April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Ab Externo Delivery Of Cell Therapy To The Sub-retinal Space Of Pigs By Means Of A Microcatheter
Author Affiliations & Notes
  • Marc D. de Smet
    Ophthalmology, Clinique de Montchoisi, Lausanne, Switzerland
    Ophthalmology, University of Amsterdam, Amsterdam, The Netherlands
  • Sylvie Wise
    Preclinical Services, Charles River Laboratory, Montreal, Quebec, Canada
  • Mark Vezina
    Preclinical Services, Charles River Laboratory, Montreal, Quebec, Canada
  • Stan Conston
    iScience Interventional, Menlo Park, California
  • Darin J. Messina
    Centocor R & D, Radnor, Pennsylvania
  • Cliff Sachs
    Centocor R & D, Radnor, Pennsylvania
  • Sicco H. Popma
    Centocor R & D, Radnor, Pennsylvania
  • Footnotes
    Commercial Relationships  Marc D. de Smet, iscience, Centocor (C); Sylvie Wise, Charles River (E); Mark Vezina, Charles River (E); Stan Conston, iScience (E); Darin J. Messina, Centocor R&D (E); Cliff Sachs, Centocor R&D (E); Sicco H. Popma, Centocor R&D (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 553. doi:
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      Marc D. de Smet, Sylvie Wise, Mark Vezina, Stan Conston, Darin J. Messina, Cliff Sachs, Sicco H. Popma; Ab Externo Delivery Of Cell Therapy To The Sub-retinal Space Of Pigs By Means Of A Microcatheter. Invest. Ophthalmol. Vis. Sci. 2011;52(14):553.

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

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Purpose: : To determine the feasibility and safety of delivering cell therapy to the sub-retinal space ab-externo without penetration of the intraocular space.

Methods: : 22 Göttingen miniature pigs (10-15 Kg) were placed under inhalation anesthesia and prepared for ocular surgery. A sclerotomy was performed 8.5 mm posterior to the limbus of each eye, followed by the atraumatic creation of a choroidal fistula and a peripheral sub-retinal bleb by viscodissection. An illuminated microcatheter (iTRACK-275TM, iScience Interventional) was primed and inserted into the sub-retinal space. The microcatheter’s illuminated tip was advanced to the equivalent of the submacular region in the pig eye, adjacent to the optic nerve while being visualized in through the pupillary aperture using an indirect ophthalmoscope. Staged experiments defined optimal injection conditions to successfully administer a cell therapy drug to the subretinal space using PBS, vehicle and various cell doses. A total of 40 procedures were performed in this study and all 40 eyes were subject to ophthalmic exams, optical coherence tomography (OCT) and fluorescein angiography, electroretinograms, and histological evaluation to evaluate effects due to microcatheter placement, microcatheter advancement and instillation of cells into the sub-retinal space throughout a 3 month-life follow-up period.

Results: : Successful catheterization of the sub-retinal space was achieved in all 40 eyes, and cellular products or controls were successfully injected in all cases. Seven instances of retinal perforation were noted with no immediate intraoperative or perioperative complications. The majority of perforations were attributed to improper surgical techniques such as inserting the microcatheter at a high angle of entry (3 out of 7). At 3 months minimal to moderate, non-proliferative, local histological changes were observed at the level of choroid and retinal pigment epithelium. These correlated well with observations made using OCT. Retinal function as measured by electroretinography was unaffected.

Conclusions: : Ab-externo catheterization of the sub-retinal space without penetration of the intraocular space to deliver a cell based therapy can be achieved without significant surgical trauma or adverse consequences in Göttingen miniature pigs.

Keywords: vitreoretinal surgery • injection • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) 

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