An Updated Simplified Severity Scale for Age-Related Macular Degeneration Incorporating Reticular Pseudodrusen: Age-Related Eye Disease Study Report Number 42

Elvira Agrón; Amitha Domalpally; Qingyu Chen; Zhiyong Lu; Emily Y Chew; Tiarnan D L Keenan; AREDS and AREDS2 Research Groups

doi:10.1016/j.ophtha.2024.04.011

An Updated Simplified Severity Scale for Age-Related Macular Degeneration Incorporating Reticular Pseudodrusen: Age-Related Eye Disease Study Report Number 42

Ophthalmology. 2024 Apr 23:S0161-6420(24)00263-X. doi: 10.1016/j.ophtha.2024.04.011. Online ahead of print.

Authors

Elvira Agrón¹, Amitha Domalpally², Qingyu Chen³, Zhiyong Lu⁴, Emily Y Chew¹, Tiarnan D L Keenan⁵; AREDS and AREDS2 Research Groups

Affiliations

¹ Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
² Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin.
³ National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland; Biomedical Informatics and Data Science, School of Medicine, Yale University, New Haven, Connecticut.
⁴ National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland.
⁵ Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: tiarnan.keenan@nih.gov.

PMID: 38657840
DOI: 10.1016/j.ophtha.2024.04.011

Abstract

Purpose: To update the Age-Related Eye Disease Study (AREDS) simplified severity scale for risk of late age-related macular degeneration (AMD), including incorporation of reticular pseudodrusen (RPD), and to perform external validation on the Age-Related Eye Disease Study 2 (AREDS2).

Design: Post hoc analysis of 2 clinical trial cohorts: AREDS and AREDS2.

Participants: Participants with no late AMD in either eye at baseline in AREDS (n = 2719) and AREDS2 (n = 1472).

Methods: Five-year rates of progression to late AMD were calculated according to levels 0 to 4 on the simplified severity scale after 2 updates: (1) noncentral geographic atrophy (GA) considered part of the outcome, rather than a risk feature, and (2) scale separation according to RPD status (determined by validated deep learning grading of color fundus photographs).

Main outcome measures: Five-year rate of progression to late AMD (defined as neovascular AMD or any GA).

Results: In the AREDS, after the first scale update, the 5-year rates of progression to late AMD for levels 0 to 4 were 0.3%, 4.5%, 12.9%, 32.2%, and 55.6%, respectively. As the final simplified severity scale, the 5-year progression rates for levels 0 to 4 were 0.3%, 4.3%, 11.6%, 26.7%, and 50.0%, respectively, for participants without RPD at baseline and 2.8%, 8.0%, 29.0%, 58.7%, and 72.2%, respectively, for participants with RPD at baseline. In external validation on the AREDS2, for levels 2 to 4, the progression rates were similar: 15.0%, 27.7%, and 45.7% (RPD absent) and 26.2%, 46.0%, and 73.0% (RPD present), respectively.

Conclusions: The AREDS AMD simplified severity scale has been modernized with 2 important updates. The new scale for individuals without RPD has 5-year progression rates of approximately 0.5%, 4%, 12%, 25%, and 50%, such that the rates on the original scale remain accurate. The new scale for individuals with RPD has 5-year progression rates of approximately 3%, 8%, 30%, 60%, and 70%, that is, approximately double for most levels. This scale fits updated definitions of late AMD, has increased prognostic accuracy, seems generalizable to similar populations, but remains simple for broad risk categorization.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Age-Related Eye Disease Study; Age-related macular degeneration; Geographic atrophy; Reticular pseudodrusen; Severity scale.

Published by Elsevier Inc.