June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Tolerability of a 6 month Sustained Hydrogel Delivery System for Tyrosine Kinase Inhibitors in Dutch Belted Rabbits
Author Affiliations & Notes
  • Peter K Jarrett
    Ocular Therapeutix, Lexington, Massachusetts, United States
  • Rami F Elhayek
    Ocular Therapeutix, Lexington, Massachusetts, United States
  • Tim Jarrett
    Ocular Therapeutix, Lexington, Massachusetts, United States
  • Zach Lattrell
    Ocular Therapeutix, Lexington, Massachusetts, United States
  • Michael McGrath
    Ocular Therapeutix, Lexington, Massachusetts, United States
  • Stephen Takach
    Ocular Therapeutix, Lexington, Massachusetts, United States
  • Jonathan H. Talamo
    Ocular Therapeutix, Lexington, Massachusetts, United States
  • Amar Sawhney
    Ocular Therapeutix, Lexington, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Peter Jarrett, Ocular Therapeutix (E); Rami Elhayek, Ocular Therapeutix (E); Tim Jarrett, Ocular Therapeutix (E); Zach Lattrell, Ocular Therapeutix (E); Michael McGrath, Ocular Therapeutix (E); Stephen Takach, Ocular Therapeutix (E); Jonathan Talamo, Ocular Therapeutix (E); Amar Sawhney, Ocular Therapeutix (E)
  • Footnotes
    Support  Ocular Therapeutix supported this research.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1956. doi:
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      Peter K Jarrett, Rami F Elhayek, Tim Jarrett, Zach Lattrell, Michael McGrath, Stephen Takach, Jonathan H. Talamo, Amar Sawhney; Tolerability of a 6 month Sustained Hydrogel Delivery System for Tyrosine Kinase Inhibitors in Dutch Belted Rabbits. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1956.

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

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Abstract

Purpose : We evaluated the tolerability of sustained delivery of a tyrosine kinase inhibitor (TKI) with known anti-angiogenic properties from a preformed bioabsorbable hydrogel fiber depot delivered via intravitreal injection in Dutch belted rabbits through 6 months.

Methods : Micronized TKI particles were formulated in a hydrogel matrix (OTX-TKI). Eighteen eyes of naïve Dutch belted rabbits (n=9) were bilaterally dosed with OTX-TKI at Day 0. Biweekly slit lamp, IOP, posterior segment exams using the MacDonald Shadduck scoring system. Monthly OCT was performed, and fluorescein angiography (FA), infrared fundus photography and electroretinography (ERG) were obtained at Months 1, 3 and 6. Eyes were enucleated at each time point (n=6) for histopathological evaluation.

Results : Serial clinical examinations showed no sign of inflammatory response or other abnormalities. No clinically-significant changes in IOP, OCT, ERG or FA were observed. Infrared fundus photography showed increasing translucency and shrinkage of depot size over time. At 1, 3 and 6 months, histopathologic analysis demonstrated minimal changes from baseline in cornea, conjunctiva, sclera, choroid, retina, and vitreous humor. Evidence of depot material was present at all time points.

Conclusions : OTX-TKI appears well-tolerated in a DB rabbit model. In addition to an absence of clinical findings suggestive of immunoreactivity, light microscopy of tissue sections and OCT imaging showed minimal to no evidence of inflammatory response or abnormal chorioretinal morphology suggestive of tissue toxicity. Infrared fundus photography findings were consistent with ongoing drug release through 6 months as well as depot resorption.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

OTX-TKI, in vivo OcularTolerability

OTX-TKI, in vivo OcularTolerability

 

OTX-TKI Retinal Tolerability

OTX-TKI Retinal Tolerability

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