Radiofrequency facial rejuvenation: Evidence-based effect

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DOI: 10.1016/j.jaad.2010.06.045 · Source: PubMed
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Abstract
Multiple therapies involving ablative and nonablative techniques have been developed for rejuvenation of photodamaged skin. Monopolar radiofrequency (RF) is emerging as a gentler, nonablative skin-tightening device that delivers uniform heat to the dermis at a controlled depth. We evaluated the clinical effects and objectively quantified the histologic changes of the nonablative RF device in the treatment of photoaging. Six individuals of Fitzpatrick skin type III to IV and Glogau class I to II wrinkles were subjected to 3 months of treatment (6 sessions at 2-week intervals). Standard photographs and skin biopsy specimens were obtained at baseline, and at 3 and 6 months after the start of treatment. We performed quantitative evaluation of total elastin, collagen types I and III, and newly synthesized collagen using computerized histometric and immunohistochemical techniques. Blinded photographs were independently scored for wrinkle improvement. RF produced noticeable clinical results, with high satisfaction and corresponding facial skin improvement. Compared with the baseline, there was a statistically significant increase in the mean of collagen types I and III, and newly synthesized collagen, while the mean of total elastin was significantly decreased, at the end of treatment and 3 months posttreatment. A limitation of this study is the small number of patients, yet the results show a significant improvement. Although the results may not be as impressive as those obtained by ablative treatments, RF is a promising treatment option for photoaging with fewer side effects and downtime.
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DERMATOLOGIC SURGERY
Radiofrequency facial rejuvenation:
Evidence-based effect
Moetaz El-Domyati, MD,
a
Tarek S. El-Ammawi, MD,
a
Wal id M ed ha t, M D,
a,b
Osama Moawad, MD,
c
Donna Brennan, MS,
b
My~G. Mahoney, PhD,
b
and Jouni Uitto, MD, PhD
b
Al-Minya and Cairo, Egypt, and Philadelphia, Pennsylvania
Background: Multiple therapies involving ablative and nonablative techniques have been developed for
rejuvenation of photodamaged skin. Monopolar radiofrequency (RF) is emerging as a gentler, nonablative
skin-tightening device that delivers uniform heat to the dermis at a controlled depth.
Objective: We evaluated the clinical effects and objectively quantified the histologic changes of the
nonablative RF device in the treatment of photoaging.
Methods: Six individuals of Fitzpatrick skin type III to IV and Glogau class I to II wrinkles were subjected
to 3 months of treatment (6 sessions at 2-week intervals). Standard photographs and skin biopsy specimens
were obtained at baseline, and at 3 and 6 months after the start of treatment. We performed quantitative
evaluation of total elastin, collagen types I and III, and newly synthesized collagen using computerized
histometric and immunohistochemical techniques. Blinded photographs were independently scored for
wrinkle improvement.
Results: RF produced noticeable clinical results, with high satisfaction and corresponding facial skin
improvement. Compared with the baseline, there was a statistically significant increase in the mean of
collagen types I and III, and newly synthesized collagen, while the mean of total elastin was significantly
decreased, at the end of treatment and 3 months posttreatment.
Limitations: A limitation of this study is the small number of patients, yet the results show a significant
improvement.
Conclusions: Although the results may not be as impressive as those obtained by ablative treatments, RF is
a promising treatment option for photoaging with fewer side effects and downtime. ( J Am Acad Dermatol
2011;64:524-35.)
Key words: collagen; elastin; nonablative; radiofrequency; skin aging.
There are two clinically and biologically dis-
tinct aging processes affecting the skin. The
first is intrinsic aging, ‘‘the biologic clock,’’
which affects the skin by slow, irreversible tissue
degeneration.
1
The second is extrinsic aging, ‘‘photo-
aging,’’ which was first described in 1986 as the
effects of chronic exposure to the elements, primarily
ultraviolet radiation on skin.
2-4
The histologic and
ultrastructural hallmark of photodamaged skin is the
accumulation of elastotic material in the papillary
and mid dermis, a process known as solar elastosis.
5
Collagen, which comprises more than 80% of the
total dry weight of the dermis, becomes disorganized
with enhanced breakdown and reduced network
formation.
6
These alterations contribute to the skin
sagging and wrinkling.
7
For more than half of a decade, many different laser
and other light-based systems have been developed
From the Department of Dermatology, Al-Minya University
a
;
Department of Dermatology and Cutaneous Biology, Thomas
Jefferson University, Philadelphia
b
; and Moawad Skin Institute
for Laser, Cairo.
c
Supported by the Cultural and Educational Bureau of the Republic
of Egypt and Egyptian Scholar Program (Dr Medhat); and
National Institutes of Health R01 AR28450 (Dr Uitto).
Conflicts of interest: None declared.
Reprints not available from the authors.
Correspondence to: Jouni Uitto, MD, PhD, Department of
Dermatology and Cutaneous Biology, Jefferson Medical
College, 233 S 10 St, Suite 450 BLSB, Philadelphia, PA 19107.
E-mail: Jouni.Uitto@jefferson.edu.
0190-9622/$36.00
ª2010 by the American Academy of Dermatology, Inc.
doi:10.1016/j.jaad.2010.06.045
524
and evaluated for their capability to reverse photo-
damage and age-associated rhytides, a process re-
ferred to as photorejuvenation.
7,8
Although ablative
lasers remain the gold standard for photodamaged
skin rejuvenation, their use is associated with signifi-
cant side effects, and a prolonged and an unpleasant
posttreatment downtime.
9
Thus, in recent years, inter-
est in ablative treatments has
waned and nonablative skin
rejuvenation has become an
appealing alternative treat-
ment.
10
Nonablative laser mo-
dalities are designed to
produce favorable alterations
in the dermis with no epider-
mal damage. However, laser
light can be diffracted, ab-
sorbed, or scattered, and
only small portions of the
emitted energy reach the tar-
get of concern. Consequently,
the effects are proportionally
reduced.
11
The monopolar ra-
diofrequency (RF) device is different from cosmetic
lasers, as it produces an electric current rather than
light. The energy produced is not liable to be dimin-
ished by tissue diffraction or absorption by epidermal
melanin. As such, RF-based systems are appropriate
for any skin type.
12
Monopolar RF therapy delivers
uniform heat at controlled depth to dermal layers,
causing direct collagen contraction and immediate
skin tightening.
8,13
Subsequent remodeling and reor-
ientation of collagen bundles and the formation of
newcollagenisachievedovermonthsaftertreat-
ment.
14
The purpose of the current study was to
evaluate the effects of, and objectively quantify the
histologic facial skin responses to, the monopolar RF
device as a nonablative treatment of photoaging, and
to assess whether multiple treatments would improve
clinical outcome.
METHODS
Study population
This study was conducted on a cohort of 6 female
volunteers who desired an improvement in the
appearance of facial skin laxity and wrinkles. The
individuals, ranging in age from 47 to 62 years with
an average of 51.1 65.5 years, were recruited from
the dermatology outpatient clinic of Al-Minya
University Hospital, Al-Minya, Egypt. Treatment
and study details were fully explained to subjects,
and all signed an informed consent form. The vol-
unteers were Fitzpatrick skin type III to IV, with class
I to II wrinkles based on the Glogau scale.
15
Inclusion criteria included bilateral facial changes
caused by sun damage. Exclusion criteria were
pregnancy or nursing, photosensitivity to sunlight,
any sign of infection or inflammatory skin disease,
history of hypertrophic scars or keloids, use of oral
isotretinoin in the past 12 months, and previous skin
rejuvenation procedures in the facial area.
Device and techniques
We used a monopolar
RF skin-tightening device
(Biorad, Shenzhen GSD Tech
Co, Guangdong, China)
consisting of RF generator,
computerized automatic resis-
tance test technology, a con-
tinuous cooling system, and a
3-cm
2
tip. The RF generator
produces a 6-MHz alternating
current that creates an electric
field through the skin, and
allows for the heating of tis-
sues through their resistance
to the flow of electrical cur-
rent. The physical properties, including frequency
generator, frequency of electrical field polarity, and
energy output, between the ThermaCool instrument
(SoltaMedicalInc,Hayward,CA)andourRFinstru-
ment are identical. Both instruments use capacitive
coupling rather than conductive coupling to deliver the
therapeutic energy. Conductive coupling is based on
energy concentrated at the tip of an electrode, resulting
in accumulation of produced heat at the skin surface
in contact with the electrode, which can result in
epidermal injury. Capacitive coupling creates a zone
of increased temperature through dispersing energy
across the skin surface.
10,12
Briefly, a topical anesthetic cream (lidocaine 5%)
was applied to the treatment area as a thick coating
and left for 90 minutes under occlusion, then the
cream was gently removed, and the patient was
positioned for treatment. A conductive coupling
fluid was applied to the treatment site to ensure
uniform energy conduction, and enhance the ther-
mal and electrical contact between the treatment tip
and the skin. Two initial passes of 150 J each were
performed over the entire face to allow uniform
contraction of the collagen. We made 3 or more
additional passes of 200 J each on the periorbital,
nasolabial, and forehead areas. For each session, the
total number of passes per treatment area consisted
of the two initial passes over the entire face, followed
by 3 to 6 passes targeted to treatment regions (total of
5-8 passes/treatment region). These data are de-
scribed in Table I. Any overlap of pulses was avoided
to allow appropriate cooling of the skin for at least 3
CAPSULE SUMMARY
dMonopolar radiofrequency is a valuable
procedure that can be used to effectively
tighten and rejuvenate photoaged skin
with little downtime.
dTightening appears to continue for 3
months after the end of radiofrequency
treatment.
dRadiofrequency showed long-term
effects by enhancing collagen synthesis
and content.
JAMACAD DERMATOL
VOLUME 64, NUMBER 3
El-Domyati et al 525
minutes between the passes. During each session,
we monitored the volunteers for discomfort and
intolerable hotness; none of them experienced any
signs of edema or heat discomfort.
Treatment regimen and follow-up
Volunteers were subjected to a total of 3 months of
treatment (6 sessions at 2-week intervals). They were
instructed to avoid the use of ice packs after each
session. In addition, sun exposure was avoided using
sunscreens to promote the healing response within
the dermis and enhance collagen formation.
Photographs were taken before and immediately
after each session, and at 3 months posttreatment.
Punch biopsy specimens (3 mm) were obtained from
facial skin at baseline, end of treatment, and 3 months
posttreatment. Biopsy specimens after treatment
were taken from a site near the pretreatment biopsies.
Histologic staining and measurements
Tissues were fixed in 10% buffered formalin, em-
bedded in paraffin, and sectioned into 5 m-thick
sections. All histologic and immunohistochemical
staining, evaluation, and studies were carried out in
the Department of Dermatology and Cutaneous
Biology, Thomas Jefferson University, Philadelphia,
PA. Standard hematoxylin-eosin, Verhoeff-van Gieson
(elastic fibers), and picrosirius red staining (Direct Red
80, Sigma, St. Louis, MO) (collagen) were performed.
