Ellipsoid zone reflectivity as a functional imaging biomarker for age-related macular degeneration: a MACUSTAR study report
Year: 2025
Type: article
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.
Source: Scientific Reports
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, Sarah Thiele, H. Agostini, L. Altay, R. Atia, F. Bandello, P. G. Basile, C. Behning, M. Belmouhand, M. Berger, A. Binns, C. J. F. Boon, M. Böttger, C. Bouchet, J. E. Brazier, T. Butt, C. Carapezzi, J. Carlton, A. Carneiro, A. Charil, R. Coimbra, M. Cozzi, D. P. Crabb, J. Cunha-Vaz, C. Dahlke, L. de Sisternes, H. Dunbar, R. P. Finger, E. Fletcher, H. Floyd, C. Francisco, M. Gutfleisch, R. Hogg, F. G. Holz, C. B. Hoyng, A. Kilani, J. Krätzschmar, L. Kühlewein, M. Larsen, S. Leal, Y. T. E. Lechanteur, M. Liew, U. F. O. Luhmann, A. Lüning, I. Marques, C. Martinho, A. Miliu, G. Montesano, Z. Mulyukov, M. Paques, B. Parodi, M. Parravano, S. Penas, T. Peters, T. Peto, M. Pfau, S. Priglinger, D. Rowen, G. S. Rubin, J. Sahel, C. Sánchez, O. Sander, M. Saßmannshausen, M. Schmid, S. Schmitz-Valckenberg, H. Schrinner-Fenske, J. Siedlecki, R. Silva, A. Skelly, E. Souied, G. Staurenghi, L. Stöhr, D. J. Taylor, J. H. Terheyden, S. Thiele, S. Thiele, A. Tufail, M. Varano, L. Vieweg, A. Wolf, N. Zakaria
Institutions: University of Bonn, University Hospital Bonn, Institut für Medizinische Biometrie, Informatik und Epidemiologie, Moorfields Eye Hospital NHS Foundation Trust, Moorfields Eye Hospital, University College London, Roche (Switzerland), Heidelberg University, Medizinische Fakultät Mannheim, University of Utah, Institute of Molecular and Clinical Ophthalmology Basel, The University of Melbourne, The Royal Victorian Eye & Ear Hospital, Centre for Eye Research Australia, University Medical Center Hamburg-Eppendorf, University of Freiburg, University Medical Center Freiburg, University of Cologne, Novartis (Switzerland), Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Association for Innovation and Biomedical Research on Light and Image, University of Copenhagen, Rigshospitalet, City, University of London, Leiden University Medical Center, Bayer (Germany), University of Sheffield, Fondation Voir & Entendre, Hospital de São João, University of Milan, Luigi Sacco Hospital, Gloucestershire Hospitals NHS Foundation Trust, St. Franziskus Hospital, Royal Victoria Hospital, Radboud University Nijmegen, Radboud University Medical Center, Universität Ulm, Universitätsklinikum Tübingen, STZ eyetrial, Centre hospitalier national d'ophtalmologie des Quinze-Vingts, Fondazione G.B. Bietti, LMU Klinikum, Ludwig-Maximilians-Universität München, European Clinical Research Infrastructure Network, Hôpital Intercommunal de Créteil
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W4411498031