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C. G. Wong, Y. Li, T. Lin, J. Burke, L. Wheeler, C. Ghosn; Experimental CNV in Cynomolgus Monkeys After Sustained Release of VEGF and bFGF Within the Suprachoroidal Space: A Proof of Concept Study. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3359.
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The goal of this study was to follow the natural history of experimental monkey CNV, induced by suprachoroidal sustained release of both VEGF and bFGF.
In this pilot monkey study (N = 5), either non-biodegradable placebo or VEGF/bFGF implants, shown to produce in the rabbit progressive CNV after suprachoroidal implantation (Zahn et al.), were used. One monkey eye initially was implanted with the VEGF/bFGF pellet to establish the procedure and define preliminary histology. In the other monkeys (N = 4) subsequent implants, 1x or 2x VEGF/bFGF in the OD eyes or placebo in the OS eyes, were placed suprachoroidally within 2 disc diameters of the macula at the 10 or 2 o’clock position. One day post implant using a Krypton-red laser, 3 spots were placed on retinas next to each pellet. In the following 14 weeks (wk), monkeys were anesthetized and monitored with color fundus photography, fluorescein angiography (Zeiss) and spectral domain OCT (Topcon) to evaluate CNV development. mfERG’s were performed at 3, 6 & 10 wks post implant with contact lens electrodes and a fundus camera stimulator (Veris). At either wk 7 or wk 14, eyes were enucleated for histology.
Fluorescein leakage was seen around the laser spots and above the implants in all eyes that had VEGF/bFGF implants from wk 1 up to wk 14 with varying intensities, which were not consistent with growth factor levels. Fluorescein leakage was not observed in placebo-implanted eyes. In 2 eyes the florid leak peaked at wk 8 and included vessel tortuosity. In the other 2 eyes, leakage was less and the pattern was reminiscent of polypoidal choroidal vasculopathy. OCT demonstrated that the area above the pellet increased with time with a peak at week 8. In addition, mfERGs indicated abnormalities consistent in clinical evaluations of patients with AMD. Initial histology evaluation confirmed the existence of intrachoroidal neovascularization.
Data from this initial pilot study with five animals indicates that experimental intra-CNV can be induced in the non-human primate eye through a VEGF/bFGF implant within the suprachoroidal space.
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