Lasers in Surgery and Medicine :1–8 ()
Acne Treatment With Light Absorbing Gold Microparticles
and Optical Pulses: An Open‐Label European
Multi‐Centered Study in Moderate to Moderately
Severe Acne Vulgaris Patients
Christine Sofie Krohn Fuchs,1* Christiane Bay,1 Maurice Adatto,2 Hans Lomholt,3 and Merete Haedersdal1
1
Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, DK‐2400, Denmark
2
Skinpulse Dermatology & Laser Centre, Geneva, 1205, Switzerland
3
Skincenter North and University of Aalborg, Aalborg, DK‐9220, Denmark
Background and Objective: Recently, a novel acne
treatment based on selective photothermolysis of pilose-
baceous units with follicular delivery of inert gold
microparticles as an exogenous chromophore and diode
laser pulses has been developed. To evaluate the efficacy
and safety of a single monotherapy treatment regimen
with gold microparticles and diode laser exposure in
patients with moderate and moderately severe acne.
Further, to evaluate the added benefit of a second
treatment regimen combined with pharmaceutical acne
treatment in patients with inadequate initial response.
Materials and Methods: Patients with moderate and
moderately severe facial acne were recruited in this open‐
label, pilot study. A single treatment regimen consisted of
three weekly facial treatments with topically applied gold
microparticles and diode laser pulses. Outcome measures
were the proportion of patients with ≥40% improvement
in number of acne lesions (weighted lesion count [WLC])
at 12 weeks (single treatment regimen, primary outcome
measure), 24, and 36 weeks from baseline (two treatment
regimens), safety, and patient satisfaction.
Results: A total of 28 patients were enrolled in the study
(18 males, 10 females, 19 patients with moderate acne
severity, 9 with moderately severe, mean age: 19.8 years).
Twenty‐five patients underwent analysis for outcome
measures. After a single monotherapy treatment regimen,
76% patients (19/25) achieved ≥40% reduction in WLC
(mean WLC reduction: 63%; SD: 13%). Of the patients
undergoing two treatment regimens (n = 9 patients), 56%
experienced a reduction in acne lesion burden (WLC)
≥40% at 24 weeks and 89% 36 weeks post‐baseline. Mean
pain score was 4.0 (SD: 1.3), and transient erythema and
perifollicular edema were commonly noted after treat-
ment. Most patients (81%) were either “satisfied” or “very
satisfied” with the treatment.
Conclusion: Acne therapy based on selective photother-
molysis with gold microparticles shows promise and may be
used in treatment of moderate to moderately severe acne.
Key words: gold microparticles; selective photothermo-
lysis; acne vulgaris
© 2019 Wiley Periodicals, Inc.
INTRODUCTION
Acne vulgaris is the most common dermatologic disease
worldwide with significant psychosocial impact and risk
of scarring [1]. The pathogenesis is not fully clarified,
although it is widely accepted that follicular hyperker-
atinization, increased sebum production, follicular coloni-
zation by Cutibacterium acnes (former Propionibacterium
acnes), and release of inflammatory mediators into the
skin all play a key role [1–3].
A large number of acne treatments are available,
including benzoyl peroxide, antibiotics, and retinoids.
Being a multifactorial disease, combination therapy is
often recommended, and the treatment of choice depends
on acne severity and presence or absence of inflammatory
and/or non‐inflammatory acne lesions [4–6]. In order to
target the major mechanisms of the acne pathogenesis,
patients with more severe acne are typically prescribed
either systemic antibiotics in combination with a topical
agent or systemic isotretinoin [4]. Both treatment mod-
alities are associated with potential problems. With
antibiotics, there is a risk of developing resistant strains
of C. acnes and other bacteria [4,5], whereas isotretinoin
is teratogenic and can cause a number of adverse effects
maybe including depression [7,8]. Since the above‐men-
tioned therapies need to be administered daily, patient
adherence is mandatory and compliance issues especially
with topical treatments are not rare. It is therefore
Conflict of Interest Disclosures: All authors have completed
and submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest and have disclosed the following: Dr. C. Bay
and Dr. CSK Fuchs received research grants from Sebacia Inc. M.
Haedersdal received research grants from Sebacia Inc., Procter &
Gamble, Lutronic, Leo Pharma A/S, and Galderma A/S. Dr. HL
and Dr. MA have nothing to disclose.
* Correspondence to: Christine Sofie Krohn Fuchs, MD,
Department of Dermatology, Bispebjerg Hospital, University of
Copenhagen, Nielsine Nielsens Vej 17, DK‐2400 Copenhagen, NV,
Denmark. E‐mail: christine.sofie.krohn.fuchs.04@regionh.dk
Received 2 October 2018; revised 11 April 2019; Accepted 18
April 2019
Published online in Wiley Online Library
(wileyonlinelibrary.com).
DOI 10.1002/lsm.23099
2 ACNE TREATMENT WITH MICROPARTICLES AND OPTICAL PULSES
desirable for both patients and healthcare professionals to
consider in‐office treatments [9].
Targeting sebaceous glands by selective photothermoly-
sis has been of significant interest as a new, potential acne
therapy, but so far limited success has been achieved due to
low absorption of near‐infrared light by the pilosebaceous
unit and sebaceous glands [10–12]. Introducing light
absorbing exogenous chromophores through pore openings
and exposing them to light pulses, has been demonstrated
to partially overcome this issue [10–13], and the method
carries potential as an acne therapy [14–16]. Recently
spherical gold microparticles with strong plasmon reso-
nance absorption in the near‐infrared region have been
developed as light absorbing chromophores [17,18].
Studies involving massaging of gold microparticles
followed by exposure to optical pulses have demonstrated
that selective photothermolysis of pilosebaceous units can
be achieved with this combination [19]. Specifically, in
pre‐ and postauricular human skin, histology immedi-
ately post‐treatment showed local thermal injury in 84%
of infundibula and in 47% of superficial portions of the
sebaceous glands after a single laser session [19]. To be
noticed, sebaceous glands are situated more superficially
in pre‐ and postauricular skin, compared with central
facial skin.
In this study, we evaluated efficacy, safety, and patient
satisfaction of a single monotherapy treatment regimen
with gold microparticles and diode laser exposure in
patients with moderate and moderately severe acne.
Further, for patients with the inadequate initial response,
a second treatment regimen along with pharmaceutical
acne treatment was offered and the potential added
benefit was evaluated.
MATERIAL AND METHODS
The trial was a pilot, open‐label, one‐arm, multicenter
study conducted at two centers in Denmark and one in
Switzerland from February 2016 through December 2016.
The clinical trial was approved by the Danish Research
Ethics Committee (H‐15015260), Danish Medicines
Agency, the Danish Data Protection Agency and Swiss
Ministries of Health (Swissmedic ID: 2015‐MD‐0021).
Written consent was obtained from all participants. The
trial was registered at Clinicaltrials.gov (NCT02758041)
and conducted in accordance with the guidelines for Good
Clinical Practice and the Declaration of Helsinki.
Patients and Inclusion Criteria
Eligible patients were men and women 16–45 years of
age at baseline with a clinical diagnosis of facial acne
vulgaris with an Investigator’s Global Assessment (IGA)
of acne severity score of 3 (moderate) or 4 (moderately
severe), and with 20–75 inflammatory lesions on the
cheeks, forehead, and/or chin. Patients had to be in good
general health, willing to participate, able to give
informed consent, Fitzpatrick phototypes I–III, and
comply with protocol requirements. Exclusion criteria
included pregnancy, history of keloid formation, tattoos in
the treatment area, and drug‐induced acne. Prior to
treatment, patients had to comply with the following
wash‐out periods of other acne medications; isotretinoin
for 6 months, other systemic medications for 4 weeks,
topical retinoids for 2 weeks, over‐the‐counter products
for 1 week, and any laser treatment for 8 weeks.
Study Design
Patients attended five study visits, Figure 1 sum-
marizes the study design. At baseline, a non‐blinded
investigator counted on site the number of facial inflam-
matory and non‐inflammatory acne lesions. Since proper
identification of inflammatory acne lesions requires
palpation of the lesions, photos were not used during the
counting process. The monotherapy treatment regimen
consisted of three treatments (at baseline, week 1, and
week 2). At a 12‐week follow‐up visit the number of
inflammatory and non‐inflammatory acne lesions was
counted and the change in inflammatory lesion count
(ILC) from baseline to week 12 was calculated. Based on
response to treatment and reduction in ILC, patients were
categorized as either responders or sub‐responders.
Responders were defined as patients with a ≥40%
improvement in ILC and received no further treatment.
Sub‐responders were identified as patients with <40%
improvement in ILC relative to baseline and were offered
an additional treatment regimen as well as adjuvant acne
therapy if deemed necessary. The second treatment
regimen included three treatment days (at week 12, week
13, and week 14) and two follow‐up visits at weeks 24 and
36 post‐baseline. See Figure 1 for details.
Gold Microparticles and Diode Laser Treatment
Each treatment session included facial washing, then
massaging 3 ml of a CE marked gold microparticle
suspension SEB‐250 (Sebacia, Inc., Duluth, GA) into the
patient’s facial skin, keeping the skin under the massager
constantly wet and completing two to three passes around
the face for 10 minutes [19]. Superficial suspension was
wiped with wet gauze to prevent superficial epidermal
overheating, and the skin was exposed to optical pulses
from an 800 nm diode laser (LightSheer; Lumenis Inc.,
Santa Clara, CA or Vectus Laser; Cynosure, Westford,
MA). The diode laser had either a 9 × 9 mm or a
12 × 12 mm square spot with pulse duration of 30 ms
and radiant exposures in the range of 25–35 J/cm2 (mean:
33.1 J/cm2, SD: 2.5 J/cm2). We performed thermal relaxa-
tion calculations by modeling the sebaceous gland as a
sphere to choose an optimal pulse duration. According to
the theory of selective photothermolysis, pulse duration
should be shorter than the thermal relaxation time (TRT)
of the target to minimize heat diffusion outside the
targeted volume [13,20]. Based on the formu-
la, TRT=d2/(27 × thermal diffusivity) , where d is the
diameter of the target and a thermal diffusivity of
0.0013 cm2/s, a pulse duration of 30 ms was chosen to
target sebaceous glands of ≥0.32 mm diameter, consider-
ing that sebaceous glands have a substantial uniform
optical absorption. This pulse duration was chosen as a
 FUCHS ET AL. 3

Fig. 1. Study flow chart. Each patient had one treatment regimen with treatments at baseline,
week 1, and week 2. At follow‐up, week 12, number of inflammatory acne lesions were counted
and the change in inflammatory lesion count (ILC) was calculated. Based on the change in ILC,
patients were categorized as either responders and offered no further treatment, or sub‐
responders and offered a second treatment regimen. The second treatment regimen consisted of
three additional treatments (weeks 12, 13, and 14) and follow‐up visits weeks 24 and 36 post‐
baseline. [Color figure can be viewed at wileyonlinelibrary.com]
4 ACNE TREATMENT WITH MICROPARTICLES AND OPTICAL PULSES
compromise to target small sebaceous glands (e.g.,
0.32–0.50 mm) and possibly also larger glands (0.50–
1.0 mm) per the theory of selective photothermoly-
sis [13,20]. Laser pulses were delivered in two passes
with a target overlap of 10% to all facial areas except nose
and upper lip, typically with a total of ≥450 pulses per
treatment session. Contact cooling was provided by the
laser’s actively cooled tip.
Outcome Measures
The counts of inflammatory and non‐inflammatory acne
lesions were converted to weighted lesion count (WLC,
adapted after Hongcharu et al. [21]), at weeks 12, 24, and
36 post‐baseline.
The primary outcome measure was the proportion of
patients with ≥40% improvement in WLC after a single
treatment regimen at 12‐week follow‐up visit. WLC was
calculated as a weighted sum of comedones, papules,
pustules, and nodules. Following weights were used:
open and closed comedone 0.5; papule 1; pustule 2; and
nodule 3.
