Reticular pseudodrusen promotes progression to late AMD

Individuals who present with reticular pseudodrusen (RPD) are at high risk of progression to late age-related macular degeneration (AMD), with the risk increase varying by RPD severity, as shown in a post hoc analysis of two clinical trials. The risk of progression is high at low-to-moderate RPD levels and low at high RPD levels.

The analysis included participants with no late AMD at baseline in Age-Related Eye Disease Study (AREDS; 6,959 eyes, 3,780 participants, mean age 69.4 years) and AREDS2 (3,355 eyes, 2,056 participants, mean age 72.3 years).

Researchers evaluated colour fundus photographs (CFP) from annual study visits to identify soft drusen, pigmentary abnormalities, and late AMD. They determined RPD presence by grading of fundus autofluorescence images (AREDS2) and deep learning grading of CFP (AREDS).

Proportional hazards regression analyses showed RPD to be an independent risk factor for late AMD progression (hazard ratio [HR], 2.15, 95 percent confidence interval [CI], 1.75–2.64). However, the risk with RPD differed significantly across the simplified severity scale levels, with the highest risk observed at levels 0–1 (HR, 3.23, 95 percent CI, 1.60-6.51) followed by levels 2 (HR, 3.81, 95 percent CI, 2.38–6.10), 3 (HR, 2.28, 95 percent CI, 1.59–3.27), and 4 (HR, 1.64, 95 percent CI, 1.20–2.24).

RPD, as defined using the 9-step scale (by eye), was also associated with a more than twofold increased risk of late AMD progression (HR, 2.54, 95 percent CI, 2.07–3.13). The HRs were 5.11 (95 percent CI, 3.93-6.66) at levels 1–6 and 1.78 (95 percent CI, 1.43–2.22) at levels 7–8.

In AREDS2, the risk of progression to late AMD was associated with RPD according to the 9-step scale (HR, 1.57, 95 percent CI, 1.31–1.89) but not according to modified simplified severity (HR, 1.18, 95 percent CI, 0.90-1.56). There were no significant differences in risk seen at different severity levels, for the limited spectrum in AREDS2.

In both cohorts, RPD presence conferred a greater risk of geographic atrophy than neovascular AMD.

The findings suggest that RPD status should be included in updated AMD classification systems, risk calculators, and clinical trials.