Ứng Dụng Laser Trong Da Liễu Và Y Học (Lasers In Dermatology – 2018)

240
Alexiades-Armenakas et  al. studied the response
of hypopigmented scars, including striae alba, to
the excimer laser. Thirty-one patients received up
to ten treatments starting at 1 MED minus 50 mJ/
cm2. Visual analysis found 61% and 68% increase
in pigmentation for leucoderma and striae, respec-
tively, compared to control after nine treatments.
However, the treated areas slowly depigmented
back to baseline within 6 months of treatment ces-
sation [25]. In addition, Goldberg demonstrated
76% or greater darkening of striae after an aver-
age of eight treatments [26]. Nevertheless, atrophy
remained unchanged, and the pigmentary improve-
ments were not sustained. Ostovari et al. evaluated
the efficacy of the excimer laser in treating ten sub-
jects with striae alba, finding that the laser displayed
a weakly positive effect in repigmenting the striae
alba. Additionally, the treatment produced the major
side effect of splaying the pigment [27]. For patients
with mature hypopigmented striae and hypopig-
mented scars, the 308 nm excimer laser presents a
safe option for a common cosmetic concern with
few other effective treatments, but patients should be
aware of the longevity of the treatment and possible
side effects.
Chemical leucoderma, a skin disease which
presents with depigmentation due to contact
with specific chemicals, has also been success-
fully treated with excimer laser. Ghazi et al. pre-
sented a case of chemical leucoderma caused by
hair dye which was completely resolved using
an excimer laser [28]. Similarly, Vine et  al.
described the case of an HIV patient who expe-
rienced chemical leucoderma in the nasal and
perioral areas after spilling liquid amyl nitrite,
a recreational drug, on his face. The patient was
treated with excimer laser and attained 90%
repigmentation [29]. Kim et al. presented a case
of a patient exhibiting punctate leucoderma and
melasma who was managed successfully using
combination therapy of a low-fluence 1064-nm
Q-switched
neodymium:yttrium-aluminium-
garnet (QSNY) laser and a 308-nm excimer
laser. As it is common practice in Asian coun-
tries to utilize the QSNY laser to treat melasma,
and such treatment can result in complications
like punctate leucoderma, combination therapy
was pursued to achieve a better outcome [30].
The excimer laser has also illustrated success in
treatment of linear scleroderma and pityriasis alba.
Hanson et  al. described a pediatric patient with
refractory localized scleroderma on her left flank.
The patient was initially treated with topical calci-
potriene and steroid injections. Due to progression
of the lesion, the calcipotriene was ceased, and
methotrexate was added. However, after 6 months
of methotrexate treatment without remission,
the excimer laser was added twice weekly for
7  months. The combination therapy of metho-
trexate and the excimer laser resulted in com-
plete remission of the disease [31]. Additionally,
Al-Mutairi and Hadad studied the efficacy of the
excimer laser in treating 12 patients with pityria-
sis alba, finding that near-complete resolution was
achieved after 3 months of treatment [32].
Indications and Contraindications
Psoriasis
Indications
• Patients with localized plaques that involve
less than 10% of the body surface area.
• Patients with lesions in non-exposed sites and
resistant sites.
• Mild to moderate psoriasis.
Contraindications
• Patients that report worsening of their lesions
upon light exposure.
The excimer laser is indicated for mild to mod-
erate psoriasis, for localized plaques, and for resis-
tant sites. Patients who have lesions in non-exposed
sites such as in the groin and axilla also respond
well to the excimer laser [33, 34]. These areas
are notoriously difficult to treat with traditional
NB-UVB. The excimer laser also works well for
recalcitrant psoriatic lesions in areas such as the
L. Jordan et al.

241
scalp [35]. The most difficult areas to treat are the
palms and soles, and the excimer laser has dis-
played success in these areas [4]. However, Sevrain
et al. investigated the efficacy of excimer lasers in
the treatment of palmoplantar pustular psoriasis
(PPPP) and discovered that outcome measures
varied according to the studies, concluding that
treatment for PPPP needed further evaluation [36].
The excimer laser may also be used in conjunction
with other systemic treatments for recalcitrant
lesions.
The excimer laser may be used in all skin
types; however, skin types II, III, and IV appear
to respond the best. Very fair skin may burn more
easily, and care must be taken when treating these
patients [37]. Further, patients being treated in
combination with acitretin should have their
laser exposure times managed closely as acitretin
therapy may increase the patient’s susceptibility
to erythema. Patients who have darker skin types
with very thick lesions may benefit more from
PUVA photochemotherapy as UVA offers supe-
rior penetration over the UVB from the excimer
laser [34]. Additionally, excimer laser treatment
is more beneficial for mild to moderate psoria-
sis. Schaarschmidt et  al. studied the treatment
satisfaction of 200 psoriatic patients who had
moderate to severe psoriasis using the Treatment
Satisfaction Questionnaire for Medication. The
study found that patients who received biologi-
cals and traditional systemic medications had
significantly greater satisfaction than those who
received phototherapy or topical agents [38].
Additionally, as mentioned earlier, the excimer
laser is not as beneficial as PDL in the treatment
of nail psoriasis [11]. Nevertheless, appreciating
these proper indications, the only true contrain-
dication is the rare psoriatic patient that reports
worsening of lesions upon exposure to light.
A suitable patient is one who is able to commit
to multiple treatments per week for potentially
several weeks. Thus, compliance is usually the
limiting factor for improvement. Increasing insur-
ance copayments is also a substantial obstacle.
Insurance coverage varies, and documentation of
prior treatment failure is usually required for
approval. The ideal candidate lives or works near
the unit location, has skin type II–IV, and has
disease limited to the scalp or flexural areas. Most
importantly, the patient must be committed to the
course of treatment (Figs. 14.1, 14.2, and 14.3).
Fig. 14.1  21 y/o female with scalp psoriasis
Fig. 14.2  After 12 treatments excimer laser
Fig. 14.3  One year follow up, still clear
14  Lasers for Psoriasis and Hypopigmentation

242
Vitiligo
Indications
• Patients who have vitiligo with less than 20%
involvement.
• Patients with locally distributed lesions.
Contraindications
• Patients who are light sensitive.
The excimer laser is indicated in both pediat-
ric and adult populations and in all skin types for
the treatment of limited or localized lesions of
vitiligo. However, similarly to the excimer laser
treatment of psoriasis, very fair skin may burn
more easily, so care must be taken when treating
these patients [37, 39]. Anatomic location is a
major predictor of response rate when evaluating
a vitiligo patient for possible excimer laser ther-
apy. The most to least responsive areas are: face,
scalp/neck, genitals, trunk, extremities, hands
and feet, including bony prominences [40]. Skin
type is also important, with Fitzpatrick III or
higher skin types responding the best, while
smaller lesions respond more quickly. Age, gen-
der, and duration of lesions do not appear to be a
factor. It is not practical to treat large lesions due
to the small spot size of the laser unit.
The ideal candidate has Type III skin or darker
with disease limited to the head, neck, or trunk. The
only contraindication is a photosensitive patient,
and patients taking medications that increase pho-
tosensitivity should be treated with caution. The
inconvenience of multiple office visits and poten-
tial cost of therapy are significant hurdles when
treating patients with psoriasis or vitiligo.
Techniques
Shin et  al. studied the melanin index (MI) to
UVB in different skin colors and body sites. The
study noted that following the first day of UVB
exposure, MIs lowered, especially in fairer skin.
However, the MIs increased in the light-skin
group from day 3–21 versus the dark-skin group
which experienced a peak MI at 7  days.
Ultimately, the study found that pigmentation
caused by UVB varied based on skin color and
body site [41].
Psoriasis
• Preparation.
• Determine skin type and/or MED.
• Treat two to three times per week on non-con-
secutive days.
• Start at 3 MED and increase every other ses-
sion unless burning occurs.
Initial evaluation of potential candidates
should include extent, distribution, and past treat-
ments of psoriatic lesions. The patient should be
interviewed regarding any history of worsening
psoriatic lesions upon light exposure. Risks and
benefits should be discussed including the fre-
quent and potentially long term visits for therapy.
The cost of therapy including copayments should
be addressed, and informed consent should be
reviewed and obtained. Pretreatment photographs
may also be useful, and the skin should be free of
any topical agents. Eye protection should be
worn by all persons in the treatment room, and it
is also commonly recommended to apply a small
amount of mineral oil to thick scaly plaques to
help reduce light scatter.
Initial dosing can be chosen by skin type or
determination of the MED. The MED is the mini-
mal fluence required to induce pink erythema of
unexposed skin, which is commonly tested on the
lower back or gluteal area. A template is marked
for orientation on a sun-protected area. Usually,
doses of 100 mJ/cm2 through 350 mJ/cm2 are used
in 50 mJ/cm2 increments. Therefore, six test doses
are usually given. The patient avoids additional
UV radiation to the area and returns for evaluation
24 h after test dosing. The lowest dose that induces
detectable erythema is the MED [42].
However, most manufacturers have treatment
protocols for psoriasis based on plaque thickness
and skin type. These guidelines avoid the incon-
venience of determining the MED.  Treatment
guidelines usually consist of an initial dosing
L. Jordan et al.

243
table followed by a protocol for subsequent treat-
ments based on response. These guidelines are
based on the following principles (see Tables
14.1 and 14.2). Treatments should begin two to
three times per week on non-consecutive days for
up to a month or longer if needed. Treatment ses-
sions may take longer than typical light therapy
due to the small spot size; however, it should be
emphasized that less treatments are required
(approximately 10 treatments versus 25 for con-
ventional light therapy). Treatment should start at
3 MED and increase every session, or every other
session unless burning occurs. Dosage should be
maintained to induce slight erythema within 24 h
of treatment. The erythema should not last greater
than 24 h and should not cause pain. If excessive
erythema or pain occurs, decrease the subsequent
dose by 25%. Most patients will continue topical
therapy throughout the treatment. Typically, ses-
sions are performed two to three times a week
while maintaining at least 48 h in between treat-
ments for 3–6 weeks [4].
Debbaneh et al. offer a new method of dosime-
try called Plaque-based Sub-blistering Dosimetry,
which is a more aggressive protocol in which
8–16 multiples of MED is administered to psori-
atic plaques with the goal of achieving an earlier
and longer remission than traditional dosimetry.
The authors present a patient who achieved a
PASI score of 75 after only two treatments with an
excimer laser [43].
Vitiligo
• Preparation and evaluation.
• Starting dose is 100–150 mJ/cm2 on the head
and neck.
• Dose is increased by 50 mJ/cm2 per treatment
until redness develops.
• Treatment is two to three times per week for
up to 36 weeks.
• Consider combination therapy with tacroli-
mus 0.1%.
Initial evaluation of potential candidates with vit-
iligo should include extent, distribution, and past
treatments of hypopigmented lesions. A Wood’s light
may be used to enhance any pigmentary changes.
Risks and benefits should be discussed including the
frequent and potentially long term visits for therapy.
The cost of therapy including copayments should be
addressed, and informed consent should be reviewed
and obtained. Pretreatment photographs may also be
useful, and the skin should be free of any topical
agents. Eye protection should be worn by all persons
in the treatment room, and the patient should be pro-
tected from natural light between treatments.
Determination of MED is not necessary for
vitiligo patients as the calculated MED for the
surrounding normal skin is not indicative for the
skin affected by vitiligo. Other factors such as
location, duration, and size are more important in
determining response to laser therapy. The start-
ing dose is 100–150 mJ/cm2 on the head and neck.
This dose is increased by 50 mJ/cm2 per treatment
until redness develops. If a severe burn occurs,
reduce the dose by half or skip the following treat-
ment. Avoid treatments on consecutive days [44].
Similar to the excimer treatment protocol for pso-
riasis, vitiligo treatment typically consists of ses-
sions performed two to three times a week while
keeping a minimum of 48 h in between treatments
for 4–36 weeks [37, 39]. Much like psoriasis, a
Table 14.1  First dose determination for psoriasis
Fitzpatrick skin type. Adapted from Vitiligo treatment
guidelines, 12-95362-01 Rev. A
Plaque
thickness
Induration
score
1–3 (mJ/
cm2)
4–6 (mJ/
cm2)
None
0
Mild
1
300
400
Moderate
2
500
600
Severe
3
700
900
Table 14.2  Subsequent dose determination for psoriasis. Adapted from Vitiligo treatment guidelines, 12-95362-01
Rev. A
Clinical
observation
No effect
Minimal effect
Good effect
Considerable
improvement
Moderate/severe
erythema
Typical dosing
change
Increase dose
by 25%
Increase dose
by 15%
Maintain
dose
Maintain dose or reduce
dose by 15%
Reduce dose by
25%
14  Lasers for Psoriasis and Hypopigmentation

244
table and protocol for subsequent treatments are
provided by the laser manufacturer (see Tables
14.3 and 14.4). Note the variability in initial dos-
ing for various anatomical sites.
Adverse Events
• Erythema.
• Rarely bullae and pain.
Erythema is common and is the goal of treatment
in vitiligo [45]. Patients may perceive slight warmth
upon laser application; however, most feel no sensa-
tion. Very few patients report transient stinging, blis-
ters, or perilesional pigmentation [46]. Rare possible
adverse events include sunburn reaction, corneal
burn, freckling, irregular pigmentation, increased
risk of skin cancer, and accelerated aging. Eye pro-
tection and limiting treatment to the affected areas is
recommended to minimize these risks.
Future Directions
• Psoriasis
–– Advances in medical therapy.
• Vitiligo
–– Advances in surgical techniques, grafting
techniques, and combined photodynamic
therapy.
There has been great progress in understand-
ing the nature of pigmentary and psoriatic dis-
ease. Advances in understanding the molecular
pathogenesis of psoriasis has led to the devel-
opment of the revolutionary class of medica-
tions known as the biologics. Currently, there
are 25 oral, topical, and injectable medications
in phase II trials and 15 in phase III trials for
psoriasis or psoriatic arthritis [47]. Despite
the great advances in medical treatments for
psoriasis, light therapy will likely continue to
play a role for a large number of patients who
may not be candidates for systemic therapy
or may require systemic and localized light
therapy for recalcitrant lesions. Several recent
combination therapy studies with the excimer
laser have proven successful including com-
bination with topical Calcipotriene and with
topical flumetasone [13, 14]. Other forms of
treatment that are currently being researched
include a purified gel form of adrenocortico-
tripic hormone, calcitriol ointment in pediatric
patients, newer retinoids, and photodynamic
therapies [48].
Vitiligo patients that fail multiple medical
therapies including topical and light therapy may
be candidates for surgical techniques. Various
grafting techniques such as mini-punch or blister
grafts may be tried. Tattooing has also been used.
Another new and important treatment includes
the autologous melanocyte-keratinocyte trans-
plant [21]. In this treatment, healthy skin is sam-
pled, the melanocytes are grown in culture, and
then they are transferred to the diseased skin. In
addition to surgical therapy, research in gene
therapy will shed more light on new and promis-
ing treatments.
Table 14.3  First dose determination for vitiligo. Adapted
from Vitiligo treatment guidelines, 12-95362-01 Rev. A
Vitiligo location
Initial dose (mJ/cm2)
Periocular
100
Face, scalp, ear, neck, axilla,
bikini
150
Arm, leg, trunk
200
Wrist
250
Elbow
300
Knee
350
Hands, feet
400
Fingers, toes
600
Table 14.4  Subsequent dose determination for vitiligo. Adapted from Vitiligo Treatment Guidelines, 12-95362-01
Rev. A
Clinical
observation
No effect
Good effect
Moderate erythema
Severe erythema
Typical dosing
change
Increase dose by
50 mJ/cm2
Maintain dose
Decrease dose by
50 mJ/cm2
Postpone treatment or reduce
dose by 100 mJ/cm2
L. Jordan et al.

245
Other forms of treatment for vitiligo currently
being researched include the effect of antioxi-
dants on vitiligo, biologics, and combination
therapy of betamethasone oral mini-pulse ther-
apy and oral azathioprine. Several therapies com-
bining NB-UVB are also being investigated,
including NB-UVB and fluticasone propionate
0.05%, lipoic acid tablets, and oral ginkgo biloba.
Additionally, Photocil, a topical cream that selec-
tively delivers NB-UVB therapy upon sunlight
exposure is also being researched [49].
Conclusion
Psoriasis and pigmentary disorders have a pro-
found impact on the quality of life of affected
patients. Despite multiple medical therapies for
psoriasis, certain clinical scenarios present
therapeutic dilemmas. The 308 nm xenon chlo-
ride laser provides another option that is both
safe and effective for psoriatic and hypopig-
mented lesions such as vitiligo, linear sclero-
derma, pityriasis alba, and chemical, punctate,
and post-resurfacing leucoderma. Combination
therapy, including tacrolimus 0.1% and the
308 nm excimer laser, is likely the most effec-
tive and safest option for patients suffering
from vitiligo [18, 19].
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© Springer International Publishing AG, part of Springer Nature 2018
K. Nouri (ed.), Lasers in Dermatology and Medicine,
Lasers for Adipose Tissue and
Cellulite
Molly Wanner and Mathew M. Avram
Abstract
The use of lasers and light devices for the
removal of adipose tissue and cellulite repre-
sents a new and exciting frontier in the laser
field. To date, there are few non-invasive
devices in the laser field all of which can only
claim limited efficacy. This chapter will
review the laser, light sources, as well as
devices with radiofrequency and ultrasound
devices that currently purport to treat cellulite
or adipose tissue.
Keywords
Adipose tissue · Cellulite · Laser ·
Radiofrequency · Ultrasound · Coolsculpting
The use of lasers and light devices for the removal
of adipose tissue and cellulite represents a new
frontier in the laser field. This chapter will review
the laser, light sources, radiofrequency and ultra-
sound devices that treat cellulite or adipose
tissue.
Noninvasive and Invasive
Treatments for Adipose Tissue
Removal of adipose tissue can be accomplished
non-invasively and invasively. Non invasive fat
removal is accomplished using an external hand
piece or device in combination with ultrasound,
cooling, radiofrequency, laser or light. Invasive,
also called “minimally invasive,” devices use
laser and light in combination with a fiber that is
inserted under the skin or ultrasound in combina-
tion with liposuction.
Non Invasive Fat Removal
It’s important to emphasize that non invasive fat
removal is primarily meant to be a body sculpting
procedure. These are not treatments for weight loss.
The body does not excrete fat after these procedures.
These devices remove fat non-invasively from a
localized area, not the entire body. Adipose tissue
stores triglycerides. Unlike cholesterol, which can
be excreted, triglycerides are not excreted by the
body. Rather, the triglycerides are metabolized for
energy, stored, or redistributed to the liver for further
processing to be used for such molecules as plasma
lipoproteins [1]. Studies of serum lipid levels and
liver function tests suggest that non invasive fat
removal devices do not negatively impact these
markers.
M. Wanner (*) · M. M. Avram
Department of Dermatology,
Massachusetts General Hospital,
Harvard Medical School,
Boston, MA, USA
e-mail: mwanner@partners.org
15

248
Non invasive options include focused ultra-
sound, high frequency ultrasound, radiofre-
quency, laser, and light (see Table  15.1). Non
invasive laser and light options are the focus of
this chapter; however, a description of other
energy devices will be included.
Cryolipolysis
Adipose tissue is sensitive to cool temperatures.
Cryolipolysis harnesses this fact and utilizes an
external and non invasive device to cool and
selectively destroy the fat, while avoiding injury
of the overlying skin [2, 3]. Cryolipolysis is
thought to induce apoptosis, inflammation of the
fat, and subsequent clearing of the fat by macro-
phages in a process that takes 3–4 months. On
average, this device removes approximately 20%
of fat in the treated area after 4 months [4–6]. It
has not been associated with statistically signifi-
cant changes in liver function tests or lipid panel
(cholesterol, triglycerides, LDL or VLDL) [7].
Although cryolipolysis has been FDA cleared for
the waist, it has been used on other areas such as
the inner thigh and back.
The ideal patient for cryolipolysis has a bulge
in the area of concern (Fig. 15.1). Evaluation of
the patient should include a history of cold
induced disorders, coagulation disorders, sys-
temic disease, hernia, impaired sensation or cir-
culation in the area. Patients with hernias should
not be treated as the device is a vacuum device.
Skin should be evaluated for laxity which would
not be expected to improve and for skin condi-
tions that koebnerize and may worsen with the
treatment. Patients should expect at least two
treatments for best results, although subsequent
treatments in the same area may have less effect
[6, 8]. Treatments can be scheduled 1–2 months
apart, although the results will not be see until
4 months after the final treatment.
Prior to treatment, the patient is weighed, and
photographs should be taken. The treatment
begins with surgical marking of the area. A gel
pad is applied, and then the device is attached to
the skin. The device is a vacuum suction that
pulls the area to be treated between two cooling
plates. The physician can set the strength of the
vacuum during the treatment, but the degree of
cooling, known as the “Cooling Intensity Factor”
is fixed. The treatment is 60 min. The device is
handsfree and does not require the physician to
be present in the room. Post treatment, the device
is removed, and the area is massaged. Post treat-
ment massage was shown to improved efficacy
by 68% in one study [9].
Post treatment, the area is red and swollen (see
Fig. 15.2). The erythema resolves in 24 h; edema
and tenderness can last several days. Bruising can
result. Approximately 40% of patients will experi-
ence numbness and tingling that can last 8 weeks,
but typically resolves in 3–4  weeks [10]. Less
common side effects include transient blanching
of the skin and persistent erythema and edema.
Rare side effects include severe pain, paradox-
ical hyperplasia, post inflammatory discoloration
of the skin, subcutaneous induration, treatment
area demarcation. Severe shooting or stabbing
pain can develop in the first week after treatment,
lasts 2 weeks on average and may require oral or
topical pain medication [11]. The incidence of
severe pain was reported to be approximately
0.03% [12]. The abdomen is the most common
area, and larger applicators are more likely than
smaller applicators to be associated with this
adverse event. Severe Paradoxical hyperplasia
Table 15.1  Mechanism of non invasive fat removal
Approach
Mechanism
Cryolipolysis
Cooling
High intensity high
frequency focused
ultrasound
Thermal damage
Low frequency focused
ultrasound
Mechanical damage
Low level laser
Unclear—pore in
adipocyte may cause
leakage
Field radiofrequency
Thermal damage
Monopolar radiofrequency
Thermal damage
Fig. 15.1  Bulge in lower abdomen
M. Wanner and M. M. Avram

249
has a reported incidence of 0.0051% [13]. It can
develop anywhere from 2–3 months to 6 months
after treatment. There is no spontaneous remis-
sion. Surgical intervention, such as liposuction, is
curative.
High Intensity High Frequency
Ultrasound
There are two types of focused ultrasound: high
intensity focused ultrasound (HIFU) and low fre-
quency ultrasound. HIFU utilizes high frequen-
cies to create thermal damage and fat necrosis at
a specific focal point in the fat. Low frequency
ultrasound uses low frequencies to cause mechan-
ical damage and fat lysis.
HIFU (Liposonix, Solta, CA) is FDA cleared
for treatment of the waist, although other areas
such as the leg have been treated. The efficacy
of this treatment was established in a random-
ized sham controlled trial of 180 subjects [14].
At 3 month follow up, subjects were found to
have a 2.44 cm decrease in adipose tissue in the
group treated with three passes of 59 J/cm2 for a
treatment total of 177  J/cm2 compared to a
1.43 cm decrease in the sham group. There was
a slightly smaller decrease of 2.1  cm in the
group treated with three passes of 47 J/cm2 for a
treatment total of 141  J/cm2. These findings
were statistically significant. A histologic study
found that most healing is complete at
8–14  weeks, and therefore, it will take
2–3 months for patients to notice results [15].
HIFU does not appear to cause changes in liver
tests or lipid panel [16].
The device has a fixed focal depth of 1.3 cm,
and therefore, in order to use HIFU, patients
much have at least an inch of pinchable fat in
the area. Other patient considerations include
a history of coagulation disorders which would
increase the risk of bruising; pregnancy; meta-
bolic disease; or hernia, surgery or impaired cir-
culation or sensation in the area of treatment. The
patient should also be examined for laxity, as this
condition would not be expected to improve with
this treatment.
Prior to treatment, the area is marked, the
patient is weighed, photographs are taken, and
measurements of the area to be treated are taken.
Areas close to the bone should not be treated. The
HIFU treatment typically lasts an hour if the
entire abdomen is treated. Although protocols
vary, typically 3–5 pulses per site are completed
at fluences of 30–60 J/cm2 to reach a goal of 140–
180 J/cm2. Patients should expect, on average, a
decrease of an inch after 2–3 months.
The treatment can be painful, although most
patients can complete the treatment using distrac-
tion with forced cool air, ice packs, cold spray, or
a vibrating massager. Other pain medications
such as benzodiazepines, opioid, NSAIDs, or
acetominophen can be tried.
Common side effects include erythema, swell-
ing, and tenderness. Bruising can arise in two
thirds of patients. Rare side effects include pro-
longed erythema, prolonged tenderness, and hard
lumps under the skin. Superficial burns were
reported in association with the original proto-
type [15, 17].
Low Frequency Focused Ultrasound
The Ultrashape™ System (Ultrashape Ltd, Israel)
is a focused ultrasound system that destroys adi-
pose tissue by mechanical means. It is used in
combination with radiofrequency pre and post
treatment. This system delivers focused ultra-
sound waves at a precise depths of 7, 10, and
15 mm. Typically, three treatments are completed
[18, 19]. Most of the fat reduction occurs in the
first 14  days, and response to treatment can be
assessed rapidly ([19]-Teitlebaum). The proce-
dure is 35–60 min per treatment, depending on
the size of the area treated.
Fig. 15.2  Before, Immediately after, results S/P 1 treatment
15  Lasers for Adipose Tissue and Cellulite

250
In a large prospective trial of 164 subjects with
27 controls, subjects were treated once on the abdo-
men, thighs, or flanks [19]. At 3 month follow up,
a statistically significant mean reduction of 1.9 cm
was reported after one treatment, in the setting of
weight maintenance, compared to baseline, control
group, and internal control for patients treated on
the thigh. Liver ultrasound at 14 and 28 days and
serial laboratory evaluations showed no clinically
significant treatment associated changes, with
no elevations in serum lipids or lipoproteins. No
systemic adverse effects were noted, and cutane-
ous adverse effects were rare and included a tin-
gling sensation, erythema, purpura, and blisters.
Ninety-two percent of patients reported minimal to
no discomfort after 90 min of topical anesthesia.
In a study of 30 patients, after three treatments, a
statistically significant decrease of 2.3 cm in local
deposits was found. These patients maintained
constant weight during the treatment period [18].
Several additional studies have found a decrease
in circumference [20, 21]; one study found an
increase in circumference [22].
Pain is minimal with the device. Redness,
blisters, and rarely bruising have been reported,
but are uncommon [18–22].
Low Level Laser Therapy
Low level laser therapy has been used with and
without ultrasound for fat removal. It is FDA
cleared for the hips, waist, thighs, and upper
arms. Low level laser activates cytochrome C
oxidase in mitochondria, upregulates ATP, and
induces transcription factors [23]. The mecha-
nism of fat removal is unclear. It is postulated
that low level laser creates a pore in the adipo-
cyte membrane, causing leakage of lipid into
the interstitial space [24]. An ex vivo study of
12 tissue samples and found that after 6 min of
low level laser, fat was completely removed
from the cell [25]. A change in the consistency
of fat with MRI evaluation has been reported as
well [26]. One histologic study did not find a
change in treated and untreated adipocytes [27].
Histologic analysis of the effects of low-level
laser of adipose tissue in rats found enlarge-
ment and fusion of the brown, but not yellow
fatty tissue [28].
A double blind randomized controlled trial
with a sham of 67 subjects found a decrease in cir-
cumference after six treatments [29]. A double
blind, randomized controlled trial with sham of 40
subjects found a decrease in total arm circumfer-
ence [30]. The decrease in arm circumference was
measured at three different points and added
together for a total decreased of 3.7  cm versus
0.2  cm in the control group. Two retrospective
studies of low level laser plus nutritional supple-
mentation found a statistically significant reduc-
tion in circumference [31, 32]. One small study of
five subjects found an increase in circumference in
three subjects [33].
The procedure utilizes a handsfree device
(Zerona, Erchonia, Texas) that emits 635  nm
laser at 17 mW. The device is positioned above
the patient. There is no contact between the
patient and the device. Typically six treatments
are completed, three times a week for 2 weeks.
The treatment takes 40 min.
Radiofrequency
Radiofrequency has been used for tissue tighten-
ing, skin laxity, and cellulite; only more recently
has radiofrequency been applied to non invasive
fat removal. Radiofrequency devices utilize cur-
rent to create heat. Radiofrequency has been
found to induce fat atrophy [34]. The radiofre-
quency devices used for non invasive fat removal
include monopolar radiofrequnecy and focused
field radiofrequency. Bipolar radiofrequency,
which penetrates superficially is typically used
for cellulite treatment.
Field radiofrequency (Vanquish, BTL Industries,
CR) is accomplished with a device that is posi-
tioned over the patient. There is no contact between
the patient and the device. The device is designed
to have a focal point approximately 10 mm below
the surface and to heat the area to 43–45  °C.  A
small porcine study demonstrated a reduction in
adipocytes after four 30 min treatments [35]. A non
randomized, uncontrolled study of field radiofre-
quency evaluated 40 subjects after four treatments.
Thirty-five subjects were included for analysis, and
of these subjects, 32 had an average decrease in
circumference of 4.93 cm. Three subjects did not
respond. BMI decreased on average across subjects
M. Wanner and M. M. Avram

251
0.263  kg/m2 [36]. The treatment was reported to
cause mild erythema that resolved. 90.5% of sub-
jects did not feel pain during the procedure. Patients
are monitored during the treatment.
A monopolar radiofrequency device with cool-
ing has been studied (Exilis, BTL industries, CR).
This device uses a handpiece that is continuously
circled on the patient to achieve a goal surface
temperature of 42–43 °C. Each 5 × 7 cm2 area is
treated for 6–8 min. An abdomen can be treated in
30 min. Four treatments, spaced 1 week apart are
performed. The device penetrates 0.4–2.5  cm
beneath the skin, and the depth of penetration is
controlled by cooling. In a trial of 60 subjects,
subjects received 4–5 treatments [37]. Fat was
reduced by ultrasound measurements 0.04 cm on
the thighs to 0.06 cm on the abdomen/flank areas.
1210 nm Laser
Selective photothermolysis of adipose tissue has
been reported at 1210 and 1720 nm wavelengths
and may offer another non invasive option for
treatment of adipose tissue, but a clinical device
is not yet available [38].
Invasive Fat Removal
1064 nm Laser with and Without
Liposuction
The Nd:YAG laser has been used alone or in com-
bination with suction liposuction. SmartLipo™
(Cynosure, USA), a 300  μm 1064  nm fiber
encased in a micro-cannula, is an example of
this type of device. The cannula is inserted sub-
cutaneously to destroy lipid membranes and
release lipids. Adipocytes appear to swell at
lower energies and lyse at higher energies [39].
The laser also heat coagulates collagen fibers.
This process is termed “laser lipolysis” [40]. It
is worth noting that the term “lipolysis” appears
to be misused in this context. Strictly speaking,
“lipolysis” is defined not as destruction of the
adipocyte membrane, but rather as shrinkage of
the fat cell due to the use of lipid for energy at
the cellular level.
The Nd:YAG laser has been extensively stud-
ied [6, 41–46]. There appears to be minimal cos-
metic advantage to this procedure compared with
traditional liposuction, although patients may
have less post operative pain with laser-assisted
lipoplasty. The procedure may be helpful for the
surgeon, requiring less effort, particularly in dif-
ficult to treat areas [11], but it can be more time
consuming [13].
An illustrative example is a prospective, dou-
ble blind, controlled trial of 25 patients and 110
areas of treatment with patients serving as their
own control with suction lipoplasty on one half
and laser-assisted lipoplasty on the other with a
2  mm 1064  nm Nd:YAG laser fiber follow by
suction with a 3 mm cannula [9]. No clinical dif-
ference in cosmetic result was found, although
postoperative pain was higher in the suction-
assisted side versus the laser-assisted side at the
first follow up visit only.
Without liposuction, the Nd:YAG may have a
role in the removal of local deposits of fat. The
use of a 1064 nm Nd:YAG laser with a 300 μm
fiber encased in a 1 mm microcannula, without
combining it with liposuction was studied in a
randomized study of 30 female patients with
focal areas of fat less than 100 cm3 on the arm,
submental area, thigh, and abdomen [12]. An
average 17% reduction in fat volume (p < 0.01)
was seen on MRI. Bruising, swelling, and tender-
ness were seen, and uncommonly, transient tin-
gling, hyperpigmentation, and a subcutaneous
nodule were reported. As with non invasive
approaches, use of this device without liposuc-
tion may be best suited to small collections of fat.
635 nm Laser and Liposuction
Low level laser has been used in combination with
liposuction. Neira has combined low level 635 nm
laser and liposuction in a technique labeled the
“Neira 4L technique” [47]. Patients are irradi-
ated with a low-level 635 nm laser after tumes-
cent anesthesia. Following irradiation, removal of
fat is accomplished with a cannula or other tech-
nique. Neira reported a case series of 700 patients
of whom 95% were satisfied with results [15]. A
well designed randomized, controlled, blinded
study found a statistically significant decrease in
pain and swelling post operatively after treatment
with low level laser [48]. Investigators reported a
15  Lasers for Adipose Tissue and Cellulite

252
greater ease of fat extraction after low level laser
therapy, also statistically significant. Based on
these studies, low level therapy may influence
healing, but the histologic effects and the effect on
cosmesis remain unclear.
External Ultrasound and Liposuction
External ultrasound and liposuction have been
combined to remove adipose tissue [49–51].
External ultrasound is theorized to relax the
bonds between cells, affecting the septa, enhanc-
ing skin contraction after liposuction and allow-
ing for the use of thin cannulas [52]. Fat cells can
be used for grafting [53]. The typical procedure
involves application of a 2–3 W/cm ultrasound
device for 5–15 min.
Several studies have found external ultrasound
to be beneficial [25, 54–56], although one double
blind study casts doubt on the utility of this pro-
cedure [57]. In most of the studies, there appears
to be a slight advantage of the ultrasound assisted
approach in terms of physician fatigue (50–70%
preferred the ultrasound treated side). Patients
had less bruising (40–70% of patients), swelling
(40–70% of patients), and discomfort (50–80%
of patients) on the ultrasound treated side [26–
28]. The cosmetic result appears to be similar
[26–28]. One of the studies reported increased
skin retraction of 30% on the side treated with
ultrasound [27]. These studies were randomized
and controlled, but statistical significance was
not tested. The surgeon was blinded in one of the
trials [26]. The number of patients in these stud-
ies ranged from 10 to 30. Adverse effects includ-
ing erythema, mild warmth, burns, blisters, and
seroma were reported during the procedure [22,
24, 25, 28].
A larger study of 59 patients comparing exter-
nal ultrasound assisted to standard liposuction
also reported that patients had less bruising and
discomfort [25]. A faster recovery time was
reported, but patients receiving external ultra-
sound were given different instructions about
reduction of physical activity, leading to a poten-
tial bias in recovery time. Skin shrinkage as evi-
denced by a smoothness of the skin was apparent
on the ultrasound side at 30 days and on the stan-
dard liposuction side at 6 months; however, this
smoothness was not quantitatively defined and no
statistical evaluation was done.
These studies contrast with a double blinded
study of 19 patients who served as their own
control to evaluate external ultrasound-
assisted liposuction [29]. The treatment side
received ultrasound at 2–3 W/cm2 for 10 min
and the control side received 0.2–0.3 W/cm2.
Fat was sampled in two patients. There was no
difference between resistance to removal and
the rate of fat removal in 14 of 19 patients.
Patients assessed the treatment as well, and
only 4 of 19 reported a better operative and
post operative course with external ultrasound.
Statistical significance was tested for physi-
cian and patient assessments, and no benefit to
using external ultrasound with liposuction was
found. Histologic evaluation showed no differ-
ence between the experimental and control
side. Although the study was limited by the
small number of patients, the double blind,
controlled framework provides strong support
that the use of external ultrasound may not
yield significant benefit.
Internal Ultrasound and Liposuction
Liposuction in combination with internal ultra-
sound was pioneered by Zocchi [58]. Several
studies reported large series of patients treated
with ultrasound assisted lipoplasty [59–63], and
the purported benefits of this technology include
less blood loss, less surgeon fatigue, and
improved skin retraction [64, 65]. Ultrasound
assisted liposuction has been found to be more
selective for adipocyte removal; however, this
selectivity may not yield superior results [32]. In
studies that compare standard versus ultrasound-
assisted
lipoplasty,
the
ultrasound-assisted
approach has not had better cosmetic outcome
[32, 34, 66]. It may be that ultrasound-assisted
lipoplasty is better for certain indications such as
fibrous areas [67].
A well designed study of 63 patients who
received both traditional and ultrasound-assisted
lipoplasty provides an example [34]. Patients were
blinded to the procedure in this trial. In addition to
the evaluations by patient and surgeon, an indepen-
dent panel evaluated ten randomly selective
M. Wanner and M. M. Avram

253
patients. Ultrasound-assisted lipoplasty was not
found to be superior to traditional lipoplasty with
no difference in sensory, pigment change, surface
irregularity, skin contraction, bruising, or swelling.
Similarly, a randomized, controlled study of ultra-
sound-assisted liposuction compared with tradi-
tional liposuction in 28 patients found no significant
difference in cosmetic result and adverse effects
[38]. Physicians reported less fatigue.
Skin necrosis, burn, fat necrosis and fibrosis,
sensory alteration, infection, lower limb edema,
and seromas have been reported [31–33, 38,
39, 68, 69]. Skin necrosis is a particularly con-
cerning adverse effect. It is thought to be due
to ­destruction of deep dermal vessels despite
higher perfusion with ultrasound-assisted lipo-
suction compared with suction liposuction [70,
71]. Postoperative sensory changes occur in
both traditional and ultrasound-assisted liposuc-
tion; immediately after surgery, these changes
may be more prominent in those patients treated
with ultrasound [72, 73]. Surgeon experience and
surgical technique may play a role in ultrasound
assisted complications [31].
With respect to invasive options for fat removal,
internal or external ultrasound and laser assisted
lipoplasty appear to offer minimal advantages
over traditional lipoplasty. Nearly all blinded and
controlled studies have failed to show improved
cosmetic outcome with these devices.
Cellulite Treatments
There are several devices that have been used
for noninvasive treatment of cellulite including
devices that incorporate laser or light sources
(see Table  15.2). Most of these devices have
temporary or limited efficacy or have been
poorly studied, casting doubt on their efficacy.
In this section, these devices will be reviewed
as well as those that incorporate radiofrequency.
Radiofrequency devices represent the best stud-
ied devices in the cellulite market. There is only
one energy based invasive or “minimally inva-
sive” device available. This device incorporates
laser and will be reviewed.
Theoretically, those devices that best treat
cellulite should be the devices that affect some
aspect of the pathogenesis of cellulite. There are
multiple theories to explain cellulite, but those
with the most evidence suggest that cellulite is
caused by sex specific differences in skin struc-
ture and hormonal milieu [74–80]. Cellulite is
present in the large majority of women and
rarely in men, except in cases of androgen defi-
ciency [46]. Unlike in men, the subcutaneous
tissue in women is loosely reinforced, and her-
niations of the superficial fat are more likely to
develop. Therefore, therapies that remove the
fat herniations and alter the septated connective
tissue reinforcements would be expected to
improve cellulite.
Lasers and Light Sources
Intense Pulsed Light
Intense pulsed light (IPL) has been shown to
stimulate collagen production, and it is used in
the treatment of cellulite with the purpose of
thickening the dermis to diminish the appear-
ance of cellulite [81, 82]. The theory is that a
thicker dermis will hide the fat herniations bet-
ter. A 12  week trial of 20 women of whom 8
received IPL alone and 12 received IPL in com-
bination with retinyl based cream for a total of
9–12 treatments found that the majority of
patients with improvement used the cream in
combination with IPL [83]. Nine patients
reported improvement greater than or equal to
50%, and seven maintained this improvement at
8  months. This study was limited as only 15
patients completed the study, and no statistical
analysis was done. The use of IPL alone as a
treatment for cellulite does not appear to be
indicated.
Table 15.2  Laser and light based treatments for cellulite
Non invasive
Invasive
Intense pulsed light
660–950 nm LED
1064 nm laser
810 nm laser with suction massage
650 nm light source and 915 nm
laser with suction massage
1440 nm side
firing laser
15  Lasers for Adipose Tissue and Cellulite

254
Light Emitting Diode
A light emitting diode at 660 and 950 nm has been
used in combination with a cellulite gel comprised
of several active ingredients (bupleurum falcarum,
caffeine, coenzyme A, and phosphatidylcholine).
A randomized, double blind controlled study eval-
uated nine patients who received an active gel on
one thigh and placebo controlled gel on the control
thigh in combination with light [84]. Cellulite was
improved in eight of nine patients on the active
thigh and no patients on the control side, suggest-
ing that the light emitting diode had little effect.
1064 nm Laser
Thickening the dermis to mask fat herniations is
the rationale behind a 1064 nm laser for cellulite.
This device was studied in 12 subjects. Three
months after the third treatment, a statistically
significant reduction in dermal thickness and
increase echogenic density on ultrasound was
noted. Subjects were “a little to somewhat satis-
fied”. Erythema was the main side effect [85].
Light Sources and Massage
A few devices incorporate massage with light to
treat cellulite. Massage is included in the treat-
ments based on the idea that vascular and lym-
phatic alterations promote cellulite, although
there is limited evidence to support this the-
ory [86–88]. Examples include TriActive™
(Cynosure™, USA), a low fluence 810 nm diode
laser with vacuum massage; Synergie Aesthetic
Massage System™ (Dynatronics, USA), a vac-
uum massage with or without a 660–880  nm
probe or 880 nm light pad; and SmoothShapes®
(Elemé Medical, USA), a 915  nm laser and
650 nm light source combined with vacuum and
mechanical massage.
The TriActive™ appears to yield a transient
21–25% improvement in cellulite after mul-
tiple treatments. In an uncontrolled study of 16
patients who received twice weekly treatments
of TriActive™ for 6 weeks, photographs evalu-
ated by blinded investigators showed a 21% aver-
age improvement that was not present 1 month
after the last treatment [89]. Significance was
not tested. A comparison of 20 patients treated
twice weekly for 6 weeks with the TriActive™ or
VelaSmooth™, a radiofrequency device, found
similar results [90]. In this study, photographs
were evaluated by blinded investigators and sig-
nificance was tested. The average improvement in
cellulite was 7% and 25% for the VelaSmooth™
and the TriActive™, respectively. VelaSmooth™
and TriActive™ also yielded a 28–56% and a
30–37% improvement in the thigh circumfer-
ence, respectively. The difference between the
two devices was not significant. Adverse effects
included bruising seen in 10 of 20 patients with
VelaSmooth™ and 4 of 20 with TriActive™.
SmoothShapes has been evaluated in several
studies [91–93]. Two of these studies focused on
fat reduction, finding a statistically significant
decrease in fat thickness of 1.19 cm2 on MRI and
a statistically significant reduction in thigh cir-
cumference. Another study assessed cellulite
more closely: 3D Imaging revealed a 2.3  mm
change in surface elevation and a 4.9 mm change
in flattening 6 months after treatment.
Radiofrequency
Radiofrequency represents the best studied treat-
ment for cellulite. Radiofrequency can be mono-
polar in which the current is delivered from an
electrode to a grounding pad; bipolar in which
the current is delivered between two electrodes
and unipolar in which the energy is delivered
without grounding. Multiple electrode radiofre-
quency in which the energy is delivered between
three probes, one positive and two negative has
also been reported [94, 95].
The VelaSmooth™ is a bipolar radiofre-
quency, infrared heat, and suction device that is
FDA cleared for the treatment of cellulite. The
VelaSmooth™ has been evaluated more exten-
sively than any of the other devices for cellulite;
however, many studies are flawed, without a con-
trol group or without statistical evaluation. Most
studies report a decreased circumference of the
treated area and an improvement in cellulite of
25–50% in most subjects [96–100]. The duration
of benefit is unclear, and one investigator noted a
diminution of effect at 6 months [64]. Bruising is
a common side effect noted in up to 10–31%
M. Wanner and M. M. Avram

255
[63–65]. Crusting and burn have rarely been
reported [62, 65].
One of the better and illustrative studies of
the VelaSmooth™ is a controlled trial of 20
patients [63]. Of the 20 enrolled patients, 16
were treated twice weekly for 6 weeks on one
leg, while the other leg served as control. A sta-
tistically significant decrease of thigh circum-
ference (0.44–0.53  cm) was seen at 4  weeks,
but not immediately or at 8  weeks. A greater
than 51% improvement was seen in 25–31% of
patients at 8  weeks after the last treatment.
There was no histologic evidence of structural
change, however. Lipid, hormone, and liver
function tests were tested in five patients and
showed no change. Thirty-one percent of
patients had bruising.
The Alma Accent RF System (Alma Lasers™,
Buffalo Grove IL) utilizes unipolar and bipolar
radiofrequency. The Alma Accent RF System
was evaluated in an uncontrolled study of 26
patients [101]. In this study, the patients received
two treatments on the thigh and buttock. Patients
were evaluated by ultrasound for a change in dis-
tance from the dermis to the first line of fibrous
tissue (Camper’s fascia) and the dermis to mus-
cle. The majority of patients (64–72%) showed a
15.49–27.8% decrease in these measures. On
average, there was a 6.8–11.55% decrease in the
measurements among all patients, although some
of the patients showed an increase in the distance.
Findings were not uniformly significant, and this
study is limited by the lack of a control group.
The authors evaluated ultrasound for qualitative
changes in the skin structure and found improve-
ment in 50–57% of patients. Adverse effects were
rare with small blisters developing in two patients
and bruising in three patients.
Unipolar radiofrequency was evaluated in a
study of 30 subjects that was neither controlled
nor blinded nor randomized. In this study, graded
improvement of cellulite was found to be 2.9
on a scale of 1–4 after six treatments [102]. In
a randomized, controlled, blinded study of ten
subjects treated six times with unipolar radiofre-
quency, dimples improved 8%. This finding was
not statistically significant [103].
Of the available devices on the market, those
with radiofrequency seem to have the most evi-
dence for effect, albeit marginal. These devices
generally yield a 25–50% improvement after
multiple treatments. This effect seems to dimin-
ish over time.
1440 nm Nd:YAG Laser
A 1440 nm side firing laser fiber represents the
only invasive energy based device treatment for
cellulite (CelluLaze, Cynosure Inc, MA). The
concept behind this laser is that the treatment
melts the fat herniations associated with cellulite
as well as shearing septae that contribute to these
herniations and the dimples associated with cel-
lulite. The 1440 nm wavelength is absorbed more
by adipose tissue than by water.
The treatment uses a laser fiber associated
with a cannula that is inserted under the skin. The
laser has a temperature sensor. The fiber is passed
under the skin in three positions: pointed up,
sideways, and down. After treatment, pressure is
used to remove the fat from the cannula insertion
points. The treatment requires tumescent anes-
thesia. Compression garments are worn after
treatment. Side effects of the treatment include
bruising, swelling, pain, numbness and itching.
Prolonged discomfort, bruising, swelling, and
numbness was reported and found to be resolve
by 3 months.
A preliminary study of ten subjects found an
improvement of cellulite that persisted 1 year
after a single treatment [104]. A multicenter
study of 57 subjects and 87 sites compared cel-
lulite 6 months after treatment to baseline [105].
Ninety-one percent of treated areas improved 1
point on a 5 point scale. On average, the 81 treat-
ment sites evaluated at 6 months improved 2.7
points on a 5 point scale.
Conclusion
The currently available options for laser or
light based removal of adipose tissue or cel-
lulite are limited. The 635 nm laser is the only
clinically available device that has been well
studied for non invasive removal. In fact, the
best studied devices for non invasive fat
removal, do not rely on light or laser. Cooling
and ultrasound devices may offer superior
15  Lasers for Adipose Tissue and Cellulite

