Elsevier

Ophthalmology

Volume 122, Issue 4, April 2015, Pages 809-816
Ophthalmology

Original article
Growth of Geographic Atrophy in the Comparison of Age-related Macular Degeneration Treatments Trials

Presented at: Association for Research in Vision and Ophthalmology, May 4–8, 2014, Orlando, Florida.
https://doi.org/10.1016/j.ophtha.2014.11.007Get rights and content

Purpose

To evaluate the growth of geographic atrophy (GA) during anti–vascular endothelial growth factor (VEGF) therapy.

Design

Cohort within a clinical trial.

Participants

Patients included in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).

Methods

Participants were randomly assigned to injections of ranibizumab or bevacizumab and to a 2-year dosing regimen of monthly or pro re nata (PRN) or to monthly for 1 year and PRN the following year. Digital color photographs and fluorescein angiograms at baseline and 1 and 2 years were evaluated for GA, and the total area of GA was measured by 2 graders masked to treatment; differences were adjudicated. Multivariate linear mixed models of the annual change in the square root of the area included baseline demographic, treatment, and ocular characteristics on imaging as candidate risk factors.

Main Outcome Measures

Geographic atrophy growth rate.

Results

Among 1185 participants, 86 (7.3%) had GA at baseline, 120 (10.1%) developed GA during year 1, and 36 (3.0%) developed GA during year 2. Among 194 eyes evaluable for growth, the rate was 0.43 mm/yr (standard error [SE], ±0.03 mm/year). In multivariate analysis, the growth rate was 0.37 mm/year in eyes receiving bevacizumab and 0.49 mm/year in eyes receiving ranibizumab (difference, 0.11 mm/yr; 95% confidence interval [CI], 0.01–0.22; P = 0.03). Growth rate did not differ between eyes treated monthly and PRN (P = 0.85). Eyes with subfoveal choroidal neovascularization (CNV) lesions had a lower growth rate than eyes with nonsubfoveal CNV lesions (difference, 0.12; 95% CI, 0.01–0.22; P = 0.03). Eyes with GA farther from the fovea had higher growth rates by 0.14 (95% CI, 0.01–27) mm/year for every millimeter farther from the fovea. The growth rate was 0.58 mm/year for eyes with predominantly classic lesions, 0.41 mm/year for eyes with minimally classic lesions, and 0.30 mm/year for eyes with occult only lesions (P < 0.01). The growth rate in eyes having a fellow eye with GA was higher by 0.13 mm/year (95% CI, 0.01–0.24; P = 0.03) than in eyes without GA in the fellow eye. Eyes with epiretinal membrane had a higher growth rate than eyes without epiretinal membrane (difference, 0.16; 95% CI, 0.03–0.30; P = 0.02).

Conclusions

Geographic atrophy growth depends on several ocular factors. Ranibizumab may accelerate GA growth.

Section snippets

Methods

The CATT cohort and methods have been described.8, 9, 10, 11 The CATT cohort consisted of 1185 patients with AMD and untreated choroidal/retinal neovascularization (CNV) with the CNV or its sequelae, such as intraretinal fluid, subretinal fluid, serous pigment epithelial detachment, hemorrhage, or blocked fluorescence, involving the foveal center. Patients were enrolled at 43 clinical centers in the United States between February 2008 and December 2009. Inclusion criteria included age ≥50 years

Results

Among 1185 participants, 86 (7.3%) had GA at baseline, 120 (10.1%) developed GA during year 1, and 36 (3.0%) developed GA during year 2 (Fig 1). Among the participants with GA, growth of GA could be determined from 2 or more visits in 81 prevalent cases and in 113 cases in whom GA was detected in year 1. Among these patients, 151 had blood drawn for genetic analysis.

Characteristics of prevalent and incident GA were generally similar, as shown in Table 1. Mean number of GA lesions was 2.06

Discussion

The overall GA growth rate in CATT, expressed as a square root transformation, was 0.43 (0.03) mm/year. This was similar to the square root transformed rate in 2 recent studies of dry AMD. Domalpally et al18 reported a growth rate of 0.4 mm/year in 593 Age-Related Eye Disease Study eyes with GA (mean baseline area, 3.17 mm2 [SE, 0.19]), and Yehoshua et al19 reported a growth rate of 0.37 mm/year in a small clinical trial of 30 patients with AMD (mean baseline area of 4.4 mm2 [SE, 0.81]).

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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.Y.: Biostatistical consultant – Janssen Research and Development, LLC.

    Supported by cooperative agreements U10 EY017823, U10 EY017825, U10 EY017826, and U10 EY017828 from the National Eye Institute, National Institutes of Health, Department of Health and Human Services. www.clinicaltrials.gov identifier, NCT00593450.

    Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group listed in Appendix 1 (available at www.aaojournal.org).

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