Prevalence, Risk, and Genetic Association of Reticular Pseudodrusen in AMD
Main objective : To determine the prevalence of reticular pseudodrusen (RPD) in eyes with age-related macular degeneration (AMD); to assess the role of RPD as an independent risk factor for late AMD development; and to evaluate genetic association with RPD.
It was Prospective Cohort Study where participants with intermediate AMD in one or both eyes were enrolled in the Age-Related Eye Disease Study 2 (AREDS2), a 5-year multicenter study of nutritional supplement.
METHODS: Fundus autofluorescence images (FAF) from a subset of AREDS2 participants were evaluated at annual visits for presence of RPD. 6 SNPs: rs10490924 (ARMS2), rs1061170 (CFH), rs2230199 (C3), rs116503776 and rs114254831 (C2/CFB), and rs943080 (VEGF-A) and the genetic risk score (GRS) were assessed for association with RPD.
Development of late AMD, defined as geographic atrophy (GA) or neovascular AMD (NVAMD) was identified.
MAIN OUTCOME MEASURES was the Prevalence of RPD, odds ratio of late AMD development, genetic associations of RPD.
FAF images were evaluated for 5021 eyes (2516 participants). RPD was seen in 1186 (24% of eyes, 29% participants). RPD prevalence varied with baseline AREDS AMD severity level for the eye: 6% in early AMD (n=458), 26% in intermediate AMD (n=2606), 36% in GA (n=682) and 19% in NVAMD (n=1246). Mean age of participants with RPD was 79 years (SD 7) compared with 75 (SD 8) in those without(p<0.0001). RPD was more frequent in females (65% RPD vs 53% no RPD). Odds ratio adjusted for baseline age, gender, race, educational status, smoking and AMD severity level for 1710 eyes at risk of developing late AMD at the next annual visit was 2.42 (95% CI 1.80,3.24, p < 0.001) for GA and 1.21 (95% CI 0.87,1.7, p =0.26) for NVAMD. RPD presence was significantly associated, at a Bonferroni-adjusted significance level of 0.007, with higher GRS (p<0.0001) and ARMS2 risk alleles (rs10490924; p<0.0001), and, at a nominal level, with C3 risk alleles (rs2231099; p=0.04) and CFH risk alleles (rs1061170; p=0.048 for homozygotes).
Participants with RPD have an increased risk of progression to GA but not NVAMD. ARMS2 risk alleles and higher GRS were associated with the presence of RPD. This study suggests that RPD are an important risk marker and should be included in classification systems used for patient prognosis.
The prevalence of RPD was higher among females and individuals at an older age.
Additionally, eyes with RPD had a 2-fold higher risk of progression to late AMD and a 2.5-fold higher risk for geographic atrophy, but not for neovascular AMD.
Ophthalmology 2019 Jul 29;[EPub Ahead of Print], A Domalpally, E Agron, JW Pak, TD Keenan, FL Ferris III, TE Clemons, EY Chew