The use of Low Level Laser Therapy (LLLT) or sometimes called Low Energy Laser Therapy (LELT), in medicine goes back to the late 1960s, only 8 years after the first laser was developed by Theodore Maiman, Maiman's system was built around a ruby crystal and produced an intense millisecond beam of pure, visible red light which was capable in that ultra-short time of drilling a neat hole through a stack of razor blades. First ophthalmologists and then dermatologists saw the possibilities of using this intense light energy beam in their respective fields, and other applications were quickly found. These applications increased in direct proportion to the development of other wavelengths, with their own particular absorption characteristics, and by 1964, the mainstay lasers still used today in laser surgery had made their appearance. 1961 saw the development of the helium neon (HeNe) and neodymium-yttrium aluminum garnet (Nd:YAG) lasers. In 1962, the argon laser appeared, followed in 1964 by the carbon dioxide (CO2) laser. In late 1964, semiconductor laser sources were being developed, including the first gallium arsenide laser chip.

The ruby laser, with a visible red beam, still has applications in dermatology. The HeNe, with a visible orange/red beam, is used as an aiming beam for the invisible light lasers, the Nd:YAG and the CO2. However, the HeNe has also gained fame as one of the most used systems in LLLT. The argon laser is used principally in ophthalmology and dermatology, because of its visible blue/green beam's biological pigment specificity. The Nd:YAG is used for deep vaporization of tissue mass, and with contact sapphire tips, as an incisive tool. The YAG also is used in LLLT, as its wavelength characteristics give it deep penetration. The CO2 remains one of the most versatile of the surgical medical lasers. It can produce very high power densities, capable of clean, precise linear and bulk vaporization and can also coagulate. Recent experimental data point to the possible application of CO2 lasers in low reactive-level laser therapy (LLLT).

Birth of LLLT

Incision, vaporization and coagulation seemed to be the way to use this new light source in medicine, However, the late Professor Endre' Mester, the grandfather of "'what he termed 'laser biostimulation', felt that the lower-powered beams could produce non-thermal effects in irradiated tissue, and starting in 1968 he used ruby, argon and HeNe lasers at low output powers in in-vitro experimentation on cellular behavior following low-powered irradiation, This was followed with animal in-vivo work in 1969, and in late 1969 he first published his, by now, well known work on the use of low-reactive level laser therapy, or LLLT, to induce healing in torpid non-healing or slow-to-heal ulcers, which had remained resistant to conventional therapeutic methodologies.

His work was followed by others, noticeably Freidrich Plog in Canada, who used HeNe in both acupoint and trigger point irradiation for pain attenuation: and I.B. Kovacs, another Hungarian, who also presented data on the effectiveness of HeNe on in-vivo wound healing acceleration, By the mid-70s, the base of data was increasing, but still was not readily accepted by the majority of Western medical practitioners

In 1979, a French scientist and engineer, Joseph Skovajsa, developed and patented a diode laser system for medical applications, and it is on his work that many of the present-day diode systems are based. There was a subsequent surge of interest in low level laser therapy and the emergence of 'laser acupuncture' dates from that time. In 1981, the 4th Congress of the International Society for Lasers in Surgery and Medicine, held in Tokyo, had for the first time a section dedicated to 'Laser Acupuncture'. The effectiveness of laser acupuncture was high. In addition, some papers appeared on non-acupuncture applications, including papers by Mester and Kovacs. The diode laser made its literature debut at that Congress, in a comparative study with the Nd:YAG laser for pain attenuation authored by Calderhead and Chadwick Smith.

Development of the Diode Laser System

Diode lasers were at first restricted to gallium arsenide (GaAs) systems, which usually produced a 904 nm beam, although the Japan Medical Laser Laboratory was working on an 830 nm GaAs system. GaAs systems were typically difficult to run for long periods in continuous wave because of the propensity of the chip to overheat. From late 1979, experiments were being carried out using a new diode, the gallium aluminum arsenide (GaAlAs) chip, which could produce a variety of wavelengths from 720 to 904 nm and could moreover run in continuous wave without overheating, From available data, a tissue penetration window could be observed at 820-840 nm due to the low water absorption at that waveband. The Japan Medical Laser Laboratory (JMLL) worked on developing a GaAIAs system for medical applications producing an 830 nm beam. Together with Matsushita Electrical Company (better known as National Electronics), a battery-powered, hand-held 15 mW 830 nm continuous wave system made its debut also at 'Laser Tokyo '81'. In fact, Professor Leon Goldman often referred to as the 'Godfather' of the surgical laser, was one of the first to try out and enjoy the therapeutic properties of this new totally self-contained handheld system at that 1981 Congress.

