmoscopy
pinkish white to deep pink, depending on the
It is normally impossible to examine the ocular
extent of visible vasculature. The vessels climb
fundus in pups younger than two weeks,
the ONH, and a usually incomplete venous cir-
because the eyelids remain closed and the ocu-
cle is seen on its top.
lar media, especially the cornea, are not suffi-
ciently clear. When the eyelids open and
ophthalmoscopic examination can be per-
Retinal Vasculature
formed, there is no discernible difference
The vascular architecture of the canine fundus between the tapetal and nontapetal fundi. At
is classified as holangiotic. The vasculature this stage of development, the entire ocular
­Developmental Anomalie  485

(a) (b) (c)

Figure 13.9 Maturation of the canine fundus: (a) 5 weeks of age; (b) 9 weeks of age; and (c) 12 weeks of age.

fundus has a dull, dark gray color, and the ONH tunics of the eye. CEA affects primarily the
is small and flat due to immature myelination. Collie types of dogs but also some other breeds:
The retinal blood vessels, however, are easily Rough and Smooth Collie, Shetland Sheepdog,
identifiable and appear relatively large in size. Australian Shepherd, Border Collie, Nova
The developing tapetal fundus appears paler, Scotia Duck Tolling Retriever, Longhaired
and the nontapetal region relatively darker, Whippet, Boykin Spaniel, and the Lancaster
after three to four weeks of age. The tapetal Heeler. The pathogenesis of the defect is con-
fundus then takes on a lilac to blue coloration, sidered to be an abnormal mesodermal differ-
which becomes more intense with increasing entiation, which results in defects, mainly of
age. After approximately seven to eight weeks, the sclera, choroid, optic disc, retina, and reti-
the tapetal fundus becomes more granular in nal vasculature. The severity of the disease var-
appearance. The bluish, immature tapetal fun- ies from no apparent visual deficit to total
dus then becomes more brightly colored over blindness. CEA is bilateral and has no sex pre-
time, until a tapetal fundus of adult structure disposition. There is no difference in frequency
and coloration is developed at approximately related to coat color, type of coat, or presence
three to four months of age. of the merling gene. The cardinal sign is a geo-
graphically defined region of choroidal hypo-
plasia lateral to the optic disc, which may or
Functional and Morphological
may not be accompanied by obvious retinal or
Development of the Retina
scleral defects or by colobomas. Other anoma-
Retinal differentiation and maturation (mainly lies are RD and intraocular hemorrhage.
of the photoreceptors) in dogs is complete by The hereditary trait for the disorder was
seven to eight weeks of age. At the end of established and a simple autosomal recessive
this period, the retina, as monitored by ERG and inheritance postulated by Yakely and col-
both light and electron microscopy, is adult-­like. leagues through a test breeding scheme. This
mode of inheritance was further supported by
the results of pedigree analysis and test mat-
­Developmental Anomalies ings conducted by Bedford in 1982. The genetic
studies have established the primary CEA phe-
Congenital abnormalities of the eye can either notype, choroidal hypoplasia, to segregate as
be hereditary or nonhereditary. an autosomal recessive trait with nearly 100%
penetrance. Some heterozygotes for the mutant
allele showed mild choroidal hypoplasia. The
Collie Eye Anomaly
CEA locus was mapped to a 3.9-­cM region of
CEA is a congenital ocular syndrome involving canine chromosome 37. An intronic deletion
defects of the posterior vascular and fibrous in the NEHJ1 gene was identified. The
486 Diseases and Surgery of the Canine Posterior Segment

prevalence of CEA has been high in Rough


and Smooth Collies and Shetland Sheepdogs
throughout the world. In 1969, the incidence
of CEA in the Collie was between 75% and 97%
in the United States. Because of selected breed-
ing, this prevalence decreased within several
years to 59%. The incidence of CEA in Border
Collies is low, and only sporadic cases are diag-
nosed, while in the Lancashire Heeler, a some-
what high incidence was reported: 13.7%.

Clinical Findings
Clinical findings in CEA include a high degree
of pleomorphism. In a single litter, there is
often great variation in the severity of the
changes and there may be variation between
the eyes of an affected individual. Choroidal Figure 13.11 RD is part of the CEA complex.
hypoplasia is considered the diagnostic lesion Partial RDs near the disc as well as vascular
for CEA and is always bilateral, though the abnormalities in a young Collie.
extent of the lesion may vary between eyes
(Figures 13.10 and 13.11). The four main
defects included in the CEA syndrome are syndrome is most accurately diagnosed in pups
listed in Table 13.1. Other changes also at six to seven weeks of age. These same dogs
included in this syndrome by some authors are should be examined annually (to confirm the
excessive tortuosity of the retinal vasculature puppy exam results) as well as before their first
and retinal folds in young pups. The CEA breeding.

Difficulties in Diagnosis, Interpretation,


and Control
Now that the causal gene mutation has been
identified and a commercial mutation detec-
tion test has been developed, breeders will be
able to eventually eliminate the condition (by
identification of carrier dogs) and preserve the
best of their breeds’ other characteristics. The
high incidence of CEA in some breeds dictates
that breeders should only attempt to reduce
the mutation incidence within the breed over
several generations. Restricting breeding to
homozygous normal dogs could limit the gene
pool and could lead to loss of desirable features
from the breed and possibly the emergence of
a new hereditary disease that was present at
low frequency within the breed. To avoid the
production of CEA-­affected puppies, breeders
Figure 13.10 Coloboma in conjunction with a
partially deformed disc and choroidal hypoplasia in just need to ensure that one of the breeding
a two-­year-­old Collie. pair is homozygous normal.
­Developmental Anomalie  487

Table 13.1 Ophthalmoscopic findings in Collie eye anomaly.

Lesion Appearance

Choroidal hypoplasia Bilateral, pale-­to-­white area lateral (temporal) or dorsolateral


(superotemporal) of the ONH, variable size; can be asymmetrical; difficult to
detect in merle/subalbinoid dogs
Best to exam puppies at six to seven weeks of age
Can pigment and appear normal later (Go-­Normals)
Posterior colobomas Involve the optic disc (i.e., papillary colobomas) or adjacent area (i.e.,
peripapillary colobomas)
Also called “pits” or posterior scleral ectasia
Appear as gray or pink indentations; vary from shallow depressions to more
extensive excavations or “holes” up to 30 D in depth
May occur in 10–30% of eyes with choroidal hypoplasia
Retinal detachment Partial or complete; uni-­or bilateral; in 5–10% of CEA eyes
Appear clinically as nonfixation of the eyes, a tendency to nystagmus, or even
strabismus in affected puppies
Affect both puppies and adults
Most arise adjacent to the optic disc and extend toward the peripheral fundus,
often with subretinal, intraretinal, or preretinal hemorrhages
Intraocular hyphema Occur in 5% or less of CEA eyes, often with colobomatous defects and RDs

Difficulties in trying to eliminate the condi- varying size of the globes. The defect is associ-
tion by only ophthalmoscopic screening have ated with microcornea of an irregular shape
been partly due to certain difficulties in diag- and, infrequently, with mineralization of the
nosis. The “go-­normal” phenomenon was a anterior corneal stroma. Affected dogs also
major issue with genetically affected animals exhibit heterochromia irides with dyscoria and
being indistinguishable from unaffected ani- corectopia with an oval pupil in which the long
mals by ophthalmoscopic examination as axis is vertical. The hypoplastic irides permit
described previously. Another problem of transillumination and respond poorly to
diagnosis is the differentiation between a mydriatics. False polycoria occurs in 5–10% of
small, centrally located coloboma in the optic affected dogs. Often, the defect extends into
disc and a normal physiological pit. Color-­ the iridocorneal angle and posteriorly into the
dilute animals can also cause problems in ciliary body. Cataracts occur in 60% of affected
making an ophthalmoscopic diagnosis of CEA dogs with microphthalmia and colobomas. In
when only mild choroidal hypoplasia is pre- 54% of affected Australian Shepherds, large
sent. In merles, it is important to closely evalu- equatorial staphylomas occur. The staphylo-
ate the area temporal to the optic disc for mas are either a single depression or several
changes due to choroidal hypoplasia. small excavations grouped together. The cho-
roidal vasculature is greatly reduced or absent
in the staphylomas, and the sclera is irregular
Merle Ocular Dysgenesis
and thin. Large staphylomas may extend from
The Australian Shepherd dog is affected by the ora serrata to the optic disc. Retinal vascu-
multiple ocular anomalies. Affected dogs may lature in the staphylomas may be markedly
show microphthalmia to varying extent and reduced or even absent. In 50% of cases,
488 Diseases and Surgery of the Canine Posterior Segment

complete RD occurs, and approximately 30% primary ocular defect, either as a single defect
of the detachments have intraocular hemor- or together with other lesions such as microph-
rhage. Microphthalmia with colobomas in thalmos or colobomatous defects. Known
Australian Shepherds is inherited as an auto- causes of retinal dysplasia include viral infec-
somal recessive trait with incomplete pene- tions, vitamin A deficiency, X-­ray irradiation,
trance. Affected dogs are homozygous merles certain drugs, and intrauterine trauma. Many
and have excessively white hair coats. A simi- forms in dogs have a hereditary basis.
lar syndrome has been observed but not stud-
ied in merle Collies, Shetland Sheepdogs, Spontaneous Retinal Dysplasia
Harlequin Great Danes, and other merle The pathogenesis for spontaneous retinal dys-
breeds. In general, affected puppies result plasia may vary, depending on the retinal tis-
when both parents are merles (sometimes not sues affected. Often the different forms of
very noticeable). retinal dysplasia occur in specific breeds
(Tables 13.2 and 13.3).
Retinal Dysplasia
Clinical Signs
Retinal dysplasia has been defined as an anom- Clinically, the lesions of retinal dysplasia are
alous differentiation of the retina accompa- unilateral or bilateral and may be grossly
nied by a proliferation of one or more of its divided into three different types or forms
constituent elements. It is characterized histo- (see Table 13.3). Clinically, most lesions in
pathologically by linear folding of the sensory retinal dysplasia do not appear to change with
retina and formation of rosettes composed of time. The least severe type (i.e., focal or mul-
variable numbers of neuronal retinal layers tifocal retinal dysplasia) usually remains
around a central lumen. The defect is associ- unaltered (Figure 13.12). In a few cases, how-
ated with several spontaneously occurring and ever, the lesions become less obvious, and
experimentally induced disorders of the devel- some folds may disappear. At the same time,
oping eye in both humans and animals. the area around others, especially if the
Dysplastic retinal lesions may be associated lesions are numerous, may become more
with systemic abnormalities, or they can be a demarcated, with hyperpigmented spots and

Table 13.2 Ophthalmoscopic findings in canine retinal dysplasia.

Type Ophthalmoscopic findings

Focal or multifocal Retinal folds and rosettes are seen as areas of reduced tapetal reflectivity, appearing
as gray or green dots or linear, “V,” or “Y” streaks
Occur anywhere in the tapetal region, but most often centrally and usually above
the optic disc
May appear elevated, distorting the course of the overlying vessels
Retinal folds in the nontapetal fundus appear as gray or white linear or irregular streaks
Geographic Appear as an irregular or horseshoe-­shaped area, most often in the central
tapetal fundus
May include focal retinal thinning and elevation
Usually, hyperreflective area with variable pigmentation
Complete with Usually, a completely detached neural retina floating in the vitreous, attached
detachment around the ONH
­Developmental Anomalie  489

Table 13.3 Breeds of dogs affected with retinal dysplasia (RD).

Breed (mode of inheritance) Type of RD Other abnormalities

Akita Complete Microphthalmia, cataract, posterior lenticonus


American Cocker Spaniel Multifocal None
(AR)
Multifocal Microphthalmia, cataracts, persistent pupillary
membranes
Australian Shepherd Complete Iridal heterochromia, cataracts, staphylomas, RDs
(AR, incomplete penetrance)
(any breed with homozygous
merling)
Beagle Multifocal Microphthalmia
Bedlington Terrier (AR) Complete Microphthalmia, cataracts, RDs
Cavalier King Charles Spaniel Geographic Microphthalmia, cataracts, posterior lenticonus
Chow Chow Complete Severe ocular defects
Doberman Pinscher (AR) Complete Microphthalmia, anterior segment dysplasia,
aphakia, hyperplastic primary vitreous
English Springer Spaniel (AR) Geographic Microphthalmia, cataracts, RDs
Golden Retriever Geographic None
Labrador Retriever Multifocal None
Geographic None
(AR) Complete Microphthalmia, cataracts, intraocular
hemorrhage
(AD) Complete Cataracts; retarded growth of the radius, ulna, and
tibia; separated hypoplastic anconeal and
coronoid processes; hip dysplasia; delayed
development of the epiphysis
Rottweiler Multifocal None
Sealyham Terrier (AR) Complete Microphthalmia, cataracts, RDs
Samoyed Complete Microphthalmia, cataracts, hyaloid artery
persistence, and skeletal defects as in the Labrador
Retriever
Yorkshire Terrier Multifocal None

AD, autosomal dominant trait with variable penetrance; AR, autosomal recessive trait.

streaks as well as hyperreflective areas in the Since retinal dysplasia is a defect of retinal
vicinity of the dysplastic lesions. In the geo- differentiation, lesions are mainly congenital
graphic type, the lesions never disappear but in nature. Therefore, early screening of dogs at
instead become focally more demarcated with six to eight weeks has been encouraged for
time. The most severe form, with complete breeds in which the defect is prevalent. A sec-
RD, remains unaltered in most cases, but ond examination was recommended to be per-
complications including vitreal hemorrhage, formed between six months and one year of
cataracts, and secondary glaucoma may arise age in breeds affected with the geographic
(Figure 13.13a–c). form of retinal dysplasia.
490 Diseases and Surgery of the Canine Posterior Segment

dysplasia type 1 (drd1) for the Labrador type


and dwarfism with retinal dysplasia type 2
(drd2) for the Samoyed. Dwarfism with reti-
nal dysplasia results from mutations in the
collagen 9 genes COL9A2 and COL9A3. drd1
in the Labrador results from an insertional
mutation in COL9A3, whereas drd2 in the
Samoyed results from a deletion in COL9A2.
Identification of the mutations has allowed
the development of DNA-­based genotyping
tests (see Appendix A and for up-­to-­date
information consult the European College
of Veterinary Ophthalmologists [ECVO]
Hereditary Eye Diseases Manual [http://
ECVO.org] and/or http://Optigen.com).

Figure 13.12 Multifocal retinal dysplasia in a


Inherited Retinal Dysplasia and Persistent
one-­year-­old Labrador Retriever. Several grayish
hyporeflective streaks and spots are seen in the Hyperplastic Primary Vitreous
tapetal fundus. A clinical syndrome of congenital retinal dys-
plasia and persistent primary vitreous occurs
Breed Incidence and Inheritance in the Miniature Schnauzer. Through analysis
Spontaneous retinal dysplasia occurs in sev- of an extended pedigree and by test breeding, a
eral breeds, and hereditary factors have been simple autosomal inheritance for the disorder
shown or suspected to be the cause in many has been postulated. In affected dogs, the reti-
breeds (see Table 15.3). It is not uncommon nal dysplasia is usually generalized, involves
to find retinal dysplasia in conjunction with the temporal and nasal retina most severely,
other severe ocular defects, as described in and is most extensive dorsal to the optic disc
the Doberman Pinscher, Akita, Chow Chow, (Figure 13.14a–c). Concurrently with the dys-
and Australian Shepherd dog. In some plastic retina, many dogs also show mild uni-
breeds, such as in the Samoyed and the lateral or bilateral PHPV. The PHPV changes
Labrador Retriever, retinal dysplasia occurs are usually associated with small, white poste-
in combination with other nonocular defects rior lens capsule plaques, manifested as a cen-
(termed canine oculoskeletal dysplasia). tral posterior lens capsule ring.

Canine Oculoskeletal Dysplasia – Dwarfism Induced Retinal Dysplasia


with Retinal Dysplasia Infection with canine adenovirus has been
Labrador Retrievers and Samoyed dogs are shown to cause retinal dysplasia. Another
affected by another inherited syndrome, infectious agent causing retinal dysplasia is
canine oculoskeletal dysplasia, in which there canine herpesvirus. Experimental studies have
are both ocular lesions and skeletal abnor- demonstrated that severe ocular inflammation
malities. Cataracts and complete RD are seen with subsequent retinal dysplasia and associ-
together with retarded growth of the radius, ated ocular anomalies can be induced in neo-
ulna, and tibia; separated hypoplastic anco- natal pups. The immature mammalian retina
neal and coronoid processes; hip dysplasia; is also susceptible to radiation, which has been
and delayed development of the epiphysis. In demonstrated in the dog. Irradiated newborn
the two breeds, the disease loci are nonallelic. puppies exhibited retinal rosette formation.
They have been termed dwarfism with retinal The rosettes were either few or numerous, and
­Developmental Anomalie  491

(b)

(a) (c)

Figure 13.13 Oculoskeletal dysplasia in a Labrador Retriever. (a) Note the angular limb deformities.
(b) Bilateral cataract formation is obvious. (c) Ocular ultrasound reveals the presence of RD.

(a) (b) (c)

Figure 13.14 Retinal dysplasia and PHPV in a young Miniature Schnauzer. (a) There are posterior
lenticular opacities, mainly manifested by a lens capsule ring, with some centrally located opacities.
(b) White primary vitreous strands are seen, and a pertinent hyaloid vessel extends to the Bergmeister’s
papilla. (c) Histopathological section of the posterior segment with severely dysplastic retina.
492 Diseases and Surgery of the Canine Posterior Segment

they involved both tapetal and nontapetal Great Pyrenees breed. Similar changes were
fundi. Morphological studies showed lesions then observed in the Coton de Tulear, English
indicative of aberrant development after and French Mastiff and Bullmastiff dog breeds,
radiation-­induced damage. and the Lapponian Herder. Pedigree analysis
and prospective matings in the Great Pyrenees
Difficulties in Diagnosis, Interpretation, dog indicate an autosomal recessive inherit-
and Control ance for the disorder. Ophthalmoscopic lesions
Retinal dysplasia includes a diverse group of have been described as multifocal, gray to tan
entities with variable clinical and histopatho- fundic patches that vary in size from barely vis-
logical appearances, variable pathogeneses, and ible to some lesions that are larger than the
variable etiologies. Retinal dysplasia is an abnor- optic disc. Lesions start to develop at approxi-
mality that can occur in conjunction with many mately 11 weeks of age; usually they are sparse,
other eye anomalies, with or without systemic but they develop bilaterally in the peripheral
anomalies, either unilaterally or bilaterally. tapetal fundus, around the optic discs, and
The clinical appearance of retinal dysplasia occasionally under the major veins inferior to
is often similar regardless of the cause in the optic disc (Figure 13.15). The peripapillary
selected breeds. Among the breeds in which lesions, observed as serous RDs, develop
the defect has been recognized to be inherited, within a few hours but remain the same size
certain characteristic features, such as the cen- for years, while the peripheral lesions develop
tral, mainly tapetal location of the folds and gradually over years and appear to increase
rosettes, are evident, which simplifies diagno- slowly in size and number until the age of
sis in these breeds. 20 weeks.
The high frequency of retinal folds among The lesions do not appear to be congenital
the eyes of pups in some breeds, particularly but are detected suddenly in young puppies.
the Collie and Shetland Sheepdog, has some- The retinal degeneration and RPE changes are
times been interpreted as being a very mild focal and related only to the serous retinal and
form of retinal dysplasia. Such folds, however, RPE detachments. An investigation of poten-
usually disappear as the eye grows, and they tial candidate genes revealed that affected dogs
probably represent uncoordinated growth of had a mutation in the canine BEST1 gene
the inner and outer layers of the optic cup. As
yet, there is no evidence for genetic determina-
tion except on a breed basis, and there is prob-
ably an association with the small eyes typical
of these breeds.
Retinal dysplasia represents abnormal differ-
entiation of the retina and therefore would be
expected to be permanent; however, in the
young puppy (six to eight weeks old), diagnosis
can be difficult. Thus, a follow-­up of these fun-
duscopic alterations in dogs 6–12 months of age
could indicate whether the lesions should be
designated as retinal folds or retinal dysplasia.

Canine Multifocal Retinopathy


Figure 13.15 Canine multifocal retinopathy. An
A unique inherited multifocal serious and bul- eight-­year-­old Mastiff with multiple bullae with
lous retinopathy was first described in the tan-­colored subretinal fluid.
­Inherited Retinal Degenerations/Dystrophie  493

(cBEST1). In humans, mutations of this gene the retina, and encircling these changes are
cause vitelliform macular dystrophy type 2, or areas of hyperreflectivity at the end stage. The
Best macular dystrophy. The cBEST1 gene is latter disorder is the result of a primary defect
predominantly expressed in RPE/choroid and in the RPE and does not always lead to blind-
encodes bestrophin, a 580-­amino acid protein ness. Thus, the two disease entities represent
of 66 kDa. Two disease-­specific mutations were completely different disorders. During the last
identified in the cBEST1 gene of affected dogs, few decades, PRA has been subdivided further
cmr1 mutation in mastiff-­related and the Great into more specific diseases at the cellular level
Pyrenees dog breeds, and cmr2 in the Coton de and also at the molecular level, and gene sym-
Tulear dog breed. Recently, a third form of cmr bols are used to differentiate these disorders
disease was identified in the Lapponian Herder (see Appendix A). The term CPRA has been
breed, although this also resulted from a muta- replaced by the term retinal pigment epithelial
tion in cBEST1. It manifested as a somewhat dystrophy (RPED), which more specifically
later onset of the multifocal lesions, at approxi- relates to the disease entity.
mately one year of age. The PRA diseases are subdivided grossly into
developmental and degenerative diseases. The
developmental class represents a large aggre-
I­ nherited Retinal Degenerations/ gate of genetically distinct disorders expressed
Dystrophies cytologically during the postnatal period,
when the visual cells are beginning to differen-
All cellular layers of the retina are potentially tiate, i.e., dysplasia of the rod or cone photore-
susceptible to hereditary abnormalities. Most ceptors (or both), and each has its own unique
of these, however, relate to the parts that are disease course and phenotype as assessed by
physiologically the most complex: the layers functional and morphological criteria. Typical
of the photoreceptors and the RPE. In the for the photoreceptor dysplasias is that before
dog, there is a broad range and diversity of the retina is adult-­like (approximately eight
inherited retinal diseases that affect these weeks of age in the dog), they show rather
structures. severe structural alterations of the rod or cone
photoreceptor cells, and the rate of progression
and loss of photoreceptors in the disease pro-
Classification of Canine Hereditary
cess is most often rapid.
Retinal Degenerations
In contrast, the degenerative diseases repre-
Canine retinal degenerations primarily affect sent defects in which photoreceptor cells
the photoreceptors, RPE, or both. The first degenerate after having differentiated mainly
well-­documented report of an inherited retinal in a normal way. In the latter group, disease
degeneration in a Gordon Setter from Sweden occurs more slowly and is modified by tempo-
was in 1910. To these conditions, the general ral and topographical factors. One form of pri-
term PRA has been applied. Since then, clini- mary photoreceptor degeneration (progressive
cians have divided PRA into two types depend- rod–cone degeneration, prcd) is known to be
ing on the ophthalmoscopic appearance of the allelic in many breeds of dog, and the underly-
fundus lesions: generalized PRA and central ing gene mutation has been identified. Within
PRA (CPRA). In generalized PRA, there is gen- the photoreceptor dysplasia and degeneration
eralized hyperreflectivity of the retina at the groups, the diseases are subdivided still fur-
end stage of the disease, indicating a general- ther according to the type of cell primarily
ized atrophy of the neural retinal structures affected (e.g., rod–cone dysplasia of Irish
and clinical blindness. In CPRA, there are Setters and cone degeneration of Alaskan
multifocal accumulations of pigment within Malamutes).
494 Diseases and Surgery of the Canine Posterior Segment

Clinical Signs of Hereditary Retinal an obstacle course, or by using a specially


Degeneration/Progressive designed forced-­choice vision testing device.
Retinal Atrophy In some instances, impaired day vision (day
blindness) may be observed by the owner or
Clinical manifestations of the different forms
the examiner as an initial clinical sign if the
of PRA are often remarkably similar, irre-
cone system is involved primarily in the dis-
spective of the type of disorder present at the
ease process.
cellular level. Nonspecific features associated
The ophthalmoscopic changes for PRA are
with primary photoreceptor degenerations
summarized in Table 13.4, and divided into early,
leading to retinal atrophy are described
moderate, and advanced (Figures 13.16–13.19).
briefly here; particular features associated
Secondary cataract often develops in the more
with specific genetic disorders are described
advanced stages of disease. The initial changes
later in the text.
tend to occur in the posterior cortex and include
PRA is always bilateral and almost always
vacuolation and opacification. Often, irregular
leads to blindness. The most common clinical
radiations are seen emanating from the posterior
sign of early disease is impaired vision in dim
pole of the lens and extending to involve the
light and darkness (i.e., night blindness),
equatorial cortex and, later, the entire lens.
since it is most often the rods that are affected
Mature cataracts, especially in certain breeds,
first in PRA. The reduced visual capacity in
make the evaluation of retinal function using
darkness may often be observed by visual
ERG of utmost importance before cataract sur-
testing, which is performed by testing the
gery is performed in order to rule out retinal
menace reaction, using falling cotton balls in
degeneration (Figure 13.20).
front of the dog in a dimly lit room, or using

Table 13.4 Ophthalmoscopic changes in PRA.

Stage of the disease Ophthalmoscopic changes

Early Slight change in tapetal reflectivity or hyporeflectivity is often seen, such as a


grayish discoloration mainly in the peripheral tapetal fundus
A slight vascular attenuation and beading of retinal vessels in the midperipheral
and peripheral parts of the tapetal fundus may be observed
Moderate Color changes in the tapetal fundus become more marked and generalized, as does
the vascular attenuation
Increased reflectivity, or hyperreflectivity, of the tapetal fundus, which is usually
most marked in the midperipheral tapetal fundus
Slight decrease in the pigmentation of the nontapetal fundus
ONH changes include early loss of myelin, disc changes in shape to circular, and
reduced number and calipers of blood vessels
Early optic disc atrophy
Advanced Hyperreflectivity progresses to involve the entire tapetal fundus
Continued loss of the pigmentation of the nontapetal fundus
Marked decrease in the retinal vasculature with preservation of only the large and
central blood vessels until late in the disease
Ghost vessels peripherally
Optic disc pallor, loss of myelin, and reduction in disc size
(a) (b)

Figure 13.16 Moderately advanced cases of bilateral retinal degeneration (PRA) in two different canine
breeds. Note the generalized change in reflectivity or hyperreflectivity and vascular attenuation in both
cases. (a) A three-­year-­old Irish Wolfhound. (b) A four-­year-­old Dachshund.

(a) (b) (c)

Figure 13.17 Fundus photographs showing progressive fundus changes in a Papillon with PRA: (a) 6 months
of age; (b) 12 months of age; and (c) 24 months of age. Note the progressive retinal vasculature attenuation and
initial tapetal hyporeflectivity that is apparent prior to development of generalized tapetal hyperreflectivity.

(a) (b)

Figure 13.18 An advanced case of retinal degeneration (PRA) in a five-­year-­old Tibetan Terrier. (a) The
tapetal fundus is hyperreflective, and only ghost vessels are visible. (b) The nontapetal fundus is
depigmented and hyperpigmented in striae and patches.
496 Diseases and Surgery of the Canine Posterior Segment

(a)

(b) (c)

Figure 13.19 Advanced prcd observed in a seven-­year-­old Miniature Poodle. (a) Central part of fundus,
with severe vascular attenuation and a grayish tapetal discoloration. (b) Midperipheral fundus, with
hyperreflectivity and discoloration in the peripheral part. (c) Periphery of the tapetal fundus, with a marked
striation. The contours of the choroidal vascular pattern are observed underlying the atrophic neural retina.

Early-­Onset Photoreceptor Degenerations differentiation of visual cells resulting from a


nonsense mutation in the β-­subunit of cyclic
Photoreceptor Dysplasias
guanosine monophosphate (cGMP) metabo-
The characteristics for the retinal photore- lism. The defect in Irish Setters is similar to
ceptor dysplasias in the dog are summarized that in the retinal degeneration, rd1 mouse, in
in Table 13.5. Rod–cone dysplasia type 1 which the β-­subunit of cGMP-­PDE (PDE6B)
(rcd1), initially described in the Irish Setter, was identified by Bowes and colleagues as
but also found in the Irish Red and White being defective. The PDE6B gene was subse-
Setter, is an early-­onset, recessively inherited quently considered to be a candidate gene for
disease. It is characterized by arrested the rcd1 defect.
­Inherited Retinal Degenerations/Dystrophie  497

3 Week 7 Week
+/+ –/– +/+ –/–
–1.60 –1.60
–1.19 –1.19
–0.80 –0.80
–0.40 –0.40
–0.00 –0.00
Dark-adapted 0.40 0.40
0.96 0.96
1.36 1.36

1.90 1.90

50 µV 50 µV 20 µV
20 µV
20 mS 20 mS 20 mS 20 mS

(a) (b) (c) (d)

0.00 0.00
1.06 1.06
0.40 0.40
0.85 0.85
Light-adapted 1.36 1.36
1.90 1.90
2.40
2.40
20 µV 20 µV 20 µV 10 µV
20 mS 20 mS 20 mS 20 mS
(e) (f) (g) (h)

Figure 13.20 Representative dark-­adapted (a–d) and light-­adapted (to a background light of 30 cd/m2)
(e–h) ERG intensity series responses from a normal control dog (indicated by the symbol +/+) (a, c, e, and g)
compared to a PDE6A mutant/rcd3 dog (indicated by the symbol 2/2) at three weeks (a, b, e, and f) and
seven weeks (c, d, g, and h) of age. Arrowheads indicate the onset of flash. The flash intensity is indicated in
log cd s/m2. Note the difference in scales between the tracings. The vertical scale bar indicates amplitude
in microvolts and the horizontal bars time in milliseconds. The rcd3 puppies do not develop normal
rod-­mediated responses, and there is a rapid loss of the small amplitude response that is recordable. Much
of this response is likely to represent cone responses. The light-­adapted (cone) responses are also reduced
from an early age. The cone a-­wave is reduced at three weeks, and both a-­and b-­waves at seven weeks.

The disease was the first form of PRA to be morphological characteristics as in the early-­
described clinically in great detail, first in onset disease of Irish Setter dogs, and it has
England and then in the United States. Night been suggested that it be given the gene symbol
blindness is an early behavioral sign, detect- rcd1a. Mutation-­based tests are available for
able from six to eight weeks of age. Day rcd1 for Irish Setter and for rcd1a for Sloughi
vision is usually lost during the first year, but dogs (see Appendix A and www.optigen.com).
there is considerable variation in this respect.
The first ophthalmoscopic signs are usually Rod–Cone Dysplasia Type 2
visible by three to four months of age, and Rod–cone dysplasia type 2 (rcd2) has been
the end stage, with generalized atrophic described in the Collie and is another reces-
changes, is reached at approximately one sively inherited, early-­onset retinal degenera-
year. The ERG is nonrecordable at approxi- tion (Figure 13.21). Based on clinical,
mately 18 weeks of age. electrophysiological, morphological, and bio-
A different mutation in PDE6B has been iden- chemical criteria, rcd1 and rcd2 are very simi-
tified as a cause of PRA in Sloughi dogs. The lar diseases. There is an equally early and rapid
disease in Sloughi dogs has similar clinical and increase in retinal cGMP levels in the postnatal
498 Diseases and Surgery of the Canine Posterior Segment

Table 13.5 Characteristics of the canine retinal photoreceptor dysplasias.

Mode of Diagnosis by
Breed Primary defect inheritance ophthalmoscopy Diagnosis by ERG

Alaskan Malamute Cone degeneration AR No changes 6 weeks: cone –; rod


normal
Belgian Shepherd Rod–cone dysplasia Unknown 11 weeks 4 weeks: cone –; rod –
Collie Rod–cone dysplasia AR 16 weeks 6 weeks: cone ↓; rod –
Irish Setter Rod–cone dysplasia AR 16 weeks 6 weeks: cone ↓; rod –
Miniature Schnauzer Rod–cone dysplasia AR 1.5–5 years 6 weeks; cone ↓; rod ↓
Norwegian Elkhound Rod dysplasia AR 1–1.5 years 6 weeks: cone
normal/↓; rod –
Norwegian Elkhound Early rod degeneration AR 9 months to 1 year 5 weeks: A-­wave
dominates. Cone ↓;
rod ↓
Pit Bull Terrier Cone–rod dystrophy Unknown 3–6 months 6 weeks: cone –; rod ↓
Short-­Haired Cone–rod dystrophy AR suspected 3 years 5 weeks: cone –; rod ↓
Dachshund
Long-­Haired Cone–rod dystrophy Unknown 6 months 6 weeks: cone ↓; rod
Dachshund normal

AR, autosomal recessive trait; ERG, electroretinography.

diagnosis in rcd1, it was established that the


rcd1 mutation was not present in rcd2.
Recently, the rcd2 mutation was discovered in
the C1orf36 gene (now named RD3). Mutations
in the homologous gene are responsible for a
comparable disease of humans and murines
(retinal degeneration 3, rd3). Clinically, night
blindness is the earliest sign, detectable by six
weeks of age. Visual capacity is gradually
reduced over time, just as in affected Irish
Setters, and affected dogs become blind, usu-
ally before one year of age.
Figure 13.21 Right eye of a Collie with both PRA
and CEA. Note the choroidal hypoplasia lesion and Rod–Cone Dysplasia Type 3
the marked attenuation of retinal vasculature. The
tapetal fundus is hyperreflective. Just as in Irish Setters, Sloughis, and Collies
with the rod–cone dysplasias types 1 and 2,
respectively, the disorder in the Cardigan
period, and the magnitude of this increase and Welsh Corgi is of early onset, leading to blind-
the time course are similar. There is deficient ness in young adult dogs. The causal mutation
cGMP-­PDE activity in both diseases, though in is a 1-­bp deletion in codon 616 of the α-­subunit
rcd2, the activity is calmodulin-­independent. of rod cGMP phosphodiesterase (PDE6A).
The two dysplasias of Irish Setters and Collies There is a mutation detection test available for
represent mutations of different genes. With the disorder. Ophthalmoscopic changes are
the advantage of having an early molecular present by 12 weeks of age.
­Inherited Retinal Degenerations/Dystrophie  499

Rod Dysplasia for PRA in the Miniature Schnauzer is desig-


A recessively inherited form of retinal dyspla- nated as type A PRA (www.optigen.com). There
sia was described in the Norwegian Elkhound is a mutation-­based test available for this disorder.
many years ago. Subsequently, the mutant
strain was lost. The disease was first described Cone–Rod Dystrophy
as “photoreceptor abiotrophy,” but later stud- The cone–rod dystrophies are a heterogeneous
ies, however, showed developmental abnor- group of inherited retinal degenerative disor-
malities, specifically of rods. Clinically affected ders naturally occurring in humans and in
dogs became night blind at six months of age, dogs. The diseases are characterized by simul-
and visual problems progressed to total blind- taneous involvement of cone and rod photore-
ness at three to five years. ceptors, the former being more severely
affected than the latter, initially. So far, the dis-
Early Retinal Degeneration order has been described in comparatively few
Early retinal degeneration is a recessively inher- canine breeds. These two forms of cone–rod
ited condition in the Norwegian Elkhound. dystrophy (crd) were named crd1 and crd2.
Abnormalities in retinal cyclic nucleotide crd1 is reported in the American Staffordshire
metabolism as well as mutations in the PDE6B Bull Terrier and crd2 in the American Pit Bull
gene were excluded for early retinal degenera- Terrier. The crd2 mutation has been identified
tion by breeding and molecular studies. The and a DNA-­based test offered, although the
gene defect was mapped to a region of the mutation was not published at the time of writ-
canine genome that was subsequently found to ing (www.optigen.com). Recently, crd was
be canine chromosome 27. Recently, a mutation identified in the Glen of Imaal Terrier and des-
was found in the STK38L gene, affecting a path- ignated as crd3. Thorough clinical and labora-
way important for neural and photoreceptor cell tory studies of the Glen of Imaal Terrier have
function. Clinically affected dogs are night blind shown early fundus changes at the age of
by 6 weeks of age and blind by 12–18 months. three years.
Early ophthalmoscopic alterations are present In the Short-­Haired Dachshund, an early-­
by six months and progress to atrophic changes, onset, recessively inherited crd has been
which are observed at approximately one year. described including clinical and electrophysio-
logical findings. Already at the age of five weeks,
Photoreceptor Dysplasia the cone system is affected with severely reduced
Photoreceptor dysplasia of Miniature Schnauzers or nonrecordable cone-­derived ERG responses,
is an unusual disease of the photoreceptors that, while rod responses are either normal or only
through pedigree analysis and test mating, has slightly reduced at this early age. A novel gene for
been shown to be inherited as an autosomal this early-­onset crd has been described: a deletion
recessive trait. The disease is unusual in that it in the nephronophthisis 4 (NPHP4) gene, also
has a slow clinical progression when assessed known as nephroretinin, causing simultaneous
with behavioral testing and ophthalmoscopy. eye and kidney disease in humans, and naturally
When judged with histopathology and ERG, occurring crd without additional kidney disease
however, it is an early-­onset disorder. Clinically in the canine. In the Long-­Haired Dachshund,
affected dogs show initial night blindness, fol- the clinical and morphological characteristics of
lowed by progressive loss of day vision. a rod–cone dystrophy were described. This was
Ophthalmoscopically, changes in the fundus of given the gene symbol cord1. Ophthalmoscopic
affected animals are complicated by the unusual changes were observed at the age of six months
and variable appearance of the tapetal fundus in and included changes in the granular appearance
this breed. Diagnosis on the basis of ERG is pos- of the fundus followed by tapetal hyperreflectiv-
sible from an early age. The mutation responsible ity and retinal vascular attenuation. Cone–rod
500 Diseases and Surgery of the Canine Posterior Segment

dystrophy in the Miniature Long-­Haired photoreceptor, and ganglion cell layers


Dachshund has been reported to be due to a (Table 13.6). Interestingly, a human retinitis
mutation in the RPGRIP1 (retinitis pigmentosa pigmentosa patient was identified with an
GTPase regulator-­interacting protein 1) gene. identical mutation in the human PRCD gene.
These studies were based on an inbred colony of
prcd in the Miniature and Toy Poodle
dogs. Recent studies have suggested the situation
may be more complex. Some dogs homozygous In the Toy and Miniature Poodles, structural
for the RPGRIP1 mutation do not appear to and functional abnormalities in prcd do not
develop retinal disease. become evident until after the visual cells
have developed normally. The frequency of
prcd in Poodles has been high over the years.
Night blindness is the first behavioral sign,
­ ate-­Onset Photoreceptor
L
being observed in affected dogs usually at
Degenerations three to five years of age, but there is consid-
erable variation in onset. Night blindness is
Progressive Rod–Cone Degeneration
followed by reduced vision in daylight and,
The “classical type of PRA” that is termed pro- finally, by complete blindness, which occurs
gressive rod–cone degeneration (prcd) has an at a variable age, usually between five and
autosomal recessive inheritance. The defect seven years. Development of a secondary cat-
has been known for some time to be an allelic aract may exacerbate vision loss and there-
condition in many dog breeds with late-­onset fore influence the age at which the condition
type of PRA (www.optigen.com). A mutation first becomes apparent to the owner.
in a previously unidentified gene, PRCD, has Ophthalmoscopic fundus changes are usu-
been identified and expression studies showed ally advanced by the time owners have
that this gene is predominant expressed in the noticed vision problems (see Figures 13.16
retina, with equal expression in the RPE, and 13.19, and Table 13.6).

Table 13.6 Characteristics of canine retinal photoreceptor degenerations.

Mode of Diagnosis by Diagnosis by ERG and


Breed Primary defect inheritance ophthalmoscopy changes

Akita Not established AR 1–3 years 1.5–2 years: cone ↓; rod ↓


American Cocker Spaniel Rod–cone degeneration AR 2.5–3 years 9 months: cone ↓; rod ↓
English Cocker Spaniel Rod–cone degeneration AR 3–8 years 2–3 years: cone ↓; rod ↓
Labrador Retriever Rod–cone degeneration AR 3–6 years 1.5 years: cone ↓; rod ↓
Miniature Long-­haired Unknown AR 6 months 4 months: cone ↓; rod ↓
Dachshund
Papillon Unknown AR 1.5–5 years 9 months to 1.5 years:
cone ↓; rod ↓
Portuguese Water Dog Rod–cone degeneration AR 3–6 years 1.5 years: cone ↓; rod ↓
Siberian Husky Unknown X-­linked 2 years 1 year: cone ↓; rod ↓
Tibetan Spaniel Unknown AR 3–5 years 1.5 years: cone ↓; rod ↓
Tibetan Terrier Unknown AR 1.0–1.5 years 10 months: cone ↓; rod ↓
Toy and Miniature Poodle Rod–cone degeneration AR 3–5 years 9 months: cone ↓; rod ↓

ERG, electroretinography.
­Other Generalized Retinopathies/Retinal Dystrophie  501

prcd in Other Breeds and has been shown to be due to a mutation in


There is a variation in age of onset, rate of the open reading frame 15 of the RP GTPase
progression, and topographical changes in regulator (RPGR) gene. The X-­linked PRA
the retina between (and within) breeds that described in both the Siberian Husky and the
suffer from prcd. This variation is likely to Samoyed is termed X-­linked PRA type 1
eventually prove to be due, at least in part, to (XLPRA1). A mutation-­based DNA test is avail-
background genetics (presence of modifying able for XLPRA1.
loci). Some of these breeds include English
Cocker Spaniel, American Cocker Spaniel, Dominant Progressive Retinal Atrophy
and Labrador Retriever. For an up-­to-­date In the Old English Mastiff and in Bull
and comprehensive list of other canine Mastiff dogs, a specific retinal disease unlike
breeds affected by the prcd mutation, see those previously described was discovered.
www.optigen.com. The disease displayed an ambiguous mode
of inheritance and therefore outcross mat-
Autosomal Recessive PRA (Non-­prcd) ings were performed in order to elucidate
in Other Breeds the specific mode of inheritance for the dis-
These breeds include Tibetan Terrier, Tibetan order, which was shown to follow a domi-
Spaniel, Akita, Papillon, and English Springer nant pattern. The defect found is the first
Spaniel. The Schapendoes breed of dog has opsin mutation described for dogs. The gene
recently been shown to have autosomal reces- defect is a T4R mutation (a point mutation
sive PRA caused by a mutation in a newly that changes the coding at codon 4 from
identified gene: coiled-­coil domain containing threonine to arginine), indicating a different
66 (CCDC66). The Golden Retriever is also cause of PRA than previously described in
affected by the prcd mutation. A recent study other breeds of dog.
indicated a second disease-­causing gene for
PRA in Golden Retriever: a frameshift muta- PRA in Other Breeds Not Yet Characterized
tion in the SLC4A3 gene was shown to be PRA has been described in more than 100 differ-
implicated in the disease. A large proportion of ent canine breeds. The disease in all of these
the PRA cases still remain unexplained (44%), breeds has not been reported in detail in the sci-
however, which indicates that PRA in the entific literature. Rubin provided a valuable sum-
breed is genetically heterogeneous and that mary on retinal degeneration/PRA in various
there are at least three different forms in the breeds. Specific information about retinal dis-
breed (mutations in PRCD, SLC4A3, and an as eases in the various breeds can also be obtained
yet unidentified mutation). from the American College of Veterinary
Ophthalmologists Genetic Committee (see latest
X-­Linked Progressive Retinal Atrophy edition of Hereditary Ocular Disease of Purebred
Hereditary retinal degeneration in Siberian Dogs) and from the ECVO Hereditary Eye
Huskies has been described. There seemed to Disease Committee.
be an excess of affected male dogs with the dis-
order, and further studies, including test breed-
ing schemes, showed there was an X-­linked
­ ther Generalized Retinopathies/
O
transmission for the disease. Clinical signs of
X-­linked retinal degeneration include initial
Retinal Dystrophies
night blindness and early ophthalmoscopic
Early Retinopathy
signs of the retinal degeneration, usually
observed at two to four years of age. The same These breeds include Bernese Mountain dog;
form of PRA was described in the Samoyed an early-­onset retinal degeneration has been
502 Diseases and Surgery of the Canine Posterior Segment

described. The disease can be detected by oph- Photoreceptor Dysplasia


thalmoscopy and behavioral studies at approx-
A condition was described in Belgian
imately one year of age.
Shepherds as a form of photoreceptor dyspla-
sia in which complete blindness was observed
Cone Degeneration at eight weeks in the absence of ophthalmo-
scopic changes. By 11 weeks, a multifocal pat-
A recessively inherited disease has been
tern of retinal folding or thickening was seen.
described in Alaskan Malamutes that specifi-
The foci degenerated, and subsequently, there
cally affects the cones and causes congenital
were hyperreflective lesions with a marked
day blindness (originally described as hemer-
central pigmentation. The ERG was nonre-
alopia). Clinically, behavioral signs in
cordable from at least four weeks of age.
affected dogs are usually apparent at
8–10 weeks of age. The affected dog shows
severe loss of vision in daylight and in high
levels of artificial illumination, but it
­ PE Autofluorescent
R
becomes less insecure when taken into dim Inclusion Epitheliopathy/
lighting conditions. Recovery of vision takes Retinal Pigment
several minutes, though loss of vision on Epithelial Dystrophy
returning to bright light is immediate. No
funduscopic changes are observed at any The term CPRA has been used for a group of
stage of disease, and the PLRs are normal in conditions with ophthalmoscopic changes that
both dim and bright light. The ERG of an can be characterized by an accumulation of
affected dog reveals normal rod function but irregular foci or light-­brown pigment spots in
an absence of cone responses. In the day the central tapetal fundus (Figure 13.22a and
blind dog, the cone contribution to the ERG, b). Over time, these foci increase in size and
including the response to rapidly flickering become distributed throughout the tapetal
lights, is lost. Flicker fusion studies are par- zone. At this stage, there are also atrophic
ticularly valuable in diagnosing day blind- changes, such as hyperreflectivity around the
ness: the cone branch of the bipartite flicker pigment foci that indicate atrophy of the over-
fusion response curve (20–70 Hz) is usually lying neural retina. The nontapetal fundus
absent, whereas the rod branch (less than shows similar foci, with hyperpigmentation
20 Hz) resembles a normal response. and depigmented areas in between. It is the
Cone dystrophy has also been reported in general opinion among veterinary ophthalmol-
the German Short-­Haired Pointer. Breeding ogists today that at least among those breeds in
studies showed that the disease in the which the defect has been established micro-
German Short-­Haired Pointer is allelic with scopically, the term RPED is preferred. The dis-
the Alaskan Malamute cone degeneration. A ease has been recognized in Labrador and
point mutation in CNGB3 was identified in Golden Retrievers, Border Collies, Rough and
German Short-­Haired Pointers. Gene therapy Smooth Collies, Shetland Sheepdogs, English
using an adeno-­associated viral vector to Cocker Spaniels, English Springer Spaniels,
introduce a normal copy of the CNGB3 gene Chesapeake Bay Retrievers, and others. In
to affected Alaskan Malamutes and German Briards, an unusually high frequency of the dis-
Short-­Haired Pointers restored cone function. order was reported: between 30% and 40%. In
The clinical condition has also been recent years, however, the condition is more
described in the Miniature Poodle and three rarely observed in the various breeds.
single cases: in a Rhodesian Ridgeback cross, It has been suggested that CPRA/RPED in
an Australian Cattle Dog, and a Chihuahua. Labrador Retriever is inherited as a dominant
­RPE Autofluorescent Inclusion Epitheliopathy/Retinal Pigment Epithelial Dystroph  503

(a) (b)

Figure 13.22 Advanced RPED with typical ophthalmoscopic changes. (a) A four-­year-­old English Cocker
Spaniel with multiple light brown spots across the tapetal fundus. This dog has low circulating vitamin A
levels. (b) A five-­year-­old English Cocker Spaniel with darkly pigmented spots surrounded by hyperreflective
zones and severely attenuated retinal vessels.

trait with variable penetrance. The reduction Hereditary Retinal Dystrophy/Lipid


in incidence, which has been accomplished in Retinopathy/RPE65 Null Mutation/Canine
Border Collies, through selective breeding is Leber’s Congenital Amaurosis
perhaps consistent with this view. A recessive
In the Briard dog, an interesting retinal dystro-
mode of inheritance was thought to be likely in
phy (with many names) has been described.
the Briard, but this has not been proved.
The hereditary, clinical, and morphological
Important in this context is that lesions similar
characteristics of the disease were elucidated
to CPRA/RPED have been produced in dogs
in groups of inbred and outcrossed dogs in
fed diets deficient in vitamin E, an antioxidant
Sweden. Initially, the disease was described as
that retards the intracellular accumulation of
congenital stationary night blindness, since it
lipofuscin pigment. Naturally acquired retin-
affected Briards from birth; affected dogs had
opathy resulting from vitamin E deficiency has
nonrecordable rod ERGs, and no funduscopic
also been described in the dog. The ERG is not
changes were observed until the dogs were two
diagnostic for CPRA, but there is a reduction
to three years old. Further clinical and mor-
in ERG amplitudes with disease progression.
phological studies showed that there was a
Secondary cataracts are often seen at the
progressive component in the disorder. The
advanced stage.
neural retina and the RPE were both affected
In Briards, an extremely high frequency of
by a retinal degenerative disease with unusu-
the disease was found in a five-­year survey.
ally slow progression.
Almost one-­third of dogs examined, older
Clinically affected dogs were congenitally
than 18 months, were clinically affected. In
night blind, whereas daylight vision could vary
this breed, the typical pigmentary changes
from near normal to more or less severely
were first seen toward the periphery of the
impaired. A rapid, horizontal nystagmus was
tapetal fundus, temporal to the optic disc,
seen in most (but not all) affected pups, and it
before spreading to involve the entire
was obvious in some of the animals that they
tapetal zone.
were congenitally day and night blind. The
504 Diseases and Surgery of the Canine Posterior Segment

resting pupillary diameter was approximately Neuronal Ceroid Lipofuscinosis


twice as wide both in bright and in dim light-
The neuronal ceroid lipofuscinoses (NCL) are
ing conditions among affected dogs compared
a group of recessively inherited progressive
with the diameter in normal dogs.
neurodegenerative diseases that are character-
Ophthalmoscopically, the fundus appear-
ized by brain and retinal atrophy and associ-
ance in dogs up to approximately three years of
ated with selective necrosis of neurons. The
age was normal. With progression, a subtle
term ceroid lipofuscinosis is derived from the
alteration in tapetal sheen was seen in affected
histochemical and fluorescent properties of
dogs, and in certain individuals, whitish gray
accumulated pigment, which resembles those
spots were observed in the central and midpe-
of the lipopigments ceroid and lipofuscin com-
ripheral nontapetal fundus, spreading periph-
mon to these diseases. They are also linked to
erally with increasing age.
brain atrophy, a defect not found to the same
Through candidate gene analysis, the defect
degree in other lysosomal storage diseases.
in Briards in Sweden was discovered to be a 4-­bp
These diseases affect both humans and several
deletion in the RPE65 gene. This gene defect
other animal species, such as bovine, ovine,
resulted in a frameshift and a premature stop
caprine, feline, and canine. A spectrum of bio-
codon, which truncated the protein and resulted
chemical defects has been implicated in these
in no RPE65 formation in the RPE. Clinical
disorders. Most forms reflect an accumulation
signs of the defect in affected Briard dogs had
of subunit c of mitochondrial ATP synthase,
close similarities to the human counterpart,
while in other forms there is sphingolipid acti-
Leber’s congenital amaurosis type II. In 2001,
vator protein storage in granular osmiophilic
treating three dogs affected with the retinal dys-
deposits, mainly in neuronal cells. The central
trophy with a corrective gene construct, subreti-
nervous system (CNS) appears to be the main
nal injections were performed using a
focus of the pathogenetic defect. NCLs have
recombinant adeno-­associated virus (AAV) car-
been described in several dog breeds, includ-
rying normal dog RPE65. Vision was improved
ing the English Setter, Dalmatian, Border
in eyes treated subretinally as demonstrated by
Collie, Tibetan Terrier, American Bulldog,
ERG recordings, and transmission of the retinal
Miniature Schnauzer, Polish Owczarek
activity was shown by pupillometry.
Nizinny, Longhaired Dachshund, and others
(for reviews on the disease in various breeds,
Pigmentary Chorioretinopathy see www.caninegeneticdiseases.net). A com-
mon clinical manifestation in both humans
A novel disease has recently been described to
and dogs is blindness, which occurs with a
cause retinal impairment and blindness in the
broad spectrum of neurological abnormalities
Chinese Crested Dog (CCD). The disease is
caused by the accumulation of autofluores-
bilaterally symmetrical and has been observed
cent lipopigments in neurons and in some
in CCDs from northern Europe and the United
other cells.
States. Affected animals have been negative for
The mutation for NCL in the English Setter
the prcd mutation, which previously has been
dog was elucidated: a mutation in the CLN8
described (www.optigen.com; www.embarkvet.
gene was found to be responsible for the disor-
com) to be prevalent in the breed.
der. A group of American Bulldogs were
Ophthalmoscopically, in three-­to four-­year-­old
revealed to have NCL and a defect in the gene
affected dogs, darkly pigmented lesions, with a
for cathepsin D (CTSD) was elucidated; in the
light center (doughnut-­like lesions) are seen in
Border Collie dogs, there is a mutation in the
the peripheral fundus, most easily observed in
CLN5 gene (see Appendix A). Recently, muta-
the tapetal fundus, but prevalent also in the
tions in the CLN2 gene in the Longhaired
nontapetal area.
­Inflammation and Infections Affecting the Ocular Fundu  505

Dachshund and a mutation in CLN6 in the chemistry, and urinalysis, serology for anti-
Australian Shepherd have been identified as body titers to specific infectious agents may be
causes of NCL. A young Miniature Dachshund indicated. Sensitive polymerase chain reaction
with neurological signs in keeping with NCL (PCR) diagnostic tests for the presence of the
was found to have a mutation in the PPT1 gene. DNA of pathogens in samples have been, and
are being, developed. In certain instances,
aspirates (e.g., from lymph nodes, aqueous
Mucopolysaccharide Storage Diseases
humor, vitreous, and subretinal fluid) may be
In both humans and animals, mucopolysaccha- obtained and subjected to a variety of tests,
ride storage diseases are caused by the inherited including cytology, culture, and PCR amplifi-
deficiency of lysosomal enzymes, and they rep- cation. Diagnostic testing should be fully uti-
resent generalized, multisystemic abnormali- lized in an attempt to identify the etiology of
ties, of which ocular lesions are but one the inflammation, particularly as the use of
component (see Appendix E). The lysosomal nonspecific anti-­inflammatory medications
enzymes participate in degradation of glycosa- (such as systemic corticosteroids), although
minoglycans. Morphological studies have shown desired in idiopathic or immune-­mediated
accumulation of intracellular inclusions in sec- inflammation, may be contraindicated in cer-
ondary lysosomes in the enzyme-­deficient RPE. tain infectious diseases.

I­ nflammation and Infections Chorioretinitis


Affecting the Ocular Fundus Chorioretinitis may have various causes, includ-
ing several infectious diseases, neoplasia, foreign
Inflammatory lesions of the ocular fundus are bodies, and trauma (Box 13.2 and Table 13.7).
not uncommon in the dog. Retinal involve- Infectious agents may be restricted to the eye,
ment, however, is usually secondary to disease but signs in the ocular fundus may also be part
processes extending from the choroid or some- of, or secondary to, a systemic infection. In many
times the vitreous, whereas primary retinal instances, the exact cause of the inflammatory
inflammation (i.e., retinitis) is uncommon. process cannot be identified. The appearance of
The terms chorioretinitis (i.e., starting in the the lesions in the fundus may give some guid-
choroid) and retinochoroiditis (i.e., initially ance as to the etiology, but this is seldom spe-
involving the retina) indicate the primary site cific. Sampling from the choroid and retina
and direction of spread when both the choroid presents certain difficulties and can be associ-
and retina are involved. There may also be con- ated with undesired complications. Vitreous
current involvement of the anterior uvea (also paracentesis to obtain material for cytology and
see Chapter 19) as in panuveitis (inflammation culture can be informative, but is usually
of the entire uveal tract), endophthalmitis reserved for patients presenting with severe pos-
(inflammation of the internal structures of the terior segment inflammatory disease.
eye), and panophthalmitis (inflammation of
the entire eyeball).
Active Chorioretinitis
The inflammatory process may accompany a
systemic disease; a full physical examination is An active inflammation in the retina, with or
an essential part of the workup, and further without involvement of the choroid, results in
investigations such as chest radiographs and a number of ophthalmoscopic signs, which
abdominal ultrasound should be considered. may vary according to both the severity and the
In addition to routine laboratory investigations stage of the disease process (see Table 13.7).
such as a complete blood count, serum Inflammatory lesions may be unilateral or
506 Diseases and Surgery of the Canine Posterior Segment

Box 13.2 Causes of Chorioretinitis and Retinochoroiditis in the Dog

Virus Canine distemper morbillivirus, canine herpesvirus, and Mokola virus


Rickettsia Canine Ehrlichia canis, Rickettsia rickettsii (Rocky Mountain spotted fever), and
Bartonella vinsonii
Mycotic diseases Acremonium spp., Aspergillus fumigatus, Blastomyces dermatitidis, Histoplasma
capsulatum, Cryptococcus neoformans, Coccidioides immitis, Geotrichum
candidum, and Pseudallescheria boydii
Algal diseases Achlorophyllic alga Prototheca
Protozoal diseases Toxoplasma gondii, Neospora caninum, and Leishmania donovani
Parasitic diseases Toxocara canis, Angiostrongylus vasorum, and order Diptera
Immune-­mediated Uveodermatologic/Vogt–Koyanagi–Harada (VKH) syndrome
diseases

Table 13.7 Ophthalmoscopic changes in chorioretinitis.

Stage of inflammation Tapetal changes Nontapetal changes

Acute (active) Indistinct grayish/ brownish areas Grayish-­to-­white areas


White, perivascular opacities White, perivascular opacities,
Lesion margins: irregular (fuzzy) Lesions margins: irregular (fuzzy)
Lesion often raised Lesion often raised
Chronic (inactive) Irregular, hyperreflective areas with Distinctly bordered, depigmented areas
a distinct (sharp) border
May be pigmented Blood vessels’ attenuation
Blood vessel attenuation Variable pigment proliferation

bilateral, and they are usually irregular in detachment of the neurosensory retina. The
shape. In acute inflammation, there may be detached area of retina is elevated compared
perivascular cuffing, which appears as gray-­ with the surrounding retina and appears gray-
white perivascular opacities due to inflamma- ish, with a distinct border, in contrast to areas
tory cells accumulating around the blood infiltrated only by inflammatory cells. The
vessels. There may be retinal edema or cellular cellularity of the subretinal fluid influences
infiltration that, in the tapetal area, appears as the appearance of the detached area.
grayish hyporeflective lesions and in the non- Granulomatous lesions may be seen in some
tapetal area may appear grayish to white in forms of chorioretinitis, particularly those
color. Hemorrhage may accompany more caused by fungal infections (Figure 13.23a
severe inflammatory processes. The ophthal- and b). In some instances, the ONH may also
moscopic appearance of the hemorrhages be involved in the inflammatory process,
depends on their location. showing swelling and possibly hemorrhages
Accumulation of exudate between the pho- in the acute stages and atrophy in the
toreceptors and pigment epithelium causes a chronic stages.
­Inflammation and Infections Affecting the Ocular Fundu  507

(a) (b)

Figure 13.23 Fundus lesions in dogs with cryptococcosis. (a) This dog had multiple active subretinal
granulomatous lesions scattered across the fundus. These show as small gray lesions that result in slight
elevation of the surrounding overlying retina. (b) In this dog, the cryptococcal infection has resulted in
extensive retinal degeneration (thinning) showing as tapetal hyperreflectivity. There are also small areas of
pigment proliferation and tapetal color change.

Inactive/Chronic Chorioretinitis
Ophthalmoscopic signs of an inactive, chronic
inflammatory process are quite different from
those of an acute inflammation (see Table 13.7).
Atrophy of the neural retina in the tapetal fun-
dus is seen as irregular, hyperreflective areas
with a distinct border (Figures 13.24 and 13.25a
and b). A well-­demarcated zone in the center
of the lesions may be heavily pigmented if the
RPE is affected. The color of the tapetum may
be altered in the affected area or even destroyed,
exposing choroidal vessels and sclera. Chronic
inflammatory lesions in the nontapetal fundus
appear as distinctly bordered, depigmented
areas with exposure of choroidal vessels and
sclera. Sometimes, areas of pigment clumping Figure 13.24 An inactive peripapillary chorioretinitis
will also be apparent. lesion is shown. There is retinal thinning in the tapetal
fundus resulting in an area of tapetal hyperreflectivity
with a pigmented center due to pigment proliferation
in the RPE. There is damage to the full thickness of
Choroiditis the retina that has resulted in a sector atrophy of the
Choroiditis (or posterior uveitis), which is an adjacent ONH. This damage is caused by loss of the
ganglion cell axons feeding into that sector of the
inflammation strictly confined to the choroid, optic because of destruction of the nerve fiber layer in
without involvement of the anterior uvea or the region of postinflammatory scarring.
508 Diseases and Surgery of the Canine Posterior Segment

(a) (b)

Figure 13.25 Inactive chorioretinitis lesions in the nontapetal fundus. (a) There are irregular patches of
loss of retinal pigment epithelial pigment revealing choroidal vasculature. Some white-­colored retinal
surface deposits are also present. (b) This dog had multiple small areas of depigmentation and choroidal
damage revealing the white of the underlying sclera.

retina, appears to be an uncommon condi- numerous other breeds have been affected as
tion. Ophthalmoscopically, nongranuloma- well. In the dog, cases may present with a his-
tous choroiditis in the tapetal fundus can tory of sudden blindness or with chronic uvei-
cause loss of tapetal reflectivity or changes in tis leading to secondary glaucoma.
tapetal color. In the nontapetal fundus, areas Dermatological changes include vitiligo and
of increased redness can be observed. poliosis affecting the periocular skin, lips, and
Subretinal accumulation of fluid can cause muzzle most frequently. Ocular examination
elevation of the overlying retina. Complete may reveal anterior or posterior uveitis (or
destruction of the tapetum lucidum, thereby both) and serous RD. The uveitis is usually
allowing the choroidal vessels to be readily granulomatous, with cellular infiltrates of
viewed in the affected area, can occur during lymphocytes, plasma cells, epithelioid cells,
the chronic stages of severe choroiditis. and macrophages containing ingested mel-
anocytes. The histopathology is consistent
with antimelanocyte autoimmunity, however,
Specific Retinopathies
and the breed incidence, such as in Akitas,
Uveodermatologic/Vogt–Koyanagi– suggests the involvement of genetic factors. A
Harada Syndrome similar disease was induced experimentally in
The uveodermatologic, or VKH, syndrome of two Akitas by immunizing them to tyrosine-­
humans encompasses a variety of clinical related protein 1 (also see Chapter 19).
signs, including uveitis, chorioretinitis, skin
depigmentation (i.e., vitiligo), loss of hair pig-
Sudden Acquired Retinal
ment (i.e., poliosis), and various neurological
Degeneration Syndrome
signs. The disease has been reported in the dog
as an immune-­mediated syndrome resem- Sudden acquired retinal degeneration syn-
bling VKH syndrome in humans. Several cases drome (SARDS) is a retinal disorder of
have been reported in Akitas, though unknown cause that results in a sudden and
­Retinal Toxicitie  509

permanent blindness in affected adult dogs. drug), diphenylthiocarbazone, hydroxypyridi-


There is currently no treatment that has been nethione (zinc-­chelating), quinine and some
proven to be effective for this disorder. Clinical of the cinchona derivatives, chloroquine (anti-
signs are characterized by a sudden loss of malaria drug), azalide, closantel (antihelmin-
vision, usually within days or one to two weeks. tic), and thiram (general-­purpose pesticide). A
Most affected dogs show pupillary dilatation drug encountered clinically is ivermectin.
and unresponsive pupils, although some may
retain a PLR. Typically, there is an absence of
Retinopathy Induced by Light
ophthalmoscopic fundus abnormalities at the
and Oxygen
early stage, although occasionally areas of
mild retinal edema may be noted. The main There is a well-­established association between
diagnostic technique to distinguish between high light intensity and retinotoxicity.
SARDS and central causes of sudden-­onset Illumination of the canine fundus with light
vision loss is electroretinography. In SARDS, from an indirect ophthalmoscope for 20 min
the ERG is nonrecordable, while with central may be sufficient to cause ophthalmoscopi-
causes of blindness the ERG is relatively nor- cally visible changes. Prolonged exposure
mal. It appears that all breeds, including cross-­ results in areas of increased granularity in the
breeds, may be affected, often in middle age. tapetal fundus, which is followed by retinal
After several weeks to months, slowly progres- pigmentation and increased tapetal reflectiv-
sive ophthalmoscopic changes may be ity. Exposure to high oxygen tensions produces
observed that are indicative of a generalized selective damage to the visual cells in the dog.
retinal degenerative process and confirmed by Oxygen administration has been strongly
histopathology. linked with human retinopathy of prematurity,
Affected dogs are usually healthy, but and there is evidence that light exposure may
many have a history of weight gain, polyuria, play a role in its pathogenesis. Oxidative pro-
polydipsia, and polyphagia. There are often cesses and generation of free radicals have also
clinical signs and initial laboratory blood been suggested to be important in develop-
work such as elevated serum alkaline phos- ment of the disease. The dog has been estab-
phatase, serum aminotransferase, serum lished as an experimental model for human
cholesterol, or serum bilirubin levels sugges- retinopathy of prematurity.
tive of hyperadrenocorticism.
Retinopathy Induced by Radiation
Radiation-­induced ocular injury secondary to
­Retinal Toxicities
treatment of nasal cancer occurs in both
humans and animals. In a clinical and histo-
Drug-­Induced Retinotoxicity
pathological study, immediate changes such as
Some compounds can directly cause retinal blepharitis and keratoconjunctivitis were
damage by damaging neuroretinal or RPE cells found. At three to six months post-­treatment
or indirectly cause such damage by inflamma- (i.e., 36.0–67.5 Gy in fractionated doses given
tory reactions that lead to focal or more gener- over four weeks using a 6-­mV linear accelera-
alized cell death. Assessment of retinal tor), however, a degenerative angiopathy of
integrity is an essential component in ocular retinal vessels appeared, with multifocal reti-
safety evaluations, and these retinal toxicities nal hemorrhage and mild, diffuse retinal
in dogs were detected in these safety trials. degeneration, first affecting the outer retinal
Compounds included some experimental layers but then progressing inward. At one to
vasodilating drugs, ethambutol (antitubercular two years post-­treatment, there was a
510 Diseases and Surgery of the Canine Posterior Segment

moderate retinal degeneration, with swelling Results of clinical as well as laboratory investi-
and loss of ganglion cells and, subsequently, gations showed that retinopathy resembled
optic nerve axonal degeneration. CPRA/RPED. CPRA/RPED-­affected English
Cocker Spaniels had very low plasma α-­
tocopherol levels and very low ratios of plasma
­ etinopathies of
R α-­tocopherol to cholesterol and triglycerides
compared to normal controls. This suggests
Nutritional Causes
that in the English Cocker Spaniel at least,
CPRA/RPED may be due to a familial primary
Vitamin A Deficiency
vitamin E deficiency not related to dietary
Systemic vitamin A deficiency is characterized insufficiency or evidence of any gastrointesti-
by night blindness in several species. In the nal malabsorption syndrome. α-­Tocopherol-­
dog, systemic diseases causing impaired fat deficient English Cocker Spaniels showed
absorption could result in vitamin A deficiency, neurological dysfunction in additional to fun-
but this clinical situation is extremely rare. dus changes. The neurological signs included
ataxia, proprioceptive deficits, abnormal spi-
nal reflexes, and muscle weakness.
Vitamin E Deficiency
Vitamin E is an antioxidant with an important
function in maintaining cell membrane stabil- ­Vascular Disease Processes
ity by preventing lipid peroxidation. A defi-
ciency in vitamin E may result in pathological The retinal vasculature is well suited to direct,
changes in the muscle, CNS, reproductive noninvasive ophthalmoscopic examination.
tract, and retina. In dogs fed a diet deficient in Systemic disease as well as local ocular pathol-
vitamin E, ophthalmoscopic signs of disease ogy can produce observable changes in both
developed early and were described as a mot- retinal and choroidal vessels. Except for blood
tled tapetal fundus appearance, particularly constituent analysis, blood flow and blood
centrally, with numerous, discrete yellow-­ pressure measurements, and coagulation stud-
brown foci. Over time, the central fundus ies, specific methods of examination include
became hyperreflective, and there was an ophthalmoscopy and fluorescein angiography.
attenuation of the retinal vessels. The ERG was
nonrecordable at four months of age.
Systemic Hypertension
Histopathologically, an accumulation of
autofluorescent pigment within the RPE Dogs with experimentally induced hyperten-
cells was observed, and at later stages, sion exhibit retinal hemorrhage, RD, and arteri-
within migrating cells in all retinal layers. olar changes. In cases of spontaneous systemic
Photoreceptor damage occurred in areas over- hypertension, visual disturbance is often the
lying affected regions of the pigment epithe- initial presentation. The most common ocular
lium. The obvious similarities between vitamin findings in clinical cases are posterior segment
E deficiency and hereditary CPRA/RPED sug- hemorrhage (retinal, preretinal, and vitreal),
gest some common etiological factor, and RD, and, in some cases, hyphema.
recent reports have substantiated this sugges-
tion. Retinopathy from vitamin E deficiency in
Hyperviscosity Syndromes
dogs occurred when fed a diet consisting of
meat scraps, poultry carcasses, and offal. A In dogs with hyperviscosity syndromes, for
spectrum of funduscopic changes, which var- example, with multiple myelomas or poly-
ied in severity with increasing age, was found. cythemia, distended and tortuous retinal
­Retinopathies with Immunological Disease  511

(a) (b)

Figure 13.26 Hyperviscosity syndrome. (a) Hyperviscosity due to polycythemia has resulted in retinal
vasculature dilation and a preretinal hemorrhage. (b) Hyperviscosity due to multiple myeloma has resulted
in retinal vascular dilation and a focal area of RD dorsal to the ONH. This reattached after the condition
was treated.

blood vessels are seen in conjunction with reason for a patient with diabetes to be presented
sacculation of venules, retinal hemorrhage, for the first time.
and in severe cases retinal edema, RD, and
papilledema (Figure 13.26a and b). In a single
case report of a dog with polycythemia vera, ­ etinopathies with
R
the ocular presentation was of a unilateral Immunological Diseases
anterior uveitis and active chorioretinitis.
Immune-­Mediated Thrombocytopenia
Hyperlipidemia Immune-­mediated thrombocytopenia is a
Hyperlipidemia may impart a milky pink col- clinical disease characterized by anemia,
oration to retinal vessels, which is most easily hemorrhage, and low platelet counts. The
observed in the nontapetal fundus. presenting sign is often petechiation and
ecchymosis of the gingiva or conjunctiva, and
both hyphema and retinal hemorrhage are
Diabetic Retinopathy common findings. Treatment consists of con-
Though diabetic retinopathy occurs in the dog, trolling the hemorrhage; blood transfusion
the extent and severity of the retinal lesions are may be necessary in severe cases. Systemic
milder compared with those that can develop in corticosteroid treatment, 1–2 mg/kg/day, is
diabetic humans. In the dog, the ocular lesions used for several weeks and then tapered to a
include anomalies of the retinal vasculature and low maintenance dose.
cataract formation. Whereas the vascular
changes in humans are of major importance in
Autoimmune Hemolytic Anemia
the disease and contribute to blindness, they are
much less severe and of minor clinical impor- Autoimmune hemolytic anemia is an autoim-
tance in the dog with spontaneously occurring mune disease of both humans and the dog.
diabetes. Cataract formation, on the other hand, Presenting clinical signs are acute to chronic
is an early finding in the dog, and it is often the anemia, and ophthalmoscopically, the retinal
512 Diseases and Surgery of the Canine Posterior Segment

vessels are light red and difficult to follow radiating out from the ONH. Cupping and
because of the blood disorder. Treatment is atrophy of the ONH also develop.
systemic corticosteroids, 2–4 mg/kg for two Histopathological studies of eyes removed
weeks and then decreasing to maintenance because of primary narrow-­angle glaucoma
levels. Supportive therapy is often indicated for (which usually have very high levels of IOP)
the anemia. show that essentially all retinal layers are
affected and that the progression of retinal
changes occurs rapidly. Within one day of the
Systemic Lupus Erythematosus
onset of glaucoma, necrosis of RGCs has
Systemic lupus erythematosus is a multisystem developed and is followed by the induction of
disorder with immunological abnormalities apoptosis of cells in the ganglion cell layer as
related to autoantibodies in both the blood and well as the inner and outer nuclear layers.
the lesions of the body. There is a genetic pre-
disposition for the disease, and genetic pro-
cesses may initiate the systemic problem. ­Retinal Detachments
Ocular lesions include hemorrhages and serous
RDs. Recommended treatment is the same as Various pathological conditions of the eye
that for autoimmune hemolytic anemia. can cause focal, multifocal, or total RD. The
neuroretina is usually separated from the
underlying RPE, which implies a disruption
Cancer-­Associated Retinopathy
of the intimate and essential (but structurally
Cancer-­associated retinopathy (CAR) is a weak) association between the outer seg-
form of autoimmune retinopathy in which ments of the photoreceptors and the RPE. This
cancer patients develop antibodies that cross-­ loss of structural integrity is associated with a
react with retinal antigens; the resulting loss of function and secondary retinal degen-
immunological attack on the retina causes eration in the affected area. Thus, a focal RD
retinal cell death and vision loss. Several affecting a minor area will usually not result
tumor types may lead to this condition but in clinically detectable impairment of vision,
melanomas appear to do so in particular. The whereas detachment of the entire retina is a
vision loss may be apparent before the tumor blinding condition. Detachments involving
is detected. There is little information on the large areas of the retina may result in tearing
occurrence of CAR in dogs. of the peripheral retina as the multilayered
neurosensory retina becomes thinner at the
periphery to continue as the nonpigmented
ciliary body epithelium at the ora ciliaris reti-
­Secondary Retinal Degenerations
nae. The complete tearing of the peripheral
retina is often termed disinsertion, or dialysis
Glaucoma
(Figure 13.27).Ophthalmoscopy reveals an
Glaucoma can lead to retinal degeneration, anterior displacement of the retinal surface
particularly as a result of the high IOPs that and the retinal blood vessels. Large volumes
are common in many primary canine glauco- of subretinal fluid can cause segments of the
mas. In acute stages, the retina may appear retina to balloon anteriorly, even extending to
normal ophthalmoscopically or show areas of the posterior surface of the lens in extreme
edema. When there is severe retinal damage, cases. When there is anterior displacement of
retinal degeneration becomes apparent sur- the detached retina, it can often be readily
prisingly rapidly; sometimes this may appear viewed directly through the pupil with a focal
as more severe zones of retinal thinning light source. The retina resembles a
­Neoplastic and Proliferative Condition  513

deposition (e.g., in chorioretinitis or hyperten-


sion) in the subretinal space elevates the retina
and causes an exudative detachment.
Rhegmatogenous RDs may be the most com-
mon form in the dog. This is because most
detachments are associated with ocular diseases
known to induce retinal tears, such as CEA, len-
ticular disease, retinal dysplasia, and glaucoma.
Treatment of the RDs depends on the pres-
ence of a detectable underlying disease and
both the cause and the extent of the detached
area. Even extensive detachments may be reat-
tached with return of vision provided that
treatment is commenced early. When a steroid-­
responsive exudative detachment is suspected,
Figure 13.27 This eye had previously had a systemic steroids should be started as soon as
complete bullous RD. It had been steroid
responsive and reattached. There are pigmentary
possible after ruling out potential infectious
changes that have resulted from the chorioretinitis and systemic causes for which systemic corti-
that induced the detachment. There is a resolving costeroids might be contraindicated. Failure to
hemorrhage on the ONH. reattach leads to retinal degeneration and loss
of visual capacity in the affected area. Further
grayish-­colored curtain hanging in the vitre- treatment options are discussed in the next
ous. The exposed tapetum will appear hyper- section.
reflective because there is no overlying retina.
In other instances of RD, holes or tears in the
retina may be seen and the exposed choroid
­Neoplastic and
and RPE can appear very clear through the
retinal defect, particularly if there is not a
Proliferative Conditions
great deal of cellular infiltration.
Granulomatous
RDs associated with retinal dysplasia are a
Meningoencephalitis (Reticulosis)
congenital condition caused by impaired reti-
nal structure, dysfunction of the RPE, or reti- Granulomatous meningoencephalitis (GME) is
nal nonattachment (see previous discussion of an idiopathic, nonsuppurative, inflammatory
retinal dysplasia). RDs, which are not solely disease of the CNS that can affect the eye. The
associated with the aforementioned develop- disseminated form of GME has been previously
mental defects in the neuroretina and RPE, described as inflammatory or granulomatous
can be subdivided according to the causative reticulosis, whereas the focal form was previ-
mechanism into rhegmatogenous, traction, ously described as neoplastic reticulosis. GME
and exudative detachments. A rhegmatoge- is characterized by the proliferation of reticu-
nous detachment is one associated with a tear loendothelial elements and lymphoplastic infil-
or hole in the neuroretina; the retinal defect trates of the CNS vessels. The cellular reaction
allows vitreous and fluid to dissect the neuro- of the intracranial vasculature apparently may
retina from the RPE, thus exacerbating the be shared by the blood vessels of the posterior
lesion. A force from the vitreous body pulling segment of the eye and the anterior uvea.
the neuroretina anteriorly (e.g., from an organ- Ocular signs may develop before CNS
izing hemorrhage in the vitreous body) can abnormalities. The disease is usually bilateral,
result in traction detachment. Fluid and cell but the extent of involvement varies. Papillitis
514 Diseases and Surgery of the Canine Posterior Segment

and peripapillary edema have been reported to


be the single ophthalmoscopic sign in blind
patients. Various secondary ocular disease
processes may be found depending on locali-
zation of the inflammatory lesions. Infiltration
of the uveal tract has been reported to cause
uveitis, and RD may be found secondary to
choroidal involvement. Vision may be
improved temporarily in dogs presenting with
papillitis through treatment with corticoster-
oids. The prognosis for vision, however, and
even for long-­term survival, is considered to be
very poor.

Primary Tumors
Primary tumors of the retina, choroid, and
optic disc are very rare in the dog. Tumors of Figure 13.28 Pigmented raised choroidal lesion
in the peripheral tapetal fundus of an elderly
astrocytic origin are rarely reported in the
Shetland Sheepdog. This was a very slow-­growing
dog. Immunohistochemistry aids in the pos- lesion and most likely represents a choroidal
sible identification of astrocytomas because melanoma.
of their positive staining for glial fibrillary
acid protein. Primary intraocular neuroepi-
thelial tumors are divided into two groups:
neoplasms derived from mature neuroepithe-
Ocular Melanosis
lium and neoplasms derived from primitive
medullary epithelium. Neoplasms from Ocular melanosis in Cairn Terriers manifests
mature neuroepithelium include adenomas as a proliferation of melanocytes predomi-
and adenocarcinomas, which develop from nantly involving the anterior uvea and sclera,
the ciliary epithelium. Tumors derived from which leads to a secondary glaucoma.
primitive medullary epithelium are thought However, the characteristic plump pigment-­
to originate from embryonic neuroepithelium laden cells are present histologically within
of the optic vesicle or cup; examples of this the retina and choroid of dogs with advanced
type are (teratoid) medulloepitheliomas and disease.
retinoblastomas.
Secondary Tumors
Choroidal Melanomas
In the dog, intraocular primary melanomas Tumors may involve the posterior segment by
typically arise in the anterior uvea, and the extension from a primary focus in the anterior
choroid is usually involved through extension segment, optic nerve, or extraocular tissues, or
from the anterior uvea. Melanomas with their by metastasis from a more remote site. Clinical
origin in the choroid are less frequently signs usually develop late in the disease, thus
detected. Choroidal melanomas are generally delaying both detection and diagnosis. Signs
described as darkly pigmented masses arising may include intraocular hemorrhage, uveitis,
from the choroid underlying the tapetum luci- glaucoma, and blindness. With metastatic
dum, most typically adjacent to or near the tumors, systemic signs may be present and the
optic disc (Figure 13.28). ocular findings incidental.
­Anatomical Consideration  515

Metastatic Tumors 23-­gauge sutureless PPV. Numerous innova-


tions in the vitrectomy machines now
Several tumors and sites of origin have
employed by veterinarians have led to substan-
been reported, including mammary gland
tial refinements in our techniques, with a
adenocarcinomas, thyroid adenocarcinoma,
resultant increase in success rates. Many tech-
renal adenocarcinoma, malignant melanoma,
niques such as scleral buckles, pneumatic
hemangiosarcoma, rhabdomyosarcoma, neu-
retinopexy (PR), cryoretinopexy, and transscle-
rogenic sarcoma, and pheochromocytomas.
ral laser retinopexy are no longer part of our
Tumors that metastasize to the anterior uvea
lexicon. This chapter will focus instead on 23-­
may also extend to involve the retina and
gauge surgery and its refinement in veterinary
choroid.
medicine over the past few years.

Lymphomas
­Anatomical Considerations
Malignant lymphoma, usually affecting both
eyes, seems to be the most common secondary
Knowledge of the anatomy of the posterior
intraocular tumor. Ocular involvement has
segment is crucial to understanding proper
been reported to be the second most consistent
surgical technique. Thus, the specific segments
presenting sign (after lymphadenopathy) in
involved with vitreoretinal surgery are briefly
dogs affected with multicentric lymphoma.
discussed.
Involvement of the choroid and the retina is
noticed infrequently, but signs from the poste-
rior segment may sometimes be masked by the Vitreous
more frequently observed changes in the ante-
The vitreous body is the most important
rior segment. Ophthalmic signs depend on
intraocular tissue in the pathogenesis of reti-
whether the anterior or posterior segment (or
nal detachments (RD). It is the gel that fills
both) is involved. Krohne and colleagues
the vitreous cavity and is in contact with the
detected posterior uveitis in 3% of dogs with
retina, ciliary body, lens zonules, and poste-
multicentric lymphomas, panuveitis in 5%,
rior surface of the lens. In the canine, the vit-
and retinal hemorrhages in 9% flame-­shaped
reous has been described as being of the
retinal hemorrhages are considered to be the
“nuclear type,” in which the central vitreous
earliest ophthalmoscopic sign. In more
is dense and the peripheral cortex is semi-
advanced stages, alterations in tapetal color
fluid. This is the opposite of that in humans,
occur, and papilledema may be present.
in which the center is more fluid and the cor-
tex is denser. The vitreoretinal interface
formed by the outer surface of the vitreous
Section III: Surgery of the cortex and the internal limiting membrane of
Canine Posterior Segment the retina contribute to the pathogeneses of
rhegmatogenous retinal detachment (RRD).
Since the last edition of this text, there have Normal vitreous exerts traction where it
been no radical changes in the way that vitreo- adheres to the retina; whenever the eye
retinal surgeons perform the repair of RD in moves, the vitreous follows this movement,
the canine species. However, there has been with a delay resulting from inertia. The result
steady improvement in technique, instrumen- is sudden traction wherever the vitreous
tation, and numbers of surgeons performing adheres to the retina. In normal eyes, this is
this surgery. Twenty-­gauge surgery has, for the not usually a problem, as the vitreous has
most part, been updated and supplanted by both liquid and gel components.
516 Diseases and Surgery of the Canine Posterior Segment

Figure 13.29 Giant retinal tear in a


dog intraoperatively.

Abnormal vitreous is necessary to the patho-


genesis of spontaneous RRD in humans and is
also responsible for RRD in several breeds of
dogs. Liquid vitreous, fibrillary changes, RD,
and vitreoretinal traction have been described
in the Labrador Retriever with oculoskeletal
abnormalities. We have seen several breeds
with abnormal liquid vitreous, notably the
Shih Tzu, Boston Terrier, Poodle, Jack Russell
Terrier, Italian Greyhound, and Yorkshire
Terrier. If this clinical abnormality is present
in a dog that violently shakes its head while
playing with toys, the vitreous will likely tear
the retina where it is most adherent to the ret- Figure 13.30 Tractional RD in a dog after
ina or the vitreous base. The highest incidence ocular trauma.
of clinical spontaneous giant retinal tears is in
dogs that demonstrate aggressive head shaking
(Figures 13.29 and 13.30).
Proliferative vitreoretinopathy (PVR) is an
important pathological change seen with RRD
and is probably the largest single factor result-
ing in the failure of human retinal reattach-
ment surgery.
Fortunately, PVR only occasionally occurs in
the dog. It has been reported in the Labrador
Retriever with RRD associated with oculoskel-
etal dysplasia. Canine PVR occurs in dogs with
RD secondary to full thickness after transscle-
ral laser retinopexy (Figure 13.31).

Pars Plana
Figure 13.31 PVR (double arrow) resulting in RD
To prevent damage to the lens and retina during in the dog secondary to a full-­thickness retinal hole
vitreocentesis or vitreoretinal surgery, the (arrow) caused by transscleral laser retinopexy.
­Factors Responsible for Retinal Detachmen  517

Figure 13.32 Intraoperative


photograph of wide intrascleral
venous plexus in the dog. The trocar
points to the anterior margin of the
venous plexus (circle of Hovius).

surgeon must have knowledge of the pars plana. secondary. Primary RRDs are spontaneous and
Studies on canine cadaver eyes have identified are not the result of trauma, inflammation, sur-
proper penetration sites for the four quadrants gery, or other specific ocular disorder. Primary
of the eye. Ideally, the surgeon wants to pene- RRDs are preceded by alteration or degenera-
trate the center of the pars plana. In globes tion of the vitreous, which predisposes the ret-
measuring approximately 22.2 ± 1 mm, the rec- ina to detachment. The most common type of
ommendation is a distance of 6–7 mm from the primary RRD is retinal dialysis or giant retinal
limbus in the superotemporal and inferotempo- tear, seen frequently in the Shih Tzu.
ral quadrants, 5 mm for the superonasal quad- Non-­RRDs are classified as serous or trac-
rant, and 4 mm for the inferonasal quadrant. We tional. A serous non-­RRD occurs without a
have found that, working superiorly, 5–6 mm break in the retinal tissue and results from fluid
from the limbus is adequate in most breeds of accumulation in the subretinal space between
dogs. The insertion of the extraocular muscles the photoreceptors and the RPE. Serous non-­
may be used as an anatomical landmark to RRDs are further specified as either inflamma-
guide sclerotomy placement. tory or exudative, although this distinction is
clouded by the fact that permeability factors
that lead to exudation below the retina may
Intrascleral Plexus
possess proinflammatory influences.
The vascular intrascleral plexus (circle of
Hovius) is a network of veins that receives
aqueous drainage (Figure 13.32). This venous ­ actors Responsible for
F
network, which is 4–5 mm wide, is situated Retinal Detachment
3–4 mm from the limbus, precisely in the area
where surgical sclerotomies are placed. Although the exact mechanism of RD in the
Judicious cautery is needed to avoid serious dog is unknown, it is assumed that, as in
bleeding before penetrating the eye. humans, canine RD can be ultimately attrib-
uted to retinal tear formation, exudation, or
traction.
­Types of Retinal Detachments
Postoperative Phacoemulsification
RD is the separation of the neurosensory retina
from the underlying RPE. RD can be either Cataract surgery is one of the most common
rhegmatogenous or nonrhegmatogenous (non-­ causes of RD in the dog, but the exact inci-
RRD). In RRD, fluid from the vitreous cavity dence of RD after cataract surgery is unknown.
enters the subretinal space through a break in However, in one study, the second most com-
the retina. RRD can be either primary or mon histopathological finding in eyes
518 Diseases and Surgery of the Canine Posterior Segment

enucleated or eviscerated because of complica- changes in the status of the vitreous can lead
tions following cataract surgery was RD, pre- to RD. Posterior vitreous detachment is a well-­
sent in 64% of the eyes studied. Another recognized predisposing factor for RD in
retrospective clinical study found an incidence humans. Vitreal diseases are poorly under-
of RD after phacoemulsification of 1–2% for all stood in the dog; however, it is well recognized
time periods, but a recent study demonstrated that vitreous liquefaction predisposes to RD,
the incidence of RD following cataract surgery especially in certain breeds, such as the Shih
as 7.7% and 8.9% for the Boston Terrier and Tzu. Vitreous degeneration is reported in
Shih Tzu, respectively. nearly 130 breeds

Cataracts and Lens-­Induced Uveitis Trauma


The exact mechanism by which lens-­induced Trauma is a common cause of RD in the dog.
uveitis (LIU) predisposes the canine eye to RD Penetrating trauma, including bite wounds,
is unknown. In two studies looking at complica- can result in infection, phacoclastic uveitis, or
tions of cataract surgery, LIU was responsible cyclodialysis, all of which can easily result in
for a lower success rate, with RD being one of RD. Blunt trauma can result in a retinal tear,
the reasons for failure. Possible sequelae of LIU retinal dialysis, or both, with subsequent
that could predispose to RD include vitreous RD. Early surgical intervention is important in
degeneration, obliteration of retinal vessels cases of trauma prior to the onset of endoph-
with associated retinal thinning, retinal cyst for- thalmitis, scleral or retinal necrosis, globe atro-
mation, or globe enlargement due to transient phy, or PVR in dogs.
bouts of glaucoma. Canine vitreoretinal sur-
geons very commonly perform simultaneous
Iatrogenic Causes
cataract surgery, IOL placement, and retinal
reattachment surgery with a high success rate. Several forms of iatrogenic RD exist, usually
related to either endoscopic laser or cryoabla-
tion of the ciliary body for the treatment of
Retinal Abnormalities
glaucoma. It is also possible, if the surgeon is
Retinal factors that predispose to detachment too aggressive, to cause RD during prophylac-
include genetic vitreoretinal dysplasias tic laser of the peripheral retina.
(Labrador Retriever and English Springer
Spaniel), peripheral retinal thinning and micro-
Tractional Retinal Detachment
cystoid degeneration, atrophic retinal holes, and
PVR. Vitreoretinal dysplasia results in areas of Tractional RDs occur most commonly after
abnormally thin retina and holes, which, com- membrane formation subsequent to a bleed into
bined with liquefaction of the vitreous, can lead the vitreous cavity, or after the development of
to RD. Peripheral retinal thinning with micro- PVR secondary to a full-­thickness retinal hole.
cystoid degeneration or retinoschisis, or both, Tractional detachments occasionally are seen
allows for a potential weakening of the retina with anomalous development of retinal vascula-
and/or the ora ciliaris, potentially resulting in a ture associated with persistent hyaloid rem-
retinal tear and subsequent detachment. nants. In canine cataract surgery, collectively we
have noted complications that led to RD in the
dog. Most common are posterior lens capsular
Vitreous
rents with vitreous presentation, residual lens
As previously mentioned, the vitreous plays a fibers leading to cortical regrowth, dropped
major role in retinal attachment, and thus any nuclear lens fragments, or displaced IOLs.
­Prophylactic Retinopex  519

Effusion due to optic nerve coloboma in the CEA syn-


drome is presently successfully treated, if
Effusive RD occurs when fluid accumulates in
detected before total RD, with transpupillary
the potential subretinal space elevating the
laser retinopexy.
retina away from the RPE. Effusive RD can be
caused by immune-­mediated, neoplastic, or
infectious disease. In all instances, the effusion Lens Luxation
results from a breakdown in the blood–ocular
Lens luxation predisposes the eye to RD. Lens
barrier, at the level of either the RPE or the
instability causes a disruption in the anterior
retinal vasculature. Infectious causes include
hyaloid face, causing disturbance of the vitre-
bacterial, fungal, viral, or rickettsial disease.
ous and enabling the process of RD. Traction
Systemic hypertension in cats can also cause
on the peripheral retina as the lens and vitre-
effusive RD because RPE necrosis occurs,
ous move during luxation can cause tearing of
breaking down the blood–ocular barrier.
weak areas of retina that can lead to detach-
ment. In a study by Hendrix et al., 15% of 46
Persistent Hyperplastic Primary Vitreous dogs studied with RD presented with lens luxa-
tion or had been treated surgically for anterior
PHPV has been reported sporadically in a lens luxation.
variety of breeds of dogs and as an inherited
condition in the Doberman Pinscher and the
Staffordshire Bull Terrier (Leon et al. 1986). Dropped Nuclear Fragments
It is a complicated disease of the lens–­ In humans, three-­port PPV is indicated if large
vitreous–hyaloid system that results in a wide (>25% of the nucleus) lens fragments are
spectrum of disease, which can include RD. If dropped through the posterior lens capsule
severe, PHPV can result in RD or retinal during extracapsular cataract extractions; oth-
nonattachment. erwise, serious sequelae, primarily intractable
uveitis with retinal damage and/or RD, are
Endophthalmitis likely to occur.
If lens fragments fall posteriorly into the
Endophthalmitis is an inflammatory response vitreous, the surgeon should remove any
to ocular infection – bacterial, viral, fungal, or lens material that can be easily obtained
parasitic. The most common cause of endoph- from the anterior segment and perform an
thalmitis in the veterinary population is cata- anterior vitrectomy. Manipulation of lens
ract surgery. material in the vitreous should be avoided or
minimized because this will increase the
inflammation and significantly increase the
Collie Eye Anomaly
occurrence of RD.
The CEA syndrome encompasses several man-
ifestations, including chorioretinal hypoplasia,
optic nerve colobomas, RD, intraocular hemor- ­Prophylactic Retinopexy
rhage, and scleral staphyloma. As it relates to
RD, the phenotype of interest in dogs with Although there has been an increasing aware-
CEA is optic nerve coloboma. A defect has ness that prophylactic treatment of normal
been shown to exist in the optic nerve colo- fellow eyes in cases of spontaneous RD may
boma or pit that directly communicates with be beneficial, it remains a controversial
the subretinal space and can allow fluid from issue. In humans, the natural history of fel-
liquefied vitreous to create an RD. Serous RD low eyes on nontraumatic giant retinal tears is
520 Diseases and Surgery of the Canine Posterior Segment

(a) (b)

Figure 13.33 Sonograms of canine eyes with RD. (a) Partial RD. (b) Complete detachment.

characterized by a high combined incidence Procedure for Retinopexy


of retinal breaks and RDs in up to 60% of
Retinopexy can be performed with cryotherapy
cases. Although there may still be controversy
or with either a red or green laser. Laser sur-
in humans regarding prophylactic treatment,
gery is best performed in a transpupillary fash-
very few studies have been performed in the
ion with the indirect ophthalmoscope when
veterinary field. One such study compared
possible or transsclerally when observation of
treatment versus no treatment in the Bichon
the retina is not possible. It is important not to
Frise with cataracts associated with
give excessive treatment because it can result
LIU. Although the study consisted of only 57
in vitreous contraction or retinal holes and
dogs, it was statistically significant that pro-
induce a giant retinal tear.
phylactic treatment is beneficial. Of the 39
dogs that received prior laser photocoagula-
tion retinopexy before surgery, RRD devel-
­ urgical Procedures for Treatment
S
oped in 5 dogs (12%). In 18 dogs that did not
receive treatment, 10 dogs (55%) experienced
of Retinal Detachment
RRD. It is important to obtain ultrasonograms
Pneumatic Retinopexy
in eyes before performing retinopexy to be
sure the retina has not already detached PR was first described in human patients in the
(Figure 13.33). Because RDs occur frequently mid-­1980s; however, the technique using air
with luxated lenses or luxated lens surgery, we for somewhat similar surgery had been
recommend retinopexy before surgery if pos- described a half century earlier. PR involves
sible or shortly afterward. In dogs with vitre- the transscleral injection of gas into the vitre-
ous degeneration, especially certain breeds ous cavity, combined with cryosurgery or laser
(Shih Tzu, Boston Terrier, Jack Russell Terrier, retinopexy followed by positioning of the gas
Italian Greyhound, Yorkshire Terrier, Maltese, tamponade over the retinal break until a chori-
and Poodle), there is a risk of developing giant oretinal adhesion occurs. The technique was
retinal tears at the peripheral aspect of the introduced as an alternative surgery to scleral
retina (Figure 13.34). buckling (rarely used in canine retinal surgery)
­Surgical Procedures for Treatment of Retinal Detachmen  521

(a) (b)

Figure 13.34 Degenerative vitreous characterized by corkscrews, tendrils, and pigment. (a) Clinical
photograph. (b) Intraoperative view through silicone lens.

for retinal tears no larger than one clock hour


located in the superior half of the peripheral
retina. The most common gases used for PR
are sulfur hexafluoride (SF6) or octofluoropro-
pane (C3F8). The gases are nontoxic to the ret-
ina and have different expansile properties as
well as length of duration in the eye. Because
most RRDs seen in dogs are giant tears and
because most pet owners must travel long dis-
tances to reach a veterinary vitreoretinal spe-
cialist, the tendency has been to do the surgery
that offers the best chance of success.

Demarcation and Barrier Retinopexy


Demarcation retinopexy is an attempt to halt an Figure 13.35 Postoperative barrier retinopexy of
a retinal hole.
RD in progress. In humans, it has been helpful
in stopping temporal rhegmatogenous detach-
ments before the RD extends to the macula. This possible to stop the detachment. Barrier retin-
“salvage retinopexy” in the dog can be used for opexy is generally indicated for small tears and
vertical dialysis, either nasal or temporal, mov- retinal holes or for thin areas of retina associated
ing toward the optic disc. However, it should not with geographic retinal dysplasia.
be viewed as a definitive surgery, rather only as a
stopgap measure to slow a detachment before
Vitrectomy for Giant Retinal Tears
referral for PPV. If one or two rows of laser burns
are made along the leading edge of the RD As mentioned earlier, most RRDs seen in the
(Figures 13.35 and 13.36), it is sometimes canine are giant retinal tears or giant dialyses
522 Diseases and Surgery of the Canine Posterior Segment

(a) (b)

Figure 13.36 Retinal radial tears. (a) Before laser treatment. (b) After laser treatment.

Figure 13.37 Intraoperative view of a


chronic giant retinal tear.

(which detach at the ora with no anterior flap vision loss in their pet. In most spontaneous
of retina). These are circumferential breaks of RDs in dogs, one retina has been detached
90° (three clock hours) or more. In a series of in the long term, and only when the fellow
more than 500 surgical cases in dogs with giant retina detaches is the owner aware of a vis-
retinal tears, the tears were ≥270° in approxi- ual problem. In the dog, in a previously
mately 75% of cases. These RDs are too far published series on giant retinal tear repair
advanced to benefit from demarcation or PR and in our series of surgical treatment of
and thus require vitrectomy. giant tears, it was observed that if the retina
is reattached within four weeks, there is a
Criteria for Vitrectomy reasonable chance of return of some func-
The duration of the RD is important in pre- tional vision. Giant RDs that have remained
dicting any anticipated return of vision, but partly attached for months appear to recover
in animals, the timeline of events is often useful vision after being reattached
unknown. Astute owners will notice acute (Figure 13.37).
­Surgical Procedures for Treatment of Retinal Detachmen  523

(a) (b)

Figure 13.38 (a) Self-­retaining silicone lens (Dutch Ophthalmic USA, Exeter, NH, USA). (b) Endolaser
retinopexy viewed through a self-­retaining silicone lens.

Surgical Equipment
An operating microscope with coaxial illumi-
nation and X–Y functions is needed. A beam
splitter will give the assistant a coaxial view.
Several different lens viewing systems work
satisfactorily in the dog. Self-­retaining silicone
lenses, both wide-­angle and prism-­type, work
well in the dog (Figure 13.38a and b). New
instrumentation and devices improve the
safety and speed of vitreoretinal surgery. With
the constant updating of equipment, many
prior models become available at a lower cost.
Illuminating sources, electrocautery, air infu-
sion units, ultrasonic fragmentation, and sili-
cone oil pumps are built into these units
(Figure. 13.39). Most present-­day vitrectomy
probes (20, 23, and 25 gauge) are small, pneu-
matic, and disposable; however, some are elec-
tric with only the tip disposable. The newest
technology includes integrated lasers, intraoc-
ular tonography at the infusion port, ability to
titrate the duty cycle, and halogen and mer-
cury light sources. This technology offers 23-­,
25-­, or 27-­gauge probes (Figure 13.40).

Other Available Procedures


These include the vitreoretinal surgical (23-­
gauge) technique, the transconjunctival
sutureless vitrectomy, and the 23-­gauge PPV
for repair of RD, which are available to the vet- Figure 13.39 Eva vitrectomy system (Dutch
erinary ophthalmologist. Ophthalmic USA, Exeter, NH, USA).
524 Diseases and Surgery of the Canine Posterior Segment

Feline Retinal are challenging adaptations to this surgery that


Reattachment Surgery deviate significantly from canine retinal reat-
tachment surgery. Anatomical considerations
Feline retinal reattachment surgery is best
include a deep orbital without an option to
suited for detachments of a congenital nature
proptose, and very poor medial exposure. The
or secondary to lensectomy procedures. There
intrascleral venous plexus in the cat is wider
than that of the dog, and the pars plana is fur-
ther posterior to the limbus (7 mm). To gain
access to the posterior segment, cats are placed
in a dorsal oblique recumbency, lying perpen-
dicularly to the length of the surgery table so
that the lateral canthus is at 12 o’clock. A wide
lateral canthotomy is needed to gain exposure,
with the infusion cannula placed between the
working ports.

­ uccess of Retinal
S
Detachment Repair

Successful reattachment of the retina does


not necessarily imply visual success. In the
“Criteria for Vitrectomy” section, we men-
tion that many of our patients, if their reti-
nas are reattached within four weeks, have a
reasonable chance of achieving some func-
tional vision (Figure 13.41). Dogs can navi-
Figure 13.40 Aerial view of operating room setup gate well with limited vision. It is not
during canine vitreoretinal surgery.

(a) (b)

Figure 13.41 RD surgery on a giant retinal tear. (a) Before surgery. (b) After RD surgery.
­Structure and Function of the Optic Nerv  525

uncommon for a veterinary ophthalmologist


to encounter an owner who is unaware that
his or her pet is blind since the dog can adjust
to its environment. Many of our retinal cases
have likely been detaching for weeks or
months before the retina finally breaks loose
and the animal experiences a sudden loss
of vision.
Although the anatomical success is good
in humans – well over 90% reattach-
ment – the visual success is considerably
lower, with only a very small percentage
achieving 20/50 visual acuity. On the other
hand, our canine cases are usually first-­time
retinal surgeries. In those animals with
RRDs secondary to vitreous degeneration Figure 13.42 Subretinal bleb in a canine eye
(50% of cases), if operated on early (within immediately after successful injection. The bleb
covers the area centralis and the supratemporal
four weeks), the surgeries are anatomically central retina in this right eye.
successful 90–95% of the time, with a visual
success rate of 85%.
Section IV: Optic Nerve

­Subretinal Injection ­ iseases of the Canine


D
Optic Nerve
Direct targeting of photoreceptors and the RPE
with therapeutic agents, such as viral gene Degenerative, traumatic, and inflammatory
therapy vectors or cells, generally requires sub- optic nerve diseases are common in dogs and
retinal injection. In dogs, this technique has may either be primary, arising in and princi-
been used most commonly in the laboratory pally involving the optic nerve itself, or repre-
for the successful gene therapy of inherited sent a secondary effect of pathology elsewhere
retinopathies with AAV. Choice of injector and in the eye, as in glaucoma, or an extension of
cannula depends on the surgeon’s preference local disease from the globe, orbit, or CNS. The
and the reagent to be injected. Factors to con- optic nerve may also be involved in more gen-
sider include commercial availability and dead eralized, systemic disease processes (see
space within the device, because some rea- Chapter 18).
gents are costly to manufacture. Standard sub-
retinal injection cannulas and small-­gauge
(e.g., 27–30-­gauge) anterior chamber cannulas ­ tructure and Function
S
are well suited for the procedure, but because of the Optic Nerve
they are blunt tipped, the placement of a pars
plana port is needed to enter the vitreal cham- The optic nerve is a white matter tract of the
ber. In general, subretinal injections are tech- brain, rather than a true cranial nerve, and is
nically not difficult because the subretinal principally composed of the axons of RGCs.
space between the photoreceptors and the RPE The RCG axons project from somas in the gan-
is a natural space that easily separates glion cell layer of the inner retina, coursing
(Figure 13.42). intraocularly, approximately centripetally,
526 Diseases and Surgery of the Canine Posterior Segment

within the retinal nerve fiber layer (RNFL) disc, or optic papilla, is the only part of the
toward the ONH, where they make a sharp turn optic nerve that can be visualized on ophthal-
to exit the eye as the optic nerve. In afoveate moscopy. In humans, the ONH is surrounded
animals, such as the dog, optic nerve axons by the white, peripapillary scleral border tissue
from ganglion cells in the superior retina are of Elschnig, but pigmentation and/or myelin
located in the superior half of the ONH, and obscure the view of the ring of Elschnig in
axons from the inferior retina lie in the inferior most dogs. Bergmeister’s papilla is formed by
half of the ONH, with a similar pattern noted glial cells covering the site of the hyaloid artery
for axons in the nasal and temporal quadrants. at the ONH and may be observed ophthalmo-
Anatomically, the optic nerve is considered scopically in some dogs. The inner limiting
to extend from an anterior limit at the ONH to membrane of the retina covers the anterior
a posterior limit at which axons reach the optic surface of the ONH, where it is referred to as
chiasm. However, the RGC axons pass through the inner limiting membrane of Elschnig, or
the chiasm without synapsing, continuing the thicker central meniscus of Kuhnt. While
within the optic tracts to the lateral geniculate not readily appreciated with an ophthalmo-
nucleus (LGN), where the majority of canine scope, these features may be observed on OCT
RGC axons ultimately synapse with central images of some ONHs. The axons of the canine
neurons that project within the optic radia- optic nerve are typically myelinated anterior to
tions from the LGN to the visual cortex. the lamina cribrosa (LC). Variability in the
A minority of RGC axons, including those of extent of intraocular myelination of RGC
intrinsically photosensitive, melanopsin-­ axons within the prelaminar tissue and RNFL
containing RGCs, project to the superior colli- is responsible for pronounced interindividual
culus, the hypothalamus, the pretectal nucleus, variation in ONH ophthalmoscopic appear-
or other midbrain centers, where they play a ance in dogs (as described in a later section of
role in regulation of circadian rhythms, PLR, this chapter).
and coordination of eye and head movements. The rich ONH vasculature is associated with
The nasal and temporal halves of the retina of a high rate of blood flow necessary to meet the
carnivores are divided by an imaginary vertical high metabolic demands of this region, and is
line called the vertical meridian that passes responsible for the pink hue of the normal
through the cone-­rich area centralis. RGC healthy canine ONH. The primary blood sup-
axons nasal to the vertical meridian cross at ply to the eye of dogs is provided by the large
the optic chiasm to the contralateral LGN and external ophthalmic artery, which arises from
visual cortex, while axons from the temporal the maxillary artery and is thus extracranial in
retina remain uncrossed and project to the origin. Neural innervation to the internal oph-
ipsilateral LGN and visual cortex. The optic thalmic artery may play some role in the regu-
nerve can be subdivided into four anatomical lation of blood flow to the optic nerve. Two
regions: a short intraocular segment; a retrob- long posterior ciliary arteries, one medial and
ulbar, orbital segment, which constitutes the one lateral, and 9–14 short posterior ciliary
longest region of the optic nerve; a relatively arteries (SPCAs) arise from the anastomoses of
fixed, intracanalicular segment within the the external and internal ophthalmic arteries
optic canal; and a short intracranial segment in dogs. The SPCAs surround the canine ONH
that merges with the optic chiasm. and supply the LC, choroid, retina, and
ONH. Vascular supply to the LC is from the
SPCAs, cilioretinal arteries, and longitudinal
Intraocular Optic Nerve
pial vessels. There is compelling evidence that
The anteriormost part of the optic nerve, the optic nerve blood flow is tightly regulated
ONH, which is also referred to as the optic through a number of different mechanisms,
­Clinical Examination of the Optic Nerv  527

across a broad physiological range of perfusion conserve energy and speed neural conduction.
pressures. The canine optic nerve and retina The primary cell type in the retrobulbar,
may be relatively protected from adverse intraorbital optic nerve posterior to the LC is
effects of venous occlusion. However, the loca- the oligodendrocyte. Myelin is derived from
tion of the canine SPCAs, immediately adja- multiple wrappings of the plasma membranes
cent to and effectively within the neural canal of an oligodendrocyte around each optic
of the canine ONH, where they are relatively nerve axon.
unsupported by scleral tissue, may render
them more susceptible to compression and
Intracanalicular Optic Nerve
occlusion during episodes of pronounced IOP
elevation. This short, relatively fixed segment of the optic
The extensive, nonfenestrated capillary beds nerve begins at the orbital apex, where it is sur-
of the surface, prelaminar, laminar, and ret- rounded by the origins of the superior, medial,
rolaminar optic nerve regions are confluent. and inferior recti muscles. The optic nerve
Capillaries with a continuous basement mem- enters the bony optic canal within the sphe-
brane are surrounded by astrocytes in the ONH noid bone complex. Within the optic canal, the
laminar tissue. However, there is no cell layer dura of the optic nerve and the periosteum of
with tight junctions separating the choriocap- the canal are fused, but the subarachnoid space
illaris from the ONH such that a potential of the intraorbital optic nerve contains cere-
defect exists in the blood–ocular barrier at the brospinal fluid (CSF) and communicates with
level of the ONH. the intracranial subarachnoid space.

Intraorbital Optic Nerve Intracranial Optic Nerve


The intraorbital, or retrobulbar, optic nerve and Optic Chiasm
begins posterior to the LC and consists of optic After exiting the bony optic canal, there is only
nerve axons, oligodendrocytes, and astrocytes. a very short, intracranial portion of the optic
The orbital optic nerve is longer than the direct nerve prior to axons reaching the optic chiasm.
distance between the globe and optic canal, The optic chiasm is the site of decussation of
providing an S-­shaped curve that allows for optic nerve axons, whereby RGC axons from
globe movement. The normal dog has fewer the nasal retina cross the midline to reach the
total numbers of optic nerve axons than contralateral side of the brain, while axons
humans, but has a larger mean fiber diameter arising from RGCs in the temporal retina
of individual axons (~1.5 μm versus ~1 μm). remain ipsilateral. The percentage of axons
The diameter of the canine intraorbital optic crossing the midline at the optic chiasm varies
nerve (1825.8 ± 59.7 μm) is larger than that of between individuals but represents about 75%
the optic nerve at the level of the LC (~1592 μm), in the dog (compared to about 65% decussation
but considerably smaller than that of the in the cat, and 100% in most birds and fish).
human optic nerve (2590 ± 80.6 μm). As it exits
the globe, the canine optic nerve shows an
approximately 1.4-­fold increase in diameter at ­ linical Examination of the
C
the outer scleral canal, in contrast to the nearly
Optic Nerve
2-­fold increase in diameter of the human
optic nerve.
Neuro-­ophthalmic Examination
Although myelination of the ONH varies
according to species, all axons are myelinated In addition to a thorough general physical
posterior to the LC in mammals in order to examination, a thorough neuro-­ophthalmic
528 Diseases and Surgery of the Canine Posterior Segment

examination should be conducted in the unse- distinguish between photoreceptor and inner
dated subject, and prior to instillation of retinal, optic nerve, and CNS diseases that
mydriatics or other pupilloactive drugs. Briefly, impact vision. Chromatic pupillometry quan-
vision in dogs is typically assessed by the ani- tifies responses to luminance matched, bright
mal’s demeanor, ability to navigate a maze and and dim, red and blue stimuli. A simple chro-
track moving objects as well as menace matic PLR testing system has been developed
response and, when practical, visual placing for assessment of the canine visual pathway,
reflexes. Direct and consensual PLRs should be and applicability of this approach has been
carefully assessed with a bright light source independently validated in research and clin-
under dim light conditions. Animals with uni- ical settings. Characteristics and magnitude
lateral optic nerve or retinal disease will have of the PLR can be particularly helpful in dis-
afferent PLR deficits; notably, they are likely to tinguishing optic nerve disease from retinal
exhibit absent or diminished direct PLR, and causes of blindness.
absent or diminished consensual PLR from the
stimulated to the contralateral eye. Testing by
Ophthalmoscopy
means of a swinging flashlight or cover/
uncover test will yield a positive Marcus Gunn As described for ophthalmoscopic examina-
sign. The dazzle reflex is a subcortical response tion of the ocular fundus as a whole, detailed
that demonstrates relative functional integrity ONH examination is best accomplished with
of the retina and optic nerve, but does not the pupil dilated. Both the widest and the
determine integrity of the central visual path- smallest width illumination beams should be
ways and visual cortex and may also be used. The widest beam will provide a highly
impacted by efferent defects, e.g., in facial magnified field of view that encompasses a
nerve function. region just slightly larger than the canine
ONH. By sweeping the small beam (preferably
Pupillometry just one-­third to one-­half of the optic disc
The PLR provides valuable information about diameter) back and forth, vertically and hori-
the functional integrity of the afferent retinal zontally across the surface of the ONH, shad-
and central visual pathways, including the ows are produced that provide additional
optic nerves, as well as the efferent pathways. depth cues to enhance the observer’s ability to
While PLR assessment in a clinical setting is appreciate three-­dimensional alterations in
most often qualitative, quantitative measure- the ONH contour. This technique is especially
ment of response amplitude and latency may valuable in identifying pits and colobomas in
be achieved by pupillometry. However, useful- the ONH, and in determining the location of
ness of diagnostic tests involving the PLR may the neuroretinal rim.
be limited in subjects with efferent PLR defects, The color of the ONH in the normal canine
whether neurological or structural, e.g., associ- eye represents a composite of white myelin
ated with iris atrophy. and the red/pink hue from ONH vasculature.
Though a significant component of the Axial magnification of the canine fundus is
PLR arises from photoreceptor activity, markedly greater than lateral magnification
intrinsically photoreceptive RGCs, which with direct ophthalmoscopy. While height or
contain the photopigment melanopsin, are depth of lesions can be estimated from pub-
also responsible for initiating a significant lished values predicting diopter equivalents in
component of the PLR. By leveraging the mm, with each 1 D change in focus equivalent
peak spectral sensitivity of melanopsin to 0.275 mm, these estimates rely on assump-
(~480 nm), it is possible to use differences in tions in theoretical models and have not been
response to blue and red light stimuli to help validated in the living canine eye.
­Clinical Examination of the Optic Nerv  529

Binocular indirect ophthalmoscopy provides rotation of the scleral insertion zone of the LC,
stereopsis and allows evaluation of the optic outward bowing of the LC, and a widening of
disc even through hazy ocular media. Slit-­lamp the scleral canal delineated by Bruch’s mem-
indirect systems provide greater magnification brane. The associated enlargement of the ONH
than headset systems but are difficult to use in cup with these laminar and axonal changes is
animals. Use of a 14-­D indirect ophthalmos- specific to glaucoma, and distinct from changes
copy lens may be considered a reasonable com- observed in other optic neuropathies.
promise for evaluation of the ONH in canine Unfortunately, although similar structural
patients, although predicted lateral magnifica- changes are thought to occur in canine glau-
tion (2.6×) and axial magnification (9.03×) are coma, myelination of the canine ONH often
considerably less than those with direct obscures clinical ophthalmoscopic detection of
ophthalmoscopy. early increases in optic cup size in dogs with
Direct ophthalmoscopic examination with early glaucoma.
red-­free (i.e., green) light allows RNFL visuali- The ratio of the cup to disc diameter or area
zation, as the red-­free light does not penetrate is used to evaluate progression of glaucoma-
beyond the NFL, but is reflected back from the tous optic nerve damage in humans with pri-
innermost retinal layers as light, silvery streaks mary open angle glaucoma (POAG).
of reflection from axon bundles. Thus, areas of Enlargement of the cup to disc ratio indicates
RNFL attenuation, caused by glaucoma or by optic nerve axonal loss and is associated with
other retinal and optic nerve disease, appear deterioration in visual fields. The cup to disc
dark in red-­free light due to absorption of inci- ratio increases in advanced canine glaucoma
dent light by the RPE in the absence of these as the demyelination of optic nerve axons pro-
reflective structures. ceeds in association with RGC death and
axonal degeneration. As in human subjects,
Clinical Appearance of the Canine advances and application of confocal laser
Optic Nerve Head scanning ophthalmoscopy and OCT may pro-
A thorough clinical examination of the canine vide a means to improve accuracy in delinea-
ONH should evaluate the following features: tion of ONH topography and quantification of
color, size, caliber, and course of visible vascu- the nerve fiber layer thickness and disc area in
lature; relative extent of the optic cup and neu- dogs, and ultimately neuroretinal rim width
roretinal rim; presence of an identifiable and optic cup width and depth in dogs.
physiological pit; and the sharpness of delinea-
tion of the boundaries of these features and
Angiography
their plane of focus. The appearance of the vas-
culature and RNFL reflection in the peripapil- Fluorescein and indocyanine green (ICG)
lary retina should also be evaluated with angiography are described in detail elsewhere
red-­free light. in this book (see Chapter 4) and allow simulta-
neous, sequential visualization of blood flow
Optic Disc Cupping and the “Cup through the retina, ONH, and choroid.
to Disc” Ratio Fluorescein angiography can show areas of
Enlargement of the ONH cup, or “cupping,” is slow filling, nonperfusion, and hemorrhage in
an ophthalmoscopically visible abnormality diseased segments of the optic disc. Shifts in
associated with advanced glaucoma in humans the course of ONH arterioles occur as the ONH
and dogs. In humans and nonhuman primates, swells or is pushed forward, or as the optic cup
optic nerve “cupping” results from a combina- deepens and widens with advancing glauco-
tion of axonal loss, laminar plate compression matous damage. Unfortunately, fluorescein
and remodeling, posterior displacement and angiography is insensitive to the early phases
530 Diseases and Surgery of the Canine Posterior Segment

of tissue loss in the neuroretinal rim in optic evaluation of patients with orbital trauma,
nerve degeneration and glaucomatous atrophy. including detection and localization of metal-
Optic discs develop a persistent hyperfluores- lic foreign bodies and bone fragments.
cence that is more pronounced in association Calcification of optic nerve and orbital tumors
with optic nerve inflammation through leak- may be noted, and is a common feature of
age of fluorescein dye into the ONH extracel- canine orbital meningioma.
lular matrix from the choroid. ICG is an
alternative dye for angiography of the retina,
Ultrasonography
choroid, and optic nerve. In contrast to fluores-
cein, ICG is highly protein bound and does not Real-­time B-­scan ultrasonography enables vis-
readily leak out of the vasculature and does not ualization of the optic nerve and its dural
result in persistent hyperfluorescence of sheath, aids in localization and differentiation
the ONH. of solid, soft tissue masses from cystic orbital
space-­occupying lesions, determination of the
size and integrity of ocular and orbital struc-
Diagnostic Imaging in Optic tures in patients with known or suspected
trauma, and can assist with localization of
Nerve Disease
some orbital foreign bodies. While lacking the
diagnostic specificity and sensitivity of MRI or
Magnetic Resonance Imaging
CT in the investigation of suspected optic
and Computed Tomography
nerve disease, ultrasonography has the practi-
The MRI is considered the cross-­sectional cal and economic advantage of seldom requir-
imaging technique of choice in diagnostic ing general anesthesia in veterinary patients.
investigation of humans with suspected pre- In specialist applications, color-­flow Doppler
chiasmatic optic nerve disease. MRI can be imaging combining conventional B-­mode
used to identify or exclude intraorbital or ultrasonography with Doppler flow analysis
intracranial mass lesions in the differential has been used to evaluate blood flow in the
diagnosis of canine optic nerve swelling, and orbital vasculature of normal and glaucoma-
to diagnose optic nerve tumors, and is invalu- tous dogs.
able in localizing pathology in subjects with
suspected elevation in intracranial pressure,
Electrophysiological Testing
helping to differentiate causes of ONH swell-
in Optic Nerve Disease
ing. In a series of dogs with optic neuritis, pres-
ence of intracranial contrast-­enhancing, Electrophysiological tests, including recording
hyperintense lesions distinguished menin- of VEPs, PERGs, and the photopic negative
goencephalomyelitis of unknown origin responses of the full-­field flash ERG, provide
(MUO) from isolated optic neuritis. In another noninvasive functional measures that reflect
study, which examined MRI findings in dogs RGC axon and soma pathology. However, these
and cats with acute, postretinal blindness, tests are technically demanding, show high
lesions affecting the visual pathways were degrees of interindividual variability, and
observed on MR images in six cases. require significant expertise and specialized
CT provides details superior to those of testing equipment.
plain-­film radiography for orbital bone, soft tis-
sue, and foreign bodies. Although less favora-
Visual Evoked Potential
ble for imaging soft tissue and neural structures
than MR, CT provides information comple- The VEP is an electrical signal generated in the
mentary to MRI that can be critical in the occipital cortex in response to visual stimuli,
­Optic Nerve Disorders: Congenital Optic Neuropathie  531

and it is used to evaluate optic nerve function.


Thus, VEP can be used to help distinguish
vision loss from retinal or optic nerve pathol-
ogy, when combined with ERG. Complete optic
nerve transection results in the absence of the
flash VEP, but with preservation of the flash
ERG. Diseases such as glaucoma that directly
cause axonal degeneration and loss will tend to
reduce VEP amplitudes as well as increasing
their latencies. Studies involving flash VEP and
pattern VEP recorded to checkerboard or grat-
ing patterned stimuli have been reported in
dogs, but both techniques are considered tech-
nically demanding and require sedation or gen-
eral anesthesia in veterinary patients.

Figure 13.43 Unilateral optic nerve hypoplasia in


a Beagle puppy that was associated with a fixed
­ ptic Nerve Disorders:
O dilated pupil and blindness. Multifocal white fuzzy
Congenital areas of are present in the nontapetal fundus
indicate active chorioretinitis.
Optic Neuropathies
The size of the ONH can vary with number
Optic Nerve Hypoplasia/
of axons and, in general, larger ONHs incorpo-
Micropapilla
rate more nerve fibers than smaller ONHs, but
The distinction between micropapilla and in dogs the true dimensions of the optic nerve
optic nerve hypoplasia is based on clinical are often obscured by myelination in the
appearance of small ONH dimensions, with ONH. Together with the confounding variabil-
either presence or absence of vision, respec- ity in the extent of intraretinal and prelaminar
tively. Thus, a small optic disc in an eye with myelination of the ONH in normal dogs, accu-
clinically normal PLRs and vision is termed rate determination of true ONH dimensions is
micropapilla, whereas if the number of axons problematic in a clinical setting in this species,
is so low that PLR deficits and visual deficits meaning that assessment of the relative size of
are identifiable, the condition is termed optic the canine ONH is usually subjective.
nerve hypoplasia. Micropapilla and hypoplasia Resting pupil size is likely to be normal in
of the optic nerve may be unilateral or bilat- dogs with micropapilla, and may be slightly
eral, and are associated with an abnormally larger than normal on the affected side in dogs
small optic disc size identified by ophthalmos- with unilateral optic nerve hypoplasia. Both
copy. Optic nerves that are less than two stand- pupils may be widely dilated and unresponsive
ard deviations from the mean diameter are in dogs with bilateral optic nerve hypoplasia.
considered statistically abnormally small in Normal full-­field flash ERG responses confirm
humans (Figure 13.43). Using this same defini- intact photoreceptor and bipolar cell function.
tion, ONHs less than about 1.7 mm in diameter In the dog, both micropapilla and optic nerve
could be considered abnormally small in the hypoplasia may occur sporadically in any
dog. However, in puppies, myelination of the breed, either in isolation or accompanying
ONH is not complete until several weeks of other ocular malformations. Micropapilla, and
age so that the ONH of young puppies appears less frequently, optic nerve hypoplasia, has
small, round, and dark in color. been reported in a large number of breeds
532 Diseases and Surgery of the Canine Posterior Segment

Box 13.3 Breeds of Dogs Reported Box 13.4 Breeds of Dogs Reported
with Optic Nerve Hypoplasia with Micropapilla
●● Afghan ●● Beagle
●● American Cocker Spaniel ●● Belgian Sheepdog
●● Beagle ●● Belgian Tervuren
●● Borzoi ●● Collie
●● Collie ●● Dachshund
●● Dachshund ●● Flat-­Coated Retriever
●● English Springer Spaniel ●● German Shepherd
●● German Shepherd ●● Gordon Setter
●● Golden Retriever ●● Great Pyrenees
●● Greyhound ●● Irish Setter
●● Irish Setter ●● Irish Wolfhound
●● Italian Greyhound ●● Labrador Retriever
●● Kerry Blue Terrier ●● Miniature Poodle
●● Keeshond ●● Miniature Schnauzer
●● Labrador Retriever ●● Norfolk Terrier
●● Miniature Schnauzer ●● Old English Sheepdog
●● Old English Sheepdog ●● Puli
●● Pharaoh Hound ●● Sheltie
●● Rough Collie ●● Shih Tzu
●● Sheltie ●● Soft-­Coated Wheaten Terrier
●● Shih Tzu ●● Tibetan Spaniel
●● Skye Terrier
●● Soft-­Coated Wheaten Terrier
●● Saint Bernard with other abnormalities, including microph-
●● Standard Poodle thalmos, retinal disorganization, RD/nonat-
●● Tibetan Spaniel tachment, anterior segment dysgenesis, and
persistent hyaloid vasculature.

(Boxes 13.3 and 13.4). Optic nerve hypoplasia


Achiasmatic Belgian Sheepdogs
and micropapilla are specifically considered
inherited in the Miniature and Toy Poodles, Detailed neuropathological reports have been
and Dachshund breeds, and research aimed at published describing achiasmatic optic nerves
identifying the molecular genetic basis of optic with nystagmus in a small family of Belgian
nerve hypoplasia and micropapilla in Sheepdogs (Groenendael). Congenital nystag-
Miniature and Toy Poodles is ongoing at the mus is the most striking clinical feature. In
time of writing. Dogs with optic nerve hypo- affected dogs, all RGC axons projected directly
plasia should not be used for breeding. to ipsilateral brain targets, with no chiasmal
decussation.
Optic Nerve Aplasia
Optic Nerve Coloboma
Optic nerve aplasia is very rare and involves a
congenital complete absence of RGCs and Optic nerve colobomas are congenital malfor-
their axons. Eyes with optic nerve aplasia show mations of the ONH that result in outward dis-
a complete lack of retinal vasculature. Optic tortion of the ONH due to focal absence of
nerve aplasia may also be recognized in eyes normal tissue in the ONH and/or peripapillary
­Acquired Optic Neuropathie  533

Box 13.5 Breeds of Dogs Reported


with Optic Nerve Colobomas
●● American Cocker Spaniel
●● Australian Shepherd
●● Basenji
●● Bernese Mountain
●● English Cocker Spaniel
●● Flat-­Coated Retriever
●● German Shepherd
●● Golden Retriever
●● Huskie
●● Irish Setter
●● Labrador Retriever
●● Malamute Figure 13.44 Optic nerve coloboma with
●● Norfolk Terrier peripapillary white laser burns and preretinal
hemorrhages after laser treatment for a small RD.
●● Tibetan Spaniel
●● Samoyed
●● Sheltie ONH are generally not associated with appre-
●● Whippet ciable defects in vision in dogs, large colobo-
mas communicate with the vitreous and
subretinal space and their presence is a risk
sclera. They may appear as enlarged optic discs factor for retinal tears and detachment. For
with a deep excavation and distorted margins, this reason, dogs with a diagnosis of ONH
or as slightly enlarged, irregular discs contain- coloboma should not be bred.
ing deep pits within the borders of the nerve A homozygous intronic deletion mutation in
head. Coloboma of the ONH is most com- the NHEJ1 gene is predictive for choroidal
monly recognized along with choroidal hypo- hypoplasia in dogs with CEA. However, dis-
plasia, as a component of the clinical syndrome cordance between this gene mutation and
“Collie eye anomaly” in Collie breeds, includ- colobomas has been reported in the Nova
ing a number of breeds (Box 13.5). Scotia Duck Tolling Retriever, and it is appar-
On ophthalmoscopy, optic disc colobomas ent that it is not solely responsible for colo-
may be small and hard to differentiate from a boma. There are reports on outcomes of
prominent physiological pit or deep physiolog- selective breeding practices in Rough Collies in
ical cup, or they may be very large in diameter Sweden, which permitted breeding of dogs
and up to 30 D in depth (Figure 13.44). with choroidal hypoplasia but not colobomas
Colobomas located inferiorly in the optic nerve and resulted in substantial increase in preva-
are considered to represent faulty closure or lence of choroidal hypoplasia without con-
fusion (or both) of the fetal fissure of the ven- comitant increase in prevalence of coloboma.
tral optic stalk and cup, whereas “atypical”
peripapillary colobomas may originate from
orbital cysts, or failure of normal differentia- ­Acquired Optic Neuropathies
tion of outer layer of the optic cup. Thus, colo-
bomas may be referred to clinically as “typical” Disorders of the prechiasmatic visual path-
in location at the inferior, 6-­o’clock position in ways are a diagnostic challenge! Acquired
the location of the fetal fissure, or as “atypical” optic nerve disorders may be caused by infec-
when located in the nasal or temporal disc tion, inflammatory or neoplastic cellular infil-
margin. Although small colobomas of the tration, ischemia, trauma, or mechanical
534 Diseases and Surgery of the Canine Posterior Segment

compression. These processes may arise within papilledema or optic neuritis, there is a risk
the nerve itself but more often reflect exten- that some patients may receive misguided
sion of local disease from the CNS or adjacent diagnostic workups or therapy (or both) for
tissues, or involvement in a systemic disease intracranial disease. Autofluorescence imag-
process, underscoring the need for thorough ing is less likely to be informative in dogs with
ophthalmic, neurological, and general clinical pseudopapilledema than in humans, as age-­
examination in affected dogs. If bilateral, optic related ONH autofluorescent drusen have not
neuropathies can lead to blindness, a presenta- been recognized in dogs. Thus, distinction
tion that is often acute in dogs. Other signs of between pseudopapilledema and true
optic nerve disease include ONH swelling, vas- papilledema in dogs remains subjective and
cular congestion, or hemorrhage. These signs somewhat dependent on observer experience
may, or may not, be accompanied by other and judgment.
signs of ocular, orbital, CNS, and/or systemic
disease.
Papilledema

Differential Diagnosis of the Papilledema, or noninflammatory swelling of


“Swollen Disc” the ONH, can accompany acute glaucomuveitis,
or postoperative ocular hypotony following glau-
Pseudopapilledema
coma surgery, and there are anecdotal reports of
This elevation of the ONH surface by prelami-
ONH edema in dogs with severe arterial hyper-
nar myelination of nerve fibers in clinically
tension. Axonal swelling caused by disruption of
healthy, normal dogs may resemble optic disc
axoplasmic flow is thought to be primarily
swelling caused by neoplasia, optic neuritis, or
responsible for papilledema from elevated
elevated intracranial pressure (i.e., noninflam-
intracranial pressure as well as disc swelling
matory papilledema), and may be a cause for
caused by optic nerve compression by orbital
alarm and misdirected diagnostic procedures
tumors, ocular hypotony, and acute glaucoma.
in dogs (Box 13.6). In the dog, pseudo-
Early in the course of disease, true
papilledema is considered to simply result
papilledema may not affect vision, in contrast to
from extensive myelination of optic nerve
optic neuritis, which is associated with loss of
axons anterior to the lamina cribrosa, which is
vision that is often acute, and is accompanied by
not associated with pathology. This raised
diminished or absent PLR. Primary (e.g., men-
appearance may involve the ONH focally or
ingioma and glioma) and secondary optic nerve
regionally, extend along retinal blood vessels,
neoplasia (e.g., lymphoma) may cause a “swol-
or involve most of the ONH, which can have
len disc” (see later). Orbital mass lesions char-
an irregular, domed or “donut” appearance.
acteristically produce exophthalmos, but when
Because the funduscopic appearance mimics
slowly progressive they may also present as very
chronic, unilateral ONH edema secondary to
Box 13.6 Breeds of Dogs Reported local infiltration, compression, and/or changes
with Pseudopapilledema in the local pressure gradients.
●● Curly Coated Retriever
●● English Springer Spaniel Inflammatory Optic Neuropathies
●● English Toy Spaniel
Optic neuritis represents a clinical syndrome
●● German Shepherd
rather than a single disease. Causes of optic
●● Golden Retriever
neuritis in dogs are listed in Box 13.7, and
●● Labrador Retriever
include idiopathic, immune-­mediated, and
●● Miniature Poodle
infectious diseases, neoplasia, and toxins, as
­Acquired Optic Neuropathie  535

Box 13.7 Causes of Optic Neuritis


in the Dog
●● Infectious: distemper, tick-­ borne ence-
phalic virus, blastomycosis, cryptococcosis,
histoplasmosis, ehrlichiosis, toxoplasmosis
●● Reticulosis/GME
●● Idiopathic
●● Other: trauma, neoplasia, orbital abscess/
cellulitis

well as extension of inflammatory diseases


from adjacent paranasal sinuses, retina, brain,
and meninges, and orbit to involve the
Figure 13.45 Optic neuritis may exhibit a
optic nerve. swollen, raised, and hyperemic optic disc with
indistinct margins. There is no apparent
physiological cup or pit and there is evidence of
Clinical Signs of Optic Neuritis edema and possibly folding in the adjacent,
peripapillary retina and/or choroid.
Inflammation of the canine optic nerve may be
unilateral or, more frequently, bilateral though
not necessarily symmetrical in presentation. The
disease often presents acutely in dogs, due to
sudden blindness, and the pupils of the affected
eyes are dilated with either absent PLRs or slug-
gish and incomplete PLRs. However, some par-
ticularly astute pet owners may notice more
subtle visual deficits in their dogs, or may
observe pupil dilation, anisocoria, or other neu-
rological signs. The retrobulbar, orbital, intra-
canalicular, and/or intracranial portions of the
optic nerve may be affected without involvement
of the intraocular portion of the ONH, particu-
larly in granulomatous focal or multifocal dis-
ease. Thus, some patients with the focal,
retrobulbar form of optic neuritis show no fun-
duscopic abnormalities. The blood vessels on the Figure 13.46 Optic neuritis associated with
surface of the ONH appear raised and congested, GME. Note the swollen hyperemic disc with
and hemorrhages may be present that typically indistinct margins and no physiological cup.
have a flame-­shaped appearance as they track
centrifugally along nerve fiber bundles in the may be observed, with darkening or pallor of the
RNFL (Figures 13.45 and 13.46). Papillitis is shrunken ONH. Conventional flash ERGs are
often associated with vitreous cells and haze, typically normal in subjects with optic neuritis
and peripapillary retinal edema and neuroretini- (unless there is also clinical evidence of signifi-
tis are also commonly seen in dogs with optic cant retinochoroiditis), but VEPs may exhibit
neuritis. Ultimately, optic nerve degeneration latency delays and reduction in amplitude.
536 Diseases and Surgery of the Canine Posterior Segment

Causes of Optic Neuritis findings are unremarkable. MRI followed by


CSF analysis, including determination of pro-
Reported causes of optic neuritis in the dog are
tein concentration, cytology, and appropriate
quite variable and often with systemic dis-
serological/molecular diagnostic testing for
eases. Extension of orbital abscesses/cellulitis
potential infectious causes, is strongly recom-
and sphenoid bone osteomyelitis, as well as
mended to establish an etiological diagnosis
optic nerve involvement in systemic, CNS, and
whenever possible (see earlier and Table 13.2).
orbital neoplasia, are other reported causes of
In patients with MUO, CSF protein concentra-
optic neuritis in the dog. In a retrospective
tion is usually, but variably, elevated, and mon-
study of 96 cases of canine optic neuritis, an
onuclear or mixed pleocytosis is often observed.
etiological diagnosis was not established in
Infectious causes of optic neuritis should be
about 80% of patients. Neoplasia was diag-
managed with appropriate specific antimicro-
nosed in just under 10% of cases and infectious
bial therapy if indicated. Additional supportive
disease was identified in under 6% of dogs, and
therapy, including anticonvulsive, colloidal
extension of orbital inflammatory disease and
fluid therapy or hyperosmotic therapy (if signs
exposure to toxins were infrequent causes of
indicate elevated intracranial pressure), may
optic neuritis in that series.
be necessary in patients with other systemic
Optic neuritis is ultimately ascribed to idio-
signs or severe neurological signs. Systemic
pathic, infiltrative, immune-­mediated inflam-
corticosteroid therapy at anti-­inflammatory
matory disease in a majority of canine patients.
doses (0.25–0.5 mg/kg/day) is recommended
Diagnoses span a range of syndromes, from
pending results of serologic tests. Alternative,
ION through a range of diseases with variable
second-­line immunosuppressive and immu-
CNS involvement that now generally fall under
nomodulatory regimens that have been pro-
the umbrella term of MUO (meningoencepha-
posed for the management of MUO include
lomyelitis or reticulosis, which are inflamma-
azathioprine.
tory diseases of unknown etiology, with a
predilection for small breed dogs). More severe,
Traumatic Optic Neuropathies
presenting signs of neurological disease, such
All portions of the optic nerve (i.e., intraocular,
as seizures, altered mentation, central vestibu-
intraorbital, intracanalicular, and intracranial)
lar disease, and/or blindness in relatively
are susceptible to injury, and traumatic propto-
younger dogs, mean that dogs with NE are
sis and orbital fractures are frequently encoun-
more likely to be initially presented for neuro-
tered in the dog (Figure 13.47). In particular,
logical rather than ophthalmic evaluation. In
proptosis is a common problem in brachyce-
GME, pathology and corresponding clinical
phalic breeds, in which the initiating traumatic
signs may be subdivided into three forms,
event may be minor. Rapid deceleration of the
based on anatomical localization, as focal,
anterior portion of the optic nerve relative to
multifocal/disseminated, or ocular.
the more fixed, posterior, intracanalicular and
intracranial portions of the canine optic nerve
Diagnosis, Treatment,
in traumatic globe proptosis can result in ONH
and Prognosis
avulsion, globe rupture, optic nerve laceration,
Electroretinography and/or chromatic pupil- and atrophy, as well as ONH vascular
lometry (see earlier sections of this chapter) compromise.
are indicated to distinguish SARDS from ret-
robulbar optic nerve disease in canine patients Optic Nerve Degeneration
presenting with acute blindness and widely Optic nerve degeneration is a nonspecific
dilated pupils in which ophthalmoscopic sequela to optic nerve compression (e.g., by local
­Acquired Optic Neuropathie  537

Figure 13.47 Complete optic nerve avulsion Figure 13.48 Swelling, pronounced anterior
caused by traumatic proptosis in an American protrusion, and congestion of the ONH due to
Cocker Spaniel. The pupil was fixed and dilated, meningioma in a Labrador Retriever.
but the eye appeared completely normal in
external appearance. Glial tissue covers the site of
the ONH.
Secondary Neoplasia of the
Optic Nerve
orbital and calvarial space-­occupying lesions),
inflammation, blunt and penetrating trauma, Most neoplasia involving the optic nerve arises
and ischemia, and is a common outcome in in other structures. Intraocular and intracra-
glaucoma in which there is characteristic optic nial tumors may both involve the optic nerve
disc cupping (see later). The degenerate or by extension; common orbital tumors that
atrophic ONH will typically appear shrunken, include squamous cell carcinoma, adenocarci-
with reduced vascular perfusion recognizable as noma, fibrosarcoma and osteosarcoma may
optic disc pallor, and with loss of myelin recog- affect the optic nerve by invasion and/or com-
nizable as darkening of the optic disc that takes pression, and metastatic neoplasia may
on a dark gray appearance. involve the optic nerve or chiasm. Thorough
ophthalmic and general clinical examination,
Optic Nerve Neoplasia together with appropriate cross-­sectional
Primary neoplasms arising in the optic nerve imaging with guided biopsy, can determine
are infrequently encountered in dogs, with optic the nature and extent of the primary disease in
nerve meningioma the most common of these most cases.
tumors (Figure 13.48), followed by astrocytoma Lymphoma is another neoplastic disease
and, very rarely, medulloepithelioma. Dogs that can masquerade as optic neuritis when
with optic nerve tumors may be presented for involving the optic nerve. Unlike most primary
evaluation by diligent owners who notice differ- optic nerve neoplasms that involve just one
ences in pupil size and reactivity. Affected dogs optic nerve unless there is chiasmal involve-
may also present with exophthalmos, which ment, optic nerve lymphoma can be bilateral
may be accompanied by a unilateral or, rarely, in presentation, with acute blindness attribut-
bilateral swelling of the ONH, and with signs able to involvement of the optic chiasm and/or
that could be consistent with optic neuritis. prechiasmatic optic nerves.
538 Diseases and Surgery of the Canine Posterior Segment

Optic Neuropathy in Glaucoma


The complex pathophysiology of glaucomatous
optic neuropathy is addressed in greater detail
in Chapter 12. In dogs with glaucoma, as in
other species, characteristic optic nerve damage
occurs following IOP-­related insult to RGC
axons in the ONH, which is considered a critical
site for initial damage. Structural changes to the
LC, with active remodeling of connective tissue
extracellular matrix in response to IOP-­induced
mechanical deformation, vascular insufficiency
in the ONH and retina, due to compression of
SPCAs and stretching and compression of ONH
capillaries by IOP-­mediated stresses and strains
in the LC and peripapillary sclera, negatively
impacting mitochondrial function and axon Figure 13.49 Wedge-­shaped regions of tapetal
metabolism, disruption of normal axoplasmic hypo-­and hyperreflectivity to the left of the
flow with resulting neurotrophin deprivation, photograph and hyperreflectivity to the right,
indicative of sectoral retinal and choroidal necrosis
and activation of glial cells that can intensify
in a Basset Hound with glaucoma. It is suggested
fibrosis and inflammation, are all recognized as that this common pattern of outer retinal and
potential contributors to loss of RGC axons in choroidal degeneration represents occlusion
the optic nerve (Figure 13.49). of SPCAs.
539

Section 4

Special Species
541

14

Feline Ophthalmology
Revised from 6th edition of Veterinary Ophthalmology, Chapter 28: Feline Ophthalmology, by Mary Belle Glaze, David J. Maggs, and
Caryn E. Plummer

­Introduction entropion and corneal sequestration. The cat


has no eyelashes, but a row of thicker facial
Cats are the most popular household pet in the hairs serves as rudimentary lashes along the
United States and Europe, with populations upper lid.
numbering 94 million and 100 million, respec-
tively. This growth has increased interest in
feline well-­being, the evolution of veterinary ­Congenital Eyelid Abnormalities
practices devoted exclusively to their care, and
a demand for increasingly sophisticated Abnormalities of Eyelid Opening
healthcare that includes management of their
ocular disease. Inherited disorders of the eye On the rare occasion that the eyelids separate
are infrequent in cats, but systemic infectious prematurely, a neonatal kitten’s tear produc-
diseases often affecting the eyes are common. tion may not be sufficient to prevent desicca-
tion of the ocular surface. Frequent lubrication
using a topical artificial tear or prophylactic
­Diseases of the Eyelids antibacterial ointment is necessary to discour-
age secondary progressive ulceration until the
Kittens are born with their eyelids fused (phys- lacrimal system matures. Eyelid opening is
iological ankyloblepharon), with opening gen- more likely to be delayed than early (pathologi-
erally predicted between 10 and 14 days of age. cal ankyloblepharon) (Figure 14.1). Delayed
In the majority of kittens, both eyes open on separation occurs in Persian cats. If the lids
the same day, with separation usually begin- remain fused beyond the usual 10–14 days of
ning at the medial canthus. In the normal age with no evidence of eyelid swelling or dis-
feline eye, the lid margins should just cover the comfort, conservative therapy with warm com-
upper and lower limbal arcs of the cornea. presses may encourage natural separation. If
Limited conjunctiva is visible within the palpe- the eyelids are distended to any degree by
bral fissure, with the exception of a small por- trapped secretions, if the site is painful, or if
tion of the third eyelid medially and a small any purulent exudate is evident, it is impera-
area of bulbar conjunctiva laterally. tive to rule out neonatal conjunctivitis (also
Brachycephalic breeds tend to have slightly known as ophthalmia neonatorum) and treat
longer eyelids, a factor that may explain their promptly. Primary infectious pathogens in kit-
predilection for surface diseases such as tens include feline herpesvirus (FHV) and

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
542 Feline Ophthalmology

fused eyelids can lead to permanent corneal


scarring, symblepharon, and even corneal
perforation.