The epidermal thickness was measured between the
top (from the upper part of granular cell layer) to the
bottom (dermoepidermal junction) of the rete ridges.
Five measurements were calculated for each tissue
using a computerized software analyzer. Picrosirius
red was evaluated using a microscope (Nikon,
Melville, NY) equipped with filters to provide circu-
larly polarized illumination. Immunohistochemical
and picrosirius red staining was quantified using
computer-based software (Image-Pro Plus, Media
Cybernetics Inc, Silver Spring, MD).
Immunohistochemical staining
Immunohistochemistry was performed for total
elastin and collagen types I and III. Briefly, formalin-
fixed, paraffin-embedded tissue slides were heated
at 608C for 30 to 60 minutes. Tissues were then
deparaffinized in 100% xylene (5 minutes; 3 times),
100% ethanol (5 minutes; 2 times), 95% ethanol (5
minutes; 2 times), 75% ethanol (2 minutes), 50%
ethanol (2 minutes), and distilled water (H
2
O) (2
minutes). Antigen retrieval was performed by micro-
wave method in 0.1 mol/L sodium citrate (pH 6.0) for
5 minutes. To quench endogenous peroxidase activ-
ity, tissues were incubated with 3% hydrogen perox-
ide in deionized water for 10 minutes at room
temperature (RT). Endogenous biotin activity was
blocked using an avidin/biotin blocking kit (SP-2001,
Vector Laboratories, Burlingame, CA). Sections were
then blocked for 60 minutes at RT in blocking buffer
(5% normal goat serum, 1% bovine serum albumin
[BSA], and 0.02% triton-x-100 [TX-100] in phosphate
buffered saline [PBS]). Tissues were incubated with
antibodies to elastin (1:300; E4013; Sigma), type I
collagen (1:400; sc-59772; Santa Cruz Biotechnology,
Santa Cruz, CA), and type III collagen (1:600; ab6310;
Abcam, Cambridge, MA) overnight at 48C. After a 30-
minute wash in PBS, tissues were incubated with
biotinylated secondary antibody (1:200; PK-6102;
Vector Laboratories) for 60 minutes at RT, followed
by incubation with ABC reagent (Vectastain Elite
ABC peroxidase kits mouse; PK-6102; Vector
Laboratories) for 30 minutes at RT. Sections were
stained with DAB chromogen substrate kit (K3468;
Dako, Real Carpinteria, CA) for 2 to 5 minutes, and
then counterstained with hematoxylin (7211;
Thermo Fisher Scientific, Waltham, MA). Slides
were mounted with Permount (sp15-100; Thermo
Fisher Scientific) for viewing using a microscope
(Eclipse TE2000-U, Nikon). Digital images were
collected using Evolution MP camera (Media
Cybernetics Inc).
Statistical analysis
Histologic measurements and quantitative evalu-
ation were analyzed using the software package for
statistical science (SPSS for Windows, Version 16,
SPSS Inc, Chicago, IL). Statistical analysis was per-
formed using one-way analysis of variance,
Wilcoxon-matched pairs signed ranks, and x
2
tests.
Data were expressed as mean value 6SD. Statistical
significance was defined as Pless than or equal to .05.
RESULTS
Clinical evaluation
All 6 volunteers completed the monopolar RF
study, and showed clear clinical improvement of
skin tightening and rhytides in the periorbital and
forehead regions (Fig 1,A). At each end point
(before, at the end of, and 3 months after treatment),
Table I. Number of passes for each volunteer per
treatment area per session
Treated area (200 J)
n = 6 Whole face (150 J)
Periorbital Nasolabial
ForeheadRLRL
5233333
1233336
L, Left; R, right.
JAMACAD DERMATOL
MARCH 2011
526 El-Domyati et al
Fig 1. Clinical evaluation of volunteers in response to monopolar radiofrequency treatment. A,
Representative photographs of periorbital and forehead areas at baseline, end of treatment, and
3 months posttreatment. B, Volunteers’ evaluation rates showed mean percent improvement of
skin tightening (lane 1), skin texture (lane 2), rhytides (lane 3), and overall satisfaction (lane 4)
at end of treatment ( green) and 3 months posttreatment (red ) relative to baseline. C, One
volunteer developed slight erythema and mild transient hyperpigmentation 2 days after fourth
session (left), which subsided 5 days later (right).
JAMACAD DERMATOL
VOLUME 64, NUMBER 3
El-Domyati et al 527
the volunteers, two doctors, and two independent
observers were asked to evaluate the following
criteria: improvement of rhytides, skin tightening
and texture, and overall volunteer satisfaction. Their
evaluations were assessed on a 5-point scale (none =
0%, mild = 1-25%, moderate = 26-50%, good = 51-
75%, and very good = 76-100%). Results obtained
were tabulated and compared with baseline for
statistical significance with the Pearson x
2
test. The
volunteers’ evaluation rates are demonstrated in Fig
1,B. At the end of treatment, subjects showed 35% to
40% improvement in skin tightening (P= .02), 30%
to 35% improvement in skin texture (P= .04), 40% to
45% improvement in rhytides (P= .01), and 85%
to 90% volunteer satisfaction (P= .001). Three
months posttreatment, significant differences were
noticed among subjects as they showed 70% to 75%
improvements in skin tightening (P= .001), 65% to
70% improvement in skin texture (P= .002), 90% to
95% improvement in rhytides (P= .0001), and
volunteer satisfaction increased to 90% to 95% (P=
.0001). Regarding doctor and observer assessment
rates, data obtained were comparable with volun-
teers’ evaluation rates. The x
2
test demonstrated
statistically significant changes in differences within
each criterion compared with baseline. In addition,
potential side effects, including erythema, edema,
and hypopigmentation or hyperpigmentation were
evaluated on a 4-point scale (none, mild, moderate,
and severe). Only one volunteer developed slight
erythema and mild transient hyperpigmentation 2
days after the fourth session, which subsided 5 days
later (Fig 1,C). No scarring was observed.
