title: Assessment of subconjunctival and intrascleral drug delivery to the posterior segment using dynamic contrast-enhanced magnetic resonance imaging.
abstract: OBJECTIVE
  Sustained-release intravitreal drug implants for posterior segment diseases are associated with significant complications. As an alternative, subconjunctival infusions of drug to the episclera of the back of the eye have been performed, but results in clinical trials for macular diseases showed mixed
  
  
  RESULTS
  To improve understanding of transscleral drug delivery to the posterior segment, the distribution and clearance of gadolinium-diethylene-triamino-penta-acetic acid (Gd-DTPA) infused in the subconjunctival or intrascleral space was investigated by means of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
  
  
  METHODS
  In anesthetized rabbits, catheters were placed anteriorly in the subconjunctival or intrascleral space and infused with Gd-DTPA at 1 and 10 muL/min. Distribution and clearance of Gd-DTPA were measured using DCE-MRI. Histologic examination was performed to assess ocular toxicity of the delivery system. results. Subconjunctival infusions failed to produce detectable levels of Gd-DTPA in the back of the eye. In contrast, intrascleral infusions expanded the suprachoroidal layer and delivered Gd-DTPA to the posterior segment. Suprachoroidal clearance of Gd-DTPA followed first-order kinetics with an average half-life of 5.4 and 11.8 minutes after intrascleral infusions at 1 and 10 muL/min, respectively. Histologic examination demonstrated expansion of the tissues in the suprachoroidal space that normalized after infusion termination.
  
  
  CONCLUSIONS
  An intrascleral infusion was successful in transporting Gd-DTPA to the posterior segment from an anterior infusion site with limited anterior segment exposure. The suprachoroidal space appears to be an expandible conduit for drug transport to the posterior segment. Further studies are indicated to explore the feasibility of clinical applications.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland, USA. kimstep@mail.nih.gov
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Kim
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Galbán
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lutz
authors.forename: Robert L
authors.initials: RL
authors.lastname: Dedrick
authors.forename: Karl G
authors.initials: KG
authors.lastname: Csaky
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Lizak
authors.forename: Nam Sun
authors.initials: NS
authors.lastname: Wang
authors.forename: Ginger
authors.initials: G
authors.lastname: Tansey
authors.forename: Michael R
authors.initials: MR
authors.lastname: Robinson
mesh_terms: D000818:Animals; D002829:Choroid / Q000378:metabolism*; D003228:Conjunctiva / Q000187:drug effects*; D003287:Contrast Media / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007263:Infusions, Parenteral; D008279:Magnetic Resonance Imaging / Q000379:methods; D011817:Rabbits; D012160:Retina / Q000378:metabolism*; D012590:Sclera / Q000187:drug effects*
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA