TY - JOUR
T1 - Progression of Geographic Atrophy in Age-related Macular Degeneration
T2 - AREDS2 Report Number 16
AU - AREDS2 Research Group
AU - Keenan, Tiarnan D.
AU - Agrón, Elvira
AU - Domalpally, Amitha
AU - Clemons, Traci E.
AU - van Asten, Freekje
AU - Wong, Wai T.
AU - Danis, Ronald G.
AU - Sadda, Srini Vas
AU - Rosenfeld, Philip J.
AU - Klein, Michael L.
AU - Ratnapriya, Rinki
AU - Swaroop, Anand
AU - Ferris, Frederick L.
AU - Chew, Emily Y.
AU - Chew, Emily Y.
AU - Ferris, Frederick L.
AU - SanGiovanni, John Paul
AU - Agrón, Elvira
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 - Domalpally, Amitha
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 - Ufret-Vincenty, Rafael L.
N1 - Publisher Copyright:
© 2018
PY - 2018/12
Y1 - 2018/12
N2 - Purpose: To analyze the prevalence, incidence, and clinical characteristics of eyes with geographic atrophy (GA) in age-related macular degeneration (AMD), including clinical and genetic factors affecting enlargement. Design: Prospective cohort study within a controlled clinical trial. Participants: Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50–85 years. Methods: Baseline and annual stereoscopic color fundus photographs were evaluated for GA presence and area. Analyses included GA prevalence and incidence rates, Kaplan-Meier rates, mixed-model regression, and multivariable analysis of the square root of GA, area adjusted for covariates, including clinical/imaging characteristics and genotype. Main Outcome Measures: (1) Presence or development of GA; (2) change in the square root of GA area over time. Results: At baseline, 517 eyes (6.2%) of 411 participants (9.8%) had pre-existing GA (without neovascular AMD), with the following characteristics: 33% central, 67% noncentral; and the following configurations: 36% small, 26% solid/unifocal, 24% multifocal, 9% horseshoe/ring, and 6% indeterminate. Of the remaining 6530 eyes at risk, 1099 eyes (17.3%) of 883 participants developed incident GA without prior neovascular disease during mean follow-up of 4.4 years. The Kaplan-Meier rate of incident GA was 19% of eyes at 5 years. In eyes with incident GA, 4-year risk of subsequent neovascular AMD was 29%. In eyes with incident noncentral GA, 4-year risk of central involvement was 57%. GA enlargement rate (following square root transformation) was similar in eyes with pre-existing GA (0.29 mm/year; 95% confidence interval 0.27–0.30) and incident GA (0.28 mm/year; 0.27–0.30). In the combined group, GA enlargement was significantly faster with noncentrality, multifocality, intermediate baseline size, and bilateral GA (P < 0.0001 for interaction in each case) but not with AREDS2 treatment assignment (P = 0.33) or smoking status (P = 0.05). Enlargement was significantly faster with ARMS2 risk (P < 0.0001), C3 non-risk (P = 0.0002), and APOE non-risk (P = 0.001) genotypes. Conclusions: Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.
AB - Purpose: To analyze the prevalence, incidence, and clinical characteristics of eyes with geographic atrophy (GA) in age-related macular degeneration (AMD), including clinical and genetic factors affecting enlargement. Design: Prospective cohort study within a controlled clinical trial. Participants: Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50–85 years. Methods: Baseline and annual stereoscopic color fundus photographs were evaluated for GA presence and area. Analyses included GA prevalence and incidence rates, Kaplan-Meier rates, mixed-model regression, and multivariable analysis of the square root of GA, area adjusted for covariates, including clinical/imaging characteristics and genotype. Main Outcome Measures: (1) Presence or development of GA; (2) change in the square root of GA area over time. Results: At baseline, 517 eyes (6.2%) of 411 participants (9.8%) had pre-existing GA (without neovascular AMD), with the following characteristics: 33% central, 67% noncentral; and the following configurations: 36% small, 26% solid/unifocal, 24% multifocal, 9% horseshoe/ring, and 6% indeterminate. Of the remaining 6530 eyes at risk, 1099 eyes (17.3%) of 883 participants developed incident GA without prior neovascular disease during mean follow-up of 4.4 years. The Kaplan-Meier rate of incident GA was 19% of eyes at 5 years. In eyes with incident GA, 4-year risk of subsequent neovascular AMD was 29%. In eyes with incident noncentral GA, 4-year risk of central involvement was 57%. GA enlargement rate (following square root transformation) was similar in eyes with pre-existing GA (0.29 mm/year; 95% confidence interval 0.27–0.30) and incident GA (0.28 mm/year; 0.27–0.30). In the combined group, GA enlargement was significantly faster with noncentrality, multifocality, intermediate baseline size, and bilateral GA (P < 0.0001 for interaction in each case) but not with AREDS2 treatment assignment (P = 0.33) or smoking status (P = 0.05). Enlargement was significantly faster with ARMS2 risk (P < 0.0001), C3 non-risk (P = 0.0002), and APOE non-risk (P = 0.001) genotypes. Conclusions: Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.
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U2 - 10.1016/j.ophtha.2018.05.028
DO - 10.1016/j.ophtha.2018.05.028
M3 - Article
C2 - 30060980
AN - SCOPUS:85050484301
SN - 0161-6420
VL - 125
SP - 1913
EP - 1928
JO - Ophthalmology
JF - Ophthalmology
IS - 12
ER -