Essentials of Veterinary Ophthalmology 4th Edition
Essentials of Veterinary Ophthalmology 4th Edition
Fourth Edition
Edition History
Lippincott, Williams, and Wilkins (1e, 2001); Blackwell Publishing (2e, 2008); John Wiley and Sons Inc (3e, 2014)
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Contents
Preface vii
Acknowledgments ix
About the Companion Website xi
18 Neuro-ophthalmology 763
Glossary 845
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
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
www.wiley.com/go/gelatt/essentials4e
Section 1
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
Gestational Gestational
Ocular part or event size (mm) Ocular part or event size (mm)
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
Surface ectoderm
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
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
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
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).
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
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
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.
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
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
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×.)
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
Lacrimal
ducts Canaliculi
Lacrimal
sac
Nasolacrimal
duct
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
(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
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×.)
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
(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
(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×.)
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.
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
(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
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×.)
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×.)
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
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
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
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
Optic Nerve
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
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
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.
Table 2.3 Elastic moduli of layers of the cornea as determined by atomic force microscopy in rabbits
and humans.
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.
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
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
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+
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
ea
rn Anterior Chamber
Co
Iris
AAP
SVP
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
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)
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
IOP results
IOP results
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
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
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
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.
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
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
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
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
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
CULAR VISIO
BINO N
65°
UNIOCU AR VISION
UNI
OCULA
146°
146°
L
R VISION
3°
B LI N D A R E A
(a)
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
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.
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)
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
Topical Administration
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
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
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
Time
FIRST ORDER KINETIC
Ophthalmic insert
Drug Concentration
Dose
Time
ZERO ORDER KINETIC
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
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
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)
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
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.
Table 3.3 Summary of Selected Topically Administered Antiviral Drugs for Treatment of Feline Herpesvirus.
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
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
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
Route/agent Indications/dose
and carprofen are classified as selective sometimes systemic anti-PG therapies are nec-
COX-2 inhibitors. essary for mydriasis to occur.
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.
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.
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.
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.
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
50
Intraocular Pressure (mmHg)
40
30
20
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.
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
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
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)
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
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
(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.
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
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
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.
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
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
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
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.
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
(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
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).
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.
(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.
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
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.)
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
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
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.
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.
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.
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
(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.
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
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
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.
(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
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
Table 5.2 Recommended treatment and prognosis for traumatic proptosis in dogs.
(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.
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.
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.
(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
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
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
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
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).
Distichiasis
and Conjunctival
Ectopic Cilia
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
(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,
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
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
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
(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.
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
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
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
(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
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
If positive:
Medial lower entropion
Lacrimal punctum obstruction:
inflammatory
Lacrimal micropunctum/displacement
Dacryocystitis
Nasolacrimal duct obstruction
Figure 7.1 Strategy and procedures for diagnosis and treatment of nasolacrimal (drainage) disease.
(a)
Clinical Manifestations
of Nasolacrimal Disease
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
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
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 7.10 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
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
Viscosity agents/
Product concentration(s) Preservative Source
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
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
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
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.
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
Suspect keratoconjunctivitis sicca (KCS) Stain with fluorescein (observe any cornea, or conjunctiva
retention, and nasolacrimal passage)
Conjunctival cytology
Figure 8.2 Clinical strategy for the diagnosis and treatment of conjunctivitis of the dog.
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.
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
onjunctival Manifestations
C
of Systemic Disease
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
Topical antibiotics/mydriatics.
Figure 8.17 Strategy for diagnosis and treatment of protrusion of the NM.
Inflammatory Condition 307
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
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
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
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
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
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
Table 9.3 Antiproteolytic agents for topical treatment of melting corneal ulcers.
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
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
(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
(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
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
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
(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.
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
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.
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
(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
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,
(a) (b)
Figure 9.34 (a) Bilateral corneal lymphosarcoma in a dog. (b) Closer image of the right cornea.
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
(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
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
10
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
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
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.
(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.
(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
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)
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
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
(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
(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.
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.
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
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
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
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
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
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
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
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
reatment of End-Stage
T
Primary Glaucomas
11
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
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
Miscellaneous Rickettsial
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
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.
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
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
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.
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
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.
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
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
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
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
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
Infantile
Nucleus
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)
Table 12.2 Canine breeds affected by PHPV/PHTVL causing lens opacification with possible mode
of inheritance.
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.
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.
(>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
Table 12.5 Canine breeds affected with PLL mode of inheritance and genetic test available.
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-
●●
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
(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
Handpiece Body
0°
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
(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
(h) (i)
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
(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
13
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
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
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
Methods of Examination
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
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
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.
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
(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
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
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.
Lesion Appearance
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
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
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
(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.
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.
(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
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.
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.
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
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
Mode of Diagnosis by
Breed Primary defect inheritance ophthalmoscopy Diagnosis by ERG
ERG, electroretinography.
Other Generalized Retinopathies/Retinal Dystrophie 501
(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.
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.
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
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
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
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
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
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
(a) (b)
Figure 13.33 Sonograms of canine eyes with RD. (a) Partial RD. (b) Complete detachment.
(a) (b)
Figure 13.34 Degenerative vitreous characterized by corkscrews, tendrils, and pigment. (a) Clinical
photograph. (b) Intraoperative view through silicone lens.
(a) (b)
Figure 13.36 Retinal radial tears. (a) Before laser treatment. (b) After laser treatment.
(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).
uccess of Retinal
S
Detachment Repair
(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
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.
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
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.
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
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
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
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
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
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.
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
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
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
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.
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
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
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
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
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
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
(a) (b)
Corneal Diseas 573
(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)
(a) (b)
(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
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.
(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
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
(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
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
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
(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.
(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
(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
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
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
(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
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.
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
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.
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
(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
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
(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
(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)
(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
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
Figure 15.14 Periorbital sinuses. The frontal (conchofrontal), maxillary (caudal and rostral), and
sphenopalatine are in close anatomical proximity to the orbit.
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
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
(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.
Reported %
Type of therapy Treatment Therapy non-recurrence
(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.
Reported %
Type of therapy Treatment Therapy non-recurrence
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
(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.
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)
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
(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.
(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)
(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
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
(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.
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
(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-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
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).
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
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
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
(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
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.
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
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
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
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
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
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.
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.
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
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).
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.
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.
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.
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.
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.
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
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.
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
17
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
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
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
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
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
(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.
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
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
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
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
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
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
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
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
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
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
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
18
Neuro-ophthalmology
Revised from 6th edition of Veterinary Ophthalmology, Chapter 36: Neuro-ophthalmology, by Aubrey A. Webb and Cheryl L. Cullen
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)
Ventral oblique
(CN III)
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
Muscles of blink
Pretectal nucleus
Parasympathetic
nucleus of CN III
Nucleus of Cajal
Facial nerve
Facial
nucleus
Optic nerve
(CN II)
Optic chiasm
Optic tract
Lateral
geniculate
nucleus
Optic
radiations
Occipital
(visual) cortex
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
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
First-, second-,
Neuroanatomical or third- Possible concurrent
location order disease clinical signs Potential causes
First-, second-,
Neuroanatomical or third- Possible concurrent
location order disease clinical signs Potential causes
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
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
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
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
Developmental
(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.
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
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.
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
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
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
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
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
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
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
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
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
(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
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.
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.
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.
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
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.
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.
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
(b)
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
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
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).
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).
Appendix A
Table A.1 Genes associated with inherited ophthalmic diseases in the dog.a
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
(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.
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852 Appendix A Inherited Ophthalmic Diseases in the Dog
Appendix B
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
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
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.
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856
Appendix E
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.
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Appendix E Lysosomal Storage Diseases in the Dog, Cat, and Food Animals 857
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
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
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
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.
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
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
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
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
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
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
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
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
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
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