Implications of bevacizumab on vascular endothelial growth factor and endostatin in human choroidal neovascularisation.
OBJECTIVE
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.
University Eye Clinic at the Centre for Ophthalmology, Eberhard-Karls-University, Tuebingen, Germany.
O
O
Tatar
K
K
Shinoda
E
E
Kaiserling
C
C
Claes
C
C
Eckardt
T
T
Eckert
G
G
Pertile
V
V
Boeyden
G B
GB
Scharioth
E
E
Yoeruek
P
P
Szurman
K U
KU
Bartz-Schmidt
S
S
Grisanti
D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D003131:Combined Modality Therapy; D019040:E-Selectin / Q000378:metabolism; D043169:Endostatins / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000150:complications; D008297:Male; D008875:Middle Aged; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019040:E-Selectin; D043169:Endostatins; D005136:Eye Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab