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Bart Jonckx, Isabelle Etienne, Tom Janssens, Jean H.M. Feyen; Ocriplasmin in a porcine model for PVD induction. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4042.
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© ARVO (1962-2015); The Authors (2016-present)
To better understand the activity profile of ocriplasmin at the inner limiting membrane (ILM), we evaluated the pharmacological activity in the pig model for induction of Posterior Vitreous Detachment (PVD).
To validate the model, thirteen farm pigs were injected mid-vitreally with ocriplasmin (96µg per eye, 29µg/mL vitreous assuming a vitreous volume of 3.3mL; injection volume 100µL) or vehicle in the contralateral eye. Following treatment, eyes were examined weekly by SD-OCT to assess for a PVD for up to 6 weeks. There were 4 volume scans averaging 48 frames per image. These scans were focused nasally, temporally, and superior to the optic nerve. Enucleated eyes were processed for detailed histopathological analysis.
A single administration of 96µg ocriplasmin resulted in a time-dependent induction of PVD. PVD was observed from Week 2 onwards (82% eyes at Week 8) in the ocriplasmin treated eyes and from Week 5 onwards (8% eyes at Week 8) in the eyes which had received vehicle. Subretinal lucencies (SRLs) were observed upon ocriplasmin treatment. Although the SRL incidence was high (85% one week post administration), the SRL volume was relatively small; 0.062±0.012mm3 (avg±SEM). Incidence and volume diminished by Week 2, disappearing completely from Week 3 onwards. SRLs were not observed in vehicle treated eyes. Hyper-reflective spots in the vitreous were observed in both ocriplasmin and vehicle treated eyes, reaching a maximum incidence of 46% and 8% for ocriplasmin and vehicle, respectively. All hyper-reflective spots had resolved by Week 3.Hematoxylin and Eosin staining did not reveal structural changes in the retina upon treatment. Immunohistochemical stains for the ILM components collagen IV, laminin and fibronectin demonstrated the specific activity of ocriplasmin on these matrix proteins by cleaving the ILM into 2 separate layers, one remaining attached to the ILM, the other associated with the PVD interface. No significant distribution changes were observed for these stains in the retina itself.
This validated pig PVD model demonstrated the ability of ocriplasmin to time-dependently induce PVD. The observed side effects such as SRLs and hyper-reflective spots proved to be transient (up to Week 3). Specific activity of ocriplasmin at the ILM could be demonstrated.
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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