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Effect of Bevacizumab on Inflammation and Proliferation in Human Choroidal Neovascularization
Olcay Tatar, MD;
Efdal Yoeruek, MD;
Peter Szurman, MD;
Karl Ulrich Bartz-Schmidt, MD; for the Tübingen Bevacizumab Study Group;
Annemarie Adam, MTA;
Kei Shinoda, MD, PhD;
Claus Eckardt, MD;
Vicky Boeyden, MD;
Carl Claes, MD;
Grazia Pertile, MD;
Gabor B. Scharioth, MD;
Salvatore Grisanti, MD
Arch Ophthalmol. 2008;126(6):782-790.
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/mm2) was higher than in the control CNV group (median, 116.87 cells/mm2; P = .07), but without significance. Density of macrophages (median, 4661.95 cells/mm2), proliferative activity (median, 160.19 cells/mm2), 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/mm2, P < .001; median, 34.34 cells/mm2, 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.
Author Affiliations: University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University, Tübingen (Drs Tatar, Yoeruek, Szurman, Bartz-Schmidt, and Grisanti), Department of Pathology, University of Tübingen (Ms Adam), Augenklinik der Staedtischen Kliniken, Frankfurt am Main (Dr Eckardt), and Augenzentrum Recklinghausen, Recklinghausen, Germany (Dr Scharioth); Laboratory of Visual Physiology, National Institute of Sensory Organs, Tokyo, Japan (Dr Shinoda); Algemeen Ziekenhuis Sint Augustinus Hospital, Department Achtersegment, Antwerp, Belgium (Drs Boeyden and Claes); and Department of Ophthalmology, Sacro Cuore Hospital, Negrar, Italy (Dr Pertile). Dr Grisanti is now with the Department of Ophthalmology, University of Lübeck, Lübeck, Germany.
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