Ophthalmology Challenge: A greyhound with red eyes

A 4-year-old spayed female greyhound was presented to Colorado State University Veterinary Teaching Hospital for evaluation of redness in both eyes, a possible corneal ulcer in the right eye, and a scratch in the skin of the medial canthus of the left eye. The owner reported that a recent fight had caused the ocular and periocular lesions. The dog was a retired racing greyhound and had been with its current owners for two years. No other health-related complaints were noted.

Physical and ocular examinations

The results of the physical examination were normal except for the eyes. Vision was present in both eyes as determined by menace reflex and tracking tests, and the pupillary light and blink reflexes were normal. Intraocular pressures were normal at 10 mm Hg in the right eye and 11 mm Hg in the left (normal = 10 to 20 mm Hg). Schirmer tear test results were also normal at 15 mm at 60 seconds in both eyes (normal ≥ 15 mm/min). The bulbar and palpebral conjunctival vessels of both eyes were mildly injected. Reddish-pink, slightly raised tissue and blood vessels were present at the midlateral limbus of each eye and appeared to be extending from the conjunctiva or sclera (Figures 1 & 2). On the left eye, the tissue extended about 5 mm onto the cornea and measured about 4 mm from top to bottom. The tissue on the right eye was more prominent and extended 7 mm onto the cornea. Both areas were well-vascularized, and on biomicroscopic examination, the masses did not appear to extend deeply into the corneas. No miosis or aqueous flare was seen in either eye, and the results of the fundic examinations were normal. Slight fluorescein dye retention occurred in the crevices of the raised tissue in both eyes. This nonspecific stain retention was due to the irregularity of the tissue and not true corneal ulceration. An 8-mm superficial scratch was present on the skin of the medial canthus of the left eye. The scratch did not extend to the left globe and was healing well.

FIGURE 1. At presentation, the greyhound eyes appear cloudy from corneal neovascularization and granulation tissue-like ingrowths. FIGURE 2. A close-up of the dog left eye shows corneal neovascularization and granulation-like tissue extending across the cornea from the lateral limbus (solid arrow). Note the small areas of infiltrate a few millimeters in front of the advancing neovascularization (dashed arrow).

Differential diagnoses and additional testing

Differential diagnoses for the dog's ocular problems included chronic superficial keratitis, granulation tissue secondary to irritation or foreign bodies, neoplasia, and metabolic infiltrates (e.g. lipids, minerals). Keratoconjunctivitis sicca is another differential diagnosis in dogs presenting with these clinical signs, but it was ruled out because of the normal Schirmer tear test results. By carefully inspecting the conjunctiva and conjunctival fornices and evaluating the dog's ability to blink and completely close its eyelids over the corneas we were able to rule out exposure keratopathy or foreign bodies. The results of a complete blood count and serum chemistry profile were normal, indicating that neither hypercholesterolemia nor hypertriglyceridemia led to corneal lipid or cholesterol deposition. After applying a topical anesthetic to both eyes, we obtained a scraping of the tissue in each eye with a Kimura spatula and submitted the material for cytologic evaluation. The results showed numerous normal epithelial cells, lymphocytes, neutrophils, and occasional mast cells.

Diagnosis and treatment

The cytologic evaluation results combined with the other findings led to a diagnosis of chronic superficial keratitis (CSK). We prescribed prednisolone acetate 1% ophthalmic drops three times a day in both eyes for an indefinite period. In addition, we augmented the corticosteroid therapy by administering 0.2% cyclosporine ophthalmic ointment (Optimmune—Schering Plough Animal Health) twice a day in both eyes.

At a recheck examination three weeks later, the dog's corneas were completely clear except for several superficial ghost vessels in each eye that were visible with the biomicroscope and some corneal cloudiness due to scarring. We continued the dog's medications at the same dosage and scheduled another recheck for six months later.

