For your convenience, Back Be Nimble’s health care consultant has
read and summarized how the use and efficacy of the Lumacare Duo Laser may
relate to the content of this article.
FOR A QUICK REVIEW OF THE DEFINITION, THEORY AND USES FOR LOW LEVEL
LASER LIGHT THERAPY (LLLT), SCAN THE YELLOW HIGHLIGHTED TEXT
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Published online 2011 Nov 2. doi:
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The Nuts
and Bolts of Low-level Laser (Light) Therapy
Hoon
Chung,1,2 Tianhong Dai,1,2 Sulbha
K. Sharma,1 Ying-Ying Huang,1,2,3 James
D. Carroll,4 and
Michael R. Hamblin1,2,5
Abstract
Soon after the
discovery of lasers in the 1960s it was realized that laser therapy had the
potential to improve wound healing and reduce pain, inflammation and swelling.
In recent years the field sometimes known as photobiomodulation has broadened
to include light-emitting diodes and other light sources, and the range of
wavelengths used now includes many in the red and near infrared. The term “low
level laser therapy” or LLLT has become widely recognized and implies the
existence of the biphasic dose response or the Arndt-Schulz curve. This review
will cover the mechanisms of action of LLLT at a cellular and at a tissular
level and will summarize the various light sources and principles of dosimetry
that are employed in clinical practice. The range of diseases, injuries, and
conditions that can be benefited by LLLT will be summarized with an emphasis on
those that have reported randomized controlled clinical trials. Serious
life-threatening diseases such as stroke, heart attack, spinal cord injury, and
traumatic brain injury may soon be amenable to LLLT therapy.
Keywords: Low level laser
therapy, Photobiomodulation, Mitochondria, Tissue optics, Wound healing, Hair
regrowth, Laser acupuncture
INTRODUCTION AND
HISTORY
Low
level laser therapy (LLLT), also known as photobiomodulation, came into being
in its modern form soon after the invention of the ruby laser in 1960, and the
helium–neon (HeNe) laser in 1961. In 1967, Endre Mester, working at Semmelweis
University in Budapest, Hungary, noticed that applying laser light to the backs
of shaven mice could induce the shaved hair to grow back more quickly than in
unshaved mice.72 He also demonstrated that the HeNe
laser could stimulate wound healing in mice.70 Mester soon
applied his findings to human patients, using
lasers to treat patients with nonhealing skin ulcers.69,71 LLLT has now developed into a
therapeutic procedure that is used in three main ways: to reduce inflammation,
edema, and chronic joint disorders9,18,40; to promote
healing of wounds, deeper tissues, and nerves24,87; and to treat neurological
disorders and pain.17
LLLT
involves exposing cells or tissue to low levels of red and near infrared (NIR)
light, and is referred to as “low level” because of its use of light at energy
densities that are low compared to other forms of laser therapy that are used
for ablation, cutting, and thermally coagulating tissue. LLLT is also
known
as “cold laser” therapy as the power densities used are
lower than those needed to produce heating of tissue. It was originally
believed that LLLT or photobiomodulation required the use of coherent laser
light, but more recently, light emitting diodes (LEDs) have been proposed as a
cheaper alternative. A great deal of debate remains over whether the two light
sources differ in their clinical effects.
Although LLLT is
now used to treat a wide variety of ailments, it remains controversial as a
therapy for two principle reasons: first, its underlying biochemical mechanisms
remain poorly understood, so its use is largely empirical. Second, a large
number of parameters such as the wavelength, fluence, power density, pulse
structure, and timing of the applied light must be chosen for each treatment. A
less than optimal choice of parameters can result in reduced effectiveness of
the treatment, or even a negative therapeutic outcome. As a result, many of the published results on LLLT include
negative results simply because of an inappropriate choice of light source and
dosage. This choice is particularly important as there is an optimal dose of light for any particular
application, and doses higher or lower than this optimal value may have no
therapeutic effect. In fact, LLLT is characterized by a biphasic dose response:
lower doses of light are often more beneficial than high doses.38,85,105,108
LASER–TISSUE
INTERACTIONS
Light and Laser
Light is part of
the spectrum of electromagnetic radiation (ER), which ranges from radio waves
to gamma rays. ER has a dual nature as both particles and waves. As a wave
which is crystallized in Maxwell’s Equations, light has amplitude, which is the
brightness of the light, wavelength, which determines the color of the light,
and an angle at which it is vibrating, called polarization. The wavelength (λ) of light is defined as the
length of a full oscillation of the wave, such as shown in Fig. 1a
. In terms of the
modern quantum theory, ER consists of particles
called photons, which are packets (“quanta”) of energy which move at the speed
of light. In this particle view of light, the
brightness of the light is the number of photons, the color of the light is the
energy contained in each photon, and four
numbers (X, Y, Z and T) are the polarization, where X, Y, Z are the directions and T is the time.
FIGURE 1
Basic physics of
LLLT. (a) Light as an electromagnetic wave. (b) Gaussian laser beam profile.
(c) Snellius’ law of reflection. (d) Optical window because of minimized
absorption and scattering of light by the most important tissue chromophores in
the near-infrared spectral region.
A laser is a device that emits light through a process
of optical amplification based on the stimulated emission of photons.
The term “laser” originated as an acronym for
light amplification by stimulated emission of radiation.65 The emitted laser
light is notable for its high degree of spatial and temporal coherence.
Spatial coherence typically is expressed through the output being a
narrow beam which is diffraction-limited, often a so-called “pencil beam.”
Laser can be launched into a beam of very low divergence to concentrate their power at a large distance.
Temporal (or longitudinal) coherence implies a polarized wave at a single
frequency whose phase is correlated over a relatively large distance (the
coherence length) along the beam. Lasers are employed in applications where
light of the required spatial or temporal coherence could not be produced using
simpler technologies.
Quite often, the
laser beam is described as though it had a uniform irradiance (the power of the
laser divided by the spot size). Most often, the laser beam assumes a Gaussian
shape (that of a normal distribution), as shown in Fig.
1b.118 There is a peak irradiance, and the
irradiance decreases with distance from the center of the beam. This may be
important in situations in which there are large variations in power. As power
is increased, the irradiance in the tail of the Gaussian profile increases, and
the distance of the critical threshold from the center of the beam becomes
larger. For this type of profile, the spot size is often referred to as the 1/e2 radius, or
diameter, of the beam; at this radial distance from the center of the beam,
irradiation is lower by a factor of 0.135 (1/e2) relative to the peak
irradiance. About 85% of the power of the laser beam is present within the 1/e2 diameter.
Light
Emitting Diodes (LED) A light-emitting diode (LED) is
a semiconductor light source. Introduced
as a practical
electronic component in 1962 early LEDs emitted low-intensity red light, but
modern versions are available across the
visible, ultraviolet and infrared wavelengths, with very high brightness.
When a light-emitting diode is forward biased (switched on), electrons are able
to recombine with electron holes within the device, releasing energy in the
form of photons. This effect is called electroluminescence and the color of the
light (corresponding to the energy of the photon) is determined by the energy
gap of the semiconductor. An LED is often
small in area (less than 1 mm2),
and integrated optical components may be used to shape its radiation pattern.78
Optical Properties of
Tissue
When
the light strikes the biological tissue, part of it is absorbed, part is
reflected or scattered, and part is further transmitted.
Some of the light
is reflected, this phenomenon is produced by a change in the air and tissue
refractive index. The reflection obeys the law of Snellius (Fig. 1c), which states:
where θ1 is the angle
between the light and the surface normal in the air, θ2 is the angle between the ray and the surface normal in the
tissue, n1 is the index of
refraction of air, n2 is the index of
refraction of tissue.
Most of the light
is absorbed by the tissue.
The energy states of molecules are quantized; therefore, absorption of a photon
takes place only when its energy corresponds to the energy difference between
such quantized states. The phenomenon of
absorption is responsible for the desired effects on the tissue. The
coefficient µa (cm−1) characterizes the absorption. The
inverse, la, defines the penetration depth
(mean free path) into the absorbing medium.
The scattering
behavior of biological tissue is also important because it determines the
volume distribution of light intensity in the tissue. This is the primary step
for tissue interaction, which is followed by absorption. Scattering of a photon
is accompanied by a change in the propagation direction without loss of energy.
The scattering, similar to absorption, is expressed by the scattering
coefficient µs (cm−1). The inverse
parameter, 1/µs (cm), is the mean
free path length until a next scattering event occurs.
Scattering is not
isotropic. Forward scattering is predominant in biological tissue. This
characteristic is described by the anisotropy factor g.g can have absolute values from 0 to 1, from isotropic scattering
(g = 0) to forward scattering (g = 1). In tissue, g can vary from 0.8 to 0.99. Taking into account the g value, a reduced scattering
coefficient, (cm−1), is defined as:
The sum of µs and µa is called the total attenuation
coefficient µt (cm−1):
µt
= µs + µa
Light Distribution in
Laser-irradiated Tissue
Most of the recent
advances in describing the transfer of light energy in tissue are based upon
transport theory.13 According to transport theory, the
radiance L(R, S) of light at
position R
traveling in the direction of unit vector S is decreased by
absorption and scattering but it is increased by light that is scattered from S′ direction into
direction S.
Radiance is a radiometric measure that describes the amount of light that
passes through or is emitted from a particular area, and falls within a given
solid angle in a specified direction. Then, the transport equation which
describes the light interaction is:
where dω′ is the differential solid angle in the direction S′, and p(S, S′) is the phase function.
Calculations of
light distribution based on the transport equation require µs , µa, and p. To solve transport equation exactly
is often difficult; therefore, several approximations have been made regarding
the representation of the radiance and phase function. The approximate
solutions of light distribution in tissue are dependent upon the type of light
irradiation (diffuse or collimated) and the optical boundary conditions
(matched or unmatched indexes of refraction).16
CELLULAR AND TISSULAR
MECHANISMS OF LLLT
The precise
biochemical mechanism underlying the therapeutic effects of LLLT are not yet
well-established. From observation, it appears
that LLLT has a wide range of effects at the molecular, cellular, and tissular
levels. In addition, its specific modes of action may vary among
different applications. Within the
cell, there is strong evidence to suggest that
LLLT acts on the mitochondria27
to increase adenosine triphosphate (ATP) production,43 modulation of reactive oxygen species (ROS), and the
induction of transcription factors.15 Several
transcription factors are regulated by changes in
cellular redox state. Among them redox factor-1 (Ref-1) dependent activator
protein-1 (AP-1) (a heterodimer of c-Fos and c-Jun), nuclear factor kappa B
(NF-κB), p53, activating
transcription factor/cAMP-response element–binding protein (ATF/CREB),
hypoxia-inducible factor (HIF)-1, and HIF-like factor.15 These transcription factors then cause protein
synthesis that triggers further effects down-stream, such as increased cell
proliferation and migration, modulation in the levels of cytokines, growth
factors and inflammatory mediators, and increased tissue oxygenation.45
Figure 2
shows the proposed cellular and
molecular mechanisms of LLLT.
FIGURE 2
Cellular
mechanisms of LLLT. Schematic diagram showing the absorption of red or near
infrared (NIR) light by specific cellular chromophores or photoacceptors
localized in the mitochondrial. During this process in mitochondria respiration
chain ATP production will increase, and reactive oxygen species (ROS) are
generated; nitric oxide is released or
generated. These cytosolic responses may in turn induce transcriptional
changes via activation of transcription factors (e.g., NF-κB and AP1).
Immune cells, in
particular, appear to be strongly affected by LLLT. Mast cells, which play a
crucial role in the movement of leukocytes, are of considerable importance in
inflammation. Specific wavelengths of light are able to trigger mast cell
degranulation,22 which results in the release of the
pro-inflammatory cytokine TNF-a from the cells.115 This leads to
increased infiltration of the tissues by leukocytes. LLLT also enhances the
proliferation, maturation, and motility of fibroblasts, and increases the production of basic fibroblast growth
factor.31,67 Lymphocytes
become activated and proliferate more rapidly, and epithelial cells become more
motile, allowing wound sites to close more quickly. The ability of macrophages to act as phagocytes is also
enhanced under the application of LLLT.
At the most basic
level, LLLT acts by inducing a photochemical reaction in the cell, a process
referred to as biostimulation or photobiomodulation. When a photon of light is
absorbed by a chromophore in the treated cells, an electron in the chromophore
can become excited and jump from a low-energy orbit to a higher-energy orbit.42,108 This stored energy can then be used
by the system to perform various cellular tasks. There are several pieces of
evidence that point to a chromophore within mitochondria being the initial
target of LLLT. Radiation of tissue with light
causes an increase in mitochondrial products such as ATP, NADH, protein, and
RNA,83 as well as a reciprocal
augmentation in oxygen consumption, and
various in vitro experiments have
confirmed that cellular respiration is
upregulated when mitochondria are exposed to an HeNe laser or other forms of
illumination.
