Elsevier

Ophthalmology

Volume 123, Issue 8, August 2016, Pages 1751-1761
Ophthalmology

Original article
Five-Year Outcomes with Anti–Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration: The Comparison of Age-Related Macular Degeneration Treatments Trials

Presented at: Association for Research in Vision and Ophthalmology Annual Meeting, May 2016, Seattle, Washington.
https://doi.org/10.1016/j.ophtha.2016.03.045Get rights and content

Purpose

To describe outcomes 5 years after initiating treatment with bevacizumab or ranibizumab for neovascular age-related macular degeneration (AMD).

Participants

Patients enrolled in the Comparison of AMD Treatments Trials.

Methods

Patients were assigned randomly to ranibizumab or bevacizumab and to 1 of 3 dosing regimens. After 2 years, patients were released from the clinical trial protocol. At 5 years, patients were recalled for examination.

Main Outcome Measures

Visual acuity (VA) and morphologic retinal features.

Results

Visual acuity was obtained for 647 of 914 (71%) living patients with average follow-up of 5.5 years. The mean number of examinations for AMD care after the clinical trial ended was 25.3, and the mean number of treatments was 15.4. Most patients (60%) were treated 1 time or more with a drug other than their assigned drug. At the 5-year visit, 50% of eyes had VA of 20/40 or better and 20% had VA of 20/200 or worse. Mean change in VA was −3 letters from baseline and −11 letters from 2 years. Among 467 eyes with fluorescein angiography, mean total lesion area was 12.9 mm2, a mean of 4.8 mm2 larger than at 2 years. Geographic atrophy was present in 213 of 515 (41%) gradable eyes and was subfoveal in 85 eyes (17%). Among 555 eyes with spectral-domain optical coherence tomography, 83% had fluid (61% intraretinal, 38% subretinal, and 36% sub–retinal pigment epithelium). Mean foveal total thickness was 278 μm, a decrease of 182 μm from baseline and 20 μm from 2 years. The retina was abnormally thin (<120 μm) in 36% of eyes. Between 2 and 5 years, the group originally assigned to ranibizumab for 2 years lost more VA than the bevacizumab group (−4 letters; P = 0.008). Otherwise, there were no statistically significant differences in VA or morphologic outcomes between drug or regimen groups.

Conclusions

Vision gains during the first 2 years were not maintained at 5 years. However, 50% of eyes had VA of 20/40 or better, confirming anti–vascular endothelial growth factor therapy as a major long-term therapeutic advance for neovascular AMD.

Section snippets

Design of the Comparison of Age-Related Macular Degeneration Treatments Trials Clinical Trial

The design and methods for the clinical trial have been published; therefore, only the key features with bearing on this study are provided.6, 7, 25, 26 Patients enrolled in CATT between February 20, 2008, and December 9, 2009. Eligible eyes (1 study eye per patient) had active choroidal neovascularization secondary to AMD; no previous treatment; VA between 20/25 and 20/320; and neovascularization, fluid, or hemorrhage under the foveal center. Patients were assigned randomly to 1 of 4 treatment

Patients

Among the 1117 patients alive at the end of the clinical trial (end of year 2), 203 (18.2%) died before the end of the CATT Follow-up Study. Of the remaining 914 patients, a VA measurement was available for 647 (70.8%) patients in the required interval of 51 months (4.3 years) to 85 months (7.1 years) after assignment of treatment in the clinical trial. The mean interval between enrollment in the clinical trial and the CATT Follow-up Study visit was 66.5 months (5.5 years; standard deviation

Discussion

The randomized clinical trials that established the efficacy of ranibizumab, bevacizumab, and aflibercept demonstrated that anti-VEGF therapy for neovascular AMD improved VA on average by 1 to 2 lines through 2 years.1, 2, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 The CATT Follow-up Study provides long-term follow-up (mean, 5.5 years) of 70.8% of survivors. Mean VA declined to 3 letters worse than at baseline and 11 letters worse than at 2 years. This decrease in vision was accompanied by

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    *Supplemental material is available at www.aaojournal.org.

    Financial Disclosure(s): The author(s) have made the following disclosure(s): M.G.M.: Financial support – Roche/Genentech; Data Safety and Monitoring Committee – Genentech

    G.Y.: Consultant – Janssen R & D; Chengdu Kanghong Biotech Co.

    G.J.J.: Consultant – Alcon/Novartis; Neurotech; Roche/Genentech

    C.A.T.: Financial support – Genentech, Inc; Royalties – Alcon, Inc; Thrombogenics; Nonfinancial support: Bioptigen; Patent − Duke University

    Supported by the National Eye Institute, National Institutes of Health, Bethesda, Maryland (cooperative agreement nos.: U10 EY017823, U10 EY017825, U10 EY017826, and U10 EY017828). The funding organization participated in the design and conduct of the study, data analysis and interpretation, and review of the manuscript.

    Author Contributions:

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

    Analysis and interpretation: Maguire, Martin, Ying, Jaffe, Daniel, Toth, Grunwald, Ferris, Fine

    Data collection: Maguire, Martin, Ying, Jaffe, Daniel, Toth, Grunwald, Ferris, Fine

    Obtained funding: Maguire, Martin

    Overall responsibility: Maguire, Martin, Ying, Jaffe, Daniel, Toth, Grunwald, Ferris, Fine

    The members of the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) Research Group are listed in the Appendix (available at www.aaojournal.org).

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