Eyelid Agenesis
Eyelid agenesis or coloboma is the most com-
mon congenital eyelid abnormality in the cat.
Although this developmental defect occurs
sporadically in any breed, agenesis has been
reported in the domestic shorthair, Burmese,
and Persian. Embryologically, the defect may
be linked to inadequate induction of the sur-
face ectoderm by an abnormally oriented optic
vesicle. In affected cats, thorough ocular exam-
inations should be performed to rule out con-
Figure 14.1 Ankyloblepharon and neonatal current colobomas of the iris, choroid, and
ophthalmia in a 2.5-­week-­old domestic shorthair
kitten. Exudate is trapped beneath the left fused
optic nerve.
lids but seeps from the partially opened right The effect of this developmental defect
palpebral fissure. ranges from a small notch in the lid margin to
complete absence of two-­thirds or more of the
upper eyelid and its conjunctival lining
Chlamydia felis as well as secondary bacteria (Figure 14.2). The temporal aspect of the supe-
that include Staphylococcus spp. or Gram-­ rior lid is most commonly affected; medial can-
negative bacteria of fecal origin. The eyelids thal involvement is rare. Lesions are typically
should be gently pried apart with firm digital bilateral but may not be symmetrical. Mildly
pressure over the medial canthus, or the closed affected animals may be asymptomatic but
tip of a small mosquito hemostat may be patients more often exhibit secondary corneal
inserted at the medial canthus where a small disease and discomfort resulting from corneal
gap often exists, sometimes identified by a contact with adjacent facial hair, failure of the
drop of exudate. The hemostat is carefully eyelid to close, or both.
opened to separate the lids, followed by liberal
flushing of the ocular surface with sterile
saline or dilute aqueous (1:50) povidone–
iodine solution until all exudate is removed.
Sharp instruments are best avoided since inad-
vertent damage to the lid margins or meibo-
mian glands could predispose to chronic
keratitis. Topical therapy is directed at the most
likely bacteria, notably C. felis, applying tetra-
cycline, erythromycin, or a fluroquinolone sev-
eral times daily for 7–10 days until signs of
infection resolve. Tear production and the
blink reflex may be inadequate in these very
Figure 14.2 Eyelid agenesis. The normal pink
young kittens, so consideration should also be
margin is missing in the temporal third of the
given to supplemental lubrication. Failure to upper eyelid, calling attention to this subtle
promptly address an infection beneath the example of agenesis.
­Structural Eyelid Abnormalitie  543

Treatment is dictated by the severity of the bucket handle technique, borrowing skin,
agenesis. Mild deformities may require only orbicularis muscle, and conjunctiva from the
supplemental lubrication with a topical artifi- lower eyelid, a modification of the Mustardé
cial tear ointment. Cryoepilation of misdi- cross-­lid technique using the full-­thickness
rected hairs or correction of the trichiasis lower eyelid to reconstruct the upper lid and a
using a Hotz–Celsus or Stades technique may technique using injectable subdermal colla-
suffice if the eyelid retains sufficient mobility gen to replace the eyelid stroma, combined
and bulk to protect the cornea. Otherwise, the with a modified Stades technique to remove
choice of surgical technique is governed by misdirected hairs.
the extent of the coloboma. Defects involving
one-­fourth to one-­third of the lid margin may
be closed directly by converting to a simple
­Structural Eyelid Abnormalities
wedge, with a releasing incision at the lateral
canthus to create an advancement flap if
Entropion
needed to minimize wound tension. The
majority of lesions are too large for primary Inversion of the eyelid is less common in cats
apposition. Reparative techniques utilize a than in dogs. Primary entropion occurs most
rotational pedicle of lower eyelid skin and often in the Persian and other brachyce-
orbicularis muscle, anchored at the lateral phalic breeds, usually involving the medial
canthus, sutured into the upper defect, and aspect of the lower eyelid. Pronounced facial
lined by neighboring conjunctiva undermined “jowls” in the intact male Maine Coon cat
and mobilized at the site (Roberts–Bistner are implicated as a predisposing breed-­
technique). The most common complication, related factor. The same facial conformation
related to corneal irritation and absence of the may accompany entropion in the occasional
lid margin, is the downward angle of hairs feral tomcat as well. Cats with entropion
within the grafted skin, often requiring a sec- tend to be either (i) young cats with chronic
ond procedure such as cryoepilation to correct surface irritation from conjunctivitis, cor-
the trichiasis. A modification of the rotational neal ulceration, or corneal sequestration, or
technique includes conjunctiva transposed (ii) older cats with eyelid laxity or enoph-
from the anterior surface of the third eyelid to thalmos from reduced orbital tissue volume.
line the newly created upper eyelid. A buccal These observations suggest feline entropion
mucosal island graft has also been used in is more likely a consequence of chronic,
conjunction with a single pedicle advance- painful ocular disease rather than faulty con-
ment flap from the dorsolateral forehead skin formation (Figure 14.3).
to recreate a rudimentary superior fornix. Surgical correction of entropion in cats must
Sliding skin grafts, Z-­plasty skin flaps, and eliminate the cause of eyelid spasm that leads
semicircular skin grafts can also be used for to recurrence and the amount of eyelid tissue
correction. Traditionally used to repair exten- that must be resected to sufficiently evert the
sive lower lid defects, the lip-­to-­lid reconstruc- lid is often surprisingly greater than that
tion technique can be modified to reconstruct required in a similarly entropic dog. If the
the upper lid with skin, muscle, and mucus entropion resolves following application of a
membrane of the commissure of the lip, which topical anesthetic, definitive surgical correc-
provides a stable upper lid and lateral canthal tion should be postponed until the underlying
margins, and avoids the problem of trichiasis cause of the blepharospasm is identified and
frequently encountered with other techniques. treated. Vertical mattress sutures or staples
Alternative multistage techniques used for may be used to temporarily evert or “tack” the
extensive defects include the Cutler–Beard or eyelids, limiting damage to the ocular surface
544 Feline Ophthalmology

(a) (b)

(c) (d)

Figure 14.3 (a and b) Chronic bilateral entropion in a two-­year-­old Persian with secondary keratitis.
(c) Entropion of the lower eyelid in a six-­year-­old domestic shorthair with a history of chronic conjunctivitis.
(d) Postoperative appearance of the same eye following a modified Hotz–Celsus technique combined with
lateral canthal closure.

in the interim. Subdermal injection of a hyalu- position the lower nasolacrimal (NL) punc-
ronic acid filler (Restylane® Silk, Galderma tum in brachycephalic cats, the Hotz–Celsus
Laboratories LP, Fort Worth, TX, USA) may be technique can be modified by excising a trian-
used to correct entropion of senile, primary, gular rather than elliptical section of skin,
and cicatricial origin. Using only manual with the tip of the triangle opposite the lower
restraint, 0.1–0.3 ml of filler is injected into the lacrimal punctum. In some cats, it may be
subdermal space 1–2 mm ventral to the eyelid necessary to also address excess lid length to
margin using a 27-­or 30-­gauge needle. successfully correct the entropion. Success
Most cases of feline entropion can be suc- rates of 88.6% are seen when the Hotz–Celsus
cessfully corrected using a Hotz–Celsus pro- procedure is combined with a lateral wedge
cedure, but recurrences are possible. To resection, shortening the lower eyelid by as
correct medial entropion and properly much as 5 mm.
­Blephariti  545

Dermoid caused by Microsporum canis, with


Microsporum gypseum and Trichophyton men-
A dermoid is a congenital malformation in which
tagrophytes accounting for the remainder.
fully differentiated tissue develops in an aberrant
Infection results from contact with another
location. An ocular dermoid contains elements of
affected cat or from environmental contamina-
normal skin, including keratinized epithelium,
tion. There is indirect evidence that Persian
hair, glandular tissue, and fat. Ocular dermoids
cats are predisposed to infection. Lesions occur
are considered rare in cats. The anomaly may
most commonly on the face, ears, and muzzle,
develop spontaneously in any breed, although a
and then progress to the paws. Eyelid lesions
multifactorial mode of inheritance has been pro-
include variably shaped areas of alopecia, ery-
posed in the Birman breed. Locations vary, but
thematous patches, and crusted plaques.
dermoids have been noted in the temporal per-
Pruritus is minimal to absent. Although der-
ilimbal conjunctiva and cornea as well as the skin
matophytosis in most healthy animals is self-­
and conjunctiva of the lateral canthus.
limiting within four months of onset, topical
Surgical excision is advisable in most cases
and systemic treatment is recommended to
of dermoid, but the proper technique must be
shorten the disease course as well as limit
determined on an individual basis. A lateral
spread to other animals and their human care-
canthal dermoid may simply require a wedge-­
takers. Spot treatment of only visible lesions is
shaped excision and two-­layer closure, with a
not recommended in cats. Twice-­weekly lime
figure-­of-­eight suture at the margin to ensure
sulfur dips or miconazole–chlorhexidine
perfect apposition. Patients with concurrent
shampoos remain the most effective choices
conjunctival and/or corneal involvement are
for topical therapy in the United States; enil-
best referred to an ophthalmologist to ensure
conazole is recommended in other parts of the
complete excision and restoration of normal
world. Topical therapy is combined with non-
anatomical relationships during repair of the
compounded itraconazole (5–10 mg/kg p.o. q
operative site. Surgical excision is curative.
24 h with food) or terbinafine (20–30 mg/kg q
24 h). A pulsed regimen of oral 10% itracona-
zole solution administered for seven days at
­Blepharitis 5 mg/kg q 24 h on alternate weeks over a five-­
week period produced a clinical cure in 97.5%
Inflammation of the eyelids may occur as an of infected cats. Treatment should be contin-
isolated problem or as part of generalized der- ued until diagnostic testing confirms a cure.
matological disease. The causes of blepharitis Systemic mycotic infections are relatively
are as varied as the causes of dermatitis in gen- uncommon in cats. Cryptococcus neoformans
eral and in the cat are usually infectious, aller- and Histoplasma capsulatum infections are
gic, or immune-­mediated in origin. Cats more often diagnosed than those of Blastomyces
presenting with blepharitis should be examined dermatitidis or Coccidioides immitis. The pre-
carefully to identify accompanying dermatolog- dominant ocular manifestations of these deep
ical lesions. If concurrent skin lesions are pre- mycoses are chorioretinitis and anterior uveitis,
sent and the eye itself is spared, consultation but papules and nodules can develop on the
with a veterinary dermatologist is advisable. face, nose, pinnae, and eyelids. In endemic areas
(Figure 14.4), these pathogens should be consid-
ered in any cat exhibiting raised erythematous
Fungal Blepharitis
nodules of the eyelid and palpebral conjunctiva.
Dermatophytosis is a common cutaneous fun- Facial nodules and ulcers commonly associated
gal infection in cats, colloquially referred to as with the subcutaneous fungus Sporothrix
“ringworm.” Over 90% of feline cases are schenckii can also extend to the eyelids.
546 Feline Ophthalmology

Figure 14.4 Mycotic blepharitis. A three-­year-­old


DSH exhibits multiple erythematous nodules of the
eyelid and conjunctiva associated with systemic
Figure 14.5 Demodicosis. Periocular skin
histoplasmosis.
scrapings were positive for Demodex spp. in this
13-­year-­old diabetic DLH with periocular alopecia,
erosion, and crusting.
Parasitic Blepharitis
Feline demodicosis is an uncommon derma- subcutaneously once weekly), topical imida-
tological disease caused by the mites Demodex cloprid–moxidectin applied q 7–14 days, or
cati, Demodex gatoi, and a third unnamed oral fluralaner (single 28 mg/kg oral dose).
Demodex sp. Localized disease affects the Treatment of choice for D. gatoi consists of at
eyelids, periocular area, head, and neck, with least four weekly 2% lime sulfur dips.
patchy alopecia, erythema, scaling, and crust- Treatment of either mite should continue
ing (Figure 14.5). Demodex gatoi is conta- until two consecutive skin scrapings, taken
gious to other cats and infestation is two weeks apart from the same site, are
distinguished by moderate to severe pruritus. negative.
Generalized demodicosis is usually associ- Notoedric mange or feline scabies is a highly
ated with underlying systemic diseases, contagious yet uncommon disorder caused by
including diabetes mellitus, or infection with Notoedres cati. Affected animals typically have
feline leukemia virus (FeLV) or feline immu- large numbers of mites that are easily found on
nodeficiency virus (FIV). Even in generalized skin scrapings or acetate tape impressions.
disease, lesions predominate on the face and Lesions first appear on the proximal edge of
head. Diagnosis is based on the presence of the ear, and then spread rapidly to the face,
mites in skin scrapings, hair plucks, or ace- eyelids, and neck. The infestation is intensely
tate tape preparations (Figure 14.5). Localized pruritic, accompanied by heavy crusts, thick-
D. cati lesions are typically self-­limiting but ened skin, and hair loss. Lime sulfur dips, topi-
can be treated with topical rotenone oint- cal selamectin (6–12 mg/kg once or twice at a
ment, lime sulfur, pyrethrin-­containing ear 14-­ or 30-­day interval), topical imidacloprid/
medications, or amitraz in mineral oil (1:9). moxidectin (Advantage Multi®, Bayer, 0.1 ml/
For generalized D. cati infestations, alterna- kg once), subcutaneous doramectin
tives to weekly 2% lime sulfur dips include (0.2–0.3 mg/kg once), oral ivermectin (0.2 mg/
oral aqueous ivermectin (0.2–0.3 mg/kg q kg twice weekly for four doses), or subcutane-
24–48 h, oral milbemycin oxime (1–2 mg/kg q ous ivermectin (0.2–0.3 mg/kg at 14-­day inter-
24 h), injectable doramectin (600 μg/kg vals) are treatment options.
­Blephariti  547

Viral Blepharitis Although uveitis is the most common ocular


lesion, blepharitis and conjunctivitis have been
FHV has been identified as a cause of dermato-
described. Cutaneous papules, nodules, exuda-
logical lesions, particularly those involving
tive crusts, and ulcers often develop on the
facial skin of domestic and wild Felidae. Feline
head and may affect the periocular skin. The
herpetic dermatitis typically but not always
most common histopathological feature is dif-
involves facial skin and is both proliferative and
fuse granulomatous inflammation with mac-
ulcerative with papules, crusts, and ulcers.
rophages that contain Leishmania amastigotes.
Concurrent or preceding upper respiratory or
The most frequently used treatment regimen is
ocular signs can be noted. Skin biopsy is critical
either long-­term oral administration of allopu-
for diagnosis and will reveal a markedly
rinol (10 mg/kg q 12 h or 20 mg/kg q 24 h) as
destructive eosinophilic furunculosis. The like-
monotherapy or allopurinol as maintenance
lihood of an etiological diagnosis will be
treatment after a course of subcutaneous injec-
improved if the pathologist is provided with the
tions of meglumine antimoniate.
clinical suspicion and directed to look for
pathognomonic intranuclear inclusion bodies.
Failing that, polymerase chain reaction (PCR) Bacterial Blepharitis
assessment of fresh or paraffin-­embedded
Bacterial infections occur most commonly as a
biopsy samples for the presence of FHV-­1 DNA
consequence of cat fight injuries. Pasteurella
is very helpful. Unlike ocular disease, where
multocida is the most common organism cul-
the high rate of viral shedding seen in normal
tured from cat bite wounds. Other isolates
cats dramatically reduces the diagnostic utility
include Staphylococcus pseudintermedius, β-­
of PCR, FHV-­1 PCR appears to be extremely
hemolytic Streptococcus, and various anaero-
useful for herpetic dermatitis. Treatment can
bic species. The treatment of choice for a
be challenging; in fact, lack of response to
discrete abscess is surgical drainage, flushing
empirical therapy for dermatitis should encour-
the site thoroughly with sterile saline, bal-
age consideration of the diagnosis of herpetic
anced electrolyte solution, or dilute (1:50) pov-
dermatitis. Twice-­daily administration of fam-
idone–iodine solution.
ciclovir at 90 mg/kg per os is recommended for
Pyoderma and bacterial folliculitis are con-
control of herpetic dermatitis. Lower doses
sidered rare in cats and usually occur as a con-
appear less successful, and a protracted course
sequence of an underlying primary dermatosis,
may be necessary. Corticosteroids are contrain-
of which hypersensitivities are most common.
dicated. Recurrence seems common.
Periocular involvement occurs in roughly half
of cats with facial lesions. Diagnosis is based
on cytological examination of adhesive tape
Protozoal Blepharitis
preparations, with neutrophils and intracellu-
Five species within the genus Leishmania have lar bacterial cocci almost always present.
been identified in cats. Leishmania infantum is Cutaneous nodules are characteristic of
the predominant pathogen in the mycobacterial infections in cats including
Mediterranean Basin, Middle East, and China, feline tuberculosis, caused almost exclusively
but only Leishmania mexicana is established in by Mycobacterium microti or Mycobacterium
North America (specifically Texas). In addition bovis, and feline leprosy syndrome, attributed
to L. infantum, there are regionally endemic to various mycobacteria including
Leishmania species in South America. The dis- Mycobacterium lepraemurium. Single or multi-
ease is transmitted by phlebotomine sand flies. ple ulcerated or fistulated nodules have been
Tissue damage is due to granulomatous inflam- described on the face and in the eyelids of cats
mation and immune complex deposition. infected with M. lepraemurium. Diagnosis is
548 Feline Ophthalmology

based on detection of acid-­fast bacilli in smears Immunosuppressive therapy is usually contin-


from fine-­needle aspirates, crush preparations ued indefinitely at the lowest possible dosage
of biopsy specimens, or histological sections. needed to maintain disease remission.
Wide surgical excision of solitary nodules is
the treatment of choice, with pre-­ and postop-
Allergic Blepharitis
erative antimicrobial therapy using clofazi-
mine, combined with clarithromycin or Localized and regional erythema, edema, and
rifampin. Treatment must be continued for pain can develop rapidly following stings by
several months or at least two months beyond bees, wasps, and other hymenopteran insects.
lesion resolution. The majority of insect stings are self-­limiting
events that resolve in a few hours without
treatment. Conservative therapy consists of
Immune-­Mediated Blepharitis
systemic antihistamines, cold compresses, and
Of the various generalized autoimmune derma- occasionally topical corticosteroid ointment.
toses that may involve the eyelids, pemphigus Patients should be monitored in the early
foliaceus is most common in the cat (Figure 14.6). stages for progressive signs suggestive of ana-
The disorder develops at any age and often pre- phylaxis. Facial and periocular edema devel-
sents with bilaterally symmetrical focal crusting oped in 5.7% of cats following vaccination.
lesions on the head, face, and ears, with periocu- Young adult cats that received multiple vac-
lar involvement. Lesions often appear first in the cines per visit are at greatest risk.
preauricular skin, accompanied by changes Although acute hypersensitivity to a topi-
across the bridge of the nose and nasal planum. cal medication can produce immediate, tran-
Claw folds are also commonly affected as the sient conjunctival and eyelid swelling, the
disease progresses. Diagnosis is based on disorder is more often a delayed lymphocyte-­
­histopathology. Prognosis is favorable when mediated reaction, the result of repeated or
treated with triamcinolone, prednisolone, pred- prolonged drug application (Figure 14.7).
nisolone plus chlorambucil, or cyclosporine.

Figure 14.7 Blepharitis attributed to adverse drug


Figure 14.6 Pemphigus erythematosus in an reaction. Repeated application of topical trifluridine
adult domestic longhair. Erythematous macular inflamed the eyelids and conjunctiva of this
dermatitis and excoriations affect the eyelids, nose, two-­year-­old DSH. The marginal depigmentation is
muzzle, and pinnae. a reliable feature of drug-­related blepharitis.
­Blephariti  549

The telltale eyelid abnormalities include Miscellaneous Blepharitis


marginal erythema, swelling, and depigmen-
Solar dermatitis is a consequence of chronic
tation, often exaggerating the meibomian
sun exposure occurring in white-­ or orange-­
gland orifices. A wider zone of periocular
faced cats. Lesions first appear on the margins
alopecia may develop. Conjunctivitis invari-
of the ear pinna, but the eyelids (particularly
ably accompanies the lid changes. Commonly
the lower lids) may also be affected. Erythema
implicated medications include neomycin,
and fine scaling are followed by skin peeling
gentamicin, tetracycline, trifluridine, atro-
and crusts, consistent with sunburn. The
pine, and dorzolamide. Blepharitis also
actinic dermatitis may be a precursor to squa-
occurs with topical cyclosporine, though the
mous cell carcinoma (SCC), since cancerous
reaction more likely reflects the type of oil
lesions appear at a younger age if preceded by
used to compound the product rather than
solar damage. Affected cats should be kept
the cyclosporine itself.
indoors from 11 a.m. to 2 p.m., when solar
Clinically, feline atopic dermatitis and food
intensity and ultraviolet exposure are greatest,
allergy appear to be indistinguishable. Young
and should not be allowed to sunbathe by open
cats appear predisposed to atopic dermatitis,
doors or windows. The potential for ocular irri-
with the majority showing clinical signs
tation limits the use of periocular topical
between 6 and 24 months of age. The mean age
sunscreens.
of onset of adverse food reactions was 3.5 years,
thought to reflect the prolonged sensitization
period before clinical signs develop. The
Lipogranulomatous Conjunctivitis
Siamese and its crosses may be predisposed to
food allergy. Signs tend to be nonseasonal in Named for its characteristic conjunctival reac-
either hypersensitivity disorder. The most tion rather than its meibomian gland associa-
common and consistent clinical sign of both is tion (Figure 14.8), lipogranulomatous
pruritus, often localized to the face and neck. conjunctivitis is a distinctive inflammatory
Crusted, erythematous papules, self-­induced ­disorder concentrated within the palpebral
excoriations, and patchy alopecia often develop conjunctiva adjacent to the eyelid margin and
in the preauricular area and may extend into
the eyelids. Some cats also develop lesions of
the eosinophilic granuloma complex, espe-
cially eosinophilic plaques. Cytology of skin
scrapings revealed eosinophils, while histolog-
ical sections of affected skin contained eosino-
phils, mast cells, and plasma cells. In a
multicenter study of feline hypersensitivity
dermatoses, conjunctivitis occurred in 19% of
cats with non-­flea-­associated pruritic dermati-
tis. The only way to definitively diagnose food
allergy is through a food elimination trial.
Symptomatic treatment of pruritus with oral
or injectable glucocorticoids, cyclosporine,
antihistamines, or serotonin antagonists is
used in conjunction with allergen-­specific
Figure 14.8 Meibomitis is less conspicuous in
immunotherapy to manage feline atopy.
cats than dogs, appearing in this six-­month-­old
Avoidance of the offending food is required to Persian as a roughened lid margin, with caseous
effectively manage food hypersensitivity. material plugging the meibomian gland orifices.
550 Feline Ophthalmology

meibomian glands. It occurs in older cats, with responsive or severely affected patients, surgi-
a mean age of 11 years (range 6–16 years), and cal excision of the conjunctival nodules may be
in predominantly white or white-­faced cats or considered.
those with limited pigmentation of the eyelid
margins. Lesions occur unilaterally or bilater-
ally but are usually more extensive in the upper ­Eyelid Cysts and Nodules
eyelid. Increased tearing, mucoid discharge,
and blepharospasm are common presenting Apocrine hidrocystomas arise from modified
signs. Smooth, nonulcerated, cream-­or white-­ sweat glands (of Moll) within the skin near the
colored 2–3 mm conjunctival nodules are eyelid margin. These benign, cystic tumors
found adjacent to the eyelid margin, usually have also been referred to as cystadenomas.
numerous and closely packed but occasionally Persian cats represent over 80% of reported
coalescing into much larger nodules that cases, with rare instances in the Himalayan
extend the length of the lid. On rare occasion, and the domestic shorthair. Older cats are typi-
the nodules may distort the overlying eyelid cally affected, with reported cases ranging in
skin (Figure 14.9). Histological features age from 3 to 15 years, for a mean of 9.6 years.
include variably sized lipid lakes within the No sex predisposition is seen. Early lesions
submucosal connective tissue, surrounded by appear flat, but typical hidrocystomas are
macrophages, multinucleated giant cells, and raised, reddish-­brown to black cystic nodules
low numbers of plasma cells and lymphocytes, distributed in the skin along the eyelids, espe-
and periglandular fibrosis. cially around the medial canthus. Aspirates of
Lipogranulomatous conjunctivitis may the fluid help differentiate the cysts from mela-
respond to a combined oral regimen of doxycy- noma, with macrophages of variable reactivity,
cline and prednisolone. Doxycycline provides phagocytosis of black-­colored debris, and
an inherent anti-­inflammatory benefit as well numerous cholesterol clefts. The color of the
as a restorative effect on lipid quality within thick, cell-­poor fluid within the cyst lumen is
meibomian gland secretions. Warm com- attributed to hemosiderin and ceroid pigments.
presses may also be of benefit. In poorly Definitive diagnosis requires excisional biopsy

(a) (b)

Figure 14.9 Lipogranulomatous conjunctivitis. (a) Lipid-­laden macrophages and retained lipid secretions
create multifocal conjunctival nodules overlying the meibomian glands in this 12-­year-­old DSH. (b) Secretions
may also coalesce to create larger lobules that protrude beyond the lid margin, as in this 13-­year-­old DSH.
­Eyelid Neoplasi  551

and histopathology characterized by multiple SCC is the most common eyelid neoplasm of
cystic structures of various sizes expanding the the cat, occurring most frequently in older cats
dermis, with intraluminal hyaline to granular and in white cats (Figure 14.10). White cats of
material. any haircoat length have a 13 times greater risk
Treatment is determined by the number and of developing SCC than cats of other colors.
size of the lesions and their effect on eyelid The Siamese cat’s coloration reportedly
function. Small and random cysts may be mon- decreases its risk of SCC. Solar dermatitis often
itored without treatment. Individual cysts may precedes development of SCC and likely
be drained by fine-­needle aspirate, but recur- increases the odds of lower eyelid involve-
rence is common within a matter of weeks to ment. The tumor occurs at or adjacent to the
months. Surgical excision can be considered eyelid margin, appearing erythematous, either
for individual lesions, but new cysts may slightly raised or depressed, and commonly
appear subsequently in some cases. Following ulcerated, often with a crusted surface. Local
incision and drainage of the cyst, the residual invasion can be extensive, with orbital and
tissue can be treated cryosurgically using regional lymph node involvement, but metas-
either liquid nitrogen or nitrous oxide or pho- tasis is rare until late in the disease. Tumor
toablated using a 1450-­nm diode laser. recurrence is common. In one retrospective
Anecdotal reports suggest that 1% polidocanol study, seven of nine cats with SCC for which
is an effective alternative sclerosing agent for follow-­up was available were euthanized, with
cyst ablation. an average survival time of 7.4 months.
SCC is best managed by complete excision
with wide, 4–5 mm surgical margins. This
­Eyelid Neoplasia approach is most likely to be curative, but exci-
sion of larger lesions will require reconstructive
Eyelid tumors are less common in cats than techniques to maintain a functional eyelid – or
dogs but more likely to be malignant. may even dictate enucleation of a visual eye. A
Histologically malignant or potentially malig- variety of techniques have been described for
nant tumors accounted for 91% of the eyelid eyelid reconstruction or wound closure follow-
masses in one study. Cats older than 10 years of ing “en bloc” tumor excision in companion ani-
age are most frequently affected, but no sex or mals, including lip-­to-­lid subdermal plexus
breed predilections for eyelid neoplasms have flaps, local transposition flaps combined with
been identified (Table 14.1). third eyelid advancement, and others.

(a) (b) (c)

Figure 14.10 Squamous cell carcinoma. The most frequent eyelid neoplasm in cats can appear (a) erosive,
as in this localized lower eyelid lesion in a 12-­year-­old DSH; (b) multifocal, involving the medial canthus
and lower eyelid in an 11-­year-­old DSH; or (c) nodular, infiltrating the lower eyelid, conjunctiva and
nictitans in a 17-­year-­old DSH.
552 Feline Ophthalmology

Reports of nonsurgical options generally Intralesional chemotherapy has rarely been


refer to sites other than the eyelid, including reported in the cat, but electrochemotherapy is
the pinnae and nasal planum. Cryosurgery advocated to improve response of SCC to sys-
may be an option for superficial tumors. temic chemotherapeutic agents. Complete
Brachytherapy with radioactive gold-­198 seeds, tumor regression occurred in 21/26 (81%) cats
accelerated, hypofractionated electron beam (including 12 cats with periocular SCC) treated
radiation, and photodynamic therapy have with intravenous bleomycin and permeabiliz-
also been reported for treatment of eyelid SCC ing electric pulses delivered across the tumor
in cats with varying successes. Beta radiation by modified caliper electrodes.
using strontium-­90 can be used for superficial Basal cell carcinoma usually appears round
SCC lesions of 3 mm or less in depth. and well circumscribed, but its tendency to

Table 14.1 Frequency of feline eyelid tumors.

McLaughlin et al. McLaughlin et al.


(1993) Total No. (%) (1993) Total No. (%)
Newkirk and Martins and
Veterinary medical Purdue comparative Rohrbach (2009) Barros (2014)
Tumor type data programa oncology program Total No. (%) Total No. (%)

Squamous cell carcinoma 56 (65%) 13 (36%) 12 (28%) 14 (54%)


Mast cell tumor 3 (4%) 4 (11%) 11 (26%) 0
Hemangiosarcoma 2 (2%) 0 6 (14%) 6 (23%)
Carcinoma/ 5 (6%) 0 4 (9%) 0
adenocarcinoma
Apocrine hidrocystoma 0 1 (3%) 3 (7%) 0
Peripheral nerve sheath 0 0 3 (7%) 0
tumor
Lymphoma 0 4 (11%) 3 (7%) 0
Hemangioma 1 (1%) 0 1 (2%) 0
Melanoma 2 (2%) 3 (8%) 0 0
Fibrosarcoma 4 (5%) 3 (8%) 0 3 (12%)
Squamous papilloma 0 3 (8%) 0 0
Basal cell carcinoma 2 (2%) 0 0 1 (4%)
Basal cell epithelioma 0 2 (6%) 0 0
Sebaceous adenoma/ 3 (4%) 2 (6%) 0 1 (4%)
epithelioma
Histiocytic sarcoma 0 0 0 1 (4%)
Histiocytoma 0 1 (3%) 0 0
Neurofibroma 1 (1%) 0 0 0
Fibroma 2 (2%) 0 0 0
Trichoepithelioma 1 (1%) 0 0 0
Total benign 8 (10%) 9 (25%) 4 (9%) 2 (8%)
Total malignant 74 (90%) 27 (75%) 39 (91%) 24 (92%)
a
Four tumors reported as “undetermined” are omitted from the original data.
­Diseases of the Nasolacrimal Syste  553

ulcerate can make it difficult to clinically dis- This tumor is typically well differentiated,
tinguish from SCC. The tumor may also appear slow growing, and characterized histopatho-
melanotic, cystic, and alopecic. This carcinoma logically by immature fibroblasts inter-
is generally benign, with slow, indolent growth spersed among bundles of collagen. Wide
and very rare metastasis from nonocular sites. surgical excision is the treatment of choice,
Most are small and singular and can be suc- with prognosis correlated with the tumor’s
cessfully treated by surgical excision or cryo- mitotic index.
therapy. However, large expansive basal cell The feline eyelid appears particularly prone
tumors may require radical excision and to peripheral nerve sheath tumors.
reconstruction. Characterized as a low-­grade spindle cell
In the eyelid, mast cell tumors often appear tumor, it is locally infiltrative but unlikely to
as single, pink, hairless, slightly raised, and metastasize. Recurrence after excision occurs
sometimes ulcerated masses, near to but typi- in nearly all cases treated conservatively.
cally sparing the lid margin (Figure 14.11).
Appearance does vary in the lid as in other
cutaneous sites, ranging from clustered, ulcer- ­ iseases of the Nasolacrimal
D
ated masses to large subcutaneous tumors. The System
age of onset tends to be significantly younger
(6.5 years) than the average age of cats with all The NL drainage system consists of the upper
other types of tumors (11.7 years). One study and lower lacrimal puncta, the lacrimal canali-
suggests an increased susceptibility to cutane- culi, the lacrimal sac, and the NL ducts that
ous mast cell tumors in the Siamese, Burmese, terminate distally in the nasal cavity vestibule
Russian Blue, and Ragdoll breeds. Mast cell beneath the ventral concha. From its origin at
tumors generally have one of the more favora- the lacrimal sac, the cat’s NL duct descends
ble prognoses of the common eyelid neoplasms vertically toward the second premolar and
in the cat. there, at an angle of approximately 90°,
Eyelid fibrosarcomas in older cats (average changes to a horizontal course that parallels
age of onset 10.4 years) are generally solitary, the hard palate. In one area, the NL duct and
nodular, alopecic, and may be ulcerated. the canine tooth are separated by only a thin

(a) (b)

Figure 14.11 Mast cell tumors range from small, lightly pigmented, alopecic nodules adjacent to the lid
margin (a), seen in this five-­year-­old DSH, to extensive subcutaneous masses (b), involving the entire upper
eyelid in this eight-­year-­old DSH.
554 Feline Ophthalmology

alveolar socket, explaining why tooth extrac- or following loss of the sympathetic tone
tion in this area may be problematic. In brach- required to maintain its tonic retraction. Third
ycephalic cats, the upper canine teeth are eyelid protrusion is commonly seen in associa-
displaced dorsally, forcing the NL ducts to tion with painful ocular disease. Gross thicken-
adopt a V-­shaped course that adversely alters ing or swelling accompanying neoplasia or
tear drainage. inflammation may also increase third eyelid
NL disorders occur infrequently in cats and visibility.
are usually characterized by epiphora. The normal membrane sweeps diagonally
Epiphora due to NL disease must be differenti- across the cornea from its inferonasal location,
ated from excessive lacrimation secondary to refreshing the tear film and physically protect-
surface irritation or ocular pain. Congenitally ing the cornea. There is conflicting informa-
imperforate lacrimal puncta are rare and tion in the literature regarding movement of
involve the upper punctum more often than the third eyelid in cats. Some describe a mech-
the lower in the cats, as is dacryocystitis. anism for active protrusion effected by
In most cases, NL blockage is difficult, if abducens-­innervated striated muscle fibers
not impossible, to resolve. Irrigation of the from the levator palpebrae superioris and lat-
NL system produces only temporary improve- eral rectus muscles that attach to the
ment in most brachycephalic cats. The rare third eyelid.
congenitally imperforate punctum is cor-
rected by carefully excising the overlying
Horner’s Syndrome
mucus membrane, identified by the transient
bleb that forms when the system is flushed Horner’s syndrome results from the interrup-
through the opposite punctum. Restoration of tion of the efferent sympathetic nervous sys-
punctal patency in cases of symblepharon is tem to the eye anywhere along its three-­neuron
unlikely. Surgical conjunctivorhinostomy has pathway, from the hypothalamus and midbrain
been used with variable success to circumvent to the globe. First-­order Horner’s syndrome is
the obstructed system and divert tears into invariably associated with additional neuro-
the nasal cavity. logical deficits that may include ataxia, paresis,
postural deficits, altered mental status, and
involvement of other cranial nerves. Horner’s
­Diseases of the Third Eyelid syndrome can be the sole neurological abnor-
mality when either second-­or third-­order neu-
The third eyelid, also called the nictitating mem- rons are affected. In the cat, protrusion of the
brane, membrana nictitans, or haw, consists of a third eyelid and miosis are the most consistent
semilunar fold of conjunctiva supported by a features, with variable ptosis and enophthal-
T-­shaped piece of elastic cartilage curved to con- mos (Figure 14.12).
form to the shape of the underlying globe. Its Causes of Horner’s syndrome in the cat
serous gland surrounds the base of the cartilage include trauma (both exogenous and iatro-
and contributes to the cat’s aqueous tear film. genic), neoplasia, and inflammation (espe-
The epithelium overlying the third eyelid con- cially of the middle ear). Horner’s syndrome is
tains numerous goblet cells on the palpebral sur- a common complication following surgery for
face, while aggregates of lymphoid tissue are middle ear disease, especially ventral bulla
present on both the inner (bulbar) and outer osteotomy, occurring in 53% of cases in one
(palpebral) surfaces of the nictitans. study. Prognosis for spontaneous recovery is
The third eyelid is normally unobtrusive in generally favorable in cases of trauma, infec-
the cat, visible only with changes in position of tion, and inflammation, but not so in neoplas-
the globe, e.g., enophthalmos or exophthalmos, tic disease.
­Diseases of the Third Eyeli  555

Figure 14.13 Prolapse of the third eyelid gland in


Figure 14.12 Horner’s syndrome. Enophthalmos, a three-­year-­old Burmese. The gland in the
ptosis, third eyelid protrusion, and miosis opposite eye prolapsed four years later. Both were
characterize the sympathetic defect in this successfully corrected using a pocket technique.
six-­year-­old DLH with a mediastinal mass.

Idiopathic Third Eyelid Protrusion with reported success similar to that for
the dog.
Idiopathic third eyelid protrusion without
other ocular is known as “haws syndrome”;
the condition is always bilateral, of acute Neoplasia
onset, and without any age, breed, or sex pre-
Although third eyelid neoplasia is uncom-
dilection. Increased peristalsis, soft stools,
mon in cats, a variety of tumors have been
and/or diarrhea are present in some cats, sug-
described that affect either the surface tissues
gesting a more generalized sympathetic neu-
and substantia propria or the gland of the
ropathy or dysautonomia. Spontaneous
third eyelid. Differentials for third eyelid
resolution is likely but clinical signs may per-
masses include eosinophilic conjunctivitis,
sist for several weeks to even a few months.
epitheliotropic mastocytic conjunctivitis, and
adnexal cryptococcosis. Hemangiomas
involving the leading edge of the third eyelid,
Prolapsed Third Eyelid Gland
mast cell tumors, and SCCs have all been
Prolapse of the gland of the third eyelid is described in the third eyelid of cats.
uncommon in cats compared with dogs. The Lymphoma has also been reported to affect
Burmese breed predominates in reports of the conjunctiva and the third eyelid of cats,
this disorder, but it has also been documented often as a periocular manifestation of gener-
in the Persian and domestic shorthaired cat. alized disease. Compared to third eyelid gland
While glandular prolapse in dogs typically neoplasms in dogs, those in cats are more
occurs during the first one to two years of likely to metastasize, recur, and substantially
life, cats tend to be older at presentation shorten patient survival times. With the
(Figure 14.13). The gland should be surgi- exception of severe, irreparable trauma, the
cally repositioned in order to preserve its sub- only indication for third eyelid removal is
stantial contribution to the cat’s tear volume, advanced and invasive neoplasia.
556 Feline Ophthalmology

­Ocular Surface Disease C. felis or FHV-­1, with chlamydial conjuncti-


vitis being nonulcerative, seen in the absence
Ocular surface disease is common in cats. of keratitis, and more likely dominated by
Owing to the frequency with which bacterial chemosis than intense hyperemia. In con-
and viral pathogens have been documented in trast, herpetic conjunctivitis often has more
cats with conjunctivitis and corneal disease, it intense hyperemia than it does chemosis and
is prudent to consider feline surface disease can be ulcerative, especially in primary infec-
infectious until proven otherwise. Unlike the tions. There is often coincident keratitis.
dog, in which most surface infections are Other conjunctival pathogens include
linked with predisposing abnormalities of the Mycoplasma spp., feline calicivirus (FCV),
adnexa and tear film, several primary patho- and Bordetella bronchiseptica.
gens are implicated in diseases of the feline
conjunctiva and cornea. The most important Chlamydia felis
of these are C. felis, a conjunctival pathogen,
and FHV-­1, a causative agent of conjunctival Chlamydiae are obligate intracellular Gram-­
or corneal disease (or both). While initial clin- negative bacteria that demonstrate a predi-
ical signs reflect a direct cytopathic effect on lection for conjunctival epithelial cells. The
ocular surface epithelium, and less commonly most significant feline pathogen is C. felis.
and less severely pathology within the under- This organism also persistently infects res-
lying corneal stroma or conjunctival lamina piratory, gastrointestinal, and genitourinary
propria, long-­term consequences of these epithelial cells, a factor that likely accounts
infections may include altered surface anat- for the relapse of clinical signs following top-
omy, tear film deficiency and dysfunction, ical therapy.
persistent or recurrent immunological reac- Chlamydia felis infection occurs primarily
tions, altered corneal clarity, and diminished through close contact with other infected cats
tissue viability. and their ocular secretions, or less commonly
via aerosol transmission. The organism can
also be spread by contaminated fomites, but
­Conjunctival Disease survives only a few days at room temperature
and is inactivated by most disinfectants.
Conjunctivitis is arguably the most common Following exposure, infectious elementary
ocular complaint in cats. Feline conjunctivi- bodies attach to and enter epithelial cells, and
tis should be considered infectious until then differentiate into reticulate bodies that
proven otherwise. The most commonly undergo binary fission within a cytoplasmic
implicated primary pathogens are C. felis and vacuole or inclusion. Organisms mature into
FHV-­1; the latter is also capable of infecting elementary bodies, infecting adjacent conjunc-
the feline cornea. Based on the volume of tival epithelial cells following cell lysis.
experimental and clinical data substantiating Chlamydia felis also spreads via the blood-
the role of these two pathogens in feline ocu- stream to other tissues, including the tonsil,
lar surface disease, a practical clinical lung, liver, spleen, gastrointestinal tract, and
approach is to first eliminate keratitis, uvei- kidney. The incubation period is approximately
tis, or glaucoma as the primary diagnosis, 3–5 days following experimental infection, but
and then to rule out less common causes of clinical signs may take 5–14 days to appear fol-
conjunctivitis in cats, such as foreign body, lowing natural infection.
neoplasia, eyelid or cilia disorders, tear film Infection with C. felis is more common in
dysfunction, or allergy. Conjunctivitis can young cats, especially those 2–12 months of
then be considered most likely caused by age. Although maternal antibody is thought to
­Conjunctival Diseas  557

protect most kittens less than 12 weeks of age, alternate between active and quiescent
they may be infected by the queen at birth phases, or resolve completely. It is unclear
based on occasional isolation of C. felis from whether chronic conjunctivitis is the result of
cats with neonatal conjunctivitis. Clinically reinfection from infected in-­contact cats or
normal cats with high Chlamydiae-­specific recrudescence stemming from persistence of
antibody titers can shed and transmit the organism in nonocular tissues. Treatment
Chlamydiae. Cats older than five years of age of the affected as well as all in-­contact cats
are less likely to be infected with C. felis. would therefore appear to be the most suc-
Clinical signs of acute chlamydial infection cessful approach to managing feline
often develop unilaterally, and then appear in chlamydiosis.
the second eye a few days later. Characteristics A variety of diagnostic tests have been used
include blepharospasm, serous ocular dis- to confirm infection with C. felis, each with
charge, and chemosis, the latter often masking limitations. Basophilic intracytoplasmic
the intensity of concurrent conjunctival hyper- inclusions, often located adjacent to the
emia (Figure 14.14). The discharge may nucleus, may be identified by light micros-
become purulent with chronicity or coinfec- copy in conjunctival scrapings collected two
tion by opportunistic resident flora. to nine days after onset of clinical signs; how-
Conjunctival follicle formation has been ever, this method is relatively insensitive due
described, but lymphoid hyperplasia is more to the transient nature of the inclusions and
likely a nonspecific sign of chronic antigenic the improbability of finding inclusions in
stimulation rather than a reliable indicator of chronically infected cats. If available, direct
C. felis infection. Upper respiratory signs are fluorescent antibody or immunocytochemi-
mild to absent. cal stains may increase sensitivity and speci-
Following initial infection, signs usually ficity of this method. Assays utilizing the
regress spontaneously within two to six PCR are the preferred method for confirming
weeks, and may improve more rapidly in active chlamydial infection. Chlamydial DNA
older cats than kittens. Conjunctivitis may can be detected in conjunctival swabs, scrap-
persist in milder form for many months, ings, or biopsies, although no significant

(a) (b)

Figure 14.14 PCR-­positive Chlamydia felis conjunctivitis in a six-­year-­old DSH. (a) Initial presentation with
conjunctival hyperemia and chemosis. (b) Following a 30-­day regimen of oral doxycycline.
558 Feline Ophthalmology

difference was found in the C. felis detection not eliminate infection. Therefore, these for-
rate between samples collected from the oro- mulations are probably best used in conjunc-
pharynx, conjunctiva, nose, or tongue of cats tion with systemic therapy to promote
with upper respiratory disease. Vigorous therapeutic drug concentrations at the ocular
swabbing is recommended to ensure ade- surface, control secondary infections not sus-
quate numbers of epithelial cells are col- ceptible to doxycycline, and lubricate the
lected. Since healthy cats can be PCR-­positive inflamed tissues. Other common topical anti-
on occasion, results must always be inter- bacterial agents such as gentamicin, triple
preted in light of the patient’s history and antibiotic, chloramphenicol, and fusidic acid
clinical signs. Other diagnostic methods such are ineffective against C. felis.
as ELISA to detect chlamydial antigen in con- Maternal antibodies usually protect kittens
junctival swabs or serology to detect circulat- from infection by C. felis until seven to nine
ing chlamydial antibodies are considered weeks of age. Natural infection confers little
inferior to PCR or culture as diagnostic tools. protection against reinfection, although there
When limitations of all available tests are may be an age-­related resistance based on the
considered, some simply rely on clinical signs lower prevalence of chlamydiosis in older
and response to therapy as a means of cats. Both inactivated and attenuated live
diagnosis. chlamydial vaccines may reduce the severity
Systemically administered doxycycline is the of clinical signs by decreasing C. felis replica-
drug of choice for feline chlamydial infections, tion, but they do not completely prevent
producing rapid improvement in clinical signs infection or shedding of the organism after
and likely clearing the organism from ocular as challenge.
well as systemic sites. Both the hyclate and
monohydrate salts are effective. Kittens over
Mycoplasma felis
four weeks of age can be treated with doxycy-
cline without enamel discoloration. Oral Mycoplasma spp. have traditionally been con-
administration of doxycycline at 5–10 mg/kg q sidered causative agents of feline conjunctivitis,
12 h for three to four weeks results in clinical but their role as primary pathogens has been
resolution in most cats. Clinical signs diminish difficult to substantiate since they may also be
within 24–72 h of the start of treatment. Client found as apparently commensal organisms of
compliance may improve using a once-­daily the feline conjunctiva and upper respiratory
regimen of oral doxycycline (10 mg/kg q 24 h), tract. Mycoplasma felis and Mycoplasma gateae
but treatment must then be continued for at are the species most often mentioned in associa-
least 28 days to eliminate the organism. Since tion with feline conjunctivitis, but one study
some group-­housed cats require treatment for utilizing PCR also detected Maianthemum
as long as six to eight weeks to clear the infec- canadense, Mycoplasma cynos, Mycoplasma
tion, a general rule is to treat for a minimum of lipophilum, and Mycoplasma hyopharyngis in
three weeks and at least two weeks beyond affected cats. Clinical signs ascribed to infection
resolution of clinical signs. Oral pradofloxacin with Mycoplasma spp. are nonspecific and
suspension (5–7.5 mg/kg q 24 h for six weeks) include unilateral or bilateral conjunctivitis,
is an acceptable alternative in cats unable to accompanied by serous to mucopurulent dis-
tolerate doxycycline. charge, conjunctival hyperemia, and chemosis
Topical therapy is not recommended as a (Figure 14.15). In one experimental study, con-
sole route for treatment of cats with chlamydio- junctival hyperemia developed two to three
sis. Treatment with tetracycline or erythromy- days after inoculation and disappeared without
cin ointment two to four times daily for as long treatment within seven days. Papillary
as 60 days can improve clinical signs but will ­hypertrophy lends a velvety texture to the
­Conjunctival Diseas  559

(a) (b)

Figure 14.15 PCR-­positive Mycoplasma spp. conjunctivitis in a two-­year-­old DSH. (a) Initial presentation
with conjunctival hyperemia and chemosis. (b) Day 16 of an oral azithromycin regimen.

conjunctival surface. An adherent conjunctival Feline Calicivirus


pseudomembrane may be misinterpreted as a FCV is a nonenveloped RNA virus, wide-
thick white exudate. Corneal stromal ulcers spread in the feline population. Between
with neutrophilic cellular infiltrates and kerato- them, FCV and FHV-­1 are estimated to
malacia have been seen in association with account for up to 90% of upper respiratory
Mycoplasma spp. infection, but predisposing tract infections in domestic cats. Infection
factors such as coinfection with FHV-­1 are prob- occurs through direct contact of oral or nasal
ably required for mycoplasmal invasion of the secretions from infected animals with con-
cornea to occur. junctival, oral, or nasal mucosa. The orophar-
Although cytology of conjunctival scrapings ynx is the primary site of viral replication.
has been suggested as a diagnostic tool, Most cats shed virus for at least 30 days fol-
Mycoplasma spp. are not dependably visible by lowing infection, but some may become life-
light microscopy because of their small size. long carriers, infecting naïve cats through
When found, the organisms appear as multiple chronic intermittent shedding.
punctate, darkly staining coccoid inclusions Clinical findings depend on the virulence
within the cytoplasm of conjunctival epithelial of the FCV strain, the age of the affected cat,
cells. Culture of this commensal organism and elements of the animal’s husbandry.
does not necessarily substantiate its role in a Acute oral and upper respiratory disease
patient’s clinical disease. Although PCR assays occurs mainly in kittens following an incuba-
provide more rapid detection of Mycoplasma tion period of 2–10 days, with transient
spp., the clinical significance of positive results viremia occurring three to four days after
is still unclear. infection. The virus induces necrosis of epi-
Tetracyclines and fluoroquinolones are thelial cells, creating vesicles on the margin
active against most Mycoplasma spp. isolates. of the tongue that coalesce into geographic,
Treatment should be continued for at least two map-­shaped ulcers, considered the hallmark
weeks, although the optimal duration of ther- of FCV infection. These erosive or ulcerative
apy in systemic infections is unknown. lesions typically heal within two to three
560 Feline Ophthalmology

weeks. Mild upper respiratory disease with this aerobic Gram-­negative coccobacillus is
sneezing and serous nasal discharge accom- likely to cause only mild ocular discharge and
panies oral ulceration. Less common manifes- conjunctivitis.
tations of FCV include pneumonia, lameness This highly contagious organism is shed in
secondary to acute synovitis, and chronic oral and nasal secretions and also grows in natu-
stomatitis. ral water sources. Strains that infect dogs can be
Despite its ability to induce epithelial cell transmitted to cats, and vice versa. Once inhaled,
necrosis, FCV has been considered a rather the bacteria adhere to respiratory cilia and
inconsequential ocular pathogen, causing ocu- secrete toxins damaging to the underlying res-
lar discharge and only mild, if any, conjuncti- piratory epithelium. The incubation period
vitis in experimentally infected cats. More ranges from 2 to 10 days. Clinical signs vary in
significant ocular surface disease has been severity, but sneezing is a conspicuous feature of
described in recent reports, including moder- feline infection, in contrast to the paroxysmal
ate to severe erosive conjunctivitis and con- cough exhibited by dogs. Disease is usually con-
junctivitis sufficiently severe to obscure the fined to the upper respiratory tract, but fatal
corneal surface. bronchopneumonia does occur in kittens.
Detection of FCV is optimized using combi- Ocular signs consist of conjunctivitis accompa-
nations of quantitative reverse transcription nied by serous to mucopurulent ocular
PCR (RT-­qPCR) or by combining RT-­qPCR discharge.
with cell culture to confirm the presence of Bordetellosis is confirmed by aerobic bacte-
replicating virus. Calicivirus RNA can be rial culture and PCR assays performed on
detected in conjunctival and oral swabs, cuta- nasal and oropharyngeal swabs. Dacron or
neous scrapings, and blood by use of PCR. Since rayon swabs are preferred for culture, since
seroprevalence of FCV is high due to natural growth may be inhibited by cotton swabs.
infection and vaccination, ­evidence of FCV Positive PCR results can occur for at least
antibodies by virus neutralization or ELISA three weeks after intranasal vaccination.
does not reliably indicate infection. Serology is of limited value for diagnosis
Therapeutic options are limited. because of the high prevalence of antibodies
Contemporary topical and systemic antiviral in the feline population.
agents used to treat FHV-­1 inhibit DNA syn- Many infections are mild or self-­limiting.
thesis and are therefore ineffective against Systemic antibacterial treatment is usually
FCV, an RNA virus. reserved for kittens less than six to eight
All healthy cats should be vaccinated weeks of age, patients with respiratory dis-
against FCV. Modified live virus vaccines, ease lasting longer than 7–10 days, or those
particularly those administered intranasally, with signs of bronchopneumonia. Doxycycline
are preferred in shelters due to rapid serocon- is the antibiotic of choice, dosed at 5 mg/kg
version. While vaccination provides protec- orally every 12 h for 21 days. Specific treat-
tion against acute oral and upper respiratory ment of the conjunctivitis is not required,
tract diseases, it does not prevent cats from since the organism does not colonize the ocu-
becoming infected or from subsequently lar surface. Supportive care can be provided
shedding FCV. with a topical mucinomimetic such as sodium
hyaluronate. Routine vaccination against
B. bronchiseptica is not ­recommended in pet
Bordetella bronchiseptica
cats but should be considered in animals
Although B. bronchiseptica is considered an group-­housed in facilities with a record of
important cause of respiratory disease in cats, confirmed bordetellosis.
­Conjunctival Diseas  561

Eosinophilic Conjunctivitis Epitheliotropic


Eosinophilic conjunctivitis appears as an Mastocytic Conjunctivitis
autonomous clinical entity, without signs of Clinical signs of epitheliotropic mastocytic
the keratitis that shares its name – and likely conjunctivitis resemble those of eosinophilic
its etiopathogenesis. One or both eyes may be conjunctivitis, albeit in an uncommonly
affected in cats ranging in age from 1 to severe proliferative form, with conjunctival
15 years. The conjunctival surface often has a hyperemia, thickening, and mucoid ocular
distinctive velvety texture, with concurrent discharge. Third eyelid abnormalities feature
swelling and hyperemia that also extends to prominently, with either solitary nodules that
the third eyelid (Figure 14.16). Mucoid to expand the third eyelid or smaller, sometimes
mucopurulent discharge is common, as is ulcerated nodules proliferating within the
depigmentation, thickening, and erosion of third eyelid conjunctiva. Its proliferative char-
the lower eyelid margin and medial canthus. acter may be clinically misinterpreted as
Conjunctival scrapings are characterized by a SCC. Topical treatment with tacrolimus or
preponderance of eosinophils and mast cells. corticosteroid is effective in controlling clini-
Eosinophils, lymphocytes, plasma cells, mast cal signs, but some cats required long-­term
cells, and macrophages are seen histologically. therapy to prevent relapse.
The same type I and IV hypersensitivity reac-
tions proposed for eosinophilic keratitis could Parasitic Conjunctivitis
explain the cellular profile of eosinophilic con- Feline conjunctivitis has been associated with
junctivitis. Topical or systemic anti-­ the nematode Thelazia californiensis, particu-
inflammatory drugs resolve clinical signs in as larly in the western United States, while
little as three to six weeks, but most cats require Thelazia callipaeda is considered an emerg-
indefinite maintenance therapy to prevent ing pathogen in Europe. Fannia spp. flies
relapse, similar to that subsequently described serve as vectors of T. californiensis; T. calli-
in detail for eosinophilic keratitis. paeda is transmitted by the fruit fly Phortica
variegata. Transmission of the parasite occurs
when flies feed on lacrimal secretions, depos-
iting third-­stage larvae that develop into adult
worms within the conjunctival cul-­de-­sac.
Cases are often diagnosed in the late summer
and autumn when the fly vectors are most
active. Clinical signs include serous to puru-
lent discharge, blepharospasm, conjunctival
hyperemia, and chemosis, although an occa-
sional cat is asymptomatic. The threadlike,
motile whitish worms are physically removed
from the conjunctival cul-­de-­sac using
­forceps. Monthly administration of milbemy-
cin oxime has been suggested to prevent
reinfection.
Figure 14.16 Eosinophilic conjunctivitis in a The larvae of Cuterebra spp. may be
seven-­year-­old DSH with a three-­year history of deposited within the conjunctival tissue,
ocular disease. Generalized conjunctival thickening leading to severe inflammation. Treatment
and a suede-­like surface texture obscure the
consists of manual removal of the larva, fol-
underlying keratitis. A conjunctival scraping
contained eosinophils, lymphocytes, and plasma cells. lowed by application of a topical antibiotic
562 Feline Ophthalmology

coupled with a topical or systemic anti-­ presentations of the palpebral or third eyelid
inflammatory drug until the conjunctivitis conjunctiva with either B-­cell or T-­cell pre-
has resolved. dominance (Figure 14.18). A marked lobulated
thickening of the conjunctiva may be appreci-
ated. Prognosis is guarded since subsequent
­Conjunctival Neoplasia development of generalized disease is typical.

Melanoma
Vascular Tumors
Feline conjunctival melanoma is an invasive
tumor that may involve the bulbar and the pal- Conjunctival vascular tumors of endothelial
pebral conjunctiva as well as that of the third origin tend to be superficial exophytic masses,
eyelid (Figure 14.17). Most tumors are heavily red to reddish-­brown in color, and either
pigmented; only five amelanotic tumors have smooth or multilobulated in character.
been described. This tumor exhibits a slightly Hemangiomas or hemangiosarcomas may
higher metastatic risk (14% versus 10%) and a develop along the leading edge of the third
decidedly higher mortality rate (61% versus ­eyelid, the temporal bulbar conjunctiva, or
5%) than affected dogs. Prognosis is guarded to the inferior palpebral conjunctiva.
poor, but aggressive surgical intervention may Hemangiosarcomas tend to have a more
improve outcome. Enucleation or exenteration chronic course, existing 10.5 months prior to
are generally recommended. presentation versus 3.5 months for hemangio-
mas. Conjunctival vascular tumors have a
favorable prognosis. Treatment of choice is
Lymphoma ­surgical excision with adjunctive cryotherapy.
Feline conjunctival lymphoma is an uncom-
mon isolated tumor, but it has been reported Squamous Cell Carcinoma
with both bilateral and unilateral SCC is most likely to affect the palpebral con-
junctiva and third eyelid as a consequence of
eyelid tumor expansion. SCC has not been
reported as a primary conjunctival tumor in

Figure 14.17 Malignant melanoma of the


conjunctiva in an 11-­year-­old DSH. A darkly Figure 14.18 Conjunctival lymphoma was
pigmented third eyelid is accompanied by bulbar diagnosed in a nine-­year-­old DSH based on biopsy
and palpebral conjunctival pigmentation and of a mass that distended the superior palpebral
thickening. and bulbar conjunctiva.
­Keratoconjunctival Diseas  563

cats, with the exception of a single case report mucosal surfaces of cats. An estimated
of a 14-­year-­old domestic shorthair (DSH) in 75–97% of the world’s cat population is sero-
which SCC and hemangioma developed on the positive, and the virus is considered to be
cornea and conjunctiva without apparent eye- responsible for 45% of all upper respiratory
lid involvement. infections and the majority of corneal ulcers
in cats.
Viral replication occurs primarily within
Conjunctival
epithelium of the upper respiratory tract and
Surface Adenocarcinoma
eye, principally the conjunctiva, nasal turbi-
Adenocarcinoma of the conjunctival surface nates, and nasopharynx, with more limited
occurs in cats of various breeds with a mean of replication in corneal epithelium. Like species
10.7 years. The conjunctiva overlying the third specificity, tissue specificity is likely mediated
eyelid is the most frequent location, but tumor by virus–host cell surface receptor interac-
cells can also infiltrate the perilimbal cornea tions. Cell damage occurs through lysis or rup-
and third eyelid gland. Local recurrence is fre- ture of the cell membrane at the time of viral
quent; enucleation or exenteration may be release, a phase of infection called “produc-
required. tive” or “cytolytic,” causing erosion and ulcera-
tion of mucosal epithelium.
During acute replication within peripheral
­Keratoconjunctival Disease epithelial cells, some viral particles ascend
neural axons to the nucleus where they may
Although corneal and conjunctival disease can establish lifelong latency (Figure 14.19).
occur independently of each other, it is more Latency is defined as a state where virus can-
common, especially with inflammatory disor- not be cultured (i.e., nonproductive infection),
ders, to see coincident involvement of both tis- viral transcription is limited to only latency-­
sues (i.e., keratoconjunctivitis), albeit with one associated transcripts (LATs), and there is no
tissue sometimes more affected than the other. clinical disease. Viral DNA has been identified
As with conjunctivitis, feline keratoconjuncti- in the trigeminal ganglion, the autonomic gan-
vitis is typically infectious in nature, with the glia, optic nerve, olfactory bulb, vestibular gan-
most important primary corneal pathogen in glia, conjunctiva, and cornea.
cats being FHV-­1. While many other patho- Periodic reactivation of latent FHV-­1 occurs
gens worsen corneal ulceration, FHV-­1 is the after physiological stresses such as rehousing,
only organism known to initiate ulcers in cats. transport, parturition, and lactation, or follow-
ing systemic administration of corticosteroids
or epinephrine. Indeed, corticosteroid admin-
Feline Herpesvirus Type 1
istration has been advocated as a method of
FHV-­1 is a DNA virus and member of the detecting carriers in endemic populations.
alphaherpesvirus subfamily of herpesviruses. Once reactivation occurs, the virus is believed
Typical of members of this subfamily, the to descend the same sensory nerve axons it
hallmark biological features of FHV-­1 are ascended during primary infection, and
“tight” host species specificity, rapid intracel- thereby reach the peripheral epithelial tissues
lular ­replication within epithelial cells, and again. Viral reactivation may occur in the
establishment of lifelong latency within neu- absence of clinical signs or with a diverse range
ral cells. Because of FHV-­1 short environmen- of recrudescent ocular, dermatological, or
tal survival, the major route of infection is via upper respiratory signs associated with recur-
direct transfer of virus-­containing macrodro- rence of cytolytic (productive) replication in
plets between oral, nasal, and conjunctival the mucosal epithelia.
564 Feline Ophthalmology

(a)

(b) (c)

Figure 14.19 A common sequela of neonatal FHV-­1 infection, symblepharon can restrict eyelid mobility,
obliterate the conjunctival cul-­de-­sac, limit tear drainage, and impact corneal clarity and vision. (a) This
young Maine Coon illustrates a reduced palpebral fissure and gross corneal opacity OS. (b) The temporal
limbus is obscured in a young DSH, with an accompanying inclusion cyst and focal sequestrum. (c) Diffuse
corneal adhesions hide intraocular detail in this four-­month-­old DSH.

In addition to the latent and cytolytic phases Finally, there is a growing appreciation that
of the FHV-­1 life cycle, a “persistent” state is FHV-­1 may cause disease through an addi-
also proposed. Persistency mimics some aspects tional mechanism – so-­called metaherpetic
of latency, especially the inability to culture via- disease. Metaherpetic disease arises from per-
ble (virulent) virus. However, persistent virus is manent or semipermanent anatomical
distinct from latent virus because (i) genes in changes as a result of cytolytic and/or immu-
addition to LATs are expressed and (ii) it is asso- nopathological disease. Some examples of
ciated with (and likely induces) a chronic, often suggested metaherpetic disease include (i)
low-­grade, inflammatory response. Persistency symblepharon following exposure of corneal
is the purported mechanism for chronic, typi- and/or conjunctival stroma due to ulcerative
cally nonulcerative, immunopathological dis- herpetic disease, (ii) chronic conjunctival gob-
eases such as herpetic stromal keratitis, let cell depletion and tear film dysfunction fol-
lymphocytic/plasmacytic conjunctivitis, and lowing apparent clinical recovery from
potentially eosinophilic keratoconjunctivitis, primary herpetic disease, (iii) neurogenic dry
herpetic dermatitis, and herpetic uveitis. eye as a result of corneal anesthesia secondary
­Keratoconjunctival Diseas  565

to herpetic injury to the trigeminal nerve, and episodes range widely among individuals and
(iv) band keratopathy or corneal sequestra as a even among disease episodes. Disease may
result of exposure and structural alteration of result from cytolytic, immunopathological, or
the anterior stroma following chronic herpetic metaherpetic mechanisms. Conjunctivitis is
corneal ulceration. usually milder and less ulcerative than seen in
There appears to be a real but relatively the acute infection. However, substantial con-
minor relationship between chronic herpetic junctival thickening and hyperemia can occur
diseases and coinfection with FeLV and secondary to inflammatory cell infiltration.
FIV. Cats with chronic FHV-­1 infection are Corneal infections may again involve epithe-
more likely to be infected with FeLV or FIV lial tissues, in which case dendritic and later
than normal cats. Coinfection rates of geographic corneal ulceration may be seen, as
FHV-­1 with other agents of upper respiratory in primary infections. Stromal keratitis may
disease such as FCV, C. felis, B. bronchiseptica, occur and is likely immunopathological, i.e.,
and Mycoplasma spp. range widely and the immune-­mediated but not necessarily auto-
likely clinical significance of coinfections is immune in origin. The events surrounding
not known. experimental FHV-­1 stromal keratitis are most
Clinical signs of infection with FHV-­1 vary compatible with a delayed type hypersensitiv-
greatly depending on the cat’s age, viral inocu- ity response (Th1 cell-­mediated, macrophage
lum, and immune status. Following primary effector cells).
infection of FHV-­1-­naïve kittens, there is A major paradox exists with respect to the
widespread and rapid viral replication in epi- diagnosis of FHV-­1. Cats experiencing pri-
thelium of nasal mucosa and conjunctiva, mary FHV-­1 infection shed virus in sufficient
marked upper respiratory and conjunctival quantities that viral detection is relatively
inflammation, fever, anorexia, and lethargy. easy. However, clinical signs during this phase
Morbidity is high but mortality is uncommon, of infection tend to be characteristic and self-­
especially with supportive care. Tissue dam- limiting, making definitive diagnosis less nec-
age is due to viral cytolysis with subsequent essary. In contrast, during the more chronic
ulceration of these mucosal surfaces, and FHV-­1-­associated syndromes, the diversity
sometimes symblepharon formation. In con- and ambiguity of clinical signs make viral
trast, FHV-­1 replicates to a more limited extent identification more desirable, especially if
in corneal epithelium; however, it can cause specific antiviral therapy is being considered.
ulceration, notably dendritic lesions. The However, the elusive nature of the virus in
cause of the branching pattern of these ulcers these chronic syndromes makes this difficult.
is unknown, but is considered to be pathogno- Indeed, the diagnosis of FHV-­1 in individual
monic for herpetic infections of all species. cats represents one of the greatest challenges
Dendritic corneal lesions occur in a biphasic in the management of chronic FHV-­1-­related
pattern on days 3 and 12 of primary infection, diseases. Although the specificity and extreme
the latter peak likely reflecting virus released sensitivity of PCR has improved detection of
from replication within and rupture of con- virus, it has also confirmed that virus can be
junctival epithelium. Little, if any, viral repli- demonstrated in a large minority of appar-
cation occurs within the corneal stroma. ently normal cats. Currently available tests
Primary disease is usually self-­limiting within rely on demonstration of an immunological
10–20 days. response (usually in serum) to the organism,
Recrudescent disease is seen in some or detection of whole, cultivable virus by
latently infected cats following periods of viral virus isolation (VI), its antigens by immuno-
reactivation. The severity of disease and the fluorescent antibody (IFA) test, or its
tissues involved in these recrudescent DNA by PCR.
566 Feline Ophthalmology

­Treatment Idoxuridine has been used as a 0.1% ophthal-


mic solution or 0.5% ophthalmic ointment.
Treatment of herpetic disease in cats inevitably This drug is reasonably well tolerated by most
involves the use of supportive care (e.g., topical cats and seems efficacious in many. It should
antibiotics if secondary infection or corneal be applied to the affected eye at least five to six
ulceration is present, artificial tears if lacrimal times daily.
insufficiency exists, etc.) but may also require Vidarabine is available as a 3% ophthalmic
antiviral therapy. In cytolytic disease, where ointment and may be better tolerated than
cell rupture occurs as a direct result of viral many of the other topical antiviral prepara-
replication, and virus can often be cultured tions but should be applied to the affected eye
from diseased tissue, antiviral drugs are rec- at least five to six times daily.
ommended and immunomodulatory therapy Trifluridine is too toxic to be administered
is generally contraindicated. In immunopatho- systemically, but topically administered triflu-
logical disease, where the host’s reaction to ridine is considered one of the most effective
viral antigens or altered autoantigens is drugs for treating HSV-­1 keratitis. This is in
believed to be the major cause of disease, virus part due to its superior corneal epithelial pen-
is less reliably isolated (but can sometimes still etration. This makes it the preferred topical
be detected by PCR), and ulceration is less agent from stromal keratitis (although the sys-
common. Here, antiviral drugs are typically temic agent – famciclovir – may be even more
ineffective when used alone, and concurrent effective). A 1% ophthalmic solution is used in
immunomodulatory therapy is often required. human herpetic keratitis at least five to six
However, if used without the “backdrop” of an times daily. Unfortunately, it often causes
antiviral agent, immunomodulatory therapy marked ocular irritation in cats.
may encourage cytolytic disease. With meta- Cidofovir dissolved in artificial tears to form
herpetic disease, antiviral or immunomodula- a 0.5% or 1.0% solution and applied is equally
tory therapies alone or together are typically effective when administered only twice daily
ineffective, and therapy specific to the anatom- as trifluridine administered four to nine times
ical and/or physiological disruption is required. daily. This is believed to be due to the long tis-
sue half-­lives of the metabolites of this drug.
The efficacy of a 0.5% solution compounded in
Antiviral Therapy
methylcellulose artificial tears and applied
Although opinions vary as to when and why topically twice daily to cats experimentally
antiviral therapy should be instituted in cats infected with FHV-­1 was associated with
believed to be experiencing herpetic diseases, reduced viral shedding and clinical disease.
it appears reasonable that antiviral agents Acyclovir has poor bioavailability and is
should be considered when signs are severe, potentially toxic when systemically adminis-
persistent, or recurrent, particularly when tered to cats. With the advent of the apparently
there is corneal involvement, and especially safer and more effective famciclovir, systemic
ulceration. Because epithelial replication, administration of acyclovir seems difficult to
latency and reactivation, and persistence are justify. However, acyclovir is available in some
such interdependent and sequential phases of countries as an ophthalmic ointment that
herpetic disease, interruption of any one of reduces systemic toxicity concerns but not nec-
them is expected to limit the virus’ abilities to essarily questions of antiviral efficacy against
cause subsequent disease. Therefore, aggres- FHV-­1. Regardless, a 0.5% ointment used five
sive treatment of FHV-­1-­associated disease times daily in naturally infected cats was asso-
may limit disease progression and minimize ciated with a median time to resolution of clin-
frequency and severity of recurrences. ical signs of 10 days.
­Treatmen  567

Valacyclovir is a prodrug of acyclovir and that predisposes to the adhesions is most often a
should never be administered to cats. consequence of neonatal herpetic keratocon-
Famciclovir is a highly bioavailable prodrug junctivitis, but symblepharon could follow any
of penciclovir that is effective against FHV-­1 severe conjunctivitis that effaces the epithelial
in vitro. While some debate continues regard- surface, including chemical or thermal burns.
ing the optimum dose of famciclovir in cats, Clinical signs are determined by the severity
90 mg famciclovir/kg twice daily has been and location of the symblepharon and range
shown to achieve adequate plasma levels and a from subtle alterations in depth of the conjunc-
reduction in clinical signs. tival cul-­de-­sac to blinding corneal opacifica-
tion. Common signs include a reduced palpebral
fissure, a prominent third eyelid, and epiphora
Lysine Therapy
due to NL punctal occlusion. The conjunctival
Lysine’s antiviral effect is believed to arise vessels that overlie the corneal surface may be
because arginine is an essential amino acid for misinterpreted as a refractory keratitis, since
FHV-­1 replication, and assumes that lysine conventional therapy will not alter these perma-
antagonizes arginine availability to or utiliza- nently transposed vessels. Symblepharon is not
tion by these viruses during protein synthesis. painful, once the causative inflammation
Studies suggest that lysine is safe when orally resolves.
administered to cats and, provided that it is Symblepharon is easier to prevent than to
administered as a bolus (250 mg [kittens] or treat. Early recognition and appropriate treat-
500 mg [adult cats] once or twice daily), may ment of neonatal conjunctivitis are essential. In
reduce viral shedding in latently infected cats cases of acute conjunctival damage, the raw
and clinical signs in cats undergoing primary surfaces must be separated until re-­
exposure to the virus. However, improvement epithelialization occurs. Soft contact lenses and
in clinical signs or their duration is unpredict- methyl methacrylate conformers have been
able and study results vary. used for that purpose following chemical injury
in people. Otherwise, the opposing tissues must
be pried apart, sometimes several times daily,
Interferons
using a sterile cotton swab or forceps inserted
The interferons (IFNs) are a group of cytokines between the topically anesthetized layers.
that have diverse immunological and antiviral Surgical treatment of chronic symblepharon is
functions. The IFNs are divided into four usually reserved for patients with impaired
groups; α, β, γ, and ω IFNs, and numerous sub- vision or altered eyelid function, since success
types. Viral infection stimulates cells to secrete of surgery is often disappointing.
IFN into the extracellular space where it binds
to specific receptors on neighboring cells and,
through mechanisms not fully understood,
Eosinophilic Keratitis/Proliferative
prevents or limits the spread of infection (i.e.,
Keratoconjunctivitis
it is not virucidal). The few peer-­reviewed
in vivo studies do not lend strong support to Eosinophilic keratitis is a gradually progres-
use of these drugs. sive, infiltrative disease that derives its name
from the eosinophils found in cytological and
histopathological samples of the affected cor-
Symblepharon
nea and adjacent conjunctiva. The age of
Adhesion of the palpebral, bulbar, and/or third affected cats ranges from 7 months to 17 years,
eyelid conjunctiva to itself or to the cornea is with a trend toward young adult males of
termed symblepharon. The epithelial ulceration 4–6 years of age (Figure 14.20).
568 Feline Ophthalmology

(a) (b) (c)

Figure 14.20 Eosinophilic keratitis. (a) Raised white plaques and vascularization in the temporal cornea of
a two-­year-­old DSH. (b) Distinctive temporal plaque formation with mild vascularization in a six-­year-­old
DSH. (c) Generalized stromal infiltration with widespread yet indistinct surface plaques and prominent
vascularization in a two-­year-­old DSH.

The disorder is more often unilateral than although there is a suspected association with
bilateral, affecting only one eye approximately FHV-­1 infection based on positive IFA or PCR
75% of the time. The classical lesion appears assays. The presence of eosinophils in cytologi-
commonly in the dorsolateral cornea, but any cal specimens of cats with conjunctival and
and all corneal quadrants may be affected. corneal lesions also correlates highly with
Pinpoint cream-­colored nodules in the per- detection of FHV-­1 DNA.
ilimbal conjunctiva and subtle superficial vas- Eosinophilic keratoconjunctivitis is more
cularization in the adjacent cornea may be likely controllable rather than curable, based
overlooked at the onset. As the infiltrative pro- on a 65.5% recurrence rate once treatment is
cess progresses, an irregular pink to flesh-­ discontinued. Local immunosuppression
colored vascularized corneal mass develops, remains the mainstay of treatment.
bordered by a zone of corneal edema. Perhaps, Traditionally, topical corticosteroids such as
the most distinguishing feature of eosinophilic 1% prednisolone acetate or 0.1% dexametha-
keratitis are the raised, variably sized, friable sone are applied q 6–12 h in a gradually taper-
white plaques that develop atop the corneal ing regimen, dictated by clinical response.
infiltrate and adjacent bulbar conjunctiva, Treatment is recommended for several weeks
described as cheesy or cottage cheese-­like. beyond resolution of clinical signs. A low-­
Corneal ulcerations may be present as well. frequency maintenance regimen may be
Blepharospasm, ocular discharge, and con- required, e.g., application three times weekly,
junctival hyperemia are variable, usually should clinical signs relapse following cessa-
intensifying over time. The nictitating mem- tion of therapy. In cats with a history of cor-
brane may appear thickened. neal ulceration, documented FHV-­1 infection,
Diagnosis of eosinophilic keratitis is con- or concurrent ulceration, topical or systemic
firmed by cytological examination of superfi- antiviral therapy is a prudent addition to any
cial corneal scrapings. Smears often contain immunosuppressive regimen.
epithelial cells, eosinophils, mast cells, neutro- Other immunomodulatory or anti-­
phils, and lymphocytes, along with nuclear inflammatory drugs have also been used to
debris and eosinophilic granules from dis- manage eosinophilic keratoconjunctivitis.
rupted cells. Eosinophils may not be the pre- Topical cyclosporine of varying concentrations
dominant cell type, but a single eosinophil is has been used successfully either alone or in
considered diagnostic. The etiopathogenesis of combination with corticosteroids. Cyclosporine
eosinophilic keratoconjunctivitis is unknown, may be better suited for long-­term
­Corneal Diseas  569

maintenance once the keratoconjunctivitis has may occur secondary to diseases disrupting para-
been initially controlled with steroids. sympathetic innervation of the lacrimal glands,
Early reports of eosinophilic keratitis relied such as dysautonomia.
almost exclusively on oral megestrol acetate When neurogenic dry eye disease is sus-
to control clinical signs. This oral progestogen pected in cats, it appears, in addition to a very
should be used with caution, since its gluco- thorough clinical exam, as well as Schirmer
corticoid activity at high or prolonged doses tear test-­1 (STT-­1) and tear film break up time
can cause adrenocortical suppression and (TFBUT) measurements, that assessment of
impaired glucose metabolism leading to dia- corneal touch threshold and a stimulated STT
betes mellitus. Following an induction regi- (similar in intent to the originally described
men of 5 mg daily for five days, and then 5 mg STT-­3) may be useful. The goal of this revised
every other day for five doses, dosage is STT-­3 is to cause reflex tearing by stimulation
quickly tapered to the lowest level needed to of a nerve other than the trigeminal nerve
sustain clinical remission. Only 2.5–5 mg while a STT strip is in place in the conjunctival
megestrol acetate as infrequently as once fornix. One described way of doing this is to
monthly may prevent relapses once clinical place a cotton ball soaked in alcohol in front of
signs are controlled. A topical regimen of but not touching the cat’s nose for 1 min prior
megestrol acetate 0.5% applied q 8–12 h also to and during performance of an otherwise
appears to successfully control eosinophilic standard STT-­1. Cats with a functional lacri-
keratitis while limiting the risk of systemic mal gland and intact efferent sympathetic and
side effects. parasympathetic pathways, and therefore
capable of tear production and secretion but
lacking the normal trigeminal reflex to initiate
Dry Eye Disease Syndromes
or promote such tearing, have dramatic
Unlike dogs, tear film dysfunction and dry eye increases in their STT result in response to this
disease in cats is less commonly recognized, olfactory stimulation. It may be that the per-
remains very poorly understood, and seems to be centage increase in tearing that occurs in
associated with more subtle clinical signs and affected eyes is of more interest and poten-
often poorly responsive to therapies typically tially more diagnostic than is the absolute STT
effective in dogs. In dogs, dry eye disease carries result achieved. Given the permanent anatom-
with it strong connotations of aqueous tear film ical, likely metaherpetic, changes associated
deficiency consequent to immune-­mediated with tear film dysfunction in cats, therapy at
destruction of the lacrimal glands and typically present is extremely limited and largely
responsive to cyclosporine. In contrast, this focused upon tear film supplementation.
appears to be a very rare syndrome in cats. There is some evidence that hyaluronate will
Rather, those cases of dry eye disease in cats in not only increase tear film stability in the
which an etiopathogenic diagnosis is made short term but also cause/facilitate goblet cell
appear more likely to result from dysfunction of regeneration.
the meibomian glands, goblet cells, or trigeminal
nerve, and it appears that this dysfunction may
result from metaherpetic (anatomical/physiolog-
­Corneal Disease
ical postherpetic) damage. Of particular rele-
vance is a specific metaherpetic syndrome in
Normal Cornea
which virally induced damage to the trigeminal
nerve axons and their ganglion is believed to The feline cornea is almost circular in shape,
reduce corneal sensation and thus reduce reflex with a mean horizontal diameter of
tearing. Neurogenic keratoconjunctivitis sicca 16.5 ± 0.6 mm and a mean vertical diameter of
570 Feline Ophthalmology

16.2 ± 0.61 mm. Values reported for the adult


cat’s central corneal thickness range from
546 μm using ultrasonic pachymetry to 767 μm
measured histologically. Corneal curvature
also changes over the first 12–15 months of
life, decreasing from a steeply curved, astig-
matic state in the young kitten to a roughly
spherical shape with 39 D of refractive power
in the adult. Normal endothelial cell density in
cats ranges from 2668 ± 211 to 2846 ± 403 cells/
mm2. With age, endothelial cell density
decreases, while endothelial cell size and pleo-
morphism increase. The central cornea is less
sensitive in brachycephalic than domestic
shorthair cats and corneal subepithelial/sub-
basal nerve fiber densities measured in mm/
mm2 are higher in domestic cats compared to Figure 14.21 Mycoplasma spp. was cultured from
the axial cornea of this 16-­year-­old cat with
Persian cats and mesocephalic and brachyce- diffuse keratomalacia and corneal vascularization.
phalic dogs.
Other potential causes of ulceration include
Corneal Ulceration eyelid abnormalities, quantitative or qualita-
tive tear deficiencies, foreign bodies, neurolog-
Until proven otherwise, it is fair to assume a ical deficits that alter eyelid function or corneal
cat’s superficial corneal ulcer is a consequence sensitivity, and trauma. With perhaps the
of FHV-­1 infection. Poorly adherent epithelial exception of trauma, these precipitating fac-
margins are also common in herpetic ulcers. tors appear less frequently in cats than in dogs
The indolent-­type ulcer or SCCED of middle-­ A normal STT measures 14.3 ± 4.7 mm/min;
aged and older dogs, characterized by failure of TFBUT in young, healthy cats is 16.7 ± 4.5 s.
epithelial adherence to the underlying stroma, Surgical grafting may be indicated if an ulcer is
seldom, if ever, occurs in cats. Accordingly, rapidly progressing, if >66% of the corneal
keratotomies with a needle have little place in thickness has been lost, or when medical ther-
the management of feline ulceration and have apy fails to resolve the ulcer.
been implicated in sequestrum formation
when performed.
Fungal Keratitis
Management of stromal ulcers in cats is not
unlike that in dogs (see Chapter 9). Keep in Mycotic keratitis is rare in cats, although the
mind that herpetic ulcers involve loss of only presence of fungi in conjunctival swabs has
corneal epithelium. Stromal involvement been demonstrated in 40% of healthy cats. In
implies persistence of another inciting cause general, predisposing factors for fungal kerati-
or opportunistic infection by bacteria or fungi tis include tear film insufficiency, treatment of
that adhere to damaged tissue. Corneal “melt- corneal ulceration with topical antimicrobials
ing” occurs when an imbalance between and/or corticosteroids, exposure to environ-
endogenous matrix metalloproteinases, bacte- mental vegetative material, and the presence
rial proteolytic enzymes, and the proteinases of fungal organisms within the normal con-
present in the cornea and precorneal tear film junctival flora.
leads to destruction of corneal collagen Clinical signs often include unusually severe
(Figure 14.21). blepharospasm, with conjunctival hyperemia
­Corneal Diseas  571

and variable discharge. Corneal ulceration Rapid confirmation is based on cytological


may be accompanied by a raised, opaque sur- evidence of fungal hyphae in corneal scrap-
face plaque with irregular margins and multi- ings. The specific fungus is ideally identified by
focal satellite lesions of gray-­white stromal culture, but samples may require prolonged
infiltrates. A pigmented plaque suggests infec- incubation. PCR is an emerging option for
tion by dematiaceous fungi. Keratomalacia can faster and thus clinically relevant fungal iden-
lead to rapid stromal loss. Secondary corneal tification. Topical 1% voriconazole, 1% micona-
vascularization and anterior uveitis are com- zole, or silver sulfadiazine has been used
mon (Figure 14.22). successfully to treat fungal keratitis in the cat.

Florida Spots
A seemingly benign corneal disease referred to
as Florida spots or tropical keratopathy has
long been recognized in cats in the southeast-
ern United States, the Caribbean Basin, and
Brazil. The disorder is characterized by singu-
lar or multiple gray to white corneal opacities
located within the anterior stroma of one or
both eyes (Figure 14.23). The lesions are varia-
bly sized, from 1 to 8 mm in diameter, round to
irregular in shape, and often appear most
dense at their center. The cornea is otherwise
unremarkable, with no signs of vasculariza-
tion or inflammation, and the affected cats
Figure 14.22 Mycotic keratitis in a seven-­year-­old
show no discomfort. The cause of the keratop-
DSH with a raised, dull corneal plaque composed
of mats of fungal hyphae, masking the underlying athy is unknown; however, affected cats suffer
stromal ulcer. no discomfort or changes in visual behavior.

(a) (b)

Figure 14.23 Tropical keratopathy (Florida spots). (a) Multiple opacities in the cornea of a 5.5-­year-­old
DSH appear pale against the medial iris and dark against the tapetal reflection. (b) Multiple pale stromal
infiltrates with typically denser centers are present in the dorsal cornea of an otherwise asymptomatic
feline eye.
572 Feline Ophthalmology

Corneal Sequestrum stroma. Accompanying clinical signs include


blepharospasm, ocular discharge, and con-
A sequestrum is characterized histologically
junctival hyperemia. The corneal epithelium is
by stromal collagen degeneration and distin-
usually absent over and immediately sur-
guished clinically by discoloration of the
rounding the sequestrum, but uptake of fluo-
affected corneal stroma, its color progressing
rescein may be limited by the stromal necrosis
from subtle amber and bronze to jet black over
or may be difficult to visualize over the seques-
time. The unmistakable stromal discoloration
trum itself. Corneal vascularization varies
is seldom, if ever, seen in these other species
from mild to severe, with no clear relationship
(Figure 14.24). Corneal sequestration occurs in
to duration of the sequestrum.
cats of all ages, with the apparent exception of
Histopathologically, the epithelium overly-
neonates, and exhibits no gender predilection.
ing the sequestrum is usually absent and
Brachycephalic breeds appear predisposed to
poorly adherent at the lesion margins. The
sequestrum formation. Persian cats have the
sequestrum itself is characterized by coagula-
highest reported incidence, followed by
tion necrosis and lacks keratocytes, inflamma-
Siamese, Burmese, Himalayan, and domestic
tory cells, and blood vessels. Vascularization or
shorthair breeds.
granulation tissue commonly encompasses or
The clinical appearance of a corneal seques-
undermines the sequestrum.
trum is unmistakable. The lesion usually
The etiopathogenesis of sequestrum forma-
develops unilaterally. Bilateral lesions can
tion remains speculative, although some form
arise simultaneously or sequentially but tend
of chronic corneal insult is thought to initiate
to occur most often in Persians or other brach-
the process. Brachycephalic breed-­related
ycephalic breeds. An oval to circular pig-
adnexal abnormalities, including lagophthal-
mented lesion commonly develops in the
mos, entropion, and medial canthal trichiasis,
central or paracentral cornea, its color pro-
are repetitively linked with corneal sequestra-
gressing from translucent amber to darker
tion. Tear film abnormalities have also been
bronze, and then to an impervious jet black
described as potential initiators of sequestra
with chronicity. Depth of the lesion varies and
formation. Chemical cauterization has also
can extend from the superficial stroma to
been incriminated as an iatrogenic stimulus.
Descemet’s membrane. As the sequestrum
FHV-­1 is implicated as a factor in seques-
progresses and opacifies, lesion depth becomes
trum formation. Chronic corneal ulceration
increasingly difficult to determine without
precedes sequestration in some cats and FHV-­1
benefit of advanced imaging modalities such
DNA has been identified in experimentally
as ultrahigh-­resolution ultrasound. The lesion
induced and naturally occurring sequestra.
may appear raised above the surrounding cor-
Interestingly, the prevalence of FHV-­1 DNA is
nea as corneal epithelium migrates beneath
greater in sequestra from domestic breeds than
the sequestrum, separating it from the deeper

Figure 14.24 Corneal sequestrum.


(a) Early stromal bronzing associated
with a central corneal ulcer in an
adult Persian. (b) Temporal
sequestrum secondary to chronic
entropion in an eight-­year-­old DSH.

(a) (b)
­Corneal Diseas  573

in Persians or Himalayans, lending support to Acute Bullous Keratopathy


the fundamental role of conformation in
Acute bullous keratopathy (ABK) is a rare but
sequestrum formation in the brachycephalic
distinctive feline disorder characterized by
breeds of cat.
sudden onset of profound but relatively well-­
Treatment must address causative factors as
circumscribed corneal edema, with coalescing
well as the sequestrum itself. Because a super-
fluid bullae that disrupt and weaken the stro-
ficial sequestrum may eventually slough as
ma’s lamellar structure and dramatically alter
the corneal epithelium undermines the
corneal contour. Synonyms include eruptive
necrotic tissue, some clinicians advocate a
bullous keratopathy and acute corneal hydrops.
conservative medical approach that combines
The disorder tends to present unilaterally in
a topical prophylactic antibiotic, a topical
young adult cats; however, both eyes may be
hyaluronan-­based lubricant, and a topical or
involved concurrently or sequentially, and cats
oral antiviral if herpesvirus is suspected.
as old as 15 years of age have been affected.
Spontaneous healing is often a prolonged pro-
Nonspecific findings accompanying the
cess and less likely to occur with deep stromal
acute corneal change include excessive tear-
lesions. Definitive removal of the sequestrum
ing, blepharospasm, and conjunctival hypere-
is indicated in persistent or deep lesions, espe-
mia. The extremely edematous stromal bulla
cially as corneal inflammation progresses and
develops within hours and without warning.
pain increases. Lamellar keratectomy is the
The lesion may vary from only a few millime-
technique of choice for definitive surgical
ters in diameter to one that encompasses the
excision, removing the sequestrum in its
entire corneal surface (Figure 14.26). There is
entirety while preserving as much healthy cor-
typically a distinct junction between the lesion
nea as possible (Figure 14.25). Time to healing
and the normal cornea that surrounds it.
is significantly shorter following surgical
The underlying cause of ABK is unknown.
removal (3.8 weeks) than with medical ther-
Proposed etiologies include a defect of
apy alone (11.2 weeks). Recurrence may be
Descemet’s membrane and the adjacent
prevented using a conjunctival graft over the
endothelium, a primary or inherited stromal
keratectomy site.
dystrophy, or endothelial dysfunction.

(a) (b)

Figure 14.25 Corneal sequestrum of one-­year duration in a six-­year-­old DSH. (a) Preoperative appearance.
At surgery, the lesion extended to Descemet’s membrane. (b) Eight weeks after, deep lamellar keratectomy
and fresh lamellar corneal graft.
574 Feline Ophthalmology

(a) (b)

Figure 14.26 ABK characterized by a well-­defined protrusion of markedly edematous, structurally


compromised corneal stroma in (a) a three-­year-­old DSH and (b) a six-­year-­old DSH. Both cats were treated
successfully using a third eyelid flap.

Some instances of feline ABK have period, culminating in bullous keratopathy.


responded to medical treatment using topical Endothelial dystrophy also occurs in domes-
5% sodium chloride and/or antibacterials (oxy- tic shorthair cats, with stromal edema begin-
tetracycline, neomycin–polymyxin B–bacitra- ning in the central cornea at three to four
cin, and/or tobramycin) administered for weeks of age, progressing peripherally but
weeks to months. Smaller lesions are realisti- ultimately sparing the perilimbal cornea.
cally the only candidates for medical manage- Bullous keratopathy and epithelial thinning
ment alone. For more extensive lesions, are late complications. There is no specific
surgical options are generally grouped into treatment, although penetrating keratoplasty
those that provide tectonic support, including may be a viable alternative in cats.
conjunctival pedicle and corneal grafts, and Lipid keratopathy/degeneration is also rare
those that tamponade the bullous tissue, in the cat and almost always associated with
including nictitating membrane flaps and tar- prior damage to the cornea (Figure 14.27b).
sorrhaphies. Resolution of ABK occurred in Lipid and/or mineral deposition accompanies
90.5% of eyes treated with nictitating mem- corneal inflammation and vascularization.
brane flap. The infiltrate can develop without concurrent
systemic lipid abnormalities, but hyperlipi-
demia may modify the appearance and pro-
Corneal Dystrophies and Degenerations
gression of the keratopathy.
Corneal dystrophy is defined as a primary Corneal cloudiness is a common feature in
inherited, bilaterally symmetrical corneal dis- cats with lysosomal storage diseases, including
ease, unassociated with prior inflammation GM1 and GM2 gangliosidoses, α-­mannosidosis,
or systemic disease. The only reports of dys- and mucopolysaccharidoses I and VI. Each of
trophy in cats describe endothelial dysfunc- these recessively inherited inborn errors of
tion and secondary stromal edema metabolism is linked to a specific enzymatic
(Figure 14.27). A recessive mode of inherit- deficiency that causes accumulation of a
ance has been proposed in the Manx cat. The ­substrate – lipid, glycoprotein, or mucopoly-
disease inevitably progresses over a two-­year saccharide – within the lysosomes.
­Diseases of the Anterior Uve  575

(a) (b)

Figure 14.27 Corneal dystrophy/degeneration. (a) Presumed endothelial dystrophy in a three-­year-­old


DSH with bilateral progressive corneal edema beginning at four months of age. (b) Corneal degeneration
with lipid deposition and vascularization following corneal ulceration in a three-­year-­old Siberian cat.

Corneal Dermoids thereof. The overall lighter coloration may


reflect a greater proportion of pheomelanin to
Although the lateral canthus may be the most
eumelanin within the iris stroma. The colored
common location for feline ocular dermoids,
feline iris also lacks a pigmented cell layer in
corneal dermoids have been described in the
the anterior iris stroma typical of brown-­eyed
domestic shorthair and Birman breeds and lat-
dogs and has less pigmentation surrounding its
eral limbal dermoids have been seen in
iridal vessels. The serpentine character of the
Burmese and domestic shorthair cats. Lamellar
major arterial circle in the peripheral iris is also
keratectomy is the treatment of choice.
easily appreciated in these lightly colored eyes.
The cat’s vertically elliptical pupil is regu-
Corneal Neoplasia lated by two autonomically innervated antago-
nistic muscles. The iris sphincter is
Neoplasia of the feline cornea is rare. Expansion parasympathetically controlled via the oculo-
of a conjunctival, limbal, or intraocular tumor motor and short ciliary nerves. The cat has only
into the cornea is considered far more likely two short ciliary nerves that exit the ciliary gan-
than development of a primary neoplasm in this glion, the nasal nerve that innervates the
normally avascular tissue. Feline corneal tumors medial half of the sphincter and the malar
resulting from extension of ocular or periocular nerve that supplies the lateral half. A lesion
tumors include SCC, limbal melanoma, lym- affecting a single short ciliary nerve produces a
phoma, anterior uveal melanoma, and post-­ hemidilated pupil with a D-­or reverse-­D shape,
traumatic ocular sarcoma (Figure 14.28). determined by the nerve and the eye affected.

Developmental or Structural Disorders


­Diseases of the Anterior Uvea
Uveal Pigmentation in White and
The neonatal feline iris appears blue to blue-­ Siamese Cats
gray, developing its adult coloration around Blue-­eyed white cats lack pigment in their iris
eight weeks of age. The mature feline iris is and choroidal stroma due to absence of pig-
lightly colored, with a spectrum that includes mented cells normally derived from the embry-
blue, green, yellow, and gold, or combinations onic neural crest (Figure 14.29). Presumably, the
576 Feline Ophthalmology

(a) (b)

Figure 14.28 (a) A subconjunctival limbal melanocytoma extends into the deep cornea in a fan-­shaped
pattern. (b) The same eye following excision and repair using a full-­thickness scleral homograft. (Image
courtesy of Dr Caryn Plummer.)

Figure 14.29 Iris heterochromia in a white domestic shorthair cat. (Image courtesy of Dr Caryn Plummer.)

progenitor cells fail to migrate to the ocular tis- typically have visual deficits but are instead
sue, fail to differentiate into uveal pigment cells, prone to deafness. The prevalence of deafness
or fail to survive. The Siamese cat is also defi- is greater when blue eyes are bilateral than if
cient in ocular pigment, but its blue eyes are the unilateral. While white coat color is clearly a
result of defective pigment production. Pigment dominant trait, inheritance of blue eyes and
cells within the Siamese iris and choroid contain deafness is described as autosomal non-­
little to no pigment. Mendelian, with incomplete penetrance.
The presence of blue irides in cats is often Neuroanatomical abnormalities in the visual
linked with other functional abnormalities. pathways of blue-­eyed Siamese cats give rise to
The white (W) pigment gene in cats is autoso- crossed eyes (convergent strabismus or esotro-
mal dominant over color but distinct from albi- pia), nystagmus, and decreased stereopsis. Part
nism. Unlike dogs homozygous for the merle of the temporal retina that normally projects to
gene, homozygous blue-­eyed white cats do not the ipsilateral lateral geniculate nucleus (LGN)
­Diseases of the Anterior Uve  577

instead projects to the contralateral LGN. While independent, view of a few degrees of frontal
abnormal retinogeniculate pathways exist in vision. Surgical correction of the strabismus is
every Siamese cat, the degree of involvement neither indicated nor recommended. Nystagmus
varies. The abnormal contralateral projection may be more common than strabismus.
creates a mirror or inverted image of the nor-
mal representation. While this misalignment Congenital Iris Anomalies
would be expected to create substantial visual Persistent pupillary membranes (PPMs) are rel-
impairment in the Siamese, adjustments in the atively uncommon in cats when compared to
cortex reduce the behavioral impact of the mis- dogs. There is no apparent breed or sex predis-
directed projections. The cats either suppress a position. Normally, the pupillary membrane
portion of the input to the visual cortex (i.e., regresses during late fetal development and into
the Midwest cat) or rearrange the relay of the the immediate postnatal period. PPMs are ves-
abnormal projections in the visual cortex (i.e., tiges of this embryonic vascular network, origi-
the Boston cat). Most Siamese cats probably nating at the iris collarette, a region of the iris
possess a mixed pattern of cortical organiza- face midway between the pupillary margin and
tion that combines both mechanisms. peripheral iris base. The point of origin helps
Nevertheless, Siamese cats lack both binocular differentiate PPMs from postinflammatory
vision and stereoscopic depth perception and adhesions (synechia) that typically incorporate
are virtually blind in the nasal hemifield when the pupillary margin. PPMs are either confined
they view the world with only one eye. to the iris surface or extend from the iris face to
Esotropia or convergent strabismus may the posterior cornea or to the anterior lens cap-
accompany these neuroanatomical abnormali- sule where they produce nonprogressive opaci-
ties, developing during the third month of age ties at the attachment site (Figure 14.31). The
(Figure 14.30). Since the patterns of visual acti- residual strands are variably pigmented, thick
vation by each eye are independent and lack or thin, singular or multiple, and may even
binocular interaction in the visual cortex, there appear as a fiber web spanning the pupil. Thin,
is no advantage to normal ocular alignment. lightly pigmented iris face PPMs may continue
The convergent strabismus may in fact be ben- to regress in kittens up to three to four months
eficial, providing an overlapping, albeit of age but are permanent thereafter. Those

Figure 14.31 A network of PPMs originates at the


Figure 14.30 Esotropia in a feral DSH cat of iris collarette and spans the pupil in this
unknown age. adult DSH.
578 Feline Ophthalmology

PPMs with corneal or lens attachments do not glaucoma. Blue-­eyed cats may be more com-
regress. Treatment of PPMs is seldom indicated. monly affected. Iris atrophy may be focal or
Rare instances of anterior segment dysgene- diffuse, recognized by an irregular pupillary
sis have been described in cats, with broad margin, by distinct defects in the iris stroma, or
adherence of the iris to the posterior cornea. by thinning that simply permits visualization
Synonyms include anterior segment cleavage of the tapetal reflection through the stroma.
syndrome and Peters’ anomaly. The space nor-
mally representing the anterior chamber is Iris Cysts
narrowed or nonexistent. Notable corneal Acquired iris cysts are more common than
opacification is associated with segmental his- those that occur congenitally (Figure 14.33).
tological defects in Descemet’s membrane and The pigmented epithelium of the iris (or, less
the corneal endothelium, where the uveal and commonly, the ciliary body’s inner epithelium)
corneal tissues blend.
Iris colobomas are characterized by a notch-­
like defect in the pupil (Figure 14.32), most
often occurring in the ventromedial iris. The
iris defect may be full or partial thickness, the
latter not only altering the pupil shape but also
exposing the posterior pigmented layers of the
iris. Though rare in cats, iris colobomas may be
associated with other colobomatous defects of
the eyelid, choroid/sclera, and optic disc.

Acquired Iris Abnormalities


Iris Atrophy
Iris atrophy occurs in cats less frequently than
in dogs. The problem is generally one of older
Figure 14.32 The left pupil tilts along its vertical
cats, but iris thinning and loss of surface tex- axis and is offset nasally in this four-­month-­old
ture can also follow chronic uveitis or Burmese with bilateral corectopia.

(a) (b)

Figure 14.33 (a) A single darkly pigmented iris cyst remains attached within the posterior chamber. (b) A
shallow anterior chamber resulted from multiple, dark-­walled iris cysts within the posterior chamber, seen
only after pupillary dilation in this adult DSH.
­Anterior Uveiti  579

may undergo spontaneous cystic hyperplasia Hyperemia results from vasodilation of con-
in the absence of inflammation or other pre- junctival and episcleral vessels. Ciliary flush
disposing factors. Cysts are also a consistent refers to a rose-­red coloration of the perilimbal
finding in cats with a history of blunt ocular sclera that reflects dilation and congestion of
trauma. In contrast to canine iris cysts, those in the deeper uveal vasculature.
cats tend to be bilateral, multiple, elongate, or Corneal opacification results from edema
ovoid in shape, more darkly pigmented, and produced when toxins, inflammatory media-
seldom, if ever, free-­floating. Treatment is sel- tors, and cellular precipitates damage the
dom necessary. endothelium. Vessels may invade the deeper
corneal layers, while inflammatory cells (ker-
atic precipitates) often settle on the cornea’s
­Anterior Uveitis inner surface. As noted previously, conjuncti-
val hyperemia and corneal edema are typically
Inflammation of the iris and ciliary body, i.e., more subtle in cats compared to dogs with
anterior uveitis, is one of the most common anterior uveitis.
and significant ocular diseases in cats, with an
immediate impact on ocular function and 1) Breakdown of the blood–aqueous barrier
patient comfort. Uveitis can be a stand-­alone increases aqueous turbidity, elevating aque-
condition affecting the eye only, or can be part ous protein (flare) and permitting inflam-
of a more generalized systemic syndrome in matory cells and fibrin to enter the eye.
which the eye is one of several organs involved. Cells may settle on the corneal endothelial
In order to return the eye’s vascular tunic to surface, the anterior lens capsule, or diffuse
normal, the attending clinician is obligated to into the anterior vitreous. The fine surface
recognize the clinical signs of uveitis in timely texture of the iris disappears and its color
fashion and treat the uveal inflammation to its changes due to edema and cellular infil-
conclusive resolution. With few pathogno- trates. With chronicity, a preiridal fibrovas-
monic signs, documenting the cause of feline cular membrane may develop, creating fine
uveitis may be the most daunting task. Even vessels on the iris surface that may ulti-
with extensive diagnostics, a cause may not be mately extend over the iridocorneal angle
discovered in as many as 70% of cats with uvei- and compromise aqueous outflow.
tis, leaving only symptomatic therapy to com- 2) The iris reddening that accompanies these
bat the inflammation, without eliminating its new vessels, referred to as rubeosis iridis, is
underlying stimulus. Reduced but not resolved, easily observed in the lightly colored feline
the inflammation may ultimately lead to com- eye. The pupil is classically constricted and
plications such as glaucoma that compel the sluggish in its reactions owing to tissue
enucleation of a blind, painful eye. edema and stimulation of the iris sphincter
by inflammatory mediators, notably prosta-
glandins. Edema and cellular infiltrates
Clinical Features of Feline Uveitis
within the iris stroma may alter pupillary
The clinical signs of anterior uveitis are similar shape, but iris-­to-­lens adhesions (i.e., poste-
regardless of the species of animal or underly- rior synechiae) are more likely to distort the
ing cause. The most reliable indicators of pupil’s vertical ellipse as the uveitis persists.
intraocular inflammation are the presence of 3) Decreased IOP follows ciliary body dys-
aqueous flare, signaling breakdown of the function and reduced aqueous production.
blood–aqueous barrier, and decreased intraoc- Prostaglandins, one of several ocular
ular pressure (IOP), a consequence of ciliary inflammatory mediators, may also decrease
body dysfunction: IOP by enhancing aqueous outflow through
580 Feline Ophthalmology

the uveoscleral pathway. In subtle uveitis, Causes of Anterior Uveitis


IOP may be within the normal range
Feline Leukemia Virus
(approximately 10–20 mmHg) but notably
Cats infected with FeLV have a twofold greater
lower (>20%) than the normal eye.
risk of developing eye disease than nonin-
fected cats. However, FeLV causes no primary
Classification of Uveitis eye disease, metastatic lymphoma is the appar-
ent cause of anterior uveal infiltration seen in
Although many diseases are known to cause
FeLV-­positive cats, and retinal lesions observed
uveitis in the cat, idiopathic uveitis remains
in anemic FeLV-­infected cats are secondary to
the most common diagnosis in clinical practice
pancytopenia rather than a direct effect of the
and an etiological conclusion substantiated by
virus. Perhaps, the most clinically important
reviews of feline uveitis throughout the years.
consequence of FeLV infection is immunosup-
Other considerations include the principal
pression that predisposes to secondary infec-
part of the uveal tract involved, the duration of
tious disease and increases tumor risk by
the inflammation, and whether the problem is
altering inherent tumor surveillance mecha-
unilateral or bilateral.
nisms. Testing for FeLV should be performed
Cats with systemic disease are generally
in any cat with a new diagnosis of uveitis, even
younger, with a mean age of 7.6 years compared
if the cat has tested negative in the past
to 9.6 years for cats with idiopathic uveitis. Two-­
(Box 14.1).
thirds of cats with systemic disease have bilat-
The early stages of uveal lymphoma may
eral ocular involvement, while only half of cats
appear similar to any other uveitis, although
with idiopathic disease are bilaterally affected.
the iris generally appears increasingly

Systemic Evaluation
Box 14.1 Causes of Uveitis in Cats
A thorough physical examination should be Trauma Blunt trauma
performed to assess the cat’s general health and Penetrating wound
to direct subsequent testing. A minimum data- Infectious Feline immunodeficiency
base that includes a complete blood count virus
Feline infectious peritonitis
(CBC), serum biochemistry profile, urinalysis,
Feline leukemia virus
and serology for FeLV and FIV is indicated in Toxoplasma gondii
patients with systemic signs of illness, those Bartonella henselae
with bilateral endogenous uveitis characterized Cryptococcus neoformans
by cells and fibrin in the anterior chamber and/ Histoplasma capsulatum
Coccidioides immitis
or concurrent posterior segment inflammation,
and those with uveitis that fails to respond as Candida albicans
Neoplastic Diffuse iridal melanoma
expected to symptomatic therapy. Ultimately
Primary ocular sarcomas
thoracic and abdominal radiography, abdomi- Primary ciliary body
nal ultrasound, and aspirates of lymph nodes, adenomas and
masses, and draining tracts for cytological adenocarcinomas
examination may be performed. Serology to Metastatic uveal neoplasms
(mainly adenocarcinomas)
confirm or eliminate infectious disease is dic- Lens Cataract induced
tated by systemic signs of illness, abnormalities Lens luxations
in the minimum database, or likelihood of Miscellaneous Periarteritis
exposure based on geographical location, as Ophthalmomyiasis
with systemic mycoses. Aqueous cytopathology Idiopathic (chronic
lymphoplasmacytic)
is primarily useful in the diagnosis of lymphoma.
­Anterior Uveiti  581

thickened and irregular as the disease pro- result from direct viral damage or secondary
gresses. Lesions usually appear flesh-­colored opportunistic infections of the eye. Coinfection
and may have a velvety texture (Figure 14.34). with Toxoplasma gondii increases the possibil-
Dyscoria or anisocoria develops as neoplastic ity of ocular disease. While cellular infiltrates
infiltration restricts pupil mobility or as a con- in the anterior vitreous (i.e., pars planitis)
sequence of FeLV-­related neurological effects. occur often with FIV, other evidence of poste-
rior segment disease is infrequent. As with any
Feline Immunodeficiency Virus chronic uveitis, formation of posterior syne-
Infection with FIV causes chronic immuno- chiae, cortical cataracts, and secondary glau-
suppression in cats and in some cats a mild to coma are likely. FIV-­infected cats are about five
moderately severe, chronic uveitis times more likely to develop lymphoma or leu-
(Figure 14.35). The ocular inflammation may kemia than noninfected cats.

(a) (b)

Figure 14.34 (a) Mild rubeosis iridis with fine keratic precipitates and a small pigmented clot in a
10-­year-­old DSH seropositive for FeLV. (b) Ocular lymphoma with diffuse iris infiltration, rubeosis iridis, and
cellular exudation in a seven-­year-­old DSH seropositive for FeLV.

(a) (b)

Figure 14.35 (a) A fibrinous exudate obscures the severe rubeosis iridis that gives the eye its orange hue in
an 11-­month-­old DSH with FIP. (b) Perivascular cuffing of retinal vessels in a 10-­month-­old Persian with FIP.
582 Feline Ophthalmology

Feline Infectious Peritonitis inflammatory response, “mutton fat” keratic


Feline infectious peritonitis (FIP) is the result precipitates tend to occur. FIP may also cause a
of a mutation in the ubiquitous feline corona- pyogranulomatous chorioretinitis and retinal
virus (FCoV). About 12% of FCoV-­infected cats vasculitis with clinically evident perivascular
will develop FIP. The majority (about 70%) of cuffing, exudative retinal detachments, and
affected cats are less than one year of age. The optic neuritis. The intraocular inflammation
systemic disease is characterized by anorexia, often progresses to panuveitis or panophthal-
weight loss, fever refractory to antibiotics, and mitis, with diffuse and severe corneal edema,
variable peritoneal and thoracic effusions. The marked anterior uveitis, marked cellular infil-
prognosis for cats with FIP is generally grave. tration of the vitreous, chorioretinitis, and
Ocular manifestations are more common in inflammatory retinal detachments.
the noneffusive (“dry”) form of the disease, Antemortem diagnosis of FIP is challenging,
occurring in about 60% of affected cats without especially in the noneffusive form of the dis-
effusions but in only 9–29% of patients with ease. The presence of FCoV antibodies only
effusions. Clinical signs result from granuloma indicates that the cat is or has been infected
formation, immune complex deposition, and with a coronavirus, though not necessarily the
pyogranulomatous vasculitis (Figure 14.36). A mutated form responsible for FIP. Nevertheless,
mixed uveal inflammatory cell infiltrate made titers ≥1:3200 are highly suggestive of
up of neutrophils and mononuclear inflamma- FIP. Hyperproteinemia resulting from poly-
tory cells is seen histologically. Anterior uveitis clonal gammopathy occurs in approximately
and/or chorioretinitis may develop with or 50% of cats with effusive FIP and 70% of cats
without concurrent systemic signs. Ocular vas- with noneffusive FIP. The albumin/globulin
culitis leads to breakdown of the blood–aque- ratio has higher diagnostic value than protein
ous barrier and fibrin exudation into the or globulin concentrations alone and FIP is
anterior chamber from uveal blood vessels. considered highly unlikely at ratio values
Because of the granulomatous nature of the over 0.8.

(a) (b)

Figure 14.36 (a) Intraretinal and subretinal exudates appear as dark foci scattered throughout the tapetal
fundus in a 12-­year-­old DSH with a T. gondii IgM titer of 1:64. (b) Toxoplasmosis was diagnosed in a
four-­year-­old DSH with a rising serum IgM titer (to 1:16 384), rubeosis iridis, a fibrin clot, and multifocal
gray iris nodules of inflammatory cells.
­Anterior Uveiti  583

Treatment for FIP is traditionally frustrating Leishmaniasis


and ineffective and mortality is extremely Leishmaniasis is a vector-­borne zoonotic dis-
high. Supportive treatment is aimed at sup- ease classically associated with the
pressing the inflammation, usually with corti- Mediterranean region but now found in
costeroids, although there are no controlled Central and South America and parts of Africa
studies to prove benefit. Uveitis resulting from and Asia. Leishmania infantum is transmitted
FIP generally responds incompletely or poorly by phlebotomine sand flies and is the species
to anti-­inflammatory therapy, particularly most frequently reported in cats in the Old
when compared to idiopathic uveitis and that World and in Central and South America.
caused by the retroviruses. Clinical disease in cats is commonly associated
with impaired immunocompetence caused by
Toxoplasmosis FIV coinfection, immunosuppressive therapy,
The cat is the definitive host for T. gondii, an or concurrent diseases, including neoplasia
intracellular protozoan considered one of the and diabetes mellitus. Lymphadenopathy and
most common parasitic infections of animals nodular and/or ulcerative dermatitis are the
and humans. As carnivores, cats are probably most common clinical signs, occurring in 50%
infected during the first six months of life by of patients. Ocular abnormalities are reported
ingesting tissue of infected intermediate hosts in one-­third of affected cats. Unilateral or
containing bradyzoite-­laden cysts, or less com- bilateral uveitis is the most common ocu-
monly by contact with sporozoites in an envi- lar lesion.
ronment contaminated by fecal oocysts. Cats Diagnosis is based on serological detection
with systemic toxoplasmosis classically dem- of specific antibodies to Leishmania antigen,
onstrate chorioretinitis characterized by multi- with antibody levels ranging from low to very
focal hyporeflective lesions in the tapetal high in affected cats. Long-­term oral adminis-
fundus and fluffy white infiltrates in the nonta- tration of allopurinol as monotherapy or main-
petal region (Figure 14.37). Anterior uveitis tenance treatment after a course of
may be present as well. subcutaneous injections of meglumine anti-
moniate is the most frequent regimens
described, but controlled studies of efficacy
and safety have yet to be conducted in cats

Systemic Fungal Infections


The systemic mycotic agents include a group
of dimorphic fungi (H. capsulatum, B. dermati-
tidis, C. immitis) usually encountered in spe-
cific geographic regions. Infection occurs by
inhalation of infectious particles from the soil,
although direct cutaneous infection has been
reported with Coccidioides. Both histoplasmo-
sis and blastomycosis have been diagnosed in
indoor-­only cats. Failure of the host immune
system to contain the infection in the respira-
tory tract results in generalized dissemination
Figure 14.37 Leishmaniasis in a 21-­year-­old to other body organs via blood and lymphatics.
European shorthair with proliferative
Cryptococcus neoformans and C. gattii are sap-
keratoconjunctivitis that obscures intraocular
detail. Ultrasound revealed a concurrent retinal rophytic yeasts with a worldwide distribution.
detachment. Infection with this organism can occur by
584 Feline Ophthalmology

inhalation, with the nasal cavity as the primary by the presence of the organism within the eye
site of infection in cats, or by direct cutaneous rather than a nonspecific uveal response to sys-
inoculation (Figure 14.38). As a species, cats temic infection.
are very susceptible to infection with Systemic therapy with antifungal agents is
Histoplasma and Cryptococcus, less susceptible indicated. With severe posterior segment
to Blastomyces, and very resistant to infection inflammation, oral corticosteroids at anti-­
by Coccidioides. inflammatory doses may be indicated in con-
With regard to the eye, these disorders have junction with antifungal therapy. If an
in common the hematogenous dissemination affected eye has lost vision, it should be
from the primary respiratory site of infection removed since the organism may persist in
to the posterior uvea and the formation of a the eye evading the immune response and any
granulomatous chorioretinitis. In all systemic medical therapies becoming a persistent
mycoses, intraocular inflammation is caused nidus of infection.

(a) (b)

(c)

Figure 14.38 Mycotic uveitis. Panuveitis in a five-­year-­old DSH with cryptococcosis, with (a) keratic
precipitates anteriorly and (b) subretinal and choroidal granulomatous exudates obscuring the tapetal
reflection. (c) An unusually severe bilateral panuveitis in a three-­year-­old DSH with histoplasmosis.
­Anterior Uveiti  585

Bartonellosis ulcer, but unsealed full-­thickness lacerations


Bartonella spp. are Gram-­negative bacteria should be surgically repaired, as described in
that persist in erythrocytes and vascular Chapter 9. Aftercare combines a topical pro-
endothelial cells, with phylogenetic similari- phylactic antibacterial solution, judicious
ties to Rickettsiae and Brucella. Bartonella application of topical atropine to reverse con-
henselae and Bartonella clarridgeiae are the current miosis, and an oral steroid or short-­
most likely species to be isolated from cats, term systemic non-­steroidal anti-­inflammatory
although Bartonella koehlerae, Bartonella drug (NSAID) to reduce inflammation. Topical
quintana, and Bartonella bovis are reported to steroids or NSAIDs are less desirable in acute
cause natural infections. The organism is management of traumatic corneal wounds due
transmitted from cat to cat by fleas, is specifi- to altered tissue viability or unrealized sepsis,
cally harbored in flea excrement rather than but either anti-­inflammatory can be used fol-
saliva, and is inoculated through individual or lowing meticulous repair of surgical incisions.
communal grooming. Infection of cats occurs Cats appear to be particularly vulnerable to
worldwide, with highest seroprevalence in ocular injury associated with dental surgery.
warm humid climates in which the flea vector Scleral perforation and lens capsule rupture
thrives. Existing data indicate that few cats were histologically confirmed in two cats that
naturally infected with Bartonella have notable developed exudative uveitis following extrac-
clinical signs. tions of maxillary premolar and molar teeth.

Ophthalmomyiasis Idiopathic Uveitis


Ophthalmomyiasis is rare in cats. The condi- While idiopathic disease is fundamentally a
tion most commonly manifests as parasite diagnosis of exclusion, in reality the label is
migration in and beneath the sensory retina. commonly assigned to feline anterior uveitis,
Most affected cats are clinically asymptomatic with no inciting cause identified in up to 70%
and the telltale tracks of the migration are of cases. Histopathological examination of
often coincidental findings on fundus exami- affected eyes demonstrates lymphocytic–plas-
nation. Several reports describe uveitis associ- macytic inflammation within the iris and cili-
ated with intraocular Cuterebra larvae. Surgical ary body. Idiopathic uveitis may occur in one
extraction may prove helpful in eliminating or both eyes, but more often unilaterally. It
the inflammation. Prognosis for vision is tends take a chronic course with complications
dependent upon the damage done by the para- and sequelae such as cataract and secondary
site prior to its removal. glaucoma occurring commonly. Treatment of
uveitis is ideally tailored to each cat, taking
Traumatic Uveitis into consideration the cause of the uveitis, its
Uveitis is always initiated by tissue injury, dis- severity and duration, the portion of the uveal
rupting the blood–ocular barrier and causing tract affected, and the presence of other ocular
release of various chemical mediators that or systemic diseases.
drive the inflammatory response. Penetrating
or perforating corneal injuries are typically
Treatment of Anterior Uveitis
accompanied by some degree of uveitis, either
initiated as a reflex mediated by the trigeminal The mainstay of uveitis therapy is the corti-
nerve or driven by inflammatory mediators costeroid. With the exception of patients with
released upon entry of the claw, foreign body, corneal ulceration, topical corticosteroid
or scalpel blade into the anterior chamber. therapy should commence in all cases of uve-
Small, partial-­thickness lacerations may only itis while the cause of the inflammation is
require medical management, as for a corneal investigated. Numerous preparations are
586 Feline Ophthalmology

available for topical use but the preferred for- exhibit a relapse of clinical signs below a criti-
mulations are 1% prednisolone acetate sus- cal topical or systemic dose.
pension or 0.1% dexamethasone solution. Atropine (1%) is a parasympatholytic mydri-
Severe inflammation demands frequent topi- atic–cycloplegic agent that decreases ocular
cal application, starting as often as q 2 h and pain by reducing iris and ciliary muscle spasm.
tapering as clinical response is noted. Concurrent pupillary dilation discourages
Systemic corticosteroid administration is adhesions of iris to lens (posterior synechia)
generally contraindicated in systemic infec- that alter normal aqueous circulation and
tions but should be considered in patients mechanically compromise vision. The drug also
with severe uveitis or with concurrent cho- reduces vascular endothelial permeability and
roiditis once infectious disease has been stabilizes the blood–aqueous barrier. An oph-
excluded. The exception may be FIP in which thalmic ointment is recommended in cats to
systemic steroids are often used to palliate decrease the likelihood of copious salivation
the associated vasculitis. Some ophthalmolo- that occurs when the bitter drug is licked off the
gists advocate systemic corticosteroids com- nose following passage through the NL system.
bined with an antifungal regimen in patients As a general rule, therapy for uveitis should
with mycotic chorioretinitis. be initially aggressive, slowly tapering fre-
NSAIDs inhibit formation of prostaglandins quency of administration as clinical signs sub-
that act as potent inflammatory mediators side. Recurrences of inflammation following
within the eye, but they are not immunosup- cessation of treatment suggest the need for
pressive, making them less desirable for man- prolonged if not indefinite maintenance ther-
agement of uveitis in the majority of cats. In apy. Ongoing diligence regarding recurrences
the United States, meloxicam and robenacoxib of inflammation, elevations in IOP, and onset
are the only systemic NSAIDs licensed for use of systemic disease is essential in the manage-
in cats, labeled for control of postoperative ment of cats with uveitis.
pain associated with orthopedic surgery, ovari-
ohysterectomy, and castration. Meloxicam can
Anterior Uveal Neoplasia
be administered once perioperatively as a sub-
cutaneous injection, and robenacoxib can be Both primary and secondary uveal neoplasms
administered orally once daily as a flavored occur in cats, affecting the anterior uvea more
tablet for no more than three consecutive days. commonly than the choroid. In general,
In some parts of the world, however, meloxi- intraocular tumors occur most commonly in
cam is approved for indefinite use in cats for middle-­aged and older cats, with mean and
the alleviation of inflammation and pain asso- median ages of 10.6 and 11 years, respectively.
ciated with chronic musculoskeletal disorders, Melanocytic tumors are by far the most com-
dosed at 0.1 mg/kg on day 1, followed by mon type of intraocular neoplasia in cats.
0.05 mg/kg orally once daily. Early detection and timely intervention are
Abrupt cessation of anti-­inflammatory ther- crucial responses, owing to the locally invasive
apy, whether topical or systemic, may be asso- nature and metastatic potential of most feline
ciated with a “rebound” of inflammation. intraocular tumors.
Treatment should be continued for at least two
weeks beyond resolution of clinical signs.
Feline Diffuse Iris Melanoma
Determination of that endpoint should include
an objective assessment of IOP, since subtle Now considered the most common form of ante-
hypotony may be the only indication of active rior uveal melanoma in cats, feline diffuse iris
inflammation as treatment progresses. Cats melanoma (FDIM) usually develops in cats over
with chronic idiopathic uveitis are likely to nine years of age, though ages at
­Anterior Uveiti  587

histopathological diagnosis range from 2.8 to increases. Serial photography is recommended


23 years. Diffuse iris melanoma begins as focal to document these slow, modest changes. The
or multifocal areas of iris pigmentation that transformation to diffuse iris melanoma is
appear as flat brown spots within the lightly marked by infiltration of pigmented cells into
colored feline iris (Figure 14.39). This earliest the iris stroma, a histological determination that
benign stage is referred to as iris melanosis, may include a change in cell morphology from a
when pigment is strictly confined to the iris sur- small angular cell to a rounded cell with a
face. Rare amelanotic variants may be clinically rounded nucleus and prominent nucleolus.
misinterpreted as inflammatory disease. Over Changes in pupil shape and reactivity may result
months to years, the extent and intensity of the as the iris thickens. Progressive infiltration of the
pigmentation increases as individual spots iris, ciliary body, iridocorneal angle, and sclera
enlarge or the number of pigmented sites follows, often complicated by glaucoma.

(a) (b)

(c) (d)

Figure 14.39 (a) A flat area of pigmentation is interpreted as iris melanosis in an eight-­year-­old DSH. (b)
Multiple flat, pigmented foci are randomly scattered across the iris face in a nine-­year-­old DSH. (c) The dull
color and suede-­like texture of the iris pigmentation in a six-­year-­old DSH suggest a transformation to
melanoma. (d) Diffuse iris melanoma was confirmed histologically in a 10-­year-­old DSH with generalized
iris thickening, ectropion uveae, and subtle pigmented cells on the anterior lens surface.
588 Feline Ophthalmology

There is no reliable way to predict the pro- chronic uveitis, with an intervening latent
gression of disease in individual cats. In some, period that averages seven years. In addition to
the pigmented foci may remain static for the life obvious perforating lens trauma such as cat
of the cat or may expand over several years with claw injuries, increased risk of feline sarcoma
no effect on vision or health. Clinically, it seems is suspected in association with lens extrac-
that lesions progress more rapidly in younger tion, and following intravitreal gentamicin
cats, though that observation is yet to be cor- injection to chemically ablate the ciliary body
roborated in the literature. Rates of metastasis in cases of chronic glaucoma. It is unclear
range from 19% to 63%, the higher percentages whether the tumors are initiated by the thera-
likely biased by the advanced tumor stage at peutic procedures or stem from an earlier
which enucleation was performed in the early event that caused the lens abnormalities and/
studies. Metastasis occurs more often to the or glaucoma in the first place. Metastasis
liver than to the lungs, but lesions have also occurs primarily by extension into the orbit
been found in the kidneys, spleen, omentum, through the sclera at the limbus or posterior
diaphragm, pericardium, parietal pleura, hilar pole or along the optic nerve to the brain. If the
lymph nodes, and brain. Abdominal ultrasound owner is not committed to diligent monitoring,
should therefore be included when staging it is prudent to enucleate blind, traumatized
patients with diffuse iris melanoma. feline globes, particularly those with lens cap-
The clinical dilemma centers on the timing of sule rupture.
enucleation in patients suspected of FDIM. There
is as yet no definitive clinical means to deter-
Metastatic Uveal Neoplasia
mine when melanosis transforms into mela-
noma, since the fundamental infiltration of Lymphoma is the most frequent metastatic
pigmented cells into the iris stroma is only intraocular tumor and the second most com-
detectable histologically. Microsurgical surface mon intraocular neoplasm in cats
biopsy of pigmented foci can be safely per- (Figure 14.40). The age of affected animals
formed, with low risk of intraocular hemor- ranges from 9 months to 18 years, with a mean
rhage, but overall diagnostic benefit has not of 9 years. Iris infiltration may be nodular or
been established. The only clinically measurable diffuse. Perivascular infiltration by neoplastic
prognostic indicator described for FDIM has cells may contribute to a significant break-
been the presence of secondary glaucoma, a fea- down of the blood–aqueous barrier and the
ture of advanced disease that conveys a poor accompanying hypopyon, fibrin, and/or
prognosis and reduced survival time. hyphema within the anterior chamber.
Enucleation remains the treatment of choice Lymphoplasmacytic uveitis is seen in approxi-
for FDIM. Evisceration and intraocular pros- mately half of uveal lymphomas. Secondary
thesis are not advised in patients with sus- glaucoma develops owing to extensive cellular
pected FDIM. There are no controlled studies infiltration of the aqueous outflow pathway or,
documenting the ability of iridectomy, laser less commonly, to peripheral anterior syne-
ablation of discrete lesions, or melanoma vac- chiae. Aqueocentesis may be particularly use-
cine to arrest FDIM progression in cats. ful in the diagnosis of ocular lymphoma.

Feline Ocular Post-­traumatic Sarcoma


­Glaucoma
Feline ocular sarcomas are the second most
common primary intraocular tumor, after dif- Glaucoma in the cat is less common than in
fuse iris melanoma. These malignant tumors the dog, and most cases of feline glaucoma
are frequently preceded by ocular trauma or appear to be secondary. As with dogs, most cats
­Glaucom  589

(a) (b)

(c) (d)

Figure 14.40 (a) The right and (b) left eye of an FeLV-­negative six-­year-­old DSH with abdominal
lymphadenopathy and localized iris infiltration secondary to lymphosarcoma. (c) Diffuse iris infiltration and
a fibrinous exudate due to lymphosarcoma in a nine-­year-­old DSH. (d) A pale mass in the temporal iris is
accompanied by hyphema and fibrin in a 16-­year-­old Siamese with metastatic mammary adenocarcinoma.

with glaucoma are presented late in the dis- have been described in the Siamese, Persian
ease, and the initial events that induced the and European shorthair, and Burmese. In most
glaucoma may be masked by secondary cats with primary glaucoma, the iridocorneal
changes. It is likely that glaucoma in the cat is angle is open. However, a description exists of
underdiagnosed due to its insidious onset and a group of closely related Siamese with pri-
gradual progression. mary congenital glaucoma resulting from pec-
Congenital glaucomas may be either unilat- tinate ligament dysplasia. In an additional
eral or bilateral and occur because of develop- report, Burmese cats were reported to have
mental abnormalities of the aqueous humor narrow-­or closed-­angle glaucoma (Box 14.2).
outflow pathways (Figure 14.41). Primary Most cases of feline glaucoma are secondary
glaucoma has been reported but appears to be to either anterior uveitis or intraocular neopla-
much less common than secondary glaucoma sia. In two separate histopathological studies,
in the cat. Breed predispositions for glaucoma the majority of glaucoma cases occurred
590 Feline Ophthalmology

Figure 14.41 Bilateral congenital


glaucoma characterized by
buphthalmos and corneal edema in
a kitten.

Medical therapy to reduce aqueous humor


Box 14.2 Types of Glaucoma in the Cat
production or improve aqueous outflow has
Primary Open/normal angle, with and variable results in these cases. In many cats,
glaucomas without collapsed cleft
(Siamese) the progression of disease is relatively slow,
Narrow/closed angle (chronic) and topical medications such as timolol
Secondary Uveitic (chronic anterior maleate and dorzolamide maintain relatively
glaucomas uveitis) normal IOPs for prolonged periods. Surgical
Lens luxations (trauma/age)
pars plana vitrectomy or lensectomy and ante-
Phakolytic/phacoclastic
uveitis (lens perforation) rior vitrectomy in some cats have been success-
Hyphema (rare) ful in controlling IOP.
Intraocular neoplasia
(primary/secondary
neoplasms) Clinical Signs
Congenital Secondary to outflow
glaucomas anomalies The criteria for making a diagnosis of glau-
coma in the cat are the same as in other animal
species; however, clinical signs in the cat may
secondary to chronic, idiopathic, lymphocytic– be more subtle and therefore easily overlooked.
plasmacytic uveitis (Figure 14.42). Other Often, the clinical signs have been present for
causes were FIP, iridal melanoma, FeLV-­ extended periods of time and the eyes are
associated lymphosarcoma, trauma, and lens-­ already permanently blind. The most com-
induced uveitis. monly reported signs include cataract, corneal
Glaucoma due to aqueous humor misdirec- edema, mydriasis, buphthalmos, and blind-
tion, sometimes termed malignant glaucoma, ness. Buphthalmia, exposure keratitis with
has been described in the cat. The pathogene- vascularization, and lens luxation (usually
sis appears to be misdirection of the aqueous subluxation and anterior luxation) are com-
humor posteriorly into the vitreous humor mon sequelae to chronic intraocular hyperten-
through small breaks in the hyaloid near the sion. Buphthalmia, however, is easily
vitreous base. The resultant increased vitreal overlooked, because the orbit and eyelids effec-
pressure causes anterior displacement of the tively camouflage the enlarged globe.
lens–iris diaphragm and marked shallowing of The goals for treatment of feline glaucoma
the anterior chamber and subsequent closure are the same as in other species. Glaucoma sec-
of the iridocorneal angle. ondary to idiopathic uveitis is sometimes
­Glaucom  591

(a)

(b) (c)

Figure 14.42 (a) Photomicrograph from a feline globe with glaucoma secondary to chronic uveitis. A
lymphoplasmacytic infiltrate is present in the iris and sclera. The iridocorneal angle and ciliary cleft are
obstructed by the inflammatory infiltrate (hematoxylin and eosin). (b) Feline eyelid conformation can mask
buphthalmos and episcleral congestion, illustrated in the left eye of a six-­year-­old DSH with glaucoma
secondary to idiopathic uveitis. (c) Idiopathic uveitis and secondary glaucoma in a two-­year-­old DSH with
cataract, rubeosis iridis, lens capsule vascularization, and an IOP of 42 mmHg.

effectively treated using aggressive anti-­ significantly reduces IOP over that seen with
inflammatory therapy. Topical corticosteroids dorzolamide alone. The topical beta-­blockers
can be very effective; however, they have some most commonly used in veterinary medicine
limitations and potential sequelae. Medical are betaxolol and timolol. When timolol
therapeutic options for cats include topical car- maleate 0.5% was administered to normoten-
bonic anhydrase inhibitors and topical beta-­ sive cats, the IOP was decreased by 22%.
blockers. Systemic carbonic anhydrase Topical prostaglandin analogues, such as
inhibitors are not recommended in cats due to latanoprost, bimatoprost, and unoprostone iso-
side effects, which include decreased appetite, propyl, have had no effect on the IOP of nor-
vomiting, and lethargy. Options for topical car- mal cats, although they do cause miosis
bonic anhydrase inhibitors are dorzolamide (decreases in IOP in cats appear to be mediated
and brinzolamide. Application of 2% dorzola- through prostanoid E and D receptors, rather
mide or 1% brinzolamide results in a signifi- than the F receptor).
cant decrease in IOP and/or in aqueous humor When medical therapy fails to control IOP,
flow rate in normotensive cats. The addition of surgical options may be considered. In globes
0.5% timolol maleate to dorzolamide that still retain vision, cyclophotocoagulation
592 Feline Ophthalmology

is a surgical option to decrease production of


aqueous humor. Cyclophotocoagulation may
be performed with the Nd:YAG or diode laser.
The risk of lens damage from laser energy with
possible development of intraocular sarcoma
has not been evaluated in cats.
Enucleation is indicated in blind, painful, or
buphthalmic eyes and is the procedure of
choice for eyes with intraocular neoplasia or
infections. Pharmacological ablation of the
ciliary epithelium by intravitreal injection of
gentamicin was historically considered
another treatment option for blind eyes.
However, this procedure is not recommended
because of the potential for sarcoma formation
from possible lens damage.
Figure 14.43 Congenital cataracts. Immature
cataracts were present bilaterally in a four-­month-­
old Himalayan kitten.
­ iseases of the Lens and
D
Cataract Formation

Congenital Cataracts and Lens Anomalies


Multiple ocular defects rarely occur in the cat,
but the few reported cases have all included
some form of lenticular abnormality.
Congenital cataracts are uncommon in cats
(Figure 14.43), but have been reported in
Himalayans, Persians, Birmans, and British
shorthair kittens.

Primary and Secondary Cataract Formation


Primary and inherited cataracts are rare in the
cat but have been documented in several
breeds, including the Persian, Himalayan,
Figure 14.44 Traumatic cataract in an adult DSH
Russian Blue, British Shorthair, Birman, and following a penetrating injury, with a corneal scar
Bengal. Most of these primary cataracts are at 10 o’clock, anterior capsular pigmentation, an
congenital. Most cataracts in the cat are sec- immature cortical cataract, and subsequent risk of
ondary and are classified according to associa- post-­traumatic sarcoma.
tion with trauma, anterior uveitis, glaucoma,
or lens luxation. Uveitis-­related cataracts raise Traumatic cataracts tend to be focal, occurring
the risk and concern for lens subluxation/luxa- primarily in the region of the insult, and often
tion and glaucoma. Traumatic cataracts are are associated with focal posterior synechia.
relatively common in the cat and are often The most common cause of secondary feline
sequelae to perforating ocular injury, particu- cataracts is chronic anterior uveitis. Cataracts
larly from cat claws or thorns (Figure 14.44). due to uveitis are typically slow to progress,
­Diseases of the Posterior Segmen  593

begin in the cortex, and may be associated with common in the cat than in the dog.
posterior synechiae, rubeosis iridis, and pre- Intracapsular lens extraction is recommended
iridal and pupillary inflammatory membranes. but the prognosis depends on the duration and
Lens luxation is a common sequalae. the underlying cause. In one study, 89.5% of
Several types of metabolic/toxic cataracts the cats undergoing lensectomy benefited from
have been reported in the cat. Kittens fed a the procedure. Primary lens luxations gener-
commercially available kitten milk replacer ally have an excellent prognosis after surgery.
deficient in arginine developed cataracts con-
sisting of diffuse anterior and posterior lens
Cataract Surgery and Lensectomy
opacification and vacuolation of the posterior
Y sutures. These lens opacities resolved in Feline cataract surgery is performed in a fash-
older kittens, becoming residual perinuclear ion identical to that of canine cataract surgery.
halos and a few incipient cortical opacities. Phacoemulsification is an effective procedure
in the cat (see Chapter 12) with success rates
similar or superior to that in the dog. Cats
Lens Luxation
require intraocular lenses of between 52 and
Feline lens luxations are most commonly asso- 55 D to achieve postoperative emmetropia.
ciated with chronic uveitis and glaucoma Cats with preexisting chronic uveitis and sec-
rather than with trauma. Damage to the lens ondary cataract have a less favorable prognosis
zonules appears to be the cause. Siamese and following phacoemulsification in the author’s
male cats are overrepresented. Complications experience.
of lens luxation in the cat are direct corneal
endothelial cell damage, secondary glaucoma,
persistent uveal inflammation, and vision loss ­Diseases of the Posterior Segment
(Figure 14.45). Because the feline anterior
chamber depth is greater than that of dogs, The posterior segment includes the vitreous,
glaucoma due to anterior lens luxation is less ocular fundus, and optic nerve. As in other spe-
cies, the ocular fundus in the cat is divided into
the tapetal fundus, the nontapetal fundus, the
optic nerve head or optic disc, and the retinal
vasculature (Figure 14.46). The feline vascular
pattern is holangiotic, with three major pairs of
cilioretinal arterioles and larger venules that
emerge near the optic nerve head periphery.
The tapetal fundus appears to be more consist-
ent in the cat than in the dog, appearing as a
highly reflective, usually yellow-­green triangu-
lar area in the dorsal fundus. Partial-­to-­
complete lack of the tapetum occasionally
occurs in blue-­eyed cats. The area centralis,
which is an area of high cone concentration, is
located approximately 3 mm lateral to the optic
nerve head. Conus or peripapillary hyperreflec-
tive areas as well as pigmented areas immedi-
Figure 14.45 Subtle rubeosis iridis and lens
ately adjacent to the optic disc are not
capsule pigmentation accompanies secondary
cataract formation and anterior lens luxation in a uncommon. The nontapetal fundus is usually
seven-­year-­old DSH with unilateral idiopathic uveitis. heavily pigmented, appearing as a dark brown
594 Feline Ophthalmology

(a) (b) (c)

Figure 14.46 (a) The normal feline fundus is characterized by a brightly reflective yellow-­green tapetum
dorsally, a pigmented nontapetal region ventrally, and three major paired vessels. The nonmyelinated disc
often appears gray in color. (b) In color dilute cats, deeper choroidal vessels are often visible due to lack of
melanin in the ventral retinal pigmented epithelium. This cat’s lack of tapetum also exposes the dorsal
choroidal vasculature. (c) On rare occasion, a myelin variation in the nerve fiber layer alters the appearance
of the normal, distinctly circular, nonmyelinated optic disc.

area surrounding the tapetal fundus. In color-­ may be caused by inflammation, trauma, neo-
dilute cats, the nontapetal fundus is nonpig- plasia, clotting disorders, systemic hyperten-
mented focally or diffusely, thereby permitting sion, and severe anemia.
visualization of the deeper choroidal vascula-
ture. The optic disc is typically situated in the Retina and Choroid
tapetal fundus; it is small, circular, nonmyeli-
nated, and somewhat gray. Occasionally, myeli- Congenital, Developmental, and Acquired
nation of the nerve fiber layer may occur about Disorders
the optic disc and is considered a variation of Focal retinal, choroidal, and optic disc colo-
normal. Retinal vessels do not cross the optic bomas are rare in the cat. These defects usually
disc as they do in the dog. occur in association with the colobomatous
syndrome in cats with eyelid agenesis. In some
eyes, focal retinal dysplasia is also present, and
Vitreous vision may or may not be impaired.
Congenital and Developmental Disorders
Persistent hyaloid arteries appear to be rare in
Retinal Dysplasia
the cat.
Retinal dysplasia is loosely defined as anoma-
lous retinal development with resultant aberrant
Acquired Disorders
organization of retinal elements to form rosettes,
Vitreal infiltrates of inflammatory and red blood folds, and gliosis. The causes of retinal dysplasia
cells may occur. Inflammatory cell infiltrates are numerous, but in the cat, the condition has
typically occur in cases of chronic anterior uvei- most often been associated with intrauterine or
tis or posterior uveitis, particularly pars planitis. early neonatal viral infections. Retinal dysplasia
Accumulation of inflammatory cells on the pos- has also been reported in feline colobomatous
terior lens capsule and within the anterior vitre- syndrome (Figure 14.47). When injected intraoc-
ous, often termed snowbanking or snowballing, ularly or intraperitoneally to fetal or neonatal
is frequently noted with pars planitis. kittens, FeLV produces retinal dysplasia. Genetic
Vitreal hemorrhage is the condition most retinal dysplasia, common in the dog, has not
likely to be encountered clinically. Hemorrhage been well documented in cats.
­Diseases of the Posterior Segmen  595

species. Taurine is stored in the liver, but the


highest tissue concentrations are found in the
heart muscle and retina, where especially
high concentrations are found in the photore-
ceptor cells. A dietary taurine level of
500–750 ppm has been suggested as being
necessary to prevent feline retinal disease.
The function of taurine is not fully under-
stood, but it has been speculated to act as a
neurotransmitter and to have a protective
influence on cell membranes.
The ophthalmoscopic appearance of tau-
rine deficiency retinopathy is considered to
be pathognomonic, and five progressive
stages have been described (Figure 14.48).
The earliest lesion, or stage 1, is increased
Figure 14.47 Congenital retinal folds appear as
dark spots and branching lines that obscure the
granularity of the area centralis. Stage 2 is
underlying tapetum in a four-­month-­old DSH with defined as an ellipsoidal, hyperreflective
retinal dysplasia and congenital cataracts. lesion. In stage 3, a second hyperreflective
lesion becomes visible nasal to the optic
papilla. The two lesions eventually coalesce
Taurine Deficiency Retinopathy
to form a large, band-­shaped area of hyper-
Taurine is a sulfur-­containing amino acid reflectivity dorsal to the optic papilla (stage
essential to cats because they have limited 4). Stage 5 is generalized retinal degenera-
ability to synthesize it from cysteine, which is tion, with attenuation or loss of retinal ves-
a precursor amino acid for most animal sels. The ophthalmoscopically visible retinal

(a) (b)

Figure 14.48 Taurine deficiency retinopathy. (a) Early in the deficiency, bilaterally symmetrical elliptical
hyperreflective lesions develop in the area centralis temporal to the optic disc. (b) As the degeneration
progresses, lesions coalesce to create a horizontal hyperreflective band that extends nasally and temporally
above the optic disc.
596 Feline Ophthalmology

lesions have been shown to have decreased


rhodopsin levels.
Dietary deficiency of taurine results in selec-
tive depletion of plasma and retinal amino acid
levels within five weeks. Because taurine defi-
ciency has been linked to feline cardiomyopa-
thy, cardiac function should be evaluated in all
cats affected with these ophthalmoscopic
abnormalities.

Inherited Rod–Cone Dysplasia,


Dystrophy, and Degenerations
With the exception of those disorders having a
nutritional basis, retinal degenerations are rela-
tively rare in the cat. Photoreceptor degenera-
Figure 14.49 Generalized tapetal hyperreflectivity
tion, which is characterized ophthalmoscopically and profound retinal vessel attenuation are seen in
by tapetal hyperreflectivity and vascular attenu- a seven-­month-­old Abyssinian, characteristic of
ation, was described in several related Persian heritable rod–cone dysplasia.
cats, with a suspected autosomal recessive mode
of inheritance. A breeding colony of Persian
Rod–Cone Degeneration in
cats was subsequently established, and an early-­
the Abyssinian
onset, autosomal recessive, progressive retinal
atrophy was confirmed. The earliest clinical A recessively inherited rod–cone degeneration
sign was reduced pupillary light reflex, which has been described in Abyssinian and Somali
could be noted at age two to three weeks. By cats. The disease typically begins at
16 weeks, retinal degeneration is complete. 1.5–2.0 years of age, and then progresses to
complete retinal degeneration over the next
two to four years. Progression of the disease
Rod–Cone Dysplasia in the Abyssinian
may be quite variable. Heterozygotes may
An autosomal dominant retinal dysplasia has exhibit abnormal electroretinogram recordings
been described in the Abyssinian breed. despite clinically normal appearing fundi.
Affected kittens as young as four weeks may
show mydriasis and nystagmus, which is vari-
Progressive Retinal Atrophy in the
able, intermittent, and often rapid. The first
Bengal Cat
ophthalmoscopically visible lesions consist of
tapetal dullness and loss of detail, present by Recently, an inherited form of early onset reti-
8–12 weeks of age (Figure 14.49). Progression nal atrophy in the Bengal cat has been identi-
of the disease is fairly rapid and is evidenced fied and characterized. Pedigree analysis
by tapetal hyperreflectivity, loss of pigmenta- suggests that the condition is inherited in an
tion in the nontapetal fundus, and retinal vas- autosomally recessive mode. Ophthalmoscopic
cular attenuation. The disease is very signs of retinal degeneration are first noted in
advanced by one year of age. The rods and affected kittens by nine weeks of age and pro-
cones are both affected, and disorganized gress noticeably over the following four
outer segments as well as diminutive inner months. Changes in visual behavior are appar-
segments can be detected as early as ent by one year of age. Histological degenera-
14 days of age. tion, including reduced photoreceptor
­Diseases of the Posterior Segmen  597

numbers, rapid deterioration of the photore- are typically extinguished, even in cats that
ceptor layer, and severe outer retinal degenera- appear to retain some vision.
tion, is first observed by eight weeks. Although enrofloxacin has been the com-
pound most identified with feline retinal
degeneration, all of the fluoroquinolones must
Drug-­Associated Retinal Toxicity
be considered potentially retinotoxic. The fluo-
The most significant ocular drug toxicity to be roquinolones as a drug class, and particularly
identified in cats is enrofloxacin-­associated enrofloxacin, should be viewed as potentially
retinal degeneration. Beginning in 1997, the dangerous to cats and used only when no alter-
enrofloxacin label dosing was changed from native exists.
the previous recommendation of 2.5 mg/kg
every 12 h to a flexible dose ranging from 5 to
Inflammation
20 mg/kg as a split or single dose. Very soon
afterward, cases of acute and severe retinal Chorioretinitis refers to inflammatory condi-
degeneration and blindness were observed in tions that arise in the choroid and extend into
cats receiving enrofloxacin. Behavioral, neuro- the retina. Retinochoroiditis refers to inflam-
logical, and musculoskeletal abnormalities mations that originate in the retina and even-
also occurred. In most cases, the blindness was tually involve the choroid, though the former
permanent, although a few cats retained some is more common. Active chorioretinal inflam-
vision (Figure 14.50). One of the remarkable mations are characterized ophthalmoscopi-
findings of this toxicity is the rapidity with cally by edema, hemorrhages, inflammatory or
which the retina degenerates. Tapetal hyperre- neoplastic cell infiltration, mycotic and para-
flectivity and vessel attenuation are dramatic sitic granulomas, and exudates or transudates.
even in cats that have received enrofloxacin as Chorioretinitis that has abated leaves scars,
a single dose. Electroretinographic responses which appear ophthalmoscopically as areas of

(a) (b)

Figure 14.50 Enrofloxacin-­associated retinal degeneration. (a) Increased tapetal reflectivity (muted by a
neutral density filter) and retinal vessel attenuation are seen in a blind eight-­year-­old DSH six days after
discontinuing enrofloxacin administration. Vision changes were noted on day 4 of treatment. (b) The same
eye examined eight months later illustrates the end-­stage effect of the toxicity, with profound tapetal
reflectivity and retinal vessel attenuation.
598 Feline Ophthalmology

(a) (b)

Figure 14.51 Mycotic chorioretinitis. (a) Multifocal circles of subretinal edema surround darker focal
granulomatous exudates in a six-­year-­old DSH with cryptococcosis. (b) Multifocal darkly colored preretinal
exudates and hemorrhages obscure the tapetal reflection and optic disc in a two-­year-­old DSH with
histoplasmosis.

hyperreflectivity, with or without pigment dep- hypertensive cats are at least 10 years old, often
osition in the tapetal fundus, and areas of older. Acute blindness is the most common
depigmentation or pigment clumping in the reason for presentation. Other presenting signs
nontapetal fundus. may be those of renal disease, hyperthyroid-
Viral chorioretinitis in the cat has been asso- ism, or neurological signs secondary to cere-
ciated with FIP virus), FIV, and FeLV. Fungal brovascular accidents (hemorrhage, infarct,
chorioretinitis has been associated with cryp- arteriolar spasm).
tococcosis (Figure 14.51), histoplasmosis, blas- In cats with renal dysfunction, the presence or
tomycosis, and coccidioidomycosis. The magnitude of hypertension is unrelated to
protozoal agent T. gondii is a documented azotemia. Persistent lack of urine concentrating
cause of chorioretinitis in cats. Feline chori- ability may be the only indication of chronic renal
oretinitis with retinal detachment has been disease. The mechanism of systemic hyperten-
associated with tuberculous M. bovis, as well as sion in cats with renal disease remains unclear.
with the nontuberculous agent Mycobacterium Hyperthyroidism may contribute to systemic
simiae. Parasitic infections such as dipteran hypertension through its effects on the heart.
larvae may cause chorioretinitis as the parasite Hyperthyroidism increases stroke volume and
migrates within or under the retina. cardiac output, leading to systolic hypertension.
The eye, because of its small caliber vessels,
is a target organ for hypertensive damage.
Hypertensive Retinopathy
Prolonged systemic hypertension leads to sus-
Systemic hypertension is a relatively common tained vasoconstriction of retinal arterioles via
disease of aged cats and has most consistently autoregulation. Beyond certain critical pres-
been associated with chronic renal insuffi- sures, autoregulation breaks down and vascu-
ciency and less frequently with hyperthyroid- lar integrity is compromised. Occlusion of
ism. Primary hypertension in cats may exist precapillary arterioles can lead to ischemia
but at this time remains undefined. Most and retinal degeneration. Leakage of plasma
­Diseases of the Posterior Segmen  599

and red blood cells occurs when endothelial Treatment of hypertensive retinopathy
cells and vascular smooth muscle become includes controlling the underlying disease
damaged (fibrosis and sclerosis). processes and treating the systemic hyperten-
Clinically, the ocular manifestations of sys- sion. There is the potential in some animals for
temic hypertension can be severe and include blindness to be reversible if systemic hyperten-
retinal arterial tortuosity, intraretinal hemor- sion can be quickly controlled. Bullous retinal
rhage, preretinal hemorrhage, subretinal hem- detachments can resolve if the underlying
orrhage, retinal edema and focal bullae, retinal effusion is controlled. Depending on the length
detachment, retinal degeneration, hyphema, of time the retina has been detached, vision
anterior uveitis, and secondary glaucoma may be regained. As the systemic hypertension
(Figure 14.52). The iris and ciliary body vessels resolves with treatment, if the degree of ocular
may be compromised, leading to bleeding damage is limited, the examiner will note
within the vitreous cavity and posterior or return of PLRs and resolution of hemorrhage
anterior chambers. More commonly, hyphema and possibly reattachment of the retina. Return
is associated with massive posterior segment of vision in all cases is dependent on the degree
(retinal or choroidal) hemorrhage with blood of damage the retina has undergone.
that migrates through the pupil. Hyphema that
does not clear quickly can lead to synechiae
Hyperviscosity Retinopathy
and secondary glaucoma.
Frequently, the first indication of systemic The retina of the domestic cat is sensitive to
hypertension is what appears to be an acutely the effects of increased plasma viscosity.
blind animal. Even though cats may have an Ocular lesions with serum hyperviscosity syn-
acute decompensation that leads to blindness, drome may include retinal hemorrhages,
hypertensive retinopathy is usually one of dilated and tortuous vessels, optic disc swell-
gradual progression over several months and ing, and partial retinal detachment.
can be recognized before blindness occurs if Fortunately, the prevalence of diseases result-
fundic examination is performed. The excep- ing in this condition appears to be low.
tion to this is bilateral, acute, serous retinal Common systemic clinical manifestations of
detachment without antecedent ocular abnor- hyperviscosity syndrome in the cat include list-
mality, which is usually associated with a rapid lessness, weight loss, neurological signs, and
increase in systemic blood pressure. heart murmur.

(a) (b) (c)

Figure 14.52 Hypertensive retinopathy. (a) Bullous retinal detachment and subretinal hemorrhage in a
14-­year-­old DLH with a systolic blood pressure of 280 mmHg. (b) Complete serous retinal detachment seen
through the dilated pupil of a blind 13-­year-­old DSH with a systolic blood pressure of 270 mmHg. (c)
Hyphema accompanies systemic hypertension in an 11-­year-­old DSH.
600 Feline Ophthalmology

Retinal Fold and Detachment are mucopolysaccharidoses I and IV, GM1


and GM2 gangliosidoses, mannosidosis, and
Retinal folds may occur as congenital lesions
mucolipidosis II.
but are also recognized in the cat as a second-
ary response to other ocular diseases.
Ophthalmoscopically, acquired retinal folds
may be focal or diffuse, and they occupy either
­ iseases of the Optic Nerve
D
the tapetal or nontapetal fundus. Their appear- and Central Nervous System
ance is characteristic. Folds are recognized as
irregular, vermiform lesions that are hypore- Congenital and Developmental Disorders
flective in the tapetal fundus and appear white Colobomas of the optic disc and peripapillary
to gray in the nontapetal fundus. Retinal region are rare in cats. Optic disc colobomas
detachment or separation of the sensory and may occur in association with eyelid agenesis
epithelial retina in the cat has been described as well as with other developmental anomalies
in association with a wide variety of ophthal- (Figure 14.53). Optic disc aplasia has been
mic and systemic abnormalities, including sys- reported in which the retinal vasculature,
temic hypertension, hyperviscosity syndromes, nerve fiber layer, ganglion cell layer, optic
periarteritis nodosa, toxoplasmosis, trauma, nerves, and optic tract also failed to develop.
cryptococcosis, blastomycosis, histoplasmosis, Optic nerve aplasia may also occur if kittens
coccidiomycosis, FIP, ethylene glycol toxicosis, are exposed to weekly doses of 500–1000 mg of
polycythemia, and primary as well as second- griseofulvin during the first half of gestation.
ary intraocular neoplasms.

Optic Neuritis
Posterior Segment Neoplasia
Optic neuritis appears to be less common in the
Primary neoplasms of the posterior segment cat than the dog. Inflammation of the optic
appear to be quite rare in the cat. An astrocy- nerve may have a variety of causes in the cat.
toma of retinal origin has been described in
one cat. The presenting signs were leukocoria
with a vascularized mass visible within the
pupil. Histopathologically, the tumor infil-
trated the optic nerve head, choroid, and vitre-
ous humor. A choroidal melanocytoma has
been reported in a cat. The cat later died from
lymphoma and at necropsy no evidence of
metastatic melanoma was detected.

­Lysosomal Storage Diseases

Storage disorders are a group of progressive,


inherited diseases caused by the deficiency of a
specific lysosomal enzyme. Disease ultimately
results from abnormal accumulation of the
Figure 14.53 An optic disc coloboma in a
deficient enzyme’s substrate within lysosomes
four-­year-­old Siamese appears as a small dark pit
of affected cells. Lysosomal storage diseases at the 6-­o’clock position along the ventral margin
reported to have ophthalmic manifestations of the optic nerve head.
­Diseases of the Orbi  601

Viral, parasitic, and fungal infections can all anophthalmia, and optic nerve aplasia.
cause optic neuritis. Of the viral diseases, FIP is Extraocular defects include numerous central
most likely to affect the central nervous system nervous system and skeletal abnormalities.
and the optic nerve. Associated ocular signs
may include anterior uveitis, chorioretinitis,
Traumatic Proptosis
perivascular cuffing, and retinal detachment.
Considerable trauma to the orbit and head is
required to proptose a cat’s globe (Figure 14.54).
Optic Nerve Atrophy
Concurrent facial fractures and optic nerve
Atrophy of the optic nerve is the sequelae to damage are more common than not. In one
any process that damages the retinal ganglion series of traumatic proptosis in 18 cats, no eyes
cells or their axons. Examples of such causes regained vision. Sexually intact males were
include injury to the optic nerve during trau- more frequently affected with vehicular
matic ocular proptosis, traction-­related dam- trauma, the most frequently established source
age to the optic nerve at the level of the optic of trauma. Concurrent facial bone fractures,
chiasm during enucleation of the contralateral hyphema, corneal perforation, and ocular des-
eye, and previous episodes of optic neuritis. iccation are common.
Chronic glaucoma and retinal degeneration
will also result in optic nerve atrophy.
Orbital Inflammations and Infections
The feline orbit has relatively limited space
­Diseases of the Orbit compared with that of the dog. Hence, space-­
occupying orbital inflammations and neo-
Congenital and Developmental Disorders plasms will produce exophthalmos, deviation
of the globe, and protrusion of the nictitating
Multiple abnormalities or colobomas of the membrane early in the disease process
eye and associated ophthalmic structures (Figure 14.55). Orbital surgeries are also more
occur in the domestic cat. The condition is difficult to perform because of the limited
characterized by congenital colobomatous peribulbar space.
defects in single or multiple ocular tissues,
which may include the eyelid, iris, optic nerve,
and sclera (see Figure 14.53). Similar ocular
anomalies have been reported in the snow
leopard and cougar. The most consistent
anomalies in affected kittens are focal dorso-
lateral eyelid agenesis and trichiasis. Both
heredity and in utero viral causes have been
proposed for this syndrome, but no supporting
evidence is currently available.

Griseofulvin Teratogenesis
The cat is particularly sensitive to the terato-
genic effects of griseofulvin. When given to
Figure 14.54 Proptosis in the cat is usually the
cats at a weekly dose of 500–1000 mg during
result of severe head trauma with cranial and
the first half of gestation, griseofulvin pro- mandibular fractures, as seen in this adult DSH
duces ocular defects consisting of cyclopia, struck by a car.
602 Feline Ophthalmology

Feline Restrictive Orbital


Myofibroblastic Sarcoma
Originally described as an idiopathic scleros-
ing orbital disease, feline restrictive orbital
myofibroblastic sarcoma (FROMS) is an insidi-
ous condition that results in progressive fixa-
tion of the eyelids and orbital structures. The
features of the condition are similar to those of
sclerosing orbital pseudotumor in humans. In
affected cats, extensive fibrosis with encapsu-
lation of normal tissues progresses over weeks
to months. In most cats, the condition becomes
Figure 14.55 Orbital cellulitis in a three-­year-­old bilateral. Exposure keratitis, corneal ulcera-
DSH with periocular swelling, a prominent third tion, and corneal perforation are prominent
eyelid, and lagophthalmos. features of the disease due to inability of the
eyelids to move. Although there are some
inflammatory cells (lymphocytes, plasma cells,
Orbital cellulitis and abscessation caused by
and occasional neutrophils) seen in affected
bacteria occur infrequently in the cat but are
tissues, invasion of collagenous tissue along
usually amenable to traditional therapy of
existing tissue planes, rather than invasion of
drainage and antibiotic administration. In a
tissues, was the predominant feature. Other
study of orbital bacterial infections, five of
systemic disease is not usually found in
seven cats had positive bacterial isolation, with
affected cats, and response to treatment was
Pasteurella and Bacteroides the most common
poor. Most affected cats are euthanized due to
genera. Onchocerca lupi has been occasionally
progression and poor quality of life.
reported as the causative agent of orbital cel-
lulitis in cats. Retrobulbar steatitis resulting in
exophthalmos and globe compromise has been
Orbital Neoplasia
reported from extension of otitis media and an
inflammatory polyp. Most orbital neoplasms (90%) in cats are
Orbital infections caused by fungal agents are malignant, where approximately two-­thirds of
occasionally reported. Clinical signs in these ani- the neoplasms were epithelial in origin, with
mals may include exophthalmos, corneal drying SCCs being the most frequent type
with possible ulceration secondary to lagophthal- (Figure 14.56). Approximately 15 different
mos, ocular discharge, oral cavity ulceration, types of orbital tumors have been reported in
pain upon opening of the mouth, and nasal dis- the cat, including osteoma of the zygomatic
charge if the infection involves the nasal cavity or arch, parosteal osteoma, and fibrosarcoma.
sinuses. Sino-­orbital aspergillus, a form of feline Orbital lymphoma may occur either unilater-
upper respiratory tract aspergillosis, is believed to ally or bilaterally in the cat. A recent report
occur from extension of the nasal disease, rather described a series of cats with clinical presen-
than the result of hematogenous spread. tations resembling those of FROMS, which
Extensive bone lysis in addition to masses within were ultimately diagnosed with orbital inva-
the orbit is seen with computed tomography, sug- sive SCC. While primary neoplasms are much
gesting that fungal disease should be considered more common in the feline orbit, metastatic
as an alternative differential to neoplasia. tumors to the orbit have been reported.
Surgical therapy alone, including orbital exen- Depending on the tissue of origin and the
teration, has not typically been successful. invasiveness of an orbital tumor, therapeutic
­Diseases of the Orbi  603

(a) (b)

Figure 14.56 (a) Orbital SCC in a 14-­year-­old DSH with secondary exophthalmos, third eyelid protrusion,
and exposure keratitis. (b) Concurrent oral SCC in the same cat.

options may include surgery (orbitotomy with higher risk for damage to the optic chiasm. The
tumor resection or ­exenteration), radiation feline optic nerve is short and lacks the same
therapy, and/or chemotherapy. degree of S-­curve present in the dog. Traction
placed on the globe during enucleation may
lead to optic chiasm damage and blindness in
Enucleation
the fellow eye. There is little free space in the
Enucleation or exenteration in the cat must be feline orbit, so the use of large instruments or
approached with more caution than the same inappropriate technique may place undue trac-
surgical procedure in the dog because of the tion on the optic nerve.
604

15

Equine Ophthalmology
Revised from 6th edition of Veterinary Ophthalmology, Chapter 29: Equine Ophthal­mology, by Caryn E. Plummer

­ xamination of the
E visualization of the globe will target either the
Equine Eye auriculopalpebral or palpebral nerves. These
motor fibers may be blocked at three points
In order to perform a thorough examination of between the origin of the auriculopalpebral
the equine eye, the patient must be adequately nerve and the palpebral nerve branch: (i) just
restrained. Chemical restraint greatly facili- anterior to the base of the ear where the auric-
tates a complete ophthalmic examination of ulopalpebral nerve emerges from the parotid
the horse. Typically, a short-­acting sedative is salivary gland and becomes subcutaneous on
administered intravenously (i.v.), followed by the lateral aspect of the coronoid process.
an auriculopalpebral motor block. Xylazine Here, a local anesthetic, such as lidocaine, may
(0.3–0.4 mg/kg i.v.) is usually adequate for be injected into the depression just caudal to
examination. Especially difficult equine the ramus of the mandible at the ventral edge
patients may require either a higher dose of of the temporal portion of the zygomatic arch;
xylazine (1.1 mg/kg i.v.) or detomidine (ii) just lateral to the highest point of the cau-
(0.02–0.04 mg/kg i.v.) or romifidine (40–120 μg/ dal zygomatic arch where the palpebral nerve
kg i.v.). If more invasive diagnostic or treat- can be “strummed” under the skin over the
ment procedures are to be performed, such as dorsal border of the bone; and (iii) where the
corneal scrapings or conjunctival biopsies or palpebral nerve lies on the zygomatic arch cau-
placement of a subpalpebral (SPL) lavage sys- dal to the bony process of the frontal bone.
tem, most animals will require the more potent Considering the branching of these motor fib-
detomidine with or without the addition of ers, more proximal blocks generally are pre-
butorphanol (0.01–0.02 mg/kg i.v.). The orbicu- ferred, because they affect more of the
laris oculi muscle closes the eyelids and, thus, orbicularis oculi muscle. A 25-­gauge, 5/8-­in.
can impair or even prevent ocular examina- needle is used to inject 1–3 ml of anesthetic
tion, especially in large animals. The pain in subfascially adjacent to the nerve.
diseased eyes may be so intense that examin- In some instances, it is helpful to desensitize
ing or manipulating the orbit and globe is dif- the skin of the eyelids to facilitate examination
ficult and potentially threatening to the of the eye or to enable surgical repair of an eye-
integrity of the globe if the horse resists. The lid wound or placement of a SPL lavage.
eyelids should never be forced open. A motor Sensation to the eyelids is provided by the oph-
block to facilitate opening of the eyelids and thalmic and maxillary divisions of the

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
­Examination of the Equine Ey  605

trigeminal nerve (i.e., cranial nerve V). In the into the supraorbital foramen. This foramen
horse, the frontal nerve innervates most of the can be identified as a small depression in the
central upper lid, the lacrimal nerve innervates supraorbital process of the frontal bone, medial
the lateral upper lid, the zygomatic nerve inner- to its most narrow aspect (Figure 15.1). It can
vates most of the lateral lower lid, and the infra- be palpated if the examiner places his or her
trochlear nerve innervates the medial canthus. thumb below the dorsal orbital rim and the
There are several different sensory blocks that middle finger in the supraorbital fossa. The
may be employed in horses depending on the examiner then places the index finger straight
location of the eyelid lesion to be addressed. down midway between the thumb and middle
The central two-­thirds of the upper eyelid is finger to locate the supraorbital foramen. The
innervated by the frontal or supraorbital nerve, lateral upper eyelid and lateral canthus are
and is blocked by injecting 2 ml of 2% lidocaine innervated by the lacrimal nerve, and can be

(a) (b)

Supraorbital foramen

Palpebral nerve
(ophthalmic branch)

Nasociliary
nerve

Maxillary nerve
(zygomatic branch)

Infratrochlear nerve

(c) (d)

Figure 15.1 Nerve blocks used in the equine eye exam. (a) The auriculopalpebral nerve block in a horse
facilitates examination of the eye and is crucial when the cornea is fragile and near perforation. This figure
illustrates the proximal placement of the block with the needle, while the arrows mark alternative locations
that will elicit a similar response. (b) The injection of anesthetic agent. (c) The frontal (supraorbital) nerve is
a branch of the trigeminal nerve and is blocked as it emerges from the supraorbital foramen within the
frontal bone. (d) The supraorbital nerve block is performed at the level of the supraorbital foramen (directly
within the foramen if possible, in the region if not) and is useful for anesthesia of the upper eyelid. To
locate the supraorbital foramen, the examiner places his/her thumb under the orbital rim, the middle finger
in the supraorbital fossa, and then places the index finger straight down midway between the thumb and
middle finger to locate the supraorbital foramen.
606 Equine Ophthalmology

blocked with a line block along the lateral third developed globe and adnexa at birth. However,
of the dorsal orbital rim. A block of the zygo- tear production and corneal sensitivity may be
matic nerve will anesthetize the lateral lower low initially, and lagophthalmos may be found
lid and is achieved with a line block along the in neonates. A menace response may not be
ventrolateral orbital rim. The medial canthal fully developed until 10–14 days after birth.
region is innervated by the infratrochlear nerve The PLRs, however, are intact, although may
and is desensitized by injecting anesthetic be sluggish initially. Hyaloid artery remnants
through the bony trochlear notch on the dorsal in foals may contain blood for several hours
rim of the orbit near the medial canthus. after birth but generally disappear by three to
After preparation, the complete ophthalmic four months of age. Lens sutures are often
examination proceeds with a systematic prominent in foals and should not be mistaken
approach. Following assessment of vision, and for a cataract. The anterior suture has a varia-
prior to instillation of any medication in or ble configuration in shape, with the posterior
around the eye, the examiner should evaluate suture varying in shape from “Y,” sawhorse, to
for symmetry of the head, bony orbits, eyelids, stellate patterns.
globes, and pupils in a well-­lit environment. The Variations of the normal equine neonatal
upper eyelashes of the healthy horse are nearly fundus are numerous, and primarily relate to
perpendicular to the cornea, while a ventral or coat color. The optic disc is oval to round, pink-­
downward direction of the eyelashes may indi- orange in color, and located slightly temporal
cate discomfort, enophthalmos, or ptosis. The in the inferior quadrant of the nontapetal fun-
menace response is assessed before sedation and dus. The retinal vessels are small and extend
motor blockade of the eyelids. Pupillary light only a short distance from the optic disc. No
and dazzle reflexes may be performed at any retinal vessels are found at the 6-­o’clock posi-
time. An assistant is helpful when assessing con- tion of the horse optic disc. The foal tapetal
sensual pupillary light reflexes (PLRs). Then, the fundus is usually blue to blue-­green, with
anterior and posterior segments of the globe are small dots and end-­on views of choroidal capil-
examined with a focal light source and magnifi- laries or “stars of Winslow” distributed in a
cation. Mydriasis is required for complete exam- uniform pattern. Color-­dilute neonates may
ination of the lens and ocular posterior segment. have light yellow zones of tapetal color with
The most common mydriatic used is tropi- red “stars of Winslow,” or have no tapetum
camide (Mydriacyl® 1%, Alcon Laboratories, Fort with resultant exposure of the choroidal vascu-
Worth, TX, USA), which takes effect in approxi- lature, thereby creating a red fundic reflection.
mately 10–20 min and lasts 4–6 h in the horse. If Light gray linear streaks arcing horizontally
the horse has intraocular inflammation or ante- nasally and temporally away from the optic
rior uveitis secondary to corneal disease or disc margin may be seen in the nontapetal fun-
trauma, a single application of tropicamide may dus of foals, and represent axon bundles in the
not fully dilate the pupil. Because of its longer nerve fiber layer. Partial albinism will result in
duration of action, the use of atropine (1%) for a lack of pigmentation in the retinal pigment
routine examination is not recommended. epithelium (RPE) of the nontapetal region per-
mitting visualization of the choroidal
vasculature.
­ cular Problems in the
O An ophthalmic examination should be per-
Equine Neonate formed in foals 12–36 h after birth. Abnormalities
are frequently noted on neonatal exams and
Ocular disorders of the equine neonate may be these foals should be monitored regularly and
congenital, inherited, or acquired. Normal carefully. Retinal and subconjunctival hemor-
embryogenesis of the foal eye results in fully rhages are common in neonates. Retinal
­Ocular Problems in the Equine Neonat  607

hemorrhages usually resolve within one week, infection or drug toxicity. Microphthalmos
whereas subconjunctival hemorrhages may take may be an isolated finding, or it may be associ-
several weeks to resolve. Ophthalmic lesions in ated with other ocular abnormalities, such as
neonatal foals with systemic disease are com- cataracts and retinal dysplasia. A small palpe-
mon; many including uveitis and ulcerative ker- bral fissure and prominence of the nictitans
atitis may be vision-­threatening. Foals with are concurrent in affected foals. Entropion
sepsis are significantly more likely to have ante- may occur from a lack of support from the
rior uveitis than were those without sepsis. Foals small globe and be associated with mild-­to-­
with sepsis and uveitis are also significantly less severe ulcerative keratitis. Corneal ulceration
likely to survive than are foals that had sepsis resulting from entropion and microphthalmia
without uveitis. may necessitate entropion repair in visual
globes or enucleation of nonvisual globes.
Congenital Anomalies
Orbit
and Abnormalities
Development of the bony equine orbit is influ-
Microphthalmos enced directly by globe development.
Microphthalmos is a congenital globe condi- Asymmetry of the face because of an underde-
tion in which the globe axial length is less than veloped bony orbit can be associated with con-
two standard deviations below the mean genital microphthalmos or phthisis bulbi
length (Figure 15.2). Thoroughbreds are at resulting from early severe globe trauma in
increased risk. Microphthalmos differs from very young foals.
phthisis bulbi, which is an initially normal-­
sized globe that degenerates and atrophies sec- Strabismus
ondary to severe injury or insult. Strabismus refers to a deviation in alignment
Microphthalmos may be spontaneous and idi- of one globe in relation to the normal visual
opathic, or it may be secondary to uterine axis. When the two eyes fail to focus on the
same image point, the brain may ignore the
input from the deviated eye to result in a form
of vision loss termed amblyopia. The two eyes
may be crossed (esotropia), turned outward
(exotropia), deviated up vertically (hypertro-
pia) (Figure 15.3), or deviated down vertically
(hypotropia). Foals with congenital or early
onset strabismus do not receive the essential
visual retinal stimulation for development of
binocular vision and thus lack true stereopsis.
Congenital strabismus and dorsomedial stra-
bismus have been reported in Appaloosa foals
with equine congenital stationary night blind-
ness (CSNB). Hypertropia associated with con-
genital cataracts may resolve following surgical
removal of the cataract.

Dermoids
Dermoids (i.e., choristomas) of the eyelids, nic-
Figure 15.2 Microphthalmos in a foal with
nictitans protrusion and conjunctival exposure. The titans, cornea, and conjunctiva have been
orbit is flattened on this side of the skull. reported in foals (Figure 15.4). Corneal and
608 Equine Ophthalmology

reconstructive blepharoplasty for eyelid der-


moids is warranted to alleviate ocular irritation.
Limbal dermoids have been noted with iridal
hypoplasia and cataracts in Quarter Horses.

Nasolacrimal System Atresia


Eyelid punctal atresia, nasolacrimal duct
(NLD) agenesis, and nasal punctal atresia must
be differentiated from acquired obstruction
causing dacryocystitis of the nasolacrimal
drainage system. NLD atresia, which is most
commonly manifested by an imperforate nasal
punctum, appears clinically as mild to moder-
ate, unilateral or bilateral epiphora at
4–6 months of age and, if not managed appro-
priately, can develop into severe mucopurulent
discharge by 10–12 months of age due to the
development of secondary bacterial dacryocys-
Figure 15.3 Strabismus (hypertropia) in a foal titis. Culture and antibiotic sensitivity testing
with congenital cataract.
of the discharge and irrigated material are rec-
ommended. Contrast dacryocystorhinography
(DCR) may be necessary to confirm the
diagnosis.
Eyelid punctal atresia may be noted visually
at the medial canthus (lack of a punctal open-
ing), because of distention of the conjunctiva
over the atretic punctum after irrigation of the
nasolacrimal system from the nasal punctum.
A diagnosis of atresia of the nasal punctum
may be presumed by noting the lack of a distal
opening to the NLD within the mucocutane-
ous junction at the medial nares, failure of the
irrigating solution to exit the nasal punctum
during flushing of the proximal nasolacrimal
system through the palpebral lacrimal punc-
tum, and distention of the floor of the nasal
vestibule in response to irrigation. Agenesis of
Figure 15.4 Corneal dermoid in a foal. Note the the osseous NLD is fortunately rare but may
pale spots within the pigmented lesion.
also accompany the eyelid or nasal punctal
atresia.
conjunctival dermoids may appear as aberrant Creation of a new proximal or distal opening
pigmentation when associated hair follicle and duct by catheter instillation is indicated
development is minimal. Glands and follicles for puncta atresia. It may be possible to flush
appear as hypopigmented foci on pigmented the nasolacrimal system from the patent nares
dermoids. Treatment depends on location. or canthal puncta to cause a dilation of the
Superficial to deep keratectomy is indicated mucosa over the site of the atretic punctum.
for corneal dermoids and excision with Once the atretic site is identified, an incision
­Ocular Problems in the Equine Neonat  609

through the eyelid conjunctiva or nasal mucosa aniridia is rare and the base of the iris is usually
with a scalpel, cautery, or laser ablation will present histologically in most cases. Discomfort
establish patency. To treat definitively, a #5 from true photophobia and glare in conditions
French male silastic or plastic urinary catheter of bright light may be present due to the inabil-
is placed normograde from a proximal nasolac- ity to regulate light entering the eye.
rimal punctum and pulled through the nares
and sutured in place. The catheter should Iridal Hypoplasia and Colobomata
remain in place for several weeks (four to eight Iris colobomas, both typical and atypical, may
weeks) to allow epithelialization of the new occur uncommonly in horses but should be
duct and puncta and resolution of the dacryo- differentiated from iris hypoplasia, which is an
cystitis. Topical and systemic antibiotics are iris defect commonly observed in lightly pig-
given for two to four weeks. mented irides (Figure 15.5a and b). Iridal
hypoplasia is a congenital underdevelopment
Corneal Disease of the iris stroma that appears as thin iris tissue
Congenital corneal disease is uncommon in often with holes or defects. In iridal hypoplasia
the horse, with megalocornea of multiple con- of heterochromic eyes, the affected thin region
genital ocular anomalies (MCOAs) of the of iris stroma may appear dark due to the expo-
Rocky Mountain Horse (RMH) and dermoids sure of the posterior pigmented epithelium of
being most common. the iris and it may appear cyst-­like if it balloons
into the anterior chamber from the higher
Aniridia pressure of the posterior chamber. It is com-
Aniridia, or complete absence of the iris, has mon in Appaloosas, Miniature Horses, and
been reported with congenital cataracts in ponies and in blue and heterochromic eyes.
Thoroughbreds, and as a sole lesion in Quarter
Horses and Belgians. Aniridia, which is charac- Persistent Pupillary Membranes
terized clinically by the visualization of ciliary Persistent pupillary membranes (PPMs) are
body processes and edge of the lens, has been remnants of the anterior tunica vasculosa len-
reported to be inherited as an autosomal domi- tis. They appear as strands of iridal tissue aris-
nant trait in the Belgian Draft breed, the Quarter ing from the mid-­iris collarette and, in most
Horse, a Thoroughbred, and a Thoroughbred/ cases, passing to attach to the iris, though
Welsh cross. In spite of the terminology, total attachment to the lens and/or cornea is

(a) (b)

Figure 15.5 Congenital iris abnormalities in foals. (a) Iris hypoplasia dorsally causes a cystic bulging of
the dorsal iris stroma. (b) In this foal, the hypoplastic iris is so thin that the equator of the lens is visible
behind the iris.
610 Equine Ophthalmology

possible. Nonprogressive corneal opacity Hyaloid Artery Remnants


results if the PPM adheres to the cornea, or a Hyaloid artery apparatus consists of the hya-
focal cataract can result if it adheres to the loid artery and the posterior tunica vasculosa
lens. These membranes generally regress to lentis. Remnants of some segment of this
some extent over the first 6–12 months of life, apparatus are apparent to some degree in both
and they require no treatment. eyes of ~80% of Thoroughbred neonates less
than four days old. It is perfused with blood in
Anterior Segment Dysgenesis about a third of the eyes at birth, and becomes
Anterior segment dysgenesis (ASD) is charac- nonperfused by 48 h postpartum. These rem-
terized variably by observation of PPMs and nants appear as white linear opacities at the
may be a component of the MCOA syndrome surface of the posterior lens capsule.
of RMHs. ASD is associated with a missense Persistence of any part of the hyaloid artery
mutation in the PMLE17 gene, often referred system does not generally cause problems,
to as the silver dapple gene in the horse. Breeds although small posterior axial cataracts may be
affected include the Shetland pony, Miniature present in some eyes.
Horses, RMH, Kentucky Mountain Saddle
Horse, Mountain Pleasure Horse, Morgan Cataracts
Horse, Bashkir-­Curly Horse, Narragansett Congenital defects of the lens may be due to
Pacer, and Haflinger. Chocolate coat color and genetic causes (inherited), toxins, nutritional
flaxen mane and tail color are often associated imbalance, ionizing radiation, inflammation,
with the ASD (Figure 15.6a and b). Hypoplasia or other idiopathic causes, although these
of the corpora nigra and iris, and temporal iris causes have not been well characterized in
and ciliary body cysts are found in the hete- horses. However, cataracts are the most com-
rozygous RMH. The homozygous state has mon congenital abnormality in foals, repre-
congenital miosis with the pupil frequently senting approximately 35% of all congenital
nonresponsive to mydriatic drugs, deep ante- ocular defects (Figure 15.7a and b). Inherited
rior chamber, macrocornea, ciliary body and congenital cataracts have been documented in
retinal cysts, cataract, lens luxation, RPE Thoroughbreds, Quarter Horses, and Morgans.
streaks, and retinal dysplasia/detachment. RMHs can also develop congenital cataracts,

(a) (b)

Figure 15.6 Horses affected with MCOA. (a) Individuals with the silver dapple coat color (mutations at the
PMEL locus) may be affected with ASD. Homozygotes tend to be more severely affected than heterozygotes.
The chocolate coat color with a flaxen mane and tail is a silver dilute version of a black horse. (b) Temporal
nonpigmented ciliary body cyst in a heterozygous RMH.
­Ocular Problems in the Equine Neonat  611

(a) (b)

Figure 15.7 Congenital cataracts in foals. (a) Remnants of the tunica vasculosa lentis remains perfused on
the posterior lens capsule of this yearling. (b) Advanced immature cataract in a Thoroughbred foal.

and lens luxation associated with ASD. A dom- therapy and monitoring is warranted. The vis-
inant mode of inheritance has been reported in ual outcome of cataract surgery can be difficult
Belgian as well as in Thoroughbred horses. to evaluate in young horses. Foals left aphakic
Morgan horses have nonprogressive, nuclear, after cataract surgery are profoundly hyper-
bilaterally symmetrical cataracts that do not opic, but in many cases have appropriate visual
seriously interfere with vision. behavior. The placement of artificial intraocu-
Healthy foals with cataracts, visual impair- lar lenses is advocated at present; however, the
ment, the personality to tolerate administra- most ideal dioptric strength is still a matter
tion of topical therapy, and free of active of debate.
anterior uveitis are candidates for cataract sur-
gery. Preoperative ocular testing to establish Congenital Glaucoma
candidacy for surgery proceeds as in small ani- Glaucoma is an elevation in intraocular pres-
mals with electroretinography (ERG) and ocu- sure (IOP) that is detrimental to normal ocular
lar ultrasonography. Foals should be carefully function. The reference ranges for normal IOP
evaluated for any subclinical infectious sys- in horses range from 17 to 28 mmHg. Elevation
temic diseases, such as Rhodococcus pneumo- IOP that is incompatible with ocular health
nia, because sight-­threatening postoperative results from an obstructed outflow of aqueous
endophthalmitis may result after surgery if the humor, eventually resulting in optic nerve
condition is not detected and treated damage and blindness. Congenital glaucoma is
preoperatively. generally associated with developmental
The most common technique for removing anomalies of the iridocorneal angle. No par-
congenital cataracts in foals is phacoemulsifi- ticular breed predisposition has been reported
cation. Recent advances in the surgical tech- for glaucoma in equine neonates. Glaucoma
nique have increased the success rate in foals can also be a sequela to severe or untreated
to nearly 80%. The logistics of general anesthe- anterior uveitis in foals.
sia and surgery as well as the surgical success Clinical signs of glaucoma include general-
rate are most favorable in foals less than six ized corneal edema, narrowing or fibrosis of the
months of age. Postoperative iridocyclitis is iridocorneal angle, deep linear and branching
generally quite minimal compared with that corneal band opacities of Descemet’s mem-
found in the dog; however, diligent medical brane (DM), and the posterior stroma, lens
612 Equine Ophthalmology

luxations, optic nerve cupping, and a fixed, Congenital Disorders of the


dilated pupil. Buphthalmia will occur if IOP is Posterior Segment
persistently elevated (Figure 15.8). Though Fortunately, congenital abnormalities of the
glaucoma can be treated medically, surgical equine posterior segment are uncommon and
therapy may be best for foals with ASD. Surgical rarely have clinical significance, such as the
therapy for equine glaucoma is directed at case with focal colobomas (Figure 15.9a).
reducing the production of aqueous humor by Other defects, such as congenital retinal
damaging the ciliary body with laser energy detachment, retinal dysplasia, CSNB, and the
(i.e., cyclophotocoagulation). High-­flow gonio- MCOA syndrome (i.e., the RMH syndrome),
implants may be considered to increase the may be associated with vision loss.
aqueous outflow in foals. This is a difficult dis- Retinal dysplasia is an in utero developmen-
ease to manage in the foal, with little to no tal or postinflammatory problem of the retina
chance of preserving vision even if the condi- in which the sensory retina is “folded” to form
tion is both detected and treated surgically early rosettes of neural tissue (Figure 15.9b). Retinal
in its course. Chronically painful and blind, dysplasia in foals is generally bilateral and
buphthalmic globes should be enucleated. often associated with other congenital ocular
problems. It can appear as either single or mul-
tiple, or linear or geographic foci or regions of
hyporeflective folds or hyperreflective thin-
ning on ophthalmoscopy.
Retinal detachments may be either unilateral
or bilateral, and they can be associated with
other ocular abnormalities (Figure 15.10). The
detached retina can be observed through the
dilated pupil as a floating veil of opaque tissue
in the vitreous. If the detachment is bilateral,
the foal will be blind and may have nystagmus.
CSNB has been reported in Appaloosas,
Quarter Horses, Miniature Horses, Standard­
Figure 15.8 Corneal edema from congenital
breds, and Appaloosa horses with leopard
glaucoma in a foal.

(a) (b)

Figure 15.9 Ocular fundus abnormalities in the foal. (a) Focal peripapillary RPE coloboma. This is a
common congenital abnormality without known clinical significance. (b) Retinal dysplasia in a
Thoroughbred foal.
­Ocular Problems in the Equine Neonat  613

(a)

Figure 15.10 Congenital retinal detachment in a


foal. The retina is torn and appears as a convoluted
opaque membrane.

complex spotting. It has also been reported in


a Thoroughbred and a Paso Fino. The fundus
appears to be structurally normal, with char- (b)
acteristic, a-­wave-­dominant ERG patterns
confirming the diagnosis. A defect in neural Figure 15.11 Eyelid abnormalities in foals.
transmission between the photoreceptor lay- (a) Severe lower lid entropion and blepharitis in a
foal. A corneal ulcer is present. Note the corneal
ers and the bipolar cells is suspected. Vision is edema and infiltrate ventrally. (b) The entropion
severely diminished in reduced light levels, was corrected with temporary tacking vertical
but functional in bright light. mattress sutures.
Optic nerve hypoplasia and optic nerve atro-
phy in foals may be secondary to developmen- a primary anatomical condition, or be second-
tal or inflammatory processes. Foals with optic ary to the enophthalmos associated with
nerve hypoplasia display smaller-­than-­normal microphthalmos or prematurity (Figure 15.11a
discs, have slow PLRs and mydriasis, and and b). Rolling in of the eyelid margin may
depending on the degree of hypoplasia may occur with dehydration or malnutrition in sys-
retain some vision. Foals with bilateral optic temically compromised foals. It is the most
nerve atrophy are blind with fixed, dilated common eyelid abnormality in foals and is
pupils, have pale discs with no retinal vessels, most commonly exhibited in only the lower
and have posterior depression of the optic disc eyelid; however, it may affect the upper eyelid
of several diopters. in Miniature Horses. Ocular pain may cause
spastic entropion that may exacerbate the
degree of anatomical entropion present.
Acquired Ocular and Adnexal
Treatment involves physical eversion of the
Problems in the Foal
eyelid margin with temporary, nonabsorbable
Entropion/Ectropion sutures in a vertical mattress pattern (4-­0 silk)
Entropion is inversion of the margin of the or with surgical staples until the underlying
lower or upper eyelids. It may occur in foals as etiology has resolved or the foal has outgrown
614 Equine Ophthalmology

its entropion. Permanent reconstructive entro- Dacryocystitis


pion surgeries should be reserved for full-­ Dacryocystitis is inflammation of the tear
grown individuals. drainage system. Obstruction of the nasolacri-
Ectropion is eversion of the lower or upper mal apparatus is the most common cause of
eyelid margins and generally follows scarring of dacryocystitis and secondary infection often
the eyelids from severe trauma or burns. It is less develops. Copious mucoid to mucopurulent
common than entropion. Surgical correction is discharge at the medial canthus is the typical
necessary for ectropion if blepharospasm, cor- presenting sign. This condition is treated by
neal ulcers, or exposure keratoconjunctivitis is flushing of the tear drainage system to reestab-
present. lish patency and then administering systemic
antibiotics and anti-­inflammatory medica-
Eyelid Trauma tions. Topical steroids and mucolytic agents
Traumatic eyelid lacerations and forehead may be helpful if they are formulated as solu-
trauma can occur in foals and adults tions or suspensions so that they can pass
(Figure 15.12a and b). Upper eyelid lesions through the duct.
are more serious than lower eyelid injuries,
because upper eyelid provides the greater Conjunctivitis and Subconjunctival
degree of globe protection and its movements Hemorrhage
distribute tear film to prevent exposure kera- Conjunctivitis caused by environmental irri-
titis. Thus, preserving the eyelid margins to tants (e.g., hay, sand, dirt, ammonia, pollen,
prevent trichiasis and exposure-­induced and ash) is common in neonates, with recum-
ulcerative keratitis is critical. Excision of lac- bent foals being at particular risk. Conjunctival
erated pedicles of eyelid marginal tissue inflammation associated with pneumonia or
should be avoided. The prominent blood sup- other systemic infectious and inflammatory
ply to the eyelids generally allows acceptable conditions is often found in older foals (i.e., one
and functional surgical repair, as well as to six months of age). Epiphora, chemosis, and
faster healing. Two-­layer closure of skin– hyperemia are typical clinical signs. If bacterial
orbicularis muscle and tarsoconjunctival lay- conjunctivitis is present, the ocular discharge
ers is recommended to maximize healing and will become mucopurulent. Conjunctival cytol-
return to function ogy and culture can be useful in making the

(a) (b)

Figure 15.12 (a) Severe upper lid laceration in a horse. (b) Surgical repair of the laceration improved
function and appearance.
­Ocular Problems in the Equine Neonat  615

diagnosis of infectious conjunctivitis. Therapy


begins by flushing the conjunctival sacs to
remove any underlying irritant. Patency of the
NLD should be established, because duct
obstructions can exacerbate conjunctivitis.
Broad-­spectrum antibiotic ophthalmic solu-
tions or eye lubricants are indicated, and corti-
costeroid ophthalmic preparations are useful if
there are no corneal ulcers present.
Subconjunctival or episcleral hemorrhages
can result from birthing trauma and generally
resolve in 7–10 days. No treatment is necessary. (a)
Traumatic hemorrhages are generally quite
large and must be differentiated from the pete-
chial or ecchymotic hemorrhages suggestive of
a coagulation disorder.

Ulcerative Keratitis in Foals


A corneal ulcer is present when there is a break
in the corneal epithelium, most commonly
caused by trauma or exposure. Foals, espe-
cially those under intensive care, should be
monitored for the development of corneal (b)
ulcers. Foals with corneal ulcerations gener-
ally will exhibit less intense pain, blepharos- Figure 15.13 Corneal ulcerations in foals. (a)
Melting ulcer (keratomalacia) in a foal. The dark
pasm, and tearing than their adult counterparts. focus is a very thin in the center of the wound. (b)
This is likely due to immature sensory innerva- Fluorescein retention delineates the borders of a
tion. The corneal surface of superficial ulcers corneal ulcer.
can appear dull, cloudy, and roughened. In
rapidly progressive or infected ulcers, the cor- uveitis must be controlled for comfort and to
neal stroma may be “melting,” as the result of prevent blinding sequelae. Anterior uveitis in
keratomalacia. foals with corneal ulcers should be treated
Although many types of ulcers in foals are with both topical atropine and systemic non-
sterile, every corneal wound is susceptible to steroidal anti-­inflammatory drugs (NSAIDs).
infection with bacterial and fungal pathogens A reduction in the tear film and stromal pro-
(Figure 15.13a and b). Diagnostic testing to tease activity is also critical to healing of cor-
look for involvement of these agents should neal ulcers in foals, particularly since they are
always be performed. A superficial corneal prone to the development of melting ulcers.
ulcer that does not improve rapidly in 24–48 h, Melting ulcers in foals may be sterile (while
rough ulcer margins, increasing stromal opaci- those in adults are usually infected); however,
fication, deepening of the ulcer, and difficulty they may progress rapidly and catastrophically
maintaining mydriasis are often signs of ulcer if the enzymes responsible for corneal degra-
infection. Medical therapy for foals with ulcer- dation are not arrested. The appearance of a
ative keratitis does not differ substantially from gray, mucoid, gelatinous corneal exudate
that initiated for corneal ulcers in adults. should prompt immediate action. Autogenous
Bacterial and fungal growth must be halted or serum from the foal or its mare may also be
prevented with antimicrobial agents. Anterior quite effective in arresting corneal melting
616 Equine Ophthalmology

when administered topically every hour. Five autogenous serum or plasma with its growth
percent acetylcysteine or 0.17% dipotassium factors and anticollagenase activity can pro-
ethylenediaminetetraacetic acid (EDTA) may mote epithelial growth and prevent stromal
be used as well until stromal liquefaction is melting from tear proteases. If healing stag-
reduced. Combinations of these anticolla- nates despite debridement and medical ther-
genase drugs should also be considered if the apy, a keratectomy may be indicated.
ulcers are rapidly progressive. Surgery should
be considered if the integrity of the cornea is Iridocyclitis in Foals
compromised. Treatment must be sustained Systemic disease can cause blinding iridocycli-
until the stroma has firmed and the epithelium tis in foals; therefore, early recognition, diag-
has completely regenerated. nosis, and therapy are imperative. Septic foals
or those with another systemic inflammatory
Noninfectious Persistent Corneal disease such as pneumonia may be afflicted
Erosions in Neonates with anterior uveitis as a manifestation of their
Very slow-­healing, persistent, superficial cor- systemic disease. Salmonella sp., Rhodococcus
neal ulcers are commonly encountered in equi, Escherichia coli, Streptococcus equi sub-
recumbent, premature, and neonatal foals. species equi, Actinobacillus equuli, adenovirus,
These ulcers or erosions often fail to vascular- and equine viral arteritis have all been associ-
ize and affected foals may not exhibit a great ated with uveitis in affected foals.
deal of discomfort. Diminished corneal sensi- Lacrimation and blepharospasm are usually
tivity and low tear production in these foals the signals of ocular involvement and will
may be associated with the delayed corneal accompany corneal edema, conjunctival
healing of these superficial ulcers. If the foals hyperemia, ciliary injection, aqueous flare,
are blinking poorly, or keratoconjunctivitis hyphema, fibrin, and hypopyon in eyes with
sicca (KCS) or entropion is present, corneal iridocyclitis. Miosis is evident initially as the
ulcers will also heal slowly. hallmark of uveitis and it can result in dyscoria
Therapy is directed at treating any underly- as well as in anterior and posterior synechiae.
ing cause (such as tacking sutures from entro- Fibrin and pigment deposition on the anterior
pion), removing abnormal epithelium, and lens capsule and cataract formation are seque-
promoting adhesion of the epithelium to its lae to anterior uveitis in foals.
basement membrane and the stroma. The cor- As long as a corneal ulcer is absent, topical
nea should be topically anesthetized and the corticosteroids are the treatment of choice for
loose abnormal epithelium gently debrided anterior uveitis and these are usually accompa-
with dry, soft cotton swabs. Debridement may nied by mydriatic/cycloplegics and systemic
need to be repeated, or may require a more NSAIDs (as long as the systemic condition of
aggressive approach and the use of a diamond the foal warrants their use). If a corneal ulcer is
burr to minimize any suprastromal membrane present, that would preclude use of topical cor-
that may be inhibiting epithelial migration and ticosteroids but not topical NSAIDs.
adhesion. Many foals with systemic disease will
Antibiotic solutions are indicated to prevent develop fibrinous uveitis. Fibrin may fill the
infection. The triple antibiotic solutions are anterior chamber and span the pupil increas-
appropriate, while solutions containing gen- ing the chances of synechia and cataract for-
tamicin should be avoided as they can retard mation. If routine anti-­inflammatory therapy
corneal healing. Five percent sodium chloride does not result in rapid degradation of the
ophthalmic preparations are beneficial in anterior chamber fibrin (48–72 h), intracam-
removing the superficial corneal edema associ- eral administration of 25–150 μg tissue plasmi-
ated with persistent ulcers and topical nogen activator (tPA) under heavy sedation or
­Equine Orbi  617

general anesthesia may be used to accelerate infraorbital foramen and medial canthus can
fibrinolysis and clear the anterior chamber of result in NLD damage. The center of a line
foals with severe iridocyclitis. tPA should be between the medial canthus and facial crest
avoided if recent hemorrhage (<48 h) is pre- indicates the location of the caudal maxillary
sent, but can still be effective up to two weeks sinus. The sphenopalatine sinus is located
after clot formation. Depending on the cause, medial and ventral to the orbit. With the excep-
the overall prognosis for anterior uveitis is tion of the anterior maxillary sinus, all sinuses
guarded in foals, depending upon its severity in the horse communicate with one another.
and response to therapy. The owner should Sinus disease (infection, neoplasia, and other
be educated about the possibility of phthisis clinical abnormalities) involving the frontal,
bulbus, vision loss, and other potential maxillary, or sphenopalatine sinuses often
complications. intrudes upon the orbit of horses.
The lacrimal gland, orbital fat, and connec-
tive tissue fascia completely fill the orbital
­Equine Orbit spaces between the globe, extraocular muscles,
optic and other cranial nerves, and orbital vas-
The orbits and globes of the horse skull are cular elements of horses to provide a cushion
directed anteriorly, slightly dorsal, and are that protects these delicate structures from
positioned 80° lateral to the midline to allow injury during ocular movements. The lacrimal
for wide panoramic vision. The orbits of the gland is situated dorsolaterally between the
skull are bony cavities formed by the frontal, zygomatic process and the globe. It is sepa-
lacrimal, zygomatic, temporal, sphenoid, and rated from the globe by periorbital fascia, and
palatine bones, and function to protect the opens via 12–16 small ducts along the lateral
globe. The orbits of the horse are open anteri- part of the conjunctival sac in a line anterior to
orly, closed posteriorly, possess a soft tissue the dorsal conjunctival fornix. A cushion of fat
ventral floor, and contain osseous canals, fis- lies in the ventral equine orbit. Orbital disease
sures, and foramina. Sinuses surround the can result in exophthalmos because of space-­
orbit. The anterior rim of the bony orbit is occupying orbital lesions, or enophthalmos if
complete in the horse. This complete bony the volume of the orbital contents decreases
orbital rim anteriorly and bony orbital walls because of malnutrition, pathology, or surgery
posteriorly is a factor in the horse sustaining (Figure 15.14).
comparatively more orbital fractures than in Both the degree and direction of exophthal-
other domestic animals. Because of this bony mos depend on the size and location of the
protection and strong extraocular muscles, lesion. Intraconal lesions cause anterior dis-
horses rarely develop orbital trauma, except placement of the globe, whereas lesions of the
penetrating injuries. The essential components medial orbit displace the globe laterally. The
of the orbital connective tissues are the perior- nictitating membrane usually protrudes with
bita, the orbital septum, and the episcleral fas- exophthalmos, and if the exophthalmos is
cia or Tenon’s capsule. severe, exposure keratitis can then result
The frontal sinus is located dorsal and ven- because of inability of the lids to cover the cor-
tral to the medial orbit. The maxillary sinus is nea. Large space-­occupying masses, such as
located ventral and nasal to the orbit. The ante- tumors, bone fragments, or hematomas, can
rior maxillary sinus can be located just ventral limit globe motility and impair the ocular cir-
to the intersection of a line between the medial culation. The size of the exophthalmic globe is
canthus and infraorbital foramen, and a per- normal and should not be confused with the
pendicular line from the fourth cheek tooth. globe enlargement (i.e., buphthalmos) with
Trephination dorsal to a line between the advanced equine glaucoma.
618 Equine Ophthalmology

Frontal
Conchofrontal
sinus
Dorsal
canchal

Nasolacrimal duct

Caudal maxillary sinus

Rostral maxillary sinus

Figure 15.14 Periorbital sinuses. The frontal (conchofrontal), maxillary (caudal and rostral), and
sphenopalatine are in close anatomical proximity to the orbit.

Diagnostic Procedures orbital disease, especially if there is concern


for bone involvement. Magnetic resonance
Making the diagnosis of orbital disease usually
imaging is useful for characterizing soft tissue
requires imaging techniques in addition to a
disease.
complete ophthalmic examination. Commonly
used diagnostic imaging tools include orbital
Retrobulbar Nerve Blocks
ultrasound and skull radiographs.
Ultrasonography allows visualization of the Retrobulbar nerve blocks can facilitate ocular
retrobulbar soft tissue space and differentia- and orbital procedures performed standing or
tion between solid, soft tissue lesions and under general anesthesia required for enuclea-
cystic orbital lesions; however, evaluation of tion surgery by minimizing the depth of the
the extent of disease is not possible with ultra- plane of anesthesia necessary. Retrobulbar
sonography. The extensive overlap of the many blocks are standard of care for enucleation and
bones of the skull makes interpretation of exenteration procedures, and should be per-
skull radiographs challenging. Although com- formed in all cases undergoing these surgeries.
monly used, the extent and severity of injury For the supraorbital technique, a 22-­gauge 3.5-­
are not well characterized by these modalities. in. spinal needle is inserted through the surgi-
When possible, computed tomography (CT) is cally prepped skin of the supraorbital fossa just
the imaging modality of choice in equine caudal to the posterior aspect of the dorsal
­Equine Orbi  619

orbital rim. The needle is advanced until it evisceration. Implants should not be placed in
reaches the retrobulbar muscle cone. This can eyes with severe corneal disease, intraocular
be detected by slight dorsal movement of the neoplasia, or infectious panophthalmitis. The
eye. Once positioned, 10–12 ml of an anes- prosthesis provides a cosmetically acceptable
thetic agent (lidocaine, bupivacaine, or mepiv- globe with normal lid movements and globe
acaine) is injected into the orbit. Slight motility.
exophthalmos and mydriasis will occur with a
properly placed block. The four-­point block
Orbital Inflammation and Cellulitis
involves placing the needle through the con-
junctival fornices and dividing the volume of Perforation by a foreign body, direct trauma,
the block among the quadrants (dorsal, ven- and seeding by septic emboli are among the
tral, medial, lateral). more common causes of orbital cellulitis.
Extension of inflammatory and infectious con-
ditions from adjacent sinuses and cavities also
Surgical Techniques for the Orbit
occurs commonly. If sinusitis is present, treph-
Enucleation is the surgical removal of the ination into the affected sinus for the culture of
globe, conjunctiva, and nictitating membrane. exudate as well as irrigation and drainage is
There are two basic approaches to enucleation indicated. If septic endophthalmitis is
in the horse: the transpalpebral technique and untreated or is poorly responsive to therapy, it
the subconjunctival technique. The transpal- may progress to panuveitis and orbital celluli-
pebral technique is most useful in cases of tis. Orbital cellulitis is manifested by blephare-
severe corneal infection and conjunctival, nic- dema, swelling of the supraorbital fossa,
titating membrane or corneal neoplasia, but it exophthalmos, orbital pain, epiphora or
does leave a larger orbital soft tissue defect mucoid discharge, and protrusion of the nicti-
than the subconjunctival technique. The sub- tans, conjunctival hyperemia and chemosis,
conjunctival approach is quicker and associ- and sometimes lagophthalmos. Fever, elevated
ated with less hemorrhage. Orbital silicone white blood count, and general malaise may
prosthetic implants to improve cosmesis also be present. Orbital ultrasonography, CT,
(decrease orbital “pitting” or “sinkage”) may and fine needle aspiration may be helpful in
be used with either method. However, there is the diagnosis. Aggressive use of systemic
an increased risk of postsurgical infection NSAIDs and broad-­spectrum antibiotics is
when orbital prostheses are placed. indicated. Rarely is there a discrete fluid pocket
Orbital exenteration is a surgical technique in the abscess, so attempts at drainage are usu-
used to remove malignant tumors of the orbit ally not fruitful or effective. If there is no
that extend beyond the confines of the globe or response to therapy and the globe is damaged,
are likely to be unresponsive to chemotherapy then enucleation or exenteration may
or radiation therapy. In this procedure, the be needed.
entire orbital contents, including the perior-
bita, are surgically removed. Periosteal eleva- Orbital Fractures and Trauma
tors may be needed to remove the periorbital Fractures of the orbital bones may present
fascia; the remaining tissue is excised using with asymmetry of the globes or face, epistaxis,
scalpel or scissors. exophthalmos, eyelid and conjunctival swell-
The intraocular (sometimes referred to as ing, depression or concavity of the periorbital
intrascleral) prosthesis has been used in the region, crepitus, and sometimes pain on peri-
horse as a cosmetic alternative to enucleation. orbital palpation. Fractures of the dorsal
The intrascleral prosthesis replaces the intraoc- orbital rim are most common (Figure 15.15a
ular contents, which are removed by and b) because the dorsal orbital rim protrudes
620 Equine Ophthalmology

ophthalmic examination and digital palpation.


Imaging by radiography, and preferably CT,
should be performed prior to considering sur-
gical intervention. Skyline views are helpful
for the orbital rim, but they can be difficult to
interpret
Periorbital fractures should be repaired
quickly, because fibrous union of the fractured
pieces begins within one week after injury
making elevation and realignment difficult.
Minor orbital rim fractures that are closed and
nondisplaced may not require surgical correc-
tion unless fracture fragments are impinging
on the globe. Any section of bone that is
impinging on the globe or orbital contents
needs to be reduced or removed. With the
horse placed under general anesthesia, zygo-
matic process fractures may be reduced or
(a) closed by manipulation of the bone piece into
position using a bone hook. Monofilament
stainless steel wire suture (20–22 gauge), cer-
clage wire, small orthopedic pins, and orthope-
dic bone plates and cancellous bone grafts are
used to stabilize bone fragments and to immo-
bilize and repair extensive orbital fractures.
Open fractures typically are managed by
debridement and cleaning of the wound,
reduction of displaced by viable bone frag-
ments, and removal of small, grossly contami-
nated fragments. Depending on the extent of
contamination, some or all of the wound is left
open for adequate drainage, or drains are
(b) placed to facilitate healing.
The complete bony orbital rim of the horse
Figure 15.15 (a) Fractures of the dorsal orbital generally protects against traumatic globe
rim are most common in horses, likely because the proptosis, but this problem has been reported
dorsal orbital rim protrudes externally and
on occasion with severe injuries. In most
laterally, and thus is highly vulnerable to trauma.
(b) Fracture of the dorsal orbital rim of a horse that instances, the degree of damage sustained by
resulted in ventral deviation of the globe and the orbit and the globe necessitates
ventral strabismus. enucleation.

externally and laterally and is thus highly vul-


Orbital Neoplasia
nerable to trauma. These fractures may result
in displacement, impingement, functional Neoplasia of the equine orbit is less common
restriction, or laceration of the globe. than that in other domestic species. The most
Diagnosis and assessment of orbital rim frac- common neoplasia of the posterior orbit are
tures should be accomplished by a thorough neuroendocrine tumors and extra-­adrenal
­Diseases and Surgery of the Eyelid  621

can usually be excised and the conjunctival


and fascia rent closed to prevent recurrence.

­ iseases and Surgery


D
of the Eyelids

Entropion
Entropion is an inward rolling of the eyelid
margin. Entropion in adults may be cicatricial
from previous eyelid trauma, or it may be
acquired or spastic secondary to chronic ocular
irritation causing spasms of the orbicularis
oculi muscle. Before attempting entropion
therapy, concurrent ocular problems such as
blepharitis, distichiasis, and corneal disease
should be identified and treated. The amount
of surgical correction for entropion in mature
Figure 15.16 Extension of SCC from the eyelids
and the nictitans into the orbit. horses must be estimated before general anes-
thesia and after local nerve block and a topical
paraganglioma. Squamous cell carcinoma anesthetic has been applied to the ocular sur-
(SCC) is the most common adnexal tumor that face. It is important to determine how much of
extends secondarily into the orbit the entropion is anatomical and how much is
(Figure 15.16). Other reported orbital tumors secondary to spasm from ocular pain. For opti-
in the horse include anaplastic sarcoma, lym- mal results, surgical techniques should always
phoma, lipoma, adenocarcinoma, lymphosar- undercorrect slightly. The modified Hotz–
coma, melanoma, meningioma, and others. Celsus procedure is simple and can be adapted
Progressive exophthalmos, displacement of to most types of entropion in the horse.
the nictitans, conjunctival hyperemia and che-
mosis, orbital swelling, bone surface distor-
Eyelid Lacerations
tion, blindness, strabismus, anisocoria,
behavioral abnormalities, and, less commonly, Eyelid trauma and lacerations are common in
epistaxis and signs referable to the involve- the horse, especially in young animals. A com-
ment of adjacent cavities are reported symp- plete ocular examination is very important to
toms in horses with orbital tumors. Although assess corneal integrity, anterior chamber clar-
surgical removal and salvage of the eye is pos- ity and depth, and scleral continuity since
sible early in the disease process, most cases damage to the globe, orbital cellulitis, orbital
require exenteration of the orbit. or periorbital fractures, corneal ulceration,
uveitis, hyphema, or posterior segment inju-
Orbital Fat Prolapse ries such as retinal detachment may accom-
Orbital fat may herniate through weakened pany the lid damage. Damage to the upper
episcleral fascia or from trauma, resulting in eyelid is most significant, however, because
lobular, subconjunctival masses that may most of the globe coverage and protective func-
resemble tumors. Aspiration, biopsy, and cyto- tions of the eyelids are performed by the upper
logical evaluation of these masses reveal the eyelid. Medial canthal lacerations may result
presence of adipose cells. The affected tissue in damage to the nasolacrimal canaliculi.
622 Equine Ophthalmology

Due to the excellent blood supply to the eye- found on horses during the warm weather
lids, most lacerations can be repaired to achieve months. House and stable flies serve as vectors
a relatively well-­functioning and cosmetic eye- to transmit eggs and larvae to these warm,
lid. Therefore, every attempt should be made moist periocular sites. Cytology from affected
to surgically repair all eyelid lacerations, tak- sites reveals numerous eosinophils, mast cells,
ing care to avoid cutting any hanging eyelid polymorphonuclear cells (PMNs), and plasma
pedicles (Figure 15.17a and b). Failure to repair cells. Larvae may be identified on histopathol-
a laceration, or amputation of a torn eyelid ogy of affected tissue. Topical therapy for soli-
pedicle rather than a surgical repair, can result tary, focal lesions of habronemiasis consists of
in exposure-­induced corneal disease. a mixture containing 135 g of nitrofurazone
ointment, 30 ml of 90% dimethyl sulfoxide,
30 ml of 0.2% dexamethasone, and 30 ml of
Blepharitis
12.3% oral trichlorfon solution. Multifocal
Primary bacterial blepharitis is uncommon in lesions should be treated with systemic aver-
the horse. Eyelid abscesses associated with for- mectins and intralesional corticosteroid injec-
eign bodies, SPL lavage systems, and bony tions (i.e., triamcinolone) and systemic
sequestra have been reported. Dermatophytosis anti-­inflammatory medications.
resulting from Trichophyton or Microsporum
sp. may cause blepharitis as well, but usually
Eyelid Neoplasia
there are skin lesions elsewhere on the body
concurrently. Habronemiasis is a common Neoplasia of the equine eyelids is very com-
cause of equine granulomas of the eyelids, mon and can be one of the most challenging
conjunctiva, lacrimal caruncle, medial can- periocular diseases to manage. SCC is the most
thus, and nictitans. Infection of periocular tis- common neoplasm, followed by sarcoids, but a
sue by Habronema larvae is a common cause variety of other neoplasms have been reported.
of conjunctivitis or blepharitis. Nonhealing, Periocular neoplasia, in general, should always
elevated, and ulcerated periocular granulomas be confirmed with histopathology, and treated
with fistulous tracts and a yellow, caseous exu- early and aggressively. Recurrent disease is
date (“sulfur-­like” granules) consisting of always more resistant to treatment and is
gritty foci of necrotic mineralized tissue are more likely to result in poor cosmesis and

(a) (b)

Figure 15.17 Eyelid lacerations are often full-­thickness and require exact reconstruction. (a) Upper eyelid
laceration with a hanging pedicle. This should be reapposed rather than excised. (b) Meticulous apposition
of the eyelid margin is critical to postoperative function and comfort, particularly with upper eyelid wounds.
­Diseases and Surgery of the Eyelid  623

compromise of the globe. In advanced cases, Actinic solar keratitis may transform to carci-
especially in untreated chronic SCC, local and noma in situ SCC that often appears as hyper-
distant metastases can occur, resulting in emic eyelid erosive plaques with dark-­staining
mortality. crusts, to eventually become papillomatous
SCC or, alternatively, SCC may appear as a
Squamous Cell Carcinoma raised mass with a pink, cobblestone appear-
SCC is the most common neoplasm of the eye ance (Figure 15.20a and b), to ultimately
and adnexa in the horse. Horses with a lack of develop into large, fleshy masses with variable
periocular pigmentation are at increased risk degrees of ulceration, necrosis, and
for development of SCC. An increased preva- inflammation.
lence of ocular SCC may occur with age, and a Treatment for SCC is highly variable, and
breed predilection for draft breeds and commonly reported therapies are summarized
Appaloosas has been reported. Development in Table 15.1 and Figure 15.21. In one large ret-
of SCC is associated with various environmen- rospective study of equine ocular SCC, a main
tal factors, including geographic influences of key to long-­term success of management was
increased longitude, decreased latitude, found to be the owner’s willingness to return
increased altitude, and increased mean annual horses for reexamination. Untreated ocular
solar radiation exposure. Ultraviolet radiation SCC can invade local soft tissues, the bony
is strongly correlated with SCC. Cyclooxygenase orbit, sinuses, and brain, and it can metasta-
(COX)-­derived prostaglandins (COX-­2) may size to the regional lymph nodes, salivary
also be responsible for tumor growth, metasta- glands, and thorax.
sis, and angiogenesis. Eyelid SCC is treated with excision and
The most common ocular locations for SCC adjunctive therapy using cryotherapy (−20 and
are the nictitating membrane or medial can- −40 °C using a double freeze–thaw technique),
thus (approximately 28%) (Figure 15.18), lim- intralesional chemotherapy (i.e., cisplatin, car-
bus (approximately 28%), and lower eyelid boplatin, and 5-­fluorouracil), immunotherapy
(approximately 23%) (Figure 15.19). Other (i.e., Bacillus Calmette–Guerin [BCG] cell wall
locations such as the cornea, conjunctiva, and extract; 1 ml extract/cm3 tumor), brachyther-
orbit represent approximately 21%. The appear- apy (i.e., iridium-­192 and cesium-­137), hyper-
ance of adnexal SCC can vary from erosive thermia (50 °C for 30 s at 3–4 mm in and
lesions resembling wounds to proliferative beyond the tumor margin), or CO2 laser abla-
lesions that can be raised and expansive. tion (3–8 W and the tumor lasered until it is

Figure 15.18 SCC is the most frequent


ophthalmic neoplasm in the adult horse. SCC of the Figure 15.19 Extensive SCC that has effaced the
nictitating membrane. entire lower eyelid.
624 Equine Ophthalmology

(a) (b)

Figure 15.20 SCC presents as either a mass or an ulcerated area. (a) SCC may appear as a raised mass with
a pink, cobblestone appearance, as seen in this horse with an eyelid SCC or (b) SCC may appear as erosive or
ulcerative lesions with variable degrees of necrosis and inflammation.

Table 15.1 Treatment for periocular squamous cell carcinoma.

Reported %
Type of therapy Treatment Therapy non-­recurrence

Intralesional Bacille 1 mL/cm2 of tumor surface. Repeat 100%


immunotherapy Calmette-­Guérin every 2–4 weeks (1 of 1 case)
Intralesional Cisplatin 1 mg/cm3 every 2 weeks for 4 71%
chemotherapy treatments
Surgical excision Excision Once 56%
Excision and cryotherapy Cryotherapy Double or triple freeze—­thaw 33%–100%
Excision and PDT 1 mg/cm2 of tumor bed area followed 80%–100%
photodynamic therapy by application of appropriate light
(PDT) source 10 J/cm2 and 200 mW/cm2
Hyperthermia Hyperthermia Tissue temperatures between 41°C 75%–100%
and 45°C
CO2 laser Laser ablation Ablate tissues 100%
Brachytherapy Radon, cobalt, gold, 5000–25,000 cGy 74%–100%
iridium, strontium

(a) (b)

Figure 15.21 There are many therapeutic options for SCC. Early and aggressive therapy is associated with
the highest rates of success. (a) Lower eyelid SCC with pre-­placed needles prior to the administration of
local chemotherapy. (b) Cryotherapy applied to an eyelid SCC.
­Diseases and Surgery of the Eyelid  625

covered with a brown char), or photodynamic Periocular sarcoids are most commonly nodu-
therapy (PDT), among others. Intralesional lar, fibroblastic, or mixed (Figure 15.22a–d).
chemotherapy may be effective; however, dili- The fibroblastic form is very locally aggressive,
gent monitoring and rebiopsy to determine and intervention can convert the verrucous to
whether the site is tumor-­free is critical. At the fibroblastic form. A variety of etiologies
least four sessions at two-­week intervals with have been proposed or suspected including ret-
1 mg cisplatin or carboplatin/cm3 for tumors roviruses and bovine papillomaviruses. Flies
10–20 cm3 in size are necessary. may also initiate sarcoid formation by translo-
Third eyelid/medial canthal SCC generally is cating sarcoid cells into open wounds of horses.
treated with excision of the third eyelid with A surgical biopsy is always required for
adjunctive treatment such as cryotherapy, definitive diagnosis, but treatment needs to be
brachytherapy, and possibly (depending on the done concurrently or soon after the biopsy
extent of the lesion) intralesional chemother- since the mass usually is stimulated to prolifer-
apy, PDT, or immunotherapy. Piroxicam ate after the surgical trauma of the biopsy.
(80 mg p.o. s.i.d.) has been reported to have Overlying skin should be included in any
some palliative effects for periocular SCC in biopsy taken since the histopathological diag-
the horse. Recurrence rates of periocular SCC nosis depends upon recognition of epidermal
when treated with both surgical excision and hyperplasia and dermal fibroplasia, with pegs
an adjunctive therapy range from 25% to 67%. of hyperkeratotic epithelium extending into
Rechecks for recurrence should continue for the depths of the dermal lesions. Various treat-
three to five years after treatment. The key to ments have been reported for the treatment of
success in the treatment of adnexal SCC in the equine periocular sarcoids (Table 15.2).
horse is early recognition and aggressive treat-
ment combined with diligent and continued Melanoma
monitoring for recurrence. Melanoma is a relatively uncommon tumor of
the horse and usually is observed in gray
Sarcoids horses. Arabians and Percherons have an
Sarcoids are solitary or multiple cutaneous increased risk (Figure 15.23). A slowly progres-
tumors of fibroblastic origin and have prolifer- sive, cutaneous, partially alopecic, pigmented
ative and hyperplastic epithelial components, mass of the eyelids is the typical clinical
and while metastasis is rare, recurrence is appearance of most equine adnexal melanoma.
common. Periocular/eyelid sarcoids are com- Caruncular and conjunctival melanomas may
mon and may result in significant pathology to appear as just a flat or nodular firm pigmented
the eye either by disrupting normal eyelid lesion. The size and location of the mass will
function or by directly rubbing on the eye. dictate the clinical signs, which may include
Sarcoids usually develop in young horses mild blepharospasm and corneal irritation.
under seven years of age, although they have Older horses are predisposed to the develop-
been reported in animals of all ages. Nearly ment of melanoma, possibly because prolifera-
all breeds have been reported to develop tion of melanocytes is a manifestation of aging.
sarcoids, but Quarter Horses, Appaloosas, Oral cimetidine (2.5 mg/kg p.o. t.i.d.) has
Thoroughbreds, and Arabians may be at been used to shrink nonocular melanomas in
increased risk, while Standardbreds and horses, but no studies have been published on
Lippizaners may be at decreased risk. There this treatment modality for adnexal melano-
are a variety of clinical types and appearances, mas. Surgical excision, CO2 laser ablation, cryo-
including occult, hyperkeratotic fibropapil- therapy, and local PDT have been recommended.
loma (i.e., verrucous), nodular types A and B, Excision of an eyelid melanoma is usually cura-
fibroblastic types A and B, and mixed forms. tive because most of the masses are benign.
626 Equine Ophthalmology

(a) (b)

(c) (d)

Figure 15.22 Sarcoids are the second most frequent ophthalmic neoplasm in adult horses. (a) Fibroblastic
sarcoid. (b) Nodular type B periocular sarcoid. (c) Intralesional injection of BCG treatments. (d) Following a
series of intralesional BCG treatments, the sarcoid resolved with some scar formation.

Table 15.2 Treatment for periocular sarcoids.

Reported %
Type of therapy Treatment Therapy non-­recurrence

Topical therapy 5% 5-­fluorouracil BID × 5 days, then qd for 67%


5 days, the QOD for 5
applications
Intralesional Bacille 1 mL/cm2 of tumor surface. 0%–100%
immunotherapy Calmette-­Guérin Repeat every 2–4 weeks
Intralesional Cisplatin 1 mg/cm3 every 2 weeks for 4 33%–95%
chemotherapy treatments
Surgical excision Excision Once 50%
Excision and cryotherapy Cryotherapy Double or triple freeze—­thaw 8%–18%
Hyperthermia Hyperthermia Tissue temperatures between 0%
41°C and 45°C
Brachytherapy Radon, gold, iridium 6000–9000 cGy 87%–100%

Modified from Giuliano (2011).


­Diseases of the Nictitating Membran  627

Figure 15.24 Nodular conjunctival lymphoma in


Figure 15.23 Multiple melanomas of the eyelids, a horse.
caruncle, and conjunctiva in a gray horse. Adnexal
melanomas are usually slowly progressive,
cutaneous, partially alopecic, pigmented masses. reported to have good success and a low rate of
recurrence if there are only a few distichiae.
Lymphoma
Lymphoma (LSA) is a relatively uncommon
neoplasm in the horse. Infiltration of the eye- ­Diseases of the Conjunctiva
lids and conjunctiva is the most common ocu-
lar manifestation of LSA, but orbital and/or Conjunctivitis is a nonspecific indicator of
third eyelid involvement can also occur ocular inflammation. The conjunctiva becomes
(Figure 15.24). Adnexal LSA must be differen- inflamed during infectious and noninfectious
tiated from other tumors or causes of swelling. diseases of the lids, cornea, sclera, anterior
Biopsy and histopathology are required for uvea, nasolacrimal system, and orbit, as well as
definitive diagnosis. LSA should be differenti- a variety of systemic diseases. Conjunctivitis is
ated from conjunctival pseudotumors’ which found in the neonatal-­onset systemic diseases
can be unilateral or bilateral, nodular or of neonatal maladjustment syndrome, neona-
smooth, pink, nonulcerated conjunctival tal septicemia, and immune-­mediated hemo-
masses. A recent retrospective series of lytic anemia. Unfortunately, a large number of
extraocular lymphoma determined that the horses with the insidious form of equine recur-
prognosis for clinical remission in horses with rent uveitis (ERU) receive diagnoses of allergic
solitary extraocular lymphoma is generally fair conjunctivitis without recognition and diagno-
to good, as long as the affected tissues are com- sis of their intraocular disease and the chroni-
pletely excised, and there is no eyelid, cutane- cally untreated uveitis leads to vision loss and
ous, or systemic involvement. discomfort.
Eyelash Disorders
Distichiasis resulting in corneal irritation or
ulceration and blepharospasm has been ­ iseases of the
D
reported in the Friesian horse. This condition Nictitating Membrane
in rarely reported and although possible in any
individual or any breed, the Friesian horse Protrusion of the nictitans is usually a sign of
appears to be predisposed. Electrocautery or pain. The eye should be examined for conjunc-
cryotherapy of the offending hair follicle per- tivitis, corneal ulcers, or anterior uveitis.
formed in the standing, sedated animal is Tetanus, inflammation because of bacteria,
628 Equine Ophthalmology

trauma, or parasites, enophthalmos because of may be considered in these cases. Correction of


pain, decreased globe size (microphthalmos or primary sinus or dental disease should be done
phthisis bulbi), protrusion of orbital fat, to minimize pressure on the NLD.
Horner’s syndrome, hyperkalemic periodic
paralysis, foreign bodies behind the nictitans
or in the conjunctival fornices, and neoplasia ­ iseases of the
D
can all cause protrusion of the third eyelid. Equine Cornea

The most common ophthalmic disease of the


­Nasolacrimal Disease horse is corneal ulceration. Ulcerative keratitis
is a major problem in horses because of the
Acquired nasolacrimal disorders include propensity for horses to develop bacterial and
obstructions from inflammation (dacryocysti- fungal infections and difficulty treating the
tis), strictures, foreign bodies, diseases of the animal. Horses also are afflicted with various
paranasal sinuses, diseases of the upper dental other inflammatory and non-­inflammatory,
arcade, neoplasia (especially SCC), and external nonulcerative keratopathies, including the
trauma. Obstruction of the NLD occurs most common group of diseases termed immune-­
commonly from accumulation of foreign mate- mediated keratitis (IMMK).
rial followed by bacterial growth and inflamma-
tion (i.e., dacryocystitis) in the NLD. Clinical
Corneal Anatomy
signs of NLD obstruction include epiphora,
conjunctivitis, and usually mucopurulent dis- The cornea is the transparent, anteriormost
charge. Initial diagnosis is made following a part of the fibrous tunic of the globe. It is nour-
complete normal ophthalmic examination (no ished anteriorly by the precorneal tear film and
cause of ocular discomfort found) and the ina- posteriorly by the aqueous humor. In healthy
bility of topical fluorescein dye to exit the ven- animals, the cornea is avascular and is the
tral nasolacrimal punctum (a negative Jones major contributor to light refraction or focus-
test). If mucopurulent discharge is present, bac- ing capacity. The horse cornea ranges in thick-
terial culture and sensitivity, and cytology of the ness from 0.770 to 0.893 mm, with the
discharge should be performed prior to admin- peripheral cornea being relatively thicker than
istering additional medications. Following the central regions. The cornea is comprised of
these tests, retrograde and normograde nasolac- three main layers: an outer multilayer epithe-
rimal irrigation should be attempted with the lium, a middle stroma, and an internal mon-
horse tranquilized. If irrigation is successful at olayer endothelium. The epithelium provides
clearing an obstruction, copious irrigation of the outermost protective barrier for the eye
the NLD should then be performed to ensure all and when intact is very effective at preventing
debris has been cleared. Unsuccessful NLD irri- invasion of the deeper corneal structures by
gation attempts with the horse under standing pathogens. The stroma makes up 90% of the
sedation warrant additional diagnostic testing corneal thickness and is poorly cellular. It con-
such as DCR via radiology or CT to locate site of sists of very regularly arranged collagen fibers
obstruction and assess the surrounding struc- and a matrix of proteoglycans. Deep to the
tures. The #5 French male silastic or plastic stroma is the basement membrane of the inner-
canine urinary catheter can be threaded either most endothelium, known as DM. This struc-
normograde (from proximal to distal) or retro- ture is much more easily appreciable than the
grade with an attempt to pass through or break epithelial basement membrane and thickens
up the obstructions. Use of oral anti-­ with age due to continued secretion. The density
inflammatory and oral antibiotic medication of horse endothelial cells is 3155 cells/mm2.
­Diseases of the Equine Corne  629

The number of equine endothelial cells immune and inflammatory cells to the site of
decreases with age. The cornea is innervated injury and may prevent perforation. Within the
diffusely by the long ciliary nerves, which arise first 12–24 h of injury, inflammatory cells such
from the ophthalmic division of the trigeminal as neutrophils, lymphocytes, macrophages, and
nerve (cranial nerve V) and terminate in naked monocytes enter the stroma via the precorneal
nerve endings in the anterior stroma and tear film and conjunctival blood vessels at the
among the wing cells of the corneal epithe- limbus. Once present, the inflammatory cells
lium. The cornea of the adult horse is very sen- work to scavenge the remnants of necrotic and
sitive with the central cornea the most sensitive apoptotic cells and remove any invasive micro-
region and the dorsal region the least sensitive. organisms in the vicinity. They do so by liberat-
Corneal sensitivity is lower in neonatal foals ing proteolytic enzymes and phagocytizing
and in sick animals compared to healthy adults. cellular and noncellular debris. If upregulated
or produced in excessive amounts, these proteo-
lytic enzymes, which include the serine pro-
Corneal Wound Healing
teases and matrix metalloproteinases (MMPs),
The basic response to injury occurs with little can contribute to progression of the original
variation, regardless of whether the stromal injury. Tear film proteases are elevated by two to
wound was created by trauma, infectious dis- four times normal levels in horse eyes with cor-
ease, surgical intervention, or other etiologies. neal ulcers, and must be reduced to baseline lev-
Epithelial defects will generally heal rapidly (as els before healing is complete.
much as 0.6 mm/day in the uncomplicated Vascularization is an expected healing
wound) via centripetal migration of basal epi- response and can provide a range of cells and
thelial cells surrounding the wound into the growth factors that encourage healing and
defect and mitotic replication of limbal stem structural integrity; however, blood vessels
cells to reform the normal epithelial structure. have the unwanted consequence of increasing
With stromal defects, the edges of the wound are corneal opacity. Corneal vascularization may
initially debrided by PMNs and then keratocytes occur at a rate of ~1 mm/day in the horse if
adjacent to the wound transform into fibroblasts unimpeded by pharmacotherapy or host or
and begin to synthesize collagen and proteogly- pathogen response.
cans to replace those missing from injury or
infectious destruction. Since the process of stro-
Perforating Injury
mal regeneration is more complex than that of
reepithelialization, it can be considerably more If a wound results in a full-­thickness rent in the
time consuming. The stroma that is initially laid cornea, the exposed hydrophilic stroma swells
down is disorganized and results in a scar. Over when exposed to tears and aqueous humor. This
time, this hastily produced collagen will be reor- swelling may seal the wound if there is not a
ganized, which is how scars fade and become large gap or a large degree of tissue loss. With
less dense. When the endothelium is damaged, larger defects, a temporary plug is formed. If the
its ability to regenerate is quite limited. Cells that wound is too expansive, surgical stabilization is
die are not replaced by new cells, instead the indicated to replace missing tissue.
adjacent cells spread out and hypertrophy.
Corneal Infections
Inflammation
Once a pathogen has eluded the passive adap-
Inflammation in most tissues is the appearance, tations of the innate immune system, the cor-
proliferation, and dilation of blood vessels. neal response to infection is a combination of
Blood vessels dramatically facilitate delivery of innate and active immune responses and
630 Equine Ophthalmology

inflammation. The nonspecific responses absence of cellular infiltration (white or yellow


include the production and upregulation of stromal infiltrate). It is important to approach
antimicrobial proteins that prevent adhesion, each case of ulcerative corneal disease in the
inactivate bacterial proteases, impair microbial horse in a systematic manner. If the ulcer is
growth, or physically degrade the cell walls of chronic (e.g., greater than five to seven days in
pathogens and the recruitment of phagocytic duration) or if there is cellular infiltrate or sig-
cells that kill and remove microbes. nificant uveitis present, then culture (bacterial
Inflammation results in increased blood flow and fungal culture and sensitivities) should be
and leukocyte delivery and recruitment from collected, followed by a Schirmer tear test
the conjunctiva, tear film, and areas of corneal (STT), and then application of fluorescein dye.
vascularization. While the profound response Corneal cultures should be obtained first, and
to infection is necessary for elimination of the then followed by corneal scrapings for cytol-
offending organism, it may contribute to fur- ogy. Sampling the edge and base of the lesion
ther damage of host tissue and the formation to detect bacteria and hyphal elements can be
of fibrosis and corneal opacity. done with the blunt handle end of a sterile
The environment of the horse is such that scalpel blade, Kimura spatula, or a cytology
the conjunctiva and cornea are constantly brush after application of topical anesthesia.
exposed to bacteria and fungi. The conjuncti- While all techniques for collection are accept-
val microbial flora of the horse varies, how- able, the highest quality specimens are col-
ever, depending on the age of the horse, season, lected via the scalpel blade technique
and the geographic area. Many bacterial and (Figure 15.25a–e).
fungal organisms normally found in the equine
conjunctival flora are potential ocular patho- Principles of Therapy
gens. Fusarium and Aspergillus sp. are both for Ulcerative Keratitis
common causes of ulcerative fungal keratitis Regardless of the stage or condition of the cor-
among horses in the United States. Gram-­ neal ulcer, the goals of therapy are identical
negative bacteria known to be associated with (Table 15.3): Horses with corneal ulcers are
equine corneal ulcers include Pseudomonas sp. often in pain, and topical treatment is usually
and assorted coliform bacteria. Staphylococcus, difficult. In a fractious horse or one with a
Listeria, and Streptococcus sp. and other Gram-­ painful eye needing frequent therapy, SPL
positive bacteria can cause infectious equine treatment systems are recommended. Various
keratitis. Mixed bacterial and fungal infections techniques have been described, but we prefer
can also be present. The intrastromal spread of to use a length of silicone tubing with a single
the pathogen is facilitated by production of hole and footplate positioned in the superior
serine proteases, elastase and alkaline pro- palpebral fornix. SPL kits are manufactured
tease, and the MMPs. and distributed commercially (Mila
International, USA) or can be made in-­house if
silastic tubing can be acquired (Figure 15.26).
Ulcerative Keratitis
Diagnosis Medical Therapy
Prior to instilling any medication, the palpe- Antimicrobials
bral conjunctiva and bulbar surface of the The ulcer must be sterilized although sterility
third eyelid are examined for the presence of a does not necessarily equate with rapid or com-
foreign body, the palpebral reflex and corneal plete healing. Infection initiates and compli-
reflex are evaluated, and the tear film is exam- cates ulcerative disease processes, but the
ined. A corneal ulcer should be characterized increased proteinase activity in the precorneal
with regard to size, depth, and the presence or tear film (PTF) and stroma perpetuates it. There
­Diseases of the Equine Corne  631

(a) (b)

(c) (d)

(e)

Figure 15.25 Corneal ulcers are characterized by the loss of epithelium and retention of topical
fluorescein. (a) Superficial ulcer exhibiting loss of only epithelium. Corneal edema surrounds the wound. (b)
Fluorescein retention in the stroma of the wound bed. (c) The deeper stromal ulcer exhibiting loss of
epithelium and anterior stroma. (d) Descemetocele. All stroma is missing, which exposes DM. This lesion is
chronic, as evidenced by the ring of vascularization and fibrosis surrounding the ulcer. (e) Full-­thickness
corneal wound. Perforation of the cornea was followed by prolapse of the iris. There is severe infiltration of
the cornea with inflammatory infiltrate and a robust vascular response.

are many considerations when choosing a topi- B may be appropriate to treat Gram-­negative
cal antibiotic for ophthalmic use, including bacterial infections. Cephalosporins, mac-
spectrum of action, bacteriostatic versus bacte- rolides, tetracyclines, second-­generation and
ricidal nature, relative toxicity, formulation, and higher fluoroquinolones, and drugs such as
the condition of the eye. The aminoglycosides, chloramphenicol and gramicidin have good
fluoroquinolones, and drugs such as polymyxin action against Gram-­positive bacteria.
632 Equine Ophthalmology

Table 15.3 Goals of corneal ulceration therapy keratitis. Uveal inflammation is incited
in the horse. through an axon reflex mediated by the oph-
thalmic branch of the trigeminal nerve, which
1) Address any primary underlying etiology if
is sensory for the cornea, conjunctiva, and
one can be identified
uvea. Miosis, aqueous flare, hypopyon, and
2) Treat or prevent infection
hypotony are present to some degree in eyes
3) Slow the breakdown/dissolution of corneal
with ulcers. Controlling the uveitis may be as
collagen
difficult as healing the cornea.
4) Address secondary uveitis
Anterior uveitis in horses with corneal ulcers
5) Provide structural support, if necessary; should be treated by both the topical and the
prevent self-­trauma
systemic route. Phenylbutazone (2 mg/kg p.o.
6) Analgesia
b.i.d.) or flunixin meglumine (1 mg/kg p.o., i.v.,
i.m. b.i.d.) can be used orally or parenterally at
anti-­inflammatory dosages, although flunixin
has the better clinical effect of the two agents.
Topically applied anticholinergics (e.g., 1%
atropine) are effective in causing pupillary
dilation and stabilizing the blood–aqueous
barrier. Pupillary dilatation protects the visual
axis from occlusion, and it may minimize
development of synechiae. Relaxation of the
ciliary muscles also eliminates ciliary spasm,
which is a factor in ocular discomfort. Horses
on topical atropine should be watched closely
for symptoms of reduced gut motility and, in
rare cases, colic. The frequency of administra-
tion will vary with the degree of uveitis present
Figure 15.26 SPL lavage treatment system placed (q 4–24 h).
in the upper conjunctival fornix.
Collagenolysis Prevention
Miconazole, natamycin, fluconazole, voricon- Activation or production of proteolytic
azole, clotrimazole, itraconazole, silver sulfadia- enzymes (or both) by corneal epithelial cells,
zine, and dilute betadine solution have been leukocytes, and microbial organisms is
used successfully topically to treat fungal ulcers responsible for stromal collagenolysis. MMPs
in the horse. Newer antifungal agents, including and serine proteases are elevated in the tears
posaconazole and caspofungin, have been used of eyes with an ulcer and may be inhibited by
with success in a few instances. Antifungals (q tissue inhibitors of metalloproteinases,
2–6 h) may need to be used for several weeks serum, EDTA, tetracyclines, ilomastat, and
since the offending agents are relatively long-­ acetylcysteine. Autologous serum and plasma
lived and large compared to bacteria and because have also been successfully used in the treat-
most antifungals are fungistatic rather than fun- ment of severe dry eye, persistent epithelial
gicidal. Systemic antifungals may be beneficial, defects, and other severe ocular surface disor-
but their true efficacy and impact are not known. ders. It is supposed that growth factors,
fibronectin, and vitamins in serum support
Control of Uveitis the proliferation of corneal epithelial cells.
In the horse, as in other species, iridocyclitis is Serum eye drops may be produced as an
the usual and expected sequela to ulcerative unpreserved blood preparation.
­Diseases of the Equine Corne  633

Inappropriate Therapy
Topical corticosteroids are contraindicated in
treatment of equine corneal infections. Even
topical corticosteroid instillation to reduce the
size of a corneal scar or reduce blood vessels
perfusion may be disastrous if pathogens
remain indolent in the corneal stroma or on
the ocular surface. Topical NSAIDs may delay
reepithelialization of the cornea and therefore
are also contraindicated.

Figure 15.27 Indolent ulcer with characteristic


Superficial Uncomplicated hyperplastic and nonadherent “lip” of epithelium
Corneal Ulcers along its margins. Blood vessel advancement
speaks to the subacute to chronic nature.
A superficial uncomplicated corneal ulcer
should have no microorganisms (on culture or with corneal ulcer healing. Treatment of indo-
cytology), no cellular infiltrate, no foreign lent ulcers requires searching for an underly-
body, and no secondary uveitis. Treatment for ing cause (foreign bodies, ectopic cilia, eyelid
an uncomplicated superficial ulcer should abnormality, and repeated trauma). Cytology
consist of a topical broad-­spectrum antibiotic and bacterial and fungal cultures should be
every 6 h (e.g., neomycin, bacitracin, gramici- carried out to eliminate an infectious etiology.
din, and ofloxacin); topical 1% atropine once Typically, the lesions are sterile and there is no
daily or as needed to keep the pupil dilated; contributing abnormality of the eyelids or pal-
and treatment of any secondary uveitis, if pre- pebral conjunctiva. If an underlying or con-
sent (e.g., systemic NSAIDs). tributing factor is not identified, the ulcer is
then designated as indolent. The etiology is
Complicated Corneal Ulcers poorly understood in all species, but is likely to
Complicated corneal ulcers are those that do involve a complex process of failure of normal
not heal within 72 h, have a collagenase com- basement membrane regeneration and absent
ponent (i.e., melting corneal ulcers), have a or delayed hemidesmosome attachments fol-
mechanical obstruction to healing (i.e., for- lowing minor superficial insult.
eign body, indolent), are infected (either with Indolent ulcer treatment is similar to that for
bacteria or fungus), and/or are in danger of small animals except that grid keratotomy was
perforation. demonstrated, in one study, not to speed heal-
ing of these ulcers in horses and may exacerbate
undiagnosed, subclinical infections. Therapy
Indolent Corneal Ulcers
may include (i) debridement of the redundant
Indolent corneal ulcers are chronic, superficial epithelial margins and base with a diamond
corneal ulcers where the healing corneal epi- burr; (ii) combined with a therapeutic soft con-
thelium will not adhere to the underlying cor- tact lens to physically protect regenerating basal
neal stroma. The characteristic appearance is a epithelium; and (iii) a temporary tarsorrhaphy
superficial ulcer with a redundant epithelial may facilitate retention of the contact lens.
border (Figure 15.27). There is no age predilec- Where initial debridement fails, superficial
tion, and foals may be affected; however, geri- lamellar keratectomy and conjunctival grafting
atric animals and those with pars pituitary are further treatment options. Thermal cautery
intermedia dysfunction (also referred to as has been used successfully with nonhealing ero-
equine Cushing’s disease) have a harder time sions where epithelial debridement had failed.
634 Equine Ophthalmology

The prognosis in all cases is guarded since non- fungal corneal invasion and infection because of
healing erosions are potentially recurrent. the large surface area and prominence of the
equine eye. Tear film instability may predispose
Corneal Foreign Bodies to fungal attachment and infection.
Infections most commonly involve
Corneal foreign bodies may be made of various
Aspergillus spp. or Fusarium spp. of fungi, but
materials, and may be superficial, deep, or even
other fungal organisms have been reported. A
perforate the cornea. Superficial foreign bodies
variety of clinical appearances and behaviors
will leave an ulcer that requires medical therapy
are possible with fungal ulcers. Most com-
once removed, while full-­thickness foreign bod-
monly, fungal keratitis appears clinically as a
ies will require suturing of the corneal wound.
worsening, subacute keratitis that generally
Infection is always a worry with corneal foreign
appears very painful, with severe secondary
bodies, especially if the foreign material is
uveitis. A typical history includes the use of
organic in nature (Figure 15.28). In cases in
previous topical corticosteroids and/or an ulcer
which it is difficult to determine the depth of
present for 7–14 days. There are four common
the foreign body or if it is unclear whether it has
clinical presentations of fungal keratitis: super-
perforated the cornea, look for evidence of
ficial ulcerative, stromal ulcerative, stromal
fibrin accumulation in the anterior chamber,
nonulcerative, and deep stromal–endothelial
which would suggest a full-­thickness rent.
nonulcerative (Figure 15.29a–d). Ulcerative
keratitis refers to a disruption of the corneal
Fungal/Mycotic Keratitis epithelium, with varying amounts of stromal
Fungi are normal inhabitants of the equine con- loss. Nonulcerative forms of fungal keratitis
junctival microflora, but they can become oppor- include stromal abscesses that result from stro-
tunistically pathogenic in the face of corneal mal inoculation with bacteria or fungi through
injury. Treatment of corneal ulceration with a small or large corneal epithelial defect. The
topical antimicrobials or corticosteroids (or organisms become encapsulated in the corneal
both) may predispose the equine cornea to fun- stroma after reepithelialization of the corneal
gal infection. Exposure to vegetative material ulcer over the infection site. Diagnosis of fun-
(e.g., hay, grasses, shavings, and straw) and dust gal keratitis is made by history, clinical appear-
in the environment may influence exposure to ance, and demonstration of the organisms on
fungi, and horses may be more susceptible to cytology, culture, or histopathology of a kera-
tectomy specimen (Figure 15.30a–e). Because
of the propensity for invasion into the deeper
layer of the cornea by fungal organisms, how-
ever, negative cytological or culture results may
be obtained from superficial specimens.

Medical Treatment
Treatment must be directed at killing the fun-
gus, killing secondary bacteria, and controlling
secondary uveitis. Because most fungal ulcers
also have a bacterial component, treatment is
initially similar to severe midstromal ulcers
(frequent topical antibiotics, atropine, and
Figure 15.28 Corneal foreign body consisting of anticollagenases). Antifungal therapy needs to
organic material in the anterior stroma. be initiated early and aggressively. The levels
­Diseases of the Equine Corne  635

(a) (b)

(c) (d)

Figure 15.29 Fungal infections are common in the horse, especially in the southeastern United States.
(a) Superficial ulcerative fungal keratitis. The gritty, “cake frosting” appearance often signals a potentially
aggressive and progressive behavior. (b) Stromal ulcerative fungal keratitis. (c) Stromal nonulcerative fungal
keratitis manifests generally as a mid-­to posterior stromal abscess. (d) Deep stromal to endothelial forms
of fungal keratitis are DSAs.

of ophthalmic antifungal drugs in the cornea Miconazole (1%) has been used successfully
needed to achieve fungicidal effects are so dif- and frequently as a topical antifungal agent.
ficult to obtain that many such agents are gen- The 1% solution does not retard corneal heal-
erally considered to exhibit fungistatic activity ing or cause pathological changes during cor-
only, even though loss of corneal epithelium neal epithelial regeneration and is well
results in increased corneal and aqueous con- tolerated. The gynecological version of micon-
centrations. Long duration of antifungal drug azole may be used topically, however, as it can
exposure is required for complete fungal be very irritating to the eye. Silver sulfadiazine
destruction and resolution of clinical signs. is a topical antimicrobial agent with both anti-
Voriconazole 1% (VFend®, Pfizer, New York, fungal and antibacterial activities that is
NY, USA) is a relatively broad-­spectrum anti- believed to be fungicidal and is used in equine
fungal agent that has a reasonable ability to eyes. Dilute (1:50) povidone–iodine is effective
penetrate corneal barriers. Natamycin against bacteria, fungi, viruses, and protozoa,
(Pimaricin®, Alcon Laboratories, Fort Worth, and it has also been used therapeutically for
TX, USA) is the only commercially available fungal corneal ulcers. Itraconazole has been
ophthalmic antifungal agent. It is very effec- used in some cases of equine keratomycosis.
tive against Fusarium and Aspergillus sp., but it Iridocyclitis is a frequent finding in horses
tends to be less effective against yeasts. with ulcerative keratomycosis, and it must be
636 Equine Ophthalmology

(a) (b)

(c) (d)

(e) (f)

Figure 15.30 Fungal keratitis can present with multiple forms of keratitis. (a) The plaque form of
ulcerative fungal keratitis. (b) Fungal keratitis in this eye manifesting as a melting ulcer. (c) Fungal keratitis
in this eye exhibits a central focus of necrotic cornea surrounded by a furrow or groove. The deep
surrounding margins are areas of increased enzymatic activity, a function of both the pathogens and the
host’s inflammatory reaction. (d) Superficial keratomycosis that is not yet ulcerated appears often as
multiple punctate opacities in the epithelium. (e) Superficial epithelial to subepithelial form of
keratomycosis often retains fluorescein in a punctate pattern. (f) Septate, branching fungal hyphae from a
cytology specimen of a corneal ulcer; (g) Keratectomy specimen after excision of a deep stromal abscess.
The arrow indicates a fungal hyphal element in Descemet’s membrane. ×40. (h) It can be difficult to predict
the behavior of a fungal ulcer at initial presentation. Superficial fungal keratitis at initial presentation.
(i) Despite appropriate and aggressive medical therapy, this ulcer progressed and required surgical
stabilization. (j) Postoperative appearance after keratectomy and conjunctival graft placement.
­Diseases of the Equine Corne  637

(g) (h)

(i) (j)

Figure 15.30 (Continued).

aggressively treated and controlled. Flunixin prognosis and suggests that rapid necrosis of
meglumine, which is a prostaglandin syn- the cornea is developing. When a furrow is
thetase inhibitor, is the most frequently used observed, emergency surgery is needed to
and efficacious NSAID for systemic treatment remove the infected cornea and place a corneal
among horses. Unfortunately, it also reduces or conjunctival graft or both. Surgeries for ker-
the speed of vascularization of corneal ulcers. atomycosis include conjunctival grafts or cor-
One percent atropine sulfate, which is a para- neal grafts following keratectomy of necrotic
sympatholytic agent, is used in all cases for its and infected cornea. Surgical treatments may
mydriatic and cycloplegic effects. leave the horse with a larger scar, but a safer,
more predictable outcome than medical ther-
Surgical Treatment apy alone. Conjunctival grafts have the advan-
Surgeries for fungal keratitis are generally indi- tages of providing physical support, a regional
cated in most cases, but especially when there blood supply, and a supply of endogenous anti-
is no response to medical management, if a proteases to the ulcer site. Amniotic mem-
corneal furrow or groove develops, or if the brane transplantation (AMT) is not
lesion is very deep in the cornea (see recommended for reconstruction of the ocular
Figure 15.30e). The development of a corneal surface in cases of keratomycosis. Deep fungal
furrow surrounding the area of keratitis in a lesions are best managed with penetrating ker-
superficial or stromal type of fungal keratitis atoplasty (PK), lamellar keratoplasty, or a deep
generally indicates a particularly poor lamellar endothelial keratoplasty (DLEK).
(a) (b)

(c) (d)

Figure 15.31 Bacterial keratitis and ulceration is also a common corneal disease. (a) An infected stromal ulcer with central cellular
infiltrate, a response to an infection with a Staphylococcus spp. (b) A progressive, melting ulcer in a horse. (c) Application of a double layer
of amniotic membrane following keratectomy to remove necrotic tissue; (d) Clinical appearance five weeks after surgery.
­Diseases of the Equine Corne  639

Bacterial Keratitis significant hyphema is present, the lens is per-


forated, if a large uveal prolapse through the
Bacterial ulcers generally have stromal involve-
incision is present, or if a dazzle and consen-
ment that produces marked edema, cellular
sual PLRs are absent.
infiltration, and deepening of the ulcer bed,
Examination of perforated eyes should
potentially accompanied by keratomalacia, or
include complete ophthalmic examination
“melting” (Figure 15.31a–d). Anterior uveitis
(including evaluation of dazzle and consen-
may be severe, manifesting as miosis, flare,
sual PLRs) with the horse adequately tran-
hypopyon, and hypotony. Microbiological cul-
quilized and eyelid nerve blocks performed to
ture should be performed in every case in
ensure that no further damage is done as a
which there is concern for the presence of a
result of the examination. If the posterior seg-
bacterial pathogen.
ment (vitreous and retina) of the eye cannot be
Treatment should be aggressive with fre-
visualized on the ophthalmic examination,
quent use of broad-­spectrum or targeted topical
then an ultrasound should be performed. If the
antibiotics every 1–2 h, topical atropine, sys-
vitreous is hyperechoic (i.e., blood or cellular
temic NSAIDs, and anticollagenase medication
infiltrate) or a retinal detachment is observed
to counteract the keratomalacia. Antimicrobial
on the ultrasound (Figure 15.32a–c), then the
therapy may need to be altered based upon the
prognosis for return to vision is very poor.
results of the culture and susceptibility testing.
Repair of the laceration or correction of the
Rapidly progressing lesions should be managed
perforation is recommended if the lens and
surgically with use of a superficial keratectomy
posterior segment are normal. Enucleation
followed by a conjunctival graft or amniotic
should be performed if there is no consensual
membrane graft (see Figure 15.31d).
PLR, a large uveal prolapse is present, or if
ultrasound shows significant blood in the vit-
reous or retinal detachment.
Corneal Perforation/Laceration
If treatment for an iris prolapse is pursued,
Iris prolapse in the horse most frequently occurs surgical stabilization and reconstruction are
after acute ocular trauma, particularly sharp and recommended. Medical therapy should con-
perforating corneal injuries or blunt injuries tinue as it would for any complicated corneal
causing rupture of the cornea, limbus, or sclera. ulcer with the addition of systemic antibiotic
Corneal perforation can also occur secondary to therapy since the globe has been compromised
rapid enzymatic degradation of stromal collagen and exposed to the outside world.
and ground substance caused by infectious and
noninfectious ulcerative keratitis. Perforating
Surgical Therapy for Corneal Ulcers
lacerations caused by sharp injuries are gener-
ally associated with a better prognosis than those Keratectomy
caused by blunt or missile injuries. Keratectomy may prove to be useful during the
High-­energy, blunt ocular trauma may result early stages of ulcerative keratitis, when infec-
in hyphema or globe rupture (or both), most tion is confined to the corneal epithelium and
often occurring at the limbus or equator, where anterior third or half of the cornea stroma.
the sclera is thinnest. In horses with traumatic Removing necrotic tissue by keratectomy
iris prolapse, corneal wound lengths of 15 mm speeds healing, minimizes scarring, and
or less are associated with a positive visual out- decreases the stimulus for iridocyclitis.
come, while wound lengths of greater than
15 mm frequently result in blindness, phthisis Conjunctival Grafts
bulbi, or enucleation. The prognosis is worse if Conjunctival grafts or flaps are frequently used
the corneal laceration involves the limbus, in equine ophthalmology for clinical treatment
640 Equine Ophthalmology

(a)

(b) (c)

Figure 15.32 (a) Iris prolapse in a horse accompanied by severe anterior uveitis. (b) Postoperative
appearance following replacement of missing tissue with a corneal graft covered by a conjunctival graft
five weeks later. Note the anterior synechia resulting in dyscoria. (c) One-­year postoperative appearance.

of deep, melting, and large corneal ulcers, tissue. Indications for its use are steadily grow-
descemetoceles, and perforated corneal ulcers ing and include grafting to replace diseased,
both with and without iris prolapse. missing, or excised tissue, patching to support
Conjunctival flaps can be transposed and diseased tissue during the healing process and
sutured onto the cornea to provide sufficient tis- as a substrate for the expansion of epithelial
sue to strengthen most weakened corneas, but cells for transplantation to the cornea. It can be
they are not as strong as corneal grafts. especially useful if a corneal wound is so large
Conjunctival grafts will result in various sizes or severe that the traditional therapy of placing
and degrees of corneal scars. Scarring can be a conjunctival graft upon a corneal wound or
minimized, however, by removal of necrotic defect would render a sighted or a potentially
cornea with keratectomy before graft placement. sighted globe blind. AMT may be the preferred
method of ocular reconstruction in cases of
Ocular Surface Reconstruction keratomalacia, whether sterile or secondary to
with Amniotic Membrane a bacterial infection. It is not recommended,
AMT is an effective clinical therapy for recon- however, when a fungal infection is present.
struction of the ocular surface in equine Other alternative materials for reconstruction
patients. Amnion is avascular and strong, con- of the ocular surface that have been used with
tains antiangiogenic and anti-­inflammatory success include porcine urinary bladder extra-
properties and growth factors, and has proper- cellular matrix grafts (ACell Vet® Corneal Discs),
ties that prevent or decrease fibrosis in healing porcine small intestinal submucosa, donor
­Diseases of the Equine Corne  641

cornea, conjunctiva, pericardium, renal capsule, however, all have a creamy-­yellow cellular cor-
peritoneum, and split-­thickness dermal grafts. neal infiltrate (Figure 15.33a–e). A mild-­to-­
fulminating iridocyclitis occurs secondary to
Penetrating Keratoplasty what initially appears to be a relatively benign
PK involves full-­thickness removal and corneal disease, thus causing severe pain and,
replacement of a portion of the cornea. Corneal possibly, blindness. Corneal vascularization is
transplantation is performed to restore vision variable at presentation and may obscure obser-
(i.e., optical), to control medically refractory vation of the precise location of the abscess. A
corneal disease (i.e., therapeutic), and to rees- culture and cytology would be helpful, but
tablish structural integrity of the eye (i.e., tec- unfortunately, this frequently requires surgery
tonic). The surgical approach in horses with a to get below the intact corneal epithelium.
corneal perforation and iris prolapse involves Reepithelialization of stromal abscesses inter-
replacement or amputation of the exposed iris feres with both routine diagnosis and treatment.
followed by placement of a corneal donor but- Most stromal abscesses are due to fungal
ton at the site of the defect. A conjunctival infections. Treatment depends on the depth of
pedicle graft may then be sutured over the graft the lesion and the degree of secondary uveitis
site in those eyes with evidence of infection or present. Superficial stromal abscesses may
vascularization to achieve more rapid assimila- respond positively to topical mydriatic/cyclo-
tion into the cornea. plegics and to topical and systemic antibiotic
and antifungal therapy and systemic NSAID
Nonulcerative Corneal Diseases therapy. Deep stromal abscesses (DSAs) are
This is a heterogeneous group of corneal dis- more frustrating and are often refractory to
eases, in which geographic ulceration is not a medical treatment. The same medical protocol
feature, although local epithelial sloughing is initiated; however, surgery can improve
associated with bullae formation may give rise results and reduce the duration of medical
to shallow erosions. therapy. Deep endothelial plaques that are
usually fungal in origin do best with PK. Horses
Corneal Stromal Abscesses that undergo early surgery in the course of this
Corneal stromal abscess is recognized in the disease tend to have a more rapid recovery
horse far more often than in other species. This than those in which surgery is delayed.
lesion in the horse can be a vision-­threatening
sequela to apparently minor superficial cor- Penetrating Keratoplasty for Deep
neal ulceration, or from an inoculation of Corneal Stromal Abscesses
organisms or foreign material via micropunc- The decision to perform surgery is made on the
ture through the epithelium into the stroma. basis of continued progression by the anterior
After epithelial cells adjacent to a small epithe- uveitis despite intense medical therapy, immi-
lial defect or puncture divide and migrate over nent or preexistent rupture of the abscess into
the puncture wound to seal infectious agents the anterior chamber, severe and unrelenting
or foreign bodies in the stroma, an abscess endophthalmitis, or anticipated poor visual out-
forms in the stroma, usually one to three weeks come resulting from a lack of vascularization of
later. This reepithelialization forms a barrier the stromal abscess. PK involves full-­thickness
that protects the bacteria or fungi from topi- removal and replacement of a portion of the
cally administered antimicrobial medications. cornea. Alternatively, two-­step PK can be per-
Diagnosis of corneal stromal abscess is usu- formed to permit placement of a partial-­
ally made based upon clinical appearance and thickness donor button, which may subjectively
history. The clinical appearance of stromal result in less postoperative swelling of the graft
abscess may vary greatly depending on severity; site as immunological rejection occurs.
642 Equine Ophthalmology

(b)

(c)

(d)

(a) (e)

Figure 15.33 Corneal abscessation in horse. (a) Large stromal abscess with surrounding vascularization
and edema accompanied by severe anterior uveitis. (b) Illustration of a midstromal corneal abscess. (c) The
abscess is removed along with a full-­thickness focus of corneal tissue. (d) The defect is repaired with a
piece of donor cornea that is approximately 1 mm in diameter wider than the section previously removed.
(e) The donor button is sutured in place, taking care that the sutures are not placed full-­thickness through
the cornea. In many instances, the donor graft is then covered by a conjunctival flap.

Lamellar Keratoplasty recommended for DSAs in the peripheral cor-


The purpose of split (partial) thickness or nea that have a clear overlying anterior stroma.
lamellar surgery is to replace only the diseased It avoids the superficial incisions and suturing
portion of the cornea, leaving the normal over- of the central cornea. These procedures should
lying tissue intact. Both the posterior lamellar be performed under general anesthesia by an
keratoplasty (PLK) and DLEK surgical meth- experienced ophthalmic surgeon. Both tech-
ods are forms of split-­thickness PK. They avoid niques and their modifications have shorter sur-
removal of superficial normal tissue but do gical times and postoperative healing ­periods
surgically enter the anterior chamber. These than full-­thickness penetrating keratoplasties.
surgical methods are important methods in
resolving DSAs in horses.
Viral Keratitis
PLK (Figure 15.34a–j) is recommended for
DSAs in the central cornea that have a clear In some cases of superficial keratitis, particu-
overlying anterior stroma. DLEK is larly those with a punctate appearance, a viral
­Diseases of the Equine Corne  643

(a) (b)

(c) (d)

(e) (f)

Figure 15.34 (a) Illustration of a corneal abscess in the posterior stroma. (b) For PLK, a hinged flap of
anterior stroma is created over the defect. (c and d) The flap is elevated and the abscess removed. (e–g) A
partial thickness graft of donor cornea replaces the removed tissue and is sutured in place. (h) The anterior
flap is then repositioned over the donor graft and sutured in place. (i) DSA preoperative appearance. (j)
Postoperative appearance three days after PLK.

etiology (equine herpesvirus type 2 [EHV-­2] or Corneal lesions appear as fine, irregular,
EHV-­5) can be presumed from the rapid clini- fluorescein-­positive epithelial fissures with
cal response to topically applied antiviral contiguous anterior stromal edema, as multifo-
drugs. Affected horses present with acute cal fluorescein-­positive superficial ulcers, less
onset, usually unilateral ocular pain with che- than 0.5 mm in diameter, with perilesional
mosis and conjunctival hyperemia. The dis- anterior stromal edema, or as multifocal sube-
ease is sporadic and is not contagious to pithelial punctate opacities (Figure 15.35a and
in-­contact horses. b) that stain variably with fluorescein but stain
644 Equine Ophthalmology

(g) (h)

(i) (j)

Figure 15.34 (Continued).

(a) (b)

Figure 15.35 Suspected viral keratitis in the horse. (a) Multifocal stromal and epithelial opacities in a
horse with type 2 viral keratitis in the United Kingdom. (b) Rose Bengal retention and superficial
vascularization with capillary tufts in a warmblood stallion with suspected viral keratitis. The condition
waxed and waned for several years.

positive with Rose Bengal. Superficial vascu- lesions have been associated with aggressive and
larization is associated with the opacities. refractory anterior uveitis in a small number of
Affected horses exhibit persistent moderate cases. A primary and important differential
ocular pain, and although uveitis is not a com- diagnosis in these cases is early fungal keratitis,
mon feature of the disease, similar corneal which may manifest as Rose Bengal-­positive
­Diseases of the Equine Corne  645

epithelial microerosions, and cytology and cul- nonulcerative or recurring corneal opacity
ture performed to rule out fungal involvement in with mild to moderate signs of cellular infil-
areas where keratomycosis is a significant clini- trate, corneal vascularization, and corneal
cal threat. Topical 0.5% idoxuridine and 1% trif- edema (Figure 15.36a–c). IMMK is character-
luridine are conventionally used in treating ized by having only mild signs of ocular dis-
affected eyes with varying success. comfort (i.e., only mild epiphora and/or slight
blepharospasm). Other characteristic features
Keratoconjunctivitis Sicca include absence of secondary uveitis, absence
KCS, caused by a deficiency in the aqueous por- of microorganisms on culture, cytology, or his-
tion of the preocular tear film, occurs relatively topathology, and clinical improvement with
rarely in the horse and is most frequently neuro- anti-­inflammatory medications.
genic, associated with traumatic injury to the There is considerable variation in the clini-
parasympathetic nerve supply to the lacrimal cal appearance and response to therapy and
gland that may occur with fractures of the stylo- subsets of disease are usually classified based
hyoid bone, the proximal part of the vertical on the depth of the lesions within the cornea.
ramus of the mandible, and some cases of tem- The most common clinical presentation of
porohyoid osteoarthropathy (middle ear disease). IMMK is superficial stromal disease (45% of
In these instances, concurrent facial palsy may cases), with midstromal (27% of cases) and
be present due to the proximity of the nerves. endothelial diseases being less common (23%
KCS may also be present in vestibular disease of cases). Unilateral presentation of IMMK is
with facial paralysis if the lesion of the facial most common although bilateral cases do
nerve is proximal to the geniculate ganglion. A occur. There is no breed or gender predilection,
less frequent cause of KCS is direct injury to the and the average age of diagnosis of all clinical
lacrimal gland due to plant toxins, in particular manifestations in the United States was
locoweed. Dacryoadenitis and KCS have been approximately 12 years.
reported in association with eosinophilic kerati- Superficial IMMK is characterized by a non-
tis (EK). Oral trimethoprim sulfa (30 mg/kg s.i.d.) painful subepithelial, superficial, white to yel-
does not reduce tear production in the horse. low infiltrate surrounded by superficial
Diagnosis is based upon clinical signs, and is con- branching corneal vascularization that follows
firmed by STT. STT I results of 0–10 mm/min or a waxing and waning course (see Figure 15.36a).
less are considered confirmatory of KCS. This form can usually be controlled with topi-
Treatment generally involves the long-­term cal steroids or CsA. Episcleral CsA implants
use of corneal lubricants and tear replacement have been shown to be effective for superficial
products every 2–6 h. Surgical transposition- IMMK if placed early in the course of the
ing of the parotid salivary duct to the medial disease.
canthus is possible in the horse and has been The stromal form appears as midstromal cel-
used with some success in treating a few cases lular infiltrate with surrounding corneal edema
of KCS; however, complications including fis- and vascularization (see Figure 15.36b). The
tula formation and avascular necrosis of the cellular infiltrate is deeper and denser than the
transposed duct have been reported. superficial form and the cornea is generally
Cyclosporine A (CsA) appears to have some more opaque. Occasionally, pockets or lacunae
lacrimomimetic effect in the horse, although of green‑tinged fluid and infiltrate are appreci-
its use in the long-­term management KCS has ated. In the acute or active phase of the disease,
not been reported. there is an extensive and dense deep stromal
edema and fibrovascular response, with iso-
Immune-­Mediated Keratitis lated blood vessels encroaching on the affected
The diagnosis of IMMK is made if there is a stroma at various levels. The intensity of the
progressive or chronic (>3 months in duration) stromal changes varies between cases and
646 Equine Ophthalmology

(a) (b)

(c) (d)

Figure 15.36 IMMK complex is divided by the depth of cornea affected. (a) Epithelial IMMK is
characterized by multifocal punctate epithelial lesions in the ventral and ventral-­paracentral corneal
epithelium, characteristic of superficial or epithelial IMMK; superficial, branching corneal vascularization;
and subepithelial, superficial, white-­to-­yellow stromal cellular infiltrate. (b) Subepithelial, superficial,
white-to-yellow stromal cellular infiltrate may be present. (c) Stromal IMMK is characterized by diffuse
midstromal cellular infiltrate, bullae formation, and peripheral corneal vascularization. (d) Endothelial IMMK
is characterized by chronic, slowly progressive, nonpainful, diffuse ventrolateral or ventral full-­thickness
areas of corneal edema that can coalesce into bullae and microulcers.

between episodes. Despite the dramatic appear- precursor to a form of refractory anterior uvei-
ance of affected eyes, the disease is associated tis and secondary glaucoma. Endothelial dis-
with no ocular pain. Medical therapy is the ease is the least amenable to therapy, but some
same as for superficial IMMK; however, the response may be seen with topical and systemic
stromal forms tend to be less responsive. steroids and nonsteroidal anti-­inflammatories
Deep or endothelial disease is also referred to such as bromfenac and systemic flunixin.
as endotheliitis. This form is characterized by a
chronic, slowly progressive, nonpainful focus Eosinophilic Keratitis
of dense corneal edema with cellular infiltrate EK occurs as either a unilateral or bilateral
that accumulates at the level of the endothe- white plaque on the surface of the cornea with
lium (see Figure 15.36c). Disruption of the surrounding corneal edema (Figure 15.37) or a
function of the endothelium results in the superficial stromal, perilimbal yellow infil-
accumulation of fluid in the stroma. Bullous trate. Cytology of corneal scrapings shows an
keratopathy may also occur and result in sec- intense eosinophil response with some plasma
ondary superficial focal or multifocal ulcera- cells, mast cells, and PMNs. Often single or
tions. This form of IMMK may emerge as a multiple shallow ulcers that are covered by
­Diseases of the Equine Corne  647

Figure 15.37 EK that appears as a white plaque Figure 15.38 Calcific band keratopathy in a
at a common location under the third eyelid chronic ERU eye with an associated superficial
adjacent the medial limbus. corneal ulceration. Note also the posterior lens
luxation and the green discoloration to the
ocular media.
dense white or gelatinous necrotic plaques
loosely attached to the underlying stroma are
which are frequently inherited. There is no
identified. Typically, the ulcers appear initially
associated inflammation or vascularization
in the perilimbal cornea and extend peripher-
(Figure 15.38). Progressive, often bilateral and
ally, although the geographic appearance of
geographically symmetrical focal thinning of
the lesions is highly variable. The most com-
the stroma in Friesian horses has been
mon location is the cornea located under the
reported. The lesions appear as well-­defined
third eyelid, followed by the ventral-­medial
circular defects, usually in the inferotemporal
and ventral-­lateral cornea. Vascularization of
quadrant of the cornea. They may be shallow
the anterior stroma accompanies the focal
initially, but can progress to a descemetocele
ulceration, and may be very intense. Moderate
and corneal rupture. Treatment to minimize
to severe ocular pain accompanies the disease.
the risk for perforation should be promptly ini-
The cause is unknown, but may involve a
tiated. In some cases, surgical reconstruction is
hypersensitivity reaction.
necessary.
EK seems to occur most commonly in the
early or late summer months and develops in
well-­managed horses given appropriate vacci- Corneal Mineralization and Calcific
nations and deworming protocols. Several ani- Band Keratopathy
mals in a barn may be affected, some with only Subepithelial mineralization is occasionally
conjunctivitis characterized by a white, cheesy observed in association with keratitis and uvei-
exudate. EK is generally self-­limiting and will tis. Calcific band keratopathy refers specifi-
resolve over 8–12 weeks. However, several cally to the deposition of calcium salts at the
treatments have been suggested to enhance or level of the epithelial basement membrane and
speed healing. Topical corticosteroids are gen- anterior stroma that is an occasional finding in
erally effective, but their use may need to be chronic ERU. The mineralized area typically
continued for 9–10 weeks or longer to achieve adopts an oblate or linear configuration, geo-
resolution of the lesions. graphically defined by the palpebral aperture,
the peripheral cornea remaining clear. The depos-
its are variably dense and may elevate the
Corneal Dystrophy
corneal surface, resulting in excoriation of
Corneal dystrophies are primary biochemical the epithelium and shallow ulceration,
abnormalities, typically presented as bilateral, and the lesions may provoke their own inflam-
symmetrical, and progressive opacities, and matory response. Spontaneous resolution may
648 Equine Ophthalmology

be promoted by topical instillation of 0.4–7.0% gender predilection, and can be bilateral. Other
EDTA to decrease calcium levels in the tear factors associated with increased prevalence
film and promote dispersal of calcium salts in include heredity, high levels of solar radiation
the cornea. In long-­standing lesions or in cases and UV light exposure, increasing longitude
of dense mineralization, superficial keratec- and altitude, and decreasing latitude.
tomy may be required, although significant Corneal SCC originates from the cornea,
corneal scarring is likely to result. conjunctiva, or limbus, with the lateral limbus
the most common location. Corneal SCC most
Linear Keratopathy commonly appears nodular, elevated, white-­
Nonedematous striate lesions with well-­ pink, and fleshy (Figure 15.39), but may resem-
defined, parallel refractile margins are occa- ble a flat vascular keratitis that does not resolve
sionally observed traversing the cornea at the with the application of a topical steroid.
level of DM in normotensive and otherwise Affected horses generally demonstrate mini-
clinically normal eyes. Typically, these striae mal to mild discomfort, no uveitis, but com-
are single and nonbranching, although multi- monly high amounts of mucopurulent ocular
ple branching lesions may be observed. discharge.
Usually, the striae traverse the horizontal Treatment involves surgical excision of the
meridian of the eye, although oblique and ver- mass (e.g., superficial keratectomy) followed
tical transcorneal lesions may be encountered, by an adjunctive therapy. The most commonly
and rarely the lesion may fail to bridge the cor- used corneal adjunctive modalities include
nea. The striae are uniformly 1–2 mm in width strontium-­90 beta irradiation, carbon dioxide
throughout their length, and histologically laser, cryotherapy, and topical chemotherapy
have been shown to be thinning of DM with a (5-­fluorouracil or mitomycin C). Twice-­yearly
normal endothelial overlay. The cause of the follow-­up examinations for three to five years
lesions in otherwise normal eyes is unknown. are recommended following any therapy for
Clinically similar striate lesions are seen in corneal SCC.
chronically hypertensive eyes and in corneas Other neoplasms involving the cornea are
following blunt trauma. In these cases, the rare but include mast cell tumors, melanoma,
striae are more typically multiple, branching, lymphoma, and vascular neoplasms, such as
and may show significant variation in width. hemangioma, hemangiosarcoma, lymphangi-
oma, and lymphangiosarcoma.
Corneal Neoplasia
SCC is the most common tumor of the equine
cornea and is most commonly, but not exclu-
sively, observed in horses with minimal ocular
and periocular pigmentation, such as
Appaloosas, Quarter Horses, Paints,
Haflingers, and draft horses (Belgians, Shires,
Clydesdales). A genetic basis for the develop-
ment of limbal SCC has been detected in the
Haflinger, Belgian, and Percheron breeds with
simple autosomal recessive mode of inherit-
ance of a missense mutation in the gene that
codes for damage-­specific DNA binding pro-
Figure 15.39 Raised, fleshy corneal SCC. Corneal
tein 2 (DDB2). The disease most commonly SCC usually arise from the limbus where it is most
develops between 9 and 13 years, has no exposed.
­Diseases of the Equine Uve  649

­Diseases of the Equine Uvea melanomas arising from the ciliary body have
been reported. Common clinical signs include
Uveal Cysts appearance of a dark mass extending from the
iris into the anterior chamber (Figure 15.41),
The corpora nigra, or granula iridica, which are or filling the anterior chamber with focal cor-
vacuolated extensions of the posterior iris epi- neal edema associated with contact with the
thelium, normally extend from the dorsal and posterior surface of the cornea. Masses may
ventral pupillary margin into the anterior cham- also appear pink and fleshy in horses with
ber. These uveal cysts are hollow structures that lightly colored irises. Early in the course of the
transilluminate with focal light sources. Large disease, there are no signs of discomfort; how-
corpora nigra and iridal cysts, depending upon ever, as the neoplasm gets larger, common
their location, may interfere with vision and clinical signs include blindness, blepharos-
cause erratic behavior, especially when the pasm, epiphora, diffuse corneal edema, and
horse is in bright light and the pupil is miotic buphthalmos. Treatment options are limited,
(Figure 15.40a). Uveal cysts must be differenti- and the prognosis for saving the eye is
ated from inflammatory or neoplastic changes
to the iris. Treatment is not usually necessary
since corpora nigra cysts rarely obstruct vision.
The most effective and noninvasive treatment is
deflation of the cystic corpora nigra with a laser
(Figure 15.40b), either a diode laser or an oph-
thalmic neodymium‑doped yttrium aluminum
garnet (Nd:YAG).

Uveal Neoplasia
Melanoma
Although melanoma is relatively rare in
horses, it usually occurs in gray or partially
gray horses between 5 and 10 years of age. The
most common site of origin is the iris, but Figure 15.41 Iris melanoma in a blue iris.

(a) (b)

Figure 15.40 Corpora nigra cysts, if large or within the pupil, can affect vision and the horse’s
performance. Note two corpora nigra cysts (a) and corpora nigra cysts immediately following laser
ablation (b).
650 Equine Ophthalmology

generally poor, but better if the lesion is small. Horses may present with an apparently
Treatments include a sector iridectomy, diode endogenous uveitis, without an inciting sys-
or surgical Nd:YAG laser therapy, or temic or ocular cause. If this inflammation is
enucleation. persistent or recurrent, it is referred to as
ERU. It is very important that the clinician not
Lymphoma assume that every case of uveitis in the horse is
In horses with lymphoma, eyelid and conjunc- ERU. As the name suggests, ERU is character-
tival swelling and inflammation were the most ized by multiple, recurrent episodes of uveitis,
common ocular signs followed by involvement whereas acute uveitis is limited to a single
of the anterior uvea. Signs associated with event. Typical clinical signs associated with
anterior uveal manifestation of systemic lym- acute anterior uveitis are all due to damage of
phoma are nonspecific uveal inflammation the anterior uvea and subsequent compromise
and include blepharospasm, episcleral injec- of the blood–aqueous barrier and include pho-
tion, corneal edema and vascularization, aque- tophobia, blepharospasm, corneal edema,
ous flare, hypopyon, hyphema, iridal aqueous flare, hypopyon, miosis, vitreous
congestion, and swelling. Intraocular lym- haze, and chorioretinitis. Treatment of uveitis
phoma cannot usually be differentiated from requires a combination of specific treatment of
other causes of primary uveitis based on ocular the underlying cause of the inflammation (if
signs. The diagnosis of systemic lymphoma one can be identified) and nonspecific treat-
should be considered in any horse with ante- ment of the uveitis with topical corticosteroids
rior uveitis, especially when it is accompanied and atropine and systemic NSAIDs.
by systemic signs of illness such as fever,
weight loss, lethargy, and swollen lymph nodes.
Equine Recurrent Uveitis
ERU (also known as moon blindness, iridocy-
­Uveitis clitis, and periodic ophthalmia) is a major oph-
thalmic disease of the horse and is the most
Uveitis broadly describes inflammatory dis- common cause of blindness in the horse. It is
ease of the iris, ciliary body, and choroid, in likely that ERU is blanket diagnosis, encom-
isolation or in combination. Uveitis in the passing various subsets of distinct endogenous
horse may arise from a variety of known or uveitides that are pathophysiologically similar,
unknown causes and may be due to primary yet distinct but are responsible for nonspecific
ophthalmic disease or related to an underlying clinical signs. The rate of prevalence for this
systemic condition. Blunt or perforating disease varies from 2% to 30% with significant
trauma, including surgical trauma, to the globe geographic differences, with a prevalence of
will result in a uveitis of varying severity 8–25% among horses in the United States and
depending upon the severity of the initiating up to 30% among horses in Central Europe.
insult. Uveitis commonly accompanies corneal The disease is relatively uncommon in the
trauma, corneal ulceration, and some nonul- United Kingdom.
cerative keratopathies, such as stromal ERU is characterized by episodes of intraocu-
abscesses. Some systemic bacterial infections lar inflammation that develop weeks to months
are recognized as uveitogenic in the horse, after an initial uveitis episode subsides. Horses
especially Salmonella, Strep equi. var. equi, can develop ERU at any age, but the peak time
Borrelia burgdorferi, and R. equi; however, any of the initial uveitis episode is four to six years.
systemic inflammatory or neoplastic disease In some instances, but not all, the uveitis associ-
can compromise the blood–ocular barriers and ated with these systemic infections may develop
result in uveitis. into immune-­medicated uveitis or ERU. One of
­Uveiti  651

the most commonly associated systemic bacte- include corneal edema, iris fibrosis and hyper-
rial diseases associated with uveitis is pigmentation, posterior synechiae, corpora
leptospirosis. nigra degeneration (smooth edges), miosis, cat-
Diagnostic testing for primary equine uveitis aract formation, vitreous degeneration and discol-
may help determine the underlying cause of a oration, and peripapillary retinal degeneration
specific episode of acute anterior uveitis. These and optic nerve atrophy (Figure 15.43a–c).
would include complete blood count, serum Secondary glaucoma may result from chronic
chemistry profiles, and serological tests for uveitis and phthisis bulbi may develop either
specific infectious causes such as leptospirosis. directly from uveitis or as a consequence of end-­
Leptospiral titers for pomona, bratislava, and stage secondary glaucoma.
autumnalis should be requested in the United Three main clinical syndromes are
States; a positive titer for serovars at dilutions observed in ERU:
of 1:400 or greater is of clinical importance. A Classic: Classic ERU is the most common
higher titer in the aqueous humor than in the form and is characterized by active inflam-
serum (positive C-­value) is indicative of local matory episodes in the eye followed by peri-
antibody production and supports a leptospiral ods of minimal ocular inflammation. After
cause for the uveitis. variable periods of time, the quiescent
phase is generally followed by further and
Clinical Signs of ERU increasingly severe episodes of uveitis (see
Acute, subacute, and chronic clinical signs of Figure 15.42a).
active ERU are similar to signs of acute primary Insidious: Insidious ERU is characterized
uveitis, including lacrimation, photophobia, by inflammation that never completely
blepharospasm, corneal edema, aqueous flare, resolves, even with appropriate anti-­
hypopyon, miosis, vitreous haze, and chorioret- inflammatory therapy. A low-­grade inflam-
initis (Figure 15.42a and b). Miosis is a hallmark matory response continues that leads to
clinical sign in horses with ERU and can result progression to chronic clinical signs of ERU
in a misshapen pupil and posterior synechiae. (see Figure 15.43a–c). This type of uveitis is
Degree of pain exhibited by the animal may most commonly seen in Appaloosa and
vary significantly with some animals appearing draft breed horses.
profoundly painful while others seem relatively Posterior: Posterior ERU has clinical signs
untroubled. Clinical signs of chronic ERU existing entirely in the vitreous and retina,

(a) (b)

Figure 15.42 Anterior uveitis is usually divided into acute and chronic, which demonstrate different
clinical signs. (a) Acute uveitis episode of anterior uveitis. There is episcleral injection, miosis, aqueous flare,
fibrin in the anterior chamber, and mild corneal edema present. (b) Fibrin and hyphema in an acute phase of
ERU eye.
652 Equine Ophthalmology

(a) (b)

(c)

Figure 15.43 Significant destructive effects of inflammation occur with chronicity. (a) Chronic ERU has
resulted in cataract and posterior synechiae. There is fibrin in the anterior chamber. (b) Vitreous cellular
infiltrate and vitreal strands in a horse with predominantly posterior uveitis. (c) This eye has become
hypotensive and is shrinking (phthisis bulbus).

with little or no anterior signs of uveitis. In Impairment of ACAID exposes the uvea to
this syndrome, there are vitreal opacities, the possibility of immune-­mediated insult.
retinal inflammation, and in some cases The well-­documented association of the onset
retinal detachment, and subsequent degen- of ERU with initial exposure to certain
eration. This is the least common type of Leptospira serovariants, notably L. interrogans
uveitis in the United States. var. pomona, suggests these organisms may be
implicated in at least some instances of the dis-
Pathogenesis of Recurrent Uveitis ease. The association of ERU with leptospires
ERU is a nonspecific immune-­mediated dis- and, possibly, other microbial pathogens may
ease that results in recurrent or persistent be based upon antigenic homology between
inflammatory episodes in the eye. Since rel- microbial peptides, potentially uveitogenic
atively minor intraocular inflammation has intraocular autoantigens, and MHCI+
potentially devastating consequences for peptides.
vision, the mammalian eye has evolved the
means to limit the intensity and extent of Leptospirosis and ERU
the local response to antigen challenge. This The association between anterior uveitis and
immunological tolerance is fundamental to leptospirosis was first made in Germany in
the integrity of the healthy eye and is gener- 1947, to be followed by several similar reports
ally referred to as immune privilege. from various parts of the world. Leptospirosis
Privilege is determined by a number of interrogans var. pomona is the most frequently
mechanisms, including anterior chamber-­ isolated serovar in the United States. In the
associated immune deviation (ACAID). United States, the United Kingdom, and
­Uveiti  653

Europe, several studies have demonstrated inflammation that can lead to blindness.
serological linkage of L. interrogans serovari- Topically administered medications are ini-
ants other than pomona with some cases of tially administered every 2–6 h depending on
equine uveitis, including grippotyphosa, ictero- the severity of disease and tapered as the prob-
hemorrhagiae, bratislava, australis var. brati- lem resolves. Topical corticosteroids are most
slava, autumnalis var. autumnalis, and sejroe commonly used to decrease inflammation.
vars sejroe and saxkoebing. However, the exact Topical NSAIDs offer as their main advantage
nature of the link remains to be elucidated. that they can be administered without concern
for potentiating infections.
Breed Susceptibility to ERU Systemic therapy is the most potent therapy
ERU susceptibility has long been suspected to for management of ERU. Oral, intramuscular,
have some heritability. This may be linked to or intravenous flunixin meglumine is one of
equine leukocyte antigen (ELA) haplotypes the most potent anti-­inflammatory medica-
influencing the occurrence and expression of, tions for the eye. Phenylbutazone and aspirin
but not directly causing, autoimmune intraocu- are much less effective. Systemic dexametha-
lar inflammatory disease. A strong association sone and prednisolone are also effective but
with the MHC1 haplotype ELA-­A9 with ERU generally are only recommended in severe
in German Warmblood horses has been identi- cases that will not respond to other anti-­
fied. In the United States, a breed predilection inflammatory medication.
to the development of the disease and to the Mydriatic/cycloplegic medications, such as
severity of clinical expression of the disease is atropine, minimize the formation of synechiae
recognized in Appaloosa horses. There is an by inducing mydriasis, and they alleviate some
80% chance that ERU will develop in both eyes of the pain of ERU by relieving ciliary body
in susceptible Appaloosas, while only 20% muscle spasms (i.e., cycloplegia). These drugs
bilateral potential in non-­Appaloosas with ERU. also narrow the capillary interendothelial cell
junctions to reduce capillary plasma leakage,
Treatment of Equine Recurrent Uveitis thereby decreasing inflammation.
The main goals of therapy for ERU are to pre- CsA is a peptide that blocks the transcription
serve vision, decrease pain, and reduce inflam- of interleukin-­2 production, thereby minimiz-
mation in an attempt to limit permanent ing T-­lymphocyte activation. CsA is a logical
damage to the eye and pain. choice for treatment of recurrent uveitis; how-
ever, CsA is hydrophobic and does not penetrate
Medical Therapy for ERU into the eye when applied topically. CsA-­
Treatment should be aggressive and prompt to releasing devices, surgically placed in or near
maintain transparency of the ocular structures the suprachoroidal space, are used routinely in
to prevent vision loss. Therapy can last for horses with chronic ERU and have been shown
weeks or months and should not be stopped to decrease the severity of inflammation,
abruptly in order to prevent acute relapse. increase the interval between flare-­ups, and
Once improvement is noted, medications delay vision loss. The CsA delivery device prep-
should be slowly reduced in frequency over a aration for use in the horse theoretically deliv-
30-­day period once the clinical signs abate. In ers 4 μg/day of CsA to the vitreous and contains
acute cases, treatment in the form of systemic enough drug for four years (Figure 15.44).
and local therapy with anti-­inflammatory
drugs and cycloplegic/mydriatic agents is used. Vitrectomy
Anti-­inflammatory medications, specifically Pars plana vitrectomy (PPV) has been used in
corticosteroids and NSAIDs, are used to con- the management of chronic endogenous uvei-
trol the generally intense intraocular tis in humans and horses, with the goal to
654 Equine Ophthalmology

Appaloosas with ERU positive to leptospirosis


became blind in all affected eyes, while
Appaloosas with ERU negative to leptospirosis
became blind in 72% of eyes. Non-­Appaloosas
with ERU positive to leptospirosis became
blind in 51% of affected eyes, while non-­
Appaloosas with ERU negative to leptospirosis
became blind in 34% of eyes.
A recent study that looked at the overall
impact of ERU on affected horses’ utility found
that while a majority of ERU horses (70.6%)
returned to the same job/role they had prior to
Figure 15.44 Placement of a CsA-­releasing device the first bout of uveitis, only 38.7% performed
under a scleral flap adjacent to the suprachoroidal this role at the same level compared with prior
space, for long-­term treatment of ERU.
to the first bout of uveitis, while the remaining
performed “worse” or “much worse.”
improve vision by clearing the media or remov- Of the horses that did not return to their pre-
ing membranes and decreasing recurrent epi- vious role, 35.1% adjusted poorly to vision
sodes of inflammation. PPV for ERU is used impairment (i.e., not safe to ride per owner,
commonly in central Europe. Long-­term fol- “spooky” behavior, or unable to see jumps),
low-­up reports describe either a decrease in 22.8% were euthanized shortly after diagnosis
recurrences or complete cessation of the uveitis of ERU, 17.5% had a change of ownership after
episodes. While PPV is reported to be a success- diagnosis (likely related to the diagnosis), and
ful treatment for ERU in Europe, less favorable 14.0% were completely retired from their previ-
results have been noted in the United States. ous role by their owners. Appaloosas have a
particularly guarded prognosis.
Long-­Term ERU Management
Reducing exposure to potential antigens
Heterochromic Iridocyclitis
through appropriate parasite control programs,
eliminating environmental contact with cattle Heterochromic iridocyclitis with secondary
and wildlife, excluding horses from ponds and keratitis (HIK) is a recently described ocular
swampy areas, limiting rodent access to horse disease in which affected horses present with
feed, decreasing the incidence of bacterial and clinical signs of pigmented keratic precipitates
viral respiratory and systemic infections, and (KPs), variable degrees of corneal edema, and,
maintaining a quality feed supply can all be in some cases, focal or multifocal iridal depig-
beneficial in reducing ERU. Multivalent bovine mentation and formation of a membrane in the
and porcine leptospiral vaccines have also anterior chamber that is attached to the corneal
been used to treat intractable cases of ERU and endothelium. Initially, these horses generally
to suppress herd outbreaks of leptospiral ERU, demonstrate minimal, if any, signs of discom-
but their routine use as a preventive for ERU is fort and mild signs of intraocular inflammation
controversial. Currently vaccination is only characterized by miosis. Corneal edema may
recommended for clinically normal horses progress and become severe, accompanied by
without serological evidence of exposure. bulla formation and corneal ulcers.
Response to anti-­inflammatory treatment
Prognosis for ERU was generally unpredictable and variable with
Serology for Leptospira pomona can be predic- many eyes requiring enucleation due to pro-
tive of developing blindness in horses. gression of disease or the development of
­Uveiti  655

complicated corneal ulceration. HIK appears aqueous humor and subsequent increase in the
not to develop a quiescence period, a hallmark pressure within the eye, referred to as glau-
clinical feature of ERU, and pigmented KPs, coma. Since horses have a greater percentage of
focal corneal edema, iris depigmentation, and aqueous humor outflow through the uveoscle-
retrocorneal membranes observed in HIK ral outflow compared to dogs and humans, the
horses are not clinical signs commonly associ- causes, clinical findings, and treatments are
ated with ERU. different for horses with glaucoma. Equine
glaucoma is not easily recognized in the early
stages of the disease due to the subtle nature of
Equine Glaucoma
the early clinical signs and the potential for
Obstruction of aqueous humor outflow can be large diurnal variations in IOP in diseased eyes.
the result of an abnormally developed drain or The glaucomas in horses are generally slowly
through damage to the drain from scarring, progressive with little evidence of pain initially,
vascularization, or accumulation of debris. The and insidious loss of vision (Figure 15.45a–c).
result of this obstruction is retention of Elevated IOP is clearly the primary risk factor

(a) (b)

(c)

Figure 15.45 Glaucoma in the horses associated with age, previous uveitis, and the Appaloosa breed.
(a) Heterochromic iridocyclitis in this eye that has developed secondary glaucoma (mydriasis and corneal
striae). Note the depigmentation of the ventral iris. Pigmented KPs are present as well. (IOP = 60 mmHg).
(b) The main initial clinical sign of glaucoma in this horse was diffuse corneal edema. (c) Atrophy of the
optic nerve head due to glaucoma. The reticular pattern in the central cup region of the optic disc is the
lamina cribrosa. The lamina is exposed and optic nerve axons are lost.
656 Equine Ophthalmology

for rapid progression of optic nerve damage directly targets the ciliary processes, is more
and blindness in the horse, but iridocyclitis is invasive and requires general anesthesia.
the primary risk factor for development of glau-
coma. Glaucoma in the horse may be primary,
secondary, or congenital. Secondary glaucoma ­Lens
is far and away the most common form in the
horse, generally occurring due to damage The horse lens measures 17–22 mm in diame-
induced by intraocular inflammation. ter and has an axial length of 12–15 mm, a vol-
ume of 2.5–3.0 ml, and a power of 14.88
Risk Factors for Equine Glaucoma D. Cataracts, or opacities of the lens of the eye,
Horses with active or quiescent uveitis, aged are the most common abnormality of the
horses (>15 years old), and Appaloosas are at equine lens, and a leading cause of blindness
increased risk for the development of glau- in horses. It is conservatively estimated that
coma. Glaucoma has also been reported in some form of lens opacity, ranging from small
most breeds. epicapsular remnants of the fetal vasculature
to dense and extensive cataract, is present in
Treatment of Equine Glaucoma 5–7% of horses with otherwise clinically nor-
Usually, treatment of equine glaucoma aims to mal eyes. Complete cataracts are invariably
decrease the underlying inflammation and associated with overt and significant visual dis-
decrease the production of aqueous humor. ability. However, focal or incomplete cataracts
Various combinations of drugs and surgery alone seldom cause any apparent visual dys-
may be necessary to reduce the IOP to target function in affected horses.
levels that are compatible with preservation of
vision. Production of aqueous humor may be
Nuclear Sclerosis
decreased with carbonic anhydrase inhibitors
and beta-­adrenergic antagonists to achieve a Nuclear sclerosis describes the altered refrac-
lowered IOP. The carbonic anhydrase inhibitor tivity of the central lens occurring in older ani-
dorzolamide 2% alone or in combination with mals, caused by progressive compression of
timolol maleate is effective in lowering IOP if the nucleus by enveloping secondary fibers as
administered topically b.i.d. to t.i.d. in horses, part of normal lens growth. However, increased
as is brinzolamide 1%. definition of the nuclear–cortical junction on
Anti-­inflammatory therapy consisting of retroillumination is a common observation in
topically administered corticosteroids such as horses over 18 years old. The nucleus remains
prednisolone acetate and systemically admin- largely optically clear in these animals.
istered NSAIDs such as flunixin meglumine is
critical to the control of the iridocyclitis when
Disorders of the Lens
it is inducing elevation in IOP. In the past, topi-
cal atropine was used in the treatment of Lens Luxation/Subluxation
equine glaucoma. It is no longer recommended Primary luxation of the lenses in adult horses
since it may exacerbate IOP elevation. has not been documented. However, acquired
When medical therapy is inadequate, sur- anterior or posterior luxation and subluxation
gery should be utilized to control IOP and pre- of the lens occur relatively frequently in the
serve vision in the horse with glaucoma. The horse as a sequela to ocular trauma and chronic
most common surgical option for a visual eye uveitis, and, less frequently, in cases of glau-
is laser cyclophotoablation (CPC). Transcleral coma. A luxated lens, a lens that has moved
CPC may be performed in the standing horse, into either the anterior or posterior chamber,
while endoscopic CPC, although it more will invariably become cataractous quickly.
­Len  657

Cataract can also be classified based on their cause (e.g.,


A variety of etiologies and initiating factors hereditary, uveitis, trauma, toxin, nutritional,
have been proposed; however, the most com- or metabolic disease), although many times,
mon cause of cataracts (and lens luxation) in the cause is not known at the time of clinical
horses is chronic uveitis, or ERU. Cataracts examination.
may also occur in horses from inherited causes Whether or not a small cataract, which may
or occur spontaneously following trauma to not affect vision, will progress to a larger, visu-
the eye. Classification of cataracts in the horse ally inhibiting cataract is often a concern in
is similar to the description in other species horses, especially on prepurchase examina-
and includes age of onset (i.e., congenital, tions. Certainly, in juvenile horses, the pres-
juvenile, or senile/geriatric), location within ence of any cataract, especially those that are
the lens (i.e., anterior capsular, anterior corti- bilateral, suggests that the defect may be
cal, perinuclear, nuclear, equatorial, posterior hereditary, especially in Thoroughbreds,
cortical, or posterior capsular), and stage of Quarter Horses, and Morgan horses. Because
maturity (i.e., incipient, immature, mature, ERU is the most common cause of cataracts in
and hypermature) (Figure 15.46a–d). Cataracts adult horses, the presence of other signs

(a) (b)

(c) (d)

Figure 15.46 Cataracts, like other species, present in different areas, shapes, and sizes in the lens.
(a) Lamellar cortical cataract in a horse. (b) Anterior and posterior cortical lamellar lens opacities suspected
to be caused by a toxin or metabolic problem. (c) Immature anterior and posterior cortical cataract.
(d) Hypermature cataract with posterior luxation. Note the aphakic crescent and the lenticular brunscense.
658 Equine Ophthalmology

typical of ERU (e.g., corpora nigra atrophy, iris retinopathy is almost invariably present in
hyperpigmentation, posterior synechia, and these eyes, any visual disability is probably a
vitreal degeneration) suggests that the cata- cumulative effect.
racts will progress as the ERU recurs.
Acquired or Secondary Cataracts
Developmental Cataracts The major cause of secondary cataracts in the
Lenticular cataracts, affecting the cortex and/ horse is unquestionably uveitis, encompassing
or nucleus, with the exception of embryonic traumatic and infectious uveitis, and the het-
nuclear cataracts, are usually bilateral but are erogeneous group of presumptively immuno-
not necessarily symmetrical. They may be genic diseases described as ERU. Typically, in
grouped into four types: (i) zonal; (ii) embry- cases of anterior uveitis or iridocyclitis, there
onic nuclear; (iii) fetal nuclear; and (iv) peri- are focal anterior capsular and subcapsular
nuclear or lamellar, which are the most cataracts, occasionally associated with poste-
commonly encountered developmental cata- rior synechiae.
racts. They appear as spherical or oblate opaci-
ties located on the periphery of the adult Cataract Surgery
nucleus. The nucleus and surrounding cortex Most veterinary ophthalmologists recommend
are usually optically clear. However, focal opal- surgical removal of cataracts in foals younger
escent opacities are commonly found in the than six months if the foal is healthy, has no
anterior cortex, and within the cataract the grossly appreciable uveitis or other ocular
suture pattern is usually accentuated. These problems, and has a temperament that will tol-
cataracts develop in early postnatal life, and in erate aggressive topical therapy. Early return of
general are nonprogressive. Equatorial cata- vision is paramount in foals for the develop-
racts are nonprogressive disruptions in the ment of the higher visual centers. Adults with
optical homogeneity of the periequatorial cor- visual impairment because of cataracts may
tex, while complete congenital cataracts pre- also be candidates for surgery; however, since
sent as dense and uniform opacifications of the the etiology of acquired cataract in adults is
nucleus and cortex. Vision may be severely uveitis, the prognosis may be less favorable.
compromised. These cataracts are frequently Patient selection and presurgical diagnostics
associated with other ocular abnormalities, (ERG, ultrasonography, preanesthetic blood-
most commonly microphthalmos. work) are similar to those in small animals.
Candidates should be systemically healthy,
Heritability of Equine Cataracts have the potential for postoperative vision,
The heritability of developmental cataracts in have well-­controlled uveitis, and have a tem-
horses has not been widely studied. Some, perament that will permit the requisite postop-
mainly nuclear cataracts, have been described erative medical care (Figure 15.47a–c).
as having a sporadic familial occurrence in
Arabs and Thoroughbreds. Although a domi-
nant mode of inheritance is most commonly ­Posterior Segment
suggested, recessive inheritance is reported. In
Morgan horses, bilateral nonprogressive There is much variation in the normal appear-
nuclear or perinuclear cataracts, inherited in ance of the equine fundus (Figure 15.48a–d).
an autosomal dominant fashion, have been Most lesions of the fundus are identified near
described. Senile cataracts are reported to be and below the optic nerve head, and typically
associated with visual impediment in more involve hyperpigmentation or depigmentation.
extensively affected horses, particularly in dim The retinal vasculature is classified as pauran-
lighting conditions. However, as senile giotic with 50–80, small-­diameter retinal
­Posterior Segmen  659

(a) (b)

(c) (d)

Figure 15.47 Two-­handed surgical technique for phacofragmentation of an equine cataract. (a) The
right-­handed surgeon generally approaches the eye from the approximately 4-­o’clock position to avoid the
corpora nigra. (b) Mild lens capsule fibrosis surrounding the intraocular lens six months after cataract
surgery in an adult horse. (c) Glaucoma has developed in this globe following phacoemulsification removal
of a uveitis cataract in an adult horse. (d) Infrared photograph of same eye improves visualization of the
globe interior.

arterioles and venules arising from the edge of Small dots (“stars of Winslow”) distributed in a
the disc and extending only a short distance uniform pattern throughout the tapetal fundus
from the optic nerve head. The retina is divided represent end-­on views of choroidal capillaries
into dorsal tapetal and ventral nontapetal penetrating the tapetum. The optic nerve head,
regions. The nontapetal region is usually brown or optic disc, is oval to round in the horse, and it
to dark brown in color because of melanin in the is located slightly temporal, in the inferior quad-
RPE, but this pigment may be absent depending rant of the nontapetal fundus. It is somewhat
on the coat and iris coloration. The tapetal fun- pink to orange in color.
dus is usually yellow to blue to blue-­green in
brown horses, but variation can occur, again,
Disorders of the Vitreous
with the horse’s coat or iris color. Palomino and
chestnuts have a paler yellow tapetum and less Vitreal alterations are commonly of develop-
pigment in the nontapetum. Color diluents, sub- mental, degenerative, age-­related, traumatic,
albinotic or albinotic coat-­colored horses, or or inflammatory origin; however, only hyalitis
horses with heterochromia iridis or blue irides (inflammation) and degeneration are common
may have no tapetum, areas of tapetal thinning, in horses, and only hyalitis has clinical signifi-
or lack of pigment in the nontapetal retina such cance (Figures 15.49 and 15.50). Hyalitis or
that choroidal vessel patterns can be observed. inflammation of the vitreous is most
(a) (b)

(c) (d)

Figure 15.48 The different ophthalmoscopic appearances of the normal equine ocular fundus. (a)
Subalbinotic normal fundus in a Paint Horse. (b) Normal fundus appearance of horse that is blind from
unknown reasons. (c) Tapetal thinning and little pigment in the nontapetum can be normal in light-­colored
horses. (d) Normal fundic appearance of a dark-­colored horse. Small spots in the tapetal fundus are
capillaries called the “stars of Winslow.” Some choroidal nevi are present dorsal to the optic disc.

Figure 15.49 Horse with posterior ERU with Figure 15.50 Horse with advanced vitreal
yellow cellular infiltrate in the anterior vitreous. degeneration, or syneresis, which is common
finding in older horses, and appears as cobweb-­like
white strands in the vitreous.
­Posterior Segmen  661

commonly observed in horses with posterior affects the other. Chorioretinitis, inflammation
ERU and appears as yellow strands in the vitre- of the choroid and retina, may be the result of
ous with vitreal cellular infiltrate (see ERU or may be a manifestation of systemic dis-
Figure 15.49). Intravitreal hemorrhage origi- ease. Active lesions are characterized by
nates from the retinal, choroidal, or ciliary vas- edema, cellular infiltrate, and hemorrhage or
culature and will usually be the result of direct retinal detachment, and they often appear
trauma to the globe or posterior uveitis, or gray, white, or hazy (Figure 15.51). The retina
rarely posterior segment neoplasms. Blood may be elevated by subretinal fluid and inflam-
appears to be removed very slowly from the matory cells. Inactive lesions, or chorioretinal
equine vitreous, and organizing hemorrhage scars, appear as hyperreflective or hyperpig-
can be the cause of vitreoretinal detachments. mented in the tapetal fundus and may appear
to be depigmented or to have pigment clump-
ing in the nontapetal fundus (Figure 15.52).
Chorioretinitis
Chorioretinitis manifests in equine eyes as
The retina and choroid are intimately related focal “bullet-­hole lesions,” diffuse chorioreti-
anatomically and an insult to one necessarily nal lesions, nontapetal “horizontal band”
lesions, and peripapillary chorioretinal scars
(Figure 15.53). The “classic” inactive chori-
oretinal scar is circumpapillary and referred to
as a butterfly lesion. This lesion has been asso-
ciated with ERU, blunt trauma, and other
causes of chorioretinitis. Chorioretinitis or
panuveitis may also be a manifestation of sys-
temic disease and has been documented with
EHV-­1, equine infectious anemia (EIA), ade-
novirus, West Nile virus, neonatal septicemia,
R. equi, S. equi var. equi, Lyme disease, brucel-
losis, Leptospira interrogans pomona, equine
granulocytic ehrlichiosis, toxoplasmosis, the
viral encephalidities, Halicephalobus gingivalis
(Halicephalobus deletrix), and onchocerciasis.
Figure 15.51 Peripapillary chorioretinitis and
focal retinal detachment in a horse with ERU.

