Fumaric Acid Esters as Modulators of Ocular Inflammation and Angiogenesis

Ocular diseases leading to irreversible vision loss are driven by convergent pathological processes, including chronic inflammation, oxidative stress, and angiogenesis. Despite therapeutic advances, corneal neovascularization, age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma remain major causes of vision impairment. Conventional therapies for these diseases pose challenges related to non-responsiveness and long-term inefficacy, highlighting the need for treatments that target upstream mechanisms shared across ocular pathologies. Fumaric acid esters (FAEs), particularly dimethyl fumarate (DMFu) and its active metabolite, monomethyl fumarate (MMF), have emerged as promising drug candidates due to their potent immunomodulatory and antioxidant properties. Mechanistically, DMFu activates nuclear factor erythroid 2-related factor 2 (Nrf2) signaling to enhance antioxidant defense while suppressing nuclear factor-κB (NF-κB)-mediated pro-inflammatory responses. Beyond inflammation, DMFu inhibits VEGF-driven angiogenesis through metabolic rewiring in endothelial cells. This review discusses the efficacy of FAEs across various ocular pathologies and addresses the pharmacokinetics of the drugs and hurdles such as rapid systemic hydrolysis and ocular barriers. Despite translational challenges, the multimodal mechanisms of FAEs offer a unique advantage over single-target therapies, positioning them as promising candidates for targeting convergent pathways in complex ocular diseases.