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Peter K Jarrett, Rami F Elhayek, Sarah Guedez, Courtney Rosales, Timothy S. Jarrett, Amar Sawhney; Tolerability of Intravitreal Hydrogel Depots for Anti-VEGF Sustained Release in a Rabbit Model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1496.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the tolerability of hydrogel intravitreal depots for sustained release of anti-VEGFs.
The release kinetics, stability and sustained release of high molecular weight proteins, antibodies and anti-VEGFs from polyethylene glycol (PEG) hydrogel depots (PHD) have been previously reported. In this study, tolerability of in situ formed placebo PHDs was tested. In vivo assessment was conducted in rabbit eyes (n=6; 25µl injection volume) for 4 and 8 weeks using ocular clinical observations and histopathology.
Intravitreal PHDs retrieved from rabbit eyes after 2 weeks are shown in Figure 1 (left). PHDs were noted to be monolithic and contained as a single mass. Infrared imaging (Figure 1 (right)) containment and restricted mobility of the depot in the vitreous humor. All eyes clinically examined using the McDonald-Shadduck scoring system were noted normal. Histopathology analysis summarized in Figure 2 shows PHDs to be biocompatible in terms of vitreal, retinal and scleral inflammation through 56 days. Fibrosis scores near implant and hyperplasia in ora serrata were also found to be negligible. [Figure 2 score description 0: No change; normal - 1: Rare foci of change; minimal - 2: Mild diffuse change or more pronounced focal change; 3: Moderate diffuse change - 4: Marked diffuse change - 5: Severe diffuse change].
The in situ formed bioresorbable hydrogel depots were shown herein to cause minimal histopathological changes in rabbit eyes through 2 months. The injectable depot resides in the eye as a single mass restricting it from floating into the visual axis. Combination of these findings with previously reported release kinetic profiles provides a new technology platform to sustain the release of high molecular weight proteins from biocompatible, bioresorbable intravitreal hydrogel depots up to 4-6 months. Sustained anti-VEGF release may decrease the frequency of intravitreal injections and reduce the risk of side effects. The frequency of the intravitreal injections is still the major challenge to overcome in treating posterior ocular diseases to prevent vision loss or even gain visual acuity.
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