Secondary outcome measures were the proportion of sub‐
responders with ≥40% improvement in WLC after two
treatment regimens evaluated at weeks 24 and 36, safety
evaluated as pain and local skin reactions (LSRs), and
patient satisfaction. Pain intensity was rated on a numeric
rating scale (NRS) from 0 to 10 (ranging from 0: no pain to
10: severe pain) and LSRs were evaluated in all patients
immediately after treatment. Patient satisfaction was
evaluated at weeks 12 and 36. Patients were asked to rate
the treatment results on a categorical scale ranging from 1
to 5 (1, very satisfied; 2, somewhat satisfied; 3, neither
satisfied nor dissatisfied; 4, somewhat dissatisfied; 5, very
dissatisfied). All clinical evaluations were performed by the
same trained physician in each center.
Statistics
Despite being a pilot study, a relatively large sample
size of 28 patients was selected to reliably assess efficacy
and to confirm that LSRs and adverse events remained at
an acceptable level. Data are presented as descriptive
statistics with before‐after comparisons. Efficacy data
(change in WLC at weeks 12, 24, and 36) were normally
distributed and are presented as proportions with means
and standard deviations. Safety parameters (pain) pre-
sented as means and standard deviations. Paired t test
was performed to compare WLC at baseline and 12‐week
follow‐up. Tests were two‐sided. A level of P < 0.05 was
considered statistically significant. SPSS software (ver-
sion 22.0; IBM Corporation, Armonk, NY) was used for
the calculations.
RESULTS
A total of 28 patients (18 males, 10 females, age
range of 16–31, mean: 19.8 years) were included in the
study. At baseline, 19 patients had moderate acne (IGA,
3), 9 moderately severe (IGA, 4). Patients were enrolled
as follows: Copenhagen, Denmark, 20 patients;
Aalborg, Denmark, 2 patients; Geneva, Switzerland, 6
patients. First treatment regimen was complete by 25
patients (89%), whereas three patients withdrew pre-
maturely (two patients started other acne medication
before week 12, one was lost to follow‐up). See Figure 1
for details.
Efficacy
At 12‐week follow‐up, 19 of 25 patients (76%) experi-
enced a decrease in WLC of ≥40% (mean reduction: 63%,
SD: 13%). Treatment efficacy varied, ranging from 3% to
89% clearance in WLC. The variation in treatment
efficacy is illustrated in Figure 2 and the treatment
response for two patients is illustrated in Figures 3 and 4.
IGA distributions at baseline, 12 weeks, and 24 weeks are
shown in Figure 5. A dramatic reduction in the fraction of
patients with higher IGA scores of 3 and 4 is seen,
especially at 24 weeks. Overall, there was a significant
decrease in WLC at week 12 compared with baseline
(P = 6.13 × 10−7).
Ten patients were categorized as sub‐responders of
whom nine received a second treatment regimen and were
offered adjuvant acne therapy as per clinical indication.
At 24 weeks follow‐up five patients (56%) had a reduction
in WLC ≥ 40%, (mean reduction: 57%; SD: 13%). Adjuvant
acne therapy was introduced at week 24, where six sub‐
responders were prescribed facial topical and/or oral acne
medication (topical adapalene and benzoyl peroxide,
topical and systemic antibiotics, and isotretinoin). At 36‐
week follow‐up 89% of patients had a WLC reduction of
≥40% (mean WLC decrease: 69%, SD: 18%).
Sub‐responders and responders were comparable at
baseline in terms of age (mean: 20.4 years vs. 19.2 years,
P = 0.42). Regarding IGA, a slightly higher fraction of sub‐
responders had IGA4 (40%) compared with responders
(27%), however not significant (P = 0.46). In terms of
gender, there was a tendency of a higher proportion of
men in the sub‐responder group compared to the
responder group (80% vs. 47%, respectively, P = 0.09).
Fig. 2. Distribution of treatment efficacy measured in change in
weighted lesion count week 12 post‐baseline. Illustration of
efficacy distribution in all 25 patients at week 12 post‐baseline.
