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H. Gao, M. Pennesi, K. Shah, W.F. Mieler, S.M. Wu, E.R. Holz; Safety of Intravitreal Voriconazole - Histopathologic and Electoretinographic Study . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1860.
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Purpose: Voriconazole, a new triazole antifungal agent, is now available for systemic treatment of fungal infections. This study was designed to examine whether voriconazole could be safely used as an intravitreal agent in the treatment of fungal endophthalmitis. The potential toxicity of intravitreal voriconazole was examined in a rodent animal model. Methods: Based on a study of microbial keratitis caused by a variety of fungal pathogens, the minimal inhibitory concentration (MIC) of voriconazole is 0.5 µg/ml to 5.0 µg/ml. Voriconazole (trade name: Vfend, Pfizer, Inc) solutions of 6 µl were injected intravitreally into eyes of normal adult Sprague-Dawley rats (N=3 for each concentration group). Voriconazole solutions were serially diluted so that the final intravitreal concentrations were 1, 10, 50, 100, and 1000 fold of MIC (5.0 µg, 50 µg, 250 µg, 500 µg, and 5000 µg/ml, respectively). Saline of equal volume was injected into the fellow eyes of each animal as controls. Following intravitreal injection, animals were kept under ambient light on a 12 hour light/dark schedule. Three weeks after injections, full field dark adapted electroretinograms (ERG) were measured, animals were subsequently sacrificed, and eyes, enucleated for histological examination. Results: In control eyes injected with saline, the maximum scotopic bwave, bmax, measured 790±100 µV and the intensity needed for half saturation I0.5 measured 0.9±0.2 Φ/rod. The saturated a-wave amplitude measured 380±65µv. There was no significant difference between ERGs recorded from control eyes and voriconazole-injected eyes in any concentration group. Even in eyes injected with 1000 fold MIC of voriconazole (5000 µg/ml), the ERGs showed little difference compared to the control eyes. Histological examination with light microscopy did not reveal any retinal abnormality in the eyes injected with 1 to 100 fold MIC of voriconazole. In the eyes injected with 1000 fold MIC, occasional small foci of retinal necrosis were observed in the outer retina. Conclusions: This study reveals that intravitreal voriconazole of up to 100 fold MIC (500 µg/ml) causes no ERG or histological abnormality in rat retina. Voriconazole appears to be a safe anti-fungal agent, which may be employed by intravitreal injection in the treatment of fungal endophthalmitis.
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