Natural History of Drusenoid Pigment Epithelial Detachment Associated with Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report No. 17.

Publication Type
Journal Article
Year of Publication
Yu, Jeannette J; Agrόn, Elvira; Clemons, Traci E; Domalpally, Amitha; van Asten, Freekje; Keenan, Tiarnan D; Cukras, Catherine; Chew, Emily Y; Age-Related Eye Disease Study 2 (AREDS2) Research Group
Date Published
age-related macular degeneration (AMD); drusenoid pigment epithelial detachment (DPED)

PURPOSE: To investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD).

DESIGN: Retrospective analysis of a prospective cohort study.

PARTICIPANTS: Of the 4203 Age-Related Eye Disease Study 2 (AREDS2) participants, 391 eyes (325 participants) were identified as having DPED without late AMD at the time of DPED detection. Genetic analyses included 120 white AREDS2 participants and 145 AREDS participants with DPED.

METHODS: Baseline and annual stereoscopic fundus photographs were graded according to a standardized protocol to detect DPED, a well-defined yellow elevated mound of confluent drusen, measuring ≥ 433 μm in diameter, and to evaluate progression rates to late AMD: geographic atrophy (GA) and neovascular (NV) AMD. Five single nucleotide polymorphisms (CFH [rs10611670], C3 [rs2230199], CFI [rs10033900], C2/CFB [rs114254831], ARMS2 [rs10490924]) and genetic risk score (GRS) group were investigated for association with DPED development. Kaplan-Meier analyses and multivariable proportional hazard regressions were performed.

MAIN OUTCOME MEASURES: Progression rates to late AMD and decrease of ≥ three lines in visual acuity (VA) from time of DPED detection; association of rate of DPED development with genotype.

RESULTS: Mean (SD) follow-up time from DPED detection was 4.7 (0.9) years. Presence of DPED was associated with increased risk of progression to late AMD (hazard ratio [HR]=2.36, 95% confidence interval [CI]=1.98-2.82, p<0.001); 67% of eyes progressed to late AMD five years after DPED detection. DPED was associated with increased risk of ≥ three lines of VA loss (HR=3.08, CI=2.41-3.93, p<0.001) with 46% of eyes experiencing vision loss at five years (with or without progression to late AMD). ARMS2 risk alleles (1 vs. 0: HR=2.72, CI=1.58-4.70, p<0.001; 2 vs. 0: HR=3.16, CI=1.60-6.21, p<0.001) and increasing GRS group (4 vs. 1) (HR=12.17, CI=3.66-40.45, p<0.001) were significantly associated with DPED development in AREDS. There were no significant genetic results in the AREDS2 analyses.

CONCLUSIONS: This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.