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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

01/01/1992

Pubmed ID

1554639

Scopus ID

2-s2.0-0026582787 (requires institutional sign-in at Scopus site)   11 Citations

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.

Author List

Murray TG, Jaffe GJ, McKay BS, Han DP, Burke JM, Abrams GW

Author

Dennis P. Han MD Adjunct Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Absorption
Animals
Anterior Eye Segment
Biological Dressings
Collagen
Drug Carriers
Drug Delivery Systems
Enzyme-Linked Immunosorbent Assay
Female
Fibrin
Male
Rabbits
Tissue Plasminogen Activator
Vitreous Body