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S.J. Wiegand, R. Dubielzig, E.P. Zimmer, T.M. Nork, P.E. Miller, B.J. Christian, J. Cao, J. Cedarbaum, G.D. Yancopoulos, E. Furfine; Histologic Evaluation of Laser–Induced Choroidal Neovascularization (CNV) in Primates Receiving Intravitreal Injections of VEGF Trap: Correlation With Fluorescein Angiography . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2188.
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To evaluate the effect of VEGF Trap on the histological development and regression of choroidal neovascular lesions in a primate model of laser–induced CNV.
Nine small, laser burns were made in the retinas of adult cynomolgus macaques. Fluorescein angiography (FA) was performed 15, 20 and 29 days later, and CNV lesions were graded on a scale of 1 (no hyperfluorescence) to 4 (hyperfluorescence, with late leakage beyond the lesion). VEGF Trap was administered by intravitreal injection (50, 250 or 500 mcg/eye) every two weeks, beginning one week before laser injury (prevention study). Alternatively, a single intravitreal injection (500 mcg) was given two weeks following laser, after active CNV had formed (treatment study). Control animals received intravitreal placebo injections. Animals were humanely euthanized on day 35, and perfused through the carotid with Karnovsky's fixative. Eyes were post–fixed for 2–3 days, and stored in formalin until processed. Each laser burn was individually sampled and graded histologically for evidence of tissue proliferation and neovascular membrane formation.
In the prevention study, Grade 4 lesions developed at 27% of the burn sites in animals receiving placebo, but only 2% of sites in animals receiving VEGF Trap, across all doses tested. Remarkably, a single injection of VEGF Trap, given following the development of active CNV, reduced the frequency of Grade 4 lesions from 44% to 0% within 2 weeks. Histological evaluation of the retinas showed decreased scores for morphologic features indicative of tissue proliferation in all VEGF Trap treated groups. Choroidal fibroplasia, retinal elevation and particularly neovascular membranes were markedly reduced, even when treatment was initiated after the formation of active lesions.
Consonant with the FA findings, histological evaluation revealed that intravitreal administration of VEGF Trap markedly reduced proliferative responses of the retina to laser injury, particularly neovascular proliferation. Histological scores were similarly reduced when VEGF Trap treatment was begun prior to laser injury, or when a single injection of VEGF Trap was given after Grade 4 lesions had developed, indicating that VEGF Trap not only prevented the development, but also induced regression of newly formed neovascular membranes.
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