In early experimental work, including in-vivo animal experiments, this 15 mW system proved more effective than the previous GaAs system, and better than the 1064 nm Nd:YAG system, even for more deeply located tissue targets, but without the heat-related side effects noticed with the YAG system used in LLLT. Particularly, the influence of its beam on vascular proliferation was noted. Spurred on by this success, the JMLL experimented with a number of output powers from 15-100 mW and wavelengths from 790-904 nm with pulsed, frequency-modulated, and continuous wave beam types, As for output powers, for anything below 60 mW a distinct falling off in immediate and delayed effective pain removal and decreased microvascular reaction was observed, At 100 mW, effects of a quasi-photothermal nature were noted, such as exacerbation of the pain involuntary muscular spasms and nerve syncope, The ideal output power was finally set at 60 m. From 60 mW up to the side-effect-producing 100 mW range there was no noticeable improvement. The wavelength experiments showed a peak penetration effect at 820-840 nm, with a corresponding increase in the effectiveness of laser beams within that waveband. Finally, JMLL produced, once again in cooperation with Matsushita, the first of the second-generation GaAlAs diode laser systems, the Panalas 4000. This was followed up with the independent JMLL design and construction of an updated third-generation microprocessor-controlled GaAlAs system, the OhLase-3DI, commercially available through Proli Japan, Ltd. The diode laser has shown itself to be superior in penetration to others, and it is based on the GaAlAs diode laser that the practical applications of LLLT have been demonstrated.

WHY A LASER?

The use of lasers in medical applications has been discussed extensively in the literature and in numberous medical congresses. In some applications, the laser is now perceived as the only way to accomplish the effect the surgeon wishes to achieve. This is especially true in ophthalmology, dermatology and gynecology, and is becoming apparent in endoscopic applications. In LLLT, where the effect of the laser is not macroscopically instantly visible, the reasons for using a laser instead of, for example, analgesics or bed rest have to be examined a little more closely.

Penetration and Absorption

Basically, the light from a laser, even a milliwatt LLLT system, can penetrate deep into tissue. This is due to the laser's unique properties. A laser beam travels in only one direction from its source, unlike a light bulb. A laser is monochromatic with its photons; (little light energy packets), all completely identical, and all traveling exactly equidistant in time and in space. The resulting beam therefore, has a considerably higher photon density than a monochromatic beam produced by filtering and collimating a conventional multi-wavelength light source. The polarization of a laser beam is also of importance in its possible applications. The end result is that the penetration of a laser beam in tissue is much greater than a conventional light source, even though the pure coherence of the beam may be lost in the first few cell layers. The photon density of the beam ensures that more photons will penetrate the tissues to reach the desired target. In-vitro studies have often pointed to no coherent-specific reaction: these ignore the simple fact that in a monosheet or ultra-thin cell medium, coherence does not make much difference as the target cells are right at the surface of the layer or medium. In in-vivo tissue targets, several layers of non-homogeneous particulate matter have to be penetrated before the beam can reach the LLLT targets, and it is the superior photon density of coherent light, which ensures this penetration, even though actual coherence may be lost in the first few cell layers.

