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

  • Yannick N. Liermann
  • , Charlotte Behning
  • , Ben Isselmann
  • , Matthias Schmid
  • , Hannah M.P. Dunbar
  • , Ulrich F.O. Luhmann
  • , Robert P. Finger
  • , S. Schmitz-Valckenberg
  • , Frank G. Holz
  • , M. Pfau
  • , Chi D. Luu
  • , M. Saßmannshausen
  • , S. Thiele*
  • , N. Zakaria
  • , A. Wolf
  • , L. Vieweg
  • , M. Varano
  • , A. Tufail
  • , S. Thiele*
  • , J. H. Terheyden
  • D. J. Taylor, L. Stöhr, G. Staurenghi, E. Souied, A. Skelly, R. Silva, J. Siedlecki, H. Schrinner-Fenske, S. Schmitz-Valckenberg, M. Schmid, M. Saßmannshausen, O. Sander, C. Sánchez, J. Sahel, G. S. Rubin, D. Rowen, S. Priglinger, M. Pfau, T. Peto, T. Peters, S. Penas, M. Parravano, B. Parodi, M. Paques, Z. Mulyukov, G. Montesano, A. Miliu, C. Martinho, R. Hogg, E. Fletcher, the MACUSTAR consortium
*Corresponding author for this work

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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.

Original languageEnglish
Article number20093
JournalScientific Reports
Volume15
DOIs
Publication statusPublished - 20 Jun 2025
Externally publishedYes

ASJC Scopus subject areas

  • General

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