A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis

Brian C. Gilger, Jacklyn H. Salmon, David A. Wilkie, Lars P J Cruysberg, Jonghyeon Kim, Matt Hayat, Hyuncheol Kim, Stephanie Kim, Peng Yuan, Susan S. Lee, Susan M. Harrington, Patrick R. Murray, Henry F. Edelhauser, Karl G. Csaky, Michael R. Robinson

Research output: Contribution to journalArticle

Abstract

PURPOSE. To determine the feasibility, safety, and effectiveness of an episcleral or deep scleral lamellar sustained release cyclosporine (CsA) device in a naturally occurring animal model of uveitis. METHODS. A two-compartment perfusion chamber was used to assess in vitro human and equine scleral permeability of fluorescein, dexamethasone-fluorescein, or CsA. A biodegradable, matrix-reservoir CsA implant was designed, and release rates of CsA were determined in vitro. Tissue CsA levels were measured in eyes with the implant. Horses with equine recurrent uveitis (ERU) received episcleral or deep scleral lamellar CsA implants and were monitored for up to 3 years. RESULTS. Dexamethasone-fluorescein and CsA penetrated the in vitro equine sclera poorly; however, low but detectable levels of CsA were detected intraocularly in vivo. The implant placed episclerally failed to control inflammatory episodes in ERU. CsA implants placed in the deep sclera adjacent to the suprachoroidal space resulted in high levels of CsA in most ocular tissues. In clinical equine patients with ERU, frequency of uveitic flare-ups was significantly decreased after implantation of a deep scleral lamellar CsA implant. CONCLUSIONS. Diffusion of CsA across the sclera from the episcleral space was not a feasible method of drug delivery to the equine eye. However, placing a deep scleral lamellar CsA implant adjacent to the suprachoroidal space was effective in achieving therapeutic ocular drug concentrations and controlling uveitis in horses with ERU.

Original languageEnglish (US)
Pages (from-to)2596-2605
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume47
Issue number6
DOIs
StatePublished - Jun 2006
Externally publishedYes

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Uveitis
Cyclosporine
Horses
Sclera
Fluorescein
Dexamethasone
Pharmaceutical Preparations
Permeability
Animal Models
Perfusion
Safety
Equipment and Supplies

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Gilger, B. C., Salmon, J. H., Wilkie, D. A., Cruysberg, L. P. J., Kim, J., Hayat, M., ... Robinson, M. R. (2006). A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis. Investigative Ophthalmology and Visual Science, 47(6), 2596-2605. https://doi.org/10.1167/iovs.05-1540

A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis. / Gilger, Brian C.; Salmon, Jacklyn H.; Wilkie, David A.; Cruysberg, Lars P J; Kim, Jonghyeon; Hayat, Matt; Kim, Hyuncheol; Kim, Stephanie; Yuan, Peng; Lee, Susan S.; Harrington, Susan M.; Murray, Patrick R.; Edelhauser, Henry F.; Csaky, Karl G.; Robinson, Michael R.

In: Investigative Ophthalmology and Visual Science, Vol. 47, No. 6, 06.2006, p. 2596-2605.

Research output: Contribution to journalArticle

Gilger, BC, Salmon, JH, Wilkie, DA, Cruysberg, LPJ, Kim, J, Hayat, M, Kim, H, Kim, S, Yuan, P, Lee, SS, Harrington, SM, Murray, PR, Edelhauser, HF, Csaky, KG & Robinson, MR 2006, 'A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis', Investigative Ophthalmology and Visual Science, vol. 47, no. 6, pp. 2596-2605. https://doi.org/10.1167/iovs.05-1540
Gilger, Brian C. ; Salmon, Jacklyn H. ; Wilkie, David A. ; Cruysberg, Lars P J ; Kim, Jonghyeon ; Hayat, Matt ; Kim, Hyuncheol ; Kim, Stephanie ; Yuan, Peng ; Lee, Susan S. ; Harrington, Susan M. ; Murray, Patrick R. ; Edelhauser, Henry F. ; Csaky, Karl G. ; Robinson, Michael R. / A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis. In: Investigative Ophthalmology and Visual Science. 2006 ; Vol. 47, No. 6. pp. 2596-2605.
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abstract = "PURPOSE. To determine the feasibility, safety, and effectiveness of an episcleral or deep scleral lamellar sustained release cyclosporine (CsA) device in a naturally occurring animal model of uveitis. METHODS. A two-compartment perfusion chamber was used to assess in vitro human and equine scleral permeability of fluorescein, dexamethasone-fluorescein, or CsA. A biodegradable, matrix-reservoir CsA implant was designed, and release rates of CsA were determined in vitro. Tissue CsA levels were measured in eyes with the implant. Horses with equine recurrent uveitis (ERU) received episcleral or deep scleral lamellar CsA implants and were monitored for up to 3 years. RESULTS. Dexamethasone-fluorescein and CsA penetrated the in vitro equine sclera poorly; however, low but detectable levels of CsA were detected intraocularly in vivo. The implant placed episclerally failed to control inflammatory episodes in ERU. CsA implants placed in the deep sclera adjacent to the suprachoroidal space resulted in high levels of CsA in most ocular tissues. In clinical equine patients with ERU, frequency of uveitic flare-ups was significantly decreased after implantation of a deep scleral lamellar CsA implant. CONCLUSIONS. Diffusion of CsA across the sclera from the episcleral space was not a feasible method of drug delivery to the equine eye. However, placing a deep scleral lamellar CsA implant adjacent to the suprachoroidal space was effective in achieving therapeutic ocular drug concentrations and controlling uveitis in horses with ERU.",
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T1 - A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis

AU - Gilger, Brian C.

AU - Salmon, Jacklyn H.

AU - Wilkie, David A.

AU - Cruysberg, Lars P J

AU - Kim, Jonghyeon

AU - Hayat, Matt

AU - Kim, Hyuncheol

AU - Kim, Stephanie

AU - Yuan, Peng

AU - Lee, Susan S.

AU - Harrington, Susan M.

AU - Murray, Patrick R.

AU - Edelhauser, Henry F.

AU - Csaky, Karl G.

AU - Robinson, Michael R.

PY - 2006/6

Y1 - 2006/6

N2 - PURPOSE. To determine the feasibility, safety, and effectiveness of an episcleral or deep scleral lamellar sustained release cyclosporine (CsA) device in a naturally occurring animal model of uveitis. METHODS. A two-compartment perfusion chamber was used to assess in vitro human and equine scleral permeability of fluorescein, dexamethasone-fluorescein, or CsA. A biodegradable, matrix-reservoir CsA implant was designed, and release rates of CsA were determined in vitro. Tissue CsA levels were measured in eyes with the implant. Horses with equine recurrent uveitis (ERU) received episcleral or deep scleral lamellar CsA implants and were monitored for up to 3 years. RESULTS. Dexamethasone-fluorescein and CsA penetrated the in vitro equine sclera poorly; however, low but detectable levels of CsA were detected intraocularly in vivo. The implant placed episclerally failed to control inflammatory episodes in ERU. CsA implants placed in the deep sclera adjacent to the suprachoroidal space resulted in high levels of CsA in most ocular tissues. In clinical equine patients with ERU, frequency of uveitic flare-ups was significantly decreased after implantation of a deep scleral lamellar CsA implant. CONCLUSIONS. Diffusion of CsA across the sclera from the episcleral space was not a feasible method of drug delivery to the equine eye. However, placing a deep scleral lamellar CsA implant adjacent to the suprachoroidal space was effective in achieving therapeutic ocular drug concentrations and controlling uveitis in horses with ERU.

AB - PURPOSE. To determine the feasibility, safety, and effectiveness of an episcleral or deep scleral lamellar sustained release cyclosporine (CsA) device in a naturally occurring animal model of uveitis. METHODS. A two-compartment perfusion chamber was used to assess in vitro human and equine scleral permeability of fluorescein, dexamethasone-fluorescein, or CsA. A biodegradable, matrix-reservoir CsA implant was designed, and release rates of CsA were determined in vitro. Tissue CsA levels were measured in eyes with the implant. Horses with equine recurrent uveitis (ERU) received episcleral or deep scleral lamellar CsA implants and were monitored for up to 3 years. RESULTS. Dexamethasone-fluorescein and CsA penetrated the in vitro equine sclera poorly; however, low but detectable levels of CsA were detected intraocularly in vivo. The implant placed episclerally failed to control inflammatory episodes in ERU. CsA implants placed in the deep sclera adjacent to the suprachoroidal space resulted in high levels of CsA in most ocular tissues. In clinical equine patients with ERU, frequency of uveitic flare-ups was significantly decreased after implantation of a deep scleral lamellar CsA implant. CONCLUSIONS. Diffusion of CsA across the sclera from the episcleral space was not a feasible method of drug delivery to the equine eye. However, placing a deep scleral lamellar CsA implant adjacent to the suprachoroidal space was effective in achieving therapeutic ocular drug concentrations and controlling uveitis in horses with ERU.

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