Purpose: To determine how the addition of topical corticosteroids would affect the anti-adenoviral inhibitory effect of topical cidofovir (S-HPMPC) in the Ad5 New Zealand (Ad5/NZ) rabbit ocular model.
Methods: In a series of experiments (two-eye design), Ad5-inoculated/NZ rabbits (10(6) pfu/eye) were treated with 1 of 3 treatment regimens. Group 1 was administered 1% cidofovir (CDV) twice a day for 3 days plus comfort tears four times a day for 14 days. Group 2 was administered 1% CDV twice a day for 3 days plus 1% Pred Forte four times a day for 14 days. Group 3 was administered vehicle twice a day for 3 days plus comfort tears four times a day for 14 days and served as the control. All eyes were evaluated for 21 days for serial eye titers, Ad5 positive eyes, and duration of Ad5 shedding.
Results: Compared to control eyes in the Ad5/NZ rabbit ocular model, CDV alone demonstrated a significant antiviral inhibitory effect: reduced mean Ad5 eye titer during the early phase of infection (days 3 to 7), fewer Ad5-positive eyes during the early and late (days 9 to 21) phases of infection, and shortened duration of shedding. However, concomitant treatment with both Pred Forte and CDV significantly reversed the antiviral inhibitory activity of CDV: increased mean Ad5 eye titer, increased Ad5-positive eyes (early and late phases) and prolonged duration of shedding.
Conclusions: These experimental data further support the clinical development of cidofovoir as a topical antiviral agent, but they do not support a treatment regimen that includes a combination of topical corticosteroids and topical cidofovir as a desirable strategy for the treatment of symptomatic adenoviral ocular infection.