Vet Clin Exot Anim 5 (2002) 391–406

Intraocular pressure and glaucoma

Ron Ofri, DVM, PhD
Department of Clinical Sciences, Koret School of Veterinary Medicine,
Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel

Production and drainage of aqueous humor

Anatomy of aqueous production and outflow pathways
Aqueous humor is produced in the ciliary body. In most mammalian spe-
cies, it is produced by the ciliary processes, which are specialized folds and
convolutions of the ciliary body. The number and size of processes vary
between species and usually are related directly to the depth of the anterior
chamber. Large herbivores such as the horse have over 100 large proces-
ses, whereas smaller carnivores have 75 medium-sized processes. Primitive
vertebrates, including many fishes, snakes, and lizards, and the mammalian
shrew do not possess ciliary processes; in these species, aqueous humor is
produced by the ciliary roll [1–4].
Aqueous humor exits the eye through two major pathways. Conventional
outflow of the aqueous humor is through the iridocorneal angle, a structure
formed by the junction of the peripheral cornea, limbal sclera, base of the
iris, and anterior part of the ciliary body. This angle opens into a meshwork
of progressively smaller pores through which the aqueous humor percolates;
it then drains out of the eye through a small plexus of collecting veins. Alter-
natively, an unconventional pathway drains the aqueous humor through the
ciliary body and anterior uvea into the suprachoridal space and sclera.
There are numerous interspecies variations in the anatomy of the irido-
corneal angle and its associated structures. These variations have been
reviewed extensively elsewhere [1,3–5]. Generally, many variations stem
from differences in the lifestyle (eg, nocturnal versus diurnal, herbivores ver-
sus carnivores) and ocular accommodative abilities of the different species.
Poor (or nonexistent) lenticular accommodation in herbivores is associated
with a poorly developed ciliary-body muscle and a concomitantly large iri-
docorneal angle [4]. Carnivores have a more developed ciliary muscle and

E-mail address: [email protected] (R. Ofri).

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392 R. Ofri / Vet Clin Exot Anim 5 (2002) 391–406

smaller drainage angle, whereas primates have the smallest angle and most
developed ciliary muscle [4]. Raptors have a deep angle, with ciliary processes
attached directly to the lens; additional accommodation of the lens and cor-
nea is achieved through skeletal muscles that are unique to avians [6,7].

Physiology of aqueous production and outflow

The substrate for the formation of aqueous humor is the blood that cir-
culates through the capillaries of the ciliary processes. Aqueous humor is
transported actively in pinocytotic vesicles from the ciliary epithelium into
the posterior chamber. Small amounts of aqueous humor are produced
through diffusion and ultrafiltration. Sympathetic and parasympathetic in-
nervation, intraocular pressure (IOP), and various hormones have a role in
regulating aqueous formation. Carbonic anhydrase is a key enzyme in this
production process and is a target for therapeutic intervention aimed at re-
ducing aqueous production and IOP [8].
The resulting aqueous humor is a transparent fluid that has a composition
resembling that of plasma ultrafiltrate. The concentrations of proteins, immu-
noglobulins, enzymes, and lipids are usually lower than those in serum, where-
as concentrations of components that are regulated through active transport,
such as amino acids and ascorbate, are usually higher than those in serum.
There are many interspecies differences in the composition of aqueous humor;
these differences usually result from the different metabolic requirements of
the cornea and lens between species. Other alterations in the composition of
aqueous humor result from uveitis; the breakdown in the blood–aqueous bar-
rier that is characteristic of the inflammatory process leads to an increase in
the concentration of proteins and other inflammatory substances.
The aqueous humor flows from the posterior chamber, through the pupil,
and into the anterior chamber. As the fluid circulates in the anterior segment
of the eye, it provides nutrients to the avascular cornea and lens and removes
waste products. Eventually, it exits the eye through the two pathways pre-
viously described. The relative contribution of the unconventional uveoscl-
eral pathway to the total outflow varies between species. It is 3% of the total
outflow in cats, 15% in dogs, and higher in horses and nonhuman primates [8].
These latter species may be less susceptible to forms of glaucoma that are
caused by narrowing and closure of the iridocorneal angle, because these spe-
cies have a safety valve in the unconventional pathway. In cases of angle clo-
sure, members of these species can drain large amounts of fluid through the
unconventional pathway.

