Lower-Fluence, Higher-Density versus Higher-Fluence,

Lower-Density Treatment with a 10,600-nm Carbon Dioxide

Fractional Laser System: A Split-Face, Evaluator-Blinded Study
JIN YOUNG JUNG, MD, JU HEE LEE, MD, PHD, DONG JIN RYU, MD, SANG JU LEE, MD, PHD,y
DONGSIK BANG, MD, PHD, AND SUNG BIN CHO, MD

BACKGROUND Adequate laser settings in the treatment of scars using a carbon dioxide fractional laser
system (CO2 FS) have not been established.
OBJECTIVE To compare the efficacy and safety of low-fluence, high-density with high-fluence, low-
density treatment with CO2 FS on acne scars and enlarged pores.
METHODS Ten patients with mild to severe atrophic acne scars and enlarged pores were enrolled. Half
of each subject’s face was treated with a single session of CO 2 FS with a fluence of 70 mJ and a density of
150 spots/cm 2; the other half was treated with a fluence of 30 mJ and a density of 250 spots/cm 2.
RESULTS Follow-up results 3 months after a single low-fluence, high-density treatment with CO2 FS
showed that four of 10 participants had clinical improvement of 51% to 75% from baseline. After the
high-fluence, low-density CO 2 FS treatment, five of 10 patients demonstrated marked clinical improve-
ments of more than 76%.
CONCLUSION Higher-energy, lower-density laser settings seem to be more effective than lower-
energy, higher-density settings for acne scars and enlarged pores, although our results do not constitute
a conclusive comparison of the two different modes of CO 2 FS.
The authors have indicated no significant interest with commercial supporters.

C onventional ablative carbon dioxide (CO2) and

erbium-doped yttrium aluminum garnet lasers
have shown promising clinical outcomes for acne
two patients showed trace or mild post-therapy
hyperpigmentation.

scarring,1,2 but their usage is frequently limited in
Asian patients because of the risk of adverse events,
including relatively long recovery time, edema,
prolonged erythema, scarring, and post-therapy
dyschromia.3,4 An ablative 10,600-nm carbon
dioxide fractional laser system (CO2 FS) is a device
adopting fractional laser technology, which enables
the increase of treatment area and use of higher pulse
energy with minimal recovery time by leaving an
intact epidermal architecture surrounding each
coagulated treatment area.3–7 Chapas and
colleagues2 reported that all 15 patients with acne
scars had at least 26% to 50% improvement of their
scars after three treatment sessions, and only
Another study in which laser treatment was
performed using two different modes (Deep FX and
Active FX modes) of a CO2 FS (Ultrapulse Encore,
Lumenis, Inc., Santa Clara, CA) postulated that the
combination of these two different modes of CO2 FS
could improve the therapeutic effect by providing
a broader treatment zone with Active FX mode
and selective coagulation of deeply located tissues
with Deep FX mode,8 but the clinical efficacy
of CO2 FS with different laser energies and densities
has not been reported. In this report, we compared
the efficacy and safety of low-fluence, high-density
CO2 FS treatment with that of high-fluence,
low-density treatment on acne scars and enlarged

Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul,
Korea; yYonsei Star Skin and Laser Clinic, Seoul, Korea

& 2010 by the American Society for Dermatologic Surgery, Inc.  Published by Wiley Periodicals, Inc. 
ISSN: 1076-0512  Dermatol Surg 2010;36:2022–2029  DOI: 10.1111/j.1524-4725.2010.01803.x

2022
 JUNG ET AL

pores in a controlled, split-face, evaluator-blinded excluded. Patients with a propensity for keloids or
study. who were pregnant, immunosuppressed, or using
isotretinoin were also excluded.

Methods
This was a prospective, split-face, evaluator-blinded
study with low-fluence, high-density and
high-fluence, low-density CO2 FS treatments for
acne scars and enlarged pores. The study was
performed in accordance with the ethical guidelines
of the 1975 Declaration of Helsinki, as reflected in
approval by the Institutional Review Board of
Severance Hospital, Yonsei University College
of Medicine, Seoul, Korea (4-2009-0154). All
participants provided written informed consent.
Patients
Ten male patients (mean age 22.2, range 19–25;
Fitzpatrick skin type IV) with mild to severe acne
scars and enlarged facial pores were enrolled in this
study. Patient characteristics are summarized in
Table 1. Patients with concomitant treatments such
as skin resurfacing procedures, chemical reconstruc-
tion of skin scars using trichloroacetic acid, collagen
induction therapy using a microneedle therapy
system, or treatment with a nonablative 1,550-nm
erbium-doped fractional photothermolysis system
or CO2 FS within the preceding 6 months were
Laser Treatment
Patients were treated in a single session of CO2 FS
using a 10,600-nm Mosaic eCO2 laser (Lutronic
Corporation, Goyang, Korea). The Food and Drug
Administration has approved this laser, which is
commercially available, for use in dermatologic
procedures. For local anesthesia, the face was
cleansed with a mild soap and 70% alcohol, and a
topical eutectic mixture of 2.5% lidocaine hydro-
chloric acid and 2.5% prilocaine (AstraZeneca AB,
Södertälje, Sweden) was applied to the entire face
under occlusion 1 hour before laser therapy. Patients
with a history of herpes virus infection were
prophylactically prescribed oral valacyclovir hydro-
chloride (Valtrex, GlaxoSmithKline, Research
Triangle Park, NC) for 3 days.
On one side of the face, laser fluences were initially
delivered with a pulse energy of 30 mJ, a density of
150 spots/cm2 in a single pass and in static operating
mode (7.7% coverage). Additional treatment with
settings of a pulse energy of 30 mJ, a density of
100 spots/cm2 in a single pass and in static operating
mode (5.1% coverage) followed on the same side of

