Nepafenac in the Prevention and Treatment of Ocular Inflammation and Pain Following Cataract Surgery and in the Prevention of Post-operative Macular Oedema in Diabetic Patients

Abstract

Nepafenac ophthalmic suspension is a topical non-steroidal anti-inflammatory drug (NSAID) approved in the US and Europe for prevention and treatment of post-operative pain and inflammation associated with cataract surgery, and recently approved in Europe for reduction in risk of post-operative macular oedema associated with cataract surgery in diabetic patients. Unlike conventional NSAIDs, nepafenac is a prodrug that is uncharged and this results in great corneal permeability. Experimental studies on nepafenac demonstrated enhanced permeability compared with other NSAIDs, and rapid bioactivation to amfenac by intraocular hydrolases within ocular tissues including ciliary body epithelium, retina, choroid and cornea, which results in targeted delivery of active drug to anterior and posterior segments. Furthermore, these study results have been confirmed in clinical trials. Nepafenac may have prolonged activity in vascularised tissues of the eye because bioconversion is targeted to the iris/ciliary body, and to a greater extent the retina and choroid. Nepafenac and amfenac are potent inhibitors of cyclo-oxygenase (COX) enzyme isoforms, COX-1 and COX-2. Topical nepafenac penetrated into the posterior segment in a rabbit model of concanavalin-A induced retinal inflammation, where it diminished vitreous protein and prostaglandin E 2 concentrations and reduced breakdown of the blood–retinal barrier. Other NSAIDs, including ketorolac, failed to reduce the increase of these inflammatory markers in the same study. A randomised clinical study showed that based on retinal thickening and vision, treatment with nepafenac beginning pre-surgery and used for up to 90 days post-cataract surgery is effective in preventing macular oedema and associated loss of visual acuity in diabetic patients.