IOP
Interspecies differences
In normal animals, the rate of aqueous formation equals the rate of
aqueous drainage, resulting in a steady-state IOP; however, interspecies
 R. Ofri / Vet Clin Exot Anim 5 (2002) 391–406 393

differences exist regarding the rate of aqueous formation, outflow through

the iridocorneal and uveroscleral pathways, and episcleral venous pressure
(responsible for resistance to the conventional outflow). This variability may
be the result of anatomic differences (eg, aqueous formation is dependent on
the volume of the anterior chamber) or metabolic differences (eg, high meta-
bolic requirements of anterior segment organs in cats cause increased flow
rates). Normal IOP values differ among various species, and range from
7.6 mm Hg in Thomson gazelles (Gazella thomsoni) [9] to 29.5 mm Hg in
Grant zebras (Equus bruchelli) [10].
Table 1 lists baseline IOP values measured in a number of wildlife species.
It is impossible to extrapolate normal values from one species to another,
even if the two species are closely related. In the Bovidae family, IOP ranges
from 7.6 mm Hg in Thomson gazelles [9] to 14.6 mm Hg in elands [11]. A
similar range of 100% is seen in different raptor species [12]. IOP may be
affected by numerous factors, including age, time of measurement, instru-
ment used, and sexual status (see later in article). For tonometry (measure-
ment of IOP) to be diagnostic, it is important to determine reference values
for each species, taking into account potential confounding factors.

Affecting factors
Methods of measuring IOP are described in a subsequent section. IOP
may be influenced by a number of short- and long-term factors. Probably
the most relevant short-term factor in wildlife work is anesthesia. IOP is
affected by skeletal factors, such as tone of extraocular muscles, closure of
eyelids, and retraction of the retractor bulbi muscle. Anesthetic agents that
cause muscle relaxation may decrease IOP, whereas drugs that increase
muscle tone may elevate IOP. Anesthesia also may exert an effect on IOP
through hemodynamic factors. Decreased blood pressure during anesthesia
leads to decreased aqueous production and increased aqueous outflow,
resulting in lower IOP; however, the effect of anesthesia on IOP is not
predictable. Ketamine increases IOP in cats [13], but lowers it in rats [14]
and has no effect in humans [15]. In lions, no differences in IOP values
were noted using four different anesthetic protocols [16].
The diurnal cycle can affect IOP. Although the time of measurement had
no influence on IOP readings in llamas and alpacas [17], rhythmic fluctua-
tions in the level of adrenocorticosteroids may affect pressure. In dogs (and
humans), IOP tends to peak during the morning and decrease in the after-
noon [8]. In cats, IOP peaks at night and decreases in the morning [8].
Intraocular pressure is also subject to long-term changes. Age has been
shown to be a determining factor in species ranging from American alliga-
tors [18], dogs, and humans. Gender and reproductive status have been
shown to influence IOP in lions, an effect that may have been mediated
by progesterone levels. Other long-term factors that may affect IOP include
obesity, season, and breed [19].
394 R. Ofri / Vet Clin Exot Anim 5 (2002) 391–406

Table 1
Reference IOP values in selected wildlife speciesa
Species IOPb (mm Hg) Reference
Herbivores
Alpaca (Lama pacos) 14.9  0.5 [17]
Arabian oryx (Oryx leucoryx) 22.7  8.2c [10]
11.8  3.4 [10]
Asian fallow deer (Dama mesopotamica) 11.9  3.3 [11]
Eland (Taurotragus oryx) 14.6  4.0 [11]
Grant zebra (Equus bruchelli) 25.3  3.1c [10]
29.5  3.4 [10]
Llama (Lama glama) 13.1  0.4 [17]
Nubian ibex (Capra ibex nubiana) 17.9  4.8c [10]
Thomson gazelle (Gazella thomsoni) 7.6  1.6 [9]
Carnivores
Lion (Panthera leo)
Juvenile males 24.9  2.0c [16]
Adult males 24.4  3.6 [19]
Lion (Panthera leo)
Juvenile females 20.9  2.4c [16]
Luteal adult females 27.1  2.2 [19]
Nonluteal adult females 24.5  2.4 [19]
Primates
Rhesus macaque (Macaca mulatta) 15.8  3.0 [21]
Reptiles
American alligator (Alligator mississippiensis)
Body length \50 cm 23.7  2.1 [18]
Body length [50 cm 11.6  0.5 [18]
Raptors
Bald eagle (Haliaeetus leucocephalus) 20.6  2.0 [12]
Golden eagle (Aquila chrysaetos) 21.5  3.0 [12]
Great horned owl (Bubo virginianus) 10.8  3.6 [12]
Red-tailed hawk (Buteo jamaicensis) 20.6  3.4 [12]
Swainson’s hawk (Buteo swainsoni) 20.8  2.3 [12]
Marine mammalsd
Bottlenose dolphin (Tursiops truncatus) 22–38 [32]
Risso’s dolphin (Grampus griseus) 23–33 [32]
Harbor seal (Phoca vitulina) 10–18 [33]
Sea lion (Zalophus californianus) 8–18 [33]
a
All measurements performed with applanation tonometers, unless otherwise indicated.
b
Mean  SD unless otherwise indicated.
c
Indentation tonometer.
d
Because of the cyclic nature of IOP in these species (in cataceans, the cyclic period is
reportedly 15–25 minutes), range of IOP, rather than mean IOP, is provided.

