Beyond Anti-VEGF: Toward Integrated Precision Care in Diabetic Retinal Disease.

Abstract

Diabetic retinal disease (DRD) remains one of the leading causes of preventable vision loss worldwide and continues to represent a major global public health challenge despite remarkable therapeutic advances over the past two decades. Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has revolutionized the management of diabetic macular edema and proliferative diabetic retinopathy, significantly improving visual outcomes and reducing vision-threatening complications. Nevertheless, a substantial proportion of patients exhibit incomplete anatomical or functional responses, require frequent lifelong intravitreal injections, or experience disease progression despite adequate VEGF suppression, underscoring the biological heterogeneity of DRD. Growing evidence recognizes DRD as a chronic neurovascular disorder extending beyond a purely microvascular disease. Inflammation, oxidative stress, mitochondrial dysfunction, neurodegeneration, vascular instability, and progressive retinal ischemia interact throughout disease progression. Concurrently, advances in multimodal retinal imaging-including optical coherence tomography (OCT), OCT angiography (OCTA), ultra-widefield imaging, and artificial intelligence-assisted image analysis-have enabled the identification of imaging biomarkers that improve diagnosis, prognostication, and individualized therapeutic decision-making. The therapeutic landscape has expanded considerably beyond conventional anti-VEGF therapy. Corticosteroid implants, dual-pathway inhibitors, sustained drug-delivery systems, vitreoretinal surgery, laser photocoagulation, and emerging pharmacological approaches have broadened treatment options. Increasing evidence supports tailoring therapy according to retinal phenotype, imaging biomarkers, inflammatory status, ischemic burden, and systemic metabolic factors rather than relying on uniform treatment algorithms. This review summarizes recent advances in the understanding and management of DRD, emphasizing pathophysiology, multimodal imaging biomarkers, pharmacological therapies and delivery systems, vitreoretinal surgery, systemic risk-factor optimization, artificial intelligence, and emerging therapeutic strategies. Finally, we introduce Integrated Precision Care (IPC) as a proposed conceptual and research framework that integrates conventional disease staging with multimodal retinal imaging, biological phenotyping, systemic risk assessment, treatment burden, and patient-specific characteristics. IPC is not intended to replace established stage-specific guidelines or to function as a prospectively validated therapeutic algorithm; rather, it provides a hypothesis-generating structure for testing whether multidimensional integration can improve risk stratification, therapeutic selection, durability, patient-centered outcomes, and long-term vision.