In a new study report published in Ophthalmology, researchers conducted a post-hoc analysis in order to update the Age-Related Eye Disease Study (AREDS) Simplified Severity Scale (SSS) to include the risk of late age-related macular degeneration (AMD) while incorporating reticular pseudodrusen (RPD).
Give me some background first.
Determining a patient’s potential risk for progression to late AMD in the clinic can provide benefits including:
- Informing and counseling patients
- Making tailored plans for follow-up and reimaging at appropriate intervals/home monitoring
- Justifying evidence-based interventions
Refresh me: What is the SSS?
SSS is a tool designed to help estimate and categorize a patient’s risk of AMD. This scale prioritizes ease of use for routine clinical practice.
Longitudinal data from the original AREDS study was used to develop several scales including the:
- SSS
- AREDS 9-Step Severity Scale
- Advanced AMD Risk Calculator
Now, talk about the study.
The investigators conducted an analysis of AREDS and AREDS2 by calculating 5-year progression rates to late AMD based on levels 0-4 on the SSS with two updates:
- Non-central geographic atrophy (GA) was considered part of the outcome instead of a risk feature
- Scale separation according to RPD status
- Determined by validated deep learning grading of color fundus photographs (CFP)
Who was included in the study?
Participants included individuals with no late AMD, including neovascular (wet) AMD or any central GA, in either eye at baseline in AREDS (n=2,719) and AREDS2 (n=1,472).
Participants were separated based on:
- A modified SSS (0-4) at baseline
- RPD presence or absence at baseline
What are the new updates to the AREDS AMD Simplified Severity Scale?
The new scale for individuals without RPD has 5-year progression rates of:
- ~0.5% (at baseline; level 0)
- ~4%,
- ~12%
- ~25%
- 50%
The new scale for individuals with RPD has 5-year progression rates of:
- 3%
- 8%
- ~30%
- ~60%
- ~70%
And the data?
In the AREDS after the first scale update, the 5-year rates of progression to late AMD for levels 0-4 were:
- 0.3%
- 4.5%
- 12.9%
- 32.2%
- 55.6%
After both updates, the ratio of progressing to late AMD by 5 years was:
- 8.4% in participants without RPD
- 40.6% in participants with RPD
Go on …
For the final SSS, the 5-year progression rates for levels 0-4 for participants without RPD at baseline were:
- 0.3% (level 0)
- 4.3%
- 11.6%
- 26.7%
- 50.0%
And for participants with RPD at baseline:
- 2.8% (level 0)
- 8.0%
- 29.0%
- 58.7%
- 72.2%
What about the external validation on the AREDS2?
For levels 2-4 progression rates for participants without RPD were:
- 15.0%
- 27.7%
- 45.7%
And for participants with RPD at baseline:
- 26.2%
- 46.0%
- 73.0%
Limitations?
Due to the absence of reading center grading for RPD presence, 5-year progression rates may be slightly overestimated in the RPD absent scale.
Additionally, there were low participant numbers in some of the subgroups, which could have led to some inaccuracy with the 5-year progression rates.
The authors also noted that the participants were predominately White, which may have limited the generalizability of the scale estimates to other ethnic groups.
Any other limitations?
Since optical coherence tomography (OCT) can detect precursor or early atrophy features that CFP may be unable to detect alone, the AREDS and AREDS2 datasets likely included eyes considered at baseline to have intermediate AMD but lacked one or more atrophy features.
Why this is important: Eyes with atrophy features are more likely to progress to GA in a shorter period; therefore, the 5-year progression rates of the study are likely to be slightly higher than if an investigation excluded eyes with OCT features at baseline
And lastly?
Lastly, CFP may have missed some cases of progression to small GA lesions that could have potentially been detected by OCT and or fundus autofluorescence (FAF)
What this means: The 5-year progression rates reported in the study may be slightly lower than they would have been in a study using OCT and or FAF.
Expert opinion?
The researchers stated that their findings demonstrate that RPD presence is a significant factor for increased risk of progression to late AMD.
Take home.
The study highlights that this new and updated scale provides greater accuracy while still offering ease of use in routine clinical practice.
The study authors concluded: “This scale fits updated definitions of late AMD, has increased prognostic accuracy, appears generalizable to similar populations, but remains simple for broad risk categorization.”