Abstract
Abstract: :
Purpose: To confirm anecortave acetate posterior juxtascleral drug delivery in rabbit eyes by ocular imaging techniques and to determine drug localization and distribution as a function of time post–injection. Methods: Four female New Zealand White Rabbits weighing 2.5 to 3.0 kilograms received a single posterior juxtascleral sub–Tenon’s injection of 0.5 or 1 ml of 30 mg/ml anecortave acetate. Rabbit eyes were imaged with ultrasonography and magnetic resonance imaging (MRI) prior to injection, immediately after injection, at 2 hours, 1 week and 4 weeks post–injection. Rabbit eyes were also imaged with b–mode ultrasonography during the juxtascleral injections. Results: Ultrasonographic and magnetic resonance imaging demonstrated that posterior juxtascleral sub–Tenon’s administration of anecortave acetate effectively delivers the drug in direct apposition to the posterior pole of the rabbit eye. The drug remained in the juxtascleral site for at least five weeks. The drug was visualized clearly by MRI immediately post injection, decreasing in intensity thereafter. Cannula insertion and drug delivery were visualized clearly by real–time b–mode ultrasound. The drug was visualized as an area of echolucency in the posterior juxtrascleral position during, immediately following and at two hours post–injection. At 1 week and 5 weeks post–injection, the anecortave acetate depot was clearly visualized as a discrete echodense area in the injection site. Conclusions: Periocular posterior juxtascleral administration of anecortave acetate via a subTenon’s approach effectively delivered the drug to the desired position in direct apposition to the globe posteriorly. Magnetic resonance and ultrasonographic imaging both demonstrated that anecortave acetate remains localized to this location for at least five weeks following initial injection. Periocular posterior juxtascleral anecortave acetate administration is currently being evaluated for the treatment of non–exudative and exudative age–related macular degeneration in humans and for the treatment of retinoblastoma in preclinical models. These data demonstrated in an animal model that the anecortave acetate administration technique is effective in delivering the drug to the desired posterior juxtascleral site where optimal transscleral passage of the drug toward its site of action is achieved.
Keywords: imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)