{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:12:25Z","timestamp":1791547945682,"version":"4.3.4"},"reference-count":27,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Purpose: To characterize, using clustering analysis, the OCT morphological and clinical phenotypes of diabetic macular edema (DME) in a very large population (&gt;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 \u00b1 10.7 years and mean best corrected visual acuity (BCVA) of 63 \u00b1 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 &lt; 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.<\/jats:p>","DOI":"10.3390\/jcm14227893","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T11:41:47Z","timestamp":1762515707000},"page":"7893","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["AI-Assisted OCT Clinical Phenotypes of Diabetic Macular Edema: A Large Cohort Clustering Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3132-6233","authenticated-orcid":false,"given":"Edoardo","family":"Midena","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Padova, 35100 Padova, Italy"},{"name":"IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6817-2488","authenticated-orcid":false,"given":"Marco","family":"Lupidi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Polytechnic University of Marche, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5311-5184","authenticated-orcid":false,"given":"Lisa","family":"Toto","sequence":"additional","affiliation":[{"name":"Ophthalmology Clinic, Department of Medicine and Science of Ageing, \u201cG. d\u2019Annunzio\u201d University Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8523-2032","authenticated-orcid":false,"given":"Giuseppe","family":"Covello","sequence":"additional","affiliation":[{"name":"Ophthalmology, Department of Surgical, Medical, Molecular Pathology and Clinical Care Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0148-5348","authenticated-orcid":false,"given":"Daniele","family":"Veritti","sequence":"additional","affiliation":[{"name":"Department of Medicine-Ophthalmology, University of Udine, 33100 Udine, Italy"},{"name":"Istituto Europeo Di Microchirurgia Oculare\u2014IEMO, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6677-7697","authenticated-orcid":false,"given":"Elisabetta","family":"Pilotto","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Padova, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Vittoria","family":"Cicinelli","sequence":"additional","affiliation":[{"name":"School of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Department of Ophthalmology, IRCCS San 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