Journal of Cosmetic and Laser Therapy

ISSN: 1476-4172 (Print) 1476-4180 (Online) Journal homepage: http://www.tandfonline.com/loi/ijcl20

A prospective, split-face, double-blinded,

randomized study of the efficacy and safety of a
fractional 1064-nm Q-switched Nd:YAG laser for
photoaging-associated mottled pigmentation in
Asian skin
Kwang Hee Won, Sang Hyung Lee, Mi Hye Lee, Do-Young Rhee, Un-Cheol Yeo
& Sung Eun Chang
To cite this article: Kwang Hee Won, Sang Hyung Lee, Mi Hye Lee, Do-Young Rhee, Un-Cheol
Yeo & Sung Eun Chang (2016): A prospective, split-face, double-blinded, randomized study
of the efficacy and safety of a fractional 1064-nm Q-switched Nd:YAG laser for photoagingassociated mottled pigmentation in Asian skin, Journal of Cosmetic and Laser Therapy, DOI:
10.1080/14764172.2016.1191645
To link to this article: http://dx.doi.org/10.1080/14764172.2016.1191645

Accepted author version posted online: 01

Jun 2016.
Published online: 19 Jul 2016.
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Date: 12 November 2016, At: 05:23

Journal of Cosmetic and Laser Therapy

http://dx.doi.org/10.1080/14764172.2016.1191645

ORIGINAL RESEARCH REPORT

A prospective, split-face, double-blinded, randomized study of the efficacy and safety

of a fractional 1064-nm Q-switched Nd:YAG laser for photoaging-associated mottled
pigmentation in Asian skin
Kwang HeeWon1*, Sang HyungLee1*, Mi HyeLee1, Do-YoungRhee2, Un-CheolYeo3, and Sung EunChang1
1Department

of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Leaders Dermatologic Clinic, Seoul, Korea;

3Jongno S and U Dermatologic Clinic, Seoul, Korea

ABSTRACT

ARTICLE HISTORY

Background: Laser toning using low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminum
laser (QSNY) has gained popularity in the treatment of photoaging-associated mottled pigmentation
(PMP). However, hypopigmentation or lack of efficacy has been reported depending on the fluences
used. Objective: To compare a novel fractional 1064-nm QSNY with conventional 1064-nm QSNY for the
treatment of photoaging-associated mottled pigmentary lesions except epidermal lesions of lentigines
and freckles through a randomized, split-face, double-blind study. Materials and methods: Thirteen Asian
women were treated every week for 6 weeks with fractional 1064-nm QSNY on one side of the face and
conventional 1064-nm QSNY on the other side. We evaluated the pigmentation area and severity index
(PSI), melanin index, erythema index, and the patients global assessment of improvement. Results: At three
months post-treatment, the PSI score improved compared with baseline, by 14.48% on the conventional
1064-nm QSNY side and 21.81% on the fractional 1064-nm QSNY side. Both groups showed improvements
in the melanin index. Conclusion: Both fractional 1064-nm QSNY and strictly low-fluence conventional
1064-nm QSNY are moderately effective against PMP and other photoaging signs. Fractional laser toning
shows better subjective outcomes than conventional toning.

Introduction
Laser toning using low-fluence 1064-nm Q-switched
neodymium-doped yttrium aluminum laser (QSNY) has gained
popularity in the treatment of photoaging-associated mottled
pigmentation (PMP), which is the most common concern in
Asian dermatologic practice. However, hypopigmentation or
lack of efficacy has been reported depending on the fluences
used.
The 1064-nm QSNY can target dermal pigmentation and has
shown efficacy in treating melasma (1). Multi-pass irradiation
with low-fluence 1064-nm QSNY, the so-called laser toning, has
been successfully used to treat melasma in patients with darker
skin (24). However, classic confluent melasma was prone to
punctate hypopigmentation under the relatively lower fluence
of laser toning from 2008 to 2013 and was often resistant to
these treatments. A classic presentation of melasma is seen in
childbearing aged women in their 30s to 40s (5). Usually, the
onset of dark confluent melasma is influenced by estrogen levels, but the standard treatments are still mainly topical agents
that are tyrosinase inhibitors. In our experience, laser toning
or intense pulsed light (IPL) is either ineffective against or in

