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Phototherapy with Light Emitting Diodes: Treating a Broad Range of Medical and Aesthetic Conditions in Dermatology

Authors:
  • Ablon Skin Institute & Research Center

Abstract and Figures

Within the field of dermatology, advances in the use of light emitting diodes (LEDs) have led to their clinical application for a variety of medical and cosmetic uses. Of note, one phototherapy device has demonstrated beneficial effects over a range of clinical applications (Omnilux™; GlobalMed Technologies, Glen Ellen, California). The study included a literature review of published studies. Using LEDs with frequencies of 415nm (blue), 633nm (red), and 830nm (infrared), this device has demonstrated significant results for the treatment of medical conditions, including mild-to-moderate acne vulgaris, wound healing, psoriasis, squamous cell carcinoma in situ (Bowen's disease), basal cell carcinoma, actinic keratosis, and cosmetic applications. Although photodynamic therapy with the photosensitizer 5-aminolevulinic acid might cause stinging and burning, phototherapy is free of adverse events. We determined that phototherapy using LEDs is beneficial for a range of medical and aesthetic conditions encountered in the dermatology practice. This treatment displays an excellent safety profile.
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JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY February 2018 • Volume 11 • Number 2
REVIEW
A
An increasing number of individuals are seeking
noninvasive procedures for improving medical and
aesthetic dermatologic conditions. Phototherapy
refers to the use of nonthermal, noninvasive light
to achieve a therapeutic outcome and can apply
to a variety of light-emitting devices. Interest in
recent advances in the use of light emitting diodes
(LEDs) has led to their clinical application for a
variety of medical and cosmetic uses. Depending
on the target chromophore, dierent wavelengths
of light are used.1 Three wavelengths of light
that have demonstrated several therapeutic
applications are blue (415nm), red (633nm), and
near-infrared (830nm). Recent publications have
reignited an interest in the numerous studies
performed or sponsored by a leader in the eld
of LED phototherapy (Omnilux™; GlobalMed
Technologies, Glen Ellen, California) which clearly
demonstrate the signicant value of phototherapy
for a range of clinical applications (Figure 1). In
my private practice, LED technology is the most
commonly performed procedure and is used each
oce day to treat a wide variety of medical and
aesthetic disorders. This review will describe the
broad range of clinical applications and signicant
results achieved for acne, wound healing, actinic
keratosis, precancerous tissue, psoriasis and skin
rejuvenation, and post-procedural erythema.
Signed photoconsent was provided by the patients
pictured herein.
MEDICAL APPLICATIONS
Mild-to-moderate acne vulgaris.
Propionibacterium acnes (P. acnes) is a gram-
positive bacterium involved in the pathogenesis
of acne vulgaris.2 In-vitro studies have
demonstrated that blue light is eective
for treating P. acnes because it produces the
strongest photoactivation of endogenous
porphyrins through a process known as
endogenous photodynamic therapy (PDT). The
result is free radical formation and destruction
of the P. acnes cell membrane.3 An open-label
clinical study assessed the safety and ecacy
of narrowband blue light on inammatory and
noninammatory acne lesions in patients with
mild-to-moderate facial acne (N=30).4 Subjects
had not used topical, oral, or systemic treatments
for two weeks and had not received oral retinoids
for six months. Baseline lesions were counted
and recorded by lesion type. Subjects received
eight 10- or 20-minute light treatments using
LEDs with peak wavelengths of 409nm to 419nm
(40mW/cm2) over a four-week period. Lesion
counts were repeated at Weeks 5, 8, and 12. A
benecial eect on inammatory lesions was
observed at Week 5, becoming signicant at
Weeks 8 and 12. The mean percent reduction
in lesion counts at each time point was 25
percent, 53 percent (p<0.001), and 60 percent
(p<0.001), respectively; however, there was
little eect on noninammatory lesions. Adverse
events included mild and transient erythema,
skin dryness, and pruritis.
A second open-label study assessed the
eects of phototherapy using LEDs emitting
blue 415nm light at 48J/cm2 to treat subjects
with mild-to-moderate acne (N=45).5 Subjects
ABSTRACT
Within the eld of dermatology, advances in the use of
light emitting diodes (LEDs) have led to their clinical
application for a variety of medical and cosmetic uses.
Of note, one phototherapy device has demonstrated
benecial eects over a range of clinical applications
(Omnilux™; GlobalMed Technologies, Glen Ellen,
California). The study included a literature review of
published studies. Using LEDs with frequencies of 415nm
(blue), 633nm (red), and 830nm (infrared), this device
has demonstrated signicant results for the treatment
of medical conditions, including mild-to-moderate
acne vulgaris, wound healing, psoriasis, squamous
cell carcinoma in situ (Bowen’s disease), basal cell
carcinoma, actinic keratosis, and cosmetic applications.
Although photodynamic therapy with the photosensitizer
5-aminolevulinic acid might cause stinging and burning,
phototherapy is free of adverse events. We determined
that phototherapy using LEDs is benecial for a range
of medical and aesthetic conditions encountered in the
dermatology practice. This treatment displays an excellent
safety prole.
KEYWORDS: Light-emitting diodes, phototherapy,
photodynamic therapy, skin rejuvenation, acne vulgaris,
periorbital wrinkles
Phototherapy with Light
Emitting Diodes: Treating a Broad
Range of Medical and Aesthetic
Conditions in Dermatology
by GLYNIS ABLON, MD, FAAD
Dr. Ablon is with the Ablon Skin Institute and Research Center in Manhattan Beach, California.
J Clin Aesthet Dermatol. 2018;11(2):21–27
FUNDING: No funding was provided for this article.
DISCLOSURES: The author has no conicts of interest to relevant to the content of this article.
CORRESPONDENCE: Glynis Ablon, MD, FAAD; Email: drablon@abloninstitute.com
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JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY February 2018 • Volume 11 • Number 2
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received two 20-minute treatments weekly for 4
to 8 weeks, and clinical assessments were made
at baseline and two, four, and eight weeks post-
treatment. Therapeutic response was measured
using a global improvement scoring system: 0
(no improvement), 1 (0–25% improvement),
2 (25–50% improvement), 3 (51–75%
improvement), and 4 (76–100% improvement).
Among the evaluable subjects (n=43), the mean
improvement score was 3.14 at four weeks and
2.90 at eight weeks. Nine patients experienced
complete clearing at eight weeks, and 50
percent of subjects were highly satised with the
treatment. There were no adverse events.
Since it had been demonstrated that
phototherapy with combined blue and red
light could achieve even greater ecacy in the
treatment of acne,6 an open-label study was
designed to assess the ecacy of combining
415nm blue light and 633nm red light for treating
subjects with mild-to-moderate facial acne.7
Enrolled subjects (N=24) with Fitzpatrick Skin
Types II to V had not received treatment with
oral or topical acne agents during the six weeks
preceding the trial or oral retinoid use in the
previous nine months. Subjects with a history
of photosensitivity disorder were excluded. Each
subject received two treatments per week, three
days apart, alternating between 415nm blue
light (20 minutes/session, 48J/cm2) and 633nm
red light (20 minutes/session, 96J/cm2) for four
weeks using an LED-based therapy system.
Patients received a mild microdermabrasion
prior to each treatment session. The purpose of
microdermabrasion is to provide a nonchemical
supercial removal of the stratum corneum.
This allows products or other procedures to pass
more readily through the protective barrier
of the epidermis. While recent studies have
reported some histologic changes in the dermis
on collagen density with microdermabrasion,
published data demonstrate improvement
of acne when microdermabrasion is used in
combination therapy.8
Acne severity was assessed at baseline and
at Weeks 2, 4, 8, and 12. Among the evaluable
subjects (n=22), a mean reduction in lesion count
was observed at each follow-up evaluation. At
the four-week follow-up, the mean lesion count
was reduced by 46 percent (p=0.001) and by 81
percent at the 12-week follow-up (p=0.001).
Severe acne showed a marginally better response
than mild acne, although comedones did not
respond as well as inammatory lesions. This
is a common nding in light therapy studies
because noninammatory acne lesions have
fewer chromophores (coproporphyrin III and
protoporphyrin IX).9 Adverse events were mild and
transient.
A similar study assessed the same treatment in
subjects with Fitzpatrick Skin Type IV and mild-to-
moderately severe facial acne (N=24).10 Subjects
had not used topical acne treatment or systemic
antibiotics within the two weeks of the trial or
systemic retinoids within three months. Subjects
with a history of photosensitivity or recent use of
photosensitizing drugs were excluded. Treatment
was performed twice weekly for four weeks with
alternating quasi-monochromatic blue (415nm)
and red (633nm) light. Clinical assessments were
conducted at baseline and following Treatments 2,
4, and 6, as well as two, four, and eight weeks after
the nal treatment. Evaluations included lesion
counts and an acne grading scale. The nal mean
percentage improvements in noninammatory
and inammatory lesions were 34.2 percent and
77.9 percent, respectively. Changes in acne lesion
type are summarized in Table 1.
Phototherapy and wound healing. Pre-
clinical in-vitro studies and early clinical studies
demonstrated LEDs developed by the National
Aeronautics and Space Administration (NASA) had
benecial eects on wound healing.11,12 Based
on these reports, the following controlled pilot
study was performed to determine whether LED
phototherapy might enhance wound healing
following surgical aesthetic and resurfacing
procedures.13 Male (n=2) and female (n=8)
subjects with a mean age of 52.3 years (range 44–
59 years) underwent combined blepharoplasty
and Er:YAG/CO2 laser ablative resurfacing.
Subsequently, one-half of each subject’s face was
randomly selected and treated with a 633nm (96J/
cm2) red LED for 20 minutes immediately after
surgery, 48 hours post-surgery, and twice more
the following week. Subjects were assessed 24
and 48 hours after surgery, at seven and 10 days,
and at two, three, and six weeks. Resolution of
erythema, edema, bruising, and days to healing
was assessed using digital photography and was
reviewed by a blinded and independent plastic
surgeon. The LED-treated side healed after a mean
(SD) of 13.5 (0.34) days versus 26.8 (0.49) days for
the untreated side (p<0.0001; Table 2).
These same investigators conducted a larger
study to further assess the benecial eects
of LED phototherapy on wound healing.14 The
study involved a prospective treatment arm and
a retrospective analysis of a matched cohort. The
prospective study population included female
patients (N=28) who underwent ablative Er:YAG/
CO2 laser resurfacing (4 full-face, 8 periocular,
16 perioral). This was immediately followed by
exposure to LEDs emitting infrared 830nm light
(55 J/cm2) for 20 minutes and red 633nm light (98
J/cm2) for 20 minutes, which was repeated after 72
hours. Two additional treatments were performed
three days apart during the following week and a
nal session during the third week. Digital images
were obtained after 24 hours, three days, one,
TABLE 1. Mean change in acne lesions at baseline and eight weeks post-treatment
LESION TYPE BASELINE, MEAN SD POSTTREATMENT
WEEK 8, MEAN SD SIGNIFICANCEA
Closed comedones 38.5 (26.1) 21.4 (15.9) 0.0007
Open comedones 9.5 (11.0) 6.4 (10.3) 0.752
Papules 28.9 (14.7) 7.2 (4.8) <0.0001
Pustules 6.5 (4.0) 0.5 (0.8) <0.0001
Nodules or cysts 1.0 (1.6) 0.1 (0.5) 0.00129
aPaired t-test from Lee et al 200710 SD: standard deviation
FIGURE 1. Light-emitting diode phototherapy device
(Omnilux™, GlobalMed Technologies, Glen Ellen, California
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JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY February 2018 • Volume 11 • Number 2
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two, four, and six weeks, and three and six months
post-resurfacing. The retrospective group included
the same number of age- and treatment-matched
subjects who did not receive LED therapy and
were evaluated three and six months post-
resurfacing. Healing response was rated as Very
Good (85–100% improvement), Good (65–84%
improvement), Fair (45–64% improvement), Poor
(<45% improvement), or Bad (little improvement
or worsened). Overall, mean ecacy results
were similar across treatment groups (Table 3).
No subjects were rated as Poor or Bad. At the
three-month assessment, the overall ecacy of
the prospective-treated group (Very Good + Good)
was signicantly better than both the prospective-
control and retrospective groups (p<0.01). At the
six-month assessment, the prospective-treated
group showed slightly better improvement than
the other two groups, but the dierence was not
signicant. The symptoms of exudation, crusting,
pain, and edema resolved approximately 50
percent faster in the prospective-treated group
(p<0.001) as did erythema (p<0.0001). At six
months, there was no signicant dierence in
wrinkle improvement between the prospective-
treated and untreated side, but the skin appeared
younger-looking on the LED-treated side. These
results have been conrmed in several subsequent
studies.13,15–17
Psoriasis. In the Unites States, the incidence
of psoriasis in adults has been increasing from
50.8/100,000 during the 1970s to 100.5/100,000
during the 1990s.18 As increasing attention was
being paid to visible red (633nm) and near infrared
(830nm) light-emitting diodes for treating
various dermatological conditions, the following
pilot study was designed to assess the ecacy of
combining 830nm and 633nm LED phototherapy
for treating recalcitrant psoriasis.19 Informed and
consenting subjects with psoriasis (N=9) with
a mean age of 34.3 years and Fitzpatrick Skin
Types I to IV were enrolled. All had chronic plaque
psoriasis (n=8) and guttate psoriasis (n=1) of up
to 35 years duration and aecting 15 to 80 percent
of their body surface area. Most had become
resistant to conventional treatments.
Each subject was treated sequentially with LED
arrays delivering continuous-wave 830nm, 60J/
cm2 and 633nm, 126J/cm2 during two weekly
20-minute sessions for 4 to 5 weeks with two days
between sessions. Specied psoriatic plaques or
guttate papules were chosen to be treated. All
subjects completed their LED regimens with ve
subjects requiring a second treatment regimen.
Among evaluable subjects (n=7) at three- to
four-month follow-up evaluations, clearance
rates ranged from 60 to 100 percent of specied
treatment sites. Overall patient satisfaction was
very high. Protoporphyrin present in psoriatic skin
apparently acts as a photosensitizer. A subsequent
study further demonstrated the benecial eects
of phototherapy for treating psoriasis.20
Photodynamic therapy (PDT): phototherapy
combined with 5-aminolevulinic acid. PDT involves
administration of a light-sensitive substance,
or photosensitizer, followed by exposure to the
wavelength of light that corresponds to the
absorbance band of the sensitizer. Both red
and blue LED, as well as intense pulsed light
technology, have been used to activate the
photosensitizer. Cytotoxic free radicals form in the
presence of oxygen which causes cell death.21 The
most common photosensitizer is 5-aminolevulinic
acid (ALA). Photodynamic therapy with ALA has
been used to treat a range of conditions, including
from pre-cancerous and cancerous lesions22,23 and
photoaged skin.24,25
Squamous cell carcinoma in situ (Bowens
disease). The safety and ecacy of PDT was
compared with cryotherapy for treating Bowens
disease.26 Lesions were randomized to undergo
cryotherapy with liquid nitrogen (n=20) or PDT
(n=20) using ALA as the photosensitizer. ALA was
applied topically four hours prior to irradiation
(125J/cm2; 70 mW/cm2). Subjects were evaluated
every two months and retreated as needed.
TABLE 2. Patient characteristics and days to healing
PATIENT SEX AGE DAYS TO HEALING SKIN TYPE
TREATED UNTREATED
1 M 58 14 27 III
2 F 46 13 27 III
3 F 49 15 29 IV
4 F 57 12 26 IV
5 F 55 14 28 III
6 F 48 13 25 II
7 F 50 14 27 III
8 F 58 15 29 II
9 M 59 13 25 III
10 F 44 12 25 IV
Mean (SD) -- 52.4 (5.6) 13.5 (0.34) 26.8 (0.49)a--
aSignicant between-group dierence (p<0.0001). From Trelles et al 200613
FIGURE 2. The eectiveness of phototherapy for the treatment of rosacea is clearly demonstrated in this patient before
(left) and three months after nine weekly treatment sessions with a red light emitting diode (right). Images courtesy of
the author.
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Cryotherapy produced clearance in 10 lesions after
one treatment, with the remaining 10 lesions
requiring two or three additional treatments.
PDT resulted in clearance of 15 lesions after one
treatment and the remaining ve lesions after a
second treatment. The probability that a lesion
cleared after one treatment was signicantly
greater with PDT (p<0.01). Cryotherapy was
associated with ulceration (n=5), infection (n=2)
and recurrent disease (n=20). No adverse events
were associated with the use of PDT.
Another controlled study assessed the relative
ecacy of red and green light for the treatment
of Bowen’s disease.27 Four hours following the
application of 20% ALA, lesions were exposed
to red 630±15nm (125J/cm2) (n=32) or green
540±15nm (62.5J/cm2) (n=29) light. The initial
clearance rate for lesions treated by red light was
94 percent versus 72 percent (21 of 29) for green
light (p=0.002). Over the following 12 months,
there were two recurrences in the red light group
and seven in the green light group, reducing
the overall clearance rates to 88 percent and 48
percent, respectively.
Based on these results, an open-label study
assessed the ecacy of PDT using 630±15nm
(100J/cm2) to treat Bowens disease consisting of
40 large lesions greater than 20mm in diameter
and 45 multiple lesions.28 ALA was used as the
photosensitizer. Among the large lesions, 35
(88%) cleared after 1 to 3 treatments. Five lesions
failed to clear but all showed partial response.
Among the multiple lesions, 44 (98%) cleared
following one or two treatments; however, four
lesions cleared after 12 months, reducing the
clearance rate to 89%.
Basal cell carcinoma. Despite the success of PDT
using ALA for Bowen’s disease, supercial basal
cell carcinoma of the skin (BCC) often respond
poorly. The results of several studies report relapse
rates of 50 percent or greater.29–31 The objective of
this open-label study was to determine whether
a second PDT treatment after seven days could
improve outcomes. One hour following the
application of 20% ALA, six subjects with 26 BCC
lesions were treated with 630±15nm red light
(120–134J/cm2; 50±100mW/cm2). The treatment
was repeated after seven days. A complete
response rate of 100 percent was observed one
month after treatment. During a median follow-
up of 27 months (range, 15–45 months), relapse
of one lesion occurred after 16 months. Cosmetic
results were excellent.
Actinic keratosis (AK). AK refers to rough, scaly
lesions that can occur following long-term sun
exposure in fair-skinned individuals. Consequently,
they most often occur on the face, forearms,
and back of the hands.32 AKs are precancerous
and might eventually progress to squamous cell
carcinoma if left untreated.21 PDT provides good
cure rates and excellent cosmetic outcomes when
used for the treatment of AK.21,33 Our review found
that when PDT was used with 20% ALA cream
or solution, long-term cure rates were reported
to be 78 to 89 percent using blue light and 85 to
89 percent using red light.21 The following trial
described the ecacy of PDT for the treatment of
AK.
Initially, human epidermal keratinocytes were
incubated for 24 hours with ALA ranging from 100
to 500µmol/L and irradiated using 633nm light
(3 to 24J/cm2).34 Cell viability was signicantly
reduced. Maximal cytotoxic eects were achieved
using a light dose of 24J/cm2. Subsequently, a
clinical ALA-PDT study was performed on 40
subjects with 294 AK lesions.34 Subjects were
included only if they showed a lesion distribution
suitable for a two-sided comparison. Most lesions
(81%) were located on the face or scalp, 15 percent
were located on the hands, and four percent were
located on the limbs. The treatment groups were
very similar with respect to number of lesions
and lesion grades. ALA 20% in a cream base was
applied to each lesion and 5mm of surrounding
normal tissue. After a four-hour incubation period,
subjects were treated with 633nm light (40J/
cm2). Immediately following treatment, subjects
scored pain severity using an 11-point (0–10)
scale. Subjects were evaluated after six, 12, and
24 weeks.
The overall six- and 24-week complete
response rates were 84.3 percent and 38.8 percent,
respectively.34 All treated lesions developed
erythema and crusting 2 to 4 days after treatment,
FIGURE 3. The eectiveness of phototherapy for the treatment demodex folliculitis is clearly evident in this patient before
(left) and after 7 weekly treatment sessions with a red light=emitting diode (right). Images courtesy of the author.
TABLE 3. Mean ecacy ratings
RATING RETROSPECTIVE N % PROSPECTIVE UNTREATED N % PROSPECTIVE TREATED N %
3 MONTHS
Very Good 17 (61) 18 (64) 19 (68)
Good 7 (25) 6 (22) 7 (25)
Fair 4 (14) 4 (14) 2 (7)
6 MONTHS
Very Good 19 (68) 20 (72) 21 (75)
Good 8 (29) 7 (25) 7 (25)
Fair 1 (3) 1 (3) 0 (0)
From Trelles et al 200614
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REVIEW
which lasted approximately 10 to 14 days. After
that time, all subjects showed excellent cosmetic
results. The most common adverse event (100%)
was stinging and burning pain during and after
irradiation with a mean (SD) pain score of 6.95
(1.73). No patient discontinued treatment due to
discomfort.
AESTHETIC APPLICATIONS
Skin rejuvenation. LEDs have also been used
to improve the appearance of photoaged skin.
In contrast with thermal-based skin-tightening
devices, such as radiofrequency and focused
ultrasound,35 LEDs do not produce thermal
injury. The skin-rejuvenating eects of LED
systems are produced by a mechanism known as
photobiomodulation.36,37 This nonthermal process
involves exciting endogenous chromophores to
elicit photophysical and photochemical events.
Photobiomodulation stimulates broblast
proliferation, collagen synthesis, growth factors,
and extracellular matrix production by activating
cellular mitochondrial respiratory pathways. The
result is lifting and tightening lax skin and the
reduction of rhytids.
One small, controlled study (N=23)
demonstrated the eectiveness of a 633nm (96 J/
cm2) LED light when administered as 20-minute
treatments three times weekly for three
weeks.38 Subjects had not received any aesthetic
treatments within the previous six months before
initiation of the study treatment. Improvements
included reduction in ne lines and wrinkles and
softer, smoother skin. No adverse events were
reported. Another small controlled study (N=31)
demonstrated the eectiveness of combining a
633nm (126J/cm2) LED and a 830nm (66J/cm2)
for treating periorbital wrinkles.39 Exclusion
criteria included laser treatment or other ablative
or nonablative cosmetic intervention within the
previous six months, including injectables or
llers, a history of laser treatment or trauma to
the test site, and Fitzpatrick Skin Type VI.
Subjects were irradiated with the 830nm
LED for 20 minutes on Days 1, 3, 5, 15, 22, and
29 and with the 633nm LED for 20 minutes
on Days 8, 10, and 12. Most subjects achieved
softening of periorbital wrinkles, improvement in
photoaging scores, and improvements in softness,
smoothness, and rmness of their skin. Mild
erythema was reported by eight subjects.
Based on these promising results, the
following randomized, double-blind, controlled
study was designed to assess the ecacy of
830nm and 633nm LEDs, alone or together, for
facial rejuvenation.40 Exclusion criteria included
a history of photosensitivity or recent use of
photosensitizing drugs including systemic
retinoids or recent use of topical retinoic acid;
recent skin disease, operation, trauma, or systemic
disease that could aect the skin status; or
aesthetic procedures, such as botulinum toxin,
dermal ller, laser resurfacing, chemical peels,
dermabrasion, or nonablative rejuvenation
treatments within the three years on enrollment
previous to the trial.
Subjects with facial wrinkles (N=76) were
randomized to receive treatment with a
quasi-monochromatic 830nm (126J/cm2) LED
alone (Group 1, n=28), 633nm (66J/cm2) LED
alone (Group 2, n=28), 830nm, 633nm LEDs
sequentially (Group 3, n=28) on one side of the
face, or sham treatment (Group 4, n=28) on the
other side of the face. Treatments were performed
twice weekly for four weeks with a 3- to 4-day
interval between sessions. Digital images of both
periorbital areas of each subject were obtained
at baseline, Week 3 during treatment, and two,
four, and eight, and 12 weeks post-treatment.
Prolometric evaluation using silicon imprints
was performed on the outer canthus of both
periorbital areas at baseline and at two, four,
eight, and 12 weeks post-treatment. Objective
measurements of the melanin level were
performed before and after each treatment
session, and measurements of the skin elasticity
were performed at baseline, Weeks 2, 3, and 4
during treatment, and at Weeks 2, 4, 8, and 12
post-treatment. There were 4 to 6 subjects in
each group who volunteered for punch biopsies
for tissue assays. Assessment scales were used
to assess clinical improvement and subject
satisfaction.
There was a signicant decrease in mean
wrinkle severity among subjects in Groups 1, 2,
and 3 and a signicant decrease in melanin in
Group 2. At the nal assessment, the proportion
of improved subjects in Group 1 (95.2%), Group 2
(72.3%), and Group 3 (95.5%) were much greater
than sham-treated subjects (13.3%). Investigator
assessments in overall wrinkle severity are
summarized in Table 4. The highest mean
scores were in Groups 1 and 3. Group 4 results
demonstrate sham treatment produced no eect.
Tissue assay results showed increased collagen
throughout the entire dermis in Groups 1, 2, and
3 and particularly in the perifollicular areas and
the papillary and upper reticular dermis. Collagen
bundles were more packed and well-organized
and the thickness of each bundle appeared
greater than before treatment. Microscopic
examination revealed the presence of highly
activated broblasts in the active treatment
groups and an increase in the size and number of
collagen and elastic bers. Fibroblasts appeared
enlarged with numerous dilated endoplasmic
reticula, surrounded by abundant thick collagen
bundles and normal-structured elastic bers.
Photodynamic rejuvenation with
5-aminolevulinic acid (5-ALA). The objective
of this two-part pilot study was to 1) evaluate
the optimum dose and tolerance of 5-ALA when
used with a 633nm LED light in healthy volunteers
compared to a placebo cream and 2) determine
whether ALA-PDT treatments improve the signs
of aging skin.41 Subjects with normal forearm
skin and Glogau Scale II photodamage were
enrolled (N=6). Subjects had no inammatory
skin conditions in the areas to be treated,
TABLE 4. Improvement in wrinkle severity, treated vs. covered side of the face
ACCESSOR
GROUP 1
830nm ALONE
GROUP 2
633nm ALONE
GROUP 3
830nm AND 633nm
GROUP 4
SHAM CONTROL
TREATED COVERED TREATED COVERED TREATED COVERED TREATED COVERED
Assessor 1, mean (SD) 2.38 (0.65) 0.29 (0.63) 2.06 (0.78) 0.33 (0.75) 2.41 (0.72) 0.32 (0.82) 0.33 (0.70) 0.20 (0.65)
Assessor 2, mean (SD) 2.57 (0.66) 0.14 (0.64) 2.17 (0.76) 0.28 (0.65) 2.45 (0.66) 0.36 (0.71) 0.13 (0.62) 0.07 (0.57)
From Lee et al 200740
26
JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY February 2018 • Volume 11 • Number 2
REVIEW
history of photosensitivity and were not taking
photosensitizing medications.
