Forum for Nordic Dermato-Venereology Nr 4, 2019 | Seite 22

Dissertation
Katrine Elisabeth Karmisholt – Laser Treatment in Early Wound Healing and the Clinical Effect on Scar Formation
Laser Treatment in Early Wound Healing and the Clinical Effect on Scar
Formation
K atrine E lisabeth K armisholt , MD
Department of Dermatology, Bispebjerg University Hospital, Copenhagen, Denmark. E-mail: [e-mail]
Katrine Elisabeth Karmisholt defended her thesis in Faculty of Health and Medical Sciences, University of
Copenhagen, Denmark on September 28, 2018. Principal Supervisor: Professor Merete Haedersdal, MD, PhD,
DMSc, Bispebjerg University Hospital, Denmark. Chairman: Claus Zachariae, MD, DMSc, Gentofte University
Hospital, Denmark. Co-supervisors: Professor Uwe Paasch, MD, Phd, University of Leipzig, Germany and Tonny
Karlsmark, MD, DMSc, Bispebjerg University Hospital, Denmark. Assessment committee: Albert Wolkerstorfer,
MD, PhD, University of Amsterdam, the Netherlands and Prof. Peter Bjerring, MD, PhD, DMSc, Moelholm
Hospital, Vejle, Denmark.
The overall aim of this thesis was to investigate the potential
In the systematic review (Study I) a total of 25 trials were
clinical effects of laser treatment in early wound healing to
found eligible. The following lasers were applied: pulsed
reduce scar formation. Previously, in vitro and clinical studies
dye laser (PDL, 585/595 nm), potassium-titanyl-phosphate
have proposed that lasers intervention in inflammation-,
laser (KTP, 532 nm), diode laser (810 nm), NAFL (1,550 nm),
proliferation- and remodeling phases of wound healing, may
fractional CO 2 -laser (10,600 nm) and yttrium aluminum
improve scar formation. However, no consensus regarding
garnet (Er:YAG, 2940 nm) lasers. Four studies initiated laser
early laser treatment procedures to improve scar formation
intervention in inflammation phase and 3 of these studies
exists. In this thesis, a systematic review of the literature on
found significant improvement on treated scars compared to
early laser intervention to reduce scar formation was per-
untreated scars. Sixteen studies initiated laser treatment in the
formed. Included studies
proliferation phase and 6 of
were presented according to
these studies found signifi-
the wound healing phases
cant improvement on laser
in which the laser treat-
treated scars compared to
ment was initiated (Study I).
untreated control scars. In
An experimental screening
5 studies laser treatment was
study was performed to
initiated in remodulation
Claus Zachariae
investigate the importance
phase and 2 studies found
of timing and fluence lev-
significant improvement on
els of a single exposure
laser treated scars compared
non-ablative fractional laser
to untreated controls. The
(NAFL, 1,540 nm) (Study
Cochrane Handbook 2011
II). Study II was performed
Risk-of-Bias evaluation was
Merete Hædersdal
Uwe Paasch
on a full-thickness punch
adopted to evaluate the
biopsy wound model in
methodological quality of
healthy volunteers with
included trials. Based on
a randomized controlled
these criteria a sufficient
intra-individual design. In
randomization procedure
Study III experimental test-
was provided in 4 studies
ing of 3 repetitive 1,540 nm
and none of the included
Peter Bjerring
Tony Karlsmark
NAFL-treatments targeting
trials described allocation
all 3 wound healing phases
concealment. Low risk of
was investigated in a ran-
bias was found with regard
domized controlled split-
to blinding of outcome
wound trial on patients un-
assessment as 15 studies
Albert Wolkerstorfer
dergoing surgical excisions.
provided a clear description
132
Forum for Nord Derm Ven 2019, Vol. 24, No. 4
of outcome assessment blinding. Information on exclusion
after randomization and loss to follow-up was provided in 16
studies. Higher quality studies are needed to fully confirm the
impact of early laser treatment to reduce scar formation, but
available evidence indicates that laser intervention applied
in early wound healing phases holds potential to reduce scar
formation.
In Study II, 16 healthy volunteers received a single NAFL-ex-
posure in a standardized full-thickness punch biopsy wound
model applied to buttocks area. NAFL-exposure one day before
wounding, immediately after wounding or two weeks after
wounding was tested at 3 fluence levels ranging from 30–70 mJ/
mB, compared to untreated control wounds. Primary outcome
was blinded on-site evaluation on Patient-Observer-Scar-As-
sessment-Scale (POSAS) with a total score ranging from 6–60
points (6 resembling normal skin and 60 worst imaginable
scar) at 3 months follow-up. According to POSAS-total, and
compared to untreated control scars, significant improvements
were found on NAFL-treated scars with NAFL-exposure one day
before wounding with medium-fluence (median difference 1,
p = 0.03), immediately after wounding with low-fluence (me-
dian difference 1.5, p < 0.05), and two weeks after wounding
with low-fluence (median difference 1, p < 0.05). Differences
between NAFL-treated and untreated control scars were sparse
but study II showed that NAFL may improve scar formation
at all 3 interventional time points and that low to medium
fluences induce beneficial outcome.
In Study III, 32 patients received medium NAFL-fluence level
(40–50 mJ/mB, fluence level determined from Study II) on
excisional wounds, split and randomized to NAFL treatment
versus untreated control. Treated wound halves received three
NAFL-treatments sequentially targeting the inflammation-,
Forum for Nord Derm Ven 2019, Vol. 24, No. 4
proliferation-, and remodeling phases. Scars were evaluated
at 3 months follow-up and primary outcome was on-site
blinded evaluations according to POSAS-total. NAFL-treated
scar halves appeared significantly improved compared to un-
treated control halves (NAFL-treated median 11 [range 9–12]
vs control median 12 [range 10–16], p < 0.001). Changes were
subtle and covered a wide range of treatment response: in
63% NAFL-treated scar halves improved, in 26% no difference
was detected and in 10% NAFL-treated scars rated worse than
corresponding control.
In conclusion, the available body of evidence indicates that
laser interventions applied during wound healing phases have
the potential to improve scar formation. Experimental studies
show promise for 1,540 nm NAFL exposure when applied
prior to or in early wound healing to reduce scar formation.
Furthermore, NAFL treatments as an integrated part of surgical
procedures hold promise for improvement of scar formation
L ist
of original publications
I.
Karmisholt KE, Haerskjold A, Karlsmark T, Waibel J, Paasch U,
Haedersdal M. Early laser intervention to reduce scar formation
– a systematic review. J Eur Acad Dermatol Venereol 2018; 32:
1099–1110.
II. Karmisholt KE, Wenande E, Thaysen-Petersen D, Philipsen PA,
Paasch U, Haedersdal M. Early intervention with non-ablative
fractional laser to improve cutaneous scarring-A randomized
controlled trial on the impact of intervention time and fluence
levels. Lasers Surg Med 2018; 50: 28–36.
III. Karmisholt KE, Banzhaf CA, Glud M, Yeung K, Paasch U, Nast A,
Haedersdal M. Laser treatments in early wound healing improve
scar appearance: a randomized split-wound trial with nonablative
fractional laser exposures vs. untreated controls.Br J Dermatol
2018; 179: 1307–1314.
D issertation
133