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Intravitreal bevacizumab (Avastin) versus ranibizumab (Lucentis) for the treatment of age-related macular degeneration: a safety review
  1. Christine Schmucker1,
  2. Yoon K Loke2,
  3. Christoph Ehlken3,
  4. Hansjuergen T Agostini3,
  5. Lutz L Hansen3,
  6. Gerd Antes1,
  7. Monika Lelgemann4
  1. 1German Cochrane Centre, University Medical Centre Freiburg, Freiburg, Germany
  2. 2School of Medicine, University of East Anglia, Norwich, UK
  3. 3University Eye Hospital, University Medical Centre Freiburg, Freiburg, Germany
  4. 4Health Technology Assessment Centre, University Bremen, Germany
  1. Correspondence to Christine Schmucker, German Cochrane Centre, Institute of Medical Biometry and Medical Informatics, Department of Medical Biometry and Statistics, University Medical Centre Freiburg, Berliner Allee 29, Freiburg 79110, Germany; schmucker{at}


Aim To conduct a systematic review in order to compare adverse effects (AE) and the reporting of harm in randomised controlled trials (RCTs) and non-RCTs evaluating intravitreal ranibizumab and bevacizumab in age-related macular degeneration.

Methods Medline, Embase and the Cochrane Library were searched with no limitations of language and year of publication. Studies which compared bevacizumab or ranibizumab as monotherapy with any other control group were included. Case series were included if they met predefined quality standards.

Results The 2 year results of phase III trials evaluating ranibizumab show that the rates of serious ocular AE were low (≤2.1%) but indicate major safety concerns (RR 3.13, 95% CI 1.10 to 8.92). A possible signal with regard to thromboembolic events (RR 1.35, 95% CI 0.66 to 2.77) and a significant increase in non-ocular haemorrhage (RR 1.62, 95% CI 1.03 to 2.55) were also noted. In contrast to ranibizumab trials, the RCTs evaluating bevacizumab are of limited value. The main shortcomings are small sample sizes and an apparent lack of rigorous monitoring for AE. A critical assessment of the large number of published case series evaluating bevacizumab also shows that no reliable conclusions on safety can be drawn using this study design. Therefore, any perception that intravitreal bevacizumab injections are not associated with major ocular or systemic AE are not supported by reliable data.

Conclusion The bevacizumab studies show too many methodological limitations to rule out any major safety concerns. Higher evidence from ranibizumab trials suggests signals for an increased ocular and systemic vascular and haemorrhagic risk which warrants further investigation.

  • systematic review
  • bevacizumab
  • ranibizumab
  • safety
  • retina
  • drugs
  • medical education

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  • Funding German health insurance fund (Verband der Ersatzkassen e. V. (vdek), Askanischer Platz 1, D-10963 Berlin, Germany).

  • Competing interests None.

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

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