Faculty Collaboration Database

Natural History of Drusenoid Pigment Epithelial Detachment Associated with Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report No. 17. Ophthalmology 2019 Feb;126(2):261-273

Date

08/25/2018

Pubmed ID

30142373

Pubmed Central ID

PMC6348044

DOI

10.1016/j.ophtha.2018.08.017

Scopus ID

2-s2.0-85053693825 (requires institutional sign-in at Scopus site)   37 Citations

Abstract

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.

Author List

Yu JJ, Agrón E, Clemons TE, Domalpally A, van Asten F, Keenan TD, Cukras C, Chew EY, Age-Related Eye Disease Study 2 Research Group

Author

Thomas B. Connor MD Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Aged, 80 and over
Disease Progression
Female
Follow-Up Studies
Genetic Predisposition to Disease
Humans
Macular Degeneration
Male
Middle Aged
Polymorphism, Single Nucleotide
Prospective Studies
Proteins
Retinal Detachment
Retinal Drusen
Retinal Pigment Epithelium
Retrospective Studies
Time Factors
Visual Acuity