ArticlePDF Available

A Controlled Trial to Determine the Efficacy of Red and Near-Infrared Light Treatment in Patient Satisfaction, Reduction of Fine Lines, Wrinkles, Skin Roughness, and Intradermal Collagen Density Increase

  • Medical Light Consulting

Abstract and Figures

Objective: The purpose of this study was to investigate the safety and efficacy of two novel light sources for large area and full body application, providing polychromatic, non-thermal photobiomodulation (PBM) for improving skin feeling and appearance. Background data: For non-thermal photorejuvenation, laser and LED light sources have been demonstrated to be safe and effective. However, lasers and LEDs may offer some disadvantages because of dot-shaped (punctiform) emission characteristics and their narrow spectral bandwidths. Because the action spectra for tissue regeneration and repair consist of more than one wavelength, we investigated if it is favorable to apply a polychromatic spectrum covering a broader spectral region for skin rejuvenation and repair. Materials and methods: A total of 136 volunteers participated in this prospective, randomized, and controlled study. Of these volunteers, 113 subjects randomly assigned into four treatment groups were treated twice a week with either 611-650 or 570-850 nm polychromatic light (normalized to ∼ 9 J/cm(2) in the range of 611-650 nm) and were compared with controls (n=23). Irradiances and treatment durations varied in all treatment groups. The data collected at baseline and after 30 sessions included blinded evaluations of clinical photography, ultrasonographic collagen density measurements, computerized digital profilometry, and an assessment of patient satisfaction. Results: The treated subjects experienced significantly improved skin complexion and skin feeling, profilometrically assessed skin roughness, and ultrasonographically measured collagen density. The blinded clinical evaluation of photographs confirmed significant improvement in the intervention groups compared with the control. Conclusions: Broadband polychromatic PBM showed no advantage over the red-light-only spectrum. However, both novel light sources that have not been previously used for PBM have demonstrated efficacy and safety for skin rejuvenation and intradermal collagen increase when compared with controls.
Content may be subject to copyright.
A Controlled Trial to Determine the Efficacy
of Red and Near-Infrared Light Treatment
in Patient Satisfaction, Reduction of Fine Lines, Wrinkles,
Skin Roughness, and Intradermal Collagen Density Increase
Alexander Wunsch
and Karsten Matuschka
Objective: The purpose of this study was to investigate the safety and efficacy of two novel light sources for
large area and full body application, providing polychromatic, non-thermal photobiomodulation (PBM) for
improving skin feeling and appearance. Background data: For non-thermal photorejuvenation, laser and LED
light sources have been demonstrated to be safe and effective. However, lasers and LEDs may offer some
disadvantages because of dot-shaped (punctiform) emission characteristics and their narrow spectral band-
widths. Because the action spectra for tissue regeneration and repair consist of more than one wavelength, we
investigated if it is favorable to apply a polychromatic spectrum covering a broader spectral region for skin
rejuvenation and repair. Materials and methods: A total of 136 volunteers participated in this prospective,
randomized, and controlled study. Of these volunteers, 113 subjects randomly assigned into four treatment
groups were treated twice a week with either 611–650 or 570–850 nm polychromatic light (normalized to
*9 J/cm
in the range of 611–650 nm) and were compared with controls (n=23). Irradiances and treatment
durations varied in all treatment groups. The data collected at baseline and after 30 sessions included blinded
evaluations of clinical photography, ultrasonographic collagen density measurements, computerized digital
profilometry, and an assessment of patient satisfaction. Results: The treated subjects experienced significantly
improved skin complexion and skin feeling, profilometrically assessed skin roughness, and ultrasonographically
measured collagen density. The blinded clinical evaluation of photographs confirmed significant improvement
in the intervention groups compared with the control. Conclusions: Broadband polychromatic PBM showed no
advantage over the red-light-only spectrum. However, both novel light sources that have not been previously
used for PBM have demonstrated efficacy and safety for skin rejuvenation and intradermal collagen increase
when compared with controls.
Altering cellular function using low level, non-
thermal LED light is called photobiomodulation (PBM)
or low-level light therapy (LLLT), and is a medical treatment
modality of increasing clinical importance.
Because of the
combination of high degree of penetration in skin
and ab-
sorption by respiratory chain components, light in the spectral
range from 600 to 1300 nm is useful for promoting wound
healing, tissue repair, and skin rejuvenation.
In contrast to
traumatic ablative (e.g., laser resurfacing) and non-ablative
(e.g., intense pulsed light [IPL]) skin rejuvenation modalities
that induce secondary tissue repair by causing controlled
damage to either the epidermis or the dermis, PBM is atrau-
matic, and bypasses the initial destructive step by directly
stimulating regenerative processes in the skin. Its action
mechanisms encompass increased cellular proliferation, mi-
gration, and adhesion.
Important cell types for skin and tis-
sue regeneration are fibroblasts, keratinocytes, and immune
cells (mast cells, neutrophils, and macrophages), which can be
stimulated using specific wavelengths with significant tissue
penetration properties.
The known severe side effects of
traumatic skin rejuvenation procedures, such as inflamma-
tion, unpleasant pain perception, and prolonged social down
are unknown in PBM; PBM has been successfully ad-
ministered to reduce common symptoms of laser resurfacing
Medical Light Consulting, Heidelberg, Germany.
JK-International GmbH, Windhagen, Germany.
Photomedicine and Laser Surgery
Volume 32, Number 2, 2014
ªMary Ann Liebert, Inc.
Pp. 93–100
DOI: 10.1089/pho.2013.3616
and IPL treatment.
Photon emitters, such as lasers or LEDs,
have proven to be effective light sources for PBM during re-
cent decades, thereby demonstrating that it is not the technical
type of light source but the treatment parameters such as
wavelength, irradiance, and fluence that are likely to be ac-
countable for the effects.
However, laser and LED light
sources may offer some disadvantages because of their dot-
shaped (punctiform) emission characteristics and narrow
spectral bandwidths. Because the action spectra for tissue
regeneration and repair consist of more than one wave-
it might be favorable to apply a polychromatic
spectrum covering a broader spectral region for skin rejuve-
nation and skin repair. We investigated the safety and efficacy
of a novel non-thermal, non-ablative, atraumatic, polychro-
matic low-level light treatment modality with a focus on
pleasant skin feeling, improved skin appearance, intradermal
collagen increase, and the visible reduction of fine lines and
wrinkles in a prospective, randomized, controlled trial that
consisted of 136 volunteers.
Materials and Methods
Study population and design
We conducted a randomized, controlled clinical trial be-
tween January 2012 and December 2012. Table 1 summarizes
the baseline (t0) characteristics of the subject groups.
The subjects were between 27 and 79 years of age. Inclu-
sion criteria were the capacity to independently position
oneself to use the device, the capacity to understand the
treatment, a signed declaration of consent, and interest in
continuous participation. The exclusion criteria were physi-
cal and psychological disease casting doubt on the capacity
to consent, preliminary treatment with red light within the
6 months prior to the beginning of the study, recent invasive
cosmetic procedures such as Botox during the 12 months
prior to the beginning of the study, acute or prior skin cancer,
acute skin disease requiring dermatological treatment,
existing or planned pregnancy, lactation, history of photo-
sensitivity or recent use of photosensitizing medication,
epilepsy, and the tendency to faint. All of the participants
gave written informed consent for this study, which was
approved by the Ethics Committee of the Medical Associa-
tion (Landesa
¨rztekammer) Baden-Wu
¨rttemberg, Stuttgart,
Germany. The investigation was conducted in accordance
with the Declaration of Helsinki (DoH/Oct2008). After the
declaration of informed consent following examination of
the inclusion and exclusion criteria, each participant was
assigned to one of four groups using a computerized ran-
domization process. Group 5 was mainly recruited from
employees of the JK company without randomization, and
served as the control. Groups 1–4 were treated twice a week
with 30 treatments in total, starting in January 2012. To
minimize the influence of seasonal changes, the time interval
for data acquisition at the baseline, t15, t30, and follow-up
examinations was restricted to 1 month. The data acquisition
at baseline was completed in February 2012, and all of the
volunteers finished treatment 30 (t30) in June 2012.