Discussion

CSK is also called pannus, German shepherd pannus, degenerative pannus, and Uberreiter's syndrome. It was first described in 19131 and further characterized in 1959.2 This progressive degenerative disease involving the subepithelial portions of the canine cornea is characterized by bilateral, fleshy-looking lesions that initially appear at the temporal limbus and then spread nasally toward the central cornea. If the disease is left untreated, lesions also arise from the nasal limbus and progress laterally, joining the laterally arising lesions. In its early stages, the disease may be difficult for owners to recognize. As it progresses, superficial vascularization may be intense and large vessels may appear. Limbal melanocytes, if present, also invade the subepithelial cornea, making the lesions appear black (Figure 3). Pigment can appear in the disease's early stages if the limbus is heavily pigmented. This can make it even more difficult for some owners to detect a problem because from a distance the eye appears dark, as it normally would in most dogs. In fact, owners may detect visual deficits before they notice the corneal lesions. The superior portion of the cornea is the last area to be affected, and eventually, the entire cornea may be pigmented, vascularized, and scarred (Figure 4). Frequently, small white dots or a white line in the cornea may precede the advancing fleshy lesion (Figure 2).3 In some dogs, thickening and depigmentation of the nictitating membrane may occur concurrently with or independently of the corneal lesions.3 This is called atypical pannus or plasmoma (Figure 5).

FIGURE 3. Pigmented CSK in a German shepherd. Note that the lesion originates from the lateral limbus. FIGURE 4. An advanced case of pigmented CSK in a German shepherd. The eyelid speculum has been placed in preparation for the dog radiation therapy. FIGURE 5. Atypical pannus, or plasmoma, in a German shepherd. The nictitating membrane is depigmented, thickened, and irregular.

Two predisposing factors to developing CSK are known. One of these factors is breed of dog. German shepherds are overrepresented, but other breeds frequently affected include greyhounds, Belgian Tervurens, dalmatians, dachshunds, and Siberian huskies.4 No specific genetic mutation leading to this disease is known of, but the disease tends to be familial. Exposure of the cornea to ultraviolet light is another predisposing factor. Both the incidence and severity of CSK increase with increasing altitudes,4,5 and dogs living at lower elevations respond more favorably to therapy than dogs living at elevations over 4,000 ft do.5

The pathogenesis of CSK is thought to be a cell-mediated immune response to corneal altered antigens (or antigens altered by ultraviolet light), but it is not a typical autoimmune disease in that there are not antibodies to normal self-proteins.1 One study demonstrated that dogs with CSK have an increased number of corneal mast cells and that these mast cells have more intense degranulation than the mast cells in the corneas of normal dogs or dogs with keratitis caused by other factors.1 In addition, in comparison with clinically normal dogs, dogs with CSK have significantly increased hypersensitivity-like cellular responses against corneal antigens.6 These findings support the theory that CSK is an immune-mediated disease. The cornea contains tissue-specific antigens that are modified by ultraviolet light. It may be that these altered antigens induce a cell-mediated immune response against the modified cornea. Further support of an immune-mediated pathogenesis of CSK comes from a study in which researchers used immunohistochemical staining to detect immunoglobulin in the corneas of dogs with CSK.1 The pattern of corneal staining that the researchers detected was diffuse in the stroma and uncharacteristic of that of autoimmune diseases. Perilimbal immunoglobulin deposition was present, suggesting that conjunctival-associated lymphoid tissue and Langerhans' cells might be involved in the disease process.1 These cells are probably involved with immune processing and the production of the antibodies responsible for CSK.

Treating CSK is directed at controlling the immune response and preserving vision. Because no cure is available, lifelong therapy is necessary. Initial therapy usually involves topical or subconjunctival corticosteroid administration. One percent prednisolone acetate or 0.1% dexamethasone ophthalmic preparations, both potent anti-inflammatory and immunosuppressive agents, should be administered two to four times a day, depending on the initial severity of the lesions. If owner compliance with the medication schedule is a problem or if the lesions are advanced when therapy is initiated, a subconjunctival injection of a medium-or long-acting corticosteroid may be given. This type of injection does have some risk because if a corneal ulcer develops, there is no way to extract or discontinue the medication. Owners should be warned of this risk and taught to recognize the clinical signs of corneal ulcers (e.g. blepharospasm, epiphora, purulent ocular exudates). Owners should bring dogs in immediately if clinical signs occur. Adding topical cyclosporine (0.2% ointment [Optimmune] to 2% oil [formulated by a compounding pharmacy]) to the treatment regimen is widely done because it appears to be beneficial and may allow a reduced topical corticosteroid dosage. 7

The affected dog's response to therapy and prognosis for preserving vision varies with its breed and genetic makeup, the dog's age at the onset of the disease, the altitude and geographic location of the dog's residence, owner compliance with drug administration, and the severity of the lesions at the initiation of therapy. If the dog lives at a lower altitude (< 4,000 ft), the prognosis for preserving vision with medical therapy alone is good.5 The younger the dog is at the onset of disease, the poorer the prognosis because the dog has more time for the disease to progress. Obviously, an owner's diligence with drug administration plays an important role in controlling the disease.

FIGURE 6. A strontium-90 beta applicator in place on the cornea of a German shepherd that is undergoing radiation therapy for severe CSK.

If the affected dog lives at a high altitude or if the disease becomes uncontrolled, surgery, radiation therapy, or both may be indicated. Strontium-90 beta radiation may be used to halt endothelial cell and pigment proliferation (Figure 6).8 This type of radiation only penetrates 1 mm, so the CSK plaque must be relatively thin for the treatment to be effective.7 After radiation therapy, the eye will improve in a week and maximum clearing of the cornea will occur by 30 days.8 Neither extended hospitalization nor isolation is required, as residual radiation is not a factor. If the lesions advance to the point that the cornea is severely scarred, a superficial keratectomy may be performed to totally remove the lesions. Beta radiation can then be applied to the limbus to prevent postsurgical neovascularization.8

The prognosis for preserving this dog's vision is guarded, as is the prognosis for all patients at Colorado State University (because of the altitude) that are diagnosed with CSK, but because treatment was initiated relatively early and because the owners are conscientious, we think that the dog will be visual for many years.

The photographs and information for this case were provided by Juliet R. Gionfriddo, DVM, MS, DACVO, and Cynthia Powell, DVM, MS, DACVO, Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80524.

REFERENCES

1. Eichenbaum JD, Lavach JD, Gould DH, et al. Immunohistochemical staining patterns of canine eyes affected with chronic superficial keratitis. Am J Vet Res 1986;47:1952-1955.

2. Uberreiter O, Sibalin M, Burki F. Etiology of chronic superficial keratitis in German shepherd dogs. [German]. Wien Tierarztl Monatsschr 1971;58:323-328.

3. Whitley RD, Gilger BC. Diseases of the canine cornea and sclera. In: Gelatt KN, ed. Veterinary ophthalmology. 3rd ed. Philadelphia, Pa: Lippincott, Williams and Wilkins, 1999;635-673.

4. Bedford PG, Longstaffe JA. Corneal pannus (chronic superficial keratitis) in the German shepherd dog. J Small Anim Pract 1979;20:41-56.

5. Slatter DH, Lavach JD, Severin GA, et al. Uberreiter's syndrome (chronic superficial keratitis) in dogs in the Rocky Mountain area: A study of 463 cases. Small Anim Pract 1977;18:757-772.

6. Campbell LH, Okuda HK, Lipton DE, et al. Chronic superficial keratitis in dogs: Detection of cellular hypersensitivity. Am J Vet Res 1975;36:669-671.

7. Williams DL, Hoey AJ, Smitherman P. Comparison of topical cyclosporine and dexamethasone for the treatment of chronic superficial keratitis in dogs. Vet Rec 1995;137:635-639.

8. Severin GA. Cornea. In: Severin's veterinary ophthalmology notes. 3rd ed. Fort Collins, Colo: Severin, 1996;285-350.