Light-Emitting Diode Phototherapy
`in Dermatological Practice
`
`R. Glen Calderhead
`
`Introduction
`
`•
`
`•
`
`•
`•
`
`Phototherapy is not new! It was being used more
`than 4,000 years ago
`Light-emitting diodes have attracted interest as a
`phototherapeutic source
`LEDs are solid state and robust
`LEDs are comparatively inexpensive
`
`History of Phototherapy
`
`Phototherapy in its broadest sense means any kind of treat-
`ment (from the Greek therapeia ‘curing, healing,’ from ther-
`apeuein ‘to cure, treat.’) with any kind of light (from the
`Greek phos, photos ‘light’). The modern accepted definition
`of phototherapy, however, has become accepted as: “the use
`of low incident levels of light energy to achieve an athermal
`and atraumatic, but clinically useful, effect in tissue”. Under
`its basic original definition, phototherapy is an ancient art
`because the oldest light source in the world is the sun, and
`therapy with sunlight, or heliotherapy, has been in use for
`over 4,000 years with the earliest recorded use being by the
`Ancient Egyptians.1 They would treat what was probably
`vitiligo by rubbing the affected area with a crushed herb sim-
`ilar to parsley, then expose the treated area to sunlight. The
`photosensitizing properties of the parsley caused an intense
`photoreaction in the skin leading to a very nasty sunburn,
`which in turn hopefully led to the appearance of postinflam-
`matory secondary hyperpigmentation, or ‘suntan’ thereby
`repigmenting the depigmented area. In their turn the Ancient
`Greeks and Romans used the healing power of the sun, and it
`
`R.G. Calderhead
`Japan Phototherapy Laboratory, Tsugamachi, Tochigi-ken, Japan
`e-mail: docrgc@cc9.ne.jp
`
`was still being actively used in Europe in the eighteenth,
`nineteenth and early twentieth century, particularly red light
`therapy carried out with the patient placed in a room with
`red-tinted windows. One famous patient was King George
`III of Great Britain and Northern Ireland who ruled from
`1760 to 1801, popularly though erroneously known as ‘Mad
`King George’. We now strongly suspect that he was actually
`suffering from the blood disease porphyria, so being shut in
`a room with red-draped walls and red tinted windows to treat
`his depression probably only served to make him even more
`mad, since porphyria is often associated with severe photo-
`sensitivity! Entities treated this way included the eruptive
`skin lesions of rubella and rubeola, and even ‘melancholia’,
`as was the case with King George III, now recognised as
`clinical depression. Hippocrates, the Father of Medicine,
`certainly concurred with the latter application some two mil-
`lennia before King George: Hippocrates prescribed sunlight
`for depressive patients and believed that the Greeks were
`more naturally cheerier than their northern neighbors because
`of the greater exposure to the sun.
`In the field of wavelength-specific phototherapy research,
`red light therapy was examined at a cellular level under the
`newly-invented microscope by Fubini and colleagues in the
`late eighteenth century,2 who were able to show that visible
`red light, provided via lenses and filters from sunlight, selec-
`tively activated the respiratory component of cellular mito-
`chondria. There is nothing new under the sun. However, the
`sun is a fickle medical tool, particularly in northern Europe,
`and modern phototherapy as we know it started around the
`turn of the last century with Finsen’s electric arc lamp-based
`system, giving phototherapy at the turn of a switch, indepen-
`dent of the sun.3 However, apart from the use of blue light
`therapy for neonatal bilirubinemia which continues to the
`present day, phototherapy was, in the majority of its applica-
`tions, overtaken in the first part of the twentieth century by
`better medication or improved treatment techniques.
`The development of the first laser systems, a race which
`was narrowly won by Theodore Maiman in 1960 with his
`flashlamp-pumped ruby-based laser, next gave clinicians and
`researchers a completely different and unique light source to
`play with. In the 4 years between 1960 and 1964, the ruby laser
`
`K. Nouri (ed.), Lasers in Dermatology and Medicine,
`DOI: 10.1007/978-0-85729-281-0_19, © Springer-Verlag London Limited 2011
`
`231
`
`
`
`

