Paper 107 Disc

Veterinary Ophthalmology (2000) 3, 227±234

REVIEW ARTICLE

Lens-induced uveitis
Alexandra van der Woerdt
Department of Medicine, Bobst Hospital of the Animal Medical Center, 510 East 62nd Street, New York, NY

Address communications to: Abstract

Alexandra van der Woerdt
The Animal Medical Center
510 East 62nd Street
New York
NY 10021
Tel.: (212) 838±8100 ext. 8729
Fax: (212) 752±2592
e-mail:
sandra.vanderwoerdt@amcny.org induced uveitis prior to cataract surgery significantly reduces the success rate of cataract
Lens-induced uveitis has been described in humans and many animal species. Traumatic
rupture of the lens capsule may result in vision-threatening intraocular inflammation that is
poorly responsive to medical management. Phthisis bulbi, persistent uveitis or glaucoma
often occurs in these eyes. Surgical removal of the lens material is generally indicated Ahed
Bhed
shortly after the injury in an effort to preserve vision. Leaking of lens proteins through an
intact lens capsule may result in a lympho-plasmacytic anterior uveitis. This is most Ched
commonly associated with the presence of a hypermature cataract. The presence of lens- Dhed
Ref mar-
ker
surgery. Small amounts of circulating lens proteins maintain a normal T-cell tolerance for
Fig mar-
lens proteins. Lens-induced uveitis develops when a breakdown occurs of this normal T- ker
cell tolerance. Immune complexes play an important role in the tissue damage associated Table
with the ensuing inflammation. Other factors associated with the tissue damage include marker
hydroxyl radicals, nitroxide radicals, and hydrogen peroxide and arachidonic acid Ref end
metabolites. Treatment consists of topical and systemic anti-inflammatory medications, Ref start
mydriatic agents, and glaucoma medications when indicated. Experimental
pharmacological agents include dual cyclooxygenase/lipoxygenase inhibitors, interleukin-1
blockers, antioxidants and hydroxyl radical scavengers.
Key Words: lens-induced uveitis, phacoanaphylactic endophthalmitis, phacoclastic uveitis,
phacolytic glaucoma, phacolytic uveitis, phacotoxic uveitis

INTRODUCTION
Lens-induced uveitis (LIU) has been described as a naturally
occurring disease in many animal species including dogs,
cats, rabbits, rats, birds, horses and a calf.1±18 It has been
experimentally produced in laboratory animals.19±25 It was
first reported in human beings over 75 years ago.26
LIU is an inflammatory response of the ocular uvea
against lens proteins. LIU in humans is divided into
phacoanaphylactic endophthalmitis (PE), phacotoxic uveitis,
and phacolytic glaucoma. In the veterinary literature, LIU
has been divided into two syndromes named `phacoclastic
uveitis' and `phacolytic uveitis'1 (Table 1).
Phacoclastic uveitis
Phacoclastic uveitis is the response of the ocular uvea against
lens proteins liberated after traumatic or spontaneous lens
capsule rupture. This has been reported in dogs,3,13,14
cats,2,3,7,8 rabbits,15±17 and occasional other species.2,6 In two
retrospective case series, young animals were overrepre-
sented.3,14 Cat-scratch injury to the cornea was the most
common cause for the lens capsule rupture (Fig. 1). The
cause of the lens capsule rupture was not known in all cases.3
Surgical removal of all lens material shortly after the injury
resulted in a visual eye 1 month after surgery in most eyes.3
In contrast, attempted medical management of the uveitis
using anti-inflammatory medications resulted in loss of
vision in nearly all eyes in which this was attempted. The
authors concluded that surgical removal of the lens material
is indicated if the tear in the lens capsule is more than 1.5
mm in length or substantial disruption of the lens cortex is
present. Histopathologic lesions in eyes enucleated second-
ary to complications from phacoclastic uveitis included a lens
capsule rupture with intralenticular neutrophils.1 A perilen-
ticular inflammation was present that ranged from suppura-
tive to lymphocytic. Perilenticular fibroplasia resulting in
massive posterior synechiae with secondary glaucoma was
common. (Fig. 2) A mild to moderate lymphocytic-
plasmacytic iridocyclitis was present in all eyes examined.
Lymphocytic-plasmacytic perivascular cuffing in the retina
was observed in 65% of eyes examined. The most common
reasons for enucleation of these globes were severe glaucoma

