title: Effects of vitreous liquefaction on the intravitreal distribution of sodium fluorescein, fluorescein dextran, and fluorescent microparticles.
abstract: OBJECTIVE
  The effects of vitreous liquefaction in the elderly on the distribution of drugs from intravitreal injections, depots, or devices remains unclear. The purpose of the present study was to develop a liquefied vitreous model that simulates the aged condition, to enable the study of clinically relevant drug distribution.
  
  
  METHODS
  Dutch-belted rabbits were used to develop a study model using hyaluronidase as a vitreolytic agent. The effects of experimental vitreous liquefaction were investigated on intravitreal sodium fluorescein, fluorescein isothiocyanate-dextran (MW 150 kDa), and a suspension of 1-μm fluorescent particles. The distribution of these model compounds was monitored by retinal angiography with a confocal laser scanning system and ocular fluorophotometer.
  
  
  RESULTS
  Hyaluronidase-treated vitreous humor (n = 6) was found to decrease the gel phase to 41% ± 9% (wt/wt; mean ± SD) compared with 81% ± 9% in the control eyes (n = 8; P < 0.05). The distribution of sodium fluorescein and fluorescein isothiocyanate dextran was greater in the liquefied vitreous than in the control. In comparison to the normal vitreous, fluorescent particles sedimented faster in the liquefied vitreous, and the distribution was more dispersed and scattered.
  
  
  CONCLUSIONS
  A model of vitreous liquefaction in rabbits was successfully generated using intravitreal hyaluronidase. Small and large fluorescent molecules as well as particulates were distributed faster in liquefied vitreous than in the control. The results suggest enhanced convective flow and subsequent faster clearance in liquefied vitreous.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
authors.forename: Lay Ean
authors.initials: LE
authors.lastname: Tan
authors.forename: Werhner
authors.initials: W
authors.lastname: Orilla
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Hughes
authors.forename: Susan
authors.initials: S
authors.lastname: Tsai
authors.forename: James A
authors.initials: JA
authors.lastname: Burke
authors.forename: Clive G
authors.initials: CG
authors.lastname: Wilson
mesh_terms: D000818:Animals; D003911:Dextrans / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005128:Eye Diseases / Q000139:chemically induced / Q000378:metabolism*; D019793:Fluorescein / Q000493:pharmacokinetics*; D005451:Fluorescein Angiography; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015590:Fluorophotometry; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology; D058449:Intravitreal Injections; D018613:Microscopy, Confocal; D008863:Microspheres; D011817:Rabbits; D014018:Tissue Distribution; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism*
chemical_list: D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D006821:Hyaluronoglucosaminidase; D016650:Fluorescein-5-isothiocyanate; D019793:Fluorescein