(a) (b) (c)

Figure 15.52 (a) Large scars from ERU-­induced chorioretinitis. (b) Peripapillary chorioretinopathy in a
horse eye can increase the size of the horse’s blind spot or scotoma. (c) Nontapetal chorioretinal scar
demonstrating sector retinal pigmented epithelial loss, pigment clumping, and exposure of choroidal blood
vessels and sclera.
662 Equine Ophthalmology

Figure 15.53 Focal chorioretinopathy, or


bullet-­hole chorioretinitis, is multifocal,
depigmented lesions that appear most commonly
ventral to the optic disc in the nontapetal fundus. Figure 15.54 Reticulated or honeycomb pattern
of accumulations of yellow-­brown to black
pigment in the tapetal and nontapetal retina in a
Congenital Stationary horse with equine lower motor neuron disease.
Night Blindness
CSNB has been reported in the Appaloosa, dark to yellow brown pigmentation in the tapetal
Quarter Horse, Thoroughbred, Paso Fino, and nontapetal retina of affected horses is noted
Standardbred, and Miniature Horse. CSNB sometimes associated with a horizontal band of
may have an incidence of up to 33% of the pigmentation at the tapetal–nontapetal junction
Appaloosa horses studied, and a significant (Figure 15.54). Consistent evidence of vitamin E
association has been demonstrated between deficiency (<1.799 μg/ml) in horses with EMND
CSNB and homozygosity of the leopard com- suggests that the RPE, retinal, and spinal lesions
plex gene (Lp). Affected horses may demon- are a result of oxidative injury associated with a
strate abnormal behavior (unease and deficiency of nutritionally derived antioxidants.
unpredictability, especially at night) or vision Retinal pigmentation not only appears to be a
loss in low-­light conditions (nyctalopia), and feature of EMND, but can also be present in neu-
some may also have decreased vision in nor- roaxonal dystrophy/equine degenerative mye-
mal light. Ophthalmic examination is normal, loencephalopathy (NAD/EDM) horses with
although some horses may also have microph- α-­tocopherol deficiency. Supplementation with
thalmia, dorsomedial strabismus, nystagmus, vitamin E may stabilize clinical signs and pre-
and an unusual dorsal ocular deviation and vent progression, but the ophthalmoscopic
head elevation, which have been termed star- changes are likely to remain.
gazing. There is no treatment for CSNB and
affected horses should not be used for breeding.
Retinal Detachment
A retinal detachment, or separation of the neu-
Equine Motor Neuron Disease
rosensory retina from the outer retinal pig-
RPE accumulation of a substance with charac- mented epithelium, can occur as a result of
teristics of ceroid lipofuscin is found associated fluid or inflammatory exudate accumulation, a
with equine motor neuron disease (EMND). A retinal tear, blunt force trauma, or traction
mosaic, reticulated or honeycomb pattern of toward the vitreous secondary to resolution of
­Posterior Segmen  663

(a)

(b) (c)

Figure 15.55 (a) Diffuse retinal detachment in the nontapetal ocular fundus in a horse. (b) Complete
retinal detachment and disinsertion in a foal with EHV-­1. (c) The retina has detached and appears as white
folds and sheets in this eye.

vitreal hemorrhage (Figure 15.55a–c). A focal head trauma and if severe can result in com-
bullous detachment appears as an elevated, plete and permanent blindness.
hazy area of retina with subretinal fluid. The
prognosis for a retinal detachment depends on
Traumatic Optic Neuropathy
the severity, underlying cause, and chronicity
of the lesions, but in general, it is poor for Stretching, shearing, or avulsion of the equine
return of vision. optic nerve or chiasm (or some combination
thereof) can result in optic nerve atrophy and
blindness from concussive cranial injuries.
Optic Nerve Atrophy
Stretching of the optic nerve from blunt head
Optic nerve atrophy in the horse occurs sec- trauma can cause blindness in horses. The
ondary to inflammation in optic neuritis and optic disc becomes pale and the pupils dilated.
ERU, and from noninflammatory causes such There is no effective therapy.
as trauma, glaucoma, toxicity, and blood loss
(Figure 15.56). Optic nerve degeneration
Proliferative Optic Neuropathy
appears as a pale, often recessed, optic nerve
head with absent or decreased vascularity. The most common optic nerve abnormality is a
Degeneration most commonly occurs after condition called proliferative optic neuropathy
664 Equine Ophthalmology

Figure 15.56 Pale optic nerve and deceased Figure 15.57 PON in a 20-­year-­old
retinal vascularity associated with optic nerve Thoroughbred mare.
degeneration.
optic neuropathy and sudden, irreversible
(PON), which appears as a slowly enlarging blindness. Optic nerve head congestion occurs
focal, white growth on typically one edge of the initially, followed within a few days by disc pal-
optic nerve protruding into the vitreous lor and extrusion of axon contents into the
(Figure 15.57). PON must be differentiated from nerve fiber layer. Optic nerve atrophy occurs in
exudative or ischemic optic neuropathy, which two to four weeks. Severe blood loss and
are acute lesions associated with complete vision thromboembolic disease may cause bilateral
loss in the affected eye. There is no therapy for blindness in horses, though the exact mecha-
PON. These are seen commonly in elderly nism for this is not understood.
horses, are rarely associated with vision deficits,
and may be benign neoplasms (e.g., glioma). Photic Headshaking
Idiopathic headshaking, or head-­tossing,
Exudative Optic Neuritis behavior in horses is recognized as uncon-
Exudative optic neuritis is found in older trollable, persistent or intermittent, seasonal
horses. It manifests as sudden onset of total or nonseasonal, spontaneous and frequently
blindness, and it is a bilateral condition. The repetitive vertical, horizontal, or rotatory
optic discs are swollen, and retinal as well as movements of the head. These signs occur
optic disc hemorrhages may be present. The with such violence that the horses are dan-
cause is not known but may be infectious gerous to themselves and riders. Rubbing of
in nature. the face, head pressing, and holding the head
low are also seen. It is not a vice, neurosis, or
Ischemic Optic Neuropathy behavioral problem. The role of light in this
Chorioretinal degeneration and optic nerve behavior in some horses was assessed by
atrophy secondary to acute blood loss caused blindfolding the horses, placing them in
by trauma or surgery have been reported in the darkened environments, or placing eye masks
horse. Surgery to eliminate equine epistaxis over their eyes. Photic headshaking behavior
because of guttural pouch mycosis by ligation improved significantly when the amount of
of the internal and external carotid and greater light striking their eyes in some horses was
palatine arteries is associated with ischemic diminished.
665

16

Food and Fiber Animal Ophthalmology


Revised from 6th edition of Veterinary Ophthalmology, Chapter 30: Food and Fiber Animal Ophthalmology, by Bianca C. Martins; and
Chapter 32: Ophthalmology of the New World Camelids, by Juliet R. Gionfriddo and Ralph E. Hamor

Food-­ and fiber-­producing animals include cat- withdraw period of 24 h is recommended when
tle, sheep, goats, pigs, and the New World came- local anesthetics are used.
lids. This chapter covers the available literature The ruminant eyes are laterally located and
by species. For each species, specific anatomical provide for a wide field of vision. Care should
and physiological characteristics, ocular param- be taken to avoid touching the eyelashes or
eters, and congenital and acquired abnormali- vibrissae, and to minimize air movement
ties of each ocular region are discussed. toward the eye, when attempting to elicit a
menace response, culminating in a false-­
positive response. It is also important to ensure
Bovine Ocular Examination that the animal is able to blink, by eliciting a
and Ophthalmic Parameters palpebral reflex. Facial nerve paralysis due to
trauma to the side of the head is not rare, and
Proper restraint is critical with examining any cranial nerve paralysis may also result from
food-­producing animal, to ensure a complete infectious diseases, such as listeriosis.
and detailed examination, and provide safety The tear production in adult cattle has been
for the examiner. Dairy cattle patients can be reported to be between 25 and 35 mm/min.
restrained in headlocks, while beef cattle are Calves exhibit lower Schirmer tear test (STT) I
better restrained in a squeeze chute. A halter values, with an average of 20 mm/min. The
or lead rope should be used to pull the head intraocular pressure (IOP) in normal dairy
laterally and secure it elevated at examiner eye cows was determined to be 26 ± 6 mmHg with
level. Sedation may be required for fractious the TonoPen-­XL™. When rebound tonometry
animals, and α2-­adrenergic agonists are the (TonoVet™) is used, values obtained vary from
most common agents used. It is important to 15.2 mmHg in calves to 23 mmHg in adult cattle.
remember that those drugs may lead to preg- The corneal sensitivity has been measured, using
nancy loss in ruminants, especially in late a Cochet–Bonnet aesthesiometer™, in healthy
pregnancy. An auriculopalpebral block may be bovine calves. Values of 1.33 ± 1.1 g/mm2,
useful to facilitate opening of the eyelids. The corresponding to a filament length of 34.56 ±­
auriculopalpebral nerve can be palpated as it 8.02 mm, were obtained. Cattle possess a small
crosses the zygomatic arch, and 1 ml of lido- corpora nigra (granula iridica) compared with
caine hydrochloride can then be injected camelids and horses, and an oval pupil on the
subcutaneously in the area. A meat and milk horizontal axis.

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
666 Food and Fiber Animal Ophthalmology

Orbit and Globe optic organogenesis and notochordal forma-


tion. Microphthalmia is usually combined
The occurrence of congenital abnormalities in with other ocular defects, including corneal
food-­ and fiber-­producing animals has opacities, cataracts, aniridia, corectopia, per-
increased over the years, likely due to a larger sistent pupillary membranes (PPMs), thicken-
number of animals being raised. Most of those ing or ossification of the choroid, and various
cases present as single occurrences in live- retinal abnormalities, such as gliosis, folds,
stock, and most affected individuals are and rosette formation, as well as retinal nonat-
euthanized. tachment and detachment. The orbit in anoph-
thalmic/microphthalmic animals also fails to
Congenital Globe Abnormalities develop, since the enlarging globe dictates the
and Blindness development of the surrounding bony struc-
The true incidence of congenital ocular abnor- tures. For that reason, anophthalmic/microph-
malities is not known. It is important to recog- thalmic animals usually will present with
nize, though, that congenital globe small orbits.
abnormalities are often linked genetically with Congenital ophthalmic anomalies in food
abnormalities in other body systems. True ano- animals have also been associated with several
phthalmos is rare. Most animals with sus- infectious organisms. The most common
pected anophthalmos actually have maternal infection causing multiple ophthal-
microphthalmia with vestigial remnants of mic defects in cattle is bovine viral diarrhea
ocular tissues (Figure 16.1). Congenital anoph- (BVD). Ocular lesions associated with BVD
thalmia/microphthalmia syndrome with mal- include cataract, PPMs, retinal dysplasia, reti-
formations of the posterior vertebral column nal degeneration, optic neuritis, and microph-
was reported in dairy and beef cattle. The exact thalmia. Bluetongue virus has also been
etiology was not known, but some cases are associated with blindness and so-­called
speculated to have a hereditary basis. In some dummy calves, which are affected with hydra-
instances, calves may have been exposed to nencephaly and are blind with normal pupil-
some unknown teratogen at the critical time of lary light responses. Profound corneal edema
has also been reported in some calves infected
in utero with bluetongue virus.

Abnormalities of Globe Position


and Movement
Abnormalities in globe position in cattle are
usually bilateral and convergent (i.e., esotro-
pia), but they can also be unilateral and diver-
gent (i.e., exotropia). Divergent bilateral
strabismus in association with hydrocephalus
has been reported as well. Bilateral convergent
strabismus with exophthalmia (BCSE) is an
eye disorder affecting many cattle breeds
worldwide (Figure 16.2). The condition is of
significant importance, as it is progressive and
often leads to complete blindness due to ante-
Figure 16.1 Microphthalmia of the left eye in a
rior–medial rotation of both globes, and the
calf. The right eye is normal in size (Courtesy of
University of Missouri Comparative Ophthalmology disappearance of the pupils beneath the nasal
Service). orbital rim. The globes are fixed in this
Orbit and Globe  667

Figure 16.2 A Holstein calf with convergent


strabismus and exophthalmos (Courtesy of
Cecil Moore).

undesirable position and unable to move. The


disease occurs as an autosomal recessive defect Figure 16.3 Marked bilateral exophthalmos due
in Jersey cattle and likely as autosomal domi- to retrobulbar fat deposition in a one-­month-­old
Holstein bull calf treated with dexamethasone as
nance with 70% incomplete penetrance in
part of a metabolic study (Courtesy of Wendy
German Brown Swiss cattle. Environmental Townsend).
effects may also be important. On the basis of
histopathological results, a defect in the motor arteriovenous fistula. Calves administered
nucleus of the abducent nerve may be respon- daily dexamethasone injections develop
sible for the symptoms of BCSE. Esotropia also exophthalmos due to increased deposition of
occurs in Holstein and Ayrshire cattle. retrobulbar adipose tissue (Figure 16.3). The
Exophthalmia and esotropia progress until the prognosis for exophthalmos depends on its eti-
animal reaches maturity. Nystagmus may be ology. Most forms of retrobulbar neoplasia in
present, and vision is compromised. cattle carry a guarded prognosis, whereas
In some cases, strabismus may be associated inflammatory disease (e.g., sinusitis) is usually
with a generalized systemic infection. Bilateral more amenable to treatment.
dorsomedial strabismus may be associated A single case of unilateral exophthalmia sec-
with polioencephalomalacia (PEM). Affected ondary to cavernous sinus syndrome was
calves are usually blind and exhibit opisthoto- reported in a Holstein bull, which had a his-
nos. Ipsilateral neurological signs in associa- tory of a resolved abscess at the base of his
tion with a medial strabismus are suggestive of right ear. While cavernous sinus syndrome in
listeriosis. Inflammation of the brainstem small animals is frequently associated with
impinges on the abducens nucleus, resulting neoplastic processes, the condition in large
in medial strabismus through loss of function animals may be related to infectious organisms
of the lateral rectus muscle. and abscesses.

Retrobulbar Space-­Occupying Lesions Orbital Neoplasia


Unilateral strabismus or exophthalmia (or Lymphoma in cattle affects the retrobulbar tis-
both) usually results from space-­occupying sues and is the most frequent cause of exoph-
orbital lesions due to inflammation or neopla- thalmos with and without strabismus
sia. However, other anatomical defects have (Figure 16.4). The complete physical examina-
been implicated. An Ayrshire calf was tion may reveal lymphadenopathy, cardiac
described with exophthalmos and an orbital arrhythmia, and melena, as well as uterine and
668 Food and Fiber Animal Ophthalmology

Orbital Inflammation
Trauma, puncture wounds of the eyelids or
conjunctiva, foreign body migration from the
mouth to the retrobulbar space, actinobacillo-
sis, and panophthalmitis are potential causes of
orbital inflammatory disease. Associated sys-
temic signs may include pyrexia, anorexia, tem-
poromandibular pain, exophthalmos and
associated sequelae, and leukocytosis.
Treatment involves identifying the underlying
cause, hot packing the area, drainage and lav-
age of any nidi of infection, possibly topical and
systemic antibiotics, and, if panophthalmitis is
present, enucleation. Exophthalmos and orbital
Figure 16.4 Exophthalmos with marked inflammation may be sequelae to chronic fron-
hyperemia and thickening of both the palpebral tal sinusitis in cattle, as a sequela to either
and bulbar conjunctiva in a cow with systemic dehorning (usually Actinomyces pyogenes) or
lymphosarcoma involving the orbit (Courtesy of respiratory disease (usually Pasteurella
L. Horstman).
multocida).

renal masses. Cases of primary ocular lym- Nystagmus


phoma have been reported without retrobul- In cattle, nystagmus may be either congenital
bar extension. Bovine leukemia virus is the or acquired. A congenital rapid pendular nys-
cause of lymphoma in cattle. Serological tests tagmus, which is usually horizontal, is
and polymerase chain reaction (PCR) are avail- observed in Holstein Friesians especially and
able to determine presence of bovine leukemia in other breeds as well. Vision does not seem to
virus, but it is important to remember that ani- be significantly compromised, and the animals
mals remain seropositive throughout life. A are affected for life. A possible genetic relation-
positive test will not confirm the diagnosis of ship may exist. Other causes include brain
lymphoma, but a negative test for bovine leu- tumors and abscesses, intoxication by chemi-
kemia virus rules out the possibility of lym- cals, plants, and heavy metals, cerebral anemia
phoma. The only definitive diagnostic for and vascular disease, and congenital or early
bovine lymphoma is a biopsy. Treatment is postnatal blindness.
usually palliative, because most cattle with
orbital lymphosarcoma die within six months.
The Eyelids
In those cases, exenteration may be performed
to relieve the pain associated with exposure Entropion and Eyelid Defects
and subsequent keratitis/panophthalmitis. Entropion is relatively rare in cattle, but it has
Other reported retrobulbar orbital neo- been reported in the Simmental breed. Spastic
plasms include invasive or metastatic squa- and cicatricial entropion are more common
mous cell carcinoma and adenocarcinoma. than congenital entropion.
While these tumors typically carry an
extremely guarded prognosis, animals may still Ectropion
live for months to years. Sporadic reports of While ectropion may pose less danger to the
other orbital tumor types in cattle exist, includ- eye, it can produce chronic exposure keratitis,
ing meningioma, lymphangiosarcoma, and conjunctivitis, keratoconjunctivitis, epiphora,
malignant histiocytoma. and tear staining, as well as scalding of the
Orbit and Globe  669

eyelids. Ectropion may result from develop- more commonly associated with infectious
mental, cicatricial, trauma, neurological, and bovine keratoconjunctivitis [IBK]) was iso-
postoperative causes. lated. Isolation of this organism came from a
cow that also had concurrent corneal ulcera-
Eyelid Trauma tion, so true etiological relationship cannot be
Lacerations are the most common traumatic confirmed.
injury to the eyelids, but they are infrequent
among food animals (Figure 16.5). The basic Mycotic
principles of eyelid closure apply when such Trichophyton spp. can affect all food-­producing
lacerations occur. animals. Despite the self-­limiting nature of
dermatophytosis, treatment is recommended
to limit any further infection of unaffected ani-
Blepharitis
mals and humans. Topical and systemic fungi-
Bacterial cidal agents, iodine shampoos, improved
Dermatophilosis (i.e., rain scald) is caused by nutrition, and dry environs all may assist in
Dermatophilus congolensis, a Gram-­positive, eliminating the disease. Vaccination of newly
aerobic, filamentous bacterium. The infective infected herds shows potential as a prophylac-
stage is a motile, coccoid zoospore that is tic measure.
released from scabs by wetting. The zoospores
then invade deeper layers of the dermis to Ectoparasites
incite an inflammatory response. The distal Sarcoptic mange is caused by Sarcoptes scabiei,
extremities, muzzle, and dorsum are usually with a subspecies specific for each host species.
involved initially, but it may spread over the This host specificity is not complete, however,
entire face. Treatment consists of providing a and transference from one host species to
dry environment and bathing with iodine or another can occur. The disease is characterized
chlorhexidine shampoos. In severe cases, peni- by intense pruritus, papules, and general ery-
cillin (20 000 IU/kg) with or without strepto- thema. The first clinical signs may include
mycin (10 mg/kg) intramuscularly for three to facial dermatitis, with thick, crusty, wrinkled,
five days or one intramuscular injection of and denuded areas around the face and eye-
long-­acting oxytetracycline (20 mg/kg) may be lids. The lesions may become widespread. The
necessary. A case series has described nine disease is uncommon in the United States. At
dairy cows with ulcerative blepharitis and con- the time of publication, it is not considered to
junctivitis where Moraxella bovoculi (an agent be a reportable disease. However, sarcoptic
mange in cattle has been cited as a reportable
disease in the past; readers are referred to
online documentation for current status of this
disease (USDA 2019). Treatment of all affected
and contact animals is indicated. For many
years, the most common way to treat infected
animals was using dip vats, but the efficacy of
new compounds that may be applied topically
as sprays, drenches, and pour-­ons has reduced
the cost and time needed to treat this disease.
Demodex spp. are host specific (Demodex
bovis affects cattle). The adult mites invade
Figure 16.5 Extensive traumatic eyelid laceration hair follicles and sebaceous glands of the face,
in a cow (Courtesy of L. Horstman). limbs, and back, which then become distended
670 Food and Fiber Animal Ophthalmology

with mites and inflammatory material. Neoplasia


Secondary bacterial invasion of these lesions
Ocular squamous cell carcinoma (OSCC) is the
will result in formation of pustules and
most common tumor of the eye and eyelids in
abscesses. Pustules may be seen around the
cattle. On the eyelid, lesions may initially
eyes, and pruritus may be present. The disease
appear as ulcerative areas or proliferative
tends to be generalized in cattle. Acaricidal
lesions or combinations thereof. Surgical exci-
treatments may be used; however, self-­
sion has been shown to be successful if lesions
resolution has been reported.
are small and limited in number. Cryotherapy
may be helpful as sole therapy for small lesions
Photosensitization or as adjunctive therapy for larger lesions.
Infection with bovine papillomavirus may
Direct solar irritation (i.e., sunburn) may occur
cause neoplastic lesions to form on the perioc-
in food animals with little periocular pigmen-
ular skin and eyelids. Manifestations include
tation, but acute periocular dermatitis is more
acanthosis (epidermal hyperplasia), papillo-
likely the result of photosensitization. If pho-
mas (Figure 16.6), and keratinized elongated
tosensitizing substances are present in suffi-
proliferative lesions (keratoacanthoma, cuta-
cient concentration in the skin, dermatitis
neous horn) (Figures 16.7 and 16.8). In most
occurs when that skin is exposed to light. The
causative photodynamic agents may be
ingested preformed (i.e., primary photosensiti-
zation), be products of abnormal metabolism,
or be normal metabolic products that accumu-
late in tissues because of faulty excretion
through the liver. Photodynamic agents
include hypericin in Hypericum perforatum (St
John’s wort), fagopyrin in Polygonum fag-
opyrum (buckwheat), and perloline from
Lolium perenne (perennial ryegrass); miscella-
neous agents include phenothiazine sulfoxide
from phenothiazine, rose Bengal, and acridine
dyes. In all cases of secondary photosensitiza- Figure 16.6 Erosive lesion on lower eyelid,
presumptive of early OSCC change. Third eyelid
tion, phylloerythrin, which is a normal end papillomatous mass is also present.
product of chlorophyll metabolism, is the pho-
todynamic agent. When biliary secretion is
obstructed by hepatitis or biliary duct obstruc-
tion, phylloerythrin accumulates in the body.
The progressive clinical manifestation of both
primary and secondary photosensitization
consists of lacrimation, photophobia, ery-
thema, cutaneous edema, fissuring of the epi-
thelium, exudation and crusting of serum and
necrosis, and sloughing of nonpigmented
exposed skin. Corneal edema is also evident in
many cases. Treatment involves removing the
affected animal from sunlight, preventing
ingestion of toxic material, and administering Figure 16.7 Papillomas of the left eyelid and
laxatives. periocular area in a steer (Courtesy of Cecil Moore).
­Conjunctiva and Corne  671

Figure 16.8 Keratoacanthomas (keratinized Figure 16.9 A large dermoid involving the
elongated proliferative lesions) of the right eyelid nictitating membrane in Hereford calf.
of a cow. These are often associated with bovine
papillomavirus infection (Courtesy of Cecil Moore).
Congenital Anomalies
cases, the disease is self-­limiting, and the Dermoid
lesions may resolve over time, but potential for Dermoids occur principally in cattle, but they
malignant transformation into squamous cell can occur in other food animal species as well
carcinoma exists. (Figure 16.9). The defect in Herefords is geneti-
cally transferred, with characteristics of auto-
somal recessive and polygenic inheritance. In
­The Nasolacrimal System cattle, the site predilection of ocular dermoids
is, in decreasing order, the limbus, third eyelid,
The tear-­producing glands in food animals
canthi, eyelid, and conjunctiva. Dermoids
rarely have any primary abnormality. Epiphora
rarely appear bilaterally, except in certain lines
is the most common abnormality and is usu-
of Hereford cattle. The clinical manifestation
ally secondary to irritative ocular disease caus-
varies from an unsightly blemish to various
ing increased tear production rather than to
degrees of visual impairment, keratoconjuncti-
defects in tear outflow.
vitis with epiphora, blepharospasm, and cor-
neal ulceration. Surgical removal is
Developmental Anomalies recommended if vision is impaired or the eye
Congenital anomalies of the nasolacrimal sys- is painful.
tem are rare in food animals. Focal intrauter-
ine infections (i.e., resulting in dacryocystitis) Congenital Porphyria and Protoporphyria
have been suggested as a contributory cause. Inherited defects of porphyrin metabolism in
Contrast dacryocystorhinography has been cattle and swine are characterized by excessive
extremely useful in diagnosing anatomical deposition of porphyrin isomers in the tissues.
defects in the nasolacrimal ducts. Congenital porphyria is similar to Gunther’s
porphyria in humans and is inherited as an
autosomal recessive trait. The incidence is
­Conjunctiva and Cornea higher in females than in males, but the dis-
ease is rare. Even so, it has been recorded in
The conjunctiva and cornea are major sites for Shorthorn, Holstein, Black and White Danish,
ophthalmic diseases in food-­producing ani- Jamaica Red and Black cattle, and Ayrshires.
mals, with profound economic effects. In cattle, Congenital erythropoietic porphyria in cattle is
IBK and OSCC are the predominant conditions caused by an inherited deficiency of the
affecting the conjunctiva and cornea. enzyme uroporphyrinogen III synthase.
672 Food and Fiber Animal Ophthalmology

Insufficient activity of this enzyme leads to the rumen as the sulfoxide and conjugated in the
formation of the metabolites uroporphyrino- liver to form leucophenothiazine ethereal sul-
gen I and coproporphyrinogen I. These por- fate, which is then excreted into the urine and
phyrinogens are oxidized to their end products the bile. Cattle are unable to detoxify all the
uroporphyrin I and coproporphyrin I, which phenothiazine sulfoxide, however, and a pro-
accumulate in the body. These high levels of portion enters the systemic circulation and
porphyrins sensitize the skin and eyes to light. aqueous humor of the eye, thereby causing
Protoporphyria is a less common, milder dis- photosensitization. Photophobia, blepharos-
ease than porphyria and is thought to be inher- pasm, epiphora, corneal edema, and keratitis
ited in cattle. In this disease, there is deficient may occur, and eyelid edema has also been
activity of the enzyme ferrochelatase, resulting reported. Treatment for the condition is symp-
in excessive synthesis of protoporphyrin. tomatic, but affected animals may show no
Ocular clinical signs related to abnormal por- clinical signs or may even recover spontane-
phyrin metabolism result from photosensitiza- ously if access to sunlight is restricted, espe-
tion. These signs include photophobia, edema, cially for 12–36 h after treatment.
inflammation, and necrosis of the eyelids and
the periocular skin. Treatment consists of
Parasitic Keratoconjunctivitis
maintaining affected animals indoors.
Thelazia Species
In North America and Europe, Thelazia spp.
Inherited Corneal Disease
are regarded as being nonpathogenic to mildly
Most cases of corneal edema seen in food ani- pathogenic. In contrast, more severe disease,
mals are secondary either to intraocular dis- and even blindness, has been reported in other
ease that affects endothelial cell function or to countries. The variability in pathogenicity may
extraocular disease that causes a defect in the result from host, parasite, livestock manage-
overlying corneal epithelium. Primary ment, and climatic factors.
endothelial disease is extremely rare in food Thelazia spp. nematodes are small, slender,
animals, but an autosomal recessive corneal white worms that occur in the conjunctival sac
disease of Holsteins. Affected animals show and nasolacrimal ducts, and move rapidly in
bilateral corneal edema either at or soon after the preocular tear film. Thelazia rhodesi,
birth. The condition is not amenable to treat- Thelazia gulosa, Thelazia skrjabini, and
ment and affected animals should not be used Thelazia lacrymalis affect cattle. The worms
for breeding. are more abundant in beef than in dairy breeds.
Unilateral chronic follicular or mucoid con-
junctivitis is most common, with irregularities
Phenothiazine-­Induced
in the lining of the nictitans gland ducts. Other
Corneal Disease
clinical signs include profuse epiphora, photo-
Phenothiazine is used as a prophylactic in the phobia, and ulcerative keratitis. Face flies,
control of manure-­breeding insects and as an especially Musca autumnalis, act as biological
anthelmintic in livestock. Corneal edema and vectors and transfer the larvae to the eyes while
keratitis have been associated with phenothia- feeding. Hence, cases are more prevalent in the
zine toxicity, but this is a condition seen mainly summer and fall months. The prevalence is
in calves and, to a lesser extent, in pigs lower among cattle grazing short and mid-­size
and goats. grass pastures than among those grazing tran-
The metabolism of orally administered phe- sitional or aspen parkland pastures, rough fes-
nothiazine varies by species. In calves and cue, or woodland-­type pastures. The diagnosis
sheep, phenothiazine is absorbed from the is usually made postmortem by identification
­Conjunctiva and Corne  673

of the parasite in the conjunctival sac or nasol-


acrimal duct. Antemortem diagnosis can be
made by careful gross examination of the
whole lacrimal apparatus or by demonstration
of fully embryonated eggs, larvae, or immature
worms using specialized techniques. Often,
the clinical diagnosis is made when the eye is
being manipulated for unrelated diagnostic or
surgical procedures. Treatment includes sim- Figure 16.10 Conjunctivitis, chemosis and white,
ple lavage, mechanical removal after topical lymphocytic, conjunctival plaques associated with
anesthesia, administration of levamisole IBR virus infection in a cow (Courtesy of
(5 mg/kg orally or 1% solution topically) or fen- Cecil Moore).
bendazole, and topical administration of iver-
mectin or echothiophate iodide. Subcutaneous
ivermectin (0.2 mg/kg) and doramectin as well
as pour-­on ivermectin have been reported to be
effective treatments.

Infectious Keratoconjunctivitis
Keratomycosis
Fungal infection of the bovine cornea is quite
uncommon. A confirmed case of Aspergillus
and Fusarium keratitis was reported in a five-­
year-­old Holstein cow. Clinical signs included
ocular discharge, periorbital swelling, an area
of full-­thickness corneal cellular infiltrate,
fibrin, hypopyon, diffuse corneal edema, and
miosis. The patient was diagnosed with a cor- Figure 16.11 Extensive corneal edema and
neal stromal abscess and secondary anterior conjunctivitis in a cow associated with IBR virus
uveitis. Response to standard topical antifun- (Courtesy of Cecil Moore).
gal therapy and supportive therapy for uveitis
was good. Listerial Keratoconjunctivitis
The etiological agent is the rod-­shaped, Gram-­
Infectious Bovine Rhinotracheitis positive bacteria Listeria monocytogenes. This
Infectious bovine rhinotracheitis (IBR) may condition is also known as silage eye, since the
cause nonulcerative keratoconjunctivitis. etiological agent is usually found in fermented
Conjunctivitis is the most common manifesta- hay silage. Ocular lesions are frequently
tion of IBR and is characterized by raised, observed in the meningoencephalitic form of
white plaques on the bulbar and palpebral con- the disease (also called listeriosis of the central
junctival surfaces (Figure 16.10). Chemosis is nervous system [CNS]). Neurological signs
also often present. Variable degrees of nonul- include vestibular ataxia and unilateral cranial
cerative keratitis can also develop with periph- deficits, with reports of facial nerve paralysis
eral edema and vascularization initially. In and keratoconjunctivitis sicca. Lesions may be
severe cases, the corneal edema and cellular located unilaterally or bilaterally, but unilat-
infiltrate can be quite extensive, resulting in eral presentation is most common. Ocular sur-
blindness (Figure 16.11). face signs include conjunctivitis with excessive
674 Food and Fiber Animal Ophthalmology

lacrimation and photophobia. Keratitis is man- poor prognosis; however, improvement of uve-
ifested by punctate abscesses, peripheral itis is not associated with a better prognosis.
clouding (corneal edema), ulceration, and cor-
neal vascularization. Uveitis is also a classic
Infectious Bovine Keratoconjunctivitis
manifestation of this condition with the pres-
ence of infiltrative uveal disease, hypopyon, IBK, also known as pink eye, contagious oph-
and miosis. thalmia, and New Forest disease, has received
considerable attention because of its world-
Chlamydial Keratoconjunctivitis wide distribution and economic impact. The
Chlamydiae have been isolated from cattle first report of presumed IBK appeared in 1888.
with conjunctivitis. Incidents of recurrent In 1952, it was determined that keratitis was
bilateral keratoconjunctivitis have been caused by Moraxella bovis.
reported in different cattle herds. The cases
were quite persistent and responded poorly to Economic Impact
antibiotic treatment. Chlamydophila spp. DNA Financial losses from IBK can be profound and
was detected in conjunctival swabs by PCR. No occur due to decreased weight gain and
other pathogens were detected. Two herdsmen decreased milk production, and treatment costs
also developed concurrent eye disease, sug- were estimated to be $150 million in the United
gesting a possible zoonotic risk. States in 1993. Less tangible economic losses can
also occur, such as a loss of value in show or
Malignant Catarrhal Fever breeding stock, weight loss and injury from han-
Malignant catarrhal fever (MCF) is a fre- dling animals for treatment, condemnation at
quently fatal infectious disease that affects cat- slaughter due to ocular lesion detection, and lost
tle, bison, buffalo, deer, and other ruminants. productivity during time devoted to treatment.
It is caused by several rhabdoviruses belonging In affected unweaned calves, it was thought that
to the gamma herpes family. In cattle, it is losses associated with IBK were temporary and
often transmitted by ovine herpesvirus-­2. would recover after weaning and resolution of
Cattle usually do not spread the virus by con- the condition. However, a study demonstrated
tact transmission and are considered dead-­end that yearlings that had evidence of IBK at wean-
hosts. The “head and eye” form is considered ing had less body weight than cohorts without
the classical form of the disease, and is accom- evidence of IBK, and associations between IBK
panied by high fever, inappetence, depression, at weaning and production variables persisted
lesions of the oral cavity and muzzle, profuse well into the postweaning period.
mucopurulent nasal discharge, dyspnea, ster-
tor, and diarrhea. The most common ocular Incidence
sign is corneal edema, which can vary from IBK occurs worldwide. In a 1997 report of the
mild perilimbal to dense complete corneal US National Animal Health Monitoring
edema. Other ocular symptoms include exoph- System, IBK (1.1% infection rate) was the
thalmos, blindness, nystagmus, photophobia, second-­most prevalent condition affecting
lacrimation and mucopurulent ocular dis- unweaned beef calves over three weeks of age
charge, eyelid edema, and other symptoms of (USDA 1997). In the same report, IBK (1.3%
conjunctivitis, keratitis, and anterior uveitis. infection rate) was the most prevalent condi-
The degree of corneal edema on first examina- tion affecting all beef heifers and cows. In
tion does not correlate with prognosis; how- studies at the University of California–Davis
ever, cases that exhibit improvement of the field station in Browns Valley, the yearly preva-
corneal edema may have a better prognosis. lence of IBK in yearling calves ranges from
Deterioration of uveitis is associated with a 57% to 98%.
­Conjunctiva and Corne  675

IBK occurs primarily during the summer provides weak evidence for a causal role for
months, though winter outbreaks occur. This M. bovoculi in IBK.
seasonal fluctuation may result from the increased
presence of hemolytic M. bovis, the fly popu- Morphology of Moraxella bovis
lation, and solar radiation during the summer The morphology of M. bovis colonies is either
months. The decline through the fall season rough or smooth. Clinical cases of IBK are
may result from the lack of susceptible calves, associated with the rough type, which have cell
fewer vectors, and decreased intensity of surface pili, autoagglutinate in distilled water,
enhancing factors. stain with crystal violet, and hemagglutinate.
The β-­hemolytic variants are usually associ-
Etiology ated with clinical disease.
While M. bovis, a Gram-­negative bacillus, is Electron microscopy has revealed that bacte-
considered to be the primary cause of IBK, ria from rough colonies of M. bovis are piliated
other microbial agents have also been impli- and able to cause disease, whereas those from
cated. However, M. bovis is the only organism smooth colonies are nonpiliated and nonpath-
for which Koch’s postulates have been satis- ogenic (Figures 16.12 and 16.13). The capsular
fied. Other infective agents that may play a role pili promote cellular adhesion and enhance
in development of IBK include Moraxella ovis the ability to overcome host defenses and
(formerly Neisseria/Branhamella ovis), M. bovoc- maintain an established infection. As a general
uli, IBR virus, Mycoplasma spp., Thelazia spp., rule, the piliated, hemolytic form is found in
and L. monocytogenes. Concurrent infection acute cases of IBK, and proportionately more
with IBR causes more severe clinical signs nonpiliated and nonhemolytic isolates are
than with IBK alone. Moraxella bovoculi has recovered from convalescent and clinically
been isolated from eyes of cattle with clinical normal carrier cattle.
signs of IBK; however, the causal role of
M. bovoculi and M. ovis in naturally occurring Transmission
IBK is unclear. Moraxella bovoculi and M. bovis The source of infection is usually a new animal
are both more frequently recovered from eyes or a carrier animal within the herd. Moraxella
with IBK lesions than unaffected eyes, which bovis can typically be found on the

Figure 16.12 Cross section of a


M. bovis bacterium harvested from
rough colony showing peritrichous
distribution of pili (P) on the cell
surface. Inset is a higher
magnification of these pili (Original
magnification, 47 570×.) (Courtesy of
the late Charles Simpson).
676 Food and Fiber Animal Ophthalmology

(a) (b)

Figure 16.13 Cells from smooth (a) and rough (b) colonies of M. bovis. Only the rough form of M. bovis
shows the peritrichous distribution of pili (P), many of which have been fractured from the cell. (Chromium
shadowed; original magnification, 20 000×.) (Courtesy of the late Charles Simpson).

conjunctivae and in the nasal secretions of cat- cattle, less than two years, consistently have an
tle without any signs or history of infection. increased risk and severity of clinical disease
Nonhemolytic M. bovis may reside in a herd compared with older cattle, even though large
over the winter months and not cause clinical numbers of older animals are infected.
signs. However, with the onset of spring and Developmental immunity is also suggested by
increased ultraviolet (UV) radiation, there can observations that infected calves develop dis-
be a reversion to the pathogenic, hemolytic ease, whereas their infected dams fail to
form, with subsequent infection of suscepti- develop clinical signs. A good correlation exists
ble calves. between the annual peak incidence of IBK and
Moraxella bovis is transmitted by animal annual peak levels of UV radiation. Increased
handlers, direct contact with infected animals, UV radiation assists in the transformation of
contact with fomites, and mechanical vectors, M. bovis from nonhemolytic to hemolytic
such as flies. The face fly (M. autumnalis) is strains. The number of face flies present cor-
considered to be the most important vector. relates well with the infection rate and the
However, the house fly (Musca domestica) and number of new isolates. Once the number of
stable fly (Stomoxys calcitrans) have also been flies exceeds 10 per animal, IBK spreads from
incriminated as mechanical vectors. These one herd to another. Cattle housed indoors
flies may harbor the organism on their legs for have a higher infection rate of longer duration,
as long as three days. Without flies, transmis- but milder clinical disease compared with
sion of IBK throughout a herd may be slow. those housed outdoors. Other environmental
factors, such as mechanical irritants to the
Predisposing Factors conjunctiva and cornea and ingestion of afla-
The sex of an animal is not a significant factor toxin, have also been suggested as enhancing
in development of the disease. All breeds may factors.
be affected, but breed-­related differences in
susceptibility occur. Bos indicus breeds are Pathogenesis
more resistant than Bos taurus breeds, and In clinical outbreaks of IBK, M. bovis can be
Herefords as well as Hereford crossbreeds isolated from most affected cattle. The initial
appear to have a much higher susceptibility, as corneal lesions probably result from bacterial
do Murray Greys. cytotoxicity, whereas advanced lesions may be
The age of cattle affects the persistence and associated with bacterial/host inflammatory
severity of infection with M. bovis. Younger interaction. While M. bovis does not produce
­Conjunctiva and Corne  677

collagenase, the pathophysiology of IBK is


likely associated with collagenase release from
damaged epithelial cells, fibroblasts, and neu-
trophils. In addition, gelatinase and DNase
have been detected in whole cultures, while
dermonecrotoxins and cytotoxins for BHK 21
cell line monolayers and soluble factors that
cause reversible detachment of cultured cor-
neal epithelial cells have been detected in
M. bovis culture filtrates. Both hemolytic and
cytotoxic activities of neutrophils and corneal
epithelial cells are important in the pathogen-
esis of IBK. Additionally, pathogenic factors of
M. bovis, including pilin and cytotoxin (hemo-
lysin, cytolysin), contribute to the pathogene-
sis of clinical disease. Pilin facilitates Figure 16.14 Early, faint fluorescein retention by
attachment to the corneal surface. Cytotoxin a central cornea affected with IBK (Courtesy of Kirk
N. Gelatt).
lyses bovine neutrophils, erythrocytes, lym-
phocytes, and corneal epithelial cells

Clinical Signs
The earliest clinical signs are varying degrees
of epiphora, blepharospasm, and photophobia;
conjunctival hyperemia and chemosis also
occur. Often, this stage may be missed clini-
cally because of an inability to carefully
observe affected animals. Within 24–48 h after
the onset of clinical signs, the axial cornea may
develop small epithelial defects. Small corneal
Figure 16.15 Midstromal corneal ulcer
vesicles may precede ulceration. A small, pale, surrounded by corneal edema and early limbal
yellow to white raised abscess may appear near corneal vascularization associated with IBK
the center of the cornea, and over the follow- (Courtesy of Jacqueline Pearce).
ing 24–48 h, the corneal opacity may increase
in size or slough, leaving a shallow, round to
oval, superficial ulcer with perilesional edema
(Figures 16.14 and 16.15). During the next few
days, the corneal ulcer may expand and deepen
(Figure 16.16).
There is marked perilimbal conjunctival vas-
cular hyperemia and initiation of superficial
corneal vascularization. Blepharospasm, mild
to moderate aqueous flare, and iridocyclitis are
present. The conjunctival exudate becomes
mucopurulent, with matting of the eyelashes.
Vascularization of the cornea proceeds rapidly Figure 16.16 Large, deep stromal corneal ulcer
surrounded by cellular infiltrate, corneal edema,
toward the primary central lesion. By seven to and ciliary flush associated with IBK (Courtesy of
nine days postinfection, an area of Jacqueline Pearce).
678 Food and Fiber Animal Ophthalmology

inflammation and corneal vascularization sur- blindness may result. The eye may also become
rounds the well-­delineated corneal ulcer hypotensive and phthisical or buphthalmic
(Figure 16.17). As the vascularization reaches from secondary glaucoma (Figure 16.19). In
the ulceration, the corneal opacity clears from 75% of cases, ocular involvement is unilateral,
the periphery toward the center. The ulcer epi- but bilateral involvement may also occur.
thelializes, and the facet gradually reduces by Affected animals are reluctant to compete for
stromal regeneration, leaving a slightly raised, food, milk production is reduced, and weight
dense scar. Corneal healing is well advanced in gain is suppressed, usually in direct relation to
two to three weeks and in one to two months the severity of the lesion. In young cattle, the
only a faint localized central corneal opacity disease process is usually more severe than in
may remain. older animals.
The keratoconjunctivitis may result in sec-
ondary iridocyclitis, with hypopyon, syne- Medical Treatment
chiae, and even panophthalmitis. Occasionally, Antibiotic treatment has been shown to be suc-
perforation of the corneal ulcer results in iris cessful in reducing healing times of IBK-­
prolapse (Figure 16.18), in which case associated corneal lesions. However, few
reports directly compare different antibiotic
classes, so it is difficult to evaluate comparative
antibiotic efficacy. Currently, oxytetracycline
formulations such as Liquamycin/LA-­200™
(Zoetis Animal Health, Parsippany, NJ, USA),
Bio-­Mycin 200™ (Boehringer Ingelheim
Vetmedica Inc., St. Joseph, MO, USA), and
Noromycin 300 LA™ (Norbrook Inc., Overland
Park, KS, USA), and the tulathromycin formu-
lation Draxxin™ (Zoetis Animal Health) are
the only parenteral antibiotics labeled for IBK
in cattle. Topical medications approved for IBK
Figure 16.17 Central corneal granulation and include the oxytetracycline formulation
fibrosis secondary to corneal ulceration during
previous IBK, now inactive (Courtesy of Jacqueline Terramycin™ (Zoetis Animal Health) and
Pearce). Vetericyn Pink Eye Spray™ (Innovacyn Inc.,
Rialto, CA, USA). Veterinarians are encour-
aged to consult current online publications for
up-­to-­date information on IBK labeled drugs.

Figure 16.18 Central corneal perforation with


staphyloma formation associated with IBK. There is
mild corneal edema and vascular response in the Figure 16.19 Secondary glaucoma with
surrounding cornea(Courtesy of Jacqueline Pearce). buphthalmos due to IBK (Courtesy of Cecil Moore).
­Conjunctiva and Corne  679

Other treatment options require extralabel various authors include penicillin, ampicillin,
drug use in food animals, which is very care- ormetoprim–sulfadimethoxine (prohibited for
fully regulated by the US Food and Drug extralabel use in lactating dairy cattle in the
Administration and by the American United States), furazolidone (prohibited for use
Veterinary Medical Association via the Animal in food animals in the United States), gen-
Medicinal Drug Use Clarification Act. tamicin, and neomycin.
Therefore, other treatment options should Moraxella bovis is usually resistant to tylosin,
only be used if currently labeled drug have lincomycin, and erythromycin, and has varia-
been shown ineffective, and as long as the ble susceptibility to cloxacillin. Some M. bovis
drugs are not prohibited for extralabel use in strains, however, may be sulfa-­resistant. While
food animals (AVMA 2007). M. bovis is sensitive to many antibiotics,
Therapy for IBK is recommended to relieve regional and strain differences may necessitate
pain and maintain productivity. Combined culture and sensitivity tests to select a specific
parenteral (20 mg/kg) and oral (alfalfa pellets antibiotic, especially during a severe outbreak.
containing 1 g/0.45 kg of pellet administered The treatment selected is influenced by the
daily for 10 days at a dosage of 2 g/calf/day) management practice of the affected animals.
administration of oxytetracycline appears to be Dairy operations usually have daily access to
an effective method of reducing the severity of the animals, but milk withdrawal times
herd outbreaks of IBK. Oxytetracycline ther- become important issues. Dairy operations
apy appears to be superior to penicillin therefore may choose procaine penicillin
G. Calves treated with oxytetracycline had because of the short milk withdrawal times.
fewer recurrences and less shedding of M. bovis Because beef cattle are infrequently handled,
compared with those treated with penicillin beef practitioners may opt for long-­lasting par-
G. Long-­acting oxytetracycline formulations enteral medications such as oxytetracycline.
(LA-­200, LA-­300, and Bio-­Mycin 200) are cur- As antibiotic drug residues vary according to
rently approved for treatment of IBK in the the drug formulation, dose, frequency, route of
United States. While parenteral long-­acting administration, and weight of the animal, the
oxytetracycline formulations can be used in Food Animal Residue Avoidance Database
lactating dairy cattle, alfalfa pellets containing should be contacted to determine withdrawal
oxytetracycline cannot. The duration of the times and legality of use of a particular drug in
carrier stage (i.e., a normal eye with hemolytic an extralabel fashion. Other medical treat-
M. bovis) is reduced by two injections of long-­ ments for IBK include topical atropine and
acting oxytetracycline at 20 mg/kg each. In nonsteroidal anti-­inflammatory drugs
addition to shortening the carrier stage, treat- (NSAIDs). These medications assist in relief of
ment reduces the progression of lesions and intraocular pain and decrease the incidence of
shortens healing times in affected animals. inflammatory-­induced ocular lesions. Some
Other antibiotics demonstrating efficacy reports detail use of local corticosteroids in
against M. bovis include tilmicosin (one dose of IBK-­affected eyes without any detrimental
5–10 mg/kg subcutaneously), long-­acting ceftio- effect. The lack of evidence-­based medicine
fur crystalline-­free acid (one dose of 6.6 mg of indicating corticosteroids is beneficial in IBK
ceftiofur equivalents/kg subcutaneously into the cases, and the possibility of potentiating colla-
posterior aspect of the pinna), florfenicol (two genases and prolonging healing times must be
injections of 20 mg/kg intramuscularly q 48 h or considered. Therefore, corticosteroids are best
a single dose of 40 mg/kg subcutaneously), avoided in IBK.
tulathromycin (2.5 mg/kg subcutaneously), and Regardless of the therapy chosen, addi-
clindamycin (150 mg subconjunctivally q 24 h tional treatment steps should be taken to con-
for three days). Other drugs recommended by trol the herd infection and minimize the
680 Food and Fiber Animal Ophthalmology

economic effects. Critical measures include Incidence


use of insecticides to control face flies, segre- Actual incidence in the general cattle popula-
gation of affected animals, personal disinfec- tion of the United States is often difficult to
tion between treatments of affected and assess. In herds of live cattle, the incidence of
noninfected animals, and frequent mowing of OSCC has shown to vary from 4.4% to 5.6%.
pastures. However, many of these studies considered
herds of Hereford or Hereford cross cattle only
Vaccination and hence it is difficult to extrapolate.
In herds severely affected by IBK, vaccination
may be worthwhile. Recommendations are to Geographic Distribution
vaccinate six weeks before onset of the Bovine OSCC occurs worldwide, but there is
expected disease season. Calves should be vac- an association between the occurrence of
cinated at 21–30 days of age, with a second vac- OSCC and an increased level of solar radiation.
cination occurring 21 days later. Vaccine The incidence of OSCC increased significantly
administration should be at least 21 days before with decreases in latitude, increases in alti-
the fly season. It is not known whether colos- tude, and mean annual hours of sunlight.
tral antibodies will interfere with the vaccines.
Adult cattle should receive two initial vaccina- Signalment
tions, followed by yearly boosters near the The onset of OSCC is age related, with older
beginning of the vector season. cattle having a significantly greater risk. The
average age of cattle with OSCC is 8.1 years.
The incidence of OSCC is significantly higher
Neoplasia of the Conjunctiva
in B. taurus than in B. indicus breeds. Though
and Cornea
other cattle breeds are affected, the Hereford is
Of the food animal species, cattle are most overrepresented. This association is partially
affected by ocular and periocular neoplasia. related to the typical periocular depigmenta-
The most common neoplasia is OSCC. tion. Age and lack of corneoconjunctival pig-
Ocular Squamous Cell Carcinoma mentation were significant risk factors.
OSCC has considerable economic impact, Ayrshires are the most susceptible dairy breed
particularly from the loss of older breeding and have a corresponding predilection for SCC
animals and due to partial carcass condemna- of the vulva. There is no true sex difference in
tion at slaughter. In a study performed in 2009, the incidence of OSCC. The higher incidence
OSCC/epithelioma was the fourth leading observed in females results from the males
cause (9.15%) of carcass condemnation at post- having been marketed before the age of peak
mortem examinations of animals sent to har- incidence.
vest for beef in the United States from 2003
through 2007. Cattle with OSCC are con- Genetic Predisposition
demned if the eye has been destroyed, if there There is considerable evidence suggestive of a
is extensive infection, if the animal is in poor genetic basis for OSCC, such as variable mor-
condition, or if there is evidence of spread to bidity rates among various breeds of cattle,
other parts of the body, including structures lines of sires, and increased rates in the prog-
around the eye. Cattle with small, localized eny of affected compared with those of unaf-
lesions may pass inspection after condemna- fected parents. Lesion development is not
tion of affected parts such as the head. The heritable directly, but the genetic effect on
presence of OSCC in slaughter animals is esti- periocular pigmentation determines to a large
mated to cause annual losses of $20 million in extent the degree to which the eye is
the United States alone. susceptible.
­Conjunctiva and Corne  681

A negative association exists between eyelid needed for tumor maintenance, BPV may play
pigmentation and the occurrence of a role initially in tumor formation. Nutritional
OSCC. Eyelid margin pigmentation clearly has status affects the development of OSCC from
an inhibitory effect on eyelid lesions but seems six to nine years of age. Cattle with high nutri-
to have little effect on development of the tional levels have an occurrence of OSCC of
much more frequent, conjunctival OSCC. 14%, whereas cattle on lower feed intakes have
Corneoscleral (i.e., limbal) and bulbar con- an occurrence of 1.5%. Animals on a high
junctival pigment have a local inhibitory effect nutritional plane also have increased severity
on the development of OSCC. and number of tumors and reduced five-­year
survival rates compared with those in animals
Etiology of OSCC at a low level of nutrition.
A specific carcinogen has not been identified.
A number of factors, including age, gender, Clinical Signs
breed, periocular and corneoscleral pigmenta- Approximately 75% of OSCC and precursor
tion, exposure to sunlight, viral infection, and lesions affect the bulbar conjunctiva and cor-
nutrition, likely contribute to development nea, and of these, 90% involve the limbus and
of OSCC. 10% involve the cornea. The remaining 25% of
Exposure to sunlight plays a significant OSCC lesions are distributed in the palpebral
causal role in the development of OSCC. In conjunctiva, nictitating membrane, and eye-
cattle, all measures of solar radiation indicate a lids. Bovine OSCC has a characteristic progres-
significant association between increasing sion through a series of benign stages and
risks of OSCC and increasing levels of radia- then, possibly, to a malignant stage. On the
tion. Associations are evident whether afflic- globe and third eyelid, the initial lesion is a
tion is defined as the occurrence of any type of plaque. Plaques may progress to a papilloma,
tumor (i.e., plaque, papilloma, and carcinoma) then to a noninvasive carcinoma (i.e., carci-
or as the occurrence of only papilloma or carci- noma in situ), and finally to an invasive carci-
noma. Average ages of affected cattle are lower noma. In the eyelids, however, extensive
at high levels than at low levels of radiation. keratosis (i.e., keratoma) may occur, particu-
Viral cofactors have been suggested in the larly near the mucocutaneous junction. This
etiology of OSCC, but there is no definite evi- keratosis may appear as a cutaneous horn and
dence. IBR virus has been isolated from ocular be the precursor to carcinoma formation. The
carcinoma and one of its precursor lesions, keratotic lesions are moistened by tears, collect
and “IBR-­type” inclusion bodies have been debris, and become brown. They can be easily
consistently observed in all types of OSCC removed, leaving a bleeding surface.
lesions. It is not known whether IBR virus has A plaque is a small area of hyperplastic epi-
a predilection for the epithelial tissue in ocular thelium that appears opaque and grayish white
tumors. In addition, because IBR virus can be (Figure 16.20). Papillomas are distributed simi-
frequently isolated from early plaque lesions, it larly to plaques, and they may be thrown up
apparently exists early in the course of the dis- into fronds. They have a connective tissue core
ease among many animals. Whether IBR has a with multiple hard, spine-­like projections of
part in initiating tumor growth is only specula- variable size, and they may be sessile or pedun-
tive. The role of bovine papilloma virus (BPV) culated (Figure 16.21).
in OSCC has also been examined. Neither the Carcinoma in situ arises directly from
use of papilloma virus-­specific antibodies nor plaques and is characterized microscopically
that of DNA hybridization assays for all six as the stage before the neoplastic cells have
known types of BPV could demonstrate a penetrated the subepithelial lamina propria.
direct association with OSCC. While not Invasive carcinomas are generally large and
682 Food and Fiber Animal Ophthalmology

protrude through the lamina propria Metastatic Potential


(Figures 16.22 and 16.23). They can invade the Systemic metastases occur late in OSCC; how-
anterior chamber and eventually infiltrate the ever, local invasion may be particularly aggres-
entire globe (Figure 16.24). Carcinomas arising sive. As the carcinomas penetrate the lamina
from the nictitating membrane are locally propria, they extend “fingers” of neoplastic
invasive, seldom invade the cartilage, but may cells into the surrounding tissues. Limbal
infiltrate the medial orbit. OSCC shows less inward invasion, resulting

Figure 16.20 Limbal gray-­white plaque in a


Hereford cow. Figure 16.21 Limbal papilloma in a cow.

Figure 16.22 Extensive invasive


limbal squamous cell carcinoma
involving more than two-­thirds of the
cornea and protruding through the
palpebral aperture (Courtesy of
L. Horstman).

Figure 16.23 Ulcerated squamous


cell carcinoma lesion involving the
lower eyelid in a Hereford cow. A local
anesthetic block has been performed
to prepare for subsequent surgical
excision (Courtesy of Cecil Moore).
­Conjunctiva and Corne  683

Figure 16.24 Invasion of the anterior


chamber and glaucoma associated
with squamous cell carcinoma in an
aged Hereford cow (Courtesy of Kirk
N. Gelatt).

from resistance of the stroma, Descemet’s examination. The predominance of medium-­


membrane, and the sclera. However, the ante- sized, round to oval cells with a high nucleus–
rior chamber of the eye may still be involved. A cytoplasm ratio, malignant-­looking nuclei, and
greater percentage of systemic metastases clear-­cut cytoplasmic evidence of squamous
occur from tumors of the lid and nictitating origin suggested a moderately differentiated
membrane. Metastases often involve the OSCC. The predominance of small, round cells
regional lymph nodes and orbital bones, with with a high nucleus–cytoplasm ratio and
occasional intracranial metastasis. Systemic malignant-­looking nuclei with a few keratohy-
metastasis usually occurs via the parotid alin granules in the cytoplasm suggests a
lymph node to the regional lymph nodes, poorly differentiated OSCC.
including the atlantal, retropharyngeal, sub- Severe inflammatory reactions may cause a
maxillary, mandibular, and cervical nodes. false diagnosis of OSCC. Inflammation can
Once the metastatic cells gain access to the increase the number of cells in karyolysis or
thoracic duct, they spread hematogenously via pyknosis, and it can also obscure the criteria
the venous circulation. for malignancy. Chronic inflammation may
irritate the epithelial cells and induce dyspla-
Diagnosis sia. Most periocular and ocular neoplasia in
Cytology should not be used as an alternative cattle is OSCC, but other tumor types have also
to histopathology, although a strong correla- been reported. Therefore, biopsies (often exci-
tion exists between cytological and histopatho- sional) with adjunctive therapy are strongly
logical diagnoses. Well-­differentiated OSCCs recommended. Lesional characteristics and
show a marked predominance of large, mark- surgical margins may then be evaluated.
edly angular, nucleated squamous cells with
nuclear features of malignancy, such as hyper- Treatment
chromatic chromatin and large multiple nucle- Before therapeutic intervention, the extent of
oli of various shapes, on cytological the lesion should be evaluated. Topical
684 Food and Fiber Animal Ophthalmology

anesthesia and a lubricated, gloved hand are anesthesia for most ocular surgeries in food
usually sufficient to palpate the orbital rim. animals may be achieved with either a Peterson
OSCC extends firm tendrils, which can be fol- nerve block or a four-­point retrobulbar block
lowed to their most invasive extent. A thor- of the orbit. Though rare, it is important to
ough physical examination concentrating on inform clients that apnea and occasionally
possible sites of metastasis is essential. death may occur 8–9 min after performing a
Extensive systemic invasion may preclude fur- Peterson nerve block. This may result from
ther treatment because of financial and prog- injection of the anesthetic agent directly into a
nostic reasons. If indicated and finances allow, blood vessel, which can be avoided by aspirat-
complete blood counts and serum biochemis- ing first, or injection into the dural sheath.
try profiles are also suggested. Orbital radiog- The Peterson nerve block is a retrobulbar
raphy may be useful in determining bony injection that when performed appropriately
involvement; dorsal oblique radiography pro- and effectively blocks the optic (II), oculomo-
vides the most useful information. Bony tor (III), trochlear (IV), abducens (VI), and
involvement carries a very guarded prognosis. ophthalmic as well as maxillary branches of
When deciding on treatment strategies, it is the trigeminal (V) nerve (Figure 16.25). Lack
important to realize that not all precancerous of pupillary constriction indicates successful
lesions progress. In one herd study, 52% exhib- application of this block, in which a slightly
ited precursor lesions (e.g., plaque, papilloma, curved, 10-­cm, 18-­gauge needle is inserted at
and keratosis) of OSCC. Of these lesions, the caudal angle between the supraorbital pro-
approximately one-­third regressed spontane- cess and the zygomatic arch. The concavity of
ously and disappeared. Other reports suggest the curvature is directed posteriorly to allow
spontaneous regression rates as high as 50%. passage of the needle anterior to the anterior
If treatment is undertaken, the options border of the coronoid process of the mandi-
include surgical excision with or without ble. The needle may need to be walked off the
adjunctive therapy, cryotherapy, hyperther- coronoid process anteriorly. The needle is
mia, immunotherapy, radiation therapy, and advanced in a slightly ventral direction to the
possibly chemotherapy. The most common pterygopalatine fossa and the foramen orbitor-
method of treatment is surgery, and when otundum; complications may be avoided if the
combined with other treatment modalities, the needle is not advanced to the bony floor of the
success rates are quite good. pterygopalatine fossa. Aspiration is then

Surgery
Salvage Procedures
Salvage procedures used together may either
cure or prolong an animal’s life, which may be
desirable for pregnant cows or for bulls to
allow semen collection. Enucleation may be
performed via subconjunctival or transpalpe-
bral approaches. The latter procedure is fre-
quently used in cattle with extensive neoplasia
of the globe, eyelids, nictitating membrane, or
conjunctiva. Exenteration should be consid-
ered if any orbital involvement by the tumor is
detected or suspected.
Figure 16.25 Lateral view of the Peterson nerve
Eyelid and orbital surgeries are performed block for retrobulbar anesthesia in cattle (Courtesy
most frequently in standing cattle, and regional of Jacqueline Pearce).
­Conjunctiva and Corne  685

performed, and approximately 15–20 ml of usually require total excision of the structure.
lidocaine (2%) is injected. Alternatively, a four-­ OSCC in this area may frequently recur after
point block may achieve sufficient anesthesia. surgical removal, and it may invade the orbit
In this block, a 6-­cm needle is inserted either hematogenously or by direct infiltration
transconjunctivally adjacent to the globe at the due to the difficulty in completely removing
12-­, 3-­, 6-­, and 9-­o’clock positions, and 5–10 ml the gland surrounding the base of the cartilage.
of lidocaine is injected at each site. A variation Surgery: Conjunctival Neoplasia
of this technique is to direct the needles Neoplasms may affect the fornix, palpebral,
through the eyelids rather than the conjunc- and bulbar conjunctivae. In the early stages,
tiva. Possible complications of retrobulbar these tumors may be amenable to local exci-
nerve block in cattle include orbital hemor- sion with a scalpel, electrocautery, or carbon
rhage, penetration of the globe, damage to the dioxide laser. Though not reported in cattle,
optic nerve, and injection of local anesthetic the CO2 laser has been used in other animals.
into the optic nerve meninges. Surgery: Limbal and Corneal Neoplasia
Akinesia of the eyelids is obtained by an Keratectomies may be used to remove corneal
auriculopalpebral nerve block. Local anes- and limbal neoplasms limited to the outer lay-
thetic is injected subcutaneously 5–7 cm cau- ers of these tissues. Postoperative corneal scar-
dal to the supraorbital process, where the nerve ring is not a significant problem in cattle.
crosses the zygomatic arch. Eyelid anesthesia Limbal lesions affecting the cornea and adja-
is achieved with local anesthetic infiltration cent bulbar conjunctiva are similarly removed.
(line block).
After enucleation, most animals do not Cryotherapy
require systemic postoperative antibiotic treat- Cryotherapy is a popular treatment of OSCC,
ment; however, an injection of flunixin meglu- and high success rates have been achieved. All
mine, 1 mg/kg, will decrease postoperative suspected premalignant lesions (e.g., focal
pain and swelling. In the presence of marked ulceration or keratosis on eyelids, with or with-
sepsis, administration of appropriate systemic out epidermal plaques) and OSCCs smaller
antibiotics for several days is indicated. Packing than 50 mm in diameter may be treated.
the orbit with sterile gauze after enucleation is Advantages of cryosurgery are its ease and
not recommended unless uncontrollable hem- rapidity, low cost, prolonged analgesia because
orrhage occurs. If used, the gauze is gradually of sensory nerve injury, minimal requirement
removed from between the sutures over a for pre-­ and postoperative medications, mini-
three-­ to four-­day period. The opening for the mal side effects, repeatability, and excellent
gauze removal is usually sutured closed after success with suspect premalignant lesions.
removal to prevent fistula formation. Disadvantages of cryotherapy include local
Surgery: Eyelid Neoplasia If any doubt hair depigmentation, lid necrosis, loss of func-
exists regarding the extent of an eyelid OSCC, tion of normal structures, and cicatrix forma-
then exenteration, with or without radical sur- tion, which can cause entropion or ectropion.
gery, is advised. If, however, there is no evi- Lesions that are not successfully treated with
dence of lymph node metastasis, some form of cryotherapy are those that have metastasized,
blepharoplastic procedure by itself may cure those larger than 50 mm in diameter and with
the animal. Use of an H-­plasty in cattle with poorly defined margins, and those with inva-
OSCC affecting the lower lid provides excellent sion of adjacent bones. Large OSCCs should be
results. debulked surgically prior to performing
Surgery: Nictitating Membrane Neoplasia cryotherapy.
Small OSCCs may be removed, leaving an Nitrous oxide and liquid nitrogen are most
intact nictitating membrane, but larger ones commonly used, and several cryosurgical units
686 Food and Fiber Animal Ophthalmology

are available. Cryosurgical units designed to Immunotherapy


deliver liquid nitrogen are more effective than Successful use of immunotherapy has been
units designed to deliver nitrogen vapor. A reported in treatment of bovine OSCC.­
closed-­tip probe or spray gun is available as Intramuscular or subconjunctival ­injections of
well. The most important factor in the success fresh tumor tissue, peritumoral injection of
or failure of cryosurgery is the extent of freez- interleukin-­2, or Bacillus Calmette–Guerin are
ing. Surgical debulking of large tumors prior to examples of immunotherapy options.
cryotherapy is ideal, and a uniform freeze of
−25 °C should be sought to address the wound Radiation
bed following debulking of the tumor. A dou- Ionizing radiation has been used to treat OSCC
ble freeze–thaw protocol is recommended with in food animals. The expense and legal require-
adequate time allowed between applications to ments to possess such radioactive materials,
ensure complete thawing of the site. however, limit its utility as a treatment modal-
ity. Disadvantages of brachytherapy include
Hyperthermia/Electrothermal Therapy temporary corneal opacity, local necrosis, hair
Hyperthermia has been successful in treat- loss, damage to normal structures, and local
ment of bovine OSCC because neoplastic cells depigmentation. Beta radiation, such as stron-
are selectively destroyed with hyperthermia. tium-­90, may be used after superficial keratec-
Often, hyperthermia is combined with some tomy. Use of beta radiation is often combined
other treatment modality, such as surgical with surgical debulking, because 75% of the
debulking or immunotherapy. beta rays are absorbed within the first 2 mm
Electrothermal treatment involves the pas- with minimal penetration in deeper or sur-
sage of radiofrequency (i.e., 2 MHz) electric rounding tissues to the field. Therefore, a
current between two electrodes. A small, lesion should be less than 2 mm thick if beta
handheld radiofrequency device™ (Western radiation therapy is attempted.
Instrument Company, Denver, CO, USA) has Interstitial brachytherapy has been used in
been developed for the treatment of various species, and implants have included
OSCC. Electrodes are placed directly on the radon, gold, iridium, cobalt, and cesium.
tumor. Resistance of the tissue to the flow of These gamma emitters, as well as roentgen
electric current causes heat to be generated in rays, are especially useful for eyelid masses.
that tissue. High-­frequency current produces However, use of brachytherapy in cattle is
no sensation of electrical shock. The tempera- often not feasible because of financial con-
ture of the tumor tissue is raised to approxi- straints. Even so, gamma emitters offer several
mately 50 °C. Temperature control is advantages, including a high dose of radiation
monitored with a temperature-­sensitive device to the tumor and not to the surrounding tis-
(i.e., a thermistor) that is built into one elec- sue, placement of the needles under heavy
trode. Thirty seconds are allowed to elapse sedation, possible increased effectiveness due
after the tissue temperature reaches 50 °C (i.e., to continuous low-­dose irradiation, a short
122 °F). therapy interval (7–10 days), and a good cos-
Hyperthermia is not recommended for metic result.
tumors that extend deeper than 3 mm or are Radioactive gold seeds have a short half-­life
larger than 4 cm in diameter. Surgical debulk- and do not induce foreign body reaction;
ing may reduce the size of the tumor suffi- therefore, they do not need to be removed.
ciently to allow adequate results from Seeds are considered to be nonhazardous
treatment with hyperthermia. Follow-­up eval- after 10 half-­lives; after 27 days, the radioac-
uation at 30 days is generally recommended, tivity in the seeds is reduced to a noninjuri-
with possible further treatment if needed. ous level.
­Glaucom  687

Figure 16.26 Buphthalmos in a


nine-­year-­old Friesian cow that has
perilimbal, localized corneal striae
with branches (black arrows),
subluxated hypermature cataract (L)
with tearing of the zonules (Z), and a
wide, aphakic crescent.

Prevention and Control


Past studies indicate that selective breeding
can be employed toward control of
OSCC. Animals should be selected with
increased amounts of lid and corneoconjuncti-
val pigment, but the latter pigmentation is not
fully expressed until five years of age. In pure-
bred herds, offspring of affected animals
should be culled. Bulls with a history of OSCC
should not be used as herd sires. Regular and
routine monitoring and treatment of early
lesions is recommended.
Figure 16.27 Funduscopic views through the
aphakic crescent of a glaucomatous eye in a
­Glaucoma nine-­year-­old Friesian cow. Dull and
nonhomogeneous, hyporeflective tapetal fundus
with retinal vascular attenuation. Reduced and
Glaucoma is an optic neuropathy usually asso- hypovascular optic disc surrounded by a
ciated with elevated IOP. The incidence of whitish border.
glaucoma in cattle is less than 1%. Congenital,
hereditary, and secondary glaucomas (from rupture, iris prolapse, and synechiae, which
inflammatory or neoplastic processes) have may also result in secondary glaucoma.
been reported. Steroid-­induced ocular hyper- Clinical signs in cattle with glaucoma
tension has been consistently produced within depend on the cause of the condition. Cattle
30 days by application of prednisolone acetate with primary glaucoma show enlarged globes
three times daily to the eyes of normal cows that are not overtly painful, little or no episcle-
and sheep. Endogenous inflammatory epi- ral injection, mild corneal edema, corneal vas-
sodes, such as those seen with neoplastic or cularization and striae, a pupil poorly
granulomatous processes, may cause both responsive to light stimulation, lens subluxa-
peripheral anterior and posterior synechiae, tion, and fundus abnormalities (Figures 16.26
which in turn may impede aqueous outflow and 16.27). Eyes with secondary glaucoma will
sufficiently to elevate IOP. Perforated corneal exhibit signs consistent with the predisposing
ulcers, especially from IBK, may result in globe condition (uveitis, intraocular neoplasia).
688 Food and Fiber Animal Ophthalmology

­Uvea Iris Abnormalities


An autosomal recessive, hereditary iridal
Congenital Disorders of the defect has been observed in Jersey calves as
Anterior Uvea part of multiple ocular defects. Affected ani-
mals may show bilateral aniridia or iridal
Congenital disorders of the anterior uvea in hypoplasia in association with microphakia,
food animals are not clinically significant, with cataracts, and ectopia lentis. The calves exhibit
a few notable exceptions. Such anomalies visual impairment or blindness.
include PPMs, heterochromia, aniridia and iris
hypoplasia, polycoria, cysts, pigment nevi, and
colobomas. Inflammation of the Uvea
Uveitis represents nonspecific ocular pathol-
Heterochromia Iridis ogy derived from inflammatory mediators.
In cattle, heterochromia iridis represented Uveitis is often associated with systemic dis-
almost 10% of ocular anomalies in one study. eases including neonatal infections, bacterial
Heterochromia iridis may be unilateral or septicemia associated with severe mastitis,
bilateral, complete or partial. Iridal pigmenta- metritis, or traumatic reticuloperitonitis, MCF,
tion may vary between white, light pink, blue, tuberculosis, IBK, thromboembolic menin-
gray, and brown (Figure 16.28). Heterochromia goencephalitis, leptospirosis, toxoplasmosis,
iridis may be associated with other ocular listeriosis, parasitic migration (Setaria digi-
anomalies (e.g., tapetal hypoplasia and colobo- tata), toxins such as lead, poisonous plants
mas of the fundus) (Figure 16.29). Among cat- such as Dryopteris filix-­mas, and lymphoma.
tle, heterochromia iridis has been reported in Clinical signs are nonspecific and similar to
various breeds, including Ayrshires, Holsteins, those experienced in other species. Lesions
Angus, Brown Swiss, and Guernseys. In most include corneal edema and vascularization,
cases, vision is unaffected; however, photopho- aqueous flare, hyphema, iritis, cataracts, poste-
bia and nystagmus have been reported. rior synechia, retinal hemorrhages, chorioreti-
nitis, chorioretinal scars, and papillitis.

Figure 16.28 Iridal heterochromia in an albino


beef Shorthorn calf. Clinically, the central iris is Figure 16.29 Tricolored heterochromic iris of a
pink, and the peripheral iris is white (Courtesy of Hereford bull with dominant albinism (Courtesy of
Kirk N. Gelatt). Kirk N. Gelatt).
­Len  689

Uveal Tumors Other ocular abnormalities in association


with cataracts have been described in the
Primary tumors of the anterior and posterior
Hereford, Holstein Friesian, Jersey, and
uvea in food animals are rare. Sarcomas and
Shorthorn breeds. Multiple ocular anomalies
ciliary body epitheliomas do occur in cattle. A
including cataracts have been attributed to a
congenital intraocular melanoma has been
dominant inherited trait in a herd of cows bred
reported in a Charolais cross-­calf as well.
with a Hereford bull. The ocular defects in
Secondary intraocular tumors of the uveal
Holstein Friesian cattle are lens luxation,
tract can occur by extension from the orbit,
buphthalmia, retinal detachment, and occa-
conjunctiva, and cornea. The sclera is resistant
sional lens rupture. Aniridia, microphakia,
to external invasion, but it may be breached by
lens luxation, and cataracts occurred in Jersey
squamous cell carcinomas. Secondary intraoc-
calves as an autosomal recessive trait in one
ular tumors are also possible by hematogenous
study and as a dominant gene in another.
metastasis from other sites. Intraocular lym-
Hydrocephalus in association with ocular
phoma is rare but has been reported.
defects, including cataracts, occurred in
Shorthorn calves with a suspected dominant
inheritance. Microphthalmia and cataracts
­Lens with retinal lesions may occur in calves
exposed to BVD in utero at days 76–150 of
Cataracts in food animals are rarely reported. gestation.
However, the actual incidence may be much
higher because careful inspection of the lens
Acquired and Secondary Cataracts
is not routinely performed unless the animal
has visual impairment. Small, focal lens opaci- Secondary cataracts occur as sequelae to an
ties do not usually result in visual impairment inflammatory episode. Examination typically
and are usually missed unless mydriasis is reveals ocular changes compatible with previ-
induced before the ophthalmic examination. ous inflammation, such as posterior synechiae
Congenital cataracts (with or without associ- and pigment deposition on the lens
ated ocular anomalies), secondary cataracts, (Figures 16.30 and 16.31). Most infectious
and cataracts of unknown origin have been
described.

Congenital and Juvenile Cataracts


Congenital bilateral cataracts are autosomal
recessively inherited in several breeds of cattle,
including the Jersey, Hereford, and Holstein
Friesian. The cataracts are usually mature
when the calves are 4–11 months of age.
Congenital, nuclear, nonprogressive cataracts
have also been reported in cattle. In Romagnola
cattle, juvenile-­onset bilateral nuclear cataract
has been reported. In this breed, the condition
has been determined to be inherited as a
Figure 16.30 Complete cataract secondary to
monogenic autosomal recessive inheritance
uveitis. Note multiple areas of posterior synechiae
associated with a deletion in the nidogen 1 and pigment deposition on the anterior lens
(NID1) gene. capsule (Courtesy of Kirk N. Gelatt).
690 Food and Fiber Animal Ophthalmology

Figure 16.31 Immature cortical and nuclear


cataract of unknown cause in an Angus cow
(Courtesy of Kirk N. Gelatt).

systemic diseases have the potential to affect Figure 16.32 Normal bovine ocular fundus. The
optic disc is predominantly in the nontapetal
the uveal tract and cause secondary cataracts.
fundus. The large, primary blood vessels emerge
Cataracts, goiter, and infertility have been from the surface of the optic disc (Courtesy of
reported as a result of an exclusive diet of Wendy Townsend).
Leucaena leucocephala. The toxic component
was suspected to be mimosine, which may lead
Three, and occasionally four, major venules
to formation of insoluble protein aggregates
drain the retina, and these are accompanied by
within the lens. Radiation-­induced cataracts
paralleling arterioles. The superior arteriole
have been seen in some cattle. The cataracts
and venule may twist about each other.
typically begin at the posterior pole and may
Additional arterioles radiate from the optic
subsequently involve the entire lens.
disc; from the major vessels, secondary and
tertiary branches may arise. The vessels also
Treatment of Cataracts project far more vitread than in most other
domestic species.
Cataract surgery has been successfully per-
The tapetal fundus varies from yellow to
formed in food animals. The decision to per-
bluish purple, and it is uniformly stippled by
form surgery is governed by economic factors,
end-­on capillaries (i.e., stars of Winslow). The
general health of the animal, presence of coex-
reflective material of the bovine tapetum is a
isting ocular disease, technical expertise of the
large array of extracellular collagen fibrils
individual, and intended use of the animal.
arranged in lamellae of varying thickness.
The suggested inherited nature of cataracts
The nontapetal fundus is generally a uniform
implies that breeding animals should not be
shade of brown, and there is little variation
operated on, or that if they are, they should not
with the coat color or breed. The optic disc is
be bred subsequently.
always located at the junctional area of the
nontapetal and the tapetal fundus, usually
within the nontapetal fundus just below the
­Ocular Fundi junction. The optic disc is in the shape of a
horizontally flattened oval. In most, the tem-
Ophthalmoscopic Examination
poral portion is located nearer to the tapetal
The bovine retina is typical of mammalian reti- fundus than is the nasal portion. Myelinization
nas (Figure 16.32). Like most domestic rumi- of the optic nerve fibers normally stops at the
nants, the retina of the cow is holangiotic. lamina cribrosa. Myelin may occasionally
­Ocular Fund  691

continue onto the retina for a short distance


and appear as white fiber bundles with feath-
erlike margins protruding from the optic disc.
These medullated fibers are not usually pre-
sent at birth, but they may develop within the
first months of life. The optic disc varies in
color. In general, the young animal
(<6 months) has a white to salmon-­pink disc
with distinct margins. Older animals may
have discs of orange, gray, tan, or various
combinations. In addition to the primary
pairs of vessels that emerge from the disc,
15–20 other vessels cross the margins of the
disc. These small arterioles and venules
emerge from the disc in a radiating fashion
and disappear from view approximately 0.5 to
1.0 disc diameters from the optic disc. An
“area striata,” the bovine equivalent of the Figure 16.33 The ocular fundus of a subalbinotic
area centralis, consists of a band-­shaped area Shorthorn calf. The tapetal fundus is light yellow
running horizontally above the disc in the clinically. The absence of pigmentation in the
lower part of the tapetal fundus. nontapetal fundus allows underlying choroidal
vasculature and white sclera to be observed
(Courtesy of Kirk N. Gelatt).
Congenital Disorders
Congenital fundic abnormalities are unusual,
but they may mimic acquired lesions. The
prognostic implications of an acquired versus a
congenital lesion may be profound. Acquired
lesions may affect the entire herd if due to
infectious diseases. Therefore, careful ophthal-
mic and systemic evaluations of affected ani-
mals should be performed.

Colobomatous Malformations
Colobomas of the choroid are relatively com-
mon among cattle. Various estimates indicate a
prevalence rate of 1–2%. Typical colobomas of
the optic disc occur in the dominant form of
incomplete albinism among Hereford cattle
(Figures 16.33 and 16.34). In this syndrome,
Figure 16.34 Typical coloboma of the optic disc
the colobomas are always bilateral, but they
and nontapetal fundus. The multiple-­depth defect
are not necessarily symmetrical. Vision in cat- is traversed by a large venule and a smaller
tle affected with colobomas may vary depend- arteriole (Courtesy of Kirk N. Gelatt).
ing on the extent of the colobomatous change.
Typical colobomas of the optic disc occur in colobomas involve the entire optic disc and
Charolais cattle; they are bilateral and often occasionally extend into the choroid and sclera
small, though not symmetrical, and are gener- in other areas of the ocular fundus. The effect
ally restricted to the posterior segment. Larger of the ocular defect on vision ranges from
692 Food and Fiber Animal Ophthalmology

slight to severe. In some extreme cases, calves Inflammations of the Posterior Segment
have been born blind with grossly affected
Various infectious agents have been impli-
eyes. The pattern of inheritance for typical
cated as causing posterior segment inflamma-
colobomas in Charolais cattle is suggestive of a
tory changes in food animals. Cattle have
dominant mode, but test breedings are indica-
been reported to be affected by neonatal sep-
tive of a polygenic inheritance.
ticemic infections (Escherichia and Pasteurella
spp.), thromboembolic meningoencephalitis
Congenital Vascular Anomalies
(Histophilus somni, formerly Haemophilus
Remnants of the hyaloid vessel appear as a
somnus), rabies and other viral causes, toxo-
white, irregular tube extending from the optic
plasmosis, tuberculosis, and listeriosis.
disc to the posterior pole of the lens. If the vit-
reous body is fluid, small movements of these
structures can occur. Normally, only a small, Degeneration of the Ocular Fundus
translucent structure (Bergmeister’s papilla)
projects from the optic disc into the posterior Possible Hereditary Retinal Degeneration
vitreous. A persistent hyaloid artery has been A condition similar to canine progressive reti-
found in 54% of calves aged six weeks or less. nal atrophy occurs in cattle. A familial occur-
Some hyaloid vestige can nearly always be rence, implying a possible genetic link, has
found. In older cattle, 80% of animals may still been suggested but not proven. Clinical signs
have some remnant of the hyaloid. initially include pupils that are poorly respon-
sive to light stimulation and nyctalopia with
Retinal Dysplasia subsequent blindness. Fundic examination is
Inherited forms of dysplasia must be differen- typical of retinal degeneration. Tapetal hyper-
tiated from those resulting from intrauterine reflectivity, small vessel attenuation (but pres-
infection with infectious agents, such as BVD ervation of the larger vessels until late in
virus. On histopathological sections, the reti- disease), and minimal optic nerve abnormali-
nal rosette is diagnostic of retinal dysplasia. ties characterize the disease initially.
Multiple inherited ocular anomalies, including A suspected inherited retinal degeneration
retinal dysplasia and internal hydrocephalus, due to a mutation in the retinitis pigmentosa 1
have been reported in Shorthorn cattle, with (RP1) gene has been documented in Normande
either recessive or incomplete penetrant domi- dairy cattle. The majority of the cows homozy-
nant mode of inheritance. The retinas were not gous for the RP1 gene mutation show signs of
only dysplastic but were often detached. bilateral retinal degeneration after four years
of age, with hyperreflective tapeta and thin-
Osteopetrosis-­Induced Ocular ning of the retinal vasculature. Although the
Fundus Disease majority of the heterozygous animals had a
Osteopetrosis in cattle is a generalized skeletal normal fundic exams, a few heterozygous ani-
disease characterized by the absence of bone mals also presented with signs of retinal
cavities because of defective bone remodeling. degeneration. Full-­field electroretinography
The disease is expressed as an autosomal reces- showed a complete absence of response in
sive trait. Clinical signs resulting from this homozygous cows.
condition include fragile bones, brachygnathia,
hypoplastic foraminae, and various neurologi- Vitamin A Deficiency
cal defects (e.g., blindness). Defects in the ret- Serum vitamin A inhibits the differentiation of
ina and optic nerves are prominent. Most preadipose cells into adipose cells, affecting
animals are premature at birth and are still- the beef marbling score. Therefore, some
born. The disease has been described only breeders try to maintain low serum vitamin A
among North American Black Angus cattle. levels in their herds (approximately 30 IU/dl).
­Ocular Fund  693

However, vitamin A is essential for rhodopsin Hypothiaminosis


regeneration, normal bone maturation and PEM, or cerebrocortical necrosis, is most often
remodeling, and normal epithelial function. caused by thiamine deficiency. It is most com-
Vitamin A deficiency may cause blindness, monly seen in young feedlot cattle on low-­fiber,
abnormal bone growth, abnormal epithelial high-­concentrate rations. Under these dietary
function, and embryologic maldevelopment conditions, ruminal concentrations of thiamine
(Figure 16.35). In Japanese Black Cattle, serum are decreased. Ingestion of thiaminase-­containing
vitamin A deficiency has been associated with plants, such as bracken fern (Pteris aquilina), can
bleaching of the tapetum, white mottling of also cause secondary thiamine deficiencies. PEM
the nontapetal fundus and pale optic discs. has also been caused by water deprivation and
intake of high levels of sulfur, either through ad
Retrobulbar Neuropathy libitum ingestion of concentrates, mineral pre-
and Retinal Degeneration mixes, plants in the family Brassicaceae, or high
Ingestion of D. filix-­mas (i.e., male fern) is asso- sulfur content in the water. Treatment with cop-
ciated with vision loss due to retrobulbar optic per, as well as vitamin B1, appears to be beneficial
nerve disease. Bilateral blindness is the main for the sulfur-­induced cases.
presenting sign, but weakness, malaise, and The basic lesion of PEM is necrosis of the cere-
constipation can also occur. In severely affected brocortical neurons, with associated perineuronal
animals, optic nerve atrophy occurs with subse- and pericapillary edema. Neurological signs are
quent retinal degeneration. Fundoscopy reveals associated with increased cerebrospinal fluid
hemorrhage on or about the optic disc and vari- pressure and neuronal necrosis; impaired vision
ous amounts of papilledema. Chronically may be an early sign. The blindness is cortical, but
affected animals exhibit blindness, optic nerve ocular signs of papilledema and decreased pupil-
atrophy, attenuated retinal vasculature, and lary light reflexes (PLRs) may occur.
tapetal degeneration. Electroretinograms (ERGs) remain normal, but
visual evoked potentials are abnormal. Bilateral
dorsomedial strabismus may be present as well.
Treatment consists of thiamine hydrochlo-
ride (6–10 mg/kg) either intramuscularly or
intravenously every 8 h. Corticosteroids may
benefit cases early in the course of disease.
Recovery may be slow and decreased vision or
blindness may persist.

Locoweed Poisoning
Poisoning with locoweed (Astragalus and
Oxytropis spp.) causes retinal degeneration in
cattle, sheep, and other species. Bipolar, gan-
glion, and ciliary body epithelial cells show
vacuolation of the cytoplasm. Similar changes
occur in brain neurons. The lacrimal gland has
marked cytoplasmic vacuolation of the secre-
tory cells, and poisoned animals show vision
disturbances and dry lackluster eyes.

Figure 16.35 Papilledema and retinal Other Toxic Plants


degeneration secondary to avitaminosis A in a Several other plant species may also cause neu-
yearling Angus steer (Courtesy of Kirk N. Gelatt). rological disease with visual impairment, and
694 Food and Fiber Animal Ophthalmology

in some cases, blindness precedes death. Water retinal veins and arteries show a distinct bend
hemlock (Cicuta spp.) causes an acute syn- as they pass down over the edge of the disc and
drome associated with sudden death. A fatal onto the retina. The retinal venules may be
mycotoxicosis of cattle has been recognized in dilated and engorged peripherally and hidden
Australia and feeding trials have demonstrated centrally within the swollen disc. Many more
a previously unknown mycotoxic species of fine veins are visible. The arterioles are a
Corallocytostroma that grows on Mitchell grass brighter red and more threadlike than the con-
(Astrebla spp.). The disease is colloquially gested venules. If the cerebrospinal fluid pres-
called “black soil blindness.” The onset of sure remains elevated, the optic nerve and disc
blindness and rapid progression to death are will atrophy. In cattle and sheep, papilledema
the main clinical features of this disease. is commonly encountered. Causes may include
Kochia scoparia (Mexican fireweed, summer vitamin A deficiency (see Figure 16.35),
cypress, or burning bush) can produce blind- acquired and congenital hydrocephalus, space-­
ness and nystagmus. Darling pea (Swainsona occupying brain lesions, meningitis, encepha-
galegifolia) causes signs similar to those of litis, and hexachlorophene toxicity.
locoweed in cattle and sheep.

Inherited Lysosomal Storage Diseases ­Sheep and Goats


A variety of inherited lysosomal storage dis-
eases with ophthalmic implications have been Ocular Examination
reported, including GM1 gangliosidosis (i.e., and Ophthalmic Parameters
leukodystrophy in Holstein cattle), GM2 gan-
gliosidosis (i.e., lipodystrophy in Angus and For proper restrain, sheep and goats can be
Beefmaster cattle), and mannosidosis. backed into a corner, with their head restrained
by an assistant. A sheep shearing stand or goat
milking stand may also be helpful. Sheep and
­Optic Nerve Diseases goats have an oval-­shaped, horizontally posi-
tioned pupil, with corpora nigra present on the
A primary demyelinating disorder of young dorsal and ventral pupil margin.
Limousin cross-­calves has been described. In a study comparing the tear production
Approximately one month after birth, affected and corneal sensitivity in several species, it was
animals showed signs of blindness, nystag- determined that sheep have a higher tear pro-
mus, rotation of the eyes, opisthotonos, duction and a more sensitive cornea, compared
hyperprotraction of the forelegs, and, in one to goats. The tear production in sheep was
case, seizures. Histopathologically, there was determined to be 26.4 ± 17.7 mm/min, while in
necrosis of the optic chiasm and focal areas of goats it was 14.5 ± 3.78 mm/min. A study com-
myelin sheath vacuolation or demyelination. paring IOP in sheep using TonoVet and
A genetic association was considered to TonoPen Avia™ revealed average pressure of
be likely. 11 and 10 mmHg, respectively. In goats, aver-
Papilledema is a descriptive term for nonin- age value obtained with the TonoVet was
flammatory swelling of the optic disc caused 23 mmHg, while the TonoPen Avia revealed
by various conditions. It may signal increased average IOP of 13 mmHg. In Saanen goats, tear
intracranial pressure. Papilledema is usually production is higher in older animals, com-
bilateral. The optic disc margins appear to be pared to young ones (13.80 mm/min versus
hazy, and the physiological depression is lost. 10.38 mm/min). The same is true of IOP, which
The disc becomes thickened and swollen and was determined to be 9.79 mmHg in adult ani-
appears to be grayish white with striations. The mals and 8.03 mmHg in young goats.
­Eyelid  695

Orbit and Globe necessary to cause clinical signs of poisoning


in the ewes.
Congenital Globe Abnormalities and Blindness
Other teratogenic effects arising from inges-
In a study of congenital malformations in the
tion of V. californicum include distortion of the
eyes of sheep, microphthalmia with multiple
facial bones, fusion of the cerebral hemi-
cysts was observed. The purported cause of
spheres, absence of the pituitary gland, hydro-
these malformations was selenium toxicity, but
cephalus, and anophthalmia. This discrepancy
this suggestion has been disputed.
could result from a difference in the develop-
Microphthalmia in Texel sheep occurs as an
mental rates of the respective embryos.
autosomal recessive trait and results from a
Teratogenic effects of V. californicum have also
missense mutation in the homeobox gene
been reported in cattle and goats.
PITX3. The most common maternal infection
causing multiple ophthalmic defects in off-
Selenium
spring is bluetongue disease in sheep.
Selenium has been credited historically with
causing “blind staggers” in livestock and being
Teratogenic Agents a teratogenic agent. Reported necropsy find-
Veratrum californicum ings associated with selenium toxicity include
Among domestic animals, the best-­ microphthalmia with multiple cysts; corneal,
documented teratogenic ocular defects have lens, and iris defects; and colobomas of various
been those associated with ingestion of structures. It has now been speculated that
Veratrum californicum in sheep. Various globe many field cases of blind staggers are sulfur-­
abnormalities, such as anophthalmia, cyclopia related PEM, rather than selenium toxicosis.
(one central globe), and synophthalmia (two Plants that bioaccumulate selenium are often
fused globes), may be induced in lambs by the associated with waters high in sulfate, and
maternal ingestion of V. californicum. The high sulfate levels have been linked with PEM.
common names of V. californicum include Other possible causes of blind staggers
skunk cabbage, western hellebore, false helle- include MCF, the polyhydroxyindolizidine
bore, and wild corn. The agents responsible are alkaloid swainsonine, chronic laminitis, para-
a group of alkaloids (e.g., jervine, pseudojer- sitism, thromboembolic meningoencephalitis,
vine, isorubijervine, and veratrosine) that lead poisoning, and starvation. The cause of
occur throughout the plant but are concen- the congenital ocular defects may actually
trated in the roots. have been maternal ingestion of V. californi-
Sheep embryos are highly susceptible to the cum or some other teratogen.
teratogenic agent cyclopamine, a steroidal
alkaloid, from the plant V. californicum when
the plant is eaten by the ewe on gestational day
­Eyelids
14. In cases of cyclopia, this timing corre-
sponds to the period of gastrulation and forma-
Entropion
tion of the neural plate, before separation of
the optic fields. Ewes fed plants on gestational Congenital entropion is relatively frequent in
days 11, 12, 13, 15, and 16 had normally devel- small domestic ruminants and usually affects
oped fetuses or normally developed embryos the lower lid (Figure 16.36). A combination of
that died between the 18th and 23rd days of orbicularis oculi muscle spasticity and globe
embryonic development. All embryonic deaths retraction by the retractor bulbi muscle encour-
occurred in ewes with severe clinical signs of ages additional eyelid inversion. The incidence
poisoning. The dose of V. californicum that had of congenital entropion in sheep varies mark-
a teratogenic effect was less than that edly between flocks, ranging from 1.0% to
696 Food and Fiber Animal Ophthalmology

Ectropion
Congenital ectropion is rare, but it has been
recorded in Piebald sheep. Affected animals
exhibit a gross deformity or notching of the
upper eyelid with entropion at either side.
Surgical intervention is recommended when
secondary ophthalmic disease results. The sur-
gical procedures primarily aim to shorten and
strengthen the affected lid.

Eyelid Colobomas
Eyelid colobomas have been seen in goats and
appear to be more frequent in rare sheep
breeds, such as Hebridean, Manx Loaghtan,
and Jacob. The defect is seen in association
Figure 16.36 Inferior eyelid entropion and
secondary keratitis in a lamb (Courtesy of Kirk with the four-­horn gene.
N. Gelatt).

Blepharitis
80.0%. Entropion in sheep is thought to be
inherited as a polygenic trait. In one study, a Bacterial
greater proportion of lambs suffered entropion Pyogranulomatous cutaneous nodules with
if sired by Charolais or Texel rams compared associated draining tracts may occur on the
with those sired by Suffolk rams. face of sheep and goats following cutaneous
Initial clinical signs are frequently bilateral. punctures and secondary infection with
Secondary corneal ulceration and vasculariza- Actinobacillus lignieresii. Eyelid edema and
tion, keratouveitis, and endophthalmitis may facial swelling are observed with “bighead”
develop as well. Treatment involves eversion of disease in sheep, in which blepharedema may
the affected eyelid, and a variety of techniques develop secondary to anaerobic infection with
are possible. Mechanical eversion using two or Clostridium novyi. Dermatophilosis (rain scald
three metal wound clips adjacent to the eyelid or lumpy wool) occurs as in cattle.
margin or vertical mattress sutures may be
used. Tissue glue has been used in other spe- Mycotic
cies to create an effect similar to that achieved Trichophyton spp. (usually verrucosum) can
using a vertical mattress suture, and subcuta- affect all food-­producing animals. Sheep and
neous injections of minor irritants (e.g., 1–2 ml goats may also be affected by Microsporum spp.
of penicillin) have also been used, but are no Dermatomycoses occur most commonly in
longer recommended. The tissue swelling thus goats and may result in crusty areas of periocu-
created corrects the entropion, and subsequent lar and facial alopecia. Owners should be
fibrosis helps to prevent recurrence. If only a informed of the zoonotic potential. The disease
few lambs are affected by severe entropion and may resolve spontaneously within four to five
corneal disease that persists into adulthood, or weeks in an individual animal, but it may per-
if highly valuable individual animals are sist in a flock for some months. Despite the
affected, a modified Hotz–Celsus technique is self-­limiting nature of the disease, treatment is
effective. Affected lambs should not be retained recommended to limit any further infection of
for breeding. unaffected animals and humans. Topical and
­Conjunctiva and Corne  697

systemic fungicidal agents, iodine shampoos, Ectoparasites


improved nutrition, and dry environs may Sarcoptic mange is caused by S. scabiei, with a
assist in eliminating the disease. Vaccination subspecies specific for each host species. The
of newly infected herds shows potential as a lesions become widespread except in sheep, in
prophylactic measure. which they are restricted to the haired skin of
the face and eyelids. Treatment with moxidec-
Viral tin at a dose of 0.2 mg/kg given twice at 10-­day
Viral diseases implicated in eyelid disease intervals or ivermectin injected subcutane-
include pox viruses, orbivirus, and papilloma ously at a dose of 0.2 mg/kg provides satisfac-
virus. Sheep and goat pox (capripoxviruses) tory results.
may have morbidity rates of up to 70%, and the Demodex caprae is a mite that can inhabit
mortality rate may reach 50%. The first ocular hair follicles in goats. Pustules form around
signs are circular, hyperemic maculae of the the mites, causing skin lumps on the head,
eyelids, which then progress to firm papules neck, and shoulders. The diagnosis is made by
elevated above the surrounding tissue. Serum microscopically identifying the cigar-­shaped
exudate and blepharospasm may occur as well. mite. Demodectic mange is generally not
Contagious viral pustular dermatitis (conta- harmful, and treatment is usually not neces-
gious ecthyma, sore mouth, and orf) is a sary. Psoroptes, Psorergates, and Chorioptes spp.
Parapoxvirus causing a sequence of papules, are cutaneous mites that may cause intense
vesicles, pustules, and scabs on the eyelids, pruritus but infrequently involve the facial area.
lips, muzzles, and nostrils of sheep and goats, Keds (Melophagus ovinus), lice (Bovicola and
but it does not usually cause systemic illness. Linognathus spp.), and ticks may cause pruri-
Ovine ulcerative dermatosis virus (lip and leg tus and self-­trauma. Periocular involvement is
ulcer) is an unclassified pox virus similar to secondary to self-­trauma and results in mild
contagious ecthyma, but the former causes conjunctivitis and blepharitis. Drugs such as
lesions that are ulcerative and destructive coumaphos, diazinon (do not use on goats),
rather than proliferative, as with contagious fenvalerate, malathion, methoxychlor, and
ecthyma. Specific treatment is neither neces- permethrin may be used to control infestations.
sary nor effective in uncomplicated cases, but
symptomatic treatment is advised. The poten- Photosensitization
tial for zoonotic infection does exist. Direct solar irritation (i.e., sunburn) may occur
Vaccinations are available for contagious in food animals with little periocular pigmen-
ecthyma, sheep pox, and goat pox. tation, but acute periocular dermatitis is more
Bluetongue virus is an acute, noncontagious likely the result of photosensitization (see the
orbivirus spread by Culicoides variipennis “Bovine” section).
midges. The virus may cause blepharitis and
conjunctivitis in sheep, and it occasionally
affects cattle. Hyperemia and eczema of the ­Conjunctiva and Cornea
periocular skin may occur. The most notable
change, however, is retinal dysplasia in lambs Similar to many other species, the normal con-
born to infected ewes. junctival microflora of sheep has a preponder-
Papillomatosis is caused by a DNA virus ance of Gram-­positive bacteria. The most
that may affect the eyelids of sheep with a pre- frequently isolated bacteria are Bacillus subtilis,
dilection for young animals up to five years of Enterococcus sp., Bacillus cereus, Escherichia
age. Papillomas are usually benign, self-­ coli, and Alcaligenes faecalis. The most common
limiting, and may have an associated reported fungi are Aspergillus sp., Penicillium
blepharitis. sp., Alternaria sp., and Cladosporium spp.
698 Food and Fiber Animal Ophthalmology

Geographic location and environment also play occurs worldwide. Outbreaks usually occur
a substantial role in ocular surface microflora. during the lambing season, when ewes and
In a study evaluating the conjunctival bacterial lambs are confined with maximal contact and
flora of goats in the midwestern United States, stress. Carrier animals may be reservoirs for
Staphylococcus and Streptococcus were the most the disease. The pathogenesis is probably mul-
common bacterial genera isolated from adult tifactorial, with the immune status of the ani-
(94%) and young (100%) animals. Moraxella mal, secondary infection, and other factors all
bovoculi was the most common single isolate in playing a role.
adult animals, while it was Staphylococcus equo- Clinical signs begin within four days of
rum in young goats. infection and initially include epiphora, che-
mosis, and conjunctival hyperemia. By 11 days
postinfection, the serous conjunctival exudates
Infectious Keratoconjunctivitis
become more purulent with associated blepha-
Decreased twinning rates in ewes, increased rospasm. Lymphoid follicles begin to develop
cases of pregnancy toxemia, starvation, weight by 23 days postinfection, but they can also
loss, blind ewes trampling offspring, and develop as early as six days after inoculation
decreased economic return have all been with C. pecorum and B. ovis. Approximately
attributed to infectious keratoconjunctivitis. 10% of patients develop interstitial keratitis
Numerous infectious agents have been impli- one week after the initial signs develop with
cated, and the terms pink eye, heather blind- deep vascularization and edema of the cornea.
ness, or blight are therefore used somewhat Because corneal ulceration is uncommon, per-
broadly. The causative agents producing the manent scarring of the cornea is infrequent.
clinical sign of keratoconjunctivitis in small A diagnosis is most easily obtained from
ruminants are probably varied, with no one scrapings of infected conjunctival epithelial
organism consistently being responsible. cells early in the course of the disease showing
the typical cytoplasmic inclusions in infected
Chlamydial Keratoconjunctivitis cells. However, fluorescent antibody staining is
Chlamydophila pecorum (formerly a serotype preferable because Chlamydiae can be con-
of Chlamydia psittaci) is an important cause of fused with melanin granules. Therefore, fluo-
keratoconjunctivitis in sheep and goats, and rescent antibody tests may be more sensitive
polyarthritis in sheep. Chlamydophila pecorum than culture in detecting Chlamydiae. PCR
is introduced into a flock by affected animals testing is a sensitive detection method.
often with mild infection. Transmission can In most clinical settings, testing is not eco-
occur between sheep and goats. Direct contact nomically viable and treatment is instituted
is the most important method of transmission. empirically. The most effective treatment is a
Chlamydiae are obligate, intracellular bacte- single intramuscular injection of long-­lasting
ria. They have a unique development cycle oxytetracycline (20 mg/kg). Daily feeding of
involving two morphological forms: the ele- 150–200 mg of tetracycline per head to lambs
mentary body and the reticulate body. The ele- and kids reduces the incidence and severity of
mentary bodies are specialized for extracellular disease. Intramuscular injection of tylosin or
survival, insensitive to antibiotics, and infec- topical application of tetracycline ophthalmic
tious. The reticulate bodies are sensitive to anti- ointment provides satisfactory results.
biotics and are obligate, intracellular organisms
engaged in active multiplication within host Mycoplasmal Keratoconjunctivitis
cells. They are found in cytoplasmic vesicles Although typically thought to be more com-
termed cytoplasmic inclusion bodies. mon in goats, Mycoplasma spp. have been
Chlamydophila pecorum is associated with associated with conjunctivitis in sheep and
an infectious keratoconjunctivitis in sheep that goats both clinically and experimentally.
­Conjunctiva and Corne  699

Subclinical carrier states of Mycoplasma spp. Goats do not usually develop corneal ulcers or
exist as well since, in some animals, the pres- hypopyon, but permanent corneal opacity and
ence of Mycoplasma conjunctivae is not associ- blindness may result.
ated with clinical disease. The lack of The diagnosis of infection with Mycoplasma
association may result from differences in the spp. is made on the basis of clinical signs and
pathogenicity between individual strains, or results of conjunctival cytology, culture, and
the samples may have been taken just before serology. In acute mycoplasmal keratoconjunc-
development of clinical signs. The respective tivitis, large numbers of neutrophils, but no
conjunctival isolates for sheep and goats were
M. conjunctivae var. ovis and Mycoplasma
mycoides var. capri. Concurrent presence of
B. ovis, E. coli, and Staphylococcus aureus may
enhance the severity of keratoconjunctivitis.
There may be a slight variation in clinical
signs between sheep and goats. There is an ini-
tial hyperemia of the palpebral and conjuncti-
val vessels, serous lacrimation, and
blepharospasm (Figure 16.37). Keratitis with
superficial and deep vascularization may also
develop. In more advanced cases in sheep, a
mucopurulent conjunctivitis, occasional folli-
cular conjunctivitis, iritis with hypopyon, and
corneal ulceration occur (Figures 16.38
and 16.39). Phthisis bulbi rarely results, and
the disease usually lasts between one and four
weeks. Older sheep are generally more affected. Figure 16.38 Keratoconjunctivitis associated with
mycoplasma infection in a sheep approximately
7–10 days after the onset of clinical signs. Note the
focal corneal opacities and neovascularization
(Courtesy of Kirk N. Gelatt).

Figure 16.37 Early stage of keratoconjunctivitis


associated with mycoplasma infection in a goat. Figure 16.39 Keratoconjunctivitis associated with
Predominant early clinical signs are hyperemia of mycoplasma infection in a goat. Extensive corneal
the palpebral and bulbar conjunctiva and epiphora abscessation, vascularization, and anterior uveitis
(Courtesy of Kirk N. Gelatt). are present (Courtesy of Cecil Moore).
700 Food and Fiber Animal Ophthalmology

plasma cells, are seen and intracytoplasmic association with M. conjunctivae, Brucella ovis
coccobacillary and ring-­shaped bodies may be contributes to the severity of the
observed in epithelial cells. In some cases, the keratoconjunctivitis.
conjunctival epithelial cells contain phagocy-
tosed neutrophils but no bacteria. The organ-
Parasitic Keratoconjunctivitis
ism can also be cultured, provided that special
nutrient requirements and incubation methods Oestrus ovis
are used. Serology, including complement fixa- Oestrus ovis (also known as sheep nasal botfly)
tion, indirect hemagglutination, and ELISA may cause conjunctivitis if larvae invade the
tests, may be used in making the diagnosis. In ocular mucous membranes. The adult flies
most cases, testing for the organism is not eco- deposit eggs around the mucous membranes
nomically viable and empirical treatment is of the face. When the eggs hatch, the larvae
pursued. migrate to the nasal cavity, turbinates, and the
Mild infections are often self-­limiting, but maxillary and frontal sinuses. Larvae may pro-
antibiotic therapy can shorten the course of gress to the nasolacrimal duct and eye. The lar-
disease and is indicated in severe cases. vae are large (2.5 cm), spiny, and cause
Treatment may not eliminate M. conjunctivae, irritation. Secondary infection, epiphora, and
however, and it may promote a carrier state. conjunctivitis may result. The larvae mature
Oxytetracycline, applied either topically or within several weeks to months and then
intramuscularly (20 mg/kg), is the drug of return to the nostril, where they drop or are
choice. Minimal inhibitory concentrations and sneezed onto the ground to pupate. Treatment
minimal mycoplasmacidal concentrations of usually involves physical removal of larvae and
various antibiotics suggest that tylosin, strepto- systemic organophosphates. The only drug
mycin, and chlortetracycline may be effica- labeled for control of sheep nasal bots in the
cious. Topical 0.5% gentamycin and systemic United States is Ivomec Sheep Drench™ (0.08%
florfenicol (20 mg/kg i.m. or s.c.) have been ivermectin), which may be administered only
shown to have clinical efficacy. to sheep at 0.2 mg/kg. Treatment is best per-
Immunity to subsequent infection may be formed in the fall months, when the larvae
possible. Lambs experimentally infected with are small.
M. conjunctivae show evidence of both local
and systemic antibody production. Thelazia Species
Diseases concurrent with mycoplasma con- Thelazia californiensis occurs in sheep, deer,
junctivitis include mastitis, pleuropneumonia, and other species.
and arthritis in sheep and goats. Mycoplasma
agalactiae has been associated with mastitis,
Ocular Squamous Cell Carcinoma
arthritis, and conjunctivitis, with pregnant
animals being more severely affected than While uncommon, OSCC has been reported in
nonpregnant animals. sheep. Papillomavirus may play a role in the
pathogenesis of the OSCC.
Branhamella Keratoconjunctivitis
Cases of keratoconjunctivitis in sheep and
Glaucoma
goats have been attributed to B. ovis (formerly
known as Neisseria ovis), either alone or in Steroid-­induced ocular hypertension is
combination with other microorganisms. The reported in sheep to occur after one week of
role of Branhamella spp. as a primary patho- prednisolone acetate topical treatment admin-
gen is questioned by some authors, however, istered three times daily. After discontinuation
because it may be normal conjunctival flora. In of the corticosteroid instillation, IOP declined
­Conjunctiva and Corne  701

to baseline values over one to three weeks. A among domestic sheep in the western United
single dose of a gene therapy vector carrying States. Diabetes mellitus has been implicated
an inducible metalloproteinase human gene is as the cause of cataracts in ram lambs.
protective against the IOP increase produced
by corticosteroid instillation in the sheep Ocular Fundi
model and quickly reverses the IOP increase Ophthalmoscopic Examination
elicited by the corticosteroid. The ocular fundi of cattle and sheep are quite
similar ophthalmoscopically. The retina of the
sheep is holangiotic (Figure 16.40). Three, and
Uvea
occasionally four, major venules drain the ret-
Iris Abnormalities ina, and these are accompanied by paralleling
Defects in iris anatomy, termed “essential iris arterioles. Occasionally, in sheep, the superior
atrophy,” have been described among purebred arteriole and venule may twist about each
Shropshire sheep in Pennsylvania. Affected other. The tapetal fundus reflects a greenish
animals are normal at birth, but by 1.0–1.5 years blue color and is a horizontal strip in shape
of age may be affected with full-­thickness with its lower edge just touching the point of
holes in the iris stroma. The corpora nigra is entry of the optic nerve. The optic disc is
rudimentary or absent, and animals are always located at the junctional area of the
affected bilaterally but not symmetrically. nontapetal and the tapetal fundus, usually
Reported lesions have not been associated with within the nontapetal fundus just below the
any previous inflammatory episodes. junction. In sheep, the optic disc has a kidney
shape. Myelinization of the optic nerve fibers
Inflammation of the Uvea normally stops at the lamina cribrosa.
In sheep and goats, neonatal pyosepticemia, The ocular fundus of the goat is somewhat
listeriosis, mycoplasma, toxoplasmosis, elaeo- different from that of cattle and sheep. The
phorosis, thiamine deficiency, trypanosomia-
sis, blunt trauma, retroviral, and toxic causes
have been reported for uveitis.

Uveal Tumors
While primary tumors of the anterior and pos-
terior uvea are rare, a malignant melanoma
has been reported in a sheep. An iridociliary
adenoma in a sheep has also been reported.

Lens
Congenital Cataracts
Congenital cataracts have been reported in
sheep, but they are rare in goats. Congenital
nuclear cataracts have been observed in sheep
and goats. The cataracts did not progress to
involve the cortex.

Acquired Cataracts Figure 16.40 Normal ovine ocular fundus. The


kidney-­shaped optic disc is at the junction of the
Inflammatory cataracts result from lenticular
tapetal and nontapetal fundi (Courtesy of the
trauma or from severe uveitis. The nematode University of California-­Davis Comparative
Elaeophora schneideri has induced cataracts Ophthalmology Service).
702 Food and Fiber Animal Ophthalmology

retinal blood vessels are more numerous, and Stypandra glauca Intoxication
five to eight primary venules often occur. The In sheep and goats, a syndrome of retrobulbar
optic disc is rounder than in sheep and cattle, optic neuropathy and retinal degeneration
and it frequently is situated totally within the occurs after ingestion of Stypandra glauca (i.e.,
tapetal fundus. A pigment ring often surrounds blind grass). Field evidence suggests that
the optic disc as well (Figure 16.41). S. glauca is toxic in the flowering stage.
Affected animals may die after an acute illness
Retinal Dysplasia with signs of neurological disturbances, or
Inherited retinal dysplasia must be differenti- they may survive but remain permanently
ated from dysplastic changes resulting from blind. Fundoscopy shows multifocal tapetal
intrauterine infection. Infectious agents, par- and peripapillary hyperpigmented foci inter-
ticularly bluetongue in sheep, have been impli- spersed with other areas of tapetal hyperreflec-
cated as causing retinal dysplasia. tivity. Optic nerve atrophy may be present
as well.
Inflammation of the Ocular Fundus
Various infectious agents have been implicated Hypothiaminosis
as causing posterior segment inflammatory PEM, or cerebrocortical necrosis, may be
changes in food animals. Small domestic rumi- caused by thiamine deficiency. The disease is
nants have been reported to have posterior seg- especially common in goats fed a sudden
ment changes related to bacterial and parasitic excess of carbohydrates. Affected animals dis-
causes (mycoplasmosis, listeriosis, elaeopho- play blindness, ataxia, depression, opisthoto-
rosis, trypanosomiasis, and toxoplasmosis) and nos, nystagmus, convulsions, coma, and can
viral causes (bluetongue and scrapie). die of respiratory failure.

Retinal Degeneration in Toggenburg Goats Pteris aquilinum-­Induced Retinal Degeneration


Retinal degeneration has been reported in Pteris aquilinum (i.e., bracken fern, brake
Toggenburg goats. Posterior segment abnor- fern, and hog brake) has been associated with
malities were the only significant lesions, con- a progressive retinal degeneration (PRD) of
sisting of generalized tapetal hyperreflectivity the outer layers in sheep. Affected animals
and retinal vascular attenuation. have variously been called “bright blind,”
“moonlight blind,” “clear blind,” or simply
“glass eyed.” The disease has been seen clini-
cally in sheep grazing bracken (P. aquilinum),
and it has been reproduced experimentally by
feeding a concentrate ration containing 50%
dried bracken at 1 kg/day for up to 63 weeks.
Ptaquiloside, which is a norsesquiterpine glu-
coside of the illudane type, is a bracken car-
cinogen and the principal causative agent of
PRD. The disease is seen in certain areas,
including northern England, Scotland, and
possibly Wales. The incidence is highest
among three-­ to four-­year-­old sheep. It is sel-
dom seen in sheep younger than two years.
Clinically, the sheep are permanently blind.
Figure 16.41 Normal caprine ocular fundus. The
round optic disc is at the junction of the tapetal Affected animals have dilated pupils and
and nontapetal fundus (Courtesy of G. Klauss). sluggish pupillary responses. The earliest
­Pig  703

ophthalmoscopic sign is an increased tapetal Congenital Globe Abnormalities


reflection. The optic disc is normal. There is and Blindness
attenuation of the retinal blood vessels. In
In a study of 319 congenitally malformed pigs,
advanced cases, the nontapetal area is
653 distinct malformations occurred. Among
affected.
these pigs, 16 had cyclopia, 13 anophthalmia,
and 7 microphthalmia. Genetic studies were
Scrapie
not reported, but 92% of the anophthalmic
Transmissible spongiform encephalopathies
defects were associated with other malforma-
are fatal neurodegenerative diseases in which
tions. Holoprosencephaly with varying degrees
an abnormal isoform of a cellular prion pro-
of optic hypotelorism, including cyclopia, has
tein accumulates in tissues of the central nerv-
also been reported in the pig.
ous system. In sheep affected with scrapie,
Maternal vitamin A deficiency has been
prion proteins also accumulate in the inner
linked with anophthalmia, microphthalmia,
and outer plexiform layers of the retina. ERGs
macrophthalmia, retinal dysplasia, and other
on scrapie-­affected sheep show reduced
ocular abnormalities in piglets. Congenital
b-­waves in one study, and reduced a-­waves and
microphthalmos is seen in Yorkshire pigs and
b-­waves in another study.
is thought to be inherited as an autosomal
recessive trait.
Central Blindness
Diseases that may cause central blindness
include pregnancy toxemia, CNS abscesses, Eyelids
Taenia multiceps (Coenurus cerebralis) cysts,
PEM, listeriosis, and lead poisoning. Entropion
The popularity of the pot-­bellied pig has
resulted in an increased number of entropion
cases presented to veterinary ophthalmolo-
­Pigs gists. The large amount of subcutaneous fat in
the forehead and periocular region of this
Orbit and Globe
breed, as well as the enophthalmos, contrib-
Pigs possess an open orbit that is continuous utes to the development of entropion
with the temporal fossa. The tear production (Figures 16.42 and 16.43). Surgical interven-
(basal + reflex tears − STT I) in normal pigs is tion is usually required, and successful use of a
15.6 mm/min, while the basal tear production modified Hotz–Celsus procedure has been
(STT II) is 12.4 mm/min. As with other species,
the tear production increases with age, with an
average of 12.6 mm/min in pigs less than six
months of age, compared to 18.7 mm/min in
adult pigs. The IOP in pigs has been measured
and found to be 15.2 mmHg using the
TonoPen-­XL in adult pigs under general anes-
thesia with ketamine and xylazine. Another
study showed average IOPs of 27.3 mmHg OD
and 26.3 mmHg OS in awake Gottingen mini-
pigs using the TonoPen-­XL. Compared to
manometry, rebound and applanation tonom-
etry underestimates the IOP values by 17–63% Figure 16.42 Normal extraocular photograph of
in porcine eyes. pot-­bellied pig.
704 Food and Fiber Animal Ophthalmology

Figure 16.43 Entropion in a pot-­bellied pig, with


secondary trichiasis.

reported. A modified brow sling, using either


Mersilene mesh or polyester suture coated Figure 16.44 Heterochromia iridis (clinically blue
with polybutylate, is effective in some cases. and white) in a white miniature pig (Courtesy of
Kirk N. Gelatt).
The large suture or mesh acts as a scaffold for
the attachment of fibroblasts. Surgical excision
of the subdermal periocular fat pads and Acquired Corneal Diseases
redundant associated skin may be helpful in Phenothiazine
some cases. A small percentage of Vietnamese Phenothiazine has caused corneal edema and
Pot-­bellied pigs are prone to abnormal fat accu- keratitis in pigs.
mulations in the facial region, particularly the
periorbital region, which results in a mechani- Neoplasia of the Conjunctiva and Cornea
cally narrowed palpebral fissure, entropion, Primary tumors of any site, including the eye,
and impaired vision. Postoperative control of are rare in swine (incidence, 0.64%).
the animal’s weight is important for long-­term
success of surgery to correct entropion in pigs,
Uveal Tract
but this is often a challenge.
Congenital Disorders of the Anterior Uvea
Infectious Keratoconjunctivitis Congenital disorders of the uvea in pigs
Pseudorabies causes a mild conjunctivitis in include PPMs, heterochromia, aniridia and iris
affected swine. Hog cholera produces a severe hypoplasia, polycoria, cysts, pigment nevi, and
conjunctivitis. Pigs with chlamydial keratocon- colobomas. Heterochromia iridis has an esti-
junctivitis (Chlamydia suis) show a combination mated incidence of 5–7% in swine
of conjunctivitis and keratoconjunc­tivitis, with (Figure 16.44). There is a higher incidence of
or without mucopurulent rhinitis. The disease heterochromia iridis in white miniature pigs
is characterized by mild to moderate, diffuse (38.3%) than in miniature pigs having a variety
lymphoplasmacytic conjunctivitis, with mild of coat colors (15.8%). The abnormality is
lymphofollicular hyperplasia. Other flora iso- inherited as an autosomal recessive trait with
lated include Mycoplasma, Klebsiella, and variable expressivity.
Pasteurella spp. in varying proportions. It is A strain of Miniature Sinclair swine has a
likely that both Chlamydiae and Mycoplasma high incidence (54%) of cutaneous malignant
play a role in the pathogenesis of some melanomas at birth, which increases to 85% of
cases of conjunctivitis and keratoconjunctivitis the population at one year of age. As tumors
in swine. spontaneously regress, this is often followed by
­Pig  705

depigmentation of the skin, hair, eyes, and the bulge internally into the vitreous body. In
presence of uveitis due to autoimmune white pigs, the fundus is pink; in heavily pig-
destruction of melanocytes by macrophages. mented animals, the background is bluish/
gray to brown.
Inflammation of the Uvea
The associations of uveitis with systemic dis- Colobomatous Malformations
eases are numerous. Causes such as hog chol- In miniature swine, large colobomas of the
era, Glasser disease, and erysipelas have been optic nerve and choroid have been occasion-
reported. ally observed. Optic nerve hypoplasia has been
observed in piglets raised for research pur-
poses. The condition was bilateral, and direct
Lens
pupillary responses to light were absent in
Congenital Cataracts both eyes. Families of swine have also been
Congenital cataracts have been reported. In reported to have optic atrophy with multiple
Yucatan Micropigs, posterior cortical pinpoint ocular anomalies, including scleral staphylo-
opacities were seen in 20.5% of 7-­ to mas, hydrophthalmos, retinal and choroidal
12-­month-­old animals. Posterior capsular pin- atrophy, retinal calcification, and microphthal-
point opacities, nuclear opacities, and suture mia, all of which are possibly hereditary
line abnormalities were seen. anomalies.

Acquired and Secondary Cataracts Congenital Vascular Anomalies


Bilateral cortical opacities have been described In Yucatan minipigs, hyaloid remnants (82.1%)
in mature sows fed hygromycin B. Formation and pupillary membrane remnants (66.1%)
of cataracts due to hygromycin B appears to be were the most frequently reported ophthalmic
dose-­dependent and potentially cumulative. findings. Persistence of the hyaloid remnants
Amount of cataract formation with hygromy- even occurs in some micropigs older than
cin B varied from small posterior polar opaci- 33 months.
ties to mature cataracts and may be asymmetric
between eyes. Sows treated with alloxan gave Inflammation of the Ocular Fundus
birth to piglets with nuclear cataracts. The cat- Most fundus abnormalities are induced by sys-
aracts were most prominent at the nuclear cor- temic disease. Chorioretinal lesions may result
tical junction and did not progress or from pseudorabies, hog cholera, listeriosis, tox-
significantly affect vision. Starvation and ribo- oplasmosis, Glasser disease, ocular cysticerco-
flavin deficiencies have been described as sis, Teschen encephalitis, and swine erysipelas.
causing incomplete cataracts. Vietnamese Pot-­
bellied pigs have juvenile cataracts that are Degeneration of the Ocular Fundus
thought to be inherited. Amaranthus retroflexus (redroot pigweed) and
Chenopodium album (lambsquarters) cause
neurological signs and decreased vision in
Ocular Fundi
pigs. Arsanilic acid toxicity may result in blind-
Ophthalmoscopic Examination ness among pigs. Arsanilic acid is used thera-
The pig ocular fundus lacks a tapetum. The peutically for swine dysentery and as a growth
disc is horizontal and sharply defined, with stimulant. Clinical signs appear when arsanilic
8–10 arterioles, 3–4 of which are more promi- acid is given in excess, for a prolonged period
nent. The vascular pattern is holangiotic and of time, or during times of restricted water
vessels branch dichotomously; a single artery intake. Affected swine shows blindness, weak-
and vein accompany each other. Vessels may ness, torticollis, and incoordination. The PLRs
706 Food and Fiber Animal Ophthalmology

are absent, and ophthalmoscopic examination 12.5–17.5 mm/min). Mean tear production in
reveals bilateral optic disc atrophy, which is alpacas (STT I) was found to be 20.88 ± 4.04 mm/
characterized by pallor, well-­defined margins, min (range 15–30 mm/min). In one study, IOPs
and narrowed retinal arterioles. taken with a TonoPen showed that there were
no differences between llamas and alpacas,
and that the mean IOP was 16.5 mmHg with a
New World Camelids range of 14.89–18.21 mmHg. In another study,
however, llamas had significantly lower IOPs
Camelids evolved in North America 40–50 mil- than alpacas (mean IOP in llamas was
lion years ago with a subsequent outward dis- 19 mmHg; mean IOP in alpaca eyes was
persion. Today, the camelids are divided into 16 mmHg). A study of normal llamas and
two categories, Old World camelids, which alpacas also demonstrated that llamas had sig-
contains the dromedary camel (Camelus drom- nificantly lower IOPs than alpacas. Mean IOP
edaries) and the Bactrian camel (Camelus bac- for llamas was 13.10 ± 0.35 mmHg and for
trianus), and New World camelids, which alpacas was 14.85 ± 0.45 mmHg. In yet another
contains llamas (Lama glama), alpacas study of alpacas, the mean IOP value for the
(Vicugna pacos), guanacos (Lama guanicoe), TonoVet was 14.21 ± 2.73 mmHg and for the
and vicunas (Vicugna vicugna). TonoPen-­XL was 12.51 ± 2.78 mmHg.

Ocular Examination Orbit and Globe


and Ocular Parameters
Anatomically, the eyes of South American
Ocular examination is optimally undertaken camelids are very similar to those of other
with the llama or alpaca restrained in stocks ruminants (pseudoruminants) with some nota-
although some can be examined in a stall or in ble exceptions. The camelid eye is well adapted
a “cushed” position. Most domestic camelids for the high-­altitude regions of South America,
are amenable to examination; however, chemi- where there is increased UV light and little
cal sedation (butorphanol 0.02–0.04 mg/kg as a shade. Structures important to preventing UV
sole agent; for deeper sedation, butorphanol light damage include their long eyelashes, the
0.07–0.1 mg/kg may be combined with robust corpora nigra, sometimes referred to as
0.2–0.3 mg/kg ketamine and 0.2–0.3 mg/kg the “pupillary ruff,” and the darkly pigmented
xylazine i.v.; or, alternatively, tiletamine–zolaz- scleral band around the limbus.
epam 2 mg/kg with xylazine 0.2–0.4 mg/kg The camelid globe is large in proportion to
i.m.) may be necessary to control head move- the head size and is only slightly smaller than
ment. A transilluminator or halogen pen light the globe of cattle. The appearance of large
is recommended as regular penlights are not eyes in these animals is accentuated by their
bright enough to elicit PLRs in camelids. Their prominent placement laterally in the skull and
menace reflex, however, is particularly pro- by the long upper and lower eyelashes present
nounced, and they will often jump or throw in most animals.
their heads in response. Mydriasis is usually The bony orbit of camelids is complete. It is
easily achieved by the application of two to made up of portions of the frontal, lacrimal,
three drops of 1% tropicamide, with maximum zygomatic, maxillary, palatine, temporal, and
dilation typically occurring within 15–20 min sphenoid bones. There is a large palpable dor-
and dilation lasting 2 h. sal notch in the frontal bone. Rostral to the
The mean STT I of llamas was found to be medial aspect of the orbit is a 2-­cm-­diameter
17.3 (range of 15–19 mm/min), while the mean opening into the nasal cavity that is probably
STT II of llamas was 15.4 mm/min (range associated with a scent gland.
New World Camelids  707

Eyelids and Nasolacrimal System treatment, but older animals may also present
because of secondary periocular dermatitis
Camelid eyelids fit tightly to the globe, and
and/or fly strike.
conformational eyelid defects are rare. Unlike
Congenital conjunctival eyelid punctal atre-
most other domestic mammals, New World
sia is treated by surgically opened and cathe-
camelids have no eyelid meibomian glands.
terized using a procedure similar to that in
Although confirmation of a lipid tear layer is
horses. More severe cases of atresia of the
lacking, it is unlikely to be missing in New
nasolacrimal ducts at the level of the nasal
World camelids and is probably produced by
puncta have been reported in llamas and
sebaceous glands in the canthal area.
alpacas. In all cases in which the atresia was
The camelid has both an upper and a lower
close to the site of the nasal punctae, the ani-
punctum. Each is located 4–6 mm from the
mals respond well to surgical opening similar
medial canthus and is large and slit-­like, mak-
to the method described below.
ing it relatively easy to cannulate. The lacrimal
Correction of an imperforate punctum
sac is small, and the nasolacrimal duct exits
involves incising the mucous membrane cover-
from it, traversing through the lacrimal and
ing the opening. If the puncta are present and
maxillary bones and terminating in the nasal
patent, the nasolacrimal duct should be flushed
cavity. In most camelids, the nasal opening can
orthograde through one of the conjunctival
be seen fairly easily as it is located laterally in
puncta (Figure 16.45). This can be performed
the nasal cavity and 1.5–2 cm proximal to the
with local anesthetic alone in some animals,
wings of the nares. In the adult llama, the duct
but some individuals are head-­shy and must be
is 11–15 cm long and 2–4 mm in diameter.
sedated or anesthetized for the procedure. If

Blepharitis
Blepharitis is the most common eyelid prob-
lem in camelids. This is often present in con-
junction with generalized dermatitis. Bacterial
infections can lead to blepharitis and concur-
rent bacterial conjunctivitis. Blepharitis caused
by chigger mites has been reported in Peruvian
alpacas. Signs include periocular and facial
blepharitis, pruritis, scaling, and alopecia.

Developmental Anomalies of the


Nasolacrimal System
Congenital nasolacrimal duct disorders that
have been reported in camelids include nasol-
acrimal duct atresia, conjunctival punctal atre-
sia, nasal punctual atresia, or combinations of
these. Alpacas seem to be more commonly Figure 16.45 Dacryocystorhinogram of a cria with
affected than llamas. Affected animals usually nasolacrimal disease showing the dye column in
present with a “wet face” due to the tear over- the nasolacrimal duct. The dye normally emerges
at the nasal opening of the duct. Here, the dye only
flow and mucopurulent ocular discharge due
reaches the central portion of the duct (distal
to secondary dacryocystitis. Most often, these arrow), which is a common site of atresia to
animals are young when they present for camelids.
708 Food and Fiber Animal Ophthalmology

the fluid fails to pass through the ducts and into will often remove foreign material, purulent
the nasal cavity, the animal should be placed exudate, and infectious agents.
under general anesthesia, and catheterization
of the nasolacrimal ducts through the conjunc-
Conjunctiva
tival puncta should be attempted.
Catheterization is performed with large suture The most common species of bacteria isolated
material or with polyethylene tubing. If the from the conjunctival of normal camelids were
material will not pass, then imaging procedures Staphylococcus epidermidis (52%), Pseudomonas
such as dacryocystorhinography are indicated spp. (41%), and Bacillus spp. (28%) in one study.
in order to localize the obstruction. Another study reported Staphylococcus xylosus
A piece of polyethylene tubing is threaded in and viridans streptococci, as well as two species
an orthograde fashion through the nasolacri- of Moraxella. Aspergillus is the most commonly
mal duct until it stops at the point where the isolated fungus.
duct prematurely terminates. Sometimes, the
tip of the tubing can be palpated through the Congenital Disorders
nasal mucosa where the nasal punctal opening Dermoids and cysts are congenital conjuncti-
should have been. An incision through the val abnormalities that have been reported in
mucosa over the tubing is made and the tubing camelids.
is passed into the nasal cavity at which point it
is anchored to the surrounding nasal mucosa Conjunctivitis
with a Chinese finger trap suture. The tubing is Conjunctivitis is common in camelids
left in place for six weeks to prevent closure of (Figure 16.46). The clinical signs are similar to
the punctum. When tubing cannot be palpated those seen in other ruminants and typically
through the nasal mucosa, dacryocystorhino- include mild blepharospasm, conjunctival
gram will help localize the blockage. When hyperemia, epiphora, and, occasionally, chemo-
there has been failure of formation of the distal sis. Irritation from dust or foreign bodies, espe-
one-­third of the nasolacrimal duct, a conjunc- cially plant material, is a common cause for
tivosinusotomy may be performed to allow for self-­limiting mild conjunctivitis. Staphylococcus
lacrimal drainage. aureus and Moraxella liquefaciens have been
implicated as causative or contributory in
camelid conjunctivitis. Chlamydiae have also
Dacryocystitis
Dacryocystitis is relatively common in camel-
ids, perhaps because their large conjunctival
puncta are vulnerable to invasion by foreign
bodies such as grass awns. Animals with this
disorder are typically adults with a history of
chronic mucopurulent ocular discharge,
which can be profuse. There can also be a his-
tory of blepharospasm and conjunctival hyper-
emia. Treatment of dacryocystitis is aimed at
clearing the nasolacrimal system of foreign
material and addressing the associated second-
ary bacterial infection. Topical antibiotics can
Figure 16.46 Severe chemosis with marked
be attempted initially but frequently do not
conjunctival hyperemia. This severity of
lead to resolution. Flushing of the nasolacri- conjunctivitis is most often found in bacterial
mal duct through the upper or lower punctum conjunctival infections.
New World Camelids  709

been isolated from camelids with conjunctivitis. in alpacas. The mean corneal thicknesses were
In general, cytological evaluation of both a con- also very similar. Because of the propensity of
junctival scraping and a microbiological culture camelids to develop marked corneal edema
(bacterial and fungal) and sensitivity testing are secondary to intraocular surgeries, trauma,
recommended in cases of conjunctivitis and and uveitis, it was thought that these animals
keratoconjunctivitis. might have low numbers of corneal endothe-
In addition to bacterial conjunctivitis, para- lial cells compared to species who do not have
sites have been reported to induce moderately problems with excessive edema formation. The
severe conjunctivitis in camelids. The larvae of densities of endothelial cells in camelids
the nematode parasite, T. californiensis, can be (2673 cells/mm2 in llamas and 2275 cells/mm2
present in the conjunctival sacs of many spe- in alpacas) are only slightly lower than those of
cies, including llamas and alpacas. Clinical other species that have been studied. However,
signs of Thelazia infection range from mild frequent polymegathism and pleomorphism of
epiphora and hyperemia to severe epiphora the endothelial cells are observed in normal
and blepharospasm. Occasionally, presence of camelids, which suggests that clinically nor-
the nematode can cause enough irritation that mal alpacas and llamas have potential corneal
the animal will self-­traumatize and that can endothelial instability and increased vulnera-
lead to a secondary corneal ulcer. bility to the development of corneal edema.
Infectious and irritative conjunctivitis
should be treated according to the cause. A cul-
Ulcerative Keratitis
ture and sensitivity should be done on all cases
of suspected bacterial conjunctivitis. Prior to Corneal trauma is probably the most common
receiving the results of culture, a broad-­ ocular disease in New World camelids. In stud-
spectrum antibiotic, such as a triple antibiotic, ies of apparently healthy camelids having no
should be applied four to six times daily. If a history of pain or squinting, many animals had
Thelazia larva is seen, mechanical removal of corneal scars suggestive of prior trauma. Of
the worm under topical anesthetic is curative. llamas that presented to veterinary teaching
Alternatively, topical diethylcarbamazine or a hospitals for all eye diseases, 41% had corneal
drop of injectable ivermectin instilled into the disease and more than half of these had an
conjunctival sac will kill the parasite, and active corneal ulcer. Most of these ulcers were
either it will be flushed out with the tears or it of unknown cause but likely traumatic
may be removed manually. Many types of flies in origin.
feed on llama lacrimal secretions and can The prominence and vulnerability of the
cause conjunctival irritation. Consequently, fly camelid cornea predispose it to injury. Trauma
control is important for minimizing this form may be caused by fighting, penetration, or
of conjunctivitis. scratching of the cornea by foreign bodies or
from prolonged recumbency due to tick paraly-
sis, meningeal worms, prolonged anesthesia,
Cornea
or lack of passive transfer in crias. Other
The corneas of llamas and alpacas are large trauma-­associated corneal diseases include
and semi-­oval shaped. Although the head size lacerations, foreign bodies, and stromal
of alpaca is smaller than that of the llama, the abscesses.
corneal diameters of the two species are very In a recent report of 56 sick neonatal camel-
similar. In one study, the mean horizontal cor- ids, the most commonly reported ophthalmi-
neal diameter of llamas was 28.2 mm while clesion was ulcerative keratitis. All flavors of
that of alpacas was 30.2 mm. The mean vertical corneal ulcer have been reported in camelids
diameters were 24.2 mm in llamas and 22.2 mm ranging from uncomplicated superficial ulcers
710 Food and Fiber Animal Ophthalmology

to indolent ulcers and complicated infected cotton-­tipped applicator and grid keratotomy
ulcers of varying depths. Infected ulcers may or a diamond burr.
involve opportunistic normal ocular flora (bac- Delivery of topical ocular medicines in came-
terial and fungal) or even obligate anaerobic lids can be facilitated by a subpalpebral lavage
bacteria such as Clostridium perfringens, system (SPLS) or nasolacrimal lavage system
Clostridium bifermentans, Peptostreptococcus (NLLS). Adaption of a commercially available
sp., and Eubacterium sp. Corneal ulcers, often equine SPLS with a soft low-­profile footplate in
very deep, can arise in camelids with facial either the upper or the lower eyelid is effective
nerve paralysis. The inability of the animal to for delivering topical medication to the camelid
blink its eyelids and keep the cornea moist ocular surface. Since the nasal punctum of
leads to progressive exposure keratitis. camelids is relatively easy to locate, an NLLS is
Spontaneous corneal epithelial defects gener- not difficult to place but may require that the
ally heal well with proper therapy similar to animal be under sedation or general anesthe-
that used in canines. sia. The procedure is accomplished by thread-
Cases of superficial, dendritic ulcers in ing soft tubing (22-­guage polyethylene) into the
camelids have been documented. These ulcers nasal opening and up the nasolacrimal duct
appear to be very similar to herpesvirus-­ until it stops at the level of the nasolacrimal
induced ulcers in cats, but as of yet, the causa- sac. The nasal end of the tubing can then exit
tive organism has not been positively identified, the nostril, or may be threaded through a large-­
and generally heal well if the animal is placed diameter needle puncture that is made in the
on topical cidofovir. alar fold of the nose, and fastened via tape tabs
Aggressive, prompt treatment of corneal to the face. Medication can be injected through
ulcers in camelids is important for a successful an injection port that has been placed into the
outcome. Numerous opportunistic bacterial end of the tubing.
pathogens such as Pseudomonas spp. grow in
the conjunctival sacs of normal camelids, and
Stromal Abscess
therefore, topical broad-­spectrum ophthalmic
antibiotics should be used in all cases in which Abscesses frequently develop in camelid cor-
the corneal epithelium has been compromised. neas from trauma that perforates the epithe-
If evidence of an infection is present, then aer- lium and enters the stroma. These appear as
obic and anaerobic bacterial culture and sus- yellowish-­white collections of purulent mate-
ceptibility testing should be performed. Topical rial at various depths within the corneal
antibiotics and antifungal drugs that can be stroma; they are often very deep. These
used in horses can be used in camelids. The abscesses may be infected by bacteria, and if
optimal treatment of corneal lacerations, per- treated aggressively, they will often resolve
forations, and ulcers depends on the initial quickly with medical support. Some may be
depth of the lesion, the duration of the prob- fungal in origin, particularly the deeper lesions.
lem, and whether or not the lesion is infected. The most common fungal isolates are the
Greater-­than-­half-­depth lacerations, which opportunistic Aspergillus spp. and Fusarium
have little to no corneal tissue missing, may be spp. The clinical presentation is similar to that
sutured directly with small-­gauge (7-­0 to 10-­0), which occurs with horses with deep stromal
absorbable, suture material. Deep ulcers and abscess (DSA), including the secondary mild to
ulcers with perforations may be successfully fulminating uveitis that accompanies the cor-
repaired using a conjunctival pedicle graft or neal lesion. Treatment, too, is similar to that in
corneal conjunctival transposition. the equine, consisting of topical antibiotics
Debridement of spontaneous chronic corneal and antifungal agents as well as topical mydri-
epithelial defects may be done with a atics and systemic nonsteroidal medications.
New World Camelids  711

Corneal Dystrophy and acts to shade the pupil. Anatomically, the


Degeneration pupillary ruff is a modified portion of the pos-
terior pigment epithelium of the iris, which is
Nonulcerative corneal degeneration is rarely
very large, protrudes into the pupil, and is
reported in camelids; however, dystrophies
folded vertically.
and degenerations have been seen in clinical
The iris pigmentation is usually moderate to
practice and have been reported in surveys of
dark brown but not uniform in color. There are
ocular diseases of camelids. Bilateral calcific
usually various shades of brown scattered
band keratopathy has also been reported in an
through an individual iris, and heterochromia
alpaca. While many of the corneal degenera-
irides is common in color dilute camelids.
tions/dystrophies seen in camelids may be
Clear blue or gray irides are also normal in
hereditary, acquired corneal degeneration has
camelids having low amounts of pigment. As
also been reported. A lipid keratopathy was
in many other species (e.g., cats), coat and iris
described in an eight-­year-­old castrated male
color may be associated with hearing loss.
alpaca, where erosions were surrounded by
There is a strong association between iridal
areas of neovascularization and dense-­white
hypopigmentation and congenital deafness in
crystalline deposits. A diagnosis of bilateral
llamas and alpacas. The blue-­eyed white
lipid keratopathy was made based on the
(BEW) phenotype inheritance pattern has not
results of a histopathological examination of
been proven but a strong association between
keratectomy samples. The source of the lipid
the BEW phenotypes and two microsatellite
was most likely due to the very high serum
alleles at KIT-­related markers has recently
cholesterol concentrations of unknown origin
been demonstrated.
that led to corneal lipid deposition as well as
atherosclerosis. Congenital Disorders of the Uvea
PPMs have been reported as congenital, and
Anterior Segment possibly hereditary, ocular defects in crias.
PPMs are usually iris to iris and do not cause
The iris of the camelid is similar to that of the any visual deficits. Heterochromia iridis and
cow except for the more pronounced “pupil- iris coloboma have been reported in closely
lary ruff” in camelids, which is a modification related alpacas (Figure 16.48).
of the corpora nigra (see Figure 16.47). This
structure is an unusual and interesting adapta- Anterior Uveitis
tion to life in areas of excessive UV radiation. It Anterior uveitis is a common sequela of trau-
is present on the dorsal and ventral papillary matic ocular injury and systemic disease in
margins but is more prominent dorsally as it camelids. Clinical signs of anterior uveitis can

Figure 16.47 A normal camelid eye.


This iris is heterochromic, containing
shades of brown and blue. The pupillary
ruff is distinct and the pupil is roughly
a dumbbell-­shaped oval.
712 Food and Fiber Animal Ophthalmology

Figure 16.48 Congenital ocular defects such as Figure 16.49 An immature cataract of unknown
this iris coloboma (thought to be two colobomas etiology in a middle-­aged llama. Due to the site of
abutting) are sometimes seen in camelids such as the cataract (cortical) within the lens and its stage
this alpaca. In most cases, the etiologies are of maturity, it is likely to progress. The streak on
unknown, but in this case a hereditary origin the central cornea is mucus.
is likely.

coat color of the animal. When observed oph-


range from mild blepharospasm and epiphora thalmoscopically, it may appear dark brown,
to severe pain signs, episcleral injection, syne- red-­brown, or nonpigmented. A single fundus
chiae, and corneal edema. Infectious diseases can contain streaks of dark pigment in some
causing anterior uveitis include bacterial sep- areas, while other areas are nonpigmented.
ticemia in neonates and crias with juvenile The prominent choroidal vessels provide a red
llama immunodeficiency syndrome, equine coloration of the fundus that is seen in many
herpesvirus type 1 (EHV-­1), and toxoplasmo- camelids. The colors of the iris and fundus are
sis, among others. Uveitis may also be second- directly related to the coat and skin color of the
ary to deep corneal ulcers and cataracts individual. Hypopigmented animals with light
(lens-­induced uveitis). Therapy is aimed at coat colors generally have various combina-
the underlying cause of the uveitis and tions of gray, blue, and brown irides and
symptomatic treatment of the intraocular reduced pigmentation of the fundus. Those
inflammation with topical and systemic anti-­ with dark coat colors generally have brown iri-
inflammatory agents (topical corticosteroids des and pigmented fundi.
and NSAIDs and systemic NSAIDs, such as flu- The retinal vasculature and optic disc of the
nixin meglumine). The exception is topical camelid are similar to those of the bovine. A
corticosteroids in pregnant animals. In a study prominent holangiotic vascular pattern is eas-
on llamas in the late stages of pregnancy, giv- ily visible, and there are often anastomoses on
ing one drop three times daily of topical the surface of the optic disc (Figure 16.49).
dexamethasone-­containing ophthalmic prepa- Three to five pairs of prominent retinal vessels
ration for eight days caused them to abort their emerge from the optic disc periphery; one pair
near-­term fetuses. of vessels emerges dorsally and extends periph-
erally with the artery and vein spiraling around
each other. Two pairs of vessels leave the optic
Posterior Segment
disc horizontally and are usually accompanied
The appearance of the camelid fundus is by myelin, which extends several disc diame-
highly variable among individuals and often ters peripherally into the fundus. A large
between eyes of the same individual. This vari- Bergmeister’s papilla (hyaloid remnant) may
ability is attributable to the amount of pigment protrude from the disc into the vitreous
in the choroid, which in turn depends on the (Figure 16.50). One interesting adaptation to
New World Camelids  713

segment findings in cria eyes include a retinal


detachment in an eye that also had vitreous
fibrosis and ossification, optic nerve hypo-
plasia, tunica vasculosa lentis, and suspected
retinal aplasia. A recent study described a
group of closely-­ related alpacas, each having
ocular defects. All had different sizes and types
of colobomas in one or both eyes. Other defects
included choroidal dysplasia/hypoplasia, sub-
albinotic fundi, and cataracts. Although it
could not be proven, the authors hypothesized
that these defects were likely hereditary.

