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

Publication ,  Journal Article
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,
Published in: Ophthalmology
February 2019

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.

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Published In

Ophthalmology

DOI

EISSN

1549-4713

Publication Date

February 2019

Volume

126

Issue

2

Start / End Page

261 / 273

Location

United States

Related Subject Headings

  • Visual Acuity
  • Time Factors
  • Retrospective Studies
  • Retinal Pigment Epithelium
  • Retinal Drusen
  • Retinal Detachment
  • Proteins
  • Prospective Studies
  • Polymorphism, Single Nucleotide
  • Ophthalmology & Optometry
 

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Yu, J. J., Agrón, E., Clemons, T. E., Domalpally, A., van Asten, F., Keenan, T. D., … Age-Related Eye Disease Study 2 Research Group, . (2019). Natural History of Drusenoid Pigment Epithelial Detachment Associated with Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report No. 17. Ophthalmology, 126(2), 261–273. https://doi.org/10.1016/j.ophtha.2018.08.017
Yu, Jeannette J., Elvira Agrón, Traci E. Clemons, Amitha Domalpally, Freekje van Asten, Tiarnan D. Keenan, Catherine Cukras, Emily Y. Chew, and Emily Y. Age-Related Eye Disease Study 2 Research Group. “Natural History of Drusenoid Pigment Epithelial Detachment Associated with Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report No. 17.Ophthalmology 126, no. 2 (February 2019): 261–73. https://doi.org/10.1016/j.ophtha.2018.08.017.
Yu JJ, Agrón E, Clemons TE, Domalpally A, van Asten F, Keenan TD, et al. 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):261–73.
Yu, Jeannette J., et al. “Natural History of Drusenoid Pigment Epithelial Detachment Associated with Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report No. 17.Ophthalmology, vol. 126, no. 2, Feb. 2019, pp. 261–73. Pubmed, doi:10.1016/j.ophtha.2018.08.017.
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. 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.
Journal cover image

Published In

Ophthalmology

DOI

EISSN

1549-4713

Publication Date

February 2019

Volume

126

Issue

2

Start / End Page

261 / 273

Location

United States

Related Subject Headings

  • Visual Acuity
  • Time Factors
  • Retrospective Studies
  • Retinal Pigment Epithelium
  • Retinal Drusen
  • Retinal Detachment
  • Proteins
  • Prospective Studies
  • Polymorphism, Single Nucleotide
  • Ophthalmology & Optometry