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Charles D Blizzard, Courtney Rosales, Timothy Jarrett, Rami F Elhayek, sarah guedez, Andrew Vanslette, Peter K Jarrett, Arthur Driscoll, Amar Sawhney; Tolerability of In Situ Forming Intravitreal Hydrogel Depots for Anti-VEGF Sustained Release in a Rabbit Model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1120.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the ocular tolerability of an in situ forming hydrogel depot containing placebo hydrogel particles after intravitreal injection in a rabbit model compared to a saline control.
Tolerability of an intravitreal injection of an in situ formed polyethylene glycol (PEG) hydrogel depot (Group 2) and a hydrogel depot containing placebo hydrogel particles (Group 3) was evaluated relative to a saline control (Group 1). The hydrogel particles are utilized to encapsulate anti-VEGF proteins to provide sustained release (Guedez et. al, IOVS. 2015; 56(7):1500). In vivo tolerability assessment was conducted in rabbit eyes (n=6; 20 µl injection volume) for 6 weeks and clinical ophthalmic examinations, intraocular pressure (IOP) and histopathology were tested.
Representative photomicrographs of retina samples comparing the saline control to the in situ formed hydrogel depot with and without hydrogel particles are shown in Figure One. Average histopathology scores, provided in Table One, demonstrate either no change or only a very minimal change when evaluated for fibrosis near the implant, epithelial hyperplasia in front of the ora serrata, and surrounding tissue inflammation (subcorneal, retinal, scleral, episcleral and vitreous chamber). All eyes were clinically examined at 2, 4, and 6 weeks using the modified McDonald-Shadduck scoring system to assess 16 ocular categories; results were normal for all eyes. IOP was normal for all eyes over the study duration.
The in situ formed hydrogel depots containing hydrogel particles delivered via an intravitreal injection were shown to cause either none or minimal histopathological changes in rabbit eyes through 6 weeks when compared to a saline control. The in situ formed hydrogel depot provides containment and restricts mobility of the hydrogel particles in the vitreous humor after intravitreal injection. The demonstrated tolerability of an intravitreal hydrogel depot is a critical element towards the development of an anti-VEGF sustained release depot that may decrease the frequency of intravitreal injections.
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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