`

`Light-Emitting Diode Phototherapy
`in Dermatological Practice
`
`R. Glen Calderhead
`
`Introduction
`
`•
`
`•
`
`•
`•
`
`Phototherapy is not new! It was being used more
`than 4,000 years ago
`Light-emitting diodes have attracted interest as a
`phototherapeutic source
`LEDs are solid state and robust
`LEDs are comparatively inexpensive
`
`History of Phototherapy
`
`Phototherapy in its broadest sense means any kind of treat-
`ment (from the Greek therapeia ‘curing, healing,’ from ther-
`apeuein ‘to cure, treat.’) with any kind of light (from the
`Greek phos, photos ‘light’). The modern accepted definition
`of phototherapy, however, has become accepted as: “the use
`of low incident levels of light energy to achieve an athermal
`and atraumatic, but clinically useful, effect in tissue”. Under
`its basic original definition, phototherapy is an ancient art
`because the oldest light source in the world is the sun, and
`therapy with sunlight, or heliotherapy, has been in use for
`over 4,000 years with the earliest recorded use being by the
`Ancient Egyptians.1 They would treat what was probably
`vitiligo by rubbing the affected area with a crushed herb sim-
`ilar to parsley, then expose the treated area to sunlight. The
`photosensitizing properties of the parsley caused an intense
`photoreaction in the skin leading to a very nasty sunburn,
`which in turn hopefully led to the appearance of postinflam-
`matory secondary hyperpigmentation, or ‘suntan’ thereby
`repigmenting the depigmented area. In their turn the Ancient
`Greeks and Romans used the healing power of the sun, and it
`
`R.G. Calderhead
`Japan Phototherapy Laboratory, Tsugamachi, Tochigi-ken, Japan
`e-mail: docrgc@cc9.ne.jp
`
`was still being actively used in Europe in the eighteenth,
`nineteenth and early twentieth century, particularly red light
`therapy carried out with the patient placed in a room with
`red-tinted windows. One famous patient was King George
`III of Great Britain and Northern Ireland who ruled from
`1760 to 1801, popularly though erroneously known as ‘Mad
`King George’. We now strongly suspect that he was actually
`suffering from the blood disease porphyria, so being shut in
`a room with red-draped walls and red tinted windows to treat
`his depression probably only served to make him even more
`mad, since porphyria is often associated with severe photo-
`sensitivity! Entities treated this way included the eruptive
`skin lesions of rubella and rubeola, and even ‘melancholia’,
`as was the case with King George III, now recognised as
`clinical depression. Hippocrates, the Father of Medicine,
`certainly concurred with the latter application some two mil-
`lennia before King George: Hippocrates prescribed sunlight
`for depressive patients and believed that the Greeks were
`more naturally cheerier than their northern neighbors because
`of the greater exposure to the sun.
`In the field of wavelength-specific phototherapy research,
`red light therapy was examined at a cellular level under the
`newly-invented microscope by Fubini and colleagues in the
`late eighteenth century,2 who were able to show that visible
`red light, provided via lenses and filters from sunlight, selec-
`tively activated the respiratory component of cellular mito-
`chondria. There is nothing new under the sun. However, the
`sun is a fickle medical tool, particularly in northern Europe,
`and modern phototherapy as we know it started around the
`turn of the last century with Finsen’s electric arc lamp-based
`system, giving phototherapy at the turn of a switch, indepen-
`dent of the sun.3 However, apart from the use of blue light
`therapy for neonatal bilirubinemia which continues to the
`present day, phototherapy was, in the majority of its applica-
`tions, overtaken in the first part of the twentieth century by
`better medication or improved treatment techniques.
`The development of the first laser systems, a race which
`was narrowly won by Theodore Maiman in 1960 with his
`flashlamp-pumped ruby-based laser, next gave clinicians and
`researchers a completely different and unique light source to
`play with. In the 4 years between 1960 and 1964, the ruby laser
`
`K. Nouri (ed.), Lasers in Dermatology and Medicine,
`DOI: 10.1007/978-0-85729-281-0_19, © Springer-Verlag London Limited 2011
`
`231
`
`
`
`

