Trial reportHealth technology assessment (Winchester, England)2021
Intravitreal ranibizumab versus aflibercept versus bevacizumab for macular oedema due to central retinal vein occlusion: the LEAVO non-inferiority three-arm RCT.
Trial report in Health technology assessment (Winchester, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.
- Language-related eligibility criteria in UK randomised trials: a systematic review of extended research reports.Trials · 2026Pooled it
- Non-inferiority trials in clinical ophthalmology: a systematic review.Eye (London, England) · 2025Pooled it
- Retinal vein occlusion-related macular edema: An updated review of current evidence and future directions.Indian journal of ophthalmology · 2026Review
- Challenging the Treatment Threshold: Early Faricimab Prevents Vision Loss in nAMD - A Real-World Welsh Experience.Clinical ophthalmology (Auckland, N.Z.) · 2026Article
- [Frequency and distribution of the active agent of intravitreal injections in German centers 2015-2021-An oregis study].Die Ophthalmologie · 2024Article
- An Introduction to Biosimilars for the Treatment of Retinal Diseases: A Narrative Review.Ophthalmology and therapy · 2022Review
- Steroid Treatment in Macular Edema: A Bibliometric Study and Visualization Analysis.Frontiers in pharmacology · 2022Article
- Cost-Effectiveness of Conbercept vs. Ranibizumab for Age-Related Macular Degeneration, Diabetic Macular Edema, and Pathological Myopia: Population-Based Cohort Study and Markov Model.Frontiers in medicine · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 8 institutions in 1 country.
Funding
Abstract
backgroundLicensed ranibizumab (0.5 mg/0.05 ml Lucentis
objectiveThe objective was to compare the clinical effectiveness and cost-effectiveness of three intravitreal antivascular endothelial growth factor agents for the management of macula oedema due to central retinal vein occlusion.
designThis was a three-arm, double-masked, randomised controlled non-inferiority trial.
settingThe trial was set in 44 UK NHS ophthalmology departments, between 2014 and 2018.
participantsA total of 463 patients with visual impairment due to macula oedema secondary to central retinal vein occlusion were included in the trial.
interventionsThe participants were treated with repeated intravitreal injections of ranibizumab (
main outcome measuresThe primary outcome was an increase in the best corrected visual acuity letter score from baseline to 100 weeks in the trial eye. The null hypothesis that aflibercept and bevacizumab are each inferior to ranibizumab was tested with a non-inferiority margin of -5 visual acuity letters over 100 weeks. Secondary outcomes included additional visual acuity, and imaging outcomes, Visual Function Questionnaire-25, EuroQol-5 Dimensions with and without a vision bolt-on, and drug side effects. Cost-effectiveness was estimated using treatment costs and Visual Function Questionnaire-Utility Index to measure quality-adjusted life-years.
resultsThe adjusted mean changes at 100 weeks in the best corrected visual acuity letter scores were as follows - ranibizumab, 12.5 letters (standard deviation 21.1 letters); aflibercept, 15.1 letters (standard deviation 18.7 letters); and bevacizumab, 9.8 letters (standard deviation 21.4 letters). Aflibercept was non-inferior to ranibizumab in the intention-to-treat population (adjusted mean best corrected visual acuity difference 2.23 letters, 95% confidence interval -2.17 to 6.63 letters; LIMITATIONS: The comparison of aflibercept and bevacizumab was a post hoc analysis.
conclusionThe study showed aflibercept to be non-inferior to ranibizumab. However, the possibility that bevacizumab is worse than ranibizumab and aflibercept by 5 visual acuity letters cannot be ruled out. Bevacizumab is an economically attractive treatment alternative and would lead to substantial cost savings to the NHS and other health-care systems. However, uncertainty about its relative effectiveness should be discussed comprehensively with patients, their representatives and funders before treatment is considered. FUTURE WORK: To obtain extensive patient feedback and discuss with all stakeholders future bevacizumab NHS use.
trial registrationCurrent Controlled Trials ISRCTN13623634.
fundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.