Received 19 November 2015

Accepted 10 May 2016
KEYWORDS

Associated mottled
pigmentation (PMP);
fractional 1064-nm
Q-switched Nd:YAG laser;
photoaging

fact often aggravates (rebound) this type of estrogen-dependent

melasma. Because the subtypes of melasma are heterogeneous,
the evidence for improvement results following laser therapy
has been mixed to date with evidence of a significant potential
for worsening (6).
The other subtype of melasma can be categorized into
photoaging-associated mottled pigmentation (PMP) lesions.
Hyperpigmentation including UV-induced melasma, illdefined spots, and flaws is the most common and earliest sign
of photoaging in Korean population. PMP lesions manifest in
the patients early 20s as mottled pigmentation and become
confluent with a mixed epidermal and dermal melanin pattern
in a chronic and a stable manner. The main target of laser toning should be PMP lesions because 1064-nm QSNY is intended
to rejuvenate the skin and PMP is the most common and earliest sign of photoaging in Asian women. However, PMP often
manifests with a less melanized appearance and in a deep layer
beyond the reach of conventional laser toning. For this reason,
fractional photothermolysis was applied to 1064-nm QSNY,
most recently under the rationale that the laser can deliver
higher pulse peak energy to targeted chromophores confirmed

CONTACT Sung Eun Chang

csesnumd@gmail.com
Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro
43 gil, Songpa-gu, Seoul 05505, Republic of Korea.
*Kwang Hee Won and Sang Hyung Lee contributed equally to this work.
Color versions of one or more of the figures in the article can be found online at http://www.tandfonline.com/ijcl.
6 Taylor & Francis Group, LLC

K. H. WON ET AL.

in a micrometer-diameter spot (79). Previously, in Western

studies, a fractional 1064-nm QSNY device with a 55 pixel
matrix on a 0.50.5-cm footprint showed safety and efficacy
in treating photoaged skin, although there was no control group
to compare its efficacy with that of other treatments (10,11).
For the first time, we have here performed a prospective, randomized study of fractional laser toning and compared it to
conventional low-fluence laser toning in the management
of photoaging-associated mixed pigmentation. Freckles and
lentigines, which are epidermal melanin-increased lesions
typically treated by a 532-nm QSNY device, were excluded
from our assessment.

Materials and methods

Study design
We performed a prospective, randomized, single-blinded,
split-lesion comparison study of the efficacy and safety of
fractional 1064-nm QSNY and conventional 1064-nm QSNY.
Our protocol was approved by the institutional review board
of the Asan Medical Center, Seoul, Korea. Written informed
consent was obtained from all patients. Investigators complied with national and international Good Clinical Practice
guidelines and the Declaration of Helsinki. Patients were
excluded if they were pregnant or breast feeding, previously
had an adverse reaction to topical anesthetics, had received
laser treatment, chemical peels, or dermabrasion within the
previous six months, or had used phototoxic drugs within the
past three months by oral ingestion or two weeks by topical
application.
Treatment
Each study patient underwent a total of six treatment sessions
that were administered at weekly intervals. The device used
for 1064-nm QSNY was a Tri-Beam laser (Jeisys Medical Inc.,
Seoul, South Korea). The 55-mm square of the fractional
handpiece incorporates a diffractive lens aligned in a 99
(81) pattern of dots, each of a 0.450.45-mm square, covering 50% of the area. The conventional handpiece comprised
a collimated round lens with a diameter of 7 mm. The treatment site was selected according to a registration number using
the block randomization method in the R project software
(R Foundation for Statistical Computing, Vienna, Austria).
According to the designated treatment side, each patient underwent split-face laser toning in three passes with a fluence of
1.5 J/cm2 for fractional 1064-nm QSNY and a fluence of
2.0 J/cm2 for conventional 1064-nm QSNY to obtain a total
energy of approximately 750 mJ per pulse.
Evaluation
Measurements were made before each treatment session and at
three follow-up visits monthly after treatment (a total of nine
visits). Before each treatment, a clinical photograph of each
patient was taken. The patients and the evaluator were blind to
the treated side. Primary efficacy was the change in the pigmentation area and severity index (PSI). In addition, Mexameter

