Elsevier

Ophthalmology

Volume 124, Issue 1, January 2017, Pages 97-104
Ophthalmology

Original article
Incidence and Growth of Geographic Atrophy during 5 Years of Comparison of Age-Related Macular Degeneration Treatments Trials

Presented at: Association for Research in Vision and Ophthalmology, September 25–29, 2016, Tokyo, Japan.
https://doi.org/10.1016/j.ophtha.2016.09.012Get rights and content

Purpose

To estimate the incidence, size, and growth rate of geographic atrophy (GA) during 5 years of follow-up among participants in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).

Design

Cohort within a clinical trial.

Participants

Participants included in CATT.

Methods

A total of 1185 CATT participants were randomly assigned to ranibizumab or bevacizumab treatment and to 3 treatment regimens. Participants were released from protocol treatment at 2 years and examined at approximately 5 years (N = 647). Two masked graders assessed the presence and size of GA in digital color photographs (CPs) and fluorescein angiograms (FAs) taken at baseline and years 1, 2, and 5. Cox proportional hazard models were used to identify risk factors for incidence of GA. Annual change in the square root of the total area of GA was the measure of growth. Multivariate linear mixed models including baseline demographic, treatment, and ocular characteristics on CP/FA and optical coherence tomography (OCT) as candidate risk factors were used to estimate adjusted growth rates, standard errors (SEs), and 95% confidence intervals (CIs).

Main Outcome Measures

Geographic atrophy incidence and growth rate.

Results

Among the 1011 participants who did not have GA at baseline and had follow-up images gradable for GA, the cumulative incidence was 12% at 1 year, 17% at 2 years, and 38% at 5 years. At baseline, older age, hypercholesterolemia, worse visual acuity, larger choroidal neovascularization (CNV) area, retinal angiomatous proliferation (RAP) lesion, GA in the fellow eye, and intraretinal fluid were associated with a higher risk of incident GA. Thicker subretinal tissue complex and presence of subretinal fluid were associated with less GA development. The overall GA growth rate was 0.33 mm/year (SE, 0.02 mm/year). Eyes treated with ranibizumab in the first 2 years of the clinical trial had a higher growth rate than eyes treated with bevacizumab (adjusted growth rate, 0.38 vs. 0.28 mm/year; P = 0.009). Geographic atrophy in the fellow eye, hemorrhage, and absence of sub–retinal pigment epithelium fluid at baseline were associated with a higher growth rate.

Conclusions

Development of GA is common 5 years after initiating therapy. Several risk factors identified at 2 years of follow-up persist at 5 years of follow-up.

Section snippets

Methods

The CATT participants and methods have been described in previous reports.2, 3, 4, 5, 6, 7 There were 1185 participants in the CATT who had AMD and untreated CNV or retinal neovascularization in the study eye. Participants were enrolled in 43 clinical centers in the United States between February 2008 and December 2009. Inclusion criteria have been described.4, 6 Participants at baseline had neovascularization or sequelae of neovascularization in the fovea and visual acuity between 20/25 and

Results

Among 1185 participants, 1183 had evaluable photographs at baseline, 1061 at year 1, 1012 at year 2, and 517 at year 5. Of these, 81 had GA at baseline, 122 developed GA during year 1, 42 developed GA during year 2, and 102 developed GA between the year 2 and the year 5 visit (Fig 1). Among the participants with GA, growth of GA could be determined from 2 or more visits in 81 prevalent cases and in 114 cases in which GA was detected at year 1 and 19 at year 2.

Discussion

Our study identified a number of risk factors for the development of GA in exudative AMD treated with anti–vascular endothelial growth factor (VEGF) therapy for up to 5 years. Among them are age, elevated cholesterol, ranibizumab treatment, poor vision, large total CNV lesion, RAP lesions, fellow eye GA, thinner subretinal tissue complex at the fovea and intraretinal fluid, especially in the fovea, and absence of subretinal fluid. Most of these factors had been identified in our previous report

References (30)

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Supplemental material is available at www.aaojournal.org.

Financial Disclosure(s): The author(s) have made the following disclosure(s): G-S.Y.: Consultant – Chengdu Kanghong Biotech Ltd.

G.J.J.: Consultant – Heidelberg Engineering, Neurotech, Alcon/Novartis, and Roche/Genentech.

C.A.T.: Research support – Genentech; Royalties – Alcon/Novartis.

M.G.M.: Consultant – Genentech/Roche.

Supported by Cooperative Agreements U10 EY023530, U10 EY017823, U10 EY017825, U10 EY017826, U10 EY017828, and R21EY023689 from the National Eye Institute, National Institutes of Health, Department of Health and Human Services. ClinicalTrials.gov identifier NCT00593450.

Author Contributions:

Conception and design: Grunwald, Pistilli, Daniel, Ying, Jaffe, Toth, Hagstrom, Maguire, Martin

Data collection: Grunwald, Pistilli, Daniel, Ying, Jaffe, Toth, Hagstrom, Maguire, Martin

Analysis and interpretation: Grunwald, Pistilli, Daniel, Ying, Pan, Jaffe, Toth, Hagstrom, Maguire, Martin

Obtained funding: Not applicable

Overall responsibility: Grunwald, Pistilli, Daniel, Ying, Pan, Jaffe, Toth, Hagstrom, Maguire, Martin

Members of the Comparison of Age-Related Macular Degeneration Treatments Trials Research Group available online at www.aaojournal.org.

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