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

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.

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.

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.

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.