Implications of bevacizumab on vascular endothelial growth factor and endostatin in human choroidal neovascularisation

Br J Ophthalmol. 2009 Feb;93(2):159-65. doi: 10.1136/bjo.2008.138594. Epub 2008 Oct 6.

Abstract

Aim: To evaluate the implications of intravitreal bevacizumab on proangiogenic vascular endothelial growth factor (VEGF) with regard to the endogenous angiogenesis inhibitor endostatin in human choroidal neovascularisation (CNV) secondary to age-related macular degeneration.

Methods: Retrospective review of an interventional case series of 48 patients who underwent full macular translocation surgery with removal of CNV. Twenty-five patients were treated with intravitreal bevacizumab injection 1 to 154 days prior to surgery (bevacizumab CNV). Twenty-three CNV without any kind of previous treatment were used as controls (control CNV). CNV were stained for CD34, cytokeratin18, VEGF, endostatin and E-selectin. A "predominance score of VEGF over endostatin" (PS) was defined by the difference between VEGF and endostatin staining scores.

Results: Bevacizumab CNV revealed a weaker VEGF expression in endothelial cells (p = 0.0245) but significantly more intense endostatin in retina pigment epithelium (RPE) (p = 0.0001) and stroma (p<0.0001). Consequently, PS was significantly lower in RPE (p = 0.02), vessels (p = 0.03) and stroma (p = 0.0004) in bevacizumab CNV. The intensity of E-selectin expression in bevacizumab CNV was comparable with that in control CNV.

Conclusions: A shift within the angiogenic balance in terms of decreased VEGF predominance over endostatin is detected in human CNV treated with bevacizumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / metabolism
  • Choroidal Neovascularization / pathology
  • Choroidal Neovascularization / surgery
  • Combined Modality Therapy
  • E-Selectin / metabolism
  • Endostatins / metabolism*
  • Eye Proteins / metabolism
  • Female
  • Humans
  • Macular Degeneration / complications
  • Male
  • Middle Aged
  • Retinal Pigment Epithelium / metabolism
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • E-Selectin
  • Endostatins
  • Eye Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab