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Lasers Med Sci

DOI 10.1007/s10103-015-1850-2

ORIGINAL ARTICLE

High versus moderate energy use of bipolar fractional


radiofrequency in the treatment of acne scars: a split-face
double-blinded randomized control trial pilot study
Weeranut Phothong 1 & Rungsima Wanitphakdeedecha 1 & Angkana Sathaworawong 1 &
Woraphong Manuskiatti 1

Received: 6 July 2015 / Accepted: 8 December 2015


# Springer-Verlag London 2015

Abstract Bipolar fractional radiofrequency (FRF) device erythema, swelling, and crusting were also recorded. Thirty
was firstly FDA-approved for treating atrophic acne scar in subjects completed the study with full 4-treatment course. The
2008 through the process of dermal coagulation and minimal mean GASS of high energy side and moderate energy side
epidermal ablation. The average energy at 60 mJ/pin was was significantly reduced at 1-, 3-, and 6-month follow-up
widely used to treat atrophic acne scars. However, the higher visits. At 1 month follow-visit, high energy side demonstrated
energy was delivered, the deeper ablation and coagulation significant improvement compared with moderate energy side
were found. At present, the new generation of a device with (p = 0.03). Postinflammatory hyperpigmentation (PIH) devel-
bipolar FRF technology with electrode-pin tip was developed oped in 21/120 sessions in high energy side (17.5 %) and 16/
to maximize ability to deliver energy up to 100 mJ/pin. The 120 sessions in moderate energy side (13.3 %). Pain score and
objective of the study was to explore and compare the efficacy the duration of erythema after treatments were significant
of utilizing high energy (100 mJ/pin) and moderate energy higher on the side that was treated with high energy. Bipolar
(60 mJ/pin) of bipolar fractional radiofrequency in treatment FRF device was safe and effective in the treatment of atrophic
of atrophic acne scar in Asians. This is a split-face, double- acne scars in Asians. High energy setting demonstrated sig-
blinded, randomized control trial, pilot study by using parallel nificant higher efficacy at 1 month follow-visit. However, the
group design technique. Thirty healthy subjects with efficacy of both energy settings was comparable at 3- and 6-
Fitzpatrick skin phototype III-IV diagnosed as atrophic acne month follow-up. In addition, side effects were significantly
scares were enrolled. All subjects received four monthly ses- more intense on the side treated with high energy.
sions of bipolar FRF treatment. Left and right facial sides of
individual patients were randomly assigned for different ener- Keywords Acne scars . Bipolar fractional radiofrequency .
gy (high energy at 100 mJ/pin versus moderate energy at Energy
60 mJ/pin). Acne scars improvement was blinded graded by
dermatologist using global acne scarring score (GASS) which
was subjectively evaluated at baseline, 1-, 3-, and 6-month Introduction
follow-up. Objective scar analysis was also done using
UVA-light video camera to measure scar volume, skin Acne scar is a burden of disfigurement following a common
smoothness, and wrinkle at baseline, 3-, and 6-month fol- dermatologic condition. Based on histopathology and patho-
low-up after the last treatment. Side effects including pain, physiology of acne scars, collagen fibers and elastin were
found to be diminished and deposited irregularly either in
whole dermis or middle to deep dermis in 74 % of scars [1,
* Rungsima Wanitphakdeedecha 2]. As a result, many dermatologic modalities have been de-
rungsima.wan@mahidol.ac.th veloped toward the goal of re-collagenosis and re-elastosis.
Laser, both ablative and non-ablative, was used with either
1
Department of Dermatology, Faculty of Medicine Siriraj Hospital,
water or hemoglobin/melanin as a chromophore targeting
Mahidol University, 2 Pran-nok Road, Bangkoknoi, Bangkok 10700, ground substance, blood vessels, and adnexal structures,
Thailand resulting in collagen stimulation [3]. Ablative lasers were
Lasers Med Sci

