Toxicity of Intrastromal Voriconazole Injection on Corneal Endothelium in Rabbits

Purpose: The aim of this study was to evaluate the toxicity of intrastromally injected voriconazole on corneal endothelial cells in rabbits. Methods: In total, 32 eyes of 16 rabbits (8 eyes for each group) were divided into 4 groups according to the concentration of voriconazole [group A: 50 mu g/0.1 mL (0.05%), group B: 100 mu g/0.1 mL (0.1%), group C: 250 mu g/0.1 mL (0.25%), or group D: 500 mu g/0.1 mL (0.5%)]. Right eyes were injected intrastromally with voriconazole at concentrations of 50 mu g/0.1 mL, 100 mu g/0.1 mL, 250 mu g/0.1 mL, or 500 mu g/0.1 mL. Left eyes were injected intrastromally with isotonic saline as controls. Central corneal thickness and endothelial cell counts were measured before and at 6 hours, 1 day, and 1 week after the injection was given. Corneas were then harvested for transmission electron microscopy. Results: Only the 0.5% group did not significantly recover from corneal edema 1 week after the injection (P = 0.167, P = 0.051, P = 0.086, P = 0.001 in groups A-D, respectively). There were significant differences in endothelial cell counts for the 0.1% and 0.25% groups (P = 0.077, P = 0.019, P = 0.008 in groups A-C, respectively). Transmission electron microscopy evaluation revealed definite necrotic changes in endothelial cells at concentrations of 0.1%, 0.25%, and 0.5%, but only microstructural changes at a concentration of 0.05%. Conclusions: Our results suggest that voriconazole could be injected safely into the intrastromal layer at a concentration of 0.05% with low endothelial cell toxicity. However, injections should be administered with caution because of the risk of microstructural damage.