Retnal Toxicty of Intravitreal Tissue Plasminogen Activator with C3F8 Injection in Rabbit Eyes

ABSTRACT

PURPOSE: To determine the concentration at which a mixed injection of tissue plasminogen activator (tPA) and C3F8 gas is toxic, we studied the histopathological changes in the rabbit retina. METHODS: Only tPA was injected into the right vitreous cavities of 18 normal pigmented rabbits at doses of 25 micro gram/0.1mL, 50 micro gram/0.1mL, and 100 micro gram/0.1mL, 6 rabbits per dosage. In the same rabbits, tPA and C3F8 (0.2cc) were simultaneously injected into the left vitreous cavities at doses of 25 micro gram/0.1mL, 50 micro gram/0.1mL, and 100 micro gram/0.1mL. All of the eyes were examined by slit lamp biomicroscopy and indirect ophthalmoscopy at 5, 10, and 15 days after the injection, and then they were enucleated for histopathological evaluation. RESULTS: Retinal pigmentary alterations were centered around the injection site 3 days postoperatively in the eyes receiving doses of 50 micro gram/0.1mL or greater. On light microscopy(LM), the involved areas showed vacuolization in the photoreceptor elements and the inner nuclear layer(INL) at a dose of 25 micro gram/0.1mL at postoperative 5 days and the vacuolar changes disappeared at postoperative 15 days. But at doses of 50 micro gram/0.1mL or greater, loss, contracture, and vacuolization of the photoreceptor outer segment (POS) and vacuolization of INL were noted at postoperative 15 days. On LM, at a dose of 25 micro gram/0.1mL, the involved areas showed vacuolization in POS and mitochondrial swelling of the photoreceptor inner segment (PIS) at postoperative 5 days. The mitochondrial swelling of PIS disappeared at postoperative 15 days. However, at doses of 50 micro gram/0.1mL or greater, loss and contracture of POS and mitochondrial swelling of PIS were noted at postoperative 15 days. The retinal damage from simultaneous injection of tPA and C3F8 at doses of 25, and 50 micro gram/0.1mL was equal to or less than that of only tPA injection, whereas at a doses of 100 micro gram/0.1mL the damage was greater. CONCLUSIONS: At doses of 50 micro gram/0.1mL or greater, irreVersible retinal toxicity was noted histopathologically in rabbit eyes. At doses of 25, and 50 micro gram/0.1mL, the degree of retianl damage did not seem to be affected by whether C3F8 was injected concomitantly or not.