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 journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)261-273
Number of pages13
JournalOphthalmology
Volume126
Issue number2
DOIs
StatePublished - Feb 1 2019

Fingerprint

Eye Diseases
Macular Degeneration
Natural History
Confidence Intervals
Visual Acuity
Geographic Atrophy
Single Nucleotide Polymorphism
Cohort Studies
Alleles
Genotype
Outcome Assessment (Health Care)
Prospective Studies

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

@article{cbc56199fbfa476597deacc01f791103,
title = "Natural History of Drusenoid Pigment Epithelial Detachment Associated with Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report No. 17",
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 = "{Age-Related Eye Disease Study 2 Research Group} and Yu, {Jeannette J.} and Elvira Agr{\'o}n and Clemons, {Traci E.} and Amitha Domalpally and {van Asten}, Freekje and Keenan, {Tiarnan D.} and Catherine Cukras and Chew, {Emily Y.} and Ferris, {Frederick L.} and SanGiovanni, {John Paul} and Traci Clemons and Anne Lindblad and Robert Lindblad and Nilay Shah and Robert Sperduto and Wendy McBee and Gary Gensler and Molly Harrington and Alice Henning and Katrina Jones and Kumar Thotapally and Diana Tull and Valerie Watson and Kayla Williams and Christina Gentry and Francine Kaufman and Chris Morrison and Elizabeth Saverino and Sherrie Schenning and Barbara Blodi and Danis, {Ronald P.} and Matthew Davis and Kathy Glander and Gregory Guilfoil and Hubbard, {Larry D.} and Kristine Johnson and Ronald Klein and Barbara Nardi and Michael Neider and Nancy Robinson and Eileen Rosensteel and Hugh Wabers and Grace Zhang and Ruby, {Alan J.} and Antonio Capone and Bawa Dass and Ingrid Scott and Esther Bowie and Kimberly Neely and David Quillen",
year = "2019",
month = "2",
day = "1",
doi = "10.1016/j.ophtha.2018.08.017",
language = "English (US)",
volume = "126",
pages = "261--273",
journal = "Ophthalmology",
issn = "0161-6420",
publisher = "Elsevier Inc.",
number = "2",

}

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.

In: Ophthalmology, Vol. 126, No. 2, 01.02.2019, p. 261-273.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Natural History of Drusenoid Pigment Epithelial Detachment Associated with Age-Related Macular Degeneration

T2 - Age-Related Eye Disease Study 2 Report No. 17

AU - Age-Related Eye Disease Study 2 Research Group

AU - Yu, Jeannette J.

AU - Agrón, Elvira

AU - Clemons, Traci E.

AU - Domalpally, Amitha

AU - van Asten, Freekje

AU - Keenan, Tiarnan D.

AU - Cukras, Catherine

AU - Chew, Emily Y.

AU - Ferris, Frederick L.

AU - SanGiovanni, John Paul

AU - Clemons, Traci

AU - Lindblad, Anne

AU - Lindblad, Robert

AU - Shah, Nilay

AU - Sperduto, Robert

AU - McBee, Wendy

AU - Gensler, Gary

AU - Harrington, Molly

AU - Henning, Alice

AU - Jones, Katrina

AU - Thotapally, Kumar

AU - Tull, Diana

AU - Watson, Valerie

AU - Williams, Kayla

AU - Gentry, Christina

AU - Kaufman, Francine

AU - Morrison, Chris

AU - Saverino, Elizabeth

AU - Schenning, Sherrie

AU - Blodi, Barbara

AU - Danis, Ronald P.

AU - Davis, Matthew

AU - Glander, Kathy

AU - Guilfoil, Gregory

AU - Hubbard, Larry D.

AU - Johnson, Kristine

AU - Klein, Ronald

AU - Nardi, Barbara

AU - Neider, Michael

AU - Robinson, Nancy

AU - Rosensteel, Eileen

AU - Wabers, Hugh

AU - Zhang, Grace

AU - Ruby, Alan J.

AU - Capone, Antonio

AU - Dass, Bawa

AU - Scott, Ingrid

AU - Bowie, Esther

AU - Neely, Kimberly

AU - Quillen, David

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85053693825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053693825&partnerID=8YFLogxK

U2 - 10.1016/j.ophtha.2018.08.017

DO - 10.1016/j.ophtha.2018.08.017

M3 - Article

C2 - 30142373

AN - SCOPUS:85053693825

VL - 126

SP - 261

EP - 273

JO - Ophthalmology

JF - Ophthalmology

SN - 0161-6420

IS - 2

ER -