Comparison Study of Fractional Carbon Dioxide Laser

Resurfacing Using Different Fluences and Densities for Acne

Scars in Asians: A Randomized Split-Face Trial
XING-HUA YUAN, MD,*† SHU-XIA ZHONG, MD,* AND SHAN-SHAN LI, MD, PHD*

BACKGROUND Ablative 10,600-nm carbon dioxide (CO2) fractional laser treatments have shown favorable
outcomes for atrophic acne scars.
OBJECTIVE To compare the efficacy and complications of fractional CO2 laser treatments with different
fluences and densities for acne scars.
METHODS Twenty patients were treated using a single session of fractional CO2 laser in Deep FX mode. In
Group A (n = 10), half of the face was treated with 20 mJ, density 10% and the other half with 20 mJ,
density 20%. In Group B (n = 10), half of the face was treated with 10 mJ, density 10% and the other half
with 20 mJ, density 10%. Patients were evaluated at baseline and 3 days, 1 week, 1 month, and 3 months
after the procedure.
RESULTS There was no significant difference in efficacy between different laser settings within the groups,
although adverse effects were more evident in patients treated with higher densities or fluences.
CONCLUSION Factional CO2 laser treatment using the Deep FX mode may provide a significant efficacy with
lower fluence and density with fewer complications than with higher energies for acne scars.
The authors have indicated no significant interest with commercial supporters.

A trophic scars are dermal depressions com-

monly caused by the destruction of collagen
after inflammatory acne. Conventional ablative laser
therapy with carbon dioxide (CO2) or erbium-doped
yttrium aluminum garnet laser is the criterion
standard for treatment of atrophic scars,1,2 although
its usage is frequently limited in Asian patients
because of the lengthy recovery time and high risk of
adverse effects, including infection, edema, and
postinflammatory hyperpigmentation (PIH).2,3 To
address these limitations, newer modalities employ-
ing the principle of fractional photothermolysis (FP)
have been developed.4,5 These laser treatments
create microscopic treatment zones (MTZs) sur-
rounded by undamaged tissues and hence result in
shorter recovery time and fewer adverse effects than
traditional ablative laser resurfacing. Recent studies
have shown favorable outcomes for atrophic acne
scars with an ablative 10,600-nm CO2 fractional
laser system (CO2 FS).6,7 A CO2 FS with two
treatment modes (Active FX and Deep FX) is one of
the more popular fractional CO2 lasers available
today, combining superficial and deep fractional
CO2 laser treatments. Cho and colleagues8 used this
laser to treat atrophic acne scars in 20 Korean
patients. The treatment combined the Deep FX
mode, which focused on the scars only, whereas the
Active FX mode was used over the entire face. After
one session, 50% of patients achieved marked
improvement (>50%). The Deep FX mode with a
smaller (120 lm) spot size has the potential to
extend treatment from the epidermis to as deep as 3–

*Department of Dermatology and Venereology, First Hospital of Jilin University, Changchun, China; †Department of
Dermatology and Venereology, Yanbian University Hospital, Yanji, China

© 2014 by the American Society for Dermatologic Surgery, Inc.  Published by Wiley Periodicals, Inc. 
ISSN: 1076-0512  Dermatol Surg 2014;40:545–552  DOI: 10.1111/dsu.12467