Acquired
Causes of acquired uveitis include systemic
infections, ocular parasites, and toxicities.
Figure 16.50 Funduscopic photograph of a Several systemic infectious diseases have been
normal camelid eye. The fundus is holangiotic, reported to cause posterior segment inflamma-
having large vessels that often stand out from the tory disease in camelids; the most notorious is
surface. The dorsal veins sometimes wind around EHV-­1. Other infectious diseases reported to
each other. The optic nerve is large, often oval, and
the retinal vessels course over the top of it. cause posterior uveitis in llamas include asper-
Pigment in the fundus can be heavy, light, absent, gillosis, toxoplasmosis, and septicemia. Retinal
or combinations of these. detachments and chorioretinitis are the most
common ocular findings.
high-­altitude living in camelids may be extrap- The most well-­known viral cause of both
olated from the retinal vascular pattern of the anterior and posterior uveitis, as well as neuro-
dromedary camel. In that species, even though logical disease, in camelids is EHV-­1. Camelids
there are specific high-­density areas of gan- acquire EHV-­1 by contact with members of the
glion cells within the retina, the major blood family Equidae, such as horses and zebras. It
vessels do not avoid these regions as they do in was first described in 1988 in a mixed herd of
other species. This could be a mechanism to camelids of which many members became
improve oxygenation to these important reti- blind after close contact with infected zebras.
nal areas at high altitudes where partial pres- The neurological signs that developed included
sure of oxygen is low. head tilt, nystagmus, and paralysis. Signs of
panuveitis developed in two alpacas as evi-
denced by hypopyon, iritis, vitritis, retinitis,
Diseases of the Posterior Segment
and optic neuritis.
Diseases of the posterior segment are relatively Toxoplasmosis, a known cause of chorioreti-
common in camelids. Congenital abnormali- nitis in dogs and cats, may also cause chori-
ties, inflammatory diseases, parasitic diseases, oretinitis and blindness in camelids. During an
toxic retinopathy, and retinal and optic nerve investigation of causes of late-­term abortions
degenerations have been noted. in llamas, a serological survey showed an
extremely high antibody titer for Toxoplasma
Congenital gondii in a blind llama that did not abort but
Reported congenital defects in crias include that had lesions consistent with chronic pano-
microphthalmia, peripapillary colobomas, and phthalmitis. Another animal with bilateral
retinal dysplasia. Other congenital posterior chorioretinitis had rising vitreous convalescent
714 Food and Fiber Animal Ophthalmology

Toxoplasma antibody titers, although serum Lens


antibody titers were negative, suggesting that
Cataract
T. gondii may have caused the posterior uveitis.
As in other mammalian species, cataracts are
Acquired retinal degeneration has been
the most common abnormalities of the
reported in camelids, including a case of pos-
camelid lens. Mature, hypermature, and
sible enrofloxacin-­induced toxic retinopathy in
immature cataracts, as well as both congenital
a male guanaco. Retinal degeneration and
and acquired opacities, have been reported
optic nerve atrophy have been reported sec-
(Figure 16.51). The significance of small,
ondary to chronic glaucoma. A case of ophthal-
immature cataracts in camelids is unknown.
momyiasis interna has been described in a
Some have been thought to progress to matu-
12-­year-­old female llama that had an acute
rity, while others have not. It also has not been
onset of recumbency and blindness. Upon
determined whether or not they are geneti-
ophthalmoscopic examination, a 2-­cm-­long
cally transmitted. Many of these immature
mobile helminth larva was observed in the
cataracts are located at the posterior “Y”
posterior vitreous near the retina of the
sutures of the lens similar to the inherited, but
right eye.
usually nonprogressive, cataracts in Golden
Camelids with uveitis, which is not attribut-
Retrievers.
able to an obvious cause, should be examined
Congenital cataracts can be solitary findings
carefully for signs of systemic disease. A thor-
or may be found in conjunction with other
ough history and physical and ophthalmic
ocular abnormalities such as persistent hyper-
examinations should be performed. Routine
plastic primary vitreous, persistent tunica vas-
blood work is indicated in these cases as well
culosa lentis, and persistent hyaloid artery.
as serology that is appropriate for the geo-
Because of the possibility of retrolental abnor-
graphic area and physical examination find-
malities in camelids with cataracts, ocular
ings. Titers should be performed for infectious
ultrasonography is recommended prior to cata-
diseases, including toxoplasmosis, leptospiro-
ract surgery in these species.
sis, brucellosis, and systemic fungal infections
While type 1 diabetes mellitus occurs in
such as blastomycosis, coccidioidomycosis,
camelids, the incidence of diabetic cataracts is
and aspergillosis. If a cause is found, then spe-
not known. In a case report of a diabetic alpaca,
cific directed therapy should be instituted
the authors reported that the animal had bilat-
along with anti-­inflammatory therapy. If not,
eral opacities that covered over 50% of the pos-
the animal should be given intensive anti-­
terior lens capsule. It is unknown whether
inflammatory therapy and monitored carefully
these were secondary to the systemic disease,
for the development of other signs of local or
but their appearance was dissimilar to diabetic
systemic disease. This generally includes topi-
cataracts in dogs that develop rapidly and pro-
cal NSAIDs or topical steroidal medications.
gress to maturity.
Topical atropine is also indicated to prevent
Surgical removal of cataracts in camelids has
synechiae and alleviate pain. Systemic NSAIDs
proven successful in restoring vision.
may also be instituted and are relatively safe in
Phacoemulsification is the technique of choice
camelids. Intravenous, intramuscular, or sub-
with endothelial-­sparing methods employed.
cutaneous flunixin meglumine can be admin-
Irrigation with balanced salt solution (BSS)
istered at a dose of 1 mg/kg once daily or 5 mg/kg
Plus (a BSS containing glutathione) rather
of oral etogesic can be given once daily.
than normal saline, intensive application of
Systemic steroids should be avoided in preg-
pre-­ and postoperative anti-­inflammatory
nant camelids as they can lead to abortions and
drugs, and the use of copious amounts of
hepatic lipidosis.
New World Camelids  715

Figure 16.51 Fundic photograph of


an alpaca. The arrow points to a
hyaloid remnant extending from the
surface of the optic disc.

viscoelastic during surgery all aid in protecting Ocular Neoplasia


the sensitive corneal endothelium. Luxated
Ocular and periocular neoplasia appear to be
lenses, traumatic lens ruptures, and lens colo-
more common in domestic camelids than pre-
bomas are rare.
viously thought. Various case reports of intraoc-
ular tumors in llamas and alpacas have
appeared in the literature. Intraocular
Glaucoma
medulloepithelioma (teratoid and nontera-
Glaucoma is uncommon in llamas and alpacas, toid), retinoblastoma, and malignant mela-
and there are no known cases of primary, noma are the reported tumor types. Metastasis
potentially inherited, glaucoma in these spe- has been associated with intraocular
cies. Therefore, glaucoma is considered to be medulloepitheliomas and melanomas in came-
either congenital or secondary to intraocular lids. Enucleation should be performed when
inflammation. intraocular neoplasia is suspected or confirmed.
716

17

Exotic Animals: Ophthalmic Diseases and Surgery


Revised from 6th edition of Veterinary Ophthalmology, Chapter 31: Avian Ophthalmology, by Lucien V. Vallone and Thomas J. Kern;
Chapter 33: Laboratory Animals Ophthalmology, by Seth Eaton; Chapter 34: Small Mammals Ophthalmology, by David L. Williams;
Chapter 35: and Exotic Animal Ophthalmology (including Fish, Amphibians, Reptiles, and Mammals), by Thomas J. Kern

­ onsiderations for Ophthalmic


C magnification of the ocular fundus when
Examinations in Laboratory Animals viewed ophthalmoscopically. Rodents’ small
globes, bearing short optical focal distances,
Ocular examination in laboratory species pre- produce considerable magnification. In
sents a number of unique challenges to the rodents, for example, this phenomenon makes
examiner. The foremost of these challenges is the normal retinal vasculature appear to
gaining familiarization with what is normal for “float.” If the examiner is unfamiliar with this
a given species. The small size of laboratory artifact, it could be falsely interpreted as a reti-
rodent eyes renders ophthalmoscopic exami- nal detachment.
nation more difficult than in dogs or cats. Slit-­ Indirect ophthalmoscopy is readily per-
lamp biomicroscopy of the adnexa, cornea, formed in lagomorphs and primates and can,
and anterior segment is relatively straightfor- with practice, be mastered in rodents. In labo-
ward, whereas fundoscopy can be difficult, ratory species, the range of globe and pupil
especially in pigmented and nontapetal strains, sizes requires examiners to use condensing
among which mydriasis may be exceptionally lenses of different dioptric strengths. Some
difficult to achieve. In all mammalian labora- examiners prefer a 90-­D lens used in conjunc-
tory species, pupil dilation is essential for thor- tion with a table-­mounted slit lamp; others
ough examination of the entire lens and prefer a 28-­D lens and an indirect headpiece.
posterior segment and is easily achieved with Still others find a 2.2 Pan Retinal lens to be use-
topical short-­acting antimuscarinics such as ful in most rodents.
0.5–1.0% tropicamide. While not always neces- The estimation of intraocular pressure (IOP)
sary, some references advocate use of topical is part of essential diagnostics. While the
phenylephrine in combination with agents TonoPen® has been favorably evaluated in the
such as tropicamide, particularly pigmented small eyes of ferrets and rats, the mouse cornea
rodents. Examiners must also be mindful of is too small to accommodate the footplate of
the inverse relationship between a species’ even the TonoPen applanation tonometer, and
globe dimensions and the lateral and axial is better suited to a rebound tonometer, which

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
­Considerations for Ophthalmic Examinations in Laboratory Animal  717

measures the speed of rebound of a small plas- stresses like restraint and transport may cause
tic probe fired at the ocular surface, and is chromodacryorrhea.
small enough to provide accurate measure-
ments of IOP in even these eyes. The majority Orbital Space-­Occupying Lesions
of animals in many laboratory animal collec- Harderian gland pathology can result in exoph-
tions are mice and rats, with far fewer rabbits, thalmos in laboratory rodents. Orbital cellulitis
dogs, and nonhuman primates (NHPs). Mini-­ with retrobulbar abscessation is most com-
and miniature pigs are becoming more popular monly associated with Pasteurella multocida in
as a replacement for NHPs, so knowledge of the rabbit, but similar conditions can occur in
swine diseases is now very important. chinchillas and other rodents with continually
growing molar and incisor teeth.
Ocular Diseases in the Mouse and Rat
Conjunctivitis
The reported ophthalmic diseases in mice and Conjunctivitis may be observed in mice or rats.
rats are listed in Table 17.1. Chromodacryorrhea In both species, clinical signs are generally non-
occurs in many laboratory rodents, but par- specific, including serous to mucoid/mucopu-
ticularly rats exhibit red crusting around their rulent ocular discharge, conjunctival
eyes in cases of ocular irritation, upper respira- hyperemia, chemosis, blepharospasm, and
tory tract infection, and general stress chromodacryorrhea. In laboratory rodents, pri-
(Figure 17.1). Porphyrin pigmented and lipid-­ mary conjunctivitis is most commonly of infec-
laden tears are produced in normal amounts tious etiology. In both rats and mice, the most
by the Harderian glands in several rodent spe- common cause of conjunctivitis unrelated to
cies. The porphyrin pigments are also autoflu- intraocular disease is mycoplasmal respiratory
orescent, which can be used to differentiate infection, but other agents can also be involved.
chromodacryorrhea from infections such as Numerous bacterial organisms have been
mycoplasmosis and sialodacryoadenitis, nutri- implicated in naturally occurring conjunctivitis
tional deficiencies, and other physiological in mice and rats, including Mycoplasma spp.,
Pseudomonas aeruginosa, Salmonella spp.,
Pasteurella spp., Streptobacillus moniliformis,
Table 17.1 Reported ophthalmic disorders in mice
and rats.
Staphylococcus aureus, and Corynebacterium
kutscheri. Viral agents have also been impli-
Chromodacryorrhea cated, including lymphocytic choriomeningitis
Orbital space-­occupying lesions
Conjunctivitis
Sialodacryoadenitis
Microphthalmos
Corneal opacification and inflammation
Corneal dystrophy
Anterior uvea lesions
Glaucoma
Cataracts
Posterior segment
Persistence of the hyaloid vasculature
Vascular anomalies and saccular aneurysms of the
retinal vessels
Retinal degeneration
Infectious lymphocytic choriomeningitis Figure 17.1 Chromodacryorrhea occurs in many
laboratory rodents, but particularly rats.
718 Exotic Animals: Ophthalmic Diseases and Surgery

(LCM) virus, ectromelia virus (the causative and hence keratitis, conjunctivitis, periorbital
agent of mousepox, which primarily causes swelling aggravated by self-­mutilation, and
dermatologic disease), and Sendai virus. chromodacryorrhea. The disease itself usually
resolves within one week, whereas resolution
Sialodacryoadenitis of the secondary signs may take as long as
The most devastating adnexal disease in rats in one month.
both its acute and chronic forms is sialodacry-
oadenitis virus infection. This coronavirus Microphthalmos
infection in rats causes ocular irritation with Microphthalmos and anophthalmos have been
conjunctivitis and periorbital swelling, fol- reported in both mice and rats. Clinically,
lowed by sneezing, edematous cervical swell- microphthalmos presents as an abnormally
ing, and enlarged lymph nodes and salivary small globe (Figure 17.2), unilaterally or bilat-
glands. This is a highly contagious but self-­ erally, often with concurrent anomalies such
limiting disease in rat colonies. The classic epi- as engorged or tortuous episcleral and/or iridal
zootic disease has a high morbidity but a low vessels, microcornea, corneal opacities, ante-
mortality rate. Acute ocular disease is charac- rior segment dysgenesis, cataract and/or
terized by conjunctivitis or keratoconjunctivi- microphakia, retinal dysplasia and detach-
tis, often associated with periorbital swelling ment, and colobomas. As with other species,
and exophthalmos, and chromodacryorrhea true microphthalmos must be differentiated
resulting from swelling and inflammation of from acquired phthisis bulbi. Several experi-
the Harderian and lacrimal glands. Primary mental microphthalmic rodent models exist,
signs include blepharospasm and photopho- but microphthalmos also occurs sporadically
bia, as well as eye rubbing. Lacrimal gland as an incidental finding in several standard rat
involvement leads to reduced tear production and mouse lines. Though microphthalmos is

OS OD

500 μm 500 μm

Figure 17.2 Microphthalmia and persistent hyaloid artery in the right eye (OD) of a mouse. The normal left
eye (OS) is provided for comparison. Note the anterior–posterior diameter of the normal mouse lens and
correspondingly narrow anterior and vitreous chambers. (Courtesy of Leandro Teixeira, DVM, DACVP, COPLOW,
University of Wisconsin–Madison.)
­Considerations for Ophthalmic Examinations in Laboratory Animal  719

rare in most strains, the inbred pigmented persistence of the pupillary vasculature. Blood
C57BL/6J mouse carries a higher relative risk, in the anterior segment is more commonly
with a reported incidence of up to 12%. associated with persistent embryonic vascula-
ture around the lens and iris than with active
Corneal Opacification and Inflammation inflammation. Similarly, blood in the vitreous
Corneal opacification is relatively common in is often associated with persistent hyaloid ves-
rodents, perhaps more so in mice than in rats. sels. Persistent pupillary membranes (PPMs)
Corneal opacities in rodents may be catego- have been reported in almost every species of
rized as traumatic, iatrogenic, toxic, infectious, laboratory animal, including rats and mice.
or heritable (e.g., corneal dystrophy [CD]).
Since most mice and rats are group housed, Glaucoma
corneal opacities/scars related to trauma are Naturally occurring glaucomas have been
common, and may present with or without reported in mice and rats. The failure of aque-
concurrent uveitis and/or intraocular findings. ous drainage is not necessarily because of an
Several causes of corneal inflammation exist abnormality of the iridocorneal angle, as in
in this species. Opacities in the nasal part of many inherited glaucomas in the dog or in the
the cornea are common, and while they may bu/bu rabbit. In rats, it often results from PPMs
relate to anterior segment inflammation, they causing pupil-­block glaucoma or from periph-
can also relate to orbital gland inflammation. eral anterior synechiae causing angle-­closure
More severe keratitis can also occur and is glaucoma. Clinical descriptions of sporadic
probably caused by reduced tear secretion, primary congenital glaucoma have been
although, as noted earlier, evaluation of tear reported in F344, Wistar, and RCS (Royal
production is rarely undertaken in these College of Surgeons) rats. Clinically, signs of
rodents, producing a secondary keratitis. Thus, glaucoma in rodents may be difficult to recog-
keratitis may occur without any obvious infec- nize, as signs like episcleral congestion, cor-
tive or environmental factors. neal edema, mydriasis, or behavioral changes
indicating vision deficits may not be as promi-
Corneal Dystrophy nent as in other species. In the laboratory set-
CD is a common, bilateral, opacifying disease ting, buphthalmos is often the first sign
in mice and rats with a putatively heritable observed, possibly developing with little delay
cause and no association with underlying sys- in the face of elevated IOP due to the rodent’s
temic disease. Corneal opacification has been comparatively thin sclera.
more frequently reported in mice than rats. In
rats, the incidence of CD is variable, depend- Cataracts
ing primarily on the age, sex, and strain of the In the rat, cataracts may occur both congenitally
animal. Incidence in both mice and rats and in aging animals. These reports concerned
increases with age. CD typically presents as the Sprague–Dawley rat, but other rat strains
fine or punctate, granular, translucent to (e.g., the albino Sherman) and the F344 are also
opaque white corneal opacities in the anterior affected. Although occurring at a low incidence,
subepithelial corneal stroma, often observed in these spontaneous lesions complicate experi-
the nasal and/or axial cornea. mental work on cataract induction and toxico-
logical studies. In rats with retinal dystrophy or
Anterior Uvea Lesions degeneration, cataracts occur secondarily, prob-
Lesions of the anterior uvea in rodents can for ably because of the release of various posterior
the most part be divided into congenital anom- segment metabolic by-­products.
alies and those secondary to inflammation. The mouse is one of the most commonly
The former lesions include keratolenticular used models for human inherited cataract,
adhesions (discussed earlier) and the with early-­ and late-­onset cataracts described
720 Exotic Animals: Ophthalmic Diseases and Surgery

in association with numerous mutations, rep- gene, for instance, is seen in C57BL/6J, CBA,
resenting varying modes of genetic inherit- C3H, and various outbred albino mouse
ance. Inherited cataracts have been strains. The RCS rat with its retinal pigment
documented in mice, such as those occurring epithelial dystrophy is one such example, as is
in the Scat and Lop-­10 strains, which have the Osborne–Mendel rat with its retinal
autosomal dominant cataracts. Iatrogenic degeneration.
transient lens opacities in rodents have been In mice, the most common infectious cause
described in association with prolonged eyelid of retinal degeneration is LCM. Mice are the
separation while under anesthesia, putatively natural carrier for this potentially zoonotic are-
a result of changes in the osmotic environment navirus, shedding the organism in saliva,
and/or temperature in the AC. urine, and/or feces. LCM virus can also be
transmitted between animals horizontally via
Posterior Segment aerosolization and direct contact, or vertically
Persistence of the hyaloid vasculature is a com- from dam to offspring.
mon spontaneous finding in both mice and
rats, typically visible on examination as a white
Guinea Pig
filamentous structure spanning the axial vitre-
ous. This finding is most common among Relative to its cranial dimensions, the guinea
weanling rodents, often regressing as animals pig possesses a large, open orbit. In compari-
age until it is negligible or no longer visible son to smaller rodents whose orbits are roughly
shortly after sexual maturity. ovoid in shape, the guinea pig orbit assumes a
Abnormalities of the fundus may be divided more spherical conformation. Like mice and
into congenital lesions, inherited retinal dys- rats, the guinea pig possesses intra-­ and
trophies, chorioretinal inflammatory lesions, extraorbital lacrimal glands, as well as a promi-
acquired retinal degenerations, and retinal nent Harderian gland. The primary lacrimal
detachments. Most congenital lesions of the gland of the guinea pig is intraorbital and
rodent fundus are either abnormalities of the resides in the lateral and anteroventral orbit.
retinal and hyaloid vasculature or coloboma- The presence of a large zygomatic salivary
tous defects of the retina or optic disc. gland has also been reported in guinea pigs,
Vascular anomalies such as preretinal loops occupying a large portion of the caudal and
have been reported in up to 12% of Sprague– superior orbit. However, some suggest that this
Dawley rats. Other vascular lesions include zygomatic gland is instead a portion of the
spontaneous saccular aneurysms of the retinal large Harderian gland. The guinea pig is also
vessels, observed sporadically in older mice one of few nonhuman species with a distin-
and rats. Nontransitional retinal folds consist- guishable Bowman’s layer in the anterior cor-
ent with retinal dysplasia have been described neal stroma and subtending the epithelial
and histologically characterized in adult rats basement membrane. The dynamics of the tear
from several strains, including the Sprague– film and ocular surface in the guinea pig
Dawley, RCS, Long–Evans, and Wistar-­derived appear to differ considerably from other ani-
WAG rats. Retinal degeneration is well charac- mals. The low blink rate in guinea pigs (2–5
terized in mice and rats, categorized as heredi- blinks/20 min) suggests the presence of an
tary, senile (age related), phototoxic, or inherently very stable tear film. The guinea pig
postinflammatory. In the mouse, there are fundus is clinically anangiotic, as it lacks a
numerous forms of hereditary retinal grossly identifiable retinal vasculature.
degeneration. Histologically, blood vessels are present within
Perhaps, the most well-­characterized form is the guinea pig optic disc; therefore, there is
one that commonly serves as a phenotypic controversy as to whether this species is anan-
model for human retinitis pigmentosa. The rd giotic or paurangiotic like equids. There is very
­Considerations for Ophthalmic Examinations in Laboratory Animal  721

little published work on ocular disease in this Eyelids and Conjunctiva


species; however, a survey of ocular disease in Eyelid abnormalities are sporadically reported
1000 apparently normal cavies reported 45% in guinea pigs. Blepharitis may be a manifesta-
had some ocular disorder, ranging from cata- tion of primary dermatophytosis, but may also
racts to heterotopic bone formation. develop secondary to the extension of general-
ized dermatologic disease or conjunctivitis.
Congenital/Developmental Anomalies Conjunctivitis is a common ophthalmic diag-
Congenital defects ranging from those as nosis in guinea pigs, observed in 3.4% of eyes
severe as clinical anophthalmos (Figure 17.3) in a survey of 1000 animals. Infectious con-
to posterior polar subcapsular cataracts are junctivitis is also reported in guinea pigs, most
seen in a significant proportion of guinea pigs, commonly in young animals. Chlamydia cav-
particularly those of roan × roan matings. iae is one of the most commonly implicated
Congenital cataracts have been reported in a bacterial organisms, resulting in a conjunctivi-
litter of guinea pigs also affected with urogeni- tis that is typically self-­limiting within three to
tal abnormalities after treatment of pregnant four weeks. Some animals have only slight red-
sows with the antibiotic tylosin. dening of the eyelid margins, whereas others
have thick purulent exudate. Infection in
Retrobulbar Disease young animals is characterized by inclusion
Space-­occupying orbital disease or exophthalmos bodies in conjunctival epithelial cells with leu-
has been reported in guinea pigs in association kocytic infiltrates. The disease is now recog-
with dental disease and/or retrobulbar abscess. nized to be associated with Chlamydophila
Primary retrobulbar neoplasia has not been psittaci. Other causative bacterial organisms
described in guinea pigs, but bilateral exophthal- include P. multocida, Listeria monocytogenes,
mos has been reported in association with ocular Bordetella bronchiseptica, Streptococcus spp.,
infiltration due to disseminated lymphoma. and both Salmonella and Shigella spp.
Bilateral exophthalmos has also been reported Conjunctival masses are common in guinea
in association with hyperadren­­­ocorticism. pigs. Smooth, benign conjunctival protrusions
typically in the inferior conjunctiva, known by
guinea pig breeders and enthusiasts as “fatty
eye,” were observed in 1.9% of eyes in the
aforementioned survey of 1000 animals. These
masses are composed of lipids, and may be
associated with diet and increased body condi-
tion. Prolapse of lacrimal tissue is the putative
cause of “flesh eye” or “pea eye,” a lesion
observed in 0.4% of eyes surveyed. This appears
as a small pink-­colored mass in the medial can-
thus (Figure 17.4) and is probably analogous to
prolapsed nictitating membrane in the dog or
rabbit although histopathological confirma-
tion of this has yet to be reported.

Cornea
In a large survey of 1000 animals, findings
attributed to ocular trauma were observed in
Figure 17.3 Clinical anophthalmos in a 25 eyes (1.25%), largely manifesting as corneal
guinea pig. lesions. In another investigation of 20 male
722 Exotic Animals: Ophthalmic Diseases and Surgery

and female guinea pigs (pigmented and non- Corneal lipidosis has been described in
pigmented American and Dunkin–Hartleys), guinea pigs and may be observed in association
fluorescein staining confirmed the presence of with conjunctival lipid deposits. Such lesions
punctate and linear superficial corneal ero- may also represent a bilateral condition with a
sions in both eyes of all animals examined, similar axial-­to-­paraxial distribution and a
despite the absence of clinical discomfort or clinical appearance similar to stromal lipid
overt corneal opacification on examination. dystrophies reported in dogs.
The authors of both of these studies propose
that the relatively high incidence of corneal Heterotopic Bone Formation
lesions in guinea pigs is likely due to environ- (Osseous Metaplasia)
mental trauma, particularly contact with hay Formation of bone in the ocular soft tissues is a
or straw bedding. unique but relatively common and well-­
characterized finding in guinea pigs, particu-
larly in older animals. Bony spicules
surrounded by a fibrous envelope form most
commonly in the ciliary body of guinea pigs
(Figure 17.5), but other anterior segment struc-
tures (e.g., iris base, iridocorneal angle, and/or
peripheral cornea) as well as extraocular sites
have also been reported. Lesions are clinically
visible when they extend anteriorly, commonly
appearing as well-­demarcated white lesions
originating at the limbus, and extending into
the adjacent cornea. Lesions involving only the
ciliary body or iridocorneal angle will not be
visible clinically, and may not produce any
clinical signs. One report identified an associa-
tion between osseous metaplasia of the iridoc-
Figure 17.4 A small pink-­colored mass (flesh eye)
in the medial canthus in guinea pigs may represent orneal angle and secondary glaucoma on
prolapsed lacrimal tissue. postmortem examination.

(a) (b)

Figure 17.5 Heterotopic bone formation (osseous metaplasia) in the ciliary body of guinea pigs as a focal
lesion (a) or a larger area (b).
­Considerations for Ophthalmic Examinations in Laboratory Animal  723

Cataracts ferret has a large retrobulbar venous sinus that


Cataracts are commonly seen in guinea pigs. has been suggested as a site for blood collec-
In the aforementioned survey of 1000 guinea tion. Given the ease of blood collection from
pigs, cataract was the most commonly observed the ventral tail vein or jugular in this species,
spontaneous ocular lesion on ophthalmic however, orbital blood collection cannot be
examination, identified in 16.9% of eyes. In recommended. The depth of the orbit in a fer-
another study, 18% of outbred animals were ret renders detection of an orbital space-­
affected with cataract. The vast majority were occupying lesion difficult until it has reached a
observed in older animals, often presenting as considerable size. A large, poorly encapsulated
an incipient or immature lens opacity (2.2% zygomatic salivary gland is located posteroin-
and 4.9% of eyes, respectively). Congenital cat- ferior in the orbit in the ferret, and head trauma
aracts were observed in 3.7% of eyes. Diabetic may result in a salivary mucocele with associ-
cataracts, some reaching maturity, have also ated exophthalmos.
been reported in guinea pigs. Inherited cata- Congenital ocular disease in ferrets is rela-
racts have been reported in the N13 strain of tively rare, although persistent hyaloid artery,
guinea pigs. Lens opacities in these latter ani- tunica vasculosa lentis, and hyperplastic pri-
mals are caused by a single splice-­site muta- mary vitreous occur. The eyelids of ferret kits
tion in the zeta-­crystallin gene. do not separate until about 20 days postpar-
tum; this late opening may account for the rel-
atively high prevalence of ophthalmia
Chinchilla neonatorum in this species. Conjunctivitis in
ferrets has been caused by human influenza
The scientific literature yields little informa-
virus, canine distemper virus, systemic myco-
tion regarding diseases of the chinchilla eye.
bacteriosis, and salmonellosis. Canine distem-
They are nocturnal and crepuscular animals
per in this species may cause photophobia and
with a vertical pupil that can close to a narrow
serous oculonasal discharge, which becomes
slit, protecting their scotopically adjusted ret-
mucopurulent with associated chemosis and
ina from bright light, which can render fun-
corneal ulceration. Canine distemper infection
doscopy somewhat difficult without mydriasis,
in ferrets is usually fatal, but with influenza,
and an anangiotic fundus with variable vascu-
the almost identical early signs often resolve.
larization of the optic disc. They have a shal-
Conjunctivitis may be a constant sign in sys-
low orbit, a rudimentary nictitating membrane,
temic mycoplasmosis.
a large cornea, and a densely pigmented iris in
Microphthalmos occurs in ferrets, and as
pigmented individuals. A significant problem
part of an autosomal dominant multiple ocular
in this species when kept in captivity is dental
anomaly syndrome with cataract and retinal
disease.
dysplasia. Cataracts have been reported several
times in ferrets. Lens luxations have been
reported in ferrets as primary lens dislocations
Ferret
and as secondary to chronic cataract. Ferrets
The ferret eye is adapted for dim light condi- have a holangiotic retina, with a reflective
tions; predation by ferrets occurs between tapetum in pigmented animals and possibly
dawn and dusk, and if in daytime, within the also in albinos. Anecdotally, retinal degenera-
scotopic conditions of rabbit warrens and prai- tion is believed to be common in the ferret,
rie dog burrows. Thus, the ferret retina is pre- with inherited atrophy and degeneration asso-
dominantly rod based, although like in the cat ciated with taurine deficiency in this obligate
there is a cone-­rich strip, the area centralis, carnivore suggested in review, but not reported
allowing a higher acuity to be achieved. The in the primary literature.
724 Exotic Animals: Ophthalmic Diseases and Surgery

Rabbits physiological pit and it enters the eye above the


optic axis, unlike in other domestic animals or
The majority of rabbits have moved from being
humans. The normal physiological appearance
a laboratory model to the third most popular
of the rabbit optic nerve head can complicate
pet in small animal practice in the United
clinical detection of pathological optic disc
Kingdom. Ocular disease in rabbits has a sig-
cupping associated with glaucoma.
nificant impact on the welfare of these animals
kept as pets, and several diseases, from dacryo-
Ocular Diseases in the Rabbit
cystitis to corneal ulceration, cataract, and
Since the 1940s, the laboratory rabbit was the
uveitis, are chronic and can be difficult
standard animal model for ophthalmic bio-
to manage.
chemistry, physiology, pharmacology, and toxi-
cology investigations (Table 17.3). Based on
Special Characteristics of the Rabbit Eye
those studies, investigations into other species,
The rabbit, as a prey animal, has laterally
including humans, were comparative and still
placed prominent eyes with a large ocular sur-
useful as reference studies to those today.
face relative to the size of the animal, giving a
Today, rabbits are used less frequently, as other
wide field of vision but also potentially an
avenues are available, and the number of the
exposed ocular surface prone to traumatic
damage or evaporative tear loss (Table 17.2).
The optic nerve is unusual with a deep normal Table 17.3 Ocular diseases in the rabbit.

Orbital diseases
Table 17.2 Important clinical characteristics Microphthalmos or anophthalmos
of the rabbit eye. Thymoma or thymic carcinoma
Retrobulbar abscesses
Laterally placed prominent eyes Adnexal diseases
Closed orbit with a large ocular surface relative to Blepharitis
the size of the animal
Infectious blepharitis
Wide field of vision orbit is closed
Entropion
Slow blink rate in the rabbit
Aberrant overgrowth of the conjunctiva
Large orbital vascular plexus
Conjunctivitis
Third eyelid moves passively, and has no muscles
Dacryocystitis
Orbital glands: the lacrimal, intraorbital, Harderian
(largest) Keratoconjunctivitis sicca
Tear drainage is through a single slit-­like lacrimal Nasolacrimal duct abnormalities
lower punctum Corneal diseases
Nasolacrimal duct is tortuous and diameter varies Corneal ulceration
along its course Lipid keratopathy
High incidence of tooth root disease Corneal epithelial dystrophy
Cornea is large for the size of eye 15 mm (diameter) Glaucoma
and radius of curvature approximately 7 m Hereditary glaucoma
Anterior chamber is deep at its center, but shallow Secondary glaucoma
at the periphery Uveitis
Iris may be darkly pigmented or devoid of pigment, Pasteurella multocida
depending on coat color
Protozoan E. cuniculi
Pupil almost circular but very slightly oval in the
vertical meridian Staphylococcus
Optic nerve head has deep normal physiological pit, Cataracts
and large lateral and medial myelinated nerve Congenital, primarily nuclear cataracts
fibers Unique to the rabbit caused by E. cuniculi
­Considerations for Ophthalmic Examinations in Laboratory Animal  725

different breeds of rabbits kept as pets proba-


bly exceeds this species currently maintained
for research. The indoor house rabbit is becom-
ing a more frequent pet because it can easily be
trained to use a litterbox and does not need to
be outside daily.

Orbital Diseases
Congenital/Developmental Anomalies
Congenital abnormalities of the globe such as
microphthalmos or anophthalmos are uncom-
mon in rabbits. A case of colobomatous micro-
phthalmos has been described in a New
Zealand white rabbit, suspected to be associ-
ated with vitamin E deficiency.
An important feature of rabbits, and one that
is vital to note during enucleation, is the ret- Figure 17.6 Exophthalmos is caused by
robulbar venous plexus. Perforation of the retrobulbar abscesses, usually originating from the
orbital venous plexus during globe removal tooth root.
can lead to significant blood loss with hemo-
stasis difficult to achieve by digital pressure. reported success with endoscopic curettage
Performing this surgery transconjunctivally after dental extraction Pasteurella is often asso-
rather than transpalpebrally, and remaining as ciated with retrobulbar abscessation in rabbits,
close as possible to the globe during dissection, and this condition is often linked to a tooth
obviates this problem in the vast majority of root abscess. Orbital exenteration is one option
cases. Another important condition arising in such cases, but the orbital venous plexus can
from this orbital venous plexus or sinus is that yield significant blood loss.
of periodic bilateral exophthalmos when the
animal is stroked or picked up. Here, the prob- Orbital Gland Diseases
lem is that venous return from the head is pre- Three orbital glands present in the rabbit (the
cluded by a mass around the jugular veins, lacrimal gland, nictitans gland, and superficial
most commonly a thymoma or thymic carci- and deep nictitans gland, also known as the
noma, which fills the orbital sinus and causes a Harderian gland) can become hyperplastic,
startling exophthalmos, which resolves when and all but the lacrimal gland can prolapse and
the stressful situation ceases. protrude from the orbit. These glands are very
Retrobulbar space-­occupying lesions that heavily vascularized. Diseases of these struc-
can cause exophthalmos can be neoplasms or tures include tear deficiency, gland protrusion,
parasitic cysts, although both of these are hyperplasia, and neoplasia.
much less common than a retrobulbar abscess.
Orbital neoplasia is rare, but lymphoma involv- Adnexal Disease
ing the Harderian gland has been reported. Blepharitis
Most cases of exophthalmos are caused by Blepharitis is rabbits is not an uncommon find-
retrobulbar abscesses, usually originating from ing. Traumatic origins are often suspected,
the tooth root retrobulbar abscesses, usually especially in group-­housed animals. Most non-
originating from the tooth root (Figure 17.6). traumatic instances are extensions of generally
These can be very difficult to manage, as can dermatitis or of keratoconjunctivitis or
any rabbit abscess, but some groups have dacryocystitis.
726 Exotic Animals: Ophthalmic Diseases and Surgery

While infectious blepharitis without concur- dysenteribiosis in rabbits and rodents, this
rent conjunctivitis and/or keratitis is uncom- treatment should be given with care and
mon in rabbits, blepharitis may be associated should be stopped if diarrhea is noted. Rabbit
with Treponema cuniculi infection, the agent poxvirus can also cause blepharitis, primarily
of rabbit syphilis (Figure 17.7) that is transmit- due to local extension of cutaneous disease.
ted to the neonates by the infected genital tract
of the mother. The definitive diagnosis is made Entropion
on the basis of identifying the spirochete on Entropion is relatively commonly seen in rab-
conjunctival cytology. Treatment is with three bits and can be corrected by the Hotz–Celsus
injections of penicillin G at 40000 IU/kg at surgical procedure. Often, the lid inversion
seven-­day intervals. Because prolonged β-­ leads to corneal ulceration with subsequent
lactam antibiotic therapy can cause fatal increased blepharospasm and worsening ocu-
lar surface trauma.

Conjunctival Overgrowth
An unusual and apparently unique abnormal-
ity in rabbits is an aberrant overgrowth of the
conjunctiva, producing a type of ankyloblepha-
ron involving the conjunctiva covering of the
ocular surface. Also referred to as precorneal
membranous occlusion, conjunctival centripe-
talization, epicorneal membrane, or pseudop-
terygium, the condition is benign and
idiopathic and has a classic appearance of an
annulus of conjunctiva growing over the cor-
nea from the limbus. This may be a narrow
Figure 17.7 Infectious blepharitis without
concurrent conjunctivitis and/or keratitis may be
band or a sizable ring of tissue with only a
associated with T. cuniculi infection, the agent of small aperture centrally (Figure 17.8). The
rabbit syphilis.

(a) (b)

Figure 17.8 Annulus of conjunctiva growing over the cornea from the limbus. This may be a narrow band
(a) or a sizable ring (b) of tissue with only a small aperture centrally.
­Considerations for Ophthalmic Examinations in Laboratory Animal  727

conjunctival growth is not adherent to the particularly unilateral conjunctivitis, is a com-


underlying cornea and is not associated with mon manifestation of underlying dental
conjunctivitis or preexisting structural con- disease.
junctival abnormalities. Dwarf rabbits are
overrepresented. Resection of this tissue Keratoconjunctivitis Sicca
merely leads to its regrowth, but surgical tech- Clinical keratoconjunctivitis sicca is seen
niques to transect and reposition the over- rarely in rabbits, but the species is used as a
growth into the conjunctival fornix have met model for human dry eye and there is exten-
with improved success. sive literature on the pathology and treatment
of aqueous tear deficiency in these animals.
Conjunctivitis Cyclosporine increases tear production in rab-
Conjunctivitis is seen commonly in pet rabbits bits with such autoimmune lacrimal adenitis.
and has several causes. In rabbits, it is impor- Rabbits treated with oral trimethoprim–
tant to distinguish conjunctivitis from dacryo- sulfamethoxazole twice daily at a dose of
cystitis. Purulent ocular discharge with 40 mg/kg had significant reductions in
conjunctival hyperemia often accompanies not Schirmer tear test (STT) readings.
only conjunctivitis, but also nasolacrimal duct
and lacrimal sac infections (Figure 17.9). The Nasolacrimal Duct Abnormalities
diagnosis of infectious conjunctivitis and Perhaps, the most common and one of the
dacryocystitis must be approached with appre- most frustrating ocular conditions in the rabbit
ciation of the normal bacterial flora of the con- is dacryocystitis (see Figure 17.9). While
junctival sac. Pasteurella spp. are considered by mostly present with a purulent ocular dis-
many to be the most common bacterial patho- charge, other rabbits can have a swollen medial
gen in the rabbit, but it is also important to canthal area or medial canthal dermatitis that
consider S. aureus. In a more recent survey of can be severe. In one study, the most common
conjunctival flora in rabbits with conjunctivitis initial treatment was topical antibiotic, but
and dacryocystitis, Staphylococcus spp. (78% of flushing of the nasolacrimal duct was per-
swabs) and not Pasteurella (12%) were not the formed in 87% of the rabbits; 80% of animals
most commonly isolated species. Conjunctival had dental treatment.
disease in the rabbit can be caused by viral as As already mentioned, the rabbit is unusual
well as bacterial agents. In rabbits, it is impor- in having only one lacrimal punctum (lower),
tant to remember that conjunctivitis, with a nasolacrimal duct that follows a tortu-
ous route through the lacrimal and maxillary
bones. Malocclusion of the molar arcades in
particular results in retropulsion of the tooth
into the weakened maxillary bone, with subse-
quent nasolacrimal occlusion; incisor maloc-
clusion may perhaps more commonly produce
this same result.
Treatment of dacryocystitis in the rabbit is
by cannulation of the single lacrimal punctum
and flushing of the duct. The copious dis-
charge needs to be flushed out, and this should
be done regularly until the condition resolves.
If cannulation from the lacrimal punctum is
Figure 17.9 Rabbit with dacryocystitis with lid difficult, cannulation of the duct opening at
swelling and purulent exudate. the nasal meatus is possible, but the small
728 Exotic Animals: Ophthalmic Diseases and Surgery

diameter of the duct at its nasal end renders Some corneal lesions may be associated with
this procedure difficult. secondary vascularization.
Corneal epithelial dystrophy in the rabbit
Corneal Disease has been reported as a peripheral lesion histo-
The most serious corneal condition in rabbits pathologically characterized by areas of epi-
is corneal ulceration. Rabbits have particularly thelial thinning adjacent to areas of epithelial
protuberant eyes with a large exposed ocular cell hyperplasia. Another report described a
surface relative to their body mass. Every post- plaque-­like paracentral granular stippling in
traumatic corneal ulcer, such as this linear ero- American Dutch Belted rabbits, which was
sion (Figure 17.10), should thus heal in under characterized histopathologically by an irregu-
one week. Treatment is similar to that in larly thickened epithelial basement membrane
affected dogs. After topical anesthetic adminis- similar to that seen in epithelial basement
tration, a sterile cotton bud or bacteriology membrane dystrophy or Reis–Buckler’s dystro-
swab is used to debride the nonadherent epi- phy in humans.
thelium at the edge of the ulcer. Diamond burr
debridement or a grid keratotomy are useful to Glaucoma
facilitate and encourage healing, but use con- Hereditary glaucoma in the New Zealand
siderable caution because the rabbit cornea is white rabbit has been studied extensively
substantially thinner than that in the dog. since the early 1960s (Figure 17.11), but also
Protection for the healing ulcer is also impor- occurs in pigmented breeds. The inheritance
tant (shield contact lenses). pattern is putatively autosomal recessive with
Lipid keratopathy has been documented in incomplete penetrance. Neonatal bu/bu
rabbits fed a cholesterol-­rich diet, and is seen homozygotes have normal IOP (15–23 mmHg),
in Watanabes with heritable hyperlipidemia. It but after one to three months of age IOP rises
has also been documented in rabbits fed a 10% to between 26 and 48 mmHg. Clinical signs
fish meal maintenance diet, and in one pet rab- are typically subtle, often limited to observa-
bit fed a predominantly milk-­based diet. tion of buphthalmos and corneal edema.
Clinical appearance is variable, with some Exposure secondary to buphthalmos may also
lesions appearing faint and translucent, and result in keratitis and/or corneal ulceration.
others more opaque and even slightly raised. In chronic cases, eventual atrophy of the

Figure 17.11 Hereditary glaucoma in the New


Zealand white rabbit has been studied extensively
since the early 1960s. Clinical signs include
Figure 17.10 Nonhealing corneal ulcer with buphthalmia, mild corneal edema, and
devitalizes nonadherent epithelial edge. dilated pupil.
­Considerations for Ophthalmic Examinations in Laboratory Animal  729

ciliary body may result in normalization of treatment is lens removal by phacoemulsifica-


IOP, though most affected eyes remain tion with concurrent topical anti-­inflammatory
buphthalmic. Histopathological features have medication. The rabbit has a significant postop-
shown goniodysgenesis involving the pecti- erative capsule fibrosis response.
nate ligaments and trabecular meshwork in Not all anterior uveitis is lens induced.
affected eyes. Vision is lost at this stage, but Pasteurella spp.-­associated cases may be
the eyes do not appear painful, probably encountered with a more classic uveitis char-
because of the increase in size of the globe acterized by episcleral congestion, miosis, and
accompanying the raised pressure. Treatment hypopyon. Some Pasteurella spp. or
with topical carbonic anhydrase inhibitors Staphylococcus-­associated iridal inflammation
such as dorzolamide three times daily reduces is difficult to differentiate from lens-­induced
the IOP but appears to make no difference to inflammatory disease; in other cases, the yel-
behavior of the affected animal. The bu gene low purulent material in the anterior chamber
is a recessive trait that is also semilethal, with is characteristic of a more obvious bacterial
heterozygotes giving birth to small litters of infection.
unthrifty kits.
Cataracts
Uveitis Congenital, primarily nuclear cataracts and
For many years, inflammatory lesions with vas- PPMs have been documented in rabbits.
cularization in the rabbit iris were ascribed to Nuclear sclerosis, the aging change in which
infection by P. multocida, which produces the continually growing cortex compresses the
white, purulent abscesses in other locations in lens nucleus, occurs in rabbits with an average
this species. Recent findings are strongly sug- age of 6.0 years. Many of these cataracts are
gestive that many of these lesions are caused by small opacities with little effect on vision,
lens-­induced uveitis (Figure 17.12), which whereas some may be much more rapidly
occurs secondary to lens capsular rupture maturing and hence blinding.
caused by intralenticular infection by the proto- One form of cataract unique to the rabbit is
zoan Encephalitozoon cuniculi. Because of the that caused by E. cuniculi (Figure 17.13). This
lens-­induced nature of this inflammation, remarkable obligate intracellular microsporid-
ian generally infects rabbits through ingestion
of contaminated urine and may cause renal or
neurological symptoms. If the organism
migrates to the developing lens, it may lie dor-
mant for many months, before moving through
the lens, causing cataract and then erupting
through the anterior lens capsule to liberate
lens material into the anterior chamber that
elicits lens-­induced uveitis.
Phacoemulsification is the method of choice
to remove a cataractous lens. However, the rab-
bit as a species has an unusual propensity to
reform lens fibers after removal surgically.
When intraocular lens implants have been
used, these have sometimes been forced out of
the lens capsule by the regrowth of lens tissue.
Figure 17.12 Uveitis in rabbits occurs secondary
to lens capsular rupture and intralenticular Careful removal of all lens fibers from the lens
infection by the protozoan E. cuniculi. capsule reduces this risk.
730 Exotic Animals: Ophthalmic Diseases and Surgery

(a) (b)

Figure 17.13 (a) Sudden-onset progressive cataract in Netherland dwarf rabbit, and (b) Mature cataract in
a 7-year-old diabetic rabbit.

Diseases of the Fundus


The fundus of the rabbit is merangiotic with a
band of blood vessels and myelinated nerve
fibers traversing the retina in a horizontal
plane from the optic disc (Figure 17.14a and b).
Few reports of retinal disease in rabbits exist.
The large physiological cup of the rabbit optic
nerve head is often misdiagnosed as an optic
nerve coloboma. Spontaneous disease of the
retina and posterior segment is rare in labora-
tory rabbits. In one large survey, the only spon-
taneous finding involving the posterior
segment was choroidal hypoplasia, a typically
(a)
bilateral lesion affecting 1.2% of examined
animals.

Surgery – Enucleation
The orbital sinus or retrobulbar venous plexus
is most important to be aware of when per-
forming an enucleation. A transpalpebral
approach runs the risk of entering this sinus
with the potentially severe side effect of blood
loss. The transconjunctival technique, gener- (b)
ally preferred in all species by most ophthal-
mologists yet little used by many general Figure 17.14 (a) Albino rabbit and (b) pigmented
rabbit. Fundus of the rabbit is merangiotic with a
veterinary surgeons, enables one to remove
band of blood vessels and myelinated nerve fibers
only the globe and not exenterate the orbit and traversing the retina in a horizontal plane from the
its contents, including the orbital sinus. optic disc.
­Nonhuman Primate  731

Miniature Pig A clinical syndrome of cutaneous malignant


melanomas and associated uveitis has been
The miniature pig (minipig) is increasingly
reported in up to 54% of miniature Sinclair pigs
being used as an animal model in vision sci-
at birth, affecting up to 85% of animals by one
ence and toxicological investigations. This is
year of age. The associated tumors may affect
partially attributable to anatomical and biomet-
the eyelids and periocular skin, may be associ-
ric similarities between features of the porcine
ated with localized cutaneous depigmentation,
eye and the human eye. Minipigs are approxi-
and spontaneously regress.
mately 25% of the size of a regular domestic pig.
Spontaneous lens opacities have been
The Göttingen and Yucatan are the most com-
described in both Yucatan and Göttingen mini-
monly cited breeds in ocular investigations.
pigs. Punctate posterior cortical lens opacities
Others that may be cited include the Hanford,
have been observed in both juveniles and
Sinclair, Ossabaw Island hog, Vietnamese Pot-­
adults of both breeds. Other opacities involv-
bellied pig, and the Chinese Bama minipig.
ing the nucleus and posterior capsule have
Domestic and miniature pigs both have deep
been described in both breeds.
open orbits, with globes that are relatively deep
set, particularly in the Yucatan. The pig has a
Posterior Segment
Harderian gland located within the ventrome-
Incidental abnormalities involving the vitreous
dial orbit, posterior to the globe. An orbital
are common in minipigs. In one study, hyaloid
venous sinus has also been identified in the
remnants were observed in 82.1% of Yucatans,
porcine orbit and, as for the rodent, was for-
in some persisting through 33 months of age
merly used as a site for venous blood collection.
and over. In Göttingens, hyaloid remnants were
observed in 83.3% and 70.4% of juveniles and
Congenital/Developmental Anomalies adults, respectively. Hyaloid remnants may
Microphthalmos (and less commonly anoph- vary in clinical appearance, forming either a
thalmos) with or without retinal dysplasia and linear structure spanning the vitreous from the
other ocular anomalies has been described in optic disc to the posterior lens capsule or a frag-
young piglets in association with maternal ment of the original structure, observed free-­
hypovitaminosis A. While rare, polycoria and floating or in close association with the
suspected anterior uveal colobomas have been posterior lens capsule.
described in pigs, and colobomatous lesions Lesions involving the optic disc are uncom-
involving the optic disc and choroid have been mon in minipigs. Bilateral optic nerve hypo-
described specifically in minipigs. plasia has been described in purpose-­bred
piglets, and has been clinically coupled to
Adnexa and Anterior Segment efferent pupillary light reflex (PLR) deficits,
Entropion is commonly diagnosed in minipig though a definitive etiology has not been
breeds such as the Vietnamese Pot-­bellied pig, reported.
related to robust subcutaneous periocular and
forehead fat. In some cases, the conformational
entropion may be severe enough to impair ­Nonhuman Primates
vision. While this condition is not common in
other minipig breeds, it has been reported in The NHP remains a widely used species in
the Göttingen. Primary conjunctivitis is uncom- ocular drug and device development in North
mon in purpose-­bred minipigs, but a transient, America, believed by many to be the most
self-­limiting blepharoconjunctivitis has been translatable model for evaluating the efficacy,
described in young (six-­ to eight-­week-­old) safety, and tolerability of ocular drugs and
Göttingens. devices. The most commonly used NHP
732 Exotic Animals: Ophthalmic Diseases and Surgery

species in preclinical eye research are Old eventually discontinued as the model (elevated
World NHPs (parvorder Catarrhini) such as IOP and optic nerve degeneration) could not
the cynomolgus macaque (“crab-­eating be validated in multiple generations.
macaque”; Macaca fascicularis) and the rhesus Secondary glaucoma is uncommonly
macaque (Macaca mulatta). Others used less reported in NHPs but, as in other species and
commonly include the African green monkey in humans, antecedent inflammatory intraoc-
(Chlorocebus sabaeus) and the common mar- ular disease may predispose any animal to
moset (Callithrix jacchus), a New World mon- impaired aqueous outflow. Endogenous uveitis
key (parvorder Platyrrhini). is uncommon in purpose-­bred macaques, but
zoonotic transmission of Mycobacterium tuber-
culosis from handlers or other vivarium
Adnexal and Ocular Surface Disease
employees to captive NHPs may occur.
Blepharitis and conjunctivitis are reported
with relative frequency in NHPs. In one survey
Posterior Segment Disease
conducted in a large primate research facility,
blepharitis and conjunctivitis accounted for Lesions involving the posterior segment are
29% and 21% of observed ophthalmic abnor- more common than those of the anterior seg-
malities, respectively. Primary infectious ment in NHPs. Incidental chorioretinal scars
blepharitis, however, is not commonly cited are commonly observed. Other lesions
and is more likely to be observed secondary to described in the posterior segment of NHPs
extension of primary infectious conjunctivitis include lipemia retinalis in cynomolgus mon-
(see later) or due to trauma. keys, and choroidal and optic nerve colobo-
Primary infectious conjunctivitis may be mas. Central retinal arterial occlusion, a
observed in captive NHPs. Viral infection with common and vision-­threatening condition in
herpesvirus simiae B, an endemic alpha her- human patients, has also been described in a
pesvirus of macaques, may cause mild con- primate. Peripheral cystoid retinal degenera-
junctivitis. Examiners and handlers must be tion and pars plana cysts may be observed in
acutely aware of possible manifestations, since older animals. In rhesus and cynomolgus
zoonotic transmission of this virus to humans macaques, a spontaneous form of age-­related
via aerosolization, mucous membrane expo- macular degeneration (AMD) analogous to
sure, or wound exposure can risk causing a human early to intermediate dry AMD has
fatal encephalitis in humans. Corneal disease been described and investigated.
is occasionally observed in captive NHPs. In
one large survey of captive macaques, corneal
ulcerations were diagnosed in 2.9% of animals ­Exotic Animals
with ocular lesions. Trauma is the presumed
origin in most instances of corneal lesions With public interest in natural history, conser-
in NHPs. vation, and ecology increasing, the demand for
competent diagnosis and treatment of the
medical disorders of captive nondomestic ani-
Anterior Segment Disease
mals presents an opportunity for veterinary
Glaucoma is uncommon in purpose-­bred profession. Once primarily concerned with
NHPs. However, a potential naturally occur- preventative medicine, nondomestic animal
ring primary glaucoma was described in a now medicine has evolved to incorporate the
well-­characterized colony of adult rhesus sophisticated treatments commonly available
macaques from Cayo Santiago, an island off for conventional pet and companion animal
the coast of Puerto Rico. The investigation was species. The challenges that fish, amphibians,
­Fis  733

reptiles, birds, and wild mammals present for the posterior pole of the globe. Extraocular
diagnosis and treatment are potentially daunt- muscles are present and variably developed,
ing. An overview of the involved species and allowing independent ocular movement,
selected ophthalmic diseases follows. although targeting is usually affected by posi-
tioning of the body. The typical globe shape is a
flattened ellipse with a short anteroposterior
Considerations for Ophthalmic Examination
axis because of corneal flattening, but some
in Exotic Animals
deep-­sea dwelling teleosts have tubular-­shaped
A surprisingly complete ocular examination globes and a few cave-­dwelling or bottom-­
may be performed in many species, especially dwelling species have vestigial blind eyes.
those with a reasonably large eye size. External Having the same refractive index as water, the
and anterior segment examination may be cornea serves no refractive function in water.
facilitated by magnification provided by a slit-­ Corneal anatomy in most fish follows the mam-
lamp biomicroscope, head loupe, or indirect malian pattern, except that it is relatively
condensing lens, used with bright illumination thicker and the epithelium is the layer primar-
in the (at least momentarily) immobilized ily responsible for maintaining corneal hydra-
patient. Posterior segment examination is pos- tion (Figure 17.15). Some fish have a
sible in many species with direct or indirect double-­layered corneal epithelium with a
ophthalmoscopy, or both, even without mydri- potential space in between. Corneal thickness
asis (which is often difficult or impossible to is generally greater in freshwater than in
achieve). Indirect condensing lenses in the marine fish. The function of corneal irides-
28–60-­D range facilitate panoramic fundus cence and pigmentation in some species
examination in small eyes and through appears to be to shade the globe and reduce
small pupils. glare. At its periphery, the corneal endothelium
thickens to form the annular ligament, which
fills the iridocorneal angle as it reflects onto the
­Fish anterior peripheral iris. Anteriorly, the sclera
contains a circumferential ring of cartilage,
Fish are often kept as pets, and very large fish variably supplemented by scleral ossicles.
raising farms are scattered throughout the Many teleosts have a lipid or guanine tape-
world. Most modern fish belong to the class of tum lucidum in the retinal pigment epithelium
teleosts (bony fishes); the others are elasmo- and many larval forms (but fewer adult fish)
branchs (cartilaginous fish). A detailed anat- possess an outer choroidal argentea consisting
omy section follows and demonstrates the of guanine-­containing cells in the choroid that
similarities for the ophthalmic morphology continues over the anterior iris, contributing
among all species. with the iris pigments to the color and irides-
cence of the iris. Most teleosts have an occlusi-
ble tapetum. The choroidal gland is a
Ocular Anatomy
well-­developed vascular plexus present within
Most fish lack eyelids (except for elasmo- the choroid of many species at the posterior
branchs). The presence of a membrane cover- pole, where it wraps around the optic nerve
ing the cornea or folds of tissue around the eyes and communicates with an accessory gill
is common. In teleosts, the orbit is bony and (pseudobranch). Its functions presumably
enclosed; some species have a tenacular liga- include nutrition and local temperature
ment that anchors the globe to the orbit. regulation.
Elasmobranchs possess an optic pedicle, a car- Adult elasmobranchs possess an entirely
tilaginous process connecting the cranium to avascular retina; it depends completely on the
734 Exotic Animals: Ophthalmic Diseases and Surgery

Choroid
Tensor chorioidae Scleral cartilage

Conjunctiva

Ora Choroidal
Annular gland
ligament Suspensory
ligament

Retina Argentea
Cornea
of choroid

Lens Vitreal
vessels Sclera

Optic nerve

Falciform process
Retractor lentis

Epichorioidal lymph space

Figure 17.15 Anatomy of the fish eye.

choriocapillaris for its nutrition and there is no and a dorsal suspensory ligament; it consists of
accessory vascular organ (choroid gland). The a hyaline lens capsule surrounding the lens
choriocapillaris is supplied by one major artery epithelium, cortex, and nucleus. The anterior
and is drained by a dorsal and ventral vein. surface nearly touches the corneal endothe-
Teleosts possess either a falciform process or a lium, forming a very narrow anterior chamber.
membrane, the tunica vasculosa retinae. The The fish lens has the highest refractive index
falciform process is an infolding of choroid of all vertebrates (~1.69 D), and the refractive
through the fetal fissure into the vitreous. The index gradients within it essentially eliminate
tunica vasculosa retinae is derived from a chromatic and spherical aberration in the
branch of the internal ophthalmic artery that image presented to the retina. A posterior mus-
enters the eye near the optic disc; it lies in the cle, the retractor lentis, is present in teleosts; it
vitreous in front of the retina. arises ventrally from the falciform process of
The ciliary body, when present, is rudimen- the retina and inserts anterior to the lens equa-
tary. Ciliary processes are absent. Complete tor on the ventral lens capsule. The suspensory
separation of aqueous and vitreous is not pre- ligament/retractor mechanism allows the lens
sent and the mechanisms of aqueous produc- position within the pupil to be changed, as well
tion and loss are poorly understood. The pupil as alteration of the lens–retina distance. There
is generally round or pear-­shaped; the iris is is an anterior aphakic crescent in the pupil,
thin and, with few exceptions, immobile. The which aligns with a far temporal fovea; this
sphincter and dilator muscles are rudimentary facilitates binocular vision when the fish tar-
or absent, except in elasmobranchs. The very gets objects in front of it by tilting the eyes for-
large spherical lens is supported by the zonule ward, allowing light to obliquely pass through
­Fis  735

the lens and stimulate the fovea. Predatory fish examination using indirect ophthalmoscopy
in general have well-­developed accommoda- and a 60-­D condensing lens.
tion, whereas bottom feeders have little or no
accommodative range. An anterior muscle, the
Ocular Diseases
protractor lentis, is present in some
elasmobranchs. The ocular disorders of fish result from infec-
Anatomical variation in retinal structure tious diseases, nutritional deficiencies, trauma,
and photoreceptor type and morphology exists. metabolic disorders, degenerations, neoplasia,
Both rods and cones are typically present; diur- and teratogenic and spontaneous malforma-
nal species have cone-­dominated retinas, and tions. Infectious agents include parasites, bacte-
deep-­sea and nocturnal species have rod-­ ria, fungi, and viruses. Parasites include ciliated
dominated retinas, with gradations dictated by protozoans (Ichthyophthirius, Cryptocaryon,
species’ visual ecology. Twin and double cones Tetrahymena), myxosporidians (the prolifera-
and oil droplets may be present. A fovea is pre- tive kidney disease agent; Myxosoma heteros-
sent. The optic nerve enters the eye via one or pora, Henneguya, Myxobilatus, Sphaerospora,
more optic discs near the posterior border of Myxobolus), trematodes (Diplostomum spp. and
the falciform process, where present. As related genera), crustaceans (copepods, Lernaea
described earlier, two protective mechanisms spp., Argulus spp.), cestodes (Gilquinia squali),
have evolved to shield photoreceptors from and microsporidia (Glugea).
excessive light promoted by the immobile A broad spectrum of pathogenic bacteria
pupil and lack of eyelids (retinomotor infects both marine and freshwater fish.
responses). Photoreceptors may contract or Bacterial septicemia commonly results in
elongate between pigmented processes of pig- intraocular involvement. Infections with
ment epithelial cells or alternatively pigment S. aureus, group B streptococci, Aeromonas,
may migrate along the apical processes of pig- Pseudomonas, and Vibrio are documented.
ment epithelium. Viral infections with endothelial tropism (e.g.,
rhabdoviruses) may cause uveitis. At least three
epizootic salmonid virus diseases (infectious
Examination Techniques
pancreatic necrosis, infectious hematopoietic
Ocular examination of fish in water is of necrosis, and viral hemorrhagic septicemia)
necessity limited to gross observation. Close have exophthalmos as a characteristic sign.
examination is facilitated by aerial examina- Nutritional ocular disorders have been
tion, often under anesthesia. Buffered tricaine extensively described in salmonids (commer-
methane sulfonate (Finquel MS-­222; Argent, cially farmed) and recently in red drum and
Redmond, WA) delivered at 50–200 mg/l, channel catfish. Deficiencies of riboflavin, thi-
depending on the species, in tank water is amine, vitamin A, methionine and cysteine,
usually satisfactory. Gross examination of the tryptophan, and zinc produce cataract. Excess
external eye and anterior segment may be calcium and phosphorus fed to juvenile
performed with a focal light source and mag- Chinook salmon produced cataract.
nification or by slit-­lamp biomicroscopy. Thioacetamide fed to rainbow trout produced
Sample collection for culture and cytology of blinding cataract characterized by massive
the cornea and lid folds may be done as for proliferation of lens epithelium.
other vertebrates, as can fluorescein staining Traumatic injury has been implicated as a
to demonstrate corneal ulceration. cause of corneal ulceration, remodeling, and
Applanation tonometry may be performed scarring in fish. Corneal ulceration caused by
only in species with larger eyes. Fundus transport, aggression, and handling is com-
examination may be possible by aerial mon. Corneal infection by the parasitic
736 Exotic Animals: Ophthalmic Diseases and Surgery

copepod Ommatokoita elongata in Greenland eyes of larval amphibians resemble teleost


sharks (Somniosus microcephalus) has been fishes. Those of urodeles (tailed amphibians)
recorded. Corneal lipid deposition was are poorly developed compared to anurans. The
described in individual captive moray eels of eyes of larval anurans (frogs and toads) have
three species associated with hyperlipidemia. poorly developed eyelids; in adults, the upper
Degeneration of the lens and retina in fish lid is immobile and, associated with the lower
occurs for some of the same reasons as in lid, a false nictitating membrane is formed by an
mammals and is associated with a few unusual elastic translucent fold of conjunctiva in the
circumstances. Possibly inherited cataract was lower fornix. When the globe is retracted, it pas-
reported in aquarium-­raised tilapia. Excessive sively covers the eye; this retraction facilitates
exposure to sunlight was postulated to cause swallowing because the globe depresses the thin
cataract in hatchery-­reared lake trout. Retinal membrane separating the orbit and pharynx,
degeneration suspected to be phototoxic in ori- forcing food down the throat. There is no orbital
gin was reported in wild-­caught Atlantic men- septum separating the two orbits. Superior eye-
haden (Brevoortia tyrannus) after four weeks lid glands and a Harderian gland are present.
of captivity in an indoor open culture system. The puncta and nasolacrimal duct are present.
The retractor bulbi is the most important
extraocular muscle, which retracts the globe
Amphibians and aids in swallowing. The globe is spherical
with hyaline cartilage in the inner sclera from
Ocular Anatomy the posterior pole as far as the equator. Other
The anatomy of amphibian eyes (Figure 17.16) anurans lack cartilage or have a ring of bones
varies with order (anuran versus urodele) and within the sclera. Urodeles lack scleral cartilage.
stage of development (larval versus adult). The The adult cornea has the mammalian pattern,

Scleral cartilage

Pupillary nodule
Choroid

Cornea
Retina

Optic nerve
Lens

Zonule Membrana
vasculosa retinae
Protractor
lentis muscle

Ciliary Sclera
venous sinus

Hyloid vein
Tensor choroideae

Figure 17.16 Anatomy of the amphibian eye.


Amphibians  737

but larval anurans have a duplex cornea with a and panophthalmitis have been noted in both
dermal portion separated from the sclera. A tri- natural and experimental infections of leopard
angular ciliary body is present with hypertro- frogs (Rana pipiens) with Flavobacterium
phied folds dorsally and ventrally that extend to indologenes. Severe panophthalmitis and otitis
the pupillary border to form pupillary nodules. interna were reported in a large group of
Two protractor lentis muscles arise from the recently imported fire-­bellied toads (Bombina
peripheral cornea to insert on the ciliary folds; orientalis). Corneal stromal infiltrates, scleri-
contraction causes zonular tension, which tis, hyphema, hypopyon, iridocyclitis, cataract,
moves the lens forward to effect accommoda- and chorioretinitis were prominent.
tion for distance vision. The lens in tadpoles is Opisthotonos, circling, head tilt, and loss of
spherical and near the cornea; in adult frogs, it righting reflexes were associated with otitis
is somewhat flattened and positioned more pos- interna. Several bacteria were cultured from
teriorly, leaving a visible anterior chamber. The affected eyes and normal viscera, including
urodele lens is large and the anterior chamber is Aeromonas hydrophila, Citrobacter freundii,
shallow. Urodeles lack ciliary folds and the dor- Providencia alcalifaciens, Klebsiella oxytoca,
sal protractor lentis muscle. The aqueous is and an unidentified oxidase-­positive, Gram-­
drained through an iridocorneal angle into the negative bacillus resistant to tetracycline.
dorsal and ventral ciliary sinuses. The iris is thin Corneal opacities in amphibians have sev-
and often highly colored by various stromal pig- eral potential causes. The most extensively
ments; a metallic sheen is associated with the reported and investigated disorder is lipid kera-
presence of guanine crystals. Myoepithelial topathy. Originally discovered in Cuban tree
sphincter and dilator muscles are present. Iridal frogs (Osteopilus septentrionalis), it has since
arteries have an irregular pattern and commu- been identified in species of captive hylid, lep-
nicate with deeper veins. Pupillary excursions todactylid, and ranid frogs either as a corneal
are present but limited. Resting pupil size and and hepatic lesion or as part of a generalized
shape are remarkably variable, but it is spheri- xanthomatosis affecting the brain, some vis-
cal when dilated. The avascular retina derives cera, peripheral nerves, periarticular soft tis-
its blood supply from the vascular choroid alone sues, and digital pads. Hypercholesterolemia
in urodeles, and from both the choroid and a has been noted in animals with disseminated
membrana vasculosa retinae in the vitreous on xanthomatosis. Clinically, dense white stromal
the retinal surface in anurans. The choroid con- opacities are seen, which are often raised with
tains a choriocapillaris, but no tapetum, corneal thickening and surface epithelial irreg-
although cells may contain guanine crystals or ularity (Figure 17.17). In advanced cases, the
carotenoid pigments. The optic disc is circular densest opacities are in the central cornea.
or elongated. The retina contains at least four Histologically, empty cholesterol clefts within
types of photoreceptor types based on visual keratocytes and between corneal collagen
pigments in the rods and cones. Oil droplets are lamellae are present with occasional foamy
present at the distal end of the ellipsoid of some macrophages in the stroma and between epi-
cones. Anuran photoreceptors have been the thelial cells.
subject of extensive research involving photo- Buphthalmos with glaucoma was found in a
chemistry, renewal, and electrophysiology. captive toad (Bufo bufo). Globe enlargement
prevented complete globe retraction into the
Ocular Diseases orbit, which interfered with swallowing.
Reports of spontaneous ocular diseases of Because of concerns about swallowing difficul-
amphibians are scarce. Mycobacterial panoph- ties after enucleation, globe protection was
thalmitis was reported in a South American achieved alternatively by suturing the false
bullfrog (Leptodactylus spp.). Corneal edema nictitating membrane across the cornea.
738 Exotic Animals: Ophthalmic Diseases and Surgery

Cataracts have been noted regularly by some developed from fused eyelids and separated
observers, occurring both in conjunction with from the cornea by an epithelial-­lined subspec-
other ocular disorders of the anterior segment tacular space. This tertiary spectacle contains
and alone. Phacoemulsification was success- an extensive vascular network, which is opti-
fully performed in amphibians. Dendrobatid cally transparent but demonstrable by micro-
frogs receiving 5% dextrose supportive therapy silicone injection. The anterior layers of the
rapidly develop reversible cataract. spectacle are shed during normal ecdysis with
the rest of the skin. Prior to ecdysis, the specta-
cle becomes cloudy due to thickening and
Reptiles breakdown of skin layers, with accumulation
of fluid between the new surface layer of the
Ocular Anatomy spectacle and the old. The spectacle is trans-
Four of the five orders within the class Reptilia parent immediately before its surface is shed.
have anatomically similar eyes: lizards, chelo- During the period the spectacle is cloudy, the
nians, crocodilians, and the tuatara. The fifth animal is blind; many species become more
order, snakes, lost the prototype reptilian ana- irritable and aggressive during this period. The
tomical pattern during a fossorial period in spectacle is impervious to topically applied
their evolution, only to re-­evolve eyes with cer- medications; thus, topical ocular therapy is
tain differences from other reptiles. Features of ineffective. The biometry of the eyes and spec-
the external eye and adnexa have great clinical tacles of four species of snakes has been
significance. In most reptiles, except snakes recently described using high-­frequency ultra-
and certain ablepharine skinks, the upper and sound imaging. The ocular surface in reptiles
lower eyelids are well developed, the lower is bathed by fluids secreted by lacrimal (except
being the more mobile. Crocodilians possess a snakes) and Harderian glands. The latter are
bony tarsus in the upper lid. The eyelids of large in chelonians, especially in marine spe-
chameleons are constricted around the cornea cies; the lacrimal gland functions as an extrare-
and move with the very mobile globe. In some nal site of salt excretion. The nasolacrimal
lizards of the families Lacertidae, Scincidae, duct, absent in chelonians, drains from the
and Teidae, the lower lid is variably transpar- medial canthus to the roof of the mouth to
ent. Snakes and ablepharine geckos and skinks emerge at the base of or behind the vomerona-
possess a spectacle covering the cornea, sal organ. The detailed anatomy of the head of
Boa constrictor has been recently described
using conventional radiography computed
tomography and dissection.
Anatomical features of the globe that distin-
guish reptiles include poorly developed rectus
muscles (except in lizards), well-­developed
retractor bulbi muscle (except in snakes), and
limited rotational movements (except in cha-
meleons) (Figure 17.18). Hyaline cartilage is
present in the sclera of lizards and chelonians
from the equator to the posterior pole, with
scleral ossicles extending to the limbus anteri-
orly from the equator. These form a sclero-
corneal sulcus, giving shape to the anterior
Figure 17.17 Lipid keratopathy in a frog (Courtesy
of Nicholas Millichamp, Animal Eye Care for segment and apposing the ciliary body to the
Animals, Houston, TX, USA). lens equator, which provides leverage for
Reptiles  739

defocused underwater, when other sensory


systems must be operative for prey location.
The iridocorneal angle resembles the mam-
malian pattern, but is not as well developed.
Iris color, pupil shape, and uveal vascular pat-
tern in reptiles are variable. In general, diurnal
lizards have round pupils and nocturnal liz-
ards and crocodiles have vertically elliptical
pupils. Ciliary processes are present in all rep-
tiles except lizards. The general pattern of iris
vascularity is two arteries entering the iris
stroma temporally and inferiorly, running cir-
cumferentially, and then forming a capillary
plexus around the iris sphincter. A radial
Figure 17.18 Sea turtle with extensive
proliferative ulcerative skin lesions frequently plexus of superficial iris veins is visible. Both
involving the eyelids (gray patch disease and ciliary and iris sphincter muscles are striated;
fibropapillomatosis) (Courtesy of Nicholas thus, mydriasis is not achieved with parasym-
Millichamp, Animal Eye Care for Animals, Houston,
patholytic drugs. Mydriasis can be achieved by
TX, USA).
general anesthesia or by intracameral injection
of curariform drugs. In red-­eared slider turtles
action of the ciliary muscle. Snakes lack both (Trachemys scripta elegans), topical application
scleral ossicles and cartilage, and crocodilians of four doses of 0.4% vecuronium bromide at
lack scleral ossicles. Morphometric analysis of 15-­min intervals increased pupil size by 28%,
the corneal endothelium of caiman (Caiman whereas atropine had no effect. A parallel trial
yacare) using scanning electron microscopy in the same species documented that topical
showed primarily hexagonal cells, with a cell 2.5% phenylephrine administered every 15 min
density similar to that in crocodiles, but higher for four doses dilated the turtles’ pupils, and
than that of one gecko species. The soft pliable that a combination of 2.5% phenylephrine with
lens of crocodilians and lizards has an equato- 0.4% vecuronium bromide dilated pupils more
rial pad, which is absent in snakes and poorly rapidly but to the same degree as phenyle-
developed in chelonians. Accommodation in phrine alone. These findings suggest the
most reptiles (except snakes) occurs by pres- potential presence of a smooth dilator pupillae
sure exerted by the ciliary body, mediated by muscle in turtles, but this has not been con-
the ciliary muscle, against the lens equator to firmed anatomically.
increase anteroposterior diameter of the lens. The avascular retina is supplied by the cho-
Ciliary processes are fused to the lens equator. roid in all reptiles. All have a choriocapillaris
The lenses of chameleons (Chamaeleo dilepis) and, during ocular development, a transient
have a negative refractive power, unlike other intravitreal hyaloid vascular system. In liz-
vertebrate eyes, and are capable of very rapid ards, this is complemented by the vascular
accommodation (up to 60 D/s) and very broad conus papillaris derived from the hyaloid vas-
accommodative range (up to 45 D). culature; it projects from the optic nerve head
Accommodation in snakes appears to occur by into the vitreous, in some species as far as the
forward movement of the lens and is accom- posterior pole of the lens, and is presumed to
plished indirectly by increased pressure on the have a nutritive function. In alligators, turtles,
vitreous applied by a stiff iris. Refractive and and tortoises, the retina is totally dependent
anatomical studies of crocodilians suggest that on the choriocapillaris after the hyaloid sys-
they focus images well in air, but are severely tem regresses; the alligator does have a conus
740 Exotic Animals: Ophthalmic Diseases and Surgery

that regresses. Snakes possess a conus during teratogenic, and environmental factors, at
ocular development, but it regresses in most. least, may be involved.
In a few (e.g., vipers), the conus persists. In all
snakes, a permanent preretinal vascular mesh- Infections
work develops from the embryologic hyaloid. Viral, bacterial, fungal, and parasitic infec-
In one colubrid (Tarbophis), this meshwork tions have been reported as causes of ocular
subsequently becomes an intraretinal vascular disease in reptiles. Herpesvirus infection in
system known elsewhere only in eels and a mariculture-­raised green sea turtles (Chelonia
few mammals. In crocodilians, guanine crys- mydas) between 56 days and 12 months of age
tals and calcium salts of guanine in the retinal caused extensive proliferative ulcerative skin
pigment epithelium form a semicircular supe- lesions frequently involving the eyelids (gray
rior retinal tapetum. The relative proportion patch disease and fibropapillomatosis).
of rod and cone photoreceptors varies among Intranuclear inclusions were noted histologi-
reptiles, probably correlated with their rela- cally (Figure 17.18). Secondary bacterial
tive diurnality and nocturnality. A fovea is infections needed antibacterial therapy.
present in lizards and the tuatara. The distal Herpesvirus infections have been associated
end of the ellipsoid of lizards, but not snakes, with an ocular respiratory syndrome in several
contains oil droplets. Chelonians predomi- tortoise species and in green sea turtles.
nantly have cones; crocodilians predomi- Captive spectacled Caiman (Caiman crocodi-
nantly have rods, with a few cones without oil lus) infected by poxvirus developed raised skin
droplets. Some snakes have a primarily or papules initially confined to the eyelids.
purely cone retina. Retinal response to dark Eosinophilic intracytoplasmic inclusions were
and light adaptation by cone contraction and present histologically. Infection by a herpes-­
pigment epithelial migration is minimal in like virus of Argentine and red-­footed tor-
reptiles. A single parietal eye located on the toises (Gracilaria chilensis and Geochelone
dorsum of the head is present in the tuatara carbonaria, respectively) caused necrotizing
and some lizards. These generally resemble stomatitis, ocular discharge (presumably from
lateral/frontal eyes histologically but not in all conjunctivitis), weight loss, and death.
details. They are part of the epithalamus,
which includes the pineal gland. They detect Bacterial Infections
light differently than the retinas of conven- Bacterial infections have been associated with
tional eyes and probably play a role in circa- several ocular disorders. Bacterial blepharitis
dian rhythms. with abscess formation occurs commonly.
Abscesses are usually focal and contain inspis-
Ocular Diseases sated pus. Both Gram-­negative (Escherichia
The reported ocular disorders of reptiles include coli, Pseudomonas spp.) and acid-­fast organ-
malformations, infections, nutritional disor- isms have been incriminated. Surgical excision
ders, degenerations, neoplasia, and trauma. or draining and curettage are indicated.
Subspectacular abscesses develop unilater-
Malformations ally or bilaterally secondary to ascending infec-
Malformations include anophthalmos, micro- tion from the oral cavity through the
phthalmos, cyclopia, exophthalmos, and cor- nasolacrimal duct, or from penetrating injuries
neal and pupillary defects. Microphthalmos to the spectacle, or from systemic infections.
occurs unilaterally and bilaterally alone or Chronic stomatitis may be a predisposing fac-
with other cranial malformations, including tor in the former. Clinical signs include disten-
cleft jaw and palate, maxillary hypoplasia, and sion of the spectacle to cause apparent
vertebral abnormalities. Genetic, nutritional, buphthalmos or exophthalmos and cloudiness.
Reptiles  741

White or yellow exudate is often visible below Discrimination from subspectacular abscess is
the spectacle. Therapy is directed at establish- potentially difficult on inspection, except that
ing drainage by careful excision of a 30° wedge simple obstruction causes spectacle distention
of inferior spectacle, culture and cytology of at first with clear or slightly turbid fluid.
the expressed exudate for antibiotic suscepti- Abscess formation may follow simple obstruc-
bility testing, and flushing of the space with tion. If spontaneous resolution does not occur
antibiotic solutions. Bacterial isolates have in a reasonable period, drainage by partial
included Pseudomonas and Proteus spp., and excision of the spectacle to establish drainage
Providencia rettgeri. Hemoprotozoa are some- is indicated. Recurrence is possible.
times identified in the material; their presence Panophthalmitis, generalized inflammation
is considered incidental, probably facilitated of the eye usually associated with infection,
by inflammation of the blood vessels of the develops in reptiles secondary to perforating
spectacle. Complete physical examination is injuries and infections of the ocular surface,
warranted to identify oral abnormalities and and by hematogenous distribution with bacte-
systemic infections. Some cases resolve spon- remia/septicemia. Hypopyon may be exten-
taneously without treatment, whereas others sive, and periocular swelling may be dramatic.
progress to corneal perforation and panoph- Any bacteria may be responsible; among oth-
thalmitis despite appropriate treatment. ers, Staphylococcus has been isolated from a
Blockage of the nasolacrimal duct in snakes tortoise. Enucleation may be the most expedi-
is associated with congenital malformation; ent and humane treatment for reptiles without
inflammation is associated with necrotic sto- systemic infections. Performed similarly to the
matitis and subspectacular infections, and procedure in mammals, reptile enucleations
pressure from nearby tumors and granulomas. may present the challenge of adequate closure
Sometimes termed pseudobuphthalmos, of skin over the orbital defect. Sliding skin
congenital and some acquired cases may grafts may be necessary.
resolve without treatment (Figure 17.19).
Fungal Infections
Fungal infections may cause superficial or
deep ocular disease. Fungal infections of the
skin may extend onto the spectacle in snakes
or the eyelids in chelonians. Trauma to green
sea turtles and damp environments in captive
snakes have been identified as predisposing
factors. Cultures from skin may not yield
growth; skin biopsy may be necessary to iden-
tify the nature of the infection. Correction of
environmental deficiencies may be adequate
treatment; snakes may then shed infected skin
with the next ecdysis. Snakes can be soaked in
dilute chlorhexidine (0.26 ml/l of water) for
1–2 h daily.
Figure 17.19 Blockage of the nasolacrimal duct
in snakes is associated with congenital
malformation; inflammation is associated with Parasitic Infections
necrotic stomatitis and subspectacular infections, Parasites occasionally cause ocular disease.
and pressure from nearby tumors and granulomas.
Leeches (Ozobranchus spp.) have been noted
Sometimes termed pseudobuphthalmos, congenital
and some acquired cases may resolve without on the conjunctiva of green sea turtles in mari-
treatment. culture. Local removal followed by topical
742 Exotic Animals: Ophthalmic Diseases and Surgery

antibiotic therapy resolves the condition. cataracts encountered during phacoemulsifi-


Oxyspururid and filarid nematodes have been cation in snakes, turtles, lizards, and birds are
found and manually removed from the con- quite liquefied and are removed by mostly
junctival sacs of lizards and turtles. In captive aspiration.
snakes, mites are commonly found attached to
the scales at the margin of the spectacle. Mites Retained Spectacles
can be treated using a 1-­in. dichlorvos strip Retained spectacles in snakes are not infre-
suspended in a perforated container in the quent and a challenge to manage. The causes
cage for two to three days, followed by cage dis- of retained spectacles include generalized
infection and repeat treatment 14 days later. integumentary disease, dry environment, local
Alternatively, covering the animal with a thin injury to the spectacle, mite or tick infestation,
film of olive oil (to asphyxiate the mites) or and systemic illness. Over several ecdysis
spraying with a pyrethroid (not pyrethrin) mite cycles, a thick layer of old spectacles accumu-
spray has been recommended as safer than lates. Spectacle opacification may render the
organophosphate treatment. snake blind in one or both eyes and unable or
unwilling to feed. Conservative management is
Neoplasia often effective and is safest, consisting of
Fibromas, fibropapillomas, and fibrosarcomas increasing the humidity in the environment by
develop on the integument of green sea misting or soaking the snake and lubrication
turtles (Caretta caretta) and other sea turtles with ophthalmic petrolatum ointment to pro-
in response to infection with chelo- mote natural shedding during the next cycle
nid fibropapilloma-­associated herpesvirus. (Figure 17.20). Manual spectacle removal may
Lesions may appear over an animal’s entire be carefully attempted. If unsuccessful or if the
body but are particularly problematic when spectacle has been previously damaged and is
they affect the eyelids or ocular surface. They unlikely to be shed, application of acetyl-
can become large enough that the protective cysteine (Mucomyst®, E.R. Squibb & Sons,
functions of blinking are impaired and vision L.L.C., Shirley, NY, USA) to the spectacle may
is compromised, making evading predation loosen it enough to allow atraumatic removal
and feeding a challenge. Treatment typically with forceps. Extreme care must be taken to
involves surgical removal of the tumors with avoid corneal injury.
adjunctive chemotherapeutic (e.g., cisplatin
and interferon) or physical methods (e.g., CO2
ablation and beta-­irradiation). Recurrence
is common.

Degenerations
Lenticular degeneration with opacification,
cataract, occurs sporadically in reptiles, espe-
cially snakes and tortoises, probably for most
of the same reasons that mammals are afflicted.
Cataract in very aged captive specimens has
been noted. Secondary cataracts caused by
uveitis or perforating injuries are common.
Phacoemulsification was performed on an
adult savannah monitor lizard (Varanus exan-
Figure 17.20 Retained spectacle in a snake
thematicus) and in a 10-­year-­old Texas rat (Courtesy of Nicholas Millichamp, Animal Eye Care
snake (Elaphe obsoleta lindheimeri). Most for Animals, Houston, TX, USA).
­Mammal  743

orders of placental mammals, considerable


diversity exists in normal anatomy. The other
two subclasses show features of evolution from
a reptilian to a placental mammal ocular
morphology.
Ocular examination in exotic mammals
often requires manual restraint or chemical
immobilization. Many, if not most, ocular dis-
orders that afflict domestic carnivores and her-
bivores at least occasionally involve exotic
species. In addition, husbandry and manage-
ment practices play a direct role in the develop-
ment of ocular disease in some species (e.g.,
Figure 17.21 Young red-­eared turtle with
periorbital swelling associated with marine mammals). Delivery of effective ther-
hypovitaminosis A. apy is often difficult and inconsistent, requir-
ing inventive compromises. Malformations,
Vitamin A Deficiency infections, inflammatory disorders, nutritional
Hypovitaminosis A is commonly recognized in disorders, neoplasia, and trauma are all impor-
chelonians and most frequently in aquatic spe- tant etiological factors in ocular disorders, and
cies, especially rapidly growing young turtles of variable importance in different orders of
fed diets of meat and insects. The vitamin A mammals. The majority of ophthalmic dis-
deficiency causes squamous metaplasia of the eases and surgeries in these mammals are
orbital glands and their ducts. The glands reported in the literature as individual case
increase in size as desquamated cells block reports.
their ducts. The eyelids become edematous
and blepharoconjunctivitis ensues. The palpe-
­Population Surveys of Ocular Disorders
bral fissure closes, and secondary bacterial
conjunctivitis and keratitis are common Health assessment of 81 Asian elephants
(Figure 17.21). Concomitantly, progression to under human care in India documented ocular
squamous metaplasia of renal, pancreatic, gas- lesions in 8.5% of them, consisting of cataracts
trointestinal, and respiratory epithelia is fatal. and corneal opacities. Ocular adnexal and
In the early stages of the disease while animals anterior segment examination of both eyes was
are still eating, a change of diet to commercial performed as part of an annual health check in
trout pellets supplemented with cod liver oil 1478 Asian elephants under human care in
initially can reverse the problem. Later, paren- Thailand. Eighteen percent of the elephants
teral vitamin A (1000–5000 IU) (Aquasol, USV had unilateral or bilateral lesions. The most
Pharmaceutical, New York, NY, USA) is rec- common lesions were frothy ocular discharge,
ommended weekly until resolution. Topical corneal edema, and conjunctivitis (all three
antibiotic ointment is recommended to control approximately 5% incidence), with phthisis
bacterial infection. bulbi, lens abnormalities, keratitis, and uveitis
less prevalent.
In a survey of free-­ranging rhesus macaques
­Mammals (M. mulatta) in northern India, the incidence
of traumatic injuries, corneal opacity, and cat-
The class Mammalia is comprised of three sub- aract was statistically significantly higher in
classes: placental mammals (the largest), macaques from urban compared with peri-­
monotremes, and marsupials. Among the 15 urban areas.
744 Exotic Animals: Ophthalmic Diseases and Surgery

Anterior segment lesions in 18 wild and cap- multiple ocular anomalies including corneal
tive dolphins of five species were character- dermoid and cataract were reported in a
ized. The most common lesions were unilateral dromedary camel. Unilateral anterior seg-
or bilateral keratopathy, followed by unilateral ment dysgenesis similar to Peters anomaly
or bilateral cataract and traumatic corneal and was diagnosed in a young red kangaroo
eyelid injuries. A virological survey utilizing (Macropus rufus). Congenital cataract
polymerase chain reactions of ocular tissues of afflicted a large proportion of Malayan mouse
California sea lions, northern elephant seals deer in a European zoo; no familial pattern
(Mirounga angustirostris), and Pacific harbor was detected and vitamin E deficiency was
seals () in rehabilitation discovered adenovi- suspected. Microphthalmia and cataract were
ruses and herpesviruses in all three species but found in white-­tailed deer fawns. Retinal dys-
found no Phoca vitulina richardii association plasia has been reported in wild otters (Lutra
with ocular disease. lutra). Multiple ocular anomalies were
Malformations, infections, inflammatory described in an infant rhesus macaque.
disorders, nutritional disorders, neoplasia, and
trauma are all important etiological factors in
Inflammations and Infections
ocular disorders of mammals, of variable
importance in different orders and species. Most reported ocular inflammatory disorders
have been infectious. A few were not. Examples
include ocular nodular fasciitis in an Asiatic
Malformations
black bear; chronic superficial keratitis in a
Cyclopia and limb deformity of unknown Mexican wolf resembling pannus; and nonsep-
cause in a collared peccary; anophthalmos tic uveitis associated with mast cell infiltration
and microphthalmos associated with naso- and causing glaucoma in a lion cub treated by
maxillary and central nervous system (CNS) evisceration with silicone prosthesis implanta-
abnormalities in two unrelated raccoons; and tion. Idiopathic follicular conjunctivitis was
congenital obstruction of the nasolacrimal found in 42% of African elephants shot at a
duct of a young lowland gorilla are examples national park.
of the variety of developmental ophthalmic Clinical manifestations of infectious ocular
defects reported in zoo animals. Eyelid agen- disease vary. A corneal stromal abscess in an
esis was surgically corrected in a Geoffroy’s aged Asian elephant was medically managed
cat and a cougar. A conjunctival dermoid in a to resolution with topical antibiotic and anti-
captive African lion cub was successfully fungal treatment. California sea lions with
treated by excision. The brain of a white tiger corneal ulcers in rehabilitation were treated
with strabismus showed abnormal lamina- successfully with a subconjunctiva antimicro-
tion of the lateral geniculate nucleus, which bial gel containing 2% enrofloxacin without
was similar to abnormalities noted in other additional topical therapy. Panophthalmitis
animals with reduced pigmentation. Mink was a manifestation of Trypanosoma cruzi
affected with Chediak–Higashi syndrome and Bacillus piliformis infection in a lesser
have pale irides, photophobia, and hypopig- panda. Conjunctivitis in jungle cat kittens
ment atapetal fundi. This autosomal recessive was ascribed to streptococcal and staphylo-
disorder manifests in several mammalian spe- coccal infection. Keratoconjunctivitis result-
cies as partial oculocutaneous albinism. ing from Chlamydia psittaci infection has
Multiple ocular colobomas (eyelid, optic been reported in both wild and captive koalas
nerve) and retinal dysplasia of probable in Australia. Experimental and naturally
genetic origin have been reported in captive occurring infections follow a similar course.
snow leopards on two continents. Bilateral Acute unilateral or bilateral infection may
­Mammal  745

affect up to 30% of wild populations, most treated both medically and surgically with a
commonly in the summer months. Serous conjunctival graft in a greater one-­horned rhi-
ocular discharge, conjunctival injection, and noceros and in another of the same species by
blepharospasm are followed by chemosis with tarsoconjunctival graft. Exotic felids are suscep-
eyelid eversion. By three weeks after infec- tible to infection with feline herpesvirus and
tion, corneal neovascularization is evident calicivirus. As in domestic cats, these respira-
and may progress to vision impairment. tory pathogens also cause conjunctivitis; ulcer-
Diagnosis is established by culture of the ative keratitis may be caused by the
organism or positive specific immunofluores- rhinotracheitis virus. Facial and eyelid cutane-
cence of epithelial cells collected by conjunc- ous ulcers were proven by culture and
tival or urogenital swab. histopathology to be caused by feline herpesvi-
Infectious keratoconjunctivitis of wild ungu- rus-­1 infection in a cheetah cub with a history
lates has many of the same causes as in domes- of conjunctivitis and corneal ulceration.
tic cattle, sheep, and goats. An epizootic of Proliferative vernal-­like conjunctivitis was
chlamydial keratoconjunctivitis that affected reported in a western lowland gorilla that was
60% of bighorn sheep in Yellowstone National unsuccessfully treated with appropriate topical
Park resulted in significant mortality. medication but responded to systemic immu-
Keratoconjunctivitis in wild mule deer was nosuppressive therapy.
associated with infection with Chlamydia, Uveitis and corneal edema developed in a
Moraxella spp., and Thelazia californiensis. young maned wolf (Chrysocyon brachyurus)
Keratitis in red deer responsive to subconjunc- vaccinated 14 days previously with a combina-
tival penicillin/streptomycin was suspected to tion vaccine containing canine hepatitis virus.
be due to Moraxella spp. Intraocular granulomas associated with dis-
Keratitis in reindeer in Scandinavia has been seminated tuberculosis were identified in a
extensively investigated. The clinical signs rhesus monkey. Disseminated cryptococcosis
appear identical to those of infectious bovine with ocular involvement was found in a gue-
keratoconjunctivitis in North America. non (Cercopithecus ascanius).
Summer epizootics occur in forest herds. Ocular encephalitozoonosis occurred in blue
Microbiological evaluation has documented fox pups farmed in Norway. Foxes naturally
the presence of Neisseria ovis, Colesiota-­like infected with E. cuniculi had mainly encepha-
organisms, and other bacteria, but the defini- litis, with uveitis and cataracts. Vascular
tive causative agent has not been conclusively lesions in the eyes resembled polyarteritis
determined. Lesions predominate in calves in nodosa; the posterior ciliary arteries and small
which central corneal ulceration may progress vessels of the retina and uvea were involved.
to perforation. Minor superficial ulceration The retinas were detached and necrotic and
and conjunctivitis are frequent. Ultrastructural many organisms were found in the cataractous
examination of infected corneas failed to dem- lenses. Bilateral lenticular E. cuniculi strain III
onstrate an agent. (dog) infection associated with cataract devel-
Necrotizing panophthalmitis and bilateral opment and chronic uveitis was reported in a
blindness in a black-­tailed deer resulted from young snow leopard (Panthera uncia). Lens
plague (Yersinia pestis), proven by culture. An capsule rupture, cataract, and intralenticular
Indian buffalo developed ulcerative keratomy- organisms were positively identified by poly-
cosis caused by Aspergillus fumigatus, perhaps merase chain reaction. The leopard was sero-
associated with topical antibiotic–corticoster- positive and infection was suspected to be by
oid treatment; results of therapy were not vertical transmission from its dam.
reported. Keratomalacia associated with yeast Malignant catarrhal fever (MCF) was
and staphylococcal infection was successfully fatal to Indian gaur in which it caused
746 Exotic Animals: Ophthalmic Diseases and Surgery

pyogranulomatous scleritis and keratitis but conjunctival sac of hippos without clini-
not uveitis or retinitis. Nonsuppurative uveitis, cal signs.
scleritis, and keratitis characterized fatal MCF Wallabies appear to be very susceptible to
infection in farmed Rusa deer. Farmed deer in toxoplasmosis. Uveitis has been noted in cap-
New Zealand are susceptible to MCF with ocu- tive wallabies, and is associated with cataract,
lar manifestations. An outbreak of blepharo- mild retinitis, and focal outer retinal degenera-
conjunctivitis and uveitis and oral ulceration tion. A wallaby succumbed to generalized tox-
was ascribed to infection with a virus indistin- oplasmosis following successful cataract
guishable from bovine herpesvirus-­1 in the surgery performed by the author, probably sec-
United Kingdom. ondary to related stress.
Poxviral keratoconjunctivitis and dermatitis The filarid Elaeophora schneideri may cause
were reported in free-­ranging mule deer in unilateral or bilateral chorioretinitis in elk. A
Wyoming. Contagious ecthyma in Alaskan vascular parasite, the nematode infects and
musk oxen and Dall sheep caused raised occludes the large arteries of the head and
crusted lesions of the eyelids, nostrils, and lips. neck, resulting in ischemic necrosis of the
Diagnosis was confirmed by immunofluores- brain, eyes, and other tissues of the head.
cence and transmission studies to domestic Calves and yearlings are most commonly
sheep. In the Dall sheep, affected corneas opac- affected. Blindness occurs with or without
ified and perforation occurred in one animal. neurological deficits may be secondary to ocu-
Bilateral nonsuppurative panuveitis, retini- lar or CNS lesions or both. Retinal and optic
tis, and optic neuritis caused epizootic blind- nerve atrophy may be visible ophthalmoscopi-
ness in eastern and western gray kangaroos cally through tonically dilated pupils. Retinal
and red kangaroos in Australia. A viral etiology edema and necrosis, optic neuritis, and optic
was suspected. Subsequently, orbiviruses of atrophy are present histologically. Microfilariae
the Warrego and Wallal serogroups caused epi- may be seen in ocular blood vessels. In sheep
demic blindness typified by chorioretinitis and with elaeophorosis, iridocyclitis has also been
encephalitis in Australian kangaroos. Mink noted in addition to the typical lesions in elk.
develop chronic nongranulomatous iridocycli-
tis as a manifestation of Aleutian disease, an
Corneal Degeneration
immune complex-­mediated glomerulonephri-
tis induced by a parvovirus infection. Lesions A presumptive corneal endothelial degenera-
in the posterior segment are less common, pri- tion or dystrophy was described in aged
marily a mild choroiditis causing retinal (6–11-­year-­old) ranch mink, primarily of the
detachment. Cataracts associated with ante- royal pastel coat color. Fifty-­three percent of
rior uveitis were described in wild mink, prob- mink were affected, two-­thirds bilaterally.
ably associated with Aleutian disease. Progressive corneal edema and keratoglobus
Nematodes infect the conjunctival sacs of were not associated with neovascularization or
deer. Thelazia californiensis was recovered melanosis. Histologically, the endothelium
from one-­third of black-­tailed deer in Oregon, was attenuated or absent, with guttata of a
with increased prevalence in females and older thickened Descemet’s membrane.
animals, and from California mule deer with
conjunctivitis. Thelazia skrjabini, an eyeworm
Cataract Formation
of cattle, was recovered from a white-­tailed
deer in Alberta. Thelazia californiensis were The causes of cataract include congenital
found in 8–15% of hunter-­harvested mule deer defects, advanced age, trauma, nutritional
and 40–66% of live deer in Utah. The trema- deficiencies and imbalances, inherited defects
tode Oculotrema hippopotami was found in the of the lens, metabolic disorders, and
­Mammal  747

environmental effects. In a breeding colony of other reasons and had received cow’s milk.
vervet monkeys (Chlorocebus aethiops), more These neonatal marsupials progress through a
than one-­quarter of 55 offspring produced over monogastric phase of gastrointestinal develop-
a six-­year period were diagnosed with cataract; ment to a polygastric (ruminant) form of the
a genetic basis was suspected. Elimination of adult digestive system. Prior to maturity, they
monkeys related to those with cataract from may be variably deficient in either galactoki-
the breeding pool resulted in elimination of nase or galactose-­1-­phosphate uridylyltrans-
cataract from the next generation. A high inci- ferase, which limits conversion of galactose in
dence of cataracts was observed in two colo- cow’s milk to lactose. Dulcitol accumulation in
nies of gray mouse lemurs (Microcebus the lens causes an osmotic cataract. These
murinus) (48% and 21%, respectively). Bilateral nutritional cataracts may be prevented by feed-
cataract with unilateral ocular perforation was ing proprietary milk substitutes designed for
diagnosed in a wild coyote. In Sweden, dense human infants with inherited galactosemia
cataracts have been observed in wild moose. that lack galactose and lactose. Surgical lensec-
Cataracts of suspected nutritional origin in tomy has been generally unsuccessful because
timber wolf pups were ascribed to deficiency most affected animals have vitreous opacified
or imbalance of arginine. Posterior subcapsu- by an unidentified material.
lar sutural opacification developed first in Cataracts were found in 16 of 300 African
pups fed a commercial milk replacement diet elephants culled from Tsavo National Park,
from 9 to 10 days of age. Anterior cortical cata- Kenya; only two were bilateral. Lens luxation
ract followed. By 2.5 weeks on the diet, gener- and hypermaturity and active and inactive
alized cataract had developed. When the milk uveitis were noted in some elephants. Cataracts
replacement was discontinued in favor of com- have been recognized in captive elephants as
mercial dog food, the lens opacities partially well. Cataracts of presumed traumatic origin
regressed, leaving perinuclear opacities. were noted in Turkish dancing bears from a
Arginine deficiency was suspected from die- circus, associated with corneal scarring and
tary experiments with succeeding litters phthisis in some animals.
of wolves.
Bilateral extracapsular cataract extraction
Diseases of the Ocular Fundus
was performed with good results on an eland
with senile cataracts and a young Siberian tiger Central retinal degeneration typical of taurine
with cataracts of suspected genetic origin. deficiency in the domestic cat was reported in
Bilateral phacoemulsification without intraoc- a white Bengal tiger in the United States and in
ular lens implantation has been performed on three unrelated cheetahs in Israel. The serum
two clouded leopard cubs (Neofelis nebulosa) taurine level was lower in the white tiger com-
and a roan antelope calf (Hippotragus equi- pared to other orange tigers, but not low
nus). Phacoemulsification was successfully enough compared to domestic cats with cen-
performed without intraocular lens implanta- tral retinal degeneration to account for the
tion in a mature spider monkey (Ateles geof- tigers’ retinopathy. Retinal degeneration of
froyi), a three-­month-­old clouded leopard cub, uncertain cause has been noted in culled wild
and a young adult orangutan (Pongo pyg- African elephants with cataracts and in captive
maeus), and with foldable intraocular lens Asian elephants. The unrelated Asian ele-
implantation in two young lowland gorillas. phants showed behavioral signs of reduced
Galactosemic cataracts have been reported vision and ophthalmoscopically reduced fun-
to occur in kangaroos, wallabies, wombats, dus vascularity; the normal paurangiotic fun-
Australian possums, and cuscus. Affected ani- dus is difficult at best to assess. Retinal
mals had been orphaned or hand-­reared for degeneration of unknown cause occurred in
748 Exotic Animals: Ophthalmic Diseases and Surgery

aged ranch mink. Presumptive hypertensive treated by excision and intralesional bevaci-
retinopathy and uveal vasculopathy were zumab. Surgical excision of a conjunctival
reported in a 40-­year-­old captive hippopota- squamous cell carcinoma was curative for a
mus with a pheochromocytoma. Histological reindeer (Rangifer tarandus tarandus).
lesions were consistent with pathology seen in
systemic hypertension. Idiopathic bilateral
Trauma
optic atrophy has been described in rhesus
macaques. Clinical diagnosis of hypertensive Traumatic injury is no doubt a frequent cause
encephalopathy and retinopathy was con- of ocular disease in nondomestic animals.
firmed at necropsy in a western lowland gorilla Extensive epithelial downgrowth was
(Gorilla gorilla gorilla). Presumptive age-­ described in the buphthalmic eye of a harbor
related macular degeneration was diagnosed seal that was postulated to be secondary to a
clinically in a mature captive western lowland perforating injury.
gorilla.

­Avian Ophthalmology
Neoplasia
Neoplasia seems relatively uncommon in Within the class Aves, approximately 9000 spe-
exotic species. An extensive corneal squamous cies are classified into two superorders:
cell carcinoma in a five-­year-­old cheetah was Neognathae containing 99% of extant species,
managed by exenteration; the animal was free and Palaeognathae that contains the remain-
of local recurrence and radiographic evidence der. They inhabit the land, sea, and air in a
of thoracic metastasis one year later. Intestinal diverse array of ecological niches. Only a few
and unilateral ocular lymphosarcoma was species have been truly domesticated as food or
reported in a captive adult striped hyena. The companion animals. Although their eyes pre-
optic nerve, uvea, retina, and vitreous were sent examination and therapeutic challenges
infiltrated by neoplastic lymphocytes. Bulbar to veterinarians charged with their medical
conjunctival ganglioneuromas were diagnosed and surgical ophthalmic care, these can be
in two adult Indian water buffaloes; clinical overcome by innovation and modifications of
signs and outcome were not reported. An standard veterinary ophthalmic diagnostic
African green monkey (Cercopithecus tests, examination techniques, and medical
[Chlorocebus] pygerythrus) developed exten- and surgical interventions.
sive bilateral periocular and eyelid squamous
cell carcinoma after a long-­term carcinogenic-
Ocular Anatomy
ity trial. A Harderian gland adenocarcinoma
caused exophthalmos in a Beechey ground In raptors, the upper and lower eyelids, and
squirrel (Spermophilus beecheyi). Bilateral cor- membrana nictitans are present. The lower lid
neal papilloma in a Malayan tapir resolved is more mobile than the upper, usually con-
with repeated subconjunctival injections of taining a fibroelastic tarsal plate. The palpebral
25 mg fluorouracil. A transitional cell carci- reflex can be incomplete in normal raptors,
noma of ovarian origin was metastatic to the owing to excitement, and normal spontaneous
eye of a collared peccary. Focal limbal corneo- blinking occurs less often in nocturnal species
conjunctival intraepithelial neoplasia in an relative to diurnal species. The lower lid of
Asian elephant was excised, treated with cryo- most raptors contains a fibrous plate that is
therapy, and was apparently cured. Recurrent roughly semicircular in outline, with the flat
eyelid sebaceous carcinoma in an Amur tiger edge facing the palpebral margin. The nictitans
(Panthera tigris altaica) was successfully is well developed, actively mobile, nearly
­Avian Ophthalmolog  749

transparent, thin, and covered by a papillary protection predispose the eyes to environmen-
layer of epithelium. Drawn from the medial tal trauma. The bony orbit is made up of a
canthus, the nictitans is moved by contracture number of individual elements, with contribu-
of the pyramidalis muscle that originates from tions from the frontal, prefrontal, sphenoid,
the posterior pole sclera where it loops through ethmoid, palatine, and quadrate bones as well
a sling formed by the quadratus muscle; both as the bony components of the jugal arch. The
are innervated by cranial nerve VI. Both mus- two globes are separated from each other by
cles may be derived from the crocodilian the exceedingly thin interorbital septum. The
retractor bulbi muscles otherwise absent in osseous septum is complete in owls, while in
birds. The oblique and rectus muscles are thin diurnal birds of prey, an aperture is present
and relatively poorly developed. Meibomian that is covered by a tough fibrous membrane in
glands are also absent. The Harderian gland is life. The bony component of the posterior
the major source of tears in birds and is orbital wall is less than 1 mm thick in some
attached to the posterior aspect of the globe in locations. The posterior aspect of the eye fits
raptors, ventral to the medial rectus muscle. snugly within the orbit, but the majority of the
The lacrimal gland is located inferotemporal to globe’s temporal and dorsal aspects remains
the globe, and a Harderian gland is found adja- completely outside of its protection.
cent to the posterior sclera near the base of the The globe is very large relative to body size.
nictitans, but not part of it. A lacrimal gland is The posterior segment is relatively much larger
present and associated with the ventromedial than the anterior segment. Three basic shapes
orbital rim in most raptors, but is absent in owl are typical:
species, some of which instead possess a nasal
1) The most common is a flat shape, with a
salt gland in the dorsonasal aspect of the orbit.
short anteroposterior axis and a flat or
This salt gland has also been observed in hawks
partly concave ciliary region (intermediate
and, in addition to providing an adaptive
segment) in the center of which the cornea
mechanism for living in dry habitats, may rep-
protrudes, with a hemispheric posterior
resent an alternative source of tears, or provide
segment.
tear film stability. Two lacrimal puncta drain
2) Globose, in which the ciliary region pro-
lacrimal secretions into a nasolacrimal duct
trudes further from the posterior segment
and then to the nasal cavity. The orbit is typi-
while remaining somewhat concave. This
cally, but not universally, incomplete, large,
shape is present in many diurnal birds
and open; it can be evaluated radiographically.
needing high-­resolution distance vision
Interspecies variation in orbital bone structure
(e.g., crows, insectivorous wing-­feeders,
of psittaciform birds has been described in
and diurnal raptors).
detail. Twenty-­seven skulls from 14 species of
3) Tubular, such as in owls, in which the con-
psittacines were analyzed and classified into
cave intermediate segment is elongated
two groups. One group had a complete,
anteroposteriorly, forming a tube before
enclosed bony orbit formed by the junction of
joining the posterior segment at a
the orbital and postorbital processes and form-
sharp angle.
ing a suborbital arch. The second group lacked
the suborbital arch and had an open, incom- The shape of the globe is formed and main-
plete bony orbit typical of most modern birds; tained by hyaline cartilage in the sclera of the
even in this group, orbital and postorbital pro- posterior segment and by 10–18 scleral ossicles
cesses were present. While the anatomical fea- (sometimes pneumatic) in the sclera of the
tures of the raptor globe and bony orbit intermediate segment. The cornea has the
contribute to excellent visual acuity, the large same histological layers as in mammals. in vivo
size of the eye and relative lack of orbital confocal microscopy of the corneas of five
750 Exotic Animals: Ophthalmic Diseases and Surgery

birds of different species confirmed this and but absent in raptors, allows them to keep the
identified a Bowman’s-­like layer. Conjunctiva-­ ground in focus while performing other tasks.
associated lymphoid tissue in poultry is impor- Aquatic birds, in which the corneal accommo-
tant in mucosal immunity. The iris contains dative mechanisms are neutralized under
striated sphincter and dilator muscles, and water, have accommodation of up to 50 D. The
myoepithelium and smooth muscle, and its numerous ciliary processes are tightly fused to
stroma harbors several pigments responsible the equatorial lens capsule.
for variable iris coloration. The circular pupil is The retina is avascular and atapetal but has a
subject to influence from retinal stimulation as well-­developed choroid and pecten. The pecten
well as voluntary control. Iris vascularization is a highly vascular pigmented structure of
is similar to that in lizards. The iridocorneal greatly variable size extending into the vitreous
angle is well developed and drained by two from and obscuring examination of the optic
annular channels. The lens is soft, pliable, and nerve head. As in reptiles, the vascular meso-
of variable shape: spherical in nocturnal spe- dermal core overlies the neuroectodermal cells
cies and flattened anteriorly in some diurnal and differs from the purely mesodermal falci-
species. An equatorial annular pad formed of form process of fish. The pecten probably has a
modified lens fibers is present and may be very primary nutritive function, but has been cred-
prominent. Between the central body of the ited with over 30 possible functions.
lens and the annular pad is a fluid-­filled cleft Considerable variation in photoreceptor type
or lenticular space. Though not serving a direct and density exists. Some species (most domes-
optical role, the annular pad serves an impor- tic species) are afoveate, others are monofove-
tant function in accommodation and may have ate, and some are bifoveate (hummingbirds,
a nutritive role in lens metabolism. Its size is some raptors, and passerines). Both rods and
generally related to the accommodative range cones are present (including double cones with
of the lens, which varies with species. Except oil droplets); proportions vary with the species’
in diving birds, the pad is largest in birds with visual ecology. Some avian species possess
the widest range of accommodation (e.g., diur- ultraviolet vision, the function of which is
nal birds of prey and other fast-­flying species). uncertain. One hypothesis is that it provides
The smallest are present in nocturnal species orientation for foraging and signaling. Pigment
with small accommodative ranges. epithelial processes contain pigment granules
Accommodation in birds involves changes in and respond to light by elongation between
corneal curvature, anterior movement of the rods. The fundus appearance in vivo is a gray or
lens, and lens deformation. Lens power is red background speckled with heterogeneous
increased by contraction of the striated meridi- pigmentation through which choroidal vessels
onal ciliary muscles: Brucke’s muscle posteri- may be seen in some species. The choroid of
orly and Crampton’s muscle anteriorly (which the chicken contains a conspicuous system of
inserts on the peripheral cornea) move the cili- thin-­walled lacunae not seen in mammalian
ary body axially, compressing the lens by exert- choroids, which may represent short lym-
ing pressure on the annular pad. Crampton’s phatic vessels.
muscle contraction may flatten the peripheral
cornea. In the chicken and pigeon, changes in
Examination Techniques
corneal curvature account for half or more of
the 15–17-­D accommodative range of the eye. Clinical examination of avian eyes utilizes the
In one investigation of avian accommodation, same instrumentation and diagnostic tech-
the accommodative range of 15 species of owls niques as in mammals, albeit with modifica-
was 0.7–10+ D. Lower visual field myopia pre- tion dictated by the size of the eye and
sent in some birds (chickens, pigeons, quail), physiological characteristics of the iris. Basic
­Avian Ophthalmolog  751

instrumentation should include a bright focal paralyzed by neuromuscular paralyzing


light source (e.g., transilluminator), a low-­ agents. Intracameral injection of d-­
power magnifying head loupe, 28–30-­D, 40-­D, tubocurarine, a nondepolarizing neuromuscu-
or 60-­D indirect condensing lenses (Volk lar blocking agent, has been reported to cause
Optical, Mentor, OH, USA), and a direct oph- consistent moderate-­to-­maximal mydriasis in
thalmoscope. Accessory diagnostic aids pigeons and several raptor species. Topical
include fluorescein dye strips, STT strips (Iolab application of tubocurarine (3 mg of tubocur-
Pharmaceuticals, Claremont, CA, USA), phenol arine powder/ml of 0.025% benzalkonium
red threads (Zone-­Quick; Menicon Company, chloride solution) instilled three to four times
Nagoya, Japan), culture swabs (Minitip over 20 min resulted in partial mydriasis in
Culturette; Becton-­Dickinson, Cockeysville, some species, but not others. Mydriasis was
MD, USA), microscope slides, sterile scalpel consistently and safely achieved in European
blades for conjunctival and corneal cytology col- kestrels (Falco tinnunculus) by topical admin-
lection, and an applanation and/or rebound istration of two drops of vecuronium bromide
tonometer (TonoPen-­XL®; Bio-­Rad Inc., Santa (4 mg/ml) (Norcuron®; Organon Tekneika,
Ana, CA, USA; TonoVet®, Jorgensen France) every 15 min for three instillations and
Laboratories, Loveland, CO, USA). applied to one eye only. Three curariform (d-­
Avian responses to the eye-­related reflexes tubocurarine, pancuronium, and vecuronium
differ from those of mammals in some respects. bromide) and two autonomic drugs (atropine
Palpebral response is present with the lower lid and phenylephrine) were evaluated for topical
covering the globe more extensively than the use with and without addition of surface-­
upper lid; membrana nictitans excursions are acting penetration agents (saponin or benza-
prominent. Menace responses seem inconsist- lkonium chloride) in three species of large
ent even in birds with evidently normal vision; psittacines. One eye of each bird was tested.
thus, absent menace response has little diag- Vecuronium (0.8 mg/ml, two drops adminis-
nostic significance. Avoidance behavior is a tered twice 2 min apart) without an enhanced
more reliable indicator of vision than menace penetration agent produced the most consist-
reflex. Because retractor bulbi muscles are ent and greatest mydriasis with the fewest sys-
absent in birds (replaced by the quadratus and temic side effects in all three species. Amazon
pyramidalis muscles that subserve membrana parrots treated with this protocol developed
nictitans motility), globe retraction is not a fea- mild transient systemic side effects.
ture of eye-­related reflex responses. The cor- Administration of vecuronium with 1% sapo-
neal reflex is present, manifested by blinking, nin was fatal to one cockatoo. Topical pancuro-
nictitans excursion, and avoidance behavior. nium caused mild to severe systemic effects in
Direct PLR is present. Its assessment is often some cockatoos. In juvenile double-­crested
problematic owing to presumptive voluntary cormorants (Phalacrocorax auritus), mydriasis
control of the striated components of the iris was best achieved with a combination of 1%
musculature and the emotional state of the topical atropine, 2.5% phenylephrine, and
bird. Because of complete decussation of optic 4 mg/ml of vecuronium. Mydriatic effects of
nerve fibers, consensual pupillary light 0.15 mg intramuscularly and 20 ml of a 10 mg/
responses are not expected in birds. Posterior ml solution of rocuronium bromide applied to
segment examination in birds is confounded the eyes of Hispaniolan Amazon parrots
by difficulty in achieving mydriasis. (Amazona ventralis) resulted in up to 60 min of
Parasympatholytic agents are ineffective mydriasis. Variable mydriasis can be fairly con-
because of the complex muscular arrangement sistently achieved under general anesthesia.
of the iris. Predominantly striated in Applanation tonometry poses certain diffi-
nature, the iris muscles may be partially culties in birds. High corneal and scleral
752 Exotic Animals: Ophthalmic Diseases and Surgery

rigidity compared with mammalian eyes no investigated in a variety of avian species, espe-
doubt affects the reliability and interpretive cially poultry.
value of the measurements in birds. Spuriously
elevated IOP values are commonly encountered.
Inflammations and Infections
Handlers of birds should have experience in
avian restraint techniques to ensure the Ocular inflammation in birds originates from
patient’s safety and comfort and the safety of infections, both primary ocular and systemic
the examiner. The talons of many raptor spe- diseases; nonseptic inflammation, including
cies are capable of inflicting serious harm to presumptively immune-­mediated processes;
both handlers and examiners and should be and traumatic injuries. Some reported exam-
specifically restrained or wrapped. ples are chorioretinitis and buphthalmos in
turkey poults in Britain, severe lens-­associated
endophthalmitis in a barred owl and a screech
Ophthalmic Diseases
owl, and symblepharon in two snowy owl
Avian ocular disorders may be generally albeit chicks (Nyctea scandiaca).
imperfectly categorized as malformations, The normal external ocular microflora of rap-
inflammations, infections, degenerations, neo- tors, captive cranes, psittacines, and a variety of
plasia, nutritional disorders, and traumatic exotic birds in public collections have been sur-
injuries. veyed. In 55 of 65 raptors sampled bilaterally,
bacteria and/or fungi were cultured.
Developmental Malformations Staphylococcus spp. predominated (52% of cul-
Developmental malformations have been tures). Fungi (Aspergillus or Cladosporium)
reported infrequently. In one series of ocular were cultured from only three eyes. In healthy
anomalies in 16 raptors, the most common psittacines, no growth was found in 41% of cul-
lesion was microphthalmia. Other conditions tured eyes. Staphylococcus epidermidis and
included partial upper eyelid agenesis, cryp- “hemolytic” streptococci predominated.
tophthalmos, symblepharon, corneal der- Bacteria, fungi, viruses, protozoa, micro-
moids, and several other defects. Presumptive sporidia, trematodes, and nematodes cause ocu-
keratoglobus in a juvenile great horned owl lar disease in birds. Some examples include
(Bubo virginianus) was investigated and stud- acute severe fibrinopurulent blepharitis and
ied by postmortem ocular measurements and conjunctivitis in chickens and turkeys, which
histopathology. It was determined that IOP are associated with infections with
was normal bilaterally and a keratoglobus was Staphylococcus hyicus, E. coli, and Streptococcus
present bilaterally. The bird was sighted and spp.; blepharoconjunctivitis and uveitis caused
posterior segment measurements were repre- by P. multocida in turkeys; and panophthalmitis
sentative of the normal posterior segment of following natural and experimental infection of
this species, but anterior segment measure- broiler chickens with Salmonella arizonae.
ments were larger than normal. Impatent Actinobacillus spp. were recovered from native
nasolacrimal ducts were suspected in a cocka- and exotic waterfowl with conjunctivitis.
too with choanal atresia, and ectropion was Staphylococcal blepharokeratoconjunctivitis
diagnosed in cockatiels. Cataract and optic was diagnosed in a large group of newly
nerve hypoplasia of unknown cause in turkey imported Amazon parrots. In captive Siberian
poults were reported in a commercial flock. and whooping crane chicks, an outbreak of
Iris colobomas were seen in a flock of P. aeruginosa keratitis resulted in melting cor-
Rosecomb bantam chickens. Photoreceptor neal ulceration and perforations. Mycobacterium
dysplasia, retinal dysplasia, and subsequent avium has been cultured from and implicated in
retinal degeneration have been reported and conjunctival granulomas and orbital infections,
­Avian Ophthalmolog  753

The extensive cervicocephalic air sac system literature. Birds are the natural host for this
of psittacines is commonly involved in respira- virus and among raptor species, hawks and
tory infections, leading to ophthalmic compli- owls are the most frequently affected. Systemic
cations. Infraorbital sinus nocardiosis and clinical signs of West Nile virus are nonspecific
supraorbital extension of sinusitis due to and include lethargy, weight loss, and in some
P. aeruginosa result in ophthalmic signs. instances vision loss with other neurological
Various Mycoplasma spp. have been suspected impairments. Antemortem diagnosis of this
or proven to be involved with conjunctival and virus can be challenging; however, the pres-
ocular surface inflammation in a variety of ence of characteristic chorioretinitis
species. lesions – especially when accompanied by
Avian poxvirus is responsible for the large other neurological impairments during mos-
majority of reported viral infections involving quito season – is supportive of this disease.
birds’ eyes. A wide variety of species have been Fundic lesions in red-­tailed hawks and
affected, including raptors, conures, mynahs, Cooper’s hawks consist of linear or geographic
Amazon parrots, racing pigeons, bobwhite areas of raised white exudates.
quail, peacocks, exotic pheasants, and other A variety of fungal infections have been
species. Poxvirus may occur in either or both of reported in birds. Ocular candidiasis in orna-
two forms: (i) a mild form causing proliferative mental ducks, a gull, a budgerigar, and chick-
lesions of the skin of eyelids and beak and (ii) ens was characterized by small masses on the
a severe, generalized form involving the skin of membrana nictitans, keratitis, and uveitis and
many body sites and fibrinonecrotic lesions of by conjunctival granulomas on the third eye-
the mouth or upper respiratory tract and pneu- lid. Disseminated aspergillosis has been associ-
monia. Poxvirus lesions are typically nodular, ated with endophthalmitis in turkeys. Orbital
raised, and can develop scabs and crusts, most involvement in disseminated cryptococcosis
often affecting the nonfeathered skin of the was seen in a cockatoo. Rhinosporidium seeberi
eyelids and feet. Uncomplicated poxvirus caused nodular blepharoconjunctivitis in cap-
infections are self-­limiting, with irregular nod- tive mute and black swans that was not treated.
ular lesions tending to regress after approxi- Mycotic keratitis was diagnosed in a blue-­
mately three weeks. fronted Amazon parrot. Keratomycosis due to
In chickens, cataracts and iridocyclitis have Aspergillus species was successfully treated
been associated with avian encephalomyelitis with topical voriconazole in a Khaki Campbell
infection. Marek’s disease causes iridocyclitis duck. Keratoconjunctivitis caused by
and secondary cataract. Nodular proliferative Aspergillus species in red-­legged partridges
blepharoconjunctivitis in an African gray par- (Alectoris rufa) and Scedosporium apiosper-
rot was associated with cutaneous infection mum has been diagnosed in layer pullets.
with a papilloma-­like virus demonstrated by Endophthalmitis and encephalitis due to
electron microscopy. In domestic poultry, Toxoplasma gondii have been confirmed in
infectious laryngotracheitis, duck plague, canaries and chickens. Goose parvovirus
Newcastle disease, influenza A, infectious causes blepharitis and enteritis. Papovavirus
bronchitis, quail bronchitis viruses, turkey and inclusions were reported from the eyelids of
pigeon herpesviruses, adenovirus, and pneu- budgerigars. Severe conjunctivitis due to
movirus cause conjunctivitis. cryptosporidiosis has been reported in pheas-
Endogenous and/or exogenous bacterial, ants, a domestic duck, stone curlews, and a
viral, and parasitic causes of chorioretinitis peacock. Cryptosporidiosis is a protozoal dis-
have been reported in birds, especially raptors. ease of any young and immunocompromised
Among these, West Nile virus has received the birds, but most common in chickens.
most significant attention in the scientific Conjunctivitis and respiratory disease (rhinitis
754 Exotic Animals: Ophthalmic Diseases and Surgery

and tracheitis) associated with this organism kindred of Yorkshire and Norwich canaries;
have been observed. Infected birds displayed autosomal recessive inheritance was postu-
blepharedema conjunctival hyperemia, lated in the Yorkshire. Spontaneous cataract of
mucopurulent ocular discharge, and corneal unknown cause was identified in a large flock
edema and uveitis. of bobwhite quail, detectable after three
Parasitic diseases occasionally cause avian months of age. In Brahma chickens, focal polar
ocular disease. Parasites are sometimes found cataracts that progressed to maturity by six
under the membrana nictitans, associated with months of age were associated with the con-
no clinical signs or conjunctivitis. These comitant development of crooked toes; the
include the spirurids Ceratospira and inheritance pattern was undetermined.
Oxyspirura spp. in psittacines, mynahs, and Spontaneous cataracts in chickens and turkeys
domestic and wild birds; the nematodes have been reported. Cataracts are most often
Thelazia spp. in a Senegal parrot, a captive ori- reported in raptors due to senility. Juvenile
ental white stork (Ciconia boyciana), and a cataracts have been reported in tawny, screech,
Setaria in passerines; and the trematode and great horned owls, though there is no evi-
Philophthalmus gralli in ostriches, waterfowl, dence to indicate that juvenile or congenital
and other species. In budgerigars and other cataracts in raptors are heritable. Cataracts as a
aviary and pet birds, Knemidokoptes pilae result of blunt and/or penetrating trauma and
infestation causes scaly proliferative lesions of electrocution have been reported in birds.
the legs, cere, and eyelids; other species cause Extracapsular cataract extraction was done in a
similar lesions in poultry and wild passerines. mandarin duck, an Andean condor, and a
Diagnosis is confirmed by skin scraping that black-­shouldered kite. Phacoemulsification
demonstrates the organism. Knemidokoptic has been performed on raptors, owls, and
mange has a predilection for nonfeathered macaws. Bilateral phacoemulsification was
areas and causes scaling of the skin of the face performed successfully with implantation of
and legs. Mite infestations can also affect feath- customized polymethyl methacrylate intraocu-
ered skin and can cause proliferation and lar lenses in a young great horned owl. The
inflammation of the beak. lenses had a haptic diameter of 17 mm and
optic diameter of 10 mm. Intracapsular lens
Degenerations extraction has been performed with success in
Crystalline corneal degeneration of unknown owls with anterior lens luxations.
cause was found at necropsy in 8.7% of birds at Retinal degenerations in birds occur as
a quarantine station, most commonly in cocka- inherited, postinflammatory, and post-­
tiels, budgerigars, ring-­necked parakeets, traumatic conditions. Hereditary retinal
Amazon parrots, and Gouldian finches. degeneration in Rhode Island red chickens
Similar deposits have been found in Amazon appears to follow photoreceptor dysplasia.
parrots following poxvirus infection. Idiopathic Bilateral idiopathic generalized retinal degen-
lipoidal corneal degeneration has been seen eration was diagnosed in a budgerigar. Retinal
bilaterally in falcons, barred owls, a bald eagle, degenerations due to inflammation or trauma
and a common buzzard; neutral lipid and cho- are focal to multifocal, and sometimes exten-
lesterol deposits were present in the stroma sive enough to cause blindness. Funduscopic
with subepithelial fibrosis. This rare condition appearance is characterized by pigmentary dis-
has been observed most often in aged birds. turbance and asymmetric fundus pigmenta-
Lenticular degeneration with cataract devel- tion when both eyes are compared.
opment has been commonly noted in domes- Lead toxicity is the most common toxicosis
tic, captive, and wild birds. Presumptively in raptors, with carrion-­eating birds and scav-
heritable cataract was reported in a small engers being most commonly affected. The
­Avian Ophthalmolog  755

primary route of exposure is through ingestion by multicentric or metastatic malignant mela-


of lead bullets from unretrieved carcasses of noma in an African gray parrot and a pigeon.
hunted game. Histological lesions of lead toxi- Orbital neoplasia included optic nerve glioma
cosis involving the avian posterior segment and round cell sarcoma. Malignant intraocular
were recently described in an affected bald teratoid medulloepitheliomas were identified
eagle. A choroidal vasculopathy was observed in three cockatiels. Squamous cell carcinoma
that involved severe thickening, hyalinization, of the infraorbital sinus was diagnosed at nec-
and fibrinoid necrosis of choroidal arterioles. ropsy in a Solomon eclectus parrot (Eclectus
Complete retinal detachment was also present. roratus solomonensis) with fungal tracheitis.
Surgical resection of a conjunctival xanthoma
from a blue and gold macaw (Ara ararauna)
Neoplasia
was curative. Surgical removal of a retrobulbar
Neoplasia involving the avian eye and adnexa adenoma suspected to be associated with hypo-
seems to be relatively uncommon. Marek’s dis- vitaminosis A from an African gray parrot
ease of chickens is the most common cause. (Psittacus erithacus) was complete with preser-
Marek’s disease virus-­associated ocular lym- vation of the globe and vision. Intraocular
phoma was confirmed in roulroul partridges. osteosarcoma with orbital extension in an
Orbital lymphosarcoma associated with reticu- umbrella cockatoo (Cacatua alba) was treated
loendotheliosis virus infection in a peafowl has with exenteration and radiation therapy, but
been described. Intraocular and orbital and the bird was euthanatized two months after-
periorbital lymphoma had been diagnosed in ward for neurological signs.
several species of macaw. Eyelid and conjunc-
tival neoplasia has been rarely reported: benign Vitamin A Deficiency
basaloid cell tumor in a budgerigar, a mastocy- Hypovitaminosis A, a common subclinical
toma of the lower eyelid of a chicken, a chon- condition in caged birds, may predispose them
drosarcoma of the third eyelid of a great white to diseases of the mucous membranes (e.g.,
heron, a periocular cystadenoma in an African keratitis and conjunctivitis). Clinical defi-
gray parrot, and neoplasms of the third eyelid ciency may be manifest as swollen eyelids due
(squamous cell carcinoma in a hawk, basal epi- to conjunctival hyperkeratosis, mimicking pox
thelioma in a parrot, xanthoma in a budgeri- lesions. Cytological and histological examina-
gar). A mucinous adenocarcinoma of the globe tion of lesions may be used to differentiate the
was diagnosed in a two-­year-­old male ostrich causes. Parenteral and dietary vitamin A sup-
(Struthio camelus). A subconjunctival hiber- plementation is effective.
noma, a benign neoplasm of brown fat, was
successfully excised from a domestic goose. In
Trauma
addition to herpesvirus-­induced ocular lym-
phomatosis (Marek’s disease) in chickens, pri- Traumatic ocular injury is frequent in raptors
mary uveal neoplasia reports include iris and wild passerine birds. Sharp and blunt trau-
melanoma, iris hemangioendothelioma, and mas to the eye (Figure 17.22) are responsible
anterior uveal rhabdomyosarcoma in chick- for the majority of inflammatory pathologies
ens, medulloepithelioma in two cockatiels, observed in the anterior uvea. Anterior uveitis
adenocarcinoma in a budgerigar, and uveal with hyphema, specifically, is one of the most
malignant melanoma in a duck with extrascle- common ocular examination findings follow-
ral extension. Uveal neoplasms in raptors are ing trauma. A recent histopathological survey
exceptionally rare, though an iris melanoma of traumatic ocular lesions in raptors also
has been identified in a great horned owl showed iridocyclodialysis to be a common
(B. virginianus) and the bald eagle (Haliaeetus lesion following acute or chronic blunt trauma.
leucocephalus). Periocular swelling was caused Injuries are often not confined to the eye and
756 Exotic Animals: Ophthalmic Diseases and Surgery

Figure 17.23 Eurasian eagle owl with traumatic


corneal perforation and secondary cataract of the
right eye.

Figure 17.22 Great horned owl with vitreal conjunctival masses, which required excision.
foreign body (feathers associated with traumatic Traumatic superficial corneal erosion/ulcera-
posterior segment perforation of the globe).
tion is the most commonly encountered cor-
neal lesion in raptors, especially in owls.
ocular injuries may be complex, involving the Interestingly, ulcers in raptors rarely become
external eye, and anterior and/or posterior seg- complicated by infection, nor do they develop
ments (Figure 17.23). Even bony scleral ossi- significant corneal vascularization. More
cles are subject to injury and fracture. Perhaps often, ulcers are complicated by persistence or
because of their relatively large eye size, fun- recurrence, which has been managed success-
dus evaluation is relatively easy in raptors; a fully with chronic (one to three months) pro-
high prevalence of posterior segment injuries phylactic antibiotic therapy, subconjunctival
has been found, including retinal edema, tears, antibiotic injection, or conjunctival pedicle
and detachment; intravitreal hemorrhage, flap. Penetrating keratoplasty was performed
especially surrounding the pecten; and perfo- on a California brown pelican to resolve axial
ration of the posterior segment. The tightly corneal scarring.
encased raptor globe – especially the tubular-­ Traumatic disorders of the eyelid such as
shaped globe of owls – is theorized to be par- laceration, gunshot wounds, or burns are occa-
ticularly predisposed to contrecoup injury sionally noted in large surveys of traumatized
following blunt ocular trauma. Compressive birds. Surgical repair of eyelid defects has been
forces may be easily distributed through the described, noting that the eyelid is thin, mak-
eye and transferred to the posterior segment. ing double-­layered closure impractical.
Secondary glaucoma occasionally results; Temporary partial tarsorrhaphy has been uti-
globe enlargement, if present, is usually subtle lized for prevention of exposure keratitis and
insofar as the rigid sclera probably limits the for protection of corneal or intraocular surgi-
extent of buphthalmos development. Sharp or cal sites. Eyelid disease not amenable to surgi-
penetrating ocular trauma to the eye is cal correction can lead to chronic exposure
observed less often than blunt traumatic inju- keratitis, necessitating modified evisceration.
ries and is most often associated with gunshot
injuries in raptors.
Penguins
Newly imported mynahs developed corneal
erosions associated with capture and cage Penguins (Sphenisciformes) are flightless birds
trauma. In most birds, the keratitis resolved that live in southern oceans and on their coasts.
uneventfully. Some mynahs developed chronic Penguins have a very small lacrimal gland and
keratoconjunctivitis with proliferative lack nasolacrimal ducts. They also have a
­Avian Ophthalmolog  757

supraorbital gland that extracts salt from the Humboldt (Spheniscus humboldti) are emme-
blood and excretes it in concentrated form in tropic in water and air. Spheniscus spp., which
the tears. This allows penguins to imbibe salt include African, Galapagos, Humboldt, and
water and live in both fresh and salt water envi- Magellanic penguins, do not have binocular
ronments. Aerobic bacteria normally inhabit vision. Penguin lenses are the most spherical
the corneal and conjunctival surfaces of salt lenses among birds and they are thought to
and fresh water penguins. The most commonly accommodate enough to compensate for loss
cultured bacteria from both populations of corneal refractive power in water. The only
were Corynebacterium spp., followed by ocular abnormality identified in this group of
Staphylococcus spp., and then Moraxella spp., penguins was cataracts (14% incidence).
Actinomyces canis, and others. Penguins have Abnormalities diagnosed in other penguins
eyes adapted for underwater vision. However, included chronic proliferative keratitis, cata-
they reproduce on land, so they must have ract stages ranging from incipient to hyperma-
functional aerial vision to find and protect their ture resorbed cataracts, and subluxated and
young from predators. Their eyes differ in completely luxated cataractous (Figures 17.24
shape from other diving and nondiving birds, and 17.25). Cataract surgery in penguins via
and it was suggested that a fourth shape cate-
gory be defined for penguins as quasi-­spherical.
The cornea is flattened, making the eye an
asymmetric sphere with all equatorial diame-
ters larger than the axial diameter. The eyes
also differ in vertical and horizontal measure-
ments. The vertical diameter is 85–89% of the
horizontal diameter at the equator.
The corneal endothelium of the Magellanic
penguin (Spheniscus magellanicus) is similar
to that of other vertebrates. Their pupils are
rapidly responsive; penguins were initially
thought to be myopic in air. More recent stud-
ies have found that the gentoo (Pygoscelis
papua), the rockhopper (Eudyptes crestatus), Figure 17.24 Right eye of a chinstrap penguin
the Magellanic (S. magellanicus), and the with a hypermature cataract and ectropion uveae.

(a) (b)

Figure 17.25 (a) Right eye of a chinstrap penguin pharmacologically dilated with topical rocuronium
bromide. Hypermature cataract and lens subluxation are present. (b) Right eye of a nondilated chinstrap
penguin with hypermature cataract. Note the clarity of the healthy nictitating membrane.
758 Exotic Animals: Ophthalmic Diseases and Surgery

phacoemulsification has been reported to be cetaceans, otters, sirenians (manatees and


effective. Intraoperative mydriasis may be dugongs), and polar bears. Pinnipeds include
achieved with intracameral administration of seals (phocids or true seals), sea lions and fur
atracurium. seals (otariids or eared seals), and walrus
(Odobenidae). Cetaceans include whales and
dolphins. Otters are typically Asian small-­
Enucleation and Evisceration
clawed river otters, North American river otters,
Several enucleation and evisceration tech- South American river otters, and sea otters.
niques have been described as a treatment for
end-­stage ocular disease or the chronically
Examination Techniques
painful eye. Enucleation in birds may be per-
formed by a lateral or transaural approach. In Many aquatic mammals under human care
owls specifically, their very large tubular eyes can be examined under behavioral control
may be more easily enucleated if the auricular without sedation, but otters are more likely to
skin fold bordering the external ear is tran- be examined during periodic general health
sected. In some birds, incision and collapse of examinations or anesthetized for examinations
the globe facilitate its removal. During enuclea- if needed. Polar bears (Ursus maritimus) are
tion, special care must be taken to avoid trac- evaluated from protected views such as behind
tion on the optic nerve; the fellow optic nerve glass or in back areas from a distance, or under
can be avulsed easily because of its close prox- anesthesia, but fortunately do not commonly
imity. In addition, careful hemostasis is neces- have eye problems. Limited time constraints
sary to prevent hypovolemia, shock, and death, for ophthalmic evaluation occur in many cases.
especially in small birds. Lethal oculocardiac However, it is possible to perform fluorescein
reflex has been reported. After removal of the staining, slit-­lamp evaluation, IOP measure-
globe, nictitans, conjunctiva, lacrimal and ment, tear production measurement in some
Harderian glands, and marginal eyelid skin, cases, and fundic examinations. Animals
closure is accomplished with one cutaneous known to bite may still be evaluated through
layer of absorbable or nonabsorbable suture. fencing or specially created areas where they
An alternative to enucleation is the modified can place their heads with their eyes near the
evisceration technique, in which the eyelid openings to allow slit-­lamp evaluation, fluores-
margins, conjunctiva, cornea, and intraocular cein staining, and tonometry. Specially made
contents are removed. The eyelids are then transparent plexiglass shields facilitate safe
closed in one or two layers of absorbable suture. examinations of unpredictable pinnipeds.
This technique avoids many of the possible
intraoperative complications associated with
Pinnipeds
enucleation, is associated with decreased anes-
thetic time, and preserves the symmetry of the Pinnipeds are carnivorous aquatic mammals
head. Evisceration with intrascleral prosthesis of the order Pinnipedia, which includes seals,
has been described in a great horned owl. sea lions and walruses. The word pinniped
means fin-­ or flipper footed which describes
these animals that have front or rear flippers.
­ arine and Other
M
Aquatic Mammals
Ocular Diseases
Marine mammals under human care and super- Eyelids/Periocular Region Diseases
vision, usually that of veterinarians specialized Eyelid diseases in pinnipeds include der-
in marine animal medicine, include pinnipeds, matopathies and traumatic injuries, including
­Marine and Other Aquatic Mammal  759

lacerations. The only species encountered so infections. Diffuse edema is present surround-
far with periocular skin lesions is the southern ing and throughout the obvious ulcer or non-
sea lion (Otaria flavescens), which develops debrided indolent lesion. Perilimbal edema is
intermittent skin lesions on all areas of the more apparent, and limbal pigmentation is
body, including the periocular areas. increased, sometimes crossing onto the adja-
cent cornea. In the advanced stage, the
Corneal Diseases medium-­sized lesion is deeper and larger and
Corneal diseases are one of the two main eye the diffuse edema typically encompasses most
problems that occur in both wild and captive of the cornea, with perilimbal edema still
pinnipeds. In one report, corneal disease was denser than the rest of the cornea but some-
the leading issue in California sea lions. This times difficult to distinguish.
was later confirmed by a survey that reported Successful treatment of OK requires appro-
an incidence of 64.6% in California sea lions priate management of the secondary bacterial
and other otariids. The most common eye or yeast/fungal infections. Doxycycline is often
problems seen in pinniped pups were corneal used for its anti-­inflammatory and healing
edema and nonspecific opacities, followed by properties. Doxycycline administered orally
ulcers. The most common concurrent systemic can be detected in the tear film of pinnipeds
abnormality identified was malnutrition. In and achieves concentrations likely to have anti-
yearlings, corneal ulcers were the most com- microbial and anti-­inflammatory effects at the
mon and, like pups, malnutrition was the most ocular surface. Collaboration with the facility
common concurrent systemic abnormality. veterinarian is important to address concerns
Corneal perforations and phthisis bulbi were for extended use of antibiotics and to investi-
the most common ocular findings, and gun- gate the possible factors that may impede heal-
shots the most common systemic abnormality. ing, such as resistant or new infections.
In subadults, phthisis bulbi was the most com-
mon eye problem, and in adults, corneal edema Walrus
and corneal ulcers were the most common eye Walrus under human care develops corneal
abnormalities. changes beginning at approximately 7–10 years
For decades, anterior segment disease has of age. Males appear to be affected more often
been observed in pinnipeds under human than females overall, but ocular problems in
care. Type of water (i.e., fresh or salinated) females are more concentrated during breed-
varies by facility. Most facilities around the ing season, whereas the males can have lesions
world now use some type of salinated water, year-­round but with more during breeding sea-
including synthetic ocean water such as son. Corneal lesions include diffuse gray-­white
Instant Ocean® or city water salinated to corneal opacities consistent with edema. With
approximate the salinity of the ocean (32–35 time, the lesions are denser and appear con-
parts per 1000). Problems with water quality sistent with fibrosis.
may not be apparent until the acute onset of
“otariid keratopathy” (OK) or acute edema in
Lens Disorders
pinniped species in one or more animals at
once. OK, characterized by a focal gray lesion, Cataracts are the other main eye problem that
is often not visible without proper magnifica- affects both wild and captive pinnipeds.
tion. Clinical signs of blepharospasm and epi- Cataracts are the most common eye problem in
phora occur when the lesion becomes phocids and are the second most common
ulcerated. Small fluorescein-­positive superfi- problem in otariids. The overall prevalence of
cial indolent ulcers at that location should be cataracts in harbor seals was 24%; harbor seals
treated to prevent opportunistic bacterial maintained in fresh water were three times
760 Exotic Animals: Ophthalmic Diseases and Surgery

more likely to develop cataracts than those in Unlike in most terrestrial mammals, topical
salt water. The most common clinical signs of mydriatics do not cause pupil dilation in pin-
uveitis in pinnipeds include corneal edema nipeds. The anatomy of the dilator muscle dif-
(already present with corneal problems) and fers from that in terrestrial mammals. It is
miosis (not always apparent due to normal perpendicular to the sphincter muscle and is
miosis in ambient light). In a recent retrospec- most robust near the iris base. In addition, the
tive study evaluating stranded pinnipeds from dilator muscle extends posteriorly over the
two Californian facilities, the incidence of cat- widened base of each ciliary process.
aracts was 0.77% overall in all age groups and Subconjunctival atropine partially dilated the
species. pupils of a fur seal for up to four days.
Cataract surgery in pinnipeds has been Improvements in general anesthesia in pinni-
described. These reports described phacoemul- peds, including participation of experienced
sification in two fur seals and a northern ele- anesthesiologists, have made cataract removal
phant seal pup and extracapsular cataract successful for clinically luxated lenses and
extraction in seals and sea lions. Generally, those not yet luxated. Overall, eyes without
phacoemulsification is most efficient in young luxation have better vision results because the
animals. corneas are not permanently damaged.
761

Section 5

Ophthalmic and Systemic Diseases


763

18

Neuro-­ophthalmology
Revised from 6th edition of Veterinary Ophthalmology, Chapter 36: Neuro-­ophthalmology, by Aubrey A. Webb and Cheryl L. Cullen

Neuro-­ophthalmology has emphasis on the direction) and may represent abnormalities of


animal’s head, the visual system, the cranial the visual pathway, as is seen sometimes in
nerves, and those diseases that affect both sys- Siamese, and other pointed-­coat colored cats.
tems. For this chapter, the material is presented Nystagmus may also be in a particular direction
based on the following: (i) basic neuroanat- and is described as being in the direction of the
omy; (ii) the neuro-­ophthalmic examination; fast phase of the ocular movement.
(iii) the neuro-­ophthalmic reflexes and their Spontaneous, pathological, nystagmus repre-
basic neuroanatomy; (iv) specific neuro-­ sents dysfunction of the vestibular system and
ophthalmic syndromes; and (v) diseases in may be either central or peripheral in origin.
selected animal species that present with both The central vestibular system is that portion of
ophthalmic and neurological clinical signs. the nervous system located within the central
nervous system (CNS) and includes the vestib-
ular nuclei and the vestibulocerebellum (i.e.,
­Neuro-­ophthalmic flocculonodular lobe and the fastigial nuclei of
the cerebellum). The peripheral vestibular sys-
Examination
tem neuroanatomically includes the bilaterally
located vestibular apparatus (i.e., the utricle,
The Distant Examination
saccule, and three semicircular canals within
Using careful observation of the patient from a the petrous temporal bone) and the vestibular
distance permits one to not lose site of the for- portion of the vestibulocochlear nerve.
est for the trees!
Strabismus
Nystagmus With respect to abnormalities of eye position
Upon first examining a patient from a distance, that can be determined during a distant exami-
it may be clearly evident that the patient exhib- nation, these can be the result of vestibular dis-
its nystagmus, strabismus, or inappropriate ease or a disease process involving the
pupil size(s). Nystagmus can be described as a extraocular muscles or the cranial nerves inner-
rhythmic and involuntary movement of the vating the extraocular muscles (cranial nerves
eyes. Nystagmus may be pendular (spontane- III, IV, and VI) (Figure 18.1). With respect to
ous ocular movements without predilection for vestibular strabismus, this is most often evident
a fast or slow movement in any particular when the patient’s head is held in extension.

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
764 Neuro-­ophthalmology

Dorsal rectus
(CN III)

Dorsal oblique
(CN IV - trochlear)

Lateral rectus Medial rectus


(CN VI - abducens) (CN III)

Ventral oblique
(CN III)

LATERAL (TEMPORAL) MEDIAL (NASAL)

Ventral rectus
(CN III)

Figure 18.1 Drawing illustrating the insertions of the various extraocular muscles on the globe of the eye,
and also indicates the innervation of the various muscles. Arrows indicate the direction of movement of the
eye with contraction of the respective muscle.

Normally, the eyes remain in a central position, sphincter muscle forms a ring around the
though animals with vestibular disease may pupillary margin. It has been shown that the
have a strabismus characterized by ventral stra- iris sphincter and dilator muscles receive
bismus ipsilateral to the side of the lesion. double reciprocal innervation by both the
sympathetic and the parasympathetic sys-
tems. Specifically, it has been shown that
Anisocoria and Pupil Size
cholinergic (parasympathetic) excitatory
Anisocoria, or unequally sized pupils, is a use- nerves causing contraction of the iridal
ful finding during the distant examination. sphincter work together with cholinergic
The presence of anisocoria, however, should inhibitory nerves to cause relaxation of the
be evaluated in conjunction with history, counteracting dilator muscles
pupillary light reflex (PLR) and vision testing. Interestingly, there are many differences
During the distant examination, anisocoria among various species of animals with regard
should be observed in normal ambient light to the ciliary ganglion and the ciliary nerves
(photopic) and in dim light (scotopic) condi- arising from it. Specifically, two short ciliary
tions. In so doing, it will become evident which nerves arise from the ciliary ganglion in the
eye is abnormal. cat. The lateral one is called the malar nerve;
In our common domesticated mammalian the medial one is called the nasal nerve. The
species, two groups of antagonistic muscles malar nerve innervates the lateral half of the
within the iris control pupil size, shape, and iridal sphincter muscle, and the nasal nerve
reaction to light. The dilator muscle consists innervates the medial half of the sphincter.
of smooth muscle fibers distributed radi- Meanwhile, the dog has five to eight short
ally throughout the iris. The smooth iris ciliary nerves. Therefore, parasympathetic
­Neuro-­ophthalmic Examinatio  765

denervation in the dog will cause pupillary (Figure 18.2). Because neurons in each PTN
dilation, while in the cat, lesions to either the send projections to the parasympathetic nuclei
nasal or the malar short ciliary nerves will bilaterally, both the right and the left pupils
result in sphincter hemiplegia and a D-­shaped will constrict in response to light stimulation
or reverse D-­shaped pupil, respectively. of either eye. Since the afferent PLR pathway
contains two levels of fiber crossings, first at
the optic chiasm and later after exiting the
Reflex and Response Testing
PTN, in most species the direct PLR is stronger
Prior to our discussion of reflex and response than the indirect one. More precisely, the direct
testing in neuro-­ophthalmology, it is likely PLR is stronger in those species that have more
important to provide a definition of reflex and than 50% decussation at the optic chiasm
how this differs from other stimulus responses. because it is assumed that the same percentage
A reflex is an almost instantaneous, transient, of fibers that cross over at the optic chiasm
predictable reaction to a given stimulus. A cross again between the PTN and the parasym-
reflex follows a typical reflex arc characterized pathetic nucleus at the tegmentum. In species
by some sensory receptor, an afferent neuron, such as birds, in which all the optic nerve fib-
one or more interneurons, and an efferent neu- ers cross over, there is no consensual
ron. Reflexes, unlike responses, are not learned PLR. However, in some avian species, a thin
and do not require input from “higher centers” interorbital septum separating the two eyes
in the brain. may allow light shone into one eye to pass
through and stimulate the contralateral retina,
Pupillary Light Reflex resulting in a pseudo-­indirect PLR.
The PLR is a reflex where after the retina is
stimulated by light a resultant constriction of
the pupil ipsilateral (direct PLR) and contralat-
Postganglionic
eral (indirect/consensual PLR) to the stimulus parasympathetic
results. The PLR is present as early as when the supply to iris
eyes are open after birth (10–16 days postna-
tally in puppies, 5–14 days postnatally in kit- Ciliary ganglion
tens), albeit PLRs may be initially sluggish and
may not react similarly to the adult until matu- Oculomotor nerve
(CN III)
ration of the retina is complete (28 days post-
natally in the puppy). The PLR is present
immediately after birth in foals. Pretectal nucleus
The afferent pathway of the PLR runs
through the cranial nerve II (optic nerve) to the
optic chiasm to synapse bilaterally on neurons Parasympathetic
nucleus of CN III
located in the pretectal nuclei (PTNs). These
nuclei are located in the transition zone
between the diencephalon and the midbrain.
Axons from each PTN relay to both the left and
the right parasympathetic nuclei of cranial
nerve III (oculomotor nerve), though the
majority of axons cross over and synapse in
the contralateral parasympathetic nucleus. The
parasympathetic nucleus of cranial nerve III is Figure 18.2 Drawing illustrating the
located in the tegmentum of the midbrain neuroanatomical pathway for the PLR.
766 Neuro-­ophthalmology

Swinging Flashlight Test less obvious, and possibly absent, when com-
The swinging flashlight test is done by moving pared to the ipsilateral eye. Importantly, ani-
a focal light source from the tested eye to the mals having facial nerve paresis or paralysis
opposite eye to check the direct and indirect may have a reduced or absent dazzle reflex on
light reflexes. In a clinically normal animal, the the ipsilateral side to the facial nerve lesion.
pupil that is not directly stimulated will par- The dazzle reflex is present as early as one to
tially constrict (due to the consensual reflex) two days postnatally in puppies and kittens.
and will then constrict further when it is Though the anatomical path of the dazzle
directly stimulated by the swinging flashlight. reflex has not been elucidated in animals, evi-
If the pupil dilates during direct light stimula- dence from the human literature suggests that
tion instead of performing the expected con- it is present when the optic nerve is intact to
striction, the swinging flashlight test is said to the level of the midbrain, and particularly to
be positive for the eye with the dilating pupil. reflex centers in the rostral colliculi and/or the
The Marcus–Gunn sign is the name ascribed to supraoptic nuclei of the hypothalamus (Figure
the pupillary reflex observed during a positive 18.3). The reflex also requires association fib-
swinging flashlight test. A positive swinging ers between these nuclei to the facial nuclei as
flashlight test is pathognomonic for unilateral well as intact facial nerves. The dazzle reflex is
retinal disease or unilateral prechiasmal optic particularly useful when the pupils cannot be
nerve disease (or both). Such a lesion does not observed to evaluate the PLR (e.g., in cases of
prevent the constriction resulting from the severe corneal edema or hyphema). Because
indirect PLR when the unaffected eye is stimu- the exact anatomical pathway of this reflex has
lated. However, when the flashlight is swung to not been described, this test should not be used
the affected eye, the loss of the indirect stimula- as the only tool for localizing subcortical
tion (combined with lack of direct stimulation) lesions in the visual pathway.
causes mydriasis. Therefore, this test is used to
differentiate lesions at these locations from
Menace Response
other neurological causes of anisocoria. The
swinging flashlight test is also considered to be The menace response is performed by making
positive if, as the light shifts from the normal to a threatening movement toward the eye being
the abnormal eye, the direct stimulus is no evaluated, remembering to not touch the
longer sufficient to maintain the previously patient or cause stimulation of the cornea or
evoked degree of pupillary constriction; there- eyelashes. An appropriate response is charac-
fore, both pupils dilate while maintaining the terized by the patient blinking, retracting their
relative anisocoria usually present in domestic globe, and/or turning their head away from
animals with optic nerve disease. A positive the menacing stimulus. As opposed to a sim-
swinging flashlight test should be followed by a ple reflex, the menace response is learned.
cover–uncover test done in a normal room light This response takes longer to develop com-
where the alternation of light stimulus is done pared to a simple reflex like the PLR and may
by using the examiner’s hand to cover and not be present for up to four weeks postnatally
uncover the examined eye. This test is done to in puppies and kittens, or 8 and 14 days post-
eliminate the influence of scatter illumination. natally in lambs and goat kids, respectively.
The menace response is not complete until
Dazzle Reflex (Photic Blink Reflex) two to three weeks.
This reflex is characterized by bilateral, partial The afferent component of the central vis-
eyelid blink in response to a very bright light ual pathway consists of optic nerve axons
shone into each eye separate. Closure of the projecting to the lateral geniculate nucleus
eye contralateral to the eye being stimulated is (LGN) as the optic tract, after having decussated
­Neuro-­ophthalmic Examinatio  767

Figure 18.3 Drawing illustrating the


postulated pathway of the dazzle
reflex – a subcortical reflex blink
associated with a bright light stimulus.

Muscles of blink

Pretectal nucleus

Parasympathetic
nucleus of CN III

Nucleus of Cajal

Facial nerve
Facial
nucleus

varying amounts (species dependent) at the functional integrity of additional neuroana-


optic chiasm (Figure 18.4). After having pro- tomical structures. In all domestic species, it
jected to neurons within the LGN, optic tract has been observed that diffuse cerebellar corti-
axons synapse on neurons within the LGN. In cal degenerative lesions cause bilateral absence
turn, LGN neurons project as the optic radia- of the menace response without any associated
tion to the visual cortex in the occipital lobe visual deficits or facial nerve dysfunction.
where an image is perceived (see Chapter 4).
From the visual cortex, the visual informa- Palpebral Reflex
tion is transmitted through communication The palpebral reflex is elicited by touching the
fibers to different regions of the cortex and skin of the lateral and medial canthi of the eye,
finally to the primary motor cortex, which separately, and observing an appropriate
initiates the efferent component of the men- response after each touch. An expected and
ace response. appropriate response is a blink of the eyelids
As suggested earlier, the menace response following a single touch. The portion of this
involves cerebral cortical integration and inter- reflex is via the ophthalmic and maxillary
pretation, and therefore is not a reflex. Rather, branches of cranial nerve V (trigeminal nerve)
it is a cortical response that requires the entire for medial and lateral canthus stimulation,
peripheral and central visual pathways, as well respectively. The efferent component of the
as the visual cortex and the facial nucleus of reflex is via cranial nerve VII (facial nerve).
cranial nerve VII, to be intact for the response The palpebral reflex is reportedly present as
to occur. early as two to four days postnatally in the
In addition to the neuroanatomical struc- puppy, and one to three days postnatally in the
tures required to elicit a positive menace kitten. Palpebral reflexes are present immedi-
response, the menace response requires ately after birth in foals.
768 Neuro-­ophthalmology

Figure 18.4 The visual pathways,


demonstrating how each side of the
visual field is represented within the
opposite occipital (visual) cortex. As
the degree of binocular vision in
different species decreases, a greater
proportion of optic nerve fibers
decussate at the optic chiasm.

