Dec. 16, 2024
Photobiomodulation (PBM) is a treatment method based on research findings showing that irradiation with certain wavelengths of red or near-infrared light has been shown to produce a range of physiological effects in cells, tissues, animals and humans. Scientific research into PBM was initially started in the late s by utilizing the newly invented () lasers, and the therapy rapidly became known as &#;low-level laser therapy&#;. It was mainly used for wound healing and reduction of pain and inflammation. Despite other light sources being available during the first 40 years of PBM research, lasers remained by far the most commonly employed device, and in fact, some authors insisted that lasers were essential to the therapeutic benefit. Collimated, coherent, highly monochromatic beams with the possibility of high power densities were considered preferable. However in recent years, non-coherent light sources such as light-emitting diodes (LEDs) and broad-band lamps have become common. Advantages of LEDs include no laser safety considerations, ease of home use, ability to irradiate a large area of tissue at once, possibility of wearable devices, and much lower cost per mW. LED photobiomodulation is here to stay.
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Keywords: photobiomodulation therapy, low-level laser (light) therapy, light emitting diodes, mechanisms: medical indications
Distinct wavelengths of light have been known to have various biological effects on humans. Ultraviolet-B radiation promotes vitamin D synthesis and visible light has important effects on circadian rhythm entrainment and alertness. For more than three thousand years, sunlight has been used as a medical treatment for a variety of diseases by the ancient Egyptians, Indian Ayurveda and traditional Chinese medicine, but it is only since the invention of the electric light in the latter part of the 19th century, that an alternative has emerged.
Since the beginning of the 21st century, over PubMed-indexed scientific articles have also been published focusing on the various physiological effects of red light and near-infrared radiation. These wavelengths of light have been shown to penetrate through human tissues and to locally (and possibly systemically) affect cellular metabolism, cellular signaling, inflammatory processes and growth factor production.
This treatment is nowadays called &#;photobiomodulation therapy&#; (PBM), but it has also had more than 60 other names in the scientific literature; &#;low-level laser therapy&#; (LLLT) has been the most commonly used term. The reasons to prefer the use of &#;PBM&#; over &#;LLLT&#; are twofold [1]. Firstly PBM does not imply that a laser is necessary for the therapeutic benefits to occur. Secondly PBM implies that the therapeutic effects could in some circumstances be due to inhibition effects, as well as to the more usual stimulation effects.
Table 1 illustrates various medical conditions (or their animal models), for which PBM has already been investigated, in animals and/or clinical human studies. These indications include a multitude of diseases of brain, bone, eyes, internal organs, connective tissue, skin and muscles. Most of the published results have been positive. More than 40 clinical studies are currently underway based on information currently available in the ClinicalTrials.gov database.
Medical indications studied in photobiomodulation research
Acne Crescentic glomerulonephritis Liver regeneration Periodontitis Achilles tendinitis Delayed hypersensitivity Lung fibrosis Peritonitis Acute pain Dentin regeneration Lung hemorrhage Pleurisy Acute respiratory distress syndrome Depression Lung inflammation Pressure ulcer Adipose tissue inflammation Dermal abrasions Lung injury Radiation injury Age-related macular degeneration Diabetic kidney Lymphedema Restenosis Allergic asthma Diabetic eyes Mastitis Retinitis pigmentosa Allergic contact dermatitis Diaphragm muscle dysfunction Methanol toxicity of retina Rheumatoid arthritis Allergic rhinitis Eardrum perforation Morphine withdrawal Sarcopenia Allodynia Endophthalmitis Multiple sclerosis Sciatica Alzheimer&#;s disease Exercise performance Muscle injury Spinal cord injury Amyotrophic lateral sclerosis Haemarthrosis Myocardial infarct Stroke Aneurysm Hair loss Myonecrosis Submandibular gland inflammation Arthritis Heart failure Myopathy Surgical wound infection Atherosclerosis Hearing loss Nerve injury Teeth re-implantation Atrophic gastritis Hyperalgesia Neuropathic pain Tendinopathy Auditory neuropathy Hypertension Oral mucositis Thrombocytopenia Bone fracture Kidney fibrosis Oral ulcer by formocresol Tinnitus Bone grafts Kidney injury Osteoarthritis TMJ inflammation Burn injury Laryngitis Osteomyelitis Tracheal incision healing Cancer Ligament injury Osteoporosis Traumatic brain injury Colitis Listeria infection Parkinson&#;s disease Wound healing COPD Liver cirrhosis Paw edema Open in a new tabIt has been shown that many cellular molecules are able to absorb various wavelengths of light. In photobiomodulation with visible red light and near-infrared radiation, evidence suggests that the primary cellular photoacceptors are the copper centers of cytochrome c oxidase (CCO), a complex protein functioning as unit IV in the mitochondrial electron transport chain [2, 3].