256
results for non invasive fat removal. Although
SmartLipo™ may have a role for removal of
small collections of adipose tissue, it has not
been shown to be cosmetically advantageous
as compared with traditional lipoplasty.
With respect to cellulite treatment, non inva-
sive laser and light devices have either not been
studied or have been proven to have modest,
temporary effect. The best studied non-invasive
approach is radiofrequency; however, this too
offers results that are generally mild and tempo-
rary. CelluLaze is a newer, minimally invasive
treatment that may provide better and longer
term results, but is associated with a greater pain
requiring tumescent anesthesia and greater risks
compared with non invasive devices.
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© Springer International Publishing AG, part of Springer Nature 2018
K. Nouri (ed.), Lasers in Dermatology and Medicine,
Photodynamic Therapy
Ariel E. Eber, Marina Perper, Sebastian H. Verne,
Robert Magno, Ibrahim Abdullah Omair ALOmair,
Mana ALHarbi, and Keyvan Nouri
Abstract
Photodynamic therapy with ALA or MAL
is an excellent treatment for multiple actinic
keratoses.
Large field photodynamic therapy can
eradicate multiple actinic keratoses with a
shorter downtime than 5-fluorouracil or
imiquimod.
Multiple large field photodynamic therapy
sessions can delay the appearance of actinic
keratosis.
Keywords
Photodynamic therapy (PDT) ·
Aminolevulinic acid (ALA) · Methyl
aminolevulinate (MAL) · Actinic keratosis
Introduction
It was a medical student, Oscar Raab, who first
discovered photodynamic therapy (PDT) at the
beginning of the twentieth century [1]. PDT
­combines the administration of a photosensi-
tizer or photosensitizer precursor with its activa-
tion by light of appropriate wavelength. Reactive
oxygen species (ROS), which can be used to
destroy a target cell, are created in the presence
of oxygen. The concept, however, that a mole-
cule activated by light could be used to destruct
pre-malignant and malignant cells, did not enter
wide practice until the 1990s. Since then, uses
for PDT have been expanded to treat a variety of
dermatologic ailments including sun-damaged
skin and acne [1].
Kennedy and Pottier were the first to dis-
cover the application of Aminolevulinic Acid
(ALA) [2] for treating skin disorders and the
first to successfully treat them [3]. ALA has
been approved for dermatologic indications by
the Food and Drug administration (FDA) for
many years. PDT utilizes the heme biosynthetic
pathway to produce endogenous porphyrins,
particularly protoporphyrin IX, which is an effec-
tive photosensitizer. Protoporphyrin IX has two
important spectral peaks, 404–420  nm and
635 nm in the blue and red wavelengths, respec-
A. E. Eber · M. Perper · S. H. Verne · R. Magno ·
K. Nouri (*)
Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine,
Miami, FL, USA
e-mail: knouri@med.miami.edu
I. A. O. ALOmair · M. ALHarbi
Department of Dermatology, College of Medicine,
Al Imam Muhammad Ibn Saud Islamic University
(IMSIU), Riyadh, Kingdom of Saudi Arabia
16

262
tively. In order to achieve optimal therapeutic
effect, the light source used in PDT should cor-
respond to the excitation peaks of the photosen-
sitizer [1].
Biochemically, heme is normally synthe-
sized from glycine and succinyl CoA. The rate-
limiting step in the pathway is the conversion of
glycine and succinyl CoA to ALA, which is
under negative feedback control by heme.
Excess exogenous ALA, however, can bypass
this feedback mechanism and produce an accu-
mulation of porphyrins that, when activated by
visible light, generate the photosensitizing
effect of PDT [4]. Methyl aminolevulinate
(MAL) is another photosensitizer approved by
the FDA. MAL theoretically works in the same
manner as ALA because it is converted to ALA
in the cytosol of cells, however it have a slower
onset of action.
Since the approval of ALA and MAL in the
United States for actinic keratosis, PDT is now a
well-established procedure. Furthermore, these
drugs are approved in several other countries for
the treatment of non-melanoma skin cancers
and they are used for other indications as well.
Indications and Contraindications
Indications
Aminolevulinic acid is approved in the US,
Canada, and Brazil for the treatment of mini-
mally to moderately thick actinic keratosis of
the face and scalp in combination with the
Blu-U unit (Fig.  16.1). It was originally
approved for nonhypertrophic actinic keratoses,
but is now indicated for minimally to moder-
ately thick AK at the FDA’s request. In practice,
this wording is similar and refers to the fact that
PDT is not approved for thick and hypertrophic
AKs. There are two issues related to treatment
of hypertrophic AKs with PDT. The first is inad-
equate penetration of ALA through the hyper-
keratotic portion of the lesion and the second is
the possibility that some of the more hypertro-
phic lesions might be micro-invasive squamous
cell carcinomas (SCCs). The current approval is
based on phase III studies where ALA was
applied to visible lesions for 14–18 h followed
by 10 J/cm2 of blue light from a Blu-U unit [4].
However, in practice very few physicians use
ALA-PDT with a 14–18 h incubation. Most will
use a shorter incubation of 45 minutes (min) to
2 h. This off label use is supported by a small
pilot study which showed that incubation of
1–3  h in patients with extensive sun exposure
leads to AK lesion cure rates that are similar to
what has been shown with longer incubations in
phase III studies [5].
Complete responses on basal cell carcino-
mas (BCCs) have been reported following
ALA-PDT [6]; however, the efficacy of ALA-
PDT for the treatment of BCC has never been
studied in multicenter phase III trials and the
long term recurrence rates have not been well
studied. MAL is currently FDA-approved for
the treatment of non-hypertrophic actinic kera-
toses of the face and scalp in immunocompetent
patients when used in conjunction with lesion
preparation and when other therapies are con-
sidered medically less appropriate. Use of PDT
has evolved from its application as a monother-
apy to an adjunct with other treatments. The
value of sequential treatment with MAL-PDT
and imiquimod was investigated in a random-
ized trial (n = 105). Better response rates were
seen for combination treatment than for either
monotherapy; however, the difference in
response was statistically significant only for
the comparison between combination therapy
and MAL-PDT monotherapy [5, 6]. AK cure
rates following either a single MAL-­PDT ses-
sion repeated at 3 months if necessary or two
MAL-PDT sessions performed 7  days apart
have been reported to be around 90% [7, 8].
Studies presented at meetings suggest that mul-
tiple large surface ALA or MAL PDT sessions
can delay the appearance of new actinic kerato-
ses in organ transplant patients. This suggests
that large surface PDT may be able to prevent
skin cancer. Combination therapy with sequen-
A. E. Eber et al.

263
tial MAL-PDT and imiquimod has also shown
effectiveness in the treatment of AKs.
Several countries have also granted approval
of MAL-PDT for the treatment of various non-­
melanoma skin cancers. The indications vary
from one country to another, but in general
most countries approved MAL-PDT for the
treatment of Bowen’s disease and superficial
BCC when other therapies such as surgery were
considered inappropriate [9–11]. The complete
response rate of superficial BCC (sBCC) fol-
lowing MAL-PDT has been shown to be 97%
and the 48-month long-term recurrence rate
was 22% [12, 13]. The main advantage of
PDT for the treatment of sBCC and Bowen’s
disease are the excellent ­cosmetic outcome as
compared to surgery, cryotherapy or electrodes-
sication, and curettage [6, 9]. Some countries
have also approved MAL-PDT for thin nodular
BCC, but because the cure rate is lower than
for sBCC, many countries have restricted their
approval to sBCC.  Recurrences with superfi-
cial BCCs, nodular BCCs and Bowen’s disease
usually occur during the first 2–3 years after
therapy with no increase in recurrence between
the third and the fifth year. PDT demonstrated
Fig. 16.1  Blu-U device.
This non-coherent light
source is approved for
the treatment of actinic
keratosis with ALA
16  Photodynamic Therapy

264
superior efficacy and less scarring in the treat-
ment of SCC in situ when compared with cryo-
therapy or 5-fluorouracil in a Cochrane review
(n  =  363). In particular, ALA-PDT appeared
to have greater efficacy than 5-­fluorouracil but
MAL-PDT was not demonstrated to be supe-
rior over 5-fluorouracil. Also, there was no dif-
ference in recurrence rates at 12 months with
either MAL-PDT or ALA-PDT when compared
with 5-fluorouracil [6, 7]. A consensus group in
Canada and Europe analyzed nine studies and
reported that use of MAL-PDT can be consid-
ered as a safe and effective treatment for BCC
in patients with Gorlin syndrome, with an effi-
cacy level being proportionate to the thickness
of the lesion. PDT has been observed to have
chemopreventive effects in patients with Gorlin
syndrome [8]. MAL is not yet commercially
available in the US because the FDA approved
MAL only in combination with the Curelight
device, an earlier LED light source that is
rather cumbersome. In most countries MAL is
approved with the Aktilite (Fig. 16.2), a smaller
and more convenient device. Studies comparing
the efficacy of the Curelight and the Aktilite in
the treatment of AK are currently being com-
pleted in the US, and should ultimately lead to
FDA approval of MAL-PDT performed with
the Aktilite device. Initial studies conducted
with PDT for skin diseases often used lasers.
However, the current off-label trend with ALA-
PDT is to use broad area application ALA or
MAL in order to treat non-visible lesions,
improve photoaging, and eventually prevent
the appearance of new lesions. This trend,
combined with the cost and limited availability
of lasers in the 400–450 nm and 630–640 nm
ranges, has limited the use of lasers for PDT in
dermatology. When physicians are using ALA
with a non-approved light source, they tend to
favor LEDs or intense pulsed light. However,
the pulsed dye laser at 595 nm has also been
used for the treatment of actinic keratoses and
acne [14]. PDT has been widely used in the
treatment of mycosis fungoides, an indolent
subtype of cutaneous T cell lymphoma. Most of
these report efficacy of MAL-PDT and ALA-­
PDT in the treatment of plaque-type (stage
I) mycosis fungoides, but decreased efficacy
against tumor-type (stage II) mycosis fun-
goides, and there has been a single report of
erosive mycosis fungoides on the face treated
successfully with ALA-PDT using red light
[9]. One prospective study (n = 29) reported an
objective response in 75% of plaque or patchy
lesions after monthly treatments for 6 months.
However, a recent study observed two of five
patients who appeared to have had a complete
response initially, but relapsed at follow-up
(10.0 ± 10.5 months). MAL-PDT was success-
ful in treatment-­refractory mycosis fungoides
(four patients with complete remission and one
with partial remission). In conclusion, several
consecutive treatments of PDT can be consid-
ered as an adjunct for treatment of mycosis fun-
goides, particularly for patch and plaque-stage
Fig. 16.2  Aktilite device. This LED light source is
approved in several countries for the treatment of AK and/
or Bowen’s disease and/or superficial basal cell carcinoma
with MAL
A. E. Eber et al.

265
mycosis fungoides, with good cosmetic results
in sensitive skin areas [10].
ALA and MAL have been reported to success-
fully treat various non oncologic skin conditions
in small pilot studies or in single case reports.
These include acne, rosacea, sebaceous hyperpla-
sia, hidradenitis suppurativa, photoaging, and
other cutaneous infections [14–19]. MAL and
ALA are both in phase II for the treatment of
acne [14, 15, 20, 21]. This is in part due to the
intense accumulation of porphyrin in sebaceous
glands following topical application of ALA and
MAL (Fig.  16.3). Light exposure could induce
partial necrosis of sebaceous glands and reduce
sebum excretion thus reducing acne lesions.
Preliminary findings with ALA suggest that this
is one of the mechanisms of ALA-PDT when
used for the treatment of acne [22]. Studies per-
formed with PDT in acne are complicated by the
fact that blue or red light alone can improve acne
by elimination of Propionibacterium acnes as
these bacteria naturally accumulate porphyrins.
Studies have also shown that blue light with and
without ALA is more effective than red light. In
vitro studies comparing ALA followed by blue
light, 415 nm, or red light, 635 nm, and examin-
ing the bactericidal effects on P. acnes, found that
red light phototherapy was less effective for the
eradication of P. acnes than blue light photother-
apy with or without ALA. Therefore, there may
still be a role for combined blue and red light
activation of ALA in the treatment of acne [11].
Most controlled studies which have shown good
efficacy report a strong post PDT phototoxic
reaction. Clinical photographs published in some
of the articles which used MAL under occlusion
for 3 h show moderate to severe erythema with
crusting 1 day post-PDT. These publications also
report severe pain in many patients during light
exposure [15, 21]. Such a strong phototoxic reac-
tion is probably not needed to see improvement
in acne. However, it is possible that prolonged
remission requires a certain degree of phototoxic
reaction as necrosis of sebaceous gland tissue
might be necessary. The current literature sug-
gests that PDT for acne is more efficacious for
patients with moderate to severe inflammatory
acne, although the best treatment parameters
remain unknown. The use of ALA-PDT in rosa-
cea is primarily anecdotal, with few randomized
controlled studies published thus far. MAL-PDT
with red light has been shown to improve the
appearance of rosacea, in particular papulopustu-
lar lesions, when compared with the erythemato-
telangiectatic types [12]. Evidence for the use of
PDT in treating rosacea is minimal, but MAL-­
PDT with red light has resulted in rosacea
improvement. Touma and colleagues have dem-
onstrated that the use of ALA-PDT with a 1–3 h
incubation followed by blue light exposure in
a
b
Fig. 16.3  (a) Porphyrin fluorescence in sebaceous glands 3 h after application of MAL. (b) Same section stained with
hematoxylin
16  Photodynamic Therapy

266
patients with multiple actinic keratoses can
improve photoaging [5]. Small wrinkles, pig-
mentation, and sallowness parameters best
improved with ALA-PDT. ALA-PDT performed
with IPL has also been shown to improve photo-
aging [18, 24]. Small studies have also shown
complete response in AKs treated with ALA and
IPL [24, 25]. There is currently a very wide vari-
ety of devices approved and used for the treat-
ment of photoaging. Most physicians using ALA
or MAL-PDT for photoaging either combine
PDT with other devices and treatments or favor
ALA or MAL-PDT for patients with actinic kera-
toses who would also like to have improvement
in photoaging.
PDT has been used to treat different types of
infections. ALA-PDT has been shown to suc-
cessfully treat cutaneous warts caused by human
papilloma viruses without significant side effects
and excellent cosmetic results in several studies.
Reported clearance rates are as high as 88%. The
clearance rate seems proportionate to the size of
the warts, and mean treatment time. ALA-PDT
with white light (halogen lamp; 250 W Osram;
delivered via slide projector) was found to be
more efficacious than red or blue light and stan-
dard cryotherapy [13, 14]. Several studies have
showed that PDT is an effective modality in
treating onychomycosis. One clinical trial
(n = 30) used chemical avulsion (occlusion with
urea for ten consecutive nights prior to PDT) and
20% ALA-PDT (3-h incubation) followed by red
light therapy, and demonstrated a 43.3% cure
rate at 12-month follow-up, which dropped to
36.6% at 18-month follow-up [15]. Two other
case series reported complete resolution of fun-
gal infection with PDT. One case demonstrated
successful treatment of subungual onychomyco-
sis after occlusion with urea for 7 days followed
by MAL-­PDT with broadband red light (37  J/
cm2). This was repeated every 2 weeks for a total
of three treatments. In this case, Trichophyton
rubrum was the causative organism and it has
been previously demonstrated to be sensitive to
PDT in vitro. Nondermatophyte molds have also
been cleared with MAL-PDT and red light [16,
17]. Cutaneous leishmaniasis, erythrasma, and
Candida albicans intertrigo have been treated
successfully using PDT [2, 18–20]. Treating
warts caused by human papilloma virus, ALA-­
PDT has been used with clearance rates as high
as 88%. ALA-PDT with white light was shown
to be more effective than red or blue light PDT
or cryotherapy. One study used chemical avul-
sion to treat onychomycosis with urea followed
by ALA-PDT with red light with a cure rate
of  36.6% at 18  months. Other studies demon-
strated complete resolution using urea and
MAL-PDT or PDT alone. Both dermatophyte
and nondermatophyte molds have been cleared
with PDT; cutaneous leishmaniasis, erythrasma,
and Candida albicans intertrigo have also been
treated with PDT.
Contraindications
It may be obvious but, ALA and MAL are contra-
indicated in patients sensitive to visible light cor-
responding to the spectral output of the light
source used (400–450  nm for Blu-U and 630–
640 nm for Aktilite). Patients with porphyria and
those with solar urticaria, systemic lupus erythe-
matosus, and other photosensitive dermatoses are
also sensitive to the visible light of PDT [1]. PDT
has not been thoroughly studied on patients using
concomitant photo-sensitizing drugs such as phe-
nothiazines, tetracyclines, thiazides and sulphon-
amides. Theoretically, this could increase the
phototoxic reaction seen after PDT. Additionally,
current use of topical or systemic retinoids such
as tretinoin, adapalene, acitretin or isotretinoin
could also increase the phototoxic reaction.
Interestingly MAL contains peanut oil. It should
not contain the protein allergen present in pea-
nuts, but many physicians refrain from using
MAL-PDT in patients allergic to peanuts. Further,
histologic variants of BCCs at high risk of recur-
rence such as morpheaform BCC, are a contrain-
dication to PDT with MAL. Pigmented basal cell
carcinoma is usually considered a contraindica-
tion to PDT as well as pigment limits light pene-
tration. Despite this, several physicians have
reported complete responses of pigmented BCCs
A. E. Eber et al.

