In vitro evaluation of the effects of metronidazole on rabbit corneal epithelial cells

Because of its usefulness in treating facial rosacea, metronidazole may also be an effective treatment for ocular rosacea. The toxicity of metronidazole on the corneal epithelium has not previously been reported. In this study, the effects of metronidazole on rabbit corneal epithelium in vitro were evaluated. Epithelial cell cultures were exposed to various concentrations of metronidazole to determine its effect on cell morphology, viability, and wound healing. Both morphological changes and cell loss were seen after 1 day of incubation in media containing metronidazole at concentrations of > or = 3.0 mg/ml. In media with metronidazole at 1.0 mg/ml, these toxic effects were not seen. The effects of metronidazole on wound healing were determined by comparing the area of wounds in the epithelial cell layer for time periods of up to 44 h. There was no statistically significant delay in wound closure when cells were incubated in media containing metronidazole at a concentration of 2.0 mg/ml as compared with cultures incubated in media without metronidazole. However, a significant delay in wound closure occurred at concentrations of > or = 3.0 mg/ml. The results at these drug concentrations suggest that metronidazole has low corneal epithelial toxicity. Allowing for the dilutional effects of tears in patients with normal tear function, concentrations of 4.0-5.0 mg/ml (0.4-0.5%) would probably be tolerated by the corneal epithelium. Clinical safety and efficacy studies are necessary to determine if topical metronidazole will prove useful for the treatment of ocular rosacea.