Laurence S Lim,1,2 Wei Yan Ng,2 Ranjana Mathur,2 Doric Wong,2 Edmund YM Wong,2 Ian Yeo,2 Chui Ming Gemmy Cheung,2 Shu Yen Lee,2 Tien Yin Wong,2 Thanos D Papakostas,1 Leo A Kim1 1Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA; 2Vitreoretinal Department, Singapore National Eye Centre, Singapore Background: The purpose of this study was to determine if eyes with diabetic macular edema (DME) unresponsive to ranibizumab or bevacizumab would benefit from conversion to aflibercept.Methods: This study was conducted as a retrospective chart review of subjects with DME unresponsive to ranibizumab and/or bevacizumab and subsequently converted to aflibercept.Results: In total, 21 eyes from 19 subjects of mean age 62±15 years were included. The majority of subjects were male (63%). The median number of ranibizumab or bevacizumab injections before switching to aflibercept was six, and the median number of aflibercept injections after switching was three. Median follow-up was 5 months after the switch. Mean central foveal thickness (CFT) was 453.52±143.39 mm immediately prior to the switch. Morphologically, intraretinal cysts were present in all cases. Mean CFT after the first injection decreased significantly to 362.57±92.82 mm (Wilcoxon signed-rank test; P<0.001). At the end of follow-up, the mean CFT was 324.17±98.76 mm (P<0.001). Mean visual acuity was 0.42±0.23 logMAR just prior to the switch, 0.39±0.31 logMAR after one aflibercept injection, and 0.37±0.22 logMAR at the end of follow-up. The final visual acuity was significantly better than visual acuity before the switch (P=0.04).Conclusion: Eyes with DME unresponsive to multiple ranibizumab/bevacizumab injections demonstrate anatomical and visual improvement on conversion to aflibercept. Keywords: diabetic retinopathy, macular edema, aflibercept, bevacizumab, ranibizumab