The relevant
chromophore can be identified by matching the action spectra for the biological
response to light in the NIR range to the absorption spectra of the four
membrane-bound complexes identified in mitochondria.42 This procedure
indicates that complex IV, also known as cytochrome c oxidase (CCO), is the crucial chromophore in the cellular
response to LLLT.44 CCO is a large transmembrane
protein complex, consisting of two copper centers and two heme–iron centers,
which is a component of the respiratory electron transport chain.10 The electron
transport chain passes high-energy electrons from electron carriers through a
series of transmembrane complexes (including CCO) to the final electron
acceptor,
generating a proton gradient that is used to produce ATP. Thus, the application
of light directly influences ATP production by affecting one of the
transmembrane complexes in the chain: in particular, LLLT results in increased
ATP production and electron transport.47,84
The precise manner
in which light affects CCO is not yet known. The observation that NO is
released from cells during LLLT has led to speculation that CCO and NO release
are linked by two possible pathways (Fig. 3).
It is possible that LLLT may cause photodissociation of NO from CCO.46,52 Cellular respiration is
downregulated by the production of NO by mitochondrial NO synthase (mtNOS, a
NOS isoform specific to mitochondria), that binds to CCO and inhibits it. The
NO displaces oxygen from CCO, inhibiting cellular respiration and thus
decreasing the production of ATP.5 By dissociating
NO from CCO, LLLT prevents this process from taking place and results in
increased ATP production. An alternative or parallel mechanism to explain the
biological activity of red or NIR light to release NO from cells or tissue is
the following.61,127 A new explanation has been recently
proposed for how light increases NO bioavailability. 88 CCO can act as a
nitrite reductase enzyme (a one electron reduction of nitrite gives NO)
particularly when the oxygen partial pressure is low.6 Ball et al. showed 590 ± 14 nm LED light
stimulated CCO/NO synthesis at physiological nitrite concentrations at hypoxia
condition.6 The following reaction may take place:
FIGURE 3
Two possible
sources of nitric oxide (NO) release from cytochrome c oxidase (CCO). Path1 shows CCO can act as a nitrite reductase
enzyme: Path 2 shows possible photo-dissociation of NO from CCO.
The influence of
LLLT on the electron transport chain extends far beyond simply increasing the
levels of ATP produced by a cell. Oxygen acts as the final electron acceptor in
the electron transport chain and
is, in the
process, converted to water. Part of the oxygen that is metabolized produces
reactive oxygen species (ROS) as a natural by-product. ROS are chemically
active molecules that play an important role in cell signaling, regulation of
cell cycle progression, enzyme activation, and nucleic acid and protein
synthesis. Because LLLT promotes the
metabolism of oxygen, it also acts to increase ROS production. In turn, ROS
activates transcription factors, which leads to the upregulation of various
stimulatory and protective genes. These genes are most likely related to
cellular proliferation,76 migration,32 and the
production of
cytokines and growth factors,
which have all been shown to be stimulated by low-level light.125,128
The processes
described above are almost certainly only part of the story needed to explain
all the effects of LLLT. Among its many effects, LLLT
has been shown to cause vasodilation by triggering the relaxation of smooth
muscle associated with endothelium, which is highly relevant to the treatment
of joint inflammation. This vasodilation increases the availability of oxygen
to treated cells, and also allows for greater traffic of immune cells into
tissue. These two effects contribute to accelerated healing. NO is a
potent vasodilator via its effect on cyclic guanine monophosphate production,
and it has been hypothesized that LLLT
may cause photodissociation of NO, not only from CCO, but from intracellular
stores such as nitrosylated forms of both hemoglobin and myoglobin, leading to
vasodilation.61
LIGHT SOURCES AND
DOSIMETRY
Currently, one of
the biggest sources of debate in the choice of light sources for LLLT is the
choice between lasers and LEDs. LEDs have become wide-spread in LLLT devices.
Most initial work in LLLT used the HeNe laser, which emits light of wavelength
632.8-nm, while nowadays semi-conductor diode lasers such as gallium arsenide
(GaAs) lasers have increased in popularity. It was originally believed that the
coherence of laser light was crucial to achieve the therapeutic effects of
LLLT, but recently this notion has been challenged by the use of LEDs, which
emit non-coherent light over a wider range of wavelengths than lasers. It has yet to be determined whether there is a real
difference between laser and LED, and if it indeed exists, whether the
difference results from the coherence or the monochromaticity of laser light,
as opposed to the non-coherence and wider bandwidth of LED light.
A future development
in LLLT devices will be the use of organic light emitting diodes (OLEDs). These
are LEDs in which the emissive electroluminescent layer is a film of organic
compounds which emit light in response to an electric current.122 They operate in a
similar manner to traditional semiconductor material whereby electrons and the
holes recombine forming an exciton. The decay of this excited state results in
a relaxation of the energy levels of the electron, accompanied by emission of
radiation whose frequency is in the visible region.
The wavelengths of light used for LLLT fall into an
“optical window” at red and NIR wavelengths (600–1070 nm) (Fig. 1d). Effective
tissue penetration is maximized in this range, as the principal tissue
chromophores (hemoglobin and melanin) have high absorption bands at wavelengths
shorter than 600 nm. Wavelengths in the range 600–700 nm are used to treat
superficial tissue, and longer wavelengths in the range 780–950 nm, which
penetrate further, are used to treat deeper-seated tissues. Wavelengths in the
range 700–770 nm have been found to have limited biochemical activity and are
therefore not used. There are also reports of the effectiveness of
wavelengths outside the range of absorption of NIR
light by CCO. These wavelengths are in the near IR,36 the mid-IR region
including carbon dioxide laser (10.6 µm)126 and also include
broad band IR sources in the 10–50 µm
range.39 The chromophore in these situations is almost certainly
water, possible present in biological membranes in some nanostructured form,
that is different from bulk water allowing biological effects without gross
heating of the tissue.94,95 It is at present not clear at which
wavelength CCO absorption ceases and water
absorption commences to be
important.
Dosimetry
The power of light
used typically lies in the range 1–1000 mW, and varies widely depending on the
particular application. There is evidence to suggest that the effectiveness of
the treatment varies greatly on both the energy and power density used: there
appears to be upper and lower thresholds for both parameters between which LLLT
is effective. Outside these thresholds, the light is either too weak to have
any effect, or so strong that its harmful effects outweigh its benefits.
Response to LLLT
changes with wavelength, irradiance, time, pulses and maybe even coherence and
polarization, the treatment should cover an adequate area of the pathology, and
then there is a matter of how long to irradiate for.
Dosimetry is best described in two
parts,
1. Irradiation parameters (“the
medicine”) see Table 1
Wavelength nm
Irradiance |
W/cm2 |
Pulse |
Peak power (W) |
structure |
Pulse freq (Hz) |
|
Pulse width (s) |
|
Duty cycle (%) |
Light is packets
of electromagnetic energy that also have a wave-like property. Wavelength is
measure in nanometers (nm) and is visible in the 400–700 nm range. Wavelength
determines which chromophores will absorb the light. LLLT devices are typically
in the range 600–1000 nm as there are many peaks for cytochrome c oxidase in that range and clinical
trials have been successful with them. There is some contention as wavelengths
above 900 nm are probably more absorbed by water than CCO and excitation seems
less likely so it introduces the possibility that maybe IR absorption by water
in the phospholipid bilayers causes molecular vibration and rotation)
sufficient to perturb ion channels alter cellular function
Often called Power
Density (technically incorrect) and is calculated as Power (W)/Area (cm2) = Irradiance
If the beam is
pulsed then the Power reported should be the Average Power and calculated as
follows: Peak Power (W) × pulse width (s) × pulse frequency (Hz) = Average
Power (W). Pulses can be significantly more effective than CW30 however, the
optimal frequencies and pulse duration (or pulse intervals) remain to be
determined
Coherence |
Coherence length |
Coherent light produces laser
speckle, which has been postulated to |
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Polarization |
Linear polarized |
Polarized light may have different
effects than otherwise identical |
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2. Time/energy/fluence delivered
(“the dose”) see Table 2
TABLE 2
Irradiation time/energy/fluence
(“dose”).
Energy |
J |
Calculated as: Power (W) × time
(s) = Energy (Joules) This mixes medicine |
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(Joules) |
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and ignores irradiance. Using Joules as an |
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Dosimetry in LLLT
is highly complicated. The large of number of interrelated parameters (see Table 1) has meant that there has not yet
been a comprehensive study reported that examined the effect of varying all the
individual parameters one by one, and it must be pointed out that it is
unlikely there will ever be such a study carried out. This considerable level
of complexity has meant that the choice of parameters has often depended on the
experimenter’s or the practitioner’s personal preference or experience rather
than on a consensus statement by an authoritative body. Nevertheless, the World
Association of Laser Therapy (WALT) has attempted to provide dosage guidelines
(http://www.walt.nu /dosage-recommendations.html).
Biphasic Dose Response
It is well
established that if the light applied is not of sufficient irradiance or the
irradiation time is too short then there is no response. If the irradiance is
too high or irradiation time is too long then the response may be inhibited.11,33,53 Somewhere in
between is the optimal combination of irradiance and time for stimulation. This
dose response often likened to the biphasic response known as “Arndt-Schulz
Law”68,105,116 which dates back to 1887 when Hugo
Schulz published a paper showing that various poisons at low doses have a
stimulatory effect on yeast metabolism when given in low doses116 then later with
Rudolph Arndt they developed their principle claiming that a weak stimuli
slightly accelerates activity, stronger stimuli raise it further, but a peak is
reached and that a stronger stimulus will suppress activity.63 A more credible
term better known in other areas of science and medicine is Hueppe’s Rule. In
1896 Ferdinand Hueppe built on Hugo Schulz’s initial findings by showing low
dose
stimulation/high
dose inhibition of bacteria by toxic agents. This is better known today by the
term “hormesis” first coined in 1941 and first referenced in 1943,63 which has
subsequently been discussed multiple times in LLLT research.34,38
A graphical
depiction of how the response to LLLT varies as a function of the combination
of irradiance (medicine) and time (dose) is shown in
Fig. 4, as a 3D model to represent the possible biphasic
responses to the various combinations of irradiance and time or fluence.
FIGURE 4
Biphasic dose
response in LLLT. Three dimensional plot illustrating effects of varying
irradiation time equivalent to fluence or irradiance on the biological response
resulting in stimulation or inhibition.
SURVEY OF CONDITIONS
TREATED WITH LLLT
LLLT is used for
three main purposes: to promote wound healing, tissue repair, and the
prevention of tissue death; to relieve inflammation and edema because of
injuries or chronic diseases; and as an analgesic and a treatment for other
neurological problems. These applications appear in a wide range of clinical
settings, ranging from dentistry, to dermatology, to rheumatology and
physiotherapy. Table 3 summarizes
some of the published studies in animal models of diseases and conditions
treated with LLLT. Table 4 summarizes
some of the published clinical trials of LLLT.
TABLE 3
Pre-clinical studies on animals with
low level light therapy for different conditions.
Disease |
Parameters ab |
Subject |
Effect |
References |
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Myocardial |
804 nm; 38 mW; 4.5 ± |
Rats |
Reduced the loss of myocardial
tissue |
2 |
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|
infarction |
0.1 mW/cm2; 0.27 |
|
|
|
|
|
|
|
J/cm2; CW, 1.5 × 3.5 |
|
|
|
|
|
|
|
mm |
|
|
|
|
|
|
Myocardial |
635 nm, 5 mW, 6 |
Rats |
The expression of multiple
cytokines was |
123 |
|||
infarction |
mW/cm2; 0.8 J–1 |
|
regulated in the acute phase after
LLLI |
|
|
|
|
|
J/cm2; CW; 0.8 cm2; |
|
|
|
|
|
|
|
150 s |
|
|
|
|
|
|
Myocardial |
804 nm; 400 mW 8 |
Rats |
VEGF and iNOS expression markedly |
113 |
|
||
infarction |
mW/cm2; 0.96 J/cm2; |
and |
