was applied (4 min, 1 mA) using a Coulomb-controlled iontophoresis system (EyeGate, Optis France, Paris, France), with a fluidic contact surface of 0.5 cm2. The transcorneal applicator lead was connected to the positive output and the return to a disposable patch (3M, St. Paul, MN, USA) was applied to the patient’s frontal skin surface. A miconazole solution with a concentration of 10 mg/mL was applied. The treatment was well tolerated and after a week penetrating keratoplasty was performed in the eye for optical and therapeutic purposes. Histology sections showed a corneal button with intact epithelium. Fungal elements consistent with Paecilomyces were present within the posterior stroma with an acute and chronic inflammatory cell infiltrate. No bacteria were isolated from the aqueous or corneal tissue in 7 days. Attempts to recover viable fungus from the corneal tissue remained negative after 3 weeks. Postoperatively, the patient’s condition has improved, and no signs of infection have been detected over a 6-month follow-up period (Yoo et al. 2002). To our knowledge, this is the only human application of antibacterial delivery to the cornea using iontophoresis.

In conclusion, transcorneal iontophoresis has been shown to be an efficient method capable of enhancing the aqueous and corneal antibiotics concentrations by a factor 25–100, compared to topical applications. Except in aphakic rabbits, transcorneal iontophoresis did not achieve high drug concentrations into the posterior segment of the eye.

15.3.2.3  Transcorneal Iontophoresis of Antiviral Drugs

Antiviral drugs have been delivered into the eye using transcorneal iontophoresis for the treatment of herpetic keratitis and uveitis. Hill et al. (1977) have demonstrated that IDU, phosphoacetic acid (PAA) and vidarabine monophosphate could be delivered by iontophoresis into the mouse cornea. The authors studied the pharmacokinetics of radiolabelled vidarabine monophosphate (Ara-AMP) following transcorneal cathodal iontophoresis (0.5 mA, 4 min) on rabbits Hill et al. (1978). When compared to topical applications, the amount of radioactivity measured in the cornea, the iris and aqueous humor was 3–12 times higher. Moreover, such treatments did not appear to induce corneal changes at the observational level. Transcorneal iontophoresis of Ara-AMP was also efficient in treating a herpetic keratitis model in the rabbit and required a lower treatment frequency and dose than topical treatment (Kwon et al. 1979). On a stromal herpetic lesion induced on the rabbit cornea, iontophoresis of 3.4% Ara-AMP (0.5 mA, 4 min) or 5% acyclovir (ACV) (0.5 mA for 4 min) was compared to 50 mg/kg intravenous ACV. Iontophoresis was performed daily for five consecutive days, and intravenous injections twice daily for eight consecutive days. The relative efficacy of the two treatments was evaluated clinically by slit-lamp examination. Iontophoresis of either Ara-AMP or ACV was as efficient as intravenous treatment but at significantly reduced total administrated drug dose. This study suggested that iontophoresis could be a good adjuvant for the treatment of profound corneal herpetic lesions, alone or combined with systemic therapy (Hill et al. 1982).

15.3.2.4  Other Drugs for Transcorneal Iontophoresis

Other drugs have been transferred into the anterior segment of the eye using transcorneal iontophoresis such as adrenergic agents to create models of recurrent herpes keratitis. Kwon et al. gave the earliest demonstration that iontophoresis of 0.01% epinephrine (0.8 mA for 8 min over three consecutive days) could induce herpes simplex virus 1 (HSV-1) shedding in rabbits harboring latent HSV-1 (Kwon et al. 1981). Since this report, many studies have contributed to establish highly reliable animal models for the study of herpes reactivation using corneal iontophoresis either on rabbits or on mice (Kwon et al. 1982; Shimomura et al. 1983, 1985; Hill et al. 1983).

We have used transcorneal iontophoresis to deliver analog of arginine (L-NAME) for inhibiting the inducible nitric oxide synthase activity in endotoxin-induced uveitis in rats. This study demonstrated that under controlled experimental conditions, iontophoresis of L-NAME could reduce nitric oxide production in aqueous humor and reduce the corneal edema observed during this inflammation stage. Iontophoresis could therefore be an interesting way to assay novel anti-inflammatory drugs and avoid undesirable systemic side effects (Behar-Cohen et al. 1998).

15.3.2.5  Is Transcorneal Iontophoresis Safe?

Safety of corneal iontophoresis is dependent on the density of current applied. According to Maurice, current densities up to 20 mA/cm2 for 5 min are well tolerated (Hughes and Maurice 1984). Table 15.2 gives a summary of lesions observed after transcorneal iontophoresis in various studies. It seems that current densities up to 2 mA/cm2 for 10 min allow both efficacy and safety. However, because topical treatment is efficient for the majority of anterior segment pathologies, iontophoresis could be of particular interest in clinical practice for drugs that show poor corneal permeability or when high stromal concentrations are needed with an intact epithelial barrier (i.e., stromal herpetic keratitis).