September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Repeated injections of ocriplasmin in the Göttingen mini-pig
Author Affiliations & Notes
  • Jean H.M. Feyen
    Preclinical Research, ThromboGenics NV, Leuven, Flemish Brabant, Belgium
  • Kelly Tenneson
    Ocular and Neuroscience, Charles River Laboratories, Montreal, Quebec, Canada
  • Mark Vezina
    Ocular and Neuroscience, Charles River Laboratories, Montreal, Quebec, Canada
  • Bart Jonckx
    Preclinical Research, ThromboGenics NV, Leuven, Flemish Brabant, Belgium
  • Footnotes
    Commercial Relationships   Jean Feyen, ThromboGenics NV (E); Kelly Tenneson, Charles River Laboratories (E); Mark Vezina, Charles River Laboratories (E); Bart Jonckx, ThromboGenics NV (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4043. doi:
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    • Get Citation

      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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The purpose of this study was to determine the safety of up to six consecutive injections of ocriplasmin in the mini–pig.

Methods : 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.

Results : 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.

Conclusions : 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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