A Clinical Study on Biomarkers Affecting the Prognosis of Anti-VEGF Treatment in Diabetic Macular Edema

Objective This study aimed to investigate prognostic biomarkers associated with the heterogeneous response to anti-VEGF therapy in patients with diabetic macular edema (DME) using multimodal data analysis, including aqueous humor cytokines, peripheral blood inflammatory markers, lipid profiles, renal function indicators and optical coherence tomography (OCT) features, so as to provide evidence for individualized treatment. Methods In this retrospective cohort study, DME patients treated with anti-VEGF between April 2023 and May 2024 were enrolled and categorized into good responders (central macular thickness [CMT]reduction ≥ 25%) and poor responders (CMT reduction < 25%), with non-diabetic cataract patients as controls. Analyzed parameters included aqueous humor factors (VEGF, ICAM-1, MCP-1, IP-10, IL-6, IL-8), peripheral blood indices (neutrophil-to-lymphocyte ratio [NLR], systemic immune-inflammation index[SII], systemic inflammation response index [SIRI]), lipid profiles, renal function markers, and OCT biomarkers. Statistical analyses involved univariate analysis, Spearman correlation, and receiver operating characteristic (ROC) curve analysis (P < 0.05). Results DME patients had significantly higher aqueous levels of VEGF,ICAM-1, IL-6, and IL-8 than controls(P < 0.05).Poor responders exhibited lower VEGF levels but higher IP-10, IL-8, SII, SIRI, total cholesterol (TC), and cystatin C (Cys-C) levels (P < 0.05).Baseline CMT was lower in poor responders, while hyperreflective foci(HRF), disorganization of retinal inner layers (DRIL),and vitreomacular interface abnormalities (VIMA) were more frequent (P < 0.05). ROC analysis identified VEGF, IP-10, IL-8, SII, SIRI, TC, Cys-C, CMT, HRF, DRIL, and VIMA as predictive biomarkers. Conclusion Aqueous humor cytokines, systemic inflammatory indices, lipid parameters, renal function markers, baseline CMT, and OCT biomarkers are potential predictors for anti-VEGF treatment response in DME, emphasizing the role of inflammation and systemic factors in therapeutic outcomes and supporting the development of personalized strategies