For the dose ranging study, 5%, 10%, and
20% ALA or placebo cream were applied to the
forearm and an occlusive dressing applied. After
30 to 120 minutes, the dressing and excess cream
were removed, and the test areas were exposed
to 633nm at 126 J/cm2 light for 20 minutes. The
treated areas were examined for evidence of
edema, erythema, and changes in pigmentation
immediately post-exposure and one, two, three,
and seven days post-exposure. Subjects were
queried about potential adverse events during
each assessment.
Minimum erythema with no signicant change
in pigmentation was achieved with 5% ALA and
a 30-minute occlusion time. The 10% ALA with a
30-minute occlusion resulted in more consistent
erythema and mild pigmentation. The 10%
ALA with a 60-minute occlusion time increased
pigmentation in several sites with adverse textural
changes to the skin. The 20% ALA caused severe
erythema, some ulceration and pigmentation,
and adverse textural skin changes at all occlusion
times. For this reason, the combination of 5%
5-ALA incubated for 30 minutes was chosen as
the treatment parameter that gave the desired
amount of erythema with no side eects.
For the second part of the study, 5% ALA
was applied to the skin immediately around
the periorbital region and an occlusive dressing
was applied for 30 minutes. After that time, the
dressing and excess cream were removed and the
area was exposed to 633nm light for 20 minutes.
Digital photography was used to record baseline
appearance of the lateral canthal areas and
changes after one, two, three, and seven days.
Subjects were queried about potential adverse
events during each assessment.
The use of 5% ALA and a 30-minute occlusion
time resulted in mild, self-limiting erythema
at Day 1 and mild skin peeling at Day 3, which
resolved by Day 7. Clinical assessment of the
periorbital region showed a signicant treatment
response in four subjects (67%) with a reduction
in ne lines. Skin softness was improved in all
subjects at the test area. The treatment was well
tolerated with no reported adverse events.
DISCUSSION
LED phototherapy is a valuable tool in the
dermatologist’s armamentarium. It can be used
alone or in combination with other therapies to
treat a wide variety of dermatological conditions,
many of which have been described in this
paper. Moreover, the technology has numerous
aesthetic applications, both as a stand-alone
treatment and as an adjunctive to other aesthetic
procedures, including such commonly performed
procedures as injections, laser resurfacing, peels,
intense pulsed light, and microneedling. There is
no other technology available to the practicing
dermatologist that has such broad utility in
such a wide variety of medical and aesthetic
applications. The eectiveness of other devices
used for phototherapy, primarily PDL, has also
been clinically demonstrated.42–45 Devices with
published ecacy data are shown in Table 5.
One of the most important aspects of LED
phototherapy devices is their safety. LEDs are
nonablative and nonthermal, and when used
alone (i.e., without topical photosensitizers in
PDT applications) do not cause damage to the
epidermis or dermal tissue. There are no adverse
events associated with the use of these devices
and little to no downtime for the patient. When
LED phototherapy is used alone, patients do not
experience redness, peeling, blistering, swelling, or
pain. In fact, patients can have a treatment during
their lunch hour and return to work immediately
afterwards.
While home use devices have been available
for several years, there are many dierences
between those devices and those specically
designed for use by physicians. The home use
devices necessarily deliver signicantly less
power and typically do not have light panel arrays
large enough to treat the entire face at once, for
example. As they often are hand-held, it might be
cumbersome, time-consuming, and impractical to
treat the entire face in a single session. In contrast
with the medical LED units and their protocols,
home use devices have not been validated by
controlled clinical studies published in peer-
reviewed journals. In some cases, home units may
be used adjunctively with dermatologist-provided
treatment to address specic areas of concern, but
they are dissimilar enough from the medical-
grade units to not be considered an alternative to
these tested technologies.
CONCLUSION
Phototherapy using LEDs is benecial for a
broad range of medical and aesthetic conditions
encountered in the dermatology practice.
The treatment modality displays an excellent
safety prole and can be eectively used for
the treatment of acne vulgaris, wound healing
applications following surgical aesthetic and
resurfacing procedures, actinic keratosis,
squamous cell carcinoma in situ, and basal cell
carcinoma. LED phototherapy is also an eective
means for rejuvenating aged skin when used alone
or together with a photosensitizer, such as 5-ALA,
as well as post-procedural erythema. Having
implemented this technology in my practice
since 2009, I have also had success treating
TABLE 5. Other commercially available phototherapy devices
DEVICE MANUFACTURER DESCRIPTION INDICATIONS PUBLICATIONS
Blue-U® DUSA® Pharmaceuticals, Inc.,
Wilmington, Massachusetts
Blue light PDT illuminator, used
with 5-ALA moderate inammatory acne vulgaris Melnick, 200542
BF-RhodoLED® Biofrontera AG, Leverkusen,
Germany
Red light PDT illuminator, used
with 5-ALA actinic keratosis and supercial and/or nodular basal cell carcinoma Reinhold et al, 201643
Aktilite®
Galderma Laboratories, LP,
Fort Worth, Texas Red light PDT illuminator, used
with methyl-aminolaevulinic acid actinic keratosis Sung and Kim, 201744
Healite II® Lutronic North America,
Burlington, Massachusetts Low-level light therapy
temporary relief of minor muscle and joint pain, arthritis and muscle
spasm; relieving stiness; promoting the relaxation of muscle tissue;
temporarily increase local blood circulation
Min and Goo, 201345
5-ALA: 5-aminolevulinic acid; PDT: photodynamic therapy
27
JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY February 2018 • Volume 11 • Number 2
REVIEW
chemotherapy-induced rashes and many other
dicult to treat skin conditions. More research
should be performed, as this type of phototherapy
shows great promise treating even more
diagnostic conditions than are currently published.
ACKNOWLEDGMENTS
The author acknowledges the editorial
assistance of Dr. Carl S. Hornfeldt, Apothekon, Inc.,
with funding provided by GlobalMed Technologies,
Glen Ellen, CA.
REFERENCES
1. Calderhead RG. The photobiological basics behind
light-emitting diode (LED) phototherapy. Laser Ther
2007;16:97–108.
2. Zaenglein AL, Thiboutot DM. Acne Vulgaris. In: Bolognia
JL, Jorizzo JL, Schaer JV, editors. Dermatology. Atlanta:
Elsevier Inc; 2016.
3. Ashkenazi H, Malik Z, Harth Y, et al. Eradication of
Propionibacterium acnes by its endogenic porphyrins
after illumination with high intensity blue light. FEMS
Immunol Med Microbiol. 2003;35:17–24.
4. Morton CA, Scholeeld RD, Whitehurst C, et al. An open
study to determine the ecacy of blue light in the
treatment of mild to moderate acne. J Dermatolog Treat.
2005;16:219–23.