The control group did not receive any treatment, as the
therapy cannot be blinded, and a sham light source without
any effect most likely does not exist. The control group
volunteers participated in the clinical measurements only,
and the acquisition of subjective parameters such as skin
feeling and skin complexion was not conducted. Because of
the similar spectral lamp characteristics for groups 1 and 2
and groups 3 and 4, groups 1 and 2 were combined for
evaluation as the ‘‘mid-pressure lamp group’’ [energizing
light technology (ELT)], and groups 3 and 4 were evaluated
together as the ‘‘low-pressure lamp group’’ [red light tech-
nology (RLT)] to obtain larger group sizes and, therefore,
higher statistical power. Nevertheless, the subdivision into
groups 1–4 allowed us to compare outcomes based on dif-
ferent treatment parameters, such as spectral distribution,
irradiance, and fluence. A questionnaire concerning the tol-
erability of the application was filled in after each treatment
(t1–t30). Digital photographs and clinical measurements
were taken, and subjective questionnaires were used to as-
sess complexion and skin feeling at the baseline (t0) and after
15 (t15) and 30 treatments (t30). The follow-up acquisition of
Table 1. Baseline (t0) Characteristics of the Subject Groups
RLT (n=57) ELT (n=48) Controls (n=23)
Female 49/86.0% 34/70.8% 15/65.2%
Male 8/14.0% 14/29.2% 8/34.8%
46.2 9.0 48.6 9.8 44.4 10.2
72.9 15.22 73.4 13.7 73.7 13.4
Skin complexion (subjective)
4.54 1.92 4.87 2.02
Skin feeling (subjective)
5.33 2.04 5.24 2.18
Skin roughness (R
15.29 4.20 14.84 4.04 11.79 2.17
Collagen intensity score
20.40 6.55 18.96 3.54 23.22 7.36
Expert wrinkle assessment
No/shallow or fine wrinkles 14/24.6% 17/35.4% 5/21.7%
Moderate wrinkles 20/35.1% 11/22.9% 6/26.1%
Prominent or deep wrinkles 13/22.8% 11/22.9% 9/39.1%
No majority vote possible 10/17.5% 9/18.8% 3/13.0%
Values represent means SD at t0.
Values represent means SD at t0; small numbers indicate good values.
Values represent means SD at t0; large numbers indicate good values.
Majority vote of three blinded expert reviewers, based on the Modified Fitzpatrick Wrinkle Scale.
RLT, red light technology; ELT, energizing light technology.
subjective and clinical parameters was conducted at t30 +6
Light Sources
Four units equipped with two different types of poly-
chromatic light sources (low-pressure vs. mid-pressure
lamps) were used to conduct this study. Table 2 lists the
lamp technologies, lamp types, treatment area (full or part of
the body), spectral values, session duration, and treatment
doses for the units used in this study.
Treatment units 2, 3, and 4 provided full-body irradiation,
covering the ventral and dorsal surfaces of the head, neck,
trunk, upper limbs, and lower limbs at the same time. Full-
body irradiation units 2 and 3 enabled treatment with the
patient in a horizontal, reclined position, whereas unit 4 was
engineered as a cabin for vertical treatment orientation. Unit 1
was designed for the local treatment of the face and de
area with the patient sitting in a chair in a semi-reclined posi-
tion. Units 1 and 2 were equipped with medium-pressure gas
discharge lamps in combination with spectrally selective re-
flectors and corresponding filter systems, to eliminate spectral
emissions in wavelengths <570 and >850 nm; these units
were denoted as ELT. Units 3 and 4 were equipped with low-
pressure gas discharge fluorescent lamp tubes providing a
spectral emission peak predominantly within the range of 611–
650 nm, denoted as RLT. Because of the different spectral
properties and irradiances, we defined the spectral range be-
tween 611 and 650 nm for the calculation of treatment fluences.
This wavelength window encompasses 632.8 nm, which is a
paramount wavelength in LLLT and PBM, representing the
dominant wavelength of a HeNe-laser. The spectral dose
distributions of the ELT and RLT light sources are shown in
Fig. 1, with the doses of both light sources normalized to 100 %
for the 611–650 nm range. The treatment doses were kept
constant for this spectral range, whereas irradiances and treat-
ment durations varied for all four treatment groups in order to
investigate the applicability of the Bunsen–Roscoe law of reci-
procity within the given parametrical limits.
All units emitted almost no erythemogenic UV radiation
(minimal erythema dose would not be reached after several
hours of exposure, comparable to the UV emission of fluo-
rescent lamps for general lighting service applications).
The primary objective of the study was the improvement
of subjective skin complexion and skin feeling. The volun-
teers were asked to specify their level of agreement to the
statements in the questionnaire by marking a position along
a continuous black line between two end points measuring
10 cm, which served as a visual analog scale (VAS). The
secondary objectives were the improvement of measurement
parameters using a DermaLab Combo (Cortex Technology,
Hadsund, Denmark), a computer-supported skin diagnostics
system equipped with a rotating high-resolution ultrasound
sensor probe (20 MHz) for the determination of changes in
intradermal collagen density, measured as a collagen inten-
sity score (CIS). A Primos
digital fringe projection system
(GFM Messtechnik, Berlin, Germany) was used to measure
the objective arithmetical roughness (R
) of the skin surface
in the periorbital region.
The digital photographs for the blinded wrinkle assess-
ment were taken using a Nikon D5100 camera equipped
with a Nikkor AF 50 mm 1:1.4 lens (Nikon Corporation,
Chiyoda, Tokyo, Japan) and a Walimex RFL-3 ring light
(Walser GmbH & Co. KG, Burgheim, Germany).
Subject outcome assessment
The subjective efficacy parameters were self-assessed at
the baseline (t0), after 15 (t15) and 30 (t30) treatments, and
Table 2. Characteristics of the Treatment Units, Light Sources, and Application Parameters
Treatment units (groups 1 – 4)
ELT 2 ELT 30 C 46 sun CVT/RVT
Technology Energizing light (ELT) Energizing light (ELT) Red light (RLT) Red light (RLT)
Lamp type Medium pressure Medium pressure Low pressure Low pressure
Treatment area Partial-body Full-body Full-body Full-body
Treatment position Semi-reclined Horizontal Horizontal Vertical
Irradiance (611–650 nm) 7.1 mW/cm
10.4 mW/cm
5.9 mW/cm
13.3 mW/cm
Total irradiance (570–850 nm) 42.8 mW/cm
54.8 mW/cm
10.3 mW/cm
23.4 mW/cm
Treatment duration 20 min 15 min 25 min 12 min
Treatment dose (611–650 nm) 8.5 J/cm
9.4 J/cm
8.9 J/cm
9.6 J/cm
Total radiant exposure (570–850 nm) 51.4 J/cm
49.3 J/cm
15.5 J/cm
16.8 J/cm
FIG. 1. Spectral dose distributions of energizing light tech-
nology (ELT) and red light technology (RLT) light sources.
Relationship between doses and wavelength ranges for
ELT and RLT light sources, normalized to the spectral range
611–650 nm. Colored bars represent the spectral doses in
after t30 +6 months using 10 cm VAS for the improvements
in skin complexion and skin feeling. These parameters were
not assessed in the control group.
Objective clinical parameter assessment
The high-resolution ultrasound examination of collagen
has enabled the measurement of visible changes in collagen
density and numerical CISs representing the intradermal
collagen fiber density. Profilometry yielded a numerical va-
lue for the R
of the skin area under examination.
Investigator assessment
Three independent physicians who were blinded to the
clinical patient data, analyzed the clinical photographs ob-
tained at t0 and t30. The investigators were instructed to
arrange the randomly assorted sets of clinical photographs
taken at t0 and t30 into a before/after treatment sequence.
