Toxicity of simultaneous intrastromal and intracameral injection of voriconazole on corneal endothelium in a rabbit model

Purpose: To investigate the toxicity of repeated simultaneous intrastromal and intracameral injections of voriconazole in corneal endothelial cells in a rabbit model. Methods: Thirty-six eyes of 18 New Zealand white rabbits (six eyes per group) were divided into 6 groups according to the concentration of voriconazole (Group A, 0%; Group B, 0.05%; Group C, 0.1%; Group D, 0.25%; Group E, 0.5%; Group F, 1%). A combination of intrastromal and intracameral voriconazole injections were administrated to the eyes of each group three times on days 0, 3, and 7. Corneal clouding grades and central corneal thickness (CCT) were examined on days 0, 3, 7, 10, and 14. The endothelial cell counts (ECC) were measured on days 0 and 14. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were performed on day 14. Results: Group F (1%) showed more severe corneal clouding than the other groups (Groups A–E) from day 7 (p < 0.05, respectively). There were no significant differences in CCT and ECC among the six groups at any time point (p > 0.05, respectively). SEM revealed blurring of the cell border and loss of microvilli at concentrations ≥0.25% (Groups D–F). TEM revealed microstructural changes in endothelial cells at concentrations ≥0.1% (Groups C–F), and multiple vacuoles were observed at a concentration of 1% voriconazole (Group F). Conclusions: Repeated simultaneous intrastromal and intracameral voriconazole injections at a concentration of 0.1% or higher induced microstructural endothelial damage in rabbit corneal endothelial cells.