title: Cannulation of the suprachoroidal space: a novel drug delivery methodology to the posterior segment.
abstract: OBJECTIVE
  To describe, test, and evaluate the pharmacokinetics of a novel posterior drug delivery system (PDS) by means of microcannulation of the suprachoroidal space in both the primate and pig animal model.
  
  
  METHODS
  Animal study.
  
  
  METHODS
  A rhesus macaque (Macaca mulatta) (n = 1) and pig model (n = 93) were used to evaluate the PDS, a microcannula that combines a drug delivery channel with a fiber-optic illumination and optimal transition properties. The surgical technique, safety profile, histopathology, retinal and choroidal blood flow, injection of tracer dyes, and triamcinolone pharmacokinetics were studied. Pre- and postsurgical high-speed video confocal scanning laser ophthalmoscopy (cSLO) that used fluorescein and indocyanine green (ICG) imaging and wide-field fundus imaging studies were performed. Globes were enucleated for either histopathology or pharmacokinetics.
  
  
  RESULTS
  Cannulation was performed in 93 of 94 animals. Complications included: endophthalmitis (1/94), choroidal tear (1/94), choroidal blood flow irregularities (4/94), postoperative inflammation (6/94), scleral ectasia (4/94), wound abscess (1/94), and others. Histopathology demonstrated normal anatomy in uncomplicated cases. Triamcinolone remains in the local ocular tissue for at least 120 days, and measurable at very low levels in the systemic circulation.
  
  
  CONCLUSIONS
  Accessing the suprachoroidal space by the microcannulation system can be performed in a safe and reproducible manner by using careful surgical technique. Forceful PDS tip impact into connective tissues in the macular and optic nerve regions should be avoided. Triamcinolone pharmacokinetics are unique and suggest long-term local tissue levels with low systemic levels. PDS access to the suprachoroidal space represents a novel drug delivery method, applicable to a wide variety of pharmacotherapies to the macula, optic nerve, and posterior pole.
authors.affiliation: University of Minnesota, Department of Ophthalmology, Minneapolis, Minnesota 55455-0501, USA. olsen010@umn.edu
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Olsen
authors.forename: Xiao
authors.initials: X
authors.lastname: Feng
authors.forename: Kathy
authors.initials: K
authors.lastname: Wabner
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Conston
authors.forename: David H
authors.initials: DH
authors.lastname: Sierra
authors.forename: David V
authors.initials: DV
authors.lastname: Folden
authors.forename: Morton E
authors.initials: ME
authors.lastname: Smith
authors.forename: J Douglas
authors.initials: JD
authors.lastname: Cameron
mesh_terms: D000818:Animals; D002404:Catheterization / Q000379:methods*; D002829:Choroid / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D004396:Coloring Agents; D016503:Drug Delivery Systems; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism; D005451:Fluorescein Angiography; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007208:Indocyanine Green; D008253:Macaca mulatta; D009887:Ophthalmoscopy; D012171:Retinal Vessels / Q000502:physiology; D013552:Swine; D014222:Triamcinolone Acetonide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014741:Video Recording
chemical_list: D004396:Coloring Agents; D005938:Glucocorticoids; D014222:Triamcinolone Acetonide; D007208:Indocyanine Green