Fenofibrate - A Potential Systemic Treatment for Diabetic Retinopathy?

PURPOSE: To review clinical and experimental data for fenofibrate as a possible systemic treatment for diabetic retinopathy. DESIGN: Perspective. METHODS: Review of clinical studies focused on 2 major randomized controlled trials: the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) and ACCORD (Action to Control Cardiovascular Risk in Diabetes)-Eye studies. Progression was defined in FIELD as laser treatment for proliferative retinopathy or macular edema or increase by >= 2 steps on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, and in ACCORD-Eye as >= 3 steps (ETDRS scale) or proliferative disease requiring laser or vitrectomy treatment. Experimental studies investigating the mode of action of fenofibrate were reviewed. RESULTS: The 2 trials included 11 388 patients with type 2 diabetes mellitus, of whom 5701 were treated with fenofibrate (+/- statin) for up to 5 years. Fenofibrate reduced first laser treatment by 31% (P = .0002), and progression of diabetic retinopathy with absolute reductions of 5.0% over 5 years (P = .022, FIELD) and 3.7% over 4 years (P = .006, ACCORD-Eye). There was greater benefit in patients with than without preexisting retinopathy. The putative mechanisms implicated in the mode of action of fenofibrate involve lipid and nonlipid pathways, including beneficial effects on apoptosis, oxidative stress, inflammation, blood-retinal barrier breakdown, and neuroprotection. CONCLUSIONS: There are now robust and consistent clinical data to recommend fenofibrate as an adjunctive treatment for early diabetic retinopathy in patients with type 2 diabetes mellitus, taking into account the risks vs benefits of therapy. Further elucidating its mode of action will help to refine how best to use fenofibrate in the management of diabetic retinopathy. (Am J Ophthalmol 2012;154:6-12. (C) 2012 by Elsevier Inc. All rights reserved.)