Table 1 Technical parameters of


high versus moderate energy Technical parameters High energy Moderate energy
settings
Energy (mJ/pin) 100 mJ/pin 60 mJ/pin
Power (watts) for 200 ohms skin resistance 200 W 200 W
RF frequency (hertz) 1 MHz 1 MHz
RF pulse duration (seconds) 20 ms for 200 ohms 32 ms for 200 ohms

preferred to non-ablative ones due to their superior efficacies. and coagulation and greater mitigation of the atrophic scar-
However, the high incidence of postinflammatory hyperpig- ring. However, this hypothesis remained to be tested and
mentation (PIH) followed by ablative technology were found therefore we undertook this study.
several studies, especially in Asian population ranging from The primary objective of this study was to compare the
45.5 to 90 % [4–7]. efficacy of utilizing high energy (100 mJ/pin) and moderate
Radiofrequency (RF), a non-laser source of energy, was energy (60 mJ/pin) of bipolar FRF in treatment of atrophic
then developed to treat atrophic acne scars. Instead of acne scar in Asians. In addition, adverse reactions such as pain
chromophore-dependent mechanism of action, radiofrequen- and PIH were also studied as secondary objective.
cy exerts in impedance-specific fashion (the inherit resistance
property of each tissue) [8]. In bipolar fractional radiofrequen-
cy device (FRF), arrays of negative and positive electrodes are Methods
orderly placed on the contact tip in order to generate multiple
waves at radiofrequency [9]. When meeting the high imped- This is a split-face double-blinded randomized control trial
ance tissue, this electromagnetic energy creates a bulk of heat pilot study. Based on statistical calculation with 80 % power,
through either microneedles or multi-electrode pins resulting 30 healthy subjects enrolled at Siriraj Skin Laser Center,
in coagulation of the dermis with minor epidermal ablation Siriraj Hospital. Patients were eligible for entry the study if
[10]. The higher energy of FRF is related to both deeper ab- they were 18–60 years old, Fitzpatrick skin type III-IV, and
lation and deeper dermal depth of coagulation [11]. The stan- had mild to moderate atrophic acne scars without concurrent
dard energy for bipolar FRF has been 60 mJ/pin for the treat- hypertrophic scar. We excluded patients with specific facial
ment of acne scars. At present, the new generation MatrixTM conditions; active acne, current infection, and photosensitive
RF (Syneron Medical Ltd., Yokneam Illit Israel), a device dermatoses. Patients must have neither laser/radiofrequency
with bipolar FRF technology with electrode-pin tip, was de- treatment within 3 months nor history of alpha hydroxyl
veloped to maximize ability to deliver energy up to 100 mJ/ acid/topical retinoid use within 6 months. Other exclusion
pin. On the theory that more energy means deeper ablation criteria were current smoking, pregnancy, and lactation.

Fig. 1 The study flow diagram


Lasers Med Sci

Table 2 Subjective evaluation of


acne scar improvement between Global Acne Scarring High energy Moderate energy p value 95 % CI
high energy and moderate energy Scale (GASS) (100/mJ/pin) (60 mJ/pin)
sides (Mean ± SD) (Mean ± SD)

Baseline 4.9 ± 3.0 5.4 ± 2.8 0.11 −1.3 to 0.1


1-month follow-up 4.0 ± 2.8 4.6 ± 2.7 0.03 −1.1 to −0.1
3-month follow-up 3.8 ± 2.5 4.1 ± 2.5 0.16 −0.7 to 0.1
6-month follow-up 3.1 ± 2.5 3.3 ± 2.5 0.34 −0.5 to 0.2
p value <0.001 <0.001

