Prophylactic low‐level light therapy for the treatment of hypertrophic scars and keloids: A case series

Abstract

Hypertrophic and keloid scars result from alterations in the wound healing process. Treating abnormal scars remains an important challenge. The aim of this case series was to investigate the effectiveness of near infrared (NIR) light emitting diode (LED) treatment as a prophylactic method to alter the wound healing process in order to avoid or attenuate the formation of hypertrophic scars or keloids.
Three patients (age 27-57) of phototypes I-III with hypertrophic scars or keloids due to acne or surgery participated in this case series. Following scar revision by surgery or CO(2) laser ablation on bilateral areas, one scar was treated daily by the patient at home with non-thermal, non-ablative NIR LED (805 nm at 30 mW/cm(2)) for 30 days. Efficacy assessments, conducted up to a year post-treatment, included the Vancouver Scar scale (VSS), clinical global assessment of digital photographs, and quantitative profilometry analysis using PRIMOS. Safety was documented by adverse effects monitoring.
Significant improvements on the NIR-treated versus the control scar were seen in all efficacy measures. No significant treatment-related adverse effects were reported.
Possible mechanisms involved are inhibition of TGF-beta I expression. Further studies in larger group of patients are needed to evaluate this promising technique.

Full text

Lasers in Surgery and Medicine 42:597–601 (2010)
Case Report
Prophylactic Low-Level Light Therapy for the Treatment of
Hypertrophic Scars and Keloids: A Case Series
Daniel Barolet, MD
1,2
* and Annie Boucher, PhD
1
1
RoseLab Skin Optics Research Laboratory, Montreal, Quebec, Canada H3R 3L5
2
Dermatology Division, Department of Medicine, McGill University, Montreal, Quebec, Canada H3A 1A1
Background and Objectives: Hypertrophic and keloid
scars result from alterations in the wound healing process.
Treating abnormal scars remains an important challenge.
The aim of this case series was to investigate the
effectiveness of near infrared (NIR) light emitting diode
(LED) treatment as a prophylactic method to alter
the wound healing process in order to avoid or attenuate
the formation of hypertrophic scars or keloids.
Study Design/Patients and Methods: Three patients
(age 27–57) of phototypes I– III with hypertrophic scars or
keloids due to acne or surgery participated in this case
series. Following scar revision by surgery or CO
2
laser
ablation on bilateral areas, one scar was treated daily by the
patient at home with non-thermal, non-ablative NIR LED
(805 nm at 30 mW/cm
2
) for 30 days. Efficacy assessments,
conducted up to a year post-treatment, included the
Vancouver Scar scale (VSS), clinical global assessment
of digital photographs, and quantitative profilometry
analysis using PRIMOS. Safety was documented by
adverse effects monitoring.
Results: Significant improvements on the NIR-treated
versus the control scar were seen in all efficacy measures.
No significant treatment-related adverse effects were
reported.
Conclusion: Possible mechanisms involved are inhibition
of TGF-bI expression. Further studies in larger group of
patients are needed to evaluate this promising technique.
Lasers Surg. Med. 42:597–601, 2010.
ß2010 Wiley-Liss, Inc.
Key words: CO
2
laser ablation; near infrared (NIR);
photobiomodulation; prevention; surgical scars; trans-
forming growth factor beta-I
INTRODUCTION
Wound healing is a complex tissue-response to injury
leading to skin restoration. Alterations in the wound
healing process can result in hypertrophic or keloid
scarring. Cutaneous aberrant scaring, characterized by
an imbalance between cell growth and excessive extrac-
ellular matrix deposition, can form after surgery, laser
treatment or acne. Keloids take the form of a raised
distorted growth that grow beyond the boundaries of the
original wound site and are frequently associated with
pruritus and pain. Hypertrophic scars have the clinical
appearance of a red raised lump on the skin, do not extend
beyond the original skin trauma area, and often regress
with time to a certain extent. Aside from their appearance,
clinical features and histological characteristics also dis-
tinguish between hypertrophic scars and keloids [1].
Recent research has underlined a lowered self-esteem and
impaired quality of life in affected individuals which
underlines the need for better treatment options for these
patients [2]. Treating abnormal scars remains an important
challenge for both the clinician and the affected person.
A wide range of surgical (e.g., cryotherapy, excision),
non-surgical (e.g., pharmacological, mechanical pressure,
silicone gel dressings), and laser therapies (CO
2
, pulsed
dye, fractional ablative, and non-ablative lasers) have been
tested with variable success [1,3,4]. The inconsistencies
and sub-optimal results obtained to date call for the
investigation of new therapeutic interventions. Moreover,
potential differential effects on keloids and hypertrophic
scars must be considered in the search for new treatments
[5].
Wound healing is a complex cascade of multistep
physiologic events regulated at the biochemical level by a
vast array of signaling mechanisms. Understanding the
molecular mechanisms involved in the dysregulation of
wound healing leading to aberrant scaring might allow the
development of targeted therapies for keloids and hyper-
trophic cells. Recent evidence point to the transforming
growth factor beta-I (TGF-bI) has a major player in the
formation of hypertrophic scars and keloids [6–8]. Results
of wound healing research over the past decades have
demonstrated that keloidal and hypertrophic scar tissues
show higher expression levels of receptors, overproduction
No conflict of interest declared.
Contract grant sponsor: RoseLab Skin Optics Laboratory.
*Correspondence to: Daniel Barolet, MD, RoseLab Skin Optics
Laboratory, 3333 Graham Blvd., Suite 206, Montreal, Quebec,
Canada H3R 3L5. E-mail: daniel.barolet@mcgill.ca
Accepted 11 June 2010
Published online 15 July 2010 in Wiley InterScience
(www.interscience.wiley.com).
DOI 10.1002/lsm.20952
ß2010 Wiley-Liss, Inc.

and poor regulation of TGF-bI, leading to fibroblastic proli-
feration and excess collagen deposition. Thus, TGF-bI
appears to be a prom ising target for therapeutic int ervention.
It has been shown that low-level light therapy (LLLT) can
trigger natural intracellular photobiochemical reactions
involved in wound healing, including TGF-bI modulation
[9– 11]. LLLT with red light and near infrared (NIR) light
acts on the mitochondria and at the cell membrane level
[12]. Absorbed light converted to chemical kinetic energy
causes changes in membrane permeability, improves
signaling between mitochondria, nucleus and cytosol, nitric
oxide formation and increase oxidative metabolism to
produce more ATP, ultimately leading to normalization of
cell activity [13–16]. Hence, LLLT might be helpful in scar
treatment. The aim of this case series was to investigate
the efficacy of LLLT, by means of light emitting diode
(LED), as an adjunct prophylactic therapy to conventional
scar revision interventions in the healing process of
abnormal scars.
In the present case series, patients with bilateral
abnormal scars were treated with LED in the NIR
spectrum (805 nm, 30 mW/cm
2
) following scar revision by
surgery or CO
2
laser ablation on both sides. Patients self
treated at home and daily for 30 days on one side of the
affected area while the other side served as control, not
receiving LED treatment (split-study; the patient being its
own control). Clinical improvements were assessed with in
vivo 3D microtopography quantitative measurement for
scar height, blinded clinical assessment of change using
digital photographs, and the Vancouver Scar scale (VSS).
Cutaneous adverse response was also documented. It
was expected that the NIR-treated side would yield
better clinical outcomes in comparison to the control side.
STUDY DESIGN/PATIENTS AND METHODS
Case 1
The patient was a Caucasian 57-year old female with
Fitzpatrick phototype II. The patient underwent face-lift
surgery for treatment of facial chalasia (rhytides and
laxity). The patient had no history of abnormal scarring.
She was not taking any medication prior to and after
surgery. Post-operative care consisted of standard wound
care. The post-operative course was unremarkable until
day 20 when abnormal wound healing was noted on pre-
auricular areas bilaterally. Wound care then included
massage and silicon sheets. On post-operative day 45, the
diagnosis was confirmed (keloids) and the patient was
referred to our clinic. Scar revision for this patient consisted
in surgical removal of the scars with primary closure (see
Fig. 1; upper panels; 1 week post-revision). Scar revision
was performed 8 months after the facelift.
Case 2
The patient was a 27-year-old Caucasian male with
Fitzpatrick skin type I. The patient presented with hyper-
trophic scars due to abnormal wound healing post-acne
lesions of the chest (sternal area). The scars were 6-year old.
