Progression of Geographic Atrophy in Age-related Macular Degeneration

AREDS2 Report Number 16

AREDS2 Research Group

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1913-1928
Number of pages16
JournalOphthalmology
Volume125
Issue number12
DOIs
StatePublished - Dec 1 2018

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Geographic Atrophy
Eye Diseases
Macular Degeneration

All Science Journal Classification (ASJC) codes

  • Ophthalmology

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Progression of Geographic Atrophy in Age-related Macular Degeneration : AREDS2 Report Number 16. / AREDS2 Research Group.

In: Ophthalmology, Vol. 125, No. 12, 01.12.2018, p. 1913-1928.

Research output: Contribution to journalArticle

AREDS2 Research Group. / Progression of Geographic Atrophy in Age-related Macular Degeneration : AREDS2 Report Number 16. In: Ophthalmology. 2018 ; Vol. 125, No. 12. pp. 1913-1928.
@article{4135ab715afd4a2faad24d66ef1b48de,
title = "Progression of Geographic Atrophy in Age-related Macular Degeneration: AREDS2 Report Number 16",
abstract = "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.",
author = "{AREDS2 Research Group} and Keenan, {Tiarnan D.} and Elvira Agr{\'o}n and Amitha Domalpally and Clemons, {Traci E.} and {van Asten}, Freekje and Wong, {Wai T.} and Danis, {Ronald G.} and Sadda, {Srini Vas} and Rosenfeld, {Philip J.} and Klein, {Michael L.} and Rinki Ratnapriya and Anand Swaroop and Ferris, {Frederick L.} and Chew, {Emily Y.} and Chew, {Emily Y.} and Ferris, {Frederick L.} and SanGiovanni, {John Paul} and Elvira Agr{\'o}n 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 Amitha Domalpally and Kathy Glander and Gregory Guilfoil and Hubbard, {Larry D.} and Kristine Johnson and Ronald Klein and Barbara Nardi and Michael Neider and Nicholas Anderson and Joseph Googe",
year = "2018",
month = "12",
day = "1",
doi = "10.1016/j.ophtha.2018.05.028",
language = "English (US)",
volume = "125",
pages = "1913--1928",
journal = "Ophthalmology",
issn = "0161-6420",
publisher = "Elsevier Inc.",
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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 - Anderson, Nicholas

AU - Googe, Joseph

PY - 2018/12/1

Y1 - 2018/12/1

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

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JO - Ophthalmology

JF - Ophthalmology

SN - 0161-6420

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