Implications of bevacizumab on vascular endothelial growth factor and endostatin in human choroidal neovascularisation
- O Tatar1,
- K Shinoda2,
- E Kaiserling3,
- C Claes4,
- C Eckardt5,
- T Eckert5,
- G Pertile6,
- V Boeyden4,
- G B Scharioth7,
- E Yoeruek1,
- P Szurman1,
- K U Bartz-Schmidt1,
- Tuebingen Bevacizumab Study Group1,
- S Grisanti8
- 1University Eye Clinic at the Centre for Ophthalmology of the Eberhard-Karls-University, Tuebingen, Germany
- 2Laboratory of Visual Physiology, National Institute of Sensory Organs, Tokyo, Japan
- 3Department of Pathology, Eberhard-Karls University, Tuebingen, Germany
- 4AZ- Sint Augustinus Hospital, Department Achtersegment, Antwerp, Belgium
- 5Augenklinik der Staedtischen Kliniken, Frankfurt am Main, Germany
- 6Department of Ophthalmology, Sacro Cuore Hospital, Negrar, Italy
- 7Augenzentrum Recklinghausen, Germany
- 8Department of Ophthalmology at the University of Luebeck, Luebeck, Germany
- 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
- Accepted 17 September 2008
- Published Online First 6 October 2008
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.
Footnotes
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Funding: Grant Support: Vision 100 Foundation and Jung Foundation.
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Competing interests: None.
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Ethics approval: Ethics approval was provided by the Ethics Committee of the University of Tuebingen.
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Patient consent: Obtained.
