Intravitreal voriconazole - An electroretinographic and histopathologic study

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 mug/mL, 10 mug/mL, 25 mug/mL, 50 mug/mL, and 500 mug/mL (n=3 for each concentration group). Saline was injected into the fellow eyes of all animals as controls. Three weeks after injections, etectroretinograms 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 mug/mL of intravitreal voriconazole. In the eyes with 50 mug/mL and 500 mug/mL of voriconazole, small foci of retinal necrosis were occasionally observed in the outer retina, especially in the eyes with 500 mug/mL of voriconazole. Conclusions: Our results demonstrate that intravitreal voriconazole of up to 25 mg/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.