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  • Author(s): You, Qi Sheng;
  • Gaber, Raouf;
  • Meshi, Amit;
  • Ramkumar, Hema L;
  • Alam, Mostafa;
  • Muftuoglu, Ilkay Kilic;
  • Freeman, William R
  • et al.


To determine the efficacy of monthly (0.1 mL/4 mg) aflibercept for refractory neovascular age-related macular degeneration (wet age-related macular degeneration).


This was a retrospective interventional case series in which patients with wet age-related macular degeneration were treated with stepwise dose escalation. Nonvitrectomized patients resistant to monthly (Q4W) ranibizumab/bevacizumab were switched to 2 mg aflibercept every 8 weeks. With resistance, they were escalated to Q4W 2 mg aflibercept, then Q4W 4 mg (high dose high frequency, 4Q4W) aflibercept. Resistance was defined as ≥2 recurrences after being dry following ≥3 injections or persistent exudation on treatment of ≥5 injections.


Thirty-three eyes of 28 patients were treated with 4Q4W aflibercept and followed for a mean of 16 months. A dry retina (no intraretinal or subretinal fluid) was achieved after initiating 4Q4W aflibercept treatment at a mean of 3.8 months. Central foveal thickness, maximum foveal thickness, intraretinal fluid, subretinal fluid, and retinal pigment detachment height decreased significantly at 1 month after initiating the 4Q4W aflibercept, and the morphologic therapeutic effect was sustained until the last visit. Forty-five percent of eyes had one or more lines of vision improvement. New geographic atrophy developed in 9% of eyes during follow-up. No ocular or systemic adverse events occurred after initiating 4Q4W aflibercept.


Intravitreal high-dose high-frequency aflibercept is an effective treatment for patients with refractory wet age-related macular degeneration.

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