The baseline wrinkle depth according to the Modified Fitz-
patrick Wrinkle Scale (MFWS)
and the degree of wrinkle
reduction after treatment had to be assessed after sequenc-
ing. The votes of the investigators were summarized by the
following majority rules: if two or three experts voted the
same way, the agreed-upon classification was the summary
measure; if all three experts voted differently, ‘‘no change’’
was the summary measure.
Statistical methods
The data in the tables are given as means standard
deviations. Comparisons of the changes in skin feeling, skin
complexion, roughness, and collagen intensity from the
baseline to t30 between the different treatment groups (in-
tergroup comparisons) were performed using a linear model,
with the baseline value of each volunteer as a covariate.
Within-group differences from the baseline to values at t30
were assessed using the Mann–Whitney–Wilcoxon test. To
compare wrinkle difference assessments among groups, we
used the v
test. Within groups, we tested the hypothesis of
equal probabilities of improvement and worsening using
binomial tests. All tests were two sided, and pvalues <0.05
were considered statistically significant.
Patient characteristics
Initially, 144 volunteers were recruited for the trial. Eight
volunteers did not appear for the first appointment after
randomization; therefore, the total number of patients finally
included in the study was 136. Five volunteers stopped
participating because of schedule incompatibilities and lack
of time. One volunteer could not finish the treatment because
of receiving antibiotic medication, which was one of the ex-
clusion criteria; one volunteer terminated participation be-
cause of moving away; and one participant missed more
than four treatments because of a period of residence at a
health resort. Ultimately, 128 volunteers completed the
treatment and the follow-up evaluation course, of whom
57 were treated with RLT, 48 were treated with ELT, and 23
were controls. The volunteers in the RLT and ELT groups
were similar with respect to age, weight, skin complexion,
skin feeling, skin roughness, and intradermal collagen
density. The percentage of women was lower in the ELT
group than in the RLT group. The controls had a slightly
higher mean collagen density and a lower mean skin
Adverse events
None of the volunteers dropped out because of an adverse
event. No severe adverse events were registered during the
study or the follow-up phase. One volunteer with facial
telangiectasia noticed an increased visibility after the first
treatments, and decided to protect the zones in question
from the light influence using a concealer for the rest of the
treatment series. One volunteer experienced a reddening of
scar tissue from a 40-year-old knee injury that was likely
reactivated by the ELT 30 treatment. The affected scar healed
completely within 1 week, and the treatments were contin-
ued without interruption.
Assessment of effects
Figure 2 shows two series of collagen ultrasonography
scans, demonstrating the collagen density increase from t0 to
t30 for one subject each in the RLT group and the ELT group.
Clinical photography revealed visible changes in wrinkles
and skin roughness. Figure 3 shows an example for one
FIG. 2. Collagen ultrasonography examples.
subject in each treatment group, comparing the baseline (t0)
status with t30.
In Table 3, the results of the t30 -t0 measurements for each
parameter in the different patient groups and the results of
the expert wrinkle assessment are summarized. Within-
group comparisons addressed whether the t30 -t0 differ-
ences had means of zero for each patient group separately.
Within-group comparisons, t30 -t0. In the RLT and ELT
groups, skin complexion, skin feeling, collagen intensity
score, skin roughness, and wrinkle status improved signifi-
cantly ( p<0.001, Table 3). The skin feeling, skin complexion,
and roughness changes were significantly ( p<0.001, covari-
ance analysis) correlated with baseline values in all groups.
In contrast, the control subjects showed no significant dif-
ference in collagen density and significant worsening of skin
roughness and wrinkle status. These results are described in
greater detail in Fig. 4. Here, baseline measurements on the
x-axis and the respective gain or reduction in the t30 values
on the y-axis are color coded for the different treatment
groups. In Fig. 4A, B and D, nearly all of the ELT and RLT
points plotted below the baseline x-axis =0.00, indicating that
the skin feeling, skin complexion, and roughness improved
for nearly all of the volunteers ( p<0.01). In Fig. 4C (CIS), the
baseline effect is not significant, whereas the CIS increase is
significant ( p<0.001), and values above the x-axis indicate
Between-group comparisons. For the main efficacy pa-
rameters, skin complexion and skin feeling, we observed no
significant differences between the RLT and ELT groups. The
collagen density, roughness, and wrinkle status were sig-
nificantly different among the three groups, as shown in
Table 3. There was no difference between the RLT and ELT
groups, but there was a difference between both groups
compared with controls, as shown by the blue points in Fig.
4C and D.
Subgroup analyses. We wanted to assess whether the
two RLT treatment groups and the two ELT treatment
groups showed different results; therefore, we compared the
two groups. The RLT subgroups had 25 volunteers using
CVT/RVT and 32 using C46 sun. There were no differences
between the two groups with respect to skin complexion,
skin feeling, skin roughness, collagen density, and wrinkle
status. All of these parameters improved significantly be-
tween t0 and t30 (data not shown). We obtained very similar
results for the two ELT groups, with 27 volunteers in ELT 30
and 21 volunteers in ELT 2.
The RLT group consisted of a lower percentage of male
volunteers than did the ELT group and the control. Gender
differences regarding the response to the PBM treatment for
the main parameters were tested within each of the RLT/
ELT/control subgroups using the Mann–Whitney Utest, and
we found no significant differences ( p>0.1 for all tests).
Including gender as an additional covariate in the covariance
analysis resulted in very similar pvalues for the tests re-
garding the comparison of study groups, compared with the
analysis without gender. Only for collagen increase were
gender and treatment both significant.
Long-term follow-up
The long-term results were analyzed for all subjects who
were available for long-term follow-up in November/
December 2012. A total of 52 of the 77 subjects who took part
in the long-term follow-up finished after 30 treatments, 18
FIG. 3. Patient photography examples. (A) 64-year-old
woman, energizing light technology (ELT). (B) 41-year-old
woman, red light technology (RLT).
Table 3. Comparison of the t30 -t0 Results Between and Within Subject Groups
RLT (n=57)
pvalue ELT (n=48)
group pvalue
Skin complexion (subjective)
-1.29 1.98 <0.001 -1.72 2.35 <0.001 0.064
Skin feeling (subjective)
-1.01 2.30 <0.001 -1.65 2.17 <0.001 0.167
Skin roughness (R
-1.79 2.46 <0.001 -1.58 2.22 <0.001 0.95 1.45 0.003 0.003
Collagen intensity score
5.75 4.54 <0.001 6.40 5.17 <0.001 -0.26 5.09 0.84 <0.001
Expert wrinkle assessment
<0.001 <0.001 <0.001 <0.001
Better 40/69% 36/75% 1/4%
Equal 8/14% 7/15% 5/22%
Worse 10/17% 5/10% 17/74%
Values represent means SD of the difference t30 -t0; negative numbers indicate improvement.
Values represent means SD of the difference t30 -t0; positive numbers indicate improvement.
Majority vote of three blinded expert reviewers, v
test for comparisons between groups, binomial test for within-group comparisons.
Analysis of covariance for the between-group comparison, one sample Wilcoxon-test for the within-group comparisons.
RLT, red light technology; ELT, energizing light technology.
volunteers continued to a total of 45 treatments, and 7 vol-
unteers received a total of 60 treatments (t60). To analyze the
long-term effects, we tested whether the t60 measurements of
skin feeling, skin complexion, CIS, and R
were better than
the t0 measurements for the group of volunteers with 30
treatments. All volunteers had significantly better results at
t60 (Wilcoxon test £0.001 for each). The t60 -t0 differences
were as follows: mean 0.99, SD 1.95 for skin feeling; mean
-1.00, SD 2.10 for skin complexion; mean 5.10, SD 7.56 for
CIS; and mean -0.64, SD 3.53 for R
. As expected, these
differences displayed lower effect sizes than at t30. Only a
group of seven volunteers continued the therapy with good
results for a further 30 treatments, which may be partly the
result of selection bias. Therefore, the long-term efficacy
must be systematically evaluated in further studies. During
the follow-up period, no delayed adverse events were
The use of LED light sources with 590, 633, and 830 nm
wavelengths for athermal light-only photorejuvenation has
grown rapidly in recent years. Additional wavelengths
have been shown to be efficient in altering cellular functions,
such as 570,
620, 680, 760, and 820 nm.
