ORIGINAL ARTICLE

Fractional carbon-dioxide (CO2) laser-assisted topical

therapy for the treatment of onychomycosis
Anil Kumar Bhatta, MD, Uma Keyal, MD, Xin Huang, PhD, and Jing Jun Zhao, PhD
Shanghai, China

Background: Inability of topical medications to penetrate via nail plate brings a great challenge to
clinicians in treating onychomycosis. Furthermore, oral medications are not appropriate for all patients
because of drug interactions, adverse effects, and contraindications.

Objective: We sought to evaluate the clinical efficacy of fractional carbon-dioxide laser-assisted topical
therapy for onychomycosis.

Methods: In total, 75 patients with 356 onychomycotic nails confirmed by mycologic examination were
included in this study. All the affected nails received 3 sessions of laser therapy at 4-week intervals and
once-daily application of terbinafine cream for 3 months.

Results: In all, 94.66% and 92% of the treated patients were potassium hydroxide and culture negative,
respectively, after 3 months of treatment. However, only 84% and 80% were potassium hydroxide and
culture negative, respectively, at 6 months of follow-up. Using Scoring Clinical Index for Onychomycosis
electronic calculator, 73.33% of the patients scored higher than 6 and 26.66% of the patients scored 6 or less.
Those who scored more than 6 were evaluated clinically and 98.18% of them showed response to treatment
at 3 months and 78.18% of them at 6 months of follow-up.

Limitation: Lack of control group and short duration of follow-up are limitations.

Conclusions: Fractional carbon-dioxide laser therapy combined with topical antifungal was found to be
effective in the treatment of onychomycosis. However, randomized clinical studies are needed before it can
be widely used in clinics. ( J Am Acad Dermatol http://dx.doi.org/10.1016/j.jaad.2015.12.002.)

Key words: dermatophytes; fractional laser; onychomycosis; topical therapy.

O nychomycosis, a fungal infection of the

nail, is considered one of the most preva-
lent disorders of the nail. It occurs after
primary infection of the nail bed, which may lead to
Abbreviations used:
CO2:
DLSO:
KOH:
carbon dioxide
distal lateral subungual onychomycosis
potassium hydroxide
subungual hyperkeratosis.1 Other than a cosmetic Nd:YAG: neodymium:yttrium-aluminium-garnet
concern, onychomycosis is also frequently associ- PSO: proximal subungual onychomycosis
SCIO: Scoring Clinical Index for
ated with tinea pedis, which can result in serious Onychomycosis
secondary infections such as osteomyelitis and SWO: superficial white onychomycosis
cellulitis, particularly in diabetic patients. TDO: total dystrophic onychomycosis

From the Department of Dermatology, Shanghai Tongji Hospital,
Tongji University School of Medicine.
Drs Bhatta and Keyal contributed equally to this article.
Supported by the Natural Science Foundation of Science and Techno-
logy Commission of Shanghai Municipality (No.13ZR1437900).
Presented orally at the sixth Five Continent Congress for Aesthetic
and Laser Medicine, Cannes, France, September 3-6, 2015, and
as a poster at the 24th European Academy of Dermatology and
Venereology Congress, Copenhagen, Denmark, October 7-11,
2015.
Conflicts of interest: None declared.
Accepted for publication December 1, 2015.
Reprint requests: Xin Huang, PhD, Department of Dermatology,
Shanghai Tongji Hospital, Tongji University School of Medicine,
389 Xincun Road, Putuo District, Shanghai China. E-mail:
alida_huang@163.com.
Published online February 9, 2016.
0190-9622/$36.00
2015 by the American Academy of Dermatology, Inc.
http://dx.doi.org/10.1016/j.jaad.2015.12.002