5. Tremblay JF, Sire DJ, Lowe NJ, et al. Light-emitting diode
415nm in the treatment of inammatory acne: an open-
label, multicentric, pilot investigation. J Cosmet Laser
Ther. 2006;8:31–3.
6. Papageorgiou P, Katsambas A, Chu A. Phototherapy with
blue (415nm) and red (660nm) light in the treatment of
acne vulgaris. Br J Dermatol. 2000;142:973–8.
7. Goldberg DJ, Russell BA. Combination blue (415nm) and
red (633nm) LED phototherapy in the treatment of mild
to severe acne vulgaris. J Cosmet Laser Ther. 2006;8:71–5.
8. El-Domyati M, Hosam W, Abdel-Azim E, et al.
Microdermabrasion: a clinical, histometric, and
histopathologic study. J Cosmet Dermatol. 2016;15:503–
13.
9. Lee SYC. Shedding Light on Acne: From Myth to Science
(Laser and Light Therapy for Acne). In: Roth DE, editor.
Dermatology Research Focus on Acne. Hauppauge, NY:
Nova Science Publishers, Inc; 2009.
10. Lee SY, You CE, Park MY. Blue and red light combination
LED phototherapy for acne vulgaris in patients with skin
phototype IV. Lasers Surg Med. 2007;39:180–8.
11. Whelan HT, Smits RL Jr, Buchman EV, et al. Eect of NASA
light-emitting diode irradiation on wound healing. J Clin
Laser Med Surg. 2001;19:305–14.
12. Whelan HT, Buchmann EV, Dhokalia A, et al. Eect of
NASA light-emitting diode irradiation on molecular
changes for wound healing in diabetic mice. J Clin Laser
Med Surg. 2003;21:67–74.
13. Trelles MA, Allones I. Red light-emitting diode (LED)
therapy accelerates wound healing post-blepharoplasty
and periocular laser ablative resurfacing. J Cosmet Laser
Ther. 2006;8:39–42.
14. Trelles MA, Allones I, Mayo E. Combined visible light
and infrared light-emitting diode (LED) therapy
enhances wound healing after laser ablative resurfacing
of photodamaged facial skin. Med Laser Appl.
2006;21:165–75.
15. Kim JW, Lee JO. Low level laser therapy and
phototherapy-assisted hydrogel dressing in burn wound
healing: light-guided epithelial stem cell biomodulation.
In: Innovations in Plastic and Aesthetic Surgery. New
York: Springer; 2008. p. 36–41.
16. Kim JW, Lee JO, Calderhead RG. The improvement
of hypertrophic scar and keloidal scar by combining
drilling tiny pinholes with carbon dioxide laser and
830 nm Omnilux PDT LED. J Korean Soc Laser Med Surg.
2005;9:1–6.
17. Kim JW, Lee JO, Calderhead RG, et al. Synergic eect of
ablating erbium Yag laser skin resurfacing combined
with non-ablating quasilaser light 415nm, 633nm,
830nm LED array in Asian patients. J Korean Soc Laser
Med Surg. 2005;9:15–23.
18. Griths CE, van de Kerkhof P, C zarnecka-Operacz M.
Psoriasis and atopic dermatitis. Dermatol Ther (Heidelb).
2017;7:31–41.
19. Ablon G. Combination 830nm and 633nm light-emitting
diode phototherapy shows promise in the treatment of
recalcitrant psoriasis: preliminary ndings. Photomed
Laser Surg. 2010;28:141–6.
20. Kleinpenning MM, Otero ME, van Erp PE, et al. Ecacy
of blue light vs. red light in the treatment of psoriasis: a
double-blind, randomized comparative study. J Eur Acad
Dermatol Venereol. 2012;26:219–25.
21. Ericson MB, Wennberg AM, Larkö O. Review of
photodynamic therapy in actinic keratosis and basal cell
carcinoma. Ther Clin Risk Manag. 2008;4:1–9.
22. Yang X, Palasuberniam P, Kraus D, et al. Aminolevulinic
acid-based tumor detection and therapy: molecular
mechanisms and strategies for enhancement. Int J Mol
Sci. 2015;16:25865–80.
23. Saini R, Lee NV, Liu KY, et al. Prospects in the
application of photodynamic therapy in oral cancer and
premalignant lesions. Cancers (Basel). 2016;8:E83.
24. Yang G, Xiang LF, Gold MH. 5-Aminolevulinic acid-based
photodynamic intense pulsed light therapy shows better
eects in the treatment of skin photoaging in Asian
skin: a prospective, single-blinded, controlled trial. J Clin
Aesthet Dermatol. 2010;3:40–3.
25. Le Pillouer-Prost A, Cartier H. Photodynamic
photorejuvenation: a review. Dermatol Surg.
2016;42:21–30.
26. Morton CA, Whitehurst C, Moseley H, et al. Comparison
of photodynamic therapy with cryotherapy in
the treatment of Bowen’s disease. Br J Dermatol.
1996;135:766–71.
27. Morton CA, Whitehurst C, Moore JV, et al. Comparison
of red and green light in the treatment of Bowen’s
disease by photodynamic therapy. Br J Dermatol.
2000;143:767–72.
28. Morton CA, Whitehurst C, McColl JH, et al. Photodynamic
therapy for large or multiple patches of Bowen disease
and basal cell carcinoma. Arch Dermatol. 2001;137:319–
24.
29. Cairndu F, Stringer MR, Hudson EJ, et al. Supercial
photodynamic therapy with topical 5-aminolaevulinic
acid for supercial primary and secondary skin cancer. Br
J Cancer. 1994;69:605–8.
30. Fink-Puches R, Soyer HP, Hofer A, et al. Long-term
follow-up and histological changes of supercial
nonmelanoma skin cancers treated with topical
delta-aminolevulinic acid photodynamic therapy. Arch
Dermatol. 1998;134:821–6.
31. Lui H, Salasche S, Kollias N, et al. Photodynamic therapy
of nonmelanoma skin cancer with topical aminolevulinic
acid: a clinical and histologic study. Arch Dermatol.
1995;131:737–8.
32. Pariser DM, Houlihan A, Ferdon MB, et al. Randomized
vehicle-controlled study of short drug incubation
aminolevulinic acid photodynamic therapy for
actinic keratoses of the face or scalp. Dermatol Surg.
2016;42:296–304.
33. Berman B, Ablon GR, Bhatia ND, et al. Expert consensus
on cosmetic outcomes after treatment of actinic
keratosis. J Drugs Dermatol. 2017;16:260–64.
34. Babilas P, Kohl E, Maisch T, et al. In vitro and in vivo
comparison of two dierent light sources for topical
photodynamic therapy. Br J Dermatol. 2006;154:712–8.
35. Britt CJ, Marcus B. Energy-based facial rejuvenation:
advances in diagnosis and treatment. JAMA Facial Plast
Surg. 2017;19:64–71.
