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Emily Han Shao, Ying L Dong, Reena Dave, Simon Richard Taylor, Vasuki Sivagnanavel; Rebound increase in VEGF levels following intravitreal injection of bevacizumab in a child. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1939.
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Vascular endothelial growth factor (VEGF) is one of the most potent cytokines targeted in anti-angiogenic therapies and anti-VEGF agents have become widely used in the treatment of macular degeneration and retinal vascular disease. However, the effects of intraocular administration of anti-VEGF drugs on systemic levels remain controversial. This may be important, as VEGF is essential for angiogenesis and thus the function of the developing brain, lung, and kidneys in children, as well as in maintaining normal organ function in adults. In this study we analysed systemic changes in VEGF levels in a child with congenital toxoplasmosis who was treated with a course of bevacizumab injections for a secondary choroidal neovascular membrane.
Serum samples were obtained from a nine-year-old child with a choroidal rupture from blunt trauma, who developed a secondary choroidal neovascular membrane and was then treated with 5 bevacizumab injections over a period of 12 months. Peripheral venous blood samples were taken at each visit and centrifuged at 3,000 rpm for 10 minutes followed by being stored at - 70°C until analysis. Serum VEGF 165 levels were determined using enzyme-linked immunosorbent assay (R&D systems, UK) both pre and post immunodepletion to remove complexed VEGF.
Serum VEGF 165 levels were initially suppressed by intravitreal bevacizumab, with levels remaining low for 11 weeks after the end of the first course of two injections (Figure 1). Levels then rebounded significantly and remained high despite three further intravitreal bevacizumab injections, before returning to baseline at 12 months.
These results suggest that repeated intravitreal bevacizumab injections initially lead to a decrease in systemic VEGF levels, but that there may be a later rebound increase to above baseline levels. This may be of particular clinical significance in children as VEGF is vital in the development of major organs, but VEGF metabolism is also known to be important in the maintenance of normal organ function in adults.
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