What is the best intravitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) medication, such as Eylea (aflibercept) or Lucentis (ranibizumab) or Avastin (bevacizumab), for a patient with diabetic macular edema?

Best Intravitreal Anti-VEGF for Diabetic Macular Edema

For diabetic macular edema with moderate to severe vision impairment (20/50 or worse), aflibercept is superior to bevacizumab and should be the preferred first-line agent. 1

Treatment Selection Based on Baseline Visual Acuity

Moderate to Severe Vision Impairment (20/50 or worse)

Aflibercept demonstrates superior visual outcomes compared to bevacizumab in this population and should be the agent of choice. 1 The American Diabetes Association 2025 guidelines explicitly state that aflibercept provides vision outcomes superior to bevacizumab when eyes have moderate visual impairment from diabetic macular edema. 1

• At 2 years, eyes with baseline vision of 20/50 to 20/320 gained a mean of 18.1 letters with aflibercept versus 13.3 letters with bevacizumab (P=0.02), representing a clinically meaningful 5-letter advantage. 2
• Aflibercept was superior to bevacizumab for anatomic outcomes (macular thickness reduction) regardless of baseline vision (P<0.001). 2
• While aflibercept showed superiority over ranibizumab at 1 year in this subgroup (16.1 letters gained), this difference was no longer statistically significant at 2 years (P=0.18), though aflibercept still trended toward better outcomes. 2

Good Vision (20/25 to 20/40)

All three major anti-VEGF agents (aflibercept, ranibizumab, bevacizumab) produce comparable visual outcomes in this population. 1, 2

• Eyes with baseline vision of 20/32 to 20/40 gained 7.8.6, and 6.8 letters with aflibercept, ranibizumab, and bevacizumab respectively, with no significant differences between agents (P>0.10 for all pairwise comparisons). 2
• For eyes with vision of 20/25 or better despite center-involved diabetic macular edema, close monitoring with initiation of anti-VEGF therapy only if vision worsens provides 2-year outcomes similar to immediate treatment. 1, 3
• This observation strategy resulted in only 16-19% of eyes experiencing ≥5-letter vision loss at 2 years across all management approaches. 3

FDA-Approved Agents and Current Options

Five anti-VEGF agents are currently used for center-involved diabetic macular edema: bevacizumab, ranibizumab, aflibercept (2 mg and 8 mg formulations), brolucizumab, and faricimab. 1 However, only aflibercept and ranibizumab have FDA approval specifically for diabetic retinopathy treatment. 1

Treatment Protocols and Injection Frequency

Standard dosing requires intensive initial treatment with injections every 4-8 weeks during the first 12 months, followed by less frequent maintenance dosing in subsequent years. 1

• Aflibercept protocol: 2 mg every 4 weeks for the first 5 injections, then every 8 weeks. 4
• Median injection numbers over 2 years were 15 for aflibercept, 16 for bevacizumab, and 15 for ranibizumab. 2
• Year 2 required fewer injections (median 5-6) compared to year 1 across all agents. 2

Switching Between Anti-VEGF Agents

For eyes with persistent diabetic macular edema despite bevacizumab or ranibizumab treatment, switching to aflibercept produces meaningful anatomic and visual improvements. 5, 6

• After switching from bevacizumab to aflibercept, central macular thickness reduced by 59 μm and vision improved by 3.9 letters at 48 weeks (P=0.002 and P=0.001 respectively). 5
• 79% of eyes showed anatomic improvement within 1 month of switching from ranibizumab/bevacizumab to aflibercept. 6
• Patients demonstrating ≥5-letter improvement after the first aflibercept injection following a switch had significantly better outcomes at 48 weeks (8.9 vs 1.8 letter gain, P=0.002), suggesting early response predicts long-term benefit. 5

Critical Safety Considerations

Anti-VEGF therapy requires strict adherence to scheduled follow-up, as nonintentional lapses in treatment lead to worse visual and anatomic outcomes. 1

• Antiplatelet Trialists' Collaboration (APTC) vascular events occurred in 5% with aflibercept, 8% with bevacizumab, and 12% with ranibizumab over 2 years (global P=0.047). 2
• The higher APTC event rate with ranibizumab compared to aflibercept was statistically significant (P=0.047), though this finding requires continued evaluation. 2

Rescue Therapy for Persistent Edema

Eyes with persistent diabetic macular edema despite anti-VEGF treatment should receive macular laser photocoagulation or intravitreal corticosteroids. 1

• Focal/grid laser was required in 41% of aflibercept-treated eyes, 64% of bevacizumab-treated eyes, and 52% of ranibizumab-treated eyes by 2 years (aflibercept vs bevacizumab P<0.001). 2
• Corticosteroids and laser are also reasonable first-line approaches for patients who cannot receive anti-VEGF therapy due to pregnancy or other systemic contraindications. 1