Note that no patients had 0% or an increase in weighted lesion
count. [Color figure can be viewed at wileyonlinelibrary.com]
 FUCHS ET AL. 5

Fig. 3. Photographs of a patient at baseline and 12 weeks post‐baseline. (a)–(c) Baseline images
of an acne patient with moderate acne (Investigators Global Assessment scale, 3). (d)–(f) 12
weeks post‐baseline images. After a single treatment regimen, the patient had a reduction in
weighted lesion count at 71% and an Investigators Global Assessment scale of 2. [Color figure can
be viewed at wileyonlinelibrary.com]

Safety
Mean pain score during treatment was 4.0 (SD: 1.3).
LSRs included erythema and perifollicular edema and
were commonly observed but resolved within hours. In
three patients, superficial epidermal erosions were ob-
served after laser treatment. Small 2 × 2 mm dark
macules were observed in treatment areas in three
patients, either during or after treatment procedures,
and dermoscopy revealed nonspecific homogenous pig-
mentation. Clinically, the dark macules lightened sig-
nificantly over time. Two patients decided to have the
remnants removed by punch biopsies whereas a third
opted for no intervention.
Patient Satisfaction
At 12‐week follow‐up visit 81% of all patients reported
that they were either “very satisfied” or “somewhat
satisfied” with the treatment. For sub‐responders 78%
(seven of nine patients) responded “very satisfied” or
“somewhat satisfied” with the treatment at 36‐week
follow‐up visit.
DISCUSSION
This is the first clinical, multicenter, pilot study that
investigates efficacy and safety of monotherapy with gold
microparticles and diode laser pulses in patients with
moderate and moderately severe acne. It is also the first
study to investigate the potential added benefit from a
second treatment regimen in patients with the inade-
quate initial response, defined as <40% reduction in ILC.
We found that 76% of patients achieved a WLC decrease
of ≥40% after one treatment regimen, with a mean
reduction of non‐inflammatory and inflammatory acne
lesions at 63%. In sub‐responders receiving a second
treatment regimen, 56% had a decrease of ≥40% in their
WLC after 24 weeks. It should be noted that none of the
sub‐responders received any concomitant acne medica-
tion before week 24, hence the decrease in WLC can be
attributed to the monotherapy alone. Thirty‐six weeks
after the final treatment, 89% exhibited an improvement
in WLC of ≥40%. Amongst the 89%, 67% (six of nine
patients) received adjuvant acne therapy. The results
indicate that a single monotherapy treatment regimen
was efficacious in reducing acne lesions, and that
6 ACNE TREATMENT WITH MICROPARTICLES AND OPTICAL PULSES

Fig. 4. A good responding patient before and after a single treatment regimen. (a)–(c) Baseline
images of a patient with moderate acne (Investigators Global Assessment scale, 3). (d)–(f) Images
12 weeks post‐baseline. An 80% reduction in weighted lesion count was observed in this patient
after a single treatment regimen. [Color figure can be viewed at wileyonlinelibrary.com]

patients may benefit from a second treatment regimen,

Fig. 5. Investigators global assessment score distribution
amongst patients from baseline to 24 weeks post‐baseline.
Distribution of Investigators Global Assessment (IGA) scores
between patients illustrated at baseline, 12 and 24 weeks post‐
baseline. Baseline and 12 weeks post‐baseline include all 25
patients, week 24 include the sub‐responders receiving a second
treatment regimen. Week 36 data are not included in the graph,
as six of nine sub‐responders received concomitant acne
treatment after week 24.
even more so when used in conjunction with adjuvant
acne medication. Additionally, treatment had long‐term
effect on acne severity, supporting previous study’s
results [19].
In the current study, microparticles acting as chromo-
phores for near‐infrared light are delivered to pore
openings, followed by exposure of near‐infrared
light [19,22]. The putative mechanism of action is that
the pilosebaceous unit with infundibulum and sebaceous
gland is heated due to light absorption by gold micro-
particles, leading to localized thermal damage which
vaporizes follicular content and injures the sebaceous
glands resulting in a decrease in sebum production.
Collectively, these changes retard the formation of acne
lesions resulting in improved lesion counts over
time [15,19,23]. This mechanism is considered to be
somewhat similar to that of isotretinoin, which also has
an impact on sebum production [24].