TABLE 1. Improvement Grade and Patients’ Satisfaction Rate after a Single Session of Carbon Dioxide
Fractional Laser System Treatment

Improvement Grade Patient Satisfaction Grade

Patient Sex/ 70 mJ, 30 mJ, 70 mJ, 30 mJ,

Number Age 150 spot/cm2 250 spot/cm2 150 spot/cm2 250 spot/cm2

1 M/22 3 2 Slightly satisfied Slightly satisfied

2 M/24
3 M/24
4 M/25
5 M/21
6 M/20
7 M/22
8 M/25
9 M/19
10 M/20
3 2 Satisfied Satisfied
3 3 Satisfied Satisfied
4 3 Satisfied Satisfied
4 3 Satisfied Slightly satisfied
4 3 Very satisfied Satisfied
4 2 Very satisfied Very satisfied
2 2 Slightly satisfied Unsatisfied
2 2 Slightly satisfied Slightly satisfied
4 2 Satisfied Slightly satisfied

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 T R E AT M E N T PA R A M E T E R S O F C O 2 F S
the face, resulting in total treatment density with a
pulse energy of 30 mJ on one side of the face of
250 spots/cm2 (12.8% coverage). The other half of
the face was treated with a fluence of 70 mJ, a
density of 150 spots/cm2 in a single pass and in
static operating mode (12.3% coverage). The
manufacturer provided calculated percentage
coverage at each setting. To prevent an inflammatory
reaction and reduce facial edema, patients were
prescribed 10 mg of oral prednisolone for 3 days.
Patients were instructed to use a moisturizer
(Physiogel Cream, Stiefel Laboratories, Sligo,
Ireland) several times daily for the first few days
after treatment to promote wound healing and
prevent dryness and to avoid overexposure to
sunlight and use a broad-spectrum sunscreen after
treatment. Patients were instructed to avoid the use
of any bleaching or antiwrinkle agents during the
course of treatment.
Objective and Subjective Evaluations
Photographs were obtained using identical
camera settings, lighting, and patient positioning at
baseline and 3 months after the treatment. Objective
clinical assessments consisted of two blinded
dermatologists comparing before and after
photos separately on each side of the face in
nonchronological order. The two evaluators were
not informed as to the study design. We used a
quartile grading scale on the evaluations (grade 1,
o25% = minimal to no improvement; grade 2,
26–50% = moderate improvement; grade 3,
51–75% = marked improvement; and grade 4,
475% = near total improvement).9
The patients were asked 3 months after the treat-
ment about their overall rates of satisfaction
(very satisfied, satisfied, slightly satisfied, unsatis-
fied) separately for each side of the face. Patients also
reported on the side effects of the treatment, espe-
cially bleeding, oozing, post-therapy dyschromias,
scaling or crusting, erythema, and aggravation of
inflammatory acne lesions, also separately on each
side of the face. Difference in relative pain intensity
2024 D E R M AT O L O G I C S U R G E RY
depending on the laser settings were evaluated
within 1 hour after laser therapy.
Histologic Evaluation
To compare the histologic effects of the laser
depending on the settings, we took biopsy specimens
immediately after one treatment with the laser on the
cheek at settings of 30 mJ and 250 spots/cm2 and
70 mJ and 150 spots/cm2, respectively, as described
above from one of the healthy volunteers after
obtaining informed consent, but because it is
impossible to histologically compare the identical
pore and scar before and after treatment, the follow-
up biopsy was not performed. Mean diameter
and depth of CO2 FS-induced necrotic columns were
calculated by measuring 10 necrotic columns on
serial sections of the biopsy specimens.
Statistical Analysis
We compared clinical assessment scores, overall
patient satisfaction levels, and the characteristics of
adverse events associated with low-fluence,
high-density and high-fluence, low-density treatment
using the nonparametric Mann-Whitney U test with
SPSS version 13.0 (SPSS, Inc., Chicago, IL).
Differences were considered statistically significant
at po.05.
Results
Follow-up results 3 months after a single low-flu-
ence, high-density treatment with CO2 FS, pulse
energy of 30 mJ and density of 250 spots/cm2,
indicated that six of 10 participants demonstrated
clinical improvements of 26% to 50% from baseline
(Table 1, Figures 1 and 2). Four of the patients
showed moderate improvement of 51% to 75%
(Figure 3). After the high-fluence and low-density
CO2 FS treatment, a pulse energy of 70 mJ and
density of 150 spots/cm2, five of 10 participants
demonstrated marked clinical improvements of more
than 76% from baseline (Figure 3). Three
patients showed moderate improvement of 51% to
75% (Figures 1 and 2), and two had clinical
 JUNG ET AL

