Efficacy and safety of injecting increasing volumes into the extravascular spaces of the choroid using a blunt adjustabl

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ORIGINAL PAPER

Efficacy and safety of injecting increasing volumes into the extravascular spaces of the choroid using a blunt adjustable depth injector Ifat Sher . Ettel Bubis . Hadas Ketter-Katz . Zehavit Goldberg . Rawan Saeed . Ygal Rotenstreich

Received: 27 April 2020 / Accepted: 20 June 2020 Ó Springer Nature B.V. 2020

Abstract Purpose To evaluate the efficacy and safety of injecting increasing volumes into the extravascular spaces of the choroid (EVSC) in rabbit eyes in vivo using a blunt adjustable depth injector. Methods Indocyanine green (ICG) was injected in the superior–temporal quadrant, 2 mm posterior to the limbus at increasing volumes (0.1–0.3 ml) into the EVSC of New Zealand rabbit eyes in vivo. Intraocular pressure (IOP) measurements, spectral domain optical coherence tomography (SD-OCT), fundus imaging and histology analysis were performed to assess the safety and efficacy of the injection. Results Volumes up to 0.3 ml were administered consistently. ICG injection was successfully monitored in vivo using infrared fundus imaging and SDOCT. ICG was detected across the EVSC

compartment, reaching the retinal pigment epithelium, optic nerve head and visual streak. Injection of 0.3 ml yielded maximal dye distribution with a coverage area of 61.8% ± 6.7% (mean ± standard error, SE) of the posterior segment. Maximal IOP elevation was recorded 5 min following injection of 0.2 and 0.3 ml ICG (? 20.0 mmHg, ? 19.4 mmHg, respectively). Twenty minutes post-injection, the IOP was \ 15 mmHg in all injection volumes. No retinal detachment or hemorrhages were detected in any of the injected eyes. Conclusions This study demonstrates consistent and safe delivery of large volumes within the EVSC using a blunt adjustable depth injector that distributes the dye over 60% of the retinal surface. This injection system may offer a minimally invasive and easy way to deliver large volumes of pharmaceuticals into the posterior segment.

Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10792-020-01471-9) contains supplementary material, which is available to authorized users.

Keywords Posterior segment  Retina  Choroid  Extravascular space  Drug delivery

I. Sher  E. Bubis  H. Ketter-Katz  Z. Goldberg  R. Saeed  Y. Rotenstreich (&) Goldschleger Eye Institute, Sheba Medical Center, 52621 Tel-Hashomer, Israel e-mail: [email protected] I. Sher  E. Bubis  H. Ketter-Katz  Z. Goldberg  R. Saeed  Y. Rotenstreich The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Introduction Treatment of posterior segment diseases that affect millions of patients worldwide is limited by the difficulty in delivering drugs to the posterior segment of the eye in close proximity to the affected tissues—

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Int Ophthalmol

choroid, retinal pigmented epithelium (RPE) and retina [1]. Currently, steroids and anti-angiogenic antibodies are administrated by intravitreal injections. However, relatively fast