May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Characterization and Validation of Refillable Episcleral Drug Delivery Devices for Unidirectional and Controlled Transscleral Drug Delivery
Author Affiliations & Notes
  • M. Krause
    Ophthalmology, Johns Hopkins University, Baltimore, MD
  • R.L. e Silva
    Ophthalmology, Johns Hopkins University, Baltimore, MD
  • I.H. Maumenee
    Ophthalmology, Johns Hopkins University, Baltimore, MD
  • P. Campochiaro
    Ophthalmology, Johns Hopkins University, Baltimore, MD
  • E.E. Schmitt
    Landec Corp., Menlo Park, CA
  • A.L. Murphree
    Children Hospital Los Angeles, Los Angeles, CA
  • R.A. P. de Carvalho
    Ophthalmology, Johns Hopkins University, Baltimore, MD
  • Footnotes
    Commercial Relationships  M. Krause, None; R.L. e Silva, None; I.H. Maumenee, None; P. Campochiaro, None; E.E. Schmitt, None; A.L. Murphree, None; R.A.P. de Carvalho, None.
  • Footnotes
    Support  William and Ella Owens Medical Foundation
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 499. doi:
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      M. Krause, R.L. e Silva, I.H. Maumenee, P. Campochiaro, E.E. Schmitt, A.L. Murphree, R.A. P. de Carvalho; Characterization and Validation of Refillable Episcleral Drug Delivery Devices for Unidirectional and Controlled Transscleral Drug Delivery . Invest. Ophthalmol. Vis. Sci. 2005;46(13):499.

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

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Abstract

Abstract: : Purpose:To characterize implantable and refillable episcleral devices designed to provide controlled transscleral target delivery systems (TTDS) after being sealed to the scleral surface; to validate the ocular fit of two different designs and methods used to accomplish their seal to the eye; and to investigate the biocompatibility of episcleral devices made of poly–ethylene and silicone elastomer. Material and Methods: (1) Infant eyes enucleated for retinoblastoma (n=20) at different ages had the distances between rectus muscle insertions and between the limbus and vortex veins measured to characterize the effective area available for implantation of episcleral devices; (2) Iohexol–loaded (1.75 mg and 3.5 mg) devices were implanted in the right eye of two rabbits. A third animal was implanted with a carboplatin–loaded (20 mg) device. X–ray computed tomography (CT) was performed 3, 24 hours, and 5 days after implantation/injection of iohexol, and 3, 24 hours and 8 days after implantation of carboplatin–loaded devices. (3) Sodium fluorescein (n=15) and FITC–dextran 10 KDa (1mg, n=6) loaded devices were implanted in one eye of White New Zealand rabbits. Control groups consisted of periocular injections of the same doses of the respective compounds. Eyes were enucleated and either frozen in OCT for fluorescence microscopy or embedded in paraffin for HE staining and optic microscopy. Results: The device designs were adequate to be placed on infant eyes. After periocular injection, the iohexol CT signal was detected diffusely only at the 3–hour time point. In eyes implanted with devices, the signal originating from the reservoir decreased over time but was still present at 5 or 7 days after implantation. The encapsulation of the device spared the drug diffusion window in eyes where the seal was present. Fluorescence microscopy demonstrated preferential concentration of the fluorescence in sclera, choroid and retina overlying the implant area after exposure to the FITC–dextran contained in the reservoir. Conclusions: Feasibility and biocompatibility of materials, designs and attachment methods were demonstrated for the TTDS. It offers advantages of selective delivery to the eye and protection of the periocular and orbital tissues while preventing encapsulation of the drug diffusion window with time. This approach should ultimately provide a better control of intraocular pharmacokinetics.

Keywords: pharmacology • sclera • retinoblastoma 
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