March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Repeated Ab-Externo Catheterization of the Sub-retinal Space Using a Microcatheter for Targeted Delivery of a Cell Therapy Product in a Pig Model
Author Affiliations & Notes
  • Marc D. de Smet
    Ophthalmology, Clinique de Montchoisi, Lausanne, Switzerland
  • Sylvie Wyse
    Preclinical Services, Charles River Laboratories, Montreal, Quebec, Canada
  • Mark Vezina
    Preclinical Services, Charles River Laboratories, Montreal, Quebec, Canada
  • Stan Conston
    iScience Interventional, Menlo Park, California
  • Cliff Sachs
    Janssen Pharmaceuticals Companies of Johnson & Johnson, Radnor, Pennsylvania
  • Sicco H. Popma
    Janssen Pharmaceuticals Companies of Johnson & Johnson, Radnor, Pennsylvania
  • Footnotes
    Commercial Relationships  Marc D. de Smet, Janssen {harmaceuticals (R); Sylvie Wyse, Charles River Laboratory (E); Mark Vezina, Charles River Laboratories (E); Stan Conston, iScience Interventional (E); Cliff Sachs, Johnson & Johnson (E); Sicco H. Popma, Johnson & Johnson (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 5844. doi:
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      Marc D. de Smet, Sylvie Wyse, Mark Vezina, Stan Conston, Cliff Sachs, Sicco H. Popma; Repeated Ab-Externo Catheterization of the Sub-retinal Space Using a Microcatheter for Targeted Delivery of a Cell Therapy Product in a Pig Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5844.

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

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Abstract

Purpose: : Evaluate the feasibility and safety of repeated sub-retinal injections via a microcatheter.

Methods: : 21 Göttingen miniature pigs 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 TM -275, 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 through the pupillary aperture using an indirect ophthalmoscope. BSS+, vehicle and various cell doses were administered at 6 month dose intervals. Three doses were given to each eye over a 12 month period with an additional 3 month follow up. 124 procedures were performed in this study. All 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 15 month follow-up period.

Results: : nterim results showed that recatherization 6 months post first sub-retinal catherization was achieved in all eyes. Cells and vehicle controls were successfully injected at the same or adjacent sites forming blebs on the initial and the second dosing occasion. Iatrogenic retinal perforations were noted in approximately 14% of treated eyes but resulted in no immediate intraoperative or perioperative complications. After two injections, minimal to moderate, non-proliferative, changes were observed at the level of choroid and retinal pigment epithelium as assessed via imaging technology (Heidelberg, Spectralis, Fundus imaging and SD-OCT). No damage was observed in the overlying retina.

Conclusions: : Repeat ab-externo catheterization of the sub-retinal space can be achieved without significant surgical trauma or adverse consequences in Göttingen miniature pigs.

Keywords: age-related macular degeneration • retina • macula/fovea 
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