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Y. H. Yoon, J. Lee, J.-G. Kim, H. Chung, J. Chae, S. Yang; The Effects of Bevacizumab on the Vessel Development in Normal Rat and Model of Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):46.
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Use of anti-vascular endothelial growth factor (VEGF) antibody has become an alternative or adjunctive treatment option for the various angiogenic disorders. Also, recent study has reported that intravitreal injection of bevacizumab for retinopathy of prematurity (ROP) showed promising clinical results of reduced neovascularization (NV) without apparent ocular or systemic adverse effects. The present study examined the potential toxicity of the inhibition of VEGF signaling after intracardiac bevacizumab injection in normal rat and oxygen-induced retinopathy (OIR) model.
OIR was induced in postnatal day 5 (P5) rat pups by raising them in 75±5% hyperoxic conditions for 7 days and in normoxic conditions for the next 5 days. Dextran fluorescence retinal angiography was used to quantitatively assess OIR. Animals were divided in three groups: group 1 that received intracardiac bevacizumab (0.25mg/0.01ml per gram), group 2 that received no treatment after hyperoxic condition, group 3 that raised in normoxic condition and received intracardiac bevacizumab (0.25mg/0.01ml per gram). Bevacizumab injection was done once daily from P6 to P7. Severity of NV, retinal vascular area, and retinal vascular density were scored in a masked manner.
The mean score (±standard deviation) of the retinopathy in group 1 (4.6±2.6, n=5), group 2 (3.0±0.7, n=5), and group 3 (5.5±3.7, n=4) did not show statistically difference among the groups. However, in group that raised in normoxic condition and received intracardiac bevacizumab showed comparable retinal ischemic changes, such as blood vessel tufts, central vasoconstriction and blood vessel tortuosity.
These findings confirm that inhibition of VEGF signaling in developing period of normal retinal vasculature causes normal retinal vessel growth inhibition. Thus, high dose bevacizumab may be harmful especially in the premature retina and in treating ROP patients with anti-VEGF drugs, caution may be needed to prevent the inhibition of retinal normal vessel development. Also, early treatment with bevacizumab in OIR model has no beneficial effect on retinal neovascularization.
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