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

Abstract

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.

Full text

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
1
and Karsten Matuschka
2
Abstract
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
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.
Introduction
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.
1
Because of the
combination of high degree of penetration in skin
2
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.
3–5
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.
6
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.
7
The known severe side effects of
traumatic skin rejuvenation procedures, such as inflamma-
tion, unpleasant pain perception, and prolonged social down
time,
8
are unknown in PBM; PBM has been successfully ad-
ministered to reduce common symptoms of laser resurfacing
1
Medical Light Consulting, Heidelberg, Germany.
2
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
93

and IPL treatment.
9
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.
10
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-
length,
7,11
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)
Sex
Female 49/86.0% 34/70.8% 15/65.2%
Male 8/14.0% 14/29.2% 8/34.8%
Age
a
46.2 –9.0 48.6 –9.8 44.4 –10.2
Weight
a
72.9 –15.22 73.4 –13.7 73.7 –13.4
Skin complexion (subjective)
b
4.54 –1.92 4.87 –2.02
Skin feeling (subjective)
b
5.33 –2.04 5.24 –2.18
Skin roughness (R
a
)
b
15.29 –4.20 14.84 –4.04 11.79 –2.17
Collagen intensity score
c
20.40 –6.55 18.96 –3.54 23.22 –7.36
Expert wrinkle assessment
d
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%
a
Values represent means –SD at t0.
b
Values represent means –SD at t0; small numbers indicate good values.
c
Values represent means –SD at t0; large numbers indicate good values.
d
Majority vote of three blinded expert reviewers, based on the Modified Fitzpatrick Wrinkle Scale.
RLT, red light technology; ELT, energizing light technology.
94 WUNSCH AND MATUSCHKA

subjective and clinical parameters was conducted at t30 +6
months.
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
´colletage
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).
Measurements
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
lite
digital fringe projection system
(GFM Messtechnik, Berlin, Germany) was used to measure
the objective arithmetical roughness (R
a
) of the skin surface
in the periorbital region.
Photography
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
2
10.4 mW/cm
2
5.9 mW/cm
2
13.3 mW/cm
2
Total irradiance (570–850 nm) 42.8 mW/cm
2
54.8 mW/cm
2
10.3 mW/cm
2
23.4 mW/cm
2
Treatment duration 20 min 15 min 25 min 12 min
Treatment dose (611–650 nm) 8.5 J/cm
2
9.4 J/cm
2
8.9 J/cm
2
9.6 J/cm
2
Total radiant exposure (570–850 nm) 51.4 J/cm
2
49.3 J/cm
2
15.5 J/cm
2
16.8 J/cm
2
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
percentages.
BELT STUDY 95

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
a
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)
12
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
2
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.
Results
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
roughness.
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.
96 WUNSCH AND MATUSCHKA

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
improvement.
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)
Within-group
pvalue ELT (n=48)
Within-group
pvalue
Controls
(n=23)
Within-group
pvalue
Between-
group pvalue
Skin complexion (subjective)
a
-1.29 –1.98 <0.001 -1.72 –2.35 <0.001 0.064
Skin feeling (subjective)
a
-1.01 –2.30 <0.001 -1.65 –2.17 <0.001 0.167
Skin roughness (R
a
)
a
-1.79 –2.46 <0.001 -1.58 –2.22 <0.001 0.95 –1.45 0.003 0.003
Collagen intensity score
b
5.75 –4.54 <0.001 6.40 –5.17 <0.001 -0.26 –5.09 0.84 <0.001
Expert wrinkle assessment
c
<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%
a
Values represent means –SD of the difference t30 -t0; negative numbers indicate improvement.
b
Values represent means –SD of the difference t30 -t0; positive numbers indicate improvement.
c
Majority vote of three blinded expert reviewers, v
2
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.
BELT STUDY 97

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
a
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
a
. 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
recorded.
Discussion
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,
13
620, 680, 760, and 820 nm.
14
The treatment
doses vary significantly, ranging from 0.1 J/cm
2
for 590 nm
LED light with a specific sequence of pulsing,
15
up to 126 J/
cm
2
for 633 nm continuous LED light.
16,17
The power of the
light typically ranges between 1 and 1000 mW, depending
upon the type of light source and the application.
1
Efficacy
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.
98 WUNSCH AND MATUSCHKA

intradermal collagen density and reduced signs of aging.
18
The proposed underlying mechanisms include the photo-
stimulation of terminal molecules in the electron transport
chain and the subsequent adenosine triphosphate (ATP)
concentration increase,
14
along with the selective light-driven
activation of water molecules,
19
thereby enhancing metabolic
exchange and influencing the ion transporter systems found
in cellular membranes.
20
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
functions.
21
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.
22
The
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.
23
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
process.
24
A report of the stimulatory effects of 660 nm wavelength
laser light on scar fibroblasts
25
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.
16–18,26–28
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
29,30
on endocrine and extracellular
matrix levels. However, gender-specific differences should
be evaluated in greater detail in further investigations.
Conclusions
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.
Acknowledgments
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.
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Address correspondence to:
Alexander Wunsch
Hirschgasse 11
69120 Heidelberg
Germany
E-mail: praxis@alexanderwunsch.de
100 WUNSCH AND MATUSCHKA