One-Year Results of a Trial Comparing 2 Doses of Intravitreal Ziv-aflibercept versus Bevacizumab for Treatment of Diabetic Macular Edema Mohammad Hossein Jabbarpoor Bonyadi, MD, 1 Ahmadreza Baghi, MD, 1 Alireza Ramezani, MD, 1,2,3 Mehdi Yaseri, PhD, 1 Masoud Soheilian, MD 1,2 Purpose: To report 1-year findings of a trial comparing 2 doses of intravitreal ziv-aflibercept (IVZ) with intravitreal bevacizumab (IVB) for treatment of center-involving diabetic macular edema (DME). Design: Three-armed double-blind randomized clinical trial. Participants: A total of 123 eyes with center-involving DME. Methods: In this clinical trial, eyes with DME were randomly assigned to 2.5 mg intravitreal ziv-aflibercept (42 eyes), 1.25 mg intravitreal ziv-aflibercept (42 eyes), and 1.25 mg IVB injections (39 eyes), every 4 weeks for 3 loading injections and then every 4 weeks for IVB and every 8 weeks for ziv-aflibercept injections. The patients were followed up to 1 year with complete ophthalmologic examination and central macular thickness (CMT) measurement by optical coherence tomography. Main Outcome Measures: Change in best-corrected visual acuity (BCVA) at 1 year. Results: Although no significant difference was evident between the 2 ziv-aflibercept groups at 1 year, BCVA change was significantly better in both ziv-aflibercept groups (0.330.26 and 0.380.34 logarithm of the minimum angle of resolution (logMAR) equal to 16 and 18 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, for IVZ 2.5 and 1.25 mg, respectively) than in the IVB group (0.260.35 logMAR, equal to 14 ETDRS letters) at final follow-up (P ¼ 0.007 for IVZ 2.5 mg and P ¼ 0.029 for IVZ 1.25 mg). Regarding CMT changes, there was no significant difference between the 2 ziv-aflibercept groups; however, a significantly greater reduction in CMT was observed in the ziv-aflibercept 2.5 mg group in comparison to the IVB group at 1 year (P ¼ 0.029). Subgroup analysis disclosed no difference in BCVA outcomes at 1 year among the eyes with baseline BCVA >20/50. In the eyes with baseline BCVA 20/50, however, the improvement was significantly better at 1 year in both ziv-aflibercept groups compared with the IVB group (P ¼ 0.002 for IVZ 2.5 mg and P ¼ 0.001 for IVZ 1.25 mg). Conclusions: The 1-year results of this trial disclosed more vision improvement with IVZ compared with IVB in the treatment of center-involving DME. This stronger effect of IVZ, however, was detected in the eyes with initial worse level of vision (20/50). Ophthalmology Retina 2017;-:1e13 ª 2017 by the American Academy of Ophthalmology Diabetic macular edema (DME) is 1 of the main causes of visual loss among diabetic patients, and vascular endothelial growth factor (VEGF) is 1 of the important mediators causing abnormal vascular permeability in such cases. Based on several large clinical trials, intravitreal injections of anti-VEGF agents have progressively evolved to be the first-line treatment of center-involving DME, with useful clinical response. 1e4 Having access to different anti-VEGF agents could help physicians to find potential therapeutic substitutes for treatment switch in cases of persistent or refractory DME. 5 Ziv-aflibercept, a recombinant fusion protein, has a mechanism similar to aflibercept. These agents are comprised of main domains from human VEGF receptors 1 and 2 fused to the Fc domain of human immunoglobulin-G1. In addition to prolongation of the retreatment intervals, aflibercept has been proven to have a long-term effect on vision improve- ment in DME cases. 6,7 Having a similar mechanism to afli- bercept, ziv-aflibercept, with its much lower cost, could be a potential substitute for aflibercept. A few recent published studies have reported intravitreal ziv-aflibercept (IVZ) as a safe and effective treatment in some retinal disorders, including DME, retinal vein occlusions, and age-related macular degeneration, with no ocular toxicity. 8e13 In a 12-week published report of a randomized clinical trial, we have recently disclosed a stronger effect of IVZ compared with intravitreal bevacizumab (IVB) in terms of both visual acuity improvement and macular thickness reduction in center-involving DME cases. 14 Herein, we report the 1-year results of the same trial evaluating the efficacy of 2 doses of IVZ (1.25 mg and 2.5 mg) compared with IVB (1.25 mg) in eyes with DME. 1 Ó 2017 by the American Academy of Ophthalmology Published by Elsevier Inc. https://doi.org/10.1016/j.oret.2017.09.010 ISSN 2468-6530/17