Optic nerve
(CN II)
Optic chiasm

Optic tract
Lateral
geniculate
nucleus

Optic
radiations

Occipital
(visual) cortex

Corneal Reflex pattern also exists in humans. Those regions of


The corneal reflex is elicited by touching the the cornea that are less exposed to potential
surface of the cornea with a relatively nonin- injury (i.e., the dorsal and ventral corneal
jurious object (e.g., cotton-­tipped applicator regions near the lid margins) are the least sen-
or fiber from a Cochet–Bonnet esthesiometer) sitive. In diseases such as diabetes mellitus, it
and then observing an expected and appropri- has been demonstrated that corneal touch
ate eyelid blink. As with the palpebral reflex, threshold (CTT) is greater in diabetic com-
the afferent arm of this reflex is mediated via pared to nondiabetic patients. This implies
cranial nerve V (trigeminal), while the effer- that diabetes mellitus likely induces a diabetic
ent arm is mediated by the cranial nerve VII neuropathy involving the long ciliary nerve of
(facial). The cornea is highly sensitive to the cornea and these patients may be more
touch and painful stimuli. Branches of the prone to corneal injury.
long ciliary nerves enter the corneal stroma in
a radial manner from the sclera, episclera, Vestibulo-­ocular Reflex
and conjunctiva. and Physiological Nystagmus
In the dog, it has been demonstrated that the The vestibulo-­ocular reflex is a reflex that per-
central cornea is the most sensitive region, fol- mits stabilization of an image on the retina
lowed by the nasal and temporal cornea. This during movement of the head. Without an
­Neuro-­ophthalmic Examinatio  769

appropriate vestibulo-­ocular reflex, images patient’s vision. Numbers can also be assigned
would appear blurred. The vestibulo-­ocular to the various obstacles in the maze course;
reflex is present for rotational or translational therefore, the test results can be quantified.
movement of the head and assists in stabiliz-
ing images on the retina (as exemplified in the Visual Placing
above-­mentioned example). This reflex results In patients that are small enough, the animal is
in a rapidly adjusting movement of the eyes in held up, supporting its sternum and abdomen,
a direction opposite that of the direction of the and the patient is brought toward the edge of a
head movement. It is this alternation between flat hard surface. Importantly, the flat surface
slow and fast phases that comprises the nor- should be able to be seen by the animal. A nor-
mal physiological nystagmus that is evaluated mal response is for the animal to attempt to
clinically in veterinary medicine. Like the place its limbs on the top of the flat surface. If
example mentioned earlier, the vestibulo-­ an animal fails to attempt to place its limb on
ocular reflex is evaluated by inducing a physi- the surface, this implies that the surface was
ological nystagmus by rotating the patient’s not seen. One must keep in mind that the ani-
head in clockwise and counterclockwise direc- mal should be alert and strong enough to
tions. The expected and normal response is attempt to place its limb, however. It is impor-
that the patient will slowly move its eyes, rela- tant to recognize that the patient’s limb should
tive to the orbit, in a position opposite that of not touch the edge of the flat surface. Animals
the head being turned. A fast, compensatory, that are blind, without any evidence of other
movement of the eyes will occur toward the neurological disease, will attempt to step up
direction of the head rotation. when their limb makes contact with the edge
of the hard surface. When this happens, one is
evaluating tactile placing and not visual
Vision Testing
placing.
Obstacle Course (Maze Testing)
For obstacle course testing, the patient is
Schirmer Tear Testing
placed in an unfamiliar environment and
allowed to move freely. Within the environ- Though not traditionally considered a part of
ment, there are randomly placed objects that the neuro-­ophthalmic examination, quantita-
the patient must navigate through during their tive testing of tear production provides rele-
exploratory behavior. Obstacle course testing is vant information concerning the function of
performed in well lit (photopic) and dimly lit the parasympathetic nervous system.
(scotopic) conditions. In instances when the Specifically, measurement of aqueous tear pro-
patient is believed to have hemianopia, having duction can be done by way of the Schirmer
the patient navigate the obstacle course with tear test type I (see Chapter 4).
each eye separately blindfolded can be valua- The preganglionic parasympathetic neurons
ble. For canine patients who are seemingly responsible for lacrimal secretion originate
nervous, it is often times valuable to have the from the parasympathetic nucleus of the facial
owner present and calling the patient’s name nerve (i.e., the rostral salivatory nucleus)
on the side of the room opposite that of the located within the rostral portion of the
patient. The examiner watches for and notes medulla oblongata. The lacrimal gland’s
any evidence of the patient bumping into or preganglionic parasympathetic fibers run as
stumbling over objects, or signs of them being part of the facial nerve through the facial canal
apprehensive while navigating. If such behav- of the petrous temporal bone. Within the facial
iors happen consistently, this leads the exam- canal, some of these preganglionic fibers
iner to believe there is a problem with the branch off as the major (greater) petrosal
770 Neuro-­ophthalmology

nerve. The major (greater) petrosal nerve exits lesions of the parasympathetic and sympa-
the temporal bone and synapses on neurons thetic nervous systems, respectively. The basis
(postganglionic neurons) within the pterygo- for pharmacological testing, whether parasym-
palatine ganglion. With respect to lacrimal pathetic or sympathetic, relies upon (i) the
gland innervations, postganglionic parasympa- ability of neurotransmitter to be released from
thetic axons join with branches of the trigemi- the postganglionic neuron or (ii) the phenom-
nal nerve – the zygomatic nerve (a branch of enon of denervation hypersensitivity.
the maxillary nerve) and the lacrimal nerve (a
branch of the ophthalmic nerve). Both zygo- Parasympathetic Lesions
matic and lacrimal nerves innervate the lacri- In order to differentiate between pre-­and post-
mal gland and hence are important in tear ganglionic parasympathetic lesions, the fol-
production. As is hopefully apparent, some lowing series of tests can be attempted. The
instances of diseases affecting the trigeminal drugs used include the following:
nerve (e.g., trigeminal neuritis) may result in
●● Indirect parasympathomimetic drugs such as
reduced tear production.
physostigmine (anticholinesterase). This class
Another branch of the facial nerve (branched
of drug requires an intact postganglionic neu-
while still within the facial canal), the chorda
ron to induce miosis. The drug acts to extend
tympani, runs through the middle ear and also
the action of endogenous acetylcholine being
carries preganglionic parasympathetic fibers,
released at the neuromuscular junction by the
and these fibers join the mandibular branch of
postganglionic parasympathetic neuron.
the trigeminal nerve to ultimately synapse in
●● Direct-­acting parasympathomimetic drugs,
the submandibular and sublingual ganglia
such as pilocarpine. These drugs act on the
that, in turn, send postganglionic fibers to their
iris sphincter itself by binding to the acetyl-
respective salivary glands. Given that pregan-
choline receptor. These drugs will cause
glionic parasympathetic fibers run through the
miosis in both pre-­ and postganglionic
middle ear, it is possible for preganglionic
lesions. If the lesion is postganglionic, how-
fibers to become affected during diseases like
ever, there will be an upregulation in the
otitis media, thus resulting in neurogenic kera-
number of acetylcholine receptors at the
toconjunctivitis sicca (KCS).
postsynaptic membrane, resulting in dener-
Sensory innervation to the lacrimal gland is
vation hypersensitivity.
provided by the lacrimal nerve, the first branch
of the ophthalmic nerve after it enters the orbit
Sympathetic Lesions
through the orbital fissure. The nerve runs to
In order to differentiate between pre-­and post-
the lateral part of the orbit and gives branches
ganglionic sympathetic lesions, the following
to the lacrimal gland, to other deeper struc-
series of tests can be attempted. The drugs
tures, and then to the skin of the lateral can-
used include the following:
thus of the eye.
●● Indirect-­acting sympathomimetic drugs,
such as 1% hydroxyamphetamine. These
Pharmacological Testing
drugs will induce release of norepinephrine
In some instances, arriving at a neuroanatomi- from vesicles in the postganglionic neurons.
cal diagnosis, that is, identifying where along After application of one to two drops of 1%
the neuroanatomical pathway a lesion is hydroxyamphetamine, if the lesion is in the
located, one must provocatively test the nerv- central component (i.e., hypothalamospinal
ous system pharmacologically. Here, we pathway) of the sympathetic pathway or
describe the pharmacological approach to dif- along the preganglionic neuron, the pupil
ferentiating between pre-­ and postganglionic will dilate immediately and fully. If a lesion
­Neuroanatomical Lesion Localizatio  771

involves the postganglionic neuron, norepi- Horner’s Syndrome


nephrine cannot or will be minimally released,
Horner’s syndrome is that cluster of clinical
and therefore treatment will cause minimal
signs referable to the loss of ocular sympa-
or no dilatation of the pupil.
thetic innervation (Figure 18.5), and occurs
●● Direct-­acting sympathomimetic drugs, such
most frequently in the dog. Remember that the
as 0.001% epinephrine. Such a test is based on
sympathetic nervous pathway to the eye essen-
the fact that a lesion involving the postgangli-
tially involves presympathetic neurons from
onic neuron causes denervation hypersensi-
the brain to the sympathetic preganglionic
tivity of the smooth dilator muscle of the iris.
neurons located in the intermediolateral gray
The sensitized muscle will respond to low
matter of spinal cord segments T1–T3, and
concentrations of a direct-­acting sympatho-
finally postganglionic sympathetic neurons
mimetic drug that would be ineffective under
located in the cranial cervical ganglion.
normal conditions. For example, 0.001% epi-
Postganglionic sympathetic fibers innervate
nephrine (0.1 ml) will cause mydriasis within
the ciliary body, iris dilator and iris sphincter
20 min following topical administration to a
muscles (keep in mind reciprocal iris innerva-
denervated pupil. The same response will
tions), the smooth muscles of the periorbita,
take about 40 min to occur if the lesion is in
and Müller’s muscles of the upper and lower
the central part of the sympathetic pathway
eyelids. Normal sympathetic tone in these
(i.e., hypothalamospinal pathway) or if the
smooth muscles keeps the globe slightly pro-
lesion involves the preganglionic neuron.
truded, the palpebral fissure opened, the third
eyelid retracted, and the pupil partially dilated.
­Neuroanatomical When there is a disease process affecting the
sympathetic innervation, however, the follow-
Lesion Localization
ing signs are found with variable expression:
Localization of the lesion is, as previously ●● Miosis
stated, one of the most important steps in ●● Ptosis
reaching a diagnosis (Table 18.1). Without an ●● Enophthalmos
accurate neuroanatomical diagnosis, one will ●● Protruded third eyelid
be unable to formulate an appropriate differen- ●● Facial sweating (only in horses) (may see
tial diagnostic list or diagnostic plan. neck sweating if preganglionic lesion
involved) (see Figure 18.5)
Braund’s Syndromes ●● Hyperthermia of the facial area
●● Anhydrosis of the planum nasolabiale
Behavior can be defined as the motor and in cattle
autonomic manifestation of physiological ●● Hyperthermia of the ear (ruminants)
processes. Accepting this, and understanding
that various components of the nervous sys-
Cavernous Sinus Syndrome
tem are responsible for various behaviors,
though of course, the nervous system is very Cavernous sinus syndrome is that group of clin-
“plastic” and not “hard-­wired.” Arriving at a ical signs that refers to disease processes involv-
neuroanatomical diagnosis is key prior to for- ing the cavernous sinus (see Box 18.3). The
mulating a list of differential diagnoses. The cavernous sinus is a venous sinus located bilat-
list of Braund’s clinical syndromes includes erally on the floor of the middle cranial vault
the cerebral syndrome, dicephalic syndrome, and extending from the orbital fissure to the
unilateral vestibular disease, midbrain, and petro-­occipital canal. Each cavernous sinus is
others (Boxes 18.1–18.3 and Table 18.2). connected rostrally and caudally by rostral and
Table 18.1 Neuroanatomical location of various nuclei and ganglia important in neuro-­ophthalmology.

Entry/exit to/from the


Cranial nerve or brain nuclei Origination cranial vault Termination Function

Cranial nerve II (optic Retinal ganglion cells in Optic canal Lateral geniculate nucleus Vision
nerve) retina Rostral colliculi Afferent arm of PLR
Thalamic nuclei Afferent arm of menace
Note: variable decussation at the response
optic chiasm (species dependent)
Afferent arm of dazzle
reflex
Motor nucleus of cranial Tegmentum (floor) of the Orbital fissure Medial, dorsal, and ventral recti Ocular movements
nerve III (oculomotor midbrain muscles
nucleus) Caudal to PTN Ventral oblique muscle
Rostral to trochlear nucleus Levator palpebrae superioris
muscle
All ipsilateral to the nucleus
Parasympathetic nucleus Tegmentum (floor) of the Orbital fissure Ciliary ganglion Efferent arm of
of cranial nerve III midbrain PLR – pupillary
(Edinger–Westphal Caudal to PTN constriction via
nucleus) constriction of ciliary
Rostral to trochlear nucleus muscle of iris (sphincter
pupillae muscle)
Motor nucleus of cranial Caudal mesencephalon at Orbital fissure Dorsal oblique muscle on side Ocular movement
nerve IV (trochlear nerve) level of caudal colliculi opposite the location of the
nucleus
Caudal to oculomotor nuclei
Motor nucleus of cranial Rostral medulla oblongata Orbital fissure Lateral rectus and retractor bulbi Ocular movement and
nerve VI (abducens nerve) muscles ipsilateral to the nucleus retraction
Motor nucleus of cranial Pons at level of middle and Canal for the trigeminal Masseter, temporal, pterygoid, Motor to muscles of
nerve V (trigeminal nerve) rostral cerebellar peduncles nerve in petrous temporal rostral digastricus, and mylohyoid mastication
bone and then exits with muscles
the mandibular branch of
the nerve via the oval
foramen

0005300335.INDD 772 04-26-2022 13:20:06


Sensory ganglion of Neuron cell bodies of the Canal for the trigeminal Various somatic efferent nuclei Mandibular
cranial nerve V (trigeminal mandibular, ophthalmic, nerve in the petrous within the brainstem branch – sensory to cheek,
nerve) and maxillary branches are temporal bone Spinal tract of the trigeminal mandibular teeth, and
located in trigeminal nerve tongue
ganglion located in the canal Ophthalmic branch –
for the trigeminal nerve in sensory to orbit, medial
the petrous temporal bone part of upper eyelid, and
Receiving sensory dorsum of the rostral nose
information from the head Maxillary branch – sensory
to most of face, cheek,
lateral aspect of nose, and
lateral aspect of eyelids
Motor nucleus of cranial Rostral medulla oblongata Stylomastoid foramen via Muscles of facial expression Motor to muscles
nerve VII (facial nerve) the facial canal in the Caudal portion of the digastricus innervated
petrous temporal bone muscle
Parasympathetic nucleus Rostral medulla oblongata Preganglionic traverse in Preganglionic: synapse in Lacrimation
of cranial nerve VII the facial canal and exit pterygopalatine ganglion Nasal wetting
with the maxillary and Postganglionic: innervate lacrimal,
mandibular branches of palatine, and nasal glands
the trigeminal nerve
Cranial nerve VIII Pons and medulla oblongata Internal acoustic meatus Rostral, medial, lateral, and Coordinate eye, neck,
(vestibular portion) caudal vestibular nuclei trunk, and limb position
Minority to fastigial nucleus and with position and
flocculonodular lobe of the movements of the head
cerebellum Maintain balance
Lateral geniculate nucleus Diencephalon Not applicable Visual cortex (lateral, caudal, and Project visual information
medial aspects of the occipital from optic tracts to visual
lobe) cortex
Pretectal nucleus Mesencephalon Not applicable Bilateral projections to Maintenance of the PLR
parasympathetic nuclei of cranial
nerve III (Edinger– Westphal
nuclei)

0005300335.INDD 773 04-26-2022 13:20:06


774 Neuro-­ophthalmology

Box 18.1 Cerebral Syndrome Box 18.2 Midbrain Syndrome

Normal gait Spastic paresis/paralysis is observed to


Altered mentation (e.g., apathy, somnolence, involve one of the following:
depression, disorientation, lethargy, and coma)
Change in behavior (e.g., loss of trained
●● All four limbs
behaviors, forgetfulness [e.g., not recognizing ●● Limbs contralateral to the lesion
owner/surroundings], aggression, and
hyperexcitability) Increased spinal reflex response and
muscle tone in all limbs or limbs con-
Abnormal movements/postures (e.g., pacing,
wandering, circling, head pressing, and tralateral to the lesion
pleurothotonus) Postural reaction deficits in all limbs or
Postural reaction deficits in contralateral limbs limbs contralateral to the lesion
Alterations in vision (e.g., failed obstacle course Altered mentation (e.g., depressed,
and menace deficit contralateral to lesion with stuporous, and coma)
normal PLRs) Ipsilateral deficits of cranial nerve III
Seizures (oculomotor nerve)
±Papilledema ●● Ventrolateral strabismus
●● Mydriasis at rest with internal ophthal-
moparesis/paralysis
caudal intercavernous sinuses, respectively. ●● Ptosis
Neuro-­ophthalmically important structures
that are in close proximity to the cavernous Hyperventilation
sinus include cranial nerves III, IV, and VI, and ±Head pressing (i.e., obstinate
the ophthalmic and maxillary branches of cra- progression)
nial nerve V. In addition, postganglionic sympa- ±Bilateral miosis (i.e., after severe
thetic axons are also found near the cavernous cranial trauma; animals will become
sinus. It is this close association with the cav- mydriatic afterward)
ernous sinus, and the constellation of clinical
signs that are referable to these nerves’ dysfunc-
constant state of contraction. As such, the
tion, that this syndrome gets its name. It should
term hemifacial spasm is more aptly termed
be recognized also that cavernous sinus syn-
hemifacial tetany. Hemifacial tetany may
drome can be either unilateral or bilateral, albeit
manifest as primarily blepharospasm, ipsilat-
bilateral cavernous sinus syndrome is rarer. The
eral deviation of the nasal planum, ipsilateral
clinical signs found in cavernous sinus syn-
narrowing of the palpebral fissure, and ipsi-
drome typically include the following:
lateral elevated or caudal displacement of the
●● External and internal ophthalmoparesis ear. Other clinical neurological signs may
●● Ptosis occur concurrently, especially if there is
●● Mydriasis brainstem involvement. Disease processes
●● Reduced corneal sensation reported in dogs with hemifacial spasm
●● Reduced periorbital and nasofacial sensation include degenerative or neoplastic brainstem
●● ± Horner’s syndrome disease, and otitis media/interna. The clini-
cal signs of hemifacial tetany should not be
confused with chronic facial nerve paralysis
Hemifacial Spasm
with neurogenic atrophy and fibrosis of the
(Hemifacial Tetany)
facial muscles. In cases of chronic facial
The clinical sign of hemifacial spasm is nerve paralysis, these patients will have a
where the facial muscles on one side are in a diminished or absent palpebral reflex.
­Neuroanatomical Lesion Localizatio  775

of the affected pupil occurs. In cats with miotic


Box 18.3 Cavernous Sinus Syndrome
static anisocoria, the miosis does not respond
Cranial nerve Clinical signs to dark adaptation.
Hemidilated pupil is seen in cats and is char-
III (oculomotor) Mydriasis
including
acterized by a D-­shaped or reverse D-­shaped
Paralysis or paresis of pupil. The proposed pathophysiology of hemi-
parasympathetic
levator palpebrae,
fibers of cranial
dorsal rectus, medial dilated pupil is explained by a lesion involving
nerve III the malar (lateral) or nasal (medial) short cili-
rectus, ventral rectus,
and retractor bulbi ary nerves (Figure 18.6). Pharmacological test-
muscles ing with pilocarpine supports this notion.
IV (trochlear) Paralysis or paresis of
the dorsal oblique
VI (abducens) Paralysis or paresis of ­Neuro-­ophthalmic Diseases
the lateral rectus and
This section is divided into dog, cat, horse, and
retractor bulbi muscles
food animal. Within each of these categories,
V (ophthalmic Corneal anesthesia
we have further subdivided diseases into con-
branch)
genital, developmental, or acquired. Selected
Periorbital and medial
canthal anesthesia
diseases are presented, and the complete list is
available in the sixth edition of Veterinary
V (maxillary Periorbital and facial
branch) anesthesia Ophthalmology.
Postganglionic Horner’s syndrome –
sympathetic ptosis, enophthalmos, Congenital – Dog
miosis, and protruding
third eyelid Achiasmatic Sheepdog
An autosomal recessive defect resulting in lack
of decussation of the optic nerve (achiasmatic)
has been described in Belgian sheepdogs. In
Pourfour du Petit Syndrome
these dogs, all optic nerve axons from one eye
Pourfour du Petit syndrome is described in project directly into the ipsilateral optic tract.
humans as consisting of mydriasis, widened Nasal optic nerve axons (i.e., those that should
palpebral fissure, exophthalmos, and cool peri- have decussated) make synaptic contact in the
ocular skin with increased sweating. A similar LGN as though they had crossed at the chiasm.
condition has been described in cats having This results in noncongruent, mirror image
undergone flushing of the middle ear during maps of visual space in adjacent layers of the
diagnostic workup of middle ear disease. In LGN. Affected animals have pronounced hori-
these cats, anisocoria was noted with the zontal pendular nystagmus.
affected pupil being mydriatic with a brisk but
incomplete direct PLR, ipsilateral exophthal- Congenital Deafness
mia, and an enlarged palpebral fissure without and Vestibular Disease
evidence of third eyelid protrusion. Menace Congenital deafness and vestibular disease has
response and palpebral reflexes were normal. been described in the Doberman Pinscher. The
Mydriasis resolves within one week. condition is present at birth, is bilateral, and
affected puppies have varying degrees of neu-
rological impairment. Affected puppies will
Static Anisocoria (Spastic Pupil
tend to fall over and roll, may have a head tilt,
Syndrome) and Hemidilated Pupil
have a “bobble-­head” appearance, have wide-­
Static anisocoria describes a clinical sign seen head excursions, have evidence of vestibular
in cats where miosis, or less commonly mydriasis, ataxia, lack vestibulo-­ocular reflex, lack
776 Neuro-­ophthalmology

Table 18.2 Neuroanatomical localization of Horner’s syndrome.

First-­, second-­,
Neuroanatomical or third-­ Possible concurrent
location order disease clinical signs Potential causes

Brainstem First Altered level of consciousness Neoplasia


Abnormalities in Inflammatory (primary or
thermoregulation, eating, secondary)
drinking, breathing pattern, Vascular
and endocrine function Trauma
Cranial nerve abnormalities
Cervical spinal First Ipsilateral hemiparesis/ Neoplasia
cord paralysis
Tetraparesis/quadriplegia Trauma
Upper motor neuron signs to Ischemic myelopathy (e.g.,
all four limbs fibrocartilaginous
±Signs of neck pain embolism)
Intervertebral disc disease
T1–T3 spinal Second Lower motor neuron signs to Neoplasia
cord the forelimb(s)
Upper motor neuron signs to Trauma
the hind limbs
Upper motor neuron bladder Ischemic myelopathy (e.g.,
Upper thoracic back pain fibrocartilaginous
embolism)
Ipsilateral or bilateral loss of Intervertebral disc disease
cutaneous trunci reflex
T1–T3 ventral Second Lower motor neuron signs to Trauma to brachial plexus
nerve roots ipsilateral limb
Ipsilateral forelimb lameness Nerve sheath tumor
Ipsilateral loss of cutaneous
trunci reflex
Sympathetic Second Dysphagia Mediastinal mass
trunk Cough Trauma (e.g., intravenous
Lethargy injection and carotid
ligation for surgery in
horses)
Regurgitation
Cough
Reduced compressibility of
thorax
Middle ear Third Ipsilateral signs of peripheral Otitis media
vestibular disease Middle ear mass
Ipsilateral facial nerve Guttural pouch disease
paralysis
Ipsilateral KCS Trauma
­Neuroanatomical Lesion Localizatio  777

Table 18.2 (Continued)

First-­, second-­,
Neuroanatomical or third-­ Possible concurrent
location order disease clinical signs Potential causes

Cavernous sinus Third Internal, external, or complete Neoplasia


ophthalmoplegia Inflammatory disease
(primary or secondary)
Vascular disease (e.g.,
aneurysm)
Retrobulbar Third Signs of orbital disease (e.g., Neoplasia
exophthalmos and pain upon Abscess
opening mouth)
Involvement of one or more of Trauma
cranial nerves II, III, IV, V, and
VI

Figure 18.6 Right eye: D-­shaped pupil in miosis,


fibrinous exudate in the nasal inferior part of the
anterior chamber, and moderate rubeosis iridis
resulting from anterior uveitis.

postrotational nystagmus, and have significant


bilateral sensorineural hearing loss ranging
from profound elevations in hearing threshold
bilaterally to being bilaterally deaf. Cochlear
histopathology demonstrates complete degen-
eration of the organ of Corti. This condition is
Figure 18.5 Horner’s syndrome in a horse is inherited in an autosomal recessive fashion
characterized by profuse ipsilateral facial sweating. with a mutation in MYO7A on chromosome
778 Neuro-­ophthalmology

21. Approximately 13% of the population Canidae (e.g., dogs), Procyonidae (e.g., rac-
(n = 865) is carrier of the mutation. coons), Ursidae (e.g., bears), Mustelidae (e.g.,
ferrets and skunks), and Hyaenidae (e.g.,
Hydrocephalus hyaena). Acute ocular signs of CDV are usually
Hydrocephalus refers to increased amount of associated with a bilateral conjunctivitis with
cerebrospinal fluid (CSF) within the cranial serous ocular discharge that progresses to
vault. Congenital hydrocephalus is common in mucopurulent in nature. The palpebral con-
some breeds of dogs, with toy and brachyce- junctiva is primarily involved, but the cause of
phalic breeds at highest risk for the disease, this conjunctivitis may be difficult to diagnose
thereby suggesting a hereditary basis in many of if respiratory and gastrointestinal signs are
these breeds. The most common cause of con- either minimal or subclinical.
genital hydrocephalus is a primary congenital CDV often produces a multifocal, nongranu-
stenosis or aplasia of the mesencephalic aque- lomatous chorioretinitis, which is usually an
duct associated with fused rostral colliculi. incidental finding. In one study, dogs with
Congenital hydrocephalus may produce enlarge- neurological forms of CDV had a 41% overall
ment of the calvarium and failure of closure of prevalence of chorioretinal lesions; in contrast,
the suture lines of the skull. Consequently, 83% of dogs with chronic leukoencephalopa-
affected puppies may have a persistently open thy syndromes had chorioretinal lesions. These
fontanelle. Clinical signs of hydrocephalus lesions are typically multifocal, and they are
include behavioral changes, ataxia, and seizures. reportedly more frequent in the peripheral to
Ventrolateral strabismus is a common ocular midperipheral nontapetal fundus. Occasionally,
manifestation of congenital hydrocephalus due, chorioretinal lesions are diffuse, blinding, and
in part, to enlargement of the calvarium with may mimic the genetic syndrome of progres-
subsequent impingement on the orbits from the sive retinal atrophy, with diffuse tapetal hyper-
dorsolateral aspects. On relatively rare occa- reflectivity, optic nerve atrophy, and nontapetal
sions, hydrocephalus may produce papilledema. pigment dispersion.
The most dramatic clinical ocular problem
associated with CDV is optic neuritis, which is
Developmental – Dog characterized by an acute onset of bilateral blind-
Fibrosing Esotropia ness and mydriasis. If inflammation extends ros-
Fibrosing esotropia is a progressive esotropia trally to the optic disc/papilla, ophthalmoscopic
that is seen in juvenile large or giant breed signs of peripapillary hemorrhages and edema,
dogs affected by extraocular muscle myositis. retinal vascular congestion, and elevation of the
The disease is of unknown origin; it causes papilla are observed. If the optic neuritis remains
fibrosis of the medial rectus and dorsal oblique retrobulbar, however, the diagnosis is made on
muscles. The condition can be unilateral but the basis of exclusion [i.e., blind eyes with dilated
generally is bilateral, and there does not seem pupils and normal retinal function as tested by
to be a sex predilection. Affected animals may electroretinogram] (ERG). The optic neuritis
have impaired vision due to the severity of the syndrome may be isolated, prodromal, or concur-
esotropia. Surgical correction may restore eye rent with other neurological signs of
position and vision in some patients. CDV. Distemper-­associated blindness also may
occur with inflammation of the optic tracts,
LGN, optic radiation, or occipital cortex.
Acquired – Dog
Ocular signs are suggestive of, but not defini-
Canine Distemper tive for, CDV. Acute lesions of chorioretinitis
Canine distemper virus (CDV) infects a wide usually correlate well with concurrent sys-
variety of families of animals, including temic disease, but chorioretinal scars may not.
­Neuroanatomical Lesion Localizatio  779

Alternatively, positive immunofluorescence by (ii) focal, or (iii) ocular. In the last form, GME
detection of viral antigen from conjunctival may involve the optic nerves, thus producing a
swabs/scrapings or blood smears, using meth- syndrome of acute blindness, papilledema, reti-
ods such as fluorescent antibody testing, may nal and peripapillary hemorrhages, and, occa-
be helpful in diagnosing CDV early in the sionally, extension into the globe, which in
course of systemic disease (5–21 days postin- turn produces retinal detachments and retinal
oculation), but negative findings are inconclu- infiltrates.
sive. Acute optic neuritis is treated with Treatment involves aggressive use of immu-
systemic anti-­inflammatory dosages of gluco- nosuppressive levels of corticosteroids with or
corticoids if other signs of CDV are absent. without radiation therapy or immunosuppres-
Vaccination is the key to preventing CDV. The sion, using a combination of corticosteroids
prognosis for dogs with neurological disease is with one or more of cytosine arabinoside,
considered guarded to poor. azathioprine, leflunomide, or cyclosporine
A. Prognosis for survival varies from weeks to
Idiopathic Facial Nerve Paralysis years, but clinical signs progress and dogs will
The cause of idiopathic facial nerve paralysis is succumb to the disease.
unknown, though it shares clinical features of
Bell’s palsy in humans. Facial nerve paralysis Myasthenia Gravis
has been found to be idiopathic in 75% of dogs, Myasthenia gravis is a disease affecting the
while 25% of cases of facial nerve paralysis are neuromuscular junction. Myasthenia gravis is
due to conditions such as otitis media/interna either congenital or acquired. Congenital
and hypothyroidism. An important feature of myasthenia gravis occurs when there is a func-
this condition is that patients with idiopathic tional disorder or depletion of nicotinic acetyl-
facial nerve paralysis do not have signs of ves- choline receptors. Congenital myasthenia
tibular dysfunction. Prognosis is variable with gravis is inherited as an autosomal recessive
idiopathic facial nerve paralysis. Some patients trait in Smooth Fox Terriers, Jack Russell
may have return of facial function within Terriers, and English Springer Spaniels.
weeks to months or never. Clinical signs associated with congenital myas-
thenia gravis include generalized muscle
Meningoencephalitis weakness that worsens with exercise, possible
of Unknown Etiology megaesophagus, facial weakness, and tendon
Granulomatous meningoencephalitis (GME) is reflexes that weaken with repeated testing. It is
an idiopathic nonsuppurative meningoenceph- also possible, as has been reported in the
alomyelitis seen in dogs. Histopathologically, acquired form, that facial weakness, including
GME is characterized by perivascular cuffing a weakened palpebral reflex, may be observed.
with mononuclear cells. Proposed pathogene- Diagnosis of congenital myasthenia gravis
ses for GME have included a primary immune-­ requires detailed histopathological, immuno-
mediated phenomenon, precancerous form of histopathological, and ultrastructural exami-
lymphoma, and various infectious etiologies. nation of skeletal muscle neuromuscular
The disease is typically seen in young small junctions. Prognosis for dogs with congenital
breeds, although any breed or age of dog may myasthenia gravis is poor in most instances.
be affected. GME is characterized typically by
neurological signs suggestive of multifocal CNS
Neoplasia – Central
lesions that, at least temporarily, are responsive
Nervous System
to systemic corticosteroids or other immuno-
suppressive therapies. GME is described as being Intracranial neoplasia, whether primary or
one of three types, namely (i) disseminated, secondary, often produces ocular and/or
780 Neuro-­ophthalmology

orbital signs. All animals with a suspected nasal mucosa). Regardless of the cause of
space-­occupying CNS lesion should undergo neurogenic KCS, patients with primary
ophthalmoscopy to determine whether neurogenic KCS are unlikely to respond to
papilledema, optic neuritis, or optic nerve atro- immunomodulating drugs such as cyclo-
phy is present. The neuro-­ophthalmic signs sporine. However, denervation hypersensi-
associated with intracranial neoplasia are tivity occurring after postganglionic lesions
highly variable and dogs may present with makes patients with neurogenic KCS respon-
signs as subtle as internal ophthalmoparesis as sive to direct-­acting parasympathomimetic
the predominant clinical sign or with ophthal- drugs (oral pilocarpine).
mic signs associated with abnormalities of
multiple cranial nerves and abnormal changes
Congenital – Feline
in mentation and/or gait. Intracranial neopla-
sia frequently produces visual deficits and Visual System Anomalies and Forms
papilledema in association with neurologi- of Albinism
cal signs. Visual system abnormalities associated with
forms of albinism have been reported in ani-
Neurogenic Keratoconjunctivitis Sicca mals for years. A commonly studied model is
KCS is a progressive inflammation of the cor- the Siamese cat, demonstrating a form of par-
nea and conjunctiva caused by neurogenically tial albinism with retinal hypopigmentation.
derived tear production deficiency. Lesions In particular, Siamese cats possess a mutant
anywhere along the efferent path, including allele of the albino series at the C locus (chch).
the parasympathetic nucleus of the facial Siamese cats, therefore, have reduced ocular
nerve, the main trunk of the facial nerve, pigmentation, including a lack of stromal pig-
geniculate ganglion, major petrosal nerve, the mentation of the iris or choroid, and a reduc-
nerve of the pterygoid canal, the pterygopala- tion in pigment of the iridal and retinal
tine ganglion, or the postganglionic parasym- pigment epithelia.
pathetic fibers, will reduce tear production and The abnormal retinogeniculate projections
result in neurogenic KCS. in Siamese cats were first described in 1969.
Lesions to the preganglionic parasympa- Siamese cats have reduced ipsilateral retinal
thetic fibers may be caused by otitis (media or projections since many axons originating in
interna) or by petrositis (i.e., inflammation of the temporal retina that normally project ipsi-
the petrous temporal bone). In such cases, the laterally project contralaterally in Siamese
reduced tear production may be accompanied cats. As a consequence, each LGN contains an
by signs of facial paralysis and Horner’s syn- abnormally greater representation of the ipsi-
drome if the adjacent facial nerve motor neu- lateral visual field. Convergent strabismus
rons or sympathetic fibers are involved. with or without involuntary horizontal or
Neurogenic KCS may also present without rotary nystagmus is a possible ocular manifes-
signs of facial paralysis if the major petrosal tation as a result of this retinogeniculate misdi-
nerve is damaged distal to the geniculate gan- rection (Figure 18.7).
glion of the facial nerve.
Preganglionic parasympathetic denervation
Developmental – Feline
can also occur due to erosive lesions involving
the floor of the middle fossa of the skull and Chediak–Higashi Syndrome
affecting the major petrosal nerve. In such Chediak–Higashi syndrome (CHS) is an autoso-
cases, the trigeminal nerve may frequently be mal recessive disorder of cats and other species.
involved, and the KCS will be accompanied by In cats, CHS is characterized by partial oculocu-
facial anesthesia and xeromycteria (i.e., dry taneous albinism, increased susceptibility to
­Neuroanatomical Lesion Localizatio  781

Feline Leukemia Virus


Anisocoria or dyscoria may arise due to neuro-
logical effects of feline leukemia virus (FeLV)
on the ciliary ganglia and short ciliary nerves
of affected cats. Alternatively, dyscoria may
result from lymphocytic infiltration of the cili-
ary body and iris. In particular, spastic pupil
syndrome, involving a static anisocoria during
dark adaptation, has been reported in FeLV-­
positive cats. These cats are positive for FeLV
but may have no other clinical signs. C-­type
viral particles have been identified in the cili-
Figure 18.7 Photograph of Siamese cat with ary ganglia and short ciliary nerves of these
congenital esotropia related to coat color (Emery). cats, however, which is suggestive that the
virus has invaded these nerves. The prognosis
infections, and bleeding tendencies. To date, for long-­term survival in these cats is poor.
CHS has only been reported in the Persian
breed. Ocular manifestations of CHS in cats Fluoroquinolones
include photophobia, pale irides, hypopigmen- The fluoroquinolones are a group of antibiot-
tation of the nontapetal fundus, tapetal degen- ics frequently used in the treatment of infec-
eration, cataracts ranging from incipient tious diseases in cats. Rarely (1 in 122 414
posterior suture-­line associated to mature cata- treated cats), an acute and typically irreversible
racts, and spontaneous nystagmus. retinal degeneration develops. The involved
fluoroquinolones include enrofloxacin, mar-
bofloxacin, and orbifloxacin. For more infor-
Acquired – Feline
mation, see Chapter 19.
Dysautonomia (Key–Gaskell or Dilated
Pupil Syndrome) Nictitating Membrane Protrusion
Feline dysautonomia, which is also known as Idiopathic bilateral protrusion of the feline
Key–Gaskell or dilated pupil syndrome, was nictitating membranes is a common, poorly
first reported in England in 1982. The disease, understood ophthalmic disorder. Retraction of
which produces widespread autonomic nerv- the nictitating membranes following instilla-
ous system dysfunction, has since been tion of topical adrenergic drugs, in affected
reported in many cats throughout Europe, but cats, is suggestive of a loss of sympathetic
the number of documented cases in the United innervation such as that seen in Horner’s syn-
States remains small. The cause of dysautono- drome; however, other ophthalmic signs of
mia has not been determined. Horner’s syndrome are absent. Cats with this
Common systemic signs of feline dysautono- syndrome have normal intraocular structures,
mia include general malaise, dehydration, and vision is unaffected unless the nictitating
reduced apetitie or anorexia, dysphagia, vomiting membranes protrude to the extent that they
or regurgitation, xerostomia, bradycardia, cover the pupil. Affected cats often have con-
urinary bladder distention, and constipation. current watery diarrhea that precedes nictitat-
Ocular signs that have been reported most ing membrane protrusion. Some cats may have
consistently include dilated unresponsive diarrhea for weeks. Many cats, however,
pupils, decreased tear production, and protrud- recover from diarrhea quickly, yet will still
ing nictitating membranes. Vision is unaf- have nictitating membrane protrusion. A Tora-­
fected, and photophobia is variable. like virus has been isolated from the feces of
782 Neuro-­ophthalmology

several affected cats in England. In that study, signs include aggression, head pressing,
17 of 45 cats had nictitating membrane protru- blindness, paralyzed tongue and pharynx,
sion for more than four weeks, and 16 of 41 nystagmus, strabismus, and pupillary dilata-
cats had diarrhea for more than four weeks. tion. Diagnosis of equine viral encephalomy-
The prognosis for this condition is good. The elitis is made based upon time of year (are
diarrhea and nictitating membrane protrusion mosquitos present?), consistent clinical signs,
are self-­limiting, although clinical signs may rising serum antibody titers, and, in acute
be long-­lasting cases, isolation of the virus from CSF or
demonstration of the virus using reverse
Neoplasia – Central Nervous System transcriptase-­polymerase chain reaction (RT-­
Blindness associated with intracranial neopla- PCR). Treatment is nonspecific and support-
sia has been reported in cats. In a series of 36 ive in nature. The mortality rate is high, but
cats with meningiomas, blindness or visual horses can recover from viral encephalitis
field deficits were found in 7 cats. Six of these
seven cats had unilateral visual deficits, Equine Protozoal Myeloencephalitis
whereas the remaining cat was completely Equine protozoal myeloencephalitis (EPM) is a
blind, with dilated pupils from compression of multifocal, progressive disease of the CNS
the optic chiasm by a third ventricle meningi- caused by infection with Sarcocystis neurona.
oma. Six cats also had positional nystagmus, The disease has been reported only in horses
and one cat with tentorial herniation had ani- born and raised in the Americas, including
socoria, with the smaller pupil being contralat- Canada, United States, Brazil, and Panama,
eral to the tumor with young horses being affected more than
older horses and a breed predilection for
Standardbred, Thoroughbred, and Quarter
Equine – Congenital
Horses. The parasite causes inflammation and
Congenital Stationary Night Blindness necrosis of the caudal brainstem and spi-
A condition long thought to be related to the nal cord.
incompletely dominant leopard spotting (LP) Clinical signs include ataxia, tetraparesis,
allele is congenital stationary night blindness head tilt, facial paralysis, circling, nystagmus,
in Appaloosa horses. The condition is nonpro- and blindness (with or without pupillary light
gressive; affected animals have cautious behav- abnormalities). Horner’s syndrome has also
ior in dim light conditions and may be difficult been seen in horses with EPM. Diagnosis of
to train. Neuro-­ophthalmic signs may include EPM is made based upon demonstrating anti-
bilateral dorsomedial strabismus, spontaneous ­S. neurona antibody titers within the CSF,
nystagmus, and a dark-­adapted ERG lacking immunohistochemical detection of parasites
a b-­wave. in the CNS, and detection of S. neurona DNA
by PCR in conjunction with consistent clini-
Equine Viral Encephalomyelitis cal signs.
Viruses of the family Togaviridae are insect-­
transmitted and cause encephalitis in the West Nile Virus
horse. The most pathogenic of these viruses West Nile virus (WNV) is single-­stranded RNA
are called alphaviruses, and these include virus of the family Flaviviridae that is main-
eastern, western, and Venezuelan equine tained in the environment by a bird–mosquito
encephalomyelitis viruses, all of which occur relationship. Birds are the reservoir host, while
in the Americas. Early clinical signs, regard- mosquitos transmit the virus to a variety of
less of the type of virus, include fever, stupor- animal species, including birds, horses, cats,
ous state, ataxia, and hyperesthesia. Later dogs, bats, alligators, and humans. Horses are
­Neuroanatomical Lesion Localizatio  783

similar to humans in that they are considered Brown, and Jersey breeds of cattle. The condi-
dead-­end hosts (cannot transmit the disease), tion is characterized by a progressive, bilater-
although transfusion of infected blood prod- ally convergent strabismus and mild to severe
ucts can result in transmission of the disease to exophthalmos. Affected animals can become
the recipient. blind due to severe strabismus. Clinical signs
Clinical signs in horses include ataxia, paresis, are first noticed as early as six months of age,
generalized muscle fasciculations, pyrexia, or much more commonly just prior to an ani-
hyperesthesia, general malaise, lip droop, bruxism, mal’s first breeding.
circling, and animals may be recumbent. With
regard to ophthalmic manifestations of
Food Animals – Acquired
WNV infection, horses may be blind and
have facial nerve paralysis, mild keratitis of Bovine Virus Diarrhea
undetermined cause, and protrusion of the Bovine virus diarrhea (BVD) results from a pes-
third eyelid. tivirus with a worldwide distribution that
Diagnosis of WNV infection is made based infects cattle, sheep, goats, and wild ruminants.
upon determining IgM concentrations in the In cattle, in utero infection with BVD virus
serum and/or CSF, amplifying WNV DNA between 76 and 150 days of gestation may result
using PCR, or isolating the virus. Therapy for in congenital defects of the eye and brain. In
WNV infection involves supportive care and addition, following experimentally induced
administering systemic anti-­inflammatory BVD infection, persistently infected calves have
drugs to reduce cerebral edema. Prognosis is minor skeletal abnormalities, including short
variable. Older horses, horses not vaccinated limbs, narrow skull with bulging eyes, and/or
for WNV, and horses that are recumbent are prognathism. Ocular lesions of cataracts, reti-
more likely to succumb to the disease. nal degeneration and retinal dysplasia, optic
Specifically, up to approximately 80% of WNV-­ nerve gliosis, optic neuritis, and microphthal-
infected and recumbent horses will succumb mia have also been described with experimen-
to the disease. tally induced disease. Diagnosis of BVDV is
confirmed based upon the demonstration of
the virus via microtiter virus isolation or sand-
Food Animals – Congenital
wich ELISAs using serum.
Pendular Nystagmus
Benign pendular nystagmus has been reported Bracken Fern Poisoning
in Holstein, Jersey, Ayrshire, and Guernsey (Bright Blindness)
breeds of cattle. The condition is characterized Ingestion of bracken fern (Pteridium aquili-
by vertical, horizontal, or rotary pendular nys- num) in chronic, low-­level amounts has been
tagmus (i.e., spontaneous nystagmus occur- suspected of causing the syndrome of bright
ring with no clear fast or slow phase). The blindness among sheep and cattle in the United
condition is presumed inherited, though this Kingdom. The syndrome manifests as a retinal
has not been confirmed. degeneration with blindness. Retinal lesions
are most severe centrally and involve degener-
ation of the rods and cones. Ophthalmoscopic
Food Animals – Developmental
findings include retinal vascular attenuation,
Bilateral Convergent Strabismus tapetal hyperreflectivity, and optic nerve atro-
with Exophthalmos phy. The active chemical in bracken to cause
Bilateral convergent strabismus with exoph- progressive retinal degeneration following
thalmos is an inherited disease affecting Pteridium sp. ingestion is ptaquiloside, a carci-
German Fleckvieh, German Holstein, German nogenic norsesquiterpene.
784

19

Ocular Manifestations of Systemic Disease


Revised from 6th edition of Veterinary Ophthalmology, Chapter 37, Parts 1 (Canine), 2 (Feline), 3 (Equine), and 4 (Food Animals): Ocular
Manifestations of Systemic Disease, by Aubrey A. Webb and Cheryl L. Cullen

­Introduction For the purposes of this chapter, ocular man-


ifestations of systemic disease include any dis-
Ocular examination of animals with systemic order not of primary ocular origin that
disease is an essential diagnostic component of manifests as ocular clinical signs. Selected sys-
a complete physical examination that can help temic diseases have been categorized accord-
reduce the list of probable differential diagno- ing to species (dog, cat, horse, and food
ses and can assist in organizing such a differ- animals), stage of onset (congenital, develop-
ential diagnostic list from most to least likely. mental, or acquired), and have been alphabeti-
In addition, the visual prognosis for the animal cally arranged according to the mechanism
may be crucial to owners when deciding how and/or cause of the systemic disease.
aggressively they wish to pursue diagnostic
and therapeutic alternatives. Often, the
changes in the disease can be monitored by Section I: Dogs
ophthalmic examination and assist in adjust-
ments in medications as the animal recovers. ­Congenital
Diseases affecting the vascular and nervous
systems are particularly prone to ocular mani- Coat Color-­Related Diseases/
festation. Inspection of the uvea and retina, Conditions in Dogs
and optic disc of the animal through the trans-
Complete albinism (complete lack of pigmen-
parent cornea, lens, and neurosensory retina
tation) or partial or localized albinism (an
permits evaluation of both the peripheral vas-
absence or reduction in the degree of pigmen-
culature and central nervous system (CNS),
tation) is associated with not only the pheno-
respectively. Since the rate of ocular blood flow
typic appearance of an animal’s coat and skin
is very high, there is increased likelihood that
color, but also conditions affecting the ear and
the uveal and retinal vasculature will be
eye (Table 19.1). Albinism or partial albinism
exposed to, and possibly filter out, hematoge-
may result from the failure of migration of
nously spread neoplastic cells and/or infec-
neural crest cells (precursors to melanocytes)
tious organisms.

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
­Congenita  785

Table 19.1 Coat color-­related diseases/conditions


in dogs.

Coat color genetics complicated in the different


canine breeds. S-­gene (white spotting gene)
determines body pigmentation pattern and has
identified more specifically as the microphthalmia-­
associated transcription factor (MITF). It has four
alleles: the dominant S allele, and the recessive si
(Irish spotting), sp (piebald), and sw (extreme-­
white piebald) alleles.
Animals homozygous for the recessive S-­alleles
are predisposed to developing congenital
sensorineural deafness. Dalmatian, English Setter,
and English Cocker Spaniel affected.
Another gene known as the M-­gene or merle gene
has both a dominant (M) and a recessive (m) allele
and is associated with deafness and ocular
abnormalities in Collies, Shetland Sheepdogs,
Great Danes, and Long-­Haired Dachshunds;
heterozygote ([Mm] – merle colored) animals can
be predisposed to unilateral or bilateral inner ear
defects resulting in deafness.
Figure 19.1 Clinical presentation associated with
Dogs homozygous for the dominant merle allele oculoskeletal dysplasia, including forelimb varus
([MM] – typically have more white than defects. Inset demonstrates hyphema secondary to
heterozygotes, or may be completely white) are retinal detachment.
typically deaf, microphthalmic eyes with multiple
defects and often visual problems, and may be
sterile.
red merle Australian Shepherd has been stud-
ied rather extensively, and the mode of inherit-
and hence results in reduced numbers of mel- ance for the ocular lesions in the merle dog has
anocytes in a nonpigmented area, or may result been demonstrated to be a recessive trait with
because of impaired production of pigment incomplete penetrance.
due to some intrinsic deficiency in melanin
production (e.g., tyrosinase deficiency), but Dwarfism (Skeletal
where the number of melanocytes in nonpig- Dysplasia–Osteochondrodysplasia)
mented or hypopigmented areas is normal.
Inherited sensorineural deafness and ocular These forms of skeletal dysplasia have been
abnormalities have been linked to coat color described in several breeds of dogs as a syn-
genes in many breeds of dogs. Hearing loss drome of short appendages with a normal axial
related to coat color in dogs typically results skeleton (i.e., short-­limbed dwarfism) and ocu-
from cochleosaccular degeneration and can be lar lesions, so-­called ocular–skeletal dysplasia,
associated with the absence of pigment within have been recorded as being inherited in the
the stria vascularis of the cochlea. Coat color is Labrador Retriever and the Samoyed
often associated, not only with deafness, but (Figure 19.1).
also with heterochromia irides, blue irides, The complete phenotype in both breeds is
and lack of retinal pigment. Coat color genet- transmitted as an autosomal recessive trait,
ics soon becomes complicated when one con- while ophthalmoscopic findings have indi-
siders all of the combinations and permutations cated a semidominant mode of inheritance in
of coat colors seen in the numerous breeds of which skeletally normal, heterozygous dogs
dogs that have been developed. The blue and can have no ophthalmoscopic abnormalities or
786 Ocular Manifestations of Systemic Disease

multiple retinal folds, vitreal membranes, or (Figure 19.2). Consequently, affected puppies
vitreous degeneration. Syndrome in the may have a persistently open fontanelle.
Labrador Retriever was felt to be recessive for
the skeletal lesions and incomplete dominant
Myasthenia Gravis
trait for the ocular lesions. The causative locus
in ocular–skeletal dysplasia of the Labrador Myasthenia gravis affects the neuromuscular
Retriever has been termed drd1 and it is junction, and may be either congenital or
mapped to canine chromosome 24, and an acquired. Congenital myasthenia gravis occurs
insertional mutation in exon 1 of the gene when there is a functional disorder or deple-
COL9A3 cosegregates with the disease. tion of nicotinic acetylcholine receptors.
The Samoyed syndrome of ocular–skeletal Congenital myasthenia gravis has rarely been
dysplasia is an autosomal recessive trait. In reported in dogs. Congenital myasthenia gravis
particular, the causative locus in ocular–skele- is inherited as an autosomal recessive trait in
tal dysplasia of the Samoyed has been termed Smooth Fox Terriers, Jack Russell Terriers, and
drd2 and it is mapped to canine chromosome English Springer Spaniels. Clinical signs asso-
15 and cosegregates with a 1267-­bp deletion ciated with congenital myasthenia gravis
mutation in the 5′ end of COL9A2. include generalized muscle weakness that
worsens with exercise, possible megaesopha-
gus, facial weakness, and tendon reflexes that
Hydrocephalus in Dogs
weaken with repeated testing.
Hydrocephalus in dogs is defined as increased
amount of cerebrospinal fluid (CSF) within
Quadriplegia and Amblyopia
the cranial vault (Table 19.2). Most common
cause of congenital hydrocephalus is a primary A syndrome of decreased vision with nystag-
congenital stenosis or aplasia of the mesence- mus, ataxia, and tremors has been described in
phalic aqueduct associated with fused rostral the Irish Setter. This syndrome is thought to be
colliculi. Congenital hydrocephalus may pro- inherited as a postnatally lethal, autosomal
duce enlargement of the calvarium and failure recessive trait. Most animals, however, are
of closure of the suture lines of the skull unable to stand at birth, though walking move-
ments are made that propel them in a “seal-­
like” manner when prone. Vision is difficult to
Table 19.2 Hydrocephalus in dogs. evaluate in a very young animal, but those

Congenital hydrocephalus common in some


breeds of dogs, with toy and brachycephalic breeds
at highest risk.
Clinical signs include behavioral changes, ataxia,
and seizures. Ventrolateral strabismus is a
common ocular manifestation of congenital
hydrocephalus due, in part, to enlargement of the
calvarium with subsequent impingement on the
orbits from the dorsolateral aspects. This
consequently pushes the eyes in a ventrolateral
direction and produces a “sunset” appearance to
the corneas (Figure 19.2).
Congenital hydrocephalus may cause cranial
nerve compromise and subsequent ventrolateral
strabismus. On relatively rare occasions, Figure 19.2 Congenital hydrocephalus in a toy
hydrocephalus may produce papilledema. breed with “sunset eyes.” The calvarium is pushing
the globes ventrolaterally.
­Developmenta  787

affected lack fixation responses as well as men-


ace responses and dazzle reflexes. The pupil-
lary light reflexes (PLRs) are normal. The
ocular fundus is normal on fundic examina-
tion. CNS lesions include degeneration and
necrosis of the cerebellar cortex, with severe
loss of Purkinje cells.

­Developmental

Inborn Errors of Intermediary Metabolism


Several inborn defects have been reported in
the dog. They are relatively rare, but offer mod-
els for similar metabolic errors in man. These
Figure 19.3 Fundus photograph of NCL-­affected
include (i) tyrosinemia from a deficiency in Polish Owczarek Nizinny dog at 18 months of age.
hepatic tyrosine aminotransferase and (ii) stor- Note the generalized grayish to brown spots, the
age diseases characterized by an accumulation hyperreflective areas, and the severely attenuated
of metabolic by-­products within lysosomes, retinal vessels.
the cellular organelles that degrade complex
macromolecules (see Appendix E). Lysosomal
storage diseases, with known mode of inherit- GM1 gangliosidosis is a member of the
ance, are inherited as an autosomal recessive sphingolipidoses. A deficiency of lysosomal
trait. When homozygous, the syndromes are hydrolase, β-­galactosidase, produces an accu-
usually severe, thus resulting in neurological mulation of GM1 ganglioside in the cerebral
disease and, eventually, death. cortex and visceral organs. GM2 gangliosido-
Ceroid lipofuscinosis has been described in sis is caused by a deficiency of hexosamini-
many species, including cats, cattle, dogs, dase. Variant forms of GM2 gangliosidosis
goats, humans, mice, and sheep (Figure 19.3). have been reported in the Japanese Spaniel
Fucosidosis is an autosomal recessive glyco- (AB variant gangliosidosis), the German
proteinosis in the English Springer Spaniel. Shorthair Pointer (Tay–Sachs disease), and
The disease is produced by a deficiency of the also in the Golden Retriever and Toy Poodle
lysosomal enzyme α-­l-­fucosidase. Deficiency (Sandhoff disease). The mucopolysacchari-
of lysosomal α-­l-­fucosidase causes the accu- doses (MPSs) are a group of diseases charac-
mulation of these glycolipids and oligosaccha- terized by defective metabolism of
rides. Galactocerebrosidosis, or globoid cell mucopolysaccharides (glycosaminoglycans).
leukodystrophy or Krabbe’s disease, is an auto- Five types of MPSs have been identified in
somal recessive trait in West Highland White dogs (MPSs I, II, III, VI, and VII). MPS I
and Cairn Terriers, Australian Kelpies, and (Hurler syndrome) has been described in the
Irish Setters. Galactocerebrosidosis in Irish Plott Hound, and other breeds of dogs, as a
Setters has been characterized by an insertion deficiency of α-­l-­iduronidase. Affected dogs
mutation of 78 bp in the sequence of the galac- have stunted growth, excessive joint laxity,
tocerebrosidase (GALC) cDNA consisting of multiple degenerative joint disease and car-
16 bp of insertion site duplication and 62 bp of diac valvular disease, and develop diffuse cor-
sequence derived from the U4 small neal opacities from the accumulation of
nuclear RNA. substrate in the keratocytes.
788 Ocular Manifestations of Systemic Disease

­Acquired Hematological Diseases


Anemia is the reduction in red blood cells
Cardiovascular Diseases (RBCs) per volume of whole blood. Severe ane-
Cerebrovascular accidents occur much less fre- mia often manifests systemically as varying pal-
quently in dogs than in people. Although with lor of mucous membranes, cool mucous
the ever-­increasing access to magnetic reso- membranes, tachycardia, polypnea, weakness,
nance imaging, cerebrovascular disease in as well as signs specific to the underlying pri-
dogs is being recognized more frequently. mary condition. Conjunctival pallor is even
Because cerebrovascular accidents are acute, used as an indicator of anemia due to gastroin-
clinical signs are acute ± progressive in nature. testinal parasitism in sheep and goats. Ocular
Systemic arterial blood pressure is the prod- manifestations of severe anemia include pale
uct of cardiac output (CO) (CO = heart rate × retinal vasculature, varying degrees of retinal
stroke volume) and total peripheral resistance. hemorrhage, and subtle changes in tapetal
Primary (essential) hypertension has been reflectivity. Retinal hemorrhages are more likely
described, although rarely, in dogs. Secondary to be observed, however, and are more dramatic
hypertension is now recognized as being a if accompanied by thrombocytopenia.
common complication of renal disease Hyperlipidemia refers to an elevation in
(60–80% of cases), hyperadrenocorticism plasma concentrations of cholesterol and/or
(59–86% of cases), pheochromocytoma (>50% triglycerides, and arises due to a disturbance in
of cases), diabetes mellitus, primary aldoster- plasma lipoprotein metabolism.
onism, hypothyroidism, and hyperthyroidism. Hyperlipidemia represents an abnormal find-
Ocular lesions associated with canine hyper- ing in fasted dogs and, when present, is indica-
tension include tortuous retinal vessels, tive of either increased production or reduced
variable-­sized retinal and preretinal hemor- degradation of lipoproteins. Primary hyperlipi-
rhages, papilledema, variable degrees of reti- demia/hypercholesterolemia has been
nal detachment (Figure 19.4), and tapetal described in various breeds, including the
reflectivity changes. Beagle, Briard, Collie, Miniature Schnauzer,
and Shetland Sheepdog. Hyperlipidemia is
seen in variety of systemic diseases, including
hypothyroidism, diabetes mellitus, hyper-
adrenocorticism, pancreatitis, and renal (e.g.,
nephrotic syndrome) as well as hepatic (e.g.,
cholestasis) diseases. Common diseases associ-
ated with secondary hypercholesterolemia in
the dog are hypothyroidism, diabetes mellitus,
and pancreatitis.
Visible lipemia in the dog is produced by
elevations of triglyceride levels, and it can be
detected in the ocular vessels of the conjunc-
tiva and retina (i.e., lipemia retinalis) as pink,
engorged vessels. It is most easily observed in
the retinal vessels over the nontapetal region.
Hyperlipidemia may also manifest with lipids
in the anterior chamber. A prerequisite for
Figure 19.4 Multiple retinal hemorrhages and gaining access to the anterior chamber by the
possible papilledema associated with hypertension large, lipid-­laden molecules is alteration of the
in a dog.
­Acquire  789

(a) (b)

Figure 19.5 Fundus photographs of a dog with multiple myeloma. (a) Left fundus. Note the retinal
detachment dorsal to the optic disc and the focal retinal hemorrhage in the medial fundus at the tapetal–
nontapetal junction. (b) Right fundus. Note the multifocal retinal and subretinal hemorrhages and the
retinal detachment in the dorsal tapetal region.

blood–aqueous barrier, presumably resulting


from preexisting uveitis.
Hyperviscosity syndrome comprises single
or multiple clinicopathological abnormalities
resulting from increased serum viscosity. The
severity of hyperviscosity syndrome is linked
to the size, shape, type, and concentration of
large molecules (e.g., immunoglobulins [Ig])
in the bloodstream. This syndrome is seen with
IgA, IgG, or IgM macroglobulinemia. The
underlying cause is usually a malignancy, such
as lymphoma, chronic lymphocytic leukemia,
Figure 19.6 Yellow-­appearing iris in a dog with
plasmacytoma, or multiple myeloma, but
icterus. The clinically normal appearing iris in this
infectious diseases such as ehrlichiosis may dog was blue.
also produce the syndrome. The ocular lesions
most frequently noted include dilated, tortu-
ous retinal vessels, which may develop kinking icterus may be detected in the intraocular
or “box carring,” or venous dilatation and sac- structures as well (e.g., blue irides may turn
culation; papilledema; retinal hemorrhages; green [Figure 19.6] and yellow hues may be
intraretinal cysts; and bullous retinal detach- imparted on the tapetal fundus).
ments (Figure 19.5). Anterior segment compli- Polycythemia is classified as relative or abso-
cations such as anterior uveitis and glaucoma lute (primary and secondary forms). Relative
may develop as well. polycythemia is an increased packed cell vol-
Icterus or jaundice is a condition character- ume with normal RBC mass occurring as a
ized by hyperbilirubinemia and deposition of result of a reduction in plasma volume as may
bile pigments in the skin, sclera, and mucous arise from external losses of body fluids (e.g.,
membranes causing them to appear a shade of diarrhea and burns).
yellow. The sclera is the classic location for Thrombocytopenia results from decreased
detection of icterus given its relative lack of platelet production, increased removal, seques-
pigmentation. The yellow appearance of tration, or any combination of these. The most
790 Ocular Manifestations of Systemic Disease

common causes of thrombocytopenia include remission has been noted. Eventually, while
infectious diseases, neoplasia, drug-­induced this animal was off therapy, massive granu-
reactions, and immune-­mediated disease. In lomatous disease developed in the chest and
particular, the numerous pathogens implicated abdomen. Necropsy and histopathology did
in causing infectious thrombocytopenia in not reveal the cause of the granulomas.
dogs include arthropod-­borne agents (e.g., A case of idiopathic ocular and nasal granu-
Babesia, Borrelia, Cytauxzoon, Dirofilaria spp., lomatous disease in a dog without dermato-
Ehrlichia spp., Leishmania, and Rickettsia), logical lesions has been described and may be a
viral agents (e.g., canine distemper virus different form of the classically described
[CDV], herpesvirus, parvovirus, and adenovi- canine idiopathic granulomatous disease. In
rus), and fungal and bacterial organisms (e.g., this case, bilateral limbal and intranasal granu-
Candida, Histoplasma, and Leptospira spp.). lomatous masses were observed. These masses
Thrombocytopenia is also seen in association were predominantly T-­cell-­rich granuloma-
with (i) many forms of neoplasia, including tous reactions and the dog responded favorably
lymphoma, leukemia, and multiple myeloma to immunosuppressive doses of oral predniso-
and (ii) medications that impair platelet pro- lone, topical prednisolone acetate, and
duction or cause secondary immune destruc- azathioprine.
tion of the platelets (e.g., chloramphenicol,
azathioprine, cyclophosphamide, and doxoru- Dysautonomia
bicin); or (iii) it may develop as an idiopathic Canine dysautonomia is an idiopathic disease
or primary immune-­mediated condition. In resulting from a generalized loss of autonomic
particular, of the 36 dogs with thrombocytope- function. Dogs affected are typically young
nia alone, 9/36 had mild ocular lesions, includ- adults of medium to large physical stature that
ing conjunctival (n = 3), iridal (n = 1), or typically live in rural areas. It is important to
retinal petechiae (n = 3), or focal retinal edema note, however, that animals ranging in age
(n = 2), and 6/36 had severe ocular lesions, from 5 weeks to 15 years of age and of a variety
including hyphema (n = 5) and retinal hemor- of breeds can be affected. Canine dysautono-
rhage (n = 1). mia has been reported in Europe and the
United States. The disease is prevalent in dogs
living in the midwestern United States, specifi-
Idiopathic Systemic Diseases
cally Kansas and Missouri. Affected dogs pre-
Canine Idiopathic sent with an acute (days) or subacute (two to
Granulomatous Disease three weeks) history of clinical signs referable
Idiopathic granulomatous disease in the dog is to loss of autonomic (sympathetic and para-
thought to be immune-­mediated because of sympathetic) function. Common nonocular
the absence of any demonstrable infectious clinical signs include regurgitation, vomiting,
agent and because favorable responses to diarrhea, anorexia, weight loss, dry mucous
immunosuppressive doses of corticosteroids or membranes, and purulent nasal discharge.
other immunosuppressive drugs have been Ocular signs include ocular discharge, pro-
reported. Syndromes of sterile granulomatous truding third eyelid, mydriasis, and a reduc-
inflammation are poorly defined and relatively tion in Schirmer tear test (STT) values. Ocular
rare. Multiple sterile granulomas of the eye- pharmacological testing with topical 0.05%
lids, conjunctiva, and sclera that accompanied pilocarpine in dogs with mydriatic pupils, and
dermal granulomas have been described in signalment, history, and clinical signs consist-
another case. Bilateral orbital granulomatous ent with dysautonomia provides useful infor-
disease that was very responsive to corticoster- mation supporting a diagnosis of
oids and required therapy indefinitely for dysautonomia. In affected dogs, instillation of
­Acquire  791

0.05% pilocarpine will cause rapid (<45 min) detachments and retinal infiltrates.
miosis compared to unaffected animals. Confinement to the retrobulbar optic nerves
Severe neuronal degeneration has been may limit ocular lesions to blindness and
reported in a variety of autonomic ganglia, dilated pupils. A definitive antemortem diag-
including the cranial cervical and ciliary gan- nosis is difficult to make, but multifocal CNS
glia. In addition, neuronal degeneration of deficits, increased CSF protein levels, pleocyto-
various brainstem nuclei, including the facial, sis with mononuclear cells, and a response to
oculomotor, and motor nucleus of the trigemi- corticosteroids are suggestive. Definitive ante-
nal nerve, has also been reported. At least 85% mortem diagnosis can be made based on the
of dogs affected with dysautonomia succumb above in concert with brain.
to the disease and are euthanized. Treatment involves aggressive use of immu-
nosuppressive corticosteroids with or without
Granulomatous Meningoencephalitis radiation therapy or immunosuppression
Granulomatous meningoencephalitis (GME) using a combination of corticosteroids with
is an idiopathic nonsuppurative meningoen- one or more of cytosine arabinoside, azathio-
cephalomyelitis seen in dogs. prine, leflunomide, or cyclosporine
Histopathologically, GME is characterized by A. Prognosis for survival varies from weeks to
perivascular cuffing with mononuclear cells. years, but clinical signs progress and dogs will
One study has demonstrated that perivascular succumb to the disease.
cuffs were composed of a heterogeneous popu-
lation of major histocompatibility complex Sudden Acquired Retinal
class II antigen-­positive macrophages and Degeneration Syndrome
mainly CD3 antigen-­positive lymphocytes, Sudden acquired retinal degeneration syn-
supporting a hypothesis of T-­cell-­mediated, drome (SARDS) is an idiopathic blinding con-
delayed-­type hypersensitivity of an organ-­ dition consisting of acute blindness in the
specific autoimmune disease. Proposed patho- absence of funduscopic disease (early in dis-
geneses for GME have included a primary ease), and clinical signs suggestive of an under-
immune-­mediated phenomenon, precancer- lying metabolic disease. The cause of SARDS is
ous form of lymphoma, and various infectious unknown, and epidemiological questionnaires
etiologies. Studies have failed to identify an have not been suggestive of any common
infectious etiology from the brains of dogs thread for an environmental toxin. Preliminary
affected by GME. investigations into excitotoxins (e.g., gluta-
GME is typically seen in young small breeds, mate) have found increased levels in the vitre-
although any breed or age of dog may be ous of affected animals, but the significance of
affected. GME is characterized typically by this is unknown. Recently, analysis of tissues
neurological signs suggestive of multifocal from SARDS-­affected dogs revealed the pres-
CNS lesions that, at least temporarily, are ence of Ig-­producing plasma cells in affected
responsive to systemic corticosteroids or other retinas that may account for localized intrareti-
immunosuppressive therapies. GME is divided nal production of autoantibodies and subse-
into three types, namely (i) disseminated, (ii) quent development of an antibody-­mediated
focal, or (iii) ocular. Any combination or per- retinopathy.
mutation of these forms can occur. In the last Animals are characteristically presented
form, GME may involve the optic nerves, thus with acute blindness and a normal to near-­
producing a syndrome of acute blindness, normal ocular fundus. Because of the acute
papilledema, retinal and peripapillary hemor- onset, most dogs are quite disoriented. In most
rhages, and, occasionally, extension into the patients, vision loss occurs over the course of
globe, which in turn produces retinal one to two weeks, and nyctalopia may be
792 Ocular Manifestations of Systemic Disease

observed. The mean age of affliction is SARDS. The ERG response is extinguished
8.5–10 years. The syndrome occurs predomi- with SARDS. A recent study documented the
nantly in neutered females, in both pure and spectral properties of the PLR in eyes of
mixed breeds, and with a predisposition for healthy dogs compared to eyes of SARDS-­
Dachshunds. A seasonal incidence has been affected dog. Dogs that have SARDS have com-
reported as well, with 46% of cases occurring plete pupillary constriction in response to blue
in December and January. Laboratory values light of a narrow wavelength (480 nm) and
are variable, but lymphopenia (30% of cases), high light intensity (200 kcd/m2) most likely
lymphopenia with neutrophilia (21%), and due to stimulation of a photosensitive pig-
abnormal biochemical profiles (68%) may be ment, melanopsin, located in a subpopulation
present. Elevated levels of alkaline phos- of retinal ganglion cells that can drive PLRs in
phatase (30–40% of cases) and cholesterol the absence of photoreceptor activity. When
(42%) are the most common biochemical red light of a given wavelength (630 nm) and
changes. Overall, 12–17% of patients have high light intensity (200 kcd/m2) was used to
adrenal profile changes compatible with those evaluate PLRs in SARDS-­affected patients, the
of Cushing’s disease, but these changes may be pupils remained fixed and dilated as this wave-
adaptations to other diseases as well. Most length of red light does not activate the mel-
recently, serum cortisol and sex hormone con- anopsin pathway but rather activates the
centrations were measured prior to and follow- photoreceptor-­mediated pathway that is absent
ing adrenocorticotropic hormone (ACTH) in dogs with SARDS. A portable, diode-­based
stimulation in 13 dogs with SARDS. Serum light source with narrow wavelengths for blue
cortisol was elevated in 9 of 13 dogs; elevations and red light that matches the spectral proper-
in one or more sex hormones were found in 11 ties of canine visual pigments is available for
of 13 patients with SARDS, while only 1 dog colorimetric PLR testing (Melan-­100 unit;
had normal ACTH stimulation results. BioMed Vision Technologies, Inc., Ames, IA,
On ophthalmic examination, dogs with USA). SARDS has long been considered an
SARDS appear blind and lack a menace untreatable, irreversible blinding disease of
response, while they tend to blink in response dogs. Most dogs with SARDS still make accept-
to bright light (positive dazzle reflex). The able house pets provided they adjust well to
pupils are usually dilated at rest and demon- being blind.
strate sluggish PLRs. In the early stages, all
dogs with SARDS have a characteristic pale
Immune-­Mediated Diseases
optic disc due to the presence of vascular atten-
uation of the optic nerve head. In patients with Dermatological Diseases
SARDS of typically greater than two months in Immune-­mediated and allergic skin diseases
duration, subtle tapetal hyperreflective spots often produce a facial dermatitis involving the
may be observed with these hyperreflective eyelids and conjunctiva. Immune-­mediated
spots having been detected in some affected skin diseases are divided into two main catego-
dogs only seven days following the onset of ries: primary autoimmune diseases, in which
acute blindness. After several weeks to months, the disease results from an attack against self-­
more advanced retinal vascular attenuation antigens, and secondary immune-­mediated
and tapetal hyperreflectivity become apparent. disease, in which the disease results from exog-
The funduscopic appearance in chronic enous material, inducing autoimmune disease.
SARDS is similar to that of inherited retinal Such causes of secondary immune-­mediated
degeneration (progressive retinal atrophy). diseases include bacteria, drugs, and viruses.
Electroretinography (ERG) is considered The pemphigus complex consists of five auto-
essential for establishing a diagnosis of immune skin diseases: (i) pemphigus vulgaris,
­Acquire  793

(ii) pemphigus vegetans, (iii) pemphigus folia-


ceus, (iv) pemphigus erythematosus, and (v)
bullous pemphigoid. The pemphigus complex
is characterized by autoantibodies directed
against intercellular substances. In most cases,
facial lesions involve the mucocutaneous
regions and are characterized by pustules and
vesicles that eventually rupture, thereby leav-
ing erosions and ulcers, crusting, scaling, and
hypopigmentation.

Juvenile Pyoderma/Cellulitis
(Puppy Strangles)
Juvenile sterile granulomatous dermatitis (i.e.,
pyoderma/cellulitis) and lymphadenitis is a
syndrome of dogs that usually manifests in
animals less than eight months of age. Adult
dogs, however, may become affected by this
condition. Predisposed breeds include the
Dachshund, Golden Retriever, Labrador
Figure 19.7 Juvenile pyoderma in a young Saint
Retriever, Gordon Setter, and Lhasa Apso. Bernard.
Acute pyoderma affecting mainly the head
manifests as pustules that then fistulate and Cocker Spaniel, Jack Russell Terrier, Samoyed,
drain, thereby creating several moist, crusty and Welsh Corgi. The condition is thought to be
lesions of the pinna, muzzle, and periocular inherited as an autosomal dominant condition
skin (Figure 19.7). Though the lesions appear with incomplete penetrance in the Collie.
caused by bacteria, they are actually sterile and Dermatomyositis in the Shetland Sheepdog has
cannot be transmitted. Bacterial hypersensitiv- been linked to a microsatellite marker, FH3570,
ity has been postulated to explain the response on chromosome 35. Dermatological lesions are
to corticosteroids and the explosive course of seen around the face (especially the periocular
the disease. region), digits, footpads, and tail. Characteristic
Without systemic therapy, the lesions will dermatological findings include alopecia, vesi-
progress to involve other typical areas. cles, ulceration, erythema, scaling, and crusting.
Immunosuppressive doses of systemic corticos- Clinical signs of myositis occur after the devel-
teroids, tapered following three to four weeks opment of the skin lesions and include dyspha-
after resolution of the clinical signs, and sys- gia, megaesophagus, generalized weakness, stiff
temic broad-­spectrum antibiotics to treat the gait, and muscle atrophy.
secondary bacterial pyoderma, are indicated. Treatment of dermatomyositis includes the
use of oral vitamin E or fatty acid supplements.
Myositides Pentoxifylline is also recommended to help
Dermatomyositis improve microvascular blood flow. Prognosis
Dermatomyositis is an idiopathic, hereditary is variable depending on the severity of the
condition resulting from a suspected immune-­ disease.
mediated inflammation involving skeletal mus-
cle, skin, and vasculature. The disease is typically Masticatory Myositis and Extraocular Myositis
described in Collies and Shetland Sheepdogs. Masticatory myositis (masseter, temporalis,
Other breeds affected include the American pterygoid muscles) and extraocular myositis
794 Ocular Manifestations of Systemic Disease

are two forms of focal inflammatory myopa- Extraocular myositis seems to be a different
thies. Masticatory myositis typically affects disease affecting the extraocular myositis and
young to middle-­aged adult dogs and predomi- affects predominantly young large breed dogs
nantly medium to large breeds. Signs include (Figure 19.8). Bilateral exophthalmos is the
spasm of the masticatory muscles and diffi- predominant clinical sign in the acute form of
culty in opening the mouth, pain on palpation the disease. Chronic extraocular myositis can
of the muscles, muscle swelling, or muscle result in restrictive strabismus and is due to
atrophy. Muscular atrophy is a more common chronic fibrosis of the extraocular muscles.
clinical sign (72% of cases) than muscle swell- As opposed to masticatory myositis, circulat-
ing (14% of cases). ing antibodies to type 2M muscle fibers are not
Ocular signs occur in 45% of cases and are present. Inflammatory infiltrate of affected
variable depending on the chronicity of the muscles includes lymphocytes and mac-
disease. Ocular manifestations of acute masti- rophages and fibrosis may be present depend-
catory myositis include exophthalmos and pro- ing on the chronicity of the disease.
lapse of the third eyelid due to swelling of the Immunosuppressive corticosteroid therapy is
pterygoid muscle, and possible optic nerve ten- indicated in cases of extraocular myositis (as
sion/compression causing blindness. In for masticatory myositis). Adjunctive correc-
chronic masticatory myositis, enophthalmos tive strabismus surgery may be useful in some
includes bilateral clinical signs, ±peripheral cases of chronic extraocular myositis where
eosinophilia, ±elevated levels of serum creati- the disease is in remission.
nine kinase, ±abnormal electromyograms, and
±presence of circulating antibodies for type
2 M fibers, and positive muscle immunohisto-
chemistry for antibodies against type 2M fibers
is used to provide a diagnosis of masticatory
myositis (Table 19.3). Immunosuppressive
doses of systemic corticosteroids (prednisone
1–2 mg/kg p.o. b.i.d.) for a minimum of one
month before tapering are recommended at
any stage of the disease. Prognosis is good for
dogs treated appropriately with immunosup- (a)
pressive dosages of corticosteroids, although
some dogs may require lifelong therapy with
these drugs.

Table 19.3 Histopathological lesions


in masticatory myositis.

Masticatory myositis:
1) Cellular infiltration with varying degrees of
lymphocytes, and/or macrophages, and/or
eosinophils.
2) Histological evidence of muscle atrophy, (b)
necrosis, and fibrosis.
3) Presence of fibrosis depending upon the Figure 19.8 Extraocular myositis. (a) Golden
chronicity of the disease. Retriever, 1-­year-­old male, with left ventral
4) Immune complexes bound to type 2M muscle strabismus at initial presentation. (b) Close-­up of
fibers. the left eye, only sclera visible due to severe globe
deviation.
­Acquire  795

Uveodermatologic Syndrome (Vogt–


Koyanagi–Harada-­Like Syndrome)
Vogt–Koyanagi–Harada (VKH) syndrome is an
idiopathic condition in humans characterized
by uveitis, poliosis, vitiligo, ±changes in hear-
ing ability, and meningitis. A similar syndrome
is recognized in the dog, except that meningitis
is rarely reported, hence the terms uveoderma-
tologic or VKH-­like syndrome have been
applied. A relatively recent study examining
ocular and dermatological tissue from two
dogs with VKH-­like syndrome has suggested
that skin lesions are the result of a Th1-­
mediated inflammatory response, while ocular
lesions are the result of a Th2-­mediated inflam-
matory response. Further, the role of certain
Figure 19.9 Multifocal, depigmented lesions in
dog leukocyte antigen class II gene alleles may the nontapetal fundus of a dog with VKH
be important. syndrome.
Several other breeds, including the
Australian Shepherd, Beagle, Brazilian Fila, specimens have lichenoid dermatitis, histio-
Chow Chow, Dachshund, Golden Retriever, cytes, and small mononuclear cell as well as
Irish Setter, Old English Sheepdog, Saint giant cell infiltrations. The prognosis for dogs
Bernard, Samoyed, Shetland Sheepdog, and affected with uveodermatologic syndrome is
Siberian Husky, are affected. Animals are typi- guarded, and therapy should be considered to
cally affected in adulthood and ocular lesions be lifelong. Relapses are frequent if therapy is
usually precede the dermatological lesions. stopped or tapered. Because of the immuno-
Patients are presented for a complaint of sud- suppressive therapy, periodic rechecks as well
den blindness or gradual vision loss. Ocular as blood and liver evaluations are necessary.
lesions vary from bilateral anterior uveitis to Initial therapy involves immunosuppressive
severe panuveitis. Bullous retinal detachments doses of oral prednisone ± azathioprine or
may occur, and secondary cataracts and glau- cyclophosphamide. Maintenance therapy may
coma are common. The iris and retinal pig- require one or both drugs at a markedly
ment epithelium develop progressive reduced dose. Topical corticosteroids may be
depigmentation (Figure 19.9). As the depig- used for anterior segment lesions.
mentation progresses, the tapetal fundus
becomes hyperreflective, and retinal vascular
Infectious Diseases
attenuation as well as optic nerve atrophy may
develop. Dermal and hair depigmentation (vit- Algal Diseases
iligo and poliosis, respectively) develop either Protothecosis
gradually or rapidly, and they may be ulcera- Protothecosis is a rare disease in humans and a
tive in nature. variety of animals caused by a colorless, ubiq-
No specific diagnostic tests are available for uitous, saprophytic alga of the genus
the uveodermatologic syndrome. The diagno- Prototheca. Prototheca spp. have a wide geo-
sis is made on the basis of clinical signs and graphic distribution and are found in soil,
histopathological examination of skin biop- water, sewage, and some vegetable matter.
sies. Routine laboratory tests, including blood- Prototheca spp. are thought to be achlorophyl-
work, are typically unremarkable. Skin biopsy lous mutants of green algae. Three species
796 Ocular Manifestations of Systemic Disease

have been recognized, but only Prototheca The most commonly attempted therapy
wickerhamii and Prototheca zopfii are known has been amphotericin B, an imidazole anti-
to be pathogens. Prototheca zopfii is usually fungal drug, or both. A recent review of sys-
isolated from disseminated cases, whereas temic protothecosis in 17 Australian dogs
P. wickerhamii produces a cutaneous syn- revealed that combination therapy with
drome. Prototheca spp. appear in tissue as amphotericin B and itraconazole was effec-
thick-­walled, nonbudding, round to ovoid, tive in only two cases, although one of these
yeast-­like cells. dogs should have had treatment for longer
The disease is not considered to be transmis- duration. Prognosis for dogs with protothe-
sible and the large breeds of dogs are overrep- cosis is grave.
resented, and ≥50% of animals with
protothecosis may have ocular involvement. Bacterial
Tissues most commonly affected include the Any sporadic bacteremia may result in seeding
eyes, digestive tract, kidney, heart, bone, and of the uveal tract and create various degrees of
brain. Ocular lesions include a granulomatous, inflammation, but only a few bacterial syn-
posterior uveitis or panuveitis that is often dromes are relatively consistent regarding
bilateral and blinding (Figure 19.10). Exudative involvement of the eye (Table 19.4).
retinal detachments are the usual cause for
blindness. Chorioretinal lesions may be either
diffuse or focal, and they will need to be dif-
ferentiated from the more common causes of
granulomatous uveitis. A definitive diagnosis Table 19.4 Canine infectious diseases
with ophthalmic signs.
is usually made on the basis of finding the
organism in ocular aspirates, tissue exudates,
Algal diseases:
excretions (i.e., urine sediment), or biopsy
Protothecosis
specimens.
Bacterial:
Bartonellosis
Borreliosis (Lyme disease)
Brucellosis
Leptospirosis
Tetanus
Mycotic:
Aspergillosis
Blastomycosis
Coccidioidomycosis (valley fever; San Joaquin
Valley fever)
Cryptococcosis
Virus:
Canine distemper virus
Herpesviruses
Canine herpesvirus

Figure 19.10 Gross image of a sectioned globe Infectious canine hepatitis (CAV-­1)
infected with Prototheca. There is diffuse retinal Papillomavirus
detachment with associated retinal exudate and
Tick-­borne encephalitis virus
hyphema.
­Acquire  797

Bartonellosis motile microaerophilic bacteria of the order


Canine bartonellosis results from infection Spirochaetales. Successful transmission of the
with the Gram-­negative, intracellular bacilli or agent relates directly to contact time of the tick
coccobacilli bacterium, Bartonella spp. There on the host, requiring 48–72 h for a 38–92% trans-
are numerous species of Bartonella. Bartonella mission rate. In the dog, the horse, and humans,
henselae (causative agent of cat scratch disease B. burgdorferi can produce ocular lesions.
[CSD]), Bartonella vinsonii (berkhoffii), Documented ocular lesions included conjuncti-
Bartonella clarridgeiae, and Bartonella eliza- vitis, corneal edema, anterior uveitis, retinal
bethae are known or likely to cause naturally petechia, chorioretinitis, retinal detachment, and
occurring disease in dogs and B. vinsonii (berk- sometimes orbital disease.
hoffii) appears to be an important species to Because of the limitations of current tests
cause clinical disease in dogs. Canine bartonel- that measure antibody response, other con-
losis has been associated with numerous path- firmatory tests must be performed including
ological conditions, including anterior uveitis, the Western blot assay and the C6 ELISA. A
hyphema, retinal detachment due to systemic presumptive diagnosis of borreliosis can be
hypertension, and choroiditis (Figure 19.11), made on the basis of compatible signs (usually
endocarditis, cutaneous vasculitis, granuloma- lameness, joint pain, pyrexia, and lymphade-
tous lymphadenitis, myocarditis, and polyar- nopathy of lymph nodes of the limbs), ruling
thritis. Treatment of canine bartonellosis out other causes of systemic disease in endemic
consists of systemic antimicrobial therapy. areas, and on the basis of response to antibiotic
That include macrolides (e.g., azithromycin), therapy. Vaccination and tick control, both in
fluoroquinolones (e.g., enrofloxacin), and dox- the environment and on the animal, are impor-
ycycline (recommended to be used at high dos- tant for preventing infection. Various antimi-
ages 10 mg/kg q 12 h for four to six weeks). crobials including tetracyclines, some
cephalosporins (e.g., ceftriaxone), and mac-
Borreliosis (Lyme Disease) rolides are useful for treating borreliosis.
Lyme disease, or borreliosis, is a tick-­borne spi- Doxycycline is one of the first-­line antimicro-
rochetosis produced by Borrelia burgdorferi, bials of choice.
which comprises several species that affect
humans and dogs worldwide. Borrelia organ- Brucellosis
isms, like most spirochetes, are small, 25 μm Canine brucellosis is caused by Brucella canis.
long and 0.2 μm in diameter, corkscrew-­shaped, Brucella canis is a zoonotic aerobic, Gram-­
negative coccobacillus. Brucella canis naturally
infects dogs by penetrating mucous mem-
branes such as occurs via coitus. Aside from
venereal transmission, Brucella spp. can be
transmitted via fomites such as cages or equip-
ment, and can persist for extended periods in
mononuclear phagocytes and produce a pro-
longed bacteremia.
Brucella canis has been isolated from the eye
and is recognized as a cause of uveitis or
endophthalmitis in both experimental and nat-
urally occurring brucellosis (Figures 19.12
and 19.13). Infected dogs are often times not
Figure 19.11 Bartonellosis in a dog. Fundus
photograph demonstrating multifocal, gray, systemically ill. Because of the insidious nature
hyporeflective areas in the tapetal fundus. of the systemic disease, infected dogs are often
798 Ocular Manifestations of Systemic Disease

risk of transmission to humans. Currently,


there is no effective vaccine against
brucellosis.

Leptospirosis
Canine leptospirosis is caused by Leptospira
interrogans sensu lato. It appears, however,
that the disease causing serovars, namely grip-
potyphosa, pomona, and bratislava, are becom-
ing more prevalent. The bacterium is
maintained in host-­adapted species that act as
reservoir hosts and is shed in the urine. Direct
transmission can occur through contact with
Figure 19.12 Photograph of the left eye (OS) of a infected urine, bites, ingestion of infected
dog with Brucella canis endophthalmitis. Numerous material, and contact with contaminated
punctate, yellow and white opacities are water. Leptospirosis is a significant zoonotic
suspended in the peripheral anterior vitreous.
Generalized vitreal haze is present. disease with worldwide distribution that
causes human disease and death, mostly in
regions of Asia and South America.
In the acute phase of infection, conjunctivi-
tis, scleritis, and anterior uveitis may be pre-
sent in concert with other systemic signs.
Diagnosis of leptospirosis is dependent on con-
sistent clinical signs and detection of antibod-
ies using the microscopic agglutination test or
ELISA and/or evidence of the presence of the
organism in urine using dark-­field microscopy,
or by visualizing the organism in histological
preparations. Treatment of leptospirosis is
directed at (i) eliminating the bacteremia by
initially using penicillins, specifically ampicil-
Figure 19.13 Fundus photograph of the OS of a
lin and amoxicillin, and (ii) eliminating the
dog with Brucella canis endophthalmitis. Irregular carrier state by administering tetracyclines.
zones of hyporeflectivity with indistinct margins
are visible in the peripheral tapetal fundus and Tetanus
adjacent to the optic disc endophthalmitis.
Irregular zones of hyporeflectivity with indistinct
Tetanus is caused by the neurotoxin produced
margins are visible in the peripheral tapetal fundus by the bacterium Clostridium tetani.
and adjacent to the optic disk. Clostridium tetani is a motile, Gram-­positive,
nonencapsulated, anaerobic, rod-­shaped,
presented for ocular disease rather than for spore-­forming bacterium. Dogs and cats are
systemic signs. Before treatment is recom- naturally resistant when compared to other
mended, the zoonotic potential and difficulty species such as humans and horses. Clinical
in clearing the organism from the animal signs of tetanus develop when spores of
should be carefully explained to the owner. C. tetani enter the body through skin wounds
Because brucella can be harbored in reproduc- or during surgical procedures. Clinical signs
tive organs, neutering of intact affected ani- may be localized or generalized. In the local-
mals should be encouraged to decrease any ized form, increases in stiffness of specific
­Acquire  799

muscle groups or a given limb may be noted. In malaise, pyrexia, anorexia and weight loss, and
the generalized form, affected dogs will ini- bone pain. Disseminated aspergillosis has been
tially have a characteristic smiling/sneering reported to cause panuveitis, chorioretinitis,
appearance (risus sardonicus) and a stiff gait exudative retinal detachments, and endoph-
that may progress to megaesophagus ± hiatal thalmitis. Diagnosis is made based on identifi-
hernia, and complete rigid paralysis with the cation and culture of urine sediment, serum,
appearance of periodic generalized convulsive-­ synovial fluid, vitreous, lymph node, or
type behavior. Ocular signs seen in a tetanic intervertebral disc centesis specimens.
animal include protrusion of the third eyelid Treatment is directed at eliminating the organ-
and enophthalmos resulting from globe retrac- ism by administering amphotericin B, itracon-
tion due to the hypertonicity of the extraocular azole, or fluconazole intravenously. Regardless,
muscles. the prognosis for recovery from disseminated
aspergillosis is poor.
Mycotic
Acremoniosis Blastomycosis
Acremoniosis is a systemic mycotic infection Blastomycosis is a systemic mycotic infection
caused by Acremonium spp. Systemic signs in caused by the dimorphic fungus, Blastomyces
this dog were similar to those seen in cases of dermatitidis. Blastomyces dermatitidis is a
disseminated aspergillosis. Clinical signs thick-­walled yeast that reproduces by budding
include various general malaise, weight loss in infected tissues (i.e., yeast phase), and in
and anorexia, lymphomegaly, neurological nature, it is most likely a soil saprophyte that
signs (depending on the neuroanatomic focus produces infective spores called conidia (i.e.,
of the principle pathological process), and var- mycelial phase). The tissue budding yeast form
ious ocular signs. Ophthalmological signs is 5–20 μm in size, with a thick, double-­
include chemosis, corneal edema, anterior contoured wall.
uveitis, focal chorioretinitis, and bullous reti- Young, large breed sporting dogs and hounds
nal detachments. Diagnosis is made based on living near water are at increased risk of blas-
detection of the organism on histopathological tomycosis, presumably because of outdoor
examination of tissues and by culturing the exposure. Blastomycosis is not a contagious or
organism from tissues and urine. zoonotic disease but has been transmitted to a
person through an accidental needlestick with
Aspergillosis a syringe and needle.
Aspergillosis is caused by the filamentous fun- Clinical signs in dogs with blastomycosis
gus Aspergillus spp. Aspergillus spp. are consid- vary significantly due to the multisystemic
ered ubiquitous in the environment, and nature of the disease. Pulmonary signs are
animals are infected opportunistically after seen in 43–88% of dogs affected with blastomy-
inhaling Aspergillus spores. Localized aspergil- cosis, ranging from mild respiratory distress
losis involves colonization of the respiratory during physical exertion to severe dyspnea at
sinuses and nasal mucosa. Secondary CNS rest. Nearly 60% of dogs with blastomycosis
involvement may result from erosion of the cri- develop lymphadenopathy, while cutaneous
briform plate. Disseminated infection occurs lesions are reported in approximately 30% of
typically in the immunocompromised patient affected dogs. Ocular involvement has been
and involves a whole host of organ systems. reported in as many as 48% of dogs with blasto-
Disseminated aspergillosis occurs frequently mycosis. Ocular signs have been reported as
in German Shepherd dogs. In general, the most the sole indicator of B. dermatitidis infection in
common clinical signs relate to multiple organ up to 3.0% of diagnosed cases. Approximately
system involvement, and include general 50% of the ocular lesions caused by B.
800 Ocular Manifestations of Systemic Disease

dermatitidis are bilateral. For prognostic pur- ocular manifestations were most frequent in
poses, the ocular lesions have been divided the anterior segment, but they were also diffi-
into anterior segment only (5–30%), anterior cult to classify because of use of the redundant
and posterior segment lesions (endophthalmi- terms of iritis, uveitis, and chorioretinitis.
tis, 26–72%), and posterior segment (22–43%). Ocular signs included keratitis in 49%, anterior
Though anterior segment inflammation may uveitis in 43%, and glaucoma in 31% of cases.
be severe, B. dermatitidis is infrequently found The typical histopathological change in ocular
in the anterior uvea, and this anterior uveal coccidioidomycosis is granulomatous inflam-
inflammation has been attributed to a diffusi- mation in the filtration angle, ciliary body, cho-
ble substance from the posterior segment. roid, and retina.
Additional ocular lesions of canine blastomy- Diagnosis of coccidioidomycosis requires
cosis are optic neuritis, retinal and vitreal hem- the visualization of the organism, or determin-
orrhages, and orbital cellulitis. ing the presence of antibodies specific for the
Therapy for systemic mycoses, no matter organism in light of consistent travel.
what etiology, is a financial dilemma. Therapy Treatment of coccidioidomycosis is similar to
becomes prohibitively expensive for many that for other systemic mycoses (i.e., extended
owners because most of the affected dogs are azole therapy or amphotericin B, or these
large breeds, therapy may be very protracted, drugs used in combination or in succession).
and imidazole medications are very costly. Response to treatment may also be monitored
Currently, itraconazole is considered the drug by evaluating radiographs of the lesions in the
of choice for the treatment of blastomycosis. thorax and bone (if involved). Relapses
are common.
Coccidioidomycosis (Valley Fever; San Joaquin
Valley Fever) Cryptococcosis
Coccidioidomycosis is caused by the dimor- Cryptococcosis is caused by Cryptococcus neo-
phic fungus Coccidioides immitis. The organ- formans or Cryptococcus gattii (previously
ism is found in sandy, alkaline soils of the dry C. neoformans var. gattii). Cryptococcus neofor-
regions of the southwestern United States, mans is associated with high nitrogen-­
western Mexico, and Central and South containing environments such as avian feces
America. Coccidioides spp. produce mycelia or soil enriched with avian feces. Cryptococcus
during seasonal rainfall. The major route of neoformans is a variably sized yeast-­like organ-
Coccidioides spp. infection is via inhalation. ism (3.5–7 μm) that typically contains a thick
Cutaneous entry of the organism through a capsule.
penetrating skin wound is possible but Cryptococcosis has been described in a vari-
occurs rarely. ety of mammals as well as in humans.
Coccidioidomycosis may produce a wide Importantly, cryptococcosis is not contagious.
variety of clinical diseases, depending on the Rather, inhalation of the yeast-­like organism is
immunocompetence of the host, ranging from the likely mode of infection. Canine cryptococ-
a mild, subclinical respiratory disease to a cosis is uncommonly reported in comparison
severe multisystemic disseminated disease. to other systemic mycotic infections such as
Clinical signs are variable and include pyrexia, blastomycosis and in comparison to feline
lymphadenomegaly, coughing, neck pain, cryptococcosis. Clinical manifestations of
chronic lameness, swollen joints, back pain, canine cryptococcosis pertain mainly to CNS
muscle wasting, and signs of uveitis. involvement, and ocular, upper respiratory, or
In one study, 42% of patients with ocular cutaneous lesions. Common, nonspecific clini-
lesions had no systemic clinical signs, and 80% cal signs of canine cryptococcosis include ano-
of the ocular lesions were unilateral. Clinical rexia, lethargy, and depression. Fever is not a
­Acquire  801

common clinical finding in dogs with C. neo- Parasitic – Dipteric Larvae


formans infection. Twenty to forty percent of Ophthalmomyiasis
dogs with cryptococcosis have ocular and/or Ophthalmomyiasis interna has been observed
periorbital involvement, including granuloma- in the dog and the cat, and refers to either the
tous to pyogranulomatous chorioretinitis with intraocular (ophthalmomyiasis interna) or
or without exudative retinal detachment external (ophthalmomyiasis externa) migra-
(Figure 19.14). Although less common than tion of fly (Diptera) larvae. The three forms are
posterior segment disease, mild to moderate named according to location of the larvae and
anterior uveitis may occur as well. include (i) ophthalmomyiasis externa, where
Identification of the causative agent permits the larvae are found in the orbital and extraoc-
confirmation of the diagnosis of cryptococco- ular tissues; (ii) ophthalmomyiasis interna
sis. The thin wall and large capsule of anterior, where the larvae are found in the
Cryptococcus allow ready differentiation from anterior chamber of the eye; and (iii) ophthal-
Blastomyces. Cryptococcal organisms can also momyiasis interna posterior, where larvae are
be readily cultured on Sabouraud’s agar from found in the posterior segment of the eye. The
infected tissue, CSF, exudate, blood, urine, and point of entry of the fly larvae is unknown, but
joint fluid. it is postulated that fly larvae cross the con-
Treatment of cryptococcosis involves subcu- junctival surfaces.
taneous, diluted amphotericin B in combina- The characteristic ophthalmoscopic lesions
tion with oral flucytosine (especially helpful are wandering, curvilinear tracts that fre-
for treating CNS-­infected cases) or azole ther- quently intersect and are associated with reti-
apy. Fluconazole is recommended for cases of nal and preretinal hemorrhages in the acute
ocular or CNS cryptococcosis. stage. If the larva is observed, it is typically
photosensitive, moving away from a
strong light.
Manual removal of externally located organ-
isms with appropriate anti-­inflammatory and
antimicrobial therapy, along with correcting
any extraocular conformational defects, has
shown positive outcomes.

Parasitic – Nematodes
Angiostrongylosis (Heartworm of France;
French Heartworm)
Angiostrongylosis is caused by the nematode,
Angiostrongylus vasorum. Angiostrongylus
vasorum inhabits the pulmonary arteries and
right heart of dogs and wild carnivores in
parts of Europe, Africa, and Asia. A case of
A. vasorum infection in a dog from northeast-
ern Canada has been described. Dogs are
Figure 19.14 Labrador Retriever with tetraparesis infected by eating intermediate hosts such as
and Cryptococcus in the CSF. Optic neuritis and snails and slugs. Migrating larvae may become
multiple retinal hemorrhages are present, and a aberrant and may be found in the eye. Severe
granuloma adjacent to the disc is obscured by a
granulomatous uveitis and secondary glau-
hemorrhage. Vasculitis is evident, with multiple
hemorrhages, perivascular infiltrate around smaller coma have been observed with chronic
vessels, and marked hyperemia. involvement.
802 Ocular Manifestations of Systemic Disease

Dirofilariasis (Canine Heartworm Disease) canine ocular onchocerciasis has only been
Dirofilariasis, canine heartworm infection, reported in dogs from Germany, Greece,
caused by Dirofilaria immitis, is the most com- Hungary, Portugal, and the western
monly reported intraocular nematode among United States.
dogs in North America. Heartworm disease is Clinically, there are two forms of ocular
widely distributed. Dirofilariasis is recognized onchocerciasis, namely acute and chronic
in dogs worldwide. Approximately 240 000 ocular onchocerciasis. In acute cases, ocular
cases of heartworm disease were diagnosed in onchocerciasis is characterized by conjuncti-
2001 in the United States. In Canada, dirofila- vitis, chemosis, and periorbital swelling. In
riasis is relatively infrequent and limited to the some cases, parts of the parasite are observed
southern-­most portions of the country. on the conjunctival surface or other periocu-
Transmission of D. immitis is by mosquitoes. lar tissues. In chronic cases, parasite-­
The life cycle of D. immitis is complex; thus, containing granulomatous nodules are found
readers are referred to current internal medi- in various parts of the eye and periocular tis-
cine or infectious disease textbooks for further sues. Diagnosis is made based on consistent
details. Adult heartworms are known to live up clinical examination findings and, in acute
to five years, while microfilaria live up to cases, by identifying the presence of worm
30 months in dogs. fragments on the conjunctiva or in periocular
Ocular involvement with D. immitis is postu- tissues. In chronic cases, diagnosis is made by
lated to arise as a result of aberrant migration grossly and/or histopathologically identifying
of fourth-­stage larvae from the subconjuncti- Onchocerca spp. within the granulomatous
val space into the eye, with subsequent devel- nodules or within the periocular tissues.
opment to immature adults or fifth-­stage Therapy for ocular onchocerciasis involves, in
larvae. The worm is usually in the anterior part, surgical removal of the granulomatous
chamber, but it may also be found in the vitre- nodules and other tissues containing the
ous. Anterior uveitis was a consistent ocular worm. Administration of antimicrobials
manifestation, and ocular discomfort was effective against the endosymbiont (tetracy-
exacerbated by examination of the affected eye clines) may be useful at eliminating the para-
with a light, which stimulated parasitic move- site. Antiparasitic agents such as ivermectin
ment. The diagnosis of intraocular dirofilaria- and diethylcarbamazine are not effective
sis is established by finding the worm, usually against adult worms but are effective against
present in the anterior chamber of dogs in dirofilaria.
areas endemic for heartworm. Severe corneal
edema, however, may preclude visualization of
Strongyloidiasis (Hookworms)
the parasite. Therapy has involved removal of
Strongyloidiasis is caused by the aberrant
the D. immitis worm through a limbal incision,
migration of strongyles (order Strongylida).
and has been successful in 90% of patients so
The most common routes of infection of a
treated.
common strongyle of dogs, Ancylostoma sp., is
through ingestion of larvae or direct penetra-
Onchocerciasis (Onchocercosis)
tion of larvae through intact skin.
Ocular onchocerciasis is caused by the nema-
tode, Onchocerca spp. The exact species of
Onchocerca causing canine ocular onchocerci- Toxocariasis (Roundworm Ascarids)
asis is still speculative, and consensus has yet Toxocariasis is caused by the nematode
to be reached. The life cycle of Onchocerca lupi Toxocara canis. Toxocara canis is an extremely
is not completely understood, but is likely sim- common roundworm or ascarid of the dog,
ilar to that of other Onchocerca spp. To date, and is thought to be responsible for migrating
­Acquire  803

larvae that may, occasionally, aberrantly eruptions of infected areas. Commonly affected
migrate to the eye of humans and dogs. sites include the ventral ears, abdomen, chest,
Both visceral and ocular larval migrans as a and legs, and in severe cases the entire body,
result of T. canis pose a public health problem. including periocular regions.
Ocular larval migrans is migration of nema- Diagnosis of sarcoptic mange is dependent
tode larvae through the eye. Aberrant migra- upon visualizing the mite, eggs, or mite feces
tion of T. canis to the canine eye has been via microscopic examination of skin scrapings.
described as an incidental finding manifesting It should be noted, however, that skin scrap-
as small (one-­fourth to one-­sixth disc diame- ings are oftentimes negative in affected ani-
ter), solitary focal granulomas in the posterior mals. Treatment of sarcoptic mange involves
segment in four dogs. the use of amitraz (monoamine oxidase inhibi-
tor), fipronil (GABA receptor inhibitor), or
Parasitic – Mites avermectin drugs (i.e., ivermectin, milbemycin
Demodicosis oxime, moxidectin, and selamectin).
Canine demodicosis is caused by the parasitic
mite Demodex canis. Demodex spp. live as com- Leishmaniasis
mensals in the skin of most mammals, includ- Leishmania spp. are diphasic protozoal para-
ing dogs. Predisposing factors contributing to sites that infect a wide range of vertebrates,
overgrowth of Demodex include poor nutri- including dogs and humans. Dogs and other
tion, concurrent parasites/infectious disease, are primary reservoirs of Leishmania spp., and
short hair coat, nonenrolment into preventive sandflies (Phlebotomus spp. or Lutzomyia spp.)
wellness plan, stress, and immunosuppressive are the vectors. Leishmania infantum is the
drug therapy. Localized demodicosis typically species responsible for endemic leishmaniasis
develops in young dogs (three to six months of in dogs from Greece, Spain, Portugal, Turkey,
age), starting preferentially around the eyes, parts of Africa, Central and South America,
lips, and forelegs. and India. Alterations in socioeconomic and
Skin scrapings are the main method of estab- possible climate factors have resulted in
lishing a diagnosis, and the mites are typically changes in the distribution in L. infantum in
easy to find. All forms of blepharitis should Europe. Leishmania spp. cause cutaneous,
indicate the need for skin scrapings, and mucocutaneous, and visceral diseases. Dogs
demodicosis should be an important differen- will typically develop a combination of these
tial diagnosis in young dogs with blepharitis. forms of leishmaniasis. The disseminated dis-
Treatment of canine demodicosis involves the ease produces emaciation with muscular
use of amitraz dips and/or oral ivermectin or weakness, chronic renal failure, and chronic,
milbemycin administration. Use of avermectin nonpruritic skin lesions. The cutaneous lesions
drugs should be limited to animals lacking begin on the head, thereby producing a
mutation for the P-­glycoprotein gene (MDR1). blepharitis characterized by scaliness and loss
of hair that begin at the medial canthus. Focal
Sarcoptic Acariasis (Sarcoptic Mange, Canine Scabies) granulomatous blepharitis is also a typical eye-
Sarcoptic mange is caused by the mite Sarcoptes lid reaction.
scabiei var. canis. Although sarcoptic mites Ocular manifestations of leishmaniasis
have host species preference, they are able to occur in up to 81% of dogs with the disease
cause disease in nonpreferred hosts. (Figure 19.15). Ocular manifestations of leish-
Consequently, sarcoptes can be transmitted maniasis consist of blepharitis, simple or gran-
from dogs to people, and vice versa. Clinical ulomatous conjunctivitis, scleritis, superficial
signs of sarcoptic mange include intense pruri- or deep keratitis, anterior uveitis, keratocon-
tis, alopecia, and reddish papulocrustus junctivitis sicca (KCS), and secondary
804 Ocular Manifestations of Systemic Disease

diseases in veterinary medicine include (i)


rickettsioses caused by bacteria of the genus
Rickettsia, and (ii) ehrlichioses and anaplas-
moses caused by bacteria in the family
Anaplasmataceae. Many rickettsial diseases
are considered zoonotic.

Canine Cyclic Thrombocytopenia


Canine cyclic thrombocytopenia is caused by
Anaplasma platys (formerly Ehrlichia platys), a
bacterial organism that strictly replicates in
Figure 19.15 Conjunctivitis in a dog with
leishmaniasis. Note the prominent thickening of
platelets, and is not considered zoonotic. A tick
the ventral bulbar conjunctiva. Cytological vector is the presumed mode of transmission of
evaluation of the conjunctiva revealed A. platys. Anaplasma. platys is distributed in the
mononuclear inflammatory cells and numerous southeastern United States, southern Europe
amastigotes of Leishmania infantum.
(Greece, Italy, France), and South America.
The disease follows a cyclical course.
glaucoma; signs are typically bilateral. The Specifically, platelet counts decline dramati-
anterior vitreous may have an inflammatory cally within a few days of A. platys infection,
reaction, but the posterior choroid and retina and then they rise within a few days, thereby
are usually spared. The inflammation is mono- following a cyclical course at one-­to two-­week
nuclear, and the organism can be found in his- intervals. Anaplasma platys has been described
tiocytes. Leishmania spp. and associated as producing uveitis in a dog, but the syndrome
granulomatous inflammatory infiltrates have was mild and improved rapidly. Diagnosis of
been recently described in intraocular, extraoc- A. platys depends upon observing the organ-
ular, and adnexal smooth and striated muscles ism within platelets, detecting serum antibod-
in affected dogs. ies for the organism, or detecting the presence
Allopurinol combined with sodium stiboglu- of organismal DNA via polymerase chain reac-
conate has been successful for the treatment of tion (PCR). Treatment is aimed at eliminating
canine leishmaniasis with none of the treated the bacteria by using doxycycline as the first
animals having relapse up to 24 months after drug of choice.
therapy. Second-­line medications such as
miltefosine and paromomycin require further Canine Ehrlichiosis
clinical studies regarding their efficacy in dogs. Canine ehrlichiosis is a tick-­borne disease pro-
There is no effective vaccine against canine vis- duced by Ehrlichia canis, Ehrlichia chaffeensis,
ceral leishmaniasis in the United States, Ehrlichia ewingii, Ehrlichia equi, A. platys (for-
although a secreted parasite antigen-­based merly Enchytraeus platys), A. phagocytophila
vaccine has recently been licensed for use in (formerly Ehrlichia phagocytophila), and
dogs in Brazil. The prognosis for dogs with Neorickettsia risticii (formerly Ehrlichia risticii).
leishmaniasis is variable. Relapses are com- As mentioned in the introduction to this section,
mon with leishmaniasis. Ehrlichia spp. and Anaplasma spp. are small,
Gram-­negative, pleomorphic, obligate intracellu-
Rickettsial Diseases lar bacteria. The distribution of canine ehrlichio-
All members of the order Rickettsiales are sis is related, in part, to the geographical
obligate intracellular parasitic bacteria that distribution of ticks that act as vectors for these
require host cells to replicate. Two common bacteria. Canine ehrlichiosis is divided into an
groups of diseases still considered rickettsial acute disease phase (two to four weeks), a
­Acquire  805

subclinical phase (months to years), and a engorged and have perivascular infiltrates.
chronic disease phase. Acute disease phase clini- Retinal hemorrhages are common, and retinal
cal signs, including general malaise, anorexia, detachments may be observed, either from
fever, and ocular and nasal discharge, are typi- massive subretinal hemorrhage or from exu-
cally transient and animals will typically recover dates. Optic neuritis with engorged retinal ves-
spontaneously without treatment. Hematological sels and papillary hemorrhages may also occur.
findings in the acute phase of the disease also In addition, corneal ulceration, necrotic scleri-
include thrombocytopenia, leucopenia, and non- tis, low tear production, and orbital cellulitis
regenerative anemia. During the chronic disease have been reported.
phase of ehrlichiosis, common clinical signs Diagnosis of ehrlichiosis involves the direct
include general malaise, bleeding tendencies, visualization of morulae in peripheral blood
anorexia, pale mucous membranes, fever, lym- smears (only been found in 11% of dogs with
phadenopathy, splenomegaly, and uveitis. Ocular chronic ehrlichiosis), detection of E. canis anti-
signs may be present in all stages, but animals are bodies, or PCR amplification of Ehrlichia spp.
not usually presented for diagnosis until the DNA. The mainstay of therapy for canine ehr-
chronic stage. lichiosis includes the administration of doxy-
The prevalence of ocular lesions in canine cycline or tetracycline.
ehrlichiosis has been reported as 10–37%;
when present, such ocular lesions can produce Rocky Mountain Spotted Fever
devastating ocular disease that is typically Rickettsia rickettsii, a small coccobacillary,
bilateral. It has also been reported that approx- Gram-­negative, obligate intracellular bacte-
imately 18% of the cases of uveitis in North rium, is the causative agent of Rocky Mountain
Carolina are the result of some infectious etiol- spotted fever (RMSF). Rickettsia rickettsii is
ogy. Massive orbital and ocular hemorrhages transmitted by ticks; the vector and reservoir
have been observed, but more commonly, a ticks are Dermacentor andersoni (Rocky
uveitis with hemorrhagic overtones is the basic Mountain wood tick), Dermacentor variabilis
lesion (Figure 19.16). Retinal vessels may be (American dog tick), Amblyomma america-
num (lone star tick), Amblyomma cajennense
(Cayenne tick), Rhipicephalus sanguineus
(brown dog tick), and Haemaphysalis leporis-
palustrus (rabbit tick).
Common clinicopathological findings
include thrombocytopenia, leukocytosis,
hypoalbuminemia, and proteinuria. Ocular
and neurological involvement is common with
R. rickettsia infection, and clinical findings are
consistently due to vasculitis. Signs of conjunc-
tivitis, chemosis, petechiae of the conjunctiva,
iris, and retina, hyphema, mild anterior uvei-
tis, retinal edema, and retinal vasculitis
are common.
Diagnosis of RMSF is made based upon con-
sistent history, clinical and hematological find-
ings consistent with RMSF, and identifying
Figure 19.16 Left fundus of a four-­year-­old,
R. rickettsii through immunofluorescent test-
female German Shepherd dog with monocytic
ehrlichiosis. Note the exudative retinal detachment ing (tissue), presence of circulating antibodies,
and vitreous hemorrhage. or by identifying organism DNA using PCR.
806 Ocular Manifestations of Systemic Disease

Response to therapy is usually rapid and may lesions in the nontapetal region are white,
be used in establishing a presumptive diagno- somewhat fluffy, and have mildly indistinct
sis. The inflammatory lesion of the anterior (Figure 19.17). Acute lesions progress to scars
ocular segment should be treated with topical that are white, flat, and have sharply demar-
corticosteroids and atropine. The ocular cated borders. In the tapetal region, the acute
lesions of RMSF usually resolve quickly with lesions are subtle, with loss of tapetal detail,
therapy. Immunity following infection with and they may have a mild, overlying haziness.
R. rickettsii is long-­lasting and provides protec- With time, these develop into hyperreflective
tion against subsequent reinfection. Reducing lesions with sharp ­borders and varying
the dog’s exposure to ticks and prompt removal degrees of pigment clumping.
of attached ticks are helpful to prevent RMSF. The most dramatic clinical ocular problem
associated with CDV is optic neuritis, which is
Viral characterized by an acute onset of bilateral
Canine Distemper blindness and mydriasis borders. If inflamma-
CDV is caused by an enveloped, single-­stranded tion extends rostrally to the optic disc/papilla,
RNA Morbillivirus in the Paramyxoviridae fam- ophthalmoscopic signs of peripapillary hemor-
ily. CDV infects a wide variety of families of rhages and edema, retinal vascular congestion,
animals, including Canidae (e.g., dogs), and elevation of the papilla are observed
Procyonidae (e.g., raccoons), Ursidae (e.g., (Figure 19.18). The optic neuritis syndrome
bears), Mustelidae (e.g., ferrets and skunks), may be isolated, prodromal, or concurrent
and Hyaenidae (e.g., hyaenas). The disease is with other neurological signs of
rare in countries where the majority of dogs are CDV. Distemper-­associated blindness also may
vaccinated, but not infrequent in countries occur with inflammation of the optic tracts,
where CDV vaccinations are lacking. lateral geniculate nucleus, optic radiation, or
Acute ocular signs of CDV are usually asso- occipital cortex.
ciated with a bilateral conjunctivitis with Ocular signs are suggestive of, but not defini-
serous ocular discharge that progresses to tive for, CDV. Acute lesions of chorioretinitis
mucopurulent in nature. The CDV may pro-
duce an inflammatory reaction in the lacri-
mal gland characterized by mononuclear and
neutrophilic inflammatory infiltration as
well as by marked degenerative changes in
the glandular tissue. Corneal ulceration is
often profound with the development of mul-
tiple descemetoceles with or without corneal
perforations in one or both eyes. KCS usually
resolves in four to eight weeks if the animal
recovers from the systemic infection.
CDV often produces a multifocal, nongran-
ulomatous chorioretinitis, which is usually an
incidental finding. The incidence of chori-
oretinitis is unknown but probably varies, as
do those of the neurological signs, with the
strain of virus and the immunocompetency of
Figure 19.17 Distemper-­induced, multifocal white
the host. Acute lesions must be differentiated
lesions deep to the retinal vessels. Most lesions are
from scars, because the latter will not corre- active, as evidenced by hazy borders, and do not
late well with acute systemic signs. Active displace the vessels.
­Acquire  807

Young puppies (<2–3 weeks of age) most fre-


quently develop clinical signs of canine her-
pesvirus, while infection tends to be confined
to the respiratory and genital tracts in
older dogs.
Canine herpesvirus infection in adults tends
to be restricted to ocular surface diseases affect-
ing the cornea, conjunctiva, and eyelids, includ-
ing combinations of blepharitis, conjunctivitis,
and keratitis (ulcerative and nonulcerative).

Infectious Canine Hepatitis (Canine Adenovirus Type-­1)


Canine adenovirus type-­1 (CAV-­1), a nonen-
veloped, double-­stranded DNA virus in the
Adenoviridae family, is the causative agent of
infectious canine hepatitis (ICH). ICH pro-
Figure 19.18 Acute blindness in a dog with duces clinical disease in dogs, foxes, and bears.
distemper associated with papillitis. Note the
The ocular lesions of ICH have mostly become
elevated, hyperemic optic disc. A slight vitreal haze
interferes with detail. a historical footnote since Rubarth described
them in 1947. CAV-­1 may produce ocular
usually correlate well with concurrent sys- lesions of anterior uveitis and corneal edema
temic disease, but chorioretinal scars may not. and has been estimated to produce ocular
Because no specific antiviral therapy against lesions in approximately 20% of dogs during
CDV is, as yet, commercially available, treat- the recovery phase of a natural infection
ment is mainly symptomatic. Conjunctivitis (Figure 19.19). The universal use of CAV-­2 for
and decreased tear production are treated with immunization against ICH, however, has all
topical antibiotics and lubricants. Acute optic but eliminated this complication of vaccina-
neuritis is treated with systemic anti-­ tion. ICH and its ocular manifestations still
inflammatory dosages of glucocorticoids if occur in countries without routine ICH
other signs of CDV are absent. Vaccination is immunizations.
the key to preventing CDV. The prognosis for
dogs with neurological disease is considered
guarded to poor.

Herpesviruses
Canine Herpesvirus Canine herpesvirus is an
enveloped, double-­stranded DNA virus of the
Alphaherpesvirdae family and infects all can-
ids. Transmission of the virus can occur in
utero or during parturition. Puppies make con-
tact with the virus in infectious secretions on
passing through the birth canal of an infected
bitch or may contract viral infection from con-
tact with other infected puppies. The virus may
Figure 19.19 “Blue eye.” Mild but extensive
remain latent in sensory ganglia and lymphoid corneal edema in a puppy 10–14 days after
tissue. Litters of stillborn puppies or abortions vaccination with CAV-­1. Note the typical mottled
may occur following transplacental infections. appearance of the corneal edema.
808 Ocular Manifestations of Systemic Disease

Papillomavirus from an absolute or relative insulin deficiency


Papillomaviruses are nonenveloped, double-­ due to deficient insulin secretion by the β-­cells
stranded DNA viruses in the family of the islets of Langerhans. The most common
Papillomaviridae. Two forms of papillomavi- form of canine diabetes mellitus is insulin-­
ruses (oral form and conjunctival form) have dependent diabetes mellitus (IDDM) that is
been associated with causing papillomas characterized by permanent hypoinsulinemia,
involving the canine eye and adnexa. thereby necessitating exogenous insulin to
Papillomaviruses are usually species-­specific maintain glycemic regulation.
and antigenically distinct. Oral papillomas, Ocular manifestations of diabetes mellitus
which are usually found in young animals, in dogs include cataract formation, corneal
result from infection with a canine oral papil- endothelial cell loss, corneal endothelial pleo-
lomavirus, and the solitary skin lesions of older morphism and polymegathism, and retinal
animals result from infection with a cutaneous vascular damage such as microaneurysms. In
papilloma-­producing virus. Excision should addition, reduced corneal sensitivity and sig-
involve minimal handling of the papilloma, nificantly altered keratoconjunctival parame-
wide excision (if possible), and, perhaps, cryo- ters have also been reported in diabetic dogs.
therapy at the base of the lesion. There is no In particular, diabetic cataractous dogs had (i)
vaccine to prevent canine papillomaviruses. significantly lower STT values and signifi-
cantly higher corneal touch thresholds than
Tick-­Borne Encephalitis Virus nondiabetic noncataractous dogs.
Tick-­borne encephalitis virus (TBEV) is a The most common ocular manifestation of
single-­stranded, enveloped RNA virus belong- diabetes mellitus in the dog is cataract forma-
ing to the genus Flavivirus. TBEV is seen in tion. This percentage of cataracts in the dog
Europe and Asia. The virus is transmitted to increases even after the diagnosis of diabetes is
humans and animals via the bite of an infected established, because diabetic control is usually
tick (Ixodes ricinus – central Europe; Ixodes erratic.
persulcatus – Ural, Siberia, Far East). Cataractous changes are initially observed as
Dogs infected with TBEV can either (i) sero- vacuoles in the equatorial cortex that extend
convert without clinical signs or (ii) manifest into the anterior and posterior cortex. The cor-
with peracute (death within one week), acute tical sutures may be accentuated as well
(animals recover, clinical signs improve within (Figure 19.20). The process progresses to
three weeks), or chronic disease (clinical signs
resolve between one to six months). Diagnosis
of TBEV is made based on measuring acute
and convalescent serum and CSF IgG for TBEV
using an ELISA or by using immunohisto-
chemistry on CNS tissue. Treatment of dogs
with TBEV infection is purely supportive as
there is no virucidal therapy for the disease.
Prognosis is variable depending on the clinical
form of the disease.

Metabolic Diseases
Diabetes Mellitus
Figure 19.20 Immature cortical cataracts in a
Diabetes mellitus is the most common disorder mixed-­breed dog with diabetes mellitus. Note the
of the endocrine pancreas in dogs, resulting accentuated anterior and posterior cortical sutures.
­Acquire  809

complete cortical opacification of the lens, and seizures occur with a total serum calcium level
the sutures are often either fractured or wid- of 6–7 mg/dl or a serum ionized calcium level
ened because of water imbibition. Cataracts of less than 2.5 mg/dl.
from a variety of causes may progress rapidly,
but diabetes should be considered when a dog
is presented with rapidly progressive bilateral Neoplasia – Central Nervous System
cataracts.
Intracranial neoplasia, whether primary or
secondary, often produces ocular and/or
Hyperadrenocorticism (Cushing’s
orbital signs. All animals with a suspected
Syndrome)
space-­occupying CNS lesion should undergo
Hyperadrenocorticism, or Cushing’s syn-
ophthalmoscopy to determine whether
drome, is one of the most common endo-
papilledema, optic neuritis, or optic nerve atro-
crinopathies in dogs. Hyperadrenocorticism is
phy is present.
pathophysiologically divided into three forms:
The ophthalmic signs associated with intrac-
(i) pituitary-­dependent hyperadrenocorticism;
ranial neoplasia are highly variable and dogs
(ii) hyperadrenocorticism from functional
may present with signs as subtle as internal
adrenocortical tumors; and (iii) iatrogenic
ophthalmoparesis as the predominant clinical
hyperadrenocorticism. Hyperadrenocorticism
sign or with ophthalmic signs associated with
has been associated with ocular lesions of pro-
abnormalities of multiple cranial nerves and
gressive corneal ulceration, nonhealing cor-
abnormal changes in mentation and/or gait.
neal ulceration, corneal calcification, cataracts,
Intracranial neoplasia frequently produces vis-
KCS, lipemia retinalis, and lesions associated
ual deficits and papilledema in association
with systemic hypertension.
with neurological signs.

Hypothyroidism
Hypothyroidism develops as a result of Cavernous Sinus Syndrome
decreased production of thyroxine (T4) and The cavernous sinus is a paired venous sinus
triiodothyronine (T3) by the thyroid gland. anatomically located on the floor of the cranial
Hypothyroidism is a common naturally occur- vault and extending from the orbital fissures to
ring disease in dogs, with reported prevalence the petro-­occipital canals. Cranial nerves III,
rates of 0.2–0.8%. The mean age of dogs diag- IV, and VI, and the ophthalmic and maxillary
nosed with hypothyroidism is seven years. As branches of V lie in close proximity to the cav-
many as 20% of dogs with hypothyroidism ernous sinus. Consequently, diseases (includ-
have been reported to have KCS. ing neoplasia) involving the region of the
cavernous sinus can result in deficits in any or
Ionic Disturbances all of these cranial nerves. Cavernous sinus
Hypocalcemia syndrome can be either unilateral or bilateral.
Hypocalcemia in dogs may be caused by sev- Clinical signs related to deficits of these cranial
eral conditions, including hypoparathy- nerves may include a fixed and dilated pupil on
roidism, postparturient hypocalcemia, acute or testing direct and consensual PLRs, ptosis,
chronic renal failure, acute pancreatitis, vita- decreased corneal sensation, decreased ability
min D toxicity, severe nutritional secondary to retract the globe, and complete (i.e., internal
hyperparathyroidism (rare in dogs fed diets and external) ophthalmoplegia. The most com-
containing low calcium-­to‑phosphorus ratios), mon cause of cavernous sinus syndrome in
and intestinal malabsorption syndromes, dogs is neoplasia. Consequently, prognosis for
among others. Neurological signs of restless- cavernous sinus syndrome is considered
ness, muscle fasciculations, and tonic–clonic guarded to poor.
810 Ocular Manifestations of Systemic Disease

Neoplasia – Systemic Nutritional Disorders


Lymphosarcoma Milk Replacer-­Induced Disease
Lymphosarcoma is the most common sec- Cataract formation has been recognized in
ondary intraocular neoplasia of dogs, and it puppies and a variety of other species fed com-
usually affects both eyes. In most cases, sys- mercial or homemade orphan milk formulas.
temic involvement is obvious at the physical Levels of arginine have been found to be defi-
examination, but ocular disease may be the cient in canine and feline formulas, and sup-
presenting complaint. Very rarely, the sys- plementation has prevented cataracts in wolf
temic disease is occult and the ocular lesion cubs, puppies, and kittens. Various attempts to
is the primary clinical sign. In one large pro- correct commercial milk formulas, however,
spective study, 37% of cases of lymphosar- still result in cataract formation.
coma had ocular lesions. Of these ocular
lesions, 49% were anterior uveitis, 9% poste- Vitamin A Deficiency
rior uveitis, 14% panuveitis, 23% retinal hem- Vitamin A (retinol), a fat-­soluble vitamin, is
orrhages only, and 6% adnexal diseases. Most derived from its precursors (carotenoids) that
animals with ocular lesions were in the are found in plants. With regards to the impor-
advanced stages of lymphoma (i.e., stage V), tance of vitamin A in the ocular system, vita-
and 78% of the cases with leukemia involved min A (retinol) is stored and transformed into
ocular disease. Lymphosarcoma with ocular retinal, which is translocated between the reti-
involvement equates to advanced disease and nal pigment epithelium and the photorecep-
translates to a shorter survival period for tors. The earliest sign of such deficiency in
the dog. young dogs, however, is vestibular disease, but
blindness may also be an early manifesting
Other – Metastases sign. Papilledema has been noted in some dogs
Though relatively rare, a variety of carcino- with a deficiency in vitamin A; however, the
mas and sarcomas have been described as resultant papilledema could not be correlated
metastasizing to the eye and orbit. Bilateral with increased CSF pressure.
ocular involvement may occur, because most
tumors spread via a hematogenous route. The Vitamin E Deficiency
typical site of ocular metastasis is the uveal The antioxidant action of vitamin E limits lipid
tract, and, specifically, the ciliary body. The peroxidation and production of free radicals,
neoplasms may be masked by intraocular which are very damaging to cellular constitu-
hemorrhage, inflammation, and glaucoma; ents. The major sites of oxidant damage are the
thus, intraocular neoplasia, whether primary membranes of subcellular organelles.
or secondary, should be included in the dif- Lipofuscin is a yellow-­brown, autofluorescent
ferential diagnosis of undetermined sponta- pigment.
neous intraocular hemorrhage or secondary Ocular consequences of vitamin E deficiency
glaucoma. Ocular metastasis is usually a late in the dog include muscular and testicular
occurrence, so the history and/or physical degeneration, reproductive problems, hemo-
examination of the affected dog will often be lytic anemia, and weak and dying puppies.
indicative of significant systemic disease; Ocular lesions in both clinical and research
malignant melanoma; adenocarcinoma of the animals occur only with prolonged deficiency,
pancreas, mammary, salivary, sweat, and thy- and they consist of cataracts, decreased vision
roid glands; squamous cell carcinoma; transi- to blindness, and retinal degeneration. The reti-
tional carcinoma; mastocytoma; and canine nal degeneration has been described in detail
transmissible venereal tumor. and is first noted on ophthalmoscopy as a fine
­Acquire  811

stippling in the central deep retina. The mot- neonatal or weanling puppies, either debili-
tling increases in intensity, with brown accu- tated or overdosed toxic signs might develop,
mulations and night blindness later developing. relating to an increased metabolic rate.
Diagnosis is made based upon identifying char- Experimentally, cataracts could be routinely
acteristic clinical signs and identifying low produced with three times (30 mg/kg) the rec-
serum concentrations of vitamin E. Therapy is ommended parenteral dose.
directed at supplementation with vitamin E. Ivermectin is an antiparasitic drug that exerts
its antiparasitic actions by activating ligand-­
gated chloride channels in a variety of inverte-
Toxicities
brates. Activation of chloride channels prevents
Ophthalmic lesions caused by various sub- synaptic transmission, thereby causing paraly-
stances are listed in Table 19.5, and they are sis of the invertebrate parasite. Ivermectin con-
relatively rare. Most dogs affected by centrations do not typically reach toxic levels
ketoconazole-­induced cataracts are young within the mammalian CNS when adminis-
(<5 years) and have medium to large physical tered at therapeutic antiparasitic dosages. The
stature. Sulfa and related drugs are involved in reason for this is that the mammalian CNS vas-
several species. Idiosyncratic reactions (non-­ cular endothelial cell of the blood–brain barrier
dose-­dependent) to sulfonamides result in a has a specific ATP-­dependent transporter,
variety of medical conditions, including pol- known as P-­glycoprotein, that prevents a vari-
yarthropathy, hepatopathy, blood dyscrasias, ety of molecules (drugs) from entering the
skin eruptions, and ocular disease. One of the CNS. It has been known for some time that
most common clinical findings in dogs with herding dogs, especially Collies, are sensitive to
idiosyncratic reactions to potentiated sulfona- therapeutic dosages of ivermectin. A genetic
mides is KCS. defect in MDR-­1 has been found as the cause of
Disophenol (2,6-­diiodo-­4-­nitrophenol) was a ivermectin sensitivity. The mutant allele (gene)
popular, injectable anthelmintic for canine is thought to have descended from a common
ancylostomiasis during the 1970s. In young ancestor in Great Britain sometime in the nine-
teenth century.
Table 19.5 Toxicities producing ophthalmic Amiodarone is a class III antiarrhythmic
lesions in the dog. drug used in dogs with dilated cardiomyopathy
and ventricular arrhythmias. Adverse reac-
Antimicrobials tions to this drug include hepatotoxicosis and
Ketoconazole blood dyscrasias. In addition, it has been dem-
Sulfa drugs onstrated, experimentally, that corneal opaci-
Antiparasitic drugs ties may develop following long-­term use of
amiodarone in dogs. Only one of six dogs
Disophenol
treated with amiodarone, however, developed
Ivermectin
corneal opacities in this study.
Cardiovascular drugs
Tocainide is an oral, antiarrhythmic agent
Amiodarone that has been used in veterinary cardiology.
Tocainide When used in 12 Doberman Pinschers with
Hypolipidemic drugs cardiomyopathies at recommended doses for
Nonsteroidal anti-­inflammatory drugs more than two months, however, a bilateral,
Etodolac progressive corneal edema developed in 3 of
Phenazopyridine
the animals that was irreversible when well
established. When advanced, the edema was
Rodenticides (anticoagulant rodenticides)
severe enough to hinder vision.
812 Ocular Manifestations of Systemic Disease

Hypolipidemic compounds of the eyelid masses, episcleral masses, exophthal-


hydroxymethylglutaryl-­coenzyme A reductase mos, corneal edema, anterior and posterior
inhibitor group, when administered at high uveitis, retinal detachment, and glaucoma.
dosages, produce cataracts in the dog. These Systemic histiocytosis is a progressive dis-
cataracts typically begin as posterior subcapsu- ease that may wax and wane, especially early
lar equatorial opacities and, occasionally, ante- in the course of the disease, but typically
rior equatorial cortical cataracts. necessitates continuous immunosuppressive
Etodolac is a nonsteroidal anti-­inflammatory therapy such as corticosteroids. Immunosup­
drug that selectively inhibits cyclooxygenase-­2 pressive doses of systemic cyclosporine A or
and is used in the management of pain in a leflunomide, both potent inhibitors of T-­cell
variety of conditions, especially osteoarthritis. activation, are often warranted to treat intrac-
KCS has been reported with its use in dogs. table cases of systemic histiocytosis. However,
The mean age of affected dogs is 10 years and in severe cases, lesions may become persistent
there does not appear to be a breed or gender and fail to respond to therapy.
predisposition.
Phenazopyridine has been used as a urinary
analgesic, and in the dog, it has a unique lacri- Section II: Cats
mal toxicity. Within 7–10 days after doses of
25 mg/kg in the dog, the STT decreased below
­Congenital
10 mm/min, and signs of KCS develop. Cats,
rabbits, and humans do not develop lacrimal
Coat Color-­Related Diseases/Conditions
toxicity to phenazopyridine.
In all species, coumarin poisoning may man- White Coat Color, Blue Irides,
ifest with ocular or orbital hemorrhages. In the and Deafness
dog, the source of coumarin is typically found Complete albinism (complete lack of pigmen-
in anticoagulant rodenticides. tation) or partial or localized albinism (an
absence or reduction in the degree of pigmen-
Miscellaneous Diseases tation) is associated with not only the pheno-
Systemic Histiocytosis typic appearance of an animal’s coat and skin
Systemic histiocytosis is a familial disease of color, but also conditions affecting the ear and
Bernese Mountain Dogs and also occurs less eye. Domestic cats with white coat color and
frequently in other breeds. As opposed to blue irides have been reported to have a domi-
malignant histiocytosis (disseminated histio- nantly inherited deafness characterized by
cytic sarcoma), systemic histiocytosis is con- alterations to the membranous labyrinth and
sidered a non-­neoplastic, generalized bony modiolus. The syndrome results from an
histiocytic proliferative disease that causes autosomal dominant gene, W, that is fully
prominent skin lesions identical to those dominant with complete penetrance in pro-
reported with cutaneous histiocytosis; how- ducing white fur, with incomplete penetrance
ever, ocular and nasal mucous membranes, of deafness, and is incompletely dominant in
and other organs such as the lungs, bone mar- producing blue irides. The blue iris is also con-
row, and peripheral lymph nodes may also be ditioned by other genes that produce high
frequently affected. Systemic signs vary but degrees of white spotting that are allelic to
include anorexia, depression, weight loss, gene W and by other independent genes.
cutaneous nodules, and nasal infiltration. Importantly, therefore, not all blue-­eyed white
Ulceration of the skin overlying the cutaneous cats are deaf, while white cats with non-­blue
nodules is common. Ocular lesions occurred in irides may also be deaf. However, in one study,
three of six affected animals, manifesting as white cats with bilateral blue eyes were more
­Developmenta  813

frequently deaf than were heterochromic posterior suture-­line associated to mature cata-
white cats, which in turn were more fre- racts, and spontaneous nystagmus. The tape-
quently deaf than were white cats with bilat- tum develops normally in CHS-­affected
eral “brown” eyes. kittens, but it later rapidly degenerates, so that
by 56 days of age, tapetal rods have disappeared
Visual System Anomalies and Forms and tapetal cells are disorganized.
of Albinism
Visual system abnormalities associated with
forms of albinism have been reported in the
­Developmental
Siamese cat, demonstrating a form of partial
albinism with retinal hypopigmentation. In
Lysosomal Storage Diseases
particular, Siamese cats possess a mutant allele
of the albino series at the C locus (chch). Many lysosomal storage diseases have been
Siamese cats, therefore, have reduced ocular identified in cats (see Appendix E). These
pigmentation, including a lack of stromal pig- inborn errors of metabolism are, however, rela-
mentation of the iris or choroid, and a reduc- tively rare diseases. Storage diseases are charac-
tion in pigment of the iridal and retinal terized by an accumulation of metabolic
pigment epithelia. The retinal hypopigmenta- by-­products within lysosomes, the cellular orga-
tion in these cats is the critical factor resulting nelles that degrade complex macromolecules.
in misrouting of many of the projections of the The substrates for catabolism within lysosomes
retina to the brain, the nature of the projection include glycoproteins, mucopolysaccharides,
error, and the developmental consequences of oligosaccharides, proteins, and sphingolipids.
the relay of the misrouted retinal inputs to the
visual cortex. The abnormal retinogeniculate Alpha-­Mannosidosis
projections in Siamese cats have reduced ipsi- Alpha-­mannosidosis is a member of the inher-
lateral retinal projections since many axons ited oligosaccharidoses described in Persian,
originating in the temporal retina that nor- domestic shorthair, and domestic longhair
mally project ipsilaterally project contralater- cats, which results from a deficiency in acidic
ally in Siamese cats. As a consequence, each α-­mannosidase. Specifically, the disease in cats
lateral geniculate nucleus contains an abnor- is caused by a 4-­bp deletion in the feline α-­
mally greater representation of the ipsilateral mannosidase gene. Systemic manifestations of
visual field. Convergent strabismus with or α-­mannosidosis in cats include stunted growth,
without involuntary horizontal or rotary nys- skeletal deformities, emaciation, hepatomeg-
tagmus results from this retinogeniculate aly, and neurological dysfunction, including
misdirection. tremors, ataxia, dysmetria, and progressive
weakness. Ocular abnormalities described in
Chediak–Higashi Syndrome affected cats include progressive corneal and
Chediak–Higashi syndrome (CHS) is an auto- lenticular opacification and resting nystagmus.
somal recessive disorder of cats and other spe- Globoid Cell Leukodystrophy (Krabbe’s
cies. In cats, CHS is characterized by partial Disease)
oculocutaneous albinism, increased suscepti- Globoid cell leukodystrophy, or Krabbe’s dis-
bility to infections, and bleeding tendencies. To ease, is a member of the inherited sphingolipi-
date, CHS has only been reported in the Persian doses described in the cat, which results from a
breed. Ocular manifestations of CHS in cats deficiency in GALC activity. The substrate
include photophobia, pale irides, hypopigmen- galactocerebroside (i.e., galactosylceramide), a
tation of the nontapetal fundus, tapetal degen- constituent of myelin, and another metabolite
eration, cataracts ranging from incipient of myelin turnover, psychosine (galactosyl
814 Ocular Manifestations of Systemic Disease

sphingosine), accumulate. Psychosine is highly a 25-­bp inversion at the extreme 3′ end of the
cytotoxic to oligodendroglia and is thought to β-­subunit (HEXB) coding sequence.
be the primary metabolite involved in the
pathogenesis of the disease. Globoid cell leu- Mucolipidosis II (I-­Cell Disease)
kodystrophy in cats is generally characterized Mucolipidosis II, or inclusion cell (I-­cell) disease,
by an early-­onset, rapidly progressive, and is caused by deficient activity of the enzyme N-­
severe disease that has pathological lesions acetylglucosamine-­1 -­p hosphotransferase.
identical to those reported in other domestic Clinical signs in affected kittens initially
animals. Clinical signs are characterized by include facial dysmorphism and failure to
early posterior dysmetria and ascending inco- thrive, with death or euthanasia due to disease
ordination, and generalized tremors, in associ- progression being reported to occur between
ation with paraplegia and inability to perceive the first postnatal day and 216 days of age
deep pain. Ocular manifestations of this dis- (mean = 47 days). Neurological signs in
ease in cats include lack of vestibular ocular affected cats included dull, quiet behavior, and
reflexes, and signs associated with visual defi- progressive hind limb ataxia. Skeletal deformi-
cits, including diminished PLRs and reduced ties, such as carpal valgus or varus, were also
menace responses. described. Congenital facial abnormalities in
affected cats included thickened eyelids,
Gangliosidoses hypertelorism (widely spaced eyes), depressed
GM1-­Gangliosidosis nasal bridge, a flat broad face, frontal bossing,
GM1 gangliosidosis is caused by a deficiency of and low-­set ears.
lysosomal hydrolase, β-­d-­galactosidase, which
produces an accumulation of GM1 ganglioside Mucopolysaccharidosis
in the cerebral cortex and visceral organs. Such The MPSs are a group of diseases characterized
deficiencies have been reported in cats, dogs, by defective metabolism of mucopolysaccha-
cattle, and sheep The mode of inheritance of rides (glycosaminoglycans). Three types of
feline GM1 gangliosidosis is autosomal reces- MPSs have been identified in cats (MPSs I, VI,
sive. GM1 gangliosidosis is characterized by and VII). Defects in the degradation of glycosa-
mild (3–7 months of age) to severe (>7 months minoglycans and other proteoglycans result in
of age) progressive neurological disease and accumulation of these compounds in many
early death. In particular, clinical manifesta- cell types, including cells of the most severely
tions of feline GM1 gangliosidosis include dis- affected axial and appendicular skeleton. MPS
crete head and/or limb tremors, ataxia with I (Hurler syndrome), caused by a deficiency of
hypermetria, and progressive paraparesis, the lysosomal enzyme α-­l-­iduronidase, has
often with blindness and seizures. been reported in domestic shorthair cats
(Figure 19.21). The result of this enzyme defi-
GM2 Gangliosidosis (Sandhoff Disease) ciency is the tissue accumulation and urinary
GM2 gangliosidosis is caused by a deficiency of excretion of dermatan and heparan sulfate.
hexosaminidase. Hexosaminidase has two sub- Affected cats have an abnormal gait due to
units, α and β, each coded for by HEXA and bony dysplasia, vertebral fusion and polyar-
HEXB genes, respectively. Feline GM2 gangli- thropathies, stunted growth, joint immobility,
osidosis (Sandhoff disease or O-­variant) has cardiac valvular disease, facial deformities,
been reported in domestic shorthair and Korat and develop corneal clouding.
cats. The mode of inheritance of feline GM2 MPS VI (Maroteaux–Lamy syndrome),
gangliosidosis is autosomal recessive. The caus- caused by a deficiency of the lysosomal enzyme
ative mutation of GM2 gangliosidosis in the arylsulfatase B, has been reported in cats. MPS
domestic shorthair cat has been documented as VI is one of the more prevalent inherited
­Acquire  815

diseases in cats, and occurs commonly in cats


with Siamese ancestry. Corneal clouding asso-
ciated with feline MPSs I and VI is felt to be
due, in part, to accumulation of substrate in the
keratocytes. Corneal endothelial cells of MPS
I-­affected cats were shown to function nor-
mally in affected cats, despite these cells having
numerous vacuolated lysosomal inclusions or a
granular matrix. Structural alterations in the
(a) corneal stroma, including abnormal spacing,
size, and arrangement of collagen fibrils in
feline models of MPSs I and VI, were also
reported to account, in part, for the corneal
cloudiness observed in affected cats. MPS VII
(Sly syndrome), resulting from a deficiency of
β-­glucuronidase, has also been described in
domestic shorthair cats. β-­Glucuronidase defi-
ciency results in impaired catabolism of chon-
droitin, dermatin, and heparan sulfates.

Sphingomyelin Lipidosis (Niemann–


Pick Disease)
In humans, there are six types of Niemann–
Pick diseases (NPDs; types A–F), with types A,
B, and F demonstrating a deficiency in sphin-
(b)
gomyelinase, while a feline model of NPD type
C exhibited a defect in cholesterol transport.
Sphingomyelin lipidosis, or NPD, is character-
ized by sphingomyelin and cholesterol accu-
mulation in tissues. Cats with NPD type A may
also exhibit hepatomegaly. NPD type C has
been reported in domestic shorthair cats.
Clinical signs in NPD type C-­affected cats
involve progressive neurological dysfunction,
including intention tremors at 8–12 weeks of
age, followed by ataxia, hypermetria, lack of
menace response with intact vision, and, occa-
sionally, positional nystagmus.
(c)

Figure 19.21 Three cats with MPS showing the


­Acquired
typical features of this class of disease including
small ears, wide-­spaced eyes, thick eyelid margins, Cardiovascular Diseases
tear staining due to occluded nasolacrimal ducts,
flattened face with protuberant tongue and corneal Hypertension
clouding. (a) MPS I (α-­l-­iduronidase deficiency). Systemic arterial blood pressure is the product of
(b) MPS VI (4-­sulfatase deficiency). (c) MPS VII CO (CO = heart rate × stroke volume) and total
(β-­glucuronidase deficiency).
peripheral resistance. Primary hypertension is
816 Ocular Manifestations of Systemic Disease

hypertension resulting from unknown reasons. retinal degeneration, and papilledema.


A previous definition of the high “normal” Potential complications of systemic hyperten-
range of systolic blood pressure for cats was sion include anterior segment and vitreous
between 160 and 200 mmHg. Cats aged 11 years hemorrhage, uveitis, and glaucoma.
of age and older have been noted to have signifi- Hypertension should therefore be ruled out
cantly higher systolic, diastolic, and mean arte- when presented with intraocular hemorrhage
rial, and pulse pressures than cats under 11 years or bullous retinal detachment of
of age. Systemic hypertension is a relatively unknown origin.
common disease of older cats, and it has most The goals of antihypertensive therapy
consistently been associated with chronic renal include lowering blood pressure and slowing
failure and hyperthyroidism A recent study the progression of target organ damage
reported that 20/103 cats (19.4%) with chronic caused by chronic hypertension. Successful
renal failure were hypertensive. therapy requires good client compliance with
The ocular manifestations of systemic hyper- frequent reassessment of the blood pressure.
tension can be severe and lead to blindness If an underlying cause of the hypertension
(Figure 19.22). The consequence of ocular vas- has been identified, the primary condition
cular hypertensive changes is an initial vascu- should be addressed therapeutically, when
lar constriction in the retinal arterioles in possible. However, even if the presumed
response to increased blood pressure; when underlying cause of the hypertension is con-
sustained, it results in occlusion and ischemic trolled, antihypertensive therapy is typically
necrosis of the vessel walls, with resultant required in the long term. Amlodipine, a cal-
increased vascular permeability. Ocular lesions cium channel blocker, has been shown to be
associated with feline hypertension include an effective antihypertensive agent in cats
retinal hemorrhages, retinal detachments, reti- and is now considered a mainstay of therapy
nal edema, retinoschisis, varying degrees of for feline hypertension.

