INTRAOCULAR PRESSURE

AND AQUEOUS HUMOR

DYNAMICS
Glaucoma Unit
Introduction
◦ Aqueous humor (aqueous) is produced by ciliary epithelium in the posterior chamber and flows through
the pupil into the anterior chamber.
◦ Aqueous humor exits the eye by passing through conventional pathway ;the trabecular meshwork and
into the Schlemm canal before draining into the venous system through a plexus of collector channels.
◦ Some aqueous exits the eye via the uveoscleral pathway, which is proposed to pass through the root of
the iris and the ciliary body face, into the suprachoroidal space. The proportion of aqueous flowing
through the trabecular pathway versus the uveoscleral pathway varies as a result of multiple factors.
 ◦ Goldmann equation
P0 = (F – U)/C + Pv
P0 : IOP in mm Hg
F : rate of aqueous formation
U : rate of aqueous humor drainage
through the pressure-insensitive
uveoscleral pathway
C : outflow through the pressure-
sensitive trabecular pathway
Pv : episcleral venous pressure
Resistance to outflow (R) is the
inverse of facility (C).

Figure 2-1 The effect of outflow facility on intraocular pressure (IOP),

based on the modified Goldmann equation (assuming a constant aqueous
humor production rate of 2.5 μL/min, uveoscleral outflow rate of 35%, and episcleral
venous pressure of 7 mm Hg). (Courtesy of Arthur J. Sit, MD.)
 Aqueous Humor Production
◦ Production : at ciliary process.
Ciliary body contain 80 ciliary process, which has outer pigmented and
inner nonpigmented epithelial cell layer. The inner nonpigmented
epithelial cells contain numerous mitochondria and microvilli; these
cells are thought to be the actual site of aqueous production.
Rate : 2-3 μL/min
◦ Aqueous humor enters the posterior chamber via the following
physiologic mechanisms:
1.Active secretion
2.Ultrafitration
3.Simple diffusion
◦ Active secretion : transport that requires energy to move sodium, chloride, bicarbonate, and other
ions, against an electrochemical gradient. Active secretion is independent of pressure and accounts
for the majority of aqueous production. It involves, at least in part, activity of the enzyme carbonic
anhydrase II.

◦ Ultrafiltration : pressure-dependent movement along a pressure gradient. In the ciliary processes, the
hydrostatic pressure difference between capillary pressure and IOP favors fluid movement into the
eye, whereas the oncotic gradient between the two resists fluid movement.

◦ Diffusion : the passive movement of ions, based on charge and concentration, across a membrane.
 Aqueous Humor Composition
 Hydrogen , chloride ions, ascorbate ↑ relative to plasma
 Bicarbonate ↓ relative to plasma
 Protein free (1/200–1/500 of the protein found in plasma)  optical clarity and reflecting the
integrity of the blood–aqueous barrier of the normal eye. Albumin accounts for approximately
half of the total protein.
 Other components of aqueous humor : growth factors; several enzymes, such as carbonic
anhydrase, lysozyme, diamine oxidase, plasminogen activator, dopamine β-hydroxylase, and
phospholipase A2; and prostaglandins, cyclic adenosine monophosphate, catecholamines, steroid
hormones, and hyaluronic acid.
 Suppression of Aqueous Formation
 Inhibition of the enzyme carbonic anhydrase  suppresses aqueous humor formation.
Carbonic anhydrase may also provide bicarbonate or hydrogen ions for an intracellular
buffering system.
 Blockade of β2-receptors : adrenergic receptors in the ciliary epithelium can affect active
secretion by causing a decrease either in the efficiency of Na+,K+-ATPase or in the number of
pump sites.
 Stimulation of α2-receptors : via a reduction of ciliary body blood flow mediated through
inhibition of cyclic adenosine monophosphate (cAMP).
 Measurement of Aqueous Formation
 The most common method used to measure the rate of
aqueous formation is fluorophotometry.
 Steps :
1. Fluorescein is administered systemically or topically
2. Its gradual dilution in the anterior chamber is measured
optically
3. Change in fluorescein concentration over time is then used
to calculate aqueous flow.
Rate of the normal flow is approximately 2–3 μL/min, and the
aqueous volume is turned over at a rate of approximately 1%
per minute.
◦ The rate of aqueous humor formation varies diurnally and decreases by half during sleep. It also
decreases with age.

