May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Toxicity, Pharmacokinetics, and Effect on Growth of Leptospires of a Novel Bioerodible Suprachoroidal Cyclosporine Implant for Uveitis
Author Affiliations & Notes
  • B.C. Gilger
    Clinical Sciences, North Carolina State University, Raleigh, NC
  • J.H. Salmon
    Clinical Sciences, North Carolina State University, Raleigh, NC
  • H. Kim
    National Eye Institute,
    National Institutes of Health, Bethesda, MD
  • S. Kim
    National Eye Institute,
    National Institutes of Health, Bethesda, MD
  • P. Yuan
    Pharmacy Department,
    National Institutes of Health, Bethesda, MD
  • S.S. Lee
    National Eye Institute,
    National Institutes of Health, Bethesda, MD
  • S.M. Harrington
    Department of Laboratory Medicine,
    National Institutes of Health, Bethesda, MD
  • P.R. Murray
    Department of Laboratory Medicine,
    National Institutes of Health, Bethesda, MD
  • K.G. Csaky
    National Eye Institute,
    National Institutes of Health, Bethesda, MD
  • M.R. Robinson
    National Eye Institute,
    National Institutes of Health, Bethesda, MD
  • Footnotes
    Commercial Relationships  B.C. Gilger, None; J.H. Salmon, None; H. Kim, None; S. Kim, None; P. Yuan, None; S.S. Lee, None; S.M. Harrington, None; P.R. Murray, None; K.G. Csaky, None; M.R. Robinson, None.
  • Footnotes
    Support  NIH Contract, Equine Uveitis Research Fund, State of North Carolina
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 5128. doi:
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      B.C. Gilger, J.H. Salmon, H. Kim, S. Kim, P. Yuan, S.S. Lee, S.M. Harrington, P.R. Murray, K.G. Csaky, M.R. Robinson; Toxicity, Pharmacokinetics, and Effect on Growth of Leptospires of a Novel Bioerodible Suprachoroidal Cyclosporine Implant for Uveitis . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5128.

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

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Abstract

Purpose: : The purpose of this study was to determine the safety and pharmacokinetics of a sustained release cyclosporine (CsA) device placed in the suprachoroidal space in an animal that develops naturally–occurring uveitis.

Methods: : Normal horses were implanted with a 6 mm diameter matrix–reservoir bioerodible CsA implant under a superior–temporal scleral flap in contact with the suprachoroidal space. The animals were examined for signs of toxicity and euthanized at 3, 9, and 12 weeks. CsA levels in ocular tissues, ocular fluids, and whole blood were measured by HPLC. Eyes and peripheral organs were evaluated histologically for signs of toxicity. Leptospira interrogans serotype pomona growth was determined in vitro when cultured with CsA.

Results: : CsA implants placed in the suprachoroidal space resulted in high levels of CsA in most ocular tissues (e.g., ciliary body: 0.028+/–0.002 ug/mg; superior retina/choroid: 0.076+/–0.006 ug/mg; Optic nerve: 0.096+/–0.065 ug/mg). Mean vitreous concentrations were 0.20+/–0.14 ug/ml at 4 weeks and 0.14+/–SD 0.04 ug/ml at 9 weeks. Peripheral blood CsA blood levels were below detection. No evidence of ocular toxicity was observed clinically or histologically. No peripheral organ abnormalities were observed. CsA was rapidly bactericidal at a concentration of 50 ug/ml and bacteristatic for seven days at 25 ug/ml when cultured in vitro with leptospires.

Conclusions: : Placing a CsA releasing device in the suprachoroidal space was effective in achieving ocular CsA concentrations without signs of toxicity in horses. Concentrations of CsA achieved in the eye with the implant was higher than that required to inhibit growth of leptospires in vitro. Therefore, the use of CsA implants in known leptospiral uveitis is not contraindicated.

Keywords: cyclosporine • uveitis-clinical/animal model • autoimmune disease 
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