1
2 Bhatta et al J AM ACAD DERMATOL
n 2015

Etiologically, dermatophytes such as Trichophyton white onychomycosis [SWO], and total dystrophic
rubrum and T mentagrophytes account for 80% to onychomycosis [TDO]) were considered for treat-
90% of all cases.2 Other causative organisms are ment. Only those affected nails that were positive
nondermatophyte molds and yeasts. Candida for both potassium hydroxide (KOH) and culture
albicans accounts for approximately 70% of were included in the study. Shanghai Tongji
onychomycosis caused by yeasts. The predisposing Hospital Ethics Committee approved the research
factors include advanced age, diabetes, peripheral (trial no. 244) and the research was registered
vascular disease, low im- (no. ChiCTR-OOC-14005547)
mune status, HIV, obesity, in China Clinical Trials
and smoking. CAPSULE SUMMARY Registry, a World Health
The available treatment Organizationerecognized or-
options for onychomycosis
d Treatment options for onychomycosis
ganization.
are topical drugs such as are limited.
ciclopirox, amorolfine, efi- d Fractional carbon-dioxide laser-assisted
naconazole, or tavaborole topical therapy provides an alternative to Scoring Clinical Index for
in mild cases and systemic effectively treat onychomycosis. Onychomycosis
drugs such as terbinafine, d
This technique provides new treatment The Scoring Clinical Index
fluconazole, itraconazole, options for this condition. for Onychomycosis (SCIO)
or griseofulvin in severe (range 1-30) was calculated
cases.3 Topical antifungals using the clinical index
are often ineffective because component and the growth
of their inability to penetrate via nail plate. Systemic component in the following equation6:
treatments, although effective, have limited appli- h i12f3f=2
cation because of adverse effects such as hepato- d=33f f h3  f
toxicity and potential drug interactions, especially
in patients with comorbidities. Moreover, successful Where d = depth of involvement, f = clinical form,
therapy of onychomycosis has at least a 20% to 25% and h = degree of hyperkeratosis.
4
rate of relapse or reoccurrence. Therefore, many We used an electronic calculator for SCIO and
in vitro and in vivo therapeutic trials are being found that only 20 of 75 patients scored 1 to 6 and
conducted in a search of a safe and effective would receive topical treatment, whereas 55 patients
alternative therapy. scored 6 to 30 indicating they would require systemic
Recently, photodynamic therapy and laser-based therapy, combination therapy, or nail avulsion.
treatments have been explored as a possible
alternative treatment for onychomycosis. Long- KOH preparation and fungal culture
pulse 1064-nm neodymium:yttrium-aluminium- Fungal examination was done at the beginning of
garnet (Nd:YAG) laser, diode laser, Q-switched treatment, at 3 months, and at 6 months. KOH
Nd:YAG laser, titanium:sapphire laser, and short- preparation showing septate hyphae or pseudohy-
pulse Nd:YAG 1064-nm laser have all been phae was considered positive. Sabouraud dextrose
studied and found to be safe and effective for agar medium was used for culture.
treating onychomycosis. In our study we used
fractional carbon-dioxide (CO2) laser and topical Photography
terbinafine to treat onychomycosis. The fractional Photographs were taken using the same camera
CO2 laser systems were developed to maximize the settings, lighting, nail position, and background
effect of ablative laser therapies and minimize side on a digital single-lens camera (Power Shot, G12
effects.5 lens, 35 zoom, 10 megapixel [Canon, Tokyo,
Japan]). Photographs were taken at the beginning
of treatment, and at first, second, third, and sixth
METHODS months.
Patient selection
In total, 75 patients with 356 onychomycotic Topical anesthesia
nails were enrolled in the study. Both fingernails Before laser therapy, 5% lidocaine cream (Beijing
and toenails with all 4 types of onychomycosis Ziguang Zhiyao Youxian Co) was applied under
(distal lateral subungual onychomycosis [DLSO], occlusion on the infected nail and periungual area
proximal subungual onychomycosis [PSO], superficial for 30 minutes.
J AM ACAD DERMATOL Bhatta et al 3
VOLUME jj, NUMBER j

Table I. Patient characteristics

Sex Age, y Affected nails Comorbid condition
Total no.
of patients Male Female #60 [60 Fingernails Toenails Diabetic Liver cirrhosis
75 33 (44%) 42 (56%) 55 (73.33%) 20 (26.66%) 73 (20.50%) 283 (79.50%) 3 1

Fig 1. Nails before and after fractional carbon-dioxide laser treatment. There was substantial
improvement in the nails 6 months after treatment. DLSO, Distal lateral subungual onychomy-
cosis; PSO, proximal subungual onychomycosis; SWO, superficial white onychomycosis; TDO,
total dystrophic onychomycosis.

