Iontophoresis for the Treatment of Paecilomyces Keratitis

It is often difficult for a clinician to decide which antifungal to use and the route of administration in fungal infections. Current selection of antifungal agents is based on animal experiments, clinical experience, and published sensitivity data. 1,2 Another problem in the treatment of fungal keratitis is that the corneal epithelium serves as a barrier to the penetration of most topical antifungal agents because the annular tight junctions (zonula occludens) completely surround and effectively seal the superficial epithelial cells. Debridement of the corneal epithelium is often necessary, especially early in the course of treatment, 3 though this may decrease host defenses, increase pain and inflammation, and delay the healing process. Iontophoresis is a potential modality for the treatment of fungal keratitis that could increase the penetration of antifungal drugs into the cornea and aqueous humor, 4,5 as has been demonstrated with other drugs, in other intraocular tissues. 6,7 The following is a report of a case of Paecilomyces keratitis, in which iontophoresis was used to increase topical penetration of miconazole using Coulomb controlled iontophoresis, as well as oral therapy. CASE REPORT A 51-year-old male patient was referred with an existing diagnosis of fungal keratitis (Paecilomyces) in his left eye for 7 weeks. He was initially treated with fluoroquinolones and mild steroids, which made his condition worse. After the cultures were positive for Paecilomyces microorganism, he was started on miconazole 1% topical drops every hour. The species and sensitivities of the Paecilomyces could not be obtained from the laboratory where the cultures were taken. His medical history was significant for extended soft contact lens wear and familial bilateral cataracts that were removed 3 years before. On presentation, he had a visual acuity of 20/20 in his right eye, and 20/200 in his left eye. Slit-lamp examination revealed 3+ conjunctival injection, a 1-mm hypopyon with 4+ cells and flare in the anterior chamber, a central 3 × 2-mm corneal ulcer with feathered borders, and approximately 30% thinning of the cornea in the area of the ulcer. An opaque plaque behind the intraocular lens was observed (Fig. 1A and B). B-scan ultrasonographic examinations showed a flat retina and clear vitreous. With these findings, the patient was started with ketoconazole topical drops every hour, topical hyoscine three times a day, and 400 mg ketoconazole orally. The patient responded to topical treatment and in 3 days his hypopyon regressed, but the central corneal infiltrate and the inflammation persisted. Over a 40-day follow up period, the visual acuity gradually deteriorated (4/200 “E”), the infiltrate stayed the same, anterior chamber inflammation increased, and a 0.5-mm hypopyon recurred. The patient was re-evaluated for an iontophoretic delivery of miconazole.FIG. 1.: A: Intact corneal and conjunctival epithelium, a deep stromal infectious foci of approximately 3-mm diameter is located in central cornea. B: Retroillumination showing a retrolenticular plaque. C: Six months after penetrating keratoplasty.Prior to iontophoresis treatment, a slit-lamp examination confirmed the integrity of the cornea and conjunctival epithelium, and the presence of a deep-stroma, infectious foci of approximately 3-mm diameter located in the center of the cornea. There was a plaque just behind the posterior chamber lens implant. Iontophoresis was applied (4 min, 1 mA) using a Coulomb-controlled iontophoresis system (EyeGate, Optis France, Paris, France) and a transcorneal applicator 6 with a fluidic contact surface of 0.5 cm 2 (Fig. 2A and B). The transcorneal applicator lead was connected to the positive output and the return to a disposable patch (3M, St. Paul, MN, U.S.A.) applied to the patient's frontal skin surface. A miconazole solution (10 mg/mL concentration) was infused in the transcorneal cup using a 2-cc syringe as suction was applied on the other line using a 1-cc syringe to create the slight suction needed to hold the cup to the cornea and assure a constant drug flow across the corneal surface. A total of 1.5 cc drug solution was used during the 4-minute treatment. The patient indicated slight discomfort when the corneal applicator was placed on the eye, but did not notice when the iontophoretic treatment started. A slit-lamp examination performed the next morning showed that the corneal epithelium, stroma, and anterior chamber remained stable. A penetrating keratoplasty was performed in that eye for optical and therapeutic purposes (Fig. 1C). The corneal tissue was minced and inoculated onto chocolate, 5% sheep blood agar, sabouraud agar, and thioglycollate, and incubated at 35°C for 7 days. Histologic sections showed a corneal button with intact epithelium. Fungal elements consistent with Paecilomyces were present within the posterior stroma. An acute and chronic inflammatory cell infiltrate, which contained a moderate number of giant cells, was present within the posterior stroma and along the posterior surface of Descemet's membrane. 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.FIG. 2.: A: CCI system with eye-cup. B: A transcorneal applicator with a fluidic contact surface of 0.5 cm 2 . Iontophoresis was applied (4 min, 1 mA) using a Coulomb controlled iontophoresis system.Coulomb controlled iontophoresis of the eye was experimentally shown to be safe by using electron microscopy. 8 Recent clinical studies confirmed the safety of Coulomb controlled iontophoresis. 9 This case demonstrates that it can be used safely as an adjunctive treatment of fungal keratitis.