Safety and Pharmokinetics of Triamcinolone Hexacetonide in Rabbit Eyes

Purpose: The aim of this study was to evaluate whether intravitreal triamcinolone hexace-tonide (TH) is a safe, longer lasting alternative to intravitreal triamcinolone acetonide (TA) in the rabbit eye. Methods: Three groups, each comprising of 15 Dutch-belted rabbits, received a unilateral injection of 0.1 mL of drug and 0.1 mL of physiologic salt solution in the fellow eye. Group I received TA, group II received commercially available TH, and group III received refor-mulated iso-osmolar triamcinolone hexacetonide (rTH). Simultaneous bilateral dark-adapted electroretinography was performed following the injection. Retinal morphology was assessed by using histopathology in each group enucleated 12 weeks after injection. High-performance liquid chromatography of vitreous isolated from the enucleated eyes was used to determine drug concentrations. Results: A significant reduction in saturated a-wave and maximal scotopic b-wave was ob-served in the group II eyes relative to the fellow control eyes at both 2 and 12 weeks postin-jection (P 0.001 for each comparison) but not in the other groups. Histopathology showed no differences between drug-injected eyes and fellow control eyes in groups I and III, but in group II there was severe degeneration of all retina layers. In group I, the drug half-life was 17.7 1.7 days, group II 44 13 days, and group III 12.8 2.3 days. Conclusions: The half-life of commercially available TH in the vitreous is double that of TA, but the former is toxic to the retina in this rabbit model. Reformulated iso-osmolar TH showed no evidence of deleterious effects to retina function or structure but had a similar half-life to TA. 19