Laser treatment spots/cm2, pulse interval of 0.5 mm, pulse duration

All the infected nails were treated with fractional of 0.1 milliseconds, and a rectangular spot size of 2-
CO2 laser (2030CI, Wuhan Qi Zhi Laser Technology to 10-mm length and 0.6- to 5-mm breadth. These
Co) using pulse energy of 99 mJ, a density of 410 parameters were chosen after a few clinical trials
4 Bhatta et al
Fig 1. (continued).
with different parameters. Depending on the severity
of the lesions, 2 to 6 passes were given at the same
site in static operating mode over the affected area
including 1-mm normal-appearing areas around
them. Altogether 3 sessions of laser therapy were
given, each at 4-week intervals.
Pain assessment
Pain experienced by patients was quantified using
visual analog scale from 0 to 10, where 0 indicates
no pain and 10 indicates worst possible pain.
Topical antifungal
Patients were prescribed 1% terbinafine cream to
apply once daily for 3 months.
Statistical analysis
Data were analyzed by x 2 test, Fisher exact test,
Cochran-Mantel-Haenszel test, independent 2-
sample t test, and Wilcoxon rank sum test using
J AM ACAD DERMATOL
n 2015
software (SAS 9.4, SAS Institute Inc, Cary, NC).
P value of less than .05 was considered to be
significant.
RESULTS
Of 87 patients who were initially enrolled, 12 did
not complete the study. Among 75 patients who
completed the study (Table I), culture was positive
for T rubrum in 35, T mentagrophytes in 2, C albicans
in 23, C tropicalis in 3, C krusei in 4, Aspergillus niger
in 5, and A fumigatus in 3 patients. The duration of
disease ranged from 2 months to 40 years, with a
mean duration of 6.4 years. All 4 types of onycho-
mycosis were involved in the study with 36 patients
having DLSO, 27 TDO, 4 PSO, and 8 SWO.
Clinical evaluation
Clinical improvement (Fig 1) was evaluated as
complete response, significant response ([60%
improvement), moderate response (20%-60%
J AM ACAD DERMATOL
VOLUME jj, NUMBER j
Fig 2. Evaluation of treatment clinical response after
6 months of treatment with fractional carbon-dioxide laser.
NA, No response.
Fig 3. Evaluation of treatment response based on patient
satisfaction after 6 months of treatment with fractional
carbon-dioxide laser.
improvement), and no response (\20% improve-
ment) in 11 (14.66%), 44 (58.66%), 19 (25.33%), and 1
(1.33%) patient, respectively, at 3 months of follow-
up; and in 25 (33.33%), 30 (40%), 5 (6.66%), and 15
(20%) patients, respectively, at 6 months of follow-
up (Fig 2).
Mycologic evaluation
In all, 71 patients (94.66%) were KOH negative
and 69 patients (92%) culture negative at 3 months of
treatment. Nevertheless at the 6-month follow-up,
only 63 patients (84%) were KOH negative and 60
patients (80%) were culture negative because of
recurrence of disease in few patients. In all, 69
Bhatta et al 5
Fig 4. Comparison of treatment clinical response among
different types of onychomycosis after 6 months of
treatment with fractional carbon-dioxide laser. DLSO,
Distal lateral subungual onychomycosis; NA, no response;
PSO, proximal subungual onychomycosis; SWO, superfi-
cial white onychomycosis; TDO, total dystrophic
onychomycosis.
patients (92%) and 60 patients (80%) were both
KOH and culture negative at 3 months and 6 months,
respectively.
Subjective evaluation
Subjective evaluation was done by the patients at
6 months of follow-up and reported as very satisfied,
satisfied, slightly satisfied, and not satisfied by 50, 8,
10, and 7 patients, respectively (Fig 3).
Comparative evaluation among 4 different
types of onychomycosis
The treatment response among different types of
onychomycosis was compared (Fig 4) and evaluated
at 6 months of follow-up as complete response,
significant response, moderate response, and no
response. The maximum number of patients
showing complete response was 17 patients with
DLSO followed by 2 patients with TDO, 5 with SWO,
and 3 with PSO. Similarly, the maximum number of
patients showing significant response was 13 pa-
tients with DLSO, followed by 11 patients with TDO,
3 with SWO, and 1 with PSO. The number of patients
showing moderate response was 2, 3, 0, and 0 for
DLSO, TDO, SWO, and PSO, respectively. Similarly,
the number of patients showing no response was 4,
11, 0, and 0 for DLSO, TDO, SWO, and PSO,
respectively.
6 Bhatta et al J AM ACAD DERMATOL
n 2015