Glaucoma
Causes and pathogenesis
Traditionally, glaucoma has been defined as an elevation in IOP that
is detrimental to normal ocular function and vision. With improved
 R. Ofri / Vet Clin Exot Anim 5 (2002) 391–406 395

understanding of the neurodegenerative processes that affect retinal gang-

lion cells (RGCs) during the course of the disease, the definition of glau-
coma has been modified to a group of diseases characterized by decreased
RGC sensitivity and function, progressing to RGC death and loss of
optic-nerve axons; these changes result in incremental reduction in visual
function and blindness [20]. This revised definition does not include increases
in IOP, because glaucoma-induced damage can continue after IOP has been
lowered successfully and because some forms of the disease (especially in
primates) may be observed in normotensive patients. Increased IOP is still
the primary risk factor in the pathogenesis of glaucoma, and most forms
of the disease in animals are characterized by ocular hypertension [20].
Theoretically, an elevation in IOP could be the result of increased aque-
ous production or decreased aqueous humor drainage. In practice, however,
the elevation is caused by obstructions in aqueous outflow pathways and
not by increased production. Depending on the nature of the obstruction,
the disease can be classified as primary, secondary, or congenital. All three
forms of the disease have been documented in wildlife species (see next sec-
tion). Primary glaucoma is defined as an elevation in IOP that is not caused
by any concurrent ocular disease. Rather, the disturbances in outflow are
caused by progressive narrowing of the iridocorneal angle or by
biochemical changes in the trabecular meshwork, leading to a reduction
in the volume of aqueous humor that is draining out of the eye. These
diseases typically are inherited, are bilateral, and require life-long medical
treatment (or surgery). In secondary glaucoma, the obstruction to aqueous
outflow is a complication caused by another primary ocular disease. Uve-
itis can cause obstruction of the iridocorneal angle with inflammatory
cells and mediators. Posterior or peripheral anterior synechia could fur-
ther impede aqueous flow from the eye in uveitis. Obstruction of the
angle by vitreous (caused by lens luxation), red blood cells (caused by
hyphema), melanocytes, or intraocular neoplasms results in secondary
glaucoma [20].
Documented causes of secondary glaucoma in wildlife species are dis-
cussed in the next section. Depending on the primary cause, secondary glau-
coma can be unilateral or bilateral and may be resolved with successful
treatment of the primary cause. Congenital glaucoma is the result of mal-
development of the iridocorneal angle or trabecular meshwork, which may
be associated with other ocular or systemic developmental abnormalities.
Another method of classifying glaucoma is based on the iridocorneal
angle. Glaucoma can be classified as open angle if the iridocorneal angle
is normal and obstruction to outflow is at the level of the trabecular mesh-
work or further downstream. Alternatively, the disease can be classified as
narrow angle or angle closure, depending on the distance between the cor-
nea and base of the iris. The two classification methods are complementary
rather than exclusive. An animal may be suffering from primary open-angle
glaucoma (as seen in beagle dogs) or primary narrow-angle glaucoma
396 R. Ofri / Vet Clin Exot Anim 5 (2002) 391–406

(as seen in American cocker spaniels) [20]. Alternatively, an existing ocular

disease could induce secondary open-angle or narrow-angle glaucoma.

Reported cases of glaucoma in wildlife species

Glaucoma has been diagnosed in most domesticated species, including
dogs, cats, horses, cows, chickens, and various rodents; however, there are
only a few reports of glaucoma in wildlife species, which does not mean that
wildlife species are immune from glaucoma. Rather, the paucity of reports
probably stems from the objective problems associated with veterinary care
for wildlife animals—the need for chemical restraint, the relatively small
number of animals that are kept in zoos and receive daily supervision, and
the lack of normal reference IOP values in most species.
Primary glaucomas have been diagnosed in a colony of free-ranging
Rhesus monkeys (Macaca mulatta) living on an uninhabited island near
Puerto Rico [21]. Some of these monkeys are afflicted with normotensive
glaucoma (all of the retinal and optic nerve changes associated with glau-
coma are present, but IOP remains normal), whereas other monkeys are
afflicted with primary open-angle glaucoma. In the Japanese quail (Coturnix
japonica), angle-closure glaucoma develops as a result of changes in intra-
ocular dimensions, leading to peripheral anterior synechia (adhesion of the
peripheral iris to the cornea) [22]. This effect results in elevation of mean
IOP to 25.2 mm Hg (compared with 17.3 mm Hg in normal birds), with
pressure in some individuals rising to over 35 mm Hg. A case of primary
glaucoma was reported in a 15-year old, captive-bred great horned owl
(Bubo virginanus) [23]. IOP was 26.4 to 42.4 mm Hg (mean reference value,
7.1 mm Hg), and dysplastic trabecular meshwork was the primary histologic
lesion. No treatment was attempted.
Secondary glaucoma is the most prevalent form of glaucoma described in
wildlife animals. Two cases of glaucoma secondary to uveitis were reported
in llamas (Lama glama), out of 3243 llama medical records examined [24]. No
details were provided regarding IOP or case histories. Congenital glaucoma
was reported in another llama that had multiple ocular and skeletal abnor-
malities. IOP was 28 to 31 mm Hg, and anterior segment dysgenesis may have
caused the obstruction in aqueous outflow [24]. Glaucoma has been reported
in additional camelid species. A case of buphthalmia (globe enlargement) has
been reported in 1 alpaca (Lama pacos) out of 29 animals examined [25]. No
details were provided, but additional ocular findings suggested that ocular
trauma was the primary cause. A dromedary camel (Camelus dromedarius)
was diagnosed with primary glaucoma caused by dysgenesis of the anterior
segment of the eye [26]. Although multiple congenital ocular and cardiac
abnormalities were noted, glaucoma (with IOP of 45 mm Hg in one eye)
developed at 14 months of age. Other mammalian species in which glaucoma
was reported include three lemurs (Lemur fulvus rufus) that developed spon-
taneous buphthalmos, which was probably secondary to anterior uveitis [27].
 R. Ofri / Vet Clin Exot Anim 5 (2002) 391–406 397

