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Comparative effectiveness and harms of intravitreal antivascular endothelial growth factor agents for three retinal conditions: a systematic review and meta-analysis
  1. Allison Low1,
  2. Ambar Faridi2,3,
  3. Kavita V Bhavsar2,3,
  4. Glenn C Cockerham4,
  5. Michele Freeman1,
  6. Rochelle Fu5,6,
  7. Robin Paynter1,
  8. Karli Kondo1,6,
  9. Devan Kansagara1,5,7
  1. 1 Evidence-based Synthesis Program, VA Portland Health Care System, Portland, Oregon, USA
  2. 2 Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science University, Portland, Oregon, USA
  3. 3 Operative Care Division, Department of Ophthalmology, VA Portland Health Care System, Portland, Oregon, USA
  4. 4 Veterans Health Administration Ophthalmology Service, Department of Veterans Affairs, Palo Alto, California, USA
  5. 5 Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon, USA
  6. 6 Oregon Health & Science University-Portland State University School of Public Health, Portland, Oregon, USA
  7. 7 Department of Medicine, VA Portland Healthcare System, Portland, Oregon, USA
  1. Correspondence to Allison Low, Evidence-based Synthesis Program, VA Portland Health Care System, Portland, OR 97239, USA; low{at}


Intravitreal antivascular endothelial growth factor (VEGF) agents are widely used to treat ocular conditions but the benefits and harms of these treatments are uncertain. We conducted a systematic review to compare the effects of aflibercept, bevacizumab and ranibizumab on best-corrected visual acuity (BCVA) changes, quality of life and ocular or systemic adverse events in patients with neovascular age-related macular degeneration (NVAMD), diabetic macular oedema (DME) and central or branch retinal vein occlusion (RVO). We searched published and unpublished literature sources to February 2017 for randomised controlled trials and cohort or modelling studies reporting comparative costs in the USA. Two reviewers extracted data and graded the strength of the evidence using established methods. Of 17 included trials, none reported a clinically important difference (≥ 5 letters) in visual acuity gains between agents. Nine trials provide high-strength evidence of no difference between bevacizumab and ranibizumab for NVAMD. Three trials provide moderate-strength evidence of no difference between bevacizumab and ranibizumab for DME. There was low-strength evidence of similar effects between aflibercept and ranibizumab for NVAMD, aflibercept and bevacizumab for RVO and all three agents for DME. There was insufficient evidence to compare bevacizumab and ranibizumab for RVO. Rates of ocular adverse events were low, and systemic harms were generally similar between groups, although 1 DME trial reported more arterial thrombotic events with ranibizumab versus aflibercept. Overall, no agent had a clear advantage over another for effectiveness or safety. Aflibercept and ranibizumab were significantly less cost-effective than repackaged bevacizumab in two trials. Systematic review registration number: CRD42016034076.

  • Anti-VEGF therapy
  • age-related macular degeneration
  • central or branch retinal vein occlusion
  • diabetic macular edema
  • aflibercept
  • bevacizumab
  • ranibizumab

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  • Contributors AL, AF, KVB, DK, GCC contributed to the planning, conduct and reporting of this manuscript. RF conducted the meta-analyses. RP, MF and KK contributed to data collection, analyses and reporting.

  • Funding This research was funded by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative.

  • Disclaimer No investigators have any affiliations or financial involvement (e.g., employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties) that conflict with material presented in the report.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No individual participant data were used in this work. Additional data not included in this work: a list of all citations identified by the literature search, including studies that were excluded from the systematic review, may be made available on request to anyone who wishes to access the data for any purpose by contacting the corresponding author by email. Data may be made available immediately after publication, no end date. The protocol for this work is available on PROSPERO Registration Number: CRD42016034076.