Immunohistopathologic Evaluation of Choroidal Neovascular Membranes Following Intravitreal Bevacizumab (Avastin®) Therapy

Abstract

Purpose: : Recently, intravitreal injection of anti–angiogenic agents, especially those inhibiting vascular endothelial growth factor (VEGF), has been in use as a treatment modality for neovascular age–related macular degeneration (AMD). We aimed to evaluate the impacts of intravitreally injected bevacizumab (Avastin), a recombinant humanized monoclonal anti–VEGF antibody, on proliferative activity, inflammatory cell infiltration and VEGF expression in human choroidal neovascularization membranes (CNV).

Methods: : Retrospective review of an interventional case series of five patients (five eyes) who underwent removal of CNV. CNV was secondary to AMD in all cases. Five patients were treated with intravitreally applied bevacizumab (1 mg) 3 to 43 days before surgery. CNV were stained for CD34, CD105, CD68, CD45, cytokeratin18, Ki–67 and VEGF.

Results: : Specimens were highly cellular and vascularized with healthy, activated, proliferating endothelial cells. All CNV were inflammatory active characterized by intense CD68 expression in retinal pigment epithelium (RPE) layer and stromal cells and prominent infiltration with CD45 expressing cells supposed to be leukocytes. High proliferative activity (range: 170.89 –806.39 Ki–67 expressing nuclei / mm2, median :209.98) was detected in all membranes. Moderate to intense VEGF expression was detected in stromal cells of the three membranes. RPE cells expressed VEGF weakly in four CNV. Histological findings did not show a chronological change.

Conclusions: : CNV membranes treated by intravitreal bevacizumab seem to be inflammatory active with high proliferative activity. VEGF, when detected, is expressed mostly by proliferating stromal cells rather than RPE or EC.

Keywords: age-related macular degeneration • choroid: neovascularization • growth factors/growth factor receptors