title: A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA. brian_gilger@ncsu.edu
authors.forename: Brian C
authors.initials: BC
authors.lastname: Gilger
authors.forename: Jacklyn H
authors.initials: JH
authors.lastname: Salmon
authors.forename: David A
authors.initials: DA
authors.lastname: Wilkie
authors.forename: Lars P J
authors.initials: LP
authors.lastname: Cruysberg
authors.forename: Jonghyeon
authors.initials: J
authors.lastname: Kim
authors.forename: Matt
authors.initials: M
authors.lastname: Hayat
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Kim
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kim
authors.forename: Peng
authors.initials: P
authors.lastname: Yuan
authors.forename: Susan S
authors.initials: SS
authors.lastname: Lee
authors.forename: Susan M
authors.initials: SM
authors.lastname: Harrington
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Murray
authors.forename: Henry F
authors.initials: HF
authors.lastname: Edelhauser
authors.forename: Karl G
authors.initials: KG
authors.lastname: Csaky
authors.forename: Michael R
authors.initials: MR
authors.lastname: Robinson
mesh_terms: D020341:Absorbable Implants / Q000662:veterinary*; D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000662:veterinary*; D005240:Feasibility Studies; D006734:Horse Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006736:Horses; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007921:Leptospira interrogans / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D015864:Panuveitis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D010539:Permeability; D012008:Recurrence; D012590:Sclera / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine