Current status of multi-target therapeutics for diabetic macular oedema: Mechanisms and outcomes from clinical trials

Diabetic macular oedema (DME) remains a major cause of vision loss globally, with a growing population leading to a substantial economic burden. Characterised by complex and intricately interconnected pathogenic pathways, DME presents suboptimal responses and a lack of durability in a substantial proportion of patients. The significant limitations of first-line anti-VEGF monotherapy underscore the critical need for multi-targeted therapeutic strategies that address this multifaceted pathophysiology. Although the individual therapeutic classes for DME have been summarised by previous literature, there is a lack of comprehensive evaluation on the entire spectrum of emerging multi-target therapeutics. Therefore, to highlight the rationale and development of diverse therapeutics designed to simultaneously modulate key pathogenic mechanisms, this review summarises the current landscape of emerging multi-pathway therapeutics for DME. Each strategy offers distinct profiles of efficacy, durability, safety, and reduced treatment burden. It provides a crucial overview of how targeting multiple targets within the DME pathogenic network holds promise for overcoming the limitations of single-target therapy. By comprehensively evaluating the mechanisms, clinical evidence, and relative merits of these diverse multi-targeted strategies, this review serves as an essential resource for guiding future research and informing rational therapeutic selection. In the near future, the advancement of multi-pathway interventions will represent a pivotal step towards achieving more effective, durable, and personalised management of DME, aiming to preserve vision for a greater number of patients worldwide.