Ranibizumab and Bevacizumab for Treatment of Neovascular Age-related Macular Degeneration
Open accessAbstract
Objective To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment.Design Multicenter, randomized clinical trial.Participants Patients (n = 1107) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial.Interventions At enrollment, patients were assigned to 4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment.Main outcome measures Mean change in visual acuity.Results Among patients following the same regimen for 2 years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, -1.4 letters; 95% confidence interval [CI], -3.7 to 0.8; P = 0.21). Mean gain was greater for monthly than for as-needed treatment (difference, -2.4 letters; 95% CI, -4.8 to -0.1; P = 0.046). The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, P = 0.0003; regimen, P < 0.0001). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (-2.2 letters; P = 0.03) and a lower proportion without fluid (-19%; P < 0.0001). Rates of death and arteriothrombotic events were similar for both drugs (P > 0.60). The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07-1.57; P = 0.009). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF).Conclusions Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.
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The current intravitreal VEGF inhibitors in clinical use are bevacizumab, ranibizumab, aflibercept, and brolucizumab.
“The current intravitreal VEGF inhibitors in clinical use are bevacizumab (Avastin, Genentech, San Francisco, CA), ranibizumab (Lucentis, Genentech, San Francisco, CA), aflibercept (Regeneron, Tarrytown, NY), and brolucizumab (Beovu, Novartis, Basel, Switzerland) [4–8].”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [4]
The Introduction describes ranibizumab and bevacizumab as treatments for neovascular AMD, and Methods > Treatment specifies intravitreal injections of both drugs (page numbers unavailable). The paper does not establish the full claimed list of drugs in current clinical use: searches for aflibercept and brolucizumab found no supporting passages. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn CATT at Year 2, monthly dosing was associated with more geographic atrophy than PRN (24% vs 15%, p=0.003).
“At the end of Year 2 of CATT, eyes that received monthly treatment were more likely to have developed geographic atrophy than those treated with PRN therapy (24% vs 15%, p=0.003).7”
From Five-Year Outcomes with Anti–Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration (2016) · cites this paper as [7]
During CATT, both ranibizumab use and monthly treatment were associated with an increased rate of geographic atrophy development.
“During CATT, both the use of ranibizumab and monthly treatment were associated with an increased rate of development of geographic atrophy.”
From Five-Year Outcomes with Anti–Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration (2016) · cites this paper as [7]
In CATT at Year 2, geographic atrophy was more frequent with ranibizumab (21%) than bevacizumab (17%; p=0.02).
“At the end of Year 2, eyes treated with ranibizumab had a higher incidence (21%) of geographic atrophy than eyes treated with bevacizumab (17%; p=0.02).7”
From Five-Year Outcomes with Anti–Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration (2016) · cites this paper as [7]
In CATT, patients who switched at 1 year from monthly to PRN dosing received 5 to 6 injections on average and lost 2 to 3 letters of mean visual acuity over the second year.
“In CATT, patients who switched at 1 year from a monthly to a PRN dosing regimen received 5 to 6 injections on average and experienced a mean visual acuity decrease of 2 to 3 letters over the second year.7”
From Five-Year Outcomes with Anti–Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration (2016) · cites this paper as [7]
Geographic atrophy affected 20% of eyes at 2 years and 41% at 5 years; subfoveal geographic atrophy rose from 6% to 17%.
“We also previously reported that the proportion of eyes with geographic atrophy was 20% at 2 years and this proportion increased to 41% at 5 years, with an increase in subfoveal geographic atrophy from 6% to 17%.7,37”
From Five-Year Outcomes with Anti–Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration (2016) · cites this paper as [7]
In CATT and all randomized trials of anti-VEGF treatment for neovascular AMD, most improvement in mean visual acuity from baseline occurred within the first 3 to 6 months, with little erosion of benefit through 2 years when a fixed monthly or bi-monthly schedule was maintained.
“In CATT and all randomized clinical trials of anti-VEGF treatment for neovascular AMD, most of the improvement in mean visual acuity from baseline occurred within the first 3 to 6 months with little erosion of the benefit through 2 years when a fixed schedule of monthly (ranibizumab, bevacizumab, aflibercept) or bi-monthly (aflibercept) treatment was maintained.1,7,9,17,34”
From Five-Year Outcomes with Anti–Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration (2016) · cites this paper as [7]
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Parmeggiani, F., Gallenga, C. E., Costagliola, C., Semeraro, F., Romano, M. R., Dell’Omo, R., Russo, A., De Nadai, K., Gemmati, D., D’Angelo, S., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-38919-7 · Cited by 7 · see citing works
- Authors
- Martin, D. F., Maguire, M. G., Fine, S. L., Ying, G.-S., Jaffe, G. J., Grunwald, J. E., Toth, C., Redford, M., & Ferris, F. L.
- Affiliations
- Cleveland Clinic (US)
- University of Pennsylvania (US)
- University of Colorado Denver (US)
- Duke University (US)
- National Institutes of Health (US)
- Corresponding author
- Maguire, Maureen G.
- ORCID
- Venue
- Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 119
- Issue
- 7
- Pages
- 1388-1398
- ISSN
- 0161-6420 (ISSN-L)
- PMC
- PMC3389193
- OpenAlex
- W1500728559
- Cited by
- 1,715
- References
- 21
- Citations by year
- 2026: 32 · 2025: 67 · 2024: 76 · 2023: 58 · 2022: 90 · 2021: 155 · 2020: 133 · 2019: 109 · 2018: 106 · 2017: 123 · 2016: 163 · 2015: 193 · 2014: 204 · 2013: 161 · 2012: 41
- FWCI
- 179.23
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (U10EY017825, U10EY017826, U10EY017823, U10EY017828)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal and Macular Surgery
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- ranibizumab, bevacizumab, neovascular age-related macular degeneration, anti-VEGF therapy, monthly dosing, as-needed dosing, treatment switching, visual acuity, subretinal fluid, systemic adverse events, long-term follow-up
- MeSH terms
- Bevacizumab, Ranibizumab, Aged, Aged, 80 and over, Female, Fluorescein Angiography, Follow-Up Studies, Humans, Male, Middle Aged, Visual Acuity, Treatment Outcome, Angiogenesis Inhibitors, Tomography, Optical Coherence, Vascular Endothelial Growth Factor A, Wet Macular Degeneration, Intravitreal Injections, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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