Diabetic retinopathy (DR) is the leading cause of vision loss in working-age adults, and diabetic macular edema (DME) is the most common cause of visual impairment in individuals with DR. This review focuses on the pathophysiology, previous treatment paradigms, and emerging treatment options in the management of DME. 1. Introduction Diabetic retinopathy (DR) is the leading cause of vision loss in working-age adults. In 2002, there were estimated to be just over 13.5 million individuals afflicted with diabetes mellitus (DM) in the USA, or about 6% of the population. Since then, revised estimates for 2011 indicate that 25.8 million people have DM in the USA, of which 18.8 million are diagnosed and 7 million cases are undiagnosed [1, 2]. Approximately 28.5% of individuals with DM have some form of retinopathy; 4.4% of individuals are at risk of severe vision loss secondary to advanced disease. Present estimates indicate that the incidences of DM and DR are both significantly increasing with as many as 50 million or more individuals in the USA having DM by the year 2050, of which half are expected to have some form of retinopathy [1–5]. DR can be categorized into two broad groups: (1) nonproliferative diabetic retinopathy (NPDR) and (2) proliferative diabetic retinopathy (PDR). Within NPDR, patients are classified as mild, moderate, or severe; severe NPDR is based on at least one of the following findings: diffuse intraretinal hemorrhages in all quadrants, venous beading in at least 2 quadrants, or the presence of intraretinal microvascular abnormalities. Of the two broad categories, proliferative disease, while it is less common, results in more severe vision loss. In nonproliferative disease, the most common cause of vision loss is due to diabetic macular edema (DME). At present, individuals with DR in the USA have a prevalence of DME between 3 and 5%, with this percentage increasing with age [6]. A recent meta-analysis of 35 population-based studies pooling data from the USA, Europe, Asia, and Australia found that in individuals with DM the prevalence of any type of DR is 35%, with DME present in 7.5% and PDR present in 7.2% of individuals. These prevalence rates were found to be significantly higher in individuals with type 1 DM compared to type 2 DM [7]. In the USA, over 90% of individuals with DM are type 2 diabetics [8]. Summarizing the above data as it applies to the USA, at present, approximately 1.1 million individuals are at serious risk of sight-threatening vision loss from DR. Of these “at risk” individuals, DME is the major etiology of visual
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