Ellipsoid zone reflectivity as a functional imaging biomarker for age-related macular degeneration: a MACUSTAR study report
Liermann, Y. N., Behning, C., Isselmann, B. , Schmid, M., Dunbar, H. M. P., Luhmann, U. F. O., Finger, R. P., Schmitz-Valckenberg, S., Holz, F. G., Pfau, M., Luu, C. D., Saßmannshausen, M., Thiele, S., Agostini, H., Altay, L., Atia, R., Bandello, F., Basile, P. G., Behning, C., Belmouhand, M., Berger, M., Binns, A., Boon, C. J. F., Böttger, M., Bouchet, C., Brazier, J. E., Butt, T., Carapezzi, C., Carlton, J., Carneiro, A., Charil, A., Coimbra, R., Cozzi, M., Crabb, D. P. 
ORCID: 0000-0001-8611-1155, Cunha-Vaz, J., Dahlke, C., de Sisternes, L., Dunbar, H., Finger, R. P., Fletcher, E., Floyd, H., Francisco, C., Gutfleisch, M., Hogg, R., Holz, F. G., Hoyng, C. B., Kilani, A., Krätzschmar, J., Kühlewein, L., Larsen, M., Leal, S., Lechanteur, Y. T. E., Liew, M., Luhmann, U. F. O., Lüning, A., Marques, I., Martinho, C., Miliu, A., Montesano, G. ORCID: 0000-0002-9148-2804, Mulyukov, Z., Paques, M., Parodi, B., Parravano, M., Penas, S., Peters, T., Peto, T., Pfau, M., Priglinger, S., Rowen, D., Rubin, G. S., Sahel, J., Sánchez, C., Sander, O., Saßmannshausen, M., Schmid, M., Schmitz-Valckenberg, S., Schrinner-Fenske, H., Siedlecki, J., Silva, R., Skelly, A., Souied, E., Staurenghi, G., Stöhr, L., Taylor, D. J., Terheyden, J. H., Thiele, S., Tufail, A., Varano, M., Vieweg, L., Wolf, A. & Zakaria, N. (2025).
Ellipsoid zone reflectivity as a functional imaging biomarker for age-related macular degeneration: a MACUSTAR study report.
Scientific Reports, 15(1),
article number 20093.
doi: 10.1038/s41598-025-00735-7
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.
| Publication Type: | Article |
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| Additional Information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Publisher Keywords: | Diagnostic markers, Macular degeneration |
| Subjects: | R Medicine > RE Ophthalmology |
| Departments: | School of Health & Medical Sciences School of Health & Medical Sciences > Department of Optometry & Visual Science |
| SWORD Depositor: |
Available under License Creative Commons: Attribution International Public License 4.0.
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