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 language | English (US) |
|---|---|
| Pages (from-to) | 2596-2605 |
| Number of pages | 10 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 47 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Ophthalmology
Cite this
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 journal › Article
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TY - JOUR
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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UR - http://www.scopus.com/inward/citedby.url?scp=33745655043&partnerID=8YFLogxK
U2 - 10.1167/iovs.05-1540
DO - 10.1167/iovs.05-1540
M3 - Article
C2 - 16723476
AN - SCOPUS:33745655043
VL - 47
SP - 2596
EP - 2605
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 6
ER -