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C. G. Wong, T. Fedoruk, M. Bonakdar, T. T. You; Comparison of Lucentis and Avastin in the Suprachoroidal VEGF/bFGF-Implant Rabbit CNV Model Provides a Potential Standardized Pre-Clinical Approach in the Rational Development of More Effective QSAR-Based Drugs, Sustained Release Formulations, & Drug Delivery Systems for Ameliorating AMD. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1786.
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The goal of this study is to compare the actions of Lucentis and Avastin on the various neovascular lesions that are induced by a suprachoroidal VEGF/bFGF implant in an experimental rabbit model of choroidal neovascularization (CNV). This approach provides a tool for standardizing pre-clinical studies in the development of more effective therapeutics against aging-related macular degeneration (AMD).
Both color fundus and fluorescein angiographic (FA) images were captured by a TOPCON 50EX digital IMAGEnet retinal camera system on adult female New Zealand white rabbits (N=13) with experimental CNV, which was induced by suprachoroidal implantation of a non-biodegradable 1 mm Hydron pellet to provide sustained release of both VEGF and bFGF (Wong et al., 2001 Curr Eye Res). Four preliminary arms include: (a) Positive/negative controls; (b) Prophylactic arm with 1 IVT injection at time of implant; (c) Prophylactic arm with 2 IVT injections at both time of implant and 1 wk later; (d) Therapeutic arm with 1 IVT injection at 2 weeks after VEGF/bFGF implantation with established presence of both fluid accumulation and leakage. Resulting lesions were evaluated over a 30-day period.
CNV lesions developed reproducibly in all positive controls (N = 3) between 7 and 11 days after VEGF/bFGF pellet implantation. These lesions showed no signs of regression while the negative blank pellet control (N = 1) displayed neither leakage nor fluid accumulation. Avastin appeared to delay onset of experimental CNV with either 1 or 2 IVT injections and ameliorated leakage when injected after onset of CNV while Lucentis reversed lesions after onset.
Effectiveness, ease, and reproducibility of the suprachoroidal VEGF/bFGF rabbit CNV model in the assessment of Lucentis and Avastin therapeutic activities suggest practical approaches for standardizing future pre-clinical studies. Further studies in comparing the therapeutic effectiveness of Avastin with Lucentis during experimental CNV progression after sustained release of VEGF and bFGF in the suprachoroidal space will establish a rational basis for selective QSAR development of novel drugs, formulations, and delivery device systems in the amelioration and ultimate prevention of AMD.
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