Five-Year Outcomes with Anti–Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration

Abstract

Purpose To describe outcomes 5 years after initiation of 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 (CATT). Methods Patients were randomly assigned to ranibizumab or bevacizumab and to 1 of 3 dosing regimens. After 2 years, patients were released from the clinical trial protocol. At approximately 5 years, patients were recalled for examination. Main Outcome Measures Visual acuity (VA) and morphologic retinal features. Results VA was obtained for 647 (71%) of 914 living patients with average follow-up time 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 in the study eye was 15.4. Most (60%) patients were treated ≥1 times with a drug other than their randomly assigned drug. At the 5-year visit, 50% of study eyes had VA 20/40 or better and 20% had VA 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 (41%) of 515 gradable eyes and was subfoveal in 85 (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. An abnormally thin retina at the foveal center (<120 μm) was present in 36%. 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 morphological outcomes between drug or regimen groups. Conclusion Vision gains during the first 2 years of the trial were not maintained at 5 years. However, 50% of eyes had VA 20/40 or better, confirming anti-VEGF therapy as a major long-term therapeutic advance for neovascular AMD.

VEGF/VEGFR2 blockade does not cause retinal atrophy in AMD-relevant models

“…At the 2-year endpoint of the CATT trial, subjects in all 4 of the anti-VEGF treatment arms showed large mean improvements in visual acuity from baseline. During the next 3 years, patients received fewer mean number of injections as part of standard care and for the population as a whole, all of the visual gains achieved during the first 2 years were lost (45). While there are a number of possible causes for this loss of vision, it appears that insufficient treatment may have contributed because (a) the goal of treatment is to eliminate fluid within or under the macula, but fluid was present in 83% of 555 eyes in which spectral domain OCT was obtained, a very large percentage; (b) intraretinal fluid is particularly problematic because it is a risk factor for poor outcome and more eyes had intraretinal fluid at 5 years than at 2 years (61% versus 50%); and (c) VEGF suppression prevents growth of choroidal NV, but in 467 eyes in which fluorescein angiography was done at 5 years, total lesion area was 4.8 mm 2 larger than at 2 years, an increase of more than 50%, indicating that there had been poor VEGF suppression.…”

Generation and characterization of ABBV642, a dual variable domain immunoglobulin molecule (DVD-Ig) that potently neutralizes VEGF and PDGF-BB and is designed for the treatment of exudative age-related macular degeneration

“…[6][7][8][9] However, the striking visual acuity gains seen after two years of treatment in a clinical trial were completely lost three years after patients exited the trial and initiated standard care methodologies. 10 Many of the patients who lost initial visual acuity gains had subretinal hyper-reflective material suggestive of subretinal fibrosis or areas of macular atrophy. Subretinal hyper-reflective material is a risk factor for macular atrophy, so one possible hypothesis is that over time many patients develop subretinal fibrosis despite treatment with anti-VEGF agents because other HIF-1-stimulated vasoactive agent stimulates subretinal fibrosis.…”

The Role of Fish Oil in Inflammatory Eye Diseases

“…There is no effective treatment for most cases of AMD; however, a small proportion of patients with well-defined CNV benefit from laser photocoagulation [24] . Recent advances in the development of intravitreal antiangiogenic therapies (anti-VEGF antibody injection) for neovascular AMD have greatly improved clinical outcomes in the last decade; however, vision improvement during the first 2 years was not maintained at 5 years, and monthly treatments were associated with an increased risk of developing geographic atrophy [27] . Currently, treatments remain inadequate for atrophic AMD [26] .…”