His past medical history was negative. He did not receive
any medical treatment but used a topical cream with
vitamin E. CO
2
laser ablation was performed to remove scar
tissue. First, local anesthesia was completed with Xylo-
caine 2% with epinephrine 1:100,000. Then, the CO
2
laser
was used in the focused bistouri mode (1 mm spot size, 15 W,
CW mode) for debulking the scar in order to reduce the
volume of the fibrotic lesion. What was left at the base of the
lesion was further treated but in the resurfacing mode
using a scanner to remove very thin layers of scar tissue.
The CO
2
laser parameters were the following; 18 W, 7.1 mm
dia, circles, 0.1 second on/0.1 second off, with up to five
consecutive passes performed until normal skin was
reached. Bilateral lesions (similar ones on each side) were
chosen and treated the same way. Post-treatment wound
care included daily application of topical antibiotics and a
telfa dressing for 10 days.
Case 3
This patient was a 36-year old Caucasian female with
Fitzpatrick phototype III presenting several bilateral
hypertrophic scars as a result of surgical removal of nevi
(areola area). The scars were 3-year old. She had experi-
enced abnormal wound healing in the past with residual
textural changes after trauma. Hypertrophic scars were
raised by 2– 5 mm and showed diffuse telangiectasia. No
pain was present with occasional pruritus. CO
2
laser
resurfacing was performed as described for Case 2.
Table 1 presents a summary of the patients character-
istics.
Study Procedure
Following scar revision, one side was randomly selected
(flip of a coin) for NIR treatment by the patient at home
and daily for 15 minutes with LED emitting at 805 nm
Fig. 1. Case 1 after pre-auricular scar revision (upper panel)
and 1-year follow-up (lower panel). Left: NIR-treated side;
Right: control side. [Figure can be viewed in color online via
www.interscience.wiley.com.]
598 BAROLET AND BOUCHER

(30 mW/cm
2
) at a treatment distance of 2.5 cm, for 30 days
(total dose ¼27 J/cm
2
). Patients were instructed to start the
NIR treatment upon their return home. Before returning
home, patients received post-treatment wound care
instructions, which included applying a topical antibiotics
and a daily telfa dressing for 10 days. Furthermore,
following the acute healing phase, sun avoidance and the
use of a sunscreen (SPF 30) was mandatory in the unlikely
event of direct sun exposure on the treated area. Digital
photographs of the NIR-treated and control scars (Canon
Dual Flash EOS 10D, Canon, Tokyo, Japan with EX
SIGMA 50 mm 1:2.8 macro lens; Sigma, Aizu, Japan) were
taken at base line and at follow-up visits. Each photograph
was taken maintaining identical ambient lighting, pose,
and camera angles.
Clinical Global Impression of Change (CGIC)
The photographs were analyzed for clinical improvement
by a blinded non-treating physician using a 5-point scale for
degree of improvement from baseline for NIR-treated and
control scars (0 ¼none; 1 ¼mild; 2 ¼moderate; 3 ¼good;
4¼excellent).
Severity Assessment
A scar severity score was determined using the VSS for
the NIR-treated and control scars by a blinded non-treating
physician [17]. The Vancouver scale consists of four
variables: vascularity, height (thickness), pliability, and
pigmentation. Each variable has 4–6 possible scores. A
total score ranges from 0 to 14, whereby a score of 0 reflects
normal skin.
Skin Surface Topography
The measurements of the skin surface topography were
performed using the Phaseshift Rapid in vivo Measure-
ment of Skin optical 3D device (PRIMOS
TM
, GFM, Teltow,
Germany) on the NIR-treated and control areas to quantify
scar height (Cases 2 and 3). To accurately assess the degree
of improvement, scars were analyzed to determine the
cross-sectional area after the pre- and post-topographical
images were aligned. A cross-sectional line graph across
each scar compared 24 points to determine the mean
change from baseline to post-treatment. Related Samples
Wilcoxon’s signed rank test was used to assess the differ-
ence between pre- and post-scar heights.
Cutaneous Response
On each visit, the presence of adverse effects including
erythema, edema, pruritus, hypopigmentation, hyperpig-
mentation, and textural changes were documented.