It appears that specific wavelength ranges of red light and near-infrared radiation can be utilized to promote electron transport, based on a multitude of findings showing increased mitochondrial membrane potential, oxygen consumption and ATP levels after irradiation. There is also some preliminary evidence suggesting that some other wavelengths can be used to inhibit electron transport, which could be useful in the treatment of ischemia-reperfusion damage [4].
The physiological effects of longer wavelengths than 900nm might, on the other hand, depend on transient receptor potential (TRP) calcium channels [5]. Photobiomodulation-like effects have also been observed with blue and green light, and it is hypothesized that these effects might also be mediated by calcium channels [6]. While plenty of basic research on photobiomodulation has already been published, there is a lot of room for additional experiments examining the exact molecular mechanisms of light-cell-interactions.
The initial interaction between light and cellular photoacceptors (called a &#;primary photoreceptor mechanism&#;) is followed by the activation of multiple secondary mediators. These eventually lead to broad shifts in gene expression, cell signaling, cellular metabolism and cytokine secretion. These effects been described in numerous review articles in the literature [7, 8].
While medical treatments are often able treat only location-specific diseases, the observed effects of PBM on more than a hundred different treatment indications might be related to its observed mitochondrial effects. Since majority of aging-related chronic diseases have been linked to dysfunctional mitochondria and oxidative stress, it seems plausible that improving the mitochondrial function and antioxidant defenses could also alleviate these diseases [9, 10]. Since many chronic diseases share common metabolic causes, systemic treatment methods that alter metabolism could alleviate ailments of many different body parts.
The effects of PBM could possibly be compared with the mitochondrial-boosting and health-supporting effects of supplements, such as nicotinamide riboside (NR), an NAD+ precursor. NR has been shown to protect against animal models of metabolic syndrome, liver disease, stroke, Alzheimer&#;s disease, heart failure and myopathy [11]. Early PBM studies also showed comparable effects between red light and a chemical called methylene blue, which has also been shown to improve mitochondrial respiration and simultaneusly protect animals from a remarkably wide range of chronic diseases [2, 12, 13].
Laser is an acronym for &#;light amplification by stimulated emission of radiation&#;. Lasers are light sources that utilize the physical phenomenon of stimulated emission to create a monochromatic and coherent beam of light of low divergence. The first working laser was invented in by Theodore Maiman [14] who was the first past the finishing post in an epic race that came to be called &#;The race to make the laser&#; [15].
The basic mechanims of action of a laser is shown in Figure 1. It relies on pumping the electrons of a &#;laser gain medium&#; E1 to an excited state E2 using light, electricity or a chemical reaction as the energy source. Once a majority of electrons are in the excited state (population inversion) an incoming photon Ephoton will lead to stimulated emission of a torrent of new photons (coherent and polarized) and the light will be amplified (Figure 1A). Mirrors placed at either end of the laser cavity allow the light to bounce back and forth while pumping continues leading to significant aplification. One of the mirrors is only partly reflective to allow the laser beam to escape from the cavity (Figure 1B).
(A): Principle of population inversion and stimulated emission; when a majority of the atoms in a laser material are pumped to a higher electronic state, an incoming photon can cause release of the excess energy as coherent photons of the same wavelength. (B) Principle of a laser cavity confined by two mirrors, one of which is partially transmissive.