# 2000 American College of Veterinary Ophthalmologists

 Paper 107 Disc

228 VAN DER WOERDT

induce monocyte migration into

or uveitis. (Fig. 3) This is consistent with another large

iridocorneal angle. g-crystallins

retrospective study evaluating 36 enucleated globes with lens

Macrophages with engulfed

Glaucoma associated with
capsule rupture and a histopathologic diagnosis of LIU.6

a resorbing cataract with

lens material obstructing

soluble proteins obstruct
Macrophages filled with

heavy-molecular weight

the iridocorneal angle.

the anterior chamber.
lens material obstruct
The most common reason for enucleation in this study was
Phacolytic glaucoma

intact lens capsule.

iridocorneal angle,
persistent nonresponsive uveitis. LIU was not diagnosed in
Human beings

any of these eyes prior to enucleation. Anterior and posterior

synechiae leading to either glaucoma or phthisis bulbi were
commonly observed in this study.
Spontaneous lens capsule rupture resulting in phacoclastic
uveitis has been described in the rabbit.2,6,15±17 The breed
most commonly affected is the dwarf rabbit.15 Clinically, a

anterior uveitis with intact

Lymphocytic-plasmacytic
Phagocytosis of released
with intact lens capsule.

white mass is often observed in the anterior chamber overlying

with resorbing cataract
Mild uveitis associated

lens proteins without

a rupture in the anterior lens capsule.15 An anterior uveitis is

Phacolytic uveitis

T-cell activation.

also present that is poorly responsive to treatment with topical

lens capsule. antibiotics and corticosteroids. Histopathologic examination
reveals the presence of intralenticular neutrophils surrounded
by foamy macrophages and fibrous tissue containing lympho-
Dog

cytes and plasma cells. Encephalitozoon cuniculi has been isolated

from affected lenses.15 A cause-and-effect relationship between
anterior uveitis with intact

the cataract and LIU and E. cuniculi has not yet been clearly
Lymphocytic-plasmacytic
Phagocytosis of released
with intact lens capsule.
with resorbing cataract
Mild uveitis associated

defined. Surgical removal of affected lenses has been

lens proteins without

suggested as treatment for this condition.16±17

Table 1 Comparison of clinical findings, pathogenesis and histopathologic findings in various types of lens-induced uvetis
Phacotoxic uveitis

T-cell activation.
Human beings

lens capsule.

Phacolytic uveitis
Phacolytic uveitis is a lymphocytic-plasmacytic anterior
uveitis that may occur secondary to release of lens protein
through an intact lens capsule.1,5,9±12,27 Phacolytic uveitis in
animals closely resembles phacotoxic uveitis in humans.
Dog, cat, horse, cattle, rabbit, rat

May not be diagnosed clinically.

Histopathologic examination reveals a mild nonsuppurative

neutrophils. Moderate to severe
lens proteins, immune complex
Breakdown T-cell tolerance to

centered around break in lens

iridocyclitis with infiltration of lymphocytes and plasma cells

after rupture of lens capsule.
Severe nonresponsive uveitis

Suppurative to lymphocytic
perilenticular inflammation

capsule with intralenticular

metaplasia of residual lens

into the uveal stroma. The lens shows degenerative

reaction to lens proteins.
Proliferation and fibrous

cataractous changes, but lacks a capsular tear or intralenti-

Phacoclastic uveitis

cular neutrophils.1
epithelial cells.

Miniature Poodles, Toy Poodles and American Cocker

Spaniels are breeds commonly affected, reflecting the high
fibroplasia.

incidence of cataract formation in these breeds.5,11,27 The

age of onset of phacolytic uveitis is variable among the
various breeds; the mean age for affected poodles was
significantly higher than the mean age for affected cocker
of a noncataractous lens. Rarely diagnosed
Severe nonresponsive uveitis after rupture

spaniels in one study.5 Phacolytic uveitis is most commonly

neutrophils, surrounded by epithelioid
inflammation centered around break

associated with the presence of a hypermature catar-

Zonal, perilenticular granulomatous

and giant cells. Minimal fibroplasia.

