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Assessment of Ellipsoid Zone Integrity and Other Quantitative OCT Biomarkers for Intermediate Age-Related Macular
Karen Matar1, Adrienne Delaney2, Asmita Indurkar1
1The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Department of Ophthalmology, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio; Cole Eye Institute, Department of Ophthalmology, Cleveland Clinic Foundation, Cleveland, Ohio.
Purpose:
To evaluate the association between baseline OCT biomarkers and 2-year disease progression from intermediate age-related macular degeneration (iAMD) to advanced atrophic age-related macular degeneration (AMD), defined by OCT, with emphasis on ellipsoid zone (EZ) attenuation/loss and other quantitative structural features.
Design:
A retrospective cohort study.
Participants:
A total of 502 eyes with iAMD and no evidence of atrophy (i.e., retinal pigment epithelium [RPE] loss with associated outer retinal atrophy) or exudation at baseline, each with 2-year follow-up OCT imaging.
Methods:
Baseline and 2-year spectral-domain OCT scans were analyzed using a validated, machine learning-enhanced multilayer segmentation platform with subsequent certified reader review and correction. Quantitative OCT parameters included EZ-RPE thickness, partial and total EZ attenuation, drusen volume (DV), hyperreflective foci (HRF) count, total RPE loss, and outer nuclear layer (ONL)-RPE thickness. Fully automated deep-learning models quantified hypertransmission (HT) and EZ at-risk (i.e., a model developed to identify areas of abnormal EZ-RPE thinning in the absence of RPE loss). A random forest classifier was trained using baseline features, with performance assessed using fivefold stratified cross-validation.
Main Outcome Measures:
Development of OCT-defined advanced atrophic AMD defined by total RPE loss with associated outer retinal atrophy with an area of ≥0.05 mm2 (i.e., complete RPE and outer retinal atrophy equivalent) at 2 years and baseline OCT biomarkers associated with progression.
Results:
Eyes that developed advanced atrophic AMD showed significantly greater partial and total EZ attenuation, reduced EZ-RPE and ONL-RPE thickness, higher DV, and greater HRF counts than nonconverters (all P < 0.05). Deep learning-derived EZ at-risk and HT metrics were also significantly higher in converters. The cross-validated predictive model incorporating all baseline features achieved a mean area under the receiver operating characteristic curve of 0.853. Ellipsoid zone integrity metrics and HRF count ranked as the most influential predictors of progression.
Conclusions:
Quantitative OCT biomarkers, particularly EZ integrity measures and HRF count, are strongly associated with 2-year progression to advanced atrophic AMD in iAMD. These findings support the role of quantitative EZ integrity metrics and HRF features for early disease risk stratification and may inform the design of prevention-focused or early intervention clinical trials aimed at delaying the onset of atrophic changes.
Financial Disclosure(S):
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