upregulated; angiogenesis and |
|
|
|
|
|
CW; 2 cm2; 120 s |
dogs |
cardioprotection enhanced |
|
|
|
|
Stroke |
808-nm; .5 mW/cm2; |
Rabbits |
The results showed that laser
administered 6 |
54 |
|
||
|
0.9 J/cm2 at cortical |
|
h following embolic strokes in
rabbits in P |
|
|
|
|
|
surface; CW; 300
µs |
|
mode can result
in significant clinical |
|
|
|
|
|
pulse at 1 kHz; 2.2 ms at |
|
improvement and should be
considered for |
|
|
|
|
|
100 Hz |
|
clinical development |
|
|
|
|
Stroke |
808-nm; 7.5
mW/cm2; |
Rats |
LLLT issued 24 h after acute
stroke may |
81 |
|
||
|
0.9 J/cm2; 3.6 J/cm2 at |
|
provide a significant functional
benefit with |
|
|
|
|
|
cortical
surface; CW and |
|
an underlying
mechanism possibly being |
|
|
|
|
|
70 Hz, 4-mm diameter |
|
induction of neurogenesis |
|
|
|
|
TBI |
808 ± 10 nm; 70 mW; |
Rats |
Single and multiple applications
of |
64 |
|
||
|
2230 mW/cm2; 268 |
|
transcranial laser therapy with
808-nm CW |
|
|
|
|
|
J/cm2 at the scalp; 10 |
|
laser light appears to be safe in
Sprague– |
|
|
|
|
|
mW/cm2; 1.2 J/cm2 at |
|
Dawley rats 1 year after treatment |
|
|
|
|
|
cortical
surface; CW; 2 |
|
|
|
|
|
|
|
mm2 |
|
|
|
|
|
|
TBI |
808-nm; 200 mW; 10 |
Mice |
LLLT given 4 h following TBI
provides a |
82 |
|
||
|
and 20 mW/cm2; |
|
significant long-term functional
neurological |
|
|
|
|
|
1.2–2.4 J/cm2 at cortical |
|
benefit |
|
|
|
|
|
surface; 4 h
post-trauma |
|
|
|
|
|
|
TBI |
660 nm or 780 nm, 40 |
Rats |
LLLT affected TNF-alpha, IL-1beta,
and |
77 |
|
||
|
mW; 3 J/cm2 or 5 |
|
IL-6 levels in the brain and in
circulation in |
|
|
|
|
|
J/cm2; CW; 0.042 cm2 |
|
the first 24 h following cryogenic
brain |
|
|
|
|
|
(3 s and 5 s)
irradiated |
|
injury |
|
|
|
|
|
twice (3 h interval) |
|
|
|
|
|
|
Spinal cord |
830 nm; 100 mW; 30 |
Rats |
LLLT initiated a positive
bone-tissue |
66 |
|
||
injury |
mW/cm2; 250 J/cm2; |
|
response, maybe through
stimulation of |
|
|
|
|
|
CW, 0.028 cm2 |
|
osteoblasts. However, the evoked
tissue |
|
|
|
|
|
|
|
response did not
affect biomechanical or |
|
|
|
|
|
|
|
densitometric modifications |
|
|
|
|
Spinal cord |
810 nm; 1589
J/cm2; 0.3 |
Rats |
Promotes axonal regeneration and
functional |
120 |
|||
injury |
cm2, 2997 s; daily for |
|
recovery in acute SCI |
|
|
|
|
14 days
Disease |
Parameters ab |
Subject |
Effect |
References |
||
Arthritis |
632.8 nm; 5 mW; 8 |
Rats |
Laser reduced the intensity of the |
92 |
||
|
J/cm2, CW; 2-mm |
|
inflammatory process in the
arthritis model |
|
|
|
|
diameter; 50 s;
daily for |
|
induced by
hydroxyapatite and calcium |
|
|
|
|
5 days |
|
pyrophosphate crystals |
|
|
|
Arthritis |
632.8-nm; 3.1
mW/cm2 |
Rats |
He–Ne laser treatment enhanced the |
59 |
||
|
CW, 1 cm diameter; 15 |
|
biosynthesis of
arthritic cartilage |
|
|
|
|
min; 3 times a week for |
|
|
|
|
|
|
8 weeks |
|
|
|
|
|
Arthritis |
810-nm;
5 or 50 |
Rats |
Highly
effective in treating inflammatory |
11 |
|
|
|
mW/cm2; 3 or 30 J/cm2; |
|
arthritis. Illumination time may be an |
|
|
|
|
CW; 4.5-cm
diameter; 1, |
|
important
parameter |
|
|
|
|
10 or 100 min; daily for |
|
|
|
|
|
|
5 days |
|
|
|
|
|
Wound |
632.8-nm laser; 635, |
Mice |
635-nm light
had a maximum positive effect |
20 |
||
healing |
670, 720 or 810-nm |
|
at 2 J/cm2. 820 nm was found to be the best |
|
|
|
|
(±15-nm filtered
lamp); |
|
wavelength. No
difference between non- |
|
|
|
|
0.59, 0.79, and 0.86 |
|
coherent 635 ± 15-nm light from a
lamp and |
|
|
|
|
mW/cm2; 1, 2, 10 and |
|
coherent 633-nm light from a He/Ne
laser. |
|
|
|
|
50 J/cm2; CW; 3-cm |
|
LLLT increased the number of α-smooth |
|
|
|
|
diameter |
|
muscle actin
(SMA)-positive cells at the |
|
|
|
|
|
|
wound edge |
|
|
|
Familial |
810 nm; 140-mW; 12 |
Mice |
Rotarod test showed significant
improvement |
75 |
||
amyotropic |
J/cm2; CW; 1.4 cm2 |
|
in the light group in the early
stage of the |
|
|
|
lateral |
|
|
disease.
Immunohistochemical expression of |
|
|
|
sclerosis |
|
|
the astrocyte marker, glial
fibrilary acidic |
|
|
|
(FALS) |
|
|
protein, was significantly reduced
in the |
|
|
|
|
|
|
cervical and lumbar enlargements
of the |
|
|
|
|
|
|
spinal cord as a result of LLLT |
|
|
|
Open in a separate
window
aThe light sources were all lasers
unless LED is specifically mentioned.
bThe laser
parameters are given in the following order: wavelength (nm); power (mW), power
density (mW/cm2); energy (J); energy density (J/cm2); mode (CW) or
pulsed (Hz); spot size (cm2); illumination time (sec); treatment repetition. In many
cases, the parameters are partially unavailable.
TABLE 4
Clinical studies on patients with
low level light therapy for different conditions.
Myocardial 632.8-nm, 5 mW; CW; 15
infarction min; 6 days a week for 4
weeks on chest skin
Stroke 808-nm; 700 mW/cm2
on
(NEST-1) shaved scalp with cooling;
1 J/cm2 at cortical
surface;
20 predetermined
locations
2 min each
Stroke 808-nm; 700 mW/cm2
on
(NEST-2) shaved scalp with cooling;
1 J/cm2 at cortical
surface;
20 predetermined
locations
2 min each
Chronic TBI |
9 × 635 and 52 × 870-nm |
|
LED cluster; 12-15 mW |
|
per diode; 500 mW; 22.2 |
|
mW/cm2; 13.3 J/cm2 at |
|
scalp (estimated
0.4 J/cm2 |
|
to cortex); 2.1″
diameter |
Major |
810-nm, 250
mW/cm2; 60 |
depression |
J/cm2 on scalp; 2.1 J/cm2 |
and anxiety |
at cortical
surface; CW; 4 |
|
cm2; 240 s at each of 2 |
|
sites on
forehead |
39 |
An improvement of functional
capacity |
131 |
|
patients |
and less frequent angina symptoms
during |
|
|
|
exercise tests |
|
|
120 |
The NEST-1 study indicated that
infrared |
51 |
|
patients |
laser therapy has shown initial
safety and |
|
|
|
effectiveness for the treatment of
ischemic |
|
|
|
stroke in humans when initiated
within 24 |
|
|
|
h of stroke onset |
|
|
660 |
TLT within 24 h from stroke onset |
130 |
|
patients |
demonstrated safety but did not
meet |
|
|
|
formal statistical significance
for efficacy. |
|
|
|
However, all predefined analyses
showed a |
|
|
|
favorable trend, consistent with
the |
|
|
|
previous clinical trial (NEST-1).
