The effects of topical nonsteroidal anti-inflammatory drugs on adenoviral replication

Objective: To evaluate the antiviral activity of topical diclofenac sodium (Voltaren Ophthalmic) and ketorolac tromethamine (Acular) (2 nonsteroidal antiinflammatory drugs [NSAIDs]) on adenoviral replication in vitro and in the adenovirus (Ad) 5 McEwen-New Zealand rabbit ocular model. Methods: The 50% inhibitory concentration of ketorolac and diclofenac and their respective preservative components were determined for common ocular adenoviral serotypes (Ad8, Ad19, Ad1, and Ad5). In a series of experiments, Ad5 McEwen-inoculated New Zealand rabbit eyes were treated topically 4 times daily for 18 days with either ketorolac, diclofenac, prednisolone acetate (Pred Forte), or control vehicle (Comfort Tears). Main Outcome Measures: Outcome measures included serial ocular tear film titers and the formation of subepithelial immune corneal infiltrates. Results: In vitro, neither ketorolac nor diclofenac demonstrated significant inhibitory activity against Ad1, Ad5, Ad8. or Ad19. In the rabbit model, there were no statistically significant differences among ketorolac, diclofenac, and the control vehicle with respect to viral replication or the formation of subepithelial immune infiltrates. In contrast, 1% prednisolone prolonged viral shedding and inhibited immune infiltrates (P<,001 for both). Conclusions: Our experimental study suggests that treatment of epidemic keratoconjunctivitis with topical NSAIDs may be a safer alternative than topical steroids. Only controlled clinical trials can determine whether topical NSAIDs can provide symptomatic relief and not interfere with normal viral clearance.