545
 COMPARISON STUDY OF CO2 AFR
4 mm into the reticular dermis, but data on the
efficacy and adverse effects of this novel resurfacing
technique in dark-skinned patients are limited.
In this study, we compared the efficacy and com-
plications of fractional CO2 laser treatment with the
Deep FX mode using different fluences and densities
for acne scars in Asian patients in a randomized,
split-face, evaluator-blinded study.
Methods
Patients
This study followed the principles of the 1975
Declaration of Helsinki. Twenty Chinese subjects,
10 female and 10 male, aged 22–31, with Fitzpatrick
skin types III–IV and moderate to severe atrophic
acne scars were enrolled. Informed consent was
obtained from each patient. Patients with a history
of keloid scarring, isotretinoin use, pregnancy,
lactation, immunosuppression, history of filler
injection within the past year, or ablative or
nonablative laser resurfacing within 1 year of study
initiation were excluded from the study.
Laser Treatment
Patients were treated with a single session of the
Deep FX microscanner handpiece of the fractional
ultrapulse CO2 laser (Ultrapulse Encore; Lumenis
Inc., Santa Clara, CA). The treatment areas were
cleansed with a mild cleanser and 70% alcohol.
Local anesthesia, comprising a topical eutectic
mixture of 2.5% lidocaine hydrochloric acid and
2.5% prilocaine cream (Compound Lidocaine
Cream; Ziguang, Beijing, China), was applied to the
entire face under occlusion before laser therapy.
After an hour of application, the anesthetic cream
was gently removed, and then, to obtain a com-
pletely dry skin surface, alcohol was used to
degrease the skin.
Twenty patients were randomly divided into two
groups. In Group A (n = 10), half of the face was
treated with 20 mJ, density 10% and the other half
546 DERMATOLOGIC SURGERY
with 20 mJ, density 20%. In Group B (n = 10), half
of the face was treated with 10 mJ, density 10% and
the other half with 20 mJ, density 10%. Facial
treatment halves were also randomized. A single
operator then administered a full-face, single-pass
treatment without overlapping pulse.
Immediately after each procedure, a thin layer of
fluticasone propionate cream (Ketinv; Glaxo Oper-
ations UK Limited, Durham, UK) and a recombinant
human epidermal growth factor hydrogel (Yifu;
Huanuowei, Guilin, China) was applied to prevent
an inflammatory reaction and reduce facial dryness.
Ice packing (4°C) was applied to the treated surface
for 30 minutes or more until the pain or burning
sensation decreased. Subjects were instructed to
clean the treated sites gently with a mild cleanser
24 hours after the treatment. The fluticasone pro-
pionate cream was applied twice daily for the first
3 days and the recombinant human epidermal
growth factor hydrogel 4 times daily for 1 week.
After complete decrustation, all patients
were instructed to wear a broad-spectrum sunscreen
with a sun protection factor of 30 and to avoid
sun exposure.
Objective and Subjective Evaluations
Photographs were taken using identical camera
settings, lighting, and patient positioning at baseline
and 3 days, 1 week, 1 month, and 3 months after
treatment. Two blinded dermatologists compared
before and after photographs in nonchronological
order and provided objective clinical assessments of
the acne scars. Acne scars were graded using the
echelle d’evaluation clinique des cicatrices d’acne
grading scale at baseline and 1 and 3 months after
the treatment.9 The degree of improvement was
further assessed on a 4-point scale (0, no improve-
ment; 1, 0–25% [minimal improvement]; 2,
26–50% [moderate] improvement; 3, 51–75%
[marked] improvement; 4, >75% [near total]
improvement). Subjects also performed a
self-assessment of their results (range 0–10) 1 and
3 months after the treatment.
 YUAN ET AL

