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U. B. Kompella, X. Li, G. Zhan, S. S. Lee; Influence of Intravitreal Implant Location on Ocular Disposition of Fluocinolone Acetonide. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5971.
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Fluocinolone acetonide (FA) sustained release implants are in clinical use for treating chronic noninfectious uveitis. Also, clinical trials are underway for their use in treating macular edema. Using a custom made fluocinolone implant, the purpose of this study was to determine whether the implant placement in the anterior vs. posterior regions of the vitreous cavity influences the distribution of the drug to target tissues as well as tissues associated with drug toxicity.
Sixteen male Dutch-belted rabbits were randomly assigned to receive either anterior or posterior intravitreal implants of FA. Rabbits were sacrificed at 2 or 4 weeks after dosing. Cornea, aqueous humor, iris, ciliary body, trabecular meshwork, lens, vitreous, retina, choroid-RPE, and sclera were isolated and processed for drug analysis. Among these tissues, retina, choroid, and sclera were further separated into anterior and posterior parts to understand regional differences in drug distribution. Each of the other tissue was analyzed as a whole. A validated LC/MS/MS method was used to determine the tissue concentrations of FA.
The lowest concentration of FA was found in aqueous humor (1.2-6.1 ng/g) with both implant placements. FA distribution in cornea, iris, and lens for anterior implants was much higher than that of posterior implants. Relatively stable and high concentration of FA was found in trabecular meshwork (596.1-1064.8 ng/g) and ciliary body (547.5-725.8 ng/g) after either anterior or posterior implants. The vitreous concentrations were relatively steady at 192.9-221.0 ng/g after 2 or 4-weeks of anterior dosing and at 76.7-102.4 ng/g after 2 or 4-weeks of posterior dosing. The posterior parts of retina, choroid, and sclera received greater drug delivery with posterior intravitreal implant administration compared to the anterior implant.
Localization of sustained release intravitreal implants near the target regions in the retina is more advantageous than the conventional anterior placement of such systems. Posterior placement of implants, while enhancing retinal drug delivery and efficacy, reduces drug levels in lens and decreases the potential for cataracts. Drug distribution to trabecular meshwork is implicated in corticosteroid induced glaucoma. However, trabecular meshwork received similar fluocinolone levels with both placements of the implant.
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