RETINAL TOXICITY OF HUMAN TISSUE PLASMINOGEN-ACTIVATOR IN VITRECTOMIZED RABBIT EYES

The retinal toxicity of human tissue plasminogen activator in normal rabbit eyes has recently been reported. We now report the retinal toxicity of tissue plasminogen activator in three groups of vitrectomized rabbit eyes. Group 1 underwent gas compression of the vitreous followed by tissue plasminogen activator injection in doses of 25, 50, and 100-mu-g (all doses were administered in 100-mu-L of fluid). Group 2 underwent lensectomy and vitrectomy followed by tissue plasminogen activator injection of 100-mu-g. Group 3 underwent lensectomy, vitrectomy, and complete fluid/gas exchange prior to injections of 12.5 and 25-mu-g of tissue plasminogen activator. Control eyes received 100-mu-L of balanced salt solution. In group 1, no retinal toxic reactions were observed after administration of 25 or 50-mu-g of tissue plasminogen activator, but all eyes receiving 100-mu-g demonstrated retinal damage on ophthalmoscopy, electroretinography, and light microscopy. In group 2, no retinal toxic reactions were seen after administration of 100-mu-g of tissue plasminogen activator. In group 3, two of 11 eyes receiving 25-mu-g of tissue plasminogen activator demonstrated toxic retinal changes by ophthalmoscopy, electroretinography, and light microscopy. These results suggest that gas compression of the vitreous does not significantly alter the toxic changes seen caused by tissue plasminogen activator. While lensectomy and vitrectomy appears to widen the therapeutic window for tissue plasminogen activator, the margin of safety is reduced with the addition of a large gas bubble.