Immediately after each procedure, subjects were

TABLE 1. Clinical Comparison of Different Energies
asked to rate the pain associated with the treatment in Group A and Group B
using a 10-point pain scale (0 = no pain to Improvement
10 = severe pain). The investigators evaluated the Improvement Grade Grade Group
presence of bleeding, oozing, and edema during the Group A B
treatment was on a 3-point scale (0 = absent, Cases Density 10% Density 20% 10 mJ 20 mJ
1 = mild, 2 = moderate, 3 = severe). Erythema was
1 1 1 2 2
also assessed on a 3-point scale at the 3-day follow- 2 2 3 2 3
up. Recovery times and other potential adverse 3 2 2 1 1
effects, including hyper- and hypopigmentation, 4 2 2 2 3
5 3 3 3 3
crusting, scarring, infection, and acneiform eruption, 6 3 3 2 2
were recorded at each follow-up visit. 7 2 3 2 2
8 1 1 1 1
Statistical Analysis 9 2 2 2 2
10 3 3 3 3
We compared clinical assessment scores of acne
scars using the nonparametric Wilcoxon signed rank
test with SPSS version 17.0 (SPSS, Inc., Chicago, IL). improvement (51–75%) (Figure 1C–D), four
Overall patient satisfaction levels and the grading showed moderate improvement of (26–50%), and
scores of adverse effects associated with the treat- two showed minimal improvement (<25%)
ments were analyzed using the Student t-test (paired (Table 1). Overall patient satisfaction levels at the
samples), while the data which did not follow a 3-month follow-up are shown in Tables 2 and 3.
normal distribution was analyzed using a There was no statistically significant difference
nonparametric test. Differences were considered between different densities (Group A) or fluences
statistically significant at p < .05. (Group B) in clinical efficacy or patient satisfaction
(p > .05). It was also observed that scar
improvements and patient satisfaction were
Results
significantly higher at the 3-month follow-up than
Follow-up results 3 months after a single laser at 1 month (p < .05).
treatment with the same fluence and different
densities (Group A) indicated that three of 10 The results of adverse effects are shown in Tables 2
patients treated using the lower density showed and 3. Pain, bleeding, oozing, edema, crusting,
marked improvement (51–75%), five showed mod- erythema, and PIH were found to be more evident or
erate improvement (26–50%), and two showed persisted for longer periods of time in patients treated
minimal improvement (<25%). Five of 10 patients with higher densities (Group A, p < .05) or higher
treated using the higher density showed marked fluences (Group B, p < .05). Both sides of the faces in
improvement (51–75%), three showed moderate all 20 subjects showed PIH that resolved within
improvement of (26–50%), and two showed min- 3 months except for a patient treated with the higher-
imal improvement (<25%) (Table 1). Three months density setting in Group A. There was no intervention
after the laser procedure with the same density and for the PIH other than daily sunscreen use. Acneiform
different fluences (Group B), two of 10 patients eruption (10%, n = 1), cutaneous pruritus (30%,
treated using the lower fluence showed marked n = 3), and skin dryness (60%, n = 6) were observed
improvement (51–75%) (Figure 1A–B), six showed in patients in Group A. Four patients in Group B
moderate improvement (26–50%), and two showed experienced cutaneous pruritus, and five experienced
minimal improvement (<25%). Four patients trea- skin dryness. All subjects with skin dryness were
ted using the higher fluence showed marked successfully treated within 2 weeks using a moistur-

40:5:MAY 2014 547

 COMPARISON STUDY OF CO2 AFR

(A) (B)

(C) (D)

Figure 1. Twenty-seven-year-old male patient before (A) and 3 months after (B) treatment with 10 mJ, density 10% and
before (C) and 3 months after (D) treatment with 20 mJ, density 10%.

TABLE 2. Overall Comparative Data Between Different Densities in Group A

Density 10% Density 20% p-Value
Pain, mean  SD (range 0–10) 4.36  1.10 6.12  1.24 <.001
Edema, days, mean  SD 3.10  0.57 4.50  0.53 .004
Crusting, days, mean  SD 4.80  0.79 6.60  0.52 .003
Postinflammatory hyperpigmentation duration, days, mean  SD 50.50  8.64 62.50  11.06 .005
Infection, n 0/10 0/10
Scarring, n 0/10 0/10
Acneiform eruption, n 1/10 1/10
Cutaneous pruritus, n 3/10 3/10
Skin dryness, n 6/10 6/10
Hypopigmentation, n 0/10 0/10
Patient satisfaction, mean  SD (range 0–10) 5.90  1.37 5.95  1.40 .85

SD, standard deviation.

izing cream (Lauzome; Canada Highview & Ever-
bright Medical Technology Co., Ltd., Changchun,
China) three times daily. Acneiform eruptions in one
subject were successfully treated within 2 weeks using
clindamycin phosphate gel and adapalene gel applied
day and night, respectively. Some subjects also expe-
rienced cutaneous pruritus in irradiation areas 2–5 days
after treatment. The sensation was sustainable
and automatically resolved within 1 week. Severe
complications such as hypopigmentation, scarring,
and infection were not observed in any of the 20
subjects.
Discussion
Ablative fractional resurfacing (AFR) with 10,600-
nm CO2 lasers uses fractionated laser beams to
produce an array of microscopic columns of con-
trolled deep dermal tissue volumetric ablation and
vaporization surrounded by thermally induced

548 DERMATOLOGIC SURGERY

 YUAN ET AL

TABLE 3. Overall Comparative Data Between Different Fluences in Group B

10 mJ 20 mJ p-Value
Pain, mean  SD (range 0–10) 4.39  1.19 4.98  1.13 .02
Edema, days, mean  SD 2.50  0.52 3.50  0.53 .001
Crusting, days, mean  SD 4.00  0.67 4.80  0.79 .003
Postinflammatory hyperpigmentation duration, days, mean  SD 46.80  11.51 56.80  11.46 .004
Infection, n 0/10 0/10
Scarring, n 0/10 0/10
Acneiform eruption, n 0/10 0/10
Cutaneous pruritus, n 4/10 4/10
Skin dryness, n 5/10 5/10
Hypopigmentation, n 0/10 0/10
Patient satisfaction, mean  SD (range 0–10) 5.30  1.25 5.42  1.30 .83

