IOVS Journal of Experimental Medicine
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(Investigative Ophthalmology and Visual Science. 2005;46:3295-3299.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.04-1517
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Safety of In Vivo Pharmacologic Vitreolysis with Recombinant Microplasmin in Rabbit Eyes

Toshiro Sakuma,1 Minoru Tanaka,1 Atsushi Mizota,1 Junji Inoue,1 and Steve Pakola2

1From the Department of Ophthalmology, Juntendo University, Urayasu Hospital, Chiba, Japan; and 2ThromboGenics Inc., New York, New York.

PURPOSE. To investigate the safety of intravitreal microplasmin in rabbits and to confirm previous findings of posterior vitreous detachment (PVD).

METHODS. Different doses of microplasmin, from 12.5 µg to 250 µg, in 0.1 mL balanced salt solution (BSS) were injected into the vitreous cavity of rabbit eyes to induce PVD. Fellow eyes were injected with the same volume of BSS. Slit-lamp biomicroscopy, ophthalmoscopic fundus examinations, A- and B-mode ultrasonography, and electroretinography were performed to assess the retina. Electroretinograms (ERGs) were recorded up to 90 days after injection. Morphologic alterations were assessed by light microscopy, scanning electron microscopy (SEM), and transmission (TEM) electron microscopy.

RESULTS. A slight aqueous flare and cells were observed in the anterior chamber after microplasmin and BSS injection. A slight inflammatory reaction was also observed transiently in the vitreous cavity. In control eyes, B-mode ultrasonography and SEM examination demonstrated that PVD did not develop after BSS injection. Intravitreal injections of 125 µg or greater of microplasmin induced complete PVD with an internal limiting membrane (ILM) devoid of vitreous collagen fibrils. Eyes injected with 12.5 µg microplasmin had partial PVD, and SEM showed residual fibrils covering the ILM. In all eyes, there was a transient reduction in the a- and b-waves of the ERG on days 2 through 7. The ERGs showed less effect with <250 µg microplasmin.

CONCLUSIONS. Intravitreal injection of recombinant microplasmin in the rabbit induces no ERG or retinal ultrastructural abnormalities. Pharmacologic vitreolysis with this agent may be a useful adjunct to vitreous surgery and could be used to induce PVD without vitreous surgery.






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