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Arthur Driscoll, Charles D Blizzard, Jonathan H Talamo, Peter K Jarrett, Rami F Elhayek, Tim Jarrett, Zach Lattrell, Michael McGrath, Stephen Takach, Amar Sawhney; Tolerability of a Shape Changing Intravitreal Hydrogel Depot. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1980. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
We evaluated the tolerability of a shape changing bioabsorbable hydrogel in Dutch belted rabbits. This hydrogel can be used as a vehicle for the sustained delivery of tyrosine kinase inhibitors (TKI) as well as large molecule anti-VEGF agents delivered via intravitreal injection in Dutch belted rabbits through 6 months.
Eighteen eyes of naïve Dutch belted rabbits (n=9) were bilaterally dosed with the vehicle control at Day 0. Biweekly slit lamp, IOP, and posterior segment exams were performed. 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.
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.
The shape changing hydrogel 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. Infrared fundus photography findings were consistent with depot resorption through 6 months.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
Histopathologic analysis demonstrated minimal to no vitreal, retinal or scleral inflammation, or fibrosis around the injected material
Infrared fundus photography showed increasing shrinkage of depot size over time. OCT shows normal chorioretinal morphology through 6 months. In some cases, hydrogel was not present at the 6 month time point
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