SD, standard deviation.

annular coagulation zones of denatured collagen
with interspersed regions of untreated tissue.7,10 An
ex vivo histologic study demonstrated that the depth
of ablation in AFR depends on the pulse energy
used, with higher energies resulting in greater
penetration depth.10 In turn, the depth of ablation
and coagulation correlated directly with treatment
efficacy in laser resurfacing.10–12 Various types of
fractional ablative CO2 lasers have been used for
acne scar treatments with different penetration
depths at variable energy levels. Manuskiatti and
colleagues12 treated 13 patients using a fractional
CO2 laser for three sessions. Patients with mild to
moderate scars were irradiated with lower energy
levels (75–90 mJ/MTZ), whereas deeper scars were
treated using a high-pulse energy level (105 mJ/
MTZ). A fractionated CO2 laser system used in their
study creates 150- to 200-lm-deep MTZs. At the
3-month follow-up, 69% of subjects had at least 25–
50% improvement. Likewise, in a controlled split--
face trial, Jung and colleagues13 treated mild to
severe acne scars with a fractional CO2 laser.
Lower-fluence, higher-density settings (30 mJ/pulse,
250 MTZs/cm2) were compared with higher-fluence,
lower-density settings (70 mJ/pulse, 150 MTZs/
cm2). More-pronounced effects were demonstrated
on the sides treated with higher fluence and lower
density. Energy levels of 30 and 70 mJ corresponded
to a depth of the necrotic columns approximately up
to 282 and 486 lm, respectively, with the CO2 FS
used in their study, as assessed through histologic
evaluation. Chapas and colleagues6 treated 13
patients with moderate to severe acne scars using the
novel ablative 30W CO2 Fraxel re:pair device at
pulse energies of 20–100 mJ for two to three
full-face treatments. Patients treated with higher
energy levels (70–100 mJ) on deeper scars on the
cheeks for the second and third treatments received
the highest improvement scores, with average over-
all improvement of 51–75% 3 months after the final
treatment. A previous study with this device showed
tissue ablation and thermal effects as deep as 1–
1.6 mm into the skin at the higher energies of 70–
100 mJ.14 Thus, based on previous studies, it was
estimated that higher energy producing deeper tissue
injury into the dermis correlated with more-pro-
nounced clinical efficacy in laser resurfacing,15,16
although it is unknown how deep the tissue injury
depth would tend to balance the biologic effects of
modulating and suppressing in wound healing
responses, which presents in similar clinical efficacy
with different energies. In our comparison study, we
treated patients with moderate to severe acne scars
using the Deep FX mode at energy levels of 10 and
20 mJ (Group B). Farkas and colleagues17 reported
that, with a single pulse, the Deep FX mode
demonstrated tissue injury up to 1 mm from the
tissue surface at 10 mJ and up to 2 mm at 20 mJ as
assessed through histopathologic evaluation. At the
3-month follow-up, 80% of subjects had at least
25–50% improvement, and 30% had 51–75%
improvement in their scar conditions. There was no

