Effect of bevacizumab on inflammation and proliferation in human choroidal neovascularization.
OBJECTIVE
To evaluate the effect of bevacizumab (Avastin; Genentech, Inc, South San Francisco, California) on inflammation and proliferation in human choroidal neovascularization (CNV) secondary to age-related macular degeneration.


METHODS
Retrospective review of interventional series of 38 patients who underwent choroidal neaovascular membrane (CNVM) extraction. Twenty-four patients received intravitreal bevacizumab 1 to 154 days preoperatively (bevacizumab CNV group). Fourteen patients received no preoperative therapy (control CNV group). The CNVM were stained for cytokeratin 18, CD68, CD45, intercellular adhesion molecule (ICAM)-1, E-selectin, Ki-67, Thy-1, and endostatin.


RESULTS
No significant difference was detected in ICAM-1 and E-selectin expression between groups. The density of leukocytes in the bevacizumab CNV group (median, 271.61 cells/mm(2)) was higher than in the control CNV group (median, 116.87 cells/mm(2); P = .07), but without significance. Density of macrophages (median, 4661.95 cells/mm(2)), proliferative activity (median, 160.19 cells/mm(2)), and percentage of Thy-1-expressing vessels (median, 100%) were significantly higher in the bevacizumab CNV group than in the control CNV group (median, 882.66 cells/mm(2), P < .001; median, 34.34 cells/mm(2), P < .001; and median, 80%, P < .001, respectively). Endostatin immunoreactivity was considerably stronger in the retina pigment epithelium (RPE)-Bruch membrane complex (median, 3; range, 2-3; P < .001), and stroma (median, 3; range, 1-3; P < .001) of the bevacizumab CNV group than control CNV group (median, 1.5; range, 0-3 and median, 1; range, 0-3, respectively).


CONCLUSIONS
Unexpectedly, CNVM from patients treated by bevacizumab are characterized by significantly high inflammatory and proliferative activity and enhanced endostatin expression. These characteristics need to be considered when protocols for combination therapies are established.
Tatar
Olcay
O
University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University, Tübingen.
Yoeruek
Efdal
E
Szurman
Peter
P
Bartz-Schmidt
Karl Ulrich
KU
Adam
Annemarie
A
Shinoda
Kei
K
Eckardt
Claus
C
Boeyden
Vicky
V
Claes
Carl
C
Pertile
Grazia
G
Scharioth
Gabor B
GB
Grisanti
Salvatore
S
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; D049109:Cell Proliferation / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D043169:Endostatins / Q000378:metabolism; D005260:Female; D006801:Humans; D007158:Immunologic Techniques; D007249:Inflammation / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D012189:Retrospective Studies; D013194:Staining and Labeling; D014018:Tissue Distribution
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D043169:Endostatins; D000068258:Bevacizumab