Electrophysiologic and retinal penetration studies following intravitreal injection of bevacizumab (Avastin)

Retina. 2006 Mar;26(3):262-9. doi: 10.1097/00006982-200603000-00002.

Abstract

Purpose: Intravitreal bevacizumab (Avastin; Genentech Inc., San Francisco, CA) is a new treatment for age-related macular degeneration. The aim of this study was to evaluate retinal penetration and toxicity of bevacizumab.

Methods: Ten albino rabbits were injected intravitreally with 0.1 mL (2.5 mg) of Avastin into one eye and 0.1 mL saline into the fellow eye. The electroretinogram (ERG) was recorded after 3 hours, 3 days, and 1, 2, and 4 weeks. The visual evoked potential (VEP) was recorded after 4 weeks. Confocal immunohistochemistry was used to assess retinal penetration.

Results: The ERG responses of the control and experimental eyes were similar in amplitude and pattern throughout the follow-up period. The flash VEP responses of the experimental eyes were of normal pattern and amplitude and did not differ from those recorded by stimulation of the control eye alone. Full thickness retinal penetration was present at 24 hours and was essentially absent at 4 weeks.

Conclusions: Bevacizumab was found to be nontoxic to the retina of rabbits based on electrophysiologic studies. Full thickness retinal penetration may explain observed clinical effects of intravitreal bevacizumab. Although it is difficult to directly extrapolate to humans, our study supports the safe use of intravitreal bevacizumab injection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / toxicity*
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Drug Evaluation, Preclinical
  • Electroretinography / drug effects
  • Evoked Potentials, Visual / drug effects
  • Fluorescent Antibody Technique, Indirect
  • Injections
  • Rabbits
  • Retina / drug effects
  • Retina / metabolism*
  • Retina / physiology
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism
  • Vascular Endothelial Growth Factor A / immunology
  • Vitreous Body

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab