Collagen shield delivery of tissue plasminogen activator: functional and pharmacokinetic studies of anterior segment delivery. Refract Corneal Surg 1992;8(1):44-8; discussion 48-53
Date
01/01/1992Pubmed ID
1554639Scopus ID
2-s2.0-0026582787 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
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.
Author List
Murray TG, Jaffe GJ, McKay BS, Han DP, Burke JM, Abrams GWMESH terms used to index this publication - Major topics in bold
AbsorptionAnimals
Anterior Eye Segment
Biological Dressings
Collagen
Drug Carriers
Drug Delivery Systems
Enzyme-Linked Immunosorbent Assay
Female
Fibrin
Male
Rabbits
Tissue Plasminogen Activator
Vitreous Body