Ophthalmology Challenge: Aggressive ulcerative keratitis in a dog - Veterinary Medicine
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Ophthalmology Challenge: Aggressive ulcerative keratitis in a dog


Melting corneal ulcers result from excessive production of proteolytic enzymes that digest the corneal stroma. The clinical appearance of melting corneal ulcers includes a gelatinous and liquefied corneal stroma with corneal edema. Ocular pain, mucopurulent ocular discharge, and secondary uveitis often accompany the process. Proteases are normally produced by the corneal epithelium, keratocytes, and neutrophils to aid in corneal repair.2 Certain bacteria and fungi, most notably Pseudomonas species, can also produce these enzymes, resulting in rapid digestion of the corneal stroma and possibly leading to corneal perforation.2 Melting corneal ulcers may indicate an infectious etiology, but nonseptic insults such as exposure to certain caustic agents, especially alkaline substances, may activate the matrix metalloproteinase.

Fungal keratitis is infrequently reported in dogs but should be considered as a differential diagnosis for keratitis. The typical appearance of keratomycosis in any species is a corneal ulcer, a plaque with white fluffy stromal infiltrates, or both. Occasionally, dematiaceous fungi will produce brown corneal pigment.3 Fungi are opportunistic saprophytes that require damage to the corneal epithelium or decreased local immunity to establish an infection in the cornea.4 Most cases of keratomycosis in small animals are associated with prior corneal disease or trauma, systemic diseases such as hyperadrenocorticism or diabetes mellitus, or therapy with antibiotics or corticosteroids, any of which may predispose an animal to fungal infection.3,5-7 This patient had Schirmer tear test values below normal in both eyes during treatment, which could have been a predisposing factor in this case.8

Fungal keratitis in dogs generally presents as acute, progressive ulcers; keratitis characterized by plaque formation; or chronic, nonprogressive, superficial ulcers or erosions.3 The most commonly implicated fungal pathogen in dogs is Aspergillus species.3,9 Keratomycosis in canine corneas in previous reports was also caused by Fusarium,3 Acremonium,5 Curvularia,6 Pseudallescheria,7 and Alternaria species.10 Fungi were isolated from the conjunctiva in 11 of 50 (22%) normal dogs in one study.11 In a previous report in dogs with keratoconjunctivitis sicca, fungi were isolated from the corneal surface in nine of 61 eyes (15%), with Alternaria species being the most common (two of 61, 3%).10

Fungal infection is diagnosed based on both cytologic examination and culture performed on deep corneal scrapings.11,12 Cytologic examination is ideally performed by using a modified Gomori's methenamine silver stain of a corneal scraping, but hyphae can usually be seen with Wright's-Giemsa stain. Gomori's methenamine silver stain is reported to be 86% sensitive for identifying fungal elements in tissue.13 On cytologic examination, Acremonium species appear as septate, hyaline, branching hyphae 2- to 4-μm wide with tapering phialides.4 Fungal culture is most commonly performed by using Sabouraud's dextrose agar between 25 to 30 C; growth is generally evident within five days.4,14 Ideally, fungal sensitivity testing should be performed in cases of fungal keratitis, but results are usually not available for several weeks, thus diminishing the clinical utility of this diagnostic test.

Both corneal cytology and culture identified Acremonium species in this patient. Acremonium species are saprophytic fungi commonly found in decaying plant material and as soil contaminants; they infrequently infect people and dogs.5,14-16 Most commonly, Acremonium species infections in people lead to the formation of mycetomas or keratitis, although endophthalmitis and systemic infections can occur.14,16 Acremonium species infections have been previously reported in dogs, causing systemic infection and keratoconjunctivitis.5,15

Medical management of ulcerative fungal keratitis should include antimicrobials, nonsteroidal anti-inflammatory drugs (NSAIDs), collagenase or protease inhibitors, and parasympatholytics. The antifungal of choice for treating ocular Acremonium species infection in dogs is unknown. In people, topical antifungal therapy (natamycin 5% or amphotericin B 0.15%) and keratoplasty appear to effectively treat Acremonium species keratitis.14 Amphotericin B has the best in vitro activity against various Acremonium species.16 In one previous report of Acremonium species keratitis in dogs, treatment with natamycin and 2% yellow mercury oxide was effective.5 Members of this genus are also reported to be susceptible to posaconazole (Noxafil—Schering-Plough),17 but in this case a good response to natamycin was seen. Topical antifungal therapy should be applied three or four times a day initially, theoretically, to reduce iridocyclitis due to death of fungi, and then should be increased up to every four hours after the first few days.

Adjunctive therapy with broad-spectrum topical antibiotic therapy (neomycin-polymyxin B-gramicidin, gentamicin, chloramphenicol, or tobramycin)2,18,19 should be used with fungal keratitis to treat or prevent secondary bacterial keratitis. Topical or systemic NSAIDs should be used if anterior uveitis is present (aqueous flare, miosis, hypotonia). Topical collagenase and protease inhibitors are valuable in slowing the progression of melting corneal ulcers.18 The most commonly used protease inhibitors in veterinary medicine are acetylcysteine and autogenous serum applied four to six times a day. A topical parasympatholytic, 1% atropine sulfate solution, should be included in the treatment of ulcerative keratitis for its mydriatic and cycloplegic effects and to reduce synechiae formation. Superficial keratectomy of the fungal plaque can be performed with topical anesthesia to reduce the infectious burden and enhance penetration of topical medications. Surgery, consisting of either creating conjunctival flaps or grafts or performing corneal transplantation, should be considered in severe cases in which a descemetocele or a melting ulcer affecting greater than half the depth of the cornea is present.

Cases of canine fungal keratitis generally respond favorably to medical treatment, although corneal surgery or enucleation or both may be required in severe cases.3 In this case, only the decreased tear production was identified as a potential predisposing factor to explain the fungal keratitis. After about one month of topical antifungal treatment, the ulcer in this case healed, leaving only ghost vessels and granulation tissue in the cornea. Less than three months after initial presentation, the dog exhibited no pain and could see from its left eye, and only a faint white corneal scar remained.

The photographs and information for "Ophthalmology Challenge" were provided by Matthew P. Landry, DVM; Mary E. Lassaline, DVM, PhD; Andras M. Komaromy, DVM, PhD, DACVO; Maria E. Kallberg, DVM, PhD; Dennis E. Brooks, DVM, PhD, DACVO; and Kirk N. Gelatt, VMD, DACVO, Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0126.


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