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Implications of bevacizumab on vascular endothelial growth factor and endostatin in human choroidal neovascularisation
  1. O Tatar1,
  2. K Shinoda2,
  3. E Kaiserling3,
  4. C Claes4,
  5. C Eckardt5,
  6. T Eckert5,
  7. G Pertile6,
  8. V Boeyden4,
  9. G B Scharioth7,
  10. E Yoeruek1,
  11. P Szurman1,
  12. K U Bartz-Schmidt1,
  13. Tuebingen Bevacizumab Study Group1,
  14. S Grisanti8
  1. 1
    University Eye Clinic at the Centre for Ophthalmology of the Eberhard-Karls-University, Tuebingen, Germany
  2. 2
    Laboratory of Visual Physiology, National Institute of Sensory Organs, Tokyo, Japan
  3. 3
    Department of Pathology, Eberhard-Karls University, Tuebingen, Germany
  4. 4
    AZ- Sint Augustinus Hospital, Department Achtersegment, Antwerp, Belgium
  5. 5
    Augenklinik der Staedtischen Kliniken, Frankfurt am Main, Germany
  6. 6
    Department of Ophthalmology, Sacro Cuore Hospital, Negrar, Italy
  7. 7
    Augenzentrum Recklinghausen, Germany
  8. 8
    Department of Ophthalmology at the University of Luebeck, Luebeck, Germany
  1. Professor S Grisanti, Department of Ophthalmology at the University of Luebeck, Luebeck Germany, Ratzeburger Allee 160, 23538 Luebeck, Germany; salvatore.grisanti{at}uk-sh.de

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.

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Footnotes

  • Funding: Grant Support: Vision 100 Foundation and Jung Foundation.

  • Competing interests: None.

  • Ethics approval: Ethics approval was provided by the Ethics Committee of the University of Tuebingen.

  • Patient consent: Obtained.