Objective: To compare topical cidofovir with topical trifluridine for the prevention and treatment of herpes simplex type 1 stromal keratitis in rabbits.
Methods: The RE strain of herpes simplex virus 1 was injected into the central stroma of both eyes of New Zealand white rabbits. Two to 3 days after virus inoculation, the rabbits were randomized to treatment groups of 10 each and treated with 1% trifluridine administered 5 or 7 times a day, 1%, 0.5%, or 0.2% cidofovir administered twice a day, fluorometholone administered twice a day, or balanced salt solution (BSS) administered twice a day (control) until day 21 after injection. The treated corneas were examined 3 times a week and the severity of stromal keratitis was graded in a masked fashion. To evaluate the ability of cidofovir to treat established stromal disease, groups of 10 rabbits each were inoculated with herpes simplex virus and treated with 1% cidofovir twice a day, 1% trifluridine 5 times a day, fluorometholone twice a day, or BSS twice a day beginning on day 7 after virus inoculation through day 21.
Results: Treatment with 0.2% cidofovir twice a day was not effective in preventing the appearance of stromal disease (P = .89), whereas treatment with 0.5% (P<.001) or 1% (P<.001) cidofovir twice a day or 1% trifluridine 5 times a day (P<.001) or 7 times a day (P = .006) significantly reduced the appearance of stromal keratitis on the 8 evaluation days, compared with BSS treatment (F test analysis of variance). There was no difference between the eyes treated with 0.5% cidofovir twice a day and those treated with 1% trifluridine 5 times a day. Treatment with 1% cidofovir was not effective in treating established stromal disease.
Conclusions: Cidofovir and trifluridine are highly effective in preventing the appearance of herpetic stromal disease. Cidofovir is as effective as, but no more effective than, trifluridine in this model. Neither cidofovir nor trifluridine benefits established stromal disease, however.
Clinical relevance: Cidofovir is a new, potent antiviral that seems similar in efficacy to trifluridine and is effective in the prevention of the development of stromal herpes, but is not effective in the treatment of established stromal disease in which hypersensitivity predominates.