INTRODUCTION emit a wavelength that is specific for the

INTRODUCTION

Melasma is a common, chronic acquired pigmentary
disorder which is recurrent and resistant to the treatment. Management of
melasma includes use of topical agents like combination of hydroquinone,
tretinoin and low potency steroid, glycolic acid, azelaic acid, kojic acid,
arbutin, mandelic acid, ferulic acid, vitamin C etc.), chemical peels, lasers
and light therapy. In melasma, different
types of lasers have been studied with variable results. In the present chapter, we will discuss the various lasers used in
melasma

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Overview
of Lasers in melasma

Lasers, nowadays, play a pivotal role in the
management of numerous dermatological conditions, especially in pigmentary
disorders like melasma.
Laser treatment of pigmented lesions is based on the
theory of selective photothermolysis proposed by Anderson et al in 1983. It
states that when a specific wavelength of energy is delivered in a period of
time shorter than the thermal relaxation time (TRT) of the target chromophore,
the energy is restricted to the target and causes less damage to the
surrounding tissue. So, a laser should emit a wavelength that is specific for
the chromophore being targeted and well absorbed by it. 

Melanin has a broad absorption
spectrum (wavelength between 630 nm and 1,100 nm). The
longer wavelength (>600 nm) penetrates deeper in skin and required more
energy for melanosomal damage. As the melanosomes have a short thermal relaxation time (250–1,000 nanoseconds),
submicrosecond laser pulses are required for their selective
destruction.

In 2004, Manstein et al introduced the fractional
photothermolysis theory. Fractional lasers in melasma works by creating
microthermal zones and photothermolysis leads to tissue destruction of
melanocytes and melanin containing keratinocytes, which are further eliminated
from the skin via melanin shuttle. This decreases the pigment content of both
epidermal and dermal, thus resulting in improvement in melasma.

 

Preoperative preparation (Box 1)

Box
1: Preoperative preparation

•               
Fully informed written
consent for the procedure
•               
Patient’s counselling
according to expected reasonable results
•               
History of allergy to
topical anesthetics
•               
History of herpes labialis,
if present, then prophylactic oral acyclovir or valacyclovir should be
started 1 day prior to procedure and continued after procedure for 5 days. 
•               
Presence of keloid and/or
hypertrophic scars.
•               
History of topical/oral
retinoid use
•               
Pretreatment photographs
•               
Pre- and post-treatment application
of topical depigmenting agents, photoprotection, use of sunscreens
•               
Test spots (for Q-switched
lasers)
•               
Eye protection, eye shields,
universal precautions

 

Various
lasers in melasma

Following types of lasers have been used in the
management of melasma:

1.           
Near-infrared: Q-switched neodymium: yttrium
aluminium garnet QS Nd:YAG (1,064 nm).

2.           
Red light: QS ruby (694 nm), QS alexandrite
(755 nm)

3.           
Green light: flash
lamp-pumped pulsed dye laser (PDL) (585 nm),

                Frequency
doubled Q-switched neodymium: yttrium aluminium garnet-532 nm (QS Nd:YAG)

Q-SWITCHED
LASERS

Q-switched lasers (QS Nd:YAG, QS ruby and QS
alexandrite laser) works on the principal of selective photothermolysis of with
nanosecond pulse duration for targeting the melanin.

Q-Switched Nd:YAG (1064 nm)

Mechanism of Action

The QS Nd:YAG laser with its longer wavelength
(1064nm) ,penetrate deep into the dermis and selectively absorbed by the
melanin chromophore, thus leading to less damage of the epidermis and
surrounding dermal tissue as it is not absorbed by hemoglobin. Low-dose QS
Nd:YAG laser exposure results in the sublethal injuryof the melanosomes by causing
fragmentation and expulsion of melanin granules into the cytoplasm. Dermal
vascular also play role in the pathogenesis of melasma. This factor is taken
care of by the QS Nd:YAG  (1064 nm) laser
by causing subcellular damage to the upper dermal vascular plexus. Thus,
leading to the resolution of melasma.1Also, the injury to the
surrounding dermal tissue by the subthreshold engery leads to cutaneous
rejuvenation by neocollagen formation. This leads to brighter and younger
looking skin.  

Efficacy

The QS Nd:YAG (1064 nm) laser is the most
commonly used laser in pigmentary disorders including melasma. The parameter
used for the laser  includes fluence less
than 5 J/cm2, spot size of 6 mm, and frequency of 10 Hz. The
number of treatment sessions varies from 5 to 10 at 1-week intervals depending
upon the response to the treatment.

 

Figure 1: Centrofacial melasma at baseline.

(Courtesy: Dr
Latika Arya).

 

 

Figure 2: Good
improvement in epidermal melasma (50–75%) on Physician Global Assessment scale
after 4 sessions of low
fluence Q switched Nd:YAG laser, performed every 10 days.