267
with PDT.  Also, recurrent lesions and large
lesions may be better treated with other modali-
ties [21].
Techniques
Pre-operative management
• Informed consent with emphasis on difficulty
to predict phototoxic response
• Thorough examination of skin areas to be
exposed to detect malignant lesions
• Consider herpes simplex prophylaxis
Description of the technique
• Skin preparation to enhance penetration
• Photosensitizer application
• Interval to allow porphyrin build-up
• Light exposure
Post-operative management
• Sun avoidance
• Ferrous oxide containing sunscreen
• Moisturizer
Pre-operative Management
A complete skin examination of the areas to be
treated is necessary. This is of the utmost impor-
tance when performing large surface PDT. The
examination should focus on the identification of
malignancies such as basal cell carcinoma, squa-
mous cell carcinoma and melanoma. Sub-optimal
treatment of these malignant lesions could lead to
later, deeper recurrences. Any suspicious lesion
should be biopsied. If PDT is performed to treat a
malignant lesion such as BCC or Bowen’s dis-
ease, a pre-treatment biopsy is recommended. A
complete medical history including the existence
of visible light sensitivity diseases such as por-
phyria or solar urticaria should be recorded.
Patients should be asked about current use of any
topical product on the areas to be treated. Products
that can alter the stratum corneum such as topical
retinoids can increase ALA and MAL penetration
and create a more severe phototoxic reaction fol-
lowing PDT. The use of systemic treatments that
increase visible light sensitivity such as St-John’s
wort should be avoided.
Patients should be well informed about the
procedure including difficulty in predicting the
phototoxic reaction generated by PDT. If only a
few AKs or a single BCC are treated, the photo-
toxic reaction is usually not a problem. However,
a full-face treatment can lead to erythema associ-
ated with tenderness and sometimes with focal
areas of crusting. It is suggested to obtain a writ-
ten informed consent that mentions this informa-
tion as well as potential complications like
hyperpigmentation, hypopigmentation, scarring
(mostly when treating basal cell carcinoma), sun
and visible light sensitivity, and prolonged ery-
thema. Patients should be advised to bring a hat
(when treating the face) or other pieces of cloth-
ing to cover the treated area.
The risks of triggering light sensitive recur-
rences of herpes labialis following PDT are cur-
rently unknown. For patients who experience
recurrences following sun exposure, antiviral
prophylaxis should be discussed. Light exposure
during PDT sometimes leads to an urticarial
reaction immediately after PDT.  This is more
intense when red light is used and when large sur-
faces are exposed. This phenomenon has recently
been attributed to histamine release by mast cells
and could be prevented by pre-treatment with
antihistamines such as cetirizine.
Description of the Technique
Treatment of Actinic Keratoses
with ALA
A gentle curettage of keratotic AKs should be per-
formed prior to ALA application. This is not
included in the current product monograph but the
author finds that this increases the clinical response
of individual lesions, probably by increasing drug
penetration. Skin preparation is suggested when
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268
performing short ALA incubations. The face can
be washed vigorously with acetone or treated with
microdermabrasion. These techniques are believed
to increase ALA penetration through degreasing
and/or partially removing the stratum corneum.
Microdermabrasion can significantly reduce
ALA incubation time [27]. Care should be taken
to use the same technique with the same pre-­
treatment method by the same person when treat-
ing a patient at different sessions as differences in
skin preparation can have a dramatic impact on
porphyrin build-up and therefore on the extent of
the post-PDT phototoxic reaction.
ALA (Levulan) is available in the form of two
glass vials inserted in a plastic tube that is cov-
ered by cardboard (Fig.  16.4). The two vials
should be crushed with fingers and the stick
shaken for about 3 min to ensure proper mixing
of ALA powder and hydroalcoholic vehicle. ALA
should be applied on all AKs present in the treat-
ment area. Most physicians will also apply ALA
on the entire face in order to treat non-visible
lesions and prevent new AKs. Broad area ALA
application also has the advantage of improving
signs of photoaging [5]. Care should be taken to
avoid applying ALA too close to the eyes as the
solution will sting if it inadvertently gets into
them. Facial zones with more sebaceous glands,
such as the nose and chin, often display a more
pronounced phototoxic reaction than the rest of
the face when performing PDT. This is probably
due to more intense accumulation of porphyrins
in the sebaceous glands. If ALA or MAL is
applied on these zones during a full-face treat-
ment, patients should be told to expect a strong
phototoxic reaction the day following light expo-
sure. A delay of 45  min to 2  h is suggested
between ALA application and light exposure
when ALA-PDT is used on large skin surfaces
for the treatment of AKs. The intensity of the
phototoxic reaction generated by ALA-PDT var-
ies greatly from one patient to another and is
highly dependent on the type of pre-treatment
used. For patients with extensive photodamage
and numerous ill-defined AKs, a 45–60 min incu-
bation period is usually sufficient, and this dura-
tion time can even lead to a severe phototoxic
reaction post-PDT.  Some physicians prefer to
perform the first treatment with a 30–45  min
incubation time in these patients. The incubation
time can be adjusted at subsequent treatments
based on the phototoxic reaction and the clinical
response observed.
After a proper incubation time, patients are
placed inside the Blue-U device with appropriate
eyeshields to protect their eyes. As the U-shaped
unit rotates, treatments can be performed with the
patient sitting or lying down. The current product
monograph recommends a light dose of 10 J/cm2
of blue light that corresponds to an incubation
time of 16 min and 40 s. This was the fluence
used in phase III, but a lower fluence is probably
enough in most patients to completely photo-­
bleach porphyrins present in lesions. Many phy-
sicians use a shorter incubation time, but the
efficacy of shorter incubation times has not been
thoroughly studied in clinical trials.
Blue light exposure after ALA applica-
tion generates a burning sensation that gradu-
ally increases until it reaches a plateau around
3–8 min, which is then followed by a gradual
decrease. This decrease in burning sensation
intensity corresponds to photo-inactivation of
porphyrins present in skin lesions. Blue light
exposure is usually well tolerated by most
patients if they have been properly warned about
the sensation to expect during light exposure. An
assistant should be present in the room ­during
Fig. 16.4  ALA
(LEVULAN Kerastick).
The cardboard has been
removed to show the
two glass vials. Areas
where pressure needs to
be applied to crush the
two glass vials are
identified in red
A. E. Eber et al.

269
PDT, especially for the first PDT session, to
reassure patients and to monitor the burning
­sensation. The assistant can use cool air, spray
cool water or even temporarily interrupt light
exposure if the pain is too intense.
Treatment of BCC with MAL
A biopsy is suggested before treating a BCC
with MAL-PDT. The biopsy serves to confirm
the diagnosis and exclude histological subtypes,
such as morpheaform BCCs, for which PDT is
contraindicated. Gentle curettage of the lesion is
mandatory before MAL application as 5-year
cure rates have been established for MAL-PDT
with pre-treatment curettage. Figure 16.5 shows
a patient with multiple BCCs before and imme-
diately after lesion preparation. MAL is pro-
vided in 2 g tubes. Once opened, the cream must
be used within 7 days. This allows for treatment
of more than one patient with the same tube or
treatment of the same patient 7 days later with
the same tube. MAL should be applied on the
entire lesion including a 1-cm margin and should
be occluded. Three hours after application, the
occlusion is removed, the cream is wiped out of
the treatment field, and the device (Aktilite) is
positioned at 5–8 cm from the skin. There is a
risk of unsatisfactory treatment if the device is
positioned beyond 8  cm. The irradiance varies
according to the distance between skin and light
source. The area where MAL has been applied
should be exposed to 37 J/cm2 (Aktilite device)
of red light, which corresponds to approximately
7 min and 30 s.
Post-operative Management
Excess ALA and MAL should be removed by
thoroughly washing the skin with tap water
to prevent further porphyrin synthesis. This is
especially important when ALA or MAL has
been applied to large areas such as the entire
face. Since patients are mostly sensitive to the
visible part of the electromagnetic spectrum,
the use of high SPF sunscreens does not provide
adequate sun protection in the days following
PDT.  Patients can use a sunscreen containing
inorganic sunscreening agents, such as Avene
50 Compact which provides some, although not
complete, protection [28]. Patients should avoid
sun exposure or exposure to intense visible light
such as surgical lighting or a high power dentist
lamp for 2 days after PDT. Patients should also
avoid driving or walking under the sun on the
day PDT is performed. They should be reminded
that there is significant visible light exposure
even on cloudy days and through window glass.
There is no visible light sensitivity beyond
2 days after PDT with ALA or MAL. However,
patients should use a high SPF sunscreen which
provides adequate UVA protection to prevent
hyperpigmentation. The use of Avene thermal
water, a low mineral content water, after PDT
a
b
Fig. 16.5  Patient with multiple BCCs (Gorlin’s syndrome) on the back before lesion preparation (a) and immediately
after lesion preparation but before MAL application (b)
16  Photodynamic Therapy

270
has been shown to be superior to a higher min-
eral content water ­comparatively for decreasing
post-treatment pruritus [29]. Crusting and ero-
sions over AKs and BCCs is expected and desir-
able when treating malignant or pre-malignant
lesions with PDT. Simple occlusion combined
with the use of petrolatum jelly or an antibiotic
ointment is usually all that is required to pro-
mote healing and decrease pain. The regular use
of a bland moisturizer is recommended. Patients
should avoid any topical products containing
urea, retinoic acid or other alpha hydroxyl acids,
alcohol or propylene glycol in the weeks follow-
ing PDT. Patients should also be advised to call
their physician if the reaction increases beyond
2  days, as this may be suggestive of bacterial
infection or reactivation of extensive herpes
simplex.
Adverse Events
Expected
• Erythema
• Burning sensation during light exposure
• Crusting on AKs and BCCs possible
• Pain after light exposure
• Hyperpigmentation
• Hypopigmentation
• Scarring by loss of substance (e.g., nodular
basal cell carcinoma)
• Urticarial reaction on exposed area
• Prolonged erythema
• Cellulitis, impetigo
• Reactivation of herpes simplex
Rare
• Allergic contact dermatitis
• Keratoacanthoma
• Squamous cell carcinoma
• Erosive pustular dermatosis of the scalp
• Koebner phenomenon
• Leg ulceration
• Peripheral facial palsy
• Amnesia
• Hypertension
Side Effects/Complications
Most patients will report a burning sensation,
pain, or pruritus during light exposure. This is
usually well tolerated. All patients should
expect a phototoxic reaction after PDT.  The
absence of a phototoxic reaction on pre-malig-
nant or malignant lesions following PDT is
usually a sign that the treatment will not be effi-
cacious. The phototoxic reaction manifests
itself primarily by mild to severe erythema on
exposed sites. This is usually associated with
crusting on areas were AKs were present and
sometimes associated with vesicles, pustules,
and/or erosions.
Erythema and edema are often more severe
when the lesion to be treated is located on the
nose. This is probably related to the abundance of
sebaceous glands on the nose. Tenderness is usu-
ally present for a few days after PDT. Whole face
treatments are often associated with pain and ten-
derness that are exacerbated with pressure (con-
tact with pillow when sleeping for example) and
followed by desquamation.
Bacterial infections such as impetigo and/or
cellulitis or reactivation of herpes simplex are
possible but very rarely seen with ALA and
MAL-PDT. PDT can induce hyperpigmentation
on treated areas. This is rarely seen in patients
with phototype I or II.  Hypopigmentation is
possible but rare. Scarring by loss of substance
can be seen after treatment of lesions that
invade the dermis such as nodular basal cell
carcinoma. A few cases of prolonged erythema
have been reported following PDT on the face
[22]. This phenomenon can sometimes last
many months. In the author’s experience, this is
more frequent in patients with rosacea and usu-
ally fades over time.
Allergic contact dermatitis to MAL has been
reported and documented by patch testing. One
case of contact dermatitis was occupational as the
patient was working as a nurse in the dermatol-
ogy department [23, 24]. Clinicians should think
about this possibility in patients who have under-
gone several MAL-PDT treatments and present
with a dermatitis type of reaction that was not
present at previous treatments.
A. E. Eber et al.

