Fenofibrate in ophthalmology: therapeutic efficacy and mechanisms

Ophthalmic diseases are a growing global cause of visual impairment, driven by population aging and the rising prevalence of diabetes mellitus. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist widely used for dyslipidemia, has emerged as a candidate for therapeutic repurposing in ophthalmology. This narrative review synthesizes current preclinical and clinical evidence on fenofibrate across anterior and posterior segment diseases, including diabetic corneal neuropathy, diabetic keratopathy, dry eye disease, corneal burns, Fuchs endothelial corneal dystrophy, diabetic retinopathy, diabetic macular edema, neovascular age-related macular degeneration, and central retinal artery occlusion. Across ocular disease models, fenofibrate demonstrates neuroprotective, vascular stabilizing, and tissue-remodeling effects. These actions appear to involve modulation of shared pathogenic pathways, including PPARα-dependentregulation of inflammatory signaling, mitochondrial and lipid metabolism, and preservation of epithelial, endothelial, neuronal, and vascular integrity. Clinical evidence is strongest for diabetic retinopathy, where randomized trials support a potential adjunctive role in slowing progression and reducing interventions in patients with early-to-moderate disease. Preliminary clinical evidence for diabetic corneal neuropathy is promising but limited, whereas data for dry eye disease, corneal burns, Fuchs endothelial corneal dystrophy, neovascular age-related macular degeneration, and retinal ischemic injury remains preclinical. Emerging experimental ocular delivery strategies may improve local bioavailability while reducing systemic exposure. Overall, fenofibrate represents a biologically plausible adjunctive ophthalmic therapy, but further randomized trials, mechanistic studies, pharmacokinetic evaluation, and long-term safety assessments are required to define its therapeutic role beyond diabetic retinopathy.