Modern photobiomodulation literature is founded on the basis of original findings by Endre Mester, a physician from Hungary, who published a report describing hair-growing effects in mice treated with ruby laser (694 nm) in the late s [16]. After that, he supplemented these findings by clinical reports suggesting that red laser light could improve the healing of various ulcers in humans [17].
These initial observations soon led to additional scientific studies investigating the effects of red and near-infrared wavelengths of laser light in the treatment of a huge variety of chronic diseases. The Soviet Union was a pioneering country by conducting early research with helium-neon (He-Ne laser) in the s and s. Tiina Karu working in Troitsk in Russia published over 100 papers in this field (https://www.isan.troitsk.ru/dls/karu.htm). By the end of s, many research groups around the world (eg. USA, Japan, Sweden, Israel, Italy) had already started their photobiomodulation research projects. Nowadays PBM has been studied in approximately 40 different countries [18, 19].
To this day, more than scientific articles on photobiomodulation have been published. Approximately 85&#;90% of the original research has utilized lasers as light sources. Practically all of the photobiomodulation research before the 21th century was based on lasers.
This laser-centered history of photobiomodulation has been the reason fot the assumption that the beneficial physiological effects of red and near-infrared light are somehow dependent of the &#;laser properties&#; of light, such as monochromaticity, coherence, collimation or polarization. According to current knowledge, this is certainly debatable and probably not true, and will be critically discussed in this review.
Light-emitting diodes (LEDs) are light sources based on the phenomenon of electroluminescence of semiconductor materials, most often InGaN (60%) and AlInGaP (38%) [20]. The earliest historical accounts of LEDs were written by Henry Round and Oleg Losev in the and , respectively. These scientists showed that crystals of a semiconductor material, silicon carbide (SiC), glowed when an electrical current passed through them.
Nick Holonyak, Jr. (born November 3, ) invented the first visible LED in while working as a consulting scientist at a General Electric Company laboratory in Syracuse, New York, and he has been called &#;the father of the light-emitting diode&#; [21]. A few decades later, electroluminescence properties of other semiconductors were studied especially in the United States, which eventually led to the invention of orange, yellow and green LEDs in the s and s. Since then, LED technology has undergone many improvements, and LEDs represent a growing portion of the sales of indoor, and even outdoor lighting. Nowadays one of the most important challenges in the industry is to improve the luminous efficacy of LEDs [22].
It should be noted that the basic principle of operation is the same in LEDs and diode lasers, and is termed the PIN semiconductor diode (Figure 2). An electric potential applied to the semiconductor causes separation of electrons in the N (negative)-section and holes in the P (positive)-section. When the electrons and holes recombine in the I (intrinsic)-section, light is produced whose wavelength depends on the energy of the electrons. In order to produce a laser diode a waveguide is applied to the outside of the PIN diode which acts in the same way as the mirrors in the traditional laser cavity.
In a PIN-type semiconductor, positive holes occur in the P-region, negative electrons in the N-region, and these recombine in the I (intrinsic)-region to give non-coherent light whose wavelength is determined by the semiconductor composition
Unlike incandescent and halogen lamps, which are based on electrical resistive heating and subsequent thermal radiation including both visible wavelengths and infrared radiation, LED light emission is based on non-thermal emission of light.
An important difference between laser light and LED light (in addition to coherence discussed below) is the band width. Lasers can have a very narrow bandwidth; for instance in gas lasers it can be a fraction of a nanometer, while in diode lasers the bandwidth is typically 1&#;2 nm.
Photobiomodulation by light-emitting diodes is a relatively new phenomenon. With the exception of a few papers published towards the end of the 20th century, LED-LLLT (or LED-PBM) has started appearing regularly in the literature only since . In these early years, some of the basic research with LEDs was conducted by Harry Whelan&#;s group located in Wisconsin-Milwaukee [23]. Because the development of these LEDs was funded by the US National Aeronautic and Space Administration (NASA) as a light source for plant growth experiments in space, they were often referred to as NASA LEDs [24].
Nowadays the use of LEDs in photobiomodulation and other healthcare applications has been quite well established and their efficacy has been demonstrated in many reports [25].
LEDs are much cheaper than laser devices on average. As a rule of thumb, the cost per mW of optical power is approximately one hundred times lower for LEDs compared to lasers. In the past, laser light sources were predominantly marketed to clinicians, who could cover the high costs of their devices by treating a large number of patients. However, during the recent years, patients themselves or even healthy individuals, have been able to buy their own LED devices for personal use at home. Various LED-based quasimonochromatic in-home devices are nowadays widely available, and the prices appear to be steadily falling due to increasing demand and competition between companies.
One of the most important factors hindering the acceptance of PBM/LLLT in the healthcare is cost-effectiveness. In addition to the high device prices, additional costs come when the therapeutic session is carried out by healthcare practitioners such as physical therapists, chiropractors, nurses or physicians. Only in few cases is this cost-effective when the lasers are used [26]. In this sense, the adoption of LED lights into PBM/LLLT treatment practices could support the wider acceptance of PBM/LLLT by the medical community.
Also, multiple LEDs can be arranged into planar arrays. This increases the beam area significantly, making it easier to treat large body areas, which has been a limitation of lasers that typically have tiny to small spot sizes. The only limit on the power output of a LED array is caused by the need to remove heat from the actual diodes. Since the typical LED is only 20&#;30% efficient in converting electrical energy to light energy, this means that heat is generated and excessive heat can lead to degradation of the semiconductior material and reduction in its lifetime. Moreover if the LED array is designed to be used in contact with the tissue, it cannot be allowed to get too hot. Heat is removed by heat-sinks (heat conducting metal substrates) or in some cases by incorporation of a small fan to cool the diodes.
Flexible wearable LED arrays are becoming available for use as bandages (to be wrapped around joints for instance). There is a flexible LED belt designed to be wrapped around the abdominal area for fat reduction. Light emitting clothing might become a future way to apply light [27]. Therapeutic lasers have been integrated into caps, helmets, and hair combs for stimulation of hair regrowth [28]. With LEDs, the same applications would cost less to the customers. However the laser hair growth industry has so far remained committed to lasers at the expense of LEDs, and several manufacturers maintain that red lasers (~650 nm) are the best light source to stimulate the hair follicle and its progenitor cells.
There are several properties of lasers that proponents claim may be reasons why laser light is superior to LED light for PBM. The most often discussed property is that of coherence. Laser devices generate coherent light with various coherence lengths depending on the band-width of the specific laser. Coherence lengths of lasers can range from many meters for the He-Ne laser to only a few mm for diode lasers. When coherent laser light interacts with tissue, small imperfections in the tissue structure lead to different phases occurring in the individual wavefronts leading to mutual interference patterns. These interference patterns are called &#;laser speckles&#; and the size of the speckles is related to the wavelength of the light. In the visible range speckles are less than 1 micron in diameter. Subcellular organelles (such as mitochondria) have dimensions of this order and one theory proposes that the laser speckles are better able to stimulate mitochondria than non-coherent LED light [29&#;31] as illustrated in Figure 3.
The size of the laser speckles approximately matches the size of mitochondria inside the cell.
Another very common assertion is that lasers penetrate deeper than LEDs. The so-called &#;superpulsed&#; gallium-arsenide laser at 905 nm emits light with a pulse duration of around 100&#;200 nsec. The pulse frequency can be varied from 25 Hz to Hz. The typical average power is 60 mW and the peak power is therefore about 20W. The depth into tissue at which a threshold power density is obtained, is directly related to the power density at the surface, and this means that manufacturers claim deeper penetration. However it is usually not mentioned that the actual amonut of energy that penetrates to a depth is only a fraction since the pulses are only &#;on&#; a small fraction of the time. Another way to generate pulsed laser light is simply to &#;chop&#; the beam, i.e. turn the laser on and off. A review paper [32] examined the effect of pulsing in PBM and concluded &#;There is some evidence that pulsed light does have effects that are different from those of continuous wave light. However further work is needed to define these effects for different disease conditions and pulse structures.&#;
There is also an argument that a collimated laser beam is more likely to be forward scattered in tissue than a divergent LED beam.