Table II. Comparison of 2 groups according to influencing factors

DLSO, n = 36 TDO, n = 27 Statistics P value
Age, y
Mean 6 SD 44.83 6 16.68 49.48 6 17.92 t = 1.06 .2931
Sex
Male, n (%) 16 (44.44) 9 (33.33) x 2 = 0.80 .3724
Female, n (%) 20 (55.56) 18 (66.67)
Duration of disease, mo
Mean 6 SD 67.19 6 94.11 105.11 6 102.22 Z = 2.06 .0397
SCIO
Mean 6 SD 10.24 6 5.58 17.42 6 7.87 t = 4.24 \.0001
Microscopic improvement
KOH at first visit
Negative n (%) 0 (0.00) 0 (0.00) 1.0000
Positive n (%) 36 (100.00) 27 (100.00)
KOH after 12 wk
Negative n (%) 35 (97.22) 24 (88.89) x 2 = 0.67 .4120
Positive n (%) 1 (2.78) 3 (11.11)
KOH after 6 mo
Negative n (%) 33 (91.67) 18 (66.67) x 2 = 6.25 .0124
Positive n (%) 3 (8.33) 9 (33.33)
Culture reports
First visit
Trichophyton rubrum n (%) 18 (50.00) 9 (33.33) x 2 = 7.08 .3135
Trichophyton mentagrophytes n (%) 1 (2.78) 0 (0.00)
Candida albicans n (%) 11 (30.56) 11 (40.74)
Candida tropicalis n (%) 2 (5.56) 1 (3.70)
Candida krusei n (%) 1 (2.78) 3 (11.11)
Aspergillus niger n (%) 3 (8.33) 1 (3.70)
Aspergillus fumigatus n (%) 0 (0.00) 2 (7.41)
After 12 wk
Negative n (%) 35 (97.22) 24 (88.89) x 2 = 1.77 .1830
Candida albicans n (%) 1 (2.78) 3 (11.11)
After 6 mo
Negative n (%) 33 (91.67) 15 (55.56) x 2 = 13.02 .0427
Trichophyton rubrum n (%) 0 (0.00) 3 (11.11)
Trichophyton mentagrophytes n (%) 0 (0.00) 1 (3.70)
Candida albicans n (%) 3 (8.33) 5 (18.52)
Candida krusei n (%) 0 (0.00) 1 (3.70)

DLSO, Distal lateral subungual onychomycosis; KOH, potassium hydroxide; SCIO, Scoring Clinical Index for Onychomycosis; TDO, total
dystrophic onychomycosis.

Comparative evaluation between the 2 most
common types of onychomycosis
Because DLSO and TDO are the 2 most common
types of onychomycosis, we statistically compared
the effectiveness of therapy on these types on the
basis of age and sex of patients, duration of disease,
mycologic examination, SCIO, and clinical and
subjective evaluation and found that the response
in DLSO was superior to TDO (Tables II and III).
SCIO evaluation
The SCIO was evaluated using SCIO electronic
calculator.6 Of 75 patients, 55 patients scored higher
than 6 and 20 patients scored 6 or less. Those who
scored greater than 6 were evaluated clinically for
treatment response. The number of patients showing
complete, significant, moderate, and no response
was 3, 35, 16, and 1, respectively, at 3 months and 13,
23, 7, and 12, respectively, at 6 months. On average,
98.18% of patients showed response to treatment at
3 months and 78.18% at 6 months. The results
emphasize that patients who were candidate for
systemic therapy according to the SCIO ([6) showed
good clinical response to the laser-assisted topical
treatment.
Pain evaluation
Pain experienced during laser therapy was as-
sessed by visual analog scale. The mean visual
analog scale score for pain was 1.93. As reported
J AM ACAD DERMATOL Bhatta et al 7
VOLUME jj, NUMBER j