Both |
|
|
|
studies indicate that mortality
and adverse |
|
|
|
event rates were not adversely
affected by |
|
|
|
TLT. A definitive trial with
refined |
|
|
|
baseline National Institutes of
Health |
|
|
|
Stroke Scale exclusion criteria is
planned |
|
|
2 |
Transcranial LED may improve
cognition |
79 |
|
patients |
in chronic TBI patients even years
after |
|
|
|
injury |
|
|
10 |
Significant improvement in
Hamilton |
96 |
patients |
depression and anxiety scales at 2
weeks |
|
Oral |
830 nm; 150 mW; repeated |
16 |
Immediate pain relief and improved |
12 |
mucositis |
every 48 h |
patients |
wound healing resolved functional |
|
|
|
|
impairment that was obtained in
all cases |
|
Oral 830 nm; 15 mW; 12 J/cm2;
mucositis CW; 0.2 cm2; daily for 5
days commencing at
start
of radio/chemotherapy
12 |
The prophylactic use of the
treatment |
58 |
patients |
proposed in this study seemed to
reduce |
|
|
the incidence of severe oral
mucositis |
|
|
lesions. LLLT was effective in
delaying |
|
|
the appearance of severe oral
mucosistis |
|
Oral |
660-nm; 10-mW; 2.5 |
75 |
LLLT therapy was not effective in |
26 |
mucositis |
J/cm2, CW; 4 mm2; daily |
patients |
reducing severe oral mucositis,
although a |
|
|
for 5 days |
|
marginal benefit
could not be excluded. It |
|
|
|
|
reduced radiation therapy
interruptions in |
|
|
|
|
these head-and-neck cancer
patients, |
|
|
|
|
which might translate into
improved CRT |
|
|
|
|
efficacy |
|
Disease |
Parameters ab |
Subject |
Effect |
References |
||
Carpal tunnel |
830-nm; 60 mW; 9.7 |
75 |
Alleviate pain and symptoms,
improve |
14 |
|
|
syndrome |
J/cm2; 10 Hz, 50% duty |
patients |
functional ability and finger and
hand |
|
|
|
(CTS) |
cycle, 10-min
per day for 5 |
|
strength for
mild and moderate CTS |
|
|
|
|
days a week |
|
patients |
|
|
|
Carpal tunnel |
632.8-nm; 9–11
J/cm2; |
80 |
Effective in treating CTS
paresthesia and |
102 |
||
syndrome |
CW; 5 times/week for 3 |
patients |
numbness and improved the
subjects’ |
|
|
|
(CTS) |
weeks |
|
power of hand-grip and |
|
|
|
|
|
|
electrophysiological parameters |
|
|
|
Carpal tunnel |
830-nm; 50 mW; 1.2 |
60 |
LLLT was no more effective than
placebo |
110 |
|
|
syndrome |
J/point; CW; 1 mm |
patients |
in CTS |
|
|
|
(CTS) |
diameter. 2 min/point; 5 |
|
|
|
|
|
|
points across the median |
|
|
|
|
|
|
nerve trace; 5 times per |
|
|
|
|
|
|
week for 3 weeks |
|
|
|
|
|
Lateral |
905 nm; 100 mW;
1 J/cm2; |
49 |
No advantage
for the short term; |
23 |
|
|
epicondylitis |
1000 Hz; 2 min; 5 days per |
patients |
significant improvement
in functional |
|
|
|
(LE) |
week for 3 weeks |
|
parameters in
the long term |
|
|
|
Lateral |
904-nm; 25 mW, 0.275 |
39 |
LLLT in addition to exercise is
effective in |
50 |
|
|
epicondylitis |
J/point; 2.4
J/cm2; pulse |
patients |
relieving pain, and in improving
the grip |
|
|
|
(LE) |
duration 200
nsec; 5000 |
|
strength and
subjective rating of physical |
|
|
|
|
Hz; 4-mm diameter 11 |
|
function of patients with lateral |
|
|
|
|
s/point; 3 times/week for 3 |
|
epicondylitis |
|
|
|
|
weeks |
|
|
|
|
|
Lateral |
830 nm; 120 mW; CW; |
324 |
It was observed that under-and |
103 |
||
epicondylitis |
5-mm diameter; 632.8 nm, |
patients |
overirradiation can result in the
absence of |
|
|
|
(LE) |
10 mW, CW; 2-mm |
|
positive therapy effects or even
opposite, |
|
|
|
|
diameter; 904 nm, 10 mW; |
|
negative (e.g., inhibitory)
effects. The |
|
|
|
|
pulsed; 2.5–4 J/point; 12 |
|
current clinical study provides
further |
|
|
|
|
J/cm2; 3–5 times/week for |
|
evidence of the efficacy of LLLT
in the |
|
|
|
|
2–5 weeks |
|
management of
lateral and medial |
|
|
|
|
|
|
epicondylitis |
|
|
|
Arthritis |
830 nm, 50 mW; 10 |
27 |
Reduces pain in
knee osteoarthritis
and |
35 |
|
|
|
W/cm2; 6 J/point; 48 |
patients |
improves microcirculation |
|
|
|
|
J/cm2; CW, 0.5-mm2; 2 |
|
|
|
|
|
|
times/week for 4
weeks |
|
|
|
|
|
Arthritis |
904-nm; 10 mW; 3 J/point; |
90 |
The study demonstrated that
applications |
28 |
|
|
|
3 J/cm2; 200 nsec; 2500 |
patients |
of LLLT in regardless of dose and
duration |
|
|
|
|
Hz; 1 cm2; 2 points 5 |
|
were a safe and effective method
in |
|
|
|
|
times/week for 2
weeks |
|
treatment of
knee osteoarthritis |
|
|
|
Leg ulcers |
685 nm; 50 mW; 50 |
23 |
The study provided evidence that
LLLT |
48 |
|
|
|
mW/cm2; 10 J/cm2; CW; 1 |
patients |
can accelerate the healing process
of |
|
|
|
|
cm2; 200 s; 6 times per |
|
chronic diabetic foot ulcers, and
it can be |
|
|
|
|
week, for 2
weeks then |
|
presumed that
LLLT may shorten the time |
|
|
|
|
every 2 days |
|
period needed to achieve complete
healing |
|
|
|
Disease |
Parameters ab |
Subject |
Effect |
References |
|
Leg ulcers |
685-nm; 200 mW;
4 J/cm2 |
44 |
No statistically significant
differences in |
49 |
|
|
|
patients |
reduction of wound size |
|
|
Open in a separate
window
aThe light sources were all lasers
unless LED is specifically mentioned.
bThe laser
parameters are given in the following order: wavelength (nm); power (mW), power
density (mW/cm2); energy (J); energy density (J/cm2); mode (CW) or
pulsed (Hz); spot size (cm2); illumination time (sec); treatment repetition. In many
cases, the parameters are partially unavailable.
Wound healing was one of the first
applications of LLLT, when HeNe lasers were used by Mester et al. to treat skin ulcers.69-71 LLLT is believed to affect all
three phases of wound healing111: the inflammatory phase, in which immune cells migrate to
the wound, the proliferative phase, which results in increased production of
fibroblasts and macrophages, and the remodeling phase, in which collagen
deposition occurs at the wound site and the extra-cellular matrix is rebuilt.
LLLT is believed
to promote wound healing by inducing the local release of cytokines,
chemokines, and other biological response modifiers that reduce the time
required for wound closure, and increase the mean breaking strength of the
wound.8,32,73 Proponents of LLLT speculate that
this result is achieved by increasing the production and activity of
fibroblasts and macrophages, improving the mobility of leukocytes, promoting
collagen formation, and inducing neovascularization.
31,60,67,80,90,104
However, there is a lack of convincing clinical studies that
either prove or disprove the efficacy of LLLT in wound healing. The results
that are currently available are conflicting and do not lead to any clear
conclusions. For example, Abergel et
al. found that the 632.8 nm HeNe laser did not have any effect on the cellular proliferation of
fibroblasts, while the 904 nm GaAs laser actually lowered fibroblasts proliferation.1 In contrast,
other studies noted an increase in proliferation of human fibroblasts exposed
to 904 nm GaAs lasers,85 rat myofibroblasts exposed to 670
nm GaAs lasers,67 and gingival fibroblasts exposed to
diode lasers (670, 692, 780, and 786 nm).3 In vivo studies in both animal and human
models show similar discrepancies. A study by Kana et al. claimed that treatment of open wounds in rats with HeNe and
argon lasers resulted in faster wound closure.41 Bisht et al. found a similar increase in
granulation tissue and collagen expression in rats using the same treatment as
Kana.7 However, Anneroth et
al. failed to observe any beneficial effects after laser treatment in a
comparable rat model.4 In human studies, Schindl et al. reported that application of a
HeNe laser was beneficial in promoting wound healing in 3 patients,99 whereas Lundeberg
et al. found no statistically
significant difference between leg ulcer patients treated with an HeNe laser
and those treated with a placebo.62
The scarcity of
well-designed clinical trials makes it difficult to assess the impact of LLLT
on wound healing. Our task is further complicated by the difficulty in
comparing studies, because of the large number of factors involved. In addition
to the multiple parameters that must be adjusted to apply LLLT, such as the
wavelength and power of the light, the effectiveness of the treatment also
depends on many factors such as the location and nature of the wound, and the
physiologic state of the patient. For example, impaired wound healing is one of
the major chronic complications of diabetes,25,89 and is thought to result from
various factors, including decreased collagen production and impaired
functionality of fibroblasts, leukocytes, and endothelial cells.25,106 It has therefore been hypothesized
that LLLT could
have beneficial effects in stimulating wound healing in diabetic patients.98,100,124 Thus, in order to
obtain a convincing verdict on the impact of LLLT on wound healing, we will
require several large, randomized, placebo controlled, and double blind trials
that compare the effects of LLLT on wounds that are as similar as possible. A
greater understanding of the cellular and biochemical mechanisms of LLLT would
also be useful in assessing these studies, as it would enable us to pinpoint exactly
what criteria to use in determining the effectiveness of the therapy.
There
appears to be more firm evidence to support the success of LLLT in alleviating
pain and treating chronic joint disorders, than in healing wounds. A review of 16
randomized clinical trials including a total of 820 patients found that LLLT
reduces acute neck pain immediately after treatment, and up to 22 weeks after
completion of treatment in patients with chronic neck pain.17 LLLT has also
been shown to relieve pain because of cervical dentinal hypersensitivity,93 or from
periodontal pain during orthodontic tooth movement. 114 A study of 88
randomized controlled trials indicated that LLLT can significantly reduce pain
and mprove health in chronic joint disorders such as osteoarthritis,
patellofemoral pain syndrome, and mechanical spine disorders.9 However, the
authors of the study urge caution in interpreting the results because of the
wide range of patients, treatments, and trial designs involved.
LLLT for Serious
Diseases
LLLT is also being considered as a viable treatment for
serious neurological conditions such as traumatic brain injury (TBI), stroke,
spinal cord injury, and degenerative central nervous system disease.
Although traumatic
brain injury is a severe health concern, the search for better therapies in
recent years has not been successful. This has led to interest in more radical
alternatives to existing procedures, such as LLLT. LLLT is hypothesized to be
beneficial in the treatment of TBI. In addition to its effects in increasing
mitochondrial activity and activating transcription factors, LLLT could benefit TBI patients by inhibiting
apoptosis, stimulating angiogenesis, and increasing neurogenesis.29 Experiments
carried out with two mouse models
indicated that LLLT could reduce the brain damaged area at 3 days after
treatment, and treatment with a 665 nm and 810 nm laser could lead to a
statistically significant difference in the Neurological Severity Score (NSS)
of mice that had been injured by a weight being dropped onto the exposed skull.121
Transcranial
LLLT has also been shown to have a noticeable effect on acute human stroke
patients, with significantly greater improvement being seen in patients 5 days
after LLLT treatment compared to sham treatment (p < 0.05, National Institutes of Health Stroke Severity Scale.)51 This difference
persisted up to 90 days after the stroke, with 70% of patients treated with
LLLT having a successful outcome compared to 51% of control patients. The
improvement in functional outcome because of applying transcranial LLLT after a
stroke has been confirmed by studies in rat and rabbit models.54,81
Further
experiments have tried to pinpoint the mechanism underlying these results. As
expected, increased mitochondrial activity has been found in brain cells
irradiated with LLLT,54 indicating that the increased
respiration and ATP production that usually follow laser therapy are at least
partly responsible for the improvement shown in stroke patients. However, there
is still the possibility that LLLT has other effects specific to the brain.