(Courtesy: Dr
Latika Arya).

Studies on use of lasers
in pigmentary disorders have reported variable results in both efficacy and
side effect profile, including hypopigmentation and depigmentation after laser
sessions.2,3 Laser induced depigmentation may occur because of the
direct phototoxicity and cellular destruction of melanocytes caused by the use
of high fluence. Also, the sub-threshold injury of the dermal tissue during
repeated sessions, intrinsic uneven distribution of melanin pigmentation in the
skin and non-uniform laser energy output may further lead to depigmentation.2
Follicular pigmentation loss may lead to whitening of
fine hair. So, the number and frequency of laser sessions should be adjusted
according to the clinical response and to be kept minimum (5-10) to prevent
such post-laser therapy side effects. Laser therapy sessions should be stopped
after earliest sign of hypopigmentation.

In contrast to the
above findings, some studies have also reported rebound hyperpigmentation
caused by the multiple sub-threshold injuries that lead to the stimulation of melanogenesis
in some areas. Other reported side effects include herpes simplex reactivation,
physical urticaria, acneiform eruption and petechiae.

Even after the initial good response to the
laser therapy, there is a high recurrence rate of melasma. This warrants the repeated
QS Nd: YAG laser sessions. Hence, lasers should be reserved only for refractory
cases of melasma who have shown no or partial response to the treatment.

Q-Switched Ruby Laser (QSRL
694 nm)

Mechanism of Action

QSRL (694 nm) work on the principle of
selective photothermolysis and causes highly selective destruction of
melanosomes. However, due to its wavelength of 694 nm, QSRL is more selective
for melanin as compared to QS Nd:YAG laser (1,064 nm).

Efficacy

Studies have reported
variable results in the efficacy of QSRL in the management of melasma. Tse et
al. compared the efficacy and side effect profile of QSRL and QS Nd:YAG (1,064 nm)
lasers in pigmentary disorders including melasma. They reported that QSRL
showed better response as compared to QS Nd:YAG laser.4 However, QSRL
treatment sessions were found to be more painful, while more postoperative
discomfort was found in QS Nd:YAG laser. Further studies are required to
support its role in the management of melasma. Zhou et al used a high density
coverage fractional QSRL (694 nm) combined with levorotatory vitamin C in the
treatment of melasma. They observed significant decrease in MASI score with fewer
side effects.5

Erbium:YAG Laser (2940 nm)

Mechanism of Action

Water works as the chromophore for the
Erbium:Yttrium-Aluminium-Garnet (er:YAG)
laser, that emits light of 2,940 nm wavelength. Er:YAG  laser causes skin ablation with minimal
thermal damage and so, there is minimum risk of post inflammatory
hyperpigmentation.

Efficacy

There is paucity of evidence on the efficacy
and safety of use of Er:YAG laser in melasma. Er:YAG laser was used by Manaloto
et al  to treat 10 female patients with
refractory melasma with fluence levels of 5.1–7.6 J/cm. It showed remarkable
improvement of melasma immediately after treatment.6 Most common
side effect noted in the study was the development of post inflammatory
hyperpigmentation in 3 weeks to6 weeks after the laser sessions in all the
patients. This may be because of paradoxical stimulation of melanocytes in the
treated area and inflammatory dermal reaction after the laser. However, the
pigmentation resolved after use of depigmenting agents like azelaic acid, glycolic
acid peel and sunscreens. But, this side effect limits its use in melasma.

Pulsed
Dye Laser (585 nm)

Mechanism of Action

Recent data
suggests the role of cutaneous vasculature in the pathogenesis of melasma.
Pulsed dye laser (585 nm) targets the melanin and cutaneous vasculature. Vascular
endothelial growth factor receptors 1 and 2, expressed by melanocytes, are involved
in the pigmentation process. Thus, by targeting the vascular component, the
stimulation of melanocytes can be prevented. This resultsinto better clinical
response and decrease risk of recurrence of melasma.

Efficacy

There is paucity of studies of efficacy and
safety profile of PDL in melasma. Passeron et al studied 17 patients with
melasma with PDL and triple combination cream (hydroquinone, 4%; tretinoin, 0.05%; and fluocinolone acetonide, 0.01%)
in a split face  study.7 Three sessions were performed at 3 weekly intervals at
the following settings: fluence 7–10 J/cm2 and pulse duration 1.5
ms. They found that the combination treatment had a greater treatment
satisfaction in patients with skin phototypes II and III. Post inflammatory
hyperpigmentation  was reported in 3
cases.

