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S.E. Varner, P.A. A. Mello–Filho, D. Guven, N.R. F. Beeley, E. de Juan, Jr; Helical Intravitreal Triamcinolone Implant: Safety and Elution in the Rabbit Eye . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3534.
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Purpose: To evaluate the ocular safety and elution characteristics of the Helical Intravitreal Triamcinolone Implant in the rabbit eye. Methods: Three formulations of the implant were investigated: a polymer–only Control, Dose A (slow release formulation), and Dose B (fast release formulation). Both Dose A and Dose B contained approximately 925 micrograms of drug. The right eyes of forty pigmented rabbits were implanted intravitreally (10 control, 15 Dose A, and 15 Dose B). Animals were followed up to 6 months, with complete ocular examinations at baseline, 1 week, 4 weeks, 3 months, and 6 months. Electroretinography (ERG) was performed at 6 months. At each sacrifice timepoint (4 weeks, 3 months, and 6 months), eyes were prepared for histology or implants removed and assayed by HPLC for remaining drug content. Results: One rabbit was sacrificed at 17 days due to infectious endophthalmitis. Of the remaining 39 animals, all remained in good general health throughout the study. Follow–up clinical examinations reflected good biocompatibility. Focal superotemporal cataracts were observed in 10/15 (67%) of eyes at 6 months and were attributed to contact with the tip of the implant, owing to the relatively large size and posterior position of the rabbit lens. No higher incidence of cataract was statistically correlated to Dose A or Dose B vs. Control implants. No clinically significant trends in intraocular pressure were observed over the course the study. Implantation, regardless of formulation (Dose A, Dose B, or Control), did not result in any clinically or statistically significant electrophysiological changes. Histological analysis revealed minimal fibrosis and inflammation. Mean percentages of cumulative triamcinolone released were 12.6, 13.6, and 25.6 for Dose A at the 1, 3, and 6 month time points, respectively. For Dose B, the mean percentages released were 28.4, 51.3, and 77.1. Based upon these results, the predicted durations of release for Dose A and Dose B are 23 months and 10 months, respectively. Conclusions:The helical implant was demonstrated to be safe in this study. No clinically significant ocular effects were attributed to the test article, as measured by fundus examination, ERG, histological analysis, and IOP. In addition, the elution pattern of the implants was well controlled throughout the duration of the study, with good separation of the two dosage forms.
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