Several groups have suggested that the improvements in patient outcomes are
because of the promotion of neurogenesis, and migration of neurons.81 This hypothesis
is supported by the fact that the benefits of LLLT following a stroke may take
2–4 weeks to manifest, reflecting the time necessary for new neurons to form
and gather at the damaged site in the brain.21,101 However, the exact processes
underlying the effects of LLLT in a stroke patient are still poorly understood.
LLLT has also been
considered as a candidate for treating degenerative brain disorders such as
familial amyotropic lateral sclerosis (FALS), Alzheimer’s disease, and
Parkinson’s disease (PD).75,129 Although only preliminary studies
have been carried out, there are encouraging indications that merit further
investigation. Michalikova et al.
found that LLLT could reverse memory degradation and induce improved cognitive
performance in middle-aged mice,74 and Trimmer et al. found that motor function was
significantly improved in human patients treated with LLLT in an early stage of
FALS.112
Intravascular Laser
Therapy
Intravenous or
intravascular blood irradiation involves the in vivo illumination of the blood by feeding low level laser light
generated by a 1–3 mW low power laser at a variety of wavelengths through a
fiber optic inserted in a vascular channel, usually a vein in the forearm (Fig. 5a), under the assumption that any
therapeutic effect will be circulated through the circulatory system117 (see Fig. 5b). The feasibility of intravascular
laser irradiation for therapy of cardio-circulatory diseases was first
presented in the American Heart Journal in 1982.57 The technique was
developed primarily in Asia (including Russia) and is not extensively used in
other parts of the world. It is claimed to improve blood flow and its transport
activities, but has not been subject to randomized controlled trials and is
subject to skepticism. Although it is at present uncertain what the mechanisms
of intravascular laser actually are, and why it differs from traditional laser
therapy; it has been hypothesized to affect particular components of the blood.
Blood lipids (low density lipoprotein, high density lipoprotein, and
cholesterol) are said to be “normalized”56; platelets are
thought to be rendered less likely to aggregate thus lessening the
likelihood of clot
formation,107 and the immune system (dendritic cells, macrophages and
lymphocytes) may be activated.109
FIGURE 5
Some examples of
LLLT devices and applications. (a and b) Intravascular laser therapy (Institute
of Biological Laser therapy, Gottingen, Germany). (c and d) Laserneedle
acupuncture system (Laserneedle GmbH, Glienicke-Nordbahn, Germany). (e and f)
Lasercomb (Lexington Int LLC, Boca Raton, FL) for hair regrowth. (g) Laser cap
(Transdermal Cap Inc, Gates Mills, OH) for hair regrowth.
Laser Acupuncture and
Trigger Points
Low power lasers
with small focused spots can be used to stimulate acupuncture points using the
same rules of point selection as in traditional Chinese needle acupuncture.119 Laser acupuncture
may be used solely or in combination with needles for any given condition over
a course of treatment. Trigger points are defined as hyperirritable spots in
skeletal muscle that are associated with palpable nodules in taut bands of
muscle fibers. They may also be found in ligaments, tendons, and periosteum. Higher doses of LLLT may be used for the
deactivation of trigger points. Direct irradiation over tendons, joint margins,
bursae etc. may be effective in the treatment of conditions in which trigger
points may play a part. The Laserneedle
system (see Figs. 5c, 5d) can be used
to stimulate multiple acupuncture points or trigger points simultaneously.97
LLLT for Hair Regrowth
One
of the most commercially successful applications of LLLT is the stimulation of
hair regrowth in balding individuals. The photobiomodulation activity of LLLT
can cause more hair follicles to move from telogen phase into anagen phase. The newly formed
hair is thicker and also more pigmented. The Hairmax Lasercomb (Fig. 5e) was shown55 to give a
statistically significant improvement in hair growth in a randomized,
double-blind, sham device-controlled, multicenter trial in 110 men with
androgenetic alopecia and this led to FDA clearance for efficacy (FDA 510(k)
number K060305). The teeth of the comb are supposed to improve the penetration
of light though the existing hair to the
follicles requiring
stimulation (Fig. 5f). Recently, a
different LLLT device received FDA clearance in women suffering from
androgenetic alopecia (FDA 510(k) numberK091496). This group of patients have
fewer treatment options than men. In order to make the application of light to
the head more user-friendly and increase patient compliance, companies have
developed “laser caps” (Fig. 5g).
CONCLUSION AND OUTLOOK
Advances in design
and manufacturing of LLLT devices in the years to come will continue to widen
the acceptability and increase adoption of the therapy among the medical
profession, physical therapists and the general public. While the body of
evidence for LLLT and its mechanisms is still weighted in favor of lasers and
directly comparative studies are scarce, ongoing work using non-laser
irradiation sources is encouraging and provides support for growth in the
manufacture and marketing of affordable home-use LED devices. The almost complete lack of reports of side effects
or adverse events associated with LLLT gives security for issues of safety that
will be required.
We
believe that LLLT will steadily progress to be better accepted by both the
medical profession and the general public at large. The number of published
negative reports will continue to decline as the optimum LLLT parameters become
better understood, and as reviewers and editors of journals become aware of
LLLT as a scientifically based therapy. On the clinical side, the public’s
distrust of big pharmaceutical companies and their products is also likely to
continue to grow. This may be a powerful force for adoption of therapies that
once were considered as “alternative and complementary,” but now are becoming
more scientifically accepted. LLLT is not the only example of this type of
therapy, but needle acupuncture, transcranial magnetic stimulation and
microcurrent therapy also fall into this class. The day may not be far off when
most homes will have a light source (most likely a LED device) to be used for
aches, pains, cuts, bruises, joints, and which can also be applied to the hair
and even transcranially to the brain.
Acknowledgments
Funding: Research
in the Hamblin laboratory is supported by NIH grant R01AI050875, Center for
Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), CDMRP
Program in TBI (W81XWH-09-1-0514) and Air Force Office of Scientific Research
(FA9950-04-1-0079). Tianhong Dai was supported by an Airlift Research
Foundation Extremity Trauma Research Grant (grant 109421).
Footnotes
CONFLICTS OF INTEREST James D. Carroll
is the owner of THOR Photomedicine, a company which sells LLLT devices.
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