`

`232
`
`R.G. Calderhead
`
`was followed by the argon, helium-neon (HeNe), neodymium:
`yttrium-aluminum-garnet (Nd:YAG) and carbon dioxide (CO2)
`lasers all of which have remained as workhorses in the medical
`field, and the HeNe laser (632.8 nm) has in fact provided a
`large bulk of the phototherapy literature over the last three
`decades. As for light-emitting diodes (LEDs), the first light
`from a semiconductor was produced in 1907 by the British
`experimenter H. J. Round. Independently in the mid 1920s,
`noncoherent infrared light was produced from a semiconduc-
`tor (diode) by O-V Losev in Russia. These studies were pub-
`lished in Russia, Germany and the UK, but their work was
`completely ignored in the USA.4 It was not till 1962 that the
`first practical and commercially-available visible-spectrum
`(633 nm, red) LED was developed in the USA by Holonyak,
`regarded as the ‘Father of the LED’ while working with the
`General Electric Company. In the next few years, LEDs deliv-
`ering other visible wavelengths were produced, with powers
`ten times or more that of Holonyak’s original LED. For rea-
`sons which will be discussed later, these LEDs were really
`inappropriate as therapeutic sources, although they were
`extremely bright and very cheap compared with laser diodes,
`and it was not till the late 1990s that a new generation of
`extremely powerful, quasimonochromatic LEDs was devel-
`oped by Whelan and colleagues as a spin-off from the National
`Aeronautic and Space Administration (NASA) Space Medicine
`Program.5 Unlike their cheap and cheerful predecessors, the
`so-called ‘NASA LEDs’ finally offered clinicians and research-
`ers a new and truly practical therapeutic tool.6
`
`The What and Why of LEDs
`
` What Is an LED?
`
`Light-emitting diodes belong to the solid state device family
`known as semiconductors. These are devices which fall
`somewhere between an electrical conductor and an insulator,
`although when no electrical current is applied to a semicon-
`ductor, it has almost the same properties as an insulator.
`Simply explained, light-emitting semiconductors or diodes
`consist of negative (N-type) and positive (P-type) materials,
`which are ‘doped’ with specific impurities to produce the
`desired wavelength. The n-area contains electrons in their
`ground or resting state, and the p-area contains positively
`charged ‘holes’, both of which remain more or less stationary
`(Fig. 1a–c). When a direct current electric potential with the
`correct polarity is applied to an LED, the electrons in the
`N-area are boosted to a higher energy state, and they and the
`holes in the P-area start to move towards each other (Fig. 1d),
`meeting at the N/P junction where the negatively-charged
`electrons are attracted into the positively-charged holes. The
`electrons then return to their resting energy state and, in doing
`
`so, emit their stored energy in the form of a photon, a particle
`of light energy (Fig. 1e). The wavelength emitted is nonco-
`herent, ideally very narrow-band, and depends on both the
`materials from which the LED is constructed, the substrates,
`and the p-n junction gap. Table 1 shows a list of the main
`substrates and associated colors. Figure 2 shows the anatomy
`of a typical dome-type LED. These can be mounted on cir-
`cuit boards at regular and precise distances from each other
`to provide an LED array, part of which is shown in Fig. 3.
`However, the latest generation of LEDs actually form part of
`the board (so-called ‘on-board’ chips) which are much more
`compact than the dome-type LED and more efficient.
`
`What Is the Difference Between LEDs
`and Lasers or IPLs?
`
`The laser is a unique form of light energy, possessing the three
`qualities of monochromaticity, collimation and phase which
`make up the overall property of ‘coherence’. Monochromaticity
`means all the photons are of exactly the same wavelength or
`color; collimation means the built-in parallel quality of the
`beam superimposed by the conditions of the laser resonator;
`and phase means that all of the photons march along together
`exactly equidistant from each other in time and in space. Laser
`diodes do not have inherent collimation, but because they are
`still true lasers, and therefore a so-called point source, the
`light can be gathered and optically collimated: the humble but
`ubiquitous laser pointer works on this principle. Intense
`pulsed light is, on the other hand, totally noncoherent, with a
`very large range of polychromatic (multicolored) light from
`near infrared all the way down to blue; has no possibility of
`collimation with extreme divergence; and has its vast variety
`of photons totally out of phase. The new generation of LEDs,
`on the other hand, has an output plus or minus a few nanome-
`ters of the rated wavelength, and so are classed as quasimono-
`chromatic; some form of optical collimation can be imposed
`on the photons which are divergent but do have some direc-
`tionality; but they are not in phase. 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 4 schemati-
`cally illustrates the differences between lasers, IPLs and
`LEDs. In short, LEDs for therapeutic applications must be
`quasimonochromatic, be capable of targeting wavelength-
`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 dermatologist. Why should LEDs be
`
`