(a) (b)

Figure 19.22 (a) Fundus photograph of a geriatric cat with systemic hypertension. Note the multifocal
intraretinal and subretinal hemorrhages, and the peripapillary and dorsal tapetal retinal detachments.
(b) Domestic shorthair, eight years, M(n). Hypertensive ocular disease (right eye illustrated, both eyes
affected). Mean systolic blood pressure, 183 mmHg. Pigmentary disturbance and retinal degeneration in
chronic hypertensive disease presenting initially with bullous serous detachments.
­Acquire  817

Hematological Diseases Hyperviscosity Syndrome


Hyperviscosity syndrome comprises single or
Anemia
multiple clinicopathological abnormalities result-
Anemia is the reduction in RBCs per volume
ing from increased serum viscosity. The underly-
of whole blood. Ocular manifestations of
ing cause is usually a malignancy, such as
severe anemia include pale retinal vascula-
lymphoma, chronic lymphocytic leukemia, plas-
ture, varying degrees of retinal hemorrhage,
macytoma, or multiple myeloma. Hyperviscosity
and subtle changes in tapetal reflectivity.
syndrome in cats has most frequently been associ-
Retinal hemorrhages are more likely to be
ated with multiple myeloma, in which a certain
observed, however, and are more dramatic if
class of Ig is produced in excess.
accompanied by thrombocytopenia. Small
intraretinal hemorrhages are typical and may
Hypoxia
reabsorb quickly with correction of the ane-
Hypoxia most commonly occurs during anes-
mia, but pigmentary disturbances may be a
thetic episodes, and it may relate to apnea,
residual retinal alteration. In one study of 26
cardiopulmonary failure, improper intuba-
cats with anemia and hemoglobin values of
tion, overdose of anesthetic agent, failure of
less than 5 g/dl, 20/26 affected cats had retinal
anesthetic equipment, paralysis of the mus-
hemorrhages. Causes of anemia in these cats
cles of respiration, and severe systemic hypo-
included Mycoplasma haemofelis (previously
tension. Neurons are more sensitive to
Haemobartonella felis) infection, thrombocy-
hypoxia than other support tissues, and neu-
topenia, autoimmune hemolytic anemia,
ronal tissue affected by severe and prolonged
aplastic anemia, lymphosarcoma, and bleed-
hypoxia ± reperfusion will undergo severe
ing duodenal ulcer.
cellular metabolic dysfunction leading to
apoptosis and ischemic necrosis. Clinical
Thrombocytopenia signs of cerebral hypoxia include blindness,
and Thrombopathies stupor or coma, paralysis with decerebrate
Thrombocytopenia is an acquired hemostatic rigidity, seizures, and deafness. PLRs, how-
defect of cats. Thrombocytopenia results from ever, are generally normal. These signs may
decreased platelet production, increased plate- be either partially or wholly reversible after a
let removal, sequestration of platelets, or any period of days to months.
combination of these. The most common
causes of thrombocytopenia include infectious
diseases, neoplasia, drug-­induced reactions, Idiopathic Systemic Diseases
and immune-­mediated disease. Dysautonomia (Key–Gaskell or Dilated
Pupil Syndrome)
Hyperlipidemia Feline dysautonomia, which is also known as
Hyperlipidemia refers to an elevation in plasma Key–Gaskell or dilated pupil syndrome, was
concentrations of cholesterol and/or triglycer- first reported in England in 1982. The disease,
ides, and arises due to a disturbance in plasma which produces widespread autonomic nervous
lipoprotein metabolism. Hyperlipidemia can system dysfunction, has since been reported in
occur in cats for several reasons, including many cats throughout Europe, but the number
postprandial hyperlipidemia, diabetes mellitus, of documented cases in the United States
exogenous corticosteroid administration, remains small. The cause of dysautonomia has
megestrol acetate administration, nephrotic not been determined. Common systemic signs
syndrome, lipoprotein lipase deficiency, idio- of feline dysautonomia include general malaise,
pathic hyperchylomicronemia, and familial dehydration, reduced appetite or anorexia, dys-
hyperchylomicronemia. phagia, vomiting or regurgitation, xerostomia,
818 Ocular Manifestations of Systemic Disease

bradycardia, urinary bladder distention, and and 16 of 41 cats had diarrhea for more than
constipation. Ocular signs that have been four weeks. In 87% of the cases from multicat
reported most consistently include dilated unre- households, more than one cat was affected,
sponsive pupils, decreased tear production, and suggesting an infectious etiology. The progno-
protruding nictitating membranes. Vision is sis for this condition is good.
unaffected, and photophobia is variable.
Pharmacological testing with ocular autonomic
Immune-­Mediated Diseases
stimulants can aid in establishing the diagnosis
of feline dysautonomia. Results of these tests Dermatological Diseases
are based on denervation supersensitivity. Several immune-­mediated skin diseases may
affect the eyelids of cats, usually accompanying
Ischemic Encephalopathy other head lesions and with variable lesions on
Ischemic encephalopathy occurs when the arte- the rest of the body. These include pemphigus
rial supply to part of the brain is disrupted. A foliaceous, pemphigus erythematosus, pemphi-
portion of one side of the cerebrum supplied by gus vulgaris, food hypersensitivity, and feline
the middle cerebral artery is most often involved, atopy. However, pemphigus foliaceous is the
thereby resulting in necrosis. The cause is most common immune-­mediated dermatologi-
unknown in most cases; however, there is some cal condition affecting the feline eyelid. Biopsy
evidence that Cuterebra infection may play a role is necessary to establish the diagnosis of pem-
in some cases. In the cat, the condition manifests phigus complex diseases. Food hypersensitivity
by a sudden onset of behavior change, seizures, may be diagnosed on the basis of food elimina-
ataxia, and motor deficits. Visual deficits may tion trials, whereas atopy may be best diagnosed
accompany other neurological signs and are on the basis of skin testing. Treatment is aimed
usually cortical in origin. Treatment involves at the underlying disease process, but it often
supportive care with improvement in clinical includes anti-­inflammatory therapy, either topi-
signs typically occurring over days to weeks. cally or systemically, as well.

Nictitating Membrane Protrusion


Infectious Diseases
Idiopathic bilateral protrusion of the feline nic-
titating membranes is a common, poorly under- Bacterial
stood ophthalmic disorder. Retraction of the Sporadically, bacteremia arising from bacterial
nictitating membranes following instillation of infections involving other organ systems (e.g.,
topical adrenergic drugs, in affected cats, is sug- periodontitis or endodontic disease) may result
gestive of a loss of sympathetic innervation in varying degrees of focal chorioretinal lesions
such as that seen in Horner’s syndrome; how- consisting of hemorrhage or exudates (or
ever, other ophthalmic signs of Horner’s syn- both), which often go unnoted.
drome are absent. Cats with this syndrome have
normal intraocular structures, and vision is Bartonellosis
unaffected unless the nictitating membranes Bartonella spp. are fastidious, hemotropic,
protrude to the extent that they cover the pupil. short, pleomorphic, Gram-­negative rod-­
Affected cats often have concurrent watery shaped bacteria identified in a wide range of
diarrhea that precedes nictitating membrane domestic and wild animals. Bartonella organ-
protrusion. Some cats may have diarrhea for isms are considered emerging zoonotic
weeks. A Tora-­like virus has been isolated from agents. Bartonella henselae, the causative
the feces of several affected cats in England. In agent for human CSD, is the prototypic
that study, 17 of 45 cats had nictitating mem- Bartonella disease that was originally recog-
brane protrusion for more than four weeks, nized in humans in 1889. In cats, infection
­Acquire  819

with B. henselae is common with 55–81% of although C. felis appears to have a predilection
cats being seropositive for the bacterium; toward conjunctival epithelial cells.
however, many infected cats do not show
clinical signs. Bartonella spp. are typically Mycobacteriosis
vector-­borne with the vector varying accord- Mycobacteria are aerobic, non-­spore-­forming,
ing to the species of Bartonella. Cat and dog nonmotile, acid-­fast staining bacteria.
fleas and, less commonly, dog and deer ticks Mycobacteria have been associated with causing
carry the bacteria and act as vectors for trans- tuberculosis characterized by internal tubercu-
mitting Bartonella from cat to cat, and as lar granulomas, leprosy characterized cutane-
potential vectors for transmitting the organ- ous nodules, or progressive subcutaneous
ism from cats to humans. inflammation. The incidence of mycobacterial
Systemic manifestations of bartonellosis in infections in the cat has decreased dramatically
cats include fever, lymphadenopathy, lethargy, since the decline in bovine tuberculosis
anorexia, CNS disorders, urological diseases, (Mycobacterium bovis) and pasteurization of
and endocarditis. Bartonella-­associated feline milk, although new cases still occur. Feline
uveitis has also been reported following posi- mycobacteriosis has been reported to be caused
tive serology for Bartonella, and detection of by M. bovis, Mycobacterium tuberculosis,
Bartonella antibodies and DNA (i.e., via PCR) Mycobacterium simiae, Mycobacterium genavense,
in samples of aqueous humor. Recently, a and Mycobacterium avium. Ocular lesions
study evaluated serum from 113 cats with uvei- involve primarily of the posterior segment and
tis, 156 clinically ill cats without uveitis, and 97 include retinal hemorrhage, retinal detach-
healthy cats. The healthy group of cats had the ment, and granulomatous choroiditis associ-
highest percentage of serum samples (68 of 97 ated with large numbers of tubercle organisms
[70%]) that were ELISA positive for Bartonella within the eye (Figure 19.24).
spp. IgG antibodies. In addition, a recent study
used immunofluorescent antibody (IFA) and Mycoplasmosis
blood culture to detect Bartonella spp. serum Mycoplasma spp. are the smallest free-­living
antibody and DNA in 298 ill cats. organisms, and they are classified as prokary-
Treatment of bartonellosis in cats involves otes. Mycoplasma felis, Mycoplasma gateae,
the use of systemic antibiotics such as azithro- and Mycoplasma arginini have all been iso-
mycin or doxycycline. The current recommen- lated from both sick and healthy cats. The role
dation for treating ill cats with bartonellosis is of Mycoplasma spp. as a cause of conjunctivitis
using doxycycline at a dose of 10–22 mg/kg p.o. in the cat has been controversial because the
q 12 h for two to six weeks, with the dose being organism has been isolated from the eyes of
adjusted (up or down) to permit administration normal cats as well as from those of cats with
of a whole tablet to avoid esophageal irritation. conjunctivitis.

Chlamydophilosis Tetanus
Chlamydophilosis is caused by Gram-­negative, Tetanus is caused by the neurotoxin produced by
obligate intracellular bacteria of the genus the bacterium C. tetani. Clostridium tetani is a
Chlamydophila. Chlamydophila psittaci (for- motile, Gram-­positive, nonencapsulated, anaer-
merly Chlamydia psittaci) primarily infects obic, rod-­shaped, spore-­forming bacterium.
birds, and is a common pathogen of cats (for- Dogs and cats are naturally resistant when com-
merly Chlamydia psittaci var. felis), although the pared to other species such as humans and
strain affecting cats has been renamed horses. Clinical signs of tetanus develop when
Chlamydophila felis. The pathogenesis of chla- spores of C. tetani enter the body through skin
mydophilosis in cats remains largely unknown, wounds or during surgical procedures.
820 Ocular Manifestations of Systemic Disease

(a) (b)

Figure 19.23 (a) Photograph of the OS of a cat with ocular coccidioidomycosis. Fleshy mass-­like
protrusions from the upper palpebral and bulbar conjunctiva, enophthalmos, conjunctival hyperemia, and
mild aqueous flare are present. Fibrin strands extend from the cornea to cover the anterior lens capsule.
(b) OD of a cat with ocular coccidioidomycosis. In addition to the fleshy conjunctival lesions, there is severe
anterior uveitis and deep corneal vascularization.

Mycotic successfully treated, however, one with a com-


Blastomycosis bination of amphotericin B and ketoconazole
Blastomycosis is a systemic mycotic infection and the other with ketoconazole alone.
caused by the dimorphic fungus, Blastomyces
dermatitidis. Blastomyces dermatitidis is a Coccidioidomycosis
thick-­walled yeast that reproduces by budding Coccidioidomycosis is caused by the dimor-
in infected tissues (i.e., yeast phase), and in phic fungus C. immitis. The organism is found
nature, it is most likely a soil saprophyte that in sandy, alkaline soils of the dry regions of the
produces infective spores called conidia (i.e., southwestern United States, western Mexico,
mycelial phase). The tissue budding yeast form and Central and South America. Coccidioides
is 5–20 μm in size, with a thick, double-­ spp. produce mycelia during seasonal rainfall.
contoured wall. Blastomyces dermatitidis is As the soil dries, arthrospores develop and
endemic to various river valleys in the United become airborne under dry and windy condi-
States, Canada, Europe, Mexico, Latin tions. The major route of Coccidioides spp.
America, and Africa. Blastomyces dermatitidis infection is via inhalation. In a retrospective
has been reported in the cat, though to a much study of 48 cats, 19% had ocular signs that,
lesser extent than it has been reported in the though not described in detail, included retinal
dog. Reported ocular lesions in cats include detachments, uveitis, and iritis (Figure 19.23a
retinal detachment, pyogranulomatous chori- and b). The most common systemic signs of
oretinitis, and panophthalmitis. The posterior systemic coccidioidomycosis in cats are skin
segment of the globe is more commonly lesions, respiratory disease, and bone lesions.
affected that the anterior segment. The most reliable means of diagnosis is identi-
A diagnosis of blastomycosis is made based fication of the organism from fluid or tissue
upon cytological identification of the organ- aspirates. Forty-­four of these cats were treated,
ism. A positive agar gel immunodiffusion test 40 with ketoconazole and 4 with fluconazole
is considered to be highly suggestive of disease. and itraconazole. Thirty-­two cats became
Few cases in the literature include treatment asymptomatic, though relapses were common
for blastomycosis in cats. Two cats have been in cats treated with ketoconazole.
­Acquire  821

Figure 19.24 Two-­year-­old female European cat


with a conjunctivocorneal mass of the OS at
presentation. A nodular vascularized mass arising
in the dorsal bulbar conjunctiva at the temporal
canthus of OS and invading the sclera and cornea
is apparent. Histological examination confirmed a
granulomatous lesion with acid-­fast bacilli within Figure 19.25 Chorioretinitis with a circumscribed
macrophages. lesion in a cat with cryptococcosis.

Cryptococcosis Cats with cryptococcosis have been success-


Cryptococcosis is caused by C. neoformans or fully treated with itraconazole, which seems to
C. gattii (previously C. neoformans var. gattii). cause less side effects than ketoconazole or
Cryptococcus neoformans is associated with amphotericin B in this species. The recom-
high nitrogen-­containing environments such mended dose for itraconazole in the cat is
as avian feces or soil enriched with avian feces. 5 mg/kg every 12 h, and the drug is well toler-
Hence, birds such as pigeons are considered to ated by most cats. Anorexia and hepatic toxico-
be significant vectors of Cryptococcus spp. sis can occur, however, and blood chemistry
Cryptococcus gattii, however, is associated with profiles should be monitored.
eucalyptus and fir trees in Australia and
Canada, respectively. It is a yeast-­like organism Histoplasmosis
(3.5–7 μm) that typically contains a thick Histoplasmosis is caused by a dimorphic fungus,
capsule. Histoplasma capsulatum, which exists in various
Cryptococcus neoformans is the most com- river bottoms as a mycelial-­phase, soil sapro-
monly reported feline mycotic infection. The phyte. Histoplasma capsulatum grows best in
most frequent sites of disease are the nasal pas- nitrogen-­rich organic matter, such as bat and bird
sages, skin, and CNS. Chorioretinitis with feces. Though quite widespread in North and
granulomatous inflammation and retinal South America, endemic areas are in the Ohio,
detachments (Figure 19.25), anterior uveitis, Missouri, and Mississippi river valleys. Two cats
and exophthalmos have been reported, and with histoplasmosis have also been reported in
optic neuritis may also occur, particularly if San Joaquin Valley, a nonendemic region of
the CNS is involved. A diagnosis of cryptococ- California. The life cycle of H. capsulatum is sim-
cosis is made on the basis of cytological identi- ilar to that of Blastomyces and Coccidioides spp.,
fication of the organism aspirated from affected with a mycelial phase in the soil that produces
tissue. Antigen can be identified in serum by conidia, which once in the pulmonary system
latex cryptococcal agglutination kits, and convert to a budding yeast phase. Histoplasma
serum antigen titers can be used to monitor the organisms can then be disseminated via hema-
response to therapy. togenous or lymphatic spread.
822 Ocular Manifestations of Systemic Disease

Histoplasmosis has been observed in cats. In another affected cat, the Cuterebra larva had
Cats in endemic areas commonly have asymp- directly penetrated the sclera resulting in
tomatic pulmonary infections but may develop severe anterior uveitis characterized by a large
disseminated disease when the organism fibrin clot followed by generalized retinal
extends beyond the lungs. Common sites of degeneration and blindness. Ophthalmomyiasis
infection in disseminated disease include interna in which the Cuterebra spp. was found
bone, skin, and visceral organs. Ocular lesions in the vitreous slightly lateral to the optic nerve
include granulomatous chorioretinitis, ante- has been described (Figure 19.26).
rior uveitis, retinal detachment, and optic neu-
ritis. A diagnosis of histoplasmosis is made Parasitic – Nematodes
based upon cytological identification of the Onchocerciasis (Onchocercosis)
fungal organism and culture of the organism. Ocular onchocerciasis is caused by the nema-
Cats with histoplasmosis have been success- tode, Onchocerca spp. The life cycle of O. lupi is
fully treated with itraconazole without adverse not completely understood, but is likely simi-
effect during treatment. In one study, eight cats lar to that of other Onchocerca spp. Larval mat-
were reportedly cured of histoplasmosis with uration is thought to occur in black flies
use of itraconazole, though two cats relapsed (Simulium) or gnats/midges (Culicoides), the
and required additional therapy. intermediate hosts. Larvae are then transmit-
ted to the definitive host via blood feeding of
Parasitic – Dipteric Larvae the insect. The parasites then mature, mate,
Ophthalmomyiasis Interna/Externa and produce microfilariae that are ingested by
Ophthalmomyiasis interna refers to the the intermediate host, and so on. Most recently,
intraocular migration of fly (Diptera) larvae. two domestic shorthair cats residing in the
The syndrome has been observed in the cat southwestern United States were confirmed
and in the dog. The syndrome is quite charac- histologically and by molecular identification
teristic, but it is uncommon to determine the to have feline ocular onchocerciasis due to
type of fly larvae present. The point of entry is infection with O. lupi. The ophthalmic findings
unknown but postulated to be across mucous reported included chemosis and conjunctivitis,
membrane-­lined sites such as the conjunctival
surfaces, oral cavity, nasal cavity, skin, or other
body orifice or wound. The syndrome may be
presented in the acute stages if an anterior uve-
itis is produced, but usually the syndrome is
noted as an incidental finding in the chronic
stages. The characteristic ophthalmoscopic
lesions are wandering, curvilinear tracts that
frequently intersect and are associated with
retinal and preretinal hemorrhages in the
acute stage. Only acute cases warrant therapy,
and topical or systemic steroids are indicated
depending on the location of the lesion (or
lesions).
Three cases of intracameral Cuterebra spp.
larvae in cats have also been reported. In one
Figure 19.26 Cuterebriasis in a cat. Fundus
case, severe panophthalmitis was present, and
photograph of the organism in the vitreous with
even though the larva was surgically removed vitreal hemorrhage overlying the optic disc. The
from the anterior chamber, the eye was blind. black cuticular spines can be observed.
­Acquire  823

opacity within the anterior chamber, and dys- Leishmaniasis has only been described in three
coric pupil with progression to secondary glau- cats, two of which had panuveitis. A case of
coma and eventual enucleation following two ocular and visceral leishmaniasis has been
years. Histopathological assessment of this reported in a cat. This affected cat had bilateral
globe revealed a multinodular, predominantly melting ulcerative keratitis, exudative panuve-
granulomatous inflammatory infiltrate cen- itis and secondary glaucoma, diabetes melli-
tered on these parasites affecting the posterior tus, and macrophages with intracytoplasmic
episclera and orbital tissues. The second Leishmania detected cytologically on bone
affected cat had persistent conjunctivitis, ipsi- marrow aspirates. Leishmaniasis has also been
lateral facial nerve paralysis, facial hypalgesia, reported in cats with coinfections with feline
and corneal ulceration that resulted in subse- leukemia virus (FeLV) and/or feline immuno-
quent enucleation. Ocular onchocerciasis deficiency virus (FIV), and in one cat with con-
should be included in the differential diagnosis current pemphigus foliaceus.
list for cats with conjunctivitis and orbital dis- Diagnosis of feline leishmaniasis may be dif-
ease. The antiparasitic treatment commenced ficult since serology and serum protein electro-
in the two O. lupi-­affected cats was empirical, phoresis patterns are usually less specific than
and consisted of two broad-­spectrum parasiti- in affected dogs. The diagnosis is confirmed on
cides, including an avermectin class parasiti- the basis of finding the organisms (i.e., amas-
cide, selamectin, that were selected, in part, tigotes), which are round to oval and 2.5–5.0 μm
based on known safety in cats. Further investi- by 1.5–2.0 μm in size, in bone marrow aspi-
gation into therapies for onchocerciasis in cats rates, lymph node aspirates, or skin impression
is warranted. smears stained with Wright’s or Giemsa stains.
Other means of identifying the leishmania
Parasitic – Protozoal organism include histopathological or immun-
Leishmaniasis operoxidase evaluation of cutaneous or organ
Leishmania spp. are diphasic protozoal para- biopsy specimens, PCR performed on antico-
sites that infect a wide range of vertebrates, agulated blood, or bone marrow or lymph node
including dogs, cats, and humans. Feline leish- aspirates, or culture inoculation of hamsters.
maniasis is generally caused by different Leishmania spp. are difficult to eliminate
Leishmania spp. than those affecting dogs, from the body and recurrences are common. A
including Leishmania mexicana in Texas, variety of drugs have been used for the treat-
Leishmania major in Egypt, and Leishmania ment of leishmaniasis. Due to the limited
(Viannia) panamensis in Brazil. However, number of reported cases of feline leishmania-
L. infantum, a causative agent of feline leish- sis, treatment is not clearly defined.
maniasis in southern France and Italy, also
causes leishmaniasis in dogs in the “Old World.” Toxoplasmosis
Leishmania spp. cause cutaneous, mucocu- Toxoplasmosis is caused by the obligate intra-
taneous, and visceral diseases. Visceral forms cellular protozoal parasite, Toxoplasma gondii.
of leishmaniasis are not typically described in Toxoplasma gondii has a worldwide distribu-
cats, although reports of leishmania-­induced tion. Cats are both definitive and intermediate
cutaneous lesions have been more commonly hosts of T. gondii. Ocular disease associated
described. Cutaneous lesions are variable but with T. gondii is more commonly observed in
typically involve an ulcerative dermatitis on cats than in dogs, and in the cat, it is commonly
the face, pinnae, neck, thorax, and bony protu- associated with systemic disease, including ano-
berances. In addition, generalized alopecia and rexia, fever, hepatitis, myositis, pneumonia, gas-
scaling, and cutaneous nodules on the head trointestinal signs, and neurological signs.
and extremities have been reported. Clinical feline toxoplasmosis may also manifest
824 Ocular Manifestations of Systemic Disease

initially as cutaneous nodules. Toxoplasma gon- over approximately three to four months after
dii has been implicated as being a major con- infection, whereas those of the IgG class of
tributor to feline uveitis, yet its role in causing antibody may rise more slowly and remain
anterior uveitis in an otherwise asymptomatic elevated in cats for years after exposure to
cat is unclear. The uveitis may be anterior, pos- T. gondii. Current treatment recommendations
terior, or both (Figure 19.27). However, chori- for cats with toxoplasmosis-­induced uveitis
oretinitis is the most common ocular include oral clindamycin hydrochloride,
manifestation. 12.5 mg/kg twice daily for 21–30 days, in addi-
Uveitis secondary to toxoplasmosis may tion to treatment with a topical corticosteroid,
result from rapid replication of tachyzoites such as 1% prednisolone acetate every 6 h, and
within ocular tissue or from deposition of atropine (as needed to maintain mydriasis).
immune complexes within uveal tissue.
Intraocular production of antibodies specific Viral
for T. gondii has been documented, and the Calicivirus
organism has been identified within the uveal Feline calicivirus (FCV), a picornavirus, is pri-
tract by histopathology and in the aqueous marily a respiratory tract pathogen of cats but
humor by PCR. Stressors that may relate to may cause oral ulcers and polyarthritis. One
reactivation include coinfection with agents study reported that FCV had become a major
such FIV or with immunosuppressive doses of viral pathogen of the upper respiratory tract of
corticosteroids. cats in Japan with increased prevalence over
A diagnosis of ocular toxoplasmosis in an feline herpesvirus type 1 (FHV-­1). The diagnosis
otherwise asymptomatic cat is difficult, and of FCV can be made using laboratory tech-
histological demonstration of the parasite is niques such as virus isolation, immunofluores-
the sole definitive means of confirmation. The cence, and PCR assay. Vaccination with
diagnosis of toxoplasmosis-­related uveitis is, standard inactivated trivalent vaccine including
however, generally established on the basis of FCV has been correlated with resistance to
a positive serum T. gondii antibody titer, infection and clinical disease. Furthermore, a
though PCR tests to identify T. gondii DNA in study has reported that most vaccinated cats
biologic samples have also been developed. develop a serological response to all three viral
Laboratory tests that measure both T. gondii-­ antigens (feline panleukopenia virus [FPV]/
specific IgM and IgG are most helpful, because FCV/FHV-­1) that surpasses presumed protec-
levels of the IgM class of antibody rise and fall tive levels, lasting up to and beyond two years.

Feline Coronavirus (Feline Infectious Peritonitis)


Feline coronavirus infection in cats may lead to
no clinical disease, enteric disease, or feline
infectious peritonitis (FIP), which is a dissemi-
nated pyogranulomatous vasculitis. FIP repli-
cates within macrophages resulting in the
deposition of virus-­laden macrophages within
the endothelium of small blood vessels. FIP is
a fatal arthus-­type immune reaction of cats to
infection with the virus. Large multicat indoor
environments are known to favor feline enteric
Figure 19.27 Acute anterior uveitis with keratic
coronavirus (FECV) infection and FIP. Sexually
precipitates in a cat with naturally occurring
generalized toxoplasmosis. A chorioretinitis was intact cats and purebred cats are more likely to
concurrently present. develop FIP. A recent study evaluating the
­Acquire  825

prevalence of FIP in individual breeds reported FHV-­1 produces disease via at least two
increased risk of development of disease in mechanisms. The first mechanism involves
Abyssinians, Bengals, Birmans, Himalayans, cytolytic infection during active viral replica-
Ragdolls, and Rexes. FIP most commonly tion. Cell rupture can occur during primary
occurs in young cats, and it may manifest by an FHV-­1 infection or following viral reactivation
effusive or wet form of the disease, which from latency. FHV-­1 infection can also induce
includes fibrin-­rich fluid within the abdominal disease via a second mechanism, immune-­
and peritoneal cavities, or as a noneffusive or mediated inflammation. Primary FHV-­1 dis-
dry form of the disease. Ocular and neural ease in kittens generally produces upper
lesions are more likely to be present with the respiratory and ocular diseases.
noneffusive form. Clinical ophthalmic manifestations of
The most common ocular manifestation of FHV-­1 cytolytic infection are numerous and
FIP is bilateral granulomatous anterior uveitis, include conjunctivitis characterized by hyper-
often with large, mutton-­fat keratic precipi- emia, blepharospasm, chemosis, and ocular
tates and a fibrinous exudate into the anterior discharge. Conjunctivitis, whether unilateral
chamber Chorioretinitis is also frequently or bilateral, is probably the most common
observed, and a pyogranulomatous exudate FHV-­1-­related ocular disorder in adult cats
sheathing the retinal vessels may be present as without active respiratory disease, though
well. Additional findings may include retinal some of these cats will have concurrent sneez-
hemorrhages, detachments, and optic neuritis. ing or other mild signs of respiratory tract
In many cases, the definitive diagnosis of FIP infection. KCS has been reported in cats with
antemortem is difficult. Confirming a diagnosis FHV-­1-­related conjunctivitis as well. FHV-­1 is
of FIP infection based upon the measurement the sole documented viral cause of keratitis in
of several variables within serum, including cats. Corneal ulcers, whether dendritic or geo-
serum coronavirus titers, is impossible. Many graphic, are thus a common manifestation of
cats with FIP have low antibody titers, and fluc- cytolytically induced FHV-­1 ocular disease
tuating or high titers may, in fact, be more likely usually accompanied by conjunctivitis. If both
among cats with chronic re-­exposure to FECV the cornea and conjunctiva are ulcerated due
in the environment. There is no effective treat- to the cytolytic effects of FHV-­1, corneal
ment at present for FIP. Treatment of ocular stroma and conjunctival substantia propria
disease is symptomatic and includes use of become exposed, thereby facilitating adhesion
topical, subconjunctival, or systemic corticos- formation between these tissues (i.e., sym-
teroids as well as topical atropine. blepharon). Neonatal ophthalmia may be
caused by FHV-­1, either from maternal trans-
Feline Herpesvirus Type 1 mission to the kitten or from infection shortly
FHV-­1, a double-­stranded DNA virus and a after birth.
member of the alphaherpesvirus subfamily, is Clinical disease caused by the immuno-
highly species-­specific. Infection with FHV-­1 pathological mechanism of FHV-­1 is an
is common, and the virus is widespread among uncommon response to the viral infection.
cat populations. Studies have estimated that Stromal keratitis results from immune-­
over 90% of cats are seropositive to the virus mediated response to viral antigen, and is
with as much as 80% of infected cats remaining probably the most serious ocular manifesta-
latently infected on a lifelong basis, and with tion of FHV-­1. Stromal keratitis is often sec-
approximately 45% of these latently infected ondary to chronic ulceration and is
cats shedding virus throughout life. The virus characterized by deep corneal vascularization,
is spread from cat to cat either by direct con- edema, and cellular infiltrates. Stromal kerati-
tact, fomites, or by aerosolization of virus. tis may be a source of chronic pain, and it can
826 Ocular Manifestations of Systemic Disease

lead to significant corneal scarring as well. and to prevent development of keratitis or


Corneal sequestration is a common disorder in sequestration. Antiviral agents can be used in
the cat, particularly in the Persian and cats with chronic conjunctivitis as well, though
Himalayan breeds. The cause in many cats the results in these cases are variable.
remains undetermined, but sequestra may Treatment with oral lysine has been of some
occur after chronic corneal ulcers or keratitis benefit among humans in accelerating recov-
caused by infection with FHV-­1. ery from herpes simplex infection and in sup-
Establishing an accurate diagnosis of FHV-­1-­ pressing recurrence. An in vitro study has
related ocular disease in adult cats without res- shown lysine to be effective at reducing FHV-­1
piratory tract disease has been problematic. synthesis, in conjunction with low arginine
Diagnostic tests such as virus isolation and levels, by antagonizing the availability of argi-
fluorescent antibody test, both of which are nine, an essential amino acid used for viral
widely available, are relatively insensitive in synthesis. Recent clinical studies reveal that
cats with chronic or recurrent ocular disease. oral lysine is safe, and reduces both the sever-
In addition, serum antibody titers are only ity of conjunctivitis in cats with primary
potentially useful in unvaccinated cats, and FHV-­1 infection and the ocular viral shedding
even then, such titers may not rise in a predict- rate in FHV-­1 latently infected cats.
able manner. More recently available tech-
niques to identify viral DNA, such as the PCR Feline Immunodeficiency Virus
assay, are more sensitive and will likely become FIV is a lentivirus. The transmission of FIV is
the preferred diagnostic tests. most likely via bites between animals.
Treatment of recurrent FHV-­1 ocular disease However, FIV has been detected in semen
may, or may not, be required. Many cats with from acutely and chronically infected male
transient conjunctivitis recover spontaneously cats, indicating that FIV may also potentially
and need no therapy. The combined results of be transmitted to queens via infected semen.
two in vitro studies have shown FHV-­1 to be Earlier in the course of disease, FIV infection
susceptible to the following antiviral agents, results in progressive loss of CD4+ T-­helper
which are listed in order of decreasing effect: cells, followed by depletion of CD8+ T-­cells in
trifluridine, idoxuridine ≈ ganciclovir, cidofo- the advanced stages of the disease. FIV was
vir ≈ penciclovir, vidarabine, and others. first reported in 1987 and has subsequently
Certain above-­mentioned medications (e.g., been related to a number of diseases in the cat,
topical trifluridine, idoxuridine, and vidara- including ocular manifestations. The virus
bine) have been widely tested and used in cats causes ocular lesions via (i) direct damage of
with FHV-­1 infection, while the clinical effi- ocular tissues, (ii) inciting secondary immune
cacy and safety of others remain unknown. phenomena, and/or (iii) promoting opportun-
Recent studies have evaluated the effectiveness istic ocular infections. In a study of 54 clini-
and safety of an oral antiviral medication in cally ill cats seropositive for antibody to FIV,
cats called famciclovir. Recently, oral adminis- 19 had ocular disease, and 76% of these 19 were
tration of famciclovir at 90 mg/kg q 8 h for also positive for T. gondii-­specific serum anti-
21 days improved outcomes for not only oph- bodies. Anterior uveitis and chorioretinitis
thalmic but also systemic, clinicopathological, were the most common ocular findings.
virological, and histological variables in cats The diagnosis of FIV infection has depended
experimentally infected with FHV-­1. upon the use of positive antibody results in
Treatment of cats with viral corneal ulcers ELISA, western blot, or IFA tests. This has
should include debridement to reduce the made it difficult to reliably assess the FIV
number of viral particles and an ophthalmic infection status of cats using current serologi-
antiviral medication, both to hasten healing cal tests because the antibodies produced in
­Acquire  827

response to vaccination against FIV are indis- urine, saliva, and vomitus). Fleas may also
tinguishable from those used to diagnose FIV transmit FPV from infected to susceptible cats.
infection. In addition, the virus may be spread by contact
Treatment of uveitis in cats with both FIV with fomites, such as food bowls, litter pans,
and toxoplasmosis should be the same as that bedding, and cages. Kittens infected with FPV
for toxoplasmosis. Cats with uveitis associated during gestation or shortly after birth develop
only with FIV, however, should be treated with cerebellar hypoplasia and retinal dysplasia.
a topical corticosteroid, such as prednisolone
acetate 1%, and atropine 1% (as the uveitis dic- Feline Sarcoma Virus
tates). Some cats may also benefit from oral Feline sarcoma virus (FeSV) is a naturally
prednisolone, and long-­term use of topical occurring, replication-­defective, acute, trans-
prednisolone acetate may be needed to control forming FeLV that has incorporated one of sev-
the anterior uveitis. Response of pars planitis eral cellular oncogenes. These viruses can be
to oral and topical prednisolone, however, is transmitted either horizontally or vertically,
often poor. and they can cause spontaneous tumors in the
cat. The role of FeSV in naturally occurring
Feline Leukemia Virus feline uveitis is unknown. Recent studies have,
FeLV is a retrovirus that replicates in many epi- however, investigated the role of FeLV/FeSV in
thelial tissues. Transmission of FeLV is primar- the tumorigenesis of naturally occurring feline
ily through saliva. FeLV infection eventually uveal melanomas and ocular sarcomas.
results in malignant transformation or cyto-
pathic depletion of specific lymphocytic/
Metabolic Diseases
hematopoietic cell lines. Infection with FeLV
appears to cause little in the way of ocular dis- Diabetes Mellitus
ease, with primarily the exception of its role in Diabetes mellitus is a relatively common endo-
lymphosarcoma. The uveal tract is a common crine disorder of cats. It has been estimated
site for metastasis of neoplastic lymphocytes, that 1 in 400 cats is affected by diabetes melli-
probably via hematogenous spread. Cats with tus. Two clinically recognized forms of diabe-
ocular lymphosarcoma may present initially tes mellitus exist in cats: IDDM – type I, and
with signs of mild uveitis, including miosis, non-­insulin-­dependent diabetes melli-
aqueous flare and keratic precipitates, or sub- tus – type II. The most common form of feline
tle iridal masses. As the disease progresses, the diabetes mellitus is type II diabetes mellitus,
iris becomes greatly thickened and distorted although many cats are insulin dependent
with the infiltration of tumor cells upon initial diagnosis.
(Figure 19.27), and glaucoma is a common The most common ocular manifestation of
sequela as tumor cells infiltrate the iridoc- diabetes mellitus in the dog is cataract forma-
orneal angle. In association with neoplastic tion. Cataracts were present at the initial
invasion of the anterior uvea, iris motility examination of almost 60% of spontaneous
becomes restricted. Aqueous centesis may be canine diabetics, whereas no cataracts were
helpful in establishing the diagnosis, because noted in a series of 30 cats. Aldose reductase
neoplastic lymphocytes exfoliate into the aque- plays a role in the formation of cataracts when
ous humor. glucose levels are elevated in diabetes mellitus.
One of the reasons for variations in susceptibil-
Feline Panleukopenia Virus ity among species, ages, and individuals to dia-
FPV is a parvovirus. Transmission of FPV betic cataracts is the lenticular activity of
occurs most commonly by direct contact with aldose reductase. Older cats are not susceptible
infected cats or their excretions (e.g., feces, to diabetic cataracts since the level of
828 Ocular Manifestations of Systemic Disease

intralenticular aldose reductase is low in com- anisocoria, with the smaller pupil being con-
parison to that of dogs. tralateral to the tumor.

Hyperthyroidism
Neoplasia – Systemic
Hyperthyroidism is the most common endo-
crine disease of the cat. Feline hyperthyroid- Lymphosarcoma
ism usually develops as a result of functional The most common disease of this nature is
adenomatous hyperplasia, or less commonly probably lymphosarcoma (Figure 19.28). In
adenoma, of one or both thyroid lobules. a retrospective study of 49 cats with lympho-
Hyperthyroidism causes systemic hyperten- sarcoma confirmed at histopathology, ocular
sion in cats, which in turn, causes hypertensive manifestations of disease preceded systemic
retinopathy (see the “Hypertension” section disease in most cases. The uveal tract was
above). Retinal hemorrhages and retinal involved in all eyes, and nodular iris lesions
detachment have also been reported in hyper- were the most common manifestation, being
thyroid cats secondary to systemic present in 35 of 50 eyes. Seventeen of these
hypertension. cats were tested for FeLV, and seven
were positive. Survival ranged from 0 days to
Ionic Disturbances 31 months, with a mean survival of
Hypocalcemia 14 months.
Hypocalcemia in cats may be caused by several
conditions, including hypoparathyroidism, Other – Metastases
postparturient hypocalcemia, acute or chronic Adenocarcinomas have been reported to metas-
renal failure, acute pancreatitis, vitamin D tox- tasize to the feline eye, with the site of origin
icity, severe nutritional secondary hyperpar- being the lung, mammary tissue, uterus, and
athyroidism, and following surgical disseminated adenocarcinoma of undetermined
thyroidectomy, among others. Neurological origin. Four cases of feline pulmonary carci-
signs of restlessness, muscle fasciculations, noma have been reported to metastasize to the
and tonic–clonic seizures occur with a total posterior segment of the eye. Squamous cell car-
serum calcium level of 6–7 mg/dl or a serum cinoma has also been reported to invade intraoc-
ionized calcium level of less than 2.5 mg/dl. ular structures, either by direct extension from
Hypocalcemia in the cat has been documented
clinically to be associated with focal punctate
to linear opacities in the anterior and posterior
cortices of the lens.

Neoplasia – Central Nervous System


Blindness associated with intracranial neopla-
sia has been reported in cats. In a series of 36
cats with meningiomas, blindness or visual
field deficits were found in 7 cats. Six of these
seven cats had unilateral visual deficits,
whereas the remaining cat was completely
blind, with dilated pupils from compression of
Figure 19.28 Early intraocular lymphosarcoma
the optic chiasm by a third ventricle meningi-
(FeLV) presented as anterior uveitis. Note the
oma. Six cats also had positional nystagmus, raised infiltrate of cells and neovascularization in
and one cat with tentorial herniation had the lateral iris.
­Acquire  829

the head or via hematogenous spread from a FCRD. During the ensuing years, controversy
more distant site. existed regarding whether these were the same
or two different syndromes. In the mid-­1980s,
taurine deficiency was determined to be a
Nutritional Disorders
cause of dilated cardiomyopathy in the cat.
Milk Replacer-­Induced Disease Subsequently, cat food companies increased
Cataracts have been reported in growing kit- the levels of taurine in commercial, processed
tens fed a commercial milk replacer diet. The cat foods. Typical lesions of taurine deficiency
low serum arginine concentration in these kit- begin with a granular appearance, which pro-
tens was thought to relate to the diet and, pos- gresses to a hyperreflective focus in the area
sibly, to the cataract formation. A study of centralis. A nasal focus of degeneration may
growing kittens documented cataract develop- develop next (Figure 19.29), extending to a
ment in kittens fed diets containing less than horizontal streak on both sides of the optic
3.0 g of histidine per kilogram of body weight. disc. Further degeneration also occurs, eventu-
ally encompassing the entire retina, but there
Taurine Deficiency is no predictable time frame for lesion
Feline central retinal degeneration (FCRD) progression.
was first described by Bellhorn et al. in 1970 Taurine is essential for photoreceptor sur-
and 1974. The lesion was characterized as a vival, and it is highly concentrated in the
focus of outer retinal layer degeneration in the inner and outer segments. Possible functions
area centralis. A few years later, taurine defi- of taurine in the retina include protection of
ciency retinopathy was described, with early the photoreceptors from light and chemical
lesions being identical to those described with damage, regulation of calcium ion transport,

Figure 19.29 Early taurine deficiency retinopathy in a cat. In the area centralis, there is a small, oval,
hyperreflective lesion with a darker border (left). The same eye eight months later. The original lesion has
enlarged considerably, forming a horizontal dark band immediately above the optic disc (right).
830 Ocular Manifestations of Systemic Disease

and regulation of signal transduction. pigment epithelium. Given the findings in this
Ultrastructural studies of the taurine-­ study, the adverse retinal reaction to enrofloxa-
deficient feline retina show initial disorgani- cin in cats appears to be a rare, idiosyncratic
zation and vesiculation of rod and cone outer reaction. Adherence to the manufacturer’s cur-
segment lamellar discs in the area centralis. rent recommendation for enrofloxacin dosage
in cats of 5 mg/kg p.o. q 24 h is advisable.
Thiamine Deficiency Safety studies evaluating the incidence of
Thiamine deficiency may occur in cats eating retinal degeneration with orbifloxacin, another
large amounts of raw fish, which contains thia- veterinary-­labeled fluoroquinolone, revealed a
minases, or in cats eating processed commer- dose-­ and concentration-­dependent adverse
cial foods in which thiamine has been destroyed ophthalmic reaction, with cats receiving
by heat processing and not replaced adequately. higher doses of the medication developing
Thiamine deficiency has also been reported in focal retinal degeneration. Safety studies con-
cats being fed commercial food containing sul- ducted on marbofloxacin, another veterinary-­
fur dioxide as a food preservative. approved fluoroquinolone, did not demonstrate
The diagnosis can be made on the basis of any ocular lesions following oral administra-
dietary history, clinical signs, and measure- tion of up to 20 times the minimum recom-
ment of thiamine concentration in food as well mended daily dosage. Nonetheless, the
as in blood. Normal blood thiamine levels for manufacturer of marbofloxacin indicates that
cats are approximately 32 μg/dl. Before devel- it is a prudent precaution to consider that all
opment of a comatose state, cats will respond fluoroquinolones may have the potential to
favorably to parenterally administered vitamin induce feline ocular lesions; therefore, all fluo-
B complex preparations containing 50–75 mg roquinolones should be used with caution in
of thiamine per dose every 8 h. this species.

Griseofulvin
Systemic Toxicities
Griseofulvin is a fungistatic agent used in cats
Antimicrobials to treat dermatophytosis. Griseofulvin is tera-
Fluoroquinolones togenic in the cat. Ocular anomalies reported
Enrofloxacin, a fluoroquinolone antibiotic, has in affected offspring of cats having received
been associated with a rare adverse ophthal- griseofulvin in the first half of gestation
mic reaction causing an acute, typically irre- include cyclopia, anophthalmia, optic nerve
versible, retinal degeneration in cats. In aplasia, and rudimentary optic tracts.
addition, this reaction has reportedly been Mesencephalic aqueductal stenosis has also
seen with other fluoroquinolones, including been reported in kittens following in utero
marbofloxacin and orbifloxacin. exposure to griseofulvin.
Affected cats develop signs of partial, tempo-
rary, or total blindness. The reported estimated Ivermectin
incidence of this adverse reaction is 1 in Ivermectin is a broad-­spectrum anthelmintic
122 414 treated cats or 0.0008%. Affected cats that has been used in cats for the treatment of
had generalized retinal degeneration, and ear mites and notoedric mange. Ivermectin toxi-
vision only returned in a few cases (Figure 19.30 cosis has been reported mainly in kittens, but
a–c). Histological assessment of two affected also occurs in adult cats. Signs of toxicosis typi-
globes showed mainly outer retinal degenera- cally become apparent within 1–12 h of admin-
tion as evidenced by a diffuse loss of the photo- istration of the ivermectin and include altered
receptor and outer nuclear layers, and behavior, lethargy, weakness, ataxia, recum-
hypertrophy and proliferation of the retinal bency, coma, and death. Ocular manifestations
­Congenita  831

(a) (b)

(c)

Figure 19.30 Acute retinal degeneration in a 15-­year-­old, male castrated cat after 196 days of
enrofloxacin administration. (a) Tapetal changes characterized by loss of retinal vessels, focal increased
tapetal reflectivity, and large gold-­to rust-­colored foci scattered throughout the tapetal fundus. (b) Pigment
loss and clumping within the nontapetal fundus. (c) Fundus photograph from a mature domestic shorthair
cat following five days of enrofloxacin therapy. Note the tapetal granularity, focal tapetal hyperreflectivity,
and moderate generalized retinal vessel attenuation.

of feline ivermectin toxicosis include apparent Section III: Horses


blindness, and alterations in pupil size includ-
ing mydriasis and miosis. ­Congenital
Megestrol Acetate
Coat Color-­Related Diseases/Conditions
Megestrol acetate is a synthetic derivative of
progesterone. It is generally used in the treat- Complete albinism (complete lack of pigmen-
ment of dermatological disorders, and has tation) or partial or localized albinism (an
been used to treat proliferative (eosinophilic) absence or reduction in the degree of pigmen-
keratoconjunctivitis in cats. Two cats treated tation) is associated with not only the pheno-
with long-­term megestrol acetate for dermato- typic appearance of an animal’s coat and skin
logical disease developed diabetes mellitus and color, but also conditions affecting the eye and
diabetic retinopathy. Both cats had bilateral other organ systems. Albinism or partial albi-
retinal hemorrhage and retinal detachment, nism may result from the failure of migration
and in one cat, microaneurysms were seen of neural crest cells (precursors to melanocytes)
832 Ocular Manifestations of Systemic Disease

and hence result in reduced numbers of mel- sabino, minimally white calico overo,
anocytes in a nonpigmented area, or may result splashed white overo, nonframe overo, and
because of impaired production of pigment due breeding stock solid coat colors may also
to some intrinsic deficiency in melanin produc- exist, however. Importantly, however, not all
tion (e.g., tyrosinase deficiency), but where the white foals of Paint Horse breeding with blue
number of melanocytes in nonpigmented or eyes will be homozygous for the endothelin B
hypopigmented areas is normal. In any case, receptor gene mutation, and consequently
albinism or partial albinism may manifest ocu- will not have lethal white foal syndrome. A
larly as something as benign as pale blue irides genetic test has been developed to screen for
and/or subalbinotic fundi or be associated with carrier animals or to test white blue-­eyed
generalized systemic disease such as lethal foals and thereby reduce the prevalence of
white foal syndrome. this condition in the American Paint Horse
population and prevent the premature eutha-
Lethal White Foal Syndrome (Lethal nasia of white, blue-­eyed foals. Genetic test-
White Overo Syndrome) ing for lethal white foal syndrome is
In horses, coat color is oftentimes associated commercially available (Animal Genetics
with iris color and heterochromia irides. For Incorporated [http://www.horsetesting.com/
example, it is not uncommon to see Paint LWO.htm]; Veterinary Genetics Laboratory,
Horses with one blue eye and one darkly pig- University of California at Davis [http://www.
mented eye or with two blue eyes. A condition vgl.ucdavis.edu]).
known as lethal white foal syndrome (an
equine model of Hirschsprung disease in Congenital Stationary Night Blindness
humans) is seen in white, typically blue-­eyed A condition long thought to be related to the
foals with typically two overo-­colored parents. incompletely dominant leopard spotting (LP)
In this instance, these foals are born with two allele is congenital stationary night blindness
copies (homozygous) of a mutated endothelin (CSNB) in Appaloosa horses. The condition is
B receptor gene. Endothelin-­3, a ligand for the nonprogressive; affected animals have cau-
endothelin B receptor, is a signaling molecule tious behavior in dim light conditions and may
important in the maturation and migration of be difficult to train. Neuro-­ophthalmic signs
neural crest cells. Neural crest cells are precur- may include bilateral dorsomedial strabismus,
sors to melanocytes and neurons in the periph- spontaneous nystagmus, and a dark-­adapted
eral nervous (including enteric) systems. In ERG lacking a b-­wave.
addition, neural crest cells also migrate to the CSNB has been reported in a variety of
inner ear and are important in maintenance of breeds of horses, including Appaloosa,
normal hearing ability. Consequently, foals Miniature Horses, Thoroughbred, and Paso
afflicted with lethal white foal syndrome are Fino. Recognizing, of course, CSNB is most
not only white with blue eyes but also have commonly documented in breeds with the LP
aganglionic colon resulting in gastrointestinal allele. Specifically, it has been shown that of
motility dysfunction and may also be deaf. the cases of CSNB occurring in breeds with the
Lethal white foal syndrome is inherited as LP allele, CSNB is only found in those animals
an autosomal recessive trait and therefore homozygous for LP (i.e., LP/LP). Animals with
both parents of affected foals are carriers of LP are characterized along a spectrum of white
the affected gene. Specifically, coat colors patterning (very little white patterning to sig-
associated with heterozygotes for the endothe- nificant white patterning). In heterozygous
lin receptor B mutation include frame overo, animals (LP/lp), there is typically more “spot-
highly white calico overo, and frame blend ting” within the white-­patterned regions of the
overo. Heterozygous animals with tobiano, body. Animals homozygous for LP (LP/LP)
­Congenita  833

typically have little to no spotting in the areas MCOAvphenotype have all of the anomalies
of white patterning. seen within the cyst phenotype but also have
It has been shown, phenotypically, that ani- varying severity and combination of congeni-
mals homozygous for LP, but not heterozy- tal cataracts, cornea globosa, iris hypoplasia,
gous (LP/lp) or noncarriers (lp/lp), are iridocorneal angle abnormalities, lens sublux-
affected by CSNB. Additionally, decreased ation, microphthalmia, and macropalpebral
expression of transient receptor potential cat- fissures. Neuro-­ophthalmic abnormalities con-
ion channel member 1 (TRPM1) gene in the sist of miotic pupils, abnormal PLRs with
skin and retina has been described in horses pupils that respond poorly to pharmacologi-
homozygote for LP and having CSNB. Recently, cally induced mydriasis. Affected individuals
three single-­nucleotide polymorphisms also have varying degrees of vision loss.
(SNPs) have been identified as completely Congenital ocular abnormalities observed in
associating with CSNB and LP. Though the Rocky Mountain Horses is, in part, related to
causative mutation for CSNB and LP is pres- coat color.
ently unknown, these SNPs can be used as a Mane and tail color was found to be associ-
genetic test for CSNB and LP. ated with the presence of multiple ocular
abnormalities. Specifically, 45% of Rocky
Multiple Congenital Ocular Mountain Horses with chocolate-­colored coats
Anomaly Syndrome with white manes and tails (Figure 19.31) had
Multiple congenital ocular anomaly syndrome multiple ocular abnormalities, including meg-
(MCOAS) was described in Rocky Mountain alocornea, congenital miosis, ciliary cysts, and
Horses in 1999. Since this time, MCOAS has retinal dysplasia (Figures 19.32–19.34).
been described in cross-­bred Rocky Mountain Meanwhile, only 12%, 6%, and 4% of horses
Horses, Kentucky Mountain Horses, Mountain with chocolate-­colored coat with flaxen mane
Pleasure Horse, Morgans, Belgians, American and tail, chestnut-­colored coat, or some other
Miniature Horses, and Icelandic Horses. coat color, respectively, had multiple ocular
MCOAS exists in two phenotypes, namely (i) abnormalities. Moreover, Rocky Mountain
cyst phenotype and (ii) MCOA phenotype. Horses with white manes and tails were more
Animals with the cyst phenotype have cysts likely to have multiple ocular abnormalities
arising from the ciliary body, peripheral retina, compared to animals with nonwhite manes
and/or iris. These patients may also have con- and tails. It has been shown that a genetic
comitant retinal dysplasia and/or retinal mutation occurring at the Silver Dapple locus
detachment. Animals with the is responsible, in part, for the multiple ocular

Figure 19.31 White pattern continuum for heterozygote (LP/lp) and homozygote (LP/LP) leopard complex
gene. There is a continuum of white pattern in horses heterozygous and homozygous for LP. Horses
homozygous for lp, however, have little to no pigmented spotting within the white patterned areas.
(Source: Courtesy of Sheila Archer.)
834 Ocular Manifestations of Systemic Disease

Figure 19.32 (a) Photograph of the


eye of a Rocky Mountain Horse with
congenital miosis and megalocornea.
Abnormalities include a miotic pupil,
stromal hypoplasia with a flattened,
circumferentially oriented granula
iridica at the papillary ruff, visible
sphincter pupillae muscle, and an
absence of a discernable collarette.
Radially oriented deep stromal strands
of iris tissue extend from the papillary
ruff toward the ciliary zone of the iris.
(b) Photograph of a normal iris of an
age-­and gender-­matched Rocky
Mountain Horse.
(a)

(b)

Figure 19.34 Fundus photograph of the left eye


of a Rocky Mountain Horse. Note the multiple,
Figure 19.33 (a) Right eye of affected animal darkly pigmented curvilinear streaks of retinal
with large and translucent cyst arising from the pigment epithelium in the peripheral tapetal
ciliary body (Courtesy of David Ramsey). fundus (Courtesy of David Ramsey).
­Congenita  835

abnormalities seen in Rocky Mountain Horses.


A recent study has narrowed the MCOAS locus
to 208 kb on chromosome 6. In particular, this
narrow region contains 15 genes requiring fur-
ther investigation into their role in MCOAS;
one of these genes is PMEL17 (gene responsi-
ble for silver coloration).

Severe Combined Immunodeficiency


Severe combined immunodeficiency is a con-
dition that manifests as lymphopenia (both
combined B and T lymphocyte deficiency) and
lack of lymphocytes in lymph nodes and the
spleen, subsequent lack of Ig synthesis, and
thymic hypoplasia. The condition is inherited Figure 19.35 Tapetal fundus from the right eye of
as an autosomal recessive trait in purebred and WB3, diagnosed with clinical equine motor neuron
disease. Note the distinct reticulated arrangement
part-­bred Arabian foals with as many as 25% of of pigment through the tapetal zone.
Arabian horses being carriers. The prevalence
is estimated to be 2.3% in foals of Arabian
descent. Affected foals may survive as long as
four months provided they have developed
passive immunity from ingesting the dam’s
colostrum. Clinical signs include general
malaise, serous to mucopurulent nasal and/or
ocular discharge, coughing, diarrhea, and are
nonresponsive to antimicrobial therapy.
Affected foals may have uveitis secondary to
sepsis or other disseminated opportunistic
pathogens. Diagnosis is made based on meas-
uring serum Ig levels and detecting a persistent
lymphopenia. Prognosis is grave. The cause of
death is usually adenoviral pneumonia, other
secondary infections, or both. Considering that
the condition is inherited, carrier animals Figure 19.36 Tapetal–nontapetal junction from
should be identified and culled from the breed- the left eye of WB2, diagnosed with postmortem
ing population. confirmed concurrent equine degenerative
myeloencephalopathy and equine motor neuron
disease. Note the pigment bars along the entire
Vitamin E-­Deficient Retinopathy tapetal–nontapetal junction with pigment
Vitamin E is a potent antioxidant and plays an clumping in the tapetal fundus.
important role in neuromuscular function.
Vitamin E-­deficient retinopathy has been degenerative myeloencephalopathy. Another
identified and described in neurological/neu- vitamin E deficiency-­related disease in horses
romuscular diseases where vitamin E defi- is vitamin E-­deficient myopathy, though reti-
ciency plays an important role, namely, equine nal lesions have not been described in patients
motor neuron disease (EMND) (Figures 19.35 affected by this condition. EMND is a disease
and 19.36) and neuroaxonal dystrophy/equine characterized by spinal and brainstem motor
836 Ocular Manifestations of Systemic Disease

neuron loss and degeneration. EMND can be will have a normal blood lymphocyte count
observed in horses of any age or gender, though (both B and T cells) but will have reduced or
is most common in middle-­aged to older horses absent serum IgM concentrations. Affected
of Thoroughbred or Quarter Horse ancestry. foals may have uveitis resulting from this
Clinical signs are typically attributed to mus- inherited immunodeficiency.
cular weakness (paresis) and lower motor neu-
ron disease. Affected animals will often have a
short-­strided gait and will have muscular fas- ­Acquired
ciculations that worsen following exercise.
These animals will also frequently shift their Photic Headshaking
body weight between limbs when standing in Photic headshaking is a condition character-
one position and have evidence of varying ized clinically by excessive and possibly vio-
degrees of generalized muscle atrophy and lent movement of the head in the vertical,
weight loss. In more severe cases, horses are horizontal, or rotary directions. The underly-
unable to stand. With regard to ophthalmic ing pathophysiology of photic headshaking in
signs, horses with EMND may have fundic horses remains unknown. Photic headshaking
changes characterized by a honeycomb pattern is thought to be similar to photic sneezing in
of yellow/brown pigment within the tapetal humans. Specifically, photic headshaking is
fundus similar to that seen in dogs with vita- oftentimes stimulated by exposure to bright
min E deficiency. This yellow/brown pigment light and the behavior improves when ocular
has been identified as accumulation of ceroid/ exposure to light is diminished. In one study
lipofuscin. In some instances, PLRs may be of seven horses, six experienced the onset of
abnormal. signs during the spring months. Diagnosis of
Diagnosis of EMND is made based on con- photic headshaking is made based upon con-
sistent clinical findings, reduced serum vitamin sistent history and by ruling out other causes
E concentration, and electromyography and of headshaking, including otitis and guttural
muscular peripheral nerve histopathology. pouch disease. Treatment with cyprohepta-
Vitamin E supplementation can be helpful in dine, an antihistamine and serotonergic
slowing or stopping the progress of the clinical antagonist, has successfully eliminated head-
signs. Approximately 40% of patients with shaking in five of seven treated horses in one
EMND will respond to treatment, though com- study, but the exact mechanism of its apparent
plete return to performance/working is varia- clinical efficacy is unknown. Surgical therapy
ble and may be dangerous for the rider/handler. for photic headshaking includes bilateral
Another 40% may have clinical signs stabilize infraorbital neurectomy, but this is considered
but be permanently disfigured, and 20% will a salvage procedure.
continue to decline despite appropriate therapy.
Infectious Diseases
Immunoglobulin M Deficiency
Borreliosis (Lyme Disease)
Deficiency of IgM is common in all breeds of Lyme disease is a tick-­borne disease caused by
horse, especially Arabians and Quarter Horses. B. burgdorferi, a spirochete bacterium.
It may occur as a primary genetic disorder or as Borreliosis is transmitted to vertebrates by
a result of immunosuppression. Most com- Ixodes spp. and A. americanum. Typically, ticks
monly, foals will present at four to eight must remain attached for more than 24 h in
months of age with respiratory tract infection order to transmit the spirochaete. Horses in
or enteritis. As opposed to severe combined endemic areas show serological evidence of
immunodeficiency, foals with IgM deficiency exposure to B. burgdorferi, but most are
­Acquire  837

clinically unaffected. Clinical signs reported in infection. Immunocompromised foals (e.g.,


association with equine Lyme disease include foals having failure of passive transfer and
arthritis and lameness, encephalitis, limb severe combined immunodeficiency), how-
edema, dermatitis, abortion, and foal mortal- ever, are susceptible to infection with R. equi
ity. Diagnosis of Lyme disease is made based infection. Foals will typically present with
upon consistent clinical signs, positive sero- pyrexia, nasal discharge, and other signs of res-
logical tests (e.g., IFA, ELISA, or Western blot), piratory tract infection. In addition to respira-
and positive response to therapy. Detection of tory illness, foals may have clinical signs
B. burgdorferi DNA using PCR for B. burgdor- related to gastrointestinal, orthopedic, or ocu-
feri on skin, synovia, and connective tissue lar disease.
samples may be useful in diagnosing borrelio- Diagnosis of R. equi infection is made based
sis. Treatment for Lyme disease should include upon culturing the organism from fluid
systemic antibiotics. Tetracyclines, amoxicil- attained from transtracheal wash or bron-
lin, ceftriaxone, and imipenem are effective choalveolar lavage. Ocular therapy, when indi-
against B. burgdorferi. Treatment of borreliosis-­ cated, should include frequent topical
related uveitis is nonspecific, but should administration of corticosteroids (e.g., predni-
include systemic nonsteroidal anti-­ solone acetate or dexamethasone) and atro-
inflammatory drugs, topical corticosteroids, pine. Prognosis for foals with R. equi infection
and/or nonsteroidal anti-­inflammatory drugs, is variable depending upon the severity of the
and atropine. disease and the duration of illness prior to
commencing therapy.
Leptospirosis
Leptospirosis is caused by systemic infection Salmonellosis (Paratyphoid)
by spirochetal bacteria of the genus Leptospira. Salmonellosis is caused by Gram-­negative
More than 200 serovars have been identified. motile rod-­shaped bacteria of the genus
Of these serovars, those most commonly iso- Salmonella. Salmonellosis frequently occurs in
lated in horses include Leptospira autumnalis, the horse, and it is a commonly diagnosed
Leptospira bratislava, Leptospira icterohaemor- infectious cause of diarrhea among adult
rhagiae, and Leptospira pomona. The bacte- horses. Salmonella spp. are frequently present
rium is commonly excreted in the urine of in the environment, and disease occurs mainly
infected animals, but any bodily secretion may among stressed animals or in those with
contain the bacteria during the acute stage of altered host defenses. Diarrhea results from
the disease. Horses typically become infected malabsorption secondary to gut epithelial cell
by ingesting water or feed previously contami- destruction and host inflammatory response to
nated by a carrier host’s urine (e.g., wildlife bacterial endotoxin. Ocular manifestations of
and cattle). Horses with leptospirosis may have salmonellosis may include iridocyclitis and
clinical signs attributed to acute renal failure, hypopyon, and such manifestations are most
abortion, and hepatitis in foals. Leptospirosis is likely to be seen in bacteremic animals.
also highly incriminated in equine recurrent
uveitis (see Chapter 15). Streptococcus equi (Strangles, Distemper)
Streptococcus equi var. equi is a Gram-­positive
Rhodococcus equi coccoid bacterium. Infection occurs via direct
Rhodococcus equi is a soil-­dwelling, Gram-­ contact from infected horses’ nasal secretions
positive, catalase-­positive, aerobic, coccoid or from coming in contact with fomites, includ-
bacterium. This bacterium is well known, ing feed and water troughs, housing, etc.
worldwide, to cause pneumonia in foals. Adult Streptococcus equi var. equi colonizes within
horses are typically spared from R. equi the pharyngeal and nasal mucosae and then
838 Ocular Manifestations of Systemic Disease

drains into regional lymph nodes and in some appearance (Figure 19.37). Affected tissue tends
instances can result in bacteremia. to bleed easily, and pruritus and self-­trauma may
Streptococcus equi var. equi infection is rela- be evident.
tively common and is often observed as an out- Diagnosis of cutaneous habronemiasis is
break on a farm or in a stable. Clinical signs of made based upon consistent clinical signs and
S. equi var. equi infection include pyrexia, gen- histopathologically consistent features observed
eral malaise, anorexia, serous (initial) and in biopsy specimens. Specifically, granuloma-
purulent (later) nasal discharge, pharyngitis tous inflammatory infiltrate with eosinophils
manifesting as an inability to swallow, and and mast cells is seen, along with collagenolysis.
pharyngeal, submaxillary, and parotid lym- Therapy is aimed at destroying the nematodal
phadenitis that may become abscessed. Ocular larvae by administering systemic doses of iver-
abnormalities associated with strangles include mectin. Debulking large nodules may be
initially serous and later mucopurulent ocular ­necessary. Further, topical or systemic anti-
discharge, panophthalmitis, and chorioretini- inflammatory drugs may be used to control
tis. In some cases, blindness may occur because inflammatory responses to dead and dying larvae.
of the development of brain abscessation.
Diagnosis of S. equi var. equi infection is Onchocerciasis (Onchocercosis)
made based on characteristic clinical signs and Onchocerciasis is a parasitic disease that
positive culture of S. equi from abscesses. affects a variety of species, including horses. In
Therapy for S. equi var. equi infection is contro- horses, onchocerciasis causing clinically rele-
versial and the reader is referred to recent vant ocular signs is caused by Onchocerca cer-
internal medicine textbooks. vicalis. Onchocerca larvae are transmitted to
animals by infected gnats/midges or black flies
Parasitic – Nematodes (Culicoides or Simulium spp., respectively).
Habronemiasis (Habronemiosis, Summer Sores, Following infection, larvae migrate to the
Swamp Cancer) nuchal ligament where they develop into adult
Habronemiasis is a parasitic disease caused by worms. The adult worms persist and produce
the aberrant migration by larvae of the nema- microfilaria that migrate to various subcutane-
todes Habronema muscae, Hypericum majus, ous sites where the intermediate host (midges/
and Draschia megastoma. Habronemiasis is seen gnats and blackflies) can become infected and
in tropical and temperate climates worldwide then infect another host.
These nematodes normally are found within the
stomach of horses. Flies, including Musca
domestica (house fly) and Stomoxys calcitrans
(stable fly), are used as the intermediate host.
Larvae are passed in the feces and are consumed
by maggots of the intermediate host. When the
adult fly emerges, the third-­stage larvae (L3)
within the fly are infective, and horses become
infected by ingesting the fly or the L3 larvae that
have been deposited near the mouth of the
horse. Lesions are typically concurrent with the
fly season and may regress with cold weather
only to resume when the weather becomes Figure 19.37 Ulcerative granuloma of the medial
canthus of the right eye of a horse with ocular
warm again. Lesions may affect the conjunctiva
habronemiasis. Raised nonhealing lesions, such as
or the periocular area, and the papules have a the one illustrated, are often pruritic and self-­
raised, irregular, yellow (i.e., “sulfur granules”) trauma is common.
­Acquire  839

Before the availability of ivermectin, the Equine Viral Arteritis


prevalence of O. cervicalis microfilariae in most Equine viral arteritis is a contagious equine
countries varied and often was quite high. The disease caused by a togavirus known as equine
most common sites of ocular microfilariae are viral arteritis virus. Equine viral arteritis virus
the conjunctiva and eyelids, followed by cor- is transmitted via inhalation of the virus and
nea/sclera and the intraocular structures or through sexual contact. The virus causes a pan-
aqueous humor. Other ocular manifestations vasculitis, with necrotizing arteritis of the
of onchocerciasis include anterior and poste- small arteries of muscles commonly being
rior uveitis, peripapillary chorioretinitis, kera- seen. Outbreaks and serological evidence of
titis, keratoconjunctivitis, and lateral the virus have been reported from many coun-
conjunctival vitiligo. Diagnosis of onchocerci- tries around the world. Clinical signs include
asis is made based upon microscopically iden- fever, depression, coughing, nasal and ocular
tifying the nematode in biopsy specimens of discharge (Figure 19.38), and abortion.
affected tissues, including conjunctiva or skin. Periorbital and peripheral edema, conjunctivi-
Treatment of onchocerciasis has been most tis, corneal opacity, and photophobia have also
effective with systemically administered iver- been described. Diagnosis of equine viral arte-
mectin (0.2 mg/kg) or moxidectin (0.4 mg/kg). ritis is made based upon consistent clinical
signs, detecting a rising serum titer and/or iso-
lation of the virus and/or detecting the organ-
Parasitic – Protozoal ism using reverse transcriptase PCR (RT-­PCR).
Babesiosis (Equine Piroplasmosis, Biliary Fever) Treatment is aimed at supportive care, and
Equine babesiosis is caused by the tick-­borne, most adult horses make a full recovery,
intraerythrocytic, protozoal parasites Babesia although stallions may become chronic carri-
equi and Babesia caballi. The disease occurs in ers of the virus.
tropical and subtropical climates. Tick vectors
for equine babesiosis belong to a variety of gen-
era, including Dermacentor, Hyalomma,
Amblyomma, Boophilus, Anocentor, and
Rhipicephalus. The incubation period is from 5
to 28 days, and clinical signs include pyrexia,
hemolytic anemia, jaundice, hemoglobinuria,
and death. Ophthalmic signs include swelling
of the eyelids as well as icterus of the conjunc-
tiva and sclera. The color of the conjunctiva
varies from yellow to dark brown, often with
petechial and ecchymotic hemorrhages over
the third eyelid and other conjunctiva. Red-­
colored, serous ocular discharge has also been
noted in some horses, and distention of the
supraorbital fossa may be seen. Diagnosis of
equine babesiosis is made based upon identify-
ing the organism within erythrocytes on a
blood smear. A variety of drugs, including
diminazene diaceturate (11 mg/kg i.m.), ami-
carbalide diisethionate (9 mg/kg i.m.), and imi-
Figure 19.38 Left eye of a horse with equine viral
docarb dipropionate (2 mg/kg s.q. or i.m.), are arteritis. Note the marked conjunctival hyperemia
effective against both B. caballi and B. equi. and mild chemosis (Courtesy of R. Holyoak).
840 Ocular Manifestations of Systemic Disease

Equine Viral Encephalomyelitis Diagnosis of WNV infection is made based


Viruses of the family Togaviridae are insect-­ upon determining IgM concentrations in the
transmitted and cause encephalitis in the serum and/or CSF, amplifying WNV DNA
horse. The most pathogenic of these viruses using PCR, or isolating the virus. Therapy for
are called alphaviruses, and these include east- WNV infection involves supportive care and
ern, western, and Venezuelan equine encepha- administering systemic anti-­inflammatory
lomyelitis viruses, all of which occur in the drugs to reduce cerebral edema. Prognosis is
Americas. All of these viruses are transmitted variable. Older horses, horses not vaccinated
by biting insects, especially mosquitos. Also for WNV, and horses that are recumbent are
important to note, these viruses are considered more likely to succumb to the disease.
zoonotic. Early clinical signs, regardless of the
type of virus, include fever, stuporous state,
ataxia, and hyperesthesia. Later signs include
aggression, head pressing, blindness, para- Section IV: Food Animals
lyzed tongue and pharynx, nystagmus, strabis-
mus, and pupillary dilatation. Diagnosis of
­Congenital
equine viral encephalomyelitis is made based
upon time of year (are mosquitos present?),
Complete or Incomplete Albinism
consistent clinical signs, rising serum antibody
titers, and, in acute cases, isolation of the virus Complete albinism, although rare in cattle, has
from CSF or demonstration of the virus using been reported in several breeds, including
RT-­PCR. Treatment is nonspecific and sup- Swiss Brown “Braunvieh” in Europe, a
portive in nature. The mortality rate is high, Guernsey and Shorthorns in the United States,
but horses can recover from viral encephalitis. and Murboden in Austria. Inheritance of com-
plete albinism in these breeds appears to be
West Nile Virus recessive. Clinical and ophthalmoscopic mani-
West Nile virus (WNV) is single-­stranded RNA festations of complete albinism in cattle include
virus of the family Flaviviridae that is main- white coat, photophobia, blepharospasm, nys-
tained in the environment by a bird–mosquito tagmus, and nonpigmented irides and ciliary
relationship. Birds are the reservoir host, while processes. In contrast, forms of dominant
mosquitos transmit the virus to a variety of ani- incomplete albinism have been reported in cat-
mal species, including birds, horses, cats, dogs, tle in which the coat color of these animals is
bats, alligators, and humans. Horses are similar white with occasional pigmented spots over the
to humans in that they are considered dead-­end body. The irides of cattle with incomplete albi-
hosts (cannot transmit the disease), although nism vary from white to blue to gray with occa-
transfusion of infected blood products can sional brown sectors. In addition, tapetal
result in transmission of the disease to the recip- hypoplasia and optic disc colobomas are com-
ient. Crows and other members of the Corvidae monly noted. The fundi of both complete and
family are highly susceptible to WNV infection incomplete albino cattle have yellow tapeta
and carry a large virus load, and are considered lucida and nonpigmented tapeta nigra with
important in the transmission of the disease. large choroidal blood vessels distributed nor-
Clinical signs in horses include ataxia, pare- mally throughout this nontapetal region.
sis, generalized muscle fasciculations, pyrexia,
hyperesthesia, general malaise, lip droop, brux-
Infectious Diseases
ism, circling, and animals may be recumbent.
With regard to ophthalmic manifestations of Chlamydiosis
WNV infection, horses may be blind and have Chlamydial diseases in ruminants and swine may
facial nerve paralysis, mild keratitis of undeter- be caused by the species Chlamydia pecorum,
mined cause, and protrusion of the third eyelid. C. abortus, and C. suis. However, C. pecorum is the
­Congenita  841

main chlamydial pathogen responsible for ­disease therapy, although recurrence of clinical signs
in domestic ruminants. C. pecorum may produce or chronic persistent infections can occur.
a wide range of diseases in cattle, sheep, and
swine including encephalomyelitis, enteritis, pol- Mycoplasmosis
yarthritis, metritis, pneumonia, and conjunctivitis. (Infectious Keratoconjunctivitis)
Chlamydiosis among lambs and kids may Mycoplasmosis occurring in sheep and goats,
produce both ocular signs and polyarthritis. The and other small ruminants (wild and domesti-
ocular signs are bilateral in 80% of cases. cated), is caused by members of the genus
Conjunctival lesions include conjunctivitis, Mycoplasma, including Mycoplasma conjuncti-
petechial hemorrhages, epiphora and mucopu- vae, Mycoplasma mycoides, Mycoplasma aga-
rulent exudation, and conjunctival lymphoid lactiae, and Mycoplasma arginini. The disease
follicular proliferation that become confluent, may be seen in individual animals or may be
thereby producing folds. The cornea may seen as an epidemic. Mycoplasmosis in sheep
become involved in advanced cases with periph- and goats has been reported to cause kerato-
eral edema and vascularization (Figure 19.39). conjunctivitis as a sole manifestation of infec-
Rarely, the entire cornea may become opacified, tion or in association with various other
and corneal ulceration may develop. In uncom- systemic abnormalities, including respiratory
plicated cases, the condition is self-limiting, disease, arthritis, and mastitis. Mycoplasmosis
with resolution occurring within 2–3 weeks. has also been reported to cause an anterior
A definitive diagnosis of chlamydiosis is uveitis, choroiditis, and hyalitis.
made based upon the isolation or demonstra- Diagnosis of mycoplasmosis is made based
tion of the organism from infected tissues, upon consistent clinical signs, identifying the
combined with the presence of consistent clin- organism cytologically from conjunctival
ical and/or pathological findings. Chlamydial swabs, positively culturing the organism from
agents may be indicated by conjunctival cytol- conjunctival swabs and/or body fluids (e.g.,
ogy, which may be positive for chlamydial synovial fluid), or identifying organismal DNA
inclusions in 35% of cases. Treatment usually from affected animals. Treatment is aimed at
includes topical or systemic tetracycline appropriate topical and/or systemic antimicro-
bial therapy (e.g., tetracyclines).

Histophilus somnus (Thromboembolic Meningo­


encephalitis, Histophilosis Sleeper Calves)
Histophilosis is caused by infection with a pleo-
morphic, Gram-­negative bacterium, Histophilus
somnus of the family Pasteurellaceae.
Histophilus somnus produces a peracute to
chronic septicemia of yearling cattle, usually in
feedlots, though pastured animals have also
experienced outbreaks. Most infections occur
during the early winter months, and mortality
rates may be as high as 95%. The infection pro-
duces a vasculitis with thrombosis. Histophilus
somnus can cause mastitis, meningoencephali-
tis, myocarditis, otitis, orchitis, metritis
(Figure 19.40). Focal retinal detachments may
Figure 19.39 Chlamydial conjunctivitis in a be associated with the exudates as well, and
young goat. Conjunctival inclusion bodies were
present on conjunctival scrapings, and the
modest papilledema is often present. In the
condition responded well to treatment with topical later stages of the disease, fibrous chorioretinal
tetracycline. Note the peripheral keratitis. adhesions are also seen.
842 Ocular Manifestations of Systemic Disease

infects cattle, sheep, goats, and wild rumi-


nants. It is transmitted via inhalation or inges-
tion of infective secretions or excretions,
semen, and transplacentally. Results of one
study showed that BVD virus can also be trans-
mitted to susceptible animals if they come into
contact with fetal fluids during the birth of
persistently infected calves. BVD virus has
been implicated with causing abortion, and
cerebellar and ocular disease. In cattle, in utero
infection with BVD virus between 76 and
150 days of gestation may result in congenital
defects of the eye and brain. Ocular lesions of
cataracts, retinal degeneration and retinal dys-
plasia, optic nerve gliosis, optic neuritis, and
Figure 19.40 Recumbent heifer with
microphthalmia have also been described with
thromboembolic meningoencephalitis-­related experimentally induced disease.
retinal lesions. Multiple intraretinal hemorrhages
were associated with the small retinal vessels, Infectious Bovine Rhinotracheitis
subretinal exudate, and a bullous retinal
detachment.
Infectious bovine rhinotracheitis (IBR), caused
by bovine herpesvirus type 1 (BHV-­1), a mem-
Peracute to acute deaths with neurological ber of the alphaherpesvirus family, is an
signs as well as retinal hemorrhages and exu- important pathogen of cattle. Infection with
dates in feedlot cattle are highly suggestive of BHV-­1 typically arises ocularly or via the nasal
the diagnosis. Lesions of fibrinopurulent men- cavity. Following acute infection, the primary
ingitis and multifocal hemorrhagic necrosis of site for BHV-­1 latency is within sensory neu-
the brain at necropsy are “pathognomonic.” rons in the trigeminal ganglia. Sporadically,
Early treatment before the animal is recum- reactivation of the virus from latency occurs,
bent using appropriate antimicrobials may causing viral shedding and transmission to
prevent death. Vaccination is available. susceptible cattle. The persistence and reacti-
vation of BHV-­1 has also been reported within
Bluetongue the germinal centers of pharyngeal tonsil of
Bluetongue is caused by an arbovirus. The latently infected calves. Depending on the
virus is transmitted by Culicoides gnats and strain of virus involved, IBR can cause various
causes disease in ruminants. Clinical signs of forms of disease, including conjunctivitis/ker-
bluetongue in cattle include fever and vascu- atitis, severe respiratory infection, abortion,
litis, and severe conjunctivitis accompanied vulvovaginitis, balanoposthitis, and systemic
by mucosal lesions, laminitis, and edema of infection in neonatal calves.
the lips. In sheep, attenuated, modified live The ocular form may be the only sign or it
vaccine strains of bluetongue virus may pro- may be associated with respiratory signs. The
duce deformed lambs, brain deformities, and ocular lesions of IBR are either unilateral or
ocular lesions when injected during the 8th bilateral and may be confined to the conjunc-
to 11th week of pregnancy. tiva. Conjunctivitis is thus the most common
ocular manifestation of IBR, and may be char-
Bovine Virus Diarrhea acterized by raised, red to white plaques of
Bovine virus diarrhea (BVD) results from a lymphocyte follicles in chemotic bulbar and
pestivirus with a worldwide distribution that palpebral conjunctivae. The ocular discharge is
­Congenita  843

initially serous, following which it progresses


to become mucopurulent. A nonulcerative ker-
atitis of varying degrees may develop in some
animals. Anterior uveitis, which is evidenced
by miotic pupils and thickened iris, may
accompany the keratitis. The course of the
conjunctivitis is approximately two weeks.

Malignant Catarrhal Fever


Malignant catarrhal fever (MCF), caused by
ovine herpesvirus-­2 or alcelaphine herpesvirus-
Figure 19.41 Malignant catarrhal fever in a cow.
­1, is an often fatal and communicable disease in
Note the conjunctival and scleral injection, marked
cattle. The disease may affect other cloven-­ limbal-­based corneal edema, and signs of uveitis
hoofed animals, including some wild ruminants including miotic pupil (Courtesy of Ralph Hamor).
and occasionally domestic pigs as well. It may
produce either sporadic disease affecting one or
in mental status, including apprehension and
more animals in a herd or epizootics involving
occasional aggression, and stupor, and (iii)
large numbers of animals. It typically produces
postural and locomotion changes such as low
an acute syndrome of pansystemic vasculopa-
carriage of the head, wide-­based or cross-­
thy that results in death from 1 to 10 days after
legged stance, pacing, and ataxia.
the onset of clinical signs. Ocular lesions associ-
Ocular manifestations of scrapie infection of
ated with this form of MCF include corneal
sheep and goats include multifocal, round
edema, uveitis, exophthalmos, bilateral blind-
tapetal lesions that can be as large as the optic
ness, photophobia, nystagmus, and severe lacri-
disc (Figure 19.42). Histologically, these lesions
mation (Figure 19.41). Corneal edema is the
are focal retinal detachments resulting from
most obvious ocular lesion and develops within
36 h of the onset of disease.

Scrapie
Scrapie is a neurodegenerative disease of the
group of transmissible spongiform encepha-
lopathies affecting sheep and goats. Sheep are
regarded as the natural reservoir for scrapie.
The incubation period is typically between 2.5
and 3.5 years. According to the prion hypoth-
esis, which explains most of the biological
features pertaining to the scrapie agent, scra-
pie lesions are triggered by the conversion of
the cellular prion protein (PrPc) into the
abnormal isoform (PrPsc) resulting in its path-
ological accumulation. Scrapie produces pro-
gressive neurological signs, the lesions of
which consist mainly of vacuoles within the
nervous system, and eventual death. In par-
ticular, clinical signs are categorized into
Figure 19.42 Retinal photograph from scrapie-­
three main groups, including (i) sensation affected sheep showing raised blister-­like areas
abnormalities, namely pruritus, (ii) changes scattered in the tapetum lucidum.
844 Ocular Manifestations of Systemic Disease

(a) (b)

Figure 19.43 (a) Normal fundus appearance of a Friesian calf. Note the presence of the conus vestigialis,
the obvious difference between arteries and veins, and the color and clear outline of the optic disc.
(b) Papilledema due to vitamin A deficiency in a calf of comparable age and breed. Note the size of the disc,
the indistinct and raised border, and the small flame-­shaped hemorrhage at 11 o’clock (Courtesy of the late
Keith C. Barnett).

subretinal accumulations of eosinophilic these effects depend on age of onset, degree


material (characterized as lipids). These fundic of deficiency, and the amount of liver stores.
lesions are typical enough to be suggestive of Animals younger than six months of age are
the diagnosis when combined with chronic, more susceptible and more likely to have
progressive neurological disease. There is no blindness as a presenting sign because of
effective treatment for scrapie. Animals sus- sphenoid bone overgrowth constricting the
pected of having scrapie should be euthanized, optic nerve. On critical examination of ani-
and their brain should be submitted for labora- mals, night blindness, the first clinical sign
tory examination. noted in experimentally affected animals,
may be noted, but it is unlikely to be noted
Vitamin A Deficiency under typical husbandry conditions.
Vitamin A deficiency has been studied exten- Blindness is accompanied by fixed, dilated
sively among cattle, both in spontaneous pupils, and on ophthalmoscopy, papilledema
cases and with experimental induction. In will be present (Figure 19.43). Papilledema
young, growing animals, vitamin A defi- occurs well before blindness in both adult-­
ciency produces clinical signs when the vita- and young-­onset deficiencies. Papilledema
min A levels fall to less than 20 μg/dl of presumably results from increased CSF pres-
plasma and less than 2 μg/g of liver tissue. sure, which develops from fibrosis and thick-
A sexual predilection for males has been ening of the dura mater that, in turn, results
noted in two clinical reports. A lag period of in decreased absorption of the CSF by the
3–12 months may be necessary before the arachnoid villi. Increased CSF pressure is the
effects of vitamin A deficiency are noted, and first change noted with vitamin A deficiency.
851

Appendix A

Inherited Ophthalmic Diseases in the Dog

Table A.1 Genes associated with inherited ophthalmic diseases in the dog.a

Ophthalmic disorder Gene Breeds

Glaucoma:
Primary open-­angle ADAMTS10 Beagle, Norwegian Elkhound
glaucoma
Primary open-­angle ADAMTS17 Petit Basset Griffon Vendéen, Basset Hound,
glaucoma Basset Fauve de Bretagne, and Chinese
Shar-­Peis
Primary angle closure OLFML3 Border Collie
glaucoma

Lens and cataract:


Lens luxation ADAM17 Several breeds, mostly terriers
Hereditary cataract HSF4 Staffordshire Bull Terrier, Boston Terrier,
French Bulldog, and Australian Shepherd
Retina:
Autosomal dominant RHO English Mastiff
progressive retinal atrophy
Canine multifocal VMD2/BEST1 Great Pyrenees, English Mastiff, Bullmastiff,
retinopathy Cotton de Tulears, and Lapponian Herder
Congenital stationary RPE65 Briard
night blindness
Collie eye anomaly NHEj1 Collies, Nova Scotia Duck Trolling Retriever,
Japanese Hokkaido Inu dogs, Norwegian
Border Collies, and Danish Shetland
Sheepdogs.
Cone degeneration CNGB3 Alaskan Malamute, and German
Shorthaired Pointer
Cone–rod dystrophy ADAM9 Glen of Imaal Terrier
Cone–rod dystrophy NPHP4 Standard Wirehaired Dachshund
Cone-­rod dystrophy RPGRlP Dachshunds

(Continued)

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
852 Appendix A Inherited Ophthalmic Diseases in the Dog

Table A.1 (Continued)

Ophthalmic disorder Gene Breeds

Dwarfism with retinal COL9A Samoyed


dysplasia
Dwarfism with retinal COL9A3 Labrador Retriever
dysplasia
Early retinal degeneration STK38L Norwegian Elkhound
Generalized progressive CCDC66 Schapendoes
retinal atrophy
Photoreceptor dysplasia PDC Miniature Schnauzer
Progressive retinal atrophy CNGB1 Papillon
Progressive rod–cone PRCD Multiple breeds
degeneration
Rod–cone degeneration C2orf71 Gordon Setter, Irish Setter, Tibetan Terrier
Rod–cone dysplasia PDE6B Irish Setter and Sloughi
Rod cone dysplasia PDE6A Cardigan Welsh Corgi
Rod–cone dysplasia RD3 Collie
X-­linked progressive RPGR Mixed breeds, Siberian Husky, and Samoyed
retinal atrophy
a
For the most recent information, contact http://Optigen.com, University of California Santa Cruz Genome
Browser (http://genome.unsc.edu), Ensembl (http://enxembl.org), and NCBI (http://nchi.nlm.nih.gov/genome).
853

Appendix B

Inherited Eye Diseases in the Cat

Breed Ophthalmic disease

Abyssinian Early onset progressive retinal atrophy, late-­onset progressive retinal atrophy
Birman Dermoids, cataracts
Burmese Dermoids, congenital nictitans gland enlargement
Himalayan Epiphora, cataracts
Korat GM1 and GM2 gangliosidoses
Manx Corneal endothelial dystrophy
Persian Multiple ocular anomalies, epiphora, entropion, iridal heterochromia,
cataracts, retinal atrophy, α-­mannosidase
Shorthair Multiple ocular anomalies, dermoids, cataracts, GM1 and GM2
gangliosidoses, α-­mannosidosis, mucopolysaccharidosis I
Siamese Esotropia, nystagmus, iridal heterochromia, glaucoma, GM1 gangliosidosis,
mucopolysaccharidosis VI

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
854

Appendix C

Inherited Eye Diseases in the Horse

American Saddlebred Rocky Mountain Horse


Cataracts Anterior segment dysgenesis (chocolate coat color).
Esotropia Includes congenital miosis; corpora nigra and iridal
hypoplasia; macrocornea; ciliary body cysts;
Appaloosa
cataract; lens luxation; retinal dysplasia; retinal
Congenital stationary night blindness detachment
Congenital cataracts Standardbred
Glaucoma Retinal detachments
Equine recurrent uveitis Congenital stationary night blindness
Optic disc colobomas Thoroughbred
Squamous cell carcinomas Congenital cataracts
Arabian Microphthalmia associated with multiple ocular
Congenital cataracts defects
Vitiligo Retinal dysplasia associated with retinal
Belgian detachments in some cases
Aniridia and secondary cataracts Entropion
Squamous cell carcinomas Warmbloods
Color-­dilute breeds Glaucoma
Iridal hypoplasia (photophobia) Equine recurrent uveitis
Squamous cell carcinomas
Morgan
Cataracts: nuclear, bilateral, symmetrical, and
nonprogressive
Paso Fino
Congenital stationary night blindness
Glaucoma
Quarter Horse
Congenital cataracts
Entropion

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
855

Appendix D

Inherited Eye Diseases in Production Animals

Cattle:
Aberdeen Osteopetrosis, mannosidosis
Angus
Ayrshire Heterochromia iridis, porphyria, nystagmus
Beefmaster Neuronal lipodystrophy
Brown Swiss Supernumerary lacrimal drainage openings, multiple ocular anomalies
Charolais Posterior segment/optic disc colobomata
Devon Ceroid lipofuscinosis
Guernsey Heterochromia iridis, multiple ocular anomalies, nystagmus
Hereford Iridal heterochromia, optic disc coloboma with incomplete albinism, dermoids, cataracts,
retinal dysplasia and hydrocephalus, Chediak–Higashi syndrome, squamous cell
carcinoma
Holstein Cataracts, gangliosidosis, heterochromia iridis, nystagmus, corneal edema, porphyria,
Friesian glaucoma
Jersey Strabismus, cataracts, multiple ocular anomalies, nystagmus
Shorthorn Corneal edema, strabismus, exophthalmia, cataracts, retinal dysplasia and hydrocephalus,
porphyria, glycogen storage disease type II
Sheep:
Many breeds Entropion, upper eyelid coloboma
Corriedale Glucocerebroside storage disease type II, glycogen storage disease type II
South Ceroid lipofuscinosis
Hampshire
New Zealand Cataracts
Romney

Swine:
Breeds with Heterochromia irides
white hair
Sinclair Cutaneous melanomas/uveitis
miniature
Yorkshire Cerebrospinal lipodystrophy, glucocerebroside storage disease

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
856

Appendix E

Lysosomal Storage Diseases in the Dog, Cat, and Food Animals

Disease Breeds affected

Dog:
Gangliosidoses
GM1 Alaskan Huskie, English Springer Spaniel, Portuguese Water Dog, Shiba
Inus
GM2 Japanese Spaniel, German Shorthair Pointer, Golden Retriever
Fucosidosis English Springer Spaniel
Mucopolysaccharidosis Plott Hound
Globoid cell leukodystrophy Cairn Terrier and West Highland White Terrier
Ceroid lipofuscinosis English Setter, Australian Blue Heeler, Chihuahua, Border Collie, Saluki,
Tibetan Terrier, Dachshund, Dalmatian, Miniature Schnauzer, and
American Cocker Spaniel
Tyrosinemia

Cat:
GM1 gangliosidosis Domestic Shorthair, Siamese, Korat
GM2 gangliosidosis Domestic Shorthair, Korat
α-­Mannosidosis Persian, Domestic Shorthair, Domestic Longhair
Mucopolysaccharidosis I Domestic Shorthair
Mucopolysaccharidosis IV Siamese
Mucopolysaccharidosis VI Siamese
Mucopolysaccharidosis VII Domestic Shorthair
Mucolipidosis II Cat
Sphingomyelin lipidosis Cat

Food animals:
GM1 gangliosidosis Cattle and sheep
GM2 gangliosidosis Yorkshire pigs

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
Appendix E Lysosomal Storage Diseases in the Dog, Cat, and Food Animals 857

Disease Breeds affected

α-­Mannosidosis Angus, Galloway and Murray Gray cattle and Nubian goats
β-­Mannosidosis Salers cattle and Nubian goats
Globoid cell leukodystrophy, or Sheep
Krabbe’s disease
Ceroid lipofuscinosis Devon cattle, Hampshire sheep, and goats
845

Glossary

Common ophthalmic roots: Ankyloblepharon – Adhesion of the eyelids to


each other. Physiological in kittens and
1) blepharo – lid puppies for the first 10–14 days.
2) cor – pupil Anophthalmia – Congenital absence of the
3) cyclo – ciliary body globes. Usually, a severe ­hypoplasia of the
4) dacryo – tears globe (i.e., microphthalmia).
5) hyal – vitreous Aphakia – Absence of the lens.
6) hyp – anterior chamber Aphakic crescent – Area of the pupil not
7) irido – iris covered by a luxated or displaced lens.
8) kerato – cornea Aqueous flare – Aqueous humor with
9) ophthalmo – globe or eye increased levels of proteins. Best
10) papilla – optic disc demonstrated by a focal light beam
11) phako/phaco – lens projected across the anterior chamber or by
a commercial laser flare meter.
Asteroid hyalosis – Calcium lipid bodies/
Common words: opacities suspended in the vitreous.
Bergmeister’s papilla – Remnants of
Ablation – Removal of globe or part of the posterior hyaloid artery appearing as small
eye (as destruction of the ­ciliary body). white projection from the center of the
Ablepharon – Partial or complete ­congenital optic disc’s surface.
absence of the eyelids. Bernard–Horner syndrome (commonly
Accommodation – Changes in the shape called Horner’s syndrome) – Ptosis,
(and power) of the lens for ­seeing near miosis, enophthalmos, and protrusion of
objects. Limited in the domestic species. the nictitating membrane (also regional
Amaurosis – Total loss of vision. sweating in the horse).
Amblyopia – Reduced or partial loss of sight Biomicroscopy – Microscopic examination of
without detectable lesions in the eye and the various ocular structures.
optic nerve. Blepharitis – Inflammation of the eyelids.
Aniridia – Iris is absent clinically: some May be diffuse or focal.
remnants can usually be demonstrated Blepharospasm – Contractions of the
histologically. orbicularis oculi muscles, usually secondary
Anisocoria – Unequal pupils. to pain.

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
846 Glossary

Blepharostenosis (blepharophimosis) – Consensual pupillary reflex – Constriction


Inability to open the palpebral fissure to a of the pupil when the opposite eye (retina)
normal extent; smaller than normal is stimulated. Sometimes called the indirect
palpebral fissure. pupillary response.
Buphthalmos (hydrophthalmia or Corectasia – Dilation of pupil.
megaloglobus) – Enlargement of Corectopia – Off-­center pupil.
the globe. Coreoplasty – Construction of a new pupil.
Canaliculus – Connects each lacrimal Corneal dystrophy – Bilateral inherited
punctum to the nasolacrimal sac. corneal disease characterized by the
Canthotomy – Incision of either the lateral deposition of materials, usually lipid
or medial canthus. substances. Distinguish from the unilateral
Caruncle – Small mass often covered with corneal degeneration, secondary to other
hair at the medial canthus in front of corneal diseases.
nictitating membrane. Corpora nigrum/nigra – More recent term
Cataract – Opacity of the lens and its granula iridica. Pigmented irregular mass
capsules. on the dorsal and occasionally the ventral
Chalazion – Chronic and often pupillary margin of the iris in herbivores.
granulomatous inflammation of the tarsal Cul-­de-­sac – Junction of the palpebral and
or Meibomian glands. bulbar conjunctiva; also termed fornix.
Chemosis – Edema of the conjunctiva. Cryoextraction – Removal of the lens with
Choroid – Posterior uvea; consists of ultra-­cold devices.
pigmented cells, blood vessels, and in some Cyclitis – Inflammation of the ciliary body.
animal species a special layer in the dorsal Cyclocryothermy – Application of ultra-­cold
fundus, the tapetum lucidum [tapetum probe on the sclera to destroy the ciliary
cellulosum (carnivores) or tapetum fibrosum body epithelium and reduce aqueous human
(herbivores)]. formation.
Choroiditis – Inflammation of the choroid. Cyclodialysis – Surgical fistula from anterior
Ciliary body – Part of the anterior uvea; chamber beneath the iris and ciliary body to
primary source of aqueous humor. exit thorough the sclera.
Ciliary flush – Hyperemia of the bulbar Cycloplegia – Usually drug-­induced paralysis
conjunctiva usually associated with of the ciliary body and the resultant loss of
intraocular inflammations. accommodation.
Cilium/cilia – Another name for eyelash(es). Dacryoadenitis – Inflammation of the
Coloboma – A defect of the eye. Commonly lacrimal gland.
divided into typical (6-­o’clock position) and Dacryocystitis – Inflammation of the
atypical (all other positions). nasolacrimal sac.
Conjunctiva – Mucous membrane Dacryocystorhinography – Radiopaque
connecting eyelid margin to limbus of the studies of the nasolacrimal apparatus.
globe. Divided into palpebral, fornix (or Dermoid – Congenital mass involving the
cul-­de-­sac), and bulbar. eyelids, conjunctiva, nictitating
Conjunctivorhinostomy – Surgically membrane, and/or cornea consisting of
created fistula between the medial normal skin and its components.
conjunctival fornix and the nasal ­cavity as Sometimes called choristoma.
an alternate drainage route for tears. Descemetocele – A deep corneal ulcer
Conjunctivobuccostomy – Surgically created characterized by exposure and possible
fistula for the passage of tears from the protrusion of Descemet’s membrane. Does
ventral conjunctival fornix to the mouth. not stain with topical fluorescein.
Glossary 847

Dialysis – Retinal tear at the ora ciliaris External hordeolum (stye) – Inflammation
retinae with separation of the neurosensory and frequent abscessation of the glands of
retina from the retinal pigment epithelium. Zeis and Moll.
Diathermy – Application of heat to various Exotropia – Divergent strabismus.
parts of the eye (especially the ciliary body). “Flare” – Increase in protein levels in the
Diopter – Refracting power of a lenses whose aqueous humor with a positive Tyndall
focus in 1 m (D = 1/1 m). phenomenon.
Discission – Incision of a structure, usually the Fluorescein–resorcinol–phthalein:
anterior capsule of the lens. Water-­soluble compound that yields a
Distichiasis – Presence of abnormal bright green fluorescence. Used
eyelashes (cilia). for detection of corneal ulcers;
Dyscoria – Irregular pupil. chorioretinal circulation time; integrity of
Ectasia – Protrusion of the cornea or sclera. the blood–aqueous barrier; aqueous humor
Ectopic lentis – Luxation or displacement of production, and patency of the
the lens. nasolacrimal apparatus.
Ectropion – Outward folding of the eyelid Glands of Moll – apocrine (sweat) glands
and its margin. near the eyelid margin. When inflamed,
Electroretinography – Recording of retinal stye (or external hordeolum).
electrical potentials generated by a rapid Glands of Zeiss – Sebaceous glands of the
change in illumination. eyelid margins. When inflamed, stye (or
Emmetropia – Normal eye in refraction. external hordeolum).
Image focused on the retina with the eye Glaucoma – Abnormal increase in
at rest. intraocular pressure and optic neuropathy.
Endophthalmitis – Inflammation of the globe Gonioscopy – Examination of the anterior
involving the inner structures. chamber angle (iridocorneal angle and
Enophthalmos – Recession of the globe in sclerociliary cleft) using a special
the orbit. contact lens.
Entropion – Infolding of the eyelid and Granula iridica – Pigmented mass of the
its margin. edge of the upper and lower pupil in
Enucleation – Surgical removal of the globe. herbivores.
Epilation – manual removal by forceps of Haws – Lay term for the nictitating
cilia (eyelashes). membrane.
Epiphora – Overflow of tears onto the medial Hemeralopia – Day blindness.
canthus or eyelid margin. May signal Heterochromia iridis – Two or more colors
overproduction and/or inadequate in an iris, or between two irides in an
drainage. individual.
Equine recurrent uveitis – Recurrent (or Hordeolum (internal) – Also called
chronic) iridocyclochoroiditis of horses. chalazion. Inflammation of the Meibomian
Esotropia – Convergent strabismus. gland; an abscess or granuloma. External
Evisceration – Removal of structures of the hordeolum – inflammation of the glands of
eye leaving only the sclera or cornea Moll and Zeiss (also called stye).
and sclera. Horner’s syndrome – Sympathetic
Exenteration – Removal of all contents from denervation of the eye and orbit. Clinical
the orbit. signs include miosis, nictitating membrane
Exophthalmos – Protrusion of the globe; protrusion, enophthalmos, ptosis, and in
eyelids can usually still function and cover some animal species regional vascular
the cornea. hyperemia and sweating.
848 Glossary

Hyaloid – Vitreous. Keratocentesis – Puncture of the cornea and


Hydrophthalmos – Congenital globe removal of aqueous humor.
enlargement. A dated term buphthalmos Keratoconus (anterior) – Conical
preferred. anterior protrusion of the center of
Hyperopia – Farsightedness. Objects seen the cornea.
distinctly when at a distance. Image is not Keratoglobus – Enlarged cornea, usually
in focus at the level of the retina (actually in with buphthalmos.
focus behind the retina). Keratoplasty – Corneal grafts. Divided into
Hyphema – Hemorrhage in the anterior lamellar (superficial) and complete (full
chamber. thickness).
Hypopyon – Pus in the anterior chamber. Krause’s glands – Accessory lacrimal glands
Hypotony – Abnormally low intraocular of the upper and lower conjunctiva
pressure. Intraocular pressure is usually fornices.
less than 5 mmHg. Lacrimation – Used clinically to imply
Intraocular lens – Artificial lens placed after excessive rates of tear formation.
cataract surgery to replace preoperative Lagophthalmos – Inability to close the
lens optics. palpebral fissure, mainly the inability of the
Iridectomy – Excision of the iris. Divided upper eyelid to close.
into basal, peripheral, and sphincterectomy. Lenticular – Lens.
Iridencleisis – A surgical procedure used to Lenticulodenesis – Instability of the lens
treat glaucoma consisting of a pillar of iris associated with zonulary loss.
through a scleral incision (creating Leukoma – A dense corneal scar.
a “wick”). Limbus – The transitional zone between the
Iridocorneal angle – The angle created by cornea and sclera. Sometimes called the
the iris and cornea. In nonprimate “blue zone.”
mammals, the angle composed of the basal Luxation – Dislocation of a structure; in
iris, ciliary body (ciliary cleft), and the ophthalmology, term is used for the globe
sclera. Also termed anterior chamber angle (proptosis), and dislocation of the lens.
and/or filtration angle. Manometry – Measurement directly of
Iridocyclitis – Inflammation of iris and intraocular pressure by needle inserted into
ciliary body. Also called anterior uveitis. the anterior chamber or vitreous body.
Iridodonesis – Tremulousness of the iris Megalocornea – Enlarged cornea, usually
usually associated with lens instability, with buphthalmos.
intraocular lens, or a small lens. Observed Microcornea – Small or hypoplastic cornea.
with lens luxation, aphakia, hypermature Microphakia – Abnormally small lens.
cataracts, and cataract resorption. Microphthalmia – Abnormally small eye.
Iridoplegia – Pupillary dilation and paralysis Miosis – Contraction of the pupil.
of the iridal sphincter muscles. Miotic – Drug that causes constriction of the
Iridotomy – Incision of the iris. pupil. Two types available: direct
Iris bombé – Focal or generalized bulging of (parasympathomimetic) and indirect
the iris, indicating impairment of pupillary (anticholinesterase).
passage of aqueous humor. Associated Mittendorf’s dot – Hyaloid vascular remnant
with focal or annular posterior synechiae. at lens posterior pole.
Iritis – Inflammation of the iris. Morgagnian cataract – Type of hypermature
Keratectomy – Excision (usually superficial) cataract with liquified cortex and solid
of the cornea. nucleus.
Keratitis – Inflammation of the cornea. Motility – Movement of the globe.
Glossary 849

Mydriatic – Drug that produces dilation of the Phacoemulsification – Type of ­cataract


pupil. Two types: parasympatholytic and surgery in which the lens matter is
sympathomimetic. emulsified in situ using high-­frequency
Myopia – Nearsightedness. Objects seen ultrasound waves.
distinctly when close. Image is not in focus at Photophobia – Increased sensitivity to light.
the level of the retina (actually in focus in Photopic – Under light or bright illumination
front of the retina). conditions, as with photopic vision or
Nevus – Focal pigmented area in the iris, electroretinography.
choroid, etc. Phthisis bulbus – Atrophy of the globe with
Nyctalopia – Night blindness. low intraocular pressure, usually associated
Nystagmus – Oscillation of the globe. with trauma and inflammation.
OD – The right (oculus dexter) eye. Polycoria – Two or more pupils in an eye.
Ophthalmia neonatorum – Conjunctivitis False (no sphincter muscle) and true types
in the neonate with physiological (with sphincter muscle). Differentiate from
ankyloblepharon (in kittens and pups). iris atrophy.
Ophthalmoplegia – Paralysis of the Proptosis – Forward displacement of the
extraocular muscles. Divided into internal globe out of the orbit.
and external types.
Provocative tests (corticosteroid; water;
Ophthalmoscopy – Examination of the
mydriatic and dark room) – Procedures
ocular fundus by an ophthalmoscope
to demonstrate tendency toward glaucoma
(direct and indirect methods).
in an eye.
OS – The left (oculus sinister) eye.
Pterygium – Invasion of the cornea by the
OU – Both eyes (oculi unitas).
bulbar conjunctiva. Not documented in
Pannus – Invasion of the cornea with
animals.
subepithelial neovascularization and
Ptosis – Drooping of the upper eyelid.
pigmentation.
Pupil – Opening in the central iris.
Panophthalmitis – Inflammation of the
Rose Bengal – Topical ophthalmic stain used
globe involving all layers of the globe.
to outline dead and degenerating corneal
Papilla – Another term for the optic nerve
head (or disc). and conjunctival cells.
Papilledema – Edema of the optic disc or Rubeosis iridis – Neovascularization of the
papilla. iris, with frequent involvement of the
Papillitis – Inflammation of the optic disc or anterior chamber angle, pupil, anterior
papilla. surface of the lens, and ciliary body
Periodic ophthalmia – Older term for processes.
equine recurrent uveitis. Sclerotomy – Incision of the sclera.
Peripheral anterior synechia – Scleritis – Inflammation of the
Inflammatory attachments of the basal iris sclera.
and the peripheral posterior cornea. Scotopic – Dark conditions, as with vision or
Persistent pupillary membrane – electroretinography.
Congenital remnants of the prenatal Spherophakia – Round or spherical-­
pupillary vascular membrane that extend shaped lens.
from the collarette region of the iris to the Sicca – Dryness.
cornea, lens, or other areas of the iris. Squint – Strabismus.
Phacodonesis – Instability of the lens usually Staphyloma – Protrusion of the cornea and/
secondary to the loss of zonulary or sclera lined with uveal tissue. May be
attachments. congenital, traumatic, and/or surgical.
850 Glossary

Strabismus – Heterotropia. Visual axes of the Tenon’s capsule – Fascia bulbus.


eyes are not parallel. Common types: (i) Tonography – Continuous measurement of
strabismus convergens – internal squint intraocular pressure to estimate pressure-­
and (ii) strabismus divergens – sensitive aqueous humor outflow (in μl/
external squint. mmHg/min).
Striate – Keratopathy. Irregular linear lines in Tonometry – Measurement of intraocular
the cornea usually associated with glaucoma pressure. Divided into indentation,
(breaks) and phthisis bulbi (folds), and applanation, and rebound.
changes in Descemet’s membrane. Transillumination – Passage of light
Stye – Inflammations of the glands of Moll through tissues. May facilitate
and Zeiss. differentiation between solid and hollow
Subluxation – Associated with partial loss of tissue masses.
the lens zonule; partial lens displacement. Trichiasis – Contact of hair with the eye; as
Symblepharon – Adhesion of the eyelid or in entropion or nasal fold trichiasis.
both eyelids to the conjunctiva, and/ Uvea – Iris, ciliary body, and choroid.
or cornea. Anterior uvea – iris and ciliary body.
Synechia – Adhesions of the iris to cornea Posterior uvea – choroid.
(anterior synechia), iris to lens (posterior Uveitis – Inflammation of the uvea tract.
synechia), and in the iridocorneal angle Anterior uveitis – inflammation of the iritis
(peripheral anterior synechia). and ciliary body; posterior uveitis –
Syneresis – Liquefaction of the vitreous. inflammation of the choroid. Panuveitis –
Synchysis scintillans – Liquified vitreous inflammation of the iris, ciliary body, and
with cholesterol crystals. choroid.
Tapetum lucidum – A special reflective Vibrissae – Large tactile hair about the
layer within the dorsal choroid providing eyelids and face of large animals.
additional reflection of light permitting Wolfring – Accessory lacrimal gland of the
double retinal stimulation of the retina. dorsal palpebral conjunctiva.
Tapetum cellulosum in carnivores; Tapetum Xerophthalmia – Same as keratoconjunctivitis
fibrosum in herbivores. sicca or xerosis. Dryness of the cornea and
Tarsorrhaphy – Temporary (by sutures) or conjunctiva.
permanent apposition of part (partial) or all Zonules – Suspensory ligaments connecting
(complete) eyelids. the lens periphery (equator) to the
Tear film breakup – The development of dry ciliary body.
spots (measured in seconds) in the tear Zonulolysis – Enzymatic (alpha
film, as observed by biomicroscopy with the chymotrypsin) or surgical transection of the
preocular film stained with fluorescein. lens zonules.
858

Index

Note:–
Page numbers in italic refer to figures.
Page numbers in bold refer to tables.
Page numbers followed by ‘b’ refer to boxes.
Page numbers followed by ‘g’ refer to the glossary.

a amphibians 737 surface 563


A‐mode ultrasonography 203–204, birds 750 glaucoma and 386
206, 207 lens 51 lacrimal secretory system 289
glaucomas 366 fish 735 meibomian glands 264–265
abducens nerve lens 41–42, 49 metastases 828
BCSE 667 birds 51 nictitating membrane gland 307
motor nucleus 772 lower‐field 99 adenomas 424, 514
muscles supplied 19, 87 reptiles 739 glaucoma and 386
aberrant dermis 300 role of vitreous 86 lacrimal secretory system 289
ablation (term), 845g acepromazine, side effects 165 lobular orbital 297
ablepharon, 845g acetazolamide 149, 153, 154 meibomian glands 264–265
abscesses acetylcholinesterase inhibitors 150 nictitating membrane gland 308
bacterial blepharitis 259–260 acetylcysteine 284, 323, 616, 742 adenoviruses (canine adenovirus‐1)
after cataract surgery 464 achiasmatic Belgian Sheepdog 415, 807
cats 547 532, 775 adherent leukoma 320
cornea 343, 635, 641, 642, achromatopsia 110 adhesives, cornea 328
643–644, 710 acid burns 337, 338 adrenal cortex
fungal keratitis 634 acidosis 154 hyperadrenocorticism 809
hordeolum 262–263 acoustic impedance 203 sudden acquired retinal degeneration
orbit. See also retrobulbar abscess acremoniasis 799 syndrome 792
cats 602 acrylic IOLs 460 adrenergic agents 146, 770–771
dogs 225–226 actinic dermatitis 549, 551, 670, 697 adrenergic neurons. See sympathetic
horses 619 Actinobacillus lignieresii 696 nerve supply
rodents 717 action potentials 101, 104 adrenergic receptors
ultrasonography 207, 222 active chorioretinitis 505–506 aqueous humor regulation 77
Pasteurella multocida 729 acute bullous keratopathy 573–574 on blood flow 71, 72
reptiles 740–741 acute uveitis 401 drugs acting on 152–153
retrobulbar. See retrobulbar abscess acyclovir 137, 566 by species 70
absorption of light 92 ADAMTS10 gene 359–360, 374, 375 adrenocorticotropic hormone
Abyssinian cat ADAMTS17 gene 359–360, 377, 453 stimulation
inherited eye diseases 853 adaptive optics 479–480 sudden acquired retinal degeneration
rod–cone dysplasia and adeno‐associated virus syndrome 792
degeneration 596 gene therapy 504 aerial images 93
accessory lacrimal glands 21 adenocarcinomas 424, 514 Afghan Hound, developmental
nictitating membrane 23 cattle 668 cataracts 437, 440–441
accommodation 95–96, 845g conjunctiva against‐the‐rule astigmatism 99

Essentials of Veterinary Ophthalmology, Fourth Edition. Kirk N. Gelatt and Caryn E. Plummer.
© 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/gelatt/essentials4e
Index 859

age‐related macular degeneration, amacrine cells 12, 53, 104, 105 Angiostrongylus vasorum 412, 801
macaques 732 Amaranthus retroflexus 705 angle opening distance 43, 208
agenesis (aplasia palpebrae) 245 amastigotes, leishmaniasis 823 angle‐closure/occlusion secondary
aging amaurosis (term), 845g glaucoma, 385–386.
cataracts (ARC) 442 ambient lighting, examination in See also primary narrow/
corneal endothelium 32–33 168–175 closed glaucoma
glaucomas, dogs 370 amblyopia, 845g angular aqueous plexus (AAP)
lens 84, 427 American Cocker Spaniel 32, 44
lens luxation 452, 453 congenital cataract 434, 440, 441 aniridia, 396–397, 609, 845g
refraction 97 glaucomas 356, 357, 369, 370, anisocoria, 764–765, 845g
transmission of light 92 372–373 meningioma 828
vitreous 85–86 nictitating membrane 303 static 775, 781
akinesia prolapsed gland 305 swinging flashlight test 766
cataract surgery 457 punctal atresia 274 ankyloblepharon, 541, 845g
eyelids 165–166 trichomegaly 257 cats 541–542
Akita (dog breed) American College of Veterinary pathological 244–245, 541
photoreceptor degenerations 500 Ophthalmologists, on annular ligament, fish 733
Vogt–Koyanagi–Harada‐like gonioscopy 363, 364 annular pad, equatorial 750
syndrome 508 American Dutch Belted rabbits, annulus of Zinn 17
Alaskan Malamute corneal dystrophy 728 anophthalmia, 845g
cone degeneration 502 American Saddlebred Horse, inherited cattle 666
albinism. See also Chédiak–Higashi eye diseases 854 dogs 223
syndrome; subalbinism ametropia 96–97 guinea pigs 721
cats 780, 812–813 amicarbalide diisethionate, pigs 703
cattle 691, 840–841 babesiosis 839 anterior aphakic crescent, fish 734
dogs 784–785 amikacin 130 anterior chamber
horses 606, 831–835 amino acids depth 171–172
albumin/globulin ratio, feline aqueous humor 76–77 development 10–11
infectious peritonitis 582 aminoglycosides 128 drug administration 125
alcohol, tear film stimulation 569 amiodarone 811 fish 734
aldose reductase 85, 445, 827–828 amlodipine 816 shunts. See gonioimplants
Aleutian disease 746 amniotic membrane, surgical volumes 195
alfalfa pellets 679 placement 319, 331, 638, anterior chamber‐associated immune
algal disease 416, 795–796 640 deviation (ACAID) 652
chorioretinitis, 506b amoxicillin 126–127 anterior choroidal veins 37
alkali burns 337–338 amphibians 736–738 anterior ciliary arteries 42–43
allergic blepharitis 263, 548–549 amphotericin B 132–134, 413, 796 anterior lens luxations 381
allergic conjunctivitis 295 ampicillin 126–127 anterior segment
alligators amplitude, light 90 development 8
conus papillaris 739–740 anangiotic pattern, retina 57 dysgenesis 397, 578, 610
intraocular pressure 82 guinea pigs 720 glaucoma 612
allopurinol Anaplasma (spp.), ehrlichiosis 804 examination 173
leishmaniasis 261, 547, 804 Anaplasma platys 804 hemorrhage, rodents 719
alloxan 705 anatomy. See morphology ultrasonography 205–206
alpacas anchoring, nictitating membrane anterior uvea
corneal diameter 709 305 cats 575–588
intraocular pressure 706 anemia 788 dogs 394–425
pupils 172 autoimmune hemolytic 511–512 developmental disorders 394–397
tear production 706 cats 817 food animals 688
visual acuity 112 conjunctiva 301 horses, lymphomas 650
alpha‐mannosidosis 813 anesthesia. See general anesthesia; pigs 704–705
cat breeds 856 regional anesthesia rodents 719
food animals affected 857 aneurysms, rodents 720 anterior uveitis. See also iridocyclitis
14α‐sterol demethylase 134 angiogenesis Basset Hound 370
α‐tocopherol deficiency 510 cornea 318 camelids 711–712, 713
α1‐proteinase inhibitor retina 9 cataract surgery 465
for keratomalacia 323 angiography, retina (fluorescein cats 579–586
α2‐adrenergic agonists 152 angiography) 202–203, cataracts 592–593
alphaviruses 782, 840 480, 529–530 treatment 585–586
altitude angiokeratoma, nictitating chronic 383, 405–406
adaptations 706, 713 membrane 307 corneal ulcers 410–411
pannus 340, 342 angiostrongylosis 801 dogs 318, 394, 399
860 Index

anterior uveitis. See also iridocyclitis aphakic glaucomas 383–384 ferrets 723
(cont’d) aplasia palpebrae 245 taurine deficiency 829–830
chronic 383 apocrine glands 21 area striata 691
corneal edema 317 apocrine hidrocystoma, feline eyelids, argentea, choroidal 733
glaucoma 385 frequency 552 arginine deficiency 446, 593, 829
miosis 299 Appaloosas arrectores ciliorum 21
neurogenic 324 congenital stationary night arrowhead procedure 250
systemic diseases 300 blindness 612–613, arsanilic acid 705–706
foals 616–617 782, 832 arteries. See also vascular system;
horses 632 equine recurrent uveitis 653, 654 specific arteries
neonates 607 inherited eye diseases 854 choroid 47–48
lens rupture 457 applanation tonometry 193–194 iris 36
neurogenic reflex 324 birds 751–752 arterioles, retina 484
treatment 406–410 dogs 362–363 arteriovenous fistula 223
anterior vitrectomy 472 pigs 703 arteritis, equine viral 839
anti‐inflammatory drugs 138–144. apraclonidine 152 artificial tears, 285–287b
See also corticosteroids; aprotinin, spontaneous chronic antiviral agents in 566
immunosuppressants; corneal epithelial defects infusion pumps 121
nonsteroidal anti‐ 326 aspergillosis
inflammatory drugs aquatic species cats, sino‐orbital 602
latanoprost and 158 mammals 758–760 dogs 799
antibacterial agents 126–132 refraction 99, 750 Indian buffalo 745
anterior uveitis 407, 409 aqueous flare, 73, 76, 172, 401, 404, Aspergillus (spp.)
camelids 710 845g. See also laser flare‐cell cataracts 446
cataract surgery 457, 464 photometry keratitis 337, 673
conjunctivitis 292–293 aqueous humor (AH), 43, 44–46, aspirin 142
corneal ulcers 324, 327, 409, 616 74–81. See also blood– asteroid hyalosis, 475–476, 845g
corticosteroids with 140 aqueous barrier; fibrinous astigmatism 98–99
fungal infections 337 aqueous; plasmoid aqueous astrocytes 100–101
infectious bovine amphibians 737 astrocytomas 514, 600
keratoconjunctivitis composition 76–77 atopic dermatitis, cats 549
678–679 cytology 405 atopy 295
keratoconjunctivitis sicca 284 drug turnover 120 atorvastatin 443
orbital abscesses 225 drugs affecting 149 atropine 144, 145–146, 164
postoperative 259 fluorophotometry 80, 202 anterior uveitis 407, 409, 586, 632
spontaneous chronic corneal formation 74–76 cataract surgery and 457
epithelial defects 326 inspection 172 corneal ulcers and 287, 327
superficial punctate keratitis 344 light transmission 92 equine recurrent uveitis 653
for ulcerative keratitis, horses measurements 80–81 horses and 606, 632
630–632 misdirection (malignant glaucoma) hyphema and 422
anticholinergic drugs 145 384, 590 melanin on effects 120
anticholinesterases 151, 770 outflow, 76, 77. See also side effects 409
anticollagenases 284 nasolacrimal system spontaneous chronic corneal
antifungal agents 132–136, 337, gonioscopy, 181–182, 358, epithelial defects 326
632, 635–636 363–364, 847g on tear production 279
antihypertensives 816 lens luxation on 451–452 trauma and 230
antimicrobials (natural), tear paracentesis 195–196 attenuation, light transmission 92
film 63 protein levels 401 atypical colobomas, optic nerve 533
antioxidants, ciliary body 74 regulation 77 augmentation canthoplasty 256–257
antiproteolytic agents, keratomalacia slit‐lamp biomicroscopy 175 auriculopalpebral nerve
323 aqueous layer of tear film 24, 63 block 165, 166
antiseptics, for hyalocentesis 471 replacement solutions 284 cattle 665, 685
antiviral agents 136–138 aqueous tear deficiency. See horses 604, 605
feline herpesvirus‐1 566–567 keratoconjunctivitis sicca auscultation, exophthalmos 221
anurans 736–737 Arabian horses Australian Shepherd dog
aphakia 97–98, 845g inherited eye diseases 854 congenital cataract 434, 441, 442
dogs 428 severe combined immunodeficiency microphthalmia 223
horses 611 835 autofluorescence imaging,
hyperopia 462 arachidonic acid 401–402 pseudopapilledema 534
ultraviolet vision 92 area centralis 55, 87 autofluorescent inclusion
aphakic crescent 450b, 845g cats 593 epitheliopathy (retina)
fish 734 dogs 484 502–505
Index 861

autogenous lamellar corneal nasolacrimal system 273 food animals 692


grafts 333 orbit Bernard–Horner syndrome, 845g
autoimmune blepharitis 261–262 cats 602 Bernese Mountain Dog
autoimmune hemolytic anemia dogs 224 early retinopathy 501–502
511–512 reptiles 740–741 histiocytosis 263–264
autopsy (human and manatee), systemic 796–799 systemic histiocytosis 812
vitreous 86 bacteriocidal vs bacteriostatic besifloxacin 132
autosomal recessive progressive drugs 126 BEST1 gene 492–493
retinal atrophy 501 bacteriology testing, dyes beta radiation for squamous cell
avermectin drugs, 546, 803. See also affecting 191 carcinoma 686
ivermectin bacteriostatic preservatives, eye β‐adrenergic nerve fibers, iris
avulsion of extraocular muscles 231 drops 117 69–70
axes of globe 26 bacteriostatic vs bactericidal beta‐blockers 152, 153
axial length 94, 96 drugs 126 carbonic anhydrase inhibitors
by species 95 ball‐and‐socket junctions, lens with 155
ultrasonography 207 fibers 50 contraindications 164
axonal reflex 402 barrier retinopexy 521 after gonioimplant placement
Ayrshire cattle, squamous cell bartonellosis 585, 797, 818–819 390
carcinoma 680 basal cell carcinoma 552–553 intraocular pressure
azathioprine basal cell epitheliomas, feline eyelids, cats 591
anterior uveitis 407, 409 frequency 552 horses 656
myositis 228 basement membrane, cornea 28–29 systemic absorption 119
recurrent proliferative Basenji breed, persistent pupillary β‐glucuronidase deficiency 815
keratoconjunctivitis 298 membranes 396 β‐lactamases, resistant penicillins
azithromycin 130–131 Basset Hound 126, 127
azoles 134–136 glaucomas 357, 358, 370, 373 β‐lactams. See penicillins
pectinate ligament beta‐mannosidosis. food animals
dysplasia 369, 370 affected 857
b primary angle‐closure betamethasone 139
B‐mode ultrasonography 204, 206 glaucoma 357–358 anterior uveitis 407, 408
optic nerve 530 BCSE (bilateral convergent subconjunctival dosage 145
trauma 418 strabismus with betaxolol 152
babesiosis 301, 839 exophthalmia) demecarium bromide vs 151
bacille Calmette–Guérin 666–667, 783 bicarbonate 153
for sarcoids 626 Beagle Bichon Frise, developmental
for squamous cell carcinoma 624 congenital cataract 434 cataracts 437
bacitracin 127 corticosteroids 141 bighead disease 696
background genetic effects 213 fundus 483 bilateral convergent strabismus with
bacteria glaucomas 373–375 exophthalmia (BCSE)
normal genetics 359, 370, 374 666–667, 783
birds 752 treatment 150, 151, 153, 154, biliary fever (babesiosis) 301, 839
conjunctiva 291, 630, 697, 708 155, 156, 157 bimatoprost 156, 157, 158, 388b
penguins 757 iris anomalies 397 binding of drugs 120
after parotid duct transposition 288 Bedford, Peter, on glaucoma 355 protein binding on absorption 119
bacterial infections 818–819 behavioral vision testing 478 binocular indirect ophthalmoscopy
amphibians 737 Belgian Horse, inherited eye 178, 179
ankyloblepharon, cats 541–542 diseases 854 binocular vision 107, 108
birds 752–753 Belgian Sheepdog, achiasmatic fish 734–735
blepharitis 259–260, 547–548, 622 532, 775 visual cortex 109
cataract surgery 457 Belgian Shepherd, photoreceptor bioavailability 121–123
conjunctivitis dysplasia 502 biomicroscopy, 845g. See also slit‐lamp
dogs 292–293 Bengal cat, progressive retinal biomicroscopy
pigs 704 atrophy 596–597 biopsy
rodents 717 bent cartilage, nictitating CT‐guided 200
corneal ulcers 637–639 membrane 304 eosinophilic myositis 227
dacryocystitis 608 benzalkonium chloride, contact feline diffuse iris melanoma 588
fish 735 hypersensitivity 296 feline herpetic dermatitis 547
horses 836–838 benzathine cloxacillin 126 orbit 222–223
uveitis 650 Bergmeister’s papilla, 10, 12–13, sarcoids 625
iridocyclitis 616 58, 845g bipedicle graft 328, 329
keratitis 335–336 camelids 712 bipolar cells, retina 53, 56, 100, 102,
keratoconjunctivitis 244–245 dogs 473, 526 104, 105
862 Index

birds, 748–758. See also raptors color Doppler ultrasound 209–210 brachycephalic dogs
accommodation 750 blood pressure, 788. See also cornea, innervation 312
lens 51 hypertension (systemic) epiphora 276
ciliary body 42 cats 816 Jones test and 274
color vision 110 blood supply. See also vascular system nasal fold trichiasis 257
extraocular muscles 87 eyelids 241 nasolacrimal duct 271
eyelids 61–62 blood–aqueous barrier 73, 114, 394 orbital emphysema 230
trauma 756 anatomical site 40 palpation of globe 220
iris 37–38, 750 anterior uveitis 399, 409 pigmentary keratitis 339
pecten oculi 71 atropine on 409 superficial corneal pigmentation
pupillary light reflex 169, 751 cataracts 448 316
pupils 70, 750 laser fluorophotometry 202 brachytherapy
restraint 165, 752 blood–brain barrier, P‐glycoprotein 811 sarcoids 626
retina 750 blood–ocular barrier defect 527 squamous cell carcinoma 552,
vasculature 57 blood–retinal barrier 73–74, 114, 623, 624, 686
scleral ossicles 34 116, 399 bracken (Pteris aquilinum)
West Nile virus 840 blood–vitreous barrier 86 702–703, 783
birefringence 201 Bloodhound, macroblepharon– Branhamella keratoconjunctivitis 700
Birman cats, inherited eye ectropion 253 Braund’s syndromes 771
diseases 853 blue light, sudden acquired retinal breakup time, precorneal tear film
black soil blindness, degeneration syndrome 792 190–191, 282, 569, 570
Corallocytostroma (spp.) blue‐eye appearance 317, 575–577, breed‐disposed corneal dystrophy
694 807 345
Blaskovic’s modification, blue‐eyed white cats breed‐disposed glaucomas 369–370
Kühnt–Szymanowski deafness 576, 812–813 breeding out
procedure 254–255 vision 577 cataracts 747
blastocyst 3 blue‐eyed white phenotype, Collie eye anomaly 486
Blastomyces dermatitidis 799, 820 camelids 711 heritable cataracts 442
blastomycosis 300, 413, 545, bluetongue virus 666, 695, 697, 842 recessive disease carriers 214–215
799–800, 820 blunt injuries 418–419 squamous cell carcinoma
antifungal agents 134 cataracts 446 and 687
conjunctivitis 294 horses 639 Briard dog
systemic 583 optic nerve 663 central progressive retinal atrophy/
blepharitis, 845g bone formation, heterotopic, guinea RPED 503
allergic 263, 548–549 pigs 722 fundus 483
camelids 707 Border Terrier, congenital retinal dystrophy 503–504
cats 545–550 cataract 441 bridge graft 328, 329
cattle 669–670 Bordetella bronchiseptica 560 bright blindness, Pteris aquilinum
dogs 259–262 borreliosis 797, 836–837 702–703, 783
marginal 282 Boston Terrier brimonidine 152
guinea pigs 721 cataracts 437, 441, 442 brinzolamide 154, 155, 388b,
horses 622 endothelial corneal dystrophy 591, 656
nonhuman primates 732 347–348 bromfenac 408
pemphigus 261–262, 819 glaucomas 347, 375 brow sling, entropion 704
rabbits 725–726 bot fly brucellosis 416, 797–798
sheep and goats 696–697 Cuterebra (spp.) 261, 561–562, Bruch’s membrane 12
blepharophimosis 256–257 585, 822 Brücke’s muscle 42, 750
blepharoplasty 266–267 Oestrus ovis 700 bu gene 729
blepharospasm, 845g Bouvier des Flandres (dog breed) buccal mucosa graft, eyelid agenesis
cats 543 glaucomas 375–376 543
blepharostenosis, 845g pectinate ligament dysplasia 358 bucket handle technique 543
microblepharon 256–257 bovine herpesvirus‐1 842 buckwheat, fagopyrin 670
blight. See infectious bovine leukemia virus 668 buffers, pilocarpine 151
keratoconjunctivitis bovine papillomavirus 670–671 bulbar conjunctiva 21–22, 290
blind grass (Stypandra glauca) squamous cell carcinoma Bull Mastiff, dominant progressive
702 and 681 retinal atrophy 501
blind staggers 695 bovine viral diarrhea (BVD) 666, bullet‐hole chorioretinitis 662
blink rates 60, 61 783, 842 bullous keratopathy 347, 348
guinea pigs 720 congenital cataract 689 acute 573–574
blink reflex, 242b. See also Bowman’s layer 31, 720 NM flaps for 308–309
palpebral reflex Boxer ulcers 324–327 bullous retinal detachment 599,
blinking 59, 60–61, 67–68, 240 brachycephalic cats, cornea, 663, 816
blood flow 71–73 sequestrum 572, 573 buphthalmos, 846g
Index 863

amphibians 737 canine oculoskeletal dysplasia camelids 714–715


cats 590 490, 491, 785–786 diabetes mellitus 714
dogs canine teeth ultrasonography 714
goniodysgenesis 387 relation to nasolacrimal duct cats 592–593
lens luxation 380, 454 553–554 diabetes mellitus 827–828
treatment 390 canthi 19, 20, 241. See also lateral congenital. See congenital cataract
rodents 719 canthotomy; medial corticosteroids and 141
Burmese cats, inherited eye diseases canthus diabetes mellitus 85, 446, 551,
853 canthoplasty 250, 253b 808–809
burning bush (Kochia scoparia) 694 augmentation 256–257 camelids 714
butorphanol 165, 604, 706 keratoconjunctivitis sicca 288–289 dogs 446, 456, 466, 511, 827–828
butterfly lesions 661 medial 258 dogs 426–457
traumatic proptosis 233 acquired 435–447
c canthotomy 846g anterior uveitis 406, 410
C57BL/6J mouse, microphthalmia capillaries classification 435
719 choroid 72, 73–74 complications 447
caiman iris 36–37 diabetes mellitus 446, 456, 466,
corneal endothelium 739 lens 429 511, 827–828
viral infections 740 optic nerve head 527 genes and breeds 851
Cairn Terrier, melanosis 514 capsulorhexis, phacoemulsification intumescent 382–383
calcific band keratopathy 647–648 460, 461 lens luxation 382, 454
corticosteroids and 141 carbachol 151 medical treatment 447
calcification carbamate inhibitors 151 persistent hyaloid artery 473
cornea 346 carbenicillin 127 prognosis 455–456
meningioma 530 carbonic anhydrase 40, 74, 75–76 progressive rod–cone
calcineurin inhibitors 148 carbonic anhydrase inhibitors (CAIs) degeneration with 500
calcium 149, 153–155, 388b resorbing hypermature 383
hypocalcemia 809, 828 adverse effects 155 secondary glaucomas with 379
on tight junctions 31 cats 591 surgery 455–468, 456, 466,
calicivirus 824. See also feline dogs 388b 517–518
calicivirus after gonioimplant placement 390 dropped nuclear fragments
exotic felids 745 horses 656 519
California, glaucoma study 357 topical formulations 154–155 examination 173
California sea lions 744, 759 carboplatin 625 exotic mammals 746–747
camelids 706–715 carcinoma. See also adenocarcinomas; surgery 747
pupils 35, 172 squamous cell carcinoma ferrets 723
restraint 165, 706 basal cell carcinoma 552–553 fish 736
visual acuity 112 feline eyelids, frequency 552 nutritional 735
canaliculi (lacrimal), 24, 64, 270, 846g carcinoma in situ. See intraepithelial food animals 689–690
atresia 275 neoplasia guinea pigs 723
lacerations 277 cardiac arrest, oculocardiac reflex 89 horses 656, 657–658, 659
misplacement 275–276 Cardigan Welsh Corgi, rod–cone surgery 611
cancer‐associated retinopathy 512 dysplasia type 3 498 hydroxymethylglutaryl‐CoA
candela (unit) 91 carnivorous type, iridocorneal reductase inhibitors
Candida (spp.), keratitis 337 angle 42 443, 812
canine adenovirus‐1 415, 807 carprofen 142 ketoconazole 134
canine adenovirus vaccines anterior uveitis 407 penguins 757–758
317, 415–416, 807 cataract surgery 457 pigs 705
corneal edema 317, 415–416 carriers pinnipeds 759–760
canine cyclic thrombocytopenia 804 Moraxella bovis 675–676, 679 surgery 760
canine distemper virus 294, recessive disease 214–215 rabbits 729, 730
778–779, 806–807 cartilage reptiles 742
ferrets 723 nictitating membrane 23, 304 rodents 719–720
canine herpesvirus 807 sclera 34 sheep and goats 701
canine herpesvirus‐1 caruncle, 846g. See also lacrimal ultrasonography 205–206
conjunctivitis 293–294 caruncle camelids 714
keratitis 293, 336–337 caruncular trichiasis 300 catheters, nasolacrimal system
canine Leber’s congenital amaurosis caspofungin 133 609, 628, 708, 710
503–504 cataracts, 846g cats 541–603. See also blue‐eyed
canine lobular orbital adenomas 297 amphibians 738 white cats
canine multifocal retinopathy 492–493 birds 754 adrenergic receptors 70
gene and breeds 851 surgery 754 apraclonidine 152
864 Index

cats (cont’d) cefadroxil 127 lens 739


blink rates 60 cefazolin 127 Charolais cattle, colobomas 691–692
ciliary nerves 575, 765 cefepime 127 Chédiak–Higashi syndrome
colobomas, eyelids. See agenesis cefotaxime 127 cats 780–781, 813
under eyelids cefotetan 127 mink 744
color vision 110 cefoxitin 127 chelating solutions, after parotid duct
eyelid hair 20 ceftazidime 127 transposition 288
eyelids 61, 541–553, 818–819 ceftiofur 127, 679 chemical burns 337–338
globe dimensions 26 ceftriaxon 127 chemosis, 846g
hemidilated pupil 775 cefuroxime 127 allergic 295
infrared vision 90 cellulitis. See also juvenile sterile chemotherapy
inherited eye diseases, breeds 853 granulomatous dermatitis sarcoids 626
intraocular lenses 98, 593 orbit squamous cell carcinoma 552,
intraocular pressure 82, 192 cats 602 623, 624, 625
lysosomal storage diseases by dogs 223–226, 300 Chenopodium album 705
breed 856 horses 619 cherry eye 289, 304–305, 555
neuro‐ophthalmic diseases 780–782 rodents 717 Chesapeake Bay Retriever, developmental
orbit 13, 14, 15, 601–603 ultrasonography 222 cataracts 440
pupils 70, 575 Celsus–Hotz resection Chesapeake Bay Terrier, congenital
refraction 97, 98 distichiasis 247 cataract 441
restraint 165 entropion 250–252, 305, 544 chickens
retina 594–600 tear‐staining syndrome 276 accommodation 95–96
development 12 central blindness 703 refraction 98
retinopexy 524 central corneal thickness 311, 570 chinchillas 723
retrobulbar block 167 central nervous system intraocular pressure 82
Schirmer’s tear test (STT) 186, 569 feline herpesvirus‐1 563 Chinese Crested Dogs, pigmentary
scotopic vision 105 hypoxia 817 chorioretinopathy 504
strabismus 89, 577 mannitol on 159 Chlamydia caviae 721
striate cortex 103 meningoencephalitic listerial Chlamydia felis 556–558
systemic diseases 812–831 keratoconjunctivitis 673–674 chlamydial keratoconjunctivitis
visual acuity 112 neoplasia 779–780, 782, 674, 698, 704, 841
visual fields 108 809, 828–829 exotic mammals 744–745
cattle 665–694 vestibular system 763 chlamydiosis 840–841
albinism 691, 840–841 central PRA (CPRA) 502–505 Chlamydophila pecorum 698
blink rates 60 retinal pigment epithelial dystrophy chlamydophilosis 819
conjunctiva 671–687 (RPED) 493, 502–505 chloramphenicol 131
squamous cell carcinoma 685 central retinal arterial occlusion, chlorhexidine, snake fungal
cornea 671–687 primates 732 infections 741
squamous cell carcinoma 685 central supporting tissue meniscus of chloroacetophenone 338
examination 665–666 Kuhnt 58 chlorpromazine, corneal edema
eyelids 61, 668–671 centripetalization, conjunctiva 726–727 317–318
squamous cell carcinoma cephalexin 127 cholesterol
670, 681, 684, 685 spontaneous chronic corneal hyperlipidemia 788
foramen orbitorotundum 14 epithelial defects 326 synchysis scintillans 476
globe dimensions 26 cephalosporins 127 cholinergic agents
inherited eye diseases by breed 855 cephalothin 127 on aqueous humor outflow 79–80
intraocular pressure 82, 192, 665 cerebral cortex, visual cortex 103 for keratoconjunctivitis sicca 283
neuro‐ophthalmic diseases 783 binocular vision 109 cholinergic antagonists 145
orbit 13 cerebral dehydration, mannitol on 159 cholinergic neurons. See
restraint 165, 665 cerebral syndrome, 774b parasympathetic nerve
systemic diseases 840–844 cerebrocortical necrosis (PEM) 667, supply
visual acuity 113 693, 702 cholinomimetics 150–151
cautery 243, 633–634 cerebrospinal fluid (CSF) chondroitin sulfates 311, 326
thermokeratoplasty 348 optic neuritis 536 chorda tympani 770
Cavalier King Charles Spaniel pressure, vitamin A deficiency 844 choriocapillaris network 48–49, 734
congenital cataract 433–434 cerebrovascular disease, dogs 788 reptiles 739
fundus 483 ceroid lipofuscinoses 504–505, 787 chorioretinitis
cavernous sinus syndrome, 667, dog breeds 856 canine distemper virus 778, 806
771–774, 775b 809 food animals affected 857 cats 597–598
Cayo Santiago, rhesus macaques 732 chalazion, 262, 846g dogs 505–507
cBEST1 gene 493 chameleons horses 661, 662
cefaclor 127 eyelids 738 choristomas. See dermoids
Index 865

choroid 34–35, 46–49, 846g ciliary nerves 764–765 collagen shields, drug delivery 123
amphibians 737 cats 575, 765 collagenases
birds 750 ciliary processes 38–41 infectious bovine
blood flow 72 permeability 115–116 keratoconjunctivitis 677
capillaries 72, 73–74 ciliary sulcus, intraocular lenses 468 keratomalacia 338
Collie eye anomaly 486, 487 cilioretinal arteries (short posterior collarette 19, 35
colobomas, cattle 691 ciliary arteries) 26, 57–58, collars, Elizabethan 244
development 12 72, 526, 526–527 Collie
hypoplasia cilioscleral cleft (CC) 42, 172, 181, 208 fundus 483
Collie eye anomaly 487 cimetidine, melanomas 625 granulomas 352–353
Rough Collies 533 ciprofloxacin 132 microphthalmia 223
IOP elevation on 367 circadian rhythm, intraocular Collie eye anomaly (CEA) 421,
melanomas 423, 514 pressure 77, 83–84 485–487, 487, 519, 533
choroidal gland, fish 733 circle of Hovius. See gene and breeds 851
choroiditis 507–508, 846g intrascleral plexus retinal detachment 486, 487, 488
Chow Chow 376, 396, 434 cisplatin vitreous 473–474
chromatic pupillometry 528 sarcoids 626 colloidal carriers, drug delivery
chromodacryorrhea, rodents 717 squamous cell carcinoma 624, 625 122, 125
chromophores 91 clarithromycin 130 colobomas, 7, 846g
chronic anterior uveitis 383, 405–406 clarity. See transparency cats 594
chronic superficial keratitis classic equine recurrent uveitis 651 eyelids. See agenesis under
(pannus) 307, clavulanic acid 127 eyelids
339–342, 849g clear blindness, Pteris aquilinum iris 578
chronic uveitis 401, 465 702–703, 783 multiple 601
cidofovir 137, 336–337, 566 clindamycin 131, 679, 824 optic disc 600
cilia 846g. See also eyelashes Cloquet’s canal 12, 53, 470 cattle 691–692
ectopic 246–248 Clostridium novyi 696 dogs 245, 322, 397
ciliary body 34–35, 38–46, 394, 846g Clostridium tetani 798, 819 Collie eye anomaly 486, 487
accommodation 95 clotrimazole 261 lens 428–429
on aqueous humor outflow 79 clotting, hyphema 421 optic nerve 519, 532–533
amphibians 737 clotting deficiencies, hemorrhages horses
anterior uveitis 579 301 fundus 612
blood flow 71 cloudy cornea, cats 574 iris 609
development 11 Clumber Spaniel, fundus 483 iris 578, 609, 712
enzymes 153 CNGB1 mutation 214 pigs 705
epitheliomas, cattle 689 CNGB3 mutation 502 sheep and goats, eyelids 696
functions 74 coat color color. See also chromatic pupillometry;
glaucoma treatment, cyclodestructive camelids 711, 712 coat color
procedures 392–393 cats 812–813 corneal sequestrum 572
heterotopic bone formation 722 cattle 840–841 iris 36, 70, 172
hypertension 599 dogs cats 575
IOP elevation on 367 diseases related 784–785 color blindness 110
muscle (Crampton’s muscle) 34, fundus 482, 483 color Doppler ultrasound 209–210
41–42, 49, 750 horses 831–835 vitreous 471
on aqueous humor outflow 79–80 anterior segment dysgenesis 610 color variants, anterior uvea 394–395
birds 95–96, 750 fundus 606 color vision 109–110, 111
parasympathomimetics on 150 cocaine 146 Color‐dilute horses, inherited eye
prostaglandin analogues 156 Coccidioides immitis 413, 545, 583, diseases 854
pain 403 584, 800, 820 complaints (history‐taking),
reptiles 739 coccidioidomycosis 800, 820, 820 primary 163–164
tumor, ultrasonography 206 Cochet–Bonnet esthesiometer 183 complement fixation, Coccidioides
vascular system 42–43 coinfections, feline herpesvirus‐1 565 immitis 413
ciliary channels 40 COL1A2 gene 358 complete incision keratectomy
ciliary cleft 42 COL9A3 mutation 786 320, 321
gonioscopy 363, 364 colic, cholinergic antagonists and 145 compliance with drug therapy 114
IOP elevation on 367 collagen complicated corneal ulcers 633
narrowing 358 cornea, 30, 65, 67, 311. See also computed tomography 197,
ciliary epithelium 74 transparency 199–200
ciliary flush, 403, 846g genes, canine oculoskeletal foreign bodies 224–225, 420
ciliary ganglion 43, 70 dysplasia 490 nasolacrimal system 274
ciliary glands (glands of Moll) 21, tapetum 48 optic nerve 530
241. See also hordeolum vitreous 85, 87, 470 orbit 222
866 Index

cone–rod dystrophy 499–500 anatomy 290–291, 303 contagious viral pustular


genes and breeds 851 goblet cell deficiency 282 dermatitis 697
cone–rod dystrophy type 1 PRA 214 goblet cells 290–291 continuous infusion, drug
cones 55, 100, 102 grafts 302–303, 328, 328–333 delivery 117, 121
birds 110 non‐neoplastic masses contralateral effects
dogs, degeneration 502, 851 297–299 beta‐blockers 153
electroretinography 212 surgery 302–303 pseudo‐indirect pupillary light
reptiles 740 systemic disease 300–301 reflex 765
congenital anomalies drug delivery 115, 119 topical administration of
birds 752 examination 170 drugs 119–120
camelids food animals 671–687 contrast enhancement, MRI 200
conjunctiva 708 flora 708 contrast radiography 198–199
nasolacrimal system 707–708 goblet cells 21, 63, 290–291 contrecoup injury, raptors 756
posterior segment 713 deficiency 282 conus papillaris 71
cats 812–813 guinea pigs, masses 721 lizards 739–740
eyelids 541–543 horses convection, aqueous humor 74
iris 577–578 flora 630 conventional pathway, aqueous
lens 592 grafts 639–642 humor outflow 78
cattle pseudotumors 627 convergence (refraction) 92
fundus 691–692 masses 297–299 convergent eye movements 88,
globe 666–667 with acid‐fast bacilli 821 108–109
iris 688 guinea pigs 721 convergent strabismus 89
dogs 274–276 rabbits, overgrowth 726–727 copper metabolism, Cooper
hyphema 421 sampling from 183–185 abnormalities 444
lens 427–435 sheep 697–701 coproporphyrinogen I 672
vascular system 223 conjunctiva‐associated lymphatic Corallocytostroma (spp.), black soil
exotic mammals 744 tissue 22, 290 blindness 694
food animals conjunctival fornix 21, 290 cord1 (cone–rod dystrophy) 499
bovine viral diarrhea 783 conjunctival glands 21 corectasia, 846g
nasolacrimal system 671 conjunctivitis corectopia, 846g
guinea pigs 721 camelids 708–709 coreoplasty, 846g
horses 607–613, 831–836 canine distemper virus 778 cornea 25
pigs 703 cats 556–562 abscesses 343, 635, 641, 642,
reptiles 740 ankyloblepharon 541 643–644, 710
rodents, posterior segment 720 feline herpesvirus‐1 825 accommodation 95–96
congenital cataract 396, 592 lipogranulomatous 549–550 amphibians 736–737
camelids 714 chlamydiosis 841 anatomy 26–33
cattle 689 dogs 292–296 birds 749–750
dogs 433–435, 441–442 ankyloblepharon 244 trauma 756
guinea pigs 721 follicular 308 camelids 709–711
horses 610–611 protozoal 343 cattle. See cornea (bovine)
Malayan mouse deer 744 exotic mammals 744–745 cats. See cornea (feline)
pigs 705 ferrets 723 collagen. See transparency
secondary 435 guinea pigs 721 corticosteroids on wound
sheep and goats 701 horses 614–615, 627 healing 140
suture lines vs 427 nonhuman primates 732 decompensation 32–33
congenital deafness, Doberman pigs 704 degeneration 711
Pinscher 775–778 rabbits 727 birds 754
congenital glaucomas 369, 387, 589, rodents 717–718 ranch mink 746
611–612, 719 conjunctivobuccostomy, 846g development 10–11
congenital neuropathies, optic conjunctivorhinostomy, 554, 846g dogs. See cornea (canine)
nerve 531–533 consensual pupillary light reflex, 765, drug delivery 115, 118–119
congenital stationary night 766, 846g enhancement 123
blindness (CSNB) constant pressure perfusion dystrophy. See corneal dystrophy
dogs, gene and breeds 851 technique 80–81 edema. See corneal edema
equine 607, 612–613, 662, 832–833 contact hypersensitivity 296 esthesiometry 182–183
conjunctiva, 21–22, 846g contact lenses examination 171, 242
cats, neoplasia 562–563 soft 633 fish 733, 735–736
cattle 671–687 solid polymeric devices for drug functions 64–68
squamous cell carcinoma 685 delivery 122 guinea pigs 721–722
centripetalization 726–727 contagious ecthyma 746 horses. See cornea (equine)
chlamydiosis 841 contagious ophthalmia. See infectious inflammatory diseases 322–344
dogs 290–303 keratoconjunctivitis rodents 719
Index 867

innervation 27, 67–68, 69 dystrophies and degenerations cortical blindness, pupillary light
dogs 311–312 574, 575 reflex 169
horses 629 Mycoplasma infection 559 corticosteroids 138–141
leukomas 320 stroma, feline herpesvirus‐1 565, 566 anterior uveitis 407, 408, 585–586
Peter’s anomaly 396 thickness 570 autoimmune hemolytic
light transmission 91–92 corneal dystrophy, 846g anemia 512
lipidosis 346, 417, 464, 722 American Dutch Belted rabbits camelids, pregnancy 712
inflammation 346–347 728 cataract surgery 457
mineralization 647–648 dogs 341, 344–345 contraindications 408
MPS I 815 endothelial 317, 345, 347–348 eosinophilic keratitis 568
opacities. See cornea under opacities horses 647–648 equine corneal infections and
penguins 757 infantile 320 633
pinnipeds 759 rodents 719 equine recurrent uveitis 653
power, by species 95 corneal edema feline herpesvirus‐1 563
rabbits 92, 728 camelids 709 hyphema 421–422
reflex. See corneal reflex canine adenovirus vaccines immune‐mediated
refraction 93–94 317, 415–416 thrombocytopenia 511
rodents 719 after cataract surgery 463–464 infectious bovine
sampling from 183–185 cats 579 keratoconjunctivitis
sensitivity 67–68, 171, 182–183, dogs 347, 348, 353, 403, 415 and 679
312, 768 food animals 672 keratoconjunctivitis sicca 284
cattle 665 malignant catarrhal fever 674, 843 latanoprost and 158
horses 629 tocainide 318, 811 masticatory muscle myositis 794
sequestration 826 corneal power, by species 95 myositis 228
sheep 697–701 corneal reflex, 60, 67–68, 169–170, ocular hypertension from 141,
specular reflection 171 182–183, 242b 768 700–701
squamous cell carcinoma birds 751 optic neuritis 536
143–144, 350 corneal touch threshold 183 pannus 342
thickness measurement diabetes mellitus 768 parasitic diseases 414
200–201, 311 corneal ulcers, 322–338, 570. See also postvaccinal reactions and 416
touch threshold 183 ulcerative keratitis pregnancy, camelids 712
diabetes mellitus 768 anterior uveitis 410–411 prodrugs 123
trauma. See perforation antibacterial agents 324, 327, puppy strangles 793
ulcers. See corneal ulcers 409, 616 side effects 140–141
ultrasonography 205 atropine and 287, 327 spontaneous chronic corneal
walrus 759 camelids 709–710 epithelial defects and 327
cornea (bovine) 671–687 after cataract surgery 463 sub‐Tenon’s drug injection 124
inherited diseases 672 corticosteroids and 408 for subconjunctival injections
sensitivity 665 depth 323–331 139, 140, 145
squamous cell carcinoma 685 drug absorption 119 trauma 230, 585
cornea (canine) 310–354 entropion 607 Vogt–Koyanagi–Harada‐like
after cataract surgery 464–466 eosinophilic keratitis 646–647 syndrome 411–412
conjunctival autografts 302–303 feline herpesvirus‐1 565, 825 cortisol, sudden acquired retinal
degeneration 341, 346–347, 464 fish 735–736 degeneration
edema 316–318, 463–464 foals 615–616 syndrome 792
entropion 249–250 horses 630–633, 639–642 cotton wool test, 171, 182, 242b
epithelium, inclusion cysts infectious bovine couching 454
297–298 keratoconjunctivitis coumarin toxicity 812
examination 242 677–678 cover–uncover test 766
inflammatory diseases 322–344 Mycoplasma felis 559 Crampton’s muscle (of ciliary body)
IOP elevation on 367 nonhuman primates 732 34, 41–42, 49, 95–96, 750
leukomas, Peter’s anomaly 396 pinnipeds 759 craniomandibular osteopathy 233
nasal fold trichiasis 257 rabbits 728 crd2 mutation 499
pigmentation 316 raptors 756 crd3 mutation 499
thickness 311 corneoconjunctival transposition crias, congenital anomalies 713
trichiasis 258 332–333 critical flicker frequency 107
cornea (equine) 628–648 corneoscleral masses 349–354 crocodilians 739
abscesses 641 corneoscleral trabecular eyelids 738
congenital diseases 609 meshwork 43–44 tapetum 740
sensitivity 629 corneoscleral transposition 332–333 cross‐lid technique 543
squamous cell carcinoma 648 corona ciliaris. See pars plicata ciliaris crossed eyes 89
thickness 628 coronavirus, feline 582, 824–825 cryoepilation 543
cornea (feline) 569–575 corpora nigra. See granula iridica cryoextraction, 846g
868 Index

