Ophthalmology Challenge: Aggressive ulcerative keratitis in a dog


Ophthalmology Challenge: Aggressive ulcerative keratitis in a dog

A 4-year-old, 66-lb (30-kg), spayed female greyhound was presented to the Ophthalmology Service at the University of Florida's College of Veterinary Medicine for ophthalmic evaluation. Two days before referral, the referring veterinarian had identified a corneal ulcer in the dog's left eye based on clinical appearance and the result of fluorescein staining.

The referring veterinarian had initiated topical treatment of the left eye that included administering 0.3% gentamicin sulfate ophthalmic solution four times a day, 5% acetylcysteine solution every two hours, autogenous canine serum four times a day, and 1% atropine sulfate solution once a day. After two days of this treatment, the corneal ulcer had progressed in diameter and depth, and the dog showed signs of increased pain, so the veterinarian referred the case. The dog had no history of trauma to the eye and no other health problems and was receiving no other medication.

Physical and ophthalmic examination findings

Figure 1. The dog's left eye stained with fluorescein on presentation (Day 1).
The dog was mildly depressed on physical examination. The results of the remainder of the physical examination were normal except for the left eye, which exhibited profound blepharospasm with severe conjunctival hyperemia and moderate epiphora. Both pupils were mobile and midrange in examination room light. Schirmer tear test results were 10 mm/min in the right eye and 18 mm/min in the left eye (normal ≥ 15 mm/min). The menace response, dazzle reflex, and pupillary light reflexes (direct and consensual) were present and bilaterally normal. The corneal lesion in the left eye stained with fluorescein (Figure 1). It was a round central corneal ulcer that was 8 mm in diameter and greater than half the stromal depth; the ulcer had a deeper pit in the center. Corneal melting and slight corneal neovascularization were present.

Slit-lamp biomicroscopy revealed a moderate amount of corneal edema and mild aqueous flare in the left eye. Intraocular pressures were not measured because of the dog's stressed condition. No apparent abnormalities were noted in the lens, vitreous, or fundus of either eye. We obtained corneal swab samples from the left eye for aerobic bacterial and fungal culture. Samples for corneal cytologic examination were not obtained because of the patient's fractious nature.

Differential diagnoses

Our initial diagnosis based on the dog's history and ophthalmic examination and fluorescein staining findings was a melting, stromal corneal ulcer. Clinical signs consistent with ulcerative keratitis included miosis, blepharospasm, epiphora, and photophobia. Causes of corneal ulceration in dogs include trauma, keratoconjunctivitis sicca, exposure keratitis, a foreign body, distichiasis, entropion, trichiasis, ectopic cilia, and exposure to caustic substances. No initiating factors were identified on initial ophthalmic examination in this patient. Given the gelatinous clinical appearance of the left cornea in this case, the likely differential diagnoses included corneal ulceration with stromal proteolysis due to secondary bacterial or mycotic infection and sterile melting corneal ulceration due to exposure to a caustic substance. Confirmation of infectious keratitis is based on the results of culture, corneal cytology, and histopathology and, presumptively, on response to treatment. We thought the subnormal Schirmer tear test result in the right eye was due to early or mild keratoconjunctivitis sicca or atropine administration.

Initial treatment

Figure 2A. A photomicrograph of a tape preparation of the fungal culture from the left eye on Day 3. Septate, hyaline, branching hyphæ with ellipsoidal conidia are present (lactol phenol cotton blue stain, 100×).
We initiated medical management to suppress the proteolytic activity and sterilize the ulcer. The owner elected to treat the dog on an outpatient basis. We discontinued the gentamicin ophthalmic solution prescribed by the referring veterinarian and initiated tobramycin ophthalmic solution given every four hours, and we increased the autogenous canine serum administration frequency to six times a day. The acetylcysteine and atropine were continued. We selected tobramycin because it causes less inhibition of corneal epithelial migration as well as fewer cytopathologic effects than gentamicin does.1

Figure 2B. Cytologic examination of a corneal scraping of the left eye on Day 3 showed oval-shaped, palely basophilic, sporelike structures (arrows) amid the basophilic cellular debris and corneal epithelial cells (Wright's-Giemsa stain, 100×).
No marked change was apparent in the eye the next day (Day 2). Superficial vessels had begun to migrate inward from the dorsal limbus by Day 3. No aqueous flare was present in the left eye on Day 3. Because the eye continued to appear painful and the pupil was not fully dilated, we added carprofen (2.5 mg/kg orally b.i.d.) and increased the topical atropine administration frequency to twice a day.

Diagnostic tests

Figure 2C. Cytologic examination of a corneal scraping of the left eye on Day 3 also revealed dark-brown-staining budding yeast (black arrow) and hyphal fragments (white arrow) (Gomori's methenamine silver stain, 100×).
On Day 3, results from the corneal fungal cultures were positive for scant growth of Acremonium species (Figure 2A); there was no growth on aerobic bacterial culture. The cornea was anesthetized with topical 0.5% proparacaine hydrochloride, and samples were collected from the left cornea with the handle end of a scalpel blade for cytologic examination. The samples stained with Wright's-Giemsa revealed basophilic cellular debris, along with a moderate number of corneal epithelial cells and nondegenerative neutrophils and several sporelike structures consistent with fungal infection (Figure 2B). Budding yeast structures and hyphal fragments were observed with Gomori's methenamine silver stain (Figure 2C).