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T.W. Olsen, X. Feng, K. Wabner, S.R. Conston, D. Sierra, T.S. Chang, M. Smith, J.D. Cameron; Microcannulation and Pharmacokinetics of Triamcinolone in the Suprachoroidal Space: A Novel Drug Delivery System to the Macula and Optic Nerve . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3882.
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To describe the delivery of triamcinolone acetonide (TA) via an illuminated–microcannula posterior segment delivery system (PDS) to the suprachoroidal space (SCS) in vivo using both the primate (rhesus macaque) and pig model. To determine the safety and characterize the pharmacokinetics (PK) of this novel drug delivery system to the macula and optic nerve in the pig animal model.
A rhesus macaque (n=1) and pig models (n=93) were used to evaluate the PDS (iScience Surgical Corp.). The cannula contains a fiberoptic illuminated tip (beacon tip, BT), a drug delivery channel, and a stainless steel wire for optimal transition properties. The surgical technique, safety profile, histopathology, retinal and choroidal blood flow, plus injected tracer dyes were studied. Pre and post surgical high–speed video confocal scanning laser ophthalmoscopy (cSLO) using fluorescein and ICG imaging plus wide–field fundus images were performed. Globes were enucleated and processed for histopathology or pharmacokinetics (t= 0, 0.5, 1, 2, 4, 7, 14, 28, 30, 45, 60, 90, and 120 days) using a spectrophotometric method. Three doses were evaluated: 3 mg, 1.5 mg, and 0.75 mg.
Cannulation was performed in 93/94 animals. The PDS had superb cannulation properties, and the BT was visualized in the perimacular or optic nerve region. Complications in the animal models included: endophthalmitis (2/94), choroidal tear (1/94), choroidal blood flow irregularities (4/94), post–operative inflammation (6/94), and scleral ectasia (4/94). PK data demonstrates that the higher dose had stable choroid and retinal drug levels at 120 days (0.56 mg/g of tissue ± 0.17, and 0.12±0.04; respectively), similar to the low dose at 90 days (0.45±0.26 and 0.09±0.01). Histopathology demonstrated normal anatomy in uncomplicated cases.
Accessing the SCS using the microcannulation system is performed in a safe and reproducible manner. The pharmacokinetics are unique and suggest sustained drug levels beyond 120 days are likely. Care should be taken to avoid impact with the macular and optic nerve. The tip should not be modified. Microsurgical access to the SCS using the PDS represents a novel drug delivery method, applicable to a wide variety of pharmacotherapies that target the macula and posterior pole.
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