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D. E. Berezovsky, S. R. Patel, W. Gao, B. E. McCarey, H. F. Edelhauser; Pharmacokinetics of Fluorescein Delivered via Intra- and Periocular Injections: An in vivo Study Using Noninvasive Fluorophotometry. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5111.
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© ARVO (1962-2015); The Authors (2016-present)
To compare the intraocular distribution and pharmacokinetics of a small, hydrophilic molecule using noninvasive fluorophotometry and three injection techniques: intravitreal, sub-Tenon and suprachoroidal.Materials/
Nine NZW rabbits weighing 6-7lbs. were used in accordance with ARVO’s Statement for the Use of Animals in Ophthalmic and Visual Research. Three rabbits received an injection of 0.3ug sodium fluorescein (NaF) in 50ul balanced salt solution (BSS, Alcon Laboratories) in the left eye. Three rabbits received 30ug NaF in 50uL BSS via suprachoroidal injection, and three received 400ug NaF in 200uL BSS via sub-Tenon injection. Right eyes were used as negative controls. Ocular fluorescence was determined noninvasively using a Fluorotron Master Fluorometer (Ocumetrics) on both eyes prior to injection and hourly through six hours post injection.
Intravitreal injections exhibited a large fluorescence peak at the mid-vitreous immediately following the injection, achieving homogeneous vitreous fluorescence by 3 hours and complete clearance from the posterior segment by 24 hours. Suprachoroidal and sub-Tenon injections exhibited a peak at the retina/choroid/sclera within minutes of injection, reaching maximum fluorescence by 3 hours and complete clearance by 24 hours post injection. The average maximum fluorescence level achieved at the mid-vitreous was 614ng/mL, 48ng/mL and 20ng/mL for intravitreal, suprachoroidal and sub-Tenon injections, respectively. Average maximum fluorescence levels achieved at the retina/choroid/sclera were 256ng/mL, 1843ng/mL and 287ng/mL for intravitreal, suprachoroidal and sub-Tenon injections, respectively.
This comparative in vivo study shows that a small hydrophilic molecule (NaF) exhibits a similar pharmacokinetic profile when injected using three different delivery techniques, but differs in the relative concentrations reached at the various tissues of the posterior segment. Suprachoroidal injection achieved the highest concentration of drug at the retina/choroid, while intravitreal injection showed higher levels throughout the vitreous cavity.
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