An Updated Simplified Severity Scale for Age-Related Macular Degeneration Incorporating Reticular Pseudodrusen

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 AREDS2.

Design

Post hoc analysis of two 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 0-4 on the Simplified Severity Scale, following two updates: (i) non-central GA considered part of the outcome rather than a risk feature, and (ii) 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, following the first scale update, the five-year rates of progression to late AMD for levels 0-4 were 0.3%, 4.5%, 12.9%, 32.2%, and 55.6%, respectively. Following both updates, the proportion progressing to late AMD by five years was 8.4% in participants without RPD and 40.6% in those with RPD. As the final Simplified Severity Scale, the five-year progression rates for levels 0-4, respectively, were 0.3%, 4.3%, 11.6%, 26.7%, and 50.0%, for participants without RPD at baseline, and 2.8%, 8.0%, 29.0%, 58.7%, and 72.2%, for participants with RPD at baseline. In external validation on the AREDS2, for levels 2-4, the progression rates were similar, at 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 two important updates. The new scale for individuals without RPD has five-year progression rates of ∼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 five-year progression rates of 3%, 8%, ∼30%, ∼60%, and ∼70%, i.e., approximately double for most levels. This scale fits updated definitions of late AMD, has increased prognostic accuracy, appears generalizable to similar populations, but remains simple for broad risk categorization.