All subjects received four monthly sessions of bipolar In addition, acne scars analysis was objectively done by
FRF for the treatment of atrophic acne scars (eMatrixTM; using UVA-light video camera (VisioScan® 186 VC 98,
Syneron Medical Ltd., Yokneam Illit, Israel). Before each Courage-Khazaka, Köln, Germany) with analysis software
session, topical 2.5 % lidocaine and 2.5 % prilocaine (Surface Evaluation of the Living Skin; SELS, Courage-
(RACSER cream; Zenta Healthcare, India) were applied Khazaka). Concerned parameters included scar volume, skin
1 h prior to treatment. Left and right facial sides of indi- smoothness, and wrinkle. The measurement was performed
vidual patients were randomly assigned for different ener- on the same selected area by the same technician at baseline,
gy (moderate energy of 60 mJ/pin or high energy of 1-, 3-, and 6-month follow-up after the last treatment. PIH was
100 mJ/pin) using block randomization. The technical pa- also graded as the followings; 0 = none, 1 = mild, 2 = normal,
rameters of these two energy settings were described in and 3 = severe. The pain score was rated by using visual analog
Table 1. At each treatment session, two passes were per- scale (VAS). Other side effects including erythema, swelling,
formed with assigned energy for each facial side in non- and crusting were also recorded.
overlap fashion all over the face. Then, additional up to GASS of two energy levels was compared and analyzed
three passes were done on the area with deep acne scars, using paired T test while GASS of each energy level at differ-
depending on severity of scars and response from patients. ent follow-up period was analyzed by repeated measure
After the treatment, patients were instructed to use petro- ANOVA. SELS parameters and post-treatment reaction pa-
latum ointment to apply on the treatment area four times a rameters were compared using paired T test. Cumulative
day for 7 days. Sun avoidance and protection were also PIH scale was compared using Wilcoxon signed-rank test.
emphasized. All statistical analysis was performed with SPSS statistical
All subjects and evaluators were blinded for energy level analysis software version 18.0 (SPSS Inc., Chicago, IL, USA).
used. Global acne scarring score (GASS) [12] which assessed This study was approved by the Siriraj Institutional Review
both morphological and quantity aspects of scarring was sub- Board (SIRB), Faculty of Medicine Siriraj Hospital’s human
jectively graded by a dermatologist as a primary outcome at research review committee, Mahidol University, and
baseline, 1-week, 1-, 3-, and 6-month follow-up visit. All dig- conformed to the guidelines of the 1975 Declaration of
ital photographs used for evaluation were performed with a Helsinki. Written informed consent was obtained from all
facial photo fixture using a Canon PowerShot G10 stand-off study subjects. In addition, this study has been registered in
camera (OMNIA ImagingSystem, Canfield Scientific, Inc, Thai Clinical Trials Registry (TCTR). The TCTR identifica-
Fairfield, NJ). tion of this study was TCTR20150629004.

Fig. 2 Clinical improvement of


acne scars after bipolar FRF
treatments with high and
moderate energy
Lasers Med Sci

Fig. 3 Clinical improvement was


demonstrated in the photographs
taken with UVA-light video
camera. The improvement could
be seen over time with both high
and moderate energy used

Results Objective evaluation with various parameters (scali-


ness, smoothness, roughness, wrinkles, surface, and vol-
Thirty subjects completed the study with full 4- ume) by using UVA-light video camera was analyzed by
treatment course. Two subjects missed the 6-month fol- SLES software. Only Wrinkles parameter demonstrated
low-up visit. Intention to treat analysis with last- statistically improvement over time in both high energy
observation-carried-forward method was then applied. and moderate energy sides (p = 0.001 and p = 0.039, re-
The study flow diagram was shown in Fig. 1. Of all spectively). However, there was no statistically signifi-
30 subjects, there were 17 male (56.7 %) and 13 female cant difference found between two groups of different
(43.3 %) patients with mean age of 31.1 years and energy (p = 0.590) (Fig. 3).
standard deviation of 7.6 years. Most of the subjects PIH developed in 21/120 sessions in high energy side
had Fitzpatrick skin type IV (73.3 %), followed by type (17.5 %) and 16/120 sessions in moderate energy side
V and III which were 23.3 and 3.3 %, respectively. (13.3 %). Cumulative PIH scales of both high and mod-
Median of acne scar duration was 8 years with inter- erate energy side were not statistically significant differ-
quartile range of 3.8–10.5 years. ent (p = 0.142). Most of PIH were mild to moderate in
Subjective evaluation of acne scars improvement intensity and spontaneous resolved within 4 weeks. The
using mean GASS was shown in Table 2. Baseline mean pain score on the side that was treated with high
GASS of high energy and moderate energy sides was energy was significantly higher than the side that was
not statistically significant difference (4.9 vs. 5.4, treated with moderate energy (5.0 vs. 4.5, p = 0.001). In
p = 0.11, mean difference = −0.6). The mean GASS of addition, erythema after bipolar FRF with high energy
high energy side and moderate energy side was signifi- was lasted longer when comparing to moderate energy
cantly reduced at 1-, 3-, and 6-month follow-up visits (3.6 vs. 3.4, p = 0.04, respectively). Other side effects
(p < 0.001 and p < 0.001, respectively). Significant differ- found in this study were also demonstrated in Table 3.
ence of GASS between two energy levels was found at
1-month follow-up visit (p = 0.03, 95 % CI −1.1 to
−0.06). We follow up subjects at 3 and 6 months after Discussion
the last treatment and found no significant difference in
GASS (p = 0.16 and 0.34, respectively). The clinical im- Radiofrequency (RF) technology is classified as unipo-
provement of acne scars was shown in Fig. 2. lar, bipolar, or multipolar depending on the number of