271
Recently, a small number of patients were
reported to develop keratoacanthomas after treat-
ment with PDT and some of these were self-­
limited [25–28]. Additionally, squamous cell
carcinoma has also occurred post treatment with
PDT [29, 30]. Other anecdotal situations have
been reported including a Koebner phenomenon
in one patient, resulting in re-activation of inac-
tive psoriasis [31]. Although uncommon, an
elderly patient with peripheral vascular disease
and Bowen’s disease on her leg was treated with
PDT and resulted in leg ulcer [32]. Other rare
complications include erosive pustular dermato-
sis of the scalp, peripheral facial palsy (bell’s
palsy), amnesia, and elevation of blood pressure
requiring immediate treatment [33–36].
Prevention and Treatment of Side
Effects/Complications
Pain during the treatment session is a common side
effect that might cause discomfort for patients.
When large surfaces are treated with MAL or
ALA, the use of water spray, ice packs, fan or cold
air (such as from a Zimmer device), can allevi-
ate this sensation [37]. Temporary interruption of
light exposure is another alternative as the burning
sensation subsides rapidly when the light device
is turned off. If the pain is severe enough, other
methods such as subcutaneous infiltration anesthe-
sia or even nerve block can be considered [38, 39].
Topical anesthetic creams such as eutectic mix-
tures of local anesthetics (EMLA cream) do not
seem to be effective [40]. Super-potent topical cor-
ticosteroids can decrease inflammation and ery-
thema associated with PDT if used immediately
before or after the treatment session without com-
promising the therapeutic outcome [41]. Careful
history taking for other diseases such as psoriasis
or peripheral vascular diseases and hypertension
may decrease unwanted side effects.
As discussed in the “Post-operative Manage­
ment” section, application of petrolatum jelly, a
bland moisturizer or an antibiotic ointment will
make the phototoxic reaction more tolerable.
Furthermore, removal of MAL and ALA after
treatment is important in order to reduce the
continuous synthesis of porphyrin, which
increases post-treatment sensitivity to visible
light. Patients should thoroughly wash their face
with soap and water after light exposure. In a
small pilot study where MAL was applied for
3 h under occlusion, porphyrin fluorescence was
maximum at 1 h after cream removal but there
was enough porphyrin present in the skin at 24 h
after MAL application to induce a phototoxic
reaction following light exposure in 6 out of 16
subjects [42]. Patients must be warned to avoid
sun exposure for 2 days after PDT. The use of
a sunscreen containing a physical sunscreening
agent is recommended during the first 2  days.
Sun protection with a high SPF sunscreen and
good UVA protection is also important during
the weeks following PDT in order to prevent
hyperpigmentation.
Future Directions
• Treatment of Acne
• Hidradenitis Suppurativa
• Daylight PDT
• Personalized Medicine
• Sonodynamic PDT
PDT has been available for over a century and
will most likely continue to be used as a stand-­
alone treatment or in combination with other ther-
apies for various medical and cosmetic purposes.
It has been implicated with aminolevuninic acid
(ALA) and methylaminolevulinate (MAL) for
treating acne, possibly through the decrease of
sebaceous gland activity from light activation of
the photosensitizer [43]. While PDT is not the
standard of care for treating hidradenitis suppura-
tiva, it may be a beneficial adjuvant to treatments
such as rifampin and clindamycin [44]. Moreover,
although cancer was the main target for PDT
research from the 1970s to 2010, PDT is now also
being explored for its antimicrobial properties, for
there is currently a dangerously high rise of multi-
drug-resistance among pathogenic microbes [45].
Daylight PDT is also becoming increasingly pop-
ular, especially in European nations, for treating
actinic keratoses. Instead of performing therapy
16  Photodynamic Therapy

272
with a conventional light source, daylight PDT
harnesses daylight exposure to continuously acti-
vate protoporphyrin IX (PpIX) 30 min after MAL
application, when the protoporphyrin begins
forming in the skin. Daylight PDT facilitates
treatment to much larger areas of skin than con-
ventional PDT and also has the advantage of
inducing fewer adverse effects [46]. Additional
prospective uses for PDT and future directions
include photochemical internalization, theranos-
tics, genetically coded protein photosensitizers,
sonodynamic therapy using ultrasound, and two-­
photon absorption PDT [45]. Lastly, combination
therapy with PDT is on the horizon. In fact, a
study recently demonstrated that sequential appli-
cation of PDT and imiquimod provides a signifi-
cantly better clinical and histologic response in
the treatment of AK’s than PDT or imiquimod
alone [5].
Conclusion
To conclude, photodynamic therapy is a
unique modality currently widely used as field
therapy for the treatment of actinic keratosis,
in situ squamous cell carcinomas (Bowen’s
disease), and superficial basal cell carcino-
mas. For multiple AK’s, PDT treatment is
associated with less downtime than other full-
face or large surface treatments like 5-fluoro-
uracil or imiquimod alone. Further, PDT in
dermatology is being used to treat acne vul-
garis, combat microbial disease, and other
skin conditions. Daylight PDT is gaining pop-
ularity and so is the use of other vehicles,
delivery methods, and combination therapy.
Currently, PDT is still more widely used in
Europe most likely due poor reimbursement
rates for PDT in the US.  Strong studies are
needed to show the efficacy of PDT in order to
justify its use, and hopefully insurance com-
panies will follow suit.
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16  Photodynamic Therapy

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© Springer International Publishing AG, part of Springer Nature 2018
K. Nouri (ed.), Lasers in Dermatology and Medicine,
Intense Pulsed Light (IPL)
Sanjana Iyengar, Keyvan Nouri, Peter Bjerring,
Kåre Christiansen, Robert A. Weiss,
Girish S. Munavalli, Sonal Choudhary,
and Angel Leiva
Abstract
Intense Pulsed Light (IPL) is a light-emitting
system that is capable of emitting filtered
polychromatic broad bandwidth wavelengths
between 515 and 1200 nm.
The emission of wavelengths is con-
trolled by both an internal filter that blocks
undesired wavelengths from being emitted
and a “heat-­sink” effect that allows the con-
trolled transfer of thermal energy from an
object at high temperature to an object at
lower temperature.
Keywords
Intense pulsed light · Leg vein treatment ·
Telangiectasias · Hemangiomas ·
Poikiloderma of Civatte · Pigmentation ·
Photorejuvenation · Scarring · Hair removal ·
Acne · Seborrheic keratosis · Sarcoidosis ·
Hidradenitis suppurativa · Nail psoriasis
S. Iyengar
Department of Dermatology, Feinberg School
of Medicine, Northwestern University,
Chicago, IL, USA
K. Nouri
Dermatology, University of Miami, Miami, FL, USA
Ophthalmology, University of Miami,
Miami, FL, USA
Otolaryngology, University of Miami,
Miami, FL, USA
Dermatologic Surgery, University of Miami,
Miami, FL, USA
Department of Dermatology and Cutaneous Surgery,
University of Miami Medical Group,
University of Miami, Miami, FL, USA
Dermatology Services at Sylvester Comprehensive
Cancer Center, University of Miami Hospital
and Clinics, Miami, FL, USA
MOHS, Dermatologic and Laser Surgery,
University of Miami, Miami, FL, USA
Surgical Training, University of Miami,
Miami, FL, USA
17
P. Bjerring
Department of Dermatology, Swansea University,
Swansea, Wales, UK
K. Christiansen
Molholm Research, Molholm Hospital,
Vejle, Denmark
R. A. Weiss (*)
Department of Dermatology, Maryland Dermatology
Laser Skin and Vein Institute, University of Maryland
School of Medicine, Hunt Valley, MD, USA
e-mail: rweiss@mdlsv.com
G. S. Munavalli
Dermatology, Laser, and Vein Specialists of the
Carolinas, Charlotte, NC, USA
S. Choudhary · A. Leiva
Department of Dermatology and Cutaneous Surgery,
Miller School of Medicine, University of Miami,
Miami, FL, USA

276
Introduction
Intense pulsed light (IPL) treatments are based
on selective photothermolysis where a specific
target is selectively heated up by a light pulse and
heat damaged, without destroying the surround-
ing tissue components [1].
The IPL technology was clinically intro-
duced in 1994 and Photoderm™ (ESC/Sharplan,
Norwood, MA, now Lumenis, Santa Clara, CA)
received as the first FDA clearance for the treat-
ment of lower extremity telangiectasias in 1995
[2]. The IPL technology has evolved a great deal
since its introduction 20  years ago [3]. Today
there are more than a dozen companies produc-
ing IPL systems FDA-cleared for several differ-
ent dermatologic treatment procedures, including
vascular and pigment lesions, hair removal,
photo-rejuvenation, acne, and PDT treatments.
Recently, small and still relatively effective IPL
devices for at-home-use have entered the market,
allowing patients to treat themselves in the pri-
vacy of their homes [2].
On the high-end clinical IPL devices, the
emitted band of wavelengths, the pulse duration
(or train of pulses), and energy per pulse can be
set individually [3]. All IPL systems on the mar-
ket today are based on pulsed xenon-flash lamps
emitting non-coherent, polychromatic light with
wavelengths ranging from 400 to 1200  nm.
Different optical filters restrict the emitted band
of wavelengths reaching the skin surface to fit
with the absorption spectrum of a specific skin
chromophore and hence the treatment proce-
dure. This flexibility gives IPL system the
advantage of being able to perform several clini-
cal procedures using a single system compared
to lasers where a separate laser is often needed
for each treatment indication. Laser light is by
nature coherent, but due to the high scattering
coefficient in human skin, the laser light will be
in-coherent after few tens of μm penetration of
the skin. Therefore for practical purposes, there
is no clinical difference between selective pho-
tothermolysis treatments with coherent (lasers)
and incoherent light (IPLs).
Medical lasers intended for vascular treat-
ments deliver sub-millisecond light pulses with
high energy for the treatment of very thin vessels
in portwine stains and hemangiomas [2]. IPL sys-
tems have until now not been able to produce suf-
ficiently high energy levels at pulse durations
shorter than approximately 2.5 ms. However, in
2015 the first real sub-millisecond IPL system
was introduced (Nordlys, Ellipse A/S, Hoersholm,
Denmark), making IPL a genuine competitor to
pulse dye laser [4].
The IPL Device
In the IPL, the xenon flash lamp is located inside
a handheld applicator where a sapphire or quartz
crystal guides the light from the flashlamp to the
skin surface [3]. A water-filled gel is normally
used as an optical matching layer between the
crystal light guide and the skin surface. The light
guide may be actively cooled to lower the skin
temperature for patient comfort and to protect
the skin surface. As the xenon lamp produces
light with wavelengths ranging from the UV to
the infrared region, one or more filters are placed
in the light path to restrict the band of wave-
lengths reaching the skin. Commonly used low-­
wavelength cut-off filters are 515, 550, 560, 570,
590, 615, 645, 690, 755 nm. The longer infrared
wavelengths are blocked from reaching the skin
surface by the use of an infrared glass filter or by
passing the light through a water chamber which
acts an infrared light filter.
Wavelengths
The band of wavelengths has to be selected
according to the absorption of light in the tar-
S. Iyengar et al.

277
get chromophores. For blood containing tar-
gets, these chromophores may be reduced
hemoglobin, oxyhemoglobin, and methemo-
globin; for pigment and hair treatment, the
chromophore is eumelanin and pheomelanin
located inside the hair or in the epidermis [5].
If the optical target is located deeper in the der-
mis, longer wavelengths will be chosen as
these penetrate deeper with less absorption in
the upper skin layers.
Pulse Duration
The IPL pulse duration can be adjusted according
to the target type and size. The duration of the
light pulse is selected so that only minimal
amounts of heat is conducted to the surrounding
tissue. The optimal pulse duration can be calcu-
lated according to the theory of selective photo-
thermolysis and will approximately be equal to
the thermal relaxation time (TRT) for the target.
TRT is the time taken for the target to dissipate
about 63% of the incident thermal energy. A large
volume target will have a longer TRT and hence
requires longer IPL pulse durations to reach a
destructive target temperature than a target with a
smaller volume.
The TRT for a target with a diameter d can be
calculated by [1]:

TRT
d
where
m
=
×
=
×
-
2
7
2
16
1 3 10
/
.
.
k
k

However, according to the extended theory of
photothermolyisis, the IPL light pulse duration
for treatment of non-uniformly pigmented struc-
tures in biological tissues (thicker vessels and
hairs) can be calculated according to the “Thermal
Damage Time” (TDT), which is significantly
longer than the TRT. TDT is defined as the time
required for the entire target, including the pri-
mary chromophore and the surrounding target
(hair follicle, vessel wall etc.), to cool by about
63%. It includes cooling of the primary chromo-
phore (e.g. melanosomes) as well as the entire
target (e.g. a hair). In clinical practice, the TDT is
often the TRT multiplied with a factor 2–5.
Energy
The correct energy level is obtained when enough
heat is delivered to lethally damage the target by
reaching a tissue temperature of 70° for at least
1 ms.
Spot Size
The IPL light spot size, similar to the wave-
length band, is important for light penetration
depth. The smaller the spot size, the relatively
more lateral light scattering occurs and less
energy will reach the deeper skin layer. The lat-
eral scattering is relatively less in larger spot
sizes resulting in deeper penetration. Clinical
practice as well as computer simulations of
light penetration have shown that a spot size
greater than 10 mm does not add further to the
penetration depth [5].
Clinical Treatment Indications
• Leg Vein Treatment
• Telangiectasias
• Hemangiomas
• Poikiloderma of Civatte
• Pigmentation
• Photorejuvenation
• Scarring
• Hair Removal
• Acne
• Seborrheic Keratosis
• Sarcoidosis
• Hidradenitis Suppurativa
• Nail Psoriasis
17  Intense Pulsed Light (IPL)

278
Reticular Leg Veins with Associated
Telangiectasias
Leg telangiectasias are visible dermal arterioles,
capillaries, or veins with a diameter of 0.1–2 mm.
The primary chromophores for vascular lesions
are hemoglobin and its derivatives: oxyhemoglo-
bin, deoxyhemoglobin, and methemoglobin.
Oxyhemoglobin absorbs up to 630  nm, while
deoxyhemoglobin absorbs up to 750 nm. Multiple
closely spaced light pulses (train of single pulses)
convert oxygenated hemoglobin to deoxygenated
hemoglobin in the early part of the light pulse
making the procedure more effective. Hence,
blue telangiectasias, which are more deoxygen-
ated, are treated with light pulses between 530
and 750 nm. Shorter wavelength bands are more
effective in treating superficial, oxygenized red
vessels but not deeper blue veins. Longer wave-
lengths may also be used to treat larger diameter
blue venulectasia and smaller veins due to better
penetration of these wavelengths [6–8].
The IPL device can be adjusted to provide
optimal fluence, pulse, wavelength band, and
pulse duration based on the vessel characteristics.
Spot size can be altered to provide more or less
light penetration [5]. Longer pulse durations,
higher low wavelength cut-off filters, and cooling
mechanisms allow IPLs to minimize epidermal
injury while effectively treating the lower extrem-
ity telangiectasias.
Facial Telangiectasias
Facial telangiectasias can be classified as linear,
arborizing, spider, and punctiform. Sun exposure,
steroids, and hormone replacement may play a
role in the development. IPL can be used to
improve these telangiectasias. Until recently, the
pulsed dye laser (PDL) with 0.5 ms pulse dura-
tion was the preferred treatment, but often lead to
intracutaneous hematomas and purpura. IPL sys-
tems have less side effects and are the patients’
choice for telangiectasia treatment. A study by
Angermeier showed clearance rates of 75–100%
in treating over 100 patients with essential telan-
giectasias. Clearance rates of 90–95% was
achieved using IPL in another study by Schroeter
et al. in 45 patients with telangiectasias and spi-
der nevi [9–15].
Erythematotelangiectatic (ET) rosacea mani-
fests as facial telangiectasias, persistent ery-
thema, and flushing involving the central face.
PDL with wavelengths of 585 and 595 nm have
previously been widely used and are considered
effective [16, 17]. In a study published by
Schroeter et al., the effect of IPL on 60 patients
resulted in 77.8% clearance of facial telangiecta-
sias with the forehead showing the best clearance
of 87% [18]. Out of all the areas, the nose required
the highest number of treatment sessions for
lesions to disappear.
Compared to lasers, IPLs offer several advan-
tages. IPL emits non-coherent broad spectrum
light which allows deeper penetration into the
skin via wide wavelength bands that incorporate
longer wavelengths. The IPL also treats a larger
surface area in a single shot (>5 cm2) compared
to the small spot size of a PDL (80 mm2). In addi-
tion, through the use of multiple pulses, IPL
allows the skin to cool between the individual
pulses in the pulse train and thus minimize the
risk of epidermal damage.
Hemangiomas
Hemangiomas are proliferative tumors which
slowly regress overtime. Lesions persist in
35–50% of children with 15% of children having
residual discoloration [19]. Ulceration is a com-
plication of infantile hemangiomas. While sys-
temic beta-blocker therapy is now the mainstay
of hemangioma treatment, the IPL is often used
to treat residual hemangioma after the primary
involution.
Poikiloderma of Civatte
Poikiloderma of Civatte (POC) is a condition
resulting from photodamage and hence, is found
on sun exposed areas such as the neck, forehead,
and upper chest. Skin appears erythematous, pig-
mented and wrinkled in appearance. IPL can be
S. Iyengar et al.

