Ellipsoid zone reflectivity as a functional imaging biomarker for age-related macular degeneration: a MACUSTAR study report

Abstract This study evaluated the functional relevance of relative ellipsoid zone reflectivity (rEZR) on spectral-domain optical coherence tomography as a structural biomarker for retinal integrity, focusing on its association with retinal function. Participants with age-related macular degeneration...

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Main Authors: Yannick N. Liermann, Charlotte Behning, Ben Isselmann, Matthias Schmid, Hannah M. P. Dunbar, Ulrich F. O. Luhmann, Robert P. Finger, Steffen Schmitz-Valckenberg, Frank G. Holz, Maximilian Pfau, Chi D. Luu, Marlene Saßmannshausen, Sarah Thiele, the MACUSTAR consortium
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-00735-7
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author Yannick N. Liermann
Charlotte Behning
Ben Isselmann
Matthias Schmid
Hannah M. P. Dunbar
Ulrich F. O. Luhmann
Robert P. Finger
Steffen Schmitz-Valckenberg
Frank G. Holz
Maximilian Pfau
Chi D. Luu
Marlene Saßmannshausen
Sarah Thiele
the MACUSTAR consortium
author_facet Yannick N. Liermann
Charlotte Behning
Ben Isselmann
Matthias Schmid
Hannah M. P. Dunbar
Ulrich F. O. Luhmann
Robert P. Finger
Steffen Schmitz-Valckenberg
Frank G. Holz
Maximilian Pfau
Chi D. Luu
Marlene Saßmannshausen
Sarah Thiele
the MACUSTAR consortium
author_sort Yannick N. Liermann
collection DOAJ
description Abstract This study evaluated the functional relevance of relative ellipsoid zone reflectivity (rEZR) on spectral-domain optical coherence tomography as a structural biomarker for retinal integrity, focusing on its association with retinal function. Participants with age-related macular degeneration (AMD) and controls from the MACUSTAR study underwent functional testing, including mesopic fundus-controlled perimetry, best-corrected visual acuity, low-luminance visual acuity, low-luminance deficit, Moorfields Acuity Test, and Pelli-Robson contrast sensitivity, along with spectral-domain optical coherence tomography imaging. Structural and functional data were analyzed globally and spatially aligned for topographic analysis. Linear-mixed effects models, adjusted for age, sex, and eccentricity of the rEZR, assessed associations between rEZR and functional metrics. A total of 275 eyes (early AMD, n = 34; intermediate AMD, n = 152; late AMD, n = 36; controls, n = 53) from 275 participants (mean ± standard deviation age: 71.1 ± 7.2 years; 63.3% female) were included. In global analyses, rEZR was associated with the mean average threshold in mesopic fundus-controlled perimetry (coefficient estimate 0.0492, 95% confidence interval 0.0190–0.0794, p = 0.0015), low-luminance visual acuity (coefficient estimate − 0.0015, 95% confidence interval − 0.0026 to − 0.0004, p = 0.0092), Moorfields Acuity Test (coefficient estimate 0.0092, 95% confidence interval − 0.0022 to − 0.0001, p = 0.0285), and Pelli-Robson contrast sensitivity (coefficient estimate 0.0030, 95% confidence interval 0.0015–0.0045, p = 0.0001). Topographic analysis further revealed an association of rEZR with mesopic retinal sensitivity (coefficient estimate 0.0065, 95% confidence interval 0.0026–0.0104, p < 0.0001). Higher outer retinal reflectivity is linked to better retinal function in AMD and controls, supporting its potential as a biomarker for retinal integrity and function.
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spelling doaj-art-c73dd4c3fc5e46889a7b6ee0d16748722025-08-20T02:37:14ZengNature PortfolioScientific Reports2045-23222025-06-0115111210.1038/s41598-025-00735-7Ellipsoid zone reflectivity as a functional imaging biomarker for age-related macular degeneration: a MACUSTAR study reportYannick N. Liermann0Charlotte Behning1Ben Isselmann2Matthias Schmid3Hannah M. P. Dunbar4Ulrich F. O. Luhmann5Robert P. Finger6Steffen Schmitz-Valckenberg7Frank G. Holz8Maximilian Pfau9Chi D. Luu10Marlene Saßmannshausen11Sarah Thiele12the MACUSTAR consortiumDepartment of Ophthalmology, University of BonnInstitute of Medical Biometry, Informatics and Epidemiology, University Hospital BonnDepartment of Ophthalmology, University of BonnInstitute of Medical Biometry, Informatics and Epidemiology, University Hospital BonnInstitute of Ophthalmology, University College LondonRoche Pharmaceutical Research and Early Development, Translational Medicine Ophthalmology, Roche Innovation Center BaselDepartment of Ophthalmology, Medical Faculty Mannheim, University of HeidelbergDepartment of Ophthalmology, University of BonnDepartment of Ophthalmology, University of BonnDepartment of Ophthalmology, University of BonnCenter for Eye Research Australia, Royal Victorian Eye and Ear HospitalDepartment of Ophthalmology, University of BonnDepartment of Ophthalmology, University of BonnAbstract This study evaluated the functional relevance of relative ellipsoid zone reflectivity (rEZR) on spectral-domain optical coherence tomography as a structural biomarker for retinal integrity, focusing on its association with retinal function. Participants with age-related macular degeneration (AMD) and controls from the MACUSTAR study underwent functional testing, including mesopic fundus-controlled perimetry, best-corrected visual acuity, low-luminance visual acuity, low-luminance deficit, Moorfields Acuity Test, and Pelli-Robson contrast sensitivity, along with spectral-domain optical coherence tomography imaging. Structural and functional data were analyzed globally and spatially aligned for topographic analysis. Linear-mixed effects models, adjusted for age, sex, and eccentricity of the rEZR, assessed associations between rEZR and functional metrics. A total of 275 eyes (early AMD, n = 34; intermediate AMD, n = 152; late AMD, n = 36; controls, n = 53) from 275 participants (mean ± standard deviation age: 71.1 ± 7.2 years; 63.3% female) were included. In global analyses, rEZR was associated with the mean average threshold in mesopic fundus-controlled perimetry (coefficient estimate 0.0492, 95% confidence interval 0.0190–0.0794, p = 0.0015), low-luminance visual acuity (coefficient estimate − 0.0015, 95% confidence interval − 0.0026 to − 0.0004, p = 0.0092), Moorfields Acuity Test (coefficient estimate 0.0092, 95% confidence interval − 0.0022 to − 0.0001, p = 0.0285), and Pelli-Robson contrast sensitivity (coefficient estimate 0.0030, 95% confidence interval 0.0015–0.0045, p = 0.0001). Topographic analysis further revealed an association of rEZR with mesopic retinal sensitivity (coefficient estimate 0.0065, 95% confidence interval 0.0026–0.0104, p < 0.0001). Higher outer retinal reflectivity is linked to better retinal function in AMD and controls, supporting its potential as a biomarker for retinal integrity and function.https://doi.org/10.1038/s41598-025-00735-7
spellingShingle Yannick N. Liermann
Charlotte Behning
Ben Isselmann
Matthias Schmid
Hannah M. P. Dunbar
Ulrich F. O. Luhmann
Robert P. Finger
Steffen Schmitz-Valckenberg
Frank G. Holz
Maximilian Pfau
Chi D. Luu
Marlene Saßmannshausen
Sarah Thiele
the MACUSTAR consortium
Ellipsoid zone reflectivity as a functional imaging biomarker for age-related macular degeneration: a MACUSTAR study report
Scientific Reports
title Ellipsoid zone reflectivity as a functional imaging biomarker for age-related macular degeneration: a MACUSTAR study report
title_full Ellipsoid zone reflectivity as a functional imaging biomarker for age-related macular degeneration: a MACUSTAR study report
title_fullStr Ellipsoid zone reflectivity as a functional imaging biomarker for age-related macular degeneration: a MACUSTAR study report
title_full_unstemmed Ellipsoid zone reflectivity as a functional imaging biomarker for age-related macular degeneration: a MACUSTAR study report
title_short Ellipsoid zone reflectivity as a functional imaging biomarker for age-related macular degeneration: a MACUSTAR study report
title_sort ellipsoid zone reflectivity as a functional imaging biomarker for age related macular degeneration a macustar study report
url https://doi.org/10.1038/s41598-025-00735-7
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