Elsevier

Ophthalmology

Volume 121, Issue 1, January 2014, Pages 150-161
Ophthalmology

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

Presented at: ARVO 2013, Orlando, Florida, May 7, 2013.
https://doi.org/10.1016/j.ophtha.2013.08.015Get rights and content

Purpose

To describe risk factors for geographic atrophy (GA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).

Design

Cohort within a randomized clinical trial.

Participants

We analyzed 1024 CATT patients with no GA visible on color fundus photographs (CFPs) and/or fluorescein angiograms (FAs) at enrollment.

Methods

Eyes were assigned to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a 2-year monthly or pro re nata (PRN) injection regimen, or monthly injections for 1 year and PRN for 1 year. Demographic, genetic, and baseline ocular characteristics and lesion features of CFP/FA and optical coherence tomography (OCT) were evaluated as risk factors for GA through 2 years of follow-up. Time-dependent Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs).

Main Outcome Measures

Development of GA.

Results

By 2 years, GA developed in 187 of 1024 patients (18.3%). Baseline risk factors for GA development included baseline visual acuity (VA) ≤20/200 (aHR, 2.65; 95% confidence interval [CI], 1.43–4.93), retinal angiomatous proliferation (RAP; aHR, 1.69; 95% CI, 1.16–2.47), GA in the fellow eye (aHR, 2.07; 95% CI, 1.40–3.08), and intraretinal fluid at the foveal center (aHR, 2.10; 95% CI, 1.34–3.31). Baseline factors associated with lower risk for GA development included blocked fluorescence (aHR, 0.49; 95% CI, 0.29–0.82), OCT measurements of subretinal fluid thickness of >25 μ (aHR, 0.52; 95% CI, 0.35–0.78), subretinal tissue complex thickness of >275 compared with ≤75 μ (aHR, 0.31; 95% CI, 0.19–0.50), and vitreomacular attachment (aHR, 0.55; 95% CI, 0.31–0.97). Ranibizumab compared with bevacizumab had a higher risk (aHR, 1.43; 95% CI, 1.06–1.93), and monthly dosing had a higher risk (aHR, 1.59; 95% CI, 1.17–2.16) than PRN dosing. There were no strong associations between development of GA and the presence of risk alleles for CFH, ARMS 2, HTRA1, C3, or TLR3.

Conclusions

Approximately one fifth of CATT patients developed GA within 2 years of treatment. Independent baseline risk factors included poor VA, RAP, foveal intraretinal fluid, monthly dosing, and treatment with ranibizumab. Anti-vascular endothelial growth factor therapy may have a role in the development of GA.

Section snippets

Methods

The CATT cohort and the methods used by the study have been described elsewhere.8, 9, 10, 11 Briefly, the cohort consisted of 1185 patients with AMD and untreated choroidal/retinal neovascularization (CNV) with either the CNV or its sequalae, such as intraretinal fluid, subretinal fluid, serous pigment epithelial detachment, hemorrhage, or blocked fluorescence involving the foveal center. Patients enrolled in 43 clinical centers in the United States between February 2008 and December 2009.

Statistical Methods

Risk factors assessed as the presence or absence of a particular feature (such as lesion features, OCT fluid) were included as categorical variables. We classified risk factors measured on a continuous scale (e.g., VA, CNV area, OCT thickness) into categories for easier clinical interpretation. Categories for continuous variables were based on either the normal range (as for retinal thickness), quartiles of the distribution (as for subretinal tissue complex thickness), or clinically relevant

Results

After excluding 82 subjects with GA at baseline and 79 subjects with missing or unknown GA, there were 1024 subjects at risk of developing GA in the CATT study (Fig 3). Among the 1024 subjects, 773 (75.5%) provided a blood sample for genotyping. Among the 1024 patients, 109 (10.6%) developed GA by the end of 1 year (Kaplan-Meier cumulative incidence rate, 0.11; 95% CI, 0.09–0.13), and 187 (18.3%) developed GA by the end of 2 years (Kaplan-Meier cumulative incidence rate, 0.19; 95% CI,

Discussion

Our study assessed lesions developing during 2 years of anti-VEGF therapy that have the characteristics of GA on color photography and FA. It is possible that the lesions that we describe in this article as GA developing in the area of total CNV lesion may not be histologically similar to the GA lesions that develop de novo in areas where no CNV lesion was previously present. However, the lesions are clinically indistinguishable at 2 years. The GA associated with CNV has been described

References (30)

  • D.M. Brown et al.

    ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration

    N Engl J Med

    (2006)
  • P.J. Rosenfeld et al.

    Optical coherence tomography after an intravitreal injection of bevacizumab (Avastin) for neovascular age-related macular degeneration

    Ophthalmic Surg Lasers Imaging

    (2005)
  • R.L. Avery et al.

    Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration

    Ophthalmology

    (2006)
  • CATT Research Group

    Ranibizumab and bevacizumab for neovascular age-related macular degeneration

    N Engl J Med

    (2011)
  • Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group et al.

    Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results

    Ophthalmology

    (2012)
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    Financial Disclosures: The authors have no proprietary or commercial interest in any of the materials discussed in this article.

    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. ClinicalTrials.gov number, NCT00593450.

    Group members listed online in Appendix 1 (at http://aaojournal.org).

    A full listing of the CATT Research Group in available at http://aaojournal.org.

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