Serum microRNA-34a as a circulating biomarker for age-related macular degeneration and short-term anti-VEGF response in neovascular AMD

To evaluate whether serum microRNA-34a (miR-34a) is associated with age-related macular degeneration (AMD) and whether baseline serum miR-34a has the potential to predict short-term response to anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with neovascular AMD (nAMD). In a cross-sectional cohort recruited at Qingdao Municipal Hospital between January and December 2024, serum miR-34a was quantified in 160 AMD patients and 122 age- and sex-matched healthy controls. AMD was staged according to Age-related Eye Disease Study (AREDS) criteria. Patients with nAMD received three consecutive monthly intravitreal anti-VEGF injections during the loading phase and were classified as good or poor responders according to prespecified anatomical and functional criteria based on optical coherence tomography (OCT) and best-corrected visual acuity (BCVA) after the loading phase. Peripheral blood samples were collected, and serum miR-34a expression was quantified using standard qPCR protocols. Serum miR-34a was significantly higher in patients with AMD than in controls ( p < 0.001). Receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.740 (95% CI 0.681–0.799; p < 0.0001) for discriminating AMD from controls. Across AMD subgroups, serum miR-34a differed significantly overall; patients with geographic atrophy (GA) exhibited higher miR-34a levels than those with nAMD ( p < 0.05). Among patients with nAMD, baseline serum miR-34a was remarkably higher in good responders than in poor responders after the loading phase ( p < 0.001). ROC analysis showed an AUC of 0.772 (95% CI 0.687–0.857; p < 0.0001) for predicting treatment response, and multivariable logistic regression identified higher serum miR-34a as independently associated with lower odds of poor response (OR 0.143, 95% CI 0.042–0.489; p = 0.002). Elevated serum miR-34a is associated with AMD and may serve as a minimally invasive biomarker for distinguishing AMD from controls. In nAMD, baseline serum miR-34a also showed potential for predicting short-term response to loading-phase anti-VEGF therapy. These findings warrant validation in larger, longitudinal, and preferably multicenter cohorts.