Intraocular penetration of topical tissue plasminogen activator
J. I. Lim, R. Fiscella, H. Tessler, D. A. Gagliano, V. Chaques-Alepuz and M. A. Mohler
Department of Ophthalmology, University of Illinois, College of Medicine, Chicago.
Fifty-eight eyes of 31 anesthetized rabbits received one drop of
proparacaine hydrochloride, 0.05%, and two drops of tissue plasminogen
activator (tPA) separated by 5 minutes. Four eyes of two additional rabbits
had epithelial defects created before drug delivery. Tissue plasminogen
activator in multiple doses was given to eight eyes of four other rabbits.
We used this dosing regimen to investigate the effect of topical tPA on
anterior chamber fibrin clots in three rabbits. A two-site enzyme-linked
immunosorbent assay test was used to measure tPA levels in the aqueous
samples, obtained by paracentesis in each eye. Of 53 eyes treated with the
original dosing regimen, 21 (40%) had detectable tPA aqueous levels. Blood
and aqueous from eyes of untreated control rabbits, contralateral control
eyes of treated rabbits, and eyes with epithelial defects had nondetectable
tPA. Multiple tPA drop dosing resulted in 75% of aqueous samples with
detectable tPA and a higher average tPA concentration than the original
dosing regimen. Eyes treated with tPA showed a significantly faster
resolution of anterior chamber fibrin clots than did control eyes.
