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Author Notes:

Correspondence: Mark R. Prausnitz, School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, GA 30332, USA; prausnitz@gatech.edu.

This work was carried out at the Institute for Bioengineering and Bioscience and Center for Drug Design, Development and Delivery at Georgia Tech.

The authors thank Cathy Payne (Broad River Pastures) for graciously providing rabbit eye specimens, Sha'Aqua Asberry for help with histology, Machelle Pardue for use of the RetCam, Victor Breedveld for helpful discussion, and Donna Bondy for administrative support.

Disclosure: B. Chiang, P; N. Venugopal, None; H.E. Grossniklaus, None; J.H. Jung, None; H.F. Edelhauser, Clearside Biomedical (I, C); M.R. Prausnitz, Clearside Biomedical (I, C)

Subjects:

Research Funding:

Supported by National Eye Institute (NEI) Grants EY017045 (BC, HFE, MRP), NEI EY022097 (BC, MRP), NEI EY007092 (BC), NEI EY025154 (BC), and NIH P30EY06360 (HEG).

Keywords:

  • suprachoroidal space
  • suprachoroidal space thickness
  • microneedle injection
  • ocular drug deliver
  • 3D cryo-reconstruction

Thickness and closure kinetics of the suprachoroidal space following microneedle injection of liquid formulations

Tools:

Journal Title:

Investigative Ophthalmology & Visual Science

Volume:

Volume 58, Number 1

Publisher:

, Pages 555-564

Type of Work:

Article | Final Publisher PDF

Abstract:

Purpose To determine the effect of injection volume and formulation of a microneedle injection into the suprachoroidal space (SCS) on SCS thickness and closure kinetics. Methods Microneedle injections containing 25 to 150 μL Hanks' balanced salt solution (HBSS) were performed in the rabbit SCS ex vivo. Distribution of SCS thickness was measured by ultrasonography and three-dimensional (3D) cryo-reconstruction. Microneedle injections were performed in the rabbit SCS in vivo using HBSS, Discovisc, and 1% to 5% carboxymethyl cellulose (CMC) in HBSS. Ultrasonography was used to track SCS thickness over time. Results Increasing HBSS injection volume increased the area of expanded SCS, but did not increase SCS thickness ex vivo. With SCS injections in vivo, the SCS initially expanded to thicknesses of 0.43 ± 0.06 mm with HBSS, 1.5 ± 0.4 mm with Discovisc, and 0.69 to 2.1 mm with 1% to 5% CMC. After injection with HBSS, Discovisc, and 1% CMC solution, the SCS collapsed to baseline with time constants of 19 minutes, 6 hours, and 2.4 days, respectively. In contrast, injections with 3% to 5% CMC solution resulted in SCS expansion to 2.3 to 2.8 mm over the course of 2.8 to 9.1 hours, after which the SCS collapsed to baseline with time constants of 4.5 to 9.2 days. Conclusions With low-viscosity formulations, SCS expands to a thickness that remains roughly constant, independent of the volume of fluid injected. Increasing injection fluid viscosity significantly increased SCS thickness. Expansion of the SCS is hypothesized to be controlled by a balance between the viscous forces of the liquid formulation and the resistive biomechanical forces of the tissue.

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© 2017, Association for Research in Vision and Ophthalmology Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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