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Study finds high inflammation, proliferation in bevacizumab-treated CNV patients

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Choroidal neovascular membrane in patients with age-related macular degeneration treated with bevacizumab appears to have significantly high inflammatory and proliferative properties, as well as an enhanced expression of endostatin, a retrospective, multinational study found. These characteristics should be taken into consideration when establishing protocols for bevacizumab combination therapies, the authors noted.

"The results of this study ... were truly unexpected and appear to be, to some extent, paradoxical to the inhibition of angiogenesis," they said.

Olcay Tatar, MD, and colleagues evaluated the effect of Avastin (bevacizumab, Genentech) on inflammation and proliferation after performing CNV membrane extraction on 38 patients with CNV due to AMD. Specifically, 24 patients received intravitreal bevacizumab 1 to 154 days preoperatively, and 14 controls received no preoperative therapy. All CNV membrane were stained for cytokeratin 18, CD68, CD45, intercellular adhesion molecule-1 (ICAM-1), E-selectin, Ki-67, Thy-1 and endostatin.

The investigators found no significant difference between groups in ICAM-1 and E-selectin expression.

While the median density of leukocytes in the bevacizumab group (271.61 cells/mm²) was higher than in controls (116.87 cells/mm²), the difference was not significant, the authors noted.

However, the median densities of macrophages (4,661.95 cells/mm²), proliferative activity (160.19 cells/mm²) and the median percentage of Thy-1-expressing vessels (100%) were significantly higher in the bevacizumab group than in the control group (882.66 cells/mm², 34.34 cells/mm² and 80%, respectively; P < .001 for all).

In addition, the median endostatin immunoreactivity was considerably stronger in the retina pigment epithelium-Bruch membrane complex and stroma of the bevacizumab group than in controls (P < .001 for both), according to the study.

The study is published in the June issue of Archives of Ophthalmology.