Introduction

Keratomycosis is a relatively common ocular disease of horses, and to a much lesser extent, other species. Dusty, moldy environments and the probability of corneal abrasions due to feed and/or bedding materials are probably responsible for the increased incidence in this species.^1,2 Other than the occasional anecdotal report, no published references were found regarding this condition in cetaceans, even though fungi and yeasts are a normal part of the cetacean mucocutaneous flora and trauma to the cornea is not an uncommon sequel to vigorous play.

Cetaceans present unique challenges in the diagnosis and treatment of ophthalmic disease. Strong blepharospasm often makes examination impossible, and often makes topical treatment futile. Options for oral treatment are limited, but in this case, Fluconazole (Diflucan, Pfizer) P.O. resolved the blepharospasm, clearing most of the cornea and restoring visual acuity.

Case STUDY

Two weeks following transport from Japan (August 13/01), a 15-year-old Pacific white-sided dolphin (Lagenorhyncus obliquidens) named Spinnaker acutely developed a complete and unrelenting blepharospasm. No ocular trauma had been observed, but the assumption was that perhaps a tail flick from the other dolphin in the pool might have injured the cornea.

On several occasions, the animal was restrained out of the water for examination, but in each instance, and in spite of repeated infusion of copious quantities of ophthalmic topical anesthetic (Alcaine, Alcon) between the lids, we were not able to resolve the blepharospasm and accomplish an examination. We did not attempt to block of the auriculo-palpebral nerve due to our unfamiliarity with the anatomy of this species. Conjunctival cultures were obtained and grew Candida spp.--a microorganism commonly considered part of the normal flora of the mucocutaneous junctions of cetaceans.

At that time, we decided, after consultation with several veterinary ophthalmologists and marine mammal veterinarians, to not attempt further diagnostics and treatment, and to rely on the blepharospasm to provide both a protective and physiological bandage.

After several more months of complete blepharospasm, an ultrasound examination was undertaken (Dec 14/01) to ascertain whether the globe was intact, and if so, could any ophthalmic pathology be observed. The examination demonstrated an intact globe and was compatible with an anterior segment inflammatory condition; most probably keratitis and anterior uveitis.

Over the next few months the blepharospasm began to resolve until eight months after the initial clinical signs the eye was 50 percent open and the corneal lesion could finally be visualized. The area involved covered 70 percent of the cornea. The lesion was white, raised, irregular in surface contours and had a "feathery" appearance at the periphery, much as has been described previously in cases of equine keratomycosis.

Also at this time, the upper and lower left eyelids developed 10 to 12 small white punctiform lesions. These areas were scraped and cultured and grew Candida spp. This condition resolved readily after treatment with Ketoconazole topical cream two percent in petrolatum jelly three times daily for 40 days.

The appearance and successful treatment of a Candida blepharitis along with the clinical appearance of the newly visible corneal lesions caused us to consider the possibility of a keratomycosis.

Spin was again restrained out of the water for an ocular examination. Topical anesthetic was applied along with a fluorescein stain. There was minimal retention of the fluorescein. The cornea was scraped and specimens submitted for both cytology and culture. Cytology samples were stained with Wright's Giemsa stain and demonstrated masses of pseudohyphae. Culture on Sabouraud's agar grew Candida albicans. The presence of pseudohyphae is thought to be definitive evidence of tissue invasion by the yeast organism.

Having now arrived at the definitive diagnosis of keratomycosis, oral therapy with Fluconazole (Diflucan, Pfizer) was initiated at a dosage rate of 2 mg/kg Q 12 hours. Fluconazole was chosen because of its demonstrated superior efficacy over the other azole derivatives in the treatment of Candida infections and because of its incorporation at a therapeutic level into the tear film. As was the case earlier, no topical treatment was possible.

Because of the paucity of reports on the use of fluconazole in this species, plasma levels of the drug were evaluated on several occasions. These levels were 5.2 and 5.5 mg/L on two occasions, approximately two hours post dosing. These values are at the low end of a wide spectrum reported for humans.

We continued fluconazole therapy for 35 days during which time the size of the corneal lesion decreased from 70 percent of the corneal area to 10 percent. During this time the blepharospasm resolved completely and Spin's trainers assessed visual acuity to be within normal limits.

As previously mentioned, duration of the initial fluconazole therapy was 35 days. Ideally, we would have treated for a longer period of time, but coincident with his ocular lesions, Spin also was being treated with Trimethoprim sulfadiazine (Coptin, Axcan Pharma) for skin eruptions on his peduncle and had developed significant elevations in ALT, AST and AP levels. Both drugs were terminated until these enzyme levels returned to normal approximately three weeks later. After resolution of the enzyme values, Spin was put on Ciprofloxacin (Cipro, Bayer) for the tail wounds, and 25 days later (Dec 24/02) on fluconazole, both to augment our prior treatment of the keratomycosis and as a precaution against generalized fungal overgrowth while on Ciprofloxacin. These therapies did not result in any increase of liver enzymes, leaving Trimethoprim sulfadiazine as the prime suspect.

Interestingly, during the 12 weeks in which we discontinued antifungal therapy in order to allow the liver enzymes to return to normal, the size of the corneal lesion continued to decrease at a significant rate.

We initially considered two possibilities for this phenomenon. One was that our antifungal therapy had indeed eliminated the Candida from the corneal lesion and we were now observing an ongoing resolution of corneal scar tissue. The other possibility was that of continuing therapeutic plasma levels of fluconazole caused by sequestration in the blubber during treatment, and then release from the blubber for several weeks after treatment cessation. This phenomenon is commonly observed with itraconazole therapy in cetaceans, but in at least this instance of fluconazole therapy, plasma levels were negligible (<2.5mg/L) six days after cessation of treatment. This difference in activity between fluconazole and itraconazole probably is due to the much stronger lipophilic properties of the latter.

Fifteen months after the start of clinical signs, blepharospasm is resolved, a 4-mm central corneal scar remains, and visual acuity appears, at least subjectively, to be within normal limits.

Acknowledgements

The author acknowledges the following veterinarians who assisted generously in the diagnosis and management of this case: M.N. Bussanich--ocular examination and photography; Bruce Grahn--ultrasound examination and review of abstract; Charlotte Keller--ocular examination; Sally Lester--cytology of corneal scraping; Mark Papich--therapeutics

References

1.  Ball M. Equine Fungal Keratitis. Compend. Cont Educ Pract Vet: (22) 182-185, 2000

2.  Grahn B. Equine Keratomycosis: Clinical and Laboratory Findings in 23 Cases. Prog in Veterinary and Comparative Ophthalmology 3: 2-7