RETINAL DISORDERS Aflibercept in diabetic macular edema refractory to previous bevacizumab: outcomes and predictors of success Rita Laiginhas 1,2 & Marta Inês Silva 1 & Vitor Rosas 1 & Susana Penas 1 & Vitor Adriano Fernandes 1 & Amândio Rocha-Sousa 1,3 & Ângela Carneiro 1,3 & Fernando Falcão-Reis 1,3 & Manuel Sousa Falcão 1,3 Received: 12 July 2017 /Revised: 5 October 2017 /Accepted: 16 October 2017 # Springer-Verlag GmbH Germany 2017 Abstract Purpose To evaluate functional and anatomical outcomes af- ter aflibercept in patients with diabetic macular edema (DME) with poor response to bevacizumab. Methods We retrospectively reviewed patients with DME re- calcitrant to bevacizumab who were switched to aflibercept between January and December 2015. All patients had a min- imal follow-up of three months before the conversion and underwent at least three injections of bevacizumab. Functional outcome consisted in best corrected visual acuity (VA). Anatomical outcomes were demonstrated through cen- tral macular thickness (CMT) measured by optical coherence tomography. Results Forty-nine eyes of 34 subjects were reviewed. Mean VA improved from 0.55 ± 0.32 logMAR to 0.46 ± 0.33 logMAR ( p = 0.038). Mean CMT decreased from 473 ± 146 μm to 349 ± 85 μm(p < 0.001). Twelve eyes (24%) demonstrated absence of macular edema after aflibercept. Previous bevacizumab exposure did not correlate with different outcomes. The variation of VA in response to aflibercept was significantly superior in the group with poorer VA before the switch (mean variation of -0.097 ± 0.21 logMAR) when compared to eyes with VA < 0.4 logMAR (mean variation of +0.019 ± 0.090 logMAR; p = 0.036). The same scenario was verified for anatomical outcomes as eyes with poor vision before the switch (≥0.4 logMAR) achieved superior reduction in CMT in response to aflibercept (mean CMT variation of -157 ± 171 μm versus -49.5 ± 39.9 μm; p < 0.01). Pre-switch CMT was a predictor of CMT reduction after switching (B = –0.945; confidence interval 95% –1.1; -0.76; p < 0.001). Conclusions Conversion to aflibercept for persistent DME resulted in functional and anatomical improvements and these outcomes were not influenced by previous bevacizumab ex- posure. Pre-switch CMT was a predictor of anatomical chang- es after aflibercept. Keywords Diabetic macular edema . Refractory . Bevacizumab . Aflibercept Introduction Diabetic macular edema (DME), a manifestation of diabetic retinopathy, is a leading cause of vision loss [1]. Vascular endothelial growth factor (VEGF) is an important mediator of abnormal vascular permeability in DME and several clini- cal trials have provided evidence for the use of anti-VEGF agents as first-line therapy for center-involved DME [2]. Ranibizumab (Lucentis, Genentech, Inc., San Francisco, CA, USA), bevacizumab (Avastin, Genentech, Inc., San Francisco, CA, USA) and most recently aflibercept (Eylea, Regeneron, Tarrytown, NY, USA) are the three most commonly used in- travitreal anti-VEGF agents in this context [3]. As they have different profiles and associated costs, the adequate first-line therapy remains controversial. A head-to-head comparison only recently became available when the Diabetic Rita Laiginhas and Marta Inês Silva contributed equally to this work and should be considered as equal first authors. * Manuel Sousa Falcão falcao@med.up.pt 1 Department of Ophthalmology, Centro Hospitalar de São João, Porto, Portugal 2 Centro Hospitalar de Entre o Douro e Vouga, Santa Maria da Feira, Portugal 3 Department of Surgery and Physiology, Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200– 319 Porto, Portugal Graefes Arch Clin Exp Ophthalmol https://doi.org/10.1007/s00417-017-3836-1