AI-Assisted OCT Clinical Phenotypes of Diabetic Macular Edema: A Large Cohort Clustering Study

Purpose: To characterize, using clustering analysis, the OCT morphological and clinical phenotypes of diabetic macular edema (DME) in a very large population (>2000 DME eyes) using standardized and validated OCT-based biomarkers. Methods: A cross-sectional study was conducted on OCT scans collected from 2355 eyes of 1688 patients with DME and performed during real-world clinical practice. OCT scans were automatically analyzed by a software able to automatically quantify OCT key biomarkers: intraretinal fluid (IRF), subretinal fluid (SRF), hyperreflective retinal foci (I-HRF), and external limiting membrane (ELM) and ellipsoid zone (EZ) interruption. Clustering analysis was performed using the above-mentioned biomarkers, including the distribution of IRF across the three ETDRS rings. Results: The overall population was predominantly composed of type 2 diabetes patients (89%), with a mean diabetes duration of 15.6 ± 10.7 years and mean best corrected visual acuity (BCVA) of 63 ± 18 ETDRS letters. Multivariate clustering identified four morphological phenotypes with distinct patterns of fluid distribution associated with different I-HRF counts, SRF volume, and percentages of ELM/EZ integrity (p < 0.0001). Conclusions: This large OCT analysis identified distinct morphological subtypes of DME, confirming the clinical relevance of key imaging biomarkers. The distribution and severity of DME features differ among clusters, supporting the importance of OCT-based phenotyping in tailoring treatment strategies and understanding disease evolution.