Next-Generation Long-Acting Anti-VEGF Therapies for the Treatment of Diabetic Macular Edema

Abstract

The outcomes of diabetic macular edema (DMO) treatment have improved following the introduction of intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors. However, real-world data indicate that the treatment burden associated with intravitreal injections in DMO patients leads to significant differences in outcomes between randomized clinical trials and everyday clinical practice. Long-acting intravitreal drugs and devices used in DMO may help bridge this gap by achieving optimal treatment with more feasible injection regimens. Purpose: The purpose of this chapter is to analyze new drugs and devices for the treatment of DMO, explain their mechanisms of action, summarize key research findings, and discuss potential limitations and safety profiles. The analysis covers: brolucizumab, faricimab, conbercept, KSI-301, and the port delivery system (PDS). Treatment strategies using these drugs and technologies may serve as the first step in controlling the global epidemic of diabetic eye disease. Material and Methods:  A review and analysis of randomized clinical trials and clinical studies from 2014 to 2025 available in PubMed and Google Scholar. Findings: Longer-acting anti-VEGF therapies can reduce treatment burden by extending intervals between injections (up to 12–16 weeks or more). Brolucizumab and faricimab showed non-inferior visual acuity gains compared to aflibercept, with fewer injections. KSI-301 and PDS platforms also demonstrated promising safety and extended dosing intervals, although further data are needed. Research and practical limitations: Some trials remain ongoing, and long-term safety profiles require further confirmation. High treatment costs, varied patient adherence, and the logistics of regular monitoring still pose significant challenges.