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Ayman G Elnahry,1 Alia M Noureldine,1 Ahmed A Abdel-Kader,1 Osama A Sorour,2 David J Ramsey3 1Department of Ophthalmology, Faculty of Medicine, Cairo University, Cairo, Egypt; 2Department of Ophthalmology, Faculty of Medicine, Tanta University, Tanta, Egypt; 3Division of Ophthalmology, Lahey Hospital & Medical Center, Tufts University School of Medicine, Boston, MA, USACorrespondence: Ayman G ElnahryDepartment of Ophthalmology, Faculty of Medicine, Cairo University, Cairo, 11956, Egypt, Tel +20 1224927604, Fax +20 223682030, Email ayman_elnahri@hotmail.comPurpose: To identify biomarkers that may predict an early anatomical response to the treatment of diabetic macular edema (DME) with intravitreal bevacizumab (IVB) by means of optical coherence tomography angiography (OCTA).Methods: This study is a retrospective study of treatment-naïve patients with DME who underwent 6 × 6 mm OCTA imaging of the macula at baseline and after three monthly IVB injections. Thirty-six eyes of 23 patients were included. Eyes that demonstrated evidence of an early anatomical response, consisting of a > 10% decrease in central macular thickness (CMT) (n = 18), were compared with those eyes that failed to show such an improvement (n = 18).Results: At baseline, early-response eyes had worse starting best-corrected visual acuity (BCVA, LogMAR 0.84 ± 0.41 versus LogMAR 0.51 ± 0.15, p = 0.004) and a larger CMT (490 ± 135 μm versus 356 ± 33 μm, p = 0.001), but smaller foveal avascular zones (FAZ) (0.309 ± 0.098mm versus 0.413 ± 0.095 mm, p = 0.003) compared with eyes that proved refractory to three monthly injections of IVB. The vascular density (VD) in both the foveal superficial and deep capillary plexuses was significantly greater in eyes that showed an early-treatment response compared with eyes that were non-responders (24.86 ± 6.90% versus 19.98 ± 7.13%, p = 0.045 and 32.30 ± 4.88% versus 26.95 ± 7.25%, p = 0.028, respectively). Early-treatment response to IVB was predicted by starting CMT (r2= 0.266, p = 0.001), FAZ size (r2= 0.234, p = 0.003), and VD in the superficial parafovea (r2= 0.217, p = 0.004) and deep fovea (r2= 0.157, p = 0.037).Conclusion: Projection-resolved OCTA may be useful in predicting an early anatomical response of DME to treatment with IVB.Keywords: anti-VEGF agents, bevacizumab, biomarkers, diabetic macular edema, macular ischemia, macular perfusion, optical coherence tomography angiography