May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
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
Author Affiliations & Notes
  • C. G. Wong
    Ophthalmic Drug Dev, SCLERA LLC, Carlsbad, California
  • T. Fedoruk
    Ophthalmic Drug Dev, SCLERA LLC, Carlsbad, California
  • M. Bonakdar
    Ophthalmic Drug Dev, SCLERA LLC, Carlsbad, California
  • T. T. You
    Consulting, Orange County, California
  • Footnotes
    Commercial Relationships C.G. Wong, SCLERA LLC/Univ California, P; T. Fedoruk, None; M. Bonakdar, None; T.T. You, SCLERA, C.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1786. doi:https://doi.org/
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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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: 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).

Methods:: 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.

Results:: 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.

Conclusions:: 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.

Keywords: age-related macular degeneration • choroid: neovascularization • growth factors/growth factor receptors 
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