Figure 1. Atrophic acne scars and facial pores in patient 1 before (A) and 3 months after (B) treatment with 70 mJ and 150
spots/cm2 and before (C) and 3 months after (D) treatment with 30 mJ and 250 spots/cm2.

improvements of 26% to 50%. The mean grade of
clinical improvement based on clinical assessment
was 2.4 7 0.5 for low-fluence, high-density CO2 FS
and 3.3 7 0.8 for high-fluence, low-density CO2 FS
(p = .02, Figure 4).
After low-fluence, high-density CO2 FS treatment,
surveys evaluating overall patient satisfaction
revealed that one of the 10 patients (10%) was
very satisfied, five (50%) were satisfied, three
(30%) were slightly satisfied, and one (10%)
was unsatisfied (Table 1 and Figure 5). After high-
fluence, low-density CO2 FS treatment, two of
the 10 patients (20%) were very satisfied, four
(40%) were satisfied, and four (40%) were
slightly satisfied. The overall satisfaction levels of

Figure 2. Atrophic acne scars and facial pores in patient 2 before (A) and 3 months after (B) treatment with 70 mJ and 150
spots/cm2 and before (C) and 3 months after (D) treatment with 30 mJ and 250 spots/cm2.

36:12:DECEMBER 2010 2025

 T R E AT M E N T PA R A M E T E R S O F C O 2 F S
Figure 3. Atrophic acne scars and facial pores in patient 5 before (A) and 3 months after (B) treatment with 70 mJ and
150 spots/cm2 and before (C) and 3 months after (D) treatment with 30 mJ and 250 spots/cm2.
high fluence, low-density CO2 FS and low-fluence,
high-density CO2 FS were not significantly different
(p = .29).
Side effects included pain during treatment, post-
treatment crusting or scaling, edema, post-therapy
hyperpigmentation, bleeding and oozing from the
treated sites, and aggravation of inflammatory acne
lesions. All of the 10 participants replied that post-
therapy crusting and scaling were resolved within a
Figure 4. Mean grade of clinical improvement according to
laser settings; low-fluence, high-density (70 mJ and 150
spots/cm2) versus high-fluence, low-density (30 mJ and 250
spots/cm2). p = .02.
2026 D E R M AT O L O G I C S U R G E RY
week, and no noticeable difference between the sides
of the face was reported. The half of the face treated
with higher fluence and lower density had a longer
duration of postoperative erythema than the half
with lower fluence and higher density in six of 10
patients (60%, cases 2, 4, 6, 7, 8, and 9). The
difference in relative pain intensity revealed that
seven of 10 patients (70%) could not feel a difference
between the sides of the face, two (20%) had more
pain on the side of the face treated with 70 mJ and
150 spots/cm2, and one (10%) had more pain on the
side treated with 30 mJ and 250 spots/cm2. One
Figure 5. Patient satisfaction levels according to treatment
settings.
 JUNG ET AL

patient experienced post-therapy hyperpigmentation

(case 5) on both sides of the face that spontaneously
resolved within 2 months. Other possible adverse
events, including post-therapy blister formation,
scarring, hypopigmentation, secondary bacterial
infection, and viral infection, were not encountered
on either side of the face.

The specimens obtained from the cheek immediately

after treatment showed formation of necrotic col-
umns on the epidermis and upper dermis. The biopsy
specimen from the side of the face treated with 30 mJ
and 250 spots/cm2 showed two necrotic columns
(original magnification  100) and the mean diam-
eter and depth 7 standard deviation of the necrotic
columns were 182.3 7 27.8 and 259.2 7 22.5 mm,
respectively (Figure 6A). The specimen from the
other side of the face treated with 70 mJ and
150 spots/cm2 presented one necrotic column at the
same magnification, and the mean diameter and
depth 7 standard deviation were 295.3 7 13.3 and
475.1 7 11.3 mm, respectively (Figure 6B).