RESULTS
The CGIC assessment revealed a greater improvement
on the NIR-treated scars in comparison to the control scars
in the three patients (Table 2): clinical improvements were
deemed ‘‘moderate’’ to ‘‘excellent’’ (scores 2– 4) on the NIR-
treated scars while the control scars yielded lesser degrees
of improvements (score of 1 or mild). Clinical improvements
in appearance and outline of the scars and can be noted for
Case 1 in Fig. 1. Similarly, the VSS revealed a greater
reduction in severity score on the NIR-treated scars in all
cases in comparison to the control scars at follow-up. The
greatest reduction in VSS for the NIR-treated scars was of
77% (Case 1) whereas for the control scars, of 29% (Case 2;
Table 3). The measurements of the skin surface micro-
topography revealed that scar height was significantly
reduced for the NIR-treated scars (Case 2: P¼0.07; Case 3:
P<0.001) but not for the control scars (Case 2: P¼0.55;
Case 3: P¼0.31). Fig. 2 depicts digital photographs and
surface microtopography analyses for the NIR-treated and
control scars at baseline and post-treatment for Case 2.
Treatment was overall well tolerated with patients
reporting a slight but bearable sensation of heat during
the procedure. Aside from slight erythema and mild
crusting following CO
2
, no other adverse signs, such as
post-inflammatory hyperpigmentation (PIH), were observed
in patients.
TABLE 2. Clinical Global Impression of Change
Individual Results
NIR-treated Control
Case 1 4 1
Case 2 3 1
Case 3 2 1
TABLE 1. Patient Characteristics
ID Case 1 Case 2 Case 3
Gender F M F
Age 57 27 36
Phototype II I III
Scar type Pre-auricular linear keloids
bilaterally
Hypertrophic scars on chest
bilaterally
Hypertrophic scars on back
bilaterally
Scaring cause Post-face lift Post-acne Post-excision
Scar revision method Surgical scar revision/excision CO
2
laser resurfacing CO
2
laser resurfacing
Scar age 8 months 6 years 3 years
Last assessment visit Week 77 Week 12 Week 8
LLLT TREATMENT OF HYPERTROPHIC SCARS AND KELOIDS 599

DISCUSSION
Keloids and hypertrophic scars are benign skin tumours
and are the effect of a dysregulated wound-healing process.
These scar types are difficult to eradicate and conventional
treatments are not always successful. In the present study,
we investigated the effect of LLLT by LED therapy in the
reduction of aberrant scars following scar revision by CO
2
or surgery. Patients were treated in a within-subject design
with NIR (805 nm) on one area while the other area served
as control.
The results from this case series revealed that abnormal
wound healing can potentially be modulated with LLLT
and that the volume of scar tissue, reduced after surgical
scar revision or CO
2
laser resurfacing in prone patients.
The results from this case series also showed that LED
therapy was well tolerated with no significant adverse
reactions, likely due to the low-level characteristics of this
treatment modality. Other light sources, such as PDL,
often induce, although transiently, important adverse
effects such as severe swelling, purpura, and erythema
which may compel subjects to discontinue treatment. From
a clinical perspective, the absence of thermal injury (peak
power effects) to the skin during light treatment may yield a
significant advantage over laser-based methods, given that
improvements can be achieved without thermal damage
and with limited adverse reactions.
NIR irradiation may enhance the wound healing process
presumably by its biomodulatory effects. The mechanisms
at play have not been investigated in the present context. It
is possible that multiple cell signaling pathways contrib-
uted to the observed therapeutic effect. TGF-bI and other
families of molecules have been shown to be modulated by
LLLT, including transforming growth factor platelet-
Fig. 2. Digital photographs (a) and PRIMOS color coded
topographic images (b) obtained from Case 2 shows that
there is a notable improvement in the scars height. This is
represented by the increase of red to blue hue, and the loss of
yellow hue. c: Cross-sectional representation of the scar height
at baseline and post-treatment for the NIR-treated and control
scars. Twenty-four points between these curves were compared
to assess the overall mean improvement post-treatment in scar
height for the NIR-treated and control scars. [Figure can be
viewed in color online via www.interscience.wiley.com.]
TABLE 3. Vancouver Scar Scale Individual Results
NIR-treated Control
Pre Post % Reduction Pre Post % Reduction
Case 1 9 2 77.78 9 8 11.11
Case 2 11 7 36.36 7 5 28.57
Case 3 8 7 12.50 6 6 0.00
600 BAROLET AND BOUCHER

derived growth factor (PDGF), interleukins (IL-6, 13, 15)
and matrix metalloproteinases (MMPs) which are all also
associated with (abnormal) wound repair [9]. Moreover, it
has been shown that CO
2
therapy can reduce TGF-bI
expression, which might have played a part in the overall
effect in patients treated with this modality [7].