Table III. Comparison of clinical improvement and subjective evaluation between 2 groups
DLSO, n = 36 TDO, n = 27 Statistics P value
Clinical improvement at 3 mo
Complete response 6 (16.67) 1 (3.70) x 2 = 5.36 .0206
Significant response 24 (66.67) 14 (51.85)
Moderate response 5 (13.89) 12 (44.44)
No response 1 (2.78) 0 (0.00)
Effective, % 83.33 55.56 x 2 = 5.74 .0166
Clinical improvement at 6 mo
Complete response 17 (47.22) 2 (7.41) x 2 = 13.10 .0003
Significant response 13 (36.11) 11 (40.74)
Moderate response 2 (5.56) 3 (11.11)
No response 4 (11.11) 11 (40.74)
Effective, % 83.33 48.15 x 2 = 8.68 .0032
Satisfaction evaluation
Very satisfied 27 (75.00) 12 (44.44) x 2 = 9.87 .0017
Satisfied 4 (11.11) 3 (11.11)
Slightly satisfied 5 (13.89) 5 (18.52)
Not satisfied 0 (0.00) 7 (25.93)
Effective, % 86.11 55.56 x 2 = 7.20 .0073

Efficacy = (complete response 1 significant response)/total cases 3 100. Satisfaction = (extremely satisfied 1 very satisfied 1 satisfied)/total
cases 3 100.
DLSO, Distal lateral subungual onychomycosis; TDO, total dystrophic onychomycosis.

Table IV. Effectiveness of different treatment modalities in past and current studies
Treatment method Topical7 Oral7 Oral 1 topical7 Laser treatment9 Current study
Efficacy 16%-46% 38%-76% 71%-86% 33%-70% 80%

