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N. Ianopol, B. Kirchhof; Modulation of Fibrosis and Neovascularization by Bevacizumab Anti-VEGF Blockade in Proliferative Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5052.
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Clinical observation is inconclusive whether Bevacizumab (B) stimulates or inhibits fibrosis in proliferative diabetic retinopathy (PDR). We therefore analyze the evolution of intra- / epiretinal fibrosis and neovascularization after anti-VEGF blockade realized by intravitreally injected Bevacizumab (ivit B) in PDR.
5 eyes with PDR receiving one or several intravitreal doses of 1.25mg or 2.5mg of B were followed up between 1-17 months. The evolution of fibrosis and neovascularization was assessed prior to and post ivit B, qualitatively and quantitatively. We used the colored fundus images (FI) and black white ones, recorded during red-free examination (RFI) and fluorescein angiography (FAI). The quantitative analysis consisted of measurements of the area covered by "white lesions" inside a standardized retinal area, concentric to the optic disc. The results were presented in pixels. The change in the area of "white lesions" in FAI and RFI revealed change of fibrosis and/or of neovascularization.
In all 5 eyes, the qualitative assessment of FI revealed that the neovascularization regressed continuously. The quantitative interpretation was realized on the fundus photographs of 2 eyes describing 2 different categories of situations observed in PDR. One eye was characterized by delicate fibrosis accompanying fine neovascular network. In this case, the number of "white pixels" on FAI decreased after ivit B, demonstrating that the neovascularization and fibrosis regress after ivit B. On RFI, the number of "white pixels" increased in the same standardized retinal area. This aspect was explained by the fact that before ivit B, when neovascularization is active, the blood flow masks the fibrotic new vessels walls. When the neovascularization quieted as the effect of anti-VEGF blockade, the fibrotic neovascular walls appeared visible as "fibrotic tissue". The regression of both proliferative tissues in PDR, neovascularization and fibrosis, was revealed by the 2nd eye, characterizing the category of cases in which heavy fibrosis accompanies strong new vessels. In this case, the measurements performed on both examinations, RFI and FAI, showed a continuous decrease of number of "white pixels".
Ivit B induces regression of neovascularization correlated to a maturation of fibrosis similar to the processes observed in the wound healing. Further research is necessary to investigate microscopically the phenomena.
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