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Ranibizumab for Neovascular Age-Related Macular Degeneration
Open accessAbstract
BACKGROUND: Ranibizumab--a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A--has been evaluated for the treatment of neovascular age-related macular degeneration. METHODS: In this multicenter, 2-year, double-blind, sham-controlled study, we randomly assigned patients with age-related macular degeneration with either minimally classic or occult (with no classic lesions) choroidal neovascularization to receive 24 monthly intravitreal injections of ranibizumab (either 0.3 mg or 0.5 mg) or sham injections. The primary end point was the proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months. RESULTS: We enrolled 716 patients in the study. At 12 months, 94.5% of the group given 0.3 mg of ranibizumab and 94.6% of those given 0.5 mg lost fewer than 15 letters, as compared with 62.2% of patients receiving sham injections (P<0.001 for both comparisons). Visual acuity improved by 15 or more letters in 24.8% of the 0.3-mg group and 33.8% of the 0.5-mg group, as compared with 5.0% of the sham-injection group (P<0.001 for both doses). Mean increases in visual acuity were 6.5 letters in the 0.3-mg group and 7.2 letters in the 0.5-mg group, as compared with a decrease of 10.4 letters in the sham-injection group (P<0.001 for both comparisons). The benefit in visual acuity was maintained at 24 months. During 24 months, presumed endophthalmitis was identified in five patients (1.0%) and serious uveitis in six patients (1.3%) given ranibizumab. CONCLUSIONS: Intravitreal administration of ranibizumab for 2 years prevented vision loss and improved mean visual acuity, with low rates of serious adverse events, in patients with minimally classic or occult (with no classic lesions) choroidal neovascularization secondary to age-related macular degeneration. (ClinicalTrials.gov number, NCT00056836 [ClinicalTrials.gov].).
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In the citing paper
“Ranibizumab anti-Fab immunoreactivity in treatment-naïve patients was between 0–0.9% in the MARINA and ANCHOR trials [30, 31].”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [30]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The MARINA and ANCHOR trials with ranibizumab showed an incidence of 0.05% [30, 31], and a subsequent comparison study of ranibizumab and bevacizumab for neovascular AMD reported rates of 0.16% for ranibizumab and 0.5% for bevacizumab [32].”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [30]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Regardless of anti-VEGF agent, pre-treatment ADA titers have not been shown to have any clinically relevant difference in BCVA outcomes [30, 33, 41, 43].”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [30]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Repeated intravitreal (IVT) injections of anti-VEGF therapies effectively slow vision loss in the majority of treatment-compliant patients with wet AMD. 7 – 13”
From Design and Characterization of a Novel Intravitreal Dual-Transgene Genetic Medicine for Neovascular Retinopathies (2024) · cites this paper as [12]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the ANCHOR and MARINA studies, 8-14% of eyes gained 415 letters during months 4 to 12. [22][23][24]”
From Defining response to anti-VEGF therapies in neovascular AMD (2015) · cites this paper as [22]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“It is now accepted that the best outcomes with anti-VEGF therapies in n-AMD are achieved with regular dosing at specific intervals, usually monthly, as demonstrated in the pivotal trials of ranibizumab, and sometimes two monthly in the first year with aflibercept after the ' three monthly initiation doses'.[22][23][24][25]”
From Defining response to anti-VEGF therapies in neovascular AMD (2015) · cites this paper as [22]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, this initial response at month 4 is not always predictive of long-term VA gains, as a proportion of such eyes continue to accrue gains in vision even after month 4 as in the ANCHOR and MARINA studies, 22,24 HARBOR study 30 and subsequent case series.31”
From Defining response to anti-VEGF therapies in neovascular AMD (2015) · cites this paper as [22]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Other major anti-VEGF clinical trials excluded such patients.18,19,20”
From Development and Course of Scars in the Comparison of Age-Related Macular Degeneration Treatments Trials (2018) · cites this paper as [19]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“However, such lesions may be difficult to categorise as there are a group of 'delayed responders' who will not gain vision until well after 3 and sometimes not until after 12 months.22,24”
From Defining response to anti-VEGF therapies in neovascular AMD (2015) · cites this paper as [22]
Experimental — accuracy not yet measuredIn the citing paper
“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 [1]
In the citing paper
“was associated with a remarkable proportion of patients with an improvement in vision”
From Age-related macular degeneration (2008) · cites this paper as [164]
In the citing paper
“Ranibizumab is a fragment of a monoclonal antibody that binds to and inhibits all forms of VEGF-A.164,165”
From Age-related macular degeneration (2008) · cites this paper as [164]
In the citing paper
“This drug, when injected intravitreally on a monthly basis, prevented vision loss”
From Age-related macular degeneration (2008) · cites this paper as [164]
In the citing paper
“These benefits persisted through 24 months of follow-up.”
