fibrin and Corneal-Opacity

Excimer laser photorefractive keratectomy creates a nonvascular wound of the cornea. Fibrin deposition and resolution after excimer laser photokeratectomy were investigated in relation to corneal repair and restoration of clarity in mice with a genetic deficiency of plasminogen.. A Summit Apex Laser (Summit, Waltham, MA) was used to perform 2-mm, 175-pulse, transepithelial photoablations that resulted in deep stromal keratectomies. Photokeratectomy was performed on the corneas of plasminogen-deficient (Plg-/-) mice and littermate control animals. Eyes were examined for re-epithelialization and clarity throughout the 21-day observational period. Histologic sections were taken during the observational period and fibrin(ogen) was detected immunohistochemically.. Re-epithelialization was rapid and complete within 3 days in both control and Plg-/- animals. Exuberant corneal fibrin(ogen) deposition was noted in Plg-/- mice and sparse fibrin(ogen) deposition in control mice on days 1 and 3 after injury. Fibrin(ogen) deposits resolved in control mice but persisted in Plg-/- mice (74% of eyes at 21 days; P < 0.004). Corneal opacification, scarring, and the presence of anterior chamber fibrin(ogen) occurred in plasminogen-deficient mice but not in control mice.. Fibrin(ogen) deposition occurs during corneal wound repair after photokeratectomy. Impaired fibrinolysis in Plg-/- mice caused persistent stromal fibrin deposits that correlated with the development of corneal opacity.

Topics: Animals; Cornea; Corneal Opacity; Fibrin; Fibrinogen; Immunoenzyme Techniques; Lasers, Excimer; Mice; Mice, Mutant Strains; Photorefractive Keratectomy; Plasminogen; Wound Healing

Intracameral fibrin formation, a complication of ocular inflammation and intraocular operations, sometimes results in glaucoma and/or corneal damage leading to permanent visual loss. We transferred a therapeutic gene to the corneal endothelium in order to use it as a therapeutic organ. A plasmid encoding tissue plasminogen activator (tPA) was injected into the anterior chamber of rats and electric pulses (EPs) were given subsequently, which transferred a plasmid gene to a highly selected area of corneal endothelium with no inflammation. The biologically active tPA was clearly present for 4 days after treatment. Fibrin formation induced by YAG laser-generated bleeding in the anterior chamber decreased significantly more in treated eyes than in control eyes. Corneal opacity was significantly lower in treated eyes than in control eyes and histological damage was not apparent in the treated eyes. This genetic modification allows us to use the corneal endothelium to treat various ocular diseases and could be a new and effective type of pharmacologic gene therapy.

Topics: Animals; Cornea; Corneal Opacity; DNA, Complementary; Electricity; Endothelium; Fibrin; Gene Transfer Techniques; Genetic Vectors; Male; Rats; Rats, Wistar; Tissue Plasminogen Activator

In recent years TPA (tissue-plasminogen activator) has been increasingly and successfully used for the treatment of severe, postoperative fibrin reaction in the anterior chamber. So far no serious side effects of this treatment have been reported.. Altogether, 32 patients received 0.2 ml solution with 20 micrograms TPA intracamerally. In 2 cases a dense corneal opacity was observed 12-24 hours after the injection of TPA which was resistant to treatment with local dexamethasone and lubricants. Therefore it was removed by superficial keratectomy. In one case the keratectomy specimen could be examined by light- and electronmicroscopy.. In the keratectomy specimen a selective, fine-granular calcification of Bowman's membrane could be demonstrated.. The intracameral TPA treatment for postoperative fibrin reaction can cause a rapid band keratopathy. Therefore the application of TPA should be restricted to severe therapy-resistant cases of intracameral fibrin reaction. In cases with the development of a band keratopathy EDTA-treatment is recommended.

Topics: Aged; Aged, 80 and over; Anterior Chamber; Cornea; Corneal Opacity; Female; Fibrin; Humans; Injections; Male; Postoperative Complications; Tissue Plasminogen Activator

Intraocular fibrinolysis with recombinant tissue-plasminogen activator (rt-PA) in patients with severe fibrin reactions following anterior segment surgery is widely accepted because of the low complication rate.. We present two eyes of two patients developing acute bandkeratopathy within the first week after intraocular rt-PA fibrinolysis (10 mg/100 ml). In the first patient, calcium deposition occurred inferiorly of the optic axis without visual impairment. In the second patient, a dense bandkeratopathy reaching from limbus to limbus developed, with a severe decrease of vision. A corneal abrasion together with the chelating agent disodium ethylene diamine tetra-acetate (EDTA) 0.5% in neutral solution led only to an incomplete resolution of the depositions.. Acute development of a bandkeratopathy is very rare. Several risk factors are identified so far, e.g. the use of phosphate containing eye drops. Their interactions and the possible pathomechanism are discussed in detail. The close coincidence of intraocular rt-PA fibrinolysis and acute band-keratopathy in our two patients is in favor of an at least additive causative role of rt-PA fibrinolysis. Therefore, the indication should be limited to severe fibrin reactions and local application of phosphate containing drugs should be avoided.

Topics: Aged; Aged, 80 and over; Corneal Opacity; Female; Fibrin; Humans; Lenses, Intraocular; Postoperative Complications; Recombinant Proteins; Thrombolytic Therapy; Tissue Plasminogen Activator