Clinical trial landscape of diabetic retinopathy: global advancements and future directions

Plain Language Summary Diabetic retinopathy (DR) remains a leading cause of preventable blindness worldwide, with the affected population projected to reach 270 million by 2045. Our study analyzed 2 434 interventional trials registered between 2007 and 2024 in the Informa Pharma Intelligence database and found that anti-VEGF agents dominate the therapeutic landscape—bevacizumab represents 24.0 % of studies, ranibizumab 15.6 %, and aflibercept 13.9 %—with the greatest activity occurring in Phase IV trials. The number of Phase IV studies rose to 154 in 2024, reflecting intensified post-marketing surveillance and heightened interest in combination regimens such as bevacizumab plus triamcinolone. Persistent gaps remain: heterogeneous endpoints (for example, inconsistent use of ETDRS BCVA and OCT metrics), suboptimal trial designs, high attrition, emerging drug resistance, and limited attention to low-responder subgroups all hamper progress and leave advanced DR inadequately treated. To bridge these translational gaps, future investigations should incorporate precision-medicine strategies that integrate artificial-intelligence-driven imaging modalities, including optical coherence tomography angiography, apply standardized endpoints such as the Diabetic Retinopathy Severity Scale, and rigorously evaluate multimodal approaches combining pharmacologic, laser, and surgical interventions. This study offers a comprehensive snapshot of global DR research, highlighting achievements and unmet needs to guide researchers and clinicians toward more personalized and effective management paradigms. Plain Language SummaryDiabetic retinopathy (DR) is a major cause of blindness, with cases expected to reach 270 million by 2045. Our study analyzed 2,434 interventional trials registered between 2007 and 2024, showing that anti-VEGF drugs like bevacizumab, ranibizumab, and aflibercept are widely studied, with the greatest activity occurring in Phase IV trials, which rose to 154 in 2024. Challenges such as inconsistent trial endpoints, high dropout rates, drug resistance, and lack of focus on low-responder groups hinder progress. Future research should incorporate precision-medicine strategies that integrate artificial-intelligence-driven imaging modalities, apply standardized endpoints, and rigorously evaluate multimodal approaches combining pharmacologic, laser, and surgical interventions to better address advanced DR. Text is machine generated and may contain inaccuracies. View Plain Language Summary safety and compliance information