Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice

Current Status of Light-Emitting
Diode Phototherapy 18
in Dermatological Practice
R. Glen Calderhead
Abstract and Romans used the healing power of the sun,

Phototherapy in its broadest sense means any and it was still being actively used in Europe in
kind of treatment (from the Greek therapeia the eighteenth, nineteenth and early twentieth
‘curing, healing,’ from therapeuein ‘to cure, century, particularly red light therapy carried
treat.’) with any kind of light (from the Greek out with the patient placed in a room with red-
phos, photos ‘light’). The modern accepted tinted windows. One famous patient was King
definition of phototherapy, however, has George III of Great Britain and Northern
become accepted as: “the use of low incident Ireland who ruled from 1760 to 1801, popu-
levels of light energy to achieve an athermal larly though erroneously known as ‘Mad King
and atraumatic, but clinically useful, effect in George’. We now strongly suspect that he was
tissue”. Under its basic original definition, actually suffering from the blood disease por-
phototherapy is an ancient art because the old- phyria, so being shut in a room with red-draped
est light source in the world is the sun, and walls and red tinted windows to treat his
therapy with sunlight, or heliotherapy, has depression probably only served to make him
been in use for over 4000 years with the earli- even more mad, since porphyria is often asso-
est recorded use being by the Ancient Egyptians ciated with severe photosensitivity! Entities
(Giese, Living with our Sun’s ultraviolet rays, treated this way included the eruptive skin
Springer, New York, 1976). They would treat lesions of rubella and rubeola, and even ‘mel-
what was probably vitiligo by rubbing the ancholia’, as was the case with King George III,
affected area with a crushed herb similar to now recognised as clinical depression.
parsley, then expose the treated area to sun- Hippocrates, the Father of Medicine, certainly
light. The photosensitizing properties of the concurred with the latter application some two
parsley caused an intense photoreaction in the millennia before King George: Hippocrates
skin leading to a very nasty sunburn, which in prescribed sunlight for depressive patients and
turn hopefully led to the appearance of postin- believed that the Greeks were more naturally
flammatory secondary hyperpigmentation, or cheerier than their northern neighbors because
‘suntan’ thereby repigmenting the depig- of the greater exposure to the sun.
mented area. In their turn the Ancient Greeks
Keywords
R. G. Calderhead LED-LLLT · Photobiomodulation · Collagenesis
Research Division, VP Medicoscientific Affairs, · Elastinogenesis · Wound healing · Adenosine
Clinique L, Goyang-shi, Gyeonggi-Do, South Korea triphosphate · Mitochondrion
e-mail: docrgc@cc9.ne.jp
© Springer International Publishing AG, part of Springer Nature 2018 285

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_18
18 Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice
286 R. G. Calderhead
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famous patient was King George III of Great

Box 18.1 Britain and Northern Ireland who ruled from
• Phototherapy is not new! It was being 1760 to 1801, popularly though erroneously
used more than 4000 years ago known as ‘Mad King George’. We now strongly
• Light-emitting diodes (LEDs) have suspect that he was actually suffering from the
attracted great interest as a photo- blood disease porphyria [2], so being shut in a
therapeutic source room with red-draped walls and red tinted win-
• An LED is not a laser, so although dows to treat his depression probably only served
LED energy is noncoherent it is to make him even more mad, since porphyria is
quasimonochromatic often associated with severe photosensitivity!
• LEDs are solid state and robust Entities treated this way included the eruptive skin
• LEDs are comparatively inexpensive 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
Introduction concurred with the latter application some two
millennia before King George: Hippocrates pre-
History of Phototherapy scribed sunlight for depressive patients and
believed that the Greeks were more naturally
Phototherapy in its broadest sense means any kind cheerier than their northern neighbors because of
of treatment (from the Greek therapeia ‘curing, the greater exposure to the sun.
healing,’ from therapeuein ‘to cure, treat.’) with In the field of wavelength-specific photother-
any kind of light (from the Greek phos, photos apy research, red light therapy was examined at a
‘light’). The modern accepted definition of cellular level under the newly-invented micro-
phototherapy, however, has become accepted as: scope by Fubini and colleagues in the late eigh-
“the use of low incident levels of light energy to teenth century [3], who were able to show that
achieve an athermal and atraumatic, but clinically visible red light, provided via lenses and filters
useful, effect in tissue”. Under its basic original from sunlight, selectively activated the respira-
definition, phototherapy is an ancient art because tory component of cellular mitochondria. There
the oldest light source in the world is the sun, and is nothing new under the sun. However, the sun is
therapy with sunlight, or heliotherapy, has been a fickle medical tool, particularly in northern
in use for over 4000 years with the earliest Europe, and modern phototherapy as we know it
recorded use being by the Ancient Egyptians [1]. started around the turn of the last century with
They would treat what was probably vitiligo by Finsen’s electric arc lamp-based system, giving
rubbing the affected area with a crushed herb phototherapy at the turn of a switch, independent
similar to parsley, then expose the treated area to of the sun [4]. However, apart from the use of blue
sunlight. The photosensitizing properties of the light therapy for neonatal bilirubinemia which
parsley caused an intense photoreaction in the continues to the present day, phototherapy was, in
skin leading to a very nasty sunburn, which in turn the majority of its applications, overtaken in the
hopefully led to the appearance of postin- first part of the twentieth century by better
flammatory secondary hyperpigmentation, or medication or improved treatment techniques.
‘suntan’ thereby repigmenting the depigmented The development of the first laser systems, a
area. In their turn the Ancient Greeks and Romans race which was narrowly won by Theodore
used the healing power of the sun, and it was still Maiman in 1960 with his flashlamp-pumped
being actively used in Europe in the eighteenth, ruby-based laser, next gave clinicians and
nineteenth and early twentieth century, particu- researchers a completely different and unique
larly red light therapy carried out with the patient light source to play with. In the 4 years between
placed in a room with red-tinted windows. One 1960 and 1964, the ruby laser was followed by
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the argon, helium-neon (HeNe), neodymium: insulator. Simply explained, light-emitting semi-
yttrium-aluminum-garnet (Nd:YAG), solid state conductors or diodes consist of negative (N-type)
semiconductor laser (diode laser) and carbon and positive (P-type) materials, which are ‘doped’
dioxide (CO2) lasers all of which have remained with specific impurities to produce the desired
as workhorses in the medical field, and the HeNe wavelength. The n-area contains electrons in
laser (632.8 nm) has in fact provided a large bulk their ground or resting state, and the p-area con-
of the phototherapy literature over the last three tains positively charged ‘holes’, both of which
decades. As for light-emitting diodes (LEDs), the remain more or less stationary (Fig. 18.1a–c).
first light from a semiconductor was produced in When a direct current electric potential with the
1907 by the British experimenter H. J. Round. correct polarity is applied to an LED, the elec-
Independently in the mid 1920s, noncoherent trons in the N-area are boosted to a higher energy
infrared light was produced from a semiconduc- state, and they and the holes in the P-area start to
tor (diode) by O-V Losev in Russia. These stud- move towards each other (Fig. 18.1d), meeting at
ies were published in Russia, Germany and the the N/P junction where the negatively-charged
UK, but their work was completely ignored in the electrons are attracted into the positively-charged
USA [5]. It was not till 1962 that the first practi- holes. The electrons then return to their resting
cal and commercially-available visible-spectrum energy state and, in doing so, emit their stored
(633 nm, red) LED was developed in the USA by energy in the form of a photon, a particle of light
Holonyak, regarded as the ‘Father of the LED’ energy (Fig. 18.1e). The wavelength emitted is
while working with the General Electric noncoherent, ideally very narrow-band, and
Company. In the next few years, LEDs delivering depends on both the materials from which the
other visible wavelengths were produced, with LED is constructed, the substrates, and the p-n
powers ten times or more that of Holonyak’s junction gap. Table 18.1 shows a list of the main
original LED. For reasons which will be dis- substrates and associated colors. LEDs fall into
cussed later, these LEDs were really inappropri- two shapes: there is the older dome-type LED,
ate as therapeutic sources, although they were and the more recent, and currently more often
extremely bright and very cheap compared with used, “on board chip” (OBC) which is much more
laser diodes, and it was not till the late 1990s that compact and less expensive than the older dome
a new generation of extremely powerful, qua- type. They are also more efficient. Figure
simonochromatic LEDs was developed by 18.2 shows the anatomy of both types of LED.
Whelan and colleagues as a spin-off from the The dome types can be mounted on printed circuit
National Aeronautic and Space Administration boards (PCBs) at regular and precise dis- tances
(NASA) Space Medicine Program [6]. Unlike from each other to provide an LED array, whereas
their cheap and cheerful predecessors, the so- the OBC type is already part of the PCB, in other
called ‘NASA LEDs’ finally offered clinicians words, LED system manufacturers can purchase
and researchers a new and truly practical thera- preloaded PCBs in whatever configura- tion and
peutic tool [7]. 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
The What and Why of LEDs reflect the wavelength of the LEDs mounted on
it. Some of the light energy emitted from the LED
What Is an LED? array will be reflected back off the stratum
Light-emitting diodes belong to the solid state corneum, or horny layer, of the skin, and a por-
device family known as semiconductors. These tion of the incident light which enters the skin will
are devices which fall somewhere between an be scattered backwards out of the skin. The
electrical conductor and an insulator, although reflective coating on the PCB captures these pho-
when no electrical current is applied to a semi- tons, the energy of which would otherwise be lost
conductor, it has almost the same properties as an into the air or could be absorbed by the PCB and
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a b
Direction of motion Direction of motion
Electrons
(– charge)
N-type material
Holes Direction of motion
(+ charge)
Direction of motion d Current flows through

this N/P junction
P-type material Direction of motion
c DEPLETION
ZONE
Electrons reach
higher energy level
Direction of motion
e – +
DC power
source
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? called the N/P junction, and movement of both electrons
(a) An LED is basically composed of two materials, the and holes starts again, but with power applied the elec-
N-type or negative material and the P-type or positive trons move to a higher energy level from their ground or
material. The N-material contains negatively charged resting state. (e) As in b above, the N-electrons are
electrons which move as shown, and the P-material con- attracted to the P-holes, but in moving down through the
tains positively charged holes, which move in the opposite N/P junction they must return to their ground energy level,
direction. When the materials are apart and not connected and lose their extra stored energy in the form of a photon,
to any power source, movement continues, so both materi- the smallest packet of light energy. Unlike the situation in
als are conductors. (b) When the materials are sandwiched b, however, when power is applied this action continues
together, however, without any power applied to the elec- endlessly and no depletion layer is formed. The N- and
trodes attached to opposite ends, the negatively charged P-materials are ‘doped’ with other materials which deter-
electrons in the center of the chip are attracted to the holes, mine the distance of the ‘fall’ between electrons and holes:
and form an area called the depletion layer as seen in (c) the greater the distance the electrons have to fall, the higher
and all movement ceases in both the N- and P- is the energy level of the photons emitted. Photons with
materials: the chip is now an insulator. (d) Power is applied high energy levels have shorter wavelengths than those
to the electrodes, with the positive electrode or anode at the with lower energy levels, thus the wavelengths of the
origin of movement of the holes and the negative electrode emitted light are determined by the substrate materials
or cathode at the origin of movement of the electrons. and their doping. High quality N- and P-materials and pure
Observing the polarity when connecting a direct current doping substances will give photons of very nearly the
(DC) power source is extremely important. Power flows same wavelength, i.e., quasimonochromatic light
through the junction between the materials,
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Table 18.1 Most common substrate combinations and

the colors they are capable of producing
Substrates Formula Colors produced
Aluminum (AlGaAs) Red, infrared
gallium
arsenide
Aluminum (AlGaP) Green
gallium
phosphide
Aluminum (AlGaInP) Green, yellow, orange,
gallium orange-red (all
indium high-intensity)
phosphide
Gallium (GaAsP) Yellow, orange,
arsenide orange-red, red
phosphide
Gallium (GaP) Green, yellow, red
phosphide
Gallium (GaN) Blue, green, pure green
nitride (emerald green): also
white (if it has an AlGaN Fig. 18.2 Anatomy of the older high-quality dome-type
Quantum Barrier, LED and the newer on board chip (OBC) type (inset box).
so-called ‘white light’ In the case of the dome type, the cathode is always shorter
LED) than the anode and there is a flat surface in the base of the
Indium (InGaN) Near ultraviolet, blue, LED by the cathode so polarity is clearly determined when
gallium bluish-green connecting to a DC power source or mounting on a printed
nitride 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,
produce unwanted heat, and recycles them back with a consistent angle of divergence, typically 60°
into the skin. This can significantly increase the steradian or less depending on the specifications of the
efficiency of an LED panel. The bodies of the lat- LED. A fine wire connects the positive electrode of the
est generation of LEDs are designed to recycle the chip to the anode post, thus completing the circuit. The
entire assembly is encapsulated in an optical quality clear
photons the LEDs emit, thereby adding even more plastic envelope, giving the final assembly its robust
efficiency. As LED phototherapy uses low nature. In the OBC type, the chip comes premounted to the
incident levels of power, even a small loss of that PCB, but shares more or less the same anatomy as the
incident power could negatively affect the desired dome-type LED, with the chip mounted above the para-
bolic reflector. The OBC tye LEDs are much more com-
clinical result: higher efficiency of the LED pact than the dome type
panel, i.e. more light out for less electrical energy
in, is therefore the ideal.
collimating optics; and phase means that all of the
What Is the Difference Between LEDs photons march along together exactly equidistant
and Lasers or IPLs? from each other in time and in space. Laser diodes
The laser is a unique form of light energy, pos- do not have inherent collimation, but because they
sessing the three qualities of monochromaticity, are still true lasers, and therefore a so-called point
collimation and phase which make up the overall source, the light can be gathered and optically col-
property of ‘coherence’. Monochromaticity limated: the humble but ubiquitous laser pointer
means all the photons are of exactly the same works on this principle. Intense pulsed light is, on
wavelength or color; collimation means the built- the other hand, totally noncoherent, with a very
in parallel quality of the beam superimposed by large range of polychromatic (multiwavelength)
the conditions of the laser resonator or by light from near infrared all the way down to blue;
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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 provided
LEDs are correctly arrayed, they are capable of
almost laser-like incident intensities. Figure
18.4 schematically illustrates the differences
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
Fig. 18.3 Close-up view of LEDs mounted on PCBs than the previous generation of LEDs. This made
from actual therapeutic systems, dome type in the upper
LEDs for the first time a suitable pho-
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 totherapeutic light source (see Figs. 18.2 and
reflective backing into which they are mounted. The pur- 18.4 above). In addition to their output powers
pose of the reflective backing of the array is to capture and narrow-band output, the other reasons for
these photons and reflect them back into the skin, known
using LEDs in clinical practice are efficiency
as ‘photon recycling’
and price.
has no possibility of collimation with extreme The electricity-light conversion ratio of a
divergence; and has its vast variety of photons typical laser is very low, requiring hundreds or
totally out of phase. The new generation of LEDs, even thousands of watts in to give an output of
on the other hand, has an output plus or minus a a few watts. The same applies to IPL systems,
few nanometers of the rated wavelength, and so where the flashlamp has to be pumped with
these LEDs are classed as quasimonochromatic; enormous amounts of energy to provide poly-
some form of optical collimation can be imposed chromatic light, which may however be filtered
on the photons which are divergent but do have (cut-on or cut-off). Even when filtered, IPL
some directionality; however they are not in phase energy is delivered over a waveband rather
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a laser (e.g., HeNe)
b laser diode
10 a&b
Relative intensity
5
c IPL 0
10 c 400 700 1000
Relative intensity
Wavelength (nm)
0
400 700 1000
Wavelength (nm) 10
d
Relative intensity
d LED
0
400 700 1000
Wavelength (nm)
Fig. 18.4 Comparison among the output characteristics pulse of broad-band polychromatic noncoherent light, so
of a laser, laser diode, intense pulsed light system and a the ‘magnifying glass’ would show a plethora of widely
new generation LED. (a) A laser emits all of its energy at divergent photons of many different wavelengths, but with
one precise wavelength, in a coherent beam, i.e., mono- the majority in the near infrared as seen from the spectro-
chromatic, collimated and with the photons all in phase gram. Because of the very broad waveband, the relative
both temporally and spatially. If a ‘special magnifying intensity at any given wavelength is low to very low. (d)
glass’ could view the beam, it would show the situation as The LED is somewhat similar to the laser diode, but the
seen in the figure. All of the energy is delivered at a pre- light is noncoherent, highly divergent and quasimono-
cise wavelength, as illustrated in the spectrogram, so the chromatic. The ‘magnifying glass’ shows plenty of pho-
relative intensity of the beam is extremely high. (b) A tons, mostly the same color (wavelength), with some
laser diode has all the characteristics of a laser, except that degree of directionality but without any of the phase and
the beam is divergent, without collimation. However, potential collimation associated with the laser diode. The
because it is a point source the beam can be collimated relative intensity is still very high, however, because the
with condensing optics. The magnified view of the beam vast majority of the photons are being delivered at the
shows a lower photon intensity than the laser, but the rela- nominal wavelength with a very narrow waveband of plus
tive intensity is still very high. (c) An IPL system emits a or minus a very few nanometers
than at a specific wavelength (cf. IPL output LEDs are much less expensive than even laser
with laser or LED output in Fig. 18.4). In the diodes. Depending on quality and wavelength,
case of LEDs, which are quasimonochromatic anywhere from 200 new-generation LEDs can
and therefore require no filtering, the conver- be purchased for the cost of a single laser
sion efficiency is very high so that very few diode.
watts of electrical current at a low voltage are The cost of laser and IPL systems is very high,
required to produce a clinically useful output. so a much cheaper LED-based system offers the
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possibility to halt the ever-upward spiralling ‘set-it-and-forget-it’ microprocessor-controlled

costs of health care for both the clinicians and technology, the clinician or their assistant simply
their patients. A further advantage is the solid sets the head up over the area to be treated fol-
state nature of LEDs. There are no filaments to be lowing the manufacturer’s recommendations,
heated up, and no flashlamps are required to pro- turns the system on, and he or she can then leave
duce light or to pump the laser medium: LEDs the patient for the requisite treatment time and
thus run much cooler than their extremely higher- attend to other patients or tasks. Moreover, in
powered cousins, so less is required in the way of most cases a suitably trained nurse or therapist can
dedicated cooling systems, again helping to carry out the treatment once the clinician has
reduce the cost. However, some cooling of LEDs prescribed it, because LED systems are much
is still required, especially when LEDs of the new more inherently safe for the patient than lasers or
OBC type are mounted in multiple arrays, IPLs. Figure 18.5 shows an example of one of the
because the driver circuits of the new type of LED new generation of well-designed, robust but ele-
generate heat, rather than the LEDs themselves, gant, mobile and very versatile LED photother-
and the temperature of the PCBs increases: this is apy systems.
transferred to the OBC LEDs by conduction,
and as the temperature of an LED increases,
its output will move away from the rated
wavelength. When wavelength cell- or target-
specificity is required, this could be a major
problem.
The solid state nature of LEDs also makes
them much more robust than either lasers or IPL
systems, so they tend to be able to take the some-
times not-so-gentle handling which is part of a
busy clinical practice without causing either out-
put power loss or alignment problems. LEDs can
be mounted in flat panel arrays, which may in
turn be joined together in a treatment head that
can be adjustable to fit the contour of the large
area of tissue being treated, whether it is the face,
an arm, the chest or back, or a leg. Compare this
potentially very large treatment area of some
hundreds of square centimeters with that of a
laser, usually a very few millimeters in diameter,
or that of an IPL treatment head, typically
1 cm × 3 cm, and the clinician-intensive nature of
the latter two is quickly evident when large areas
are to be treated such as the entire face. Multiple
shots are required, and the handpiece has to be
manually applied and controlled by the user. The Fig. 18.5 Example of a state-of-the-art FDA-cleared new
LED-based treatment head can be attached to an generation LED phototherapy system which offers a vari-
ety of wavelengths (830, 633 and 415 nm, alone or in dual-
articulated arm to make individual adjustment
wavelength combinations) with a flexible put-and- stay
even easier. hinged treatment array to match any body contour from
Finally, if multiple wavelength-specific targets flat (back or décolleté) to extremely curved (arm or leg),
are to be treated, LED arrays with different wave- and friction hinges in the arm allowing easy exten- sion
and positioning of the treatment head without the need for
lengths can be designed to be easily interchange-
locking nuts. (HEALITE II, Lutronic Corporation, Goyang,
able, controlled by the same base unit. With South Korea, and Freemont, CA, USA)
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Basics of Light-Tissue Interaction wound healing or pain relief. If the incident power
is too high, heat will be the end product as with
the surgical laser. If a too-low photon intensity
Box 18.2 is delivered, there will be very little or no reaction.
• Light-emitting diodes deliver ather- The trick in LED phototherapy is to deliver just
mal and atraumatic cellular the right amount of photon intensity to achieve the
photoactivation desired clinical effect but in an athermal and
• “All light is absorbed in the first mil- atraumatic manner.
limeter of tissue”—FALSE!
• LEDs are a viable and valuable pho-
totherapeutic tool Photothermal and Athermal
• LEDs are capable of interesting light- Reactions
tissue interactions, provided certain
criteria are met. The most important Despite their very different output powers, lasers,
criteria are: IPLs and LEDs all depend on the ‘L’ which is
– Wavelength. found in all their names, standing for ‘light’. It
Determines both the target and the could be said that they are all different facets of
depth at which the target can be the same coin, but even in photosurgery, photo-
reached therapy plays a very important role. If we con-
Quasimonochromaticity is essential sider the typical beam pattern of a surgical CO2
Wavelengths should be applied sepa- laser in tissue, we see the range of temperature-
rately and not combined at the dependent bioeffects as illustrated schematically
same time in Fig. 18.6, ranging from carbonization above
– Irradiance (power density). 200 °C, vaporization above 100 °C, through coag-
Gives suitably high intensity at all ulation around 60–85 °C, all the way down to
levels of target cells or materials photobiomodulation, which occurs atraumatically
Ensures sufficient athermal energy when there is no appreciable rise in the tissue tem-
transfer to raise targets’ action perature at the very perimeter of the treated area.
potentials These effects occur virtually simultaneously as the
– Dosimetry. light energy propagates into the target tissue with
Provided the wavelength and power photon intensity decreasing with depth, and can be
density are appropriate, correct divided as shown into varying degrees of
dosage obtains the optimum effect photosurgical destruction and reversible photo-
with the shortest irradiation time damage, and athermal, atraumatic photobiomodu-
– Temporal beam profile. lation. The photothermal and athermal zones are
Continuous wave would appear to be also shown in a typical CO2 laser specimen stained
more efficient for most cell types with hematoxylin and eosin (Fig. 18.6).
in vivo, compared with ‘pulsed’ Photophysics tells us that each photon is a
(frequency modulated) light weightless packet of pure energy, with the energy
• Usually, cells should be targeted with measurable in electron volts (eV). Photobiology
only one LED wavelength at a time tells us that the photobiomodulation zone com-
• “Watts a joule”—the parameters prises cells which have absorbed the incident
must be appropriate photons, directly or indirectly transferred the
photon energy to the cells’ own energy stores in
an athermal and atraumatic manner, and have
The main purpose of using phototherapy is to become photoactivated. Photoactivated cells are
achieve some kind of clinical effect in the target associated with three reactions, one, two or all
tissue through the use of light energy, such as three of which may occur in photoactivated cells:
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Phototherapy Carbonization & Burn-off

(>200°C)
TARGET TISSUE
Vaporization (>100°C)
Laser surgery
Coagulation (>60°C)
Protein Degradation (>55°C)

Protein Denaturation (>40°C)
ATHERMAL CELLULAR
PHOTOBIOACTIVATION
Fig. 18.6 Range of photothermal and athermal photobio- shows normal tissue architecture, even though some pho-
reactions in tissue following a typical surgical laser impact, tons will have reached this layer and transferred their
e.g., a CO2 laser. A hematoxylin and eosin stained energy to the cells in an athermal and atraumatic manner.
specimen of actual CO2 laser treated skin is also included Laser surgery involves all levels of bioreactions.
to show the typical histopathological changes for each of Photothermal nonablative skin rejuvenation (NSR) deliv-
the bioreactions: the epidermis has been totally vaporized ers controlled coagulative photothermal damage, with all
leaving a layer of carbon char above the coagulated der- the subsequent layers, whereas phototherapy only delivers
mis. The outermost layer, the photobioactivation layer, athermal and atraumatic photobioactivation
• if the cells are damaged or compromised, they nevi: all that was available then to him was a 1 ms
will repair themselves, or be repaired pulsed ruby laser and a C/W argon laser. In
• if the cells have a function, they will perform Fig. 18.7a can be seen a case of hemangioma
it more efficiently simplex (port wine stain) that had been somewhat
• if more of the cells are required for either of the unsuccessfully treated previously with needle
above, the cells will proliferate, or more will electrolysis: the abnormal color was not removed,
be recruited into the area through and the site of each needle application was
photochemotaxis marked with a small raised white scar. The argon
laser was used in Ohshiro’s zebra technique,
Laser surgery usually creates all the whereby linear areas 2 mm wide were treated
photothermally-mediated zones mentioned, but leaving a 2 mm area of untreated tissue between
the importance of the photoactivation zone them [8]. As can be seen in Fig. 18.7b, not only
cannot be stressed enough. It is the existence of did the argon laser treatment remove the port wine
this zone which sets laser surgery apart from any stain color, it also treated the abnormal con-
other thermally-dependent treatment, such as figuration in the form of the pinpoint scarring left
electrosurgery, or even athermal incision with the by the previous electrolysis treatment. Four to
conventional scalpel, and it is the photoactivated 6 weeks later, when the treated areas had com-
cells in this zone which provided the results that pletely healed, the untreated areas were then irra-
interested the early adopters of the surgical laser diated to complete the treatment. This was the
compared with the cold scalpel or electrosurgery, power of the “L” component of laser, the light,
namely equally good healing but with less inflam- aided by the photobioactivation zone, referred to
mation and much less postoperative pain. by Ohshiro as “simultaneous LLLT” [8].
Figure 18.7 demonstrates this in action, courtesy IPL systems, and the so-called nonablative
of Toshio Ohshiro MD PhD, a pioneer of laser lasers, produce areas of deliberate but controlled
surgery in Japan and worldwide. In the late coagulative damage beneath a cooled and intact
1970s, Ohshiro started using lasers in the treat- epidermis (Fig. 18.8), however they also produce
ment of vascular and melanin group anomaly the zone of simultaneous LLLT to help achieve
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a b
Fig. 18.7 Illustration of how the “L” in laser, “light”, lesion was treated with Ohshiro’s zebra method (large
made it different from other surgical systems. (a) This open arrow shows the treated linear area). Normal skin
example of a hemangioma simplex lesion (port-wine stain) color can be seen. In areas where hypertrophy existed,
had been treated previously with needle electrolysis. The these too have been treated successfully with heat plus
abnormal color of the lesion has not been removed, and light. The area between the black arrows shows an
small white hypertrophic scars can be seen where the untreated zone where the hypertrophic spots are clearly
needle was inserted. Heat only (electrothermal damage) seen. (Courtesy of Prof Toshio Ohshiro MD PhD—Ref.
was not successful in treating this lesion. (b) The [8], used with permission)
the desired effect of neocollagenesis and neoelas-

or photophysical reaction. However, any such
tinogenesis through the wound healing process in reaction is not an automatic consequence of
the dermal extracellular matrix (ECM). LED- energy absorption. It may be converted swiftly
based phototherapy systems, on the other hand, into heat, as in the surgical and non-ablative lasers
athermally and atraumatically induce only cellu- or IPL systems, or re-emitted at a different
lar photobioactivation, but are still capable of ini-
wavelength (fluorescence). The prime arbitrator
tiating the wound healing process almost as of this ‘no absorption-no reaction’ precept is not
efficiently as IPLs and nonablative lasers, as will
the output power of the incident light, but the
be shown in detail in a later section. wavelength of the photons making up the beam,
and this comprises two important considerations:
wavelength specificity of the target, or the target
Wavelength and Its Importance chromophore; and the depth of the target. Based
on these two considerations, the wavelength must
The first law of photobiology, the Grotthuss- not only be appropriate for the chosen chromo-
Draper Law, states that only energy which is phore, but it must also penetrate deeply enough to
absorbed in a target can produce a photochemical reach enough of the target chromophores with a
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Fig. 18.9 Photospectrogram of a human hand in vivo. The

generator, delivering uniform ‘white light’ at the waveband
shown on the x-axis, was placed above the hand and the sen-
sor below the hand. Optical density on the y-axis is shown in
logarithmic units. Penetration is shown on the right-hand
axis. The further down the curve reaches, the better the pen-
etration at that wavelength into living human tissue.
(Adapted from Smith KC: The Science of Photobiology.
1977. Plenum Press, New York, USA—Ref. [9])
millimeter of tissue’. Anyone who has shone a

Fig. 18.8 Theory behind photothermal nonablative skin
rejuvenation: the laser energy passes through the cooled
red laser pointer through their finger, transillumi-
epidermis without harming it, and delivers a controlled area nating the entire fingertip and completely visible
of coagulation in the typically elastotic dermis associated on the other side, has already disproved that
with photoaged skin. However, the photons do not stop statement. A totally different finding is seen with
there, and there are zones of protein denaturation and, most
importantly for the good result, athermal and atraumatic
green or yellow laser pointers, however, because
photoactivation around and beyond the controlled thermal of their poor scattering and penetration character-
damage. The photoactivated cells in the last of these three istics. Figure 18.9 is based on a transmission pho-
zones will assist with the wound healing process tospectrogram of a human hand captured in vivo
over the waveband from 500 nm (visible blue/
high enough photon density to induce the desired green) to 1100 nm in the near infrared [9]. The
reaction. In theory, a single photon can activate a photospectrometer generator was positioned
cell, but in actual practice multiple photon above the hand, delivering a ‘flat spectrum’ of
absorption is required to achieve the desired ‘white light’, and the recorder placed beneath it.
degree of reaction. The wavelength is shown along the x-axis, and the
Phototherapy is athermal and atraumatic, calculated optical density (OD) is on the y-
hence achieving selective photothermolysis is of axis, from lower ODs to higher. The higher the
no concern as it would be for surgical or other OD, the greater is the absorption of incident light,
photothermal applications. The penetration of and hence the lower the transmission, or penetra-
light into living tissue is, however, extremely tion depth into the tissue. It must also be remem-
important in phototherapy, and very frequently bered that the OD is not an arithmetic but a
displays characteristics which are often in dis- logarithmic progression, so that the difference
cord with results produced by mathematical between an OD of 3 and one of 8 is not simply 5,
models, a point frequently totally ignored by but 5 orders of magnitude, i.e. a factor of 10,000.
some researchers. A favorite, but photobiologi- From 500 to 595 nm (blue-green to yellow),
cally false, axiom beloved of phototherapy oppo- the OD was from 8.2 to approximately 7.6,
nents, is that ‘all light is absorbed within the first respectively, resulting in poor penetration. At
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633 nm, the approximate wavelength of the HeNe around 610 nm visible orange-red and 860 nm
laser, the photobiological efficacy of which is near-infrared [12]. LED systems delivering
well recorded, the OD was approximately 4.5. In 633 nm or thereabout in the visible red and
other words, red light at 633 nm penetrated living 830 nm in the near infrared, and at high enough
human tissue by 3 orders of magnitude better than photon densities were therefore developed, and
yellow at 595 nm, because of the pigment- have been reported as having significant effects
specific absorption characteristics of the 2 on their target tissues at a good range of depths
wavelengths. Visible yellow at 595 nm is at the well into the mid and deep reticular dermis, and
peak of the oxyhaemoglobin absorption curve, even into the muscle and bone. The usefulness of
and is also much more highly absorbed in epider- visible red and near IR LED phototherapy has
mal melanin than 633 nm, which is why the yel- already been reported in a wide range of medical
low light in the spectrogram did not transmit at all specialties, including dermatology. Yellow light
well into the tissue due to the competing chro- at 590–595 nm has also attracted attention, but the
mophores of epidermal melanin and superficial penetration properties of yellow light must be
dermal blood. Accordingly, cellular and other tar- carefully considered, as illustrated in vivo in
gets in the mid to deep reticular dermis are inac- Fig. 18.9. From the standpoint of photobiological
cessible to yellow light with sufficient photon theory, yellow light has very good potential spec-
intensities to achieve multiple photon absorption ificity in a number of subcellular targets such as
in the target cells. On the other hand, epidermal cytochrome-c oxidase, and superficial vascular-
cellular targets such as the mother keratinocytes related targets, however its very poor penetration
in the stratum basale, or basal layer, are definitely into the intermediate and deeper dermis, where
accessible to 595 nm yellow light. cellular targets such as fibroblasts lie, limits the
The deepest penetration in this experiment was practical efficacy of yellow light for these deeper
achieved at 820–840 nm in the near infrared. At targets. On the other hand, there are interesting
this waveband, pigment is not a primary chro- targets in and around the basal layer of the epi-
mophore with the cell membrane, and flavonoids dermis which do react well to visible yellow light,
in it, as the major chromophore, and this 820– such as the mother keratinocytes, melano- cytes
830 nm waveband coincides with the bottom of and the epidermal Merkel cells, all of which are
the water absorption curve. The most successful rich in mitochondria and therefore contain
of the laser diode systems used in laser therapy as cytochrome-c oxidase, a major chromophore for
distinct to laser surgery, delivered a wavelength of visible yellow light, and the source of intra- and
830 nm for this very reason [10], and was shown intercellular adenosine triphosphate (ATP) and
to penetrate living hands, and even bone, very enhanced levels of cell-cell signaling compounds
successfully [11]. After around 1000 nm, water such as Ca2+ ions.
absorption once again starts to play a significant Blue light at around 415 nm has very interest-
role, and in the curve in Fig. 18.9 the OD was seen ing properties regarding the eradication of the
to increase thereafter. In general, shorter visible bacterium Propionibacterium acnes (P. acnes)
wavelengths penetrate less than longer visible and through endogenous photodynamic therapy
near IR wavelengths, up to a given waveband, (PDT) although the photoreaction is different
depending on the absorbing chromophore. from photoactivation and will be discussed later
Following these findings, it made a great deal in the chapter. LED energy at 1072 nm has pro-
of sense to source LEDs for LED-based photo- vided a convenient and easy-to-use LED irradia-
therapy systems at wavelengths already tried, tor for effective treatment of herpes simplex
tested and proven in the more than three decades labialis in the home [13]. LED systems with many
of laser therapy application and research. other wavelengths have been produced, gaily
Furthermore, Karu has clearly shown that there is flashing or not, but basically these other
a “tissue window” for phototherapy between wavelengths have very little or no published work
to back up the claims of the manufacturers, and a
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careful consideration of the wavelength/penetra- primary photoaction i.e., photochemical or pho-

tion ratio will rule out many of the shorter visible tophysical. Wavelength is thus probably the sin-
light wavelengths. “Any old LED will not do” is gle most important consideration in LED
an axiom which must be borne in mind by the phototherapy, because without absorption, there
dermatologist wishing to incorporate LED photo- can be no reaction.
therapy into his or her practice.
Finally, the different wavebands, visible light
and invisible infrared light, have different pri- Irradiance (Photon Intensity)
mary mechanisms even though the therapeutic
endpoint may be similar. Absorption of visible Light energy travels in the form of photons. It is
light photons at appropriate levels induces a pho- obvious that the more photons which are incident
tochemical reaction, and a primary photochemi- per unit area of tissue, the greater will be the
cal cascade occurs within the cell induced mainly bioeffect as the energy is transferred to the target
by cytochrome-c oxidase, the end enzyme of cells and the tissues. This incident photon inten-
respiratory chain of the mitochondria which, as sity is called the power density, or irradiance, of a
mentioned above, are the adenosine triphosphate beam of light. The power density (PD) is an
(ATP)-producing power-houses of the cell [14]. extremely important factor in laser surgery and
ATP is not just required to fuel cells, but the medicine, but taking second place to wavelength,
energy of the entire organism is based on ade- and is calculated using the following formula:
quate levels of ATP. Infrared photons, unlike vis-
OP
ible light, are primarily involved in photophysical PD =
TA
(
W / cm2 )
reactions which occur mostly in the cellular
membrane, changing the rotational and vibra- where OP is the output power incident on the tar-
tional characteristics of the membrane molecules. get in watts (W) and TA is the irradiated target
Through subsequent activation of the various area in square centimeters (cm2). PD is usually
membrane-located transport mechanisms, such expressed in watts per square centimeter (W/cm2)
as Na+/K+-ATPase (better known as the Na+/K+ or milliwatts (mW)/cm2. It is the power density of
pump) and Ca+-ATPase (Ca+ pump) the cell per- a beam that will determine more than anything
meability is altered allowing in- and excellulation else (apart from wavelength) the magnitude of
of compounds. The chemical and osmotic bal- the bioeffect in the target tissue. Consider Table
ance in the cytosol are swiftly altered in turn 18.2, where a laser with a constant incident output
increasing the energy requirements of the cell power of 2 W targets tissue with a range of spot
and energy in the form of ATP is demanded from sizes from 100 μm to 1 cm. Simply changing the
the mitochondria. This finally results in the spot size, and thus the power density, can have
induction of a secondary chemical ATP- dramatically different effects on the target tissue.
producing cascade which gives more or less the Because the power density is worked out per unit
same endpoint as the visible light photons, area, calculated by the formula πr2, where π is the
namely cellular activation or proliferation [15]. constant pi, 3.142, and r is the radius (half the
These photoreactions are illustrated schemati- diameter) of the irradiated area, we have to
cally in Fig. 18.10. remember that there is an inverse square ratio
To sum up, the wavelength of a therapeutic between spot size and power density for a
source therefore has a double importance, namely constant output power. Doubling the spot size will
to ensure absorption of the incident photons by not cut the power density by one-half, but by one
the target chromophores, and to be able to do so quarter: increasing the spot size by a factor of 10
at the depths at which these chromophores exist. will cut the power density by one- hundredth, and
The waveband in which the wavelength of the vice-versa.
incident photons is located determines not only In LED phototherapy, it is therefore necessary
which part of the cell is the target, but also the to achieve a high enough incident photon intensity
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BASIC REACTION
SIGNAL TRANSDUCTION
PHOTORECEPTION AND AMPLIFICATION PHOTORESPONSE
a b
Visible red light Invisible near infrared light
Cell
membrane
1
3 Cytoplasm
5
2 2
1 4
4 6
3
5 7
Mitochondrion Nucleus
Same end result
Cell proliferation enhanced Cell function upregulated

