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Sara Wetzstein, Jana T Sellers, Kevin Donaldson, Gretchen Unger, Shanu Markand, priyanka priyadarshani, Jeffrey H Boatright, J M Nickerson; Intravitreal injection vs. topical eye drop application of nanoparticles using a mouse model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1748. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study was to test the hypothesis that intravitreal injection of nanoparticles (NPs) coated with hyaluronic acid (HA) impacts retinal morphology more than topical application in mouse eyes.
Male 129S2 mice at postnatal day 185 were subjected to either topical eye drop application (n=8) or intravitreal injection using a transcorneal route (n=8) of nanoparticles. Two hours post injection, mice were euthanized and eyes were enucleated with neutral buffered formalin with zinc fixation, sectioning, H&E staining, and imaging. A score system was employed using 3 separate blind examiners for evaluation of representative eye sections at 10X. Each section was graded for cracks, peeling, and histological damage. Evaluation followed a 4-point grading system for cornea, retina, lens, and an overall score, with 0=intact morphology, 1=light damage, 2=mild damage, and 3=heavy damage. A Mann-Whitney test was used to assess statistical significance between treatment groups.
Histological analysis revealed that intravitreal injection significantly damaged overall eye morphology (Topical: 1.055; Intravitreal: 2.055, p<0.0002) with a lower score indicating more intact morphology. Intravitreal injected eyes were significantly damaged for the cornea (Topical: 0.670; Intravitreal: 1.915, p <0.0061), lens (Topical: 1.165; Intravitreal: 2.250, p <0.0025), and retina (Topical: 1.250; Intravitreal: 2.000, p <0.0146) when analyzed individually. More intravitreal eyes hemorrhaged (50%) compared with topical eyes (12.5%).
Our data support the hypothesis that intravitreal nanoparticle injection significantly impacts eye morphology. Topical drops had fewer lens fractures, better-attached retinas, straight irises, and undamaged corneal epithelium and endothelium in H&E sections. Thus, the adverse impact of intravitreal injections should be counterbalanced with the potential benefit of direct nanoparticle delivery.
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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