Histologic evaluation showing epidermal
changes
Microscopic examination of hematoxylin-eosine
stained sections showed epidermal hyperplasia at
the end of treatment, which continued to increase 3
months after treatment (Fig 2). The results showed a
significant increase in the mean of epidermal thick-
ness from 62.7 62.4 m before treatment to 67 6
3.9 m at the end of treatment (P= .044), followed by
a significant increase to 79.5 69.8 m at 3 months
posttreatment (P= .002) (Table II). This was associ-
ated with overall morphologic and architectural
improvement of the epidermis with development
of rete ridges (marked undulations of the dermo-
epidermal junction). Finally, we observed an in-
crease in granular layer thickness from 6.4 61.1 m
before treatment to 9.9 61.5 m at the end of
treatment and 17.7 63.1 m at 3 months posttreat-
ment (P= .001 and .0001, respectively) (Table II and
Fig 2). This may have resulted from increase in the
number and size of the cells in the granular layer.
Quantitation of elastin amount in dermis
In photodamaged skin, the level of the connective
tissue protein elastin increases, and abnormally ac-
cumulates under the epidermis, forming so-called
Fig 2. Radiofrequency treatment enhances epidermal hyperplasia. Skin biopsy specimens
were formalin fixed and paraffin embedded. Tissue sections were stained with hematoxylin-
eosin, showing increased thickness of epidermis and granular cell layer (brackets) associated
with development of rete ridges (arrows) after RF treatment.
Table II. Histometric analysis of epidermal and granular cell layer thickness
Thickness, m*Statistical significance
Baseline
End of
treatment
3mo
Posttreatment
Baseline vs end
of treatment
End of treatment vs
3 mo posttreatment
Baseline vs 3 mo
posttreatment
Epidermis 62.7 62.4 67 63.9 79.5 69.8 .044
y
.016
y
.002
y
Granular cell layer 6.4 61.1 9.9 61.5 17.7 63.1 .001
y
.0001
y
.0001
y
*Mean 6SD; n = 6.
y
P#.05.
JAMACAD DERMATOL
MARCH 2011
528 El-Domyati et al
elastotic material. Next, we examined the effects of
RF treatment on total dermal elastin by immunohis-
tochemical staining. We observed a slight decrease in
elastin level after treatment compared with baseline,
which became more pronounced 3 months after
treatment (Fig 3,A). This decline in elastin content
was associated with translocation of the solar elas-
totic material away from the epidermis, accompa-
nied by the restoration of normal-appearing elastic
fibers within the papillary and upper reticular der-
mis. These results were confirmed when we assessed
the percent area of dermis occupied by elastin using
computerized morphometric analysis (Fig 3,B). We
detected a slight, but statistically insignificant de-
crease in elastin staining after RF treatment (49.9 6
5.3%) compared with baseline (53.7 67.4%) (Fig 3,
B). However, a statistically significant decrease in
total elastin was observed 3 months after treatment
(42.2 63.6%; P= .007).
These changes in elastin content were confirmed
by Verhoeff-van Gieson special stain (Fig 3,C). This
stain is useful in differentiating elastic tissue (blue-
black to black) from collagen (red). The elastic fibers
(shown in black) are objectively decreased in con-
tent after treatment with restoration of normal-
appearing elastic fibers within the papillary and
reticular dermis.
Evaluation of collagen changes in dermis
Evaluation of immunohistochemical staining for
total collagen (Fig 4,A, top row) revealed a narrow
collagen band (grenz zone, 9.8 63m) at the
dermoepidermal junction in volunteers before treat-
ment. This band of collagen increased slightly to
11 63.6 m at the end of treatment (P= .573). Three
months posttreatment, staining of skin biopsy spec-
imens revealed a significant increase in the thickness
of the collagen band to 15.6 62.3 m(P= .004).
Quantitative assessment of the percentage of dermis-
positive collagen showed significant increase in
content of type I collagen (Fig 4,A, middle row)
from 65.8 64.7% before treatment to 72.2 64.3% at
the end of treatment (P= .034) and 81.2 64.5% at 3
months posttreatment (P= .0001). Finally, assess-
ment of collagen type III revealed a significant
increase from 60.9 62.5% at the baseline to 66.5 6
4.4% at the end of treatment and to 73.6 64.8% at 3
months posttreatment (P= .028 and .0001, respec-
tively) (Table III and Fig 4,B). In summary, our data
show that enhancement of collagen expression
continued to increase 3 months after RF treatment.
As collagen matures, the optical properties of the
fibers show signs of an increase in birefringence (the
ability to change color under polarized light) with
consequent decrease in light penetration. When
tissues are stained with picrosirius red and viewed
under polarized microscope, large collagen fibers
stain red while the thinner ones, which represent the
newly synthesized fibers, are stained yellow to
orange.
16,17
To assess whether the increase in colla-
gen level observed by immunohistochemistry was a
result of increase in newly synthesized collagen
formation, we stained the tissues with picrosirius
red. The results showed an increase in the newly
synthesized collagen formation, as reflected by the
presence of yellow-orange birefringence, which was
significantly increased from 15.3 64.3% at baseline
to 21.7 63.1% and 26.9 63.7% (P= .014 and .001) at
the end of treatment and 3 months posttreatment,
respectively (Table III and Fig 5).
