EFFICACY OF COBALT CHELATES IN THE RABBIT EYE MODEL FOR EPITHELIAL HERPETIC-KERATITIS

Purpose, A new class of antiviral agent, cobalt chelates (the CTC seri es), was evaluated for treating epithelial herpetic keratitis, consequ ent stromal disease being the major infectious cause of blindness in i ndustrial nations. Methods, Effects of CTC complexes were monitored in cell cultures and in a rabbit eye model, either infected with herpes simplex virus type 1 (HSV-1) or uninfected. Several antiviral concentr ations of CTC complexes nontoxic to Vero cells were administered to ra bbit eyes with HSV-l-induced keratitis. Corneal surface virus titers w ere measured, and corneal lesions of epithelial keratitis were monitor ed by slit-lamp microscopy and scored. Recovery rates and incidence we re compared in eyes treated with CTC complexes, placebo, or clinically formulated trifluorothymidine (Viroptic), using nonparametric statist ics. Results. All CTC complexes inhibited HSV-1 replication in vitro, CTC-96 being best. CTC-96, CTC-23, and CTC-67 eliminated (<1 plaque-fo rming unit[pful) corneal surface HSV-1 (otherwise >10(5) pfu) in order of descending potency, but CTC-82 was ineffective. CTC-96 (either 5 m u g/ml six times daily or 10 mu g/ml five times daily) accelerated her petic dendritic keratitis recovery better than or the same as trifluor othymidine (10 mg/ml nine times daily). CTC complexes were nontoxic to Vero cells continuously exposed to less than or equal to 25 mu g/ml; 50 mu g/ml of CTC 96 nine times daily did not irritate uninfected rabb it eyes. Conclusion, Topical CTC-96 applications were at least as effe ctive as Viroptic in diminishing disease signs and corneal surface vir us at concentrations less than one-thousandth that of Viroptic.