The rate of aqueous formation is affected by a variety of factors, including the following:
1. Integrity of blood-aqueous barrier
2. Blood flow to ciliary body
3. Neurohormonal regulation of vascular tissue and the ciliary epithelium
 AQUEOUS HUMOR OUTFLOW
Aqueous humor outflow occurs by 2 major mechanisms:
- pressure-sensitive trabecular outflow
- pressure-insensitive uveoscleral outflow.
 Trabecular Outflow
The trabecular meshwork is classically divided into 3
layers: uveal, corneoscleral, and juxtacanalicular .

The uveal trabecular meshwork is adjacent to the anterior

chamber and is arranged in bands that extend from the iris
root and the ciliary body to the peripheral cornea.

The corneoscleral meshwork consists of sheets of

trabeculum that extend from the scleral spur to the lateral
wall of the scleral sulcus.

The juxtacanalicular meshwork, which is thought to be

the major site of outflow resistance, is adjacent to and
actually forms the inner wall of the Schlemm canal.
Aqueous moves both across and between the endothelial
cells lining the inner wall of the Schlemm canal.
The trabecular meshwork is the site of pressure-sensitive outflow and functions as a one-way valve, permitting
aqueous to leave the eye by bulk flow but limiting flow in the other direction, independent of energy. Its cells are
phagocytic.

The Schlemm canal is completely lined with an endothelial layer that rests on a discontinuous basement membrane.
The canal is a single channel, typically with a diameter of about 200–300 μm, although there is significant
variability; it is traversed by tubules.
Schlemm canal has inner and outer wall.

The inner wall have intracellular and intercellular pores suggest bulk flow, while so-called giant vacuoles that have
direct communication with the intertrabecular spaces suggest active transport but may be artifacts.

The outer wall of the Schlemm canal is formed by a single layer of endothelial cells that do not contain pores. A
complex system of vessels connects the Schlemm canal to the episcleral veins, which subsequently drain into the
anterior ciliary and superior ophthalmic veins. These, in turn, ultimately drain into the cavernous sinus.
 Measurement of Outflow Facility
◦ Tonography is a method used to measure the facility of aqueous
outflow.
◦ Steps :
1. A weighted Schiøtz tonometer or pneumatonometer is placed on the
cornea, acutely elevating the IOP.
2. Outflow facility in μL/min/mm Hg can be computed from the rate at
which the pressure declines with time, reflecting the ease with which
aqueous leaves the eye. Mean value ranging from 0.22 to 0.30
μL/min/mm Hg.