Fractional
Lasers

Mechanism of Action

As mentioned earlier, the factional laser works
on the principle of fractional photothermolysis. There is formation of multiple
microthermal treatment zones (MTZ) of thermal damage with leaving the
surrounding skin intact. The damaged cells with melanin content (melanocytes
and kerationocytes) are expelled out of skin as microscopic epidermal necrotic
debris (MENDs). Density used in the melasma treatment varied from 2,000 MTZ/cm2
to 2,500 MTZ/cm2 and energy levels 10–15 mJ/mb. The treatment
sessions varied from 2 to 6 at an interval of 1–4 weeks. Studies have shown
variable results on efficacy.

Non ablative fractional laser therapy does not
create an open wound. The stratum corneum is found to be intact after 24 hours
of treatment. This results in faster recovery and fewer risk of scarring.
Fractional lasers are good for the treatment of dermal melasma.

Efficacy

Goldberg et al.9
has shown a reduced number of melanocytes after fractional laser which means
that this laser delayed pigmentation.

In a randomized controlled trial by Kroon et
al.,8 20 female patients with moderate to severe melasma were
treated with either nonablative fractional laser (performed every 2 weeks for a
total of four sessions) or TTT (once daily for 8 weeks). A density of
2,000–2,500 MTZ/cm2 with energy per microbeam of 10 mJ. Improvement was same in both the
groups, but treatment satisfaction and recommendation was higher in laser
group. Also, recurrence was noted in both the groups and no case of PIH was
seen.

Intense Pulse Light

Mechanism of Action

IPL works by the absorption of light energy by
melanin content present in keratinocytes and melanocytes, that lead to epidermal
coagulation due to photothermolysis followed by microcrust formation.10These
crusts containing melanin are shed off hence, the clinical improvement in
pigmentation.

Efficacy

Zoccali et al.
treated 38 patients with melasma using cut off filters of 550 nm, pulse of 5–10
ms, pulse delay of 10–20 ms, and low fluence 6–14 J/cm2 and found
80–100% clearance in 47% of patients.11 The number of sessions used
was 3–5 at interval of 40–45 days. No side effects were reported. 500–550 nm
filters can be used initially and for epidermal lesions, whereas higher
wavelength filters can be used to target deeper melanin in patients with
dermal/mixed melasma. The fluence can be modulated in relation to the anatomic
sites. Although, single pulses heat pigment well, but double or triple pulses
should be used as they reduce the thermal damage by allowing the epidermis to
cool while the target stays warm. The pulse duration used in the studies varied
from 3 ms to 5 ms. Average pulse delay used was 10–20 ms. It is important that
delay time between pulses should not be below 10 ms as this inturn increases
the risk of thermal damage as the targeted tissue cannot reduce its temperature
within that time. Average number of sessions used in these studies was 2–5 at
an interval of 4–8 weeks. However, more number of sessions is required for
maintenance and it decreases the chances of recurrence.

 

IPL is found to be effective for epidermal
melasma while, dermal or mixed or refractory melasma can be targeted with
higher fluencies. In darker skin, the risk of PIH should be always be kept in
mind. Use of low fluences and long delay between pulses in such cases can be
helpful. Also, pre and post treatment sun protection and hydroquinone should be
used.

 

Also, combination of ablative and pigment
selective lasers has been tried in melasma. Ablative lasers remove the epidermis
(containing excess melanin and abnormal melanocytes), followed by the use of
Q-switched pigment selective laser that reach deeper lesion in dermis (dermal
melanophages) have been tried without causing serious side effects.

Lasers
in the Future

Recently, FDA has approved Fractional Er:YAG
laser for melasma. The Thulium laser and Copper Bromide laser appear promising
but have been tried in small number of patients, so larger studies are needed
with cautious analysis of results.

Picosecond lasers are now available with laser
output of 532nm, 755nm and 1064nm. However, these have not been tried in
melasma. However, theoretically they may be more effective in removing pigment
due to the shorter laser pulse duration that cause pigment fragmentation. The
damage to surrounding tissue is much less.

Lasers may be used for facilitating delivery of
topical medications known as laser assisted drug delivery (LADD). LADD may be used
to treat patients with dermal type of melasma where topical therapy has not shown
good results. CO2 and Er:YAG ablative lasers can be used to create
transepidermal channels, and thus, facilitating drug delivery to the deeper
layers of the skin.

Similar to LADD, micro needle (MN) technology
can be used deliver cosmeceuticals across the skin by creating micron sized
pores through the epidermis using a roller device with needles.12

In melasma, radiofrequency (RF) devices have
also been used. Cameli et al used a mono polar RF device to facilitate drug
delivery of phytocomplex of 1% kojic acid in 50 patients of melasma.13
MASI score was improved in all patients without any adverse effects. Fractional
RF has also been tried in melasma. Fractional RF causes fractionated
transepidermal elimination of melanin with minimal risk of PIH.

Conclusion