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

Y Yannick N. Liermann C Charlotte Behning B Ben Isselmann M Matthias Schmid H Hannah M. P. Dunbar U Ulrich F. O. Luhmann R Robert P. Finger S Steffen Schmitz-Valckenberg F Frank G. Holz (Department of Ophthalmology, University of Bonn, Bonn, Germany) M Maximilian Pfau C Chi D. Luu M Marlene Saßmannshausen S Sarah Thiele H H. Agostini L L. Altay R R. Atia F F. Bandello P P. G. Basile C C. Behning M M. Belmouhand M M. Berger A A. Binns C C. J. F. Boon M M. Böttger C C. Bouchet J J. E. Brazier T T. Butt C C. Carapezzi J J. Carlton A A. Carneiro A A. Charil R R. Coimbra M M. Cozzi D D. P. Crabb J J. Cunha-Vaz C C. Dahlke L L. de Sisternes H H. Dunbar R R. P. Finger E E. Fletcher H H. Floyd C C. Francisco M M. Gutfleisch R R. Hogg F F. G. Holz C C. B. Hoyng A A. Kilani J J. Krätzschmar L L. Kühlewein M M. Larsen S S. Leal Y Y. T. E. Lechanteur M M. Liew U U. F. O. Luhmann A A. Lüning I I. Marques C C. Martinho A A. Miliu G G. Montesano Z Z. Mulyukov M M. Paques B B. Parodi M M. Parravano S S. Penas T T. Peters T T. Peto M M. Pfau S S. Priglinger D D. Rowen G G. S. Rubin J J. Sahel C C. Sánchez O O. Sander M M. Saßmannshausen M M. Schmid S S. Schmitz-Valckenberg H H. Schrinner-Fenske J J. Siedlecki R R. Silva A A. Skelly E E. Souied G G. Staurenghi L L. Stöhr D D. J. Taylor J J. H. Terheyden S S. Thiele A A. Tufail M M. Varano L L. Vieweg A A. Wolf N N. Zakaria

Abstract

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.

Article Details

Volume / Issue Vol. 15, Issue 1
Published June 20, 2025
ISSN 2045-2322
Publisher Nature Portfolio

Journal Info

Scientific Reports

Nature Portfolio

ISSN: 2045-2322 Open Access Life Sciences

Authors (91)

Y

Yannick N. Liermann

C

Charlotte Behning

B

Ben Isselmann

M

Matthias Schmid

H

Hannah M. P. Dunbar

U

Ulrich F. O. Luhmann

R

Robert P. Finger

S

Steffen Schmitz-Valckenberg

F

Frank G. Holz

Department of Ophthalmology, University of Bonn, Bonn, Germany

M

Maximilian Pfau

C

Chi D. Luu

M

Marlene Saßmannshausen

S

Sarah Thiele

H

H. Agostini

L

L. Altay

R

R. Atia

F

F. Bandello

P

P. G. Basile

C

C. Behning

M

M. Belmouhand

M

M. Berger

A

A. Binns

C

C. J. F. Boon

M

M. Böttger

C

C. Bouchet

J

J. E. Brazier

T

T. Butt

C

C. Carapezzi

J

J. Carlton

A

A. Carneiro

A

A. Charil

R

R. Coimbra

M

M. Cozzi

D

D. P. Crabb

J

J. Cunha-Vaz

C

C. Dahlke

L

L. de Sisternes

H

H. Dunbar

R

R. P. Finger

E

E. Fletcher

H

H. Floyd

C

C. Francisco

M

M. Gutfleisch

R

R. Hogg

F

F. G. Holz

C

C. B. Hoyng

A

A. Kilani

J

J. Krätzschmar

L

L. Kühlewein

M

M. Larsen

S

S. Leal

Y

Y. T. E. Lechanteur

M

M. Liew

U

U. F. O. Luhmann

A

A. Lüning

I

I. Marques

C

C. Martinho

A

A. Miliu

G

G. Montesano

Z

Z. Mulyukov

M

M. Paques

B

B. Parodi

M

M. Parravano

S

S. Penas

T

T. Peters

T

T. Peto

M

M. Pfau

S

S. Priglinger

D

D. Rowen

G

G. S. Rubin

J

J. Sahel

C

C. Sánchez

O

O. Sander

M

M. Saßmannshausen

M

M. Schmid

S

S. Schmitz-Valckenberg

H

H. Schrinner-Fenske

J

J. Siedlecki

R

R. Silva

A

A. Skelly

E

E. Souied

G

G. Staurenghi

L

L. Stöhr

D

D. J. Taylor

J

J. H. Terheyden

S

S. Thiele

A

A. Tufail

M

M. Varano

L

L. Vieweg

A

A. Wolf

N

N. Zakaria