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A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis.
Abstract: 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.
Publication Date: 2006-05-26 PubMed ID: 16723476DOI: 10.1167/iovs.05-1540Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Clinical Trial
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research investigates the suitability and effectiveness of a unique, biodegradable, sustained release implant of the drug cyclosporine (CsA) for treating uveitis. The study finds that when the implant is placed deep in the equine (horse) eye, it effectively controls the condition and maintains therapeutic levels of the drug.
Study Objectives and Methodology
- The primary aim of the study was to examine the safety, practicality, and effectiveness of a sustained release CsA device placed in sub-surface eye tissue (episcleral or deep scleral) in a naturally occurring animal (horse) model of uveitis.
- To do this, they employed a two-compartment perfusion chamber to assess the permeability of fluorescein, dexamethasone-fluorescein, or CsA across human and equine sclera (white part of the eye) in vitro (lab conditions).
- They then designed a biodegradable CsA implant and estimated the rate of CsA release in vitro. They also measured tissue CsA levels in eyes that were implanted with the device.
- Lastly, they monitored horse eyes with the implant for up to three years to assess long-term performance and effects.
Study Results
- The study found that dexamethasone-fluorescein and CsA penetrated the equine sclera poorly under lab conditions. However, when tested in live horses, low but detectable levels of CsA were found in the eye.
- When the implant was positioned episclerally (just under the surface of the eye’s white part), it was not effective in controlling inflammatory episodes in horses with ERU (equine recurrent uveitis).
- When the implant was positioned in the deep sclera (deeper in the eye) and next to the suprachoroidal space, it resulted in high levels of CsA in most ocular tissues. This positioning resulted in a significant decrease in the frequency of uveitic flare-ups in clinical equine patients with ERU.
Conclusion
- The study concluded that delivery of CsA to the equine eye via diffusion from the episcleral space was not a feasible method of drug delivery.
- However, the study also found that 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.
Cite This Article
APA
Gilger BC, Salmon JH, Wilkie DA, Cruysberg LP, 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.
Invest Ophthalmol Vis Sci, 47(6), 2596-2605.
https://doi.org/10.1167/iovs.05-1540 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA. brian_gilger@ncsu.edu
MeSH Terms
- Absorbable Implants / veterinary
- Animals
- Cyclosporine / administration & dosage
- Cyclosporine / adverse effects
- Cyclosporine / pharmacokinetics
- Drug Delivery Systems / veterinary
- Feasibility Studies
- Horse Diseases / drug therapy
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horses
- Humans
- Immunosuppressive Agents / administration & dosage
- Immunosuppressive Agents / adverse effects
- Immunosuppressive Agents / pharmacokinetics
- Leptospira interrogans / drug effects
- Leptospira interrogans / growth & development
- Microbial Sensitivity Tests
- Panuveitis / drug therapy
- Panuveitis / metabolism
- Panuveitis / pathology
- Panuveitis / veterinary
- Permeability
- Recurrence
- Sclera / metabolism
- Treatment Outcome
Citations
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