AJOCT American Journal of Ophthalmic Clinical Trials • 2019 • 2(4) | 1 Abstract Diabetic retinopathy (DR) is a common complication of diabetes mellitus. Imaging techniques such as the gold standard of fluorescein angiography (FA) and the recent advent of optical coherence tomography angiography (OCTA) have allowed for detailed visualization of the microvasculature to assess and quantify macular perfusion. The development of ultra-widefield FA (UWFA) has allowed clinicians to examine ischemia within the periphery. As our imaging and diagnostic methods continue to be refined, it is important to understand how to best utilize these technologies to characterize disease severity and determine how it can guide treatment and prognosis. With the increasing use of anti-vascular endothelial growth factor (VEGF) agents for the treatment of DR, we can characterize the changes in perfusion on the microvascular level. The focus of this review is to summarize and identify the changes in both macular and peripheral perfusion with anti-VEGF treatment for patients with DR utilizing FA, UWFA, and OCTA. There remains a need for more prospective, long-term clinical trials with controls to better understand the characterization of the retinal microvasculature using these imaging techniques. In clinical practice, physicians likely will need to utilize a multimodal imaging approach to appropriately characterize the degree and progression of ischemia in DR. Keywords: Anti-vascular endothelial growth factor, Diabetic retinopathy, Macular perfusion, Peripheral perfusion INTRODUCTION D iabetic retinopathy (DR), a common complication of diabetes mellitus, is a leading cause of blindness worldwide, [1] and the number of patients with sight-threatening DR is expected to increase in our future. [2] Early detection with appropriate staging and classification of the disease can determine prognosis and guide treatment to avoid preventable complications such as vision loss. It is estimated that >90% of vision loss can be prevented. [3] The pathophysiology of DR involves abnormal vascular function within the retinal circulation. The hyperglycemic state in uncontrolled diabetes leads to loss of pericytes, weakening retinal capillary walls. [4] Utilizing a physics perspective with the Hagen-Poiseuille equation, the dilated vessel has increased flow and thus becomes the preferred shunt vessel, causing adjacent capillaries to become non-perfused. [5] This results in ischemia and a cascade of molecular processes, including upregulation of vascular endothelial growth factor (VEGF) in response to the hypoxia. [6] Although the exact pathogenesis has not been fully defined, VEGF mediates This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. Access this article online Quick Response Code: Website: www.ajoclinicaltrials.com DOI: 10.25259/AJOCT-3-2019 REVIEW ARTICLE Changes in Macular and Peripheral Perfusion Following Anti-vascular Endothelial Growth Factor Treatment for Patients with Diabetic Retinopathy Karen M. Wai, Rishi P. Singh Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA Corresponding Author: Karen M. Wai, Cole Eye Institute, Cleveland Clinic 2022 East 105 th Street, Cleveland, OH 44106, USA. E-mail: karen.m.wai@gmail.com Received: 14 March 2019 Accepted: 19 May 2019 Published: 17 June 2019