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Michaël PORCU, Isabelle Etienne, Aurélie Candi, Anne Verborg, Marianne Eelen, Bart Jonckx, Jean H.M. Feyen; Preclinical insights into ocriplasmin safety and mechanism of action. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4044.
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© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study was to gain insight into the safety and mechanism of action of ocriplasmin, a protease used for treatment of vitreomacular traction. To achieve this, we evaluated retina and vitreous tissues from a porcine model of ocriplasmin-induced Posterior Vitreous Detachment (PVD) as well as cell-based models.
Porcine eyes were injected intravitreally with ocriplasmin (96μg per eye, equivalent to 125μg in human) or vehicle. At several time points (up to 6 weeks) post injection, animals were sacrificed and vitreoretinal tissues were studied: retinal morphology, distribution of extracellular matrix proteins as well as number of microglial cells were histologically examined. The presence of an inflammatory response was assessed by multiplex profiling of 14 inflammatory markers in the vitreous. The effect of ocriplasmin on blood-retinal-barrier permeability was assessed using an in vitro electrical resistance (TEER) assay.
Retinal morphology was not affected by vehicle or ocriplasmin at any of the investigated time points. Extracellular matrix components clearly delineated the PVD structures at the internal limiting membrane and no significant distribution changes were observed in the retina. No evidence for a major acute inflammatory response was found. Although histology indicated a minor increase of the macrophage-specific marker Iba1 in ocriplasmin treated eyes, cytokine profiling indicated no significant difference between vehicle and ocriplasmin treated eyes. A minor and transient inflammatory response related to injection in general was observed. We observed that only high doses of ocriplasmin could modulate permeability of in vitro retinal barrier models, all changes being cell specific and fully reversible after 48 hours.
A number of the transient observations on OCT (lucencies, inclusions) that have been observed in patients treated with ocriplasmin can be mimicked in a porcine model of PVD. Closer examination of the involved tissues did not indicate an underlying acute inflammatory response, neither did we observe signs of toxicity or extracellular matrix rearrangement specific to ocriplasmin. In vitro observations indicate that retinal barrier permeability can only be affected by high local doses of active ocriplasmin, and even then the effects are rapidly reversible.
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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