Nail disease is a significant part of dermatology and podiatry. While topical and oral antifungals remain the mainstay of treatment, interest is increasing among the lay public in physical modalities such as lasers and light sources for treatment. This trend is driven by interest in new technologies, a rapid treatment duration, the possibility for efficacy without systemic treatment or blood monitoring and the potential for use in most patients with few contraindications and few side effects. Particularly for toenail onychomycosis, where treatment can be lengthy and at times unsatisfactory, there is an opportunity for lasers to offer a meaningful alternative option.

A US epidemiologic study in 2000¹ found that among 1800 patients from 12 US medical centers, onychomycosis was the cause of up to 50 percent of presenting nail disorders. A US epidemiologic study because almost 90 percent of onychomycosis in the United States is caused by Trichophyton rubrum, any laser that treats it needs to be active against this species of dermatophyte. In a surveillance study from 1999-2002 in the United States,² Trichophyton rubrum was the most common cause of toenail onychomycosis, isolated in over 80 percent of cultured samples. It was also the leading cause of tinea pedis and tinea manum. For fingernail onychomycosis, Candida species had a higher incidence than T. rubrum or other causes. Several different laser and light systems have been studied to target onychomycosis, and are in different stages of the FDA approval process. The most commonly used approaches, summarized below, are near-infrared light treatment, photodynamic therapy with topical 5-amino levulinic acid followed by red light treatment, and photothermal ablative antisepsis with 1064 nm and 1320 nm Nd:YAG laser platforms.

Photodynamic Therapy

Mechanism of Action
In vitro, T. rubrum absorbs 5-amino levulinic acid and converts it into protoporphyrin IX. It then can be killed after activation with an appropriate wavelength of light. Photodynamic therapy with broadband red light after application of Metvix cream (5-aminolevulinic acid) inhibited almost 50 percent of growth of T. rubrum in vitro.³

Evidence to Date
One study from Italy⁴ reports the case of a 78-year-old woman with toenail onychomycosis, both proximal subungual and total involvement of different toenails. Her toenails were infected with T. rubrum. This patient's toenails had failed to respond to 5% amorolfine laquer (an OTC antifungal available in the United States and Europe) after 18 months of use and had medical conditions that contraindicated the use of oral medications.

The authors' protocol began with urea 40% ointment under occlusion for seven days, followed by clipping of nail plate. 5-aminolevulinic acid (Metvix cream) was then applied under an occlusive dressing for three hours. Then the nails were irradiated with the broadband red light (630 nm, 37 J/cm²) for seven minutes and 24 seconds. This regimen was repeated two more times at two-week intervals, after which the patient was followed for 24 months.

Mycologic culture and KOH examination were positive at the end of treatment, but became negative at the three-month examination point and continued to both clinical and mycologic cure at the 24-month point. With a two-year follow-up period, this study, while small, suggests a durable treatment response.

Watanabe et al.⁵ reported complete cure of onychomycosis of the great toenail in two patients after 6-7 treatments. Their irradiation was of higher intensity, at 100 J/cm² using a 630 nm excimer-dye laser. The pre-treatment regimen in this case began with 20% urea ointment applied to the affected nail for 10 hours, then the nails were incubated with 10% 5-aminolevulinic acid for five hours under light protective occlusion. The treatment was repeated weekly for six weeks in one case and seven weeks in the other. For both patients, no onychomycosis was seen by microscopy or culture at three and six months of follow up.

A larger study⁶ in Greece treated 30 patients with toenail onychomycosis with PDT. All patients had clinical nail infection confirmed by both microscopic examination and by mycologic culture. Additionally, all had concomitant conditions that contraindicated the use of oral antifungals. Again, the pre-treatment protocol was time-consuming: application of 20% urea ointment under occlusion nightly for 10 days prior to PDT treatment. Affected toenails were incubated with 20% 5-aminolevulinic acid for three hours prior to treatment. Active treatment consisted of light exposure to the affected toenails. This cycle was repeated every two weeks for three treatment courses. Adverse events in all patients included a burning sensation or pain; the pain was managed with a fan or cooling spray and all patients completed the study.

Results at 12 months showed a 43 percent rate of complete cure, both mycologic and clinical. At 18 months, the rate had decreased to 36 percent, showing likely relapse or possibly a new infection. The authors comment that in their experience the local pain, edema and phototoxic reactions may limit widespread use.

These lasers were the first to gain FDA approval for the indication of treating onychomycosis. The FDA's language in approving these 510(k) medical devices states that they are approved as follows: "For the temporary increase of clear nails in patients with onychomycosis."