Long-pulsed 1,064-nm gallium arsenide laser surgical device treatment for improving symptoms of onychomycosis: a comparative analysis.

BACKGROUND: Onychomycosis is the most common infective nail disease, and treatment includes topical and systemic antifungal medications. Recently, laser therapy has emerged as a therapeutic option for patients who are unable to take oral antifungal agents. We investigated the effectiveness and safety of a novel long-pulsed 1,064-nm gallium arsenide (GaAs) laser surgical device for onychomycosis. METHODS: This 24-week single-center, single-blind, active-controlled exploratory clinical study comparatively evaluated the long-pulsed 1,064-nm GaAs laser (Healer1064) with the short-pulsed Nd:YAG laser surgical device in 20 participants randomly assigned to receive either test or control treatment at 4-week intervals during the 12-week treatment period. The rate of clinical improvement was evaluated by two independent dermatologist evaluators using the Onychomycosis Severity Index-score (OSI-score) and Turbidity Scale with standard photographs. Overall improvement and patient satisfaction were evaluated. Safety evaluation included pain intensity and adverse events. RESULTS: In 44 (test: 25; control: 19) cases in 19 participants who completed treatment, the clinical improvement rate in the test and control groups was 52.00% (13/52 cases) and 44.44% (9/19 cases), respectively, with significantly lower pain scores in the test than the control group for every treatment visit (P < 0.05) and without severe adverse events. CONCLUSIONS: The novel long-pulsed 1,064-nm GaAs laser showed greater, albeit nonsignificant, clinical improvement and was associated with less pain during treatment. Thus, the Healer1064 can provide satisfactory treatment outcomes through painless and effective improvement in onychomycosis symptoms.

Onychomatricoma on the fourth toenail: A rare tumor in a rare localization.

Onychomatricoma is a rare benign tumor of the nail matrix, characterized by finger-like projections that invade the nail plate. The fingernails of Caucasian women are most commonly affected. Because this tumor can easily mimic other more prevalent ungual diseases, it is crucial to be acquainted with its characteristic clinical and histopathologic features. The authors present a case of a 40-year-old man with an onychomatrichoma in the fourth left toenail, which was initially misdiagnosed and treated as onychomycosis.

Fractional CO2 laser ablation leads to enhanced permeation of a fluorescent dye in healthy and mycotic nails-An imaging investigation of laser-tissue effects and their impact on ungual drug delivery.

PURPOSE: Conventional oral antifungal therapies for onychomycosis (OM) often do not achieve complete cure and may be associated with adverse effects, medical interactions, and compliance issues restricting their use in a large group of patients. Topical treatment can bypass the systemic side effects but is limited by the physical barrier of the nail plate. Ablative fractional laser (AFL) treatment can be used to improve the penetration of topical drugs into the nail. This study visualized the effects of laser ablation of nail tissue and assessed their impact on the biodistribution of a fluorescent dye in healthy and fungal nail tissue. METHODS: For the qualitative assessment of CO2 AFL effects on healthy nail tissue, scanning electron microscopy (SEM), coherent anti-Stokes Raman scattering microscopy (CARS-M), and widefield fluorescence microscopy (WFM) were used. To quantitate the effect of laser-pretreatment on the delivery of a fluorescent dye, ATTO-647N, into healthy and fungal nail tissue, ablation depth, nail plate thickness, and ATTO-647N fluorescence intensity in three nail plate layers were measured using WFM. A total of 30 nail clippings (healthy n = 18, fungal n = 12) were collected. An aqueous ATTO-647N solution was directly applied to the dorsal surface of 24 nail samples (healthy n = 12, fungal n = 12) and incubated for 4 hours, of which half (healthy n = 6, fungal n = 6) had been pretreated with AFL (30 mJ/mb, 15% density, 300 Hz, pulse duration <1 ms). RESULTS: Imaging revealed a three-layered nail structure, an AFL-induced porous ablation crater, and changes in autofluorescence. While intact fungal samples showed a 106% higher ATTO-647N signal intensity than healthy controls, microporation led to a significantly increased fluorophore permeation in all samples (p < 0.0001). AFL processing of nail tissue enhanced topical delivery of ATTO-647N in all layers, (average increase: healthy +108%, fungal +33%), most pronounced in the top nail layer (healthy +122%, fungal +68%). While proportionally deeper ablation craters correlated moderately with higher fluorescence intensities in healthy nail tissue, fungal samples showed no significant relationship. CONCLUSION: Fractional CO2 laser microporation is a simple way of enhancing the passive delivery of topically applied ATTO-647N. Although the impaired nail plate barrier in OM leads to greater diffusion of the aqueous solution, AFL can increase the permeability of both structurally deficient and intact nails.

