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Ygal Rotenstreich, Ettel Bubis, Zehavit Goldberg, Hana Ziv, Sara Pri-Chen, Ifat Sher-Rosenthal; Drug delivery to the back of the eye using A minimally invasive adjustable-depth blunt injector. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6004. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize the safety and efficacy of injecting Bevacizumab and Indocyanine Green (ICG) at different volumes in the extravascular spaces of the choroid (EVSC) of rabbit eyes using a minimally-invasive adjustable-depth blunt injector.
The adjustable-depth blunt injector was used for injection of ICG at volumes ranging from 50 microliters to 300 microliters or 150 microliters of Bevacizumab at concentration of 25 mg/ml into the EVSC of one eye of New Zealand White rabbits (n=32). The contralateral eye was not injected. Ophthalmic exam, fundus multicolor and infra-red imaging, Spectral Domain Optical Coherence Tomography (SD-OCT) and histology analysis were performed for assessment of injection safety and efficacy. Bevacizumab distribution in the posterior segment was assessed by immunofluorescence analysis with Donkey anti-Human IgG DyLight 488.
ICG injected at volumes ≥100 microliters spread circumferentially towards the macula and optic nerve head, crossing to the other hemisphere. ICG injected at volumes ≥ 200 microliters covered ≥ 75% of the posterior segment. Bevacizumab was identified throughout the choroid and sclera 1 hour and 1 day after injection. Intraocular pressure (IOP) increased by 30 ± 1.8 mmHg (mean ± SD) two minutes following ICG injection at volumes ≥ 100 microliters and returned to baseline levels (10mmHg) within 20 minutes. Bevacizumab injection (n=15) induced a milder increase in IOP (16 ± 2.3 mmHg) two minutes following injection. IOP returned to baseline levels within 10 minutes following injection. No change in IOP was recorded in the contralateral, non-injected control eyes. No retinal detachment, choroidal hemorrhage or inflammation were detected in any of the injected eyes or contralateral control eyes.
The minimally invasive delivery system may be used to safely inject large volumes of pharmaceuticals into the EVSC from the same location used for intravitreal injections. Injected pharmaceuticals are spread in close proximity to the target tissues – choroid and retinal pigment epithelium and are maintained for at least 24 hours in the EVSC and sclera. This injection system may present an innovative treatment delivery strategy and may lead to development of novel and advanced treatments as well as sustained treatments options for blinding diseases.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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