Anti-vascular endothelial growth factor therapy in clinical practice: Real-world scenarios, limitations, and outcomes

This narrative review examines the "efficacy-effectiveness gap" in anti-vascular endothelial growth factor (anti-VEGF) therapy by comparing outcomes from randomized controlled trials (RCTs) with global and Indian real-world evidence (RWE) in neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Across all three conditions, real-world outcomes consistently fall short of those observed in RCTs. In nAMD, studies such as AURA report minimal visual gains by Year 2 (+0.6 letters) compared to +8 to +10 letters in RCTs, largely attributable to fewer injections administered in practice. Indian data, including the ARMOUR study, reflect similarly reduced injection frequencies alongside issues such as delayed presentation. For DME, global RWE demonstrates modest improvements in visual acuity with fewer injections per year than in RCTs, while Indian cohorts show even lower treatment intensity, resulting in anatomical stabilization without meaningful visual gains. Outcomes in RVO are also compromised by incomplete loading doses and inadequate follow-up. The primary drivers of this gap include undertreatment, variability in patient populations, and socioeconomic barriers that affect adherence and access to care. Overall, the discrepancy appears to stem more from real-world treatment challenges than from limitations of the therapies themselves. Addressing this gap will require practical approaches such as implementing Treat-and-Extend regimens, promoting earlier diagnosis and intervention, enhancing patient engagement, and increasing the use of cost-effective or longer-acting treatment options, particularly in resource-constrained settings like India.