The treatment efficacy after a single treatment regimen
corresponds well to previous studies, investigating gold
microparticles and diode laser pulses. In a randomized,
 FUCHS ET AL.
controlled trial, 34% reduction in facial acne ILC was
shown at 12 weeks, compared with the control population
exposing a spontaneous reduction in ILC of 16%[19]. In the
present study, we found that the mean ILC reduction
amongst all patients was 45%, and further that 60% had a
reduction in ILC of ≥40%. In another trial, a reduction of
49% of inflammatory lesions was observed compared with
a 22% reduction in the placebo group, at week 12 [19]. In
contrast to the two previous studies, we applied WLC as
the primary outcome measure for efficacy. WLC includes
both inflammatory and non‐inflammatory acne lesions,
and thus provides a more comprehensive view on the
patient's skin status. However, ILC was used as the
parameter for retreatment since the majority of acne scars
originate from inflammatory‐ and post‐inflammatory le-
sions [25–27]. Thus, a second treatment regimen was
offered to patients with <40% improvement in their ILC 12
weeks post‐baseline to primarily improve their overall skin
status but also to prevent the risk of future acne scars.
Overall, the current treatment was tolerated well and with
a safety profile similar to other laser skin treatments,
including hair removal procedures [28–30]. Adverse events
included mild to moderate pain, transient erythema, and
perifollicular edema, all resolving within hours [28–30].
Hence, compared with potential adverse events seen with
isotretinoin, the treatment is safe to use [31]. The minor
epidermal erosions observed during laser treatment might
be due to increased heat deposition to the skin, either due
to insufficient cooling, bulk heating, or inadequate removal
of residual gold microparticles from the skin surface [32]
which can potentially be avoided by increased awareness to
treatment procedures. Dark macules were observed in
three patients, which is believed to stem from a ruptured
pustule. The rupture might lead to excessive deposition of
gold microparticles in the skin, followed by incorporation
after laser exposure. Future gold microparticle treatment
procedures are advised to empty sub‐epidermal collections
of microparticles and restrain from laser treatment if
localized discoloration evolves.
Strengths of this study comprise the strict and long
wash‐out periods of previous acne medications before
enrollment in the study. This enabled investigation of the
novel acne treatment in patients as a pure monotherapy,
without overlapping effects from current or previous acne
medication and following preventing false‐positive effi-
cacy results. The study design was stringent with respect
to concomitant acne medication within the first 12 weeks
of the study period and provides reliable estimates of the
true efficacy of selective photothermolysis with gold
microparticles as exogenous chromophores for treatment
of patients with moderate and moderately severe acne.
Future studies may investigate more “real world”
approaches in which acne therapeutics are not washed
out prior to gold microparticle treatment to assess if
better pore access improves outcomes, or is combined with
approved acne therapeutics to achieve the goal of
complete acne resolution.
The major limitations of this study were the uncon-
trolled study design and the relatively small number of
7
patients. Moreover, it was a drawback that 3 of 28
patients were lost to follow‐up and therefore not included
in the efficacy analysis. Coming investigations could focus
on controlled trials to better reflect the benefit of gold
microparticle treatment compared with other acne treat-
ments, as well as future split face crossover studies could
clarify the true efficacy of laser alone compared with laser
and gold microparticles. In the study, a fixed pulse
duration of 30 ms was used. This could potentially have
spared smaller (<0.32 mm size) sebaceous glands accord-
ing to the theory of selective photothermolysis, whereas
larger glands most likely would undergo selective photo-
thermolysis during the same exposure [13,20]. Exploring
other pulse durations could be a future avenue of
research.
In conclusion, a single regimen of thermal treatment
using gold microparticles led to a reduction in acne
burden for a large part of the included patients, with
high patient satisfaction, and tolerable side effects. For
patients with an initial inadequate response, a second
treatment regimen appeared safe and led to a reduction in
acne burden, both with and without adjuvant acne
therapy.
ACKNOWLEDGMENT
This trial was initiated and sponsored by Sebacia Inc.,
the manufacturer of SEB‐250 microparticle suspension.
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