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Jean H.M. Feyen, Kelly Tenneson, Mark Vezina, Bart Jonckx; Repeated injections of ocriplasmin in the Göttingen mini-pig. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4043.
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The purpose of this study was to determine the safety of up to six consecutive injections of ocriplasmin in the mini–pig.
To assess the safety of 2, 3 and 6 ocriplasmin injections 4 weeks apart, a GLP toxicity study was performed in Göttingen mini-pigs. Each group consisted of 3 males and 3 females. The experimental eye received ocriplasmin at a dose of 63μg/eye (29μg/mL assuming a vitreous volume of 2mL). The vehicle was given to the contralateral eye which acted as a control. Fifty microliters were injected mid vitreous with a 30G, ½”needle. Animals were subjected to ophthalmic toxicology screening consisting of funduscopic and biomicroscopic (slit lamp) examination (mydriatic and non-mydriatic) and tonometry. In addition a monthly full-field ERG was performed. Enucleated eyes were processed for detailed histopathological analysis at the Charles River Laboratories in Montreal.
The eyes receiving two or three ocriplasmin injections had no ERG abnormalities or evidence of retinal toxicity and were indistinguishable from control eyes. In the group receiving up to 6 injections, lens subluxation, recorded as a very small aphakic crescent in the superotemporal lens quadrant, was noted in 4/6 eyes following the 5th injection. Damage to the lens zonules is the primary etiology for lens subluxation. After 6 administrations, microscopic findings of minimal mononuclear cell infiltration (vitreous, 4/6 eyes; injection site, 2/6 eyes; iris/ciliary body, 2/6 eyes) were noted. No signs of inflammation or lens subluxation were observed in the control eyes.There were no ocriplasmin-related changes in intraocular pressure after up to six doses. Analysis of the a- and b-wave did not reveal any changes in response amplitude or latency at any interval evaluated during the course of the study both in the treated and control eyes.
Administration of ocriplasmin at 4-week intervals for up to 4 doses (3 months) was well tolerated in Göttingen mini-pigs at 63 μg/eye/injection; after 5 or 6 doses, minimal lens subluxation was present in 4/6 eyes.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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