Anemia Associated with Increase in DME Risk, Treatment Burden

Recent study links hemoglobin levels with DME risk and anti-VEGF use across both sexes, and finds a mitigating effect from iron supplementation. Collectively, these findings suggest that reduced hemoglobin concentration represents an independent systemic determinant of DME risk. Photo: Julie Torbit, OD, Anna Kathryn Bedwell, OD, and Brad Sutton, OD. Click image to enlarge. Anemia—a common comorbidity in patients with diabetes—has been suggested to influence the progression of diabetic macular edema (DME). In a recent study, researchers aimed to better understand the association between different levels of anemia and the risk of developing DME in patients with type 2 diabetes who are DME-naive. They found that reduced hemoglobin concentration represents an independent systemic determinant of DME risk. The findings were reported in Ophthalmology Retina.The study analyzed 127,260 patients from the TriNetX US Collaborative Network who were newly diagnosed with type 2 diabetes, had no prior diabetic eye disease and a recorded hemoglobin measurement within six months of their index diagnosis. Patients were stratified into four cohorts based on hemoglobin levels (mild, moderate-low, moderate-high, severe) and compared to matched controls with normal hemoglobin. The researchers evaluated whether iron supplementation in patients with baseline hemoglobin levels <12.0g/dL influenced the one-year risk of DME.The mechanisms that likely explain the relationship between anemia and DME are primarily driven by retinal hypoxia and sustained inflammation. “First, the most robust explanation lies in the hypoxia-angiogenesis axis,” the researchers wrote in their paper. The retina is highly metabolically active and requires a massive oxygen supply, they elaborated, and anemia lowers the oxygen-carrying capacity of the blood, inducing chronic retinal hypoxia. “This hypoxic state strongly upregulates the expression of VEGF, which drives vascular permeability and fluid leakage into the macula,” the authors wrote.Regarding inflammation, DME is increasingly understood to have a chronic inflammatory component. “Anemia, particularly in the setting of chronic disease or iron deficiency, often coexists with systemic inflammation,” the authors wrote. “Elevated proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), directly contribute to DME pathogenesis by breaking down tight junction proteins and promoting leukostasis.”Patients with mild anemia had a 47% increased risk of developing DME at one year, rising progressively to a 132% increased risk in those with severe anemia, likely reflecting a mixture of incident disease captured during follow-up and a small fraction of previously undiagnosed prevalent disease. A stepwise increase in the one-year hazard ratio (HR) of developing DME was observed as anemia severity increased:Mild anemia: HR, 1.47Moderate-low anemia: HR, 1.66Moderate-high anemia: HR 1.99Severe anemia: HR, 2.32The severity gradient from mild to severe suggests an underlying association between hemoglobin levels and diabetic macular disease.Sex-stratified analyses confirmed that this severity gradient persisted across both male and female subgroups, with men exhibiting more pronounced hazard ratios. This elevated disease risk translated into a higher likelihood of requiring anti-VEGF injections at one year. The authors suggest that severely anemic patients are systemically sicker and more frequently hospitalized and may experience deferred or unreceived intravitreal therapy due to medical clearance constraints, competing mortality and elevated short-term morbidity.Iron supplementation was associated with a 14% reduction in the one-year risk of developing DME (HR, 0.86), which the authors conclude warrant further prospective investigation.Click here for the journal source. Muayad J, Butt FR, Loya A, et al. Systemic anemia and the risk of diabetic macular edema and anti-VEGF injections. Ophthalmology Retina. June 22, 2026. [Epub ahead of print.] This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.