A Machine Learning Model for Predicting Anatomical Response to Anti-VEGF Therapy in Diabetic Macular Edema

Wenrui Lu¹Kunhong Xiao²Xuemei Zhang¹Yuqing Wang²Wenbin Chen²Xierong Wang²Yunxi Ye²Yan Lou³Li Li^1*

• ¹Fujian Provincial Hospital, Fuzhou, Fujian Province, China
• ²Fujian Medical University, Fuzhou, China
• ³China Medical University, Shenyang, Liaoning Province, China

To develop a machine learning model to predict anatomical response to anti-VEGF therapy in patients with diabetic macular edema (DME).This retrospective study included patients with DME who underwent intravitreal anti-VEGF treatment between January 2023 and February 2025. Baseline data included optical coherence tomography (OCT) features and blood-based metabolic and hematologic markers. The primary outcome was defined as a ≥20% reduction in central retinal thickness (CRT) post-treatment. Feature selection was performed using univariate logistic regression and LASSO regression. Five machine learning algorithms-logistic regression, decision tree, multilayer perceptron, random forest, and support vector machine-were trained and validated. Model performance was evaluated using accuracy, sensitivity, specificity, Area Under the Receiver Operating Characteristic Curve (AUC), and decision curve analysis. The best-performing model was further interpreted using SHAP analysis, and a nomogram was constructed for clinical application.Among the 37 baseline variables, five key predictors were identified: preoperative CRT >400 μm, presence of retinal edema, presence of subretinal fluid (SRF), disorganization of the inner retinal layers (DRIL), and ellipsoid zone (EZ) integrity. The logistic regression model achieved the best performance with an accuracy of 0.83, sensitivity of 0.85, specificity of 0.79, and an AUC of 0.90 (95% CI: 0.81-0.99). SHAP analysis revealed that preoperative retinal edema, DRIL, SRF, and CRT had the strongest positive contributions, while intact EZ was a negative predictor of CRT reduction. A nomogram was developed to facilitate individualized clinical decision-making.We successfully developed a predictive model for anatomical response to anti-VEGF therapy in DME patients. The model identified key features associated with treatment outcomes, providing a valuable tool for personalized therapeutic planning. Further validation in multicenter cohorts is warranted to confirm generalizability and enhance model robustness.