Systemic and ocular safety of intravitreal anti-VEGF therapies for ocular neovascular disease

Surv Ophthalmol. 2011 Mar-Apr;56(2):95-113. doi: 10.1016/j.survophthal.2010.08.006.


The treatment of ocular neovascular diseases is being revolutionized by intravitreal therapies targeting vascular endothelial growth factor (VEGF). Two agents are approved for treating neovascular age-related macular degeneration and are being evaluated for other retinal conditions: the RNA aptamer pegaptanib and the monoclonal antibody antigen-binding fragment ranibizumab. Bevacizumab, a related antibody, is being used similarly, although its use is off-label. Pegaptanib selectively binds to a VEGF isoform identified as being especially pathogenic in the eye and spares other isoforms, whereas the other two agents nonselectively bind all VEGF isoforms. Because VEGF is involved in a wide variety of physiologic processes, the ocular and systemic safety of anti-VEGF agents is of paramount concern. I provide an overview of safety data for intravitreal anti-VEGF therapies, focusing primarily on randomized, controlled trials. For pegaptanib, an accumulation of data from pivotal trials and a dedicated systemic safety study have revealed no ocular or systemic safety concerns. For ranibizumab, the principal ocular adverse event detected in clinical trials was a low frequency of ocular inflammation, and systemic adverse events included a slightly elevated risk of nonocular hemorrhage and stroke. Safety data from properly designed randomized controlled trials for bevacizumab are not available.

Publication types

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

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Aptamers, Nucleotide / adverse effects
  • Aptamers, Nucleotide / therapeutic use
  • Bevacizumab
  • Choroidal Neovascularization / drug therapy
  • Corneal Neovascularization / drug therapy
  • Eye / blood supply*
  • Glaucoma, Neovascular / drug therapy
  • Humans
  • Intravitreal Injections
  • Macular Degeneration / drug therapy
  • Neovascularization, Pathologic / drug therapy*
  • Randomized Controlled Trials as Topic
  • Ranibizumab
  • Retinal Neovascularization / drug therapy
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*


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