◦ Outflow facility decreases with age and is affected by surgery,

trauma, medications, and endocrine factors. Patients with glaucoma
and elevated IOP typically have decreased outflow facility.
 Uveoscleral Outflow
◦ Uveoscleral outflow  pressure-insensitive outflow.
Aqueous passage from the anterior chamber  ciliary muscle  supraciliary and suprachoroidal spaces 
The fluid then exits the eye through the intact sclera or along the nerves and the vessels that penetrate it.
There is evidence that outflow via the uveoscleral pathway is significant in human eyes, accounting for up to
45% of total aqueous outflow.
Uveoscleral outflow decreases with age, miotics and is reduced in patients with glaucoma.
It is increased by cycloplegia, adrenergic agents, and prostaglandin analogues. It is also increased by certain
complications of surgery and by cyclodialysis clefts.
 Episcleral Venous Pressure
◦ Episcleral venous pressure (EVP) is relatively stable, except with alterations in body position and with certain
diseases.
Episcleral venous pressure is often increased in syndromes with facial hemangiomas (eg, Sturge-Weber), carotid-
cavernous sinus fistulas, and cavernous sinus thrombosis, and it is partially responsible for the elevated IOP seen in
thyroid eye disease.
The pressure in the episcleral veins pressure has usual range of values is 6–9 mm Hg,.
However, elevation of EVP may alter other parameters of aqueous humor dynamics. Abnormally elevated EVP can
cause collapse of the Schlemm canal and potentially increase aqueous humor outflow resistance; elevated EVP may
also alter uveoscleral outflow.
Intraocular Pressure
◦ The value 21 mm Hg was traditionally used both to separate normal and abnormal pressures and to
define which patients required ocular hypotensive therapy.
◦ There is no clear IOP level below which IOP can be considered “normal” or safe and above which IOP
can be considered “elevate” or unsafe.
◦ In some eyes, damage occurs with IOP levels of 18 mmHg or lower – in other eyes, IOPs ≥ 30 mmHg are
tolerated
◦ However, elevation of IOP is considered a very important risk factors for glaucoma.
Factors
Influencing
IOP
Circadian Variation
◦ Individual w/out glaucoma: IOP varies 2-6 mmHg over 24 hours
◦ In many persons, peak daytime pressures are reached in the morning.
◦ However, around-the-clock IOP measurement performed with individuals in habitual body positions
(standing or sitting during the daytime and supine at night) indicates that in most persons (those with
glaucoma and those without) peak pressures are reached during sleep, in the early-morning hours.
 Tonometry
Noninvasive measurement of IOP. Applanation

Clinical
tonometry, the most widely used method, is based on
the Imbert-Fick principle, which states that the pressure
inside an ideal dry, thin-walled sphere equals the force
Measurement necessary to flatten its surface divided by the area of the
flattening:

of IOP P = F/A
(where P = pressure, F = force, and A = area)
Clinical Measurement
of IOP
◦ The Goldmann applanation tonometer
(measures the force necessary to flatten an area
of the cornea of 3.06 mm in diameter. At this
diameter, the material resistance of the cornea
to flattening is counterbalanced by the capillary
attraction of the tear film meniscus to the
tonometer head.

◦ Furthermore, the IOP (in mm Hg) equals the

flattening force (in grams-force) multiplied by
10. A split-image prism allows the examiner to
determine the flattened area with great
accuracy.
 Clinical
Measurement of IOP
◦ To outline the area of flattening,
topical anesthetic and fluorescein dye
are instilled in the tear film.
Fluorescein semicircles, or mires, visible
through the split-image prism move with
the ocular pulse, and the endpoint is
reached when the inner edges of the
semicircles touch each other at the
midpoint of their excursion.

◦ By properly aligning the mires, the

examiner can ensure the appropriate
area of corneal applanation and obtain
a correct IOP reading
Clinical Measurement of IOP
◦ Applanation measurements are safe, easy to perform, and relatively accurate in most clinical situations.
◦ Of the currently available devices, the Goldmann applanation tonometer is the most widely used in
clinical practice and for studies. Because applanation does not displace much fluid (approximately 0.5
μL) or substantially increase the pressure in the eye, IOP measurement by this method is relatively
unaffected by ocular rigidity, compared with indentation tonometry.
Possible Errors in Tonometry
Tonometry and central corneal thickness

