Exogenous Fungal Endophthalmitis: An Analysis of Isolates and Susceptibilities to Antifungal Agents Over a 20-Year Period (1990–2010) RUWAN A. SILVA, JAYANTH SRIDHAR, DARLENE MILLER, CHARLES C. WYKOFF, AND HARRY W. FLYNN, JR PURPOSE: To describe the isolates and susceptibilities to antifungal agents for patients with culture-proven exogenous fungal endophthalmitis. DESIGN: Noncomparative case series. METHODS: The clinical records of all patients treated for culture-proven exogenous fungal endophthalmitis at a university referral center from 1990 to 2010 were reviewed. Specimens initially used for diagnosis were recovered from the microbiology department and then un- derwent antifungal sensitivity analysis. RESULTS: The antifungal susceptibilities of 47 fungal isolates from culture-positive fungal endophthalmitis are reported. Included are 14 isolates from yeast and 33 from mold. The mean (±standard deviation) minimum inhibitory concetrations (MICs) for amphotericin B (2.6 ± 3.5 mg/mL), fluconazole (36.9 ± 30.7 mg/mL), and voriconazole (1.9 ± 2.9 mg/mL) are reported. Pre- sumed susceptibility to oral fluconazole, intravenous amphotericin B, intravitreal amphotericin B, oral vorico- nazole, and intravitreal voriconazole occurred in 34.8%– 43.5%, 0–8.3%, 68.8%, 69.8%, and 100% of isolates, respectively. CONCLUSIONS: Based on this laboratory study of iso- lates from exogenous fungal endophthalmitis, intravitreal voriconazole appears to provide the broadest spectrum of antifungal coverage and, as such, may be considered for empiric therapy of endophthalmitis caused by yeast or mold. (Am J Ophthalmol 2015;159:257–264. Ó 2015 by Elsevier Inc. All rights reserved.) W HILE FUNGAL INFECTIONS OF THE EYE (IN THE form of keratitis) were initially reported as early as 1879, exogenous fungal endophthalmitis was first described 23 years later. 1,2 The disease stems from 1 of 3 inciting factors: postoperative infections, penetrating ocular trauma, and intraocular extension of ocular surface infections. 3,4 Each precipitating mechanism of inoculation accounts for roughly one third of exogenous fungal endophthalmitis cases, though keratitis may account for a slightly higher proportion. 4,5 Clinical outcomes are generally poor, with eventual evisceration or enucleation not uncommon (24%–78%), particularly in posttraumatic cases. 4,6 Unlike endogenous fungal endophthalmitis, the vast majority of fungi identified in exogenous cases are molds (87%). 4,5 Successful treatment of exogenous fungal endophthalmitis is therefore particularly challenging owing to these species of causative molds being relatively virulent and because there is often a lag time from inciting event to endophthalmitis (generally weeks to months 5,7 ), which can delay the correct diagnosis. A final obstacle in treatment is that appropriate antifungal therapy remains largely undefined in this class of patients. 5,8,9 The current study includes a series of patients diagnosed at a university medical center with culture-proven exogenous fungal endophthalmitis and re- ports both causative fungi and susceptibility to antifungal agents. METHODS THE INSTITUTIONAL REVIEW BOARD AT THE UNIVERSITY OF Miami approved this noncomparative case series (ID# 20100943) and waived informed consent approval for this retrospective study. Compliance with the Health In- surance Portability and Accountability Act and adherence to the Declaration of Helsinki and all federal and state laws in the United States were maintained during all aspects of this research. The microbiologic and clinical records of all patients treated for culture-proven fungal endophthalmitis (n ¼ 151) between January 1, 1990, and June 30, 2010 were reviewed. Methods for fungal isolate culture and identifica- tion have been described previously. 4 Cases of definite endogenous fungal endophthalmitis (n ¼ 66) were excluded. Of the remaining 85 cases, 58 had fungal isolates that were recovered from the microbiology department’s storage freezers (80 C). Seven of the remaining 27 exog- enous cases had prior antifungal susceptibilities already Accepted for publication Oct 27, 2014. From the Department of Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida. R.A. Silva is currently affiliated with the Department of Ophthal- mology, Stanford University School of Medicine, Palo Alto, California. C.C. Wykoff is currently affiliated with Retina Consultants of Houston, Houston Methodist Hospital, Houston, Texas. Inquiries to Ruwan A. Silva, Department of Ophthalmology, Stanford University School of Medicine, 2452 Watson Court, Palo Alto, CA 94303; e-mail: ruwansilva2002@gmail.com 0002-9394/$36.00 http://dx.doi.org/10.1016/j.ajo.2014.10.027 257 Ó 2015 BY ELSEVIER INC.ALL RIGHTS RESERVED.