279
used to treat POC as the 515  nm filter allows
absorption by both the melanin and hemoglobin.
Higher low wavelength cut-off filters up to
590 nm filters may be necessary initially in more
severe cases to reduce excessive light absorption
and hence side effects. Studies have shown that
IPL has a clearance of more than 75% of telangi-
ectasias and hyperpigmentation with only 5%
developing pigmentation side effects [20].
Pigmented Lesions
Pigmented lesions, such as solar lentigines, con-
genital nevi, postinflammatory hyperpigmenta-
tion, and café-au-lait macules, can be treated
with an IPL device. A study by Bjerring et  al.
examined the use of IPL device on 96 patients
with solar lentigines and melanocytic nevi [21].
The IPL device had a dual filter configuration
with a low wavelength cut-off filter, water filter,
and water chamber, which absorbed all infrared
light and produced the desired spectrum of light
when combined. Results from one session
revealed a 96% reduction in pigment, 74.2%
clearance for solar lentigines, and 66.3% decrease
in melanocytic nevi. Similarly, IPL has been
examined in treating melasma. A study by Li
et al. reported a 51–100% improvement in 77.5%
of patients after four IPL treatments at 3 week
intervals [22]. According to the authors, epider-
mal melasma seemed to respond better to the
treatment compared to the mixed type.
Photorejuvenation
IPL is commonly used to improve signs of photo-
aging. Structural components of the skin are
altered due to the accumulation of UV damage. In
addition, the loss of elasticity due to normal aging
can be seen on the skin. Photorejuvenation through
the use of the IPL device has been described as a
dynamic non-ablative process used to smooth the
skin surface, reduce visible vessels, and reduce
mottled pigmentation [23]. Thermal damage from
the IPL device induces the formation of type 1 and
3 collagen fibers and reorganizes elastic fibers to
improve the skin’s appearance [3]. Brief thermal
damage to capillaries in the skin may induce or
release growth factors leading to neocollagenesis.
Wavelength bands utilized range from 515 to
1000 nm with longer wavelengths stimulating col-
lagen synthesis and shorter wavelengths targeting
pigmentation and telangiectasias. In two studies
by Zelickson, IPL treatments appeared to be suc-
cessful in increasing skin collagen [24, 25]. One
study showed IPL had an 81% increase in collagen
type 1 transcripts compared to the 23% increase
seen with PDL treatment. Collagen I, III, elastin,
and collagenase increased in 85–100% of patients
and procollagen increased in 50–70% of patients.
A study conducted by Negishi et al. examined IPL
for pigmentation and telangiectasias [26]. A
550 nm filter for pigment and 570 nm cut-off filter
for telangiectasia were used on 97 Japanese
patients. Subjects were treated three to six times at
2–3  week intervals with IPL 28–32  J/cm2, 2.5–
4.0/4.0–5.0 ms, and 20–40 ms delay without topi-
cal anesthesia. Results showed 49% of patients
had greater than 75% improvement in pigmenta-
tion with 33% having greater than 75% improve-
ment in telangiectasia and 13% having greater
than 75% improvement in skin texture. Another
study by this group examined the effect of
Quantum IPL every 3–4  weeks on 73 Japanese
patients. Quantum IPL has a cooling system which
cools the epidermis to 40C compared to 65C with-
out cooling. In 80% of patients, a greater than 60%
improvement in pigmentation and erythema was
noted. Similarly, the use of IPL as a therapeutic
device for freckling has been examined. A study
by Huang et al. using 550–590 nm filters (25–35 J/
cm2, 4 ms single or double pulse, 20–40 ms delay
time) for one to three treatments at 4 week inter-
vals received 91.7% satisfaction [27].
Combination procedures, such as the use of
IPL with 1064 and 1320 nm Nd:YAG laser treat-
ments [28, 29], microdermabrasion [30], and the
use of botulinum toxin A [31], may enhance pho-
torejuvenation. Higher wavelengths from the
Nd:YAG laser can stimulate collagen formation
by significantly altering the dermis. IPL treat-
ment followed immediately by a tri-chloro-acetic
acid (TCA) peel is especially effective for the
treatment of pigment disturbances.
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280
Photodynamic Therapy (PDT)
PDT uses IPL as a light source which stimu-
lates severely photodamaged skin (as in pho-
torejuvenation) and destroys pre-malignant
cells in actinic keratosis and basal cell carci-
nomas via activation of a photosensizer [32].
Topical ­administration of 5-aminolevulinic acid
[5-ALA] or its methyl ester induces formation
of protoporphyrin IX which photosensitizes
the target area prior to IPL irradiation. The IPL
light leads to the production of activated oxy-
gen species within photodamaged cells, result-
ing in their destruction. The photosensitizer is
applied between 30 min and 3 h prior to IPL
irradiation. Indications for PDT include pho-
torejuvenation, precancer and nonmelanoma
skin cancer, such as actinic keratosis, superfi-
cial basal cell carcinoma, and Bowen’s disease.
Side effects include pain during irradiation,
erythema, edema, and crusting for up to a week,
and subsequent hyperpigmentation, especially
in darker skin types. Depending on the photo-
sensitizer used, treatment size, and lesion type,
side effects may be more or less severe. In gen-
eral, PDT is well tolerated and can be used to
treat multiple areas simultaneously.
Scars
There have been few studies examining the use of
IPL in the treatment of hypertrophic scarring. It
is hypothesized that IPL works by targeting mel-
anin and vascular pigments which promote col-
lagen overgrowth [33]. Bellew et  al. compared
the efficacy of long PDL pulses with IPL on
hypertrophic surgical scars [34]. Two treatments
were performed 2 months apart. It was concluded
both treatments were equally effective in terms of
appearance, but there was less risk of developing
purpura with IPL. Subjects reported IPL as more
painful than PDL. Another study by Erol et al.
reported a 92.5% improvement in the clinical
appearance of hypertrophic or keloid scars after
utilizing IPL in 109 patients [35]. There was a
reduction in the height, erythema, and hardness
of the scars.
Similarly, IPL has been used to treat striae dis-
tensae, a type of scar characterized by linear
bands of atrophic skin. In a study by Hernandez-­
Perez et al., there was a statistically significant
improvement using IPL to treat abdominal striae
in 15 patients [36]. While there is no classical
treatment for improving the appearance of stretch
marks, the authors suggest IPL could be a prom-
ising therapy.
Hair Removal
Studies have shown IPL has very good results in
removing unwanted hair. Gold et al. reported an
average of 60% hair removal after one treatment
session and 3  month follow-up in 31 patients
with hypertrichosis [37]. Sadick et  al. reported
76% hair removal using a filtered IPL system
after a mean of 3.7 treatments in 34 patients with
excess body hair [38]. From the study, 14 patients
followed up for more than 12 months and reported
83% hair removal in the end. Efficacy and hence
patients’ satisfaction of IPL hair removal varies
according to the hair type, hair color, skin color,
number of treatments, treatment settings, and
operator. Black hairs on fair skin have the best
hair removal clearance with IPL [5, 39]. However
with increasing Fitzpatrick skin type, more side
effects such as redness, crusting, and pigmenta-
tion changes may be seen [39–41]. Yellow discol-
oration of the terminal hairs and paradoxical hair
growth in adjacent areas to the treated sites have
been noted as side effects of the IPL treatment
[42]. Effective home-treatment IPL devices have
recently been developed for hair management,
and a major part of optical hair treatments may
soon be carried out with these devices.
Acne
The use of light therapy for the treatment of acne
is increasing due to its safety and relative efficacy
[43]. Acne is a chronic inflammatory disorder of
the pilosebaceous unit and is prevalent in more
than 85% of adolescents. Bacterial proliferation
of Propionibacterium and rupture of the come-
S. Iyengar et al.

281
done provide the inflammatory appearance of
acne. While traditional therapies include sys-
temic and topical antibiotics, keratolytics and
retinoids, the issue of antibiotic resistance and
adverse side effects may result in under treat-
ment, loss of patient compliance and undesired
results. It has been hypothesized that light
decreases the amount of Propionibacterium and
reduces the size of the pilosebaceous apparatus.
More specifically, light causes photo-excitation
of porphyrins present inside the bacteria, leading
to the release of free oxygen radicals which are
bactericidal to Propionibacterium.
Intense pulse light devices for acne treatment
release 400–1000  nm polychromatic high-­
intensity pulsed light that activates the porphyrin
destruction of Propionibacterium [43]. The light
also stimulates endogenous chromophores to
indirectly reduce sebaceous gland activity by
damaging blood vessels supplying the gland. It is
postulated that IPL may also exert an anti-­
inflammatory effect by downregulating tumor
necrosis factor alpha (TNF-α) and upregulating
transforming growth factor-beta1 (TGF-β).
Seborrheic Keratosis
Seborrheic keratosis is a benign skin lesion of the
epidermis which appears yellow-brown or dark-­
brown in color [44]. The use of IPL in ten patients
with multiple seborrheic keratosis was studied.
Results showed superficial and small seborrheic
keratosis responded well to IPL compared to
larger and thicker lesions. Dermoscopy con-
firmed the heat-induced change in lesion color
from brown to grey immediately after treatment.
IPL filters with short cut-off wavelengths (400–
900 nm) should be chosen in order to act prefer-
entially on the epidermis and only treat the
superficial lesion [3].
Sarcoidosis
Sarcoidosis is a multi-organ systemic disease of
unknown origin characterized by non-caseous
granulomas [44]. Skin involvement occurs in
25% of cases. Few studies have surfaced which
examine the effect of IPL on the cutaneous mani-
festation of sarcoidosis. A study by Hasegawa
et  al. treated a 60  year old female with facial
plaques using topical ALA with IPL and later
PDT [45]. Patients completed five sessions and at
6 months had no signs of recurrence. Similarly,
Rosende et  al. reports a case of a 54  year old
female with manifestations on the extremities
and nose [46]. IPL treatment on the nose with a
590 nm cutoff filter and double pulse (initial total
dose 37 J/cm2) was delivered with a 20 ms delay
between pulses. Sessions were conducted over 2
years with an increase in fluence at each visit.
Two year later, the patient was asymptomatic. It
is postulated that the mechanism of action could
be due to the destruction of abnormal blood ves-
sels, which are an important component of
inflammatory dermatoses by delivering pro-­
inflammatory cytokines to the skin [3].
Hidradenitis Suppurativa
Hidradenitis suppurativa is a chronic and suppu-
rative inflammation of apocrine glands, most
commonly found in the axilla, inguinal folds,
perineum, genitalia, and periareolar region [44].
Follicles are plugged by keratin leading to inflam-
mation, abscess, and fistula formation. Factors
such as obesity and hormone abnormalities have
been linked to this condition. Highton et  al.
examined IPL treatment in 18 patients with
hidradenitis suppurativa over 4 weeks with ses-
sions two times per week [47]. At the end of the
study, patients reported a high degree of patient
satisfaction. More studies are needed to further
examine the therapeutic efficacy of IPL in treat-
ing hidradenitis suppurativa.
Nail Psoriasis
Nails are a common manifestation found in up to
50% of patients with psoriasis [48]. Nails appear
with “oil drop” discoloration, splinter hemor-
rhages, and onycholysis. While pulsed dye laser
has been used to successfully treat nail psoriasis,
17  Intense Pulsed Light (IPL)

282
a study by Tawfik examined the effect of IPL as
an additional treatment option for this condition.
Twenty patients were treated with IPL every
2 weeks for a maximum of 6 months. At the end
of the study, the nail bed showed a 71.2%
improvement while the nail matrix improved
32.2%. The Nail Psoriasis Severity Index
(NAPSI) score also showed significant improve-
ment post-treatment. IPL serves as a potential
promising treatment for nail psoriasis. More
studies, however, need to be performed to fully
examine this relationship.
Conclusion
Intense Pulsed Light is a non-coherent source
of pulsed light with a bandwidth ranging
from 400 to 1200 nm. Indications for its use
include treatment of leg vein telangiectasias,
hair removal, scarring, pigmentary alterations,
photorejuvenation, and vascular lesions. The
advantages of IPL are its versatility, large
treatment areas and non-­ablative nature. As
the wavelength, spot size, and pulse duration
can be widely adjusted, IPL targets skin chro-
mophores specific to the condition. Some sys-
tems require addition of cooling mechanisms
to avoid epidermal damage while treating
deeper chromophores.
Several studies have demonstrated the effi-
cacy of IPL in treating various conditions.
Various trials have confirmed the efficacy of
the new generation IPLs compared to laser
systems; however, more randomized con-
trolled studies with longer follow-ups are
needed to fully compare the IPLs to each type
of laser and for each indication.
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© Springer International Publishing AG, part of Springer Nature 2018
K. Nouri (ed.), Lasers in Dermatology and Medicine,
Current Status of Light-Emitting
Diode Phototherapy
in Dermatological Practice
R. Glen Calderhead
Abstract
Phototherapy in its broadest sense means any
kind of treatment (from the Greek therapeia
‘curing, healing,’ from therapeuein ‘to cure,
treat.’) with any kind of light (from the Greek
phos, photos ‘light’). The modern accepted
definition of phototherapy, however, has
become accepted as: “the use of low incident
levels of light energy to achieve an athermal
and atraumatic, but clinically useful, effect in
tissue”. Under its basic original definition,
phototherapy is an ancient art because the old-
est light source in the world is the sun, and
therapy with sunlight, or heliotherapy, has
been in use for over 4000 years with the earli-
est recorded use being by the Ancient Egyptians
(Giese, Living with our Sun’s ultraviolet rays,
Springer, New York, 1976). They would treat
what was probably vitiligo by rubbing the
affected area with a crushed herb similar to
parsley, then expose the treated area to sun-
light. The photosensitizing properties of the
parsley caused an intense photoreaction in the
skin leading to a very nasty sunburn, which in
turn hopefully led to the appearance of postin-
flammatory secondary hyperpigmentation, or
‘suntan’ thereby repigmenting the depig-
mented area. In their turn the Ancient Greeks
and Romans used the healing power of the sun,
and it was still being actively used in Europe in
the eighteenth, nineteenth and early twentieth
century, particularly red light therapy carried
out with the patient placed in a room with red-
tinted windows. One famous patient was King
George III of Great Britain and Northern
Ireland who ruled from 1760 to 1801, popu-
larly though erroneously known as ‘Mad King
George’. We now strongly suspect that he was
actually suffering from the blood disease por-
phyria, so being shut in a room with red-draped
walls and red tinted windows to treat his
depression probably only served to make him
even more mad, since porphyria is often asso-
ciated with severe photosensitivity! Entities
treated this way included the eruptive skin
lesions of rubella and rubeola, and even ‘mel-
ancholia’, as was the case with King George
III, now recognised as clinical depression.
Hippocrates, the Father of Medicine, certainly
concurred with the latter application some two
millennia before King George: Hippocrates
prescribed sunlight for depressive patients and
believed that the Greeks were more naturally
cheerier than their northern neighbors because
of the greater exposure to the sun.
Keywords
LED-LLLT · Photobiomodulation · Collagenesis
· Elastinogenesis · Wound healing · Adenosine
triphosphate · Mitochondrion
R. G. Calderhead
Research Division, VP Medicoscientific Affairs,
Clinique L, Goyang-shi, Gyeonggi-Do, South Korea
e-mail: docrgc@cc9.ne.jp
18

