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M Estafanous, H Lewis, H Sakaguchi, J Sears; Intravitreal Tissue Plasminogen Activator in Experimental Retinal Vein Occlusion . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1873.
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Purpose: We set out to determine if intravitreal tissue plasminogen activator (tPA) is effective in the clearance of branch retinal vein occlusions (BRVO) in an experimental setting. Methods: BRVOs were induced in both eyes of 14 rabbits by photochemical thrombosis with Rose-Bengal dye (20 mg/kg) by an argon laser (500 mJ, 0.1s, 15-30 shots). Eyes were then randomized to receive a 0.1cc intravitreal injection of either tPA (50 mcg) or balanced salt solution (BSS) immediately after occlusion. Intravenous fluorescein angiography was then performed immediately (t0), 6 hours , and 2, 4, and 7 days after injection. 10 rabbits were sacrificed on day 2, and 4 rabbits on day 7. Angiograms were read by a masked observer. Uninterpretable angiograms were excluded. Results: 23 eyes (12 tPA, 11 BSS) were interpretable at t0, 22 eyes (11 tPA, 11 BSS) at 6 hours, 20 eyes (10 tPA, 10 BSS) at 2 days, 8 eyes (4 tPA, 4 BSS) at 4 days, and 8 eyes (4 tPA, 4 BSS) at 7 days. Angiograms were uninterpretable due vitreous hemorrhage (1 eye), and to washout of the fluorescein dye (remaining eyes). At no time point were the differences between rates of clearance significant. All eyes were occluded at t0 and 6 hours. Clearance of the BRVO was noted in 40% of tPA eyes and 10% of BSS eyes (p=0.30, Fisher’s exact test) on day 2, and in 50% of tPA eyes and 33% of BSS eyes (p=0.93, Fisher’s exact test) on day 4. 75% of the eyes in each group had cleared their occlusions by day 7. Conclusion: Intravitreal tissue plasminogen activator does not appear to hasten the clearance of experimental retinal vein occlusion in rabbits. The largest difference in clearance of 30% at 2 days, was not statistically significant (p=0.30). This may be due to an inability of tPA to cross the blood-retinal barrier and reach the retinal circulation, binding of tPA within the vitreous cavity or retina, or inadequate sample size. Further work must be done to determine if intravitreal tPA may be an effective treatment option in humans with BRVO.
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