36. Kim JW. Clinical trial of nonthermal 633nm Omnilux
LED array for renewal of photoaging: clinical surface
prolometric results. J Korean Soc Laser Med Surg.
2005;9:69–76.
37. Nestor M, Andriessen A, Berman B, et al.
Photobiomodulation with non-thermal lasers:
mechanisms of action and therapeutic uses in
dermatology and aesthetic medicine. J Cosmet Laser Ther.
2017;Feb 17:1–9.
38. Bhat J, Birch J, Whitehurst C, et al. A single-blinded
randomised controlled study to determine the ecacy
of Omnilux Revive facial treatment in skin rejuvenation.
Lasers Med Sci. 2005;20:6–10.
39. Russell BA, Kellett N, Reilly LR. A study to determine the
ecacy of combination LED light therapy (633nm and
830nm) in facial skin rejuvenation. J Cosmet Laser Ther.
2005;7:196–200.
40. Lee SY, Park KH, Choi JW, et al. A prospective,
randomized, placebo-controlled, double-blinded,
and split-face clinical study on LED phototherapy for
skin rejuvenation: clinical, prolometric, histologic,
ultrastructural, and biochemical evaluations and
comparison of three dierent treatment settings. J
Photochem Photobiol B. 2007;88:51–67.
41. Lowe NJ, Lowe P. Pilot study to determine the ecacy of
ALA-PDT photo-rejuvenation for the treatment of facial
ageing. J Cosmet Laser Ther. 2005;7:159–62.
42. Melnick S. Cystic acne improved by photodynamic
therapy with short-contact 5-aminolevulinic acid and
sequential combination of intense pulsed light and blue
light activation. J Drugs Dermatol. 2005;4:742–5.
43. Reinhold U, Dirschka T, Ostendorf R, et al. A randomized,
double-blind, phase III, multicentre study to evaluate the
safety and ecacy of BF-200 ALA (Ameluz®) vs. placebo
in the eld-directed treatment of mild-to-moderate
actinic keratosis with photodynamic therapy (PDT)
when using the BF-RhodoLED® lamp. Br J Dermatol.
2016;175:696–705.
44. Sung JM, Kim YC. Photodynamic therapy with
epidermal ablation using fractional carbon-dioxide
laser in the treatment of Bowen’s disease: a case series.
Photodiagnosis Photodyn Ther. 2017;19:84–85.
45. Min PK, Goo BL. 830nm light-emitting diode low level
light therapy (LED-LLLT) enhances wound healing: a
preliminary study. Laser Ther. 2013;22:43–9. JCAD
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Oral cancer is a global health burden with significantly poor survival, especially when the diagnosis is at its late stage. Despite advances in current treatment modalities, there has been minimal improvement in survival rates over the last five decades. The development of local recurrence, regional failure, and the formation of second primary tumors accounts for this poor outcome. For survivors, cosmetic and functional compromises resulting from treatment are often devastating. These statistics underscore the need for novel approaches in the management of this deadly disease. Photodynamic therapy (PDT) is a treatment modality that involves administration of a light-sensitive drug, known as a photosensitizer, followed by light irradiation of an appropriate wavelength that corresponds to an absorbance band of the sensitizer. In the presence of tissue oxygen, cytotoxic free radicals that are produced cause direct tumor cell death, damage to the microvasculature, and induction of inflammatory reactions at the target sites. PDT offers a prospective new approach in controlling this disease at its various stages either as a stand-alone therapy for early lesions or as an adjuvant therapy for advanced cases. In this review, we aim to explore the applications of PDT in oral cancer therapy and to present an overview of the recent advances in PDT that can potentially reposition its utility for oral cancer treatment.
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Background: Multiple actinic keratosis (AK) lesions may arise from the cancerization of large, sun-damaged skin areas. Although photodynamic therapy (PDT) is considered the most effective therapeutic option, the efficacy and safety of field treatment of multiple AK lesions with PDT has never before been tested in a pivotal trial. Objectives: To evaluate the efficacy, safety and cosmetic outcome of BF-200 ALA (a nanoemulsion formulation containing 10% aminolaevulinic acid hydrochloride) combined with the BF-RhodoLED(®) lamp for the field-directed treatment of mild-to-moderate AK with PDT. Methods: The study was performed as a randomized, multicentre, double-blind, placebo-controlled, parallel-group, phase III trial with BF-200 ALA and placebo in seven centres in Germany. A total of 94 patients were enrolled in this study; 87 were randomized (55 patients received BF-200 ALA, 32 received placebo). Patients received one PDT. If residual lesions remained at 3 months after treatment, PDT was repeated. Illumination was performed with the PDT lamp BF-RhodoLED (635 nm ± 9 nm) until a total light dose of 37 J cm(-2) was achieved. Results: BF-200 ALA was superior to placebo with respect to patient complete clearance rate (91% vs. 22%, P < 0·0001) and lesion complete clearance rate (94·3% vs. 32·9%, P < 0·0001) after a maximum of two PDTs. The confirmatory analysis of all key secondary variables supported this superiority" should not be skipped since this is an important result. Treatment-emergent adverse events (TEAEs) were experienced by 100% of the BF-200 ALA group and 69% of the placebo group. The most commonly reported TEAEs were TEAEs of the application site. The cosmetic outcome was improved in the BF-200 ALA group compared with placebo. Conclusions: Field-directed therapy with BF-200 ALA and BF-RhodoLED lamp is highly effective and well tolerated for multiple mild-to-moderate AK lesions, providing greatly improved skin quality.
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Background: Aminolevulinic acid photodynamic therapy (ALA-PDT) can be effective and well tolerated when applied over a broad area and for short drug incubation times. Objective: To evaluate the effect of short-incubation time and application method on the safety and efficacy of ALA-PDT versus vehicle (VEH-PDT) in the treatment of actinic keratoses (AKs) of the face or scalp. Methods: Aminolevulinic acid or VEH was applied to face or scalp as a broad area application for 1, 2, or 3 hours or as a spot application for 2 hours before blue light activation. An identical treatment was repeated at Week 8 if any AK lesions remained. Results: Median AK clearance rate for ALA-treated subjects ranged from 68% to 79% at Week 12, compared with 7% of the VEH-treated group (p < .0001). Complete clearance rate for ALA-treated subjects ranged from 17% (8/46) to 30% (14/47) at Week 12, compared with 2% (1/46) of the VEH-treated group (p = .0041). The safety profile seen in this study is consistent with previously reported side effects of the therapy. Conclusion: Short-incubation ALA-PDT was found to be superior to VEH-PDT for AK lesion clearance. A second treatment improves efficacy.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
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p>Dermatologists treat actinic keratosis (AK) primarily because these lesions have the potential to progress to invasive squamous cell carcinoma. Patients, on the other hand, generally seek treatment to remove the lesions and achieve an improved appearance of their skin following treatment. In selecting a treatment option for AK, dermatologists should consider post-treatment cosmesis, because cosmetic outcomes differ across AK treatments. To obtain expert opinion on the cosmetic sequelae related to chronically photodamaged skin and the treatment of AK, an expert panel meeting among dermatologists was conducted in February 2016. These experts reviewed current treatment options for photodamage, including AK, and discussed the relative merits of the various cosmetic assessments commonly used by investigators and patients in both clinical trial and dermatology practice settings. A main goal of the expert panel meeting was to propose assessment tools that could be specifically designed to characterize cosmesis results after treatment of AK. The panel agreed that existing tools for measurement of cosmetic outcomes following treatment of photodamage could also be used to evaluate cosmesis after treatment of AK. Digital photography is probably the best method used for this, with validation by other technologies. Better measurement tools specifically for assessing cosmesis after AK treatment are needed. Once they are developed and validated, regulatory agencies should be educated about the importance of including cosmetic outcomes as a component of product labeling. J Drugs Dermatol. 2017;16(3):260-265. .
