Unsupervised machine learning analysis of optical coherence tomography radiomics features for predicting treatment outcomes in diabetic macular edema

This study aimed to identify distinct clusters of diabetic macular edema (DME) patients with differential anti-vascular endothelial growth factor (VEGF) treatment outcomes using an unsupervised machine learning (ML) approach based on radiomic features extracted from pre-treatment optical coherence tomography (OCT) images. Retrospective data from 234 eyes with DME treated with three anti-VEGF therapies between January 2020 and March 2024 were collected from two clinical centers. Radiomic analysis was conducted on pre-treatment OCT images. Following principal component analysis (PCA) for dimensionality reduction, two unsupervised clustering methods (K-means and hierarchical clustering) were applied. Baseline characteristics and treatment outcomes were compared across clusters to assess clustering efficacy. Feature selection employed a three-stage pipeline: exclusion of collinear features (Pearson's r > 0.8); sequential filtering through ANOVA (P < 0.05) and Boruta algorithm (500 iterations); multivariate stepwise regression (entry criteria: univariate P < 0.1) to identify outcome-associated predictors. From 1165 extracted radiomic features, four distinct DME clusters were identified. Cluster 4 exhibited a significantly lower incidence of residual/recurrent DME (RDME) (34.29%) compared to Clusters 1-3 (P = 0.003, P = 0.005 and P = 0.002, respectively). This cluster also demonstrated the highest proportion of eyes (71.43%) with best-corrected visual acuity (BCVA) exceeding 20/63 (P = 0.003, P = 0.005 and P = 0.002, respectively). Multivariate analysis identified logarithm_gldm_DependenceVariance as an independent risk factor for RDME (OR 1.75, 95% CI 1.28-2.40; P < 0.001), while Wavelet-LH_Firstorder_Mean correlated with worse visual outcomes (OR 8.76, 95% CI 1.22-62.84; P = 0.031). Unsupervised ML leveraging pre-treatment OCT radiomics successfully stratifies DME eyes into clinically distinct subgroups with divergent therapeutic responses. These quantitative features may serve as non-invasive biomarkers for personalized outcome prediction and retinal pathology assessment.