Characteristics and Spatial Distribution of Structural Features in Age-Related Macular Degeneration: A MACUSTAR Study Report

Marlene Saßmannshausen; Charlotte Behning; Jonas Weinz; Lukas Goerdt; Jan H Terheyden; Petrus Chang; Matthias Schmid; Stephen H Poor; Nadia Zakaria; Robert P Finger; Frank G Holz; Maximilian Pfau; Steffen Schmitz-Valckenberg; Sarah Thiele; MACUSTAR Consortium Members

doi:10.1016/j.oret.2022.12.007

Characteristics and Spatial Distribution of Structural Features in Age-Related Macular Degeneration: A MACUSTAR Study Report

Ophthalmol Retina. 2023 May;7(5):420-430. doi: 10.1016/j.oret.2022.12.007. Epub 2022 Dec 20.

Authors

Collaborators

MACUSTAR Consortium Members:
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, U F O Luhmann, A Lüning, I Marques, C Martinho, G Montesano, Z Mulyukov, M Paques, B Parodi, M Parravano, S Penas, T Peters, T Peto, M Pfau, S Poor, 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, A Tufail, M Varano, L Vieweg, L Wintergerst, A Wolf, N Zakaria

Affiliations

¹ Department of Ophthalmology, University Hospital Bonn, Bonn, Germany; GRADE Reading Center, University of Bonn, Bonn, Germany.
² Institute of Medical Biometry, Informatics and Epidemiology, University Hospital Bonn, Bonn, Germany.
³ GRADE Reading Center, University of Bonn, Bonn, Germany.
⁴ Department of Ophthalmology, University Hospital Bonn, Bonn, Germany.
⁵ Ophthalmology Research, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts.
⁶ Ophthalmology Translational Medicine, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts.
⁷ Department of Ophthalmology, University Hospital Bonn, Bonn, Germany; GRADE Reading Center, University of Bonn, Bonn, Germany; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.
⁸ Department of Ophthalmology, University Hospital Bonn, Bonn, Germany; GRADE Reading Center, University of Bonn, Bonn, Germany; John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, Utah.
⁹ Department of Ophthalmology, University Hospital Bonn, Bonn, Germany; GRADE Reading Center, University of Bonn, Bonn, Germany. Electronic address: sarah.thiele@ukbonn.de.

PMID: 36563964
DOI: 10.1016/j.oret.2022.12.007

Abstract

Purpose: To report the prevalence and topographic distribution of structural characteristics in study participants with age-related macular degeneration (AMD) and controls in the cross-sectional study part of the MACUSTAR study (ClinicalTrials.gov Identifier: NCT03349801).

Design: European, multicenter cohort study.

Subjects: Overall, 301 eyes of 301 subjects with early (n = 34), intermediate (n = 168), and late AMD (n = 43), as well as eyes without any AMD features (n = 56).

Methods: In study eyes with intermediate AMD (iAMD), the presence of structural AMD biomarkers, including pigmentary abnormalities (PAs), pigment epithelium detachment (PED), refractile deposits, reticular pseudodrusen (RPD), hyperreflective foci (HRF), incomplete/complete retinal pigment epithelium (RPE), and outer retinal atrophy (i/cRORA), and quiescent choroidal neovascularization (qCNV) was systematically determined in the prospectively acquired multimodal retinal imaging cross-sectional data set of MACUSTAR. Retinal layer thicknesses and the RPE drusen complex (RPEDC) volume were determined for the total study cohort in spectral-domain (SD) OCT imaging using a deep-learning-based algorithm.

Main outcome measures: Prevalence and topographic distribution of structural iAMD features.

Results: A total of 301 study eyes of 301 subjects with a mean (± standard deviation) age of 71.2 ± 7.20 years (63.1% women) were included. Besides large drusen, the most prevalent structural feature in iAMD study eyes were PA (57.1%), followed by HRF (51.8%) and RPD (22.0%). Pigment epithelium detachment lesions were observed in 4.8%, vitelliform lesions in 4.2%, refractile deposits in 3.0%, and qCNV in 2.4%. Direct precursor lesions for manifest retinal atrophy were detected in 10.7% (iRORA) and 4.2% (cRORA) in iAMD eyes. Overall, the highest RPEDC volume with a median of 98.92 × 10^-4 mm³ was found in iAMD study eyes. Spatial analysis demonstrated a predominant distribution of RPD in the superior and temporal subfields at a foveal eccentricity of 1.5 to 2 mm, whereas HRF and large drusen had a distinct topographic distribution involving the foveal center.

Conclusions: Detailed knowledge of the prevalence and distribution of structural iAMD biomarkers is vital to identify reliable outcome measure for disease progression. Longitudinal analyses are needed to evaluate their prognostic value for conversion to advanced disease stages.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Keywords: Age-related macular degeneration; Biomarker; Intermediate age-related macular degeneration; Phenotyping.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Atrophy
Choroidal Neovascularization* / diagnosis
Choroidal Neovascularization* / epidemiology
Cohort Studies
Cross-Sectional Studies
Female
Humans
Macular Degeneration* / diagnosis
Macular Degeneration* / epidemiology
Macular Degeneration* / pathology
Male
Middle Aged
Retinal Detachment*
Retinal Drusen* / diagnosis
Retinal Drusen* / epidemiology
Tomography, Optical Coherence / methods

Associated data

ClinicalTrials.gov/NCT03349801