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Intravitreal Voriconazole
An Electroretinographic and Histopathologic Study
Hua Gao, MD, PhD;
Mark E. Pennesi, PhD;
Kekul Shah, MD;
Xiaoxi Qiao, MD, PhD;
Seenu M. Hariprasad, MD;
William F. Mieler, MD;
Samuel M. Wu, PhD;
Eric R. Holz, MD
Arch Ophthalmol. 2004;122:1687-1692.
Background Voriconazole, a novel triazole antifungal agent, presents potent activity against a broad spectrum of yeast and molds.
Objective To determine whether voriconazole could be safely used as an intravitreal agent in the treatment of fungal endophthalmitis.
Methods Retinal toxicity of voriconazole was examined in a rodent animal model. Voriconazole solutions were serially diluted and injected intravitreally into the eyes of normal adult Sprague-Dawley rats so that the final intravitreal concentrations were 5 µg/mL, 10 µg/mL, 25 µg/mL, 50 µg/mL, and 500 µg/mL (n = 3 for each concentration group). Saline was injected into the fellow eyes of all animals as controls. Three weeks after injections, electroretinograms were measured, and eyes were subsequently enucleated for histologic examination.
Results In electroretinographic studies, maximum scotopic b-wave, intensity needed for half saturation, and saturated a-wave amplitude were measured. There was no statistically significant difference in these parameters recorded between control eyes and voriconazole-injected eyes in any concentration groups. Histologic examination with light microscopy did not reveal any retinal abnormality in the eyes with 5 to 25 µg/mL of intravitreal voriconazole. In the eyes with 50 µg/mL and 500 µg/mL of voriconazole, small foci of retinal necrosis were occasionally observed in the outer retina, especially in the eyes with 500 µg/mL of voriconazole.
Conclusions Our results demonstrate that intravitreal voriconazole of up to 25 µg/mL causes no electroretinographic change or histologic abnormality in rat retinas. This indicates that voriconazole is a safe antifungal agent for intravitreal injection in rodents and may be used in the treatment of human fungal endophthalmitis following further study.
Author Affiliations: Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Tex (Drs Gao, Pennesi, Shah, Hariprasad, Mieler, Wu, and Holz); and the Department of Cellular Biology and Anatomy, Louisiana State University Health Science Center, Shreveport (Dr Qiao). Dr Mieler is now with the Department of Ophthalmology and Visual Science, University of Chicago, Chicago, Ill.
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