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

Abstract

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

Design: Cohort study.

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 mm(2), a mean of 4.8 mm(2) 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.

Figure 1

Distribution of visual acuity over time for 647 patients in the Follow-up Study.

Figure 2

Mean visual acuity and 95% confidence interval for 647 patients in the Follow-up Study. A. Overall and by drug assigned in the clinical trial; B. Overall and by dosing regimen assigned in the clinical trial.

Figure 2

Mean visual acuity and 95% confidence interval for 647 patients in the Follow-up Study. A. Overall and by drug assigned in the clinical trial; B. Overall and by dosing regimen assigned in the clinical trial.

Figure 3

Mean total thickness at the foveal center and 95% confidence interval for 552 patients in the Follow-up Study with values available from optical coherent tomography. A. Overall and by drug assigned in the clinical trial; Overall and by dosing regimen assigned in the clinical trial.

Figure 3

Mean total thickness at the foveal center and 95% confidence interval for 552 patients in the Follow-up Study with values available from optical coherent tomography. A. Overall and by drug assigned in the clinical trial; Overall and by dosing regimen assigned in the clinical trial.

Figure 4

Retinal thickness at the foveal center in 553 patients with values available from optical coherent tomography, by category over time.

Figure 5

Percentage of eyes with fluid for 552 eyes in the Follow-up Study with values available from optical coherent tomography, over time.