Safety of in vivo pharmacologic vitreolysis with recombinant microplasmin in rabbit eyes.
OBJECTIVE
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 microg to 250 microg, 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 microg or greater of microplasmin induced complete PVD with an internal limiting membrane (ILM) devoid of vitreous collagen fibrils. Eyes injected with 12.5 microg 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 microg 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.
Sakuma
Toshiro
T
Department of Ophthalmology, Juntendo University, Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
Tanaka
Minoru
M
Mizota
Atsushi
A
Inoue
Junji
J
Pakola
Steve
S
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D005341:Fibrinolysin / Q000494:pharmacology*; D007267:Injections; D008855:Microscopy, Electron, Scanning; D010446:Peptide Fragments / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D012160:Retina / Q000503:physiopathology; D012449:Safety; D014463:Ultrasonography; D014821:Vitrectomy / Q000379:methods*; D014822:Vitreous Body / Q000000981:diagnostic imaging / Q000187:drug effects*; D020255:Vitreous Detachment / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000503:physiopathology
D010446:Peptide Fragments; D011994:Recombinant Proteins; C054561:microplasmin; D005341:Fibrinolysin