The main factor which can affect the actual depth to which a laser beam; penetrates is the wavelength of the beam: the output power is of some secondary importance. But the physical properties of the target tissue will limit the penetration of particular wavelengths, no matter how much power is behind them. Naturally in surgical lasers, the higher the power, the bigger the hole, but that must not be confused with penetration. Actually lasers which are well absorbed in surface tissues do not penetrate deeply, and so make better surgical lasers, with better depth control. In photodestructive surgery, this is of great importance. Surgical lasers rely mainly on an instantaneous radiant heat effect with a secondary conducted heat effect: thus high peak power with a short irradiation time gives the best radiant heat effect, limiting the secondary thermal tissue damage wave from conducted heat. When this radiant heat effect is coupled with the absorption characteristics of the target tissue, cellular- or subcellular-selective treatment can be achieved. High density CO2 laser energy is absorbed preferentially in water, thus limiting its penetration depth. Red and black biological pigments, blood and melanin, absorb blue and green light well, peaking at the yellow waveband: thus the argon, KTP-532, argon-pumped dye, flashlamp-dye, copper-vapor, and krypton lasers are all finding good applications where this absorption is important. The HeNe on the other hand is red, the color of blood, so it tends to penetrate much deeper than those previously mentioned. The YAG is not really pigment-preferentially absorbed, and is instead absorbed in protein. However, the YAG beam does have a recognizable water absorption component.

That is where the 820-840 nm penetration window comes into play, and why the GaAIAs diode laser at 830 nm offers the clinician a penetrative tool of great efficiency. From data obtained with the use of infrared and visible-light sensitive charge-coupled device-based cameras (CCO) to assess actual depth and volume penetration in in-vivo soft tissues, the penetration rates of the various wavelengths can be summarized as in Figure 1.1. These data compare well with other absorption and penetration data previously published in the literature.

Having penetrated, the light energy must go somewhere, and recent experimental work has shown that the 830 nm run beam is well absorbed in subcellular organelles, significantly increasing their capacity to do whatever they normally do, well beyond their normal state. This has been demonstrated in Ivsosomes and mast cells particularly increasing in a very short time. The density of cell-produced proteinous substances in the blood and lymphatic systems increases due to the laser-induced acceleration of these components, such as the various immunoglobulins, histamine, serotonin, and macromolecular units such as the prostaglandin complex. That is only the immediate creation. These components are carried systematically through the body by the blood and lymphatic circulatory systems, and can then have a secondary or delayed effect, producing a successive series of reactions in the body. Recent work has demonstrated increased phagocytic action in LLLT -irradiated human neutrophils. In addition, nerve fibers have now been shown to contain photosensitive components, so that the hypothesized LLLT-mediated action on neural physiochemical functions is gradually becoming a scientific reality. The work of Judith Walker and coworkers in this area is particularly interesting. Semion Rochkind and the Tel Aviv research team have shown regeneration of crush-damaged neural tissue following non-contact LLLT with a HeNe beam, to the point where the damaged nerve is performing with greater efficiency than an undamaged unirradiated control.

Figure (above) 1.1 Comparative transmission of laser wavelengths in tissue

TARGETS FOR LLLT

Appropriate targets for LLLT are found at many levels, from whole tissue units down to the organelles of the cells which make up the target unit, including the nerve, lymphatic and blood networks and expanding from there to a systemic total body consideration.

The big advantage of the laser is, therefore, not only its precision for immediate localized action, but also the 'lasting' effect which accompanies LLLT treatment, which has been demonstrated to continue for several days after a single irradiation. Additionally, LLLT has been shown to be cumulative in its therapeutic effect, with longer and longer post-irradiation effects being noticed by the patient after successive therapeutic sessions.

Essentially, the clinician has a wide range of LLLT targets to choose from. Naturally the condition being treated will determine the initial target to a very great extent. The three basic target systems can be summarized as the nerve network, the lymphatic system and the blood circulatory system, in addition to the recent work based on the humoral system. This is naturally a very simplified answer to what is actually an extremely complex series of interlinked infrastructures. Each target system exists at several levels, and the clinician must determine the optimal level for treatment. This is turn affects the treatment method- No matter which system is targeted, the end result has to be a normalization of an existing abnormality or imbalance

The imbalanced state is the result of an abnormal condition in one or more of the above systems. Simplistically put, correct the abnormality, and the condition will improve. In some acute conditions, the normalization will take place without LLLT, but the important factor is to speed up the normalizing process, so that the patient can resume normal activities sooner. Acute soft tissue trauma is a good example. The injury consists or several elements: the actual tissue architecture damage, involving dermal muscular, neural lymphatic and vascular tissue. The body's natural reaction is to 'splint' the injury with edema, preventing excessive movement. Pain is therefore of two types; actual insult pain to the injured tissue, and a secondary pressure pain from the edematous swelling. The target here is first the lymphatic system, to increase reabsorption of the edema, and then the actual injury site itself. All three main target systems are treate; to speed up the natural healing process in the damaged tissues, reduce the injury pain, and increase mobility of the area, which in turn speeds up the whole process. This interdependent functional consideration is at the heart of LLLT techniques. There is no simple rule to follow. However, once the interrelationships have been understood, the concept behind LLLT will become clearer, and consistently good results will be achieved.

