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Genetic Risk Score Analysis Supports a Joint View of Two Classification Systems for Age-Related Macular Degeneration

PURPOSE: The purpose of this study was to evaluate the utility of combining the Clinical Classification (CC) and the Three Continent age-related macular degeneration (AMD) Consortium Severity Scale (3CACSS) for classification of AMD. METHODS: In two independent cross-sectional datasets of our popula...

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Autores principales: Herold, Janina M., Zimmermann, Martina E., Gorski, Mathias, Günther, Felix, Weber, Bernhard H. F., Helbig, Horst, Stark, Klaus J., Heid, Iris M., Brandl, Caroline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511022/
https://www.ncbi.nlm.nih.gov/pubmed/37721739
http://dx.doi.org/10.1167/iovs.64.12.31
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author Herold, Janina M.
Zimmermann, Martina E.
Gorski, Mathias
Günther, Felix
Weber, Bernhard H. F.
Helbig, Horst
Stark, Klaus J.
Heid, Iris M.
Brandl, Caroline
author_facet Herold, Janina M.
Zimmermann, Martina E.
Gorski, Mathias
Günther, Felix
Weber, Bernhard H. F.
Helbig, Horst
Stark, Klaus J.
Heid, Iris M.
Brandl, Caroline
author_sort Herold, Janina M.
collection PubMed
description PURPOSE: The purpose of this study was to evaluate the utility of combining the Clinical Classification (CC) and the Three Continent age-related macular degeneration (AMD) Consortium Severity Scale (3CACSS) for classification of AMD. METHODS: In two independent cross-sectional datasets of our population-based AugUR study (Altersbezogene Untersuchungen zur Gesundheit der Universität Regensburg), we graded AMD via color fundus images applying two established classification systems (CC and 3CACSS). We calculated the genetic risk score (GRS) across 50 previously identified variants for late AMD, its association via logistic regression, and area under the curve (AUC) for each AMD stage. RESULTS: We analyzed 2188 persons aged 70 to 95 years. When comparing the two classification systems, we found a distinct pattern: CC “age-related changes” and CC “early AMD” distinguished individuals with 3CACSS “no AMD”; 3CACSS “mild/moderate/severe early AMD” stages, and distinguished CC “intermediate AMD”. This suggested a 7-step scale combining the 2 systems: (i) “no AMD”, (ii) “age-related changes”, (iii) “very early AMD”, (i.e. CC “early”), (iv) “mild early AMD”, (v) “moderate early AMD”, (vi) “severe early AMD”, and (vii) “late AMD”. GRS association and diagnostic accuracy increased stepwise by increased AMD severity in the 7-step scale and by increased restriction of controls (e.g. for CC “no AMD without age-related changes”: AUC = 55.1%, 95% confidence interval [CI] = 51.6, 58.6, AUC = 62.3%, 95% CI = 59.1, 65.6, AUC = 63.8%, 95% CI = 59.3, 68.3, AUC = 78.1%, 95% CI = 73.6, 82.5, AUC = 82.2%, 95% CI = 78.4, 86.0, and AUC = 79.2%, 95% CI = 75.4, 83.0). A stepwise increase was also observed by increased drusen size and area. CONCLUSIONS: The utility of a 7-step scale is supported by our clinical and GRS data. This harmonization and full data integration provides an immediate simplification over using either CC or 3CACSS and helps to sharpen the control group.
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spelling pubmed-105110222023-09-21 Genetic Risk Score Analysis Supports a Joint View of Two Classification Systems for Age-Related Macular Degeneration Herold, Janina M. Zimmermann, Martina E. Gorski, Mathias Günther, Felix Weber, Bernhard H. F. Helbig, Horst Stark, Klaus J. Heid, Iris M. Brandl, Caroline Invest Ophthalmol Vis Sci Clinical and Epidemiologic Research PURPOSE: The purpose of this study was to evaluate the utility of combining the Clinical Classification (CC) and the Three Continent age-related macular degeneration (AMD) Consortium Severity Scale (3CACSS) for classification of AMD. METHODS: In two independent cross-sectional datasets of our population-based AugUR study (Altersbezogene Untersuchungen zur Gesundheit der Universität Regensburg), we graded AMD via color fundus images applying two established classification systems (CC and 3CACSS). We calculated the genetic risk score (GRS) across 50 previously identified variants for late AMD, its association via logistic regression, and area under the curve (AUC) for each AMD stage. RESULTS: We analyzed 2188 persons aged 70 to 95 years. When comparing the two classification systems, we found a distinct pattern: CC “age-related changes” and CC “early AMD” distinguished individuals with 3CACSS “no AMD”; 3CACSS “mild/moderate/severe early AMD” stages, and distinguished CC “intermediate AMD”. This suggested a 7-step scale combining the 2 systems: (i) “no AMD”, (ii) “age-related changes”, (iii) “very early AMD”, (i.e. CC “early”), (iv) “mild early AMD”, (v) “moderate early AMD”, (vi) “severe early AMD”, and (vii) “late AMD”. GRS association and diagnostic accuracy increased stepwise by increased AMD severity in the 7-step scale and by increased restriction of controls (e.g. for CC “no AMD without age-related changes”: AUC = 55.1%, 95% confidence interval [CI] = 51.6, 58.6, AUC = 62.3%, 95% CI = 59.1, 65.6, AUC = 63.8%, 95% CI = 59.3, 68.3, AUC = 78.1%, 95% CI = 73.6, 82.5, AUC = 82.2%, 95% CI = 78.4, 86.0, and AUC = 79.2%, 95% CI = 75.4, 83.0). A stepwise increase was also observed by increased drusen size and area. CONCLUSIONS: The utility of a 7-step scale is supported by our clinical and GRS data. This harmonization and full data integration provides an immediate simplification over using either CC or 3CACSS and helps to sharpen the control group. The Association for Research in Vision and Ophthalmology 2023-09-18 /pmc/articles/PMC10511022/ /pubmed/37721739 http://dx.doi.org/10.1167/iovs.64.12.31 Text en Copyright 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Clinical and Epidemiologic Research
Herold, Janina M.
Zimmermann, Martina E.
Gorski, Mathias
Günther, Felix
Weber, Bernhard H. F.
Helbig, Horst
Stark, Klaus J.
Heid, Iris M.
Brandl, Caroline
Genetic Risk Score Analysis Supports a Joint View of Two Classification Systems for Age-Related Macular Degeneration
title Genetic Risk Score Analysis Supports a Joint View of Two Classification Systems for Age-Related Macular Degeneration
title_full Genetic Risk Score Analysis Supports a Joint View of Two Classification Systems for Age-Related Macular Degeneration
title_fullStr Genetic Risk Score Analysis Supports a Joint View of Two Classification Systems for Age-Related Macular Degeneration
title_full_unstemmed Genetic Risk Score Analysis Supports a Joint View of Two Classification Systems for Age-Related Macular Degeneration
title_short Genetic Risk Score Analysis Supports a Joint View of Two Classification Systems for Age-Related Macular Degeneration
title_sort genetic risk score analysis supports a joint view of two classification systems for age-related macular degeneration
topic Clinical and Epidemiologic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511022/
https://www.ncbi.nlm.nih.gov/pubmed/37721739
http://dx.doi.org/10.1167/iovs.64.12.31
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