score and patients global assessments (PGA). The PSI score

was based on three parameters, namely, the extent, darkness,
and density of the pigmented lesions (12). Only a confined
portion of one cheek was counted. The area (the extent of pigmented lesions) was classified as 0, no involvement; 1, less than
10% involvement of a single cheek; 2, 1029%; 3, 3049%; 4,
5069%; 5, 7089%; and 6, 90100% involvement. The darkness
(of the pigmented lesions) was defined as: 0, absent; 1, slight; 2,
mild; 3, marked; or 4, severe. The density (number of pigmented
lesions per unit facial area) was calculated as: 0, minimal; 1,
slight; 2, mild; 3, marked; or 4, maximum. These values were
combined to obtain the PSI score (048) as follows: (darkness
density) area. The improvement rate at the time of evaluation was defined as (PSI pretreatment PSI post-treatment)/PSI
pretreatment100%.
A Mexameter (Courage-Khazaka Electronic, Kln,
Germany) was used to measure the melanin index (MI) and
erythema index (EI). As PGA, subjective improvement of
the pigmentation (PMP), elasticity, and skin texture on each
treatment side was compared with the baseline according to the
following classification: excellent improvement, 75%; good
improvement, 5074%; moderate improvement, 2549%; and
no to mild improvement, 024%. Patients were also asked to
report on their degree of pain, discomfort, erythema, and pigment aggravation on each visit throughout the study period.
Statistical analysis
Data are reported as the meansstandard deviation.
SPSS 21.0 software (IBM Corp., Armonk, NY) was used to
analyze the data. An independent t-test was used to compare the baseline PSI, MI, and EI. A paired t-test was used to
compare the PSI, MI, and EI reductions at the end of followup from baseline and the degree of the PSI change between
the two groups. A p value0.05 was considered statistically
significant.

Results
Participants
Thirteen Korean women with photoaged facial skin being
treated at the dermatology outpatient clinic at the Asan
Medical Center from June 2014 to July 2014 were enrolled.
These patients ranged in age from 37 to 56 (mean 46.56.6)
years and had Fitzpatrick skin types III (56%) and IV (44%).
Changes in the PSI
The baseline PSI was 14.002.42 on the cheek treated with
conventional 1064-nm QSNY and 14.692.47 on the cheek
treated with fractional 1064-nm QSNY, and there was no statistically significant difference between the two sides. The changes
in the PSI scores from baseline to the end of the study were
2.080.62 on the conventional 1064-nm QSNY side (14.48%,
p0.006) and 3.310.91 on the fractional 1064-nm QSNY
side (21.81%, p0.003). There were no statistically significant
differences in the degree of the PSI decrease between the two
groups (p0.086; Figure 1A).

Journal of Cosmetic and Laser Therapy

Figure 1. Changes in the PSI, MI, and EI scores plotted against the visit number. (A) In both patient groups, the PSI score showed a gradually decreasing pattern from visit
4 (after three treatment sessions). Although the fractional 1064-nm QSNY group showed a greater reduction during follow-up, there was no significant difference in the
decrease in the PSI between the two groups (p0.086). Neither treatment group showed exacerbation during the three months of follow-up. (B) Although there was some
fluctuation in the MI score, both groups showed a tendency for a gradual decrease in the MI score. At the end of follow-up, only the fractional group showed a statistically
significant decrease in the MI score compared with baseline (p0.012). (C) The EI score also showed a fluctuation during the study period but no statistically significant
differences were found.

Changes in the MI and EI

Discussion

At the first visit before the treatment, the MIs of the conventionally and fractionally treated sides were 218.426.9
and 214.227.4, respectively, and the EIs of both sides were
321.932.0 and 309.630.0, respectively. Although there
was some fluctuation in the MI score, both groups showed a
gradual tendency for a decrease in the MI score. Three months
after the six treatment sessions (at visit nine, Week 18), the MI
had decreased to 150.119.1 on the conventionally treated side
(31.27%, p0.012) and 123.411.2 on the fractionally treated
side (42.39%, p0.082), and the EIs were 311.220.1 (3.32%,
p0.593) and 290.723.8 (6.10%, p0.512), respectively
(Figure 1B,C).

Although traditionally considered a second-line treatment, the

demand for laser and light-based therapies in treating PMP
has risen steadily. For the treatment of active melasma that
is often related to estrogen increase in childbearing women,
almost all kinds of various Q-switched lasers or IPL treatments have produced disappointing results. However, previous
studies using laser toning and IPL did not classify subtypes of
melasma (2,4,13,14). In Korean patients (Fitzpatrick skin type
IV) with melasma, laser toning with a 6-mm spot and 2.5 J/cm2
fluence for melasma and a 4-mm spot and 45 J/cm2 with two
passes for darker spots, seven sessions or weekly laser toning
with a fluence of 2.03.5 J/cm2 at three passes led to goodto-excellent improvement. However, repeated laser toning
can be a burden to patients and sometimes result in punctate
hypopigmentation (15,16). In one of the previously reported
series, 3 of 259 patients developed punctate leukoderma after
treatment with a fluence of 1.6 J/cm2 in a 6-mm spot plus two
passes of 2.22.5 J/cm2 in a 4-mm spot (16). In our previous
study, however, even this low level laser toning may not produce a real effect for active estrogen-related melasma, which is
often seen in the periorbital area and aggravated with multiple
recurrences. In another study, deep erythema with a higher EI
in melasma lesions was associated with a poorer response to
the low-fluence 1064-nm QSNY treatment (17). We suggest
that melasma should definitely be treated according to subtype. Thus, acute or active melasma cases were excluded from
our present analyses using a detailed patient history. For the
treatment of PMP, a Q-switched alexandrite laser, Q-switched
ruby laser, Erbium:YAG laser, dye laser (500520 nm), or IPL
did not completely remove the lesions. Unfortunately, the
patients showed recurrence and post-inflammatory hypopigmentation (PIH) (18).
To minimize adverse effects and enhance the removal of
residual lesions with less melanin as chromophore in our present
series, we used spatially fractional low-fluence 1064-nm QSNY
to treat melasma and PMP. In terms of histopathology, dermal
and possibly follicular components of melasma or PMP may

