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

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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Journal
Scientific Reports
Published
2025-06-20
DOI
https://doi.org/10.1038/s41598-025-00735-7
Citations
3
Primary Topic
Retinal Diseases and Treatments
Type
article
Field-Weighted Citation Impact
5.12

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article

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

Maximilian Pfau, Frank Gerhard Holz, Hannah Dunbar, Matthias Schmid et al.
3 citations
Scientific Reports
Retinal Diseases and Treatments
5.12
article

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

Maximilian Pfau, Frank Gerhard Holz, Hannah Dunbar, Matthias Schmid, Marlene Saßmannshausen, Sarah Thiele, Charlotte Behning, Ulrich F. O. Luhmann, Robert Patrick Finger, Steffen Schmitz-Valckenberg, Chi D. Luu, Ben Isselmann, Yannick Liermann
article en
3 citations

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.

Scientific ReportsVol. 15(1)
Roche (Switzerland) (CH), Novartis (Switzerland) (CH), Carl Zeiss (Germany) (DE), Moorfields Eye Hospital NHS Foundation Trust (GB), University of Bonn (DE), University of Ulster (GB), Radboud University Nijmegen (NL), Vita-Salute San Raffaele University (IT), University of Freiburg (DE), The University of Melbourne (AU), City, University of London (GB), University of Cologne (DE), University of Milan (IT), Universität Ulm (DE), University of Utah (US), Heidelberg University (DE), University Hospital Bonn (DE), Leiden University Medical Center (NL), Fondation de France (FR), Centre hospitalier national d'ophtalmologie des Quinze-Vingts (FR), Glostrup Hospital (DK), University Hospital Heidelberg (DE), Gloucestershire Hospitals NHS Foundation Trust (GB), Radboud University Medical Center (NL), Hospital de São João (PT), Luigi Sacco Hospital (IT), Institut für Medizinische Biometrie, Informatik und Epidemiologie (DE), Zimmer Biomet (Germany) (DE), Fondazione G.B. Bietti (IT), Centre for Eye Research Australia (AU), Universitätsklinik für Augenheilkunde (CH), Royal Victoria Hospital (GB), Association for Innovation and Biomedical Research on Light and Image (PT), STZ eyetrial (DE), St. Franziskus Hospital (DE), Moorfields Eye Hospital (GB), European Clinical Research Infrastructure Network (FR), University Medical Centre Mannheim (DE), Hôpital Intercommunal de Créteil (FR), Institute of Molecular and Clinical Ophthalmology Basel (CH), University College London (GB), Bayer (Germany) (DE), Ludwig-Maximilians-Universität München (DE), University of Sheffield (GB)
European Federation of Pharmaceutical Industries and Associations, European Commission, Deutsche Forschungsgemeinschaft, Rheinische Friedrich-Wilhelms-Universität Bonn, Novartis Pharma
Openalex Percentile: Top 5%
Retinal Diseases and Treatments
5.12
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