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S.J. Wiegand, E. Zimmer, T.M. Nork, P.E. Miller, B.J. Christian, J.M. Miller, J. Cao, J. Cedarbaum, G.D. Yancopoulos, E. Furfine; VEGF Trap Both Prevents Experimental Choroidal Neovascularization and Causes Regression of Established Lesions in Non–Human Primates . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1411. doi: https://doi.org/.
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Purpose: To evaluate the safety and efficacy of systemic and intravitreal administration of the VEGF Trap, a potent VEGF inhibitor composed of ligand–binding portions of human VEGF receptor–1 (VEGFR–1) and VEGFR–2 fused to the Fc segment of IgG1, in a primate model of choroidal neovascularization (CNV). Methods: The effect of VEGF Trap treatment on laser–induced choroidal neovascularization was evaluated in adult cynomolgus monkeys. Each animal received nine small, intense laser burns to each retina, and the development of active choroidal neovascular lesions was assessed by fluorescein angiography (FA), once before injury and 15, 20 and 29 days post–laser. In the prevention study, VEGF Trap was administered by intravenous (3 or 10 mg/kg, weekly) or intravitreal injection (50, 250 or 500 mcg/eye, every two weeks), beginning one week before laser injury. In the regression study, a single intravitreal injection (500 mcg) was given two weeks following laser, at which time active CNV had already formed. Control animals received weekly intravenous or biweekly intravitreal injections of placebo beginning one week before laser. Each of the above experimental and control groups comprised six animals, 3 males and 3 females. CNV lesions were visualized by FA and graded by a masked observer from Grade I (no hyperfluorescence) to Grade IV (bright hyperfluorescence with late leakage extending beyond the borders of the laser spot). Results: Active CNV lesions (Grade 4), developed at 32% and 48% of the laser burn sites in animals receiving intravitreal or intravenous administration of placebo, respectively. In contrast, the development of Grade 4 lesions was completely or nearly completely prevented in all groups of animals receiving intravenous or intravitreal injections of the VEGF Trap. Moreover a single intravitreal injectionof VEGF Trap (500 mcg) administered following the development of active CNV, reduced the frequency of Grade 4 lesions from 44% to 0% within 14 days of treatment. Conclusions: Administration of VEGF Trap prevented the development of clinically significant Grade 4 CNV following laser injury when administered at the lowest doses tested (50 mcg x 2 weeks intravitreally; or 3 mg/kg/wk, IV). Moreover, a single intravitreal injection of 500 mcg induced rapid and complete regression of established, active CNV.
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