Breakdown T-cell tolerance to lens
proteins, immune complex reaction
Phacoanaphylactic endophthalmitis

in lens capsule with intralenticular

act,5,9,10,27 but has been observed clinically in association

with immature, mature or intumescent cataract. Fluoropho-
Human beings, owl, rabbit

tometry performed in dogs with normal lenses and dogs with

lenses in various stages of cataract formation has shown that
a breakdown of the blood aqueous barrier is present in eyes
to lens proteins.

with all stages of cataract.28 The breakdown was more severe

in eyes with mature or hypermature cataract as compared to
clinically.

eyes with incipient or immature cataract.28 Resorption of a

cataractous lens is usually more complete and of shorter
duration in young dogs than in older dogs.9±11,27
The nucleus of the lens in an old dog is more resistant to
Clinical findings

Histopathologic

degradation than the nucleus of the lens of a young dog.

Pathogenesis

Various authors have suggested different age limits (less than

findings
Species

1 year, less than 3 years,10 less than 6 years11) below which

rapid resorption of a cataract is anticipated.

# 2000 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 3, 227±234


Clinical signs of phacolytic uveitis in a large retrospective
study included scleral injection, poor response to topical
administration of 1% tropicamide, and miosis (Fig. 4).
Anterior or posterior synechiae, pigment on the anterior lens
capsule, and iris hyperpigmentation were clinical signs
associated with more chronic uveitis.5 Aqueous flare was
detected in 50% of all eyes examined.5 Complications that
were believed to be secondary to the phacolytic uveitis in this
study included glaucoma and phthisis bulbi. Controversy
Figure 1. Slit-lamp photograph of a young Golden Retriever with an
acute lens capsule perforation from a penetrating cat-scratch wound,
with the parallel piped directed from right to left. Note the extrusion of
lens material above the capsular surface, cortical cataract, and focal
pigment deposition on the anterior lens capsule. Reprinted with
permission by Lippincott Williams & Wilkins.82 The slide is courtesy of
Dr Mike Davidson.
Figure 2. Clinical photograph of a dog with phacoclastic uveitis. Lens
capsule perforation had occured several weeks prior to the photograph
and a severe anterior uveitis is present. Note the leukocoria from
traumatic cataract formation. The slide is courtesy of Dr Mike
Davidson.
# 2000 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 3, 227±234
Paper 107 Disc
LENS-INDUCED UVEITIS 229
exists in the literature regarding the relation between age
and severity of phacolytic uveitis. In one study, a granulo-
matous LIU was described in older dogs, and a milder
nongranulomatous LIU was described in younger dogs.9
This was not confirmed in another study in which phacolytic
uveitis developed sooner after the onset of cataract forma-
tion and was less responsive to treatment in young dogs than
phacolytic uveitis in old dogs.5 The presence of phacolytic
uveitis prior to cataract surgery can reduce the success rate of
cataract surgery.4,5 The presence of phacolytic uveitis
reduced the success rate of cataract surgery to 52% as
compared to 95% in dogs free of phacolytic uveitis in either
eye 6 months after surgery in one study.4 In this study, no
difference existed in surgical results between eyes affected by
phacolytic uveitis or in eyes free of phacolytic uveitis but
with the other eye affected by phacolytic uveitis. This is in
contrast with another study in which a difference in success
rate was found between eyes affected by phacolytic uveitis
(39% success rate) and eyes free of phacolytic uveitis but in
Figure 3. Photomicrograph of a phacoclastic uveitis in a dog. A lens
capsule rupture, intralenticular neutrophils, and a pronounced
perilenticular fibroplasia are present. Masson's Trichrome stain. The
slide is courtesy of Dr Brian Wilcock.
Figure 4. Clinical photograph of a dog with phacolytic uveitis.
Leukocoria from a hypermature, intumescent cataract, dyscoria from
posterior synechia, and keratic precipitates are present. The slide is
courtesy of Dr Mike Davidson.

