Eligibility criteria in RCTs of anti-VEGF therapy for diabetic macular edema: A systematic review

Topic: Eligibility criteria used in randomized controlled trials of intravitreal anti–vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME). Clinical relevance: Randomized controlled trials (RCTs) guide clinical decision-making for DME treatment; however, stringent eligibility criteria may limit their representativeness and raise concerns about generalizability to real-world populations Methods: We searched 15 literature databases on 14 October 2025 to identify RCTs of intravitreal anti-VEGF for the treatment of DME. Data on eligibility criteria related to visual function, disease definition and stage, ocular comorbidities, systemic comorbidities, demographics, and additional factors not covered by other categories were extracted and summarized for a qualitative review. Due to the nature of the systematic review, neither a quantitative meta-analysis nor a formal risk-of-bias assessment was performed Results: A total of 21 eligible studies were included in this review, which together included 7353 eyes of 7320 patients. We identified a range of eligibility criteria in the areas of visual function (minimum 20–39 ETDRS letters; maximum 55–85 ETDRS letters), disease definition and stage (DME anatomy, diabetes type, and diabetic retinopathy grading), ocular and systemic comorbidities, specific demographics, as well as miscellaneous (e.g., contraception use requirement). The most frequent exclusion criteria across studies were prior laser photocoagulation (90.5%), prior intraocular surgery (90.5%), prior corticosteroid use (85.7%), active ocular inflammation or infection (81.0%), prior anti-VEGF therapy (76.2%), history of stroke or myocardial infarction (71.4%), proliferative diabetic retinopathy (66.7%), and uncontrolled blood pressure (61.9%). Conclusions: RCTs evaluating anti-VEGF therapy for DME use stringent eligibility criteria that may ultimately limit the generalizability of their findings to real-world patients with DME.