Altered vascular microenvironment by bevacizumab in diabetic fibrovascular membrane

PURPOSE: The purpose of this study was to evaluate the impact of intravitreal bevacizumab (IVB) on three cellular components (vascular endothelial cells, pericytes, and myofibroblasts) of the vascular microenvironment in fibrovascular membranes (FVMs) of patients with proliferative diabetic retinopathy. METHODS: Immunohistological studies with antibodies of CD34, αSMA, and transforming growth factor-β were performed on 20 surgical specimens obtained during a pars plana vitrectomy from 8 IVB-treated eyes, whereas 12 remained untreated. Four different indexes of vascular phenotype (vascular area, vascular major axis, CD34 endothelial area, and blood vessel density) and αSMA expression in vascular and stromal components were quantitatively analyzed. RESULTS: The intraluminal area of blood vessels, CD34 endothelial area, and the blood vessel density in IVB-treated FVMs were significantly less than in untreated FVMs. The number of CD34 blood vessels in IVB-treated FVMs was similar to that in untreated FVMs. Intravitreal bevacizumab could not affect vascular and stromal αSMA area significantly. However, the ratio of vascular αSMA area/CD34 area was significantly higher in IVB-treated FVMs than in untreated FVMs. Transforming growth factor-β expression could be observed in the IVB-treated FVM. CONCLUSION: Intravitreal bevacizumab might primarily affect blood vessels, and the effects on pericytes and myofibroblasts might be secondary. Intravitreal bevacizumab treatment regulates vascular microenvironment by the contraction of blood vessels, the increasing pericyte ratio, and transforming growth factor-β expression in FVMs of patients with proliferative diabetic retinopathy.