230 VAN DER WOERDT
dogs in which the fellow eye was affected by phacolytic
uveitis (71% success rate).5 Intraoperative complications
were common in eyes affected with phacolytic uveitis.4
Common reasons for postoperative failure in eyes affected
by phacolytic uveitis prior to surgery included glaucoma,
phthisis bulbi, posterior capsular opacification, pupillary
occlusion, and retinal detachment.4,5
Lens-induced uveitis in human beings
Phacoanaphylactic endophthalmitis (PE) in humans is similar
to, but not identical to, phacoclastic uveitis in animals. It is a
severe granulomatous inflammation that may occur after
rupture of the capsule of a noncataractous lens.29±32 It usually
occurs 1±14 days after rupture of a lens capsule,33 although
the time after injury varied from 2 days to 59 years in one
clinicopathologic study.34 Most cases of PE occur after
trauma, either surgical or nonsurgical.34 Lens capsule rupture
with associated PE without any known trauma to the eye has
been reported in humans,34±36 in dogs,3,13 and in rabbits.2,15
Microphthalmos was present clinically in a high percentage of
humans with spontaneous lens capsule rupture.34 Degenera-
tion of the lens capsule secondary to the formation of
cataract37 or the presence of an intumescent cataract could
cause rupture of the lens capsule after trauma insufficient to
cause rupture of the lens capsule of a normal lens. Both in
humans34 and animals,6 the disease is often not well
recognized clinically. It is ultimately diagnosed on histo-
pathologic examination of the eye after it has been surgically
removed because of uveitis or glaucoma that was refractory to
treatment. The classic histologic description of PE is a zonal,
granulomatous inflammation that is centered on a rupture in
the lens capsule. Intralenticular polymorphonuclear leuko-
cytes are present with an adjacent layer of mononuclear cells
including epithelioid and giant cells.31,34 In a histopathologi-
cal study,34 inflammation of the choroid was present in 76%
of cases studied and was most likely to be present in eyes with
moderate to severe PE. A retinal perivasculitis was present in
51% of cases. A retinal detachment was present in 64%, and
optic nerve atrophy in 30% of cases studied. The term
`phacoclastic uveitis' was introduced in the veterinary
literature when it became apparent that differences exist
between phacoanaphylactic endophthalmitis in humans and
phacoclastic uveitis in animals.1 Cases of PE in dogs that were
published prior to this were cases of phacoclastic uveitis
before this name was applied to the uveitis seen in dogs with
lens capsule rupture. In dogs, the perilenticular reaction is
variable in nature, but rarely granulomatous.1 Fibroplasia is
minimal in humans, but was found to be pronounced in dogs,
horses, cats, cattle, and rats.1,2 Proliferation and fibrous
metaplasia of residual lens epithelial cells often results in the
formation of posterior synechiae and glaucoma in these
species.1 Perilenticular granulomatous inflammation resem-
bling the inflammatory reaction in PE in humans has been
reported in rabbits and birds.2,18
Phacotoxic uveitis is rare in humans. It is a lymphocytic-
plasmacytic anterior uveitis that may occur when lens
# 2000 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 3, 227±234
Paper 107 Disc
proteins from a hypermature cataract escape into the
aqueous humor through an intact lens capsule.38 It has been
shown that the molecular and cellular events leading to the
formation of cataract induce increased permeability of the
lens capsule allowing release of lens proteins.37 The
predominant inflammatory cell types in phacotoxic uveitis
are mononuclear cells. Phacotoxic uveitis as described in
humans resembles phacolytic uveitis in animals both
clinically and histopathologically.
Phacolytic glaucoma in humans is a syndrome in which
macrophages with engulfed lens material obstruct the
iridocorneal angle resulting in glaucoma.39±41 This is
associated with the presence of a hypermature cataract.
The iridocorneal angle is not closed by iris adhesions and the
anterior chamber is either of normal depth or deeper than
normal. Lens removal results in resolution of clinical
signs.40,42 The posterior segment of the eye is normal.
The protein content of the aqueous humor is high, but it
lacks fibrinogen. Histopathologic findings resembling pha-
colytic glaucoma in humans have been reported once in a
Miniature Poodle.6
Pathogenesis of LIU
For many years, PE was considered to be a cell-mediated
rejection of lens proteins. The lens proteins were thought to
be sequestered by the lens capsule prior to development of
the immune system preventing these proteins from being
recognized as `self'. Release of the lens proteins would result
in a severe immune response several days after surgical or
traumatic lens capsule rupture. Incompatible with this
theory are the facts that the various lens crystallins have
been detected in normal aqueous humor,43 are thought to be
only weakly antigenic44±46 and can be found in other parts of
the eye and body.47±48 In addition, anti-a-crystallin anti-
bodies have been detected in the serum of healthy
persons.49±50 Lymphocytes which bind lens crystallins have
been found in the spleen of normal rats.51 If lens proteins
were considered to be foreign by the body, PE would occur
on a regular basis after disruption of the lens capsule such as
during cataract surgery. In contrast, PE is considered to be a
rare autoimmune inflammatory response that involves an
abrogation of normal tolerance to lens proteins.32±33 T
lymphocytes are normally tolerant to lens proteins. Phacoa-
naphylactic endophthalmitis develops when a breakdown
occurs of T-cell tolerance that is normally maintained by
small amounts of circulating lens protein.34,41,52
An immune response can be divided into an afferent
component (recognition), central component (interactions
between cells of the immunologic system and antigens that
may lead to an immunologic response), and an efferent
component (inflammation with possible tissue damage).
Little is known about the afferent and central phase of PE.
Lens proteins are recognized as normal tissue, and lens
injury does not alter normal tolerance to lens protein.32 T
cells are required for development of PE because T-cell
depleted animals can not develop PE after immunization