Patients global assessments

Self-assessed improvement results were similar between the
conventional 1064-nm QSNY side and the fractional 1064-nm
QSNY side. Approximately half of the patients reported an
excellent or good response on each site at the end of the study
(Figure 2). Figure 3 shows an example of a patient who reported
excellent satisfaction and a PSI improvement of 33% on both
sides.
Assessment of adverse effects
One woman complained of aggravation of melasma on the
conventionally treated side at visit 3. She did not have any
post-treatment erythema at the time, and continuation of
her scheduled laser toning in the clinical trial did not further aggravate her lesions. At her final visit, she reported
moderate subjective and objective improvement. Pain or
erythema was tolerable in all patients. There were no serious
and/or irreversible adverse effects such as scarring or textural changes. Punctate hypopigmentation, which was often
reported in previous studies, did not develop in patients of
this study.

K. H. WON ET AL.

Figure 2.PGA of satisfaction compared with baseline. About half of the patients reported an excellent or good response at the end of the study. Notably, early
satisfaction was reported for the conventionally treated side but excellent satisfaction was more commonly reported for the fractionally treated side in the
post-treatment follow-up.

play important roles in its resistance to treatments and the tendency for relapse (18). Thus, we decided to treat melasma and
PMP by applying a spatially fractional 1064-nm QSNY, which
theoretically delivers twice as much energy to each spot, allowing us to treat deeper lesions, at a lower fluence while avoiding
unwanted disfiguring hypopigmentation and sparing untreated
tissue. In our patients, both fractional low-fluence (1.5 J/cm2)
1064-nm QSNY and strict low-fluence (2.0 J/cm2) conventional
1064-nm QSNY were moderately effective. Fractional laser toning showed better subjective outcomes than the conventional
approach, and the fractional 1064-nm QSNY group showed a
more stable and lower EI score during follow-up.
There have been several reports on the use of a similar fractional 1064-nm QSNY device (Pixel QSW; Alma Lasers Ltd.,
Caesarea, Israel), but there have been no trials of this device in

terms of pigmentation improvement. Instead, previous studies on this device have involved a 55 pixel matrix targeting
rhytides and photodamage with higher fluence. In a pilot study
of seven patients by Luebberding and Alexiades-Armenakas
(11), an 11.3% improvement over baseline was reported for
rhytides of the face and neck. The treatment consisted of three
treatment sessions at 24-week intervals with 1.2 J/pulse for
812 passes to achieve the clinical end point of diffuse confluent erythema. In another study by Gold etal. (10), 10 patients
with photoaged skin, treated with four laser sessions at 24week intervals with a pulse energy of 8001000 mJ/pulse using
the Pixel QSNY, achieved improvements in hyperpigmentation,
telangiectasias, tactile roughness, and actinic keratoses with
minimal downtime and pain. Although other photoaging signs
were not focused in this study, our patients were also satisfied

Journal of Cosmetic and Laser Therapy

Figure 3.Photographs at baseline, the sixth visit (week 5), and the final visit (week 18) of the fractional (AC) and conventional (DF) 1064-nm QSNY-treated sides
of a study patient. This patient reported excellent satisfaction and a PSI improvement of 33% on both sides.

with the modest improvement in elasticity and skin texture as

indicated on PGA record. In conclusion, this study indicates the
efficacy and safety of fractional 1064-nm QSNY in the treatment of PMP and other photoaging signs. The use of the new
fractional handpiece versus the widely used 1064-nm QSNY
will enable finer treatment with a lower probability of adverse
effects. Further investigation of the microscopic and molecular
differences from conventional irradiation is required.

Declaration of interest
The authors report no declarations of interest. The authors alone are
responsible for the content and writing of the paper.

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