title: Collagen shield delivery of tissue plasminogen activator: functional and pharmacokinetic studies of anterior segment delivery.
abstract: BACKGROUND
  Postoperative fibrin formation remains a major complication associated with intraocular surgery, especially after vitreoretinal surgery for proliferative vitreoretinopathy, proliferative diabetic retinopathy, trauma, or endophthalmitis. Tissue plasminogen activator (tPA) has been shown, both in experimental studies and clinical trials, to specifically dissolve formed intraocular fibrin after intracameral or intravitreal injection. We studied collagen shield delivery of tPA to the anterior segment and vitreous of rabbit eyes to evaluate a noninvasive delivery modality.
  
  
  METHODS
  Anterior segment fibrin clots were formed in rabbit eyes by injecting citrated rabbit plasma. The tPA hydrated collagen shields, or control shields, were then placed on the rabbit corneas and the extent of fibrin clot was followed. In other rabbit eyes, tPA hydrated collagen shields were placed on the rabbit corneas and an enzyme-linked immunosorbent assay (ELISA) was utilized to determine aqueous, vitreous, and blood levels of tPA over time.
  
  
  RESULTS
  Collagen shield tPA delivery shortened the time to fibrin clot lysis by 50% (mean clearance time = 49 +/- 23 hours; P less than .05). ELISA for tPA levels noted measurable vitreous levels by 2 hours after tPA hydrated collagen shield application with a peak at 24 hours. Aqueous tPA levels were not measurable until 18 hours after tPA collagen shield application and peaked at 36 hours. Vitreous tPA levels were greater than aqueous tPA levels at all time points (P less than .05). No evidence of corneal edema or opacification, hemorrhage, or cataract was seen.
  
  
  CONCLUSIONS
  These results document the efficacy and safety of tPA delivery to the aqueous and vitreous via a hydrated collagen shield in this animal model.
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee.
authors.forename: T G
authors.initials: TG
authors.lastname: Murray
authors.forename: G J
authors.initials: GJ
authors.lastname: Jaffe
authors.forename: B S
authors.initials: BS
authors.lastname: McKay
authors.forename: D P
authors.initials: DP
authors.lastname: Han
authors.forename: J M
authors.initials: JM
authors.lastname: Burke
authors.forename: G W
authors.initials: GW
authors.lastname: Abrams
mesh_terms: D000042:Absorption; D000818:Animals; D000869:Anterior Eye Segment / Q000378:metabolism*; D001684:Biological Dressings; D003094:Collagen; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005337:Fibrin / Q000378:metabolism; D008297:Male; D011817:Rabbits; D010959:Tissue Plasminogen Activator / Q000493:pharmacokinetics*; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D005337:Fibrin; D003094:Collagen; D010959:Tissue Plasminogen Activator