with lens protein.53 Anterior chamber-associated immune
deviation (ACAID) does not appear to play a role in normal
tolerance to lens proteins because the concentration of lens
protein in aqueous humor, even after recent lens injury, is
too low to induce ACAID.32 Because PE can develop in an
intact eye, access of lens antigen to lymphatic drainage may
not be necessary in the development of PE. Lens protein is
recognized and tolerated, but the cellular mechanisms
involved remain largely unknown.32
Immune complexes are important in the efferent phase of
PE. An immune complex reaction (type III hypersensitivity
response) arises secondary to altered tolerance to lens
protein.54 The granulomatous inflammation that is present
on histopathologic examination is suggestive of an equal
amount of antigens and antibodies. Excess antigens stimulate
acute inflammatory reactions as seen close to the lens capsule
rupture. The nonspecific response that is present farthest
away from the lens capsule rupture suggests an excess of
antibodies relative to antigens.32 Lenses from animals
sensitized to lens proteins bind both complement and
immunoglobulins. Depletion of complement will inhibit
induction of experimental PE.24 Phacoanaphylactic en-
dophthalmitis can be transferred to normal animals by
hyperimmune serum.22
Free radicals produced by the retinal pigment epithelium
and vascular endothelium play a role in the tissue damage
associated with PE. Hydroxyl radicals and nitroxide radicals,
generated by xanthine oxidase and nitric oxide synthase in
the vascular endothelium, respectively, cause severe ocular
inflammation. Free radicals are important in neutrophil
accumulation and stimulate expression of adhesion mole-
cules. Neutrophil and endothelial adhesion molecules are
necessary for accumulation of neutrophils at the site of
inflammation.55 Blocking of CD18, an adhesion molecule on
leukocytes, and ELAM-1, an adhesion molecule on en-
dothelium, significantly suppressed intraocular neutrophil
accumulation, retinal hemorrhage, vasculitis and edema in
experimental PE.55 Activated inflammatory cells release
chemical mediators of which oxygen-derived free radicals
or toxic oxygen metabolites are the most important in the
pathogenesis of PE.32,56 Stimulated inflammatory cells
produce superoxide radicals during a `respiratory burst'.
Derivatives from superoxide include highly reactive sub-
stances such as hydrogen peroxide and hydroxyl radicals.57
Toxic effects of free radicals include lipid peroxidation,
protein denaturation, and nucleic acid mutations. Arachi-
donic acid metabolites are another source of tissue damage
produced by chemical mediators that are released by
activated inflammatory cells. Prostaglandins are responsible
for the early phase of the inflammatory response in
experimental PE (less than 3 h after lens injury). Leuko-
trienes are responsible for sustaining inflammation during
the late phase.58
The pathogenesis of phacotoxic uveitis in humans and
phacolytic uveitis in animals has received little study. In
phacolytic uveitis, lens proteins are released into the anterior