In some published editorials and review articles, it has been emphasized that photobiomodulation is a &#;photobiological phenomenon&#; and coherence is not necessarily needed [31, 33&#;35]. Some old laboratory studies with cell cultures also have concluded that coherence is not needed for photobiological effects of red light [36, 37]
Following the understanding that the photobiological effects of red and near-infrared light do not apply solely to laser light, some authors have started renaming the &#;LLLT&#; from low-level laser therapy to low-level light therapy [38].
However, other authors have still continued to insist that coherence is still important, making even bold statements that &#;[w]henever compared, coherent light has so far demonstrated better results than non-coherent light&#;, however softening these statements by admitting that &#;[t]he superiority of coherent light is shown to be relevant only for bulk tissue&#; and that &#;[t]he pain-relieving and healing effect in superficial wounds may be good also for both coherent and non-coherent polarized light&#; [30].
In the most extreme end, supporters of laser sources have used statements such as &#;would you take a knife to a gunfight - would you use LEDs instead of a laser&#;, claiming that the effectiveness of LED-based photobiomodulation is negligible compared to lasers. Our counter-word to that kind of argument would be that PBM is not about fights or cutting; instead it is ultimately a photobiological phenomenon dependent on light absorption to the photoacceptor molecule.
This debate about the importance of coherence or other laser-specific properties for photobiomodulation has been ongoing for more than 30 years already, as can be seen from Table 2 which presents some relevant quotes from the literature of the field.
Quotes showing variable opinions regarding the importance of coherence in PBM
Ref Quote Greguss () [64] &#;[We] concluded that low-level laser irradiation, when having a biostimulating effect, is not laser specific&#; Karu () [65] &#;Renewed interest in the effects of visible light action on biological objects occurred in the sixties after appearance of the first lasers, particularly the He-Ne laser. The He-Ne laser was the first widely accessible source of coherent light. No wonder that the stimulating effect of light, red in particular, was rediscovered with the use of the coherent light source.In their book on low-level laser therapy, Tunér and Hode presented an argument about the superiority of laser compared to LEDs, supported by approximately 15 study references published in the years &#;, which they also described concisely. These same studies have been also been referenced in other recent articles with similar claims about photobiomodulation light sources [39&#;41].
We summarize some of these papers in the Table 3. Despite our efforts, we could not find the full texts of the papers by Bihari (), Kubota (), Nicola (), Onac () and Paolini () mentioned in these papers. We also excluded Lederer () and Nicola () due low quality of data reporting.
Laser versus non-coherent comparison trials &#;
Study Study type Parameters (non-laser) Parameters (laser) Results Haina () [72] Rat 630nm; 4 J/cm2 633 nm; 90 mW; 50 mW/cm2; 0.5, 1.5, 4, 10 or 20 J Both He-Ne laser and non-coherent red light with similar parameters increased granulation tissue in wounds significantly, but He-Ne laser had a notably more pronounced effect. Muldiyarov () [73] Rat &#;Ordinary incandescent lamp with a simple red filter&#; 633 nm; 1 &#; 1.5 mW/cm2; 120 sec He-Ne laser decreased synovitis, while ordinary red light had no effect. Berki () [74] In vitro, lymphoid cels and macrophages 633 nm; 5.6 mW; 0.14 &#; 14.0 J/cm2 633 nm; 5.6 mW; 1 J; 0.14 &#; 28.0 J/cm2; 180 sec Laser light appeared to kill cells on higher doses, while non-coherent filtered light from xenon arc lamp with similar parameters didn&#;t have this effect in this study. Rosner () [75] Rat 904 nm; 10 or 15 mW; 2 min 633 nm; 3.5&#;10.5 mW; 1&#;10 min; many experimental groups with different dose parameters He-Ne laser showed beneficial effects on the action potential amplitude with several of the studied parameters, although there were also multiple ineffective parameters. The non-coherent light did not show beneficial effects with the studied parameters.While most of these studies have not been indexed in PubMed and they represent fairly old and low-quality photobiomodulation literature, they indeed lend some support to the idea that laser light could be more effective than narrow-band non-coherent light with comparable main parameters (wavelength, power output, energy density). However, some papers with more neutral results regarding the coherence appear to have been left out from this list [42&#;44].