Glaucoma, secondary to lens luxation, was suspected (but not confirmed) in

an adult lion (Panthera leo) [28], and a 3-week-old lion cub developed unilat-
eral congenital glaucoma, with IOP elevated to 42 mm Hg [29]. In the latter
case, the eye was unresponsive to medical therapy and was eviscerated.
Although there are few documented reports, glaucoma secondary to trau-
ma may be relatively prevalent in raptors [7,30]. A large-scale, retrospective
study revealed that 90% of ocular lesions in raptors resulted from physical
injury. Of the 135 birds, 5 went on to develop glaucoma; no additional
details were provided [30]. A more detailed report described a case of sec-
ondary glaucoma in a great horned owl [31]. The primary cause of the dis-
ease was trauma-induced bacterial endophthalmitis.

Clinical signs of glaucoma

Glaucoma is a unique disease in that almost every ocular structure is
affected by the disease process; however, interspecies differences exist regard-
ing the severity of symptoms. Increased endothelial pumping in cats makes
the cornea resistant to the marked edema seen in other species, whereas lack
of myelin in the optic disc makes diagnosing optic-disc cupping more diffi-
cult. In most cases, a comprehensive ocular examination is required before
glaucoma can be diagnosed or ruled out.
Pain may be a noticeable sign of glaucoma in nonanesthetized wildlife spe-
cies. Pain can be manifested as blepharospasm, rubbing of the eye, or excessive
tearing (epiphora); lethargy or depression also could be present. Pain is usually
a feature of acute cases of congestive glaucoma, characterized by a rapid rise in
IOP, and is less evident in chronic cases. Ocular pain does not necessarily indi-
cate glaucoma and may be caused by corneal ulceration or anterior uveitis.
Buphthalmos is another sign of the disease that can be observed from a dis-
tance. It is caused by the stretching of collagen fibers in the sclera may be more
prominent in young animals, which have more elastic fibers compared with
those in adults; in such individuals, buphthalmia may be resolved when IOP
is lowered. In older animals, the stretched fibers may not contract following
the lowering of IOP. Buphthalmos can be confused with exophthalmos (globe
protrusion), and ultrasound can help differentiate between the two conditions.
High IOP can cause dysfunction of corneal endothelium, leading to cor-
neal edema. The severity of the edema roughly may be correlated with the
magnitude of the pressure elevation. Prolonged or severe IOP elevation can
cause irreparable damage to endothelial cells, resulting in permanent edema.
Breaks in the endothelial Descemet’s membrane can occur and are noted by
white lines in the cornea (striate keratopathy). Although these streaks are
usually pathognomonic for glaucoma, there are numerous potential causes
for corneal edema, including anterior lens luxation, anterior uveitis, or cor-
neal ulcer. Episcleral vessels usually appear to be congested.
The anterior uvea also is affected by glaucoma. Increased pressure
damages the nerves and blood supply to the iris and eventually damages iris
398 R. Ofri / Vet Clin Exot Anim 5 (2002) 391–406

stroma. Slight mydriasis can be observed in early stages of the disease. In

acute or advanced stages, the animal may present with fixed, dilated pupils.
Anterior uveitis (which causes miosis) may mask this sign, whereas posterior
synechia could mimic it. Fixed, dilated pupils are also a sign of other retinal
and optic nerve diseases. The ciliary body atrophies in glaucoma, eventually
ceasing production of aqueous humor. The paradoxical end stage of many
cases of glaucoma is severe hypotony, accompanied by shrinking and degen-
eration of the entire eye (phthisis bulbi).
Glaucoma can induce cataract formation; however, a more common len-
ticular pathology associated with glaucoma is lens luxation. There is a dual
cause-and-effect relationship between the two diseases. Glaucoma can in-
duce lens luxation, because the buphthalmos leads to stretching and tearing
of zonules that suspend the lens in the eye. Conversely, glaucoma can be
caused by lens luxation, because movement of the lens may allow presenta-
tion of the vitreous into the anterior chamber, impeding aqueous outflow.
Presence of lens luxation and glaucoma frequently make it impossible to
determine which is the primary disease. Regardless of the primary cause, it
is unlikely that the glaucoma can be treated without surgical removal of
the anteriorally luxated lens.
Potentially, the most devastating effects of elevated IOP are those
observed in the retina and optic disc. Glaucoma induces apoptosis of retinal
ganglion cells, leading to progressive reduction in visual function, sensitivity,
and fields. Unfortunately, in veterinary medicine it is difficult to notice this
loss of vision in its early stages, and frequently the practitioner is presented
with a blind animal. In such patients, classic signs of retinal degeneration
may be present, including retinal vessel attenuation and tapetal hyperreflec-
tivity (in species possessing a tapetum). Further damage is incurred by the
axons of these ganglion cells, which constitute the fibers of the optic nerve.
As these axons exit the eye at the level of the lamina cribrosa, they are subject
to various mechanical forces that eventually cause neuronal degeneration,
further compromising vision. Ophthalmoscopically, these changes in the
optic nerve can be visualized as an increase in the area of the optic-disc cup,
combined with a relative decrease in the area of the uncupped disc.
There is great variability in the extent of retinal and optic nerve damage
caused by glaucoma. Moderate increases in IOP may be clinically undetect-
able for a long time, whereas a high IOP spike can cause irreversible blind-
ness within a few hours. Individual (and probably interspecies) differences in
resistance to the effect of IOP elevation also exist.

Diagnosis of glaucoma

Tonometry
As noted previously, many of the clinical signs associated with glaucoma
are noted in other ocular diseases. In some species (eg, cats), clinical signs
may be more subtle than are those in other species. To confirm the diagnosis
 R. Ofri / Vet Clin Exot Anim 5 (2002) 391–406 399

of glaucoma, IOP should be measured using a tonometer rather than one’s

fingers (digital tonometry), because digital tonometry provides an inaccu-
rate estimate of IOP.
The Schiotz indentation tonometer measures the amount of corneal
indentation caused by a given weight. This measurement must be converted
into IOP values. Conversion tables exist for the domestic dog and cat. These
tables should be used with caution in other species, because Schiotz readings
are influenced by numerous physiologic and anatomic parameters, such as
corneal curvature and corneal rigidity. In species other than the dog and cat,
Schiotz readings should be regarded as estimates of IOP rather than true
IOP values. These estimates can be used to compare readings between two
eyes (in cases of suspected unilateral glaucoma) or between a normal subject
and a patient. The Schiotz tonometer has other drawbacks, most notably
the need for the head to be held up so that the central cornea parallels the
floor, a position that can be difficult to attain in large animals; the Schiotz
tonometer is a cheap instrument that provides reproducible estimates of
IOP. Table 1 lists the baseline Schiotz values in a number of wildlife species.
Applanation tonometers, the most popular of which is the handheld Tono-
Pen, do not have the drawbacks of the Schiotz tonometer. Applanation to-
nometers provide direct pressure readings rather than estimates, and specific
head positioning is not required. Several measurements are performed, and
the instrument reports the mean IOP and its variance. Its accuracy and ease
of use make the Tono-Pen a popular instrument in specialty ophthalmology
clinics, but because of its price it is rarely available to general practitioners.
Regardless of the instrument used, tonometry results should be compared
with values obtained in age-matched subjects of the same species that were
anesthetized using a similar protocol at the same time of day. Barring the
availability of such reference values, tonometry results should be interpreted
with caution. If reference values are unavailable, it may be possible to diag-
nose glaucoma based on large differences in IOP between the two eyes (as was
the case in a lion cub with unilateral glaucoma) [29] or based on very high
bilateral readings.
Tonography is a complementary examination, whereas tonometry is per-
formed over several minutes. Such measurements result in quantification of
the conventional (iridocorneal) outflow, which, in some forms of glaucoma,
may be impaired before the appearance of clinical signs or IOP elevation.

Gonioscopy
Gonioscopy is a method for examining the iridocorneal angle and ciliary
cleft. These structures can be visualized using a specialized contact lens
mounted on the cornea. Using this goniolens, the examiner can classify
the type of glaucoma by determining whether the angle is open, narrow,
or closed. This classification is important to determine the therapeutic
approach. Antiglaucoma drugs that increase outflow by opening the angle
probably are less beneficial in treating open-angle glaucoma and are more
400 R. Ofri / Vet Clin Exot Anim 5 (2002) 391–406

beneficial in treating narrow-angle glaucoma. Periodic examination of the

angle helps monitor the progression of the disease, because the angle pro-
gressively narrows and closes in many patients. The risk for congenital glau-
coma caused by pectinate ligament dysplasia also can be assessed using a
goniolens.

