In Vitro and In Vivo Evaluation of Cidofovir as a Topical Ophthalmic Antiviral for Ocular Canine Herpesvirus-1 Infections in Dogs

摘要

Purpose: The effects of cidofovir were investigated against canine herpesvirus-1 (CHV-1) in vitro and in dogs with experimentally induced recurrent ocular CHV-1 infection, a host-adapted pathogen animal model of ocular herpes simplex virus-1 (HSV-1) infection. Methods: The cidofovir EC50 was determined for CHV-1 and HSV-1. A randomized, masked vehicle-controlled trial was performed using beagles with experimentally induced recurrent ocular CHV-1 infection. Dogs received 1 drop of 0.5% cidofovir solution or 0.9% sodium chloride solution (vehicle) in both eyes 2 times daily for 14 days. Dogs were monitored at intervals for 30 days by a clinical ophthalmic examination, in vivo confocal microscopy of the cornea and conjunctiva, ocular sample CHV-1 polymerase chain reaction assay, hemogram, and serum biochemistry panel. Clinical ocular disease scores were calculated and infiltrating leukocytes detected by in vivo confocal microscopy quantified. Results: Cidofovir displayed similar in vitro antiviral activity against CHV-1 and HSV-1. Clinical ocular disease scores were significantly higher in the cidofovir group compared to the vehicle group. Marked conjunctival pigmentation and blepharitis were also detected in the cidofovir group, but not the vehicle group. Conjunctival and corneal leukocyte infiltration scores determined by in vivo confocal microscopy were significantly higher in the cidofovir group. Dogs administered cidofovir had significantly reduced durations of ocular viral shedding compared to the vehicle group. Hemogram and serum biochemistry panel values were unremarkable. Conclusions: Twice-daily application of topical 0.5% cidofovir ophthalmic solution reduced the duration of ocular viral shedding in dogs with experimentally induced recurrent ocular CHV-1 infection, but was associated with local ocular toxicity.