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Background Bowen's disease is an intraepithelial tumor, also known as squamous cell carcinoma in situ. Among those alternative treatments, PDT usually produce better cosmetic outcomes compared with those of 5-fluorouracil and cryosurgery. Methods Before the applications of photosensitizer, epidermis of the lesions were totally ablated by fractional CO2 laser (eCO2®, Lutronic, Korea) with the following parameters: tip size 120 μm, peak power 30 W, pulse energy 50 mJ, 200 spots/cm². After the ablation of epidermis, methyl aminolevulinate (MAL) (Metvix®, Galderma, France) was applied with incubation time of 90 minutes followed by light exposure. 630 nm light from Aktilite CL 128® (Galderma, Switzerland) was utilized at a light dose of 37 J/cm². The clinical improvement of the lesion was evaluated either as a complete response (CR, complete absence of lesion), a partial response (PR, 25∼99% reduction in lesion) or no response (NR, 0∼24% reduction in lesion). Results The treatment result was excellent (87.5% of clinical CR). No scar formation after the treatment was noted in 7 patients who achieved clinical CR. Conclusions Total ablation of epidermis before PDT can enhance the treatment efficacy of PDT without adverse events in the treatment of Bowen's disease.
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Background: Non-thermal laser therapy in dermatology, is a growing medical technology by which therapeutic effects are achieved by exposing tissues to specific wavelengths of light. Objectives: The purpose of this review was to gain a better understanding of the science behind non-thermal laser and the evidence supporting its use in dermatology. Methods: A group of dermatologists and surgeons recently convened to review the evidence supporting the use of non-thermal laser for body sculpting, improving the appearance of cellulite, and treating onychomycosis. Results: The use of non-thermal laser for body sculpting is supported by three randomized, double-blind, sham-controlled studies (N=161), one prospective open-label study (N=54), and two retrospective studies (N=775). Non-thermal laser application for improving the appearance of cellulite is supported by one randomized, double-blind, sham-controlled study (N=38). The use of non-thermal laser for the treatment of onychomycosis is supported by an analysis of three non-randomized, open-label studies demonstrating clinical improvement of nails (N=292). Conclusions: Non-thermal laser is steadily moving into mainstream medical practice, such as for dermatology. Although the present studies have demonstrated safety and efficacy of non-thermal laser for body-sculpting, cellulite reduction and onychomycosis treatment, studies demonstrating the efficacy of non-thermal laser as a stand-alone procedure are still inadequate.
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Psoriasis and atopic dermatitis are common, chronic inflammatory skin diseases. We discuss several aspects of these disorders, including: risk factors; incidence and prevalence; the complex disease burden; and the comorbidities that increase the clinical significance of each disorder. We also focus on treatment management strategies and outline why individualized, patient-centered treatment regimens should be part of the care plans for patients with either psoriasis or atopic dermatitis. Finally, we conclude that, while our theoretical knowledge of the optimum care plans for these patients is increasingly sophisticated, this understanding is, unfortunately, not always reflected in daily clinical practice.
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Importance: The market for nonsurgical, energy-based facial rejuvenation techniques has increased exponentially since lasers were first used for skin rejuvenation in 1983. Advances in this area have led to a wide range of products that require the modern facial plastic surgeon to have a large repertoire of knowledge. Objective: To serve as a guide for current trends in the development of technology, applications, and outcomes of laser and laser-related technology over the past 5 years. Evidence review: We performed a review of PubMed from January 1, 2011, to March 1, 2016, and focused on randomized clinical trials, meta-analyses, systematic reviews, and clinical practice guidelines including case control, case studies and case reports when necessary, and included 14 articles we deemed landmark articles before 2011. Findings: Three broad categories of technology are leading non-energy-based rejuvenation technology: lasers, light therapy, and non-laser-based thermal tightening devices. Laser light therapy has continued to diversify with the use of ablative and nonablative resurfacing technologies, fractionated lasers, and their combined use. Light therapy has developed for use in combination with other technologies or stand alone. Finally, thermally based nonlaser skin-tightening devices, such as radiofrequency (RF) and intense focused ultrasonography (IFUS), are evolving technologies that have changed rapidly over the past 5 years. Conclusions and relevance: Improvements in safety and efficacy for energy-based treatment have expanded the patient base considering these therapies viable options. With a wide variety of options, the modern facial plastic surgeon can have a frank discussion with the patient regarding nonsurgical techniques that were never before available. Many of these patients can now derive benefit from treatments requiring significantly less downtime than before while the clinician can augment the treatment to maximize benefit to fit the patient's time schedule.
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Background. Microdermabrasion is a non chemical superficial resurfacing procedure that removes the stratum corneum. Because it is a somewhat subtle procedure, it may be difficult to demonstrate its cosmetic benefit. Objectives. To assess the efficacy of microdermabrasion in treatment of melasma, postacne scarring, striae distensae and photoaging by a series of microdermabrasion sittings through clinical, histometric and histopathologic analysis . Patients and Methods. The study was conducted on 38 patients constituting 4 groups (melasma, acne scars, striae destinsae and photoaging), each patient was subjected to a series of 8 microdermabrasion treatments performed at one week interval. Punch biopsies; at base line, one week after the 4th and the 8th session were obtained from each subject for histometric and histopathologic analysis. Results. Clinically, the improvement in melasma, acne scars and striae distensae groups was mainly mild to moderate, while in photoaging group was mainly mild. Histometric analysis of epidermal thickness showed insignificant changes in all groups. Histopathologically, decreased melanization and regular distribution of melanosomes in the epidermis was noted in melasma group while increased density of collagen fibers with more regular arrangement in collagen bundles was detected in all candidates of acne scars, striae distensae and photoaging groups. Meanwhile, Orcein stain did not show any significant changes in elastic fibers. Conclusions. Microdermabrasion is an easy and safe technique. In the present study, most cases showed mild to moderate improvement. Decreased melanization with regular distribution of melanosomes and increased collagen density with regular arrangement of collagen bundles were the most common observed histologic changes.