Cidofovir and experimental herpetic stromal disease

Objective: To compare topical cidofovir with topical trifluridine for the p revention and treatment of herpes simplex type 1 stromal keratitis in rabbi ts. Methods: The RE strain of herpes simplex virus 1 was injected into the cent ral stroma of both eyes of New Zealand white rabbits. Two to 3 days after v irus inoculation, the rabbits were randomized to treatment groups of 10 eac h 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 (con trol) until day 21 after injection. The treated corneas were examined 3 tim es a week and the severity of stromal keratitis was graded in a masked fash ion. To evaluate the ability of cidofovir to treat established stromal dise ase, groups of 10 rabbits each were inoculated with herpes simplex virus an d treated with 1% cidofovir twice a day, 1% trifluridine 5 times a day, flu orometholone 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 pre venting 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 tim es a day (P<.001) or 7 times a day (P =.006) significantly reduced the appe arance of stromal keratitis on the 8 evaluation days, compared with BSS tre atment (F test analysis of variance). There was no difference between the e yes treated with 0.5% cidofovir twice a day and those treated with 1% trifl uridine 5 times a day. Treatment with 1% cidofovir was not effective in tre ating established stromal disease. Conclusions: Cidofovir and trifluridine are highly effective in preventing the appearance of herpetic stromal disease. Cidofovir is as effective as, b ut no more effective than, trifluridine in this model. Neither cidofovir no r 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 deve lopment of stromal herpes, but is not effective in the treatment of establi shed stromal disease in which hypersensitivity predominates.