The treatment
doses vary significantly, ranging from 0.1 J/cm
for 590 nm
LED light with a specific sequence of pulsing,
up to 126 J/
for 633 nm continuous LED light.
The power of the
light typically ranges between 1 and 1000 mW, depending
upon the type of light source and the application.
comparisons of the different devices available to the physi-
cian are not known to the authors.
This study is the first prospective clinical trial investigat-
ing the safety and efficacy of novel light sources for skin
rejuvenation and the stimulation of dermal collagen syn-
thesis based on low-pressure and mid-pressure gas discharge
lamps. These light sources, in contrast to lasers and LEDs,
allow simultaneous treatment with a tailored spectrum
composed of several spectral bands that are effective in PBM.
When compared with the initial values and the controls, the
volunteers experienced significant improvements in their
personal assessments of skin feeling and complexion, in
clinical outcomes as assessed by collagen density and skin
roughness measurements and in the reduction of fine lines
and wrinkles as assessed by three blinded evaluators com-
paring t0 and t30 photographs.
Previous findings were able to correlate fibroblast activity
and dermal matrix remodeling processes, with an increase in
FIG. 4. Results for t30 -t0. Changes t30 -t0 (y-axis) are depicted in relation to the baseline value t0 on the x-axis. For A, B,
and D, points below the x-axis indicate improvement; for C, points above the x-axis indicate improvement. The red light
technology (RLT) and energizing light technology (ELT) t30 -t0 differences decrease with increasing baseline values.
intradermal collagen density and reduced signs of aging.
The proposed underlying mechanisms include the photo-
stimulation of terminal molecules in the electron transport
chain and the subsequent adenosine triphosphate (ATP)
concentration increase,
along with the selective light-driven
activation of water molecules,
thereby enhancing metabolic
exchange and influencing the ion transporter systems found
in cellular membranes.
Detailed analysis of the gene ex-
pression profiles in human fibroblasts revealed an influence
of low-intensity red light with a 628-nm wavelength on 111
different genes that are involved in cellular functions, such as
cell proliferation; apoptosis; stress response; protein, lipid
and carbohydrate metabolism; mitochondrial energy me-
tabolism; DNA synthesis and repair; antioxidant related
functions; and cytoskeleton- and cell-cell interaction-related
A specific role of reactive oxygen species (ROS)
in increasing fibroblast proliferation and motility has re-
cently been reported, suggesting that the elevation of ROS
via photodynamic therapy can enhance the cellular functions
of dermal fibroblasts through specific mitogen-activated
protein kinase (MAPK) signaling pathways in vitro.
light-induced free radical formation in human skin has been
investigated in detail, demonstrating that red light with 620
and 670 nm wavelengths increases the concentration of ROS
even without the influence of external photosensitizers.
Because fibroblasts are responsible for collagen production
in wound healing, dermal remodeling, and tissue repair, we
decided to focus on increased collagen density as a surrogate
marker for fibroblast activity, and abandoned such invasive
monitoring methods as histologic examinations following
skin biopsies for our study. Ultrasonographic collagen as-
sessment is described as a feasible noninvasive methodol-
ogy for monitoring dermal density during the senescence
A report of the stimulatory effects of 660 nm wavelength
laser light on scar fibroblasts
could conceivably explain the
potential reactivation of a >40-year-old knee injury, which
occurred in one volunteer during the ELT treatment. There-
fore, the influence of PBM on scar tissue should be subject to
further investigation.
Some authors emphasize the importance of distinct
wavelengths for optimal results.
In our study, the
differences between the RLT and ELT treatments in clinical
outcome and patient satisfaction were not significant, indi-
cating that despite spectral differences, both light sources
were commensurably effective regarding study objectives.
Further studies of the treatment parameters are necessary.
The evaluation of clinical photography revealed a partic-
ular worsening of fine lines and wrinkles from t0 to t30 in the
control group, which was not expected for a course of only
12 weeks. A possible explanation could be the seasonal
variation of skin condition between winter and summer cli-
mates and the influence of solar radiation, as the clinical
photography revealed skin pigmentation as a consequence of
exposure to sunlight.
We observed a tendency that ELT/RLT treatment led to
better results in female volunteers regarding the collagen
density increase. This gender-specific response could con-
ceivably be explained by physiological differences between
male and female skin
on endocrine and extracellular
matrix levels. However, gender-specific differences should
be evaluated in greater detail in further investigations.
RLT and ELT are large-area and full-body treatment
modalities for skin rejuvenation and improvements in skin
feeling and skin complexion. The application of RLT and
ELT provides a safe, non-ablative, non-thermal, atraumatic
photobiomodulation treatment of skin tissue with high pa-
tient satisfaction rates. RLT and ELT can extend the spectrum
of anti-aging treatment options available to patients looking
for mild and pleasant light-only skin rejuvenation.
We thank Dr. Christine Fischer, Heidelberg, for help and
advice regarding the statistical analysis of our data. We also
thank all of the volunteers for their participation in this
study. This study was fully funded by JK-Holding GmbH,
Windhagen, Germany. All materials, light sources, and
evaluation equipment were provided by the sponsor.
Author Disclosure Statement
The principal investigator (Alexander Wunsch) was
mandated and remunerated by the sponsor to conduct the
study. The authors have received funds to plan, conduct, and
evaluate the study.
1. Chung H., Dai T., Sharma S., Huang Y.Y., Carroll J., and
Hamblin M. (2012). The nuts and bolts of low-level laser
(light) therapy. Ann. Biomed. Eng. 40, 516–533.
2. Anderson R.R., and Parrish J.A. (1981). The optics of human
skin. J. Invest. Dermatol. 77, 13–19.
3. Gupta A.K., Filonenko N., Salansky N., and Sauder D.N.
(1998). The use of low energy photon therapy (LEPT) in
venous leg ulcers: a double-blind, placebo-controlled study.
Dermatol. Surg. 24, 1383–1386.
4. Minatel D.G., Frade M.A., Franca S.C., and Enwemeka C.S.
(2009). Phototherapy promotes healing of chronic diabetic
leg ulcers that failed to respond to other therapies. Lasers
Surg. Med. 41, 433–441.
5. Barolet D., Roberge C.J., Auger F.A., Boucher A., and Ger-
main L. (2009). Regulation of skin collagen metabolism
in vitro using a pulsed 660 nm LED light source: clinical
correlation with a single-blinded study. J. Invest. Dermatol.
129, 2751–2759.
6. Huang, Y.Y., Chen, A.C.H., Carroll, J.D., and Hamblin, M.R.
(2009). Biphasic dose response in low level lightherapy. Dose
Response 7, 358–383.
7. Calderhead R.G. (2007). The photobiological basics behind
light-emitting diode (LED) phototherapy. Laser Ther. 16, 97–
8. Papadavid E., and Katsambas A. (2003). Lasers for facial
rejuvenation: A review. Int. J. Dermatol. 42, 480–487.
9. Khoury J.G., and Goldman M.P. (2008). Use of light-emitting
diode photomodulation to reduce erythema and discom-
fort after intense pulsed light treatment of photodamage.
J. Cosmet. Dermatol. 7, 30–34.
10. Smith K.C. (2005). Laser (and LED) therapy is phototherapy.
Photomed. Laser Surg. 23, 78–80.
11. van Breugel H.H., and Ba
¨r P.R. (1992). Power density and
exposure time of He-Ne laser irradiation are more important
than total energy dose in photo-biomodulation of human
fibroblasts in vitro. Lasers Surg. Med. 12, 528–537.
12. Shoshani D., Markovitz E., Monsterey S.J., and Narins D.J.
(2008). The Modified Fitzpatrick Wrinkle Scale: A clinical
validated measurement tool for nasolabial wrinkle severity
assessment. Dermatol. Surg. 34, 85–91.
13. Vinck E.M., Cagnie B.J., Cornelissen M.J., Declercq H.A., and
Cambier D.C. (2005). Green light emitting diode irradiation
enhances fibroblast growth impaired by high glucose level.
Photomed. Laser Surg. 23, 167–171.
14. Karu T.I. (2010). Multiple roles of cytochrome c oxidase in
mammalian cells under action of red and IR-A radiation.
IUBMB Life 62, 607–610.
15. Weiss R.A., McDaniel D.H., Geronemus R.G., and Weiss
M.A. (2005). Clinical trial of a novel non-thermal LED array
for reversal of photoaging: clinical, histologic, and surface
profilometric results. Lasers Surg. Med. 36, 85–91.
16. Russell B.A., Kellett N., and Reilly L.R. (2005). A study to
determine the efficacy of combination LED light therapy
(633 nm and 830 nm) in facial skin rejuvenation. J. Cosmet.
Laser Ther. 7, 196–200.
17. Sadick N.S. (2008). A study to determine the efficacy of a
novel handheld light-emitting diode device in the treatment
of photoaged skin. J. Cosmet. Dermatol. 7, 263–267.
18. Lee S.Y., Park K.H., Choi J.W., et al. (2007). A prospective,
randomized, placebo-controlled, double-blinded, and split-
face clinical study on LED phototherapy for skin rejuvena-
tion: Clinical, profilometric, histologic, ultrastructural, and
biochemical evaluations and comparison of three different
treatment settings. J. Photochem. Photobiol. B. 88, 51–67.
19. Santana–Blank L., Rodrı
´guez–Santana E., and Santana–
´guez K.E. (2012). Photobiomodulation of aqueous in-
terfaces as selective rechargeable bio-batteries in complex
diseases: personal view. Photomed. Laser Surg. 30, 242–249.
20. Calderhead R.G., Kubota J., Trelles M.A., and Ohshiro T.
(2008). One mechanism behind LED phototherapy for
wound healing and skin rejuvenation: Key role of the mast
cell. Laser Therapy 17, 141–148.
21. Zhang Y., Song S., Fong C.C., et al. (2003). cDNA microarray
analysis of gene expression profiles in human fibroblast cells
irradiated with red light. J. Invest. Dermatol. 120, 849–857.
22. Jang Y.H., Koo G.B., Kim J.Y., Kim Y.S., and Kim Y.C. (2013).
Prolonged activation of ERK contributes to the photo-
rejuvenation effect in photodynamic therapy in human
dermal fibroblasts. J. Invest. Dermatol. 133, 2265–2275.
23. Zastrow L., Groth N., Klein F., et al. (2009). The missing
link–light-induced (280–1,600 nm) free radical formation in
human skin. Skin Pharmacol. Physiol. 22, 31–44.
24. Crisan D., Crisan M., Moldovan M., Lupsor M., and Badea R.
(2012). Ultrasonographic assessment of the cutaneous
changes induced by topical flavonoid therapy. Clin. Cosmet.
Investig. Dermatol. 5, 7–13.
25. Webb C., Dyson M., and Lewis W.H. (1998). Stimulatory
effect of 660 nm low level laser energy on hypertrophic scar-
derived fibroblasts: possible mechanisms for increase in cell
counts. Lasers Surg. Med. 22, 294–301.
26. Baez F., and Reilly L.R. (2007). The use of light-emitting
diode therapy in the treatment of photoaged skin. J. Cosmet.
Dermatol. 6, 189–194.
27. Vinck E.M., Cagnie B.J., Cornelissen M.J., Declercq H.A., and
Cambier D.C. (2003). Increased fibroblast proliferation in-
duced by light emitting diode and low power laser irradia-
tion. Lasers Med. Sci. 18, 95–99.
28. Goldberg D.J., Amin S., Russell B.A., Phelps R., Kellett N.,
and Reilly L.A. (2006). Combined 633-nm and 830-nm led
treatment of photoaging skin. J. Drugs Dermatol. 5, 748–753.
29. Giacomoni P.U., Mammone T., and Teri M. (2010). Gender-
linked differences in human skin. J. Dermatol. Sci. 55, 144–
30. Oh, J.H., Kim Y.K., Jung J.Y., et al. (2011). Intrinsic aging-
and photoaging-dependent level changes of glycosamino-
glycans and their correlation with water content in human
skin. J. Dermatol. Sci. 62, 192–201.
Address correspondence to:
Alexander Wunsch
Hirschgasse 11
69120 Heidelberg
... 6,[9][10][11] The clinical use of PBM has shown many promising results in inflammatory conditions, tissue repair, wound healing, and others. 9,12 For rejuvenation, in vitro data have suggested an increase in procollagen I production and gene expression, as well as a reduction in the gene and protein expression of matrix metalloproteinase 1 (MMP-1). 10,13 A few published clinical trials have assessed the effect of PBM on rejuvenation. ...
... 10,13 A few published clinical trials have assessed the effect of PBM on rejuvenation. 12,[14][15][16][17][18][19][20][21][22] However, most of them have evaluated red PBM when compared with a nontreated control, compared or associated with infrared wavelengths, or where there was no comparison with a control group. Hence, clinical trials considering these limitations and those designed to reduce the risk of bias are still needed. ...
Full-text available
Objective: This study aimed to evaluate red and amber light-emitting diode protocols for facial rejuvenation at the same light dose. Background: The demand for minimally invasive cosmetic procedures to address skin aging has grown throughout the world. In vitro red and amber photobiomodulation (PBM) has been shown to improve collagen synthesis. Meanwhile, red PBM has already been studied in clinical trials; however, a comparison of the use of different wavelengths at the same light dose to reduce periocular wrinkles has not yet been performed. Methods: This split-face, randomized clinical trial recruited 137 women (40-65 years old) presenting with skin phototypes II-IV and Glogau photoaging scale types II-IV. The individuals received 10 sessions for 4 weeks of red (660 nm) and amber (590 nm) PBM (3.8 J/cm2), one at each side of the face. The outcomes, measured before and after the treatments, were the periocular wrinkle volume measured by VisioFace® RD equipment; hydration measured by the Corneometer CM 825; skin elasticity measured by the Cutometer Dual MPA 580; and quality of life determined by adapted versions of validated questionnaires [Melasma Quality of Life Scale-Brazilian Portuguese (MelasQoL-BP) and Skindex-29]. Results: There was a significant reduction in wrinkle volume after red (31.6%) and amber (29.9%) PBM. None of the treatments improved skin hydration and viscoelasticity. Both questionnaires showed improvements in participants' quality of life. Conclusions: PBM, both at red and amber wavelengths, is an effective tool for rejuvenation, producing a 30% wrinkle volume reduction. The technique has strong potential in patients with diabetes or those presenting with keloids, conditions for which highly inflammatory rejuvenating procedures are not indicated. Clinical trial registration number: REBEC-6YFCBM.
... In addition to reducing wrinkles, it stimulates fibroblasts and thus increases the production of collagen and elastin. 9 Thanks to its ability to stimulate cellular metabolisms, confirmed in recent years by numerous studies, [10][11][12][13][14] photobiomodulation has now spread to many fields of medicine such as endocrinology, neurosurgery, dermatology and dentistry. 15 ...
Full-text available
Background: Photobiomodulation is a process by which the absorption of red light energy produces a series of physiological effects at the cellular level such as the enhancement of mitochondrial Adenosine Triphosphate (ATP) production, cell signaling and growth factor synthesis, and the reduction of oxidative stress. Light emitting diodes (LEDs) photobiomodulation is an increasingly popular therapy for treating skin problems, especially for reversing the signs of skin aging. Objective: The objective of this study is to demonstrate the effectiveness of a photobiomodulation treatment using red LEDs on the facial skin at a rate of two sessions per week for 3 months. The LED mask used is the Skin Light Dior x Lucibel mask diffusing a cold red light with a wavelength of 630 ± 10 nm and a power of 15.6 J/cm2 for a duration of 12 min. Method: In order to demonstrate the effectiveness of the mask in reversing the signs of skin aging, a clinical study was conducted on 20 healthy Caucasian women: the antiwrinkle effect by measuring the depth of the crow's feet wrinkle, the relaxation of the oval of the face by clinical scoring, the firmness and elasticity of the skin by cutometric measurement, the density of the dermis by ultrasound analysis, the smoothness of the skin by measuring the roughness at the cheek, the homogeneity of the complexion by chromametric measurement, the diameter of the pores by macrophotographs and finally the sebo-regulating effect by measurement of the rate of sebum and quantification of the number of pores containing porphyrin in the subjects presenting a mixed to oily skin. The satisfaction of the volunteers was also evaluated at the end of the study via a self-questionnaire. Results: The efficacy results measured after 1, 2, and 3 months of use are progressive and confirm the interest of LED photobiomodulation to reverse the visible signs of skin aging. All the volunteers observed an overall improvement in skin quality. Conclusion: All the results observed confirm the interest of using photobiomodulation to reverse the visible signs of aging. These results last for up to 1 month after stopping the use of the mask, which is a sign of lasting structural and functional rejuvenation of the skin.
