1022 • SECTION III: Canine Ophthalmology

SECTION III

Figure 18.58. Diffuse corneal edema in a dog with advanced corneal Figure 18.59. A Boston Terrier dog with early endothelial dystrophy.
endothelial dystrophy. The initial lesion, corneal edema, is located temporally and progresses
slowly, over several months to a few years, to involve the entire cornea.

Noncrystalline Cornea Opacities copy. The endothelium has a decreased number of cells and
exhibits fibrous metaplasia. Descemet’s membrane is thick-
Corneal Endothelial Dystrophy
ened because of fibrillar deposits and exhibits some guttata
Endothelial cell dystrophy is a disease of spontaneous, pro- (Adamis et al., 1993; Bergmanson et al., 1999).
gressive corneal edema resulting from abnormal dystrophic In dogs, on examination, the corneal opacity has a bluish-
endothelial cells. In the dog, this condition is most prevalent white appearance, with a lack of corneal vascularization or
in the Boston Terrier, Chihuahua, and Dachshund (Martin & conjunctival hyperemia. The initial lesion, corneal edema, is
Dice, 1982). It occurs more frequently in females. The age of located temporally and progresses slowly, over several months
onset in the Boston Terrier ranges from 5 to 9 years (mean to a few years, to involve the entire cornea (Fig. 18.59).
age, 7.5 years) (Fig. 18.58); the age of onset in the Chihuahua Involvement between fellow eyes is often initially asymmetric
ranges from 6 to 13 years (mean age, 9.5 years). Gwin et al. but progresses to bilateral, complete corneal opacity. On bio-
(1982a) reported four cases of primary canine corneal endo- microscopy, the main observations are increased corneal
thelial dystrophy: a 12-year-old male Boxer, a 2-year-old male thickness, corneal opacity, epithelial bullae, and subepithelial
Miniature Schnauzer, a 3-year-old male Miniature Poodle, scarring. In some dogs, the posterior corneal surface has fine,
and a 12-year-old male Boston Terrier. A similar condition bright, compacted striae and occasionally, with specular
also occurs in the aged Wire-Haired Fox Terrier and the Basset reflection, black spots or holes in the endothelial mosaic
Hound. pattern (Fig. 18.60) (Martin & Dice, 1982). Specular micros-
Canine endothelial cell dystrophy may represent a disease copy may assist in early diagnosis and therapy (Gwin et al.,
process similar to, and possibly an animal model of, Fuchs 1982a).
dystrophy in humans. Fuchs dystrophy is a progressive, Palliative therapy is most commonly used for canine endo-
bilateral degeneration of corneal endothelial cells that results thelial dystrophy. Most dogs maintain limited vision with this
in an edematous, avascular cornea (Adamis et al., 1993; Berg- disease and only develop morbidity when corneal ulcers
manson et al., 1999). It is characterized by a slow, continuous develop following rupture of epithelial bullae (Fig. 18.61).
loss of morphologically and physiologically altered endothe- These ulcers are managed using topical broad-spectrum anti-
lial cells, that leads to corneal edema. Fuchs dystrophy is biotics and topical hyperosmotic medications (e.g., 5% sodium
inherited as an autosomal-dominant inherited disease with chloride). Hyperosmotics may decrease the extent of epithe-
incomplete penetrance trait in humans and is three times more lial bullae formation, but significant corneal clearing does not
common in females. Treatment options are palliative medical occur. Ocular irritation and lacrimation, which may cause
therapy or penetrating keratoplasty (Adamis et al., 1993; drug dilution and reduce corneal contact time, from hyperos-
Bergmanson et al., 1999). The corneal endothelium and Des- motic preparations also limits their usefulness. Topical corti-
cemet’s membrane have abnormalities on specular, confocal, costeroids have been advocated on an empiric basis for
light, scanning-electron, and transmission-electron micros- stromal edema in humans with Fuchs dystrophy and in affected
 Chapter 18: Diseases and Surgery of the Canine Cornea and Sclera • 1023

lial bullae (Fig. 15.62) (Michau et al., 2003). The procedure

is performed in sedated or anesthetized dogs. A lid speculum
is placed, and the cornea and conjunctiva flushed with 1%
povidine-iodine and rinsed with sterile eyewash. Loose
corneal epithelium is debrided with sterile cellulose sponges
or cotton-tipped applicators. TKP is performed only in the
areas of exposed stroma, after debridement of nonadherent
epithelium. Post-TKP medications include the topical admin-
istration of antibiotics, topical mydriatic/cycloplegic, and oral
nonsteroidal anti-inflammatory medications for pain manage-
ment. In a study reviewing the results of TKP in 13 dogs with

SECTION III
Figure 18.60. Abnormal endothelial cell mosaic in a 12-year-old Boxer.
There are occasional very large cells (arrows) and generalized pleomor-
corneal ulcers from endothelial disease (for a mean duration
phism. Cell density is 1320 cells/mm2. (Photograph courtesy of Dr. Robert of 16.1 weeks), the mean time to corneal ulcer healing after
M. Gwin.) TKP was 2.2 ± SD 1.1 weeks (Michau et al., 2003). Thermal
cautery of the cornea is also described for treatment of
SCCEDs in dogs (discussed earlier in this chapter) (Bentley
& Murphy, 2004). The only definitive treatment for endothe-
lial dystrophy is replacement of the endothelial cells via a
homologous corneal transplant (see subsequent text); however,
nonpenetrating and penetrating keratoprosthesis implantation
is also described in a limited number of dogs with vision loss
attributed to endothelial dystrophy (Allgoewer et al., 2010b;
Isard et al., 2010).

Posterior Polymorphous Dystrophy

A syndrome of corneal endothelial cell dysfunction and
degeneration resulting in multifocal posterior corneal opaci-
ties in the dog resembles posterior polymorphous dystrophy
in humans (Presberg et al., 1985). In one study, the posterior
corneal opacities were multifocal, nonpigmented, and vesicu-
lar to linear in appearance (Fig. 18.63) (Gwin et al., 1983a).
Slit lamp examination revealed opacities limited to the endo-
thelial cell–Descemet’s membrane region (Fig. 18.63). Contact
specular microscopy revealed intracellular opacities and local
cellular enlargement (Fig. 18.64). In affected American
Figure 18.61. Bullous keratopathy in a dog with endothelial Cocker Spaniels, an autosomal-dominant or incomplete domi-
dystrophy.
nant inheritance has been suggested (Gwin et al., 1983a).
Scanning-electron microscopy demonstrated a background
of normal-appearing cells, with multifocal areas of degen­
eration. Zones of advanced cellular degeneration were
dogs; however, topical corticosteroids (e.g., dexamethasone)
manifested by exposed Descemet’s membrane. Transmission-
or nonsteroidal medications appear to have no beneficial
electron microscopy revealed a monolayer of normal cells,
effect in dogs (Gwin et al., 1982a; Martin & Dice, 1982;
with an underlying membrane immediately anterior. The
Wilson & Bourne, 1988).
affected endothelium displays sparse mitochondria and ribo-
Dogs with persistent bullous keratopathy and nonhealing
somes, and the cytoplasm has a “moth-eaten” appearance
corneal ulcers as a result of endothelial dystrophy (or degen-
(Gwin et al., 1983a).
eration, discussed earlier in this chapter) may benefit from
thermokeratoplasty (TKP) (Michau et al., 2003). In TKP, the
Florida Keratopathy
use of multifocal points of superficial thermal cautery (Fig.
18.62) applied in a circular fashion to the exposed corneal Corneal opacities, apparently unique to tropical and subtropi-
stroma results in contraction of the anterior stromal collagen cal climates, are described in the dog and cat. These opacities
fibers. The goal is to develop mild superficial stromal contrac- have been referred to as Florida keratopathy, Florida spots,
ture and opacity, and not a focal burn, with the use of minimal Florida fungus, and tropical keratopathy. Clinically, this con-
probe temperatures. The resulting subepithelial scar tissue dition is characterized by multifocal, round, gray to gray-
acts as a partial barrier to the flow of fluid through the cornea white, fluffy, cotton-like opacities of varying size in the
and helps to reduce the buildup of fluid that results in epithe- corneal stroma (Fig. 18.65) (Barros & Safatle, 1997; Peiffer
 (a) (b)
SECTION III

(c)

Figure 18.62. (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 immediately following thermokeratoplasty.
(c) Cornea 4 weeks after thermokeratoplasty. 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.

A B

Figure 18.63. Clinical (A) and slit lamp (B) photographs of posterior polymorphous dystrophy in an American Cocker Spaniel. The posterior corneal
opacities are multifocal and vesicular to linear in appearance. (Photographs courtesy of Dr. Robert M. Gwin.)

1024
 Chapter 18: Diseases and Surgery of the Canine Cornea and Sclera • 1025

SECTION III
Figure 18.64. Specular micrograph of canine posterior polymorphous
dystrophy. Note the cellular enlargement and intracellular opacities. (Pho-
tograph courtesy of Dr. Robert M. Gwin.)

Figure 18.66. Ziehl-Neelson-stained canine corneal tissue demonstrat-

ing acid-fast material (arrow). (Original magnification, 800×.) (Photograph
courtesy of Dr. Craig Fischer.)

The etiology and composition of the corneal opacities in

dogs with Florida keratopathy is unknown, but several theo-
ries have been proposed. In one study, keratectomy specimens
from diseased corneas were cultured and processed for light
microscopy (Peiffer & Jackson, 1979). Cultures failed to con-
sistently reveal pathogenic microorganisms, including fungi.
With light microscopy, numerous round-to-oval vacuoles
ranging in size from 30 to 200 µm were present in an other-
wise normal corneal stroma. It was suggested the vacuoles
could represent Rhinosporidium organisms. Staining of
corneal tissues from a dog with Florida keratopathy demon-
strated acid-fast structures within the stromal collagen lamel-
Figure 18.65. Dog with Florida keratopathy. lae (Fig. 18.66) (Fischer & Peiffer, 1987). The staining
characteristics of the bodies in the anterior stroma were con-
sidered consistent with those of acid-fast organisms. Trans-
mission electron microscopy demonstrated a homogeneous,
light-staining material that could be a lipoidal substance.
& Jackson, 1979). The corneal lesions frequently have a dense Round to oval vacuoles measuring 0.5–1 µm in diameter were
center and a less dense periphery. These opacities occur at seen scattered throughout the corneal stroma. These vacuoles
varying levels throughout the corneal stroma; however, most variably contained an amorphous material and granular,
appear in the anterior stroma. Opacities may be unilateral or nonmembrane-bound, rodlike structure that suggested myco-
bilateral. The corneal epithelium is intact and Schirmer tear bacterial organisms (Fig. 18.67). Other researchers have failed
test values are within normal limits. The condition appears to to identify histopathologic abnormalities or infectious agents
be self-limiting and does not respond to topical corticosteroids in the corneas of dogs and cats with Florida keratopathy
and antifungal drugs. Superficial lamellar keratectomy is (Sarfaty, 2009). Corneal envenomation by a fire ant (Wasman-
reported to be curative, but the need for this procedure is nia auropunctata) was recently suggested as the etiology of
questionable as the corneas are devoid of evidence of inflam- Florida keratopathy based largely upon correlation between
mation, the eyes exhibit no discomfort, and visual compro- the geographic range of the ants and the geographic distribu-
mise is generally not appreciable (Peiffer & Jackson, 1979). tion of the keratopathy (Sarfaty, 2009).
 1026 • SECTION III: Canine Ophthalmology

treated with amiodarone and are clinically and histopathologi-

cally similar to the intracytoplasmic lamellar inclusion bodies
detected more commonly in the corneas of humans after
chronic amiodarone therapy (Bicer et al., 2002; Mantyjarvi
et al., 1998). Tocainide is a narrow spectrum antiarrhythmic
drug used for ventricular arrhythmias. When administered to
Doberman Pinschers with cardiomyopathy, tocainide pro-
duced bilateral, progressive, and often severe corneal edema
in 25% of dogs after several months of therapy (Calvert et al.,
1996; Gratzek et al., 1996).
Capecitabine is an oral antineoplastic and immunosuppres-
SECTION III

sive medication that is used in dogs to prevent renal allograft

rejection and for the chemotherapy of various cancers. A
portion of dogs administered capecitabine in an experimental
model of renal transplant rejection developed superficial crys-
talline corneal deposits, geographic erosions, pigmentation,
and vascularization (Zarfoss et al., 2007). Oral administration
of the fluoropyrimidine-based antineoplastic agent designated
S-1 in dogs resulted in partially reversible corneal pigmenta-
tion, vascularization, and inflammation similar to what can
Figure 18.67. Transmission-electron micrograph of a vacuole contain- occur in humans receiving the agent clinically (Hayashi et al.,
ing a granular, non-membrane-bound, rodlike structure suggestive of a 1996; Kitajima et al., 1996; Kobashi et al., 2011).
mycobacterial organism. (Original magnification, 3200×.) (Photograph
Induction of tyrosinemia in dogs by administration of the
courtesy of Dr. Craig Fischer.)
4-hydroxyphenylpyruvate dioxygenase inhibitor 2-(2-nitro-4-
trifluoromethylbenzoyl)-cyclohexane-1,3-dione resulted in
refractile stellate-shaped corneal epithelial opacities similar to
those observed in humans with tyrosinemia II and reported in
a dog with congenital tyrosinemia (Kunke et al., 1984; Lock
Pharmaceutical Deposits and Corneal Opacities
et al., 2006). Oral administration of an ansamycin hypolipid-
Pharmaceutical corneal opacities may occur from direct depo- emic agent to dogs produced irreversible changes in some of
sition of drugs or secondary toxic reactions. Topically applied the dogs, including posterior stromal edema, deep stromal
and systemically administered pharmaceuticals may access vascularization, and polymorphic infiltrates in the region of
the cornea through the tear film, limbal vasculature, or aqueous Descemet’s membrane (Schiavo & Bentley, 2000). Histopath-
humor. Corneal opacities associated with drug administration ologic alterations in the cornea induced by the hypolipidemic
are infrequently reported in dogs. White, refractile, punctate agent consisted of vascularization, vacuolar degeneration of
corneal opacities are anecdotally described in dogs during keratocytes, and Descemet’s thickening. Lortalamine, a non-
long-term administration of topical corticosteroids including tricyclic antidepressant and selective norepinepherine reup-
prednisolone acetate and dexamethasone sodium phosphate take inhibitor, resulted in corneal opacities, progressive
(Holmberg & Maggs, 2004). Clinically similar punctate crys- ulcerative keratitis, and diffuse corneal edema in as few as 2
talline corneal opacities were detected in dogs under experi- days after administration to dogs (Mally & Thiebault, 1990).
mental conditions during topical ophthalmic prednisolone High doses of the experimental sympathomimetic agent
acetate administration (Ledbetter et al., 2010). The opacities fluoromethane-sulfonanilide were associated with the forma-
developed after 24 days of prednisolone administration and tion of corneal opacities, keratitis, and corneal ulcerations
were biomicroscopically located in the subepithelial and ante- in dogs during a preclinical safety evaluation study (Steffen
rior stromal regions. The composition of the opacities was not et al., 1980).
determined, but with in vivo corneal confocal microscopy, the
opacities appeared as linear, reflective, branching crystalline
structures that were located throughout the full thickness of
SURGERY FOR CORNEAL OPACITIES
the axial corneal stroma with the highest concentration in Several nonulcerative corneal opacities lead to vision decrease
anterior stroma. The corneas were otherwise unremarkable by or loss. These include lipid corneal degenerations, pigmentary
ophthalmic examination and in vivo confocal microscopy. The keratitis, stromal abscesses, corneal edema, corneal scarring,
crystalline opacities resolved clinically in some of the dogs corneal neoplasms, limbal melanomas, and calcific keratopa-
following discontinuation of topical prednisolone. thy. Lesions involving the superficial stroma or epithelium
Amiodarone is an antiarrhythmic drug that is used in dogs may be managed with superficial keratectomy, using either a
for both atrial and ventricular arrhythmias. Corneal microde- traditional surgical method or an excimer laser (discussed
posits in the basal epithelium occur infrequently in dogs earlier). Deep or full-thickness lesions, such as corneal or