In vitro effects of antiviral agents on human keratocytes

Purpose. To study the effects of antiviral agents on human keratocytes in v itro. Methods. Cultured human keratocytes were incubated with either gancic lovir, idoxuridine, trifluridine, or cidofovir at concentrations from 0.000 1 to 10 mg/mL. Phase-contrast microscopy and XTT (sodium [2,3-bis [2-methox y-4-nitro-5-sulphophenyl]-2h-tetrazolium-5-carboxanilide, inner salt) color imetric assay were performed after 24, 48, and 72 hours of incubation. Resu lts. When adjustments were made for time of incubation and concentration, t rifluridine reduced cell viability significantly more than ganciclovir, ido xuridine, and cidofovir (p < 0.001, three-way analysis of variance). There was significant time- and dose-dependent reduction of cell viability (p < 0 .001) with trifluridine and cidofovir. After a 72-hour incubation with ganc iclovir or idoxuridine, cell viability was reduced as compared with 24- and 48-hour incubation (p < 0.001); only the effects of the highest concentrat ion tested (1.0 mg/mL) were significantly different from those of the lower concentrations (p < 0.002). At a concentration of 1.0 mg/mL, trifluridine and cidofovir produced moderate to severe signs of cytotoxicity, whereas ga nciclovir and idoxuridine displayed much less severe morphologic signs. Con clusions. Our results indicate that antiviral agents may have both time- an d concentration-related toxic effects on stromal keratocytes. These finding s may impact the selection of the most appropriate antiviral drug when it i s needed to treat infections involving the corneal stroma.