Effects of vitreous liquefaction on the intravitreal distribution of sodium fluorescein, fluorescein dextran, and fluorescent microparticles.
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.
Tan
Lay Ean
LE
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Orilla
Werhner
W
Hughes
Patrick M
PM
Tsai
Susan
S
Burke
James A
JA
Wilson
Clive G
CG
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*
D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D006821:Hyaluronoglucosaminidase; D016650:Fluorescein-5-isothiocyanate; D019793:Fluorescein