학술논문
Natural History of Drusenoid Pigment Epithelial Detachment Associated with Age-Related Macular Degeneration Age-Related Eye Disease Study 2 Report No. 17
Document Type
article
Author
Yu, Jeannette J; Agrón, Elvira; Clemons, Traci E; Domalpally, Amitha; van Asten, Freekje; Keenan, Tiarnan D; Cukras, Catherine; Chew, Emily Y; Ferris, Frederick L; SanGiovanni, John Paul; Clemons, Traci; Lindblad, Anne; Lindblad, Robert; Shah, Nilay; Sperduto, Robert; McBee, Wendy; Gensler, Gary; Harrington, Molly; Henning, Alice; Jones, Katrina; Thotapally, Kumar; Tull, Diana; Watson, Valerie; Williams, Kayla; Gentry, Christina; Kaufman, Francine; Morrison, Chris; Saverino, Elizabeth; Schenning, Sherrie; Blodi, Barbara; Danis, Ronald P; Davis, Matthew; Glander, Kathy; Guilfoil, Gregory; Hubbard, Larry D; Johnson, Kristine; Klein, Ronald; Nardi, Barbara; Neider, Michael; Robinson, Nancy; Rosensteel, Eileen; Wabers, Hugh; Zhang, Grace; Ruby, Alan J; Capone, Antonio; Dass, Bawa; Drenser, Kimberly; Garretson, Bruce R; Hassan, Tarek S; Trese, Michael; Williams, George A; Wolfe, Jeremy; Bell, Tina; Zajechowski, Mary; Bezaire, Dennis; McIver, Fran; Medina, Anthony; Pagett, Jackie; Smith, Stephanie Hatch; Swartz, Lynn; Treuter, Tom; Antoszyk, Andrew; Brown, Justin; Browning, David J; Holland, Walter; Karow, Angella; Stalford, Kelly; Price, Angela; Ennis, Sarah; Fredenberg, Sherry; Herby, Jenna; Balasubramaniam, Uma; Clark, Loraine; McClain, Donna; McOwen, Michael; Watson, Lynn; Klein, Michael; Bailey, Steven T; Hwang, Thomas J; Lauer, Andreas; Stout, J Timothy; McCollum, Patty; Johnson, Milt; Rice, Patrick B; Kim, Ivana; Loewenstein, John; Miller, Joan; Sobrin, Lucia; Young, Lucy; Sullivan, Jacqueline; Houlihan, Patricia; Merry, Linda; Lane, Ann Marie; Bator, Ursula Lord; Evans, Claudia; Brett, Sarah; Callahan, Charleen
Source
Ophthalmology. 126(2)
Subject
Language
Abstract
PurposeTo investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD).DesignRetrospective analysis of a prospective cohort study.ParticipantsOf 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.MethodsBaseline 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 measuresProgression 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.ResultsMean (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.ConclusionsThis 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.