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 - Drenser, Kimberly
AU - Garretson, Bruce R.
AU - Hassan, Tarek S.
AU - Trese, Michael
N1 - Publisher Copyright:
© 2018
PY - 2019/2
Y1 - 2019/2
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.
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U2 - 10.1016/j.ophtha.2018.08.017
DO - 10.1016/j.ophtha.2018.08.017
M3 - Article
C2 - 30142373
AN - SCOPUS:85053693825
SN - 0161-6420
VL - 126
SP - 261
EP - 273
JO - Ophthalmology
JF - Ophthalmology
IS - 2
ER -