LED preconditioning with NIR irradiation was shown to
reduce abnormal scars in our three patients, and may
possibly become a clinically significant at home self-
administered treatment modality. The results from the
present case series are encouraging and underscore the
need for controlled studies on a larger number of patients.
Future trials should include long-term follow-up examina-
tions to assess if results are maintained over time. Further
studies are also necessary to identify the cellular processes
underlying the therapeutic effects.
ACKNOWLEDGMENTS
This study was funded by RoseLab Skin Optics Labo-
ratory. The authors acknowledge Diane Lamalice for her
technical assistance and Isabelle Lussier, PhD from
MedStrategis for the manuscript preparation.
REFERENCES
1. Wolfram D, Tzankov A, Pu¨ lzl P, Piza-Katzer H. Hypertrophic
scars and keloids—A review of their pathophysiology, risk
factors, and therapeutic management. Dermatol Surg 2009;
35(2):171– 181.
2. Bock O, Schmid-Ott G, Malewski P, Mrowietz U. Quality of
life of patients with keloid and hypertrophic scarring. Arch
Dermatol Res 2006;297:433– 438.
3. Bouzari N, Davis SC, Nouri K. Laser treatment of keloids and
hypertrophic scars. Int J Dermatol 2007;46:80– 88.
4. Louw L. The keloid phenomenon: Progress toward a solution.
Clin Anat 2007;20:3– 14.
5. Ogawa R. The most current algorithms for the treatment and
prevention of hypertrophic scars and keloids. Plast Reconstr
Surg 2010;125:557– 568.
6. Liu W, Wang DR, Cao YL. TGF-b: A fibrotic factor in wound
scarring and a potential target for anti-scarring gene
therapy. Curr Gene Ther 2004;4:123– 136.
7. Bouzari N, Davis SC, Nouri K. Laser treatment of keloids and
hypertrophic scars. Int J Dermatol 2007;46:80– 88.
8. Wolfram D, Tzankov A, Pu¨ lzl P, Piza-Katzer H. Hypertrophic
scars and keloids—A review of their pathophysiology, risk
factors, and therapeutic management. Dermatol Surg 2009;
35:171– 181.
9. Hamblin MR, Demidova TN. Mechanisms of low level light
therapy. In: Hamblin MR, Waynant RW, Anders J, eds. Proc
of SPIE Vol. 6140. 2006; 614004.
10. Toyokawa H, Matsui Y, Uhara J, Tsuchiya H, Teshima S,
Nakanishi H, Kwon AH, Azuma Y, Nagaoka T, Ogawa T,
Kamiyama Y. Promotive effects of far-infrared ray on
fullthickness skin wound healing in rats. Exp Biol Med
(Maywood) 2003;228:724– 729.
11. Danno K, Mori N, Toda K, Kobayashi T, Utani A. Near-
infrared irradiation stimulates cutaneous wound repair:
Laboratory experiments on possible mechanisms. Photo-
dermatol Photoimmunol Photomed 2001;17:261– 265.
12. Karu TI, Pyatibrat LV, Kolyakov SF, Afanasyeva NI.
Absorption measurements of a cell monolayer relevant to
phototherapy: Reduction of cytochrome c oxidase under near
IR radiation. J Photochem Photobiol B 2005;81:98–106.
13. Morimoto Y, Arai T, Kikuchi M, Nakajima S, Nakamura H.
Effect of low intensity Argon laser irradiation on mitochon-
dria respiration. Lasers Surg Med 1994;15:191– 199.
14. Yu W, Naim JO, McGowan M, Ippolito K, Lanzafame RJ.
Photomodulation of oxidative metabolism and electron chain
enzymes in rat liver mitochondria. Photochem Photobiol
1997;66:866– 871.
15. Karu T. Photobiology of low-power laser effects. Health Phys
1989;56:691– 704.
16. Zhang Y, Song S, Fong CC, Tsang CH, Yang Z, Yang M. cDNA
microarray analysis of gene expression profiles in human
fibroblast cells irradiated with red light. J Invest Dermatol
2003;120:849– 857.
17. Draaijers LJ, Tempelman FR, Botman YA, Tuinebreijer WE,
Middelkoop E, Kreis RW, van Zuijlen PP. The patient and
observer scar assessment scale: A reliable and feasible tool for
scar evaluation. Plast Reconstr Surg 2004;113:1960– 1965.
LLLT TREATMENT OF HYPERTROPHIC SCARS AND KELOIDS 601