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R.F. See, J.J. Peairs, S. Srivastava, P. Mruthyunjaya, S.S. Stinnett, H. Guo, M. Nazzaro, P. Ashton, G.J. Jaffe; Safety and Drug Release Profile of Injectable Intravitreal Sustained–Release Fluocinolone Acetonide Device . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5119.
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We determined the in–vitro drug release profile and in–vivo safety of an injectable sustained release fluocinolone acetonide (sr–FA) device in healthy rabbit eyes.
We constructed 2 groups (low–dose and high dose) of sr–FA devices small enough to inject through a modified 25g needle. Six devices from each group were placed in individual microcentrifuge tubes with 1.0mL of 0.1M PBS and placed in a water bath at 37° ± 1°C. The PBS was removed from each tube daily and replaced with fresh PBS. The amount of FA in the removed PBS was measured using HPLC at selected time points. Study animals, New Zealand White rabbits, were divided into 2 groups. The low–dose device was injected into the OD of Group 1 (n=23). Group 2 was injected with the high–dose device (n=22). Clinical exams were performed at 1, 3, 6, 9 and 12 months. Data were collected for signs of inflammation, injury, and device degradation. Four animals from each group underwent electroretinography in both the study and control eye before injection of the device and at 1 week and 1, 3, 6, 9, and 12 months post–injection.
High–dose devices had an initial release rate of 0.70 ±0.07mcg/day that declined to 0.41 ±0.05mcg/day over the next 100 days. Low–dose devices released between 0.21 ±0.04 and 0.34 ±0.03mcg/day over the same time period. The median grade for conjunctival injection, corneal and iris neovascularization, anterior chamber cell, flare, and fibrin, and vitreous opacities was 0 for all animals at all exam time points. No eyes developed retinal detachment during the study. In 2 eyes the device touched the lens. In 1 eye, the device was embedded in the lens. All 3 had lens opacities, median 1+ up to month 6; by month 9 the median opacity for the 3 eyes was 2+. Only 1 eye developed cataract (grade 1+) without device–lenticular touch. The mean B–wave amplitude ratio (implant eye:control eye) in Group 1 animals was 0.99 ±0.12 prior to injection of the device, and was 1.03 ±0.08 at 12 months. In Group 2 animals the pre–injection B–wave ratio was 1.03 ±0.20 and by month 9 was 0.97 ±0.16.
The injectable sr–FA device can be designed with a high initial drug release rate that subsequently tapers or with a lower, more constant, release rate. The device can be safely injected into the anterior vitreous and is well tolerated by the eye for up to 12 months. There is a low incidence of cataract formation most commonly associated with device–lenticular touch.
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