Evaluating the Effectiveness of Laser Treatment for Onychomycosis of the Hallux in Patients With Diabetes: A Randomized Controlled Trial

Onychomycosis is a fungal infection of the nail unit which affects one third of people with diabetes.1,2 Risk factors for onychomycosis in diabetes include age, male sex, poor glycemic control, longer duration of diabetes, use of immunosuppressive agents, and poor peripheral circulation.2-5 Etiology of onychomycosis varies across populations, but the most common causes in diabetic patients are yeasts and dermatophytes. In particular, Candida spp. (31-48.1%) are the most common yeasts, while Rhodotorula spp. (21.7%) have been reported as well.4,6-8 Trichophyton rubrum (31.7-46%) is the most common dermatophyte observed, while nondermatophytic molds are less common.

Individuals with diabetes complicated by peripheral neuropathy are at risk of developing particularly severe complications of onychomycosis. Infected nails can become brittle and sharp, injuring and compromising the adjacent skin. This breakdown allows a portal of entry for bacteria, causing cellulitis and paronychia.9 Because the nail bed is in close proximity to the underlying nail, paronychia can develop into osteomyelitis if adequate foot care is neglected.

Given the significant morbidity of onychomycosis including the potential for limb amputation, prompt and effective treatment is imperative. Currently available treatments include topical and systemic options, and each of these has significant limitations.

Topical antifungal therapies have been tested in patients with mild onychomycosis. Cure rates of 29-85% have been observed with ciclopirox 8% nail lacquer in non-diabetic populations with mild disease;10 in diabetic populations using open label methodology cure rates of approximately 54% are reported.11,12 Novel topical forms of terbinafine with various penetration-enhancing compounds are also under development.13-15 Early studies report effective nail penetration of these formulations, but there is a lack of data on clinical efficacy of topical terbinafine. One preliminary study reported 90% mycological cure after 12 weeks of treatment with a terbinafine spray, but less than half had a sustained cure at 36 weeks post-treatment.16 Although effective for mild to moderate superficial onychomycosis, because of poor nail penetration topical agents are generally not recommended where fungus appears to infect more than 50% of the nail surface.7 One recent review has suggested that monotherapy with topical agents should be avoided altogether.17 Systemic antifungal agents are often used to treat more severe onychomycosis. Two of the most common systemic agents are itraconazole and terbinafine. Itraconazole is a newer agent with the added advantage of covering Candida species in addition to dermatophytes. Both agents are associated with cure rates of approximately 50% when given for a full three month course.18 These agents have significant limitations given the potential for drug-drug interactions via inhibition of cytochrome P450 enzyme subtypes.19 Itraconazole and terbinafine are associated with increased risk of bleeding with warfarin, itraconazole with increased risk of rhabdomyolysis with statins and of hypoglycemia with oral agents for diabetes and terbinafine with metoprolol, propafenone, and tricyclic antidepressants.19 Due to the significant limitations of topical and systemic treatments for onychomycosis, there is a critical need for alternative and replacement therapies. While surgical techniques such as avulsion and nail plate removal can be employed for severe and resistant infections, these treatments are quite invasive and painful.7,20 Other device-based therapies for onychomycosis include UV light therapy21-23 and photodynamic therapy.24-27 While these modalities show evidence of in vitro efficacy, there have been no robust studies conducted yet that demonstrate any clinical effectiveness.

A promising device-based therapy is laser treatment. The neodymium-doped yttrium aluminum garnet (Nd:YAG) device emits a laser in a continuous or pulsed fashion, and the 1064 nm wavelength is thought to be optimal due to its ability to penetrate deeply into the nail bed to eradicate fungal growth.28 Although this device is approved by the US Food and Drug Administration for use in patients with onychomycosis for a "temporary increase in clear nail,"28 there is a lack of research demonstrating effectiveness beyond several pilot studies. One study demonstrated mycologic cure in 7 out of 8 patients with no major side effects aside from temporary nail discoloration and occasional pin prick sensation.29 The parameters for the laser included a 0.65 ms pulse duration, 2 mm spot size and 223 J/cm2 energy fluence, and treatment consisted of 2 to 3 sessions spaced at least 3 weeks apart. A Chinese study of 33 patients demonstrated a 51% to 53% cure rate in patients treated for eight and four sessions respectively, spaced at 1 week intervals using a 30 ms pulse duration and 3 mm spot size laser at 240-324 J/cm2.30 Results from Japan showed a similar cure rate of 51% in 19 patients treated with 1 to 3 treatments 4 to 8 weeks apart.31 To our knowledge, no randomized control trials exist to validate these preliminary findings.