Other tests
A comprehensive ophthalmic examination of all ocular structures is
mandatory in glaucoma diagnosis. A detailed examination of the optic disc
to assess (and monitor) damage to the optic nerve axons and visual function
is important. In cases in which severe corneal edema precludes visualization
of the inner structures of the eye, hyperosmotic preparations (eg, 5% NaCl
solution) can be used to temporarily ameliorate the edema and to allow
examination.
Provocative tests that are designed to differentiate between the responses
to ‘‘glaucoma attack triggers’’ in normal subjects and subjects with glau-
coma have been described in human and canine ophthalmology. In wildlife
species, these tests probably would require long periods of anesthesia and
are of little practical value. Of greater potential value is ultrasound, which
can be used to diagnose buphthalmia. Ultrasound biomicroscopy can be
used to assess the status of anterior intraocular structures, including the
iridocorneal angle, whereas color doppler ultrasound can be used to
demonstrate changes in vascular supply in patients with glaucoma. Other
imaging techniques that have not been described in wildlife but hold poten-
tial diagnostic value are retinal tomographs. These tests can be used to
quantify the loss of retinal ganglion cells and their axons by measuring the
thickness of the nerve fiber layer and depth of the optic-nerve cup.
The electroretinogram can be used to record the retina’s electrophysio-
logic response to visual stimulation. By varying the type of stimulus from
flash to pattern, responses of the outer or inner retina, respectively, can be
recorded. Changes in the response of subjects with glaucoma to flash and
pattern stimulation have been described in a large number of species, from
rodents and birds to humans. Although there are no reports of the use of
electroretinography to diagnose glaucoma in wildlife, baseline recordings
have been performed in the American alligator [34].

Treatment of glaucoma
There are two goals in the treatment of glaucoma. The first goal is to pre-
vent further loss of vision by preventing damage to the retina and optic
nerve. Current medical technology does not enable the restoration of vision
that has been lost because of glaucoma, and clinicians only can prevent
additional deterioration. Unfortunately, many glaucomatous animals are
presented to the practitioner at advanced stages of the disease when their
 R. Ofri / Vet Clin Exot Anim 5 (2002) 391–406 401

vision has been mostly, or totally, lost. Even in blind patients, however,
treatment should be initiated to achieve the second goal of glaucoma
treatment—analgesia. Glaucoma is a painful disease, and the IOP must be
lowered to relieve the animal’s pain.
Management of glaucoma also hinges on identifying its cause. In second-
ary glaucoma, treatment of the primary cause is essential for successful
treatment of the IOP elevation. Uveitis, lens luxation, cataract, and other
precipitating conditions must be treated at the same time that secondary
glaucoma is treated. In patients with these conditions, the glaucoma may
be resolved after successful treatment of the primary cause; however, if no
external cause is identified and if the glaucoma is determined to be primary,
lifelong medical treatment may be required to maintain normal IOP. Life-
long treatment with topical drugs is impractical in most wildlife cases. In
cases in which daily topical treatment cannot be administered, the clinician
should consult with a specialist regarding surgical options. Breeding of ani-
mals with suspected primary glaucoma should be restricted to prevent the
transmission of the disease to offspring.

Medical treatment
There are several categories of antiglaucoma drugs. With the possible
exception of the prostaglandin analogues, it is unusual to achieve a satisfac-
tory, long-term decrease in IOP using only one category of drugs. Usually, a
combination of two or more drugs is required for successful treatment. Pick-
ing a beneficial combination in a given patient depends on the eye’s status
(eg, state of the angle, primary cause of the disease), but also can involve
some trial and error. Some drugs lose their effectiveness with time as circum-
stances, such as the state of the angle, change.
Most antiglaucoma drugs have been tested or used on a small number
of species, and there is little or no experience regarding their efficacy and
toxicity in wildlife species. A drug may be safe in one species but toxic in
another. Apraclonidine, an a2-adrenergic agonist, seems to be safe in dogs
but is systemically toxic in cats. Clinicians are urged to use caution and judg-
ment in selecting drugs and monitoring their effects. Unless stated otherwise,
doses quoted in the next section are those used in dogs.

