The systemic (intravenous) administration of genetically modified (recombinant) tissue plasminogen activator (tPA) for thrombolysis in coronary arteries was approved by the US Federal Drug Administration in 1988. Since then, use of this approved drug has been extended to many non-approved indications, especially in the eye.¹

Tissue plasminogen activator is a naturally occurring serine protease produced by a variety of mammalian tissues, especially endothelial cells. Ocular tissues that contain tPA include the conjunctiva, cornea, trabecular meshwork, lens, vitreous, and retina.^1–3 In normal adult human eyes, the aqueous humour contains a significant amount of tPA that is some 30 times more than in plasma.⁴ The major enzymatic action of tPA is the conversion of plasminogen (a zymogen) into plasmin, an active serine protease that hydrolyses fibrin. Compared to other fibrinolytic agents (for example, urokinase and streptokinase), tPA has several advantages: fibrin forms a ternary complex with tPA and plasminogen, which increases the rate of plasminogen activation several hundred-fold; in addition, tPA serves to protect plasmin from antiplasmin inhibitors until complete clot lysis is achieved.^5–7 Even though cost effective, urokinase and streptokinase did not …