Our current review is based on our self-made PBM research database including approximately research articles. The spreadsheet has been assembled within the past two years by repeatedly scanning the research literature with a large variety of keywords such as &#;photobiomodulation&#;, &#;LLLT&#;, &#;low-level laser irradiation&#;, &#;cold laser&#;, &#;He-Ne laser&#;, &#;soft laser&#;, &#;transcranial laser&#;, &#;670nm light&#;, &#;low-level light&#;, &#;near-infrared&#;, &#;light-emitting diode&#;, &#;LED phototherapy&#;, &#;narrow-band light&#;, &#;photobioactivation&#;, &#;photobiostimulation&#;, &#;photo-enchancement&#;, &#;photoradiation&#;, &#;photostimulation&#; and &#;far-red light&#; among others.
From this above-mentioned spreadsheet, we were able to extract another spreadsheet of approximately 350 scientific articles examining specifically LED photobiomodulation in humans, animals or cell cultures. Most of these studies showed positive results, confirming that LED-based photobiomodulation can also bring observable therapeutic effects (Supplementary file 1).
In this sample, we also found approximately 40 newer papers comparing the effectiveness of laser photobiomodulation to LED photobiomodulation in either animals, cell cultures or humans. The results of these studies are shortly presented in tables 4, 5 and 6, respectively. The tables are not comprehensive, since we excluded a few papers due to difficulties in interpreting either the methods or the results [45&#;48].
Laser versus non-coherent light comparisons (animal research)
Study Animal Indication LED/non-coherent LASER parameters Results Campos () [78] Hamster Oral mucositis 635 nm; 120 mW; 1.2 J/cm2; 1.2 J; 10 s; 0.04 cm2 660 nm; 40 mW; 6 J/cm2; 1.2J; 36 s; 1 cm2 LED and laser both were effective in decreasing oral mucositis severity and TNF-α concentration. Freire Mdo () [79] Hamster Oral mucositis 670 nm; 150 mW; 4 J/cm2; 4.8 J; 16 s; 0.5 cm2 660 nm; 40 mW; 4.8 J/cm2; 16 J, 30 s, 4 mm2 LED and laser both were effective in decreasing oral mucositis severity. Nadur-Andrade () [80] Mouse Paw edema from snake venom 635 or 945 nm; 4 or 3.8 J/cm2; 41 or 38 s 685 nm, 2.2 J/cm2; 15 s LED and laser both were effective in reducing edema formation after snake venom injection. Nadur-Andrade () [81] Mouse Edema and hemorrhage from snake venom 635 or 945 nm; 110 or 120 mW; 4 J/cm2; 4.5 J/point; 41 or 38 s; 1.2 cm2 685 nm; 30 mW; 2.2 J/cm2; 0.45 J; 15 s; 0.2 cm2 LED and laser both were effective in decreasing venom-induced edema and hemorrhage. Demidova-Rice () [82] Mouse Excisional wound 635, 670, 720 and 820 nm; 2 J/cm2 633 nm; 2 J/cm2 LED and laser both had a similar beneficial effect on wound closure. Comunian () [83] Rabbit Mandibular socket healing after tooth extraction 830 nm; 26 mW; 30 J/cm2; 150 s 780 nm; 30 J/cm2; 50 s LED and laser were both associated with improved clinical and histological signs, but only LED was associated with improved alveolar bone density. Takhtfooladi & Sharifi () [84] Rabbit Transected sciatic nerve 650 nm; 2.4 J/cm2; 1.5 cm2 at 1 point 680 nm; 10 mW; 10 J/cm2; 600 s; 4 mm2 at 3 points Laser