Comparison of a fractional 2940-nm Er:YAG laser and 5% amorolfine lacquer combination therapy versus a 5% amorolfine lacquer monotherapy for the treatment of onychomycosis: a randomized controlled trial.

Onychomycosis is a fungal infection of the nail. The aim of this randomized controlled clinical trial was to compare the efficacy of 2940-nm Er:YAG laser treatment combined with a 5% amorolfine lacquer versus amorolfine monotherapy for treating onychomycosis. In this study, patients with onychomycosis of the great toenail were randomly assigned to a combination therapy group and a monotherapy group. In the combination therapy group, the included toenails were treated with a fractional 2940-nm Er:YAG laser at weeks 1, 2, 3, 4, 8, and 12, combined with a 5% amorolfine lacquer twice a week for 12 weeks, while in the monotherapy group, the included toenails were treated with only a 5% amorolfine lacquer twice a week for 12 weeks. The onychomycosis severity index (OSI) score and the mycological clearance rate (MCR) of the included toenails were assessed at baseline, week 12, and week 24. At weeks 12 and 24, the great toenails with mild and moderate onychomycosis in the combination therapy group showed obvious improvement and a greater decrease in OSI than those in the monotherapy group. At week 24, the toenails with mild and moderate onychomycosis in the combination therapy group also showed a better MCR. For the toenails with severe onychomycosis, little improvement was observed in either group at week 12 or week 24. In conclusion, fractional 2940-nm Er:YAG laser treatment combined with a 5% amorolfine lacquer is more effective than amorolfine monotherapy in short-term improvement of onychomycosis.

Clinical retrospective analysis of long-pulsed 1064-nm Nd:YAG laser in the treatment of onychomycosis and its effect on the ultrastructure of fungus pathogen.

The objective of this study was to analyze retrospectively the clinical efficacy and fungal clearance of long-pulsed 1064-nm Nd:YAG laser for treating onychomycosis and explore the inhibitory effects of laser on the fungus pathogen-induced onychomycosis in vitro. We performed a systematic retrospective analysis of clinical patients (162 effected nails) of onychomycosis treatment applying laser with or without topical ketoconazole ointment and followed up 3 months after treatment. Trichophyton rubrum- and Trichophyton mentagrophytes-induced onychomycosis was irradiated with laser superimposed for different cumulative energy, respectively; then, the areas of fungus colonies and growth curve in different days were showed, and changes in ultrastructures were observed under SEM and TEM. The clinical effective rate and fungal clearance rate in the combined group were higher than those in the laser group; however, there was no significant difference between the two groups. In vitro, the areas of T. rubrum colonies were significantly reduced at days 1, 3, and 5 after irradiation with cumulative laser energy ≥ 6400 J/cm2. When irradiated with cumulative laser energy ≥ 25600 J/cm2, significant difference in the areas of T. mentagrophytes colonies was found at day 5. And ultrastructure of the two strains before and after laser irradiation was damaged at different degrees. This study confirmed that long-pulsed 1064-nm Nd:YAG laser is effective for treating onychomycosis, and the laser irradiation can inhibit the colony growth of T. rubrum and T. mentagrophytes and change their cellular ultrastructures. The mechanism of laser treatment of onychomycosis may be related to direct damage of fungus pathogen.

Efficacy of laser treatment for onychomycotic nails: a systematic review and meta-analysis of prospective clinical trials.

Laser therapy for onychomycosis is emerging but its efficacy remains unestablished. To examine current evidence on efficacy of laser treatment of onychomycosis. A systematic review and one-arm meta-analysis, including all prospective clinical trials, identified on PubMed, Cochrane Library, and EMBASE databases. Trials with participants as unit of analysis (UOA), n = 13, were analyzed separately from trials with nails as UOA, n = 7. Summary proportions and 95% confidence intervals (95% CI) were calculated. Outcomes were mycological cure, clinical improvement, or complete cure. Twenty-two prospective trials (four randomized controlled trials and 18 uncontrolled trials) with a total of 755 participants were analyzed. Summary proportions with 95% CI for participants as UOA were mycological cure 70.4%, 95% CI 52.2-83.8%; clinical improvement 67.2%, 95% CI 43.2-84.7%; and complete cure 7.2%, 95% CI 1.9-23.5%. High statistical heterogeneity was detected (mycological cure I2 = 88%, P < 0.01; clinical improvement I2 = 69%, P < 0.01; complete cure I2 = 60%, P = 0.11). The current level of evidence is limited and with high heterogeneity, making it difficult to assess the true efficacy of laser treatment for onychomycosis. Larger randomized controlled trials with well-defined methodology are warranted.

Fractional carbon dioxide laser and topical tioconazole in the treatment of fingernail onychomycosis.

Onychomycosis is a common chronic-resistant nail disease. Traditional treatment has its limitations and side effects. This study aimed to evaluate the role of fractional CO2 laser and topical tioconazole 28% nail lacquer in the treatment of fingernail onychomycosis, as sole treatment modalities and in combination. Thirty patients with culture-proven onychomycosis were included and randomly divided into three equal groups. Laser group received six fractional carbon dioxide (CO2) laser sessions at monthly intervals; topical group received topical tioconazole 28% nail lacquer twice daily for 6 months, and combined group received six fractional CO2 laser sessions at monthly intervals with topical tioconazole twice daily for 6 months. Treatment outcome was evaluated through physician's evaluation of improvement using onychomycosis severity index score (OSI), patients' satisfaction, side effect evaluation, and mycological culture (assessed after the end of treatment). At the end of treatment, both laser and combined groups showed significantly better degrees of improvement (P = 0.036, 0.024, respectively) and patient's satisfaction (P = 0.046, 0.003, respectively) in comparison with topical group. Mycological clearance in fungal cultures was significantly higher in combined group than topical group after the end of treatment (P = 0.007). Fractional CO2 laser is a safe and effective treatment modality for onychomycosis. Its efficacy approximates that of fractional CO2 laser combined with topical tioconazole 28% nail lacquer and surpasses that of topical tioconazole 28% monotherapy. It is expected to be an excellent choice for patients in whom systemic antifungals are contraindicated or who are unresponsive or intolerant to topical antifungals.

Laser therapy for onychomycosis in patients with diabetes at risk for foot ulcers: a randomized, quadruple-blind, sham-controlled trial (LASER-1).

BACKGROUND: Patients with diabetes mellitus are at high risk for onychomycosis, which is related to the development of foot ulcers. OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of the treatment of onychomycosis with local laser therapy. METHODS: In a single-centre, randomized (1:1), quadruple-blind, sham-controlled trial, patients and microbiological confirmation with diabetes mellitus, at risk for developing diabetic foot ulcers (Sims classification score 1, 2) and a clinical suspicion on onychomycosis, were randomized to either four sessions neodymium-doped yttrium aluminium garnet (Nd-YAG) 1064 nm laser or sham treatment. The primary outcome was clinical and microbiological cure of onychomycosis after 1-year follow-up. RESULTS: From March 2015 to July 2016, 64 patients were randomized; 63 could be analysed. Trichophyton rubrum was the most detected pathogen. There was no difference in the primary outcome between laser and sham treatment. With the exception of a subungual haematoma in the fifth toenail occurring 2 weeks after laser treatment, the results suggested that treatment with Nd-YAG 1064 nm laser is safe. CONCLUSION: At this moment, there is no evidence of any effect of laser treatment for onychomycosis in patients with diabetes at increased risk for foot ulcers, at least not within 1 year after treatment.

A practical application of onychomycosis cure - combining patient, physician and regulatory body perspectives.

Due to the high relapse rates and the rise of predisposing factors, the need for curing onychomycosis is paramount. To effectively address onychomycosis, the definition of cure used in a clinical setting should be agreed upon and applied homogeneously across therapies (e.g. oral, topical and laser treatments). In order to determine what is or what should be used to define cure in a clinical setting, a literature search was conducted to identify methods used to evaluate treatment success. The limitations, strengths, prevalence and utility of each outcome measure were investigated. Seven ways to measure treatment success were identified; mycological cure, patient/investigator assessments, complete cure, quality of life instruments, severity indexes, clinical cure and temporary clearance. Despite its shortcomings, mycological cure is the most objective and consistent outcome measure used across onychomycosis studies. It is suggested that diagnostic goals of onychomycosis should be used to define cure in a clinical setting. Modifications to outcome measures such as incorporating molecular-based techniques could be a future avenue to explore.

Efficacy of combination therapy with efinaconazole 10% solution and 1064 nm Nd:YAG laser for treatment of toenail onychomycosis.

BACKGROUND: Onychomycosis is a common but difficult to treat nail disorder. Treatment strategies thus far have included oral and topical antifungals, surgical treatment and recently lasers have emerged as a therapeutic modality. OBJECTIVE: The objective of this study was to assess whether efinaconazole together with laser would result in greater clinical and mycologic cure and lower rate of relapse compared to efinaconazole alone. METHODS: Thirty subjects were randomized to either self-apply efinaconazole 10% once daily for 48 weeks, or follow the same treatment plan but also receive six treatments with a 1064 nm Nd: YAG laser every 4 weeks. The primary endpoint was to assess the proportion of subjects who achieved complete cure at week 52. RESULTS: The combination therapy group showed significantly quicker mycological cure at the 48- and 52-week follow-up. CONCLUSION: Both efinaconazole and combination with laser were efficacious treatment, but the combination therapy leads to quicker resolution with fewer rate of relapse.

The efficacy of fractional carbon dioxide (CO2) laser combined with luliconazole 1% cream for the treatment of onychomycosis: A randomized, controlled trial.

BACKGROUND: To evaluate the efficacy of fractional carbon dioxide (CO2) laser combined with luliconazole 1% cream for the treatment of onychomycosis and to compare it with that of fractional CO2 laser alone. METHODS: This was a randomized, parallel group, 2-arm, positive-controlled, single-center, superiority trial with a 1:2 allocation ratio. Sixty patients with clinical and mycological diagnosis of onychomycosis were enrolled from the Dermatology Department of the First Affiliated Hospital of Nanjing Medical University in Nanjing, China from March 2015 to May 2015. Patients were randomized following simple randomization procedures (computerized random number generator) into 2 groups; L group only received 12 sessions of laser treatment at 2-week interval for 6 months, while L + D group received 12 sessions of laser treatment at 2-week interval combined with luliconazole 1% cream once daily for 6 months. This was not a blind trial. The main outcome measures were the clinical efficacy rate (CER) assessed from the percentage of fully and >60% normal-appearing nails and the mycological clearance rate (MCR) assessed from the percentage of nails with negative fungal microscopy. There were no changes to trial outcome measures after the trial commenced. RESULTS: A total of 60 patients (N = 233 nails) completed treatments and follow-up, and were randomized and divided into 2 groups: L group (31 patients, N = 108 nails) and L + D group (29 patients, N = 115 nails). The CER and MCR of L + D group were 69.6% and 57.4%, respectively. L + D group showed significantly higher CER (69.6% vs 50.9%; χ = 8.1, P = 0.004) and MCR (57.4% vs 38.9%; χ = 7.6, P = 0.006) compared with those in L group. Some patients experienced mild pain during laser treatment, but there was no bleeding or oozing during or after treatment. There were no adverse effects reported during the observation period. CONCLUSION: Fractional CO2 laser treatment combined with 1% luliconazole cream for 6 months was an effective and safe method for the treatment of onychomycosis, and had a higher efficacy than fractional CO2 laser treatment alone.