cryopreserved corneal grafts 333–334 pannus 342 Dandie Dinmont Terrier, primary
cryoprobe method, intracapsular lens after parotid duct angle‐closure glaucoma 358
extraction 467 transposition 288 dark adaptation 105, 106
cryosurgery cyproheptadine, for photic dark cells, corneal epithelium 28
distichiasis 246, 247 headshaking 836 darkness, for examination 164
eyelids 243–244 cyst phenotype, multiple congenital darling pea 694
neoplasia 265, 266 ocular anomalies 833 day blindness
papillomas 350 cystic eye 223 Alaskan Malamute 502
cryotherapy cystic glaucoma 385–386, 417 Briard 503
cyclodestructive 392 cysts dazzle reflex 60, 169, 242b 528, 766
for sarcoids 626 cats dead‐end hosts, West Nile virus 840
squamous cell carcinoma 623, eyelids 550–551 deafness
624, 685–686 iris 578–579 blue‐eyed white cats 576, 812–813
cryptococcosis 507, 800–801, 821 dacryops 199 Doberman Pinscher 775–778
Cryptococcus gattii 583–584, 800, 821 dogs 223 dog coat color 785
Cryptococcus neoformans 413, 545, conjunctiva 299 debridement (corneal)
583–584, 584, 800, 821 inflammatory 385 dogs, 325, 326b
cryptosporidiosis 753–754 lacrimal secretory system 289 horses 616, 633
crystalline corneal opacities 341, orbit 226–227 rabbits 728
344–347 uvea 316, 398 decompensation, cornea 32–33
crystallins vitreous 477 decussation of optic nerve fibers
anterior uveitis 410 horses, uvea 649 101–103, 768
cornea 65–66 inclusion cysts, corneal birds 751
lens 84, 426 epithelium 297–298, 464 blue‐eyed white cats 576–577
cul‐de‐sac, 846g meibomian 263 dogs 527
cultures 183–185 salivary retention cysts 226–227 pupillary light reflex 765
nasolacrimal system 273 uvea 398, 649 Siamese cats 780
cup to disc ratio 529 cytobrush 184 deep corneal vessels 318
cupping, optic nerve head 529 cytology 183–185 deep lamellar endothelial keratoplasty
curvature aqueous humor 405 (DLEK) 642
astigmatism 99 bacterial keratitis 336 deep stromal abscesses (DSAs) 641
cornea, cats 570 blastomycosis 820 deep stromal ulcers 327, 331
on refraction 94 conjunctiva 291, 292 degenerations
Cushing’s syndrome 809 lymphosarcoma 297 in birds 754–755
Cuterebra (spp.) 261, 561–562, fungal keratitis 337 cornea. See degeneration
585, 822 keratoconjunctivitis sicca 296 under cornea
Cutler–Beard technique 543 nasolacrimal system 273 lens, reptiles 742
cyanoacrylate adhesive 328 squamous cell carcinoma 683 retina. See under retina
cyclic guanosine monophosphate, cytolytic phase, feline herpesvirus‐1 vitreous 474–475
photoreceptor dysplasias 563, 566, 825 degenerative pannus (chronic
496, 497–498 cytoplasmic inclusion bodies, canine superficial keratitis), 307,
cyclic thrombocytopenia, canine 804 herpesvirus‐1 294 339–342, 849g
cyclitis, 846g cytosine analogue 137 dehiscence of grafts 330–331
cyclocryothermy, 392, 846g cytotoxins, Moraxella bovis 677 delirium, from atropine 145–146
cyclodestructive procedures 392–393 demarcation retinopexy 521
cyclodialysis, 846g demecarium bromide, 151, 382, 388b
cyclooxygenase 401 d demodicosis
NSAIDs on 141–142 dacryoadenitis, 846g bovine 669–670
pathway 402, 408 dacryocystitis, 846g cats 546
cyclopamine 695 camelids 708 dogs 261, 803
cyclopentolate 144 dogs 277 goats 697
cyclophotoablation, horses 656 horses 614 demyelinating disorder, Limousin
cyclophotocoagulation 92, 591–592 bacterial infections 608 cross‐calves 694
laser cyclophotocoagulation 92, 390 rabbits 727 dendritic lesions
cycloplegia (term), 846g dacryocystorhinography, 198–199, camelids 710
cycloplegics, 144–146. See also 274, 707, 846g feline herpesvirus‐1 565
mydriatics dacryocystotomy 277 denervation hypersensitivity 780
cyclosporine (CSA) 143, 148 dacryops 199 dental surgery, ocular injuries 585
eosinophilic keratitis 568–569 dairy operations, infectious bovine depigmentation. See also albinism
equine recurrent uveitis 653, 654 keratoconjunctivitis chch mutation 813
hypersensitivity 549 679 Vogt–Koyanagi–Harada‐like
keratoconjunctivitis sicca 283, damage‐specific DNA binding protein syndrome 795
284, 296, 645, 727 2 (DDB2) gene 648 depot corticosteroids 139
Index 869

depth vision. See stereopsis diarrhea. See also bovine viral cryosurgery 246, 247
Dermacentor (spp.) 805–806 diarrhea horses 627
dermatitis nictitating membrane protrusion diurnal variation, intraocular
cats 549 and 781, 782, 818 pressure 363
contagious viral pustular 697 salmonellosis 837 divergence (refraction) 92–93
immune‐mediated 792–793 diathermy, 847g divergent eye movements 88,
juvenile sterile granulomatous, 793. diazoxide, cataracts 443 108–109
See also puppy strangles dichlorphenamide 149, 154, 155 DM. See Descemet’s membrane
solar 549, 551, 670, 697 dichlorvos 742 DNA, drugs altering bacterial
dermatomyositis 793 dichromatic vision 110 synthesis 131–132
dermatophilosis 669, 696 diclofenac 142, 407 DNA tests 214–215, 482
dermatophytosis 545 dietary deficiencies, cataracts 446, 747 Doberman Pinscher
dermis, medial aberrant 300 diffuse iris melanoma, feline 586–588 anterior segment dysgenesis 397
dermoids, 846g diffuse lights, slit‐lamp congenital deafness 775–778
cats 545, 575 biomicroscopy 174 microphthalmia 223
dogs 245, 298, 319 digital tonometry 192 persistent hyperplastic tunica
food animals 671 dilated pupil syndrome vasculosa lentis/ persistent
horses 607–608 (dysautonomia) 781, hyperplastic vitreous
descemetoceles, 331–334, 846g 790–791, 817–818 431–433
Descemet’s membrane (DM) 31–32, 65 dilator muscle of iris 37–38, 69, tocainide on 811
dogs 310, 311, 331 144, 764 dogs
endothelial corneal dystrophy pinnipeds 760 adrenergic receptors 70
347 dilution methods, aqueous humor anterior uvea 394–425
horses 628 measurements 80 developmental disorders 394–397
desmetoceles 631 dimethylsulfoxide (DMSO) blink rates 60, 61
detomidine 165, 604 itraconazole in 135 cataract. See dogs under cataracts
deturgescence, cornea 30–31 on lens 443 ciliary nerves 764–765
deuteranopia 110, 111 diminazene diaceturate, babesiosis color vision 110
development 3–13 839 conjunctiva. See dogs under
fundus diode laser photocoagulation 392, 425 conjunctiva
disorders 485–493 diopter (unit), 93, 847g cornea 310–354
dogs 484–485 dioptric power 49 eye anatomy 19
nasolacrimal system, disorders dipivalyl epinephrine 123, 152 eyelids 61, 239–269
276 Diptera. See flies surgery 242–244
role of vitreous 86 direct astigmatism 99 fundus
vitreous 12 direct goniolens 172 diseases 478–515
disorders 472–477 direct gonioscopy 181, 182 normal 482–484
developmental cataracts 436–442, 658 direct ophthalmoscopy 175–177, glaucomas. See dogs under
dexamethasone 138, 139, 140, 145 178, 479 glaucomas
anterior uveitis 407, 586 glaucomas 364 globe dimensions 26
cataract surgery 457 optic nerve head 529 inherited eye diseases 851–852
eosinophilic keratitis 568 direct pupillary light reflex 169 intraocular lenses 97
exophthalmos from 667 Dirofilaria immitis 802 intraocular pressure, normal
pannus 342 vitreous 477 values 82, 192
prodrugs 123 dirofilariasis 802 lacrimation 64
dextrose disaccommodation 95 lens 49, 426–468
dendrobatic frogs discission 847g lysosomal storage diseases by
cataracts 738 disinsertion, retina 512, 517 breed 856
diabetes mellitus 808–809 dislocation. See luxation nasolacrimal system 24–25,
anterior uveitis (treatment) 408 disodium ethylenediaminetetraacetic 64, 270–279
cataracts 85, 446, 551, 808–809 acid (EDTA). See also Beagle 374–375
camelids 714 ethylenediaminetet- diagnostic tests 272–274
dogs 446, 456, 466, 511, 827–828 raacetic acid drug drainage 118
cats 827–828 keratomalacia 323 examination 170–171
corneal touch threshold 768 disophenol 811 neuro‐ophthalmic diseases
megestrol acetate 831 dissectors, cornea 320, 321 775–780
retinopathy 808 distance examination 164b, nictitating membrane 303–309
dogs 511 168, 763–764 (O‐acyl)‐omega‐hydroxy fatty
Diabolo procedure, 253b distant direct ophthalmoscopy 176 acids 63
dialysis, retina, 847g. See also distemper. See canine distemper virus; orbit 15, 219–238
disinsertion strangles dimensions 14
diamond palpebral fissure 253, distichiasis 246, 847g surgery 234–238
254–255 Celsus–Hotz resection 247 posterior segment 469–538
870 Index

dogs (cont’d) hypersensitivity 548–549 elastin‐like fibers, trabecular


descemetoceles and 331–332 on intraocular pressure, 387b meshwork in Beagle
ophthalmomyiasis 414 nasolacrimal drainage 120 374–375
surgery 515–525 solubility 118–119 electricity, cataracts 444
prostaglandin analogues 158 thrombocytopenia 790 electrochemotherapy 552
refraction 96–97, 98 toxicities 811–812, 830–831 electrodes 211
restraint 165 dry eye, 569. See also electrodiagnostic vision testing
retina keratoconjunctivitis sicca 210–213
development 12 feline herpesvirus‐1 564–565 electrolytes
diseases 478–515 dummy calves 666 aqueous humor 75, 77
retractor anguli oculi 19 duplex cornea 737 lens 84
retrobulbar block 167 dwarfism 785–786 tear film 63
striate cortex 103 canine oculoskeletal dysplasia electromagnetic spectrum 90
systemic diseases 784–812 490 electrophysiology
visual acuity 112 genes and dog breeds 852 glaucomas 207
visual fields 108 dyes. See also fluorescein optic nerve 530
dolphins 744 external ophthalmic stains electroretinography, 210–212,
dominant progressive retinal 186–191 480–482, 847g
atrophy 501 dynamic tonometry. See rebound day blindness 502
Doppler shift 209 tonometry flicker ERG 212–213
Doppler ultrasound 209–210 dysautonomia 781, 790–791, 817–818 optic neuritis 535, 536
vitreous 471 dyscoria, 847g phacolytic uveitis 448
doramectin 546 dysplasia palpebrae 245 progressive retinal atrophy 497
dorzolamide 154–155, 388b, 591, 656 sudden acquired retinal
double cones, birds 110 e degeneration syndrome
doughnut‐like lesions, pigmentary E‐collars 244 509, 792
chorioretinopathy 504 early retinal degeneration 499 electrothermal treatment 686
downgrowth, epithelium 464, 748 gene and breeds 852 elementary bodies, Chlamydophila
doxycycline 130 early retinopathy 501–502 pecorum 698
bartonellosis 797, 819 ecdysis, spectacle 738 elephants
Bordetella bronchiseptica 560 echothiophate iodide 151 Asian 743
Chlamydia felis 558 economic impact cataracts 747
lipogranulomatous infectious bovine elimination of drugs 120
conjunctivitis 550 keratoconjunctivitis 674 Elizabethan collars 244
parasitic granulomas 299 squamous cell carcinoma 680 embryo 3
after parotid duct transposition 288 ectasia, 847g embryology
pinnipeds 759 ecthyma. See also contagious viral eyelid agenesis 542
spontaneous chronic corneal pustular dermatitis nasolacrimal system 270, 272
epithelial defects 326 contagious 746 vitreous 469–470
Draeger applanation tonometer 193 ectoderm 3 embryonic lens nucleus 8–9, 51
draping, eyelid surgery 243 lens development 8 emergency management
drd loci 786 nasolacrimal system 270, 272 intraocular pressure, 388b
dromedary camel ectoparasites, food animals keratomycosis 637
congenital anomalies 744 669–670, 697 trauma, 418, 419b
retinal vessels 713 ectopia lentis, 847g emmetropia, 96–97, 847g
dropped nuclear fragments 519 genetics 360 emphysema, orbit 231
droptainer, pilocarpine 151 ectopic cilia 246–248 Encephalitozoon cuniculi
Drualt’s bundle 12 ectromelia virus 718 cataracts 446
drug delivery, 114–125. See also ectropion, 847g exotic mammals 745
slow‐release devices cattle 668–669 rabbits 729
barriers 115–116 dogs 253–256 encircling nictitating membrane 303
pilocarpine 150 horses 614 enclosed orbits 14
drug‐induced cataracts 442–443 sheep 696 endodontic absorbent paper point
drug‐induced retinotoxicity 509, 597 edema. See also papilledema test 186
cats 597 cornea. See corneal edema endophthalmitis, 399, 519, 847g
drugs Edinger–Westphal nucleus 772 brucellosis 797
on adrenergic receptors 152–153 effusive retinal detachment 519 cataract surgery 457, 465
on aqueous humor 149 Egger’s line 470 horses 619
on bacterial DNA synthesis 131–132 Ehlers–Danlos syndrome 444–445 toxic anterior segment syndrome vs
for glaucomas 149 ehrlichiosis 294, 415, 804–805 464
in globe 120–121 Elaeophora schneideri 701, 746 endoscopic cyclophotoablation 656
for hypercholesterolemia, cataracts elasmobranchs 733–734 endoscopic photocoagulation 392
443 elastic modulus 67 endotheliitis, cornea 646
Index 871

endothelin‐3 832 visual field loss 107 breed susceptibility 653


endothelium eosinophil granuloma, eyelids 263 cataracts 657–658
cornea 32–33, 310 eosinophilic conjunctivitis 561 heterochromic iridocyclitis vs 655
camelids 709 eosinophilic keratitis 567–569, equine viral arteritis 839
cats 570 646–647 equine viral encephalomyelitis
cells 312 eosinophilic myositis 227–228 782, 840
deturgescence 30–31, 67 eosinophils, allergies 295 ergosterol, azoles on 134
drug passage 115 EP receptors 156 eruptive bullous keratopathy 573–574
dystrophy 317, 345, 347–348 ependymoglial cells, Müller erythematous macular dermatitis
edema 316–317 cells as 100 548
embryology 10 epiblast 3 erythromycin 130
fish 733 epibulbar melanomas 351–352, esotropia, 577, 607, 666, 667, 847g
food animals 672 423, 576 fibrosing 778
healing, 313, 314b epicorneal membrane 726–727 Siamese cats 781
horses 628–629 epilation, 246, 247, 847g essential iris atrophy 701
MPS I 815 epinephrine 146, 152 esterases, drug metabolism 120–121
iris 116 phacoemulsification 460, 467 esthesiometry, cornea 182–183
trabecular meshwork (TM), AH prodrug 123, 152 ethoxzolamide 149
outflow 78 superficial conjunctival hyperemia ethylenediaminetetraacetic acid
vascular system 11 vs ciliary flush 403 (EDTA). See also disodium
energy of photons 90–91 testing with 771 ethylenediaminetet-
English Cocker Spaniel topical anesthesia 147 raacetic acid
congenital cataract 396, 434 epiphora, 847g corneal mineralization 648
glaucomas 376 cats 554 after parotid duct transposition 288
photoreceptor degenerations 500 dogs 170–171, 272, 274–276 etodolac 143, 279, 408, 812
English Setter, neuronal ceroid food animals 671 European College of Veterinary
lipofuscinoses 504 episclera 34 Ophthalmologists, on
English Springer Spaniel nictitating membrane attachment gonioscopy 363, 364
glaucomas 376 309 Eva vitrectomy system 523
iridocorneal angle 358 venous congestion 385 evaporation of tears 271
enophthalmos, 219–220, 847g episcleral venous pressure 79 eversion of eyelid 696
eosinophilic myositis 228 episcleritis 352–353 everted cartilage, nictitating
medial canthal pocket epistaxis, equine 664 membrane 304
syndrome 300 epithelial thickness, cornea 311 evisceration, 236–237, 758, 847g
enrofloxacin 132 epitheliomas, ciliary body, cattle 689 modified 758
retinal degeneration 597, 830, 831 epitheliotropic mastocytic examination 163–182
Entlebucher Mountain Dogs, conjunctivitis 561 aquatic mammals 758
cataracts 440, 441 epithelium. See also pigmented birds 750–752
entropion 847g epithelium; retinal pigment cattle 665–666
cats 543–545 epithelium cornea 171, 242
cattle 668 ciliary 74 exotic animals 732–733
dogs 19, 242b 248–253 cornea 28–29, 65, 67, 628 fish 735
brachycephalic breeds 276 healing, 312, 314b 629 fundus, 173. See also
horses 607, 613–614, 621 inclusion cysts 297–298, 464 ophthalmoscopy
miniature pigs 731 rabbits 728 dogs 478–480
pot‐bellied pig 703–704 downgrowth 464, 748 horses 165, 604–606
rabbits 726 lens 50, 84 trauma 639
sheep 695–696 primitive medullary, tumors 514 laboratory animals 716–717
enucleation, 232, 234–236, 847g equatorial annular pad 750 lens 173, 426–427
birds 758 equatorial cataracts, horses 658 neuro‐ophthalmic 763–771
cats 592, 603 equatorial plane, globe 26 optic nerve 527–530
emphysema 230 equatorial vacuoles 446 orbit 170
end‐stage glaucoma 392 equine herpesvirus‐1, camelids 713 dogs 219–221
feline diffuse iris melanoma 588 equine leukocyte antigens 653 squamous cell carcinoma,
horses 619 equine motor neuron disease cattle 684
trauma 639 (EMND) 662, 835–836 uveitis 406
implants after 236–237 equine piroplasmosis (babesiosis) exenteration, 847g
rabbits 725, 730 301, 839 cats 603
reptiles, panophthalmitis 741 equine protozoal myeloencephalitis cattle, squamous cell carcinoma
retrobulbar block 167, 234 782 684
squamous cell carcinoma, cattle equine recurrent uveitis (ERU), 627, dogs 235–236
684, 685 650–654, 660, 847g horses 619
872 Index

exophthalmos, 847g. See also proptosis cattle 61, 668–671 feline diffuse iris melanoma 586–588
cattle 666–667, 668 squamous cell carcinoma 670, feline herpesvirus‐1 556, 563–567,
corticosteroids and 141 681, 684, 685 825–826
dogs 219–220, 221 development 13 corneal sequestrum 572–573
differential diagnosis 224 disorders causing corneal ulcer exotic felids 745
fish, viral infections 735 322–323 feline herpetic dermatitis 547
guinea pigs 721 dogs 61, 239–269 feline immunodeficiency virus
horses 617 surgery 242–244 (FIV) 581, 826–827
orbital abscesses 225–226 examination 170 feline herpesvirus‐1 with 565
rabbits 725 ferrets 723 feline infectious peritonitis
periodic bilateral 725 functions 59–62 582–583, 824–825
rodents 717 fusion 3, 11, 13 feline leukemia virus (FeLV)
exotic animals. See also specific types guinea pigs 721 580–581, 781, 827
examination 732–733 horses 61, 621–627 feline herpesvirus‐1 with 565
mammals 743–748 local anesthesia 604–605 lymphosarcoma 828
exotropia, 607, 666, 847g innervation 59–60, 166–167 feline ocular sarcomas,
traumatic proptosis 233 lacerations 258–259, 614, post‐traumatic 588
extended‐spectrum penicillins 126–127 621–622, 669 feline panleukopenia virus 827
external hordeolum (stye), 847g margins 241 feline restrictive orbital
external ophthalmic artery 58, 526 masses 263–266 myofibroblastic sarcoma
external ophthalmic stains 186–191 medial canthus, punctal atresia (FROMS) 602
extorsion 17 608 feline sarcoma virus 827
extracellular fluid volume, osmotic nictitating membrane flaps 308–309 ferrets 723
agents on 159 pigmentation, squamous cell intraocular pressure 82
extracellular matrix carcinoma 681 restraint 165
cornea, healing 313, 314 pigs 61, 703–704 ferrochelatase deficiency 672
embryonic 3 pinnipeds 758–759 fibrae latae 364
extraconal space 219 raptors 748 fibril volume fraction 312
extralabel drug use, infectious bovine regional anesthesia 685 fibrillin‐1 453
keratoconjunctivitis 679 reptiles 61–62, 738 fibrin
extraocular muscles 17–19, sheep 61, 695–697 after cataract surgery 464
87–89, 764 trauma uveal prolapse 419
development 13 birds 756 fibrin clots 76, 401
fascia 16–17, 219 cattle 669 fibrin plugs, corneal healing 314
fibrosing esotropia 778 dogs 258–259, 277, 669 fibrinous aqueous, 404. See also
myositis 793–794 horses 614, 621–622 plasmoid aqueous
restrictive strabismus 228 traumatic entrapment 230 fibrinous uveitis 616–617
tetanus 799 fibroblastic sarcoids 625, 626
traumatic proptosis 231 f fibroblasts, cornea, healing, 313, 314b
vestibulo‐ocular reflex 170 face flies. See Musca autumnalis fibromas
extraocular polymyositis 228 facial nerve dogs 265
extrascleral prostheses 237 nuclei 773 feline eyelids, frequency 552
exudates, uveitis 401 paralysis 342, 665, 710, 766 fibronectin 313
exudative optic neuritis 664 hemifacial spasm vs 774 fibropapillomatosis, turtles 740
eye drops 116–117 idiopathic 779 fibrosarcomas
insulin 120 fagopyrin 670 dogs 265
eyelashes 20 falciform process 734 feline eyelids 553
cats, hairs as 541 false hellebore (Veratrum frequency 552
dogs 240 californicum) 695 fibrosing esotropia 778
cutting for surgery 242 famciclovir 137, 547, 566, 567, 826 fibrous histiocytoma 298
transplantation 267 Fannia (spp.), as vectors 561 nodular granulomatous
horses 606, 627 far point 180 episcleritis 352–353
latanoprost on 158 fascia, orbit 14–17, 219 fibrous tapetum 48
eyelids fat prolapse field of stars 444
agenesis 542–543 orbit 233, 621 filaments, esthesiometry 183
akinesia 165–166 subconjunctival 233, 298–299 filariasis 412
anatomy 19–21 fatty eye 721 fine needle aspiration 222–223
anurans 736 feline calicivirus, 559–560. See also fish 733–736
birds 61–62 calicivirus lens 94, 99, 734, 736
trauma 756 feline central retinal degeneration refraction 99
camelids 707 829–830 vitreous 94
cats 61, 541–553, 818–819 feline coronavirus 582, 824–825 fistula, after enucleation 235
Index 873

5‐fluorouracil fluorometholone 140 Friesian horse


for sarcoids 626 fluorophotometry, aqueous corneal dystrophy 647
squamous cell carcinoma 350 humor 80, 202 distichiasis 627
fixation, cytology 184–185 fluoroquinolones (FQNs) 131–132, frogs 736–738
flaps 597, 781, 830 intraocular pressure 82
blepharoplasty 267 fluranaler 546 frontal nerve block 166, 604–605
conjunctiva 328, 330, 639–640 flurbiprofen 142 frontal sinus, horse 617
Gunderson flap 328, 348 anterior uveitis 407 frontal sinusitis, cattle 668
keratectomy 320 latanoprost and 158 Fuchs’ dystrophy 347
nictitating membrane 308–309 fly‐biting syndrome 475 fucosidosis 787, 856
posterior lamellar keratoplasty focal lights, slit‐lamp full field domes 211, 212
643–644 biomicroscopy 174 full‐thickness lacerations, cornea
flare, 847g. See also aqueous flare folate bacterial metabolism, drugs 313, 314, 334–335
flare‐cell photometry 202 altering 131 fundic reflex, ophthalmoscopy 176, 179
flash electroretinography 210–212, foldable IOLs 460, 462–463 fundus
480 folds birds 750
optic neuritis 535 conjunctiva, chlamydiosis 841 trauma 756
progressive retinal atrophy 497 retina camelids 712–714
flat globe 749 cats 600 canine distemper 806
Flat‐Coated Retriever, glaucomas 376 dogs 478, 492 cats 593–594
fleas, bartonellosis 819 rodents 720 cattle 690–694
flesh eye 721, 722 follicular conjunctivitis 295–296, 308 colobomas, horses 612
flicker detection 107 folliculitis (bacterial), cats 547 dogs
cone degeneration 502 Fontana’s spaces 42 diseases 478–515
flicker electroretinography 212–213 food allergy 549 normal 482–484
flies. See also ophthalmomyiasis food animals, 665–715. See also examination, 173. See also
cats 822 camelids; cattle; sheep ophthalmoscopy
conjunctivitis, camelids 709 infectious bovine dogs 478–480
Cuterebra (spp.) 261, 561–562, keratoconjunctivitis 679 exotic animals 747–748
585, 822 inherited eye diseases 855 guinea pigs 720
habronemiasis 838 lysosomal storage diseases by horses 606, 658–659, 660
horses 622 breed 856–857 pigs 705–706
sheep and goats 700 neuro‐ophthalmic diseases 783 rabbits 730
vectors 561 systemic diseases 840–844 rodents 720
Moraxella bovis 676 foramen orbitorotundum, cattle 14 sheep and goats 701–703
Thelazia (spp.) 672 foramina fungal infections 132
floaters 475 orbit 14, 16 birds 753
florfenicol 679, 700 supraorbital 605 blepharitis 545, 546
Florida keratopathy 349, 571 foreign bodies 420 cats 820–822
flow rates, tear film 62 cataracts 443, 447 chorioretinitis, 506b 598
fluconazole 133, 135 conjunctiva 299 conjunctivitis 294
flucytosine 134 cornea 323, 335, 634 corticosteroids and 140
fluid overload, osmotic agents 159 magnetic resonance imaging 418, 420 exotic mammals 745
fluid pumps, cornea 312 nasolacrimal system 277 food animals 669
flunixin meglumine 142 nictitating membrane 308 keratitis 337
anterior uveitis 407, 632 orbit 224–225 cats 570–571
camelids 714 radiography 198 cattle 673
cataract surgery 457 fornix, conjunctiva 21, 290 horses 634–637
after enucleation 685 four‐point block viral infections vs 644–645
equine recurrent uveitis 653 cattle 685 orbit, cats 602
fungal infections 636 horses 619 reptiles 741
fluorescein, 171, 187–188, 242, 847g foveae 55 sheep and goats 696–697
corneal ulcer 322 FP receptors 156 systemic 796, 799–801
Jones test 185, 187, 188–189, fractures (bone) cats 583–584
273–274, 628 keratoconjunctivitis sicca 645 ulcerative keratitis, horses 630, 632
spontaneous chronic corneal orbit 230, 619–620 uveitis 412, 413
epithelial defects 324–325 freckles, iris 422 fungi, normal, conjunctiva 291,
fluorescein angiography 202–203, French Bulldog, congenital 630, 697–698
480, 529–530 cataract 441 furrows, keratomycosis 637
fluorescence 91 French heartworm 801 Fusarium (spp.)
fluorescent antibody staining, fresh corneal grafts 333–334 cattle 673
Chlamydophila pecorum 698 Friesian cattle. See Holstein cattle itraconazole 135
874 Index

g glass eyed sheep, Pteris aquilinum palpation 220


galactocerebrosidosis 787, 813–814 702–703, 783 reinflation 333, 334
dog breeds 856 glaucomas, 847g. See also ocular reptiles 738
galactosemic cataracts 747 hypertension; specific types rupture 418, 419
gammopathy amphibians 737 surgery 234–238
monoclonal 417–418 camelids 715 globoid cell leukodystrophy. See
polyclonal, feline infectious cats 588–592 galactocerebrosidosis
peritonitis 582 cattle 687 globose globe 749
ganciclovir 137 cholinergic antagonists and 145 glucose 6‐phosphate, lens 85
circadian rhythms and 84 glucose metabolism
ganglion cells (RGC). See under retina
defined 355 cornea 67
gangliosidoses 787, 814
dogs 355–392, 355–393, 417 lens 85
cat breeds 856
breeds 356, 357 glycerin 150, 159
dog breeds 856
after cataract surgery 465 glycocalyx 24, 63, 278
gap junctions, ciliary processes 40
classification 360–362 glycogen, cornea 67
gastrulation 3–7
clinical signs 368–369 glycosaminoglycans. See also
gatifloxacin 132
diagnostics 362–367 mucopolysaccharidoses
gauze packing, after enucleation 685
duration 361–362 cornea 65, 311
Gelrite 153
epidemiology 355–357 polysulfated (PSGAGs),
gemifloxacin 132
genetics 357–360 spontaneous chronic
gender, glaucomas, dogs 356, 370
gonioscopy 182 corneal epithelial
gene therapy
inheritance 370–371 defects 326
CNGB3 mutation 502
lens luxation 371, 380–382, GM1 gangliosidosis 787, 814
hereditary retinal dystrophy 504
451–452, 453–454 cat breeds 856
steroid‐induces ocular
lens rupture 457–458 dog breeds 856
hypertension 701
lymphomas 588 GM2 gangliosidosis 787, 814
general anesthesia cat breeds 856
optic nerve cupping 529
cataract surgery 457 optic neuropathy 538 dog breeds 856
corneal ulcers after 324 pigmentary uveitis (melanocytic goats 694–703
fish 735 glaucoma) 385–386, 422 fundus 701–702
flash electroretinography 212 progress 371–379 fungal infections 696–697
intraocular pressure 79 on retina 512 intraocular pressure 82
pigs 703 surgery 389–392 mycoplasmal keratoconjunctivitis
side effects 165 treatment 387–392 841
genetics, 213–215. See also inheritance drugs for 149 restraint 165, 694
coat color in dogs 785 electrophysiology 207 scrapie 843–844
Collie eye anomaly 485–486 end‐stage goblet cells, conjunctiva 21,
glaucomas 357–360 gentamicin 392, 471, 592 63, 290–291
lethal white foal syndrome 832 treatment 392 deficiency 282
tests, heritable cataracts 442 horses 611–612, 655–656 gold seeds, radioactive 686
gentamicin 128 nonhuman primates 732 Golden Retriever
end‐stage glaucoma 392, 471, 592 prostaglandins for 155–158 cataracts 434, 440
feline ocular sarcomas 588 rabbits 728–729 pigmentary and cystic glaucoma
mycoplasmal keratoconjunctivitis rodents 719 386, 417
700 sheep 700–701 prcd mutation 501
geographic retinal dysplasia 488 watershed zones 72 progressive retinal atrophy 214
German Pincher, developmental Glen of Imaal Terrier, crd3 Goldmann applanation
cataracts 439–440 mutation 499 tonometer 193
German Shepherd, cataracts 434, glial cells, optic nerve 12–13, 100–101 Goldmann’s Imbert–Flick law 193
440, 441 globe. See also tubular globe goniodysgenesis, 387. See also
German Shepherd pannus (chronic amphibians 736 pectinate ligament dysplasia
superficial keratitis), 307, anatomy 25–58 hereditary glaucoma, rabbits 729
339–342, 849g birds 749 gonioimplants 390–392
German Short‐Haired Pointer, cone contrecoup injury 756 complications 390–392
dystrophy 502 camelids 706 goniolenses 172, 181
German Warmblood horses, equine cattle 666–667 gonioprism, indirect 172
recurrent uveitis 653 dimensions 26, 105 gonioscopy 181–182, 358,
giant retinal tears, vitrectomy 521–522 drugs in 120–121 363–364, 847g
glands of Moll, 847g. See also examination 170 Göttingen minipigs 731
ciliary glands fish 733 gradient index, lens 94
glands of Zeis, 847g. See also IOP elevation on 367 grafts
sebaceous glands orbital infections 225 blepharoplasty 267
Index 875

conjunctiva 302–303, 328, reptiles 738 hemostasis, eyelid surgery 243


328–333, 639–642, 641 rodents 717 hemostats, for ankyloblepharon 542
cornea 328–333 haws 847g. See also nictitating hepatitis, infectious canine 317,
corneal ulcers 570, 639–642 membrane 415–416, 807
eyelid agenesis 543 head and eye malignant catarrhal herbivorous type, iridocorneal angle
keratectomy 320 fever 674 41–42
keratomycosis 637 head movements 88 hereditary retinal degenerations
for limbal melanomas 352 headpieces, ophthalmoscopes 174 493–500
gramicidin 128 headshaking hereditary retinal dystrophy 503–504
granula iridica (corpora nigra), 35, 36, photic 664, 836 Hereford cattle
106, 172, 649, 847g retinal detachment 516 congenital cataract 689
camelids 706, 711 hearing loss. See deafness dermoids 671
cattle 666 heartworms incomplete albinism 691
multiple congenital ocular angiostrongylosis 801 inherited eye diseases 855
anomalies 834 dirofilariasis 802 squamous cell carcinoma 680
granulomatous disease, heat shock transcription factor 4 herpesvirus infections. See also canine
idiopathic 790 (HSF4) gene 442 herpesvirus‐1; feline
granulomatous lens‐induced heather blindness. See infectious herpesvirus‐1
uveitis 410 keratoconjunctivitis dogs 807
granulomatous meningoencephalitis hemangioma equine herpesvirus‐1,
513–514, 779, 791 cats camelids 713
granulomatous scleritis, non‐ conjunctiva 562 ovine herpesvirus‐2 674
necrotizing 353–354, 411 eyelids 552 turtles 740
gray line 241 dogs herpesvirus simiae B 732
gray patch disease 740 conjunctiva 297 herpetic conjunctivitis, feline 556
Great Dane, glaucomas 376–377, 417 cornea 351 herpetic dermatitis, feline 547
Great Pyrenees, canine multifocal nictitating membrane 307 heterochromia iridis, 847g
retinopathy 492 hemangiosarcoma camelids 711
green light (red‐free filter), cats cats 576
ophthalmoscopy 364, 529 conjunctiva 562 cattle 688
green sea turtles eyelids 552 dogs 395
fungal infections 741 dogs fundus 482
herpesvirus infections 740 conjunctiva 297 pigs 704
parasitic diseases 741–742 cornea 351 heterochromic iridocyclitis 654–655
Greyhounds, pannus 340 nictitating membrane 307 heterotopic bone formation, guinea
grid keratotomy 633 hematomas, orbit 230 pigs 722
griseofulvin hemeralopia, 164, 847g hexokinase, diabetes mellitus 445
optic nerve aplasia 600 hemidesmosomes 28 hexosamidase deficiency. See GM2
teratogenesis 601, 830 hemidilated pupil 775 gangliosidosis
Grussendorf procedure, 253b hemifacial spasm 774 hibernoma 755
guinea pigs 720–723 hemolytic anemia, autoimmune hidrocystomas 550, 552
intraocular pressure 82 511–512 high‐frequency ultrasonography
refraction 98 hemoprotozoa, reptiles 741 207–208
Gunderson flap 328, 348 hemorrhage(s) 231 high‐resolution ultrasonography,
gunshot injury 323, 447 anterior segment, rodents 719 glaucomas 365–366
Gutbrod–Tietz procedure, 250, 253b clotting deficiencies 301 Himalayan cats, inherited eye
gynecological miconazole 635 conjunctiva 299 diseases 853
ehrlichiosis 805 histamine 402
h after enucleation 235–236 histidine deficient diet 829
habronemiasis 622, 838 glaucoma 384 histiocytic sarcomas, feline eyelids,
hairs, 20–21. See also trichiasis hypertension 599, 816 frequency 552
distichiasis 246 hyphema 421 histiocytomas, 265. See also fibrous
eyelid agenesis 543 neonatal foal 607 histiocytoma
eyelids 240 optic neuritis 535 feline eyelids, frequency 552
Halberg applanation tonometer 193 retina, anemia 817 nodular granulomatous
handpiece, phacoemulsification 459 subconjunctival, foals 615 episcleritis 352–353
haptic lengths, IOLs 462 trauma 418 histiocytosis, systemic 301, 812
Harderian gland 23–24, 61 vitreous 476 histiocytosis of the Bernese Mountain
birds 749 after cataract surgery 464 Dogs 263–264
dogs 303 cats 594 histophilosis 841–842
pigs 731 dogs 476 Histoplasma capsulatum 413, 545,
rabbits 725 horses 661 583, 584, 821
876 Index

histoplasmosis 821–822 hyaloid artery 7, 9–10, 173, 429–430, hypersensitivity


history‐taking 163–164 469 contact hypersensitivity 296
cataracts 455 horses 606 drugs 548–549
hog brake (Pteris aquilinum) persistent 472–473, 692 sulfonamides 418, 811
702–703, 783 cattle 692 hypertension (ocular). See ocular
hog cholera 704 dogs 472–473 hypertension
holangiotic pattern, retina 57 rodents 720 hypertension (systemic)
Holstein cattle regression 12 cats 815–816
congenital cataract 689 remnants, 692, 705, 715. See also dogs 478, 510, 788
corneal edema 672 Bergmeister’s papilla retinopathy 598–599, 788
homatropine 144 miniature pigs 731 hyperthermia
homologous corneal grafts 333–334 hyaloid artery apparatus, horses, for sarcoids 626
hood conjunctival flap 330 remnants 610 for squamous cell carcinoma 623,
hookworms 802 hyaloideocapsular ligament 470 624, 686
hordeolum, 262–263, 847g hyaluronic acid (HA) hyperthyroidism
horizontal cells, retina 53, 56, 100, 102 for dry eye 569 cats 828
Horner’s syndrome, 554, 555, 771, filler for entropion 544 hypertension 598
776–777, 777, 847g vitreous 85, 87, 470 hypertropia 607, 608
horses 604–664 hyaluronidase, topical anesthesia 147 hyperviscosity retinopathy 599
anatomy of eye 19 hydration, cornea, 67, 316–318. See hyperviscosity syndromes 417–418,
antibacterial agents 129 also corneal edema 510–511, 789, 817
aqueous paracentesis 195 hydrocephalus 778, 786 hyphema, 401, 405, 420–422, 848g
blink rates 60, 61 hydrocortisone 140 after cataract surgery 464
canthi 20 hydrofluoric acid 338 Collie eye anomaly 487
color vision 110 hydrophilic drugs hypertension 599
continuous infusion 117, 121 peak concentrations 120 osmotic agents in 159
drug delivery 117 penetration 119 hypocalcemia 809
examination 165, 604–606 hydrophthalmos, 848g cataracts 444
trauma 639 lens luxation 454 cats 828
eyelids 61, 621–627 hydropropulsion, corneal foreign hypopyon, 401, 405, 848g
local anesthesia 604–605 bodies 335 hypothyroidism 809
globe dimensions 26 hydroxyamphetamine 146, 770–771 corneal lipidosis 346
inherited eye diseases 854 hydroxymethylglutaryl‐CoA reductase hypotony, 848g
intraocular lenses 97–98 inhibitors, hypotropia 607
intraocular pressure 82, 192, 611 cataracts 443, 812 hypoxia 817
iris hygromycin B 705
hypoplasia 609 hyperadrenocorticism 809 i
venous drainage 37 hypercalcemia, cataracts 444 I‐cell disease (mucolipidosis II) 814
lens 49, 656–658 hypercholesterolemia, drugs for, iatrogenic lens opacities, rodents
neuro‐ophthalmic diseases cataracts 443 720
782–783 hypercupremia 444 iatrogenic retinal detachment 518
orbit 13, 15, 617–621 hyperfluorescence, optic nerve IBR. See infectious bovine
congenital anomalies 607 head 530 rhinotracheitis
dimensions 14 hypericin 670 idiopathic bullous keratopathy, NM
phenol red thread tear test 186 hyperlipidemia 788–789 flaps for 308–309
pilocarpine, lack of effect 150–151 cats 817 idiopathic facial nerve paralysis 779
prostaglandin analogues 158 dogs 416–417, 511 idiopathic granulomatous disease,
pupillary light reflex 169 hypermature cataracts 383, 435, 436 canine 790
pupils 70 hypermetropia 96 idiopathic persistent corneal
refraction 97, 98 hyperopia, 848g erosions 324–327
retrobulbar block 167–168, 618–619 aphakia 462 idiopathic uveitis 585, 586
Schirmer’s tear test (STT) 186, 645 indirect ophthalmoscopy 180 idoxuridine 136–137, 336, 566
systemic diseases 831–840 hyperosmotics 348 ilomostat 323
uveoscleral outflow 46 persistent pupillary imaging, 197–210. See also specific
visual fields 107, 108 membranes 396 modalities
Hotz–Celsus repair. See Celsus–Hotz hyperreflective retina 488, 493, 494, nasolacrimal system 274
resection 495, 496, 507, 538 optic nerve 530–531
Hruby contact lens 470 enrofloxacin 597 orbit 221, 618
Hurler syndrome 787, 814 sudden acquired retinal trauma 418
hyalitis, horses 659–661 degeneration syndrome 792 vitreous 471
hyalocentesis 471, 505 taurine deficiency retinopathy 595 Imbert–Flick law (Goldmann) 193
hyalocytes 85, 470 Vogt–Koyanagi–Harada‐like imidacloprid 295
hyaloid, 848g syndrome 795 imidacloprid–moxidectin 546
Index 877

imidocarb dipropionate, babesiosis indirect gonioscopy 181 pigs 704


839 indirect ophthalmoscopy 177–180 sheep 698–700
immature cataracts 435, 436 dogs 479 inflammation
immune privilege 652 glaucomas 364 cornea 629
immune system, mucosal 279 optic nerve head 529 corneal lipidosis 346–347
immune‐mediated conditions laboratory animals 716 intraorbital optic nerve 535
792–795, 818–819 indirect pupillary light reflex 169 squamous cell carcinoma vs 683
blepharitis 261–262, 548 indirect‐acting parasympathomimetics uveitis 401–402
keratitis 645–646, 825–826 151 inflammatory diseases. See also optic
keratopathies indirect‐acting sympathomimetics neuritis
immunosuppressants 283–284 146 birds 752–754
pannus, 307, 339–342, 849g indocyanine green 530 cattle 668
retinopathies 511–512 indolent corneal ulcers 633–634 uveitis 688
thrombocytopenia 511 indolent erosions 324–327 chorioretinitis 597–598
uveitis 652 indomethacin 142 cornea 322–344
immunofluorescent antibody anterior uveitis 407 rodents 719
tests 185 induced retinal dysplasia 490–492 exotic mammals 744–746
immunoglobulin A, tear film 64 infantile corneal dystrophy 320 eyelids 259–263
immunoglobulin M deficiency 836 infections. See also parasitic diseases; fundus 505–509
immunosuppressants, 143–144. specific diseases orbit
See also cyclosporine bacterial. See bacterial infections cats 601–602
anterior uveitis 407, 409 birds 752–754 dogs 223–226
canine herpesvirus‐1 recurrence camelids horses 619
294 corneal ulcers 710 pars plana ciliaris, cats 594
feline herpesvirus‐1 566 posterior segment 713 posterior segment, food
keratoconjunctivitis sicca 283–284 cataracts 446 animals 702
squamous cell carcinoma from 350 cats 556–569, 818–827 vitreous 476–477
Vogt–Koyanagi–Harada‐like eyelids 541–542 horses 659–661
syndrome 411–412, 795 cattle inflammatory masses,
immunosuppression, feline leukemia congenital anomalies from 666 conjunctiva 298
virus 580 posterior segment 692 influenza, ferrets 723
immunotherapy corticosteroids on 140 infrared photoretinoscopy 95
sarcoids 626 exotic mammals 744–746 infrared vision 90
squamous cell carcinoma 623, ferrets 723 infratrochlear nerve block 166,
624, 686 food animals 840–843 167, 606
impact tonometry. See rebound fungal. See fungal infections inheritance. See also genetics
tonometry guinea pigs, blepharitis 721 cataracts
implants, 125. See also gonioimplants; hordeolum 262–263 horses 658
intraocular lenses; horses 836–840 mice 720
prostheses cataract surgery and 611 Collie eye anomaly 485
cyclosporine (CSA) 143, 645 cornea 629–630 congenital cataract 434, 441–442
after enucleation 236–237 after keratectomy 320 entropion, sheep 696
interstitial brachytherapy, keratoconjunctivitis 244–245, equine recurrent uveitis 653
squamous cell carcinoma 674–680 glaucomas
686 NSAIDs and 142–143 dogs 370–371
impression cytology 184 orbit rabbits 728
inactive chorioretinitis 507 cats 602 primary lens luxation 449–450,
inborn errors ofáintermediary dogs 224, 300 453
metabolism 787 pigs, fundus 705 squamous cell carcinoma
incarcerated tissue, full‐thickness reptiles 740–742 cattle 680–681
lacerations 334 retinal dysplasia 490 horses 648
incisions systemic 795–808 inherited retinal degenerations
corneal healing 314 thrombocytopenia 790 493–500
for IOLs 462 ulcerative keratitis 335–337 inner blood–retinal barrier 116
pars plana ciliaris 517 viral. See viral infections inner limiting membrane, retina 57
phacoemulsification 460, 461 vitreous 476 inner nuclear layer (INL) 100
inclusion cell disease infectious bovine rhinotracheitis inner plexiform layer, retina 56
(mucolipidosis II) 814 673, 842–843 innervation
inclusion cysts, corneal epithelium squamous cell carcinoma and 681 blockade 166–167, 604–606,
297–298, 464 infectious canine hepatitis 317, 618–619, 665, 684–685
indentation tonometry 81, 192–193 415–416, 807 ciliary body 43, 46
indirect astigmatism 99 infectious keratoconjunctivitis conjunctiva 291
indirect gonioprism 172 bovine 244–245, 674–680 cornea 27, 67–68, 69
878 Index

innervation (cont’d) beta‐blockers corneal abscesses with 641


dogs 311–312 cats 591 foals 616–617
horses 629 horses 656 fungal infections 636
eyelids 59–60, 166–167 camelids 706 glaucoma 384–385
iris 38 cattle 82, 192, 665 after gonioimplant placement
nictitating membrane 61 cholinergic antagonists on 145 390–392
inserts circadian rhythm 77, 83–84 heterochromic 654–655
drug delivery 123 control 388–389 horses 632
insidious equine recurrent uveitis 651 decrease, uveitis 406, 579–580 prostaglandin analogues 158
instability of lens. See luxation drugs to control, 388b iridodonesis, 450b, 451, 848g
instruments, surgical 459 dynamics 78–81 iridoplegia, 848g
insulin eye drops 120 effects of elevation 367–368 iridotomy, 425, 848g
insulin‐dependent diabetes mellitus fluctuations 83–84 iris, 35–38, 394, 764. See also
(IDDM) 808 on heart rate 89 heterochromia iridis
insulin‐like growth factor, spontaneous horses 82, 192, 611 adherent leukoma 320
chronic corneal epithelial hyphema 422 amphibians 737
defects 326 laboratory animals 716–717 atrophy 397–398, 578
intensity of light 91 measurements 173 birds 37–38, 750
interferometry normal values 192, 362–363 blood flow 71
low‐coherence 479 perfusion pressure and 71, 73 camelids 711
tear testing 186 pigs 703 cats 575
interferons 137–138, 567 raptors 82–83, 192 atrophy 578
interleukin‐2, immunosuppressants sheep 83, 700–701 blue 575–577
on 283 sheep and goats 694 cysts 578–579
internal carotid artery 58 by species 78, 82 colobomas 578, 712
internal maxillary artery 58 stopping anti‐inflammatory congenital anomalies
internal ophthalmic artery 58 treatment 586 cats 577–578
interorbital septum 749, 765 intraorbital optic nerve 527 cattle 688
interplexiform cells 100 inflammation 535 development 11
interstitial brachytherapy, squamous retrobulbar neuropathy and retinal dilator muscle 37–38, 69, 144, 764
cell carcinoma 686 degeneration 693 pinnipeds 760
intorsion 17 intrascleral plexus 33, 517 examination 172
intracameral drug administration 125 cats 524 feline diffuse melanoma 586–588
epinephrine 146 intrascleral prostheses 236–237, 619 fish 734
local anesthetics 147 intravenous lidocaine 147–148 freckles 422
tissue‐type plasminogen activator intravitreal drug injection 125, 471 functions 68–70
422 corticosteroids 139 horses
intracanalicular optic nerve 527 intravitreal membranes 476 hypoplasia 609
intracapsular lens extraction (ICLE) intumescent cataract 382–383 venous drainage 37
cats 593 diabetes mellitus 446 hypertension 599
lens instability 467–468 invasion, squamous cell carcinoma hypoplasia 397
intraconal space 219 682–683, 828–829 incarcerated at corneal
intracranial neoplasia 809 ionization, on drug absorption 119 lacerations 334
intracranial optic nerve 527 iridectomy, 848g jaundice 789
intraepithelial neoplasia sectors 425 melanomas 649–650
cattle 681 iridencleisis, 848g melanosis 587
cornea 350 iridociliary epithelial tumors 424 merle ocular dysgenesis 487
horses 623 iridocorneal angle (ICA), 41–42, merles 395
intraocular drug administration 125 43–46, 172, 848g nevi 422
intraocular lenses, 97–98, aqueous humor outflow 78 permeability 116
460–463, 848g birds 750 prolapse 334, 631, 639
cats 98, 593 development 11 infectious bovine
complications 465 gonioscopy 181–182, 363–364 keratoconjunctivitis 678
foals 611 high‐frequency ultrasonography reptiles 739
rabbits 729 208 rubeosis, 405, 579, 581, 849g
sulcus fixation 468 narrowing 358 sheep 701
intraocular optic nerve 526–527 osmotic agents on 158–159 sphincter 37, 38, 68–69, 144, 764
intraocular pressure. See also reptiles 739 striated muscle
glaucomas; ocular iridocyclitis, 142, 394, 848g. See also birds 70, 169, 751
hypertension; postoperative anterior uveitis; equine reptiles 739
ocular hypertension (POH); recurrent uveitis surgery 425
tonometry atropine for 145 transillumination 175
Index 879

ultrasonography 205 cattle 685 horses 638


uveitis 403 corneal degeneration 347 proteases 338, 632
iris bombé, 381, 383, 404, 848g fungal infections 337 keratomas, cattle 684
atropine on 409 horses 639 eyelids 681
laser treatment 425 lamellar 573 keratoplasty, 348, 640–644, 848g
Irish Setter superficial. See superficial Florida keratopathy 349
galactocerebrosidosis 787 keratectomy penetrating 348, 349, 640–641
quadriplegia and amblyopia keratic precipitates 74, 405 ketamine 706
786–787 keratitis, 322–344, 848g. See also side effects 165
Irish Wolfhound, fundus 483 ulcerative keratitis ketoconazole 133, 134, 413, 811
iritis, 848g canine herpesvirus‐1 293, 336–337 ketorolacromethamine 142
iron shotgun pellets 323, 447 eosinophilic 567–569, 646–647 Key–Gaskell syndrome (dysautonomia)
irrigation fungal infections 337 781, 790–791, 817–818
for chemical burns 338 cats 570–571 Kimura spatula 184
nasolacrimal system. See also cattle 673 Knemidokoptes (spp.) 754
nasolacrimal flush horses 634–637 Kochia scoparia 694
horses 628 viral infections vs 644–645 Koeppe goniolens 181
retrobulbar abscess 225 heterochromic iridocyclitis with Krabbe’s disease. See
trauma, 419b 654–655 galactocerebrosidosis
irrigation solutions, on corneal immune‐mediated 645–646, Krause’s glands, 848g
endothelium 317 825–826 Kühnt–Szymanowski procedure,
irrigation systems, drug delivery nonulcerative 339–342 Blaskovic’s modification
117, 121 pannus, 307, 339–342, 849g 254–255
irritants, conjunctivitis 296 rodents 719
ischemic encephalopathy 818 viral infections 642–645 l
ischemic optic neuropathy 664 keratitis sicca, traumatic L‐lysine 138
island conjunctival graft 330 proptosis 231 laboratory animals
isobutyl cyanoacrylate tissue keratoacanthomas 671 examination 716–717
adhesive 328 keratoconjunctivitis. See also nonhuman primates as 731–732
isopropyl unoprostone 155–156 chlamydial rabbits as 724–725
isosorbide 159 keratoconjunctivitis; Labradoodle, cataracts 440, 441
itraconazole 133, 135, 413, 545, 796 infectious Labrador Retriever
cats 821 keratoconjunctivitis canine oculoskeletal dysplasia
ivermectin 299, 414, 697 cats 563–569 490, 491, 785–786
demodicosis 546 dogs 244–245 cataracts 434, 440
Oestrus ovis 700 exotic mammals 745 surgery complications 455
onchocerciasis 839 mycoplasmal, sheep and CPRA/RPED 502–503
retinotoxicity 509 goats 698–700, 841 fundus 483
Thelazia (spp.) 673 parasitic diseases, food animals photoreceptor degenerations 500
toxicity 811, 830–831 672–673 lacerations
Ivomec Sheep Drench™ 700 recurrent proliferative 298 cataracts 446–447
keratoconjunctivitis sicca 279–289 conjunctiva
j acute 280, 281, 287 repair 302
Japanese Black Cattle, vitamin A conjunctivitis 296 cornea 639
deficiency 693 etodolac 812 bridge grafts 328, 329
jaundice 301, 789 horses 645 camelids 710
Jersey calves, congenital cataract 689 medical treatment 282–287 full‐thickness 313, 314, 334–335
JET electrode 211 neurogenic 569, 645, 780 eyelids 258–259, 614,
Jones test 185, 187, 188–189, pimecrolimus for 148, 283–284, 621–622, 669
273–274, 628 296 nasolacrimal system 277
juvenile sterile granulomatous qualitative abnormalities 281–282 nictitating membrane 308
dermatitis, 793. See also rabbits 727 uveitis 585
puppy strangles sulfonamides 131, 279, 811 lacrimal canaliculi. See canaliculi
juxtacanalicular zone, trabecular surgery for 287–289 lacrimal caruncle
meshwork (TM) 78 keratoconus (anterior), 848g dogs 241
keratocytes, cornea 30, 65–66 examination 170
keratoglobus, 752, 848g horses 20
k keratolenticular adhesions. See synechiae lacrimal gland 24–25, 63, 278–289
kanamycin 130 keratomalacia 314, 338 birds 749
kangaroos, viral infections 746 antiproteolytic agents 323 canine distemper 806
Keeler Vantage ophthalmoscope 177 cats 570 guinea pigs 720
keratectomy, 848g foals 615–616 horses 617
880 Index

lacrimal gland (cont’d) latanoprost 155–156, 157, 158 sclerosis. See nuclear sclerosis
parasympathetic nerve supply dorzolamide with 155 sheep and goats 701
64, 769–770 intraocular pressure control, 388b trauma 446–447
rabbits 725 lens luxation 454, 467 ultrasonography 205–206
reptiles 738 late‐onset photoreceptor lens bow 50
lacrimal nerve 64, 770 degenerations 500–501 lens capsule 49–50, 84–85
blockade 167 latency lens epithelial cells (LECs), after
lacrimal puncta 24, 171, 189, 270 bovine herpesvirus‐1 842 phacoemulsification 465
absence, cats 554 feline herpesvirus‐1 563 lens placode 7, 8
atresia 274–275 lateral canthal dermoid, cats 545 lens vesicle 8, 10
horses 608 lateral canthal ligament 241 lens viewing systems, retinopexy 523
blepharoplasty 267 entropion 251–252 lens‐induced uveitis 85, 383,
camelids 707 lateral canthotomy 410–411, 447–448, 518
loss in Roberts–Jensen pocket cats 524 lenticonus 429
procedure 256 phacoemulsification 460 lenticular (term), 848g
misplacement 275–276 lateral enucleation 235 lenticular cataracts, horses 658
occlusion 287 lateral geniculate nucleus 103, 526, lenticulodenesis, 848g
rabbits 727 744, 766–767, 773 lentiglobus 429
lacrimal sac 24, 270 lateral palpebral ligament 240 Leonberger (dog breed), developmental
atresia 275 lead shot 447 cataracts 440
lacrimal system 24–25, 62–64 lead toxicity, raptors 754–755 leopard spotting allele 832–833
lacrimal tissue, prolapse, guinea leashes, corneal innervation 69 leprosy, feline 547–548
pigs 721, 722 Leber’s congenital amaurosis, Leptospira kirschneri serovar
lacrimation, 64, 273, 848g canine 503–504 grippotyphosa 301
lacrimomimetics 148, 284, 285–287 leeches 741–742 leptospirosis 798, 837
lacrimostimulants 282–283 Leishmania blepharitis 261, 547 dogs 416
lactoferrin, tear film 64 Leishmania keratitis 343 horses 651, 652–653, 654
lagophthalmos, 221, 225, 848g leishmaniasis 301, 414, 583, lethal white foal syndrome 832
lambsquarters (Chenopodium 803–804, 804, 823 Leucaena leucocephala 690
album) 705 lens 49–52, 84–85 leukocytes, corneal healing 314
lamellae, cornea 30, 65, 67, 311 amphibians 737 leukomas, 848g
edema 317 artificial. See intraocular lenses cornea 320
separating devices 320, 321 birds 750 Peter’s anomaly 396
lamellar corneal grafts, degeneration 754 leukotrienes 402
autogenous 333 camelids 714–715 levamisole 673
lamellar keratectomy 573 cats 592–593 levator anguli oculi medialis 240
lamellar keratoplasty 349, ciliary body muscles 41–42 levator palpebrae superioris 19–20,
641–642, 643–644 composition 77, 84 21, 240
lamina cribrosa 13, 526 connections to ciliary body 39 development 13
IOP elevation on 367 development 8–9, 12 levofloxacin 132
lamina fusca 33 diabetes mellitus 808–809 lidocaine 147–148
laminae, pectinate ligament dogs 49, 426–468 light. See also red‐free filter
dysplasia 364 dropped nuclear fragments 519 physics 90–92, 201
Larson–Millodot esthesiometer 183 Encephalitozoon cuniculi 729 retinopathy from 509, 792
larva migrans 803 examination 173, 426–427 light adaptation 105–106
ocular (OLM) 412 fibers 50–51 light cells, corneal epithelium 28
larvae fish 94, 99, 734, 736 light reflex. See pupillary light reflex
amphibians 736, 737 food animals 689–690 light sources 91
Cuterebra spp. 261, 561–562, 822 glaucomas 380–383 for camelids 706
Dirofilaria immitis 802 horses 49, 656–658 examination of vitreous 470
flies 414, 801, 822 iatrogenic opacities, rodents 720 indirect ophthalmoscopy 178
habronemiasis 838 implants. See intraocular lenses pupillary light reflex 169
Oestrus ovis 700 IOP elevation on 367 slit‐lamp biomicroscopy 174
Toxocara spp. 803 light transmission 92 sudden acquired retinal degeneration
laser ablation luxation. See luxation of lens syndrome 792
squamous cell carcinoma 623–625 normal findings in dogs 427 ligneous conjunctivitis 296
laser cyclophotocoagulation penguins 757 limbal plexus 69
92, 390 physics 92 limbus, 33, 310, 848g
laser flare‐cell photometry 202 pigs 705 colobomas 322
laser fluorophotometry, aqueous pinnipeds 759–760 granuloma 352–353
humor 80, 202 refraction 94 horses, squamous cell carcinoma
laser photocoagulation 392, 425 reptiles 739 648
laser retinopexy 520, 522 rupture. See lens under rupture inflammatory masses 298
Index 881

melanomas 351–352, 423, 576 Long‐Haired Dachshund, cone–rod m


squamous cell carcinoma 648, dystrophy 499 macaques
682–683 loteprednol 140 corneal ulcers 732
stem cells, healing 312 Lovac–Barkan goniolens 181 ocular disorder survey
vascularization, infectious bovine low‐coherence interferometry 479 743–744
keratoconjunctivitis 677 low‐fat diets, for corneal mace (chemical) 338
Limousin cross‐calves, demyelinating dystrophy 345 Mackay–Marg applanation
disorder 694 lower‐field accommodation 99 tonometer 193
lincosamides 130 LOXL1 gene 375 macroblepharon–ectropion 253,
linear keratopathy 648 LTBP2 gene 375 254–255
lip and leg ulcer 697 luminance 91 macrolides 130–131
lip‐to‐lid reconstruction luxation (term), 848g macula
technique 543 luxation of lens. See also primary lens cornea 320
lipemia retinalis 417 luxation macula occludens 73
lipid(s). See also hyperlipidemia; cats 593 macular degeneration (age‐related),
sphingomyelin lipidosis dogs 448–455, 851 macaques 732
meibum 62–63, 241 breeds 453 magnetic resonance imaging
lipid keratopathy congenital 433 199, 200
amphibians 737, 738 diagnostics 454 foreign bodies 418, 420
camelids 711 genetics 359–360 optic nerve 530
cats 574 glaucoma with 371, 380–382, orbit 222
corticosteroids and 141 451–452, 453–454 trauma 418
dogs 281–282, 341, 345–347 retinal detachment 519, 520 magnification, ophthalmoscopy 176
fish 736 Shar‐Pei 378, 453 laboratory animals 716
rabbits 728 surgery 466–468 Magrane, William (veterinary
lipid retinopathy 503–504 vitreous and 477 ophthalmologist), on
lipid‐laden aqueous 404 ferrets 723 glaucoma 355
lipid‐secreting acini, nictitating horses 656 major arterial circle 42, 43, 71, 172
membrane gland 303 Lyme disease 797, 836–837 major petrosal nerve 769–770
lipidosis, cornea 346, 417, 464, 722 lymph nodes Maklakoff applanation tonometer
inflammation 346–347 squamous cell carcinoma 683 193
lipofuscin 810 lymphatic drainage malar ciliary nerve 575, 764
lipogranulomatous conjunctivitis conjunctiva 290 malaris artery 241, 304
549–550 eyelids 241 malaris muscle 240
lipophilic drugs lymphocytes, pannus 340 malignant catarrhal fever 674,
peak concentrations 120 lymphocytic choriomeningitis 745–746, 843
penetration 119 (LCM) 720 malignant glaucoma 384, 590
lipoproteins, dogs 416 lymphoid follicles 279 malocclusion of the molar arcades,
liposomes, drug delivery 122 lymphoid nodules, conjunctiva 290 rabbits 727
lipoxygenase pathway 402 lymphomas mammals. See also specific types
liquefaction, vitreous 85–86, birds 755 aquatic species 758–760
516, 518 cats 588, 589 exotic 743–748
liquid nitrogen, cryotherapy 686 conjunctiva 562 mandible
Lissamine green 191 eyelids 552 examination of orbit 170
listerial keratoconjunctivitis 673–674 nictitating membrane 555 orbital lesions and 220–221
llamas uvea 580–581 mane color, multiple congenital
corneal diameter 709 cattle, retrobulbar 667–668 ocular anomalies 833
intraocular pressure 706 dogs 515 mange. See demodicosis
ophthalmomyiasis interna 714 optic nerve 537 mannitol, 150, 159, 388b
pupils 172 polymerase chain reaction 230 manometry, 848g
tear production 706 horses 627, 650 tonometry vs 195, 703
lobular orbital adenomas, canine lymphoplasmacytic uveitis 588 marbofloxacin 132, 830
297 lymphosarcoma 297, 810 clearance 120
local anesthetics, 146–148. See also cats 827, 828 Marcus–Gunn pupil 169, 766
regional anesthesia nictitating membrane 307 Marek’s disease 755
topical 164 lysine 567, 826 marginal blepharitis 282
diagnosis of entropion 249 lysosomal enzymes, mucopolysaccharide marginal bundle of Drualt 12
rebound tonometry and 195 storage diseases 505 marginal meibomian cysts 263
locoweed 693 lysosomal storage diseases 856–857 marine mammals 758–760
keratoconjunctivitis sicca 645 cats 574, 600, 813–815 marmosets, endodontic absorbent
long ciliary nerves 27, 38, 629 cattle 694 paper point test 186
long posterior ciliary arteries 26, 36, dogs 787 Maroteaux–Lamy syndrome
42–43, 47, 526 lysozyme, tear film 63–64 814–815
882 Index

masses. See also neoplasia eyelids 265 feline diffuse iris melanoma 588
anterior uvea 422–425 feline diffuse iris melanoma feline ocular sarcomas 588
conjunctiva 297–299 586–588 to orbit, cats 602–603
with acid‐fast bacilli 821 feline eyelids, frequency 552 squamous cell carcinoma 682–683
guinea pigs 721 glaucoma and 386 uveal melanomas 423
corneoscleral 349–354 horses 625, 627, 649–650 uveal neoplasia 588
eyelids 263–266 laser photocoagulation 425 methazolamide, 149, 154, 388b
nodular granulomatous limbal 351–352, 423, 576 methicillin‐resistant Staphylococcus
episcleritis 352 Miniature Sinclair swine spp., antibacterial agents 129
mast cell tumors 704–705, 731 methylcellulose 121
conjunctiva 297 subconjunctival 576 methylprednisolone 139, 145
feline eyelids 553 melanopsin 528, 792 anterior uveitis 407
frequency 552 melanosis 385, 422, 514, 587 metronidazole, for tear staining 276
nictitating membrane 307 melanosomes, Beagle 397 Mexican fireweed (Kochia scoparia)
masticatory muscle myositis, 793–794. melarsomine 299, 414 694
See also eosinophilic meloxicam 586 mezlocillin 127
myositis melting. See keratomalacia miconazole 133, 134, 135, 337, 635
matrix metalloproteinases 315, 632 membrana nictitans. See nictitating micro‐osmotic pumps 121
gene mutations 359 membrane microblepharon 256–257
inhibitors 323 menace response 60, 168, 766–767 microcornea, 319, 848g
mature cataracts 435, 436 birds 751 microfibrils 375
maxillary sinus camelids 706 micropapilla 531–532
horse 617 cattle 665 microphakia, 428, 848g
neoplasia 277–278 horses, neonates 606 microphthalmia, 848g
maze tests 478, 769 meningioma cattle 666
MDR‐1 gene, ivermectin sensitivity calcification 530 dogs 223, 488
811 cats 782, 828 ferrets 723
mechanics, cornea 67 meningoencephalitic listerial horses 607
medial aberrant dermis 300 keratoconjunctivitis 673–674 pigs 703
medial canthal ligament, meningoencephalitis, granulomatous reptiles 740
brachycephalic breeds 513–514, 779, 791 rodents 718–719
276 meningoencephalomyelitis of sheep 695
medial canthal pocket syndrome 300 unknown origin (MUO) microphthalmia‐associated
medial canthal ulcerative 530, 536 transcription factor
blepharitis 262 meniscometry, tear tests 186 (MITF) 785
medial canthoplasty 258 merangiotic pattern, retina 57 microplicae, corneal epithelium 28
medial canthus meridional plane 26 micropunctum, lacrimal 275
punctal atresia 608 merle gene 785 microsaccades 89
regional anesthesia 167, 606 merle ocular dysgenesis (MOD) 319, Microsporum (spp.) 696–697
medulloepitheliomas 424, 514, 715 434, 487–488 microvilli, corneal epithelium 28
megalocornea, 319, 834, 848g merles 785 midbrain syndrome, 774b
megestrol acetate 569, 831 Collie eye anomaly 487 milbemucin doramectin 546
meibometry 186, 241 fundus 482, 483 milbemucin oxime 561
meibomian glands 21, 59, 241, 246 iris 395 milk replacer‐induced disease 593,
neoplasia 264–265 microphthalmia 223 747, 810, 829
meibomianitis 263, 549 mesenchyme 6–7, 10–11 milk withdrawal times, infectious
meibum 62–63 mesoderm 7 bovine keratoconjunctivitis
lipids 62–63, 241 mesodermal dysgenesis 360–362 679
melanin metabolism mimosine 690
cornea 316 cornea 67 mineral deposits, after parotid duct
drug binding 120, 145 of drugs 120–121 transposition 288
pigmentary keratitis 339 extraocular muscles 87 mineralization, corneal 647–648
melanocytes, iris 36, 37 inborn errors 787 Miniature Australian Shepherd,
melanocytic glaucoma 385–386, 422 lens 85 congenital cataract 441
melanocytomas 423 role of vitreous 86 Miniature Long‐Haired Dachshund
melanomas metaherpetic disease 564–565, cone–rod dystrophy 500
birds 755 566, 569 photoreceptor degenerations
camelids 715 metals, foreign bodies 447 500
cattle 689 metastases miniature pigs 731
choroidal 423, 514 camelids 715 Miniature Poodle
conjunctiva 297, 562 to eye 425, 515, 589, 810, glaucomas 377
dogs 423–424 828–829 optic nerve hypoplasia 532
Index 883

progressive rod–cone optic nerve 525–527 arrectores ciliorum 21


degeneration 500 orbit 219 ciliary body 34, 41–42, 49,
Miniature Schnauzer posterior segment 515–517 95–96, 750
cataracts 433–434, 437, 441 vitreous 469–470, 515–516 cranial nerves supplying 17,
persistent primary vitreous eyelids 19–21, 239–241 19, 87
490, 491 globe 25–26 eyelids 13
photoreceptor dysplasias 499 lacrimal system 22–24 iris 11, 37–38, 68–69
solid intraocular lens 49–52 nictitating membrane 61
xanthogranuloma 417 nasolacrimal system 24–25, orbit 15–16
Miniature Sinclair swine, 270–271 Mustardé technique 543
melanomas 704–705, 731 nictitating membrane 22–24, mutton fat precipitates 582
miosis, 69–70, 848g 303–304 muzzles 165
equine recurrent uveitis 651 optic nerve 58, 525–527 Mx protein 138
light adaptation 106 orbit 13–19, 219 myasthenia gravis 779, 786
multiple congenital ocular retina 53–58 mycobacterial infections in cats
anomalies 834 sclera 33–34 547–548, 819, 821
mydriatic‐resistant 142 uvea 34–49 chorioretinitis 598
nonsteroidal anti‐inflammatory vitreous 52–53, 469–470, Mycoplasma felis 558–559, 820
drugs on 151 515–516 mycoplasmal keratoconjunctivitis,
opioids 165 morula 3 sheep and goats 698–700,
proparacaine on 151 motility (term), 848g 841
prostaglandin analogues 158 motion perception 107 mycoplasmosis 819, 841
uveitis 403, 616 motor block, horses 604 mycotic blepharitis 261
miotics, 848g motor neuron disease, equine mycotoxicosis 694
intraocular pressure control (EMND) 662, 835–836 Mydriasert® 123
388b mouse 716–720 mydriasis, 69, 96, 164b
misplacement, canaliculi 275–276 cataracts 719–720 birds 751
mites, 546, 697, 742, 803. See also intraocular pressure 82 for examination 164, 173
demodicosis refraction 97, 98 opioids 165
Mittendorf’s dot, 10, 53, 430, visual acuity 113 pinnipeds 760
469–470, 848g movements reptiles 739
molds 132 eyes 87–89, 108–109 mydriatic‐resistant miosis 142
Mongolian gerbil, Harderian nictitating membrane 303 mydriatics, 144–146, 849g
gland 24 moxidectin 295, 697, 839 anterior uveitis 407, 409–410
monkeys moxifloxacin 132 camelids 706
adrenergic receptors 70 mucin layer of tear film 24, 63, cataract surgery 456–457
cataracts 747 290–291 cataracts 447
monochromasy 110, 111 deficiency 281–282 corneal ulcers 324
monoclonal gammopathy 417–418 mucinolytic–anticollagenase equine recurrent uveitis 653
monocular vision 13, 107, 108 agents 284 horses 606
moon blindness. See equine mucoceles 226–227, 300 laboratory animals 716
recurrent uveitis mucolipidosis II 814 persistent pupillary membranes
moonlight blindness, Pteris mucopolysaccharidoses 505, 787, and 396
aquilinum 702–703, 783 814–815 phacoemulsification 467
Moraxella bovis 675–677 cat breeds 856 uveitic glaucomas 385
drug resistance 679 dog breed 856 myelinization
Moraxella bovoculi 669, 675 mucosa‐associated lymphoid nerve fiber layer, cats 594
Morgagnian cataracts 435, 848g tissue 271–272, 279 optic nerve 13, 526, 527
Morgan horses mucosal immune system 279 cattle 690–691
cataracts 611, 658 Müller cells, retina 12, 100, 102 pseudopapilledema 534
inherited eye diseases 854 Müller’s muscle 240 myiasis. See ophthalmomyiasis
Morgan lens 121 multifocal retinopathy, canine mynahs 756
Morgan technique 305 492–493 myocilin 156
morphology 13–58 gene and breeds 851 myofibroblastic cells, trabecular
blood vessels 58 multiple congenital ocular meshwork 45
conjunctiva 21–22 anomalies (MCOAs) myogenic mechanism, retinal
cornea, 26–33, 310‐312 horses 610, 833–835 blood flow 72
dogs Shorthorn calves 692 myopia, 94, 96, 849g
cornea 310–312 multiple myeloma 301 indirect ophthalmoscopy 180
eyelids 239–241 Musca autumnalis 294–295, 672 myositis 227–228, 793–794
nasolacrimal system 270–271 Moraxella bovis 676 eosinophilic 227–228
nictitating membrane 303–304 muscles extraocular polymyositis 228
884 Index

n uveitis 412–414 nerve blocks 166–167, 604–606,


N‐acetylcysteine, 323. See also neomycin 128 618–619, 665, 684–685
acetylcysteine bacitracin with 127 nerve fiber layer, retina (RNFL)
N‐cadherin 10 contact hypersensitivity 296 53–54, 55, 201
N‐methylglucamine antimoniate, neonatal conjunctivitis ophthalmoscopy 364, 529
Leishmania blepharitis 261 ankyloblepharon 244, 541 neural crest 3–6, 10–11
N13 guinea pigs, cataracts 723 Chlamydia felis 556–557, 558 neural crest cells 832
nalidixic acid 131–132 horses 627 neural ectoderm 3
nanophthalmia 223 neonatal ophthalmia, feline neuro‐ophthalmology 763–783
nanotechnology, drug delivery 122 herpesvirus‐1 825 lesion localization 771–783
nasal cancer neonates, horses 606–617 neuroepithelial tumors 514
radiotherapy 509–510 neoplasia. See also metastases; neurofibromas, feline eyelids,
turbinates 277–278 nasal cancer frequency 552
nasal ciliary nerve 575, 764 anterior segment, ultrasonography neurogenic keratitis 342–343
nasal fold trichiasis 257, 258 205, 206 traumatic proptosis 231
nasal puncta 271 anterior uveal 422–425, 586 neurogenic keratoconjunctivitis
atresia 608 birds 755 sicca 569, 645, 780
nasolacrimal duct 24, 270–271 camelids 715 neurogenic reflex anterior uveitis,
atresia 275, 608 cats 828–829 corneal ulcers 324
camelids 707 cattle 670–671, 680–687 neuromuscular blocking agents
neoplasia 277–278 uvea 689 cataract surgery 457
obstruction central nervous system 779–780, mydriasis 751
horses 628 782, 809, 828–829 neuronal ceroid lipofuscinoses
snakes 741 conjunctiva 504–505
rabbits 727–728 cats 562–563 neuronal degeneration,
relation to teeth 553–554, 727 dogs 296–297 dysautonomia 791
reptiles 738 cornea neurons
nasolacrimal flush 189–190, 274 cats 575 disparity‐sensitive 109
camelids 707–708 horses 648 retina 56–57, 100, 104
medication 710 corneoscleral 297–299, 349–354 neuroparalytic keratitis 342–343
horses 628 exotic mammals 748 neuropathies
punctal atresia 608–609 eyelids diabetic 466
rabbits, dacryocystitis 727–728 cats 551–553 optic nerve, 531–538, 663–664, 693.
nasolacrimal system dogs 264–266 See also optic neuritis
camelids 707–708 horses 622–627 neurosensory retina 54–57
catheters 609, 628, 708, 710 glaucoma and 386–387 neurotrophic keratitis 342
cats 553–554 lacrimal secretory system 289 neurulation 3–7
dacryocystorhinography, 198–199, nasolacrimal duct 277–278 neutrophil elastase 315
274, 707, 846g nictitating membrane 306–307, 555 nevi, 849g
dogs 24–25, 64, 270–279 optic nerve 537 iris 422
Beagle 374–375 optic neuritis 536 New Forest disease. See infectious
diagnostic tests 272–274 orbit keratoconjunctivitis
drug drainage 118 cats 602–603 New Zealand white rabbit, hereditary
examination 170–171 cattle 667–668 glaucoma 728
drug drainage 120 dogs 229–230 NHEJ1 mutation 533
food animals 671 horses 620–621 niacinamide, nodular fasciitis 264
horses 628 ultrasonography 207, 222 nictitating membrane 22–24,
atresia 608–609 pigs 704 303–309
Jones test 185, 187, 188–189, posterior segment birds 61–62, 748–749
273–274, 628 cats 600 cats 61, 554–555
natamycin 132, 133, 134, 337, 635 dogs 514 epitheliotropic mastocytic
NEB gene 358 retinopathy 512 conjunctivitis 561
nebula, cornea 320 systemic 810 idiopathic protrusion 555, 818
nebulin 358 thrombocytopenia 790 cattle, squamous cell carcinoma
needles turtles 742 682, 685
eyelid suturing 243 uvea 588 enucleation of eye 235
retrobulbar block 167 cattle 689 examination 170
nematodes, 801–803. See also Thelazia horses 649–650 false, anurans 736
(spp.) sheep 701 follicular conjunctivitis 295
cats 822–823 vitreal involvement 477 gland of 23, 63
horses 838–839 Neospora caninum 414 prolapse 304–305, 555
reptiles 742 nephronophthisis 4 gene 499 rabbits 725
Index 885

globe displacements 220 horses 656 Old English Sheepdog, developmental


horses 627–628 rabbits 729 cataracts 441
lacrimal glands 278 senile cataract vs 173, 427 olfactory stimulation, tear film 569
prolapse replacement 289 nuclear type vitreous 515 oligodendrocytes 100
movement 303 nutrition, squamous cell onchocerciasis 224, 412–414, 802,
protrusion 305, 306, 555, 627–628, carcinoma and 681 822–823, 838–839
781–782, 818 nutritional cataracts 446, 747 dogs 343
squamous cell carcinoma 306, 625 nutritional disorders 810–811 masses 299
surgery 308–309 cats 829–830 180° flap 330
Niemann–Pick diseases 815 fish 735 opacities
nociceptors, polymodal 68 nutritional retinopathy, 510. See also cornea 320–322
nodular fasciitis 264, 298 vitamin E deficiency amphibians 737
nodular granulomatous nyctalopia, 164, 849g crystalline 341, 344–347
episcleritis 352–353 nystagmus, 88–89, 763, 849g. See also noncrystalline 347–349
nodular granulomatous pendular nystagmus rodents 719
episclerokeratitis 298, 307 achiasmatic Belgian Sheepdog 532 lens. See also cataracts
non‐necrotizing granulomatous cattle 668 iatrogenic 720
scleritis 353–354, 411 physiological 768–769 vitreous, 470, 474b 475
nonconventional pathway, AH nystatin 132, 134 open orbits 14
outflow 78–79 operculum, trabecular meshwork 44
noncorneal absorption, drug o ophthalmia neonatorum, 849g. See
delivery 119, 120 (O‐acyl)‐omega‐hydroxy fatty also neonatal conjunctivitis
nonhealing erosions 324–327 acids 63 ophthalmic solutions, 116–117.
nonhuman primates 731–732 oblique muscles 17, 87 See also irrigation
ciliary body 42 obstacle courses (maze tests) 478, ophthalmomyiasis 414, 585, 801
intraocular pressure 82 769 ophthalmomyiasis interna
visual acuity 112 ocean water, synthetic 759 cats 822
nonpigmented epithelium, ciliary octofluoropropane, retinopexy 521 llamas 714
body 74 ocular hypertension (POH). See also ophthalmoplegia, 849g
nonprogressive stromal ulcers 327 glaucomas ophthalmoscopes, headpieces 174
nonsteroidal anti‐inflammatory after cataract surgery 464 ophthalmoscopy, 175–180, 479, 849g
drugs 141–143 cholinergic antagonists and 145 cattle 690–691
anterior uveitis 407, 408, 586 corticosteroids and 141, 700–701 chinchillas 723
camelids 714 NSAIDs and 143 chorioretinitis 505–506, 507
cataract surgery 457 ocular larva migrans (OLM) 412 Collie eye anomaly 487
equine recurrent uveitis 653 ocular nystagmus 89 exotic animals 733
keratoconjunctivitis sicca 279 ocular rigidity 81–83 glaucomas 364
latanoprost and 158 ocular–skeletal dysplasia 785–786 laboratory animals 716
miosis inhibition 151 oculocardiac reflex 89 optic nerve head 528–529
trauma and 230, 585 oculocephalic reflex (VOR) 88, orbital lesions 221
nontapetal fundus 170, 768–769 pigs 705
canine distemper 806 oculomotor nerve 59–60, 765 progressive retinal atrophy 494
cats 593–594 muscles supplied 17, 87 sheep and goats 701–702
cattle 690 nuclei 772 vitreous 471
dogs 482–483 oculoskeletal dysplasia, canine 490, opioids
development 485 491, 785–786 side effects 165
inactive chorioretinitis 507 Ocusert® Pilo 123 opportunistic infections, cats 826
horses 606, 659 OD, 849g opsins 91
nonulcerative keratitis 339–342 Oestrus ovis 700 color vision 109–110
norfloxacin 132 off‐label drug use, infectious bovine optic chiasm 101–103
Normandy cattle, retinitis pigmentosa keratoconjunctivitis 679 cats, at enucleation 603
1 mutation 692 ofloxacin 132 dogs 526, 527
northern elephant seals 744 oil droplets, bird cones 110 optic cup 7, 11
Norwegian Buhund, cataracts oily layer, tear film 24, 62 optic disc. See optic nerve head
434–435, 440 ointments 121 optic nerve 58, 100–101, 525–538,
Norwegian Elkhound, early retinal after Roberts–Jensen pocket 772
degeneration 499 procedure 256 acquired neuropathies 533–537
notching, lens 429 triple antibiotic 127 aplasia 532
notoedric mange 546 OIP. See ophthalmomyiasis atrophy 601, 613, 663, 664, 705
Nova Scotia Duck Trolling Retriever, Old English Mastiff, dominant blue‐eyed white cats 576–577
NHEJ1 mutation 533 progressive retinal cats 600–601
nuclear sclerosis 448 atrophy 501 cattle 694
886 Index

optic nerve (cont’d) oral papillomas 808 ossicles 34, 738


colobomas 519, 532–533 orbicularis oculi 19, 21, 240 osteochondrodysplasia. See dwarfism
pigs 705 Celsus–Hotz resection 251, 305 osteopetrosis 692
congenital neuropathies 531–533 development 13 otariid keratopathy 759
degeneration 536–537, 663, 664 nerve blocks 604 otitis, keratoconjunctivitis sicca 780
development 11–12, 12–13 orbifloxacin 132, 830 otitis interna, amphibians 737
enucleation of eye 234–235 orbit otoscopes, gonioscopy 182
birds 758 abscesses. See also retrobulbar OU, 849g
fish 735 abscess outer plexiform layer 100
granulomatous meningoencephalitis cats 602 ovine herpesvirus‐2 674
779, 791 dogs 225–226 ovine ulcerative dermatosis virus
hypoplasia horses 619 697
dogs 531–532 rodents 717 oxidosqualene cyclase inhibitors,
horses 613 ultrasonography 207, 222 cataracts 443
miniature pigs 731 anatomy 13–19 oxybuprocaine 147, 166
pigs 705 birds 749 oxygen
neuropathies 531–538, 663–664, camelids 706 choroid 72
693. See also optic neuritis cats 13, 14, 15, 601–603 cornea 67
rabbits 724 cellulitis retinopathy 509
retrobulbar neuropathy and retinal cats 602 oxytetracycline
degeneration 693 dogs 223–226, 300 Chlamydophila pecorum 698
optic nerve head (ONH) 58, 526 horses 619 dermatophilosis 669
blood flow 73 ultrasonography 222 infectious bovine
cats 594 dimensions 14 keratoconjunctivitis
colobomas 600 diseases affecting conjunctiva 300 678, 679
cattle 690–691 dogs 15, 219–238 mycoplasmal keratoconjunctivitis
horses 606, 659 dimensions 14 700
hyperfluorescence 530 surgery 234–238
inflammatory diseases 506 drug injection 124 p
IOP elevation on 367, 369 examination 170 P‐glycoprotein 811
normal 484 dogs 219–221 pachymetry 200–201, 311
ophthalmoscopy 528–529 guinea pigs 720 Pacific harbor seals 744
papilledema 694 horses 13, 15, 617–621 pain
sheep 701 congenital anomalies 607 ciliary body 403
size 531 dimensions 14 distichiasis 246
sudden acquired retinal lobular adenoma 297 entropion 249, 613
degeneration syndrome neoplasia equine recurrent uveitis 651
792 cats 602–603 history‐taking 164
swelling 534 cattle 667–668 horses
vascular system 526–527 dogs 229–230 examination 604
optic neuritis horses 620–621 ulcerative keratitis 630
canine distemper virus 778, ultrasonography 207, 222 orbit, dogs 220–221
806, 807 pigs 703 reflexes 68
cats 600–601 rabbits 14, 725 spontaneous chronic corneal
dogs 534–536 radiography 197–198, 221 epithelial defects 325
optic pedicle, elasmobranchs 733 ultrasonography 207, 222 uveitis 403
optic sulci 7 orbital fascia 14–17, 219 Paint Horse 832
optic tract 101–103 orbital fat 17–19 palpation 220
optic vesicle 7, 11, 12 orbital fissure 14 palpebral conjunctiva 290
optical coherence tomography orbital optic nerve. See intraorbital palpebral fissure 19, 59, 240
201–202, 479 optic nerve oversized 253–254
corneal thickness 311 orbitectomy 237–238 permanent reduction plasty 255–256
optics (IOLs) 462 orbitotomy 237–238 palpebral ligaments 19, 240
optics (physics) 90–99 orf 697 palpebral nerve block 165, 166, 604
Optimmune® 283 organophosphorus inhibitors 151 palpebral reflex 60, 169, 767
optokinetic nystagmus 88 OS, 849g birds 751
ora ciliaris retinae 46 Osborne–Mendel rat 720 corneal esthesiometry 183
ora serrata 46 osmolarity nasal fold trichiasis 257
oral cavity eye drops 117 pan‐retinal ophthalmoscopy 178,
examination 220 tear film 63 180, 364
ultrasonography 222 osmotic agents 158–159 pannus (chronic superficial keratitis),
oral opening, nasolacrimal duct 271 osseous metaplasia, guinea pigs 722 307, 339–342, 849g
Index 887

panophthalmitis, 399, 849g paratyphoid 837 pentoxifylline, dermatomyositis 793


amphibians 737 parietal eye 740 peracute tick‐borne encephalitis 808
reptiles 741 parotid duct transposition 287–288, 645 percussion, paranasal sinuses 220
panoptic ophthalmoscopy 178, parotid gland 287–288 perennial ryegrass, perloline 670
180, 364 pars plana ciliaris 41, 516–517 perforation
pansystemic vasculopathy 843 cats 524 cornea 331–334, 333, 629, 639, 687
papilla, 849g. See also optic nerve head inflammatory diseases 594 after keratectomy 320
papilledema, 534, 694, 849g hyalocentesis 471 perfusion decay test 81
vitamin A deficiency 844 pars plana posterior vitrectomy 472 perfusion methods, aqueous humor
papillitis, 535, 849g pars plana vitrectomy (PPV) measurements 80–81
granulomatous meningoencephalitis for dropped nuclear fragments 519 perfusion pressure 71
513–514 equine recurrent uveitis 653–654 intraocular pressure and 71, 73
papillomas 265, 808 pars plicata ciliaris 38 peribulbar drug injection 124
cattle 670, 681, 682, 684 hyalocentesis 471 anesthesia 168
corneoscleral 350 partial incision keratectomy 320 periocular drug administration
squamous, feline eyelids, Partial tarsorrhaphy 288–289 123–124
frequency 552 partial tarsorrhaphy 288–289 periodic ophthalmia, 849g. See also
papillomatosis 297 birds 756 equine recurrent uveitis
viral, sheep 697 dogs 288–289 periorbita 14–16
papillomaviruses, 808. See also bovine Paso Fino Horse, inherited eye dogs 219
papillomavirus diseases 854 peripheral anterior synechia, 849g
Papillon (dog breed) Pasteurella (spp.) peripheral nerve sheath tumor, feline
fundus 483 rabbits 727 eyelids 553
photoreceptor degenerations 500 retrobulbar abscess 725 frequency 552
progressive retinal atrophy 214 Pasteurella multocida, rabbits 729 perivascular cuffing, granulomatous
paracellular route across cornea 115 patient selection, cataract surgery meningoencephalitis 791
paracentesis 455–457 Perkins applanation tonometer 193
hyalocentesis 471, 505 pattern electroretinography 480–481 perloline 670
ophthalmic 195–197 paurangiotic pattern, retina 57 Perma Tweez electroepilator™ 243
paranasal sinuses PCRD mutation 500 permanent lateral palpebral fissure
horse 617, 618 PDE6A gene 498 reduction plasty 255–256
percussion 220 PDE6B gene 496–497 permanent tarsorrhaphy 267–268
parasitic diseases. See also protozoal pea eye 721, 722 partial 288–289
infestations peak concentrations, drug delivery permeability
birds 753–754 120 ciliary processes 115–116
blepharitis 261, 546 pecten oculi 57, 71, 750 iris 116
camelids, conjunctivitis 709 pectinate ligament dysplasia (PLD) sclera 115
chorioretinitis, 506b 598 358–359, 360–361, 363–364, Persian cats, inherited eye
conjunctivitis 294–295, 561–562 369–370 diseases 853
fish 735–736 Chow Chow 376 persistency state, feline
food animals 669–670 pectinate ligaments 43, 171 herpesvirus‐1 564
keratoconjunctivitis 672–673 pedicle conjunctival graft 330 persistent corneal erosions 324–327
granulomas 299 pemphigus, blepharitis 261–262, 819 persistent hyaloid artery 472–473, 692
horses 838–839 pemphigus complex 792–793, 818 cattle 692
keratitis 343 pemphigus foliaceus 548 dogs 472–473
reptiles 741–742 penciclovir 137 rodents 720
sheep and goats 700 pendular nystagmus 763 persistent hyperplastic tunica
systemic 801–804 achiasmatic Belgian Sheepdog vasculosa lentis/ persistent
uveitis 412–415 775 hyperplastic vitreous
vitreous 477 cattle 783 (PHTVL/PHPV) 431–433,
parasympathetic lesions, penetrating foreign bodies, 473, 474
preganglionic 780 cornea 323, 335 persistent hyperplastic vitreous
testing 770 penetrating injuries 419–420 (PHPV), Miniature
parasympathetic nerve supply cataracts 446–447 Schnauzer 490
accommodation 95 uveitis 585 persistent primary vitreous, Miniature
aqueous humor regulation 77 penetrating keratoplasty 348, Schnauzer 490, 491
on blood flow 71 349, 640–641 persistent pupillary membranes, 849g
ciliary body 43 penguins 756–758 camelids 711
iris 764 visual acuity 112 cats 577–578
lacrimal gland 64, 769–770 penicillins 126–127 dogs 321–322, 395–396, 429–431
parasympatholytics. See atropine dermatophilosis 669 horses 609–610
parasympathomimetics 150–151 Treponema cuniculi 726 rodents 719
888 Index

persistent tunica vasculosa lentis photoelectric photometers 91 pigmented epithelium


431–433, 473, 474 photometry, 91. See also ciliary body 41, 74
Peter’s anomaly 396 fluorophotometry drug binding 120
Peterson nerve block 684–685 photons 90–91 pigs 703–706
Petit Basset Griffon Vendéen, photophobia, 849g blink rates 60
glaucomas 377 light adaptation 105–106 eyelids 61, 703–704
petrositis, keratoconjunctivitis photopic, 849g globe dimensions 26
sicca 780 photopic vision 100, 103, 105–106 Harderian gland 731
pH electroretinography 212 inherited eye diseases by breed 855
on drug absorption 119 photoreceptors 53, 55–56, 102, 104 miniature 731
fluorescein 187 amphibians 737 retrobulbar venous sinus 731
pilocarpine 150, 151 birds 750 piliated Moraxella bovis 675
tear film 63 degenerations pilin, Moraxella bovis 677
phacoclastic uveitis 410, 420, cats 596 pilocarpine 150–151
446–447, 448 dogs 500–501 on aqueous humor outflow 79
phacodonesis, 450b, 451, 849g dysplasia, Belgian Shepherd 502 contact hypersensitivity 296
phacoemulsification, 459–466, 849g dysplasias/degenerations 493–500 dysautonomia 791
birds 754 early‐onset 496–500 intraocular pressure control 388
camelids 714–715 Miniature Schnauzer 499 for keratoconjunctivitis sicca 283
cats 593 fish 735 melanin on effects 120
corneal edema 317 function 91, 100 Ocusert® Pilo 123
exotic mammals 747 reptiles 740 preganglionic vs postganglionic
for full‐thickness lacerations 334 taurine and 829–830 lesions 770
glaucomas 380, 383 photosensitization, food animals 670 side effects 151
horses 611 photostimulators 211, 212 on tear production 148–149
instruments 459 phototoxic retinal degeneration, fish pimecrolimus 143
lens instability 467 736 for keratoconjunctivitis sicca 148,
for lens rupture 410 phthisis bulbi, 607, 849g 283–284, 296
postoperative hypertension 384 phylloerythrin 670 pannus 342
rabbits 729 physiologic cup 58, 484 pink eye. See infectious
reptiles 742 physiology, 59–89. See also keratoconjunctivitis
retinal detachment 465–466, electrophysiology pinnipeds 758–760
517–518 aqueous humor 74–84 static accommodation 99
zonular instability 467–468 blood–ocular barriers 73–74 piperacillin 127
phacolytic glaucoma 383 cornea 64–68, piroplasmosis, equine (babesiosis)
phacolytic uveitis 410, 447, 448 eye movements 87–88 301, 839
phacomorphic glaucoma 382–383, intraocular pressure 74–84 piroxicam, squamous cell
446 iris 68–70 carcinoma 625
phagocytosis, iridocorneal angle 44 lens 84–85 plague, black‐tailed deer 745
pharmacokinetics 117–121 nutrition of tissues 71–73 planes, globe 26
pharmacology 114–159 tears 62–64 plant toxins
phenazopyridine, toxicity 812 vision 89–113 cattle 693–694
phenol red thread tear test 186 vitreous 85–87 keratoconjunctivitis sicca 645
phenothiazines 672, 704 Piebald sheep, ectropion 696 sheep 695
phenotypes 213 pigment epithelial processes 750 Stypandra glauca 702
phenylalanine deficiency 446 pigmentary and cystic glaucoma, plaques
phenylbutazone 142, 632 Golden Retriever 386, eosinophilic keratitis 568
phenylephrine 144, 146 417 fungal keratitis 571
laboratory animals 716 pigmentary chorioretinopathy 504 squamous cell carcinoma 681,
Mydriasert® 123 pigmentary glaucoma (melanocytic 682, 684
reptile mydriasis 739 glaucoma) 385–386, 422 plasma 632
with scopolamine, anterior pigmentary keratitis 339 plasmoid aqueous, 76, 172. See also
uveitis 407 pigmentary uveitis 417 fibrinous aqueous
on synechiae 409 glaucomas (melanocytic plasmoma, nictitating membrane
phenylpiperazine, cataracts 443 glaucoma) 385–386, 422 307–308
Phortica variegata 294–295 pigmentation. See also depigmentation pleomorphism 201
phosphodiesterase 106 cornea 316 PMLE17 gene (Silver Dapple
phospholine iodide 151 diffuse iris melanoma 587 locus) 610, 833–835
photic headshaking 664, 836 fundus, camelids 712 pneumatic retinopexy 520–521
photodynamic agents 670 iris 36, 422 pneumatonograph 194
photodynamic therapy, for squamous squamous cell carcinoma 681, 687 pocket syndrome, medial canthal
cell carcinoma 624 uvea, white cats 575–577 300
Index 889

pocket techniques, nictitating posterior segment guinea pigs 720


membrane repositioning birds, trauma 756 matrix metalloproteinases 315
305 camelids 712–714 refraction 93, 94
polar bears, examination 758 cats 593–600 thickness 278
polarized light 201 cattle, infections 692 prednisolone 138, 139, 140
polidocanol, cysts 551 dogs 469–538 anterior uveitis 407, 408, 586
polioencephalomalacia (PEM) 667, descemetoceles and 331–332 canine herpesvirus‐1 recurrence
693, 702 ophthalmomyiasis 414 294
poliosis 411 surgery 515–525 cataract surgery 457
polyclonal gammopathy, feline drug delivery 120 cats, viral infections 827
infectious peritonitis 582 examination 173 eosinophilic keratitis 568
polycoria, 397, 849g food animals, inflammatory after gonioimplant placement 390
polycythemia 789 diseases 702 ocular hypertension from 700–701
conjunctiva 301 horses 658–664 pannus 342
polycythemia vera 511 congenital disorders 612–613 parasitic diseases 414
polyenes 132 nonhuman primates 732 parasitic granulomas 299
Polyglactin 910 463 rodents 720 prodrugs 123
polymegathism 201 ultrasonography 206–207 recurrent proliferative
polymerase chain reaction 185 posterior uveitis (choroiditis), keratoconjunctivitis 298
Bordetella bronchiseptica 560 507–508, 846g toxoplasmosis 824
bovine leukemia virus 668 posterior vitreal detachment 86 prednisone
Chlamydia felis 557–558 postganglionic parasympathetic anterior uveitis 408
feline calicivirus 560 lesions, testing 770 masticatory muscle myositis 794
FHV‐1 547 postganglionic sympathetic lesions, Vogt–Koyanagi–Harada‐like
lymphoma 230 testing 771 syndrome 411–412
polymers, drug delivery 121–123, postoperative complications preganglionic parasympathetic
125 enucleation 235–236 lesions 780
poly(methyl methacrylate) (PMMA) tarsorrhaphy 269 testing 770
460 postoperative hypertension 383–384 preganglionic sympathetic lesions
polymodal nociceptors 68 postoperative management 770–771
polymyositis, extraocular 228 cataract surgery 463–466 pregnancy, corticosteroids,
polymyxin B 128 eyelid surgery 244 camelids 712
bacitracin with 127 gonioimplants 390–392 preiridal fibrovascular membranes
polysulfated glycosaminoglycans tarsorrhaphy 269 405, 406
(PSGAGs), spontaneous postoperative ocular hypertension prematurity, retinopathy of 509
chronic corneal epithelial (POH), after cataract preoperative treatment
defects 326 surgery 464 cataract surgery 456
polyvinylidene fluoride, high‐ postrotatory nystagmus 89 glaucomas 389
frequency ultrasonography pot‐bellied pig, entropion 703–704 preretinal vascular loops 474
208 potassium, tear film 63 preretinal vascular meshwork,
poodles, glaucomas 377 Pourcelot ratio 209–210 snakes 740
porcine grafts 640 Pourfour du Petit syndrome 775 preservatives
corneal perforation 332 povidone–iodine solution 242, eye drops 117
porphyria, food animals 671–672 635–636 topical anesthetics 146
porphyrins, tears, rodents 717 poxviruses pretectal nuclei 765, 773
Portuguese Water Dogs, photoreceptor avian 753 primary acquired cataracts 435–442
degenerations 500 caiman 740 primary angle‐closure glaucoma
posaconazole 135 mule deer 746 369–370
positioning, eyelid surgery 242–243 rabbit 726 genetics 357–358, 851
post‐traumatic feline ocular PRA diseases. See progressive primary complaints 163–164
sarcomas 588 retinal atrophy primary congenital cataract 433–435
posterior capsular opacities (PCO) pradofloxacin, Chlamydia felis 558 primary glaucomas, cats 589
cataract surgery 465 precorneal membranous occlusion primary infectious conjunctivitis,
posterior ciliary nerves 26 726–727 nonhuman primates 732
posterior equine recurrent uveitis precorneal tear film (PTF) 24, primary lens luxation 449–453
651–652 62–64, 278–279 genetics 359–360
posterior lamellar keratoplasty breakup time 190–191, 282, treatment 454
642, 643–644 569, 570 primary narrow/closed glaucoma
posterior lens luxations 380–382, 452 camelids 707 355, 369–370
posterior polar cataracts 437, 440 drug delivery 118 Basset Hound 370
posterior polymorphous dystrophy examination 171 gender 370
345 function of eyelids 20 progress 371–372
890 Index

primary open‐angle glaucoma cats 601 nodular granulomatous


355, 369–370 dogs 230–233, 234, 536, 537 episcleritis 352–353
cup to disc ratio 529 tarsorrhaphy 267 psittacines, orbit 749
gene and breeds, dogs 851 prostaglandins, 388b psychosine 813–814
genetics 359–360 analogues 70, 149, 155–158 ptaquiloside 702, 783
inheritance 370 cats 591 Pteris aquilinum 702–703, 783
prognosis 388 lens instability 467 pterygium, 849g
progress 371 endogenous 70, 71, 138, 401, 408 ptosis, 849g
primary stroma 10 NSAIDs on 141 Pugs
primary visual cortex 103 prodrugs 123 corneal pigmentation 316
primary vitreous degeneration 475 prostheses pulverulant nuclear cataract 440
primates. See also nonhuman extrascleral 237 pump–leak mechanism, cornea 67
primates intrascleral 236–237, 619 puncta adherentes 40
central retinal arterial occlusion protanopia 110, 111 pupillary blockage 371, 383, 384
732 proteases pupillary escape 169
ciliary body 42 corneal healing 313–314, 629 pupillary light reflex (PLR)
visual acuity 112 keratomalacia 338, 632 478–479, 528, 765–766
primitive medullary epithelium, Pseudomonas aeruginosa 315 birds 169, 751
tumors 514 tears 629 components 70
primitive streak 3 protein binding, on drug absorption examination 168–169
primitive vitreous 469 119 sudden acquired retinal
prion proteins, scrapie 703, 843 proteinase inhibitors, corneal degeneration syndrome
privilege, immune 652 healing 314 792
probes, vitrectomy 523 proteinases, corneal healing 314–315 pupillary membrane (PM), 9, 10–11,
prodrugs 123 proteins 429–431, 705. See also
epinephrine 123, 152 lens 84 persistent pupillary
PGF2α 156 levels in aqueous humor 401 membranes
production animals. See food animals tear film 63 pupillary ruff, camelids 711
productive phase, feline herpesvirus‐1 proteolysis, reducing 338 pupillometry 528
563, 566, 825 protoporphyria, food animals 672 pupils, 35, 849g
progressive retinal atrophy (PRA) Prototheca (spp.) 416, 795–796 on accommodation 96
Bengal cat 596–597 protothecosis 795–796 amphibians 737
dogs 493, 494, 495, 500–501 protozoal infestations birds 70, 750
cataracts 444 cats 823–824 cats 70, 575
electroretinography 497 blepharitis 547 diameters 105
genes and breeds 851, 852 chorioretinitis, 506b examination 172
genetics 214 dogs 343, 414–415 functions 68–70
progressive rod–cone degeneration reptiles 741 hemidilated 775
493, 500–501 protractor lentis hereditary retinal dystrophy 504
gene and breeds 852 amphibians 737 light adaptation 106
projection errors, visual fish 735 micropapilla 531
pathways 89, 780, 813 protrusion pharmacological dilatation 173
prolapse. See also fat prolapse nictitating membrane 305, 306, shape 70
iris 334, 631, 639 555, 627–628, 781–782, 818 sphincterotomy 425
infectious bovine vitreous 472 puppy keratopathy 320
keratoconjunctivitis 678 provocative tests puppy strangles, 259–260, 793. See
lacrimal tissue, guinea pigs glaucomas, 366–367, 849g also juvenile sterile
721, 722 proxymetacaine 166 granulomatous dermatitis
nictitans glands 289, 304–305, 555 pseudo‐indirect pupillary light corticosteroids 793
uvea 334, 418, 419–420 reflex 765 purine nucleoside analogues 137
proliferative keratoconjunctivitis, pseudobuphthalmos 741 Purkinje image, cornea 171
567–569. See also nodular Pseudomonas aeruginosa pyoderma. See also juvenile sterile
granulomatous episcleritis antibacterial agents 129 granulomatous dermatitis
recurrent 298 penicillins 127 cats 547
proliferative optic neuropathy 663–664 proteases 315 pyogranulomatous blepharitis
proliferative vitreoretinopathy 516 pseudopapilledema 534 dogs 260
proparacaine 147 pseudophakic glaucomas 383–384 sheep and goats 696
miosis inhibition 151 pseudopterygium 726–727 pyramidalis muscle 749
prophylactic retinopexy 519–520 pseudorabies 704 pyrethroid spray 742
proptosis, 849g. See also exophthalmos pseudotumors pyrimethamine 131
tarsorrhaphy, 233b conjunctiva 627 pyrimidine analogues 136–137
traumatic eyelids 263–264 pyrimidines, antifungal 134
Index 891

q reactivation of feline herpesvirus‐1 relative polycythemia 789


quadratus muscle 749 563, 565 REM sleep 89
quadriplegia, syndrome with real images 92 renal dysfunction, hypertension
786–787 real‐time echography 203 598, 816
Quarter Horse rebound tonometry 194–195, 362 repositioning
aniridia 609 cattle (values) 665 lacrimal puncta 275–276
dermoids 608 laboratory animals 716–717 nictitating membrane 305–306
inherited eye diseases 854 pigs (values) 703 reptiles 738–743
quasi‐spherical eye, penguins 757 recessive disease, carriers 214–215 conus papillaris 71
Quickert–Rathbun procedure 250 reconstruction eyelids 61–62, 738
lip‐to‐lid 543 resistance to antibiotics
r nictitating membrane 308 fluoroquinolones 132
rabbits 724–730 reconstructive blepharoplasty folate metabolism 131
adrenergic receptors 70 266–267 gentamicin 128
conjunctival overgrowth 726–727 rectus muscles 17, 87 tetracyclines 130
cornea 92, 728 recurrent erosions 324–327 resistive index 209–210
intraocular pressure 82, 192 recurrent proliferative resorbing hypermature cataracts 383
orbit 14, 725 keratoconjunctivitis 298 resorption of cataracts 435, 447
refraction 98 red light, sudden acquired retinal respiratory tract infections. See also
restraint 165 degeneration upper respiratory tract
visual acuity 113 syndrome 792 infections
radiation red‐free filter, ophthalmoscopy birds 753
cataracts 443–444, 690 364, 529 blastomycosis 799
on conjunctiva 301 redroot pigweed (Amaranthus responses, reflexes vs 765, 767
retinal dysplasia 490–492 retroflexus) 705 Restasis® (emulsion) 143
retinopathy 509–510 reduction, lens luxation 454 restraint 164–166
for sarcoids 626 reduction plasty, palpebral birds 165, 752
solar, squamous cell carcinoma fissure 255–256 camelids 165, 706
551, 623, 680, 681 redundant skin folds 257–258 cattle 165, 665
for squamous cell carcinoma reflection of light 92 goats 165, 694
552, 623, 686 specular 171 horses 604
radioactive gold seeds 686 reflex anterior uveitis, neurogenic ophthalmoscopy 176
radioactive isotopes, aqueous humor 324 sheep 165, 694
measurements 81 reflexes, 765–769. See also restrictive strabismus 228
radiofrequency treatment, squamous specific types retardation (light phase shift) 201
cell carcinoma 686 cornea, 60, 67–68, 169–170, reticulate bodies, Chlamydophila
radiography 197–200 182–183, 242b 768 pecorum 698
nasolacrimal system 274 birds 751 reticulosis 513–514
orbit 197–198, 221 eyelids 60 retina, 53–58. See also blood–retinal
uveitis 406 refraction 92–99 barrier
rain scald (dermatophilosis) 669, aquatic species 99, 750 amphibians 737
696 refractive errors angiogenesis 9
rapamycin 143 indirect ophthalmoscopy 180 angiography (fluorescein
raptors 748–756 ophthalmoscopy 175–176 angiography) 202–203,
bacteria 752 retinoscopy 96, 180–181 480, 529–530
intraocular pressure 82–83, by species 98 birds 750
192 refractive index 49 vasculature 57
lead toxicity 754–755 aqueous humor 74 blood flow 72
restraint 165, 752 eye structures 94 cats 594–600
trauma 756 fish lens 734 development 12
visual acuity 112 lens, chameleons 739 cattle 690–694
rats 716–720 tear film 93 degenerations. See also early retinal
cataracts 719 vitreous 86 degeneration; sudden
glaucomas 719 refractory corneal ulcers 324–327 acquired retinal
refraction 97, 98 regional anesthesia 147, 166–168 degeneration syndrome
visual acuity 113 agents 146–148 birds 754
ravuconazole 135 cattle 684 camelids 714
rcd1 genes 497 eyelid akinesia 165–166, 166 cattle 692
rcd2 mutation 498 eyelids 685 enrofloxacin 597, 830, 831
RCS rat 720 medial canthus 167, 606 fluoroquinolones 830
rd gene 720 retrobulbar 124, 618–619 glaucomas 364, 369
RD3 gene 498 reinflation of globe 333, 334 inherited 493–500
892 Index

retina (cont’d) phacoemulsification 465–466, retrobulbar lymphomas, cattle


non‐necrotizing granulomatous 517–518 667–668
scleritis 354 retinal dysplasia 489, 513 retrobulbar muscles,
phototoxic retinal, fish 736 rhegmatogenous 475, 513, 517 ultrasonography 205
Pteris aquilinum 702–703 glaucoma 387 retrobulbar neuropathy and retinal
rodents 720 role of vitreous 515, 516 degeneration 693
Toggenburg goats 702 Shih Tzu 475 retrobulbar optic nerve. See
vitamin E deficiency 810–811, rodents, artifact appearing as intraorbital optic nerve
835–836 716 retrobulbar space‐occupying lesions
detachment. See retinal detachment scrapie 843–844 cattle 667
development 8, 11–12, 485 surgery for 515–525 guinea pigs 721
dialysis (disinsertion) 512, 517 equipment 523, 524 rabbits 725
dogs procedures 520–524 retrobulbar steatitis 602
development 12 ultrasonography 206–207, 456 retrobulbar venous plexus, rabbits
diseases 478–515 into vitreous 474, 478, 518 725, 730
drug‐induced toxicity 509 retinal disparity 108–109 retrobulbar venous sinus
dysplasia. See retinal dysplasia retinal dysplasia. See also vitreoretinal ferrets 723
elasmobranchs 733–734 dysplasia pigs 731
examination 173 cats 594, 595 retrograde flushing, nasolacrimal
ferrets 723 cattle 692 system 274
fish 735, 736 dogs 474, 488–500 retroillumination 175, 176
fluoroquinolone toxicity 132 horses 612 rhegmatogenous retinal
folds retinal detachment 489, 513 detachments 475, 513, 517
cats 600 rodents 720 glaucoma 387
dogs 478, 492 sheep 702 role of vitreous 515, 516
rodents 720 retinal pigment epithelial dystrophy Shih Tzu 475
ganglion cells (RGC) 53–54, 56–57 (RPED) 493, 502–505 rhesus macaques
absence 532 retinal pigment epithelium Cayo Santiago 732
axons 525–526 autofluorescent inclusion survey 743–744
development 12 epitheliopathy 502–505 rhinotracheitis. See infectious bovine
function 100, 104 retinal pigment epithelium (RPE) rhinotracheitis
glaucomas 355 12, 53, 54–55, 116 rhinotracheitis virus 745
loss 538 retinitis pigmentosa, rat model 720 Rhodococcus equi 837
pupillometry 528 retinitis pigmentosa 1 mutation, rhodopsin 91
hemorrhage, anemia 817 Normande cattle 692 rickettsial diseases 415, 804–806
horses 658–659, 660 retinoblastomas 514 chorioretinitis, 506b
hypertension, cats 816 retinochoroiditis 597 conjunctivitis 294
interface with vitreous 470 retinomotor responses, fish 735 rimexolone 140
IOP elevation on 367 retinopexy 520–524 ring of Elschnig 526
layers 54 prophylactic 519–520 ringworm 545
nerve fiber layer (RNFL) success 524–525 risus sardonicus 799
53–54, 55, 201 retinoscopy (for refractive error) robenacoxib 586
ophthalmoscopy 364, 529 96, 180–181 Roberts–Bistner technique 543
ophthalmomyiasis 414 retraction sutures, entropion Roberts–Jensen pocket procedure,
refractive index 94 249–250 253b, 256. See also
reptiles 739–740 retractor anguli lateralis 241 permanent lateral palpebral
Siamese cats 813 retractor anguli oculi, dogs 19 fissure reduction plasty
vascular system. See retina under retractor bulbi 87, 736 Robertson procedure 250
vascular system retractor lentis, fish 734 Rocky Mountain Horse
vision 100–101, 102 retractor oculi 17 inherited eye diseases 854
retinal (photopigment) 91 retractor oculi muscles 220, 240 multiple congenital ocular
retinal detachment 512–513 retrobulbar abscess anomalies (MCOAs) 833
cats 600 irrigation 225 Rocky Mountain spotted fever 415,
Collie eye anomaly 486, 487, 488 Pasteurella (spp.) 725 805–806
dogs, causes 517–519 rabbits 725 rocuronium 751
horses 612, 613, 662–663 ultrasonography 207, 222 rod dysplasia 499
hypertensive retinopathy retrobulbar block. See also Peterson rod monochromasy 110
599, 816 nerve block rod–cone degeneration, gene and
hyphema 420–421 for enucleation 167, 234 breeds, dogs 852
inflammatory diseases 506 horses 167–168, 618–619 rod–cone dysplasia
after intracapsular lens retrobulbar drug injection 124 cats 596
extraction 468 anesthesia 167–168 dogs
Index 893

genes and breeds 852 for DNA tests 214 sea turtles. See also green sea turtles
type 1 496 Sandhoff disease. See GM2 neoplasia 742
type 2 497–498 gangliosidosis seals 744, 758–760
type 3 498 Sanson–Purkinje images 427 seasonality
rodenticides, toxicity 812 saponin, bird mydriasis 751 infectious bovine
rods 55, 100, 102, 104, 105 Sarcocystis neurona 782 keratoconjunctivitis 675
electroretinography 212 sarcoids 625, 626 sudden acquired retinal
reptiles 740 sarcomas degeneration syndrome 792
Romagnola cattle, congenital cattle 689 sebaceous adenomas, feline eyelids,
cataract 689 dog, 229b 265 frequency 552
romifidine 604 feline ocular, post‐traumatic 588 sebaceous glands (glands of Zeis), 21,
Rose Bengal, 191, 242, 849g sarcoptic mange 803 241. See also hordeolum
rosettes, retinal dysplasia 490–492 blepharitis 261, 669 Sec1 Family Domain Containing 2
rotational grafts lens rupture 420 (SCFD2) gene 442
eyelid agenesis 543 treatment 697 second‐order neurons 100
pedicle conjunctival graft 330 scabies, feline 546 secondary cataracts
rotatory nystagmus 88–89 scanning laser ophthalmoscopy cats 592–593
Rottweiler, developmental cataracts 479 cattle 689–690
440 scanning laser polarimetry 201 dogs 436, 442–447
Rough Collie, choroidal hypoplasia scarring progressive rod–cone
533 butterfly lesions 661 degeneration with 500
rough Moraxella bovis 675, 676 canine distemper 806 horses 658
roundworm 802–803 cornea 66, 629 secondary glaucomas 361, 379–387
RPE65 null mutation 503–504 Schapendoes (dog breed), progressive cats 589–590, 591
RPGRIP1 gene 500 retinal atrophy 501 causes 367–368
RPGRIP1 insertion 214 Scheiner’s disc phenomenon 70 epidemiology 356–357, 379
rubeosis iridis, 405, 579, 581, 849g Schiötz tonometer 81, 192–193 horses 656
rupture Schirmer’s tear test (STT) 170 infectious bovine
globe 418, 419 cats 186, 569 keratoconjunctivitis 678
lens cattle 665 after intracapsular lens
congenital 429 dogs 273, 281 extraction 468
diabetes mellitus 446 horses 186, 645 lens luxation 451–452
endophthalmitis 420 llamas 706 lens rupture 457–458
phacoemulsification for 410 topical anesthetics 146 lymphomas 588
spontaneous 457–459 scissors nonhuman primates 732
eyelid surgery and 243 signs 369
s phacoemulsification 461 treatment by cause 380
S‐gene 785 retrobulbar block 168 uveitis 406
saccadic eye movements 88 sclera 33–34, 312 secondary lens luxation 453
sagittal planes 26 development 12 treatment 454–455
Saint Bernard, dermoids 245 dogs 352–354 secondary tumors. See also metastases
salivary glands. See also zygomatic drug delivery 115, 119 optic nerve 537
gland fish 733 posterior segment 514
parotid duct transposition IOP elevation on 367 sector iridectomy 425
287–288, 645 jaundice 789 sedation
sialoadenography 198 reptiles 738 camelids 706
salivary retention cysts 226–227 scleral ossicles 34, 738 cattle 665
salmonellosis 837 scleritis, 353–354, 849g horses 604
salmonid virus diseases 735 non‐necrotizing granulomatous side effects 165
salt gland 749 353–354, 411 seed finch, endodontic absorbent
salvage procedures, squamous cell sclerociliary cleft. See ciliary cleft paper point test 186
carcinoma, cattle 684–685 sclerociliary/sclerochoroidal space Seidel test 187, 190
Samoyed 34 selamectin 546
canine oculoskeletal dysplasia sclerocorneal sulcus 738 selenium 695
490, 785–786 sclerotomy, 849g self‐retaining silicone lenses 523
emmetropia 96–97 scopolamine 144 senile cataract (ARC) 442, 658
glaucomas 378 phenylephrine with 407 nuclear sclerosis vs 173, 427
pectinate ligament dysplasia 370 scotopic (term), 849g senile iris atrophy 397
X‐linked progressive retinal scotopic vision 100, 103–105 sensitivity of cornea 67–68, 171,
atrophy 501 electroretinography 212 182–183, 312, 768
sampling scrapie 703, 843–844 cattle 665
for culture or cytology 183–185 scraping, cornea 183–184 horses 629
894 Index

sepsis, foals 607 Siberian Husky sodium, aqueous humor 77


septum orbitale 15 developmental cataracts 440 sodium chloride (5%), corneal
sequestra, cornea 338, 572–573, 826 glaucomas 378 ulcers 616
serology photoreceptor degenerations sodium stibogluconate 804
fungal infections 413 500 sodium/potassium ATPase pump 30,
leptospirosis 651 X‐linked progressive retinal 31, 74–75, 84
toxoplasmosis 824 atrophy 500, 501 soft contact lenses 633
serous retinal detachment 517 sicca (term), 849g. See also keratitis solar dermatitis 549, 551, 670, 697
serum 632 sicca; keratoconjunctivitis solar keratitis, squamous cell
for keratomalacia 323, 615–616 sicca carcinoma 623
for spontaneous chronic corneal siderosis lentis 447 solar radiation, squamous cell
epithelial defects 326–327 signalment 163 carcinoma 551, 623,
severe combined immunodeficiency silage eye 673–674 680, 681
835 silicone IOLs 460 solid intraocular xanthogranuloma,
Shar‐Pei (dog breed) silicone oil 387 Miniature Schnauzer 417
glaucomas 378 silicone tubing, gonioimplants 391 solid polymeric devices, drug
lens luxation 453 Silver Dapple locus 610, 833–835 delivery 122
sheep 694–703 silver sulfadiazine 635 solubility of drugs 118–119
bright blindness, Pteris aquilinum single‐nucleotide polymorphisms, solutions
702–703, 783 CSNB and LP 833 ophthalmic, 116–117. See also
eyelids 61, 695–697 sino‐orbital aspergillosis 602 irrigation
globe dimensions 26 skeletal dysplasia. See dwarfism subconjunctival injection 124
inherited eye diseases by breed skiascopy (retinoscopy) (for refractive tear film replacement 284
855 error) 96, 180–181 somitomeres 13
intraocular pressure 83, 700–701 skin sorbitol, cataracts 445
mycoplasmal keratoconjunctivitis eyelids 20, 240 sore mouth (contagious viral pustular
841 immune‐mediated diseases dermatitis) 697
neuro‐ophthalmic diseases 783 792–793, 818–819 space‐occupying lesions. See also
restraint 165, 694 leishmaniasis 803, 823 retrobulbar space‐
scrapie 843–844 papillomaviruses 808 occupying lesions
visual acuity 112 redundant folds 257–258 intracranial 779–780, 809
sheep and goat pox 697 sarcoids and 625 sparfloxacin 132
Sherrington’s law 87–88 Vogt–Koyanagi–Harada‐like spastic pupil syndrome (static
Shetland Sheepdog, microphthalmia syndrome 411, 508, 795 anisocoria) 775, 781
223 skunk cabbage (Veratrum spectacle 170, 738
Shiba Inu (dog breed), glaucomas californicum) 695 abscesses under 740–741
377 sleep retained 742
short ciliary nerves 43, 764–765 aqueous humor regulation 77 spectrum, electromagnetic 90
short posterior ciliary arteries 26, eye movements 89 specular microscopy 201
57–58, 72, 526, 526–527 slit beam specular reflection, cornea 171
Short‐Haired Dachshund, cone–rod anterior chamber depth 172 sphenoid bone, vitamin A
dystrophy 499 iris lesions 172 deficiency 844
Shorthair cats, inherited eye lens 173 sphenopalatine sinus, horse 617
diseases 853 slit pupils 106 spherical aberration 99
Shorthorn calves slit‐lamp biomicroscopy 173–175, spherophakia, 428, 849g
congenital cataract 689 427 sphincter, iris 37, 38, 68–69, 144, 764
multiple congenital ocular gonioscopy 182 sphincterotomy 425
anomalies 692 lens luxation 454 sphingomyelin lipidosis 815
shotgun injury 323, 447 vitreous 470 spinal needle, retrobulbar block 167
Shropshire sheep, essential iris Sloughi dogs, PDE6B gene 497 spindle cell tumors 424
atrophy 701 slow‐release devices. See also spontaneous chronic corneal epithelial
shunts, 79. See also gonioimplants sustained drug delivery defects 324–327
sialoadenography 198 cyclosporine (CSA) 143 spontaneous retinal dysplasia
sialoceles 226–227, 300 Sly syndrome 815 488–490
sialodacryoadenitis 718 smooth pursuit movements 88 Sporothrix schenckii 545
Siamese cats snakes 738, 739, 740 squamous cell carcinoma
albinism 780, 813 accommodation 739 cats
esotropia 781 mites 742 conjunctiva 562–563
inherited eye diseases 853 nasolacrimal duct obstruction 741 eyelids 551–552
uveal pigmentation 575–577 spectacles 170, 738, 741, 742 invasion 828–829
visual pathways 780 Snellen charts 111 orbit 602
projection errors 89, 780, 813 snowbanking 594 solar dermatitis 549, 551
Index 895

cattle 668, 670, 680–687 STK38L gene 499 subconjunctival fat prolapse 233,
cornea 685 storage diseases. See lysosomal storage 298–299
invasion 682–683 diseases subconjunctival hemorrhage,
surgery 684–685 strabismus 763–764, 850g foals 615
cornea 143–144, 350 cats 89, 577 subconjunctival injection 124
dogs 265 cattle 666–667 anterior uveitis 407, 408
conjunctiva 297 horses 607, 608 corticosteroids 139, 140, 145
cornea 350 hydrocephalus 778 subepithelial plexus 69, 311–312
nictitating membrane 307 restrictive 228 subluxation, 448–449, 451, 467,
horses 623–625 Siamese cats 813 656, 850g
cornea 648 strangles subpalpebral systems (SPL)
nictitating membrane 625 horses 837–838 drug delivery 121
orbit 621 puppies 259–260, 793. See also lavage, camelids 710
sheep 700 juvenile sterile for ulcerative keratitis 630–631, 632
squamous metaplasia, vitamin A granulomatous dermatitis subretinal injections 504, 525
deficiency 743 corticosteroids 793 substance P 402
squamous papillomas, feline eyelids, Streptococcus (spp.) spontaneous chronic corneal
frequency 552 antibacterial agents 129 epithelial defects 326
squint, 849g. See also strabismus penicillins 127 substantia propria 22, 29–31, 290
SRBD1 gene 358 Streptococcus equi 837–838 sudden acquired retinal degeneration
St John’s wort, hypericin 670 streptomycin, dermatophilosis 669 syndrome (SARDS)
Stades procedure, 253b striate cortex 103 508–509, 791–792
Staffordshire Bull Terrier striate lesions, 850g optic neuritis vs 536
congenital cataract 441, 442 cornea 648 sulbactam 127
developmental cataracts 439 striated muscle, iris sulcus fixation, intraocular lenses
persistent hyperplastic tunica birds 70, 169, 751 468
vasculosa lentis/ persistent reptiles 739 sulfonamides 131, 153–154
hyperplastic vitreous stroke length, phacoemulsification hypersensitivity 418, 811
(PHTVL/ PHPV) 431 459 keratoconjunctivitis sicca 131,
staging, glaucomas 372 stroma 279, 811
stains cornea 311 sulfur, dietary deficiencies caused
Chlamydophila pecorum 698 abscesses 634, 635, 641, 642, by 693
cytology 185 643–644, 710 sulfur granules, habronemiasis 838
external ophthalmic 186–191 bacterial infections 638 sulfur hexafluoride, retinopexy
Standard Poodle, developmental drug penetration 118–119 521
cataracts 437 feline herpesvirus‐1 311, 565, summer cypress (Kochia scoparia)
standardbred Horse, inherited eye 566 694
diseases 854 healing 312–313, 629 summer sores (habronemiasis)
Staphylococcus (spp.) horses 628 622, 838
blepharitis 260 ulcers 327, 570 sunlight, squamous cell carcinoma
methicillin‐resistant, antibacterial vascularization 318 551, 623, 680, 681
agents 129 primary 10 sunset eyes 786
penicillins 127 substantia propria 22, 29–31, superciliary line 61
rabbits 727 290 superficial conjunctival hyperemia,
Staphylococcus intermedius, stromal immune‐mediated keratitis ciliary flush vs 403
antibacterial agents 129 645–646 superficial corneal pigmentation 316
staphyloma 849g strongyloidiasis 802 superficial corneal ulcers 323–324
limbus 322 stye, 850g superficial corneal vessels 318
merle ocular dysgenesis 487 external hordeolum, 847g superficial immune‐mediated
stars of Winslow 48, 606, 659, 690 hordeolum, 262–263, 847g keratitis 645
static accommodation 99 Stypandra glauca 702 superficial keratectomy 319–320,
static anisocoria 775, 781 sub‐Tenon’s drug injection 124, 168 321
stay sutures, entropion 249–250 subacute uveitis 401 endothelial corneal dystrophy
steatitis, retrobulbar 602 subalbinism 348
stem cells, limbus, healing 312 camelids 711 Florida keratopathy 349
stereoacuity 109 cattle, fundus 691 superficial punctate keratitis
stereopsis (ophthalmoscopy) 178, 479 dogs 394–395 343–344
optic nerve head 529 fundus 482, 483 superficial uncomplicated corneal
stereopsis (vision) 107–108 subarachnoid space, optic nerve 527 ulcers 633
stimulators (photostimulators) subbasal plexus 69, 312 suprachoroidea 46
211, 212 subconjunctival enucleation 232, supraorbital foramen 605
stings 548 234–235, 619 supraorbital gland, penguins 757
896 Index

supraorbital ligament 14 synthetic grafts, corneal perforation tarsoconjunctival graft 328


supraorbital nerve block 166, 332 tarsorrhaphy, 234, 244, 267–269, 850g
605–606 syphilis (rabbit) 726 partial 288–289
supraorbital ridge 61 systemic diseases 164, 784–844. birds 756
supraorbital technique, retrobulbar See also specific diseases dogs 288–289
block, horse 618–619 on conjunctiva 300–301 proptosis, 233b
suprofen 142, 407 uveitis 406 trauma, 419b
suspensions systemic drug absorption 119–120 taurine, cats 595
ophthalmic 117 beta‐blockers 153 taurine deficiency retinopathy
subconjunctival injection 124 corticosteroids 141 595–596
sustained drug delivery, 117, 121–123, systemic drug administration 125 cats 829–830
125. See also slow‐ anterior uveitis 407, 408 exotic felines 747
release devices antibacterial agents 409 ferrets 723
pilocarpine 150 carbonic anhydrase inhibitors tear film breakup, 190–191, 282, 569,
sutures (lens) 50–51, 427, 446 (CAIs) 155 570, 850g
diabetes mellitus 808, 809 corticosteroids 139, 140, 586 tear stimulators 148–149
horses 606 equine recurrent uveitis 653 tear substitutes 148, 284, 285–287
sutures (surgical) for glaucoma 149 tear tests, 185–186. See also Schirmer’s
Celsus–Hotz resection 251 NSAIDs 143 tear test
conjunctiva 302 pilocarpine 148–149 tear‐staining syndrome 276
corneal grafts 332–333 tetracyclines 130 tears, 278–279. See also artificial tears;
corneal lacerations 334–335 systemic histiocytosis 301, 812 epiphora; precorneal
entropion 249–250 tear film
cats 543–544 t composition 63
enucleation 235 T cells, immunosuppressants deficiency 279–280
eyelid neoplasia 266 on 283 drainage 271–272
eyelids 243, 259 T4R mutation, dominant progressive production rates
nictitating membrane 308 retinal atrophy 501 camelids 706
after phacoemulsification 463 tacking, entropion 249–250 dogs 279
tarsorrhaphy 234, 267, 269 tacrolimus 143 pigs 703
traumatic proptosis 233 for keratoconjunctivitis sicca sheep and goats 694
swabs 183, 184 283–284, 296 proteases 629
Bordetella bronchiseptica 560 on tear production 148 rodents 717
Swainsona galegifolia (darling pea) tactile hairs 20–21 teeth
694 tail color, multiple congenital ocular ocular injuries and 585
swamp cancer (habronemiasis) anomalies 833 relation to nasolacrimal
622, 838 tapetal fundus duct 553–554, 727
swinging flashlight test 169, 766 canine distemper 806 teleosts 733
symblepharon, 564, 567, 825, cats 593 temporary tarsorrhaphy 268, 269
850g cattle 690 Tenon’s capsule, 16, 34, 850g
sympathetic nerve supply dogs 482 Tenon’s space 16
accommodation 95 development 485 teratogenesis
on blood flow 71 inactive chorioretinitis 507 griseofulvin 601, 830
ciliary body 43 horses 606, 659 sheep 695
iris 69, 70 sheep 701 terbinafine 545
lacrimal gland 64 tapetal layer, choroid 46 terriers, lens luxation 380–381
testing 770–771 tapetum cellulosum 48 tertiary vitreous 9
sympathomimetics 146, 770–771 IOP elevation on 367 tetanus 798–799, 819
synapses tapetum fibrosum 48 tetany, hemifacial 774
ciliary ganglion 70 tapetum lucidum, 48, 105, 850g tetracaine 147, 166
optic nerve 58 cattle 690 tetrachromatic vision 110
retina 56, 102, 104 crocodilians 740 tetracyclines 130
synchysis scintillans, 476, 850g destruction 508 keratomalacia 323
synechiae, 850g development 12 lacrimal cysts 289
atropine on 409 reflection, cataract classification nodular fasciitis 264
cattle 687 435 spontaneous chronic corneal
corneal pigmentation 316 retinal detachment 513 epithelial defects 326
persistent pupillary teleosts 733 for tear staining 276
membranes vs 577 targets, intraocular pressure tetramisole 295
rodents 719 control 388–389 Texel sheep, microphthalmia 695
uveitis 403–404, 579 tarsal glands. See meibomian glands Thelazia (spp.) 700
syneresis, 452, 475, 660, 850g tarsal plates 15, 241 camelids 709
Index 897

cats 561 dogs 362–363 transillumination, 850g


cattle 672 laboratory animals 716–717 iris 175
ivermectin 673 pigs 703 uveal cysts 398
deer 746 TonoPen tonometers 193–194, 362 transit times, nasolacrimal system
dogs 294–295 TonoVet rebound tonometer 195, 362 274
thermal circulation, aqueous topical administration of drugs transmissible spongiform
humor 74 114, 116–123 encephalopathies 703
thermokeratoplasty 348 carbonic anhydrase inhibitors transmission of light 91–92
thiamine deficiency 693, 702, 830 154–155 transmittance rates, light 92
thimerosal, contact contralateral effects 119–120 transoral drainage, orbital
hypersensitivity 296 corticosteroids 138, 139 abscesses 225, 226
thioacetamide 735 local anesthetics 146, 147, transoral ultrasonography 222
third eyelid. See nictitating membrane 164, 166 transpalpebral enucleation 235,
third‐order neurons (RGCs) 100 diagnosis of entropion 249 619, 684
thoroughbred horses, inherited eye rebound tonometry and 195 transparency
diseases 854 tarsorrhaphy 269 cornea 64–67, 312
360° flap (Gunderson flap) 328, 348 total conjunctival flap (Gunderson lens 426
thrombocytopenia 789–790 flap) 328, 348 vitreous 86
canine cyclic 804 toxic anterior segment syndrome transplantation
cats 817 (TASS) 464 cornea 640–641, 642, 643–644
immune‐mediated 511 toxic substances 811–812, 830–831 for endothelial corneal dystrophy
thromboembolic meningoencephalitis cataracts 443 348
841–842 fluoroquinolones 132 eyelashes 267
thymidine analogues 136–137 lead 754–755 transscleral cyclophotoablation,
Tibetan Spaniel, photoreceptor on retina 509, 597 horses 656
degenerations 500 Toxocara (spp.) 412, 802–803 transscleral photocoagulation 392
Tibetan Terrier, photoreceptor toxocariasis 802–803 trauma. See also foreign bodies;
degenerations 500 Toxoplasma gondii 414, 823 lacerations; wound healing
ticarcillin 127 camelids 713–714 birds 755–756
tick‐borne encephalitis virus 808 cats 583, 823 cataracts 446–447, 592
ticks clindamycin for 131 conjunctiva
babesiosis 839 keratitis 343 hemorrhage 299
bartonellosis 819 toxoplasmosis 582, 823–824 repair 302
rickettsial diseases 805–806 as opportunistic infection 826 cornea. See also perforation
tight junctions 73, 115 wallabies 746 endothelium 317
cornea 31, 115 Toy Australian Shepherd exotic mammals 748
iris 116 congenital cataract 441 eyelids
tiletamine–zolazepam 706 Toy Poodle birds 756
tilmicosin 679 fundus 483 cattle 669
timber wolves, cataracts 747 glaucomas 377 dogs 258–259, 277, 669
timolol 152–153 optic nerve hypoplasia 532 horses 614, 621–622
dorzolamide with 155, 591 progressive rod–cone degeneration feline ocular sarcomas 588
horses 656 500 fish 735
on iris 69–70 trabecular meshwork (TM) 43–44, glaucoma after 384
latanoprost with 158 77–78, 363 guinea pigs 721–722
tissue adhesives, cornea 328 Beagle 374–375 horses 614, 621–622, 639
tissue‐type plasminogen activator iridocorneal angle 43–44 lens luxation 453
for fibrinous uveitis 616–617 myofibroblastic cells 45 nasolacrimal system 277
after gonioimplant placement trabecular veins 44–45 nictitating membrane 308
390 tracer studies optic neuropathies 536, 537, 663
hyphema 422 aqueous humor 81 orbit
tobramycin 130 traction detachment of retina 513, dogs 230–232
tocainide, corneal edema 318, 811 516, 517, 518 horses 619–620
Togaviridae 782 lens luxation 519 proptosis
Toggenburg goats, retinal traditional pathway, AH outflow 78 cats 601
degeneration 702 transcellular route across cornea 115 dogs 230–233, 234, 536, 537
Toll‐like receptors 63 transconjunctival enucleation 730 tarsorrhaphy 267
tongue, feline calicivirus 559–560 transcorneal reduction 454 retinal detachment 518
tonography, 366, 850g transduction of light 91 ulcerative keratitis, camelids 709
tonometry, 81, 191–195, 850g transforming growth factor β 375 uvea 418–420, 585
birds 751–752 transient receptor potential cation vitreous 474
cattle 665 channel member 1 gene 833 travoprost 156, 157, 158, 388b, 467
898 Index

Treponema cuniculi 726 turtles. See also green sea turtles ultraviolet vision 90, 110, 750
triamcinolone 139, 145 herpesvirus infections 740 aphakia 92
anterior uveitis 407, 408 mydriasis 739 uncomplicated corneal ulcers,
recurrent proliferative neoplasia 742 superficial 633
keratoconjunctivitis 298 vitamin A deficiency 743 unconventional outflow. See
triazoles 135 two‐step penetrating keratoplasty 641 uveoscleral outflow
tricaine methane sulfonate 735 tylosin, guinea pigs 721 underwater accommodation 99
trichiasis, 850g Tyndall phenomenon 404 unoprostone (isopropyl) 155–156
caruncular 300 type 2M muscle fiber antibodies upper respiratory tract infections
cats, eyelid agenesis 543 794 Bordetella bronchiseptica 560
dogs 257, 258 type A PRA 499 feline calicivirus 559–560
brachycephalic breeds 276 typical colobomas, optic nerve 533 urodeles 736, 737
trichoepitheliomas, feline eyelids, tyrosinase‐related protein 411 uroporphyrinogen I 672
frequency 552 tyrosinemia 787 uroporphyrinogen III synthase
trichomegaly 257 cataracts 444 deficiency 671–672
Trichophyton (spp.), food animals Utrata forceps, phacoemulsification
669, 696–697 u 461
trichromatic vision 110, 111 U‐figure suture, entropion 249 Utrecht study, glaucomas 357
trifluridine 136, 137, 336, 566 Uberreiter’s syndrome (chronic uvea, 25, 34–49, 850g. See also
trigeminal nerve superficial keratitis), 307, anterior uvea
cornea 311–312 339–342, 849g blood flow 71–72
motor nucleus 772 ulcerative keratitis cysts 398, 649
oculocardiac reflex 89 camelids 709–710 food animals 688–689
sensory ganglion 773 corticosteroids 140–141 horses 649–656
triglycerides, lipemia 788 dogs 315, 322–338 lymphomas, cats 580–581
trimethoprim 131 atropine 279 masses 422–425
trimethoprim‐sulfonamide conjunctival autografts 302–303 neoplasia 588
combinations 131, 645, keratoconjunctivitis sicca 287 cattle 689
727 drug absorption 119 horses 649–650
triple antibiotic ophthalmic foals 615–616 sheep 701
ointments 127 horses 630–633 pigmentation, white cats 575–577
tritanopia 110, 111 fungal 630, 634 pigs 704–705
trochlear nerve tetracyclines 130 prolapse 334, 418, 419–420
motor nucleus 772 ultrafiltration, aqueous humor sheep and goats 701
muscles supplied 19, 87 from 74 surgery 425
tropical keratopathy (Florida ultrasonography 203–210 trabecular meshwork (TM)
keratopathy) 349, 571 10–12 MHz 204–207 43, 363
tropicamide 144, 145, 173, 279–280 20–100 MHz 207–210 trauma 418–420, 585
anterior uveitis 409–410 anterior segment 205–206 uveitic glaucomas 384–385
camelids 706 biomicroscopy 172, 208 uveitis, 399–410, 850g. See also
horses 606 glaucomas 365–366 anterior uveitis
hyphema 422 cataracts 205–206 bartonellosis 819
Mydriasert® 123 camelids 714 camelids 714
phacoemulsification 467 full‐thickness lacerations 334 cataracts 444
trout pellets 743 fundus 480 horses 658
trypan blue 191 horses 618 after surgery 464
Trypanosoma evansi 415 trauma 639 cats 579–586
tuberculosis lens 205–206 fungal 584
feline 547–548 optic nerve 530 investigations 580
macaques, uveitis 732 orbit 207, 222 viral 827
tubocurarine 751 pachymetry 201 cattle 688
tubular globe 749 physics 203 causes 399, 400b, 410–418,
enucleation 758 posterior segment 206–207 580–585
tubuloacinar gland, nictitating retinal detachment 206–207, 456 chronic 401, 465
membrane 303–304 trauma 418, 639 horses, 632, 650–654. See also
tulathromycin, infectious bovine vitreous 205, 206, 471 equine recurrent uveitis
keratoconjunctivitis ultraviolet filtering 92 infections 805
678, 679 ultraviolet light. See also entries lens‐induced 85, 383, 410–411,
tunica vasculosa lentis (TVL) 9, 11, beginning solar. . . 447–448, 518
429–430, 469 camelids, adaptations 706 listerial keratoconjunctivitis 674
persistent 431–433, 473, 474 hemangiosarcoma 297 lymphoplasmacytic 588
tunica vasculosa retinae 734 Moraxella bovis 676 macaques, tuberculosis 732
Index 899

phacoclastic 410, 420, 446–447, horses 606, 658–659 systemic 796, 806–808
448 pigs 705 virtual images 93
pigs 705 sheep 701 viruses. See also viral infections
posterior, 507–508, 846g sclera 33 in fluorescein 187
rabbits 729 vascular tumors, cats, conjunctiva structure 136
sheep and goats 701 562 viscoelastic, removal 463
signs 402–406 vascularization viscoelasticity, vitreous 87
toxoplasmosis 824 cornea 318, 629 viscosity, drug delivery polymers
uveodermatological syndrome 262, infectious bovine 121–122
385, 411–412, 508, 795 keratoconjunctivitis vision 89–113
uveoscleral outflow 45–46, 81 cornea 678 assessment 168–170, 528, 769
nonconventional pathway 78–79 limbus 677 birds 751
prostaglandin analogues 156 vasculitis, Rocky Mountain spotted behavioral testing 478
fever 415 blue‐eyed white cats 577
v vecuronium bromide cataracts on 447
V1 (striate cortex) 103 bird mydriasis 751 data processing 104
vaccines reptile mydriasis 739 retinal disparity 108–109
allergic reactions 548 venous drainage electrodiagnostic testing 210–213
bluetongue virus 842 on intraocular pressure 79 fish 734–735
Bordetella bronchiseptica 560 iris 37 history‐taking 164
calicivirus 824 lens 9 hypertensive retinopathy 599
canine adenoviruses 317, ventricular fibrillation, oculocardiac monocular 13, 107, 108
415–416, 807 reflex 89 neurology 100–103
corneal edema 317, 415–416 venules, retina 484 ultraviolet 90, 110, 750
Chlamydia felis 558 cattle 690, 691 aphakia 92
feline calicivirus 560 Veratrum californicum 695 visual acuity 110–111, 112–113
infectious bovine vergence (refraction) 92–93 after retinal detachment
keratoconjunctivitis 680 vergence eye movements 88 surgery 524–525
leishmaniasis 804 vervet monkeys, cataracts 747 visual evoked potentials 210, 481,
leptospirosis 654 vestibular system 763 530–531
vagus nerve, oculocardiac reflex 89 vestibulo‐ocular reflex (VOR) 88, optic neuritis 535
valacyclovir 137, 567 170, 768–769 visual fields 107, 108
vancomycin 128 vestibulocochlear nerve 773 visual pathways, 768. See also
Vannas scissors, phacoemulsification vibrissae, 20, 850g decussation of optic
461 dogs 240 nerve fibers
varices 223 horses 61 disorders, 533–534. See also
vasa hyaloidea propria 469 vidarabine 566 neuro‐ophthalmology
vascular endothelial growth factor Vienna study, glaucomas 356 Siamese cats 780
receptors 318 Vietnamese Pot‐bellied pigs 704, 705 projection errors 89, 780, 813
vascular loops, preretinal 474 viral infections testing 528
vascular system 58 birds 753 visual photometers 91
choroid 47–48 caiman 740 visual placing 769
ciliary body 42–43 cats 824–827 visual streak 55
ciliary processes 41 blepharitis 547 vitamin A (parenteral) 743
color Doppler ultrasound chorioretinitis 598 vitamin A deficiency 810
209–210 cattle, squamous cell birds 755
congenital anomalies 223 carcinoma and 681 cattle 692–693, 844
rodents 720 dogs 415–416 chelonians 743
conjunctiva 291 chorioretinitis, 506b dogs 510
development 9–10 conjunctivitis 293–294 pigs, maternal 703
endothelium 11 keratitis 336–337 vitamin B complex, dosage for
eyelids, blood supply 241 retinal dysplasia 490 cats 830
functions 71–73 equine viral encephalomyelitis 782 vitamin E deficiency 503, 510, 662,
iris 36 exotic mammals 745 810–811, 835–836
reptiles 739 fish 735 vitiligo, Vogt–Koyanagi–Harada‐like
lens, congenital anomalies 429–433 horses, keratitis 642–645 syndrome 411
optic nerve head 526–527 kangaroos 746 vitrectomy, 472. See also pars plana
retina 57–58, 71, 484 lymphocytic choriomeningitis vitrectomy
camelids 712–713 (LCM) 720 criteria 522
cats 593 nonhuman primates 732 equine recurrent uveitis 653–654
cattle 690, 691 rodents 717–718 giant retinal tears 521–522
dogs 510–511 sheep and goats, eyelids 697 probes 523
900 Index

vitreoretinal dysplasia, retinal water hemlock 694 Miniature Schnauzer 417


detachment 518 water quality, for pinnipeds 759 xerophthalmia, 850g
vitreous, 52–53. See also intravitreal water‐bath technique, XLPRA1 mutation 501
drug injection ultrasonography 204 xylazine 165, 604, 706
cats 594 water‐cleft formation 446 xylitol, toxicity 443
development 12 watershed zones 72, 364
disorders 472–477 wavelengths of light 90 y
displacement, lens luxation wedge resection Y to V plasty (Wharton–Jones) 250
and 381 ectropion 254–255, 266 yeasts 132
dogs 469–478 entropion 544 Yorkshire pigs, microphthalmia 703
elongation 86, 96 Weill Marchesani syndrome 360 Yucatan Micropigs, cataracts 705,
examination 173 Welsh Springer Spaniel 731
hemorrhage 476 cataracts 440, 441
after cataract surgery 464 glaucomas 379
cats 594 West Highland White Terriers,
z
zonulae occludentes 10, 73, 115, 317
dogs 476 cataracts 433, 439, 441
zonular attachment of lens, 51–52,
horses 661 West Nile virus 753, 782–783, 840
426, 448, 449, 454. See also
horses 659–661 western hellebore (Veratrum
luxation of lens; subluxation
IOP elevation on 367 californicum) 695
accommodation 95
malignant glaucoma 384 Wharton–Jones Y to V plasty 250
instability 467–468
miniature pigs 731 white cats. See also blue‐eyed
vitreous and 477
morphology 469–470, 515–516 white cats
zonular fibers 12
osmotic agents on 158–159 uveal pigmentation 575–577
deficiency 429
paracentesis 196–197 white pigment gene 576
degeneration 382
physiology 85–87 white spotting gene 785
zonule of Zinn 428
refraction 94 Wieger’s ligament 470
zonules, 850g
retinal detachment 474, 478, 518 wild corn (Veratrum
zonulolysis, 850g
surgery 471–472 californicum) 695
zoonotic disease
ultrasonography 205, 206, 471 Wilson’s disease, Cooper
bartonellosis 818
vitreous strands, lens luxation 454 abnormalities 444
brucellosis 798
Vogt–Koyanagi–Harada‐like with‐the‐rule astigmatism 99
equine viral encephalomyelitis
syndrome 262, 385, Wolfring glands, 21, 23, 850g
840
411–412, 508, 795 woodpecker, vitreous 87
herpesvirus simiae B 732
vomiting World Trade Center attacks, working
leptospirosis 798
cholinergic antagonists and 145 dogs 296
Zurich, glaucoma epidemiology
glycerin 159 wound healing, cornea 30, 312–315,
357
voriconazole 133, 135, 136, 337, 629
zygomatic gland
635 corticosteroids on 140
dogs
vortex veins 26, 37, 47 Wyman lateral canthoplasty 250
cysts 289
Vossius ring 446 Wyman pedicle, entropion 250
infections 224
mucoceles 226, 300
w x orbitotomy to access 237
W gene 812 X‐linked progressive retinal ferrets 723
wallabies 746 atrophy 501 guinea pigs 720
walruses 759 gene and breeds 852 zygomatic nerve 770
warmblood horses, inherited eye Siberian Husky 500, 501 blockade 166, 167, 606
diseases 854 xanthogranuloma zygomatic sialography 198
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