`

` Light-Emitting Diode Phototherapy in Dermatological Practice
`
`233
`
`Direction of motion
`
`Electrons
`(– charge)
`
`N-type material
`
`Holes
`(+ charge)
`
`Direction of motion
`
`a
`
`P-type material
`
`Direction of motion
`
`Electrode
`
`Direction of motion
`
`Electrode
`
`b
`
`c
`
`d
`
`e
`
`DEPLETION
`ZONE
`
`Current flows through
`this N/P junction
`
`Direction of motion
`
`Electrons reach
`higher energy level
`
`Direction of motion
`
`–
`
`+
`
`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. 1 What is an LED and how can it produce light? (a) An LED is
`basically composed of two materials, the N-type or negative material
`and the P-type or positive material. The N-material contains negatively
`charged electrons which move as shown, and the P-material contains
`positively charged holes, which move in the opposite direction. When
`the materials are apart and not connected to any power source, move-
`ment continues, so both materials are conductors. (b) When the mate-
`rials are sandwiched together, however, without any power applied to
`the electrodes attached to opposite ends, the negatively charged elec-
`trons in the center of the chip are attracted to the holes, and form an
`area called the depletion layer as seen in (c) and all movement ceases
`in both the N- and P-materials: the chip is now an insulator. (d) Power
`is applied to the electrodes, with the positive electrode or anode at the
`origin of movement of the holes and the negative electrode or cathode
`at the origin of movement of the electrons. Observing the polarity
`when connecting a direct current (DC) power source is extremely
`important. Power flows through the junction between the materials,
`
`called the N/P junction, and movement of both electrons and holes
`starts again, but with power applied the electrons move to a higher
`energy level from their ground or resting state. (e) As in 1b above, the
`N-electrons are attracted to the P-holes, but in moving down through
`the N/P junction they must return to their ground energy level, and lose
`their extra stored energy in the form of a photon, the smallest packet of
`light energy. Unlike the situation in 1b, however, when power is
`applied this action continues endlessly and no depletion layer is
`formed. The N- and P-materials are ‘doped’ with other materials
`which determine the distance of the ‘fall’ between electrons and holes:
`the greater the distance the electrons have to fall, the higher is the
`energy level of the photons emitted. Photons with high energy levels
`have shorter wavelengths than those with lower energy levels, thus the
`wavelengths of the emitted light are determined by the materials and
`their doping. High quality N- and P-materials and pure doping sub-
`stances will give photons of very nearly the same wavelength, i.e.,
`quasimonochromatic light
`
`

`

`234
`
`R.G. Calderhead
`
`Table 1 Most common substrate combinations and the colors they are capable of producing
`Substrates
`Formula
`Colors produced
`
`Aluminum gallium arsenide
`Aluminum gallium phosphide
`Aluminum gallium indium phosphide
`Gallium arsenide phosphide
`Gallium phosphide
`Gallium nitride
`
`Indium gallium nitride
`
`(AlGaAs)
`(AlGaP)
`(AlGaInP)
`(GaAsP)
`(GaP)
`(GaN)
`
`(InGaN)
`
`Red, infrared
`Green
`Green, yellow, orange, orange-red(all high-intensity)
`Yellow, orange, orange-red, red
`Green, yellow, red
`Blue, green, pure green (emerald green): also white (if it has an
`AlGaN Quantum Barrier, so-called ‘white light’ LED)
`Near ultraviolet, blue, bluish-green
`
`LEDs in precise arrangement
`
`Optical quality
`envelope
`
`Connecting
`wire
`
`Semiconductor
`chip
`
`Cathode
`post
`
`Parabolic
`reflector
`
`− Cathode
`
`+ Anode
`
`Fig. 2 Anatomy of a typical high-quality dome-type LED. The cathode
`is always shorter than the anode and there is a flat surface in the base of
`the LED by the cathode so polarity is clearly determined when connect-
`ing to a DC power source. 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 forwards, with a consistent angle of divergence, typically 60°
`steradian or less depending on the specifications of the LED. A fine wire
`connects the positive electrode of the chip to the anode post, thus com-
`pleting the circuit. The entire assembly is encapsulated in an optical
`quality clear plastic envelope, giving the final assembly its robust nature
`
`Reflective base for
`‘photon recycling’
`
`Fig. 3 Close-up view of dome-type LEDs mounted in an actual array
`from a therapeutic system. Note the precise x-y spacing of the LEDs,
`(cf Fig. 6 and associated text), and the reflective backing into which
`they are mounted. When light is incident on living skin, a certain
`amount will be reflected from the outer layer of skin, the stratum cor-
`neum. The longer the wavelength, the greater this reflection will be. In
`addition, some light is always back-scattered out of skin. The purpose
`of the reflective backing of the array is to capture these photons and
`reflect them back into the skin, known as ‘photon recycling’
`
`considered as a viable alternative phototherapy source? The
`main reasons are efficiency and price. The electricity-light
`conversion ratio of a typical laser is very low, requiring 100
`or even 1,000 of watts in to give an output of a few watts. The
`same applies to IPL systems, where the flashlamp has to be
`pumped with enormous amounts of energy to provide poly-
`chromatic light, which may however be filtered (cut-on or
`
`cut-off). Even when filtered, IPL energy is delivered over a
`waveband rather than at a specific wavelength. In the case of
`LEDs, which are quasimonochromatic and require no filter-
`ing, the conversion efficiency is very high so that very few
`watts at a low voltage are required to produce a clinically
`useful output. LEDs are much less expensive than even laser
`diodes. Depending on quality and wavelength, anywhere
`from 300 new-generation LEDs can be purchased for the
`cost of a single laser diode. The cost of laser and IPL systems
`
`

`

` Light-Emitting Diode Phototherapy in Dermatological Practice
`
`235
`
`a & b
`
`700
`Wavelength (nm)
`
`1000
`
`d
`
`10
`
`5
`
`0 4
`
`00
`
`Relative intensity
`
`c
`
`700
`Wavelength (nm)
`
`1000
`
`700
`Wavelength (nm)
`
`1000
`10
`
`5
`
`0 4
`
`00
`
`Relative intensity
`
`10
`
`5
`
`0 4
`
`00
`
`Relative intensity
`
`a: laser (e.g., HeNe)
`
`b: laser diode
`
`c: IPL
`
`d: LED
`
`Fig. 4 Comparison among the output characteristics of a laser,
`laser diode, intense pulsed light system and a new generation LED.
`(a) A laser emits all of its energy at one precise wavelength, in a
`coherent beam, i.e., monochromatic, collimated and with the photons
`all in phase both temporally and spatially. If a ‘special magnifying
`glass’ could view the beam, it would show the picture as seen in the
`figure. All of the energy is delivered at a precise wavelength, as illus-
`trated in the spectrogram, so the relative intensity of the beam is
`extremely high. (b) A laser diode has all the characteristics of a laser,
`except that the beam is divergent, without collimation. However,
`because it is a point source the beam can be collimated with condens-
`ing optics. The magnified view of the beam shows a lower photon
`intensity than the laser, but the relative intensity is still very high.
`
`(c) An IPL system emits a pulse of broad-band polychromatic nonco-
`herent light, so the ‘magnifying glass’ would show a plethora of
`widely divergent photons of many different wavelengths, but with the
`majority in the near infrared as seen from the spectrogram. Because
`of the very broad waveband, the relative intensity at any given wave-
`length is low to very low. (d) The LED is somewhat similar to the
`laser diode, but the light is noncoherent, highly divergent and quasi-
`monochromatic. The ‘magnifying glass’ shows plenty of photons,
`mostly the same color, with some degree of directionality but without
`the true collimation and phase associated with the laser diode. The
`relative intensity is still very high, however, because the vast major-
`ity of the photons are being delivered at the nominal wavelength with
`a very narrow waveband of plus or minus a very few nanometers
`
`is very high, so a much cheaper LED-based system offers the
`possibility to halt the ever-upward spiralling costs of health
`care for both the clinicians and their patients. A further
`advantage is the solid state nature of LEDs. There are no fila-
`ments to be heated up, and no flashlamps are required to pro-
`duce light or to pump the laser medium: LEDs thus run much
`cooler than their extremely higher-powered cousins, so less
`is required in the way of dedicated cooling systems, again
`helping to reduce the cost. However, some cooling of LEDs
`is still required, especially when LEDs are mounted in mul-
`tiple arrays, because 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 sys-
`tems, so they tend to be able to take the sometimes not-so-
`
`gentle handling which is part of a busy clinical practice with-
`out causing either output power loss or alignment problems.
`Finally, LEDs can be mounted in flat panel arrays, which
`may in turn be joined together in a treatment head which 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 100 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 LED-based treatment
`head can be attached to an articulated arm to make individual
`adjustment even easier. Heads with different wavelengths
`
`

