Abstract
Purpose :
To evaluate reticular pseudodrusen (RPD) as a risk factor for progression to late age-related macular degeneration (AMD)
Methods :
Color fundus photographs (CFP) of participants enrolled in the Age-Related Eye Diseases Study (AREDS) from annual study visits were graded for large drusen, pigmentary abnormalities, and late AMD. RPD presence was determined by deep learning grading of CFP. Proportional hazards regressions were performed that included traditional AMD severity scales (simplified severity scale (person) and 9-step scale (eye)) based upon the presence of drusen and pigmentary changes and RPD presence together. Outcomes were late AMD, geographic atrophy (GA) and neovascular AMD (NV).
Results :
For the 9-step scale analyses 6959 eyes (3780 participants) with no late AMD at baseline were analyzed. For late AMD by eye, in a model including this scale and RPD together, the hazard ratio (HR) for RPD was 2.5 (95% confidence limit (CL): 2.1-3.1). In stratified models by the scale the RPD HRs were 5.1 and 1.8 for levels 1-6 and 7-8, respectively. For GA, the RPD HRs were 2.6 (2.2-3.4) (not stratified), 5.9 and 1.9 for levels 1-6 and 7-8, respectively. For NV, the HRs were 1.7 (1.3-2.2) (not stratified), 3.7 and 1.1 for levels 1-6 and 7-8. For the simplified scale analyses 3182 participants with no late AMD at baseline in either eye were analyzed. For late AMD, in a model including this scale and RPD together, the HR for RPD was 2.2 (1.8-2.6). In stratified models by the scale the RPD HRs were 3.2, 3.8, 2.3, and 1.6 for levels 0-1, 2, 3 and 4, respectively. For GA, the RPD HRs were 2.6 (2.1-3.2) (not stratified), 3.5, 4.9, 3.1 and 1.9 for levels 0-1, 2, 3 and 4, respectively. For NV, the HRs were 1.3 (0.9-1.8) (not stratified), 2.9, 3.03, 1.1 and 0.9 for levels 0-1, 2, 3 and 4. The Table includes the 95% CL of the models performed.
Conclusions :
RPD represents an important third risk factor for progression to late AMD. This is true for both subtypes of late AMD, particularly for GA. However, the excess risk associated with RPD varies markedly by severity level. It carries highly increased risk at lower/moderate levels and less increased risk at higher levels. RPD status should be included in updated AMD classification systems, risk calculators, and clinical trials.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.