Interleukin-6 as a therapeutic target in Diabetic macular edema: current evidence and future perspectives

INTRODUCTION: Diabetic macular edema (DME) is a major cause of vision loss in diabetic retinopathy. Although anti-vascular endothelial growth factor (VEGF) therapy is the current standard treatment, many patients show incomplete responses, indicating the contribution of VEGF-independent mechanisms. Increasing evidence identifies interleukin-6 (IL-6) as a key mediator of inflammation, blood-retinal barrier disruption, and retinal vascular dysfunction in DME. AREAS COVERED: This review summarizes the biological functions and signaling pathways of IL-6 in DME and examines the clinical relevance of elevated intraocular IL-6 levels. We discuss the crosstalk between IL-6 and VEGF, review current evidence for IL-6-targeting agents, including tocilizumab and sarilumab, and evaluate their therapeutic potential, particularly in treatment-resistant DME. EXPERT OPINION: IL-6 acts as a central hub cytokine linking chronic inflammation, vascular permeability, and retinal microvascular injury. By modulating both VEGF-dependent and VEGF-independent pathways, IL-6 inhibition represents a promising therapeutic strategy for refractory DME. Although direct clinical evidence remains limited, advances in biomarker-guided patient selection, local drug delivery systems, and combination approaches with anti-VEGF therapy may facilitate the development of precision medicine for DME.