by the patients, treatments were well tolerated by
most of them. Although some patient experienced
mild pain during laser treatment, no adverse events
such as bleeding or oozing were reported.
Complications such as bacterial infections or contact
dermatitis were also not reported.
DISCUSSION
Onychomycosis is the most common nail disorder
in adults, accounting for up to 50% of all nail diseases
and evidence suggests that incidence of onychomy-
cosis is increasing.1 Therapeutic options for the
treatment of onychomycosis include palliative care,
mechanical or chemical debridement, topical and
systemic antifungal agents, and various combina-
tions of these modalities.
Treatment of advanced onychomycosis is time-
consuming, is cost-intensive, and has relatively high
failure rates. Even potent systemic antimycotics
delivered over a period of several months have
cure rates of only 40% to 80%.7 Moreover, systemic
drugs are associated with side effects. Headache,
rash, and gastrointestinal symptoms were reported
in about 7% of patients treated with itraconazole8
and about 5% of patients treated with fluconazole
experienced nausea, headache, pruritus, and liver
enzyme abnormalities.7
Now, many laser systems have been studied for
the treatment of onychomycosis and were found to
be effective.9
Lim et al10 used fractional CO2 laser and a topical
antifungal to treat toenail onychomycosis and found
it to be effective. In our study, too, using fractional
CO2 laser and topical antifungal cream, of 75
patients, 71 were KOH negative and 69 were culture
negative after 12 weeks of treatment. However, at
6 months of follow-up, only 63 patients remained
KOH negative and 60 remained culture negative. The
patients not showing mycologic cure were mostly
those who had C albicans grown in the culture. This
could be because of terbinafines poor efficacy
against Candida.
Meral and colleagues11 reported the fungicidal
effect of Nd:YAG laser on C albicans. In another
in vitro study, the diode laser Noveon (870/930 nm;
Nomir Medical Technologies, Inc, Woodmere, NY)
was found to have a fungicidal and bactericidal
effect on Staphylococcus aureus, Escherichia coli,
8 Bhatta et al
C albicans, and T rubrum.12 The successful use of
lasers largely depends on the wavelength, output
power, pulse duration, exposure time, spot size,
type, and color of the targeted tissue.13 Laser light
causes local hyperthermia, destruction of pathogenic
micro-organisms, and stimulation of the reparative
process.14
Studies of different treatment modalities for ony-
chomycosis to date are summarized in Table IV. The
studies showed that the best response is seen with
combination therapy (topical plus oral), followed by
oral therapy, then laser therapy and at last topical
therapy. To be noted is that our study and other
similar studies have shown laser-assisted topical
therapy could be as effective as combination ther-
apy. Moreover, laser-assisted topical therapy has
many advantages over combination therapy, such
as no serious adverse effects, comparatively short
treatment course, use in patients with comorbid
conditions, and no risk of development of resistance.
Conclusion
Laser treatment of onychomycosis has satisfactory
results. It can treat different types of onychomycosis
safely and effectively, and is especially suitable for
older patients with low immunity or liver and renal
dysfunction who are not appropriate candidates
for systemic antifungal agents. Thus, it can be
considered an alternative treatment modality.
Unfortunately, there are few studies demonstrating
efficacy and no randomized controlled clinical trials
comparing efficacy with oral antifungal agents. We
believe that this area of study will continue to expand
and provide new insights of treatment options for
onychomycosis. We believe that sufficient evidence
is still lacking for laser therapy for routine treatment
of onychomycosis, as has been advertised and
J AM ACAD DERMATOL
n 2015
propagated by laser manufacturers and franchises.
Randomized clinical studies are urgently needed.
REFERENCES
1. Ghannoum MA, Hajjeh RA, Scher R, et al. A large-scale
North American study of fungal isolates from nails: the
frequency of onychomycosis, fungal distribution, and anti-
fungal susceptibility patterns. J Am Acad Dermatol. 2000;43(4):
641-648.
2. Thomas J, Jacobson GA, Narkowicz CK, Peterson GM, Burnet H,
Sharpe C. Toenail onychomycosis: an important global disease
burden. J Clin Pharm Ther. 2010;35(5):497-519.
3. Baran R, Gupta AK, Pierard GE. Pharmacotherapy of onycho-
mycosis. Expert Opin Pharmacother. 2005;6(4):609-624.
4. Piraccini BM, Sisti A, Tosti A. Long-term follow-up of toenail
onychomycosis caused by dermatophytes after successful
treatment with systemic antifungal agents. J Am Acad
Dermatol. 2010;62:411-414.
5. Tierney EP, Eisen RF, Hanke CW. Fractionated CO2 laser skin
rejuvenation. Dermatol Ther. 2011;24:41-53.
6. Sergeev AY, Gupta AK, Sergeev YV. The Scoring Clinical Index
for Onychomycosis (SCIO Index). Skin Therapy Lett. 2002;1(7
Suppl):6-7.
7. Scher RK. Onychomycosis: therapeutic update. J Am Acad
Dermatol. 1999;40(6 pt 2):S21-S26.
8. Gupta AK, De Doncker P, Scher RK, et al. Itraconazole for the
treatment of onychomycosis. Int J Dermatol. 1998;37:303-308.
9. Bhatta AK, Huang X, Keyal U, Zhao JJ. Laser treatment for
onychomycosis: a review. Mycoses. 2014;57:734-740.
10. Lim EH, Kim HR, Park YO, et al. Toenail onychomycosis treated
with a fractional carbon-dioxide laser and topical antifungal
cream. J Am Acad Dermatol. 2014;70(5):918-923.
11. Meral G, Tasar F, Kocagoz S, Sener C. Factors affecting the
antibacterial effects of Nd:YAG laser in vivo. Lasers Surg Med.
2003;32:197-202, 22.
12. Bornstein E, Hermans W, Gridley S, Manni J. Near-infrared
photo inactivation of bacteria and fungi at physiologic
temperatures. Photochem Photobiol. 2009;85:1364-1374.
13. Brooks SG, Ashley S, Fisher J, et al. Exogenous chromophores
for the argon and Nd:YAG lasers: a potential application
to laser-tissue interactions. Lasers Surg Med. 1992;12(3):
294-302.
14. Dayan S, Damrose JF, Bhattacharyya TK, et al. Histological
evaluations following 1,064-nm Nd:YAG laser resurfacing.
Lasers Surg Med. 2003;33:126-131.