DISCUSSION
Facial rejuvenation is a developing art, and a
science. For a long time, the treatment of photoaged
skin and the reversal of the signs of aging were
focused on ablative laser resurfacing techniques, as
they yield impressive results.
18
Recently, the possi-
bility of complications, prolonged recovery time, and
avoidance of sun exposure essential to sustain opti-
mal results were reasons to decrease the attractive-
ness of ablative resurfacing.
19
There is now an
increased interest in a wide range of nonablative
treatments of skin aging, which are used to rejuvenate
skin with minimal downtime and complications.
7
The basic issue with all studies on nonablative reju-
venation relates to the methodology, as there are few
standard and objective approaches to the depth of
wrinkles, and the elasticity of skin studies. The
clinical results are eventually dependent on the
subjective observations of physicians, volunteers, or
both. Photodocumentation has also been shown to
be an insufficient way of representing the quality and
efficacy of treatment.
20-22
In this study, we aimed to
improve the subjective evaluation in the context of
objective means of evaluating the effects of monop-
olar RF on skin tightening and appearance. This was
accomplished with histochemical and immunostain-
ing techniques, and histometric evaluation of skin at
the baseline, end of treatment, and 3 months post-
treatment. Monopolar RF was approved by the Food
and Drug Administration in 2002 for the nonablative
treatment of wrinkles and skin tightening, and for
full-face treatment in 2004.
23,24
Many studies reported
that RF is best suited for patients with early signs of
aging, with mild to moderate wrinkles.
14,25-27
So, the
focus of this study was on subjects with relatively mild
to moderate degree of photoaging (Glogau I-II). In
our study, evaluation of subjects’ clinical results
showed noticeable improvement at the end of treat-
ment; with continued improvement 3 months
JAMACAD DERMATOL
VOLUME 64, NUMBER 3
El-Domyati et al 529
posttreatment. Improvements in skin tightening in-
creased from 35% to 40% at the end of treatment to
70% to 75% at 3 months posttreatment. Appearance of
facial rhytides was improved from 40% to 45% at the
end of treatment to 90% to 95% at 3 months posttreat-
ment. These mechanical properties of the skin can
also be objectively measured using different clinical
methods based on two main principles: (1) force is
Fig 3. Volunteers treated with monopolar radiofrequency showed decrease in total dermal
elastin. A, Skin tissues at baseline, end of treatment, and after RF treatment were
immunostained for total elastin. Representative samples show decrease in elastin level. Area
(rectangle) was used to assess elastin staining level. *Grenz zone. B, Percent of dermis occupied
by elastin showing significant decrease in total elastotic material after treatment. *P#.05.
C, Verhoeff-van Gieson special stain showing similar decrease in elastic fibers after RF
treatment.
JAMACAD DERMATOL
MARCH 2011
530 El-Domyati et al
Fig 4. Increase in dermal collagen content in response to radiofrequency. A, Immunohisto-
chemical staining of skin tissues at baseline (left), end of treatment (middle), and after RF
treatment (right) for total collagen (top) and collagen types I (middle) and III (bottom). Increase
in collagen band thickness at dermoepidermal junction was observed after RF treatment
compared with baseline (arrows). B, Collagen level was measured and values presented as
percentage of dermis-positive collagen. Data showed statistically significant increase in both
collagen I and III in response to RF. *P#.05; **P#.001.
JAMACAD DERMATOL
VOLUME 64, NUMBER 3
El-Domyati et al 531
applied, and the decrease in the force generated by
this distortion is calculated based on time; and (2) in
contrast, a twist is applied to the skin, and the recoil
time is measured.
28
Furthermore, additional methods
to assess skin elasticity and recoil include suction
chamber method, twistometry, levarometry, inden-
tometry, gas-bearing electrodynamo-meter, video-
microscopy, skin chip technology, and
ballistometry.
28-30
In previous studies of the RF
device, authors gave subjects a single RF treatment,
and evaluated the results. Ruiz-Esparza and Gomez
29
found that 14 of 15 volunteers had up to 50%
improvement in skin tightening, and in nasolabial
fold and periorbital wrinkles, 3 months after the
treatment session with single treatment and multiple
passes. However, two previous studies have shown
that multiple treatments with multiple passes could
give improved results.
30,31
Jacobson et al
30
treated 24
adult patients with the ThermaCool system (Solta
Medical Inc). The subjects received treatments every
1 to 3 months. The investigators did not specify how
many total treatments were applied in their study, yet
they stated that, ‘‘for patients who received more than
a single treatment, it appeared that subsequent treat-
ment sessions further improved their laxity.’’ In a
more recent study, Sukal and Geronemus
31
treated
patients with two passes on the forehead, 3 on the
cheeks, and one on the neck; each patient received
Fig 5. Increase in newly synthesized collagen content in response to radiofrequency
treatment. Representative examples of skin tissues stained with picrosirius red viewed under
bright field (top) and polarized field (bottom). Bright field captures total collagen content.
Polarized light showed yellow to orange birefringence reflecting newly synthesized collagen in
yellow and total collagen in red. Note increase in newly synthesized collagen as reflected by
yellow after RF treatment.
Table III. Quantitative analysis of total elastin and collagen (newly synthesized and types I and III) at the 3 time
points
Relative content, %*Statistical significance
Baseline
End of
treatment
3mo
Posttreatment
Baseline vs end
of treatment
End of treatment vs
3 mo posttreatment
Baseline vs 3 mo
posttreatment
Total elastin 53.7 67.4 49.9 65.3 42.2 63.6 .324 .015
y
.007
y
Newly synthesized collagen 15.3 64.3 21.7 63.1 26.9 63.7 .014
y
.024
y
.001
y
Total collagen type I 65.8 64.7 72.2 64.3 81.2 64.5 .034
y
.005
y
.0001
y
Total collagen type III 60.9 62.5 66.5 64.4 73.6 64.8 .028
y
.023
y
.0001
y
*Mean 6SD; n = 6.
y
P#.05.
JAMACAD DERMATOL
MARCH 2011
532 El-Domyati et al
1 to 3 treatments spaced 4 weeks apart. The authors
reported that patients had visible improvement at
1-month follow-up and even greater improvement at
the 3-month follow-up evaluation.
Initial studies revealed that after a single treatment,
patients showed better results with multiple passes as
compared with a single pass.
30
Furthermore, the
authors demonstrated that multiple sessions improved
results over a single session. Further review of the
literature indicates similar findings.
14,26,30,31
The in vivo response to thermal wound healing
consists of 3 consecutive stages: inflammatory, pro-
liferative, and remodeling.
3
This might explain why
clinically visible results were only achieved between
3 and 6 months after the start of treatment.
Photoaged skin is associated with a decrease in
epidermal thickness with flattening of the rete
ridges.
32
Although observed RF energy targets the
dermal layer, in this study we observed striking
changes in histologic features of the epidermis that
need further studies to be explained; we showed a
noticeable increase in epidermal thickness at the end
of treatment, and at 3 months posttreatment, espe-
cially in the granular cell layer (Fig 2). These findings
suggest that proliferation of cells in the epidermis is
increased, and perhaps may contribute to the im-
provement of skin appearance.
Unlike most lasers that target specific chromo-
phores, the output energy of the monopolar RF is
chromophore independent; it is transformed into
heat mainly by water within the tissues. As a result,
the energy is delivered to 3-dimensional levels of the
dermis.
10
The depth of thermal injury is limited to
100 to 400 m below the epidermis, the area where
most elastotic material is histologically seen.
33
Microscopic changes associated with wrinkles occur
primarily in the dermis. In sun-damaged skin, the
main dermal alteration is the deposition of large
clumps of abnormal elastotic material, replacing the
normally collagen-rich dermis.
34
In this study, we
evaluated the changes induced by RF on total elastin,
as it is one of the major changes occurring in aged
skin. Our results showed an insignificant change in
total elastin content at the end of treatment, followed
by significantly decreased elastic tissue 3 months
posttreatment. This decrease was accompanied by
downward placement and subsidence of the elas-
totic materials with reorientation of the elastic fibers.
Improvement of the quality of elastic fibers and solar
elastosis can be explained by the effect of RF on
collagen formation and newly synthesized collagen,
which replaces the elastotic materials with the redi-
rection of dermal matrix fibers. The reorientation of
elastic fibers may reflect the synthesis of new elastic
fibers with proper assembly.
It is speculated that heat generated by RF affects
the molecular structure of the triple helix of the
collagen molecule, with subsequent breakage of
intramolecular hydrogen bonds, resulting in colla-
gen fibril denaturation with immediate contraction.
8
Over time, as a thermally mediated healing response,
fibroblasts are stimulated to enhance new collagen
deposition and remodeling, resulting in further col-
lagen tightening, and an overall increase in collagen
content.
11
Bassichis et al
35
have revealed an addi-
tional potential mechanism of action for monopolar
RF; the subcutaneous fat lobules are separated by an
interlacing network of collagen-based fibrous septa.
As RF energy usually follows the path of least
resistance, fibrous septa are preferentially heated,
resulting in the contraction of collagen fibers,
35
which is thought to be the key in subsequent
remodeling of subcutaneous tissue and tightening
of the skin, which becomes attached to the under-
lying structures.
36
In our study, we assessed the effect of RF on
collagen content and formation, starting with the
evaluation of collagen presentation under the epi-
dermis. We found a slight increase in the narrow
collagen band grenz zone thickness present at the
dermoepidermal junction, followed by a significant
increase in thickness 3 months posttreatment.
Normal dermal collagen fibers account for approx-
imately 80% of its dry weight, and are responsible for
its tensile properties. Dermal collagen is primarily
composed of type I (80%-85%) and type III (10%-
15%) collagen.
5,34
Wrinkle reduction, by means of
thermal heat delivered to the dermis, is based on the
stimulation of new collagen formation, and in this
study, quantitative evaluation of dermal collagen
revealed a significant increase in both type I and III
collagens at the end of treatment. These findings are
in agreement with previous studies demonstrating
new formation of type I and III collagens after RF
treatment.
37-39
However, our study showed a con-
tinued significant increase in type I and III collagens
3 months posttreatment. We further assessed the
effect of RF on new collagen formation, and whether
the increase in collagen level as observed by immu-
nohistochemistry was a result of the enhancement of
newly synthesized collagen formation. Detection of
newly synthesized collagen with picrosirius red
under polarized microscopic examination showed
significantly increased newly synthesized collagen at
the end of treatment, and at 3 months posttreatment,
compared with baseline, reflecting the positive re-
sponse obtained by RF on both total collagen and
new collagen formation.
In spite of the protective mechanisms provided
with the RF tip, one volunteer developed slight
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VOLUME 64, NUMBER 3
El-Domyati et al 533
erythema and mild transient hyperpigmentation 2
days after the fourth session. This complication
might have occurred as a result of uneven contact
of the treatment tip with skin surface, resulting in an
accumulation of RF energy in a single treatment area.
This complication subsided without relapse. One
obvious limitation to our study is the relatively small
number of volunteers. Nevertheless, the results
showed evidence of clinical and histologic improve-
ment after RF treatment. Although previous publica-
tions have suggested improvement after RF with skin
changes, including face tightening, few have histo-
logically analyzed the skin of the volunteers
treated.
8,34,40,41
In conclusion, monopolar RF is an effective and
valuable procedure that can be used to tighten and
rejuvenate photoaged skin, and contour facial skin
laxity. This modality stimulates the repair process,
and reverses the clinical, and the histopathological,
signs of aging, with the advantage of relatively risk-
free procedure and with little downtime.
The authors thank Carol Kelly and Alicia Dowling for
their help in the preparation of this article.
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  • ... These modalities are either topical agents or procedural agents. Procedural agents include microdermabrasion, chemical peeling, lasers, and radiofrequency [2] . ...
    ... El-Domyati (2011), showed a modest increase in epidermal thickness at the end of treatment and after 3 months from last session, especially in the granular cell layer with a significant increase in both type I and III collagens [2] . ...
  • ... RF with the frequencies ranging from 20 kHz to 300 GHz, including radio waves and microwaves, is considered a low-energy and non-ionizing radiation. 10 RF has branched out into the medical context of various modern electrotherapies 11 and has recently been exploited in the aesthetic field, for instance, skin tightening 12 and cellulite reduction. 13 Despite its benign character and, therefore, extensive ...
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  • ... The number of individuals seeking facial rejuvenation continue to increase worldwide 6 . Data on auricular dimensions based on the age, sex, ethnicity and race of the client/patient is required by reconstructive surgeons for effective correction 7 . ...
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  • ... A typical rejuvenation procedure conducted in these beauty clinics is shown in Fig. 1, where the dermatologist (or "skin technician" [8]) visually examines the skin condition to determine the type of treatment to be performed along with the appropriate laser light parameters [9]. A non-ablative instrument is then manipulated with repetitive motion patterns over different areas of the face to stimulate the skin tissues; It must be activated with the exact amount of energy and time to produce the expected result without causing damage [10]. ...
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    In this paper, we present a novel robotic system for skin photo-rejuvenation procedures, which can uniformly deliver the laser's energy over the skin of the face. The robotised procedure is performed by a manipulator whose end-effector is instrumented with a depth sensor, a thermal camera, and a cosmetic laser generator. To plan the heat stimulating trajectories for the laser, the system computes the surface model of the face and segments it into seven regions that are automatically filled with laser shots. We report experimental results with human subjects to validate the performance of the system. To the best of the author's knowledge, this is the first time that facial skin rejuvenation has been automated by robot manipulators.
  • ... The heat causes initial collagen contraction and subsequent new collagen synthesis through long-term repair processes, resulting in dermal remodeling and skin tightening. It is hypothesized that since RF is not selectively absorbed by chromophores is safe in darker skin (13). More recently, fractional radiofrequency (FRF) has gained traction as the last generation stratagem combining efficacy and safety in skin rejuvenation. ...
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    Fractional radiofrequency (FRF) has recently emerged for the treatment of scars, cellulite and skin rejuvenation. The aim of this paper was to investigate the evidence behind its use in skin aging and evaluate efficacy, safety, and standardization of protocols. The literature was systematically searched and finally 25 full-text articles were included. Two were randomized controlled trials, 3 were comparative studies, and 20 were case series. Most studies were underpowered with low methodological quality. The participants had skin phototype I-VI with variable baseline severity of signs. Fractional radiofrequency using microneedles or electrode pins was performed on the face, neck, and décolletage. There was heterogeneity in outcomes measurement, but the efficacy of FRF was confirmed in all relevant studies. Mainly, the improvement of rhytides and skin tightening were reported. Mild to moderate pain, transient erythema and edema were the commonest adverse events. Hyperpigmentation was also noted in some cases. There was no consistency in the protocols used and in the description of procedures. A clinical impact score was created to assess the studies and to aid the generation of an evidence-based protocol for minimally invasive radiofrequency procedures. However, there is a need for large scale, well-designed trials to better investigate the efficacy and safety of FRF and to produce clear guidelines.
  • ... Unlike the non-ablative lasers, RF devices do not rely on the chromophore for efficacy or safety, and thus, are suitable for all skin types (17). RF devices utilize electrical current to produce heat (5). ...
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  • ... A similar result is obtained with the blepharoplasty. In addition, photographic registration and measurement of eyelid distances are procedures that allow quantitative assessments and reinforce the results of some treatment techniques, whether conservative or not (Domyati et al., 2011;Silva and Tokars, 2013). ...
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  • ... A similar result is obtained with the blepharoplasty. In addition, photographic registration and measurement of eyelid distances are procedures that allow quantitative assessments and reinforce the results of some treatment techniques, whether conservative or not (Domyati et al., 2011;Silva and Tokars, 2013). ...
  • Article
    Background A monopolar radiofrequency device can be used in facial tightening. The device targets the dermis and fibrous septae, and the treatment results in immediate collagen contraction and the induction of subsequent collagen remodeling. Aims We aimed to evaluate the histometric change of the subjects treated with a monopolar radiofrequency device using a novel tip. Materials and Methods Eleven subjects with skin types III and IV participated in the study. They received a single session of a monopolar radiofrequency on the face, and biopsies were performed before treatment, and 2 and 6 months after the treatment. Hematoxylin and eosin, Masson trichome, and Victoria blue stains were used. An image analysis was performed using the Image J software. The dermal density of collagen and elastic fiber, and the coherency of collagen fibers were assessed in the papillary, upper reticular, and lower reticular dermises, respectively. Results The monopolar radiofrequency treatments led to improvements in collagen fiber density and coherency. In the Masson trichome staining, the collagen fiber densities were 0.736±0.06 and 0.652±0.063 before treatment and increased to 0.773±0.044 (p=0.018) and 0.686±0.05 (p=0.045) in the papillary and lower reticular dermises, respectively. The density of the elastic fibers in all parts of the dermis showed a tendency to increase after treatment, though not statistically significantly. The mean coherency was higher after than before treatment. Conclusions In this in vivo study, we found that the collagen and elastic fiber densities were and architectural structures were improved after treatment.
