July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Geographic atrophy of age-related macular degeneration in the Age-Related Eye Disease Study 2 (AREDS2): incidence, clinical characteristics and factors influencing growth rate
Author Affiliations & Notes
  • Tiarnan D L Keenan
    Division of Epidemiology and Clinical Applications, National Eye Institute, Bethesda, Maryland, United States
    Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
  • Elvira Agron
    Division of Epidemiology and Clinical Applications, National Eye Institute, Bethesda, Maryland, United States
  • Amitha Domalpally
    Fundus Photographic Reading Center, The University of Wisconsin, Madison, Wisconsin, United States
  • Traci E Clemons
    The EMMES Corporation, Rockville, Maryland, United States
  • Freekje Van Asten
    Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, Bethesda, Maryland, United States
  • Wai T Wong
    Unit on Neuron-Glia Interactions in Retinal Disease (UNGIRD), National Eye Institute, Bethesda, Maryland, United States
  • Ronald P Danis
    Fundus Photographic Reading Center, The University of Wisconsin, Madison, Wisconsin, United States
  • Michael L Klein
    Devers Eye Institute, Portland, Oregon, United States
  • Rinki Ratnapriya
    Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, Bethesda, Maryland, United States
  • Anand Swaroop
    Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, Bethesda, Maryland, United States
  • Frederick L Ferris
    Division of Epidemiology and Clinical Applications, National Eye Institute, Bethesda, Maryland, United States
  • Emily Y. Chew
    Division of Epidemiology and Clinical Applications, National Eye Institute, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Tiarnan Keenan, Bayer (Bayer Global Ophthalmology Awards Program) (F); Elvira Agron, None; Amitha Domalpally, None; Traci Clemons, None; Freekje Van Asten, None; Wai Wong, None; Ronald Danis, None; Michael Klein, None; Rinki Ratnapriya, None; Anand Swaroop, None; Frederick Ferris, None; Emily Chew, None
  • Footnotes
    Support  Contract HHS-N-260-2005-00007-C; ADB contract N01-EY-5-0007; TK was funded in part by the Bayer Global Ophthalmology Awards Program
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 6010. doi:https://doi.org/
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      Tiarnan D L Keenan, Elvira Agron, Amitha Domalpally, Traci E Clemons, Freekje Van Asten, Wai T Wong, Ronald P Danis, Michael L Klein, Rinki Ratnapriya, Anand Swaroop, Frederick L Ferris, Emily Y. Chew; Geographic atrophy of age-related macular degeneration in the Age-Related Eye Disease Study 2 (AREDS2): incidence, clinical characteristics and factors influencing growth rate. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6010. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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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 growth.

Methods : The Age-Related Eye Disease Study 2 (AREDS2) was a randomized controlled trial of oral supplementation for AMD, comprising 4203 participants aged 50-85 years. 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 models regression of change in square root of GA area adjusted for covariates including clinical/imaging characteristics and genotype.

Results : At baseline, 517 (6.2%) eyes of 411 (9.8%) participants had pre-existing GA (without neovascular AMD). Of the remaining 6530 eyes at risk, 1099 (17.3%) eyes of 883 participants developed incident GA during mean follow-up of 4.4 years. At onset, incident GA lesions had the following distributions: centrality (33% central, 67% non-central) and focality (25% multifocal, 14% unifocal, 62% other). Over 5 years, risk of neovascular AMD following incident GA was 13% and risk of central involvement following incident non-central GA was 28%. Mean change in square root of GA area was similar in eyes with pre-existing GA (0.29mm/year, 95% CI 0.27-0.30) and incident GA (0.28mm/year, 0.27-0.30). In the combined group, GA growth was significantly faster with non-centrality (p<0.0001 for interaction), multifocality (p<0.0001) and intermediate baseline size (0.75-1.5 disc areas; p<0.0001) but not with AREDS2 treatment assignment (p=0.35) or smoking status (ever/never; p=0.14). Growth was significantly faster with ARMS2 risk genotype (p<0.0001 for interaction) and C3 non-risk genotype (p=0.0001). Additional signals for altered growth were observed with APOE and CFI genotype.

Conclusions : Analysis of GA natural history in the large AREDS2 population provided representative normative data about GA evolution and growth. GA growth rate was significantly influenced by lesion features at onset and by patient genotype. The genetic variants associated with increased growth rate were partially distinct from those known to be associated with risk of incident GA. These findings are relevant to investigations of GA pathogenesis and in clinical trial planning.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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