Emergency treatment and systemic medications

Systemically administered hyperosmotic agents can be used to achieve a
rapid decrease in IOP. The resulting increase in blood osmolarity causes
removal of fluid from the vitreous body and anterior chamber. The effect
on IOP is rapid and dramatic, and pressure may fall by scores of units. This
decrease may help prevent some acute damage caused by the disease, relieve
the animal’s pain, and allow time for consultation with a specialist. Intrave-
nous mannitol (1.0–1.5 mg/kg, administered over 30 minutes while with-
holding water for several hours) is the most popularly used hyperosmotic
402 R. Ofri / Vet Clin Exot Anim 5 (2002) 391–406

agent in canine glaucoma. Oral glycerol, administered at a similar dose

through a gastric tube, also can be used.
Acetazolamide may be administered intravenously (5–10 mg/kg) to ob-
tain a rapid decrease in IOP. This drug inhibits carbonic anhydrase, a key
enzyme in the production of aqueous humor, thereby reducing secretion
of fluid from the ciliary epithelium into the posterior chamber. Acetazola-
mide (10 mg/kg two to three times daily) and other carbonic anhydrase inhi-
bitors (methazolamide, 2–4 mg/kg twice daily; dichlorphenamide, 2 mg/kg
two to three times daily) also can be administered orally. This class of glau-
coma drugs is the only one that may be administered orally, thus constitut-
ing the only option for long-term medical management of glaucoma in many
wildlife species. These drugs cause a decrease in the concentration of bicar-
bonate in the body, and their use results in metabolic acidosis, tachypnea,
and diuresis. Kidney function should be monitored if long-term use is
needed. Cats tend to be more susceptible to side effects caused by long-term
use of carbonic anhydrase inhibitors. In this species, doses of acetazolamide
tend to be higher and doses of dichlorphenamide tend to be lower.

Topical medications
Parasympathomimetic drugs cause miosis, ciliary muscle contraction,
and increased conventional (trabecular) outflow of aqueous humor. Pilocar-
pine, a direct-acting cholinergic drug, is the most widely used drug in this
category. The drug is available in several concentrations (1% to 8%) and
is instilled two three times daily. Lower concentrations can be used in cases
in which pilocarpine causes significant local irritation (cause of its low pH).
Carbachol (0.75% to 3.0%), another drug in this category, can be used in
animals that do not tolerate pilocarpine.
Parasympathomimetic drugs can act indirectly by inhibiting acetylcho-
linesterase. Demecarium bromide (0.125% to 0.25%), echothipate iodide
(0.03%–0.25%) and isoflurophate (0.01% to 0.1%) can be used from twice
daily to every other day. Parasympathomimetic drugs should be used with
caution in cases of concurrent uveitis because of their effect on the perme-
ability of the blood–aqueous barrier and on iridal and ciliary musculature.
Prolonged use, especially of indirect-acting drugs, can result in systemic
cholinergic toxicity; elevated levels of acetylcholine could lead to salivation,
vomiting, and diarrhea. The drugs can cause a significant reduction in IOP,
but are usually not effective when used alone; rather, they are combined
typically with carbonic anhydrase inhibitors or other topical medications.
Adrenergic drugs have a profound effect on IOP. b-Adrenergic blockers
reduce aqueous production. Timolol maleate (0.25%–0.5%) is the most fre-
quently used drug in this category, though some clinicians question the effec-
tiveness of these concentrations in dogs. Betaxolol and levobunolol are also
in this category. Because of systemic absorption and possible cardiopulmon-
ary side effects, these drugs should be used with caution in elderly patients.
 R. Ofri / Vet Clin Exot Anim 5 (2002) 391–406 403

Intraocular pressure can be lowered using adrenergic agonists. Epineph-

rine (1%–2% two to three times daily) and its prodrug dipivefrin (0.1% two
to three times daily) are classified as a- and b-agonists that cause a reduction
in aqueous production and an increase in outflow. The former effect probably
is caused by the drugs’ vasoconstrictive effects on the ciliary body vasculature,
which leads to decreased blood flow that reduces the amount of substrate
available for aqueous production. Apraclonidine, an a2-adrenergic agonist,
also lowers IOP by reducing aqueous production and possibly by increasing
outflow. Systemic side effects prevent the use of this drug in cats.
Two new classes of topical antiglaucoma drugs have emerged. Dorzol-
amide (2% three times daily) is a carbonic anhydrase that can be used topi-
cally, avoiding the side effects associated with the systemic drugs in this
category. Prostaglandin analogues lower IOP by increasing the unconven-
tional (uveoscleral) outflow. This unique mechanism suggests that analogues
probably have an additive effect with other antiglaucoma medications.
Administration of latanoprost (0.005%), isopropyl unoprostone (0.12%)
and bimatprost (0.03%) once to twice daily causes significant reduction
of IOP in a number of species. No systemic side effects have been reported
with this category of drugs.