  • Chapter
    Nonsurgical techniques for rejuvenation have dramatically expanded in recent years and, with this, so have noninvasive techniques, technologies, and devices specifically directed toward tightening the skin. In general, the two technologies primarily utilized for skin tightening are ultrasound and radiofrequency. This chapter seeks to review the available literature discussing the indications, effectiveness, preoperative and postoperative considerations, treatment techniques, and safety of the presently available technologies and methods for noninvasive skin tightening. The available literature suggests noninvasive tightening modalities are generally safe and effective with little downtime and minimal side effects. However, of paramount importance are appropriate patient selection and managing patient expectations preoperatively.
  • Article
    BACKGROUND: Many subjects wish to have tightening of eyelid skin but are reluctant to undergo aesthetic blepharoplasty surgery. We wanted to perform a small pilot study to test the efficacy and safety of a 0.25-cm² monopolar radiofrequency tip in a prospective noncomparative study as a novel nonsurgical method to safely tighten upper and lower eyelid skin in subjects of differing ethnicity and sex. METHODS: Twenty adult subjects were enrolled in this prospective pilot study. All received symmetrical monopolar radiofrequency treatments in multiple passes to the pretarsal, preseptal, and lateral orbital skin. All subjects wore a protective plastic haptic contact lens to protect their vision during the radiofrequency treatment. (Haptic contact lenses fit over the entire anterior surface of the globe from superior to inferior and medial to lateral fornix. The purpose of using such a large contact lens was to protect the globe itself from radiofrequency energy.) Standardized color digital photography with eyes both open and closed was taken on each visit. Treatment efficacy was evaluated by both the expert observer and the subject at each visit. RESULTS: At 6-month follow-up, according to the expert observer, 26 upper lids (87%) showed 25% or more tightening. Twenty lower lids (67%) showed 25% or more tightening. Two subjects (3.33%) had 51% to 75% upper lid tightening at 6 months. There were no adverse events beyond one subject with minimal corneal epithelial punctate defects on the treatment day. These resolved over several hours. CONCLUSIONS: The use of this new tip was shown to be safe. Effectiveness at shrinking eyelid skin was at best mild to moderate.
  • Article
    INTRODUCTION: Monopolar radiofrequency is an effective means of nonsurgical facial skin tightening. OBJECTIVE: The objective of this study was to determine whether using larger tips at lower energy and multiple passes, using patient feedback on heat sensation and treating to a clinical end point of visible tightening, would yield better results than single passes with small tips at high energy, as measured by patient and physician satisfaction. METHODS: Fourteen physicians from four specialties were surveyed to determine the answers to the following three questions. (1) Is patient's feedback on heat sensation a valid and preferred method for optimal energy selection? (2) Do multiple passes at moderate energy settings yield substantial and consistent efficacy? (3) Is treating to a clinical end point of visible tightening predictable of results? RESULTS: A total of 5,700 patient treatments were surveyed. Comparisons were made using the original algorithm of high-energy, single pass to the new algorithm of lower energy and multiple passes with visible tightening as the end point of treatment. Using the original treatment algorithm, 26% of patients demonstrated immediate tightening, 54% observed skin tightening 6 months after treatment, 45% found the procedure too painful, and 68% of patients found the treatment results met their expectations. With the new multiple-pass algorithm, 87% observed immediate tightening, 92% had the tightening six months after treatment, 5% found the procedure too painful, while 94% found the treatment results met their expectations. CONCLUSIONS: Patient feedback on heat sensation is a valid, preferable method for optimal energy selection in monopolar radiofrequency skin-tightening treatments.
  • Article
    Clinically detectable, age-associated cutaneous changes result from two independent processes: chronologic aging and actinic irradiation. Several lines of evidence suggest that these two processes have different biologic, biochemical, and molecular mechanisms. This review summarizes the current understanding of age-associated alterations in the biochemistry and molecular biology of the extracellular matrix.
  • Article
    Nonablative remodeling has been recently proposed as an alternative to CO2 and Er:YAG resurfacing. To evaluate the efficacy and safety of a 1540 nm Er:glass laser with contact cooling in nonablative skin remodeling, focused on perioral and periorbital rhytides. Sixty patients (mean age 47 years), Fitzpatrick skin types I-IV were treated four times over 6-week intervals. Patients were evaluated using digital photographs, histology, ultrasound imaging, and profilometry with silicone imprints in order to quantitate the degree of clinical improvement. All subjects reported subjective improvement in the quality and visual aspect of their skin. This was confirmed by a 40.2% reduction of anisotropy (P <.001) 6 weeks after the fourth treatment. Ultrasound imaging demonstrated a 17% increase of dermis thickness (P <.005). Biopsy specimens showed evidence of new collagen formation. This study has clearly demonstrated that irradiation with 1540 nm Er:glass laser can lead to new collagen formation, dermis thickening, reduction of anisotropy of the skin, and clinical improvements. The lack of adverse effects confirmed that this 1540 nm laser emitting in a pulsed mode coupled with an efficient cooling system is safe.
  • Article
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