Faculty Collaboration Database

Progression of Geographic Atrophy in Age-related Macular Degeneration: AREDS2 Report Number 16. Ophthalmology 2018 Dec;125(12):1913-1928

Date

08/01/2018

Pubmed ID

30060980

Pubmed Central ID

PMC6246813

DOI

10.1016/j.ophtha.2018.05.028

Scopus ID

2-s2.0-85050484301 (requires institutional sign-in at Scopus site)   151 Citations

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 List

Keenan TD, Agrón E, Domalpally A, Clemons TE, van Asten F, Wong WT, Danis RG, Sadda S, Rosenfeld PJ, Klein ML, Ratnapriya R, Swaroop A, Ferris FL 3rd, Chew EY, AREDS2 Research Group

Author

Thomas B. Connor MD Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Aged, 80 and over
Disease Progression
Docosahexaenoic Acids
Drug Therapy, Combination
Eicosapentaenoic Acid
Female
Geographic Atrophy
Humans
Lutein
Macular Degeneration
Male
Middle Aged
Photography
Prospective Studies
Visual Acuity
Zeaxanthins