Common Anti-VEGF Agents
The most commonly used anti-VEGF agents are ranibizumab, aflibercept, bevacizumab, and pegaptanib, with ranibizumab and aflibercept being FDA-approved for ophthalmic indications while bevacizumab is used off-label despite its approval only for oncologic conditions. 1, 2
FDA-Approved Ophthalmic Anti-VEGF Agents
First-Line Approved Agents
Ranibizumab - FDA and EMA approved for treating retinal vascular diseases including neovascular AMD, diabetic macular edema, and retinal vein occlusion 3, 4
Aflibercept - FDA and EMA approved for similar ophthalmic indications as ranibizumab 3, 4
Pegaptanib - FDA approved for ophthalmic use, though less commonly utilized in current practice 1, 2
Brolucizumab - A newer FDA-approved agent for neovascular AMD treatment 4
Off-Label Anti-VEGF Agent
- Bevacizumab - FDA approved exclusively for colorectal, lung, and renal cancers, but widely used off-label for ocular vascular diseases due to cost-effectiveness 1, 3, 2
Key Mechanistic Distinctions
Aflibercept demonstrates unique binding characteristics compared to bevacizumab, forming a homogenous 1:1 complex with VEGF dimers rather than the large immune-like complexes that bevacizumab creates 1. This distinction is clinically relevant because:
Bevacizumab can form multimeric complexes with VEGF that may activate platelets and bind to cell surfaces 1
Aflibercept blocks both VEGFR1/R2 binding sites and the heparin-binding site on VEGF165, providing more complete VEGF inhibition 1
Comparative Effectiveness Evidence
High-quality evidence demonstrates no clinically meaningful difference in visual acuity outcomes between these agents (defined as ≥5 letters difference) 5:
Nine trials provide high-strength evidence showing no difference between bevacizumab and ranibizumab for neovascular AMD 5
Three trials provide moderate-strength evidence of equivalent efficacy between bevacizumab and ranibizumab for diabetic macular edema 5
Safety profiles are generally similar across agents, though one trial reported increased arterial thrombotic events with ranibizumab versus aflibercept in diabetic macular edema 5
Clinical Practice Considerations
Bevacizumab remains significantly more cost-effective than aflibercept or ranibizumab when repackaged for ophthalmic use, despite being used off-label 5. The choice between agents often depends on:
- Institutional formulary availability
- Cost considerations and insurance coverage
- Individual patient risk factors for systemic adverse events
- Specific disease indication and severity