Received: 27 August 2020 | Accepted: 19 October 2020

DOI: 10.1111/jocd.13817

ORIGINAL CONTRIBUTION

Laser-assisted delivery of tranexamic acid for melasma: Pilot

study using a novel 1927 nm fractional thulium fiber laser

Jordan V. Wang MD, MBE, MBA | Mitalee P. Christman MD | Hao Feng MD, MHS |
Georgina Ferzli MD | Hana Jeon MD | Roy G. Geronemus MD

Laser & Skin Surgery Center of New York,

New York, NY, USA
Correspondence
Jordan V. Wang, MD, MBE, MBA, Laser &
Skin Surgery Center of New York, 317 E
34th Street, 6th Floor Research Department,
New York, NY, 10016, USA.
Email: drjordanwang@gmail.com
Funding information
This study was funded and supported by
Lutronic, who also provided the topical
products used in this study.
Abstract
Background: Melasma can be associated with immense psychosocial stress, which
can impact quality of life. One theory suggests that ultraviolet light can increase plas-
min activity in keratinocytes, which has led to the investigation of tranexamic acid for
treating melasma, since it possesses anti-plasmin properties. The use of laser-assisted
drug delivery can also increase the uptake of topical medications.
Aims: A prospective pilot study was performed to assess the utility of combination
treatment with low-energy, low-density 1927 nm fractional thulium fiber laser and
topical tranexamic acid for melasma.
Patients/Methods: A total of 10 subjects were enrolled. Each received 5 treatments
to the full face with a low-energy, low-density 1927 nm fractional thulium fiber laser.
Immediately following treatment, topical tranexamic acid was applied, and subjects
were instructed to apply it twice daily for 7 days. Clinical measures, quality of life, and
patient satisfaction were assessed.
Results: Mean improvements in Melasma Area and Severity Index (MASI) scores
were 1.1 (P = .0899), 3.5 (P = .0395), and 2.5 (P = .2429) at 30-, 90-, and 180-day
follow-up, respectively. Maximum improvement occurred at 90-day follow-up. The
mean improvement of Melasma Quality of Life Scale (MELASQOL) score was 9.6
(P = .0024) at 30-day follow-up. In addition to changes in pigmentation, subjects also
believed their skin felt better, looked more radiant, and had improvements in skin
texture and tone.
Conclusion: Combination of low-energy, low-density 1927 nm fractional thulium
fiber laser and topical tranexamic acid improved clinical outcomes and quality of life
associated with melasma. This combination treatment was safe, well-tolerated, and
well-liked by subjects.

KEYWORDS

aesthetics, dermatology, lasers, melasma, tranexamic acid

1 | I NTRO D U C TI O N patches on sun-exposed areas of the face and neck, which dispro-
portionately affects those of Asian, African, and Hispanic descent.
Melasma is a common skin condition that is characterized by a Melasma has been associated with pregnancy, changes in uterine or
chronic and relapsing course. It typically manifests as gray-to-brown ovarian hormones, oral contraceptives, and excessive sun exposure.1

J Cosmet Dermatol. 2020;00:1–5. wileyonlinelibrary.com/journal/jocd© 2020 Wiley Periodicals LLC | 1

2 |
Unfortunately, many of the available treatment options offer only
temporary or partial improvement. It is likely that this has contrib-
uted to the psychosocial stress of having melasma, which can greatly
impact the quality of life of patients. 2
Although the etiology of melasma is not yet fully understood, one
prominent theory suggests that ultraviolet light can increase plasmin
activity in keratinocytes, which subsequently increases melanocyt-
ic-stimulating mediators, such as arachidonic acid and α-melanocyte
stimulating hormone.1 This model has led to the investigation of
tranexamic acid (TA) for treating melasma.3 TA is an antifibrinolytic
agent that possesses antiplasmin properties. Therefore, it has been
used to inhibit the release of paracrine melanogenic factors that nor-
mally act to stimulate melanocytes.4
Recently, laser-assisted drug delivery (LADD) has been studied in
the management of various skin disorders, including melasma, actinic
keratoses, and scars.5-9 With LADD, a laser is used to disrupt the stra-
tum corneum and create tiny microchannels, termed microscopic treat-
ment zones (MTZs). The laser-induced breakdown increases uptake of
topically applied medications, which can increase local drug absorption
and bioavailability while reducing the undesirable effects associated
with systemic absorption. Several medications have been utilized, in-
cluding tranexamic acid, bimatoprost, and poly-L lactic acid.9-14
We hypothesize that the use of a low-energy, low-density
1927 nm fractional thulium fiber laser to assist in the delivery of top-
ical TA can improve the clinical appearance of melasma, as well as the
quality of life and satisfaction of patients. We performed a prospec-
tive pilot study to assess the utility of this combination treatment.
2 | M ATE R I A L S A N D M E TH O DS
Ten healthy subjects seeking treatment for melasma were enrolled.
This study was approved by an independent IRB. Informed consent
was obtained. Subjects were excluded if they had active skin disease
that may affect wound healing; history of keloids or hypertrophic
scars; significant scarring or open wounds in the treatment area; his-
tory of collagen vascular disease or autoimmune disease; known al-
lergy to topical anesthetic, post-treatment cosmeceuticals, tranexamic
acid, or coconut; current smoking habit or use of nicotine-containing
products; excessive tanning or inability to refrain from tanning; surgi-
cal or cosmetic treatment to the treatment area in the prior 6 months;
microdermabrasion or prescription-level glycolic acid treatment to the
treatment area in the prior 4 weeks; history of hormone treatment or
oral contraceptives in the prior 3 months; use of any prescription skin-
lightening agent, photosensitizing medication, or corticosteroid in the
prior 6 months; use of systemic retinoid in the prior 12 months; and
use of anti-platelet agents or anticoagulants in the prior 2 weeks.
For all subjects, each received five treatments to the full face
with a low-energy, low-density 1927nm fractional thulium fiber laser
(LaseMD, Lutronic, South Korea) at 21 (+7)-day intervals. Subjects
were offered the option of topical EMLA cream (lidocaine 2.5%/
prilocaine 2.5%) for approximately 30 minutes prior to treatment.
The laser was set to Random Mode with an output power of 4-5W
WANG et al.
and fluence of 2-8mJ with 2-8 passes performed. Immediately
following treatment, topical TA (TA Ampoule, LaseMD, Lutronic,
South Korea) was applied, which contained TA in a liquid crystal-
line nanoparticle carrier. Approximately 1.0 cc was used to coat the
treatment area. Following treatment, subjects were instructed to
apply topical TA twice daily at home for 7 days and broad-spectrum
sunscreen daily for the entire study period.
The VISIA photography system (Canfield Scientific, Fairfield,
NJ) was utilized. Melasma was graded using the Melasma Area and
Severity Index (MASI) score at baseline and subsequent follow-up
visits at 30, 90, and 180 days. The Global Aesthetics Improvement
Scale (GAIS) (3-point scale) was used by both investigator and sub-
ject to grade clinical improvement at follow-up visits at 30, 90, and
180 days. Subject satisfaction was assessed at 30-day follow-up. The
impact of melasma on quality of life was assessed at baseline and 30-
day follow-up using the Melasma Quality of Life Scale (MELASQOL).
Adverse events were also assessed.
3 | R E S U LT S
3.1 | Subject demographics
A total of 7 subjects completed the study. Mean age was 47.0 years
(R: 30-60 years). Of all subjects, 100.0% (n = 7) were female. In
terms of Fitzpatrick skin type, 14.3% of subjects were Type II (n = 1),
28.6% (n = 2) were Type III, and 57.1% (n = 4) were Type IV.
3.2 | Melasma area and severity index
At baseline, the mean MASI score for all subjects was 10.6 (R: 6.8-
12.8). The mean improvements from baseline MASI score were 1.1
(P = .0899), 3.5 (P = .0395), and 2.5 (P = .2429) at 30, 90, and 180-
day follow-up, respectively (Figure 1). Maximum improvement oc-
curred at 90-day follow-up. At 180-day follow-up, 42.9% (n = 3) of
subjects were experiencing recurrence of their melasma and wors-
ening of their MASI score from 90-day follow-up with an overall
mean decline of 1.0.
3.3 | Clinical rating
According to investigator GAIS, 71.4% (n = 5), 71.4% (n = 5), and
85.7% (n = 6) of subjects had improvement from baseline at 30-, 90-,
and 180-day follow-up, respectively. The remaining subjects were
rated to have no clinical change. No investigator rated the condi-
tion to be worse. For subject GAIS, 85.7% (n = 6), 85.7% (n = 6), and
100.0% (n = 7) of subjects saw improvement at 30-, 90-, and 180-
day follow-up, respectively. The remaining subjects believed they
had no clinical change. No subjects rated their condition to be worse.
When GAIS differed between investigator and subject, the subject
rated their clinical improvement to be better 100% of the time.
WANG et al. | 3

F I G U R E 1 Mean MASI scores with

standard error at baseline and follow-up
at 30, 90, and 180 days

F I G U R E 2 Photographs of female
subject at baseline and follow-up at 30,
90, and 180 days, respectively (from left
to right)

3.4 | Quality of life
At baseline, the mean MELASQOL score for all subjects was 44.4
(R: 23-65). The mean improvement from baseline MELASQOL score
was 9.6 (P = .0024) at 30-day follow-up.
skin felt better and also looked more radiant, 42.9% (n = 3) believed
that they had improvements in skin texture and also skin tone, and
28.6% (n = 2) believed that their skin appeared brighter and also
more youthful.
3.6 | Safety

3.5 | Subject satisfaction
At 30-day follow-up, 71.4% (n = 5) of subjects were satisfied with
the treatment. Similarly, 71.4% (n = 5) would recommend the treat-
ment to their friends and family members with melasma. In addi-
tion to changes in pigmentation, 57.1% (n = 4) believed that their
During the study, expected treatment effects were observed, which
included transient roughness, transient dryness, and transient itch-
ing. All were mild and resolved without intervention. There was a
single adverse event that was deemed to be unrelated to the study,
which was a moderate allergic reaction due to bug bites that re-
solved with medication.
4 |
4 | D I S CU S S I O N
Recently, LADD has been studied in conjunction with several topical
formulations for an increasing number of skin disorders. The prop-
erties of MTZs, such as their density and depth, can be influenced
by adjusting certain laser parameters, including wavelength, pulse
width, and fluence. In addition to the laser settings, the properties
of the topical medication, such as lipophilic or lipophobic tenden-
cies, pH, and vehicle type, can also impact drug delivery. For these
reasons, in order to optimize LADD, the procedure should take into
account the cutaneous condition being treated, the laser being used,
and the topical medication being applied.
This study demonstrates that delivery of topical TA by a low-en-
ergy, low-density 1927 nm fractional thulium fiber laser can improve
the clinical outcomes of melasma (Figure 2 and Figure 3). The maxi-
mum benefit was achieved at 90 days following treatment. This was
likely affected by study treatments occurring in the Spring and early
Summer. Therefore, better results may have been appreciated at
30 days if this study occurred in the Winter, which would have de-
creased sun exposure during this early period. However, at 180 days
post-treatment, some subjects began to experience recurrence of
their melasma. This is consistent with the chronic and recurring na-
ture of this cutaneous condition and the previous experiences with
other treatment modalities, which have only offered short-term im-
provement before recurrences were ultimately experienced.3,14,15
Although clinical research has focused on finding an effective and
lasting maintenance strategy following initial laser or tranexamic
acid treatment, there has been limited success over the years.
In addition to changes in pigmentation, several of the subjects in
this study also noticed improvements in how their skin felt as well as
in their skin radiance, texture, and tone. This is likely an added ben-
efit of using the low-energy, low-density 1927 nm fractional thulium
fiber laser to assist in the delivery of topical TA. This wavelength has
WANG et al.
less water absorption than CO2 and Erbium:YAG lasers and can de-
liver controlled subablative tissue damage. This laser can disrupt the
stratum corneum and stratum spinosum with controlled coagulation
of the superficial dermis, which allows for epidermal and dermal re-
juvenation.16 It is important to note that the scaffold of the stratum
corneum remains intact, which contributes to the minimal downtime
associated with this treatment.
The low-energy, low-density 1927 nm fractional thulium fiber
laser causes mild vacuolation at the dermoepidermal junction, while
the stratum basale remains intact.16 The diameter of the microbeam
damage zone is uniquely small, ranging from 102 to 366 um depend-
ing on the set energy. The disrupted stratum corneum and very su-
perficial channels allow the topical TA to penetrate through in order
to reach these superficial pockets and accumulate within. The micro-
channels close over a period of about 2-30 minutes, while the mole-
cules of the topical are slowly absorbed. The location of the vacuoles
near the dermoepidermal junction is ideal for LADD of TA, since this
is where the epidermal melanocytes ultimately reside. The antiplas-
min properties of TA can decrease the activity of these melanocytes
and subsequently improve clinical hyperpigmentation.
These results evidenced an improvement in the quality of life
of subjects, which is especially salient given the significant psy-
chosocial impact of melasma. 2 Despite significant advancements
in technology and newer formulations of topical and oral medica-
tions, melasma remains a challenging condition for clinicians to treat.
Although treatments can often improve the initial appearance of
melasma, difficulty lies in the long-term maintenance of these results
and the prevention of recurrence. There still remains considerable
need for studies to evaluate the impact of treatments on quality of
life.
Although this study is limited by the number of subjects due
to a pilot study, the data suggest that the combination of low-en-
ergy, low-density 1927 nm fractional thulium fiber laser and TA
F I G U R E 3 Photographs of female
subject at baseline and follow-up at 30,
90, and 180 days, respectively (from left
to right)
WANG et al.
can improve patient outcomes. Future large-scale trials can recruit
additional subjects and also be split-face in design in order to bet-
ter assess the differences between topical TA monotherapy, laser
monotherapy, and combination treatment. Computerized imaging
can be incorporated, which can improve the measurement of pig-
mentation. Another limitation of this study is that the quality of life
and satisfaction of subjects were both evaluated at 30 days follow-
ing treatment. Since maximum clinical improvement was observed
at 90 days post-treatment, these numbers likely underestimated the
peak improvement in quality of life and subject satisfaction.
5 | CO N C LU S I O N
In this prospective pilot study, the combination of low-energy,
low-density 1927 nm fractional thulium fiber laser and topical TA
improved clinical outcomes and quality of life associated with me-
lasma. This combination treatment was demonstrated to be safe,
well-tolerated, and well-liked by subjects.
C O N FL I C T O F I N T E R E S T
Roy Geronemus is on the advisory board for Lutronic.
AU T H O R C O N T R I B U T I O N
All authors contributed equally to this study, including the design
and implementation of the research, to the analysis of the results,
and to the writing of the manuscript.
E T H I C A L A P P R OVA L
Informed consent was obtained from all individual participants in-
volved in the study. All procedures performed were in accordance
with the ethical standards of the IRB and with the 1964 Helsinki
Declaration and its later amendments or comparable ethical
standards.
DATA AVA I L A B I L I T Y S TAT E M E N T
Research data are not shared.
ORCID
Jordan V. Wang https://orcid.org/0000-0001-7437-2745
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How to cite this article: Wang JV, Christman MP, Feng H,
Ferzli G, Jeon H, Geronemus RG. Laser-assisted delivery of
tranexamic acid for melasma: Pilot study using a novel
1927 nm fractional thulium fiber laser. J Cosmet Dermatol.
2020;00:1–5. https://doi.org/10.1111/jocd.13817