Discussion

Numerous reports on nonablative and ablative FS
have demonstrated its effectiveness in the treatment
of a wide variety of dermatologic diseases, although
there have been only a few reports comparing the
therapeutic efficacy and safety of FS depending on
the laser parameters. According to a recent study
done in six subjects with photodamaged skin, higher-
density, lower-energy nonablative FS treatment has
been found to be more effective for the treatment of
pigmentary disorders.10 Also, higher-energy, lower-
density laser settings have been found to be better at
textural improvement by producing deeper injury
columns.10
11
Hu and colleagues reported the effectiveness of FS
using a nonablative 1,550-nm erbium-doped fiber
laser in treatment of atrophic acne scars. The authors
divided the participants into two groups treated
with different laser parameters; patients in the
first group were treated with a nonablative FS at a
Figure 6. Biopsy specimens obtained from cheek immedi-
ately after treatment with an ablative 10,600-nm carbon di-
oxide fractional laser system at settings of 30 mJ and 250
spots/cm2 (A) and 70 mJ and 150 spots/cm2 (B) (hematoxylin
and eosin staining, original magnification  100; scale bars,
200 mm).
setting of 15 to 20 mJ/microthermal treatment zone
(MTZ) and a density of 1,000 to 2,000 MTZ/cm2.
The other group of patients was treated with the
same laser at a setting of 30 to 40 mJ/MTZ and
a density of 392 to 520 MTZ/cm2. There was no
significant difference in therapeutic efficacy between
the two groups.11
In the present study, we performed CO2 FS treatment
using two different laser settings for acne scars and
enlarged facial pores. Parameters of fluence
and density were determined by referring to the
values of percentage coverage, which a manufacturer
provided. The concept of percentage coverage can
reflect only two-dimensional effects of the laser

36:12:DECEMBER 2010 2027

 T R E AT M E N T PA R A M E T E R S O F C O 2 F S
treatment. Moreover, our results demonstrating the
mean diameter and depth of the necrotic columns
immediately after treatment cannot exactly reflect
the therapeutic effect of CO2 FS because immediate
tissue contracture with CO2 FS treatment and
selection of reviewed tissue section may significantly
influence the data,12 and therapeutic effects are
correlated not only with the necrotic columns, but
also with the surrounding thermal coagulated areas.
However, our results may be used as reference
data because most of the manufacturers provide
percentage coverage values and penetration depth
depending on the parameters of their CO2 FS
products.
Our results showed that higher-energy, lower-density
CO2 FS treatment resulted in more pronounced
clinical outcomes than with the higher-density, low-
er-energy setting. The results of our study were
compatible with those of previous reports indicating
therapeutic effects of nonablative FS on textural
improvement and skin rejuvenation.10,13 Kono and
colleagues13 reported that pain, erythema, and
swelling were more pronounced or lasted longer in
patients treated with higher densities and fluencies of
a nonablative FS. In the present study, although the
difference in the duration of post-therapy crusting
and scaling depending on laser settings was not
remarkable, post-therapy erythema was more
pronounced and lasted longer with the setting of
70 mJ and 150 spots/cm2.
Our study group previously demonstrated the ther-
apeutic effect of a 1,550-nm erbium glass fractional
laser on acne scars and enlarged pores.14 We postu-
lated that collagen reproduction in the dermis could
result in textural changes and shrinkage of pores,
mostly due to perifollicular collagen formation, as
well as a direct effect on the follicular epithelium of
the pore,13 but multiple sessions of nonablative
fractional laser therapy are generally required to
achieve satisfactory clinical improvement.2,15 In the
present study, we observed clinical improvements in
acne scars and enlarged pores with a single CO2
FS treatment. Direct effect on the follicular
2028 D E R M AT O L O G I C S U R G E RY
epithelium of the pore was histologically shown with
higher-density, lower-energy treatment, although
considering our results, textural changes mostly
due to perifollicular collagen formation might have
mainly contributed to the pronounced clinical
outcomes.
In conclusion, we demonstrated the efficacy and
safety of single-session treatment of acne scars and
enlarged facial pores using CO2 FS depending on
different laser settings in East Asian patients in a
randomized, split-face, evaluator-blinded study
design. A higher-energy and lower-density laser
setting seems to be more effective than one with
lower energy and greater density for acne scars and
enlarged pores. We believe our study could be used
as an essential reference when choosing laser
modalities for treatment of scars and enlarged pores.
Our results do not constitute a conclusive compar-
ison of the two different modes of CO2 FS because of
the small study sample, which also consisted of only
male patients.
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Address correspondence and reprint requests to: Sung Bin
Cho, MD, Department of Dermatology and Cutaneous
Biology Research Institute, Yonsei University College of
Medicine, 250 Seongsan-no, Seodaemoon-gu, Seoul 120-
752, Korea, or e-mail: sbcho@yuhs.ac
36:12:DECEMBER 2010 2029