# 2000 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 3, 227±234
Paper 107 Disc
LENS-INDUCED UVEITIS 231
chamber and exposed to the immune system. A low-dose T-
cell tolerance to lens proteins is normally present in the eye
which is more easily terminated to a-crystallin than to b-
and g-crystallin. Released lens proteins from a hypermature
cataract may be phagocytized by macrophages without
further T-cell activation. In the case of a lens capsule
rupture, macrophages, and class 2 major histocompatibility
encoded protein-restricted T cells can react to the various
lens crystallins and lens cell membrane proteins. This may
result in the severe inflammatory response seen in PE. The
lack of T-cell activation with associated severe inflammation
may explain the relative mild uveitis associated with
phacolytic uveitis.
Phacolytic glaucoma occurs when macrophages filled with
lens material obstruct the trabecular meshwork.40 Heavy-
molecular-weight soluble protein sufficient to obstruct
outflow of aqueous humor is a factor in development of
phacolytic glaucoma as well.59 The concentration of heavy-
molecular-weight soluble protein is approximately 14-times
higher in cortices of lenses with a hypermature cataract than
in cortices of lenses with an immature cataract.59 Lens
proteins, especially the gamma crystalline fraction can
induce monocyte migration into the anterior chamber,
thereby contributing to the pathogenesis of phacolytic
glaucoma.60 The macrophages act as scavenger cells of lens
material in the anterior chamber.41
Diagnosis and differential diagnosis of LIU
Phacoanaphylactic endophthalmitis is rarely diagnosed
clinically in humans.32,54 Vitrectomy specimens of affected
eyes may show the presence of lens capsule, epithelioid cells,
lymphocytes, neutrophils and multinucleated giant cells.54
Granulomatous elements may, however, also be seen in
vitrectomy specimens from eyes with a toxic reaction to an
intraocular lens or intraocular infection.32 In a recent report,
the diagnosis of PE was confirmed by cytologic examination
of an anterior chamber aspirate.54
Differential diagnoses of phacoclastic uveitis in animals
include toxic reactions to intraocular lenses or foreign
material introduced in the eye at the time of surgery, acute
bacterial endophthalmitis or inflammation caused by bacter-
ia or fungi of low virulence.32 Acute bacterial endophthal-
mitis after surgery usually occurs within the first few days
after surgery. The most common bacteria associated with
this are Staphylococcus, Streptococcus, and Gram-negative
organisms.61
The presence of intralenticular bacteria has been demon-
strated in cases of PE in humans34 and delayed onset
endophthalmitis after lens capsule rupture in animals.62 Out
of a total of 56 eyes examined, Gram-positive cocci were
found in two eyes and Gram-positive rods and cocci in one
eye in humans.34 Gram-positive cocci were identified in
eight dog eyes.62 Gram-positive coccobacilli were found in
one cat, and a combination of Gram-positive coccobacilli
and Gram-negative bacilli were found in another cat.62
Proprionibacterium acnes introduced by wound contamination

