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Clinical Trial
. 2018 Dec;125(12):1913-1928.
doi: 10.1016/j.ophtha.2018.05.028. Epub 2018 Jul 27.

Progression of Geographic Atrophy in Age-related Macular Degeneration: AREDS2 Report Number 16

Tiarnan D Keenan  1 , Elvira Agrón  1 , Amitha Domalpally  2 , Traci E Clemons  3 , Freekje van Asten  4 , Wai T Wong  5 , Ronald G Danis  2 , SriniVas Sadda  6 , Philip J Rosenfeld  7 , Michael L Klein  8 , Rinki Ratnapriya  4 , Anand Swaroop  4 , Frederick L Ferris 3rd  1 , Emily Y Chew  9 ; AREDS2 Research Group
Collaborators, Affiliations
Clinical Trial

Progression of Geographic Atrophy in Age-related Macular Degeneration: AREDS2 Report Number 16

Tiarnan D Keenan et al. Ophthalmology. 2018 Dec.

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.

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Conflict of interest statement

Conflicts of Interest:

Tiarnan Keenan, Elvira Agrón, Amitha Domalpally, Traci Clemons, PhD Freekje van Asten, Wai Wong, Emily Chew, Rinki Ratnapriya, Michael Klein, Frederick Ferris: None.

Ronald P. Danis: Consultant to Ionis Pharmaceuticals and KangHong Pharmaceuticals and is an employee and an equity owner of EyeKor, Inc

SriniVas Sadda: Consultant to Allergan, Genentech, Novartis, Thrombogenics, Iconic, NightStar, Centervue, Heidelberg, Optos and receives research support from Genentech, Carl Zeiss Meditec, Optos.

Philip Rosenfeld: Consultant to Acuela, Apellis Boehringer-Ingelheim, Carol Zeiss Meditec, Cell Cure Neurosciences, Chengdu Kanghong Biotech, Isarna Therapeutics, Genetech, Healios K.K., Hemera Biosciences, F. Hoffman-LaRoche Ltd, Ocudyne, Ocunexus, Tyrogenex, Unity Biotechnology: receives research support: Astellas Institute for Regenerative Medicine (AIRM), Carl Zeiss Medictec, Genentech, Tyrogenex; and has equity interest in Apellis, Digisight, Ocudyne.

Figures

Figure 1
Figure 1
Kaplan-Meier plot of the development of neovascular AMD in eyes with prevalent GA (i.e. where GA was present at baseline).
Figure 2
Figure 2
Kaplan-Meier plot of the development of central GA in eyes where non-central GA was present at baseline.
Figure 3A
Figure 3A
Kaplan-Meier plot of the development of GA (without simultaneous/prior neovascular AMD) in eyes that did not have GA (or neovascular AMD) at baseline (i.e. incident GA).
Figure 4B
Figure 4B
Kaplan-Meier plot of the development of GA (without simultaneous/prior neovascular AMD) in eyes according to the presence or absence of neovascular AMD in the fellow eye at the time of GA.
Figure 5
Figure 5
Kaplan-Meier plot of the development of neovascular AMD in eyes with incident GA (i.e. where GA developed during follow-up): overall and according to the presence or absence of neovascular AMD in the fellow eye at the time of GA.
Figure 6
Figure 6
Kaplan-Meier plot of the development of central GA in eyes that developed non-central GA during follow-up (i.e. incident non-central GA).
See this image and copyright information in PMC

Comment in

References

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