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

Saßmannshausen, M., Behning, C., Weinz, J. , Goerdt, L., Terheyden, J. H., Chang, P., Schmid, M., Poor, S., Zakaria, N., Finger, R. P., Holz, F. G., Pfau, M., Schmitz-Valckenberg, S., Thiele, S., MACUSTAR consortium members, Binns, A. M. ORCID: 0000-0001-8621-498X, Carlton, J., Crabb, D. P. ORCID: 0000-0001-8611-1155, Montesano, G. ORCID: 0000-0002-9148-2804 & Taylor, D. J. ORCID: 0000-0001-8261-5225 (2023). Characteristics and Spatial Distribution of Structural Features in Age-Related Macular Degeneration: A MACUSTAR Study Report. Ophthalmology Retina, 7(5), pp. 420-430. doi: 10.1016/j.oret.2022.12.007


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 ( 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.

Publication Type: Article
Additional Information: © 2022 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (
Publisher Keywords: Age-related macular degeneration; Biomarker; Intermediate age-related macular degeneration; Phenotyping
Subjects: R Medicine > RE Ophthalmology
Departments: School of Health & Psychological Sciences > Optometry & Visual Sciences
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Text - Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

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