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M. Kamei, C.H. Jiang, X.Y. Fang, T. Yamamoto, M. Suzuki, Y. Tano; Injection of Tissue Plasminogen Activator into the Optic Disc as a Treatment of Central Retinal Vein Occlusion . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4734.
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Purpose: To investigate the safety, feasibility and efficacy of injection of tissue plasminogen activator (tPA) into the optic disc for the treatment of central retinal vein occlusion. Methods: First, 50µl of tPA or balanced saline solution (BSS) was injected into the optic nerve of 18 normal rabbit eyes, to investigate the safety and toxicity of intraneuronal tPA. Eyes of three groups (25µg tPA, 12.5µg tPA and BSS group) were compared with eyes of no–treatment group. The eyes were examined with slit lamp biomicroscopy, indirect ophthalmoscopy, VEP and ERG, and then harvested for histopathology at 28 days after injection. Second, to evaluate efficacy of tPA injection into the optic nerve, Rose Bengal–mediated argon laser retinal vein photothrombosis was produced and tPA (12.5µg/50µ) was injected into the optic nerve in the treatment group (10 eyes, 20 veins). Fluorescein angiography was repeated to determine the recanalization of the vessel at 3 and 7 days after treatment. Eyes were also examined histopathologically. Results: No obvious evidence of optic nerve or retinal toxicity was seen with ophthalmoscopy, VEP, ERG, or histopathological examination when comparing 25µg tPA, 12.5µg tPA and BSS injection group with the no–treatment control group. The mean latency of the first peak of the VEPs were 24.6±1.5, 24.1±1.9, 24.0±2.0 and 24.6±1.3 respectively (p=0.41). The mean amplitude of the first peak of the VEPs were 123.9±41.8, 145.2±41.2, 132.4±48.2 and 116.8±29.4 respectively (p=0.06). The mean latency of A–waves were 6.0±0.4, 5.9±0.4, 5.9±0.5 and 5.8±0.3 respectively (p=0.63). The mean amplitude of A–waves were 110.3±13.9, 112.0±15.3, 109.7±15.9 and 107.7±10.9 respectively (p=0.72). The mean amplitude of B–waves were 150.8±11.9, 147.6±13.6, 144.5±16.5 and 141.0±20.5 respectively (p=0.096). The incidence of the patency of the vessels in treatment animals was 70.0% (14/20), while in the control animals was 16.7% (4/24) (p=0.001). Conclusions: Injection of tPA into the optic nerve is a safe and simple procedure without apparent toxicity or damage to optic nerve or retina. Injection of tPA (12.5 µg) increased the incidence of the recanalization of the vessels in experimental retinal vein occlusion. Although further studies are needed, our data suggested that injection of tPA into optic nerve may have potential application in the treatment of central retinal vein occlusion.
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