40:5:MAY 2014 549

 COMPARISON STUDY OF CO2 AFR
significant difference in clinical efficacy between 10
and 20 mJ laser irradiation. Tissue injury after
treatment with the Deep FX mode was similar to the
super-short-pulse Fraxel re:pair system, with the
ablation microcolumns penetrating from the epi-
dermis into the underlying papillary and reticular
dermis. The penetration depth with the lower-energy
level of this specific device may be in accordance
with the depth using higher energy with other
fractional ablative CO2 lasers. In this study, with the
lower-fluence 10 mJ of the Deep FX mode corre-
sponding to a depth of 1 mm, it was possible to
achieve significant clinical efficacy, as previously
reported. It was hypothesized that penetration as
deep as 2 mm into the deep reticular dermis with
CO2 FS treatment at higher energy may not result in
greater efficacy for treating acne scars.
We also compared the efficacy of CO2 FS treatment
with different densities and found that there was no
statistically significant difference between the lower-
density 10% and higher-density 20%. The results of
our study were compatible with the previous report by
Kono and colleagues18 indicating therapeutic effects
of 1,550-nm nonablative FP laser treatment in skin
rejuvenation. It was considered from their study that,
when the fractional laser beam creates a dense pattern
of epidermal and dermal MTZs, the untreated tissues
that surround the MTZs serve as a reservoir for
thermal healing. Using higher density, the quantity of
the undamaged tissues decreased, which was likely to
result in no greater efficacy in scar improvement.
Adverse effects such as pain, edema, crusting, and
PIH were found to be more evident or persisted for
longer periods in patients treated with higher den-
sities or higher fluences, as found in a previous
study.18 PIH is one of the most troubling adverse
effects of laser irradiation when treating Asian
patients. We observed that both sides of the faces in
all 20 subjects had PIH that had almost resolved
within 3 months. The majority of patients received
laser irradiation in the summer and early autumn,
when the sun is most intense, which may be
responsible for the high rate of PIH observed. The
550 DERMATOLOGIC SURGERY
pathogenesis of PIH is unknown. Some studies have
found high density to be a causative factor of
PIH.6,18 In fractional resurfacing, too high a density
can cause overlapping thermal injury zones and, if
dense enough, act like traditional ablative laser
resurfacing, which has a high risk of PIH.18 It is
estimated that the risk of PIH may be correlated
with the extent of overlapping thermal injury zones.
The extent of the overlapping thermal injury zones
seems to be related to the density and fluence setting
of a fractional laser. Hantash and colleagues10 found
that higher fluence achieved greater thermal lesion
depth and width and resulted in greater lesion
dimensions, which is likely to enhance the degree of
overlapping thermal injury zones. When we applied
the higher density or fluence, the severity and
duration of the PIH was more significant. However,
we could not compare the effect of higher density
and fluence on the characteristics of PIH. Because in
our study, there was lack of a same control group.
To avoid PIH, the use of lower densities and fluences
is of particular importance. Delayed hypopigmen-
tation, which has been reported with traditional
ablative CO2 resurfacing, was not observed in our
patients after CO2 AFR treatments, but an extended
follow-up period is essential, because the delayed
pigment abnormality usually develops as late as
6 months to 1 year postoperatively.19
Improvement in acne scars was significantly greater
at the 3-month follow-up than at 1 month, which
was in accordance with previous reports.6,12 Several
studies have indicated that FP-induced heat shock
protein (HSP) expression and new formation of
collagen and elastic fibers lasted for 3–6 months or
even longer, which was in accordance with clinical
observation of long-term biologic effects.20,21
Expression of HSPs such as HSP70 and HSP47 plays
an important role in wound healing responses, which
lead to collagen remodeling and formation. It was
estimated that 3 months or longer may be an
appropriate treatment interval. If the interval is
short, such as 1–2 months, the wound healing
responses of the last treatment session may not
produce the extreme effect, and several postoperative

safety indexes such as sebum excretion rate, trans-
epidermal water loss, and the melanin–erythema
index may not completely recover.22
Acne scars were graded using the ECCA grading scale
at baseline and at follow-up visits.9 The ECCA
grading scale is a tool designed to help dermatologists
assess the severity of acne scars and in standardizing
discussions about the treatment of scars.9 The
advantage of the ECCA grading system is that it could
reflect the overall facial atrophic acne scar conditions
with both qualitative and quantitative grading scale,
but it cannot reflect the efficacy of each independent
scar improvement without the true pre-/post-scar
depth measured, which is a limitation of our study.
Other limitations of this study were the small sample
size and that there was only one treatment session
using a single laser modality. To maximize the
efficacy of scar treatment, various modalities should
be combined due to a diverse range of scar condi-
tions. Moreover, no treatment option available can
offer near-total improvement of moderate to severe
acne scars with only one treatment session.
In conclusion, we demonstrated the efficacy and
safety of a single-session treatment of acne scars
with fractional CO2 laser depending on different
energy settings in Asian patients in a randomized,
split-face, evaluator-blinded study design. Frac-
tional CO2 laser treatment using the Deep FX mode
may provide a significant efficacy for acne scars
with lower fluence and density and fewer compli-
cations. Future work would be beneficial, including
longer follow-up for the assessment of scar
improvement and possible late-emerging
pigmentary changes.
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Changchun, Jilin, China, or e-mail: shansalee@gmail.com

552 DERMATOLOGIC SURGERY