... Among the studied cellular mechanisms related to the biological activities stimulated by FLE, the reduced secretion of pro-inflammatory cytokines (IL-6 and TNF-α), the stimulation of collagen by the fibroblasts, and the promotion of the mechanisms of angiogenesis can have a role in skin rejuvenation processes [7,30]. The optimization of the FLE treatment tailored to the features of each opsin can maximize the benefit to the skin [23]. ...
Full-text available
This study, for the first time, evaluated the safety and efficacy of a new natural-based topical gel containing a spirulina extract. This photoconverter gel generates fluorescent light energy (FLE) via a red LED light device, which is proven to be effective for age control of facial skin. This was a one-centre, observational, uncontrolled pilot trial. Eight healthy female subjects aged 35 to 65 years old, with Fitzpatrick skin types II–V were recruited. The duration of the study was five treatment sessions of one treatment every seven days, with a final follow-up at one month after the last treatment session. The images and the related data were acquired with the SONY® Mod. DSCRX10M3, the Canfield VISIA Facial Imaging System®, and QUANTIFICARE 3D® analysis. Patient compliance was excellent (100%) and the treatment was described as warm and pleasant by the patients. After 30 days, VISIA parameters such as wrinkles, texture, red areas, and Trueskin Age® had improved. The safety and efficacy of the FLE treatment assessed in this trial were achieved for overall rejuvenation of facial skin, focusing on wrinkles evaluated via the specific VISIA algorithms.
... 13 For the past few years, light-emitting diodes (LEDs) have been demonstrated as an emerging and safe tool with fewer side effects and good results and good results for treating many skin conditions, [14][15][16][17][18] for example, facial vascular lesions. 19 This is why we decided to test it to treat facial hypervascularization. The light from the LEDs interacts directly with its target chromophore (depending on the wavelengths used) to generate photomodulation at a vascular level, reducing the caliber of these small vessels and, therefore, the reddish appearance of the skin. ...
Background: Superficial facial vascular lesions can be an aesthetic problem and a symptom of different skin diseases. Objective: It was to compare the efficacy and safety profiles of Dermalux® Tri-Wave MD, based on three combined light-emitting diodes (LEDs) technology and intense pulsed light (IPL) for reducing the excess of facial vascularization due to superficial cutaneous vascular lesions. Materials and methods: The study had a single-center, proof-of-concept, open-label, and prospective design. Two groups of adult patients were treated for facial hypervascularization, LED-Group with an LED device combining 633 and 830 nm and IPL-Group with an IPL (555-950 and 530-750 nm). Variables assessed were hemoglobin hyperconcentration (HH), hemoglobin-affected area (HAA) through Antera 3D®, and pain using the Numeric Pain Rating Scale. Results: Twenty subjects were included, 10 by group (50% female). LED-Group: Mean age 32.1 years (range, 21-46). IPL-Group: Mean age 34.5 years (range, 25-49). HH: LED-Group 100% had a moderate improvement; in the IPL-Group, 10% was moderate, and 90% was marked. HAA: LED-Group 10% had a slight improvement, 70% moderate, and 20% marked; in the IPL-Group, 100%, the improvement was marked. Seventy percent of LED-Group patients reported no pain, 30% mild; in the IPL-Group, 100% of patients reported severe pain. Conclusions: Treatment with combined red and near-infrared LEDs effectively reduced the excess of facial vascularization with moderate outcomes compared with IPL, but without secondary effects and no pain. This treatment could represent an effective, safe, and well-tolerated approach for facial vascular lesions.
Importance Police shootings can cause serious acute injury, and knowledge of subsequent health outcomes may inform interventions to improve care. Objective To analyze long-term health care costs among survivors of police shootings compared with those surviving nonfirearm police enforcement injuries using a retrospective design. Design, Setting, and Participants This population-based cohort analysis identified adults (age ≥16 years) who were injured by police and required emergency medical care between April 1, 2002, and March 31, 2022, in Ontario, Canada. Exposure Police shootings compared with other mechanisms of injury involving police. Main Outcomes and Measures Long-term health care costs determined using a validated costing algorithm. Secondary outcomes included short-term mortality, acute care treatments, and rates of subsequent disability. Results Over the study, 13 545 adults were injured from police enforcement (mean [SD] age, 35 [12] years; 11 637 males [86%]). A total of 13 520 individuals survived acute injury, and 8755 had long-term financial data available (88 surviving firearm injury, 8667 surviving nonfirearm injury). Patients surviving firearm injury had 3 times greater health care costs per year (CAD$16 223 vs CAD$5412; mean increase, CAD$9967; 95% CI, 6697-13 237; US $11 982 vs US $3997; mean increase, US $7361; 95% CI, 4946-9776; P < .001). Greater costs after a firearm injury were not explained by baseline costs and primarily reflected increased psychiatric care. Other characteristics associated with increased long-term health care costs included prior mental illness and a substance use diagnosis. Conclusions and Relevance In this longitudinal cohort study of long-term health care costs, patients surviving a police shooting had substantial health care costs compared with those injured from other forms of police enforcement. Costs primarily reflected psychiatric care and suggest the need to prioritize early recognition and prevention.
Low-level light therapy (LLLT) employs athermal and atraumatic levels of illumination, typically in the visible or near-infrared (NIR) regions of the electromagnetic spectrum, to target tissue and stimulate a clinically useful local or systemic effect. LLLT has demonstrated beneficial applications in the areas of wound healing, pain management, and various musculoskeletal conditions as well as skin rejuvenation. This chapter dives into the benefits of using LED-based devices in aesthetic applications, resulting in a safer and more convenient approach to benefit patients.
Full-text available
Organic semiconductors that emit by the process of multi‐resonance thermally activated delayed fluorescence (MR‐TADF) can deliver narrowband and efficient electroluminescence while being processable from solvents and metal‐free. This renders them attractive for use as the emitter in sustainable light‐emitting electrochemical cells (LECs), but so far reports of narrowband and efficient MR‐TADF emission from LEC devices are absent. Here, this issue is addressed through careful and systematic material selection and device development. Specifically, the authors show that the detrimental aggregation tendency of an archetypal rigid and planar carbazole‐based MR‐TADF emitter can be inhibited by its dispersion into a compatible carbazole‐based blend host and an ionic‐liquid electrolyte, and it is further demonstrated that the tuning of this active material results in a desired balanced p‐ and n‐type electrochemical doping, a high solid‐state photoluminescence quantum yield of 91%, and singlet and triplet trapping on the MR‐TADF guest emitter. The introduction of this designed metal‐free active MR‐TADF material into a LEC, employing air‐stabile electrodes, results in bright blue electroluminescence of 500 cd m ⁻² , which is delivered at a high external quantum efficiency of 3.8% and shows a narrow emission profile with a full‐width‐at‐half‐maximum of 31 nm.
