Eyeworld

EW RESIDENTS 154 March 2015 by Adam Jorgensen, MD A fungus among us Figure 1: H&E stain shows septated branching appearance of fungal hyphae in resected corneal graft. Figure 2: Gomori methenamine silver staining of corneal graft confirms fungal hyphae. Note the septated appearance with acute angled branching. Academic grand rounds: John A. Moran Eye Center Introduction from Jeff Pettey, MD T his month we describe a pa- tient who was evaluated at the John A. Moran Eye Cen- ter, University of Utah, with a challenging diagnostic di- lemma. The clinical course followed that of a common disease with a common presentation, however, she eventually developed a much rarer condition that is easily missed. A current second-year resident Adam Jorgensen, MD, followed the patient while rotating through the cornea service. Adam chose this case due to its high potential for error through confirmation bias as the patient developed new signs and symptoms that did not fit our working diagno- sis. Mark Mifflin, MD, and Adam Gess, MD, managed the patient and are the discussants for this case. Case report A 54-year-old white female with a history of recurrent herpetic infec- tion around and involving the left eye presented to the Moran Eye Cen- ter cornea service with complaints of chronic photophobia and decreased vision in the left eye. Examination showed sectoral mid-stromal corneal vascularization and scarring, de- creased corneal sensation, and upper eyelid scarring and lash loss. Central corneal scarring initially progressed despite treatment with oral acyclo- vir, topical corticosteroids, cautery of peripheral stromal vessels, and subconjunctival triamcinolone. Quiescence was eventually obtained, and after a 6-month period with no active keratitis and minimal inflam- mation, penetrating keratoplasty was performed. Pathologic analysis from the resected corneal tissue demonstrated stromal vascularization and scarring but no infectious elements. The postoperative course was compli- cated by neurotrophic keratopathy and poor epithelialization, but the graft ultimately reepithelialized over 3 months. Eleven months postoper- atively the corneal graft developed a new epithelial defect with signifi- cant thinning but no infiltrate. The patient had also developed skin lesions over her left scalp in the V1 dermatome, and a herpes zoster flare was suspected. Despite treatment with oral acyclovir and topical moxi- floxacin, ganciclovir, and preserva- tive-free dexamethasone, the graft continued to thin. Cyanoacrylate glue was placed but soon became dislodged resulting in corneal per- foration and necessitating emergent repeat penetrating keratoplasty. Pathologic analysis of the resected graft tissue demonstrated fungal hyphal elements (Figures 1 and 2). Given the clinical picture of recurrent herpetic keratitis, the fungal elements were unexpected. In the immediate postoperative period, prophylactic antifungals were not initiated due to concerns about potential surface toxicity, but the patient was monitored with biweek- ly exams. By postoperative month 3, the graft was clear with healthy intact epithelium, and the patient was maintained on oral acyclovir, topical difluprednate, and frequent preservative-free artificial tears. The patient was seen urgently 4 months after surgery for increasing redness and irritation of the left eye. A white stromal infiltrate was noted in the corneal graft, with significant anterior chamber inflammation and a fluffy white round opacity in the superonasal anterior chamber. The patient was started on topical voriconazole and oral fluconazole for presumed fungal keratitis after corneal scrapings were obtained, which ultimately did not stain posi- tive for fungal elements. Repeat cor- neal scrapings and anterior chamber tap were performed. Several days later, both prior corneal scrapings as well as the aqueous sample were found to be growing Ulocladium sp. Anterior chamber polymerase chain reaction was negative for herpes simplex or zoster viruses, and all bacterial cultures were negative. Discussion This case is a well-documented presentation of fungal keratitis in a patient recovering from penetrat- ing keratoplasty. It demonstrates many of the clinical features that can predispose a patient to fungal keratitis, including persistent epi- thelial defects and prolonged topical steroid use. What is unique about this case is the fungus involved. Ulocladium is a ubiquitous fungus, and has been traditionally considered to be nonpathogenic in humans. In fact, this fungus is sometimes sprayed on our fruits and vegetables for biolog- ic control of other plant diseases. Recent evidence has pointed toward the increasing pathogenicity of Ulocladium species. Skin infections, sinusitis, and keratitis have been re- ported in immunocompromised and even immunocompetent patients. It is likely that fungal keratitis, which has traditionally been rare in the U.S., will increase in incidence over the next 10 years. Recent pub- lications have suggested that fungal infections of all types are increasing on a global scale. Corneal infections with Microsporidia species, typically considered to be an opportunistic organism, are becoming increasing- ly prevalent in immunocompetent patients. It is important to consider fungal infection in all patients with keratitis, particularly in patients

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