 

SAFETY

LLLT and the Human Eye

Because of the inherently low powers of LLLT systems, a somewhat cavalier attitude is occasionally seen in dealing with these systems. It is understandable, when practitioners are accustomed to dealing with lasers that can cut or burn tissue that the non-thermal nature of LLLT laser / tissue interaction breeds a false sense of security. A laser is still a laser, whether it is a 15 mW HeNe or a 100 W CO2 Naturally, the potential for danger is different between the two: the high-powered system has the greater capacity for causing damage. However, all lasers share the same basic physical beam properties, and this can make the 15 mW HeNe potentially as dangerous as the 100 W CO2, The main concern for the LLLT user is the possibility of ocular damage.

The human eye is one of the most efficient focusing systems found in nature. The eye works as a lightgathering machine, and having gathered as much light as possible, the lens then focuses this light onto the retina at the back of the eye. The light usually takes the form of an inverted image of the object viewed, very much like a camera works. However, the simple experiment of taking a magnifying glass and burning a hole in a leaf with a magnified image of the sun, followed by trying to repeat the reaction by focusing the light from a 100 W light bulb with the same magnifying glass on the same leaf quickly shows the difference between light from a point source such as the sun (no matter how distant), and a diffuse source, such as a light bulb. The sun can produce an extremely small magnified spot of light. The human eye sees a light bulb, however, as merely an inverted tiny image of the bulb. The energy from a light bulb is spread over a large spectral range, and emits from the bulb in random directions over the entire surface of the bulb. The possible light gathered by the eye is therefore very small, as seen in Figure 1.2.

Figure (above) 1.2. Only a tiny fraction of available emitted light energy from a light bulb is gathered by the lens and focused onto the retina as an inverted mini-image of the bulb itself.

Figure (below) 1.3. Collimated and coherent beam of energy from a laser is completely gathered by the lens and focused totally onto the fovea. In the case of a truly collimated (i.e. non-divergent beam) the viewing distance d1 is immaterial to the amount of light gathered.

Figure (above)1.4 Most diode lasers produce a divergent beam. In such cases the eye cannot gather all the beam, and the potential eye hazard is thus less than a fully collimated beam. In the case of a divergent beam, the amount of energy reaching the retina decreases in direct proportion to the increase of distance d1 and solid angle of divergence 0o sr.

A laser is a perfect point source, even more perfect than the sun. The sun's rays come down to earth through the diffusing atmosphere, and are spread out over a large area. The actual power density of sunlight on skin at any given wavelength is measured in microwatts per square centimeter (µm/cm2). LLLT systems produce anywhere from several microwatts per square centimeter (W /cm2) to several watts per square centimeter (W /cm), several orders of magnitude greater than terrestrial sunlight, and with a much higher photon density, as already discussed above. The potential danger of accidental LLLT irradiation of the eye is thus very high. This is especially true of the infrared lasers, the diode, Nd:YAG and CO2" whose beams are infrared, are not detected by the eye, and where the automatic blink-reflex is therefore not triggered. Naturally, aiming beams will reduce this hazard. A laser beam can be focused to micrometer-sized spots on the retina. If the eye is unaccommodated, i.e. at rest, this spot strikes directly in the fovea at the center of the macular disc, the spot in the eye responsible for visual acuity, as shown in Figure 1.3. A seemingly harmless 60 mW, if focused to a 20 µm spot, produces an actual power at the tissue (power density) of over 45,000 W / cm_. This is sufficient to cause serious permanent damage. Of course, this is a 'worst case' example, assuming total gathering of available laser energy by an unaccommodated eye. In actual practice, typical diode laser beam paths are highly divergent, so that at distances of over 1 meter, only a small fraction of the laser energy is able to be gathered by the eye and focused, as shown in Figure 1.4. Please remember, however, that power densities of over 500 W/cm have the potential to injure ocular tissue seriously, particularly the retina, at wavelengths, which are capable of being transmitted through the cornea and lens.

