Effects of vitreous liquefaction on the intravitreal distribution of sodium fluorescein, fluorescein dextran and fluorescent microparticles

Lay Ean Tan, Werhner Orilla, Patrick M. Hughes, Susan Tsai, James A. Burke, Clive G. Wilson

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Purpose. 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.
LanguageEnglish
Pages1111-1118
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number2
Early online date29 Sep 2010
DOIs
Publication statusPublished - Feb 2011
EventARVO 2009 Summer Eye Research Conference (SERC 2009) on Ophthalmic Drug Delivery Systems - Bethesda, United States
Duration: 31 Jul 20091 Aug 2009

Fingerprint

Hyaluronoglucosaminidase
Fluorescein
Rabbits
Vitreous Body
Intravitreal Injections
Pharmaceutical Preparations
Suspensions
Angiography
Lasers
Gels
Equipment and Supplies
fluorescein-dextran
fluorescein isothiocyanate dextran

Keywords

  • vitreous liquefaction
  • elderly
  • intravitreal injection
  • drugs
  • drug distribution
  • sodium fluorescein
  • fluorescein dextran
  • fluorescent microparticles

Cite this

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title = "Effects of vitreous liquefaction on the intravitreal distribution of sodium fluorescein, fluorescein dextran and fluorescent microparticles",
abstract = "Purpose. 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.",
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Effects of vitreous liquefaction on the intravitreal distribution of sodium fluorescein, fluorescein dextran and fluorescent microparticles. / Tan, Lay Ean ; Orilla, Werhner ; Hughes, Patrick M. ; Tsai, Susan ; Burke, James A. ; Wilson, Clive G.

In: Investigative Ophthalmology and Visual Science, Vol. 52, No. 2, 02.2011, p. 1111-1118.

Research output: Contribution to journalArticle

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T1 - Effects of vitreous liquefaction on the intravitreal distribution of sodium fluorescein, fluorescein dextran and fluorescent microparticles

AU - Tan, Lay Ean

AU - Orilla, Werhner

AU - Hughes, Patrick M.

AU - Tsai, Susan

AU - Burke, James A.

AU - Wilson, Clive G.

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N2 - Purpose. 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.

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