Background: Photobiomodulation therapy (PBMT) can significantly reduce inflammation and relieve pain, including postoperative pain and edema. The study aimed to evaluate the performance of a photobiomodulation-based device that includes a static magnetic field (SMF) to treat laser- or intensive and fractional radiofrequency-related side effects, such as pain, redness, and edema in patients treated for different dermatological conditions. Methods: The study had a prospective, non-randomized, single-center design. Male and female patients aged 18 years or older underwent one or two PBMT-SMF (anti-inflammatory or anti-edematous) sessions on the same day, once or twice a week, after laser or radiofrequency facial treatments due to various dermatological disorders. Variables and efficacy assessments were pain, redness, edema, and their reduction from baseline to the last visit. Results: Twenty-seven patients were included, seven (25.9%) men and 20 (74.1%) women, with a mean (SD) age of 43.7 (14.1) years. Seven (25.9%) patients were treated with radiofrequency, and 20 (74.1%) patients with a vascular laser (three [15%] for angioma, two [10%] for scars, three [15%] for erythrosis, and 12 [60%] for rosacea). After the PBMT-SMF protocol, overall mean pain reduction was 40 percent, and redness and edema reduction were shown by the pictures taken before and after the PBMT-SMF procedure. Limitations: The primary limitations were the small number of patients and no quantitative variables for redness and edema. Conclusion: PBMT-SMF reduced edema and inflammation after treatment with lasers or intensive or fractional radiofrequency for facial conditions, and probably, analgesic and anti-inflammatory drugs.
Attaining effective warm white light emitting in functionally advantageous transparent polycrystalline ceramics is vitally important to guarantee the development of both human and botanical systems. In response to this aim, a series of Dy3+ doped Y2Zr2O7 (YZO) transparent ceramics were prepared via a solid‐state reaction and vacuum sintering approach in this work. These fabricated ceramics show high transparency, where the in‐line transmittance at 700 nm is about 76 %, which is very close to the theoretical limit (78%). In addition, under the excitation of UV light sources (358 nm and 384 nm), strong warm white light emissions were observed in these YZO:Dy transparent ceramics. The corresponding photoluminescence characteristics and mechanisms of YZO:Dy ceramics are investigated carefully. The Dy doped YZO ceramics integrate with high transparency and UV‐excitable warm white light emission properties, making them promising light‐emitting converter materials for light emitting source applications. This article is protected by copyright. All rights reserved
Full-text available
Background: Photobiomodulation (PBM) therapy is an increasingly popular modality for aesthetic skin rejuvenation. PBM induces genomic, proteomic and metabolomic processes within target cells but such manipulation of cell behavior has led to concerns about oncologic safety. Objectives: This article presents a summary of the clinical and pre-clinical evidence for the oncologic safety of PBM for aesthetic skin rejuvenation. Methods: A focused systematic review was performed, wherein safety data from clinical trials of PBM for skin rejuvenation was supplemented by analyses of in vitro data using cells derived from human skin and human neoplastic cells and in vivo data of tumors of the skin, oral cavity and breast. Results: Within established parameters, red/near infrared light mainly enhances proliferation of healthy cells without a clear pattern of influence on cell viability. The same light parameters mainly reduce neoplastic cell proliferation and viability or else make no difference. Invasiveness potential (appraised by cell migration assays and/or differential gene expression) is equivocal. PBM does not induce dysplastic change in healthy cells. In vivo tumor models yield varied results with no clear pattern emerging. There are no relevant clinical trials data linking PBM with any significant adverse events including the finding of a new or recurrent malignancy. Conclusions: Current clinical and pre-clinical evidence suggests that PBM is oncologically safe for skin rejuvenation and there is no evidence to support the proposition that it should be avoided by patients who have previously undergone treatment for cancer.
Full-text available
Light-emitting diodes (LEDs) have attracted a lot of attention in light-only skin rejuvenation and wound healing with an 830 nm/633 nm combination, but the mechanisms by which LED therapy speeds up the healing process and increases collagen synthesis remain unclear. One hypothesis, ex-amined in the present study, concerns the interaction between 830 nm near infrared light and the degranulation of dermal mast cells. The left forearm of 8 healthy male subjects was irradiated with an 830 nm LED array (20 min, 57 J/cm2) with the right as the unirradiated control. Biopsies were taken before and two days after irradiation and routinely prepared for transmission electron microscopy (TEM), and compared between baseline, irradiated and unirradiated tissue. The TEM in all postirradiated specimens, while clearly showing no damage to the irradiated tissue with all tissue components essentially morphologically normal, demonstrated a mild inflammatory response 48 hr after 830 nm irradiation with interstitial and perivascular oedema. A number of macrophages and leukocytes had been recruited into the irradiated tissue, and mast cells had increased in number and had either degranulated or were in the process of doing so. The unirradiated control tissue showed no such changes. The TEM findings in the present study showed a clearly-visible inflammatory response similar to the first phase of wound healing, a ‘quasi-wound’, but created athermally and atraumatically following a single treatment with 830 nm light, thereby kick-starting the inflammatory stage of the wound healing process which is recognized as absolutely necessary in achieving good subsequent collagen synthesis in the second phase of proliferation, followed by good remodeling in the third phase. Good results in skin rejuvenation, both ablative and non-ablative, have been well-linked to establishing the wound healing process. The 830 nm-mediated ‘quasi-wound’ may well be an essential element in light-only LED photorejuvenation.Furthermore, the action of 830 nm on the inflammatory cells in actual wounds will significantly accelerate the wound healing process, controlling and peaking inflammation, and allowing proliferation to occur sooner and more efficiently.
Full-text available
Phototherapy is, in its broadest sense, the use of light for any kind of surgical or nonsurgical treatment, but it is the athermal and atraumatic therapeutic application of light which is now accepted as the working definition of phototherapy. The early light-emitting diodes (LEDs) were unsuitable for clinical applications because of low unstable output powers, broad wavebands and very high angles of divergence. In the late 1990’s, the Space Medicine Programme in the United States National Aeronautics and Space Administration (NASA), developed the ‘NASA LED’ with much higher output powers, a much narrower divergence and quasimonochromatic output. With the ability to mount multiple LEDs in planar arrays, large areas of tissue can be irradiated in one hands-off session, unlike the time-consuming and therapist-intensive punctal application with laser diodes. These arrays deliver almost laser-like wavelength specificity and with clinically useful penetration depths and intensities, three of the most important considerations when considering cellular targets in the light of the first law of photobiology which states that without absorption, there can be no reaction. In the past few years, LED-based systems have been successfully applied in an increasingly large number of fields, and three major wavelengths have emerged with a good photobiological basis and proven clinical utility: blue, around 415 nm; red, around 633 nm, and near infrared, around 830 nm. Each has its own specific cellular target or targets and biological action spectrum and reaction, but it has become even more clear that no single wavelength can accomplish everything and combination LED therapy has proved necessary for greatest efficacy. The application of LEDs has ushered in a new and exciting era in phototherapy, and offers a versatile and inexpensive therapeutic modality either as a stand-alone therapy, or as an adjunctive approach to enhance the good results of existing surgical modalities.
Full-text available
Photodynamic therapy (PDT) is known to be effective in the photorejuvenation of photoaged skin. However, the molecular mechanisms of rejuvenation by PDT remain elusive. In this study we aimed to understand the molecular events occurring during the photorejuvenation after PDT in dermal fibroblasts in vitro. First, we found that PDT conditions resulted in an increased fibroblasts proliferation and motility in vitro. Under this condition, cells had increased intracellular reactive oxygen species (ROS) production. Importantly, PDT induced a prolonged activation of extracellular-signal-regulated kinase (ERK) with a corresponding increase in matrix metalloproteinase (MMP)-3 and collagen type Iα mRNA and protein. Moreover, inhibition of PDT-induced ERK activation significantly suppressed fibroblast proliferation and expression of MMP-3 and collagen type Iα following PDT. In addition, NAC (an antioxidant) inhibited PDT-induced fibroblast proliferation and ERK activation indicating that prolonged ERK activation and intracellular ROS contribute to the proliferation of fibroblasts and the dermal remodeling process for skin rejuvenation. We also identified increased collagen volume and decreased elastotic materials which are used as markers of photoaging in human skin samples using histochemistry. Results from this study suggest that intracellular ROS stimulated by PDT in dermal fibroblasts lead to prolonged activation of ERK, and eventually fibroblast proliferation and activation. Our data thus reveal a molecular mechanism underlying the skin rejuvenation effect of PDT.Journal of Investigative Dermatology accepted article preview online, 21 January 2013; doi:10.1038/jid.2013.25.