Evaluation of efficacy and tolerability of four weeks bifonazole treatment after nail ablation with 40% urea in mild to moderate distal subungual onychomycosis.

BACKGROUND: The aim of this study was to verify efficacy and tolerability of sequential therapy with 40% urea paste followed by 1% bifonazole urea in mild to moderate distal subungual onychomycosis of the toenails. METHODS: It was an seven weeks open study. Sequential patients affected by mild to moderate distal subungual onychomycosis of the toenails agreed to apply on the affected nail 40% urea paste in occlusion overnight for the first three weeks, with gentle scraping with a spatula the following day, followed by 1% bifonazole cream once a day for 4 weeks. Efficacy evaluation was based on mycology, clinical photography and investigator and patient assessment. Tolerability assessment included subjective and objective evaluations. RESULTS: The ten patients enrolled (mean age 57.5 years) completed the study. Onychomycosis was caused in nine cases by dermatophytes and by Scopulariopsis brevicaulis in one patient. At the end of the study, mycological examination was negative in all 10 patients. Clinical photographs showed a reduction of the percentage of the nail affected by onychomycosis in 8 cases, cure in 2 and considerable reduction of the nail thickness, already evident after 7 days. All patients reported to be satisfied by the treatment, which was judged easy to perform and well tolerated. CONCLUSIONS: Treatment with urea and bifonazole is effective and well tolerated, and easy to do also by elderly patients.

Evaluation of Nd:YAG laser device efficacy on onychomycosis: a case series of 30 patients.

Until recently, pharmacologic molecules have been the only available treatments for onychomycosis. Laser treatments were introduced for recurrent or resistant cases or in patients in whom oral treatments are contra-indicated. Some devices were approved by the Food and Drug Administration (FDA). Neodymium yttrium aluminium garnet (Nd:YAG) is used for onychomycosis as a short-pulse or a long-pulse system. We aim to evaluate the efficacy of the short-pulse Nd:YAG in treating onychomycosis, its side effects, cure rates, and 12-month recurrence rates. Efficacy was evaluated based on a subjective measure of patient satisfaction on a scale from 1 to 10, and an objective measure based on the results of the mycologic cultures. Medical records of 30 patients were reviewed. Ages ranged from 22 to 85, with a mean of 44. Mycologic cure at 12 months was not achieved in 5 patients (16.67%) who had received laser treatment. None of these patients showed any signs of clinical improvement. Twenty patients (66.67%) were completely cured at 12 months, with corroborating negative mycologic cultures. The remaining five patients (16.67%) had discordance between their clinical cure status and their mycologic cultures. Side effects were reported by 7 patients out of 30 (33%): pain within 48 hours of the treatment session, burning sensation in the treated nail bed area. Our primary end point of negative mycologic cultures at 12 months was seen in 24 out of 30 (80%) of our patients. Similar culture cure rates have not been reported before, not even with systemic treatments with oral antifungals. However, few limitations should warrant us (False-negative results in fungal cultures; time limitation; sample size…). Still, we propose that this alternative should be offered for patients in whom antifungals are contraindicated or for patients previously treated, but not cured by oral antifungals, and in elderly and polymedicated patients.