Basic principles and current status of transcorneal and transscleral iontophoresis

ABSTRACT

Introduction: Iontophoresis is an active non-invasive drug delivery technique that can increase the transport of charged and neutral molecules into and across biological membranes. Most research to-date has focused on (per)cutaneous iontophoretic drug delivery. However, recent studies illustrate its potential for drug delivery to the eye: corneal iontophoresis may enable targeted topical therapy of intracorneal diseases, whereas transscleral iontophoresis may enable non-invasive intraocular drug delivery.

Areas covered: We describe iontophoretic principles in the context of ocular delivery before providing a summary of recent preclinical studies involving transcorneal and transscleral iontophoresis in vitro and in vivo. Subsequently, an overview of clinical applications with special focus on the transcorneal iontophoresis of riboflavin for corneal cross-linking and transscleral iontophoresis of corticosteroids for the treatment of posterior segment diseases is provided.

Expert opinion: The feasibility of using iontophoresis for ocular drug delivery has been demonstrated. Drug formulation development and the ability to design iontophoretic applicators will now determine its success in the clinic. The specificities of the ocular globe must be taken into account; in particular, its unique morphology, and the smaller surface area available for drug diffusion and the fact that it is more susceptible to irritation and less robust than the skin.

KEYWORDS:

• Cornea
• eye
• iontophoresis
• sclera
• transcorneal
• transscleral

Article highlights

• Presents iontophoresis in the context of ocular delivery and the specificities of the eye; much higher current densities than those used for transdermal iontophoresis have been safely applied to the human eye, e.g. up to 1.8 mA/cm² for 5 min and 5.5 mA/cm² for 20 min on the cornea and sclera, respectively.

• Positive clinical outcomes have been observed following corneal and transscleral iontophoresis.

• Iontophoresis of riboflavin was shown to facilitate and to accelerate riboflavin delivery prior to UVA irradiation induced corneal cross-linking in keratoconus patients.

• Phase 3 clinical trials announced for the transscleral iontophoretic application of dexamethasone sodium phosphate for the treatment of non-infectious anterior uveitis

• Transscleral iontophoresis of macromolecules has been intensively studied to investigate its potential for the non-invasive delivery of biopharmaceuticals to the eye.

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Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

Work on this paper was funded with salary support provided by University of Geneva.