Ophthalmic Drug Delivery Using Iontophoresis: Recent Clinical Applications.

Background: Iontophoresis is a noninvasive delivery system designed to overcome barriers to ocular penetration of topical ophthalmic medications by employing a low-amplitude electrical current to promote the migration of a charged drug substance across biological membranes. Trans-scleral iontophoresis of dexamethasone phosphate has demonstrated dramatically increased intraocular concentrations of dexamethasone in rabbit ocular tissues compared with topical instillation, including 50- to 100-fold greater aqueous humor concentrations. Methods: This article reviews available data on recent clinical applications of iontophoretic ophthalmic drug delivery. Results: The EyeGate II delivery system (EGDS) is a trans-scleral iontophoresis system that has been used in conjunction with EGP-437, a proprietary-charged formulation of dexamethasone phosphate for iontophoretic delivery. In patients with noninfectious anterior uveitis, EGP-437, delivered through 2 iontophoretic treatments using the EGDS, demonstrated similar efficacy to topical prednisolone acetate 1% eye drops instilled 8 times daily over 28 days, suggesting the potential to decrease or eliminate the need for daily dosing of topical steroids in this patient population. Other applications for EGP-437 delivered through the EGDS that have been explored in clinical trials include treatment of dry eye, postsurgical inflammation and pain, and scleritis. In addition, transcorneal iontophoresis has been used outside of the United States to enhance riboflavin penetration in patients undergoing corneal cross-linking as therapy for progressive keratoconus. Conclusions: The reviewed studies demonstrate the feasibility of using iontophoresis to enhance drug delivery to ocular tissues and support the potential of this noninvasive technique across a range of ophthalmic indications.

Evaluation of dexamethasone phosphate delivered by ocular iontophoresis for treating noninfectious anterior uveitis.

PURPOSE: Determine safe, effective, iontophoretic dose(s) of EGP-437 (dexamethasone phosphate formulated for iontophoresis) in patients with noninfectious anterior uveitis; evaluate systemic drug exposures. DESIGN: Prospective, phase I/II, multicenter, double-masked, parallel group, randomized clinical trial. PARTICIPANTS: Forty outpatients with anterior uveitis. METHODS: Forty of 42 randomized patients received an iontophoresis treatment in 1 qualifying eye and completed the study. Patients were randomized into 1 of 4 iontophoresis dose groups (1.6, 4.8, 10.0, or 14.0 mA-min), treated with EGP-437 via the EyeGate II Delivery System (EGDS), and followed until day 28. MAIN OUTCOME MEASURES: The main outcome measures were anterior chamber cell (ACC) scores at days 14 and 28; time to ACC score of zero; proportion of patients with an ACC score reduction from baseline of ≥ 0.5 at day 28; mean change from baseline in ACC score at day 28; and the systemic exposures of dexamethasone and dexamethasone phosphate after EGP-437 treatment with the EGDS. RESULTS: After a single EGP-437 treatment, 19 of 40 patients (48%) achieved an ACC score of zero at day 14. By day 28, 24 of 40 patients (60%) achieved an ACC score of zero. A Kaplan-Meier analysis demonstrated that the 1.6 mA-min dose was the most effective and revealed an inverse dose response; median days to an ACC score of zero were 11.5 days in the 1.6 mA-min group versus 31 days in the 14.0 mA-min group. Twenty-six patients (65%) had an ACC score reduction from baseline of ≥ 0.5 at day 28. The mean change in ACC score from baseline to day 28 was -2.14 with a median of -2.00. Throughout the study, the mean intraocular pressure remained within normal range and mean best-corrected visual acuity at 4 meters remained relatively stable. Most adverse events were mild; no serious adverse events were reported. Pharmacokinetics results showed low short-term systemic exposure to dexamethasone after iontophoresis; no nonocular systemic corticosteroid-mediated effects were observed. CONCLUSIONS: Approximately two thirds of the patients reached an ACC score of zero within 28 days, after only receiving 1 iontophoresis treatment. The lower doses seemed to be the most effective, and treatments were well-tolerated. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Ocular iontophoresis of EGP-437 (dexamethasone phosphate) in dry eye patients: results of a randomized clinical trial.

PURPOSE: To assess safety and efficacy of EGP-437 (dexamethasone phosphate 40 mg/mL [DP]) in dry eye patients. METHODS: The study employed a prospective, single-center, double-masked design utilizing a Controlled Adverse Environment (CAE). Patients (n = 103) with confirmed signs and symptoms of dry eye syndrome were randomized into 1 of 3 iontophoresis treatment groups: 7.5 mA-min at 2.5 mA (DP 7.5, n = 41); 10.5 mA-min at 3.5 mA (DP 10.5, n = 37); or 10.5 mA-min at 3.5 mA (placebo, n = 25). Three CAE visits and 4 follow-up visits occurred over 3 weeks. Patients meeting enrollment criteria received iontophoresis in both eyes after the second CAE exposure (visit 3) and before the third CAE exposure (visit 5). Primary efficacy endpoints were corneal staining and ocular discomfort. Secondary endpoints included tear film break-up time, ocular protection index (OPI), and symptomatology. RESULTS: The DP 7.5 and DP 10.5 treatment groups showed statistically significant improvements in signs and symptoms of dry eye at various time points; however, the primary endpoints were not achieved. The DP 7.5 treatment group exhibited statistically significant improvements in corneal staining (when comparing the differences between study entry and exit, 3 weeks, P = 0.039), OPI (immediately following the second treatment, P = 0.048) and ocular discomfort at follow-up visits (a week after the first treatment, P = 0.032; 24 hours after the second treatment, P = 0.0032). Treatment-emergent adverse events (AEs) were experienced by 87% of patients and were consistent across all treatment groups. Most AEs were mild and no severe AEs were observed. CONCLUSION: Ocular iontophoresis of EGP-437 demonstrated statistically and clinically significant improvements in signs and symptoms of dry eye syndrome within a CAE model.