group showed signs of improved nerve regeneration, while LED group showed no improvement compared to control group. Rosa () [85] Rat Rapid maxillary expansion -related bone repair in midpalatal suture 850 nm; 150 mW; 36 J/cm2; 18 J; 120 s; 0.5 cm2 780 nm; 70 mW; 450 J/cm2; 18 J; 257 s; 0.04 cm2 LED and laser both were effective in increasing hydroxyapatite. Silveira () [86] Rat Burn wound 632 and 850 nm; 8.4 and 19.8 J/cm2; 160 cm2; 10 min 660 and 904 nm; 10 and 3 J/cm2; 0.10 cm2; 20 and 9 s Only 660 nm laser and 850 nm LED were effective in reducing inflammatory response and improving wound repair. de Carvalho () [87] Rat Oral ulcer induced by formocresol 630 nm; 150 mW; 4.8 J/cm2; 0.8 cm2 660 nm; 40 mW; 4.8 J/cm2; 4 mm2; LED and laser were bot heffective in accelerating the healing of oral ulcers. El-Bialy () [88] Rat Mandibular growth 655 nm; 10 mW/cm2; 6 J/cm2 655 nm; 10 mW/cm2; 6 J/cm2 LED and laser both were effective. LED groups showed most pronounced results. de Castro () [89] Rat TMJ inflammation 850 nm; 100 mW; 0.5 cm2 780 nm; 70 mW; 0.04 cm2 LED and laser both appeared to be effective in attenuating the inflammatory infiltrate in the temporomandibular joint of rat. Wu () [90] RatLaser versus non-coherent comparisons (in vitro research)
Study Cell type LED/non-coherent LASER parameters Results Khan & Arany () [103] Human dermal keratinocyte; Human normal oral keratinocyte (NOKSI) 660 and 850 nm; 1 and 3 J/cm2 for both wavelengths; 810 nm; 1 or 3 J/cm2 Laser appeared to have some effects on the number and size of mucosal colonies, while LED appeared to be ineffective. However, statistical significances were not calculated in these comparisons. Pagin () [104] Pre-osteoblast MC3T3 cell 630 nm; 60 mW/cm2; 3 and 5 J/cm2; 0.31 cm2; 3 and 5 s 660 and 780 nm; 1 W/cm2; 3 and 5 J/cm2; 0.042 cm2; 3 and 5 s LED and laser both had only limited effects on pre-osteoblast growth (at 24h), but laser was more effective. Neither showed effects on pre-osteoblast differentiation. Spitler & Berns () [105] A549 adenocarcinoma human alveolar epithelial cell; PtK2 rat kangaroo renal epithelial cell; U2OS human osteosarcoma cell 637 and 901 nm; 5.57 and 1.30 mW/cm2; 10.02 and 2.334 J/cm2; s 652 and 806 nm; 5.57 and 1.30 mW/cm2; 10.02 and 2.334 J/cm2; s LED and laser both had a comparable effects on cell migration and wound closure. Vinck () [106] Fibroblast 660 and 950 nm; 0.53 J/cm2 830 nm; 0.196 cm2; 1 J/cm2 LED and laser both showed significant effects on fibroblast proliferation in most of the individual experiments in this study. Open in a new tabLaser versus non-coherent comparisons (clinical trials)
Study Methodology Indication LED/non-coherent LASER parameters Results Panhoca () [107] Comparison trial, uncontrolled Temporomandibular disorder 630 and 850; 150 mW; 300 mW/cm2; 18 J/cm2; 9 J/point 780 nm; 70 mW; mW/cm2; 105 J/cm2; 4.2 J/point There were no significant differences in pain scores and maximum oral aperture between groups at baseline or any periods after treatment. Freitas () [108] Comparison trial, uncontrolled Oral mucositis 630 nm; 80mW; 0.24 J/point; 1 cm2 660 nm; 40 mW; 6.6 J/cm2; 0