◦ Measurements obtained with the most common types of tonometers are affected by central corneal
thickness (CCT). Measurement with the Goldmann tonometer is most accurate when the CCT is 520 μm.
◦ Thicker corneas resist the deformation inherent in most methods of tonometry, resulting in an
overestimation of IOP, while thinner corneas may give an artificially low reading.
Methods other than Goldmann-type
applanation tonometry
◦ Mackay-Marg-type tonometers use an annular ring to gently flatten a small area of the cornea. As the
area of flattening increases, the pressure in the center of the ring increases as well and is measured with a
transducer. The IOP is equivalent to the pressure when the center of the ring is just covered by the
flattened cornea.
◦ Portable electronic devices of the Mackay-Marg type (eg, Tono-Pen, Reichert Technologies, Depew,
NY) contain a strain gauge to measure the pressure at the center of an annular ring placed on the cornea.
These devices are particularly useful for measuring IOP in patients with corneal scars or edema.
Methods other than Goldmann-type
applanation tonometry
◦ Pneumatic tonometer, or pneumatonometer, is an applanation tonometer that shares some characteristics
with the Mackay-Marg-type devices. It has a cylindrical air-filled chamber and a probe tip covered with a
flexible, inert silicone elastomer (Silastic membrane) diaphragm. Because of the constant flow of air
through the chamber, there is a small gap between the diaphragm and the probe edge. As the probe tip
touches and applanates the cornea, the air pressure increases until this gap is completely closed, at which
point the IOP is equivalent to the air pressure. Because this instrument covers only a small area of the
cornea, it is especially useful in eyes with corneal scars or edema
Methods other than Goldmann-type
applanation tonometry
◦ Dynamic contour tonometer, a newer type of nonapplanation contact tonometer, is based on the principle
that when the surface of the cornea is aligned with the surface of the instrument tip, the pressure in the
tear film between these surfaces is equal to the IOP and can be measured by a pressure transducer.
Evidence suggests that IOP measurements obtained with dynamic contour tonometry are more
independent of corneal biomechanical properties and thickness than those obtained with older
tonometers.
 ◦ Noncontact (air-puff) tonometers determine IOP
by measuring the force of air required to indent
the cornea to a fixed point, thereby avoiding
contact with the eye. Readings obtained with
these instruments vary widely, and IOP is often
Methods other than overestimated. Noncontact tonometers are often
used in large-scale glaucoma-screening
Goldmann- programs or by nonmedical health care
type applanation providers

tonometry
 ◦ The Ocular Response Analyzer (ORA; Reichert
Technologies, Depew, NY) is a type of noncontact
tonometer that uses correction algorithms so that its
IOP readings more closely match applanation IOPs
and the effect of corneal biomechanical properties on
pressure measurement is reduced.
Methods other than ◦ In addition, indicators of ocular biomechanical
Goldmann- properties are calculated, including corneal hysteresis
and corneal resistance factor. Corneal hysteresis is the
type applanation difference in IOP measured during the initial corneal
tonometry indentation and IOP measured during corneal
rebound.
 ◦ Rebound tonometry determines IOP by measuring the speed
at which a small probe propelled against the cornea
decelerates and rebounds after impact. Rebound tonometers
are portable, and topical anesthesia is not required, making
them particularly suitable for pediatric populations. The
Methods other current instrument should be used upright.

than Goldmann- ◦ Schiøtz tonometry determines IOP by measuring the amount

of corneal indentation produced by a known weight. The
type applanation amount of indentation is read on a linear scale on the
tonometry instrument and converted to mm Hg by a calibration table.
Due to a number of practical and theoretical problems,
Schiøtz tonometry is now rarely used in the developed world.
• Tonometers must be cleaned after each use so that the
transfer of such agents can be prevented.
• For Goldmann-type tonometers and the Perkins
tonometer, the tonometer tips (prisms) should be cleaned
immediately after use. Infection
• The prisms should be soaked in a 1:10 sodium
hypochlorite solution (household bleach), in 3% hydrogen
control in
peroxide, or in 70% isopropyl alcohol for 5 minutes and
rinsed and dried before reuse. If alcohol is employed, it
clinical
should be allowed to evaporate or the prism head should
be dried before reuse to prevent damage to the corneal
tonometry
epithelium.
• For cleaning other tonometers, refer to the manufacturer’s
recommendations.