Evaluation of three aflibercept injections at 4-week intervals in patients with neovascular AMD showing an "insufficient anatomic response” to prior anti-VEGF therapy with ranibizumab or bevacizumab. Methods: The retrospective analysis included 96 eyes that had received at least three intravitreal 0.5mg ranibizumab or 1.25mg bevacizumab injections over a period of no more than 4 months prior to switching to aflibercept. In addition, the selected eyes had to have evidence of persisting or increasing sub- or intraretinal fluid, observed in optical coherence tomography (OCT). All patients received a loading dose of three intravitreal 2mg aflibercept injections at 4-week intervals. Evaluation included central retinal thickness (CRT) and maximum pigment epithelium (PED) height measured by spectral domain OCT and best-corrected visual acuity (BCVA) prior to the switch of therapy and 4weeks after the third aflibercept injection. Results: A significant reduction of mean CRT (−39μm; p < 0.001) and maximum PED height (−46μm; p < 0.001) as found 4weeks after the third aflibercept injection. Eighty-two out of 96 eyes (85%) had a PED just prior to switching to aflibercept. There was an improvement in BCVA of 1.9 letters 4weeks after the last aflibercept injection; the vision gain, however, did not reach statistical significance (p = 0.061). The further analysis did not show any correlation of the change in CRT, maximum PED, and BCVA with the number of prior anti-VEGF treatments. Conclusion: Retinal edema and PEDs regressed significantly after switching to aflibercept in patients insufficiently responding to prior therapy with ranibizumab or bevacizumab. No correlation could be found with regard to the number of prior treatments.