Fluocinolone acetonide device

The success of intravitreal implants, such as achieved with ganciclovir, has renewed interest in developing an intravitreal corticosteroid implant to further enhance the intravitreal route of administration, thus reducing the need for multiple injections. Bausch and Lomb and Control Delivery Systems have developed an intravitreal implant that can deliver the corticosteroid fluocinolone acetonide (Retrisert) to posterior eye tissue for up to 3 years. The implant, which was approved in 2005 by the U.S. Food and DrugAdministration (FDA), delivers 0.59 or 2.1 mg of fluocinolone acetonide. The long-term ocular side effects of this device are unknown at this time. 

Jaffe GJ, Ben-Nun J, Guo H, et al. Fluocinolone acetonide sustained drug delivery device to treat severe uveitis. Ophthalmology 2000 107 2024—2033. 

Jaffe GJ, Yang CH, Guo H, et al. Safety and pharmacokinetics of an intraocular fluocinolone acetonide sustained delivery device. Invest Ophthalmol Vis Sci 2000 41 3569-3575. 

A rabbit model of uveitis has been used to test nondegradable devices containing dexamethasone, fluocinolone acetonide, cyclosporin A, and a combination of... 

If these in vitro results also hold in vivo, more fluocinolone acetonide would be released in actively inflamed eyes with great blood-ocular barrier breakdown and higher intravitreal protein concentration than in quiet eyes. It is not possible to assess the amount of drug remaining in a device by direct inspection. However, waiting for reactivation of a disease such as CMV retinitis to indicate that device replacement or... 

Figure 4 Fluocinolone acetonide release rates after nondegradable devices containing 2mg drug were placed in PBS (open circles), then switched back to PBS with 50% plasma proteins closed circles), and then switched back to PBS (open triangles), n — 8 at each time point. Data represent mean standard deviation. First arrow denotes time at which devices were switched from PBS to PBS + plasma protein. Second arrow refers to time at which devices switched back to PBS alone. Abbreviation. PBS, phosphate-buffered saline.

Figure 6 ERG B-wave amplitude ratios (drug device implanted eye/fellow eye) in normal rabbit eyes with a fluocinolone acetonide sustained-release device in one eye. The dark adapted B-wave amplitude ratio was initially slightly greater than one during the first three weeks of the study. Thereafter, levels remained near one for more than one year after device implantation. At 28 weeks, the B-wave amplitude ratio was lower than at other time points (approximately 0.75 P<0.05) however, by 54 weeks the ratio (0.89) was once again not significantly different from 1 (P = 0.17). Abbreviation ERG, electroretinography.

Figure 7 Histological sections of a normal rabbit eye that received a 15mg fluocinolone acetonide sustained-release device demonstrated normal uveal anatomy. (A) Iris and ciliary body (hematoxylin and eosin xl2). (B) Retina in the region of the medullary ray. There is an artifactual retinal detachment (hematoxylin and eosin x40). (C) High-power view of B (hematoxylin and eosin x 100).

Figure 5 Photograph of a drug delivery device containing 2 mg of fluocinolone acetonide (left). Ganciclovir device is shown on the right for comparison. Note the smaller size of the fluocinolone device. The drug core is surrounded by a polyvinyl alcohol/silicone laminate.

Figure 6 Fluorescein angiograms of the left eye of a patient with pan-uveitis for 5.5 years treated with a fluocinolone acetonide implant. (A, C) Mid arteriovenous phase and late phase frames, respectively, before device implantation showing petaloid hyperfluorescence corresponding to cystoid macular edema. (B, D) Mid arteriovenous phase and late phase frames, respectively, four months after device implantation showing resolution of the petaloid hyperfluorescence.

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