Dexamethasone Application to the Canine Eye With Transscleral Coulomb–Controlled Iontophoresis (CCI)

Abstract

Abstract: : Purpose: To evaluate the effectiveness of transscleral Coulomb–controlled iontophoresis (CCI) in achieving measurable intraocular dexamethasone (DEX) concentrations in the canine eye. Methods: Normal dogs (n=6) were treated uniocularly with topical DEX applied by transscleral CCI (20 mg/ml DEX, 10 minutes at 400µA with a 0.5cm² applicator; 0.8mA/cm²). The treatments occurred under general isoflurane anesthesia. Two additional dogs were treated intravenously (IV) with 2 mg/kg DEX. Serum was collected before and after treatment. Aqueous humor (AH), vitreous, retina, and choroid were collected from both eyes after DEX treatment. The post–treatment samples were collected at 2 hours (n=2), 4 hours (n=2), and 24 hours (n=2) after CCI, and at 2 hours after IV treatment (n=2). Following extraction with acetonitrile, DEX levels were measured in ppb by liquid chromatography and mass spectrometry (minimal detection level = 20 ppb). Results: At 2 hours, treated eyes showed the highest DEX concentrations in choroid, retina, and AH. The levels were lowest in the vitreous. There was no detectable drug level in the non–treated eyes. At 4 hours, DEX values dropped by up to 90%, but were still highest in the retina and choroid. No DEX could be detected in any of the ocular samples after 24 hours. DEX was found in both eyes 2 hours after IV treatment. Whereas the 2–hour values in vitreous, retina and choroid were comparable for CCI and IV treatment, the AH DEX levels after IV were at least 95% lower than the 2–hour values after CCI. Measurable serum DEX levels were only found after IV treatment. Conclusions: Transscleral CCI is a noninvasive method to reach therapeutic intraocular DEX concentrations, especially in the posterior segment. DEX levels were comparable between CCI and IV applications. Because there were no detectable serum DEX levels after CCI, this technique offers the opportunity to reach high intraocular DEX concentrations without the risk of systemic steroid–induced side–effects.

Keywords: retina • corticosteroids • pharmacology