From Age-related macular degeneration (2008) · cites this paper as [164]
In the citing paper
“Mean differences in visual acuity score in the treated and control groups were also impressive, with a mean increase of seven letters in the treated group compared with a mean decrease of 10 letters in the placebo group (p<0·001).”
From Age-related macular degeneration (2008) · cites this paper as [164]
In the citing paper
“At 12 months, 95% of patients given ranibizumab 0·5 mg lost fewer than 15 letters (three lines of vision) compared with 62% of the placebo group (p<0·001).”
From Age-related macular degeneration (2008) · cites this paper as [164]
In the citing paper
“for the first time with any treatment for age-related macular degeneration, was associated with a remarkable proportion of patients with an improvement in vision”
From Age-related macular degeneration (2008) · cites this paper as [164]
In the citing paper
“Additionally, 34% of this group improved by 15 or more letters of vision compared with the 5% in the placebo group (p<0·001).”
From Age-related macular degeneration (2008) · cites this paper as [164]
In the citing paper
“The adverse effects included endophthalmitis (1%) and serious uveitis (1%).”
From Age-related macular degeneration (2008) · cites this paper as [164]
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Citations
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Self-citation
Metadata
- Authors
- Rosenfeld, P. J., Brown, D. M., Heier, J. S., Boyer, D. S., Kaiser, P. K., Chung, C. Y., & Kim, R. Y.
- Affiliations
- University of Miami (US)
- Houston Methodist (US)
- Ophthalmic Consultants of Boston (US)
- Retina Vitreous Associates Medical Group (US)
- Cleveland Clinic (US)
- Genentech (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2006-10-05
- Volume
- 355
- Issue
- 14
- Pages
- 1419-1431
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2124415048
- Cited by
- 5,886
- References
- 25
- Citations by year
- 2026: 179 · 2025: 231 · 2024: 207 · 2023: 198 · 2022: 242 · 2021: 324 · 2020: 311 · 2019: 259 · 2018: 286 · 2017: 325 · 2016: 313 · 2015: 356 · 2014: 358 · 2013: 371 · 2012: 371
- FWCI
- 240.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- Pennsylvania State University
- University of South Florida
- Towson University
- Genentech
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Retinal and Macular Surgery
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- ranibizumab, neovascular age-related macular degeneration, choroidal neovascularization, intravitreal injection, anti-VEGF therapy, VEGF-A, visual acuity, blindness prevention, endophthalmitis, uveitis, adverse events, long-term follow-up, dose comparison, occult choroidal neovascularization, anti-angiogenic therapy, VEGF inhibitors
- MeSH terms
- Ranibizumab, Aged, Aged, 80 and over, Antibodies, Monoclonal, Double-Blind Method, Female, Humans, Injections, Macular Degeneration, Male, Middle Aged, Optic Disk, Visual Acuity, Choroidal Neovascularization, Angiogenesis Inhibitors, Antibodies, Monoclonal, Humanized
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