`

`236
`
`R.G. Calderhead
`
`can be designed to be easily interchangeable, controlled by
`the same base unit. With ‘set-it-and-forget-it’ microproces-
`sor-controlled technology, the clinician simply sets the head
`up over the area to be treated, following the manufacturer’s
`recommendations, turns the system on, and he or she can
`then leave the patient for the requisite treatment time and
`attend to other patients or tasks. Moreover, in many cases a
`suitably trained nurse can carry out the treatment once the
`clinician has prescribed it, because LED systems are much
`more inherently safe for the patient than lasers or IPLs.
`
`Basics of Light-Tissue Interaction
`
`•
`
`•
`
`•
`
` –
`
`Light-emitting diodes provide athermal and atrau-
`matic photoactivation
`LEDs are a viable and valuable phototherapeutic
`tool
`LEDs are capable of interesting light-tissue inter-
`actions, provided certain criteria are met. The
`most important criteria are:
` –
`Wavelength.
`Determines both the target and the depth at
`which the target can be reached
`Quasimonochromaticity is essential
`Wavelengths should be applied separately
`and sequentially, and not combined at the
`same time
`Photon density.
`Gives suitably high intensity at all levels of
`target cells or materials
`Ensures sufficient athermal energy transfer
`to raise targets’ action potentials
`Dosimetry.
`Provided the wavelength and intensity are
`appropriate, correct dosage obtains the opti-
`mum effect with the shortest irradiation time
`Temporal beam profile.
`Continuous wave would appear to be more
`efficient for most cell types in vivo, compared
`with ‘pulsed’ (frequency modulated) light
`
` –
`
` –
`
`Photothermal and Athermal Reactions
`
`Despite their very different output powers, lasers, IPLs and
`LEDs all depend on the ‘L’ which is found in all their names,
`standing for ‘light’. It could be said that they are all different
`facets of the same coin, but even in photosurgery, photother-
`apy plays a very important role. If we consider the typical
`beam pattern of a surgical CO2 laser in tissue, we see the
`range of temperature-dependent bioeffects as illustrated
`schematically in Fig. 5, ranging from carbonization above
`200°C, vaporization above 100°C, through coagulation
`around 60–85°C, all the way down to photobiomodulation,
`which occurs atraumatically when there is no appreciable
`rise in the tissue temperature at the very perimeter of the
`treated area. These effects occur virtually simultaneously as
`the light energy propagates into the target tissue with photon
`intensity decreasing with depth, and can be divided as shown
`into varying degrees of photosurgical destruction and revers-
`ible photodamage, and athermal, atraumatic photobiomodu-
`lation. The zones are also shown in a typical CO2 laser
`specimen stained with hematoxylin and eosin (Fig. 5).
`Laser surgery involves all zones, but the importance of the
`photobiomodulative zone cannot be stressed enough. It is the
`existence of this zone which sets laser surgery apart from any
`other thermally-dependent treatment, such as electrosurgery,
`or even athermal incision with the conventional scalpel, and
`it is the photoactivated cells in this zone which provided the
`results that interested the early adopters of the surgical laser
`compared with the cold scalpel or electrosurgery, namely
`better healing with less inflammation and much less postop-
`erative pain. IPL systems, and so-called nonablative lasers,
`produce areas of deliberate but controlled coagulative dam-
`age beneath a cooled and intact epidermis (Fig. 6), however
`they also produce the photobiomodulative zone to help
`achieve the desired effect of neocollagenesis and neoelasti-
`nogenesis through the wound healing process in the dermal
`extracellular matrix (ECM). LED-based phototherapy sys-
`tems, on the other hand, deliver only athermal and atraumatic
`effects, but are still capable of inducing the wound healing
`process almost as efficiently as IPLs and nonablative lasers,
`as will be shown in detail in a later section.
`
`Wavelength and Its Importance
`
`The main purpose of using phototherapy is to achieve some
`kind of clinical reaction in the target tissue through the use of
`light energy. If the incident power is high, heat will be the
`end product as with the surgical laser. If a too-low photon
`intensity is delivered, there will be very little or no reaction.
`The trick in LED phototherapy is to deliver just the right
`amount of photon intensity to achieve the desired clinical
`effect but in an athermal and atraumatic manner.
`
`The first law of photobiology, the Grotthus-Draper Law, states
`that only energy which is absorbed in a target can produce a
`photochemical or photophysical reaction. However, any such
`reaction is not an automatic consequence of energy absorp-
`tion. It may be simply converted into heat, as in the surgical
`and non-ablative lasers or IPL systems, or re-emitted at a dif-
`ferent wavelength (fluorescence). The prime arbitrator of this
`
`

