title: Thickness and Closure Kinetics of the Suprachoroidal Space Following Microneedle Injection of Liquid Formulations.
abstract: To determine the effect of injection volume and formulation of a microneedle injection into the suprachoroidal space (SCS) on SCS thickness and closure kinetics.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, Georgia, United States.
authors.forename: Bryce
authors.initials: B
authors.lastname: Chiang
authors.affiliation: H. Milton Stewart School of Industrial & Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States.
authors.forename: Nitin
authors.initials: N
authors.lastname: Venugopal
authors.affiliation: Emory Eye Center, Emory University, Atlanta, Georgia, United States.
authors.forename: Hans E
authors.initials: HE
authors.lastname: Grossniklaus
authors.affiliation: School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States.
authors.forename: Jae Hwan
authors.initials: JH
authors.lastname: Jung
authors.affiliation: Emory Eye Center, Emory University, Atlanta, Georgia, United States.
authors.forename: Henry F
authors.initials: HF
authors.lastname: Edelhauser
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, Georgia, United States 4School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Prausnitz
mesh_terms: D000818:Animals; D002829:Choroid / Q000000981:diagnostic imaging / Q000378:metabolism*; D004867:Equipment Design; D021621:Imaging, Three-Dimensional; D056965:Injections, Intraocular; D007429:Intraocular Pressure / Q000502:physiology*; D008904:Miniaturization; D023421:Models, Animal; D009339:Needles; D011137:Polystyrenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D014018:Tissue Distribution; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D011137:Polystyrenes