15.2  Ocular Drug Delivery: The Past and the Future

extrapolation to ocular iontophoresis, with each ocular tissue possessing its own characteristics. Moreover, the distribution of the drug into ocular tissue following iontophoresis is difficult to anticipate using classical pharmacological approaches. Recent MRI studies have provided new insights into the enhancing mechanisms of transscleral iontophoresis.

Since the earliest description of zinc salt transcorneal iontophoresis by Wirtz (1908), described by Duke-Elder (1962) and numerous publications, the technique remains something of a novelty with clinical use of iontophoresis, never establishing wide acceptance. The absence of a well-accepted scientific account of drug penetration into or through ocular tissues, limited number of systematic pharmacokinetic studies, uncertain effect of pathology of the drug concentrations time course and descriptions of tissue lesions induced by iontophoretic application using high current density have hindered the clinical technique development.

Concerns over the use of iontophoresis for routine, or even specialized, drug delivery applications are twofold. First of these is the degree of variability reported in some studies (e.g., Barza et al. 1987a, b), raising the general possibility of reduced effectiveness during repeated therapeutic applications. Systemized studies using well-optimized protocols, including artifact-free sampling of attained therapeutic concentrations of delivered drugs are needed. A second area of concern in iontophoresis is patient safety. Historically, reports of several difficulties including corneal scarring and tissue damage exist (Harris 1967; Hughes and Maurice 1984). Even a cursory examination of some of these early reports reveals that sub-optimal electrode geometries and excessive current densities were sometimes employed in order to “demonstrate” the desired effects, i.e., enhanced permeant delivery. Better understanding of the underlying mechanisms behind iontophoresis together with the pharmacokinetics of sought-for treatment regimes in both healthy and diseased eyes are needed to avoid deleterious use and to enable refinement of the approach.

One variant of the basic iontophoretic technique, Controlled Coulomb Iontophoresis, designed to maximize drug transfer while preventing tissue burns was proposed (Spector et al. 1984; Nose et al. 1996) and tested in several animal studies (Behar-Cohen et al. 1997, 1998, 2001; Voigt et al. 2002a–c). These studies showed that trans-epithelial electrical fields less than 2 V were sufficient for optimal drug transfer and most of the field loss was at the return electrode interface over bare skin. The studies also showed current densities greater than 50 mA/cm2 thermally affected tissues, especially the conjunctival epithelium where burns occurred at 100–140 mA/cm2.

Given the inherent challenges of ocular drug delivery, iontophoresis continues to demonstrate potential for therapeutic applications in ophthalmology. In particular, for treating posterior segment inflammations, infections, deliver new potential antiangiogenic or trophic agents to the retina and/or the choroid. Continued commercial development of transdermal iontophoresis, based in part upon innovative application of modern electronics, material science and further developments in ocular pharmacokinetics, could yet place ocular iontophoresis amongst the more efficient means of treatment of several conditions of the posterior segment of the eye.