Full-text available
Objective We tested the hypothesis that combined 660 and 890 nm LED phototherapy will promote healing of diabetic ulcers that failed to respond to other forms of treatment.Research Design and MethodsA double-blind randomized placebo controlled design was used to study 23 diabetic leg ulcers in two groups of 14 patients. Group one ulcers were cleaned, dressed with 1% silver sulfadiazine cream and treated with “placebo” phototherapy (<1.0 J cm−2) twice per week, using a Dynatron Solaris 705® device. Group two ulcers were treated similarly but received 3 J cm−2 dose.ResultsAt each of 15, 30, 45, 60, 75, and 90 days of healing, mean ulcer granulation and healing rates were significantly higher for group two than the “placebo” group (P < 0.02). While “placebo” treated ulcers worsened during the initial 30 days, group two ulcers healed rapidly; achieving 56% more granulation and 79.2% faster healing by day 30, and maintaining similarly higher rates of granulation and healing over the “placebo” group all through. By day 90, 58.3% of group two ulcers had healed fully and 75% had achieved 90–100% healing. In contrast, only one “placebo” treated ulcer healed fully by day 90; no other ulcer attained ≥90% healing.Conclusion Combined 660 and 890 nm light promotes rapid granulation and healing of diabetic ulcers that failed to respond to other forms of treatment. Lasers Surg. Med. 41:433–441, 2009. © 2009 Wiley-Liss, Inc.
Full-text available
Ultrasonography allows the quantification of dermal density and echogenicity changes during the physiological senescence process. Some active ingredients are able to slow down the tissular degeneration and disorganization process. The purpose of this study was to assess the cutaneous changes induced by the topical use of products containing Viniferol(®) as active ingredient, using high-frequency ultrasound. The study was performed over 12 weeks and included 80 healthy Caucasian female subjects, aged 22-75 years, divided into two groups: the study group and the control group. The product was applied according to a predetermined protocol. The measurements performed for each subject were: the thickness of the epidermis and dermis (mm), the number of low, medium, and high echogenic pixels, and the number of low echogenic pixels in the upper dermis/number of low echogenic pixels in the lower dermis. All the parameters showed a significant improvement. Ultrasound measurements showed an increase of the mean thickness of the epidermis (P < 0.0001) and dermis (P < 0.0001) following the application of the Viniferol product as compared to the control group. The changes in the dermal echogenicity confirm the efficacy and direct action of Viniferol upon the cutaneous fibroblasts. No side effects related to the treatment were recorded. The study proves the efficacy of this active ingredient in the cutaneous senescence process as well, as the fact that anti-aging prophylaxis should be initiated in the 20-40 year critical age group. This interval involves specific changes in dermal echogenicity that quantify intense molecular, biochemical and structural changes, being thus mostly and highly responsive to the anti-aging therapy.
Full-text available
In this personal view, we propose that the modulation of the structure and function of water by light may come to embody a new mechanistic approach for the treatment of complex diseases. Long considered an innocuous medium, water has increasingly been found to be a key player in numerous mechanisms, including first-contact events in which cells decide between survival and apoptosis. Consequently, externally applied electromagnetic energy (light) may selectively target the organization of water to steer biological function. We survey light-water research with particular emphasis on the quasi-crystalline exclusion zone (EZ), part of the cell's aqueous interface that is just now beginning to be decoded. The current state of research, the technical challenges involved in obtaining evidence in biological systems, and some potential uses and implications of EZ water in medicine are presented. Though existing data have not yet proven the role of EZ water in photobiomodulation, research shows that EZ water can store charge and can later return it in the form of current flow, with as much as 70% of the input charge being readily obtainable. Macroscopic separation of charges can be stable for days to weeks and has unusual electric potential. Water is, thus, an unexpectedly effective charge separation and storage medium. We propose that the EZ may be selectively targeted in photobiomodulation as an efficient energy reservoir, which cells can use expeditiously to fuel cellular work, triggering signaling pathways and gene expression in the presence of injury-induced redox potentials.
Full-text available
Soon after the discovery of lasers in the 1960s it was realized that laser therapy had the potential to improve wound healing and reduce pain, inflammation and swelling. In recent years the field sometimes known as photobiomodulation has broadened to include light-emitting diodes and other light sources, and the range of wavelengths used now includes many in the red and near infrared. The term "low level laser therapy" or LLLT has become widely recognized and implies the existence of the biphasic dose response or the Arndt-Schulz curve. This review will cover the mechanisms of action of LLLT at a cellular and at a tissular level and will summarize the various light sources and principles of dosimetry that are employed in clinical practice. The range of diseases, injuries, and conditions that can be benefited by LLLT will be summarized with an emphasis on those that have reported randomized controlled clinical trials. Serious life-threatening diseases such as stroke, heart attack, spinal cord injury, and traumatic brain injury may soon be amenable to LLLT therapy.
Full-text available
The use of low levels of visible or near infrared light for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing cell death and tissue damage has been known for over forty years since the invention of lasers. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial in mainstream medicine. The biochemical mechanisms underlying the positive effects are incompletely understood, and the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength, fluence, power density, pulse structure and treatment timing has led to the publication of a number of negative studies as well as many positive ones. A biphasic dose response has been frequently observed where low levels of light have a much better effect on stimulating and repairing tissues than higher levels of light. The so-called Arndt-Schulz curve is frequently used to describe this biphasic dose response. This review will cover the molecular and cellular mechanisms in LLLT, and describe some of our recent results in vitro and in vivo that provide scientific explanations for this biphasic dose response.
Glycosaminoglycans (GAGs) have various structural and physiological regulatory functions in skin, including tissue water maintenance, due to their high water-holding capacity. To investigate changes of GAGs during intrinsic aging and photoaging of human skin and their correlations with water content. Samples of sun-protected buttock and sun-exposed forearm skin were obtained from young male (21-30 years, n=8) and female (20-33 years, n=8) subjects, as well as old male (70-78 years, n=8) and female (70-80 years, n=8) subjects, and their epidermal and dermal contents of hyaluronic acid (HA), total sulfated GAG (tsGAG), total uronic acid (tUA), and tissue water were measured. HA content was determined by enzyme-linked immunosorbent assay using HA-binding protein, tsGAG by the sulfated GAG assay kit using 1,9-dimethylmethylene blue, tUA by carbazole reaction, and tissue water by subtraction of tissue dry weight from wet weight. In the buttock, HA was higher in dermis than in epidermis, while tsGAG and tUA were higher in epidermis. In intrinsically aged buttock, epidermal HA and dermal tsGAG and tUA decreased. However, when analyzed for each gender, epidermal tsGAG, tUA, and tissue water decreased only in females. Forearm/buttock ratios of each molecule were compared for determination of photoaging-dependent changes. Forearm/buttock ratios of HA, tsGAG, tUA, and tissue water increased in aged dermis, but showed no change in aged epidermis. When analyzed for each gender, ratios of epidermal HA and tissue water increased only in aged females, while ratios of epidermal tsGAG, tUA, and tissue water decreased only in aged males. Correlations of water content with HA, tsGAG, and tUA were found in epidermis, but not with tsGAG in dermis. These intrinsic aging- and photoaging-dependent GAG changes and their correlations with water content provide new insights into the pathophysiology of dry skin in the elderly.
This article reviews the current knowledge in photobiology and photomedicine about the influence of monochromatic, quasimonochromatic, and bread-band radiation of red-to-near infrared (IR-A) part on solar spectrum upon mammalian cells and human skin. The role of cytochrome c oxidase as the photoacceptor and photosignal transducer is underlined and its photosensitivity at certain circumstances is discussed. The role of ATP as a critical signaling molecule is discussed. (C) 2010 IUBMB IUBMB Life, 62(8): 607-610, 2010