Eye Protection

Obviously, the safest anti-damage measure is to protect the eyes of all personnel and patients in the treatment room with appropriate laser glasses or goggles. Note that the clear plastic glasses supplied for the laser will not offer any protection against any other wavelength. Laser safety glass is classified by its optical density (00). An optical density of 0 allows 100% transmission. For each whole value number, the transmission decreases by an order of magnitude. Thus an 00 of 1 will allow 10% transmission; 2, 1 %; 3, 0.1% and so on. For the diode laser, eyewear providing a minimum 00 of 2 at the appropriate wavelength for the system used is therefore necessary. Note that some glasses are designed for particular wavelengths.

Other Hazards

The only other real hazard with LLLT systems is electrical from the system itself. As they are usually powered by standard single phase AC voltage, the hazards are those associated with any piece of electrical equipment, and usual common sense will prevent any mishaps. In general, read the system user's manual.

Safety with LLLT systems, with the exception of possible eye hazards, is mostly a matter of simple common sense. Obviously the greatest hazard is to the eyes of personnel in the treatment room, including the patient. Suitable protective eyewear, good training, and sensible use of the system will prevent any untoward occurrences. Safety should always be the first order of the day.

TERMINOLOGY

The basic definitions of any discipline, including LLLT, are necessary for its full understanding and correct application.

Accentuate the Positive

The late Professor Endre Mester coined the phrase 'laser biostimulation'. He was using the system to treat non-healing ulcerations, and there was a positive stimulation effect in the LLLT-irradiated tissue which induced healing in these slow-to-heal torpid ulcers. In Professor Mester's electron microscopy studies after laser irradiation, fibroblasts were found to produce more collagen by accelerated division and tropocollagen production, but without an increase in actual cell numbers, and an increase in enzymatic components was found: lysosomes and mitochondria were swollen. These all point to a stimulating effect. However, it has now been shown that LLLT will also retard overproduction in hypertrophic scars and keloids, for example, in excessive pigmentation for naevi therapy, and in the reduction of pain. Thus LLLT can be used both to increase and decrease normal physiological functions to bring about a normalization. This is the 'accelerator and brake' theory. In a car, acceleration and braking are both actions, as a result of which a system of the vehicle is activated; in the one, to produce an increase in speed; in the other, to provide the opposite effect. A more accurate description for the medical use of LLLT might then be laser bio-activation.

The Means Or the End?

The other aspect of LLLT is the profusion of terms which surround the tool being used, the laser. "Cool", "mid-level energy", "low output" and "soft" are all used in the literature. Surely, however, it is the therapeutic result in which both clinician and patient are interested. Conventional lasers produce photothermal and other effects in tissue which are distinctive in nature. There is a permanent change in the irradiated tissue following laser irradiation, and this is true of incision, vaporization and coagulation. It is also true of the non-thermal destruction of haematoporphyrin-perfused cancer cells following irradiation with low-intensity red laser light. Thus the destruction need not be only thermal. The reaction in tissue following such laser irradiation is therefore above the survival threshold of normal tissue, causing death or disruption. This could be called high energy level treatment. Because it is being performed with a laser, it could also be called high energy level laser treatment, for short. On the other hand, the reactions following laser therapy are non-thermal in nature, and leave tissue alive and well. As said before, these actions are both of a stimulating and retarding nature, but the whole idea is to leave the target tissue in a normal condition. Because no surgery is involved, this treatment can be referred to as therapy. Because the level of reaction in the laser-irradiated target tissue is below the destructive threshold, it can be called low energy level therapy. Because the laser is the therapeutic tool, it becomes low energy level laser therapy", or LLLT, with the accent on level and therapy. In other words, the clinician is not concerned with the means but with the end, the therapeutic effect in the target tissue, or target cells in experimental application.