Safety of intravitreal voriconazole: Electroretinographic and histopathologic studies

Purpose: Voriconazole, a novel triazole antifungal agent, presents potent activity against a broad spectrum of yeast and molds. To determine whether it could be safely used as an intravitreal agent in the treatment of fungal endophthalmitis, retinal toxicity of voriconazole was examined in a rodent animal model. Methods: Voriconazole solutions were serially diluted and injected intravitreally into eyes of normal adult Sprague-Dawley rats so that the final intravitreal concentrations were 5 μg, 10 μg, 25 μg, 50 μg, and 500 μg/mL (N = 3 for each concentration group), Saline was injected into the fellow eyes of each animal as controls. Three weeks after injections, electroretinograms (ERGs) were measured, and eyes were subsequently enucleated for histologic examination, exai-nination, Results: In ERG studies, maximum scotopic b-wave, b_max, intensity needed for half saturation, I_0.5, 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 intravitreal voriconazole. In the eyes with 50 μg/mL and 500 μg/mL voriconazole, small foci of retinal necrosis were occasionally observed in the outer retina, especially in the eyes with 500 mg/mL voriconazole. Conclusion: Our results demonstrate that intravitreal voriconazole of up to 25 mg/mL causes no ERG change or histologic abnormality in rat retina. This indicates that voriconazole is a safe antifungal agent that may be employed by intravitreal injection in the treatment of fungal endophthalmitis.