232 VAN DER WOERDT
may be associated with a postoperative endophthalmitis.34,63
The adjuvant qualities of P. acnes, promoting hypersensitivity
to lens proteins, in combination with mitogenic stimulatory
effects of lipopolysaccharides, may induce a granulomatous
reaction.64 In these cases the granulomatous inflammatory
response is distinct and away from the major site of bacterial
infection.34,62
The differential diagnosis of anterior uveitis in animals
includes numerous infectious agents (bacterial, fungal,
parasitic, protozoal, rickettsial, viral), trauma, immune-
mediated diseases (uveodermatologic syndrome, idiopathic),
neoplasia (primary ocular or metastatic disease), and LIU.
Anterior uveitis can lead to secondary cataract formation.
When presented with an animal with cataract and anterior
uveitis, it may be difficult to determine if the uveitis is
secondary to the cataract, or if the cataract is secondary to
the uveitis. The stage of cataract formation (incipient,
immature, mature or hypermature) in combination with
the severity of the uveitis may guide the clinical decision as
to whether the uveitis is primary or secondary to the
cataract. Systemic workup for the various infectious diseases
may further guide the clinician in the differential diagnosis
of a patient with cataract and uveitis.
Treatment
Because lens-induced uveitis is a reproducible model of
inducing ocular inflammation, many pharmacological agents
useful in treating uveitis in general have been studied using
experimental animals with LIU. Most of the agents studied
have not been used to any extent clinically.
Phacolytic uveitis in animals is usually treated nonspeci-
fically. Drugs used include topical corticosteroids (e.g. 1%
prednisolone acetate, 0.1% dexamethasone or 1% predni-
solone phosphate), topical nonsteroidal anti-inflammatory
drugs (0.03% flurbiprofen, 1% indomethacin, 1% suprofen,
or 0.1% diclofenac), topical mydriatics including 1%
tropicamide or 1% atropine sulfate, systemic corticosteroids
or systemic nonsteroidal anti-inflammatory drugs.65±67 If
glaucoma is present, appropriate antiglaucoma medications
need to be used as well.
The most important part of treatment of PE and phacolytic
glaucoma in humans and phacoclastic uveitis in animals is
surgical removal of the lens material.3,14,31,32,34,40,54 Medical
management of phacoclastic uveitis using anti-inflammatory
therapy is often not successful in preserving vision. Secondary
phthisis bulbi or glaucoma is common. It has been suggested to
use inhibitors of cell replication such as cyclophosphamide or
azathioprine if lens removal is not possible.1
Cyclooxygenase inhibitors, such as indomethacin, are
effective in reducing inflammation immediately after lens
injury; their effect decreases within hours after lens injury.58
Lipoxygenase inhibitors have their maximum anti-inflam-
matory effect after the peak effect of cyclooxygenase
inhibitors. The combination of cyclooxygenase and lipox-
ygenase inhibitors reduces inflammation both in the
immediate and the late phase of lens protein induced ocular
# 2000 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 3, 227±234
Paper 107 Disc
inflammation.58 An experimental cyclooxygenase/lipoxygen-
ase inhibitor significantly reduced ocular inflammation after
anterior capsulotomy in dogs.68 Interleukin-1 blockers have
been shown to be potent anti-inflammatory agents.69
Oxygen-derived free radicals generated by polymorpho-
nuclear leukocytes are important mediators of tissue damage
in PE. Systemic administration of catalase significantly
reduced inflammation in experimental PE.70±71 Catalases
are enzymes that catalyze the divalent reduction of hydrogen
peroxide to water. Other antioxidants used include glu-
tathione peroxidase,72 vitamin E,73 superoxide dismutase,74
ascorbate and aminonicotinamide.75 Other pharmacological
agents that reduce inflammation in experimental PE through
interaction with oxygen-derived free radicals are hydroxyl
radical scavengers (dimethyl sulfoxide,76 sodium benzoate,77
2,3-dihydroxybenzoic acid,77 and dimethyl thiourea.78)
Allopurinol and oxypurinol act as direct scavengers of free
radicals and hypochlorous acid, thereby leading to a
reduction in tissue damage.79±81 The effects of corticoster-
oids are mostly because of direct action on inflammatory
cells. In addition to this effect, methylprednisolone acts as a
mild scavenger.79
Implications for cataract surgery
The presence of phacolytic uveitis significantly reduces both
short-term and long-term success rate of cataract surgery in
veterinary medicine.4±5 This effect is present even when the
uveitis appears to be controlled prior to surgery.5 Intra-
operative complications are more common in eyes with (a
history of) phacolytic uveitis than in nonaffected eyes.
Chronic persistent uveitis after surgery may lead to severe
capsular opacification, formation of posterior synechiae,
retinal detachment, phthisis bulbi, and glaucoma.4±5 Per-
forming cataract surgery prior to the onset of phacolytic
uveitis may prevent short-and long-term complications
secondary to phacolytic uveitis. Because phacolytic uveitis
is most commonly seen in eyes with hypermature cataracts,
performing surgery when the cataract is either immature or
mature appears to be preferable to waiting until the cataract
has become hypermature. If phacolytic uveitis is present at
initial presentation to the ophthalmologist, aggressive
treatment of the uveitis both prior to and after surgery
appears to be indicated. The use of free radical scavengers
and antioxidants may become an important part of treatment
of phacolytic and phacoclastic uveitis in the future.
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