Abstract / Summary
Background: Diabetic retinopathy (DR) is a microvascular and neurodegenerative complication of diabetes and remains a leading cause of preventable visual impairment in working-age adults. Because the number of people living with diabetes continues to grow, the absolute burden of DR is expected to rise for decades. Objective: This review summarises the molecular and cellular mechanisms that drive DR, maps them onto established and emerging pharmacological targets, and appraises the clinical evidence for current drug-based management. Findings: Chronic hyperglycaemia activates several interconnected injury pathways (polyol flux, advanced glycation, protein kinase C activation, oxidative stress and low-grade inflammation) that converge on endothelial dysfunction, pericyte loss, breakdown of the blood–retinal barrier and, in advanced disease, VEGF-driven neovascularisation. Systemic control of glucose, blood pressure and lipids reduces the risk and slows progression. Fenofibrate has now shown benefit in a dedicated randomised trial. Intravitreal anti-VEGF agents, including the bispecific antibody faricimab, and corticosteroid implants are the mainstay for vision-threatening disease, while several oral agents targeting individual pathways have not translated into clinical practice. Conclusion: Effective pharmacotherapy of DR requires combining systemic risk-factor control with targeted intraocular therapy. Less invasive, longer-acting and neuroprotective strategies are the main unmet needs.