The Evolving Role of Anti-VEGF Therapy in Proliferative Diabetic Retinopathy: Evidence, Challenges, and Future Directions.

Proliferative diabetic retinopathy (PDR) is a vision-threatening complication of diabetes traditionally managed with pan-retinal photocoagulation (PRP), which remains effective but is associated with irreversible peripheral visual field loss and other functional limitations. The introduction of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy has fundamentally altered the treatment landscape by directly targeting retinal neovascularization and addressing the underlying ischemic drive. This narrative review summarizes current evidence from pivotal randomized controlled trials, key real-world studies, health economic analyses, and clinical practice guidelines comparing anti-VEGF therapy with PRP for PDR. Overall, anti-VEGF agents such as ranibizumab and aflibercept provide visual and anatomical outcomes comparable to PRP, with additional advantages including improved preservation of peripheral vision and reduced risk of certain vision-threatening complications. However, widespread adoption as first-line therapy is limited by substantial treatment burden, need for frequent intravitreal injections, high cumulative costs, concerns regarding long-term durability and disease recurrence after treatment interruption, and challenges in real-world adherence. Patient selection therefore remains critical, with anti-VEGF therapy being particularly advantageous in eyes with concurrent diabetic macular edema, whereas PRP continues to play an important role in patients with poor follow-up capacity or limited access to care. Emerging strategies aimed at overcoming current limitations include combination anti-VEGF and PRP approaches, extended-duration anti-VEGF agents, sustained-release drug delivery systems, and artificial intelligence-driven personalized treatment protocols. Current evidence suggests that anti-VEGF therapy represents an effective alternative to PRP in appropriately selected patients with PDR. However, treatment selection should remain individualized, taking into account disease characteristics, follow-up reliability, patient preferences, and healthcare resource availability.