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

Age-Related Eye Disease Study 2 Research Group

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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) had DPED without late AMD at the time of DPED detection. Genetic analyses included 120 white AREDS2 participants and 145 Age-Related Eye Disease Study (AREDS) participants with DPED. Methods: Baseline and annual stereoscopic fundus photographs were graded centrally to detect DPED, a well-defined yellow elevated mound of confluent drusen ≥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 ≥3 lines in visual acuity (VA) from the time of DPED detection; association of rate of DPED development with genotype. Results: Mean (standard deviation [SD]) follow-up time from DPED detection was 4.7 (0.9) years. 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 5 years after DPED detection. Drusenoid pigment epithelial detachment was associated with increased risk of ≥3 lines of VA loss (HR, 3.08; CI, 2.41–3.93; P < 0.001) with 46% of eyes experiencing vision loss at 5 years (with or without progression to late AMD). ARMS2 risk alleles (1 vs. 0: HR, 2.72, CI, 1.58–4.70; 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 AREDS2. 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.

Original languageEnglish (US)
Pages (from-to)261-273
Number of pages13
Issue number2
StatePublished - Feb 2019

Bibliographical note

Funding Information:
Supported by the intramural program funds and contracts from the National Eye Institute/National Institutes of Health, Department of Health and Human Services, Bethesda Maryland (Contract HHS-N-260-2005-00007-C; ADB Contract NO1-EY-5-0007). Funds were generously contributed to these contracts by the following National Institutes of Health institutes: Office of Dietary Supplements, National Center for Complementary and Alternative Medicine, National Institute on Aging, National Heart, Lung, and Blood Institute, and National Institute of Neurological Disorders and Stroke. The sponsor and funding organization participated in the design and conduct of the study; data collection, management, analysis, and interpretation; and preparation, review, and approval of the manuscript. Funding for this research of FvA was provided by the Intramural Research Program of the National Eye Institute (EY000546) and grants awarded by the following organizations: Nederlandse Oogonderzoek Stichting, Dr. P. Binkhorst Stichting, Stichting Dondersfonds, Prins Bernhard Cultuurfonds, and Stichting A.F. Deutman Oogheelkunde Researchfonds.

Funding Information:
T.D.K.: Partly funded – Bayer Global Ophthalmology Award Program grant.

Publisher Copyright:
© 2018

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