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; R. Hogg; T. Peto

doi:10.1016/j.oret.2022.12.007

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
, R. Hogg
, T. Peto

^*Corresponding author for this work

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

38 Citations (Scopus)

152 Downloads (Pure)

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.

Original language	English
Pages (from-to)	420-430
Number of pages	11
Journal	Ophthalmology Retina
Volume	7
Issue number	5
DOIs	https://doi.org/10.1016/j.oret.2022.12.007
Publication status	Published - 03 May 2023

Keywords

Age-related macular degeneration
Biomarker
Intermediate age-related macular degeneration
Phenotyping

ASJC Scopus subject areas

Ophthalmology

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10.1016/j.oret.2022.12.007Licence: CC BY-NC-ND

Characteristics and spatial distribution of structural features in age-related macular degeneration: a MACUSTAR study report
Copyright 2022 The Authors and the American Academy of Ophthalmology. This is an open access article published under a Creative Commons Attribution-NonCommercial-NoDerivatives License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited.
Final published version, 1.56 MBLicence: CC BY-NC-ND

Cite this

Saßmannshausen, M., Behning, C., Weinz, J., Goerdt, L., Terheyden, J. H., Chang, P., Schmid, M., Poor, S. H., Zakaria, N., Finger, R. P., Holz, F. G., Pfau, M., Schmitz-Valckenberg, S., Thiele, S., MACUSTAR Consortium Members, Hogg, R., & Peto, T. (2023). Characteristics and spatial distribution of structural features in age-related macular degeneration: a MACUSTAR study report. Ophthalmology Retina, 7(5), 420-430. https://doi.org/10.1016/j.oret.2022.12.007

@article{809bf7c84f984785b0e891b5e0f9f8c7,

title = "Characteristics and spatial distribution of structural features in age-related macular degeneration: a MACUSTAR study report",

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{\textendash}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 {\texttimes} 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. ",

keywords = "Age-related macular degeneration, Biomarker, Intermediate age-related macular degeneration, Phenotyping",

author = "Marlene Sa{\ss}mannshausen and Charlotte Behning and Jonas Weinz and Lukas Goerdt and Terheyden, \{Jan H.\} and Petrus Chang and Matthias Schmid and Poor, \{Stephen H.\} and Nadia Zakaria and Finger, \{Robert P.\} and Holz, \{Frank G.\} and Maximilian Pfau and Steffen Schmitz-Valckenberg and Sarah Thiele and \{MACUSTAR Consortium Members\} and R. Hogg and T. Peto",

year = "2023",

month = may,

day = "3",

doi = "10.1016/j.oret.2022.12.007",

language = "English",

volume = "7",

pages = "420--430",

journal = "Ophthalmology Retina",

issn = "2468-6530",

publisher = "Elsevier Inc.",

number = "5",

}

Saßmannshausen, M, Behning, C, Weinz, J, Goerdt, L, Terheyden, JH, Chang, P, Schmid, M, Poor, SH, Zakaria, N, Finger, RP, Holz, FG, Pfau, M, Schmitz-Valckenberg, S, Thiele, S, MACUSTAR Consortium Members, Hogg, R & Peto, T 2023, 'Characteristics and spatial distribution of structural features in age-related macular degeneration: a MACUSTAR study report', Ophthalmology Retina, vol. 7, no. 5, pp. 420-430. https://doi.org/10.1016/j.oret.2022.12.007

TY - JOUR

T1 - Characteristics and spatial distribution of structural features in age-related macular degeneration: a MACUSTAR study report

AU - Saßmannshausen, Marlene

AU - Behning, Charlotte

AU - Weinz, Jonas

AU - Goerdt, Lukas

AU - Terheyden, Jan H.

AU - Chang, Petrus

AU - Schmid, Matthias

AU - Poor, Stephen H.

AU - Zakaria, Nadia

AU - Finger, Robert P.

AU - Holz, Frank G.

AU - Pfau, Maximilian

AU - Schmitz-Valckenberg, Steffen

AU - Thiele, Sarah

AU - MACUSTAR Consortium Members

AU - Hogg, R.

AU - Peto, T.

PY - 2023/5/3

Y1 - 2023/5/3

N2 - 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.

AB - 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.

KW - Age-related macular degeneration

KW - Biomarker

KW - Intermediate age-related macular degeneration

KW - Phenotyping

U2 - 10.1016/j.oret.2022.12.007

DO - 10.1016/j.oret.2022.12.007

M3 - Article

C2 - 36563964

AN - SCOPUS:85146560660

SN - 2468-6530

VL - 7

SP - 420

EP - 430

JO - Ophthalmology Retina

JF - Ophthalmology Retina

IS - 5

ER -

Characteristics and spatial distribution of structural features in age-related macular degeneration: a MACUSTAR study report

Abstract

Keywords

ASJC Scopus subject areas

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