The use of the shock of the torpedo, an electric fish, for the treatment of gout was described by Aetius, a Greek physician, more than 1000 years ago (14). In 1747, Veratti enunciated the concept of applying an electric current to increase the penetration of drugs into surface tissues (15). In 1898, Morton demonstrated that finely powdered graphite could be driven into his arm under the positive electrode and produced small black spots that persisted for weeks (16). In 1900, Leduc reported the first controlled studies of iontophoresis as a therapeutic modality (17,18). Leduc showed that transcutaneous iontophoretic delivery of strychnine and cyanide ions into rabbits produced fatal tetanic seizures and cyanide poisoning.
The earliest description of ocular iontophoresis was published in 1908 by the German investigator Wirtz (19), who performed iontophoresis of zinc salts for the treatment of corneal ulcers. In 1927, Morisot (20) enumerated many successful ophthalmological applications of iontophoresis including iontophoresis of magnesium for treatment of glaucoma, iontophoresis of ammonium chloride for treatment of cataract, and iontophoresis of phosphoric acid for treatment of optic atrophy. Erlanger was one of the first ophthalmologists to introduce iontophoresis to England and the United States. In 1936, he delivered barium chloride iontophoretically into the eyes of guinea pigs and observed cataract formation 48 hours later (21). He went on to describe the usefulness of iontophoresis in the clinical treatment of corneal ulcers, conjunctivitis, scleritis, glaucoma, and cataract (22,23).
During the 1940s in the United States, Ludwig von Sallmann, a prominent ophthalmologist, was one of the pioneers in the clinical use of ocular iontophoresis. Von Sallmann showed that transcorneal iontophoresis of penicillin was more effective than subconjunctival injection for the delivery of penicillin into the aqueous humor (24,25) and demonstrated modest success in the treatment of intraocular staphylococcal infection (26). In 1956, Witzel and his colleagues (27) published a report on the use of ocular iontophoresis as a drug delivery system for a variety of antibiotics. They found that iontophoresis was effective in the delivery of streptomycin, neo-mycin, and penicillin.
Despite its widespread use and study during the first 60 years of the twentieth century, iontophoresis was never fully adopted as a standard procedure. The lack of carefully controlled trials and the paucity of toxicity data were among the reasons that precluded its acceptance as a viable alternative for drug delivery. However, over the past 30-40 years, iontophoresis has been adapted for use in a variety of medical specialties, includ ing anesthesiology, dermatology, dentistry, and ophthalmology. Table 1 provides a list of selected reviews and reports describing the recent evolution of this procedure and highlighting some of its medical applications.
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