Adjunct therapy
As noted previously, the primary cause of the disease must be treated in
cases of secondary glaucoma. In animals in which the glaucoma is associated
with lenticular changes (cataract, luxation), surgery to remove the lens is
required. In cases in which glaucoma is caused by uveitis, systemic and topi-
cal anti-inflammatory treatment must be included in the protocol. Because
signs of concurrent uveitis can be subtle, some clinicians advocate adding
anti-inflammatory drugs to the initial treatment protocol; however, atropine,
which can cause closure of the iridocorneal angle, should be used with
extreme caution (if at all) when glaucoma and uveitis therapies are combined.
Tissue plasminogen activator also can be injected into the anterior chamber
of uveitis patients to break down fibrin and prevent formation of adhesions.
No current discussion of medical therapy for glaucoma is complete with-
out a brief mention of neuroprotection. Rather than lower IOP, this thera-
peutic approach aims to increase survival of the retinal ganglion cells and
their optic nerve axons to preserve vision. Neuroprotection can be achieved
by inhibiting the actions of toxic substances that are secreted in the retina
and optic nerve during the disease process and by improving blood flow
to these organs. Numerous neuroprotective drugs are currently in various
stages of laboratory and clinical testing.

Surgical treatment
Surgery may be the treatment of choice in wildlife species in which frequent
topical treatment is impractical or impossible. As in the case of medical
treatment, surgical treatment can be divided into procedures that decrease
404 R. Ofri / Vet Clin Exot Anim 5 (2002) 391–406

aqueous production and procedures that increase aqueous outflow. The au-
thor’s experience in small animals has shown that these procedures frequent-
ly enable clinicians to lower the number of antiglaucoma drugs prescribed or
the frequency of their use, but the procedure usually does not eliminate the
need for medical therapy. In cases in which all surgical or medical therapies
have failed, clinicians may be forced to resort to a third category of surgical
procedures that is aimed at relieving pain in end-stage glaucoma.

Procedures to reduce aqueous production. These techniques are based on

partial destruction of the ciliary body, which is the site of aqueous production.
In cyclophotocoagulation, a laser beam delivers energy and heat through
the sclera and into the underlying ciliary epithelium. In cyclocryothermy,
a liquid-nitrogen probe is used to achieve a similar effect through freezing,
though this technique is used less frequently now that lasers are gaining
popularity. The diode and Nd:YAG lasers have been used for cyclophoto-
coagulation in dogs. The number of burn spots applied by the laser and the
amount of energy delivered in every spot can be adjusted to the desired
effect. Veterinary ophthalmologists have been modifying these parameters
for a number of years to achieve desirable results in dogs. There are no
reports of these procedures in wildlife, and deciding on parameter settings
in different species may be educated guesswork. The lasering procedure can
be repeated a second time to achieve the desired effect. More energy can be
used compared to the previous attempt. However, if unsure, err on the side
of caution and use less energy. Large-scale destruction of the ciliary body
probably results in phthisis bulbi. Other possible complications include
hyphema, acute uveitis, and retinal detachment.

Procedures to increase outflow. Procedures to increase outflow are divided

into two categories. The first category involves the use of intraocular surgery
to create new pathways for aqueous outflow. A variety of procedures that
open new outflow channels through the sclera, iris, or ciliary body have been
described. Because of the complexity of these procedures, the reported suc-
cess rate exceeds 50% in dogs. A more promising alternative may be the use
of gonioimplants, or anterior chamber shunts. In this procedure, artificial
drainage devices, typically made of silicone, are implanted in the eye. One
end of the device is introduced into the anterior chamber, and the distal
end is fixed beneath the conjunctiva. A frequent cause for failure of these
implants is their occlusion with inflammatory material, but improved results
are reported following the modification of postoperative protocols.

Analgesic procedures. Unfortunately, despite medical and surgical interven-

tion, clinicians often have patients with an irreversibly blind, and extremely
painful, eye. Several pain-relieving procedures are available. Evisceration
and intrascleral prosthesis constitute the most cosmetically acceptable
procedures. In these procedures, all intraocular contents are removed
 R. Ofri / Vet Clin Exot Anim 5 (2002) 391–406 405

through a limbal incision and are replaced with a silicone prosthesis. The in-
cision is sutured, resulting in an outer shell (consisting of cornea and sclera)
that contains the implant. The implant prevents the globe from collapsing,
and its dark color gives the appearance of a normal pupil.
If an appropriately sized prosthesis cannot be found, phthisis bulbi can
be induced. Phthisis bulbi is a possible sequela of end-stage glaucoma and
can be achieved without any intervention; however, this process would be
a long and painful, involving unnecessary suffering. Phthisis bulbi can be
induced by destroying the ciliary body with a cryo probe or through an
intraocular injection of a cytotoxic substance (typically gentamycin). After
destruction of the ciliary epithelium, aqueous production ceases, resulting
in lowered pressure and atrophy of the eye.
If all other approaches fail and the eye is still painful and blind, enuclea-
tion can be considered. After enucleation of the eyes in glaucomatous wild-
life, the specimen should be submitted to a pathologist or an ophthalmologist
to learn more about this frustrating disease in exotic species.

Acknowledgment
The author thanks Dr. Igal Horowitz from The Tel-Aviv Ramat-Gan
Zoological Center (Safari) for his dedicated support of wildlife ophthalmol-
ogy research.

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