The Behavior of the External Limiting Membrane and Ellipsoid Zone in Diabetic Macular Edema: A Population AI-Assisted Optical Coherence Tomography Study

Purpose: To investigate the behavior of the external limiting membrane (ELM) and ellipsoid zone (EZ) in diabetic macular edema (DME) using artificial intelligence (AI)-based optical coherence tomography (OCT) quantification. Methods: This was a cross-sectional study. OCT scans of eyes affected by DME were analyzed using a validated AI platform to quantify intraretinal fluid (IRF), subretinal fluid (SRF), inflammatory hyper-reflective retinal foci (I-HRF), and the percentage of interruption of the ELM and EZ. Eyes were classified according to ELM/EZ interruption and grouped into four patterns of integrity: no interruption, EZ interruption >ELM, ELM > EZ, and ELM = EZ. The distribution of the ELM/EZ disruption and associations with other biomarkers, and clinical data, including visual acuity, were analyzed. Results: We analyzed 2355 eyes from 1688 patients affected by DME. ELM interruption was observed in 21.9% of eyes and EZ interruption in 37.6%. A greater prevalence of EZ disruption was also identified in both previously treated and untreated eyes. Eyes with an interrupted ELM/EZ showed significantly greater IRF and SRF volumes and a more centrally located IRF distribution. I-HRF counts were significantly higher in eyes with predominant EZ damage. ELM disruption showed the strongest correlation with visual acuity and SRF burden. Conclusions: Quantitative AI-based OCT analysis demonstrated that the ELM and EZ have distinct yet complementary relationships with fluid biomarkers and visual acuity. EZ alterations are more prevalent and associated with I-HRF increases, whereas ELM disruption appears to reflect deeper structural damage and stronger functional impairment. Integrating outer retinal layer integrity with other features of DME may provide a more comprehensive characterization of DME and support a more personalized prognostic assessment and therapeutic strategies.

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Journal
Investigative Ophthalmology & Visual Science
Published
2026-09-21
DOI
https://doi.org/10.1167/iovs.67.11.40
Primary Topic
Retinal Diseases and Treatments
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article
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article

The Behavior of the External Limiting Membrane and Ellipsoid Zone in Diabetic Macular Edema: A Population AI-Assisted Optical Coherence Tomography Study

Daniele Veritti, Leandro Inferrera, Giuseppe Covello, Giuseppe Giannaccare et al.
Investigative Ophthalmology & Visual Science
Retinal Diseases and Treatments
article

The Behavior of the External Limiting Membrane and Ellipsoid Zone in Diabetic Macular Edema: A Population AI-Assisted Optical Coherence Tomography Study

Daniele Veritti, Leandro Inferrera, Giuseppe Covello, Giuseppe Giannaccare, Alessandro Invernizzi, Vincenzo Scorcia, Enrico Borrelli, Gilda Cennamo, Emilia Maggio, Roberto dell’Omo, F. Cappellani, Adriano Carnevali, Paolo Melillo, Nicola Valsecchi, Paolo Lanzetta, Edoardo Midena, Valentina Sarao, Federico Ricci, Luisa Frizziero, Giulia Midena, Nicola Vito Lassandro, Francesco Viola, Maria Oliva Grassi, Tommaso Bacci, Chiara Maria Eandi, Elisabetta Pilotto, Rosangela Lattanzio, Donatella Musetti, Luca Danieli, Fabiano Cavarzeran, N Castellino, Michele Figus, Grazia Pertile, Marco Nassisi, Marzia Affatato, Michele Coppola, Settimio Rossi, Valentina Folegani, Marzia Passamonti, Luca Rossetti, Giulia Gregori, Simone Donati, Marco Lupidi, Francesco Boscia, Ciro Costagliola, Mary Romano, Carlo Cagini, Michele Reibaldi, Daniele Tognetto, Lisa Toto, Maria Vittoria Cicinelli, Mariacristina Parravano, Paolo Mora, Marco Lombardo
article en

Abstract

Purpose: To investigate the behavior of the external limiting membrane (ELM) and ellipsoid zone (EZ) in diabetic macular edema (DME) using artificial intelligence (AI)-based optical coherence tomography (OCT) quantification. Methods: This was a cross-sectional study. OCT scans of eyes affected by DME were analyzed using a validated AI platform to quantify intraretinal fluid (IRF), subretinal fluid (SRF), inflammatory hyper-reflective retinal foci (I-HRF), and the percentage of interruption of the ELM and EZ. Eyes were classified according to ELM/EZ interruption and grouped into four patterns of integrity: no interruption, EZ interruption >ELM, ELM > EZ, and ELM = EZ. The distribution of the ELM/EZ disruption and associations with other biomarkers, and clinical data, including visual acuity, were analyzed. Results: We analyzed 2355 eyes from 1688 patients affected by DME. ELM interruption was observed in 21.9% of eyes and EZ interruption in 37.6%. A greater prevalence of EZ disruption was also identified in both previously treated and untreated eyes. Eyes with an interrupted ELM/EZ showed significantly greater IRF and SRF volumes and a more centrally located IRF distribution. I-HRF counts were significantly higher in eyes with predominant EZ damage. ELM disruption showed the strongest correlation with visual acuity and SRF burden. Conclusions: Quantitative AI-based OCT analysis demonstrated that the ELM and EZ have distinct yet complementary relationships with fluid biomarkers and visual acuity. EZ alterations are more prevalent and associated with I-HRF increases, whereas ELM disruption appears to reflect deeper structural damage and stronger functional impairment. Integrating outer retinal layer integrity with other features of DME may provide a more comprehensive characterization of DME and support a more personalized prognostic assessment and therapeutic strategies.

Investigative Ophthalmology & Visual ScienceVol. 67(11)
University of Siena (IT), University of Pisa (IT), University of Insubria (IT), University of Rome Tor Vergata (IT), Marche Polytechnic University (IT), University of Parma (IT), University of Udine (IT), University of Molise (IT), AOL (United States) (US), University of Padua (IT), University of Trieste (IT), Vita-Salute San Raffaele University (IT), University of Cagliari (IT), University of Milan (IT), Università degli Studi di Enna Kore (IT), University of Perugia (IT), CTO Hospital (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Magna Graecia University (IT), University of Catania (IT), University of Chieti-Pescara (IT), Luigi Sacco Hospital (IT), Saint Camillus International University of Health and Medical Sciences (IT), Fondazione G.B. Bietti (IT), Ospedale Sacro Cuore Don Calabria (IT), Azienda Ospedaliera San Gerardo (IT), Azienda USL di Bologna (IT), Istituto Europeo di Microchirurgia Oculare (IT), Fondation Asile des Aveugles (CH), University of Campania "Luigi Vanvitelli" (IT), Department of Medical Sciences (BY), Ospedale Policlinico San Martino (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Department of Public Health (US), IRCCS Humanitas Research Hospital (IT), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), University of Turin (IT), University of Bari Aldo Moro (IT), University of Naples Federico II (IT), University of Lausanne (CH)
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Openalex Percentile: Top 8%
Retinal Diseases and Treatments
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