Table 3 Side effects of bipolar


FRF treatments Side effects High energy (100/mJ/pin) Moderate energy (60 mJ/pin) p value
(Mean ± SD) (Mean ± SD)

Pain (VAS) 5.0 ± 1.6 4.5 ± 1.7 0.001*


Erythema (days) 3.6 ± 1.9 3.4 ± 2.0 0.040*
Swelling (days) 1.9 ± 1.2 1.8 ± 1.3 0.230
Crusting (days) 6.0 ± 2.4 6.1 ± 2.6 0.630

* p < 0.05
Lasers Med Sci

electrodes used with additional modalities including setting which might be a result of bigger ablative col-
FRF, sublative RF, phase-controlled RF, and combina- umn. However, the collagen formation occurred gradu-
tion RF with light, massage, or pulsed electromagnetic ally and later so the longer period of follow-up, the
fields (PEMFs) [13]. The clinical efficacy of using FRF lesser difference of scar appearance was found.
in the treatment of acne scars in Asians has been shown Higher energy level employed in FRF treatment was
in several studies [14, 15]. significantly related to the increased pain and accumulative
Many studies were conducted to evaluate efficacy of RF in heating sensation. In our study, subjects rated higher pain
the treatment of acne scar. Most of them reported 25–75 % on the high energy side and this was statistically signifi-
clinical improvement. Total number of sessions ranged from 2 cant (p ≤ 0.05). This uncomfortable experience might pre-
to 4. Gold and colleagues [16] good to excellent cosmetic vent patients from participation in the following sessions.
result in 73 % of subjects after four bipolar FRF treatments In the study of Yeung et al., 12.5 % of participants with-
at 32–56 mJ/pin at monthly interval. drawn from the study due to significant pain during the
Since bipolar FRF at higher energy causes more of procedure [22]. Higher energy setting was related to lon-
epidermal ablation and deeper coagulation, most studies ger erythematous appearance (p = 0.04). However, when
conducted in darker Fitzpatrick skin type participants 95 % CI (0.1–0.3) was taken into account, the difference
were limited the energy used to lower or moderate level could be estimated as 2–7 h which might not significantly
in order to avoid PIH. To the best of our knowledge, affect subject’s daily activities.
this study was the first to explore the use of bipolar Our limitation included different number of passes in
FRF at high energy up to 100 mJ/pin in Asians. each patient which depended on the performer’s opin-
However, there was no statistically significant difference ion. However, every patient received treatments from
in cumulative PIH scale found between high and mod- the same dermatologist; this result should be reproduc-
erate energy side (p = 0.142). But, PIH incidence in this ible. In our study, subjects rated higher pain on the high
study of high and moderate energy (17.5 and 13.3 %, energy side and this was statistically significant (p = 0.001).
respectively) was higher than other study in patients This uncomfortable experience might prevent patients from
with Fitzpatrick skin type III-IV [17]. This might result participation in the following sessions.
from our exclusion criteria of history and current uses In summary, this study demonstrated that bipolar FRF
of retinoid and/or bleaching agents while previous study device was safe and effective in the treatment of atro-
included them. phic acne scars in Asians. High energy setting demon-
Apart from the improvement of acne scar, objective strated significant higher efficacy at 1 month after treat-
evaluation by using UVA-light video camera and SLES ment when compared with moderate energy setting.
software demonstrated the improvement of wrinkles. However, pain was significantly more intense on the
