A systematic review of the adverse events of intravitreal anti-vascular endothelial growth factor injections

Retina. 2011 Sep;31(8):1449-69. doi: 10.1097/IAE.0b013e3182278ab4.


Background: Intravitreal ranibizumab and pegaptanib are registered for neovascular age-related macular degeneration. No formal safety study has been conducted for intravitreal bevacizumab. These anti-vascular endothelial growth factor (anti-VEGF) drugs are being used on a large scale in daily practice for different ocular diseases. The objective of the present study was to systematically assess and compare the incidences of adverse events of anti-VEGFs.

Methods: A systematic search was conducted in April 2009 with no date restrictions in PubMed, Embase, Toxline, and the Cochrane library. We used the terms pegaptanib, bevacizumab, ranibizumab, intravitreal, and specific and general terms for adverse events. Studies describing adverse events after anti-VEGF injections and the official safety data were included.

Results: Two hundred and seventy-eight articles were included, and the incidences of adverse events were calculated separately for effect, safety, and specific side effect studies. The incidences of serious ocular and nonocular adverse events were approximately below 1 per 100 injections for intravitreal bevacizumab, intravitreal ranibizumab, and intravitreal pegaptanib. Most mild ocular adverse events were below 5 per 100 injections.

Conclusion: The reported rates of serious adverse events were low after anti-VEGF injections. There is no sufficient evidence to conclude that there is a difference in incidences between the anti-VEGFs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects*
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Aptamers, Nucleotide / adverse effects*
  • Bevacizumab
  • Humans
  • Incidence
  • Intravitreal Injections
  • Macular Degeneration / drug therapy
  • Ranibizumab
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Aptamers, Nucleotide
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • pegaptanib
  • Bevacizumab
  • Ranibizumab