Cannulation of the suprachoroidal space: a novel drug delivery methodology to the posterior segment.

PURPOSE: To describe, test, and evaluate the pharmacokinetics of a novel posterior drug delivery system (PDS) by means of microcannulation of the suprachoroidal space in both the primate and pig animal model. DESIGN: Animal study. METHODS: A rhesus macaque (Macaca mulatta) (n = 1) and pig model (n = 93) were used to evaluate the PDS, a microcannula that combines a drug delivery channel with a fiber-optic illumination and optimal transition properties. The surgical technique, safety profile, histopathology, retinal and choroidal blood flow, injection of tracer dyes, and triamcinolone pharmacokinetics were studied. Pre- and postsurgical high-speed video confocal scanning laser ophthalmoscopy (cSLO) that used fluorescein and indocyanine green (ICG) imaging and wide-field fundus imaging studies were performed. Globes were enucleated for either histopathology or pharmacokinetics. RESULTS: Cannulation was performed in 93 of 94 animals. Complications included: endophthalmitis (1/94), choroidal tear (1/94), choroidal blood flow irregularities (4/94), postoperative inflammation (6/94), scleral ectasia (4/94), wound abscess (1/94), and others. Histopathology demonstrated normal anatomy in uncomplicated cases. Triamcinolone remains in the local ocular tissue for at least 120 days, and measurable at very low levels in the systemic circulation. CONCLUSIONS: Accessing the suprachoroidal space by the microcannulation system can be performed in a safe and reproducible manner by using careful surgical technique. Forceful PDS tip impact into connective tissues in the macular and optic nerve regions should be avoided. Triamcinolone pharmacokinetics are unique and suggest long-term local tissue levels with low systemic levels. PDS access to the suprachoroidal space represents a novel drug delivery method, applicable to a wide variety of pharmacotherapies to the macula, optic nerve, and posterior pole.

Failure characteristics of multiple-component fibrin-based adhesives.

A series of analyses were performed on fibrin-based adhesives to describe their failure characteristics. Two test methods were used: uniaxial, monotonic tensile testing of the bulk material, and blister testing using fresh porcine-source skin graft as the adherend. Two fibrin concentrations, high (HFC), and low (LFC), were used to investigate the effects of the gel matrix density upon mechanical properties. In tensile tests, fibrin gels strain hardened, as functions of percent strain and of strain rate. An increase in modulus of elasticity (E) was seen with increasing strain and strain rate at both tested fibrin concentrations. Mode I failure mechanisms were predominant. Both adhesives appeared to fracture from the outer edge to the interior of the specimen at slower strain rate tests. This trend reversed as strain rate increased, becoming a classic "cup and cone" ductile fracture. Syneresis occurred at both concentrations at lower strain rates, but was more pronounced for the LFC. Ultimate tensile strength and E were greater for the HFC than for the LFC at all strain rates, decreasing with increasing strain rate. In the blister test, the failure locus changed from cohesive to adhesive as the strain rate was increased for the HFC. Failure of fibrin gels likely occurs by percolation of the pressurized saline, displacing the entrapped liquid phase of the gel in regions of relatively low moduli and strength, leading to fracture of the matrix. For LFC, the overall fracture locus remained predominantly cohesive regardless of strain rate. Burst strength and failure energy were higher for HFC than for LFC. It would appear that fibrin acts more as a viscous liquid than a rubberlike/elastic material at lower concentrations because adhesive failures had a higher burst strength and fracture energy (Gc) than did cohesive failures.