Repair of injured/compromised cell
Fig. 18.10 Schematic depicting photoreception (absorp- ions and H+ dramatically increase. (4) This in turn upregu-
tion) of light in a cell, and the subsequent wavelength- lates intracellular signaling including mRNA production
specific response. The basic reaction as defined by Karu is from ribosomes on the rough endoplasmic reticulum, and
absorption, which is followed by signal transduction and finally (5) nuclear activity is also up regulated. (b) In the
amplification within the cytosol, and leads to the photore- case of near infrared light, the primary mechanism of
sponse involving the nucleus and membrane transport absorption is completely different (1) resulting in a photo-
mechanisms. (a) (1) Visible red light induces a primary physical reaction which changes the energy levels of the
photochemical cascade initiated in the mitochondrion, the cell membrane, in which near IR energy is absorbed. This
energy factory and cell power house, which results in kick-starts the Na2+K2+ and Ca2+K2+ pumps so that cyto-
increased levels of nicotinamide adenine dinucleotide plasmic levels of Ca2+ and H+ dramatically increase (2)
(NAD) extremely important in a wide range of redox and (4), prompting the mitochondrion to manufacture
(reduction-oxidation) reactions, one of the results of which more ATP to fuel the increased energy requirement (3),
is the generation of adenosine triphosphate (ATP) which is thereby raising cytoplasmic levels of ATP (4) which again
the ‘gasoline’ for the cell. (2) The increased levels of impacts on the transport mechanisms of the membrane not
cytoplasmic ATP fuel the membrane transport pumps, the affected by the near IR light. Despite the totally different
Na2+K2+ and Ca2+K2+ pumps (3) which induce extra- and pathways, the end result is however the same as in the case
intracellulation of messenger Ca2+ ions and pro- tons (H+) of visible light, namely further cyclic increased energy
which are elementary particles carrying a positive levels in the cytoplasm (6) and upregulation of nuclear
electric charge, the flow of which is used to generate activity (6)
energy from ATP via ATPase. Cytoplasmic levels of Ca2+
to achieve the desired degree of multiple absorp- This was adapted by Ohshiro and Calderhead in
tion in the target cells, but not so high as to cause 1988 into the Arndt-Schultz curve to explain the
any degree of photothermally-mediated changes efficacy of LLLT (Fig. 18.11) [10, 16] from which
in the tissue architecture, in other words ideal LED it is clear that photon intensity should not be too
phototherapy should achieve athermal and weak (no reaction) or too strong (retardation or
atraumatic photoactivation of the target cells. The cell death) but must be adjusted to achieve maxi-
Arndt-Schultz law, first appearing in the mid- mum optimum photobiomodulation of the target
nineteenth century, states that weak stimuli excite cells or materials.
biologic behavior, stronger ones favor it, powerful A final note on intensity: one single LED,
ones arrest it and very powerful ones retard it. even one of the new generation of LEDs, when
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Table 18.2 Illustration of the importance of altering the ever, as in the examples shown in Fig. 18.3, and
power density to achieve a complete range of bioeffects precisely positioned according to the angle of
from incision to photobiomodulation with a constant inci-
dent output power
divergence of the beam, the interaction where
the beams impact with each other gives an
Incident Spot size Power
power (∅, units density extremely intense photon density due to the phe-
(W) as given) (W/cm2) Bioeffect nomenon of photon interference. When this is
2 100 μm 25,000 Incision; excision combined with the excellent physical forward-,
2 200 μm 6250 Vaporization; deep lateral- and backward scattering characteristics of
coagulation red and near IR light, the result is that the highest
2 1 mm 250 Mild coagulation; photon intensity is beneath the surface of the skin,
protein denaturation
exactly where it should be to achieve the optimum
2 1 cm 2.5 Athermal, atraumatic
photobiomodulation therapeutic effect (Fig. 18.12b). If the distance
between the LEDs is too great, however, then the
intensity will drop off dramatically because of the
lack of interaction between the individual LED
beams (Fig. 18.12c). Furthermore, some LED
system manufacturers combine LEDs of
different wavelengths, e.g., red and yellow, and
then claim they are delivering ‘orange’ light
(Fig. 18.12d) … incorrect! The skin cells will
not ‘see’ orange from a mix- ture of red and
yellow light as our eyes do, but will react
separately to the incident red photons and yellow
photons. Karu has pointed out that there are many
pairs of wavelengths which actually inhibit
cellular activity when used together, yet enhance
activity when applied separately [12]. Light
energy represents information for cells, and then
they act on that information. Imagine a cell
receives receiving conflicting information from
Fig. 18.11 Ohshiro and Calderhead’s Arndt-Schultz
two different wavelengths: one tells the cell to
curve (1988) [10], based on the Arnd-Schultz law. From
stimulus strength A to B, no reaction occurs: the stimulus “turn right” and the other to “turn left”. At best
is too weak. From B to C there is a sharp rise in bioeffect, the cell will be confused and do nothing. At
plateauing at C–D. This curve is based mostly on incident worst, it will shut down partially or completely.
power density (photon intensity), but the ideal combina-
Unless there is a specific reason based on
tion of intensity and dose in phototherapy must therefore
be attained to reach the effect shown by the dark green photobiological knowledge, one wavelength at
shaded area, preferably as much as possible at the C–D a time should be the order of the day in LED
effect plateau. From point D onwards there is a sharp drop phototherapy.
in the effect, although it is still higher than normal until
As noted above, LEDs emit energy in a diver-
point E. Strength B–E corresponds to the zone of athermal
photobioactivation in Fig. 18.5 above. At stimulus strength gent manner thereby causing an exponential
E–F the bioeffect is gradually retarded, corresponding to drop in the available photon intensity the further
the protein denaturation/degradation zones in Fig. 18.5, the target is from the LED array. It is possible
and target death results from strength F–G corresponding
using optics to maximize the output of an LED
to the coagulation and vaporization zones in Fig. 18.5
array, and one manufacturer of an FDA-cleared
used on its own, will not achieve anywhere near LED system has overcome this by adding what
a clinically useful photon intensity in the target they term Optical Lens Array Technology, or
tissue (Fig. 18.12a). When multiple LEDs are OLAT™. An optically clear sheet embodying
mounted close together in a planar array, how- precisely-placed mini-collimating lenses is fixed
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a b c d
Fig. 18.12 Arrays of precisely spaced multiple LEDs are nomenon of photon interference. When this is coupled
required to achieve clinically useful photon densities in with the very strong forward and backward scattering
tissue. This illustration is modeled on the actual LED array characteristics of red light, which is even stronger for near
seen in Fig. 18.3 above, and is to scale. The distance from IR energy, a zone of extremely high photon density, greater
LEDs to the tissue is approximately 2.5 cm. (a) A single even than the intensity at the LEDs themselves, is created
LED has insufficient photon intensity to achieve any under the surface of the target tissue. (c) If LEDs are
recordable clinical effect. (b) On the other hand, when spaced too far apart, the photon intensity is sacrificed and
LEDs with similar output characteristics are mounted a is not clinically useful. (d) This is the case in treatment
precise distance apart to make use of the 60° divergence, heads with individual LEDs of different wavelengths,
the beams will interact where they cross each other to pro- e.g., red and yellow, claimed as delivering “orange” light
duce an extremely high photon intensity due to the phe- … but not so!
a b c
Fig. 18.13 One example of how a manufacturer has era: note the loss of energy delivered to the target through
enhanced the beam intensity without increasing the output lateral scattering. (c) The same LED array at the same
power of the LEDs. (a) An optically clear sheet incorpo- LED irradiance but fitted with the optical lens array which
rating precisely placed semi-collimating lenses (optical can be seen on top of the LED array. A much higher pho-
lens array technology, OLAT™) is placed under the same ton intensity is concentrated and delivered to the target
schematic LED array as seen in Fig. 18.12b above. The with significantly less energy lost to lateral scatter.
divergence of each LED is decreased, thereby increasing (Photography courtesy of Medicoscientific Affairs,
the photon intensity within each beam. (b) A near-IR Lutronic Corporation, Goyang, South Korea: LED array
array (830 nm, 100 mW/cm2) is captured with an IR cam- from HEALITE II 830 nm LED phototherapy system)
in front of the LED arrays, each lens being in nomenon, but the photon intensity is now 30%
front of an LED in the array. The output from higher at any given plane in the LED beam pat-
each LED is therefore partially collimated to tern. Therefore, for the same irradiance, the pho-
reduce the angle of divergence by some 30%. This ton intensity at the target has been increased to
means that there are still intersecting beams to allow for a more efficient irradiation of the target
make use of the photon interference phe- tissue (Fig. 18.13).
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Dosimetry greatest amount of energy in the table, 2000 J,

produced a phototherapeutic effect, whereas the
Up to this point in the section, the time for which smallest, 8 mJ (0.008 J), produced a photosurgi-
light of a given irradiance or power density is cal effect [17]. In an experiment performed
incident on a target has not been mentioned. 20 years ago by the author of this chapter, the
When treatment time comes into the therapeutic exposed rat knee joint, both encapsulated and
equation it quantifies the dose of light delivered. unencapsulated, was irradiated with a GaAlAs
When 1 W of power is incident on target tissue for diode laser giving an incident power density of
1 s, the energy delivered is 1 joule (J). The joule 1 W/cm2. A range of doses was applied from
in itself is a particularly useless therapeutic 20 J/cm2 (20 s exposure) up to 1800 J/cm2 (30 min
parameter since it expresses only power over exposure). Tissue was examined macroscopically
time, and does not take into account the unit area and microscopically immediately after irradia-
of tissue being treated. The most important tion for any signs of damage: none was found. The
parameter for the therapeutic dose in LED photo- wounds were closed and followed up at different
therapy is the energy density (ED). ED is calcu- time points over 2 weeks. No differences were
lated as follows: seen in coded specimens from each group at all
time points regarding morphological changes
OP ´ t
ED =
TA
(
J / cm2 ) compared with the unirradiated control speci-
mens [18]. In pharmaceutical science, the medi-
where OP is the output power incident on the tar- cine must be correct before adjusting the dosage.
get in watts, t is the time in seconds and TA is the In phototherapy, the power density is analogous
irradiated area in cm2. ED is expressed in joules/ with the medicine, and the energy density is the
cm2 (J/cm2). However, too much is often made of dose. If the medicine is incorrect, i.e., a photon
the dose as the most important parameter in pho- intensity which is too low (no effect) or too high
totherapy, and criticism has been leveled at an (photothermal damage), no amount of playing
LED system that ‘the dose is too high’. In fact, as around with the dose will achieve the optimum
stated in the previous subsection, it is the power result [17].
density, rather than the energy density, which
more than anything else determines the bioreac-
tion, and this is illustrated in Table 18.3 where a Temporal Profile of the Beam
constant dose of approximately 25 J/cm2 can
achieve the entire gamut of bioeffects from pure The temporal profile of a beam of light energy sim-
athermal photobiomodulation to severe photode- ply means the output mode in which the light is
struction. The total uselessness of joules as a delivered to the target. There are two modes, con-
meaningful parameter is also illustrated: the tinuous wave (CW) and pulsed, with Q-switching
Table 18.3 This illustrates a variety of bioeffects (Δα) achieved with the same approximate energy density, or dose, of
25 J/cm2
P S∅ [a] (cm2) PD (W/cm2) t e ED (J/cm2) Δα
100 W 10.0 cm 78.6 1.3 20 s 2000 J 25 −
50 W 3.5 mm 0.1 500 100 ms 5J 25 +
10 W 1.0 mm 0.0008 1250 20 ms 0.2 J 25 ++
1W 200 μm 0.0003 3180 8 ms 8 mJ 25 +++
75 mW 3.0 mm 0.07 1.1 23 s 1.725 J 25 −
As can be seen from the table, the power density (PD) is the most important determinant of the bioeffect and the energy
density given alone is therefore not a real determinant of effect
Key to table: P: Incident power (units as shown), S∅: spot size diameter (units as shown), [a]: irradiated area, PD: power
densityt: exposure time (units as shown), E: energy (units as shown), ED: energy densityΔα: graded bioeffects (+++,
severe photodestruction; ++, medium photodestruction; +, mild and/or reversible photodestruction; −, bioactivation)
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303 303
of a pulsed beam technology dramatically shorten- wavelength decreases, the frequency increases.
ing the pulse width and increasing the peak power Increased frequency is also positively associated
of pulsed beams. In CW, as the name suggests, with an increase in energy of the individual photons,
when the light source is activated the power reaches expressed as electron volts (ev), and for the previous
its maximum level, from mW up to 100 W or so, three wavelengths the respective photon energies
and stays there till the system is switched off are approximately 1.49, 1.96 and 2.99 ev. Photon
(Fig. 18.14a, left panel). An alternative to CW is energy determines the type of interaction between
when the beam is ‘gated’ to produce a train of the incident light and skin cells. For 830 nm, as
square waves: this is often incorrectly referred to as explained already, photophysical rotational and
‘pulsed’ light (Fig. 18.14a, right panel). Gating can vibrational changes occur in the electrons making
be accomplished by a mechanical shutter, or be up the cell membrane, whereas for visible light
achieved by simply switching the light source on there is a direct induction of an intracellular photo-
and off. The correct name for this process is ‘fre- chemical cascade. At very high ev values, such as
quency modulation’, because an exogenous fre- those associated with ultrashort wavelengths,
quency (the on-off sequence) is being superimposed namely X- and γ-radiation, the very large photon
on the inherent frequency of the beam which is pre- energies result in molecular disassociation of cells
determined by the wavelength, each wavelength with sufficient exposure, in other words the cells are
having a fixed frequency. For example, near infra- literally blown apart or “ionized”. These ultrashort
red at 830 nm, visible red at 633 nm and visible blue wavelengths are classed as ionizing radiation and
at 415 nm have ‘built in’ frequencies of approxi- are inherently extremely harmful to living tissue
mately 3.6 × 108, 4.7 × 108, and 7.2 × 108 MHz, with a strong carcinogenic potential. LED-LLLT is
respectively. From this it can be seen that as the very much nonionizing radiation.
a b
15 Peak power Interpulse interval (in ms)
15 GW
Frequency modulated C/W beam

(50% duty cycle)
Output power (GW)
C/W beam
80
Output power (mW)
Average power (in W)
0 0
on off Pulse width (in ns)
Time (s) Time (units as shown)
Fig. 18.14 Temporal profile of a beam of light. There are a 50% duty cycle is illustrated. When a laser beam is truly
two basic profiles, continuous wave (CW) (a) or pulsed pulsed, a tremendously high peak power, measured as high
(b). In CW (a, left panel), the system is switched on, the as gigawatts (GW) is released in an ultrashort pulse
light very rapidly reaches its maximum, and remains there interval, measured in nanoseconds (ns) (b, left panel). If a
till the system is switched off. This CW beam can be train of these pulses is emitted with a comparatively long
‘gated’ mechanically or electrically, i.e. rapidly switched interpulse interval of milliseconds (ms) (b, right panel),
on and off (a, right panel), which is often incorrectly then the target tissue ‘sees’ only the average power of the
referred to a ‘pulsing’. The correct name is frequency beam, measured in watts. This is called quasi-CW, also
modulation. This gives a series of rectangular waveforms: known as ‘superpulsing’ the beam
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In a true pulsed beam, from a high-powered or there are two main mechanisms of action: photody-
Q-switched laser, an extremely high peak power is namic therapy (PDT) and athermal and atraumatic
reached in a spike-like waveform, with a very short photobiomodulation, which are totally different
pulsewidth, 1 ms or less or in the nanosecond mechanisms of action.
domain for the Q-switched systems. The peak
power may be in mega- or even gigawatts (Fig.
18.14b, left panel). If a train of such true pulses is Photodynamic Therapy (PDT)
delivered with a set interpulse interval often orders
of magnitude longer than the pulse width, then the PDT can be exogenous or endogenous, the better
target tissue ‘sees’ only the average power of the known form of which is exogenous.
beam, usually at CW output levels. This is also
referred to as ‘superpulsing’, or more correctly, Exogenous PDT
quasi-CW (Fig. 18.14b, right panel). No current Exogenous PDT is typically defined as: “The
therapeutic LED system is capable of delivering a use of a chemical, given orally, intravenously or
true pulsed beam, although LED-LLLT devices are topically (directly to the skin), that can be acti-
available in which the LEDs are turned on and off vated or energized by light to destroy a target
to give flashes of energy in a range of frequencies tissue in which the chemical or substance has
which are superimposed on the frequency preferentially located. This activation causes
inherent to the wavelength of the emitted light. Thisthe formation of new molecules and free radi-
is frequency modulation, but is often incorrectly cals such as reactive oxygen species (ROS)
referred to as “pulsing” the LEDs. which may also form other chemicals that, in
turn, may destroy the targeted material to a
varying extent, such as through ROS-mediated
Box 18.3 apoptosis of the photosensitized cells or closure
• LEDs are ideal for cellular photobio- of blood vessels feeding the target tissue.” PDT
modulation (low level light therapy, is another arm of phototherapy, and whilst
LLLT), an atraumatic and athermal exogenous PDT is thus still an athermal reac-
direct exchange of energy raising the tion, it is not atraumatic as deliberate induction
target’s action potential of apoptotic cell death is the main goal. The
• LEDs can be successfully used in pho- first main application for photodynamic therapy
todynamic therapy (PDT) was in the treatment of certain cancers, with such
– Exogenous PDT with photosensitizers as hematoporphyrin derivatives
5-aminolevulinic acid (5-ALA) for activated with low incident levels of laser light,
treatment of non-melanoma skin particularly with visible red light such as from
cancers and severe photodamage. the HeNe laser due to this wavelength’s better
– - Endogenous PDT in porphyrins penetration than the shorter visible
endogenous to Propionibacterium wavelengths in living human tissue [19]. This
acnes, for example, in the treatment activated an oxygen-dependent phototoxic
of acne. cytocidal action within the cells containing the
agent, and the free radical singlet oxygen (1O2),
a short-lived product from the reaction between
an excited sensitizer molecule and oxygen,
LED Phototherapy: Mechanisms played a very important part in the induction of
of Action cell death (apoptosis) and destruction of the
microvasculature feeding the tumor.
When light energy is incident on a target, the reac- One of the first applications for LED photo-
tion in the target following absorption is known as therapy was in fact PDT for non-melanoma skin
the mechanism of action. In LED phototherapy, cancers (NMSCs), such as basal cell carcinomas
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a b c d
Fig. 18.15 Nonselective en bloc infiltration of skin by Pp appropriate wavelength activates the porphyrins to pro-
IX and Cp III of 5-ALA origin illustrated schematically. duce powerful but very short-acting reactive oxygen spe-
(a) Target lesion in superficial dermis. (b) 5-ALA oint- cies, such as singlet oxygen, and the affected skin cells die
ment applied topically to epidermis. (c) As 5-ALA pene- through oxidative-stress mediated apoptosis (induced cel-
trates en bloc into skin cells, it is transformed into Cp III lular destruction)
and Pp IX, photosensitizing porphyrins. (d) Light at an
and superficial squamous cell carcinomas, or

severe sun damage such as actinic keratosis with
the use of another exogenously-applied com-
pound, 5-aminolevulinic acid or 5-ALA in any
of its forms. This application continues to the
present with good success and robust long-last-
ing results [20, 21]. The topically applied 5-ALA
penetrates into the dermis under an occlusive
wrap, and is converted as part of the
mitochondrial-based heme cycle into copropor-
phyrin III (Cp III), a member of the powerful
porphyrin photosensitizing family. When the
maximum amount of Cp III has been converted,
Fig. 18.16 Action spectra for coproporphyrin III and
the remainder of the 5-ALA is converted into
protoporphyrin IX. Note the extremely high peak at
another porphyrin, protoporphyrin IX (Pp IX). 415 nm, and the minor peak at 633 nm, visible red, par-
These two porphyrins become the specific tar- ticularly in Pp IX, which suggests the red wavelength for
gets of the LED energy at specific wavelengths, deeper activation of 5-ALA-induced porphyrins in PDT
for cutaneous lesions
and, following photoactivation, nonselectively
damage all of the superficial dermal tissue in
which they exist, as illustrated schematically in successfully. Another series of much smaller
Fig. 18.15. peaks is however seen from the yellow to the red
When a photoreaction is desired such as in waveband (the Q-band), the latter occurring at
5-ALA PDT for any purpose, an action spectrum around 633 nm, which was used in the early days
has to be run to investigate the action potential of of hematoporphyrin derivative PDT for other
a range of wavelengths in the target compound. cancer types as a much better-penetrating wave-
Figure 18.16 shows the absorption spectra of Pp length, thus giving a much deeper zone of por-
IX and Cp III. There is a very large peak at phyrin activation and hence a deeper zone and
415 nm in the visible blue Soret band, but as will greater volume of controlled photodamage. Red
be remembered from the previous section on 633 nm LED-activated 5-ALA has been success-
wavelength, blue light has very poor penetrative fully used for NMLCs and actinic keratoses,
capability into the dermis, and so it would not photorejuvenation and inflammatory acne vul-
cause deep enough damage to treat NMSCs garis. These will be discussed in more detail
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in the appropriate subsection on LED photother- fulfills the definition of phototherapy, namely
apy in clinical practice. direct cellular activation in an athermal and
atraumatic manner which has been the umbrella
Endogenous PDT mechanism of action long-associated with LLLT
Exogenous PDT as discussed above depends on (low level light therapy) over its 30-year-plus
an external photosensitizer, such as 5-ALA. In history, whether with laser or non-laser sources.
endogenous PDT, the photosensitizer, or photo- Atraumatic and athermal LLLT thus differs
sensitizing substances, can be found occurring from PDT which actively seeks to damage the
naturally within the target cells or tissue. The target cells and tissues, although still in an
exogenous application of 5-ALA induces the athermal manner. As has already been discussed
synthesis of the porphyrins Pp IX and CP III in section “Wavelength and Its Importance” on
nonselectively in the tissues of the epidermis wavelength, near infrared and visible light have
and dermis under the area of application as different absorption targets (cell membrane and
already explained above. However, in the case subcellular organelles, respectively) but the end
of acne vulgaris the inflammatory acne lesions result is the same, and the energy level of the
are associated with the presence of their caus- cell is raised by both near IR and visible light of
ative bacterium, Propionibacterium acnes (P. appropriate wavelengths through direct absorp-
acnes). It has been well demonstrated that both tion of the incoming photon energy, which is then
Pp IX and Cp III are endogenous to active P. transferred to the receptor cell with no loss
acnes, and the more active is the bacterium, the through heat or luminescence. The main mecha-
higher the porphyrin concentration [22–24]. nism of action is connected with increased ade-
Referring again to Fig. 18.16, maximum photo- nosine triphosphate (ATP) production and
activation of both Pp IX and Cp III occurs at increased Ca2+ ion intra- and intercellular sig-
around 415 nm. Light at that wavelength, with a naling [26].
high enough photon intensity, could therefore Under photoactivation, three things can hap-
achieve activation of the porphyrins within the pen to the energized cell: if it is compromised
P. acnes, thereby selectively destroying or at or in some way damaged, the cell will heal much
least severely damaging the P. acnes through faster; if the cell is designed to perform some
oxidative stress-induced apoptosis [25], but specific function, such as fibroblast col-
without harming the surrounding skin cells. lagenesis and elastinogenesis, then the LLLT-
Endogenous PDT could therefore be applied in treated cell will perform these functions better
the light-only treatment of inflammatory P. and faster; finally, if the cell is designed to rep-
acnes lesions without the need for any exoge- licate, then it will replicate faster [14]. These
nous 5-ALA. This will be discussed in more may happen singly, or in combination, and form
detail in the appropriate part of the following the basis of the three decades of LLLT literature
section. in which some, but not all, of the mechanisms
under the umbrella of photobiomodulation have
already been at least partly elucidated as sum-
Photobiomodulation marized in Table 18.4 and at a molecular level
in Table 18.5. In addition, in the past decade in
Basically the majority of the information in sec- particular, a good number of solid clinical and
tions “Introduction” and “Basics of Light-Tissue basic science papers have corroborated the pre-
Interaction” has been based on the concept of vious basic and clinical findings for LED pho-
photobiomodulation, also known as photoacti- totherapy, and some exciting new science on
vation therapy, and this approach completely LED-LLLT has been appearing in the last
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Table 18.4 Summary of the major mechanisms associated with photobioactivation and LLLT
Mild thermal Biochemical (primary for visible
(<40 °C) light) Bioelectric Bioenergetic
↑ Nerve (Mitochondrial events) ↑ Electromotive action on ↑ Rotational and
conduction ↑ ATP production membrane bound ion transport vibrational changes to
↑ Release of nitric oxide (NO) mechanisms membrane molecule
↑ Very low levels of reactive oxygen electrons
species (ROS) (Primary for near-IR)
↑ Capillary ↑ Fibroblast ↑ Intracellular extra-cellular ion ↑ Stimulation of
dilatation proliferation → Collagen and elastin gradient changes acupuncture meridian
synthesis points
↑ Mast cell degranulation: cytokine, ↑ Depolarization of synaptic ↑ Increased
chemokine and trophic factor release cleft → closure of synaptic biophotonic activity
gate—pain control
↑ Macrophage activity (chemotaxis ↑ Activation of the dorsal horn
and internalization) → release of gate control mechanism → pain
FGF transmission slowed, pain control
increased
↑ Keratinocyte activity → cytokine
release in epidermis and dermis
↑ Opiate and nonopiate pain control
(endorphins, dynorphins and
enkephalins)
↑ RNA/DNA synthesis
↑ Enzyme production
↑ Superoxide dismutase (SOD)
production (mast cells)
Table 18.5 Molecular level activation by LLLT with appropriate LEDs (based on data from Gao X, Xing D. Molecular
mechanisms of cell proliferation induced by low power laser irradiation. J Biomedical Science. 2009 16:4 http://www.
ncbi.nlm.nih.gov/pmc/articles/PMC2644974/)
Classification Molecules LLLT-associated biological effects
Growth factors BNF, GDNF, FGF, bFGF, IGF-1, KGF, PDGF, Proliferation
TGF-β, VEGF Differentiation
Bone nodule formation
Interleukins IL-1α IL-2, IL-4,IL-6, IL-8 Proliferation
Migration
Immunological activation
Inflammatory PGE2, COX2, IL1β, TNF-α Acceleration/inhibition of inflammation
cytokines
Small molecules ATP, cGMP, ROS, CA2+, NO, H+ Normalization of cell function
Pain relief
Wound healing
Mediation of cellular activities
Migration
Angiogenesis
5 years. LED-LLLT can be used in combination exogenous or endogenous PDT in the treatment
with other conventional modalities to improve of inflammatory acne vulgaris. Once again, a
results and hasten healing time, and can also detailed discussion will be found in the follow-
offer a very interesting combination with either ing section.
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clinical arena. However, a thorough understand-

Box 18.4 ings of the true capabilities, and indeed limita-
• LED-LLLT in the adjunctive combi- tions, of LED phototherapy in clinical practice is
nation approach is the key to clinical even more essential to go about amassing the
efficacy. required evidence-based medicine in the most
• LED-LLLT is not magic … it cannot efficient manner. A large number of LED-based
target everything as monotherapy. systems is commercially available now in the
• Based on the published peer-reviewed USA and world-wide, but a very, very small
literature, certain wavelengths can number has actually made it into the peer-
accomplish different things in effec- reviewed literature with the vast majority of man-
tive LED-LLLT. ufacturers content to ride on the coat-tails of the
– 633 nm has proved effective in 5-ALA companies who have done the actual work, both
PDT for non-melanoma skin cancers, basic science and controlled clinical trials, even
and has found applications in hair res- though the science of these bandwagon-jumping
toration and baldness prevention. systems is sketchy at best, and nonexistent or even
– Blue 415 nm endogenous PDT com- erroneous at worst. Of particular concern are the
bined with red 633 or 830 nm LED- ‘look-alikes’ of far-east origin, particularly
LLLT applied sequentially has been China, based on proven systems but with inferior
reported as a very effective light-only quality LEDs which give neither the rated
therapy for moderate to severe acne wavelength, nor sufficient and stable output
vulgaris. power. Some of these systems mimic the free-
– Combined near infrared 833 and standing planar LED-based units, and others are
633 nm red LED-LLLT, applied small hand-held devices with a mesmerizing array
sequentially, was reported as very of pretty flashing multicolored LEDs, designed
effective in skin rejuvenation and all for the home-use market. These groups of ‘toy’
aspects of wound healing, but more systems are doing more harm than good to the
recent literature suggests that 830 nm reputation of LED phototherapy, although one
on its own is the key wavelength in hopes that they are not visiting actual harm on
these indications. patients with ‘no effect’ hopefully being the worst
– Visible yellow light (590 nm, that they achieve. The negative impact on
595 nm) has shown efficacy in the ‘good’ LED phototherapy has been and remains,
treatment of superficial conditions, however, very large. Hopefully this entire chapter
e.g., in the treatment of rosacea. will go some way to redressing that. Another
– Adjunctive LED phototherapy will important point for anyone considering purchas-
complement any and all existing con- ing an LED phototherapy system is that some
ventional modalities which alter in LED system manufacturers claim that their LEDs
any way the architecture of the skin to are ‘NASA technology’. This is totally mislead-
achieve the desired clinical result. ing. Although the new generation of LEDs is
based on the ‘NASA LED’, they are not actual
NASA technology, and some of the LEDs thus
described are still of the previous generation:
LED Phototherapy in Clinical caveat emptor! The reader must always bear in
Practice mind that with LED phototherapy, ‘any old LED
will NOT do’.
Good basic science is of course extremely impor- The treatment categories dealt with in this very
tant to understand how LED-LLLT can be applied important section are based on published lit-
in current dermatological practice, to help bolster erature, not so-called ‘white papers’, and so the
up evidence-based medicine from the practical reader can obtain the original articles from online
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indexing sources such as PubMed, and see in in the treatment of NMSCs [27]. The lamp was
detail what has, and what has not, been scientifi- the brainchild of Dr. Colin Whitehurst, and it was
cally proven and clinically corroborated. The he who saw the potential for using the new gen-
author would like to point out that any suggested eration of LEDs which became available in 2000
treatment protocols are inserted only for example following Whelan’s work with the NASA Space
and guidance, and must not be taken as concrete. Medicine program referenced earlier. The new
Manufacturer’s recommendations are also only generation of LEDs emits quasimonochromatic
recommendations, and the reader should look to light and does not require filtering, plus the LEDs
the published literature or presentations from can be mounted in planar arrays to irradiate large
leaders in the field at leading national and inter- areas at the same time, such as the entire face. Dr
national congresses for more detailed and accu- Whitehurst then helped found Photo Therapeutics,
rate treatment protocols. It is the hope of the who built the first large-array 633 nm LED ther-
author that the reader will see the true possibili- apy source for LED PDT for the treatment on
ties of LED phototherapy to enhance his or her NMSCs with input from Prof Whelan. Large-
clinical practice, and will moreover choose an scale clinical trials in the UK and elsewhere in
LED system based on the criteria which will Europe gave excellent results [28].
appear throughout the section, rather than on The basic protocol which has evolved for
hype, pretty flashing colors and pseudo-science. 633 nm LED PDT for NMSCs is as follows:
If the actual systems referenced seem to be please note that differences in LED systems and
extremely limited, that is because they are the photosensitizer do not make this an absolute pro-
only ones which have been published in the lit- tocol, and the recommendations of the manufac-
erature, and the author offers no apologies for turer of both the LED system being used and the
this. He can only demonstrate and present to the photosensitizer being applied must always be
reader what has been published on systems which studied and carefully followed. Following thor-
have met or exceeded the required criteria by the ough cleaning of the treatment area, 5-ALA of the
relevant regulatory bodies. appropriate strength (usually 20%) is applied, and
occluded with sterile cling film for the rec-
ommended incubation period (up to several hours,
Non-melanoma Skin Cancers (NMSCs) depending on the lesion being treated). At the end
and Actinic Keratosis of incubation, the occlusive dressing is removed
and any excess 5-ALA wiped off. Activation of
NMSCs, including Bowen’s disease and basal cell the porphyrins induced in the target tissue is then
carcinoma, were the first entity to be treated with achieved with 633 nm light, with a dose usually
LED PDT using specifically-designed around 45–90 J/cm2. This can be extremely
633 nm LED-based system to activate 5-ALA, painful, and some kind of forced air cooling may
and the pioneering company was Photo be applied during this phase for patient comfort.
Therapeutics (Fazeley UK and Carlsbad, CA) Following activation, the wound is dressed, and
with their Omnilux® PDT™ system. The the patient returns after 24 h for dressing removal
Omnilux brand is currently owned by Radiency and the situation is then followed for 4–6 weeks.
Ltd., Hod Hasheron, Israel (parent company). In a large percentage of lesions, recurrence is not
Having established that an effective activation a problem. Persistent lesions are retreated till no
peak for the relevant porphyrins created from recurrence is seen. Figure 18.17 shows a typical
exogenous PDT existed at around 633 nm, a UK example of the results of 633 nm LED PDT for an
company in 1996, working in tandem with the NMSC.
British Cancer Research Council, developed the In the case of actinic keratoses (AKs), which
Paterson Lamp, a filtered xenon-powered lamp are much more superficial than NMSCs, a much
which delivered most of its light energy at lower concentration of 5-ALA is applied with a
633 nm, to be used with exogenous 5-ALA PDT shorter incubation time. The protocol is otherwise
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a b
Fig. 18.17 A basal cell carcinoma before (a) and 4 weeks used, Omnilux® PDT™, photographs courtesy of Colin
after 633 nm 5-ALA PDT (b) (20% 5-ALA, 5 h incuba- Morton MD, Falkirk, Scotland)
tion, 20 min activation at approximately 96 J/cm2. System
a b
Fig. 18.18 Actinic keratosis on the décolleté of a 20 min activation at approximately 96 J/cm2. Same system
45 year-old female before (a) and just over 6 weeks after as in Fig. 18.14, photographs courtesy of Colin Morton
633 nm 5-ALA PDT (b) (10% 5-ALA, 30 min incubation, MD, Falkirk, Scotland)
the same and the activation dose is still recom- and psychosomatically troublesome as the active
mended to be around 96 J/cm2. Figure 18.18 lesions, but more difficult to treat. It therefore
shows AK on the upper sternum of a female made sense to attack and eradicate acne while at
patient before and after 633 nm LED PDT. One the active stage, before scarring was an issue. In
treatment usually suffices for AKs. addition to the conventional approaches, LED
exogenous 5-ALA PDT with 633 nm and nar-
rowband blue light LED and non-LED sources at
Acne Vulgaris around 410–425 nm attracted attention with good
results, but with some downtime and pain associ-
Acne vulgaris still represents a major problem for ated with the activation stage of the photosensi-
the practicing dermatologist, despite advances in tizer [29–31]. The recurrence rate was, however,
clinical and medical therapy. Many approaches still rather high. The development of quasimono-
have been tried with varying degrees of success, chromatic LEDs at the peak wavelength of
but results are inconsistent, even in the same 415 nm offered a new approach, given the
regimen with the same patient. If untreated, or extremely high peak in the activation spectra of
treated improperly, active ace almost always Pp IX and Cp III, both of which porphyrins are
leads to unsightly acne scarring, as disfiguring endogenous to active P. acnes as already
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discussed above. With a high enough photon of the different cellular and subcellular
intensity at 415 nm it would therefore theoreti- wavelength-specific targets, and the quasimono-
cally be possible to activate the endogenous por- chromatic nature of LED therapy would assist in
phyrins in P. acnes selectively, thereby disabling precise targeting. In addition, applying the blue
or eradicating the P. acnes [32, 33]. On the other and red components together might actually go
hand, trying to activate porphyrins from exoge- some way to defeating the object of the exercise,
nously-applied 5-ALA PDT with narrow band as one of the effects of the red light is to try and
415 nm LED energy should be attempted with repair damaged cells, including the P. acnes tar-
extreme caution, as the activation process will be geted by the blue light.
both extremely painful and rather shallow owing Two clinical papers were published in 2007
to the physical characteristics of 415 nm light, using this sequential approach of 415 nm LED
with a prolonged downtime owing to the serious light-only therapy followed by 633 nm red LED
damage to the irradiated tissues. treatment, repeated over a 4-week period. One
In order to understand why the blue light ther- patient group was Caucasian [36] and the other
apy on its own was achieving good results but Asian [37], and both groups had a meaningful
with a still unacceptably high recurrence rate, the number of patients (>25) with a good selection of
etiology of acne must be considered. Acne is Burton grades 3–5, representing moderate to
often considered as an inflammatory disorder, severe inflammatory acne. The system used in
full stop, with colonization of blocked follicles both studies was the Omnilux (Radiancy, Israel)
by P. acnes as the main culprit. In fact, acne is with the blue™ (415 nm) and revive™ (633 nm)
multifactorial with major influences other than heads, and the same protocol was followed in both
merely inflammation, such as hormonal and the USA and Korea study centers. A two- week
autoimmunological imbalances [34]. Acne is the washout was imposed for anyone on oral
result of the establishment of a vicious circle set medication, and no other form of topical or ther-
up between P. acnes and some t-cells originally apy was allowed during the study and followup
homing into the site to help the defence system, period. A comedonal scrub was recommended
but ultimately converted by P. acnes to the black before each treatment session. The blue head was
side as ‘rogue t-cells’. Whereas 415 nm will pre- applied first for 20 min, followed at least 48 h
cisely target the P. acnes via the endogenous por- later by the red head. This was repeated for
phyrins and thereby remove one of the major 4 weeks. Assessments were performed at pre-
causes of the inflammation, the rogue t-cells and treatment baseline, at each of the 4 weeks during
any hormonal imbalance remain untreated by the treatment, and then at 4, 8 and 12 weeks after the
415 nm light, thus leaving the vicious circle final treatment session.
unbroken and paving the way for recurrence at The most interesting point in both studies was
some stage in the near future. If light-only ther- that the improvement obtained after the final
apy for acne were to work well and with robust treatment session, which ranged from 50% to
results, it would therefore be necessary to find 60% clearance of inflammatory lesions, contin-
another approach whereby the targets not dealt ued to improve up to 12 weeks after the final
with by the blue light could be attacked with treatment with no other therapeutic intervention,
another wavelength. A very interesting paper reaching from 83% to 90% clearance, and if
appeared from Papageorgiou and colleagues in extrapolated beyond the trial period would have in
which they achieved excellent and long-lasting many patients reached 100%, which from per-
results in acne treatment with a combination of sonal communication with the authors of both
filtered blue (415 nm) and red (660 nm) non-LED papers, it in fact did. Figure 18.19 is a graphic
light applied simultaneously [35]. It was then representation of the inflamed lesion reduction
suggested that sequential rather than simultane- curves of the two referenced papers.
ous application of blue and red light might have No secondary hyperpigmentation was seen in
an even better effect through selective targeting any patients in both studies, which is of particular
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0
Goldberg & Russell (29)
Lee et al (30)
20
Extrapolated clearance
Clearance rates (% of lesions)
40
60
80
100
0 1 2 3 4 4 8 12
Treatment weeks Follow-up weeks
Fig. 18.19 Inflammatory lesion clearance rates follow- (12 weeks from baseline). However, by extrapolating the
ing the blue/red combination LED phototherapy for acne clearance rates in both studies, which were clearly linear
adapted from the studies by Goldberg and Russell [29] and in nature, the continued improvement is evident. No other
Lee et al. [30]. The Goldberg study had a 12-week follow- therapy was used in either study. System used: Omnilux®,
up after the final treatment, i.e. 16 weeks from baseline, Radiancy, Israel
whereas the Lee study had an 8-week follow-up
interest in the Asian skin type. In addition, over- severe side effects. The validity of the substitu-
all skin condition was subjectively assessed to tion of another LED wavelength to the current
have improved, and in the case of the Asian popu- protocol, namely near infrared at 830 nm with its
lation, skin lightening was objectively shown own unique cellular and tissue targets, in place of
across the population with an instrumental assay. the 633 nm visible red approach, is currently
Figure 18.20 shows examples of the treatment being assessed in ongoing clinical studies world-
efficacy courtesy of the authors of the papers. At wide, and the results are extremely promising
6 months after the final session, recurrences in probably owing to the specific cellular entities
both trial centers were extremely few and mild, targeted by 830 nm compared with those affected
easily treated with another regimen of the blue/ by 633 nm.
red LED therapy (David Goldberg and Celine SY
Lee, personal communication).
As with all approaches not involving exci- Skin Rejuvenation
sional surgery, there will always be a small per-
centage of patients in whom light-only LED Skin rejuvenation and antiageing have become
phototherapy for acne vulgaris will have disap- very ‘hot’ topics. Excessive skin exposure to solar
pointing results, but from the above studies the UVA and UVB brings about damaging mor-
overall efficacy is high enough to warrant apply- phological and metabolic changes in the epider-
ing this approach as the primary treatment of mis and dermal extracellular matrix (ECM),
choice. Sequential combination LED photother- combining with and accelerating the effects of
apy for acne can be combined with other topical chronological ageing and resulting in the lax, dull
approaches with even better results and improved and wrinkled appearance of ‘old’ skin. Oxidative
maintenance, provided none of these involves stressors such as singlet oxygen are photochemi-
any kind of photosensitizing agents, any of which cally generated following absorption of UV radi-
have the potential to create painful and possibly ation in the ECM and damage the matrix integrity
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a b
c d
Fig. 18.20 Representative examples from the Goldberg the cheek and jaw line of a 19-year-old Korean male
and Lee studies on light-only combination blue/red LED patient from the Lee series, skin type IV. (d) Eight weeks
phototherapy for inflammatory acne. (a) Cystic acne at after the final treatment session (12 weeks from baseline).
baseline in a 21-year-old female, skin phototype II, from Good clearance with no secondary hyperpigmentation, a
the Goldberg and Russell series. (b) Six weeks after the major problem in the Asian skin. The remaining small
final treatment session (10 weeks from baseline). areas of redness will fade with time. Photographs courtesy
Excellent clearance and very good cosmesis. Photographs of SY Celine Lee MD
courtesy of Bruce Russell MD. (c) Inflammatory acne on
with elevated levels of the matrix metalloprotein- matrix; the viscosity and quality of the ECM
ases (MMPs) 1 and 2, formerly known as colla- ground substance glycosaminoglycans is
genase and gelatinase; elastotic damage to the reduced; and a chronic inflammatory infiltrate
underlying connective tissue occurs, with inter- can be identified. As this damage is caused by
stitial spaces appearing in a poorly-organized light, an elegant concept to use the power of light
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to reverse the damage led to the application of facturers of the more recent second generation of
lasers, usually the CO2 or/and the Er:YAG, in fractional systems have returned to the original
what became known as ablative laser resurfacing. ablative wavelengths, the CO2 and the Er:YAG,
Although still regarded as the ‘gold standard’ in in addition to increasing the parameters of the
the rejuvenation of severely photoaged skin in nonablative fractional Er:glass systems, to deliver
general and deep wrinkles in particular, the usu- fractionated microbeams that visibly damage the
ally severe side effects and a prolonged patient both the epidermis and the dermis with a
downtime of up to several months associated recognizable amount of erythema and some
with this approach drastically reduced its edema post-treatment.
popularity. This in some way takes us back towards our
To attempt to overcome these problems, so- gold standard of ablative resurfacing, as once
called nonablative resurfacing was developed again heat deposition, combined with controlled
using specially adapted laser or intense pulse epidermal damage, becomes a pivotal consider-
light sources. The theory was to deliver a con- ation to achieve the ideal rejuvenation results on
trolled zone of deliberate photothermal damage a patient-by-patient basis [42]. This approach has
beneath an intact epidermis, so that the wound- been much more successful from the patient sat-
healing processes, including collagenesis and isfaction criterion, although at the cost of a little
remodeling, could occur under the undamaged downtime, because it is involving the epidermis
epidermis, thereby obtaining rejuvenation of the more than the previous nonablative and fractional
skin without any patient downtime and was pop- approaches.
ularized as the ‘lunch-break rejuvenation’. The In the meantime, other clinical researchers
theory was good, but in clinical practice patient were wondering if there was a role for LED pho-
satisfaction was very low, [38, 39] because the totherapy in skin rejuvenation, and the first
good dermal neocollagenesis seen in post- approach was to use a lower strength of topically-
treatment histological analysis was not reflected applied low-strength 5-ALA activated with
in a ‘younger’ epidermis [40]. In an attempt to 633 nm LED in LED-PDT [43]. The results were
bridge this gap between ablative and pure nonab- good, but begged the question as to why more
lative rejuvenation, so-called fractionated or damage, and indeed some pain, should be
fractional technology was developed whereby inflicted to treat what was essentially compara-
many spots of almost grossly invisible epidermal tively mild skin damage. Another approach has
and dermal ‘microdamage’ were delivered via a been to deliver the 5-ALA at very low concentra-
scanner or ‘stamp-type’ head, all surrounded by tions (<2%) via liposomes and activate the target
normal epidermis and dermis to obtain swift tissue using intense pulsed light, achieving com-
reepithelialization and dermal wound healing plete quenching of the porphyrins and thus avoid-
[41]. Unfortunately, once again the clinical ing the side effect of residual photosensitivity [44,
results of the first generation of nonablative frac- 45]. Because of its totally noninvasive, athermal
tional lasers were not satisfactory to the majority and atraumatic nature, light-only LED pho-
of patients, with good dermal neocollagenesis not totherapy for skin rejuvenation has also attracted
being echoed in the epidermis. In both the attention first with a single wavelength system in
nonablative laser/IPL and the first generation of the visible yellow [46], but once again a sequen-
fractional nonablative technologies, the big tial combination technique, initially at least,
problem was that what the patient first sees when proved more effective than the single wavelength
looking in a mirror is the epidermis, not the der- just as was the case with LED phototherapy for
mis. It does not matter to the patient (or her acne [47, 48]. The wavelengths used for LED skin
friends) that her dermis is wonderfully better rejuvenation in the published literature were
organized if her epidermis remains unchanged, originally near IR at 830 nm applied first, fol-
what the author refers to as the SOE syndrome— lowed by 633 nm 72 h later, repeated over
‘same old epidermis’. Recognizing this, manu- 4 weeks. The rationale for using these wave-
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lengths and the order in which they are applied are clinical photography and subjective patient
photobiologically based on the precepts of the assessment, Dr Lee tested the results with pro-
wound healing cycle, and will be covered in some filometry and instrumental measurement of
detail in the next subsection dedicated to wound skin melanin and elasticity. She also carried out
healing. Both of these wavelengths involve the histological, immunohistochemical and bio-
mother keratinocytes in the basal layer of the chemical assays. Dr Lee found that wrinkles
epidermis, however, in addition to the target and skin elasticity were best improved in the
dermal cells, with beneficial effects to both the 830 nm-treated groups and a statistically sig-
cellularity and organization of the epidermis, but nificant improvement existed between the
with no heat and no damage. treated and occluded sides in all of the experi-
Lee and colleagues, in the first and really mental groups, but not in the sham irradiated
detailed controlled study in the peer-reviewed group. Subjective patient satisfaction showed
literature, which was published in the very statistical significance between all the treated
prestigious Journal of Photochemistry and groups and the sham-irradiated group, but it
Photobiology (B), [49] compared LED skin was clear that a strong tend was shown in favor
rejuvenation in a total of 76 patients randomly of the 830 nm group compared with the
assigned to four groups: 830 nm LED therapy on 830/633 nm and 633 nm groups. Figure 18.21
its own, 633 nm LED therapy on its own, the compares the subjective patient “excellent” rat-
combination therapy with 830 and 633 nm and ings among the 633 nm, 830 nm + 633 nm and
a sham irradiated group. All patients were 830 nm groups from the final treatment ses-
treated hemifacially, so there was intrapatient sions through the 12-week assessment period.
as well as intergroup controls. In addition to For all groups, and interesting and clear
Fig. 18.21 Graphical comparison of only the “excellent’ interesting increase in satisfaction levels is seen during this
result ratings by the LED rejuvenation trial subjects in the 12-week period for all groups corresponding to the
630 nm, 830 nm plus 633 nm and 830 nm groups based on ongoing remodeling stage of the wound healing process.
data from the cited paper by Lee et al. [49]. Ratings start The patients who noted the greatest satisfaction, soonest,
from immediately after the final treatment session, then at were in the 830 nm group
4, 8 and 12 weeks thereafter with no further treatment. An
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improvement was echoed in the patient satis- photoprotective effect against degradation of the
faction during that 12-week period: that newly-formed extracellular matrix.
phenomenon can be explained by the remodel- This was an excellent and thorough study, and
ling process, continuing long after the final of the author recommends the reader to get hold of it
the eight treatment sessions. However, based on and read it, all 17 pages of it. It will go a long way
a closer examination of the study data, the best to convincing even the most skeptical of the real
results were achieved not in the combination efficacy of LED-LLLT for light-only skin
group but in the 830 nm group, and were rejuvenation, backed up with real science.
achieved fastest among the three groups. Figure 18.22 shows examples of the efficacy of
The clinical photography was backed up by light-only combination LED skin rejuvenation,
the histological findings for both collagenesis including histological findings from the Lee
and elastinogenesis, both of which were shown to study demonstrating photorejuvenation of both
take place in all dermal layers down to the deep the dermis and epidermis at only 2 weeks after the
reticular dermis. No MMP activity was noted, final treatment session: as remodeling pro-
and on the contrary the levels of tissue inhibitors gressed, these histological results would have
of MMPs (TIMPs) 1 and 2 were significantly become even better in conjunction with the steady
elevated in all treatment groups, but with a improvement in patient satisfaction in the
strong but nonsignificant trend noted for the 830 12-week follow-up after the final treatment ses-
nm group over the others, suggesting a sion, as noted above.
a b c d
e f g h
Fig. 18.22 Representative examples of combination near organized stratum corneum. (f) Histology at only 2 weeks
IR/red light-only LED skin rejuvenation. (a) A 29-year- after the final treatment session. Note the much better-
old female, skin type II, at baseline: note the mild rosacea organized dermal collagen, extending down into the deeper
on her cheek. (b) The result at 6 weeks after the final treat- reticular dermis, and the highly visible Grenz layer running
ment session (10 weeks from baseline). Smoothing of the under and attached to the basement membrane at the
periocular wrinkles can be seen, with overall better skin dermoepidermal junction. The epidermis is much thicker
tone. The rosacea has almost gone. Photographs courtesy with good cellularity and a very well-delineated stratum
of Bruce Russell MD [40]. (c) Baseline findings in a corneum. (Hematoxylin and eosin, original magnification
26-year-old Korean female, skin type IV. (d) Result ×100). The same improvement could be seen in the elastin
12 weeks after the final treatment session. Excellent content comparing baseline (g) with the findings 2 weeks
removal of the fine ‘crow’s feet’ wrinkles and overall after the final treatment (h) (Verhoeff van Giesen, original
improvement and lightening of the skin tone. (e) magnification ×200). Photographs and photomicrographs
Histological findings at baseline, showing a typical elas- courtesy of SY Celine Lee MD [42]. System used:
totic dermis under a thinned epidermis with a highly dis- Omnilux®, Radiancy, Israel
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The important point to be taken from these Wound Healing

findings is the that epidermis also showed
improved morphology and not just the dermis, Wound healing underpins all applications of LED
thus avoiding the SOE (same old epidermis) syn- phototherapy involving photoactivation therapy
drome which was the major problem with photo- (PaT), and plays a major role in obtaining good
thermal nonablative skin rejuvenation. As with cosmetic results in combination LED PDT/PaT
LED phototherapy for acne, adjunctive comple- for the treatment of acne, and in LED skin rejuve-
mentary treatment and maintenance techniques nation, in addition to the treatment of traumatic or
with high quality creams and sera will certainly post-surgical wounds themselves. A brief
improve the good results consistently shown for overview of the wound healing process is there-
light-only LED skin rejuvenation in these stud- fore warranted. Three distinct phases make up the
ies. The role of protective daily maintenance with wound healing process, namely inflammation,
a UVA/B sunblock of at least SPF 50 should also proliferation and remodeling, and although they
be considered. are distinguished by their timing and cellular
More discussion on the 830 nm/633 nm LED components, there is always some degree of
combination has appeared in Viewpoint 3 overlap between them.
(Trelles, Mordon and Calderhead) and Comment
3 (Goldberg) in an article on redressing The Three Stages of Wound Healing
UV-mediated skin damage in Volume 17 of Inflammation is often regarded as a major prob-
Experimental Dermatology [50]. However, lem, but in the wound healing process it is abso-
although Lee concluded that the combination of lutely essential that inflammation occurs before
the 830 and 633 nm was optimum, if we read proceeding into the proliferative phase.
between the lines of the study it is clear that Inflammation only becomes a problem when it is
830 nm on its own was extremely interesting out of control, such as the end product of the
(Fig. 18.21), which was backed up by a 2011 vicious circle instigated by P. acnes and rogue
article by Kim and Calderhead on the efficacy of t-cells in acne vulgaris.
LED-LLLT [51], and by a 2013 wound-healing In the inflammatory phase, from wounding
study by Min and Goo [52]. Although LED pho- until about day 3–5, mast cells (already present
totherapy has a well-proven role in stand-alone or recruited through chemotaxis), macrophages
indications, especially for wound healing (already present, recruited or differentiated from
whether traumatic, delayed or iatrogenic, the monocytes or pericytes) and neutrophils
adjunctive role of LED phototherapy is perhaps (recruited or differentiated from hematopoietic
even more exciting and is the way of the future. stem cells) peak in the wound and surrounding
Adjunctive LED low level light therapy (LED- tissue. The macrophages ensure that all debris and
LLLT) for the aesthetic dermatologist and plas- detritus from the wound are removed through
tic surgeon, especially at 830 nm, has been well engulfment and internalization, and the leuko-
argued recently in articles appearing in 2015 cytes are the first line of defence of the autoim-
and 2016, respectively, in Laser Therapy [53] mune system against invading pathogens. When
and Clinics in Plastic Surgery [54]. they are at work, the macrophages release an
The wavelengths and systems that have been important trophic factor, fibroblast growth factor
reported in the six studies cited above are 595 nm (FGF), and leukocytes are associated with TGFα
(Gentlewaves®, Light Bioscience, VA, USA) [39], and β (transformational growth factor).
the 830 nm/633 nm combination (Omnilux® Connective tissue mast cells are granule-filled
plus™ and revive™, respectively: formerly Photo cells differentiated from CD34-expressing bone
Therapeutics, Fazeley, UK & Carlsbad, CA, USA, marrow precursors which circulate in the ECM till
currently Radiancy, Ltd, Israel) [40–43] and the they mature in situ, found normally around
new generation 830 nm HEALITE II (Lutronic capillaries and arterioles. In fact, the mast cell was
Corporation, Goyang South Korea) [51–54]. first described and named by the German
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physiologist Paul Ehrilch in the latter part of the fibroblasts and endotheliocytes gradually returns
1800s. Mistakenly believing that the purpose of by day 20–22 to the pre-wound baseline, leaving
the granules was to nourish the ECM, he called the ECM in a regenerated state with newly formed
the cells ‘mastzellen’, (German for ‘feeding but somewhat haphazardly arranged clumps of
cells’), giving us our Anglicized version. Their collagen and elastin fibers, a fresh supply of gly-
part in the wound healing process is to release cosaminoglycans and well-vascularized.
their granules into the ECM. Although the gran- In the final and much longer stage of the
ules released first are proinflammatory, the later wound healing process, remodeling, which starts
granules contain antiinflammatory chemokines around day 19–23, these new fibers and struc-
and cytokines, chemotactic factors to recruit tures gradually mature and are slowly reorga-
more wound-healing cells to the area, and a mix nized into better alignment to give a strong,
of trophic factors. In the final degranulation, the flexible and plump ECM under an epidermis
most powerful antioxidant endogenous to our firmed and tightened by the Grenz layer of colla-
bodies, superoxide dismutase (SOD), is depos- gen fibers running under and attached to the der-
ited into the ECM to help protect against future moepidermal junction basement membrane.
UV exposure-related oxidative stress. The com- After the proliferative phase there are too many
bined efforts of all the inflammatory stage cells fibroblasts in the ECM. One method by which the
with their different but interlocking functions thus body reduces the number is through transforma-
leave the ECM in an ideal and favorable con- tion of some of the fibroblasts to a cell of great
dition for the proliferative stage cells. importance, namely the myofibroblast, which is
In the proliferative stage, from around day 4 to simply a fibroblast that has grown smooth mus-
day 21, the inflammatory stage cells decrease in cles (myo, Greek for muscle) at each end of its
number and fibroblasts and endotheliocytes peak. longitudinal axes. These tufts of muscles are fit-
Fibroblasts, (already in the area or differentiated ted with small barbs which hook onto the newly-
from pericytes), are an extremely important mul- formed collagen fibres and exert force on them to
tifunctional cell. They are not only responsible for bring the fibers into good linear alignment. Once
synthesizing collagen to replace damaged ECM their task is completed, myofibroblasts go into
collagen fibers, but they also produce new elastin apoptosis, programmed cell death. If there are still
to form elastic fibers and additionally manufac- too many fibroblasts, some more will be
ture the ground substance, the glycoproteinous induced to dedifferentiate into quiescent fibro-
viscous gel-like liquid which lubricates and cytes, a kind of unipotent stem cell, which join the
hydrates the ECM, and which also facilitates stem cell pool in the dermis to replace fibroblasts
intercellular signaling and oxygen transport to as they age. The remodeling process can take up
ECM components from arteries. It is also the to 6 months, or even longer, to complete, and this
fibroblasts’ task to maintain ECM morphological is important when thinking of patient education
integrity through constantly monitoring the state regarding when they can anticipate the final
of the collagen and elastic fibers, lying along optimal appearance of their treated tissue, taking
which they can often be seen. In this respect, the the findings of Fig. 18.22 above into con-
quality of both proliferative wound repair and the sideration. Figure 18.23 illustrates in schematic
final wound appearance rests firmly on the back form the time course of the wound healing pro-
of the fibroblast. Endotheliocytes (already present cess, showing the peaks and lows of the cells
in the wound or differentiated from endothelial associated with each of the three phases.
progenitor cells), clump together to start the neo-
vasculogenesis process, culminating in the repair The Influence of Different Wavelengths
of damaged blood vessels and production of new of Light on the Wound Healing Cells
blood vessels to oxygenate the newly-forming When we consider LED phototherapy, it is very
ECM and provide essential nutrients. From a peak tempting to go ahead and invent ‘new’ wave-
at around day 12–18, the increased number of lengths for ‘new’ photoprocesses. It must never
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Inflammation
Proliferation
Remodelling
Mast Macrophage
cell
Relative total number of cells
Fibroblast Myofibroblast
Leukocyte Endotheliocyte
Fibrocyte
Monocyte
0 3 20 100
Approximate time (days)
Fig. 18.23 Schematic illustration of the cell cycles and endotheliocytes, increase in number, and then as remodel-
numbers during the three phases of wound healing. During ing starts, gradually decrease. In the case of fibroblasts,
inflammation, which occurs from day zero to day some remain as active fibroblasts, but some transform into
3–5, the inflammatory cells (leukocytes, mast cells and myofibroblasts, literally fibroblasts with muscles, whose
macrophages) increase in number, peak and then return to task is to ensure good linear alignment of the new colla-
baseline levels. During proliferation, the collagen- gen fibres. It should be noted that the phases overlap, with
producing cells, fibroblasts, and neovascularization cells, no clear border between each
be forgotten that the original LLLT, low level laser the Introduction, the effect of red light specifically
therapy, has a rich and well-documented history on subcellular organelles was first published by
which extends back over almost the last four Fubini and colleagues in the late eighteenth cen-
decades, so by examining this wealth of pub- tury! [3]. The last three decades, however, have
lished literature it should be possible not to have added tremendously to the knowledge regarding
to reinvent the wheel all over again. Sadly, red light and skin cells. It was reported that
because the US Food and Drug Administration 632.8 nm red light from the HeNe laser induced
did not grant 510(k) approval to a laser therapy fibroblast monosheet formation in vitro faster and
system in the process erroneously called ‘bios- with much better alignment, almost double the
timulation’ until 2002, there is not a lot to be speed of the unirradiated controls [55].
found in the US literature until more recently. Furthermore, in the same study, a ‘wound’ created
However, those early US papers which are there, in the monosheet was repaired much faster in the
have been quietly forgotten, probably on the prin- HeNe-irradiated groups. More recent in vivo work
ciple that if one doesn’t understand it, one simply with 633 nm LED energy in human subjects dem-
ignores it. onstrated dramatic fibroplasic changes in speci-
A great deal of literature exists on red light-cell mens from irradiated subjects compared with
reactions, because the mainstay light source of the unirradiated controls [56]. Tiina Karu, probably
early pre-LED investigators was the HeNe laser, the most well-known living photobiologist, has
delivering 632.8 nm, basically the same as the produced an enormous amount of work in her
633 nm of current array-based LED systems, also lifetime on the effects of low incident levels of
in continuous wave (C/W) rather than frequency light on cells and their organelles. She confirmed
modulated as discussed already. As mentioned in the much earlier work by Fubini and further iden-
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tified the specific target for 633 nm light as the keratinocytes to release a large amount of cyto-
cytochrome-c oxidase resident at the end of the kines which drop down into the dermis to assist
mitochondrial respiratory chain [57]. She also with the dermal wound healing processes, so
showed that coherent light was not essential to much so that keratinocytes have been nicknamed
achieve effects in vivo, provided the photon inten- ‘cytocytes’ [64]. Additionally, the photoactivated
sity at the target was high enough. keratinocytes can improve the cellularity and
Mast cells have been stimulated in vitro and in organization of the epidermal strata through rais-
vivo to degranulate when irradiated with 633 nm ing the levels of extracellular ATP and the signal-
light, and much faster than when unirradiated: ing elements Ca2+ and H+, and obtaining a better
stimulation with 830 nm speeds up degranulation organized stratum corneum [64].
even more [58, 59]. The author and colleagues If the wound healing cells, including epidermal
have shown that, 48 h after a single irradiation keratinocytes, are examined for increased wave-
with 830 nm LED energy, mast cells in the fore- length-specific action potential based on the last
arms of healthy human subjects had 40–60% 30 years of both LLLT and non-laser light source
degranulated compared with specimens from literature, the wavelengths which have the most
unirradiated controls, where no degranulation was verified and published results at a cellular and sub-
seen at all [60]. In the same study, independently cellular level are 633 and 830 nm in the near
performed cell counts per field averaged over IR. Near IR at 830 has excellent results in activat-
many samples showed a significant increase in the ing the activity levels of the inflammatory stage
mast cells, macrophages and even neutrophils cells, mast cells, macrophages and neutrophils,
recruited into the irradiated area, compared with fibroblasts and in addition to epidermal keratino-
baseline and the unirradiated control arm (Table cytes. On the other hand, red light at 633 nm com-
18.6). Near IR energy at 830 nm has been pared with 595 nm yellow is excellent for
demonstrated to induce macrophages to perform photoactivating fibroblasts in vivo, due to its supe-
their chemotactic, phagocytic and internalizing rior penetrating powers, in addition to epidermal
functions better and faster, while releasing almost keratinocytes. With athermal and atraumatic LED-
30-fold the amount of fibroblast growth factor LLLT at these wavelengths, especially 830 nm,
(FGF) compared with unirradiated controls [61], there is no physical wound, but exactly the same
and the same is true for the attack and phagocytic clinical response is achieved as seen after any
functions of neutrophils [62, 63]. examples of the nonablative or even ablative
The epidermal basal layer keratinocyte is too approach involving frank photothermal damage.
often forgotten in LED phototherapy, but research Why is the 830 nm effective for skin rejuve-
has shown that 590, 633 and 830 nm noncoherent nation as monotherapy, as seen in the Lee et al.
light both in vitro and in vivo can activate the study [49]? Though this indication is not wound
Table 18.6 Numbers of mast cells, macrophages and neutrophils averaged per field (TEM, ×50,000) showing the aver-
aged value of at least eight fields per subject. (Based on data from Ref. [58])
Mast cells Macrophages Leukocytes
Patient No. Pre Post Control Pre Post Control Pre Post Control
1 1.5 5.5 1.25 0 6.0 0 0 3.35 0
2 1.5 6.75 1.5 0 8.25 0.25 0 4.0 0
3 1.0 7.0 1.25 0.5 6.75 0.25 0 4.5 0
4 0.5 4.75 0.5 0.25 5.0 0.25 0 4.0 0
5 1.0 8.0 1.0 0.75 7.75 0.5 0 4.25 0
6 1.5 7.25 1.5 1.0 7.0 0.75 0 4.5 0
7 1.25 7.0 1.5 0.5 7.5 0.75 0 3.75 0
8 0.5 6.25 0.5 0.75 6.5 0.5 0 4.0 0
The bold text indicates the significant cell count increase in the specimens from the treated arm compared with baseline
and the control arm
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healing per se, it depends on inducing the wound (see Fig. 18.21) [49], as was also the case in the
healing process to clear wrinkles and tighten up acne studies already mentioned [36, 37].
skin. The 830 nm energy degranu- lates the mast The same principle for LED-LLLT with
cells, dumping a load of proinflammatory 830 nm applies to frank wound healing, whether
substances into normal tissue, such as heparin, it is accidental or iatrogenic trauma. Burns, for
trypsin, histamine and bradykinin. This gives the example, are an ideal injury for LED photother-
tissue the impression that it has been ‘wounded’, apy, because of the noncontact and hands-free
even though there is actually no wound because application, and the large area of the treatment
of the athermal and atraumatic action of LED heads. In a recent study, the 830 nm/633 nm
phototherapy. Macrophages are also combination produced excellent results in large
photoactivated, helping to give a clean ECM area burns, as illustrated in Fig. 18.24 [65]. As
‘seeded’ with FGF, with some TGF released mentioned already above, ablative laser resur-
from neutrophils recruited into the area by the facing lost popularity due to the potential of seri-
degranulating mast cells. Because the ous side effects, especially edema and prolonged
inflammatory stage has been established erythema, leading to prolonged patient down-
especially by this mast cell-mediated ‘quasi- time. The wound left following laser ablative
wounding’, the tissue has no option but to pro- resurfacing is simply a full facial burn. In a recent
ceed into the next stages of the wound repair publication Trelles and co-workers used
process, starting with proliferation. When this 830 nm LED therapy following laser ablation of
830 nm irradiation is repeated over eight times the face with a combined Er:YAG/CO2 laser sys-
over 4 weeks, separated each week by 2–3 days, tem [66]. There were two groups of patients,
the dermal cells (and epidermal keratinocytes) 30 in each group. The experimental group
are upregulated in a step-wise manner and received the LED therapy following laser abla-
maintained in the inflammatory/proliferative tive treatment, and the control group received
stages. After the final treatment session the sham treatment from the standby setting of the
remodeling is allowed to start, and this explains system. The average healing times (full reepithe-
why the best results are not seen at this immedi- lization and resolution of erythema) for the con-
ately post-treatment stage, but later on at 4, 8 and trol and experimental groups were 13 weeks and
12 weeks or more after the final treatment 6 weeks respectively. The extent of post-procedure
a b
Fig. 18.24 A 39-year-old male patient with severe full tially applied as usual, a resting period of 4 weeks, and then
facial electric spark burn injury before (a) and (b) three another 4-week regimen. Photographs courtesy of Prof Jin-
months after the final treatment with combination wang Kim MD PhD, Burns Center, Haelym University
830 nm/633 nm LED phototherapy. One full 4 week ses- School of Medicine, Seoul, Korea. System used:
sion was performed with the wavelengths being sequen- Omnilux®, Radiancy, Israel
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Fig. 18.25 Results of a controlled study on LED photo- all significantly reduced in the group which received
therapy after full face ablative Er:YAG/CO2 resurfacing, 830 nm LED phototherapy (based on data from Ref. [64])
30 patients per group. Healing was better than one half of System used: Omnilux®, Radiancy, Israel
the time compared with the controls, and sequelae were
pain, bruising and erythema was significantly and acute herpes zoster ophthalmicus [70].
less for the LED-treated group (Fig. 18.25), Additionally, 830 nm LED treatment has cleared
whereas improvement in the skin condition was irritant contact dermatitis and dissecting follicu-
much more clearly seen in the LED-treated litis of the scalp [51].
group, with a satisfaction index (SI) of 89% Long-term nonhealing ulcers which healed
compared with 51% for the control group. The following low incident levels of red light (HeNe
SI was calculated by adding only the number of laser, 633 nm) comprised the first topic to appear
‘excellent’ and ‘very good’ scores from a stan- in the literature from the Godfather of photother-
dardized 5-element scoring system, and express- apy, the late Prof. Endre Mester of Semmelweis
ing the result as a percentage of the total University, Budapest, Hungary, with a patient
population. Healing following upper blepharo- population of over 1000, and started all the con-
plasty and periocular laser resurfacing in a hemi- troversy surrounding LLLT in the early 1970s
facial study was reported to be cut by one-half to [71]. Very interestingly, Mester reported that
one-third following LED therapy at 633 nm, and ulcers on the limb contralateral to the one treated
the improvement was subjectively rated as two- also eventually healed, although more slowly than
to fourfold better compared with the unirradiated the irradiated wounds. This was the first report on
side [67]. LED-LLLT following Er:YAG laser the systemic theory in phototherapy, whereby
ablation of deep and extensive plantar warts photoproducts created in the irradiated tissue were
roughly halved the healing time, cut the postop- carried systemically through the body to have an
erative pain by at least one-tenth and gave less effect wherever they were required. A
than 6% recurrence rate in 121 cases [68]. The 2012 study has shown the systemic effect in
study by Min and Goo already mentioned above mouse and rat models, whereby standardized
using 830 nm LED-LLLT showed excellent dorsal wounds were created with a fractional CO2
healing of a variety of difficult wounds, some laser. Only the abdomens of the animals were
of which were compromised with bacterial or irradiated with 830 nm LED-LLLT, and at the
viral infection (Fig. 18.26) [52]. As for more 6-day assessment point the indirectly LED-LLLT
difficult targets, LED-LLLT has shown excel- treated wounds were significantly better healed
lent and lasting results in treating psoriasis [69], than the unirradiated controls [72]. A study with
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a b e f
c d g h
Fig. 18.26 830 nm LED-LLLT in the control of inflam- treated elsewhere. Numbness and slight palsy also
mation and infection. (a) Fifty-two y.o. male with post- reported. (f) Improved condition after 1 week of five daily
filler ischemic ulcerative tissue necrosis, inflammation 830 nm LED-LLLT sessions. HS lesions are resolving with
and severe pain. (b) Two weeks post escharotomy without significant reduction in swelling and removal of palsy
flap and LED-LLLT sessions every other day. Pain was with return of sensation. Pain has been totally controlled.
controlled post 3 Tx. (c) Findings at 3 weeks post base- (g) Almost complete improvement, including HS
line. Wound closure continues with good granulation tis- infection, at 2 weeks post-baseline, treating every other
sue formation. (d) Final condition 6 weeks post-baseline day. (h) Final excellent result 3 weeks post-baseline with
and 1 week after the final Tx. Further improvement can be no HS recurrence in a 3-month follow-up. Clinical pho-
expected. (e) Fifty-four-year-old female with swollen lips, tography courtesy PK Min MD. System used: HEALITE
fever, severe pain, herpes simplex (HS) and bacterial II 830 nm, Lutronic, South Korea
infection following an illegal lip tattoo, unsuccessfully
830 nm on recalcitrant crural ulcers showed not only brings in oxygen and nutrients, but
accelerated healing [73]. Near IR 830 nm does not establishes a higher oxygen tension in the treated
only work in soft tissue wounds, but also in bone area which can establish gradients between the
where it accelerates the union of fractures, even in wound at the surrounding tissue, used as ‘super-
the case of delayed union healing, replac- ing the highways’ by the reparative cells [78]. In the case
usual poorly-organized callus with better- quality of bony tissues, 830 nm has been shown to
bone so that the remodeling stage is much shorter increase the metabolism of osteoblasts [79], and
[74, 75]. to upregulate some of the genetic pathways lead-
Some of the mechanisms behind the efficacy ing to better differentiation of new, active osteo-
of LED phototherapy-accelerated wound healing blasts from mesenchymal cells [80].
have already been at least partly elucidated, such In conclusion, the application of LED-LLLT,
as the wavelength-specific activation of the der- either 830 nm followed by 633 nm, or particu-
mal and epidermal cells associated with the three larly more recently, 830 nm on its own, has been
phases of wound healing. in a chapter of her lat- shown to enhance all aspects of wound healing,
est book (Ten Lectures on Basic Science of Laser always provided the incident irradiance (power
Phototherapy. 2007, Prima Books AB, density, photon intensity) is sufficiently high and
Grängesberg, Sweden), Karu has suggested that an appropriate dose is given. In addition to the
the latency effect of phototherapy in cells actu- excellent and growing reputation of LED photo-
ally continues in subsequent generations of the therapy as a stand-alone light-only therapy, this
irradiated cells which is an important consider- means that LED-LLLT has proved to be an ideal
ation in skin rejuvenation [76]. Another impor- adjunctive therapy to any of the conventional
tant mechanism involves improvement of blood approaches seen in dermatological practice and
flow following irradiation with 830 nm, and this this is perhaps the most exciting aspect of LED
has been shown to positively impact on flap sur- phototherapy in the future [53, 54]. No matter
vival in the rat model [77]. Improved blood flow how the aesthetic and cosmetic dermatologist
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alters the epidermal or dermal morphology of his cerebral trauma [81–83]. With these reports,
or her patient, be it through microdermabrasion, taken together with the already well-proven effect
ablative and nonablative skin rejuvenation, frac- of 830 nm on improving blood flow and its ability
tional technology or conventional surgery, the to pass through the skull and measure blood flow
addition of an appropriate LED phototherapy and cerebral activity in vivo in a noninvasive
regimen will help to improve already good results manner [84, 85], the indication of LED- LLLT
but at a very reasonable cost, thus improving the transcranially for the treatment of simple senile
satisfaction rates of both the clinician and the dementia, but not Alzheimer’s, merits some deep
patient. Many clinics in Australia now buy an thought. The more we can find for LED-LLLT to
830 nm LED system and add 830 nm LED-LLLT do, the more ideas will appear.
as an adjunct to anything done to their patients,
but at no cost to the patient. This value-added
treatment has resulted in excellent results, happy Box 18.5
patients and an ever-increasing number of patient • LED-LLLT is intrinsically safe
referrals, hence happy clinicians as well. • Eye protection sometimes required
against potential optical hazards
• LED-LLLT is essentially side effect
Other Clinical Indications free
• Few contraindications exist, but sen-
The indications already discussed have been sible precautions should be taken
well-researched, and are being reported in the – Patient history must be checked for
literature. Some other applications exist which any photosensitivity-related diseases
are very much at the experimental stage, but or conditions.
which should be mentioned to prepare the reader – Drugs, ointments and even cosmetics
for what’s coming in the not-too-distant future being used by the patient must be
and for which LED phototherapy is proving very checked for photosensitizing elements.
interesting. At this stage the author cannot go
into details, because of the early stage of the
clinical and related basic science experiments,
but the reader should watch for articles on the Safety with LEDs
potential use of LED phototherapy in combina-
tion with platelet-rich plasma (PRP) for wound Surgical lasers and even intense pulsed light sys-
healing and for skin rejuvenation. PRP is well- tems are by their very nature designed to create
established as a valid method in wound healing to thermal damage and are thus subject to stringent
speed up the process and give good cosmesis or safety codes to prevent accidental irradiation of
in recalcitrant healing situations. Knowing how tissue, other than the planned target tissues.
cell-specific certain LED wavelengths are, the Because LEDs are incapable of creating photo-
obvious step is to combine the two approaches to thermal damage in tissues, the same stringent
achieve even better results, even faster. Some codes regarding accidental irradiation of tissue do
studies are currently well underway in Tokyo, not apply. However, as all of the LED systems
and the results in a split-face study with 830 nm discussed above operate in the visible and near
vs. unirradiated indicate that this will be a field to infrared waveband, there is a potential for opti-
watch closely (Junichiro Kubota MD PhD, cal damage, as the eye is capable of gathering this
personal communication and as yet unpublished waveband and focusing the light onto the retina at
data). Another emerging field is the transcranial the back of the eye, particularly the macula and
indication of LED-LLLT, usually at 830 nm or a fovea, the area responsible for visual acuity. This
similar near-IR wavelength, for post-stroke will be looked at in a little more detail below.
patients, and those who have suffered severe
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Most LED phototherapy systems are run from Optical Hazards with LED
conventional mains electricity, and so present Phototherapy
potential hazards in common with any other such
mains-driven equipment as, for example, DVD As already mentioned above, any LED system
players and television sets. Common sense dic- operating in the visible to near-infrared wave-
tates the safe handling of this group of equip- band emits light which the human eye can gather,
ment, leading to the following guidelines: and focus onto the back of the retina as illustrated
in Fig. 18.27. If the incident power density is great
DO NOT connect or disconnect the mains plug enough, permanent damage to the fovea could
with wet or damp hands occur leading to uncorrectable loss of visual
DO NOT pull the plug from the mains socket acuity. For example, an incident power density
using the power cable from a laser source of as low as 75 mW focused
DO NOT place any containers with liquid in to a 50 μm spot produces a power density of over
them on top of the unit (e.g., coffee mugs) to 3800 W/cm2, perfectly capable of severely
prevent damage from accidental spillage. If damaging target biological tissue. However, a set
such spillage should occur immediately turn of values has been established for the maximum
off the system and have it serviced before permissible exposure, or MPE, to light at a range
using it again. of wavelengths, and these values are significantly
DO NOT attempt to perform and unauthorized lower for LEDs compared with laser sources,
servicing of the system which involves open- because lasers emit coherent light, and LEDs emit
ing up the case and/or defeating any interlocks. a divergent beam of noncoherent light. If an LED
DO connect the mains cable to the system before phototherapy system has been independently
plugging the mains plug into the socket tested to deliver light below the MPE for its
DO check that the power to the wall socket is off nominal wavelength, then even prolonged direct
before inserting the mains cable plug viewing of the beam is theoretically safe.
DO switch off the wall socket before removing In clinical practice, however, visible light LED
the mains plug arrays are extremely bright, even when below the
MPE for their wavelength, so some form of eye
Apart from these rather obvious points, common protection is usually a good idea if only for patient
sense should prevent any electrical-related dam- comfort. Small, opaque eye cups held in place
age to therapist or patient. with an elasticated cord are popular, which will
still allow the light to reach the periocular region
Focused spot at fovea = 50 mm dia.

Power density at fovea ≈ 3,820 W/cm2
λ = 670 nm ∼ 904 nm
75 mW, pupillary opening 1 cm

Power Density at cornea:
approx. 590 mW/cm2
Fig. 18.27 Schematic illustration of how a low incident the fovea. Although noncoherent and uncollimated LEDs
power of 75 mW from a laser beam is capable of being are significantly more intrinsically safe, the importance of
focused by the unaccommodated eye into a very small appropriate protective eyewear should always be consid-
spot, with damaging power densities, right in the center of ered. Common sense should be applied
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in the case of LED phototherapy for skin rejuve- tem’s having gone through the due regulatory
nation. However, if the system delivers light which process to obtain what is known as a 510(k)
is over the MPE, then protective eyewear becomes approval showing significant equivalence to
mandatory for the patient, and also for any another system with prior approval based on
ancillary staff spending any length of time in the which, and only on which, can that device be
treatment room to help protect their eyes against legally sold in the USA for clinical use. 510(k)
diffuse reflection from the target tissue. For approvals for existing LED systems can be
shorter visible wavelengths such as the blue searched for on the FDA website (www.fda.gov/
waveband, the inherent photon energy of the light cdrh/510khome.html), and the systems already
is approximately one-third as high again as visible mentioned by name earlier in this chapter all hold
red light even though the incident power density is such clearance.
the same, as discussed above, and so has greater
potential for optical damage. Appropriate eye-
wear is necessary in this case. Side Effects
The ‘blink reflex’ is nature’s way of helping us
protect our own eyes against an over-bright visi- Once again, the inherently ‘safe’ output of LED
ble light source, but near-IR light cannot be systems helps to keep unwanted side effects to a
‘seen’ by the human eye and so the blink reflex is minimum, but with any kind of phototherapy
not triggered by energy in this invisible wave- there is always the outside chance of triggering
band. Near-IR is still gathered and focused by the such a side effect. These are almost 100%
unaccommodated eye just as visible light is, how- photosensitivity-related, so a careful history of the
ever, so suitable protective eyewear is thus man- patient must always be taken to identify the
datory for LED systems delivering energy in the existence of pre-existing photosensitivity issues.
near-IR waveband above the rated MPE for the For example, if a patient reports that he or she
wavelength being used. regularly comes out in an itchy rash when exposed
Clinician goggles or glasses are obviously not to terrestrial sunlight, LED phototherapy,
opaque, so they have to be specifically sourced especially in the visible light waveband, should
with an appropriate optical density for the wave- not be given. Some skin types, such as the Asian
length of the system. Eyewear designed for red skin, are incredibly sensitive to epidermal
light will not protect adequately against IR or vis- inflammation caused by other wavelengths
ible blue light, for example. The eyes of the despite being very resilient to UV skin damage.
patient, and indeed anyone with the patient in the Particularly in the Asian skin, secondary hyper-
treatment room during LED therapy, must be pigmentation (PIH) can occur without any appar-
assiduously protected even though LEDs are ent physical insult, and a carefully-taken history
often discounted as inherently ‘safe’, compared will show if the patient is predisposed to this very
with a surgical laser or IPL. It is better to err on upsetting side effect. A very small proportion of
the side of caution! patients treated with LED therapy have reported
Finally, national and federal regulatory agen- post-treatment headaches of varying magnitudes,
cies, such as the US Food and Drug Administration all of which have resolved spontaneously. No
(FDA), issue approvals of systems for specific reason has been elucidated for this, and treatment
applications for which they have been proved with mild analgesics has been found to speed up
‘safe and effective’. Although some manufactur- the resolution of the headache. Almost all of
ers have received such approvals, they are few and those so afflicted have been undergoing LED
far between. Some less than truthful manu- phototherapy for facial skin rejuvenation, but
factures will claim FDA approval, when in fact all interestingly only a very few have actually
they hold is a letter from FDA recognizing that stopped turning up for their treatments. The main
their LED system is a nonsignificant risk point is to take a very careful and thorough patient
device, or NSRD. This is NOT the same as a sys- history to identify the potential of any
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LED therapy-related problems, but they are very energy in a favorable in vitro environment will
much extremely few and far between. For longer replicate at a much faster rate than control cells.
sessions of LED phototherapy, for example in However the in vitro environment is totally dif-
facial skin rejuvenation, the main “side effect” is ferent to the living body, where the cancer cell
that the patients tend to fall asleep during the is seen as an out-and-out enemy by the autoim-
treatment and ‘wake up’ feeling great! mune system, and is in a very unfavorable envi-
ronment surrounded by potential killer cells. As
mentioned above, the very first application of
Contraindications red LED PDT phototherapy was in the treat-
ment of skin cancers, and application of low
Leading on from the previous subsection, any incident levels of light have been shown to
kind of endogenous or exogenous photosensitiv- cause regression or even complete removal of
ity is a contraindication to LED phototherapy. aggressive tumors in animal models [86], and
Patients with any form of porphyria, for example, induce significantly prolonged survival times in
should never be treated with LEDs. Those whose terminally-ill cancer patients [87]. Furthermore,
history includes solar-mediated eruptions are low incident levels of light energy have been
likewise not good subjects. The careful derma- shown to boost the autoimmune system. Once
tologist should also ascertain what the patients are again, however, discretion should be used in the
putting on their skins prior to an LED therapy case of a patient with a cancerous condition
session. Ointments or creams containing known who is seeking LED phototherapy for some-
photosensitizers such as coumarins or porphyrins thing else at a site distant from the cancer, such
must be discontinued at least 2 weeks before any as skin rejuvenation. As a final note, in the more
LED treatment. Some oral drugs, e.g., amioda- than four decades since the laser and other light
rone for cardiac arrhythmia sufferers, strongly sources have been used in medicine and sur-
photosensitize patients to UV and visible light: gery, not one case of iatrogenic, phototherapy-
LED phototherapy in such patients is contraindi- linked cancer has been reported in the
cated. Even some perfumes contain recognized literature.
photosensitizers. The application or ingestion of In short, LED phototherapy systems from
photosensitizing drugs including systemic reti- reputable manufacturers are inherently safe,
noids and the recent use of topical retinoic acid provided they are used according to the manu-
should also be carefully considered, and some facturer’s recommendations regarding eye pro-
acne treatments such as Roaccutane® (isotreti- tection, and approved treatment protocols.
noin) are all contraindications. LED-LLLT systems are basically side-effect
Other potential, possibly more ‘emotional’ free, apart from the beneficial side effects, and
contraindications include patients who are preg- will give continue to deliver side-effect free
nant or lactating, although these are not as abso- therapy provided the list of contraindications
lute as the in the previous paragraph and if the discussed above, and always provided by
LED therapy is not being delivered over the womb responsible manufacturers, is carefully applied,
as in the case of facial skin rejuvenation for in addition to the taking of a careful patient his-
example, then it can be given at the discretion of tory. However, as already said, not any old LED
the treating clinician, and with the informed system will do, and the careful dermatologist
consent of the patient. In fact, possible benefits must ensure that the system has appropriate
may well accrue to both the mother and fetus from quasimonochromatic wavelengths, appropriate
the systemic nature of blood-borne beneficial photon intensities over a sufficiently large area,
photoproducts. has a proven track record in the published litera-
The most emotional contraindication is for ture and has marketing approval from regulatory
patients with some form of cancer. It is true that bodies such as CE marking and US FDA
cancer cells irradiated with visible/near-IR clearance.
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ATP production, although in practical clinical

Box 18.6 application this waveband is extremely lim-
• ‘New’ LED wavelengths not likely, ited by its poor penetration into the dermis due
but possible to absorption in the biological pigments mela-
• Further technical advances may nin and hemoglobin, which are its preferential
increase the scope of LED-LLLT chromophores. However, this waveband also
• Potential for LED-LLLT in the home has potential in the treatment of inflammatory
and OTC market rosacea and other very superficial entities. In
• LED-LLLT is safe, effective, easily addition, the epidermal keratinocytes and
applied, side effect-free and well- Merkel cells also present an interesting target
tolerated by all patients. as a form of dermal preconditioning when vis-
• Effective as a stand-alone light ther- ible yellow treatment is followed by 830 nm.
apy, LED-LLLT will also prove even One FDA-cleared LED system (HEALITE
more invaluable in adjunctive ther- II™, Lutronic, Goyang, South Korea and
apy to complement all existing modal- Freemont, CA, USA) uses the combination of
ities in dermatological practice. a period of irradiation with 595 nm-only ultra-
low-level light therapy followed by the appro-
priate dose of 830 nm near-IR energy as the
main treatment beam. The advantage of this
LED Phototherapy: Quo Vadis? lies in the fact that the yellow component con-
tinues to operate while the 830 nm beam is
There is no doubt that LED phototherapy has active. Although there is no longer a clinical
come a very long way in less than two decades, utility, the visible yellow light shows that the
with the ‘NASA LED’ being introduced in 1998. system is operating, a real benefit for the
The big question now is, where can it go? I believe patient as they can see that something is hap-
the answer depends on three main areas: pening, not the case where the invisible near-
wavelength; other technical developments; and IR at 830 nm is used on its own.
applications. • Visible red light from 620 to 680 nm, with a
‘best case’ at 633 nm because of the minor
absorption peak in the action spectrum of the
New Wavelengths porphyrins associated with exogenous 5-ALA
PDT, the major peak in the absorption spec-
It is possible that a ‘new’ (and useful) wavelength trum of cytochrome c oxidase, and its deep
will be ‘discovered’, but unlikely. Having said penetration into living skin. 633 nm is an
that, at the time of writing 1072 nm LED photo- excellent wavelength to activate fibroblasts in
therapy has attracted a great deal of attention in vivo even in the deeper dermis. It is also
the treatment of herpes simplex labialis, or cold attracting attention in hair loss and hair resto-
sores as mentioned above. Apart from that, The ration. This wavelength also has a tremendous
current main wavelengths are: published database, because it is the same as
the HeNe laser (632.8 nm).
• Soret band short wavelength visible blue light, • Near infrared at 830 nm, because it has the
with the optimum peak at 415 nm, the peak of deepest penetration of any wavelength due to
the action spectrum of the porphyrins endog- its being at the bottom of the water absorption
enous to P. acnes and created in skin treated curve, and has a well-proven track record as
with 5-ALA. the most useful laser therapy wavelength in
• Visible yellow at 590–595 nm, at a peak of the near infrared diode laser therapy for musculo-
action spectrum of cytochrome c oxidase in the skeletal and neurogenic pain, enhancement of
mitochondrial redox chain to instigate local blood and lymphatic flow, and wound
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healing. This wavelength as delivered by acted in coordination with the photoabsorption

LEDs now has a good body of literature show- effects to give excellent bone healing, even in the
ing preferential effects in degranulation of case of slow union fractures [74]. No LED photo-
mast cells, photoactivation of neutrophils and therapy system is capable of delivering a true
macrophage cells with associated release of pulsed beam, and simply modulating a continu-
trophic factors, and enhanced remodeling in ous wave beam of tens or even hundreds of mil-
the wound healing process. liwatts per square centimeter will not produce the
same effect as the very tightly delivered, narrow
There are now many LED devices currently pulse-width true pulsed diode laser beam, so this
available that have wavelengths the same or very wavelength is also not an appropriate one for an
near to those given above, but we have to remem- LED system, given that one of the main advan-
ber that in many cases an action spectrum peak tages of LED arrays is the ability to irradiate a
has very narrow shoulders, so a difference of even large area of tissue rather than a very small treat-
5 nm from the peak can in some cases dra- ment target. In all of the wavelengths bulleted
matically lower the action potential. There are above, and in their clinical application, the tar-
other wavelengths which have been proved use- gets are not precise points, and the ability to irra-
ful in the laser therapy literature, in particular diate a large tissue mass is an advantage. Despite
780 nm for neurological applications and 904 nm the present and future claims, I do not believe that
for dental and other hard tissues, including bone. we will see a ‘new’ and clinically proven
In the case of neurological indications, such as wavelength for light-only LED phototherapy in
repairing transected or crushed nerves, the punc- the near future.
tal nature of laser energy with its extremely high
photon intensity delivered within the very small
treatment area is essential to the treatment tech- New Technical Developments
nique: it is impossible to concentrate LED energy
from an array onto such a small spot, so LED sys- LED technology is constantly evolving, as seen in
tems at this wavelength would simply not have the the current transition from the individually board-
same effect as a laser diode-based handpiece mounted dome-type LED to the latest generation
(coherent LD-LLLT vs. noncoherent LED- of ‘on-board’ chips which are actually part of the
LLLT). In the case of 904 nm in hard tissue, the circuit board. There has been speculation about
laser systems used were based on a GaAs (gal- developing whole-body LED arrays, particularly in
lium arsenide) laser diode. GaAs laser diodes are the sports medicine and sports clinic environ-
capable of generating peak power outputs in the ment, so that athletes could have a complete LED
range of 15–45 W, but cannot be operated in con- ‘photobath’ after a strenuous workout to help relax
tinuous wave because of the tremendous heat they overused muscles and dissipate lactic acidosis,
generate and the need to provide a dedicated thereby enabling total retention of tonus in a delib-
cooling system. The GaAs laser diode is there- erate overtraining program to reach absolute peak
fore operated in a true pulsed mode, with pulse power and stamina. The application of such whole-
widths in nanoseconds and interpulse intervals of body arrays in the spa and beauty market would
milliseconds, so the average power seen by the also be very interesting. Some systems already
tissue is in milliwatts, usually 3 orders of magni- exist. The problem with such large arrays of good
tude less than the peak power: a 15 W peak power quality LEDs is heat. LEDs do not in themselves
would this give an average power at the tissue of generate a lot of heat because they are solid state,
15 mW. However, these ultrashort pulses create but when mounted in arrays they require on-board
effects in tissue other than photoabsorption, such driver circuitry, and this does generate a fair
as photoosmotic and photoacoustic effects. In amount of heat which must be dissipated other-
hard tissues such as bone, it was therefore pro- wise overheating of the LEDs will result in move-
posed that a physical resonance was set up which ment away from their rated wavelength, in addition
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to shortening of their useful life. Efficient cooling ately selected LEDs are concerned. There are
of the circuit boards is thus essential and this is not already a large number of very pretty colored,
an easy matter even with the current size of arrays, happily twinkling LED-based systems being
to the extent that the method of cooling has actu- touted as suitable for home use, however the vast
ally been patented in some systems. In order to majority of them are mere toys, especially the
cool the number of large arrays which would be ones with multicolored LEDs, and the poor user
necessary for a whole-body LED generator would might as well stand in front of their christmas tree
require a dedicated and powerful cooling system, lights as use these systems. This does not mean
and this raises the dual problem of developing an that responsible manufacturers have not been
appropriate method of extracting heat, whether it researching correct combinations of appropriate
was based on air- or water-based cooling, and wavelengths and intensities in ergonomically-
where the heat extracted from the LED arrays designed hand-held self-contained units which
would go. In a small treatment room, the heat will be safe and effective for home use: some
build-up could be very noticeable, as was the case indeed have. These units have become available
in the first generation of large surgical laser sys- in a number of ways: for pre- scription by a
tems. The development of on-board chips has gone dermatologist or other specialist as a maintenance
some way to solving this problem, and the program for their in-office LED treatment
emergence of electrostatic cooling systems which regimen; as an over-the-counter product from
could be built directly into or onto the LED boards chemists or pharmacists with product- related
is very interesting. This is a field which will be training; or from reputable self-health mail-order
very interesting to watch. companies. The author is aware of one company
Another area for development may well be in who has two such self-contained hand-held
the optics of the LEDs themselves. Currently products, one blue/red for treatment of acne, and
LEDs deliver a divergent beam, typically in the one infrared/red for skin rejuvenation, which
region of 60°–120° steradian. It is the deliberate have achieved FDA 510(k) clearance. Despite
overlapping of these divergent beams that causes their size, they have the same high quality LEDs
the phenomenon of photon interference, which, delivering the same intensity in mW/cm2 as the
coupled with scattering of light in target tissue, medical versions of the systems based on LED
allows LED arrays to deliver very useful photon arrays. When used for the recommended time
intensities over large areas of tissue. As men- they will thus deliver exactly the same dose as
tioned already, corrective collimating optics have their much larger cousins. Naturally they cover a
already been used in one system to reduce the very much smaller area than the full-sized planar
angle of divergence of LEDS in an array, thereby arrays, but because of their lightweight nature, it
giving a higher photon intensity for the same irra- is anticipated that the user will be able to watch
diance at the LED. However, LEDs are nonco- TV or listen to music while irradiating the target
herent, so it is extremely challenging to collimate area one bit at a time, and they will be absolutely
the beam of light from an LED completely, unlike ideal for a maintenance program following
the case of the laser diode in the ubiquitous laser office or clinic treatment with the full-sized
pointer. Likewise, focusing an LED to a very systems. Home use LED- LLLT is therefore yet
small point, as can be achieved with a laser another area to be watched with great interest.
source, is impossible, and the most efficient
focusing lens would produce simply a very small
inverted image of the LED. Semi-collimation Applications: Combination Is Key
would appear to be the limit for altering the beam
of energy from an LED, unless there are advances The applications for light-only LED photother-
in chip technology. apy continue to grow in a pan-speciality manner,
The final area is the home market, which is tied so that a large range of clinicians is finding useful
into the previous subsections as far as appropri-
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applications for LED phototherapy of appropri-

ate wavelength and incident photon intensity. Box 18.7
However, as with lasers, a saturation point will • LED phototherapy is here to stay!
be reached. This can be combatted by using • ‘Any old LED’ will NOT fit the bill!
LED phototherapy in combination with existing • When considering buying an LED
conventional surgical and nonsurgical system, ask the right questions!
approaches to achieve even better results. A per- • Combination treatment is the key!
fect example where this is happening is full face
laser ablative resurfacing. Initially hailed as a
superb approach to rejuvenating severely photo-
aged skin, in recent years it has declined dra-
Conclusions (And Questions
matically in popularity because of potential side
You Should Ask)
effects such as scarring, unpleasant-looking
LED phototherapy is certainly here to stay, but
sequelae and a very long downtime before the
unfortunately the medicoscientific waters are
patient can once again return to work or to soci-
being muddied by a number of manufacturers
ety. However, everyone agrees it is still the ‘gold
who have jumped on the LED bandwagon, mak-
standard’, particularly for deep wrinkles and
ing extravagant claims and barefacedly using the
severe photodamage. Some reports have now
data amassed by those companies who have been
appeared on the use of LED phototherapy
responsible enough to go through regulatory
together with ablative laser resurfacing. The
approvals, such as FDA 510(k) clearances, as if
controlled study already discussed above by
the data were their own. Statements such as ‘….
Trelles et al. is an excellent example which
uses NASA technology ….’ are common, but
compared two groups of full-face ablative resur-
totally misleading. The current generation of
facing patients [56]: one group was also treated
LEDs actually exceeds the 1990s NASA technol-
with LED phototherapy, and the control group
ogy as far as output power and quasimonochro-
was not, but otherwise the resurfacing and wound
maticity are concerned, and in fact have
care regimens were exactly the same. The
absolutely nothing to do with NASA! Even worse
healing time in the LED-treated group was cut by
than these manufacturers are the companies which
more than one-half, postoperative pain was cut
import ‘lookalikes’ from the Eastern block. They
by more than 70% and the erythema cleared in
may be cheap, but they are certainly not cheerful,
less than 7 weeks compared with up to 4–6
and the heart of an LED system is the quality and
months.
pedigree of the LEDs used in its arrays: you get
LED phototherapy can and does offer even
what you pay for. To make sure you get what you
better results in any case where the dermatologist
actually want, i.e., an LED phototherapy system
has in some way altered the epidermal and der-
that will actually do something that you want it to
mal architecture of his or her patient, whether it is
do, and make you and your patients happy, please
as mild as an epidermal powder peel, through
see the following, which will not only summarize
chemical peels to nonablative resurfacing with
the main points of the chapter but will also
lasers or IPL systems, fractional laser and non-
reinforce my favorite maxim which is; ‘Any old
laser approaches, like microneedling radiofre-
LED will NOT do’.
quency, and full-face ablative resurfacing. The
adjunctive application of LED phototherapy will,
I believe, drive its acceptance even more strongly Caveat Emptor (Let the Buyer
than its use as a stand-alone modality, and the Beware!)
major advantage of LED-based systems is their
very competitive pricing in addition to their por- When considering purchasing an LED-based
tability and versatility. Combination therapy is the phototherapy system for his or her practice, the
key [53, 54]. wise dermatologist should always ask the manu-
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facturer or salesperson the following questions While on the subject of wavelength, some
(and take a written note of verified or verifiable manufacturers offer all the colors of the rainbow
answers!). in the one system, in one particular system
mounted in a semicircular bar which scans over
What Regulatory Approvals Does the face with the claim that ‘blue is for serenity,
the System Have? green is for inner peace, yellow is for well-being,
This means appropriate FDA 510(k) approvals in and red is for relaxation’. In fact, this manufac-
the USA (no LED system has yet got full premar- turer is not offering phototherapy, but ‘chromo-
keting approval, PMA), Health Canada in therapy’ also known as ‘colorology’ which is an
Canada, TGA in Australia, Ministry of Health, alternative medical approach based on ‘chakras’
Labour and Welfare (Kohseishou) in Japan, and their associated colors to achieve balance in
appropriate CE marking for medical devices in an unbalanced system [88]. As with reflexology,
Europe, and so on. It does not mean having the origin of the approach is Russian, as is a great
‘NASA technology LED’s’ or ‘Approved by the deal of the literature, but chromotherapy has a
FDA’, the latter of which usually simply means a large following. The methods and English lan-
letter from FDA recognizing that the system is a guage studies used to prove that it works, how-
nonsignificant risk device (NSR) or minimal risk ever, have been severely criticized [89]. In
device (MSR). This is not an approval to market, addition, as Karu and colleagues have well-
but is simply a guide based on which the institu- demonstrated, the intermingling of wavelengths
tional review board (IRB) of a research center way well include some which cancel each other
can classify the system when it does take part in out thus having no effect, or indeed downregulate
a properly structured study. cellular activity compared to the wavelengths
applied individually [12]. The fact that the light is
What Is (Are) the Wavelength(s)? scanned over the face should sound another
As has been said many times, wavelength is the warning bell, since this dramatically lowers the
most important single factor when attempting to dose, even if the photon intensity were high
achieve a photoreaction: no absorption, no reac- enough (which it is not). The answer? Keep to
tion. Some targets can respond to a fairly broad well-proven wavelengths, applied singly and
waveband of 30–100 nm or so, but most of the with a suitable period (48–72 h) allowed between
targets in LED phototherapy are much more applications to allow the targeted cells to respond
specific. Ask what the nominal wavelength of to the information they have received.
the system is, and what is the deviation either
side. For example, the Omnilux revive™ and What Is the Intensity?
HEALITE II mentioned elsewhere in this chap- You are looking for an answer here in mW/cm2
ter have LED arrays with a nominal wavelength, (milliwatts per square centimeter) of the entire
with the range of ±5–7 nm. That means that array, not the ‘lumens’ of an individual LED or
93–95% of the photons are at the rated wave- indeed the whole array, nor should you be told that
length and will therefore optimally target the system is “very bright”. If in doubt about this
wavelength-specific chromophores at that wave- parameter and its paramount importance, next to
length such as 633 nm for cytochrome c oxi- wavelength, please re-review section “Irradiance
dase, and 415 nm for the porphyrins Cp III and (Photon Intensity)” above on photon density,
Pp IX endogenous to P. acnes. Visible red at another way of saying ‘intensity’. A good range,
670 nm, for example, will still have some effect depending on wavelength, would be anywhere
on cytochrome c oxidase, but that wavelength from 40 mW/cm2 up to 150 mW/cm2, although
just misses the boat as far as peak efficiency of the higher the intensity, the more problems will
exogenous porphyrin activation is concerned for exist in keeping the LED array cool enough to
ALA PDT, where 633 nm is the wavelength of avoid discomfort to the patient and a drift away
choice. from the LED nominal wavelength. If
333
333 333
333
this range seems low compared with a diode laser manufacturer will have arrived at by conducting
therapy system, for example, always bear in mind dose-ranging response-related studies. If the rec-
that the better LED systems cover a large area of ommended dose is, for example, 120 J/cm2 over
tissue, for example some offer an active array area 20 min, increasing the irradiation time by
of 220 cm2, unlike the laser therapy system which 10–30 min will not get a 50% better effect, but on
usually irradiates a spot of only a few mm in the other hand, cutting the time down by half to
diameter per ‘shot’. 10 min may well give a result well below 50% of
If you get an answer in joules, ignore it … bet- that achieved at the recommended time. If an
ter still, laugh loudly. If you get an answer in LED-LLLT system supports arrays with different
joules per square centimeter (J/cm2), that’s better, wavelengths, the manufacturer may well have
but it is actually the answer to the next question! standardized the treatment time to the same for
The incident intensity or power density is each of the heads, but the dose will almost always
extremely important, because a higher power be different for each wavelength, simply because
density enables a shorter irradiation time, and it of a combination of LED characteristics, wave-
has been reported for a continuous wave system length/tissue interactions and the individual pho-
that shorter irradiation times with a higher inten- ton energy associated with each wavelength.
sity got significantly better results in first passage
human gingival fibroblast proliferation in vitro How Should the LED Energy
compared with longer irradiation times at a lower Be Delivered?
intensity, even though the dose (in J/cm2) was the The answer here will be ‘in continuous wave (or
same [90]. Of course, the Arndt-Schultz curve CW)’, which is good; or ‘frequency modulated
must always be remembered (section “Irradiance (also known as photomodulated)’ which is not so
(Photon Intensity)” above), and the upper limit of good; or ‘pulsed’, which is actually the incorrect
photoactivation must never be exceeded or a pho- way of saying the second answer and is totally
tothermal reaction will occur. wrong! Light at a given wavelength already con-
tains its own frequency, as discussed in section
What Is the Recommended Dose? “Temporal Profile of the Beam” above, and light
This is where the J/cm2 unit should be the correct represents ‘information’ to cellular targets.
answer, but NOT the dreaded joule. If you see a Imposing a secondary frequency on that primary
joule running around an LED system, kill it. As frequency can not only disrupt the flow of infor-
discussed above, the joule is simply a unit of mation, it also cuts down on the dose since there
energy and has no significance whatever on the is no light incident on the target cells when the
clinical effect in a prescribed area of target tissue. source is switched off. It is true that cells have a
Correlate the dose with the recommended irradi- ‘dark reaction’ time as shown by Karu [91], but
ation time. As a matter of interest, if you cannot it occurs well after irradiation, and not in the short
find out the intensity from the manufacturer, by off-duty interval in a frequency modulated beam
dividing the dose (J/cm2) by the irradiation time cycle. Figure 18.28 is by an independent research
(in seconds), you will end up with the intensity in group, Almeida-Lopes and colleagues at the
W/cm2 (or mW/cm2). University of Sao Paulo, Brazil, who reported the
For this category, there is no ‘correct’ dose for data on power density in Ref. [90] above, and
an LED-LLLT system, although it should cer- shows the growth pattern of first passage human
tainly be no lower than 20 J/cm2 depending on gingival fibroblasts exposed in vitro to 640 nm at
the wavelength. If the intensity or power density several frequencies and continuous wave (CW),
is correct, then it is almost impossible to over- with constant incident power density and dose
dose. Overdosing is not recommended, however, as ascertained in earlier studies. There was a
simply because it wastes time and will not often significant difference seen between the group of
produce dramatically better results than the frequencies and the unirradiated controls (p >
recommended dose, which the responsible 0.01 for all), with the higher
334
334 334
334
70 Incident radiant flux (dose): 2.25 J/cm2 can produce to look like a genuine publication,
60 Incident power: 56 mW although they may actually contain good data, or
λ = 640 nm
Cell count x 1000
50 Continuous wave articles from the commercially-oriented medical

180 Hz
40 120 Hz ‡
press unless they are also in turn backed up by
60 Hz
30 10 Hz
‘real’ papers. All of the referenced works in this
Control chapter are either from peer-reviewed PubMed
20
listed journals, or books from reputable publish-
10
ers. Also, make very sure that the articles offered
0 by the manufacturer/salesperson are on their
0 2 4 6
Time (Days) specific system and wavelength(s). Very often
articles on approved systems by another manu-
Fig. 18.28 An in vitro experiment to assess the effects of facturer will be cited as ‘proof’ that their (unap-
various frequencies in frequency modulated beams com- proved) system works, even though sometimes
pared with a continuous wave beam and an unirradiated
control on the cell proliferation of first passage pooled
the intensity, dose or even wavelength is not the
human gingival fibroblasts. The dose was kept constant at same as in the published articles.
2.25 J/cm2. All of the frequencies were statistically signifi-
cantly better at increasing proliferation (§, p < 0.01 for all).
The CW beam, however, was significantly more efficient
than both the control and the frequency modulated beams
Finally ….
(‡, p < 0.001 and §, p < 0.01, respectively). The results
represent the averaged data from ten repeated experiments. Despite the moaning of the sceptics, LED photo-
(Used with the permission of Pra. Luciana Almeida- therapy has definitely arrived, has been proven to
Lopes, personal communication, data as yet unpublished)
work in many areas, and is finding a rapidly
increasing number of applications both within and
frequencies inducing better cell proliferation,
outside dermatology. LED-LLLT systems are
but the continuous wave beam induced greatest
comparatively inexpensive and robust, LED-
and most significant proliferation compared with
LLLT itself is easy to administer, safe, effective,
both the unirradiated controls (p < 0.001) and the
pain free (in fact it can be used to treat pain), side-
frequency modulated beams (p < 0.01). The
effect free, well-tolerated by patients of all ages
experiment was repeated ten times and the
from infants to centenarians, and minimally
results averaged. (Data and graph reproduced
contraindicated. It offers the possibility of a stand-
with the permission of Pra. Luciana Almeida-
alone noninvasive phototherapy method, but when
Lopes, as yet unpublished data). Cells, espe-
used together with any of the methods currently
cially first passage human gingival fibroblasts,
used by the dermatologist to alter his or her
seem to prefer CW to frequency modulated
patient’s skin, already good results can be
energy.
expected to become even better. LED photother-
apy will not turn a poor dermatologist into a good
What Has Been Published
one, but it will help the good dermatologist to
on the System/Technology?
become even better, with happier patients. And
What you are looking for here are papers by rep-
finally, please remember, above all, not any old
utable authors published in the indexed and peer-
LED will do the job!
reviewed literature, or at least in well-established
and peer-reviewed journals (15 or more volumes)
which have not yet been indexed by MedLine
and/or PubMed but which do none-the-less have
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Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice

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Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice

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Current Status of Light-Emitting

Abstract and Romans used the healing power of the sun,

© Springer International Publishing AG, part of Springer Nature 2018 285

famous patient was King George III of Great

Direction of motion d Current flows through

Table 18.1 Most common substrate combinations and

and so can never be focused to a small point. Laser

Why Use LEDs?

a laser (e.g., HeNe)

possibility to halt the ever-upward spiralling ‘set-it-and-forget-it’ microprocessor-controlled

Phototherapy Carbonization & Burn-off

Protein Degradation (>55°C)

the desired effect of neocollagenesis and neoelas-

Fig. 18.9 Photospectrogram of a human hand in vivo. The

millimeter of tissue’. Anyone who has shone a

careful consideration of the wavelength/penetra- primary photoaction i.e., photochemical or pho-

Same end result

Cell proliferation enhanced Cell function upregulated

Dosimetry greatest amount of energy in the table, 2000 J,

Frequency modulated C/W beam

Average power (in W)

Time (s) Time (units as shown)

and superficial squamous cell carcinomas, or

clinical arena. However, a thorough understand-

The important point to be taken from these Wound Healing

Focused spot at fovea = 50 mm dia.

75 mW, pupillary opening 1 cm

ATP production, although in practical clinical

healing. This wavelength as delivered by acted in coordination with the photoabsorption

applications for LED phototherapy of appropri-

50 Continuous wave articles from the commercially-oriented medical

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