`

` Light-Emitting Diode Phototherapy in Dermatological Practice
`
`237
`
`Carbonization & Burn-off
`(>200°C)
`
`Vaporization (>100°C)
`
`Coagulation (>60°C)
`
`Protein Degradation (>55°C)
`Protein Denaturation (>40°C)
`
`ATHERMAL CELLULAR
`PHOTOBIOACTIVATION
`
`Laser surgery
`
`TARGET TISSUE
`
`Phototherm al N S R
`
`Phototherapy
`
`Fig. 5 Range of photothermal and athermal photobioreactions in tissue
`following a typical surgical laser impact, e.g., a CO2 laser. A hematoxy-
`lin and eosin stained specimen of actual CO2 laser treated skin is also
`included to show the typical histopathological changes for each of the
`bioreactions: the epidermis has been totally vaporized leaving a layer of
`carbon char above the coagulated dermis. The outermost layer, the photo-
`bioactivation layer, shows normal tissue architecture, even though some
`
`photons will have reached this layer and transferred their energy to the
`cells in an athermal and atraumatic manner. Laser surgery involves all
`levels of bioreactions. Photothermal nonablative skin rejuvenation
`(NSR) delivers controlled coagulative photothermal damage, with all
`the subsequent layers, whereas phototherapy only delivers athermal and
`atraumatic photobioactivation
`
`‘no absorption-no reaction’ precept is not the output power of
`the incident photons, but their wavelength, and this comprises
`two important considerations: wavelength specificity of the
`target, or the target chromophore; and the depth of the target.
`Based on these two considerations, the wavelength must not
`only be appropriate for the chosen chromophore, but it must
`also penetrate deeply enough to reach enough of the target
`chromophores with a high enough photon density to induce
`the desired reaction. In theory, a single photon can activate a
`cell, but in actual practice multiple photon absorption is
`required to achieve the desired degree of reaction.
`Phototherapy is athermal and atraumatic, hence achieving
`selective photothermolysis is of no concern as it would be for
`surgical or other photothermal applications. On the contrary,
`penetration of light into living tissue is, however, extremely
`important in phototherapy, and very frequently displays charac-
`teristics which are often in discord with results produced by
`mathematical models, a point often totally ignored by some
`researchers. A favorite, but photobiologically false, axiom
`beloved of phototherapy opponents, is that ‘all light is absorbed
`within the first millimeter of tissue’. Anyone who has shone a
`red laser pointer through their finger, transilluminating the
`entire fingertip and completely visible on the other side, has
`already disproved that statement. A totally different finding is
`seen with green or yellow laser pointers, however. Figure 7 is
`based on a transmission photospectrogram of a human hand
`captured in vivo over the waveband from 500 nm (visible blue/
`green) to 1,100 nm in the near infrared.7 The photospectrometer
`
`generator was positioned above the hand, delivering a ‘flat
`spectrum’ of ‘white light’, and the recorder placed beneath it.
`The wavelength is shown along the x-axis, and the calculated
`optical density (OD) is on the y-axis, from lower ODs to higher.
`The higher the OD, the greater is the absorption of incident
`light, and hence the lower the transmission, or penetration
`depth into the tissue. It mu