Both high and moderate energy side demonstrated the side treated with high energy. Therefore, risks and ben-
significant improvement on wrinkle at 6-month follow- efits must be taken into account prior to changing any
up visit (p = 0.001 and p = 0.039, respectively) without treatment parameters.
any significant difference of improvement between these
two groups. This finding supported the benefit of reju-
venation by FRF in previous studies [18].
In addition, this present study demonstrated the con- Acknowledgment This research project is supported by Faculty of
Medicine Siriraj Hospital, Mahidol University. The authors wish to thank
tinued clinical improvement of acne scars over time af-
Ms. Phassara Klamsawat and Ms. Phonsuk Yamlexnoi for their assis-
ter bipolar FRF treatment when using either 100 or tances in recruiting subjects and managing the database.
60 mJ/pin (Table 2, Fig. 3). This finding was consistent
with the previous studies using ablative fractional Author contributions Dr. Manuskiatti had full access to all of the data
in the study and takes responsibility for the integrity of data and the
carbon-dioxide laser, ablative fractional erbium:YAG la-
accuracy of the data analysis.
ser, and fractional RF microneedle system [19, 20]. The Study concept and design: Dr. Manuskiatti
authors also reported the improvement of acne scars up Acquistition of data: Drs. Phothong and Sathaworawong
until 6 months after the last treatment as the replace- Analysis and interpretation of data: Drs. Phothong, Sathaworawong,
and Wanitphakdeedecha
ment of dermal tissue with newly formed collagen per-
Drafting of the manuscript: Dr. Phothong
sistently progressed [21]. Critical revision of the manuscript for important intellectual content:
At 1 month after the last treatment, high energy Drs. Wanitphakdeedecha and Manuskiatti
treated side demonstrated significant higher GASS Statistical analysis: Drs. Phothong and Sathaworawong
Obtained funding: none
while this difference was not found at 3 and 6 months
Administrative, technical, or material support: Drs.
after the last treatment. The initial effect of wound Wanitphakdeedecha and Manuskiatti
healing process was more obvious in high energy Study supervision: Dr. Manuskiatti
Lasers Med Sci

Compliance with ethical standards This study was approved by the 9. Lolis MS, Goldburg DJ (2012) Radiofrequency in cosmetic derma-
Siriraj Institutional Review Board (SIRB), Faculty of Medicine Siriraj tology: a review. Dermatol Surg 38(11):1765–1776
Hospital’s human research review committee, Mahidol University, and 10. Hruza G, Taub AF, Collier SL, Mulholland SR (2009) Skin rejuve-
conformed to the guidelines of the 1975 Declaration of Helsinki. Written nation and wrinkle reduction using a fractional radiofrequency sys-
informed consent was obtained from all study subjects. In addition, this tem. J Drugs Dermatol 83:259–65
study has been registered in Thai Clinical Trials Registry (TCTR). The 11. Sadick NS, Sato M, Palmisano D, Frank I, Cohen H, Harth Y
TCTR identification of this study was TCTR20150629004. (2011) In vivo animal histology and clinical evaluation of multi-
source fractional radiofrequency skin resurfacing (FSR) applicator.
Conflict of interest The authors declare that they have no competing J Cosmet Laser Ther 13(5):204–9
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global scarring grading system. J Cosmet Dermatol 5(1):48–52
13. Krueger N, Sadick NS (2013) New-generation radiofrequency tech-
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14. Kim JE, Lee HW, Kim JK, Moon SH, Ko JY, Lee MW et al (2014)
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