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Review Retina Update on the Management of Diabetic Macular Edema Shawn M Iverson 1 and W Lloyd Clark 1,2 1. Palmetto Health - University of South Carolina Medical Group, Columbia, South Carolina, US; 2. Assistant Clinical Professor of Ophthalmology, University of South Carolina School of Medicine, Palmetto Retina Center LLC, West Columbia, South Carolina, US D iabetic macular edema (DME) is a treatable sequela of diabetic retinopathy and a significant cause of visual morbidity among working age individuals worldwide. While anti-vascular endothelial growth factor (anti-VEGF) agents are first-line agents in the management of DME, corticosteroids and laser therapy can play a role as well. Despite a growing understanding of best clinical practices, many patients respond unpredictably to therapy. This article will briefly review current treatment modalities and discuss future treatment options for managing DME. Keywords Diabetic macular edema, anti-vascular endothelial growth factor, VEGF, macular laser, aflibercept, bevacizumab, ranibizumab Disclosure: Shawn M Iverson has nothing to disclose in relation to this article. W Lloyd Clark has received consulting fees from Bayer, Genentech/Roche, Regeneron; speakers bureau from Genentech/Roche, Regeneron; contracted research: Allergan, Inc., Genentech/Roche, Regeneron; and equity from VERSYL, Inc. No funding was received in the publicaiton of this article. This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors. Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: January 10, 2017 Accepted: February 15, 2017 Citation: US Ophthalmic Review, 2017;10(1):52–6 Corresponding Author: Lloyd Clark, MD, Palmetto Retina Center, 124 Sunset Court, West Columbia, SC 29169, US. E: LClark@PalmettoRetina.com Diabetic retinopathy is the leading cause of blindness worldwide among patients aged 20–74. 1 Among eyes with diabetic retinopathy, diabetic macular edema (DME) accounts for a significant proportion of vision loss and associated morbidity, 2,3 and the reported incidence is quite high, occuring in 26.1% of type 1 diabetics according to The Wisconsin Epidemiologic Study of Diabetic Retinopathy. 4 Tight glucose control significantly reduces the risk of development and progression of diabetic retinopathy in both type 1 and type 2 diabetics, and this remains the best preventative measure. 5–7 These studies have additionally shown other modifiable risk factors, such as hypertension control, play important roles in managing diabetic eye disease. For those eyes that do develop macular edema, a number of treatment options exist, and research into new and modified modalities is ongoing. Recently, first- line therapy for DME has shifted and patients and clinicians can expect visual improvement with consistent treatment. As research advances, it is likely that new therapies will emerge and preferred practice patterns will continue to evolve. Anti-vascular endothelial growth factor Background Anti-vascular Endothelial Growth Factor (anti-VEGF) agents have become stardard of care in the treatment of center-involving DME. The first anti-VEGF agent used in treating DME was pegaptanib (Macugen ® , Pfizer, New York, US), a pegylated anti-VEGF aptamer. In the early 2000s, a phase II study was completed showing pegaptanib reduces macular thickness and improves vision, 8 however, the development of this agent did not move forward as more efficacious anti-VEGF agents came to market. Today, clinicians choose from three commercially available anti-VEGF agents for treating DME and for treating diabetic retinopathy associated with DME; bevacizumab (Avastin ® , Genentech, California, US), ranibizumab (Lucentis ® , Genentech, California, US), and aflibercept (Eylea ® , Regeneron, New York, US), the latter two of which have Food and Drug Administration (FDA) approval. Bevacizumab, ranibizumab, and alfibercept are all anti-VEGF medications, however there are notable structural differences between these agents. Bevacizumab is a recombinant, humanized, full length monoclonal antibody to VEGF. Ranibizumab is a monoclonal antibody antigen-binding fragment to VEGF. Ranibizumab is unique in that it lacks an Fc portion, which results in a more rapid clearance from the body, 9 a characteristic some believe plays a role in differences in systemic adverse effects, although this is not conclusively proven. Aflibercept is a recombinant fusion protein consisting of binding domains to VEGF-receptors 1 and 2 bound to the Fc portion human immunoglobulin G1 (IgG1). These structural differences affect binding affinity for VEGF, which plays a role in differences in in vivo activity and clinical response. Analyzing binding affinity is highly complex and has been studied with mixed results. 10,11 While aflibercept is thought to be more potent, a recent study by 52 TOUCH ME D ICA L ME D IA