Intracameral voriconazole: In vitro safety for human ocular cells

Fungal keratitis is a sight-threatening infection of the cornea. It sometimes leads to loss of the eye. Despite an expanding range of fungal pathogens, there are only few therapeutic agents for its treatment available. Voriconazole is a second-generation synthetic triazole with a broad action against yeasts and molds. The current study investigates the safety of voriconazole for intracameral application in a cell culture model. Endothelial toxicity of voriconazole was evaluated in cultured human corneas. Possible toxic effects of voriconazole (10 mu g/mL-10 mg/mL) in corneal endothelial cells (CEC), primary human trabecular meshwork cells (TMC), and primary human retinal pigment epithelium (RPE) cells were evaluated after 24 h and under conditions of inflammatory stress by treatment with tumor-necrosis-factor alpha (TNF-alpha), lipopolysaccharides (LPS), or interleukin-6 (IL-6) and hydrogen peroxide. Toxicity was evaluated by tetra-zolium dye-reduction assay, and cell viability was quantified by a microscopic live-dead assay. No corneal endothelial toxicity could be detected after 30 days of treatment with 250 mu g/mL of voriconazole. Concentrations up to I mg/mL had no influence on CEC, TMC, or RPE cell proliferation, or on cell viability when administered for 24 h. Hydrogen peroxide exposure did not increase cellular toxicity of voriconazole at concentrations from 10 to 250 mu g/mL. After preincubation with TNF-a, LPS, or IL-6 for 24 h and subsequent voriconazole treatment for 24 h, no significant decrease in proliferation or viability was observed. This study showed no significant toxicity for voriconazole on CEC, TIVIC, RPE cells, or human corneal endothelium when administered in therapeutic concentrations up to 250 mu g/mL. (c) 2009 Elsevier Ireland Ltd. All rights reserved.