286
Introduction
History of Phototherapy
Phototherapy in its broadest sense means any
kind of treatment (from the Greek therapeia ‘cur-
ing, healing,’ from therapeuein ‘to cure, treat.’)
with any kind of light (from the Greek phos, pho-
tos ‘light’). The modern accepted definition of
phototherapy, however, has become accepted as:
“the use of low incident levels of light energy to
achieve an athermal and atraumatic, but clinically
useful, effect in tissue”. Under its basic original
definition, phototherapy is an ancient art because
the oldest light source in the world is the sun, and
therapy with sunlight, or heliotherapy, has been
in use for over 4000  years with the earliest
recorded use being by the Ancient Egyptians [1].
They would treat what was probably vitiligo by
rubbing the affected area with a crushed herb
similar to parsley, then expose the treated area to
sunlight. The photosensitizing properties of the
parsley caused an intense photoreaction in the
skin leading to a very nasty sunburn, which in
turn hopefully led to the appearance of postin-
flammatory secondary hyperpigmentation, or
‘suntan’ thereby repigmenting the depigmented
area. In their turn the Ancient Greeks and Romans
used the healing power of the sun, and it was still
being actively used in Europe in the eighteenth,
nineteenth and early twentieth century, particu-
larly red light therapy carried out with the patient
placed in a room with red-tinted windows. One
famous patient was King George III of Great
Britain and Northern Ireland who ruled from
1760 to 1801, popularly though erroneously
known as ‘Mad King George’. We now strongly
suspect that he was actually suffering from the
blood disease porphyria [2], so being shut in a
room with red-draped walls and red tinted win-
dows to treat his depression probably only served
to make him even more mad, since porphyria is
often associated with severe photosensitivity!
Entities treated this way included the eruptive
skin lesions of rubella and rubeola, and even
‘melancholia’, as was the case with King George
III, now recognised as clinical depression.
Hippocrates, the Father of Medicine, certainly
concurred with the latter application some two
millennia before King George: Hippocrates pre-
scribed sunlight for depressive patients and
believed that the Greeks were more naturally
cheerier than their northern neighbors because of
the greater exposure to the sun.
In the field of wavelength-specific photother-
apy research, red light therapy was examined at a
cellular level under the newly-invented micro-
scope by Fubini and colleagues in the late eigh-
teenth century [3], who were able to show that
visible red light, provided via lenses and filters
from sunlight, selectively activated the respira-
tory component of cellular mitochondria. There
is nothing new under the sun. However, the sun is
a fickle medical tool, particularly in northern
Europe, and modern phototherapy as we know it
started around the turn of the last century with
Finsen’s electric arc lamp-based system, giving
phototherapy at the turn of a switch, independent
of the sun [4]. However, apart from the use of
blue light therapy for neonatal bilirubinemia
which continues to the present day, phototherapy
was, in the majority of its applications, overtaken
in the first part of the twentieth century by better
medication or improved treatment techniques.
The development of the first laser systems, a
race which was narrowly won by Theodore
Maiman in 1960 with his flashlamp-pumped
ruby-based laser, next gave clinicians and
researchers a completely different and unique
light source to play with. In the 4 years between
1960 and 1964, the ruby laser was followed by
Box 18.1
• Phototherapy is not new! It was being
used more than 4000 years ago
• Light-emitting diodes (LEDs) have
attracted great interest as a photo-
therapeutic source
• An LED is not a laser, so although
LED energy is noncoherent it is
quasimonochromatic
• LEDs are solid state and robust
• LEDs are comparatively inexpensive
R. G. Calderhead

287
the argon, helium-neon (HeNe), neodymium:
yttrium-aluminum-garnet (Nd:YAG), solid state
semiconductor laser (diode laser) and carbon
dioxide (CO2) lasers all of which have remained
as workhorses in the medical field, and the HeNe
laser (632.8 nm) has in fact provided a large bulk
of the phototherapy literature over the last three
decades. As for light-emitting diodes (LEDs), the
first light from a semiconductor was produced in
1907 by the British experimenter H.  J. Round.
Independently in the mid 1920s, noncoherent
infrared light was produced from a semiconduc-
tor (diode) by O-V Losev in Russia. These stud-
ies were published in Russia, Germany and the
UK, but their work was completely ignored in the
USA [5]. It was not till 1962 that the first practi-
cal and commercially-available visible-spectrum
(633 nm, red) LED was developed in the USA by
Holonyak, regarded as the ‘Father of the LED’
while working with the General Electric
Company. In the next few years, LEDs delivering
other visible wavelengths were produced, with
powers ten times or more that of Holonyak’s
original LED.  For reasons which will be dis-
cussed later, these LEDs were really inappropri-
ate as therapeutic sources, although they were
extremely bright and very cheap compared with
laser diodes, and it was not till the late 1990s that
a new generation of extremely powerful, qua-
simonochromatic LEDs was developed by
Whelan and colleagues as a spin-off from the
National Aeronautic and Space Administration
(NASA) Space Medicine Program [6]. Unlike
their cheap and cheerful predecessors, the so-­
called ‘NASA LEDs’ finally offered clinicians
and researchers a new and truly practical thera-
peutic tool [7].
The What and Why of LEDs
What Is an LED?
Light-emitting diodes belong to the solid state
device family known as semiconductors. These
are devices which fall somewhere between an
electrical conductor and an insulator, although
when no electrical current is applied to a semi-
conductor, it has almost the same properties as an
insulator. Simply explained, light-emitting semi-
conductors or diodes consist of negative (N-type)
and positive (P-type) materials, which are ‘doped’
with specific impurities to produce the desired
wavelength. The n-area contains electrons in
their ground or resting state, and the p-area con-
tains positively charged ‘holes’, both of which
remain more or less stationary (Fig.  18.1a–c).
When a direct current electric potential with the
correct polarity is applied to an LED, the elec-
trons in the N-area are boosted to a higher energy
state, and they and the holes in the P-area start to
move towards each other (Fig. 18.1d), meeting at
the N/P junction where the negatively-charged
electrons are attracted into the positively-charged
holes. The electrons then return to their resting
energy state and, in doing so, emit their stored
energy in the form of a photon, a particle of light
energy (Fig. 18.1e). The wavelength emitted is
noncoherent, ideally very narrow-band, and
depends on both the materials from which the
LED is constructed, the substrates, and the p-n
junction gap. Table 18.1 shows a list of the main
substrates and associated colors. LEDs fall into
two shapes: there is the older dome-type LED,
and the more recent, and currently more often
used, “on board chip” (OBC) which is much
more compact and less expensive than the older
dome type. They are also more efficient.
Figure 18.2 shows the anatomy of both types of
LED. The dome types can be mounted on printed
circuit boards (PCBs) at regular and precise dis-
tances from each other to provide an LED array,
whereas the OBC type is already part of the PCB,
in other words, LED system manufacturers can
purchase preloaded PCBs in whatever configura-
tion and size are available. Figure 18.3 shows an
example of both types from an actual array.
The surface of the PCB is very often coated to
reflect the wavelength of the LEDs mounted on
it. Some of the light energy emitted from the
LED array will be reflected back off the stratum
corneum, or horny layer, of the skin, and a por-
tion of the incident light which enters the skin
will be scattered backwards out of the skin. The
reflective coating on the PCB captures these pho-
tons, the energy of which would otherwise be lost
into the air or could be absorbed by the PCB and
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288
Direction of motion
Direction of motion
Electrode
Direction of motion
Electrons
(– charge)
Direction of motion
a
b
d
c
e
P-type material
Holes
(+ charge)
N-type material
DEPLETION
ZONE
Direction of motion
Direction of motion
Electrons reach
higher energy level
DC power
source
Current flows through
this N/P junction
+
–
Electrode
Electron is attracted to
positively-charged hole:
drops back to normal
energy level:
releases stored energy
as a photon (light energy)
Fig. 18.1  What is an LED and how can it produce light?
(a) An LED is basically composed of two materials, the
N-type or negative material and the P-type or positive
material. The N-material contains negatively charged
electrons which move as shown, and the P-material con-
tains positively charged holes, which move in the opposite
direction. When the materials are apart and not connected
to any power source, movement continues, so both materi-
als are conductors. (b) When the materials are sandwiched
together, however, without any power applied to the elec-
trodes attached to opposite ends, the negatively charged
electrons in the center of the chip are attracted to the
holes, and form an area called the depletion layer as seen
in (c) and all movement ceases in both the N- and
P-materials: the chip is now an insulator. (d) Power is
applied to the electrodes, with the positive electrode or
anode at the origin of movement of the holes and the nega-
tive electrode or cathode at the origin of movement of the
electrons. Observing the polarity when connecting a
direct current (DC) power source is extremely important.
Power flows through the junction between the materials,
called the N/P junction, and movement of both electrons
and holes starts again, but with power applied the elec-
trons move to a higher energy level from their ground or
resting state. (e) As in b above, the N-electrons are
attracted to the P-holes, but in moving down through the
N/P junction they must return to their ground energy level,
and lose their extra stored energy in the form of a photon,
the smallest packet of light energy. Unlike the situation in
b, however, when power is applied this action continues
endlessly and no depletion layer is formed. The N- and
P-materials are ‘doped’ with other materials which deter-
mine the distance of the ‘fall’ between electrons and
holes: the greater the distance the electrons have to fall,
the higher is the energy level of the photons emitted.
Photons with high energy levels have shorter wavelengths
than those with lower energy levels, thus the wavelengths
of the emitted light are determined by the substrate mate-
rials and their doping. High quality N- and P-materials
and pure doping substances will give photons of very
nearly the same wavelength, i.e., quasimonochromatic
light
R. G. Calderhead

289
produce unwanted heat, and recycles them back
into the skin. This can significantly increase the
efficiency of an LED panel. The bodies of the lat-
est generation of LEDs are designed to recycle
the photons the LEDs emit, thereby adding even
more efficiency. As LED phototherapy uses low
incident levels of power, even a small loss of that
incident power could negatively affect the desired
clinical result: higher efficiency of the LED
panel, i.e. more light out for less electrical energy
in, is therefore the ideal.
What Is the Difference Between LEDs
and Lasers or IPLs?
The laser is a unique form of light energy, pos-
sessing the three qualities of monochromaticity,
collimation and phase which make up the overall
property of ‘coherence’. Monochromaticity
means all the photons are of exactly the same
wavelength or color; collimation means the built-
­in parallel quality of the beam superimposed by
the conditions of the laser resonator or by
collimating optics; and phase means that all of the
photons march along together exactly equidistant
from each other in time and in space. Laser diodes
do not have inherent collimation, but because they
are still true lasers, and therefore a so-called point
source, the light can be gathered and optically col-
limated: the humble but ubiquitous laser pointer
works on this principle. Intense pulsed light is, on
the other hand, totally noncoherent, with a very
large range of polychromatic (multiwavelength)
light from near infrared all the way down to blue;
Table 18.1  Most common substrate combinations and
the colors they are capable of producing
Substrates
Formula
Colors produced
Aluminum
gallium
arsenide
(AlGaAs)
Red, infrared
Aluminum
gallium
phosphide
(AlGaP)
Green
Aluminum
gallium
indium
phosphide
(AlGaInP)
Green, yellow, orange,
orange-red (all
high-intensity)
Gallium
arsenide
phosphide
(GaAsP)
Yellow, orange,
orange-red, red
Gallium
phosphide
(GaP)
Green, yellow, red
Gallium
nitride
(GaN)
Blue, green, pure green
(emerald green): also
white (if it has an AlGaN
Quantum Barrier,
so-called ‘white light’
LED)
Indium
gallium
nitride
(InGaN)
Near ultraviolet, blue,
bluish-green
Fig. 18.2  Anatomy of the older high-quality dome-type
LED and the newer on board chip (OBC) type (inset box).
In the case of the dome type, the cathode is always shorter
than the anode and there is a flat surface in the base of the
LED by the cathode so polarity is clearly determined
when connecting to a DC power source or mounting on a
printed circuit board (PCB). On top of the cathode post
and forming part of the negative electrode of the LED chip
is a parabolic reflector in which the chip itself is mounted
thus ensuring as much light as possible is directed for-
wards, with a consistent angle of divergence, typically 60°
steradian or less depending on the specifications of the
LED. A fine wire connects the positive electrode of the
chip to the anode post, thus completing the circuit. The
entire assembly is encapsulated in an optical quality clear
plastic envelope, giving the final assembly its robust
nature. In the OBC type, the chip comes premounted to
the PCB, but shares more or less the same anatomy as the
dome-type LED, with the chip mounted above the para-
bolic reflector. The OBC tye LEDs are much more com-
pact than the dome type
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice

290
has no possibility of collimation with extreme
divergence; and has its vast variety of photons
totally out of phase. The new generation of LEDs,
on the other hand, has an output plus or minus a
few nanometers of the rated wavelength, and so
these LEDs are classed as quasimonochromatic;
some form of optical collimation can be imposed
on the photons which are divergent but do have
some directionality; however they are not in phase
and so can never be focused to a small point.
Laser energy can easily produce high photon
intensity per unit area, IPLs much less so, but pro-
vided LEDs are correctly arrayed, they are capa-
ble of almost laser-like incident intensities.
Figure  18.4 schematically illustrates the differ-
ences between lasers, IPLs and LEDs. In short,
LEDs for therapeutic applications must be qua-
simonochromatic, be capable of targeting wave-
length-specific cells or materials, have stable
output, and be able to deliver clinically useful
photon intensities.
Why Use LEDs?
There are many excellent laser and intense
pulsed light (IPL) systems available to the der-
matologist. Why should LEDs be considered as
a viable alternative phototherapy source? If the
author had been asked this question before the
end of the 1990s, he would have been enjoying a
quiet chuckle. Up until Prof Harry Whelan and
his NASA colleagues in the Space Medicine
Laboratory developed the “NASA LED” in
1998, LEDs were cheap, bright and cheerful, but
not really suitable for clinical applications
because in addition to being highly divergent,
they had a waveband, rather than a wavelength
and therefore had extremely poor chromophore
selectivity. As discussed above, the NASA LED
offered quasichromaticity, i.e., the vast majority
of the photons were at the same wavelength, and
output powers some 5 orders of magnitude
higher than the previous generation of LEDs.
This made LEDs for the first time a suitable pho-
totherapeutic light source (see Figs.  18.2 and
18.4 above). In addition to their output powers
and narrow-band output, the other reasons for
using LEDs in clinical practice are efficiency
and price.
The electricity-light conversion ratio of a
typical laser is very low, requiring hundreds or
even thousands of watts in to give an output of
a few watts. The same applies to IPL systems,
where the flashlamp has to be pumped with
enormous amounts of energy to provide poly-
chromatic light, which may however be filtered
(cut-on or cut-off). Even when filtered, IPL
energy is ­delivered over a waveband rather
Fig. 18.3  Close-up view of LEDs mounted on PCBs
from actual therapeutic systems, dome type in the upper
part of the figure and OBC type in the lower part. In both
types, Note the precise x-y spacing of the LEDs, and the
reflective backing into which they are mounted. The pur-
pose of the reflective backing of the array is to capture
these photons and reflect them back into the skin, known
as ‘photon recycling’
R. G. Calderhead

291
than at a specific wavelength (cf. IPL output
with laser or LED output in Fig. 18.4). In the
case of LEDs, which are quasimonochromatic
and therefore require no filtering, the conver-
sion efficiency is very high so that very few
watts of electrical current at a low voltage are
required to produce a clinically useful output.
LEDs are much less expensive than even laser
diodes. Depending on quality and wavelength,
anywhere from 200 new-generation LEDs can
be purchased for the cost of a single laser
diode.
The cost of laser and IPL systems is very high,
so a much cheaper LED-based system offers the
a & b
d
c
laser (e.g., HeNe)
laser diode
IPL
LED
Relative intensity
Relative intensity
10
10
5
0
400
700
1000
5
0
400
700
1000
Wavelength (nm)
Relative intensity
10
5
0
400
700
1000
Wavelength (nm)
Wavelength (nm)
a
b
c
d
Fig. 18.4  Comparison among the output characteristics
of a laser, laser diode, intense pulsed light system and a
new generation LED. (a) A laser emits all of its energy at
one precise wavelength, in a coherent beam, i.e., mono-
chromatic, collimated and with the photons all in phase
both temporally and spatially. If a ‘special magnifying
glass’ could view the beam, it would show the situation as
seen in the figure. All of the energy is delivered at a pre-
cise wavelength, as illustrated in the spectrogram, so the
relative intensity of the beam is extremely high. (b) A
laser diode has all the characteristics of a laser, except that
the beam is divergent, without collimation. However,
because it is a point source the beam can be collimated
with condensing optics. The magnified view of the beam
shows a lower photon intensity than the laser, but the rela-
tive intensity is still very high. (c) An IPL system emits a
pulse of broad-band polychromatic noncoherent light, so
the ‘magnifying glass’ would show a plethora of widely
divergent photons of many different wavelengths, but with
the majority in the near infrared as seen from the spectro-
gram. Because of the very broad waveband, the relative
intensity at any given wavelength is low to very low. (d)
The LED is somewhat similar to the laser diode, but the
light is noncoherent, highly divergent and quasimono-
chromatic. The ‘magnifying glass’ shows plenty of pho-
tons, mostly the same color (wavelength), with some
degree of directionality but without any of the phase and
potential collimation associated with the laser diode. The
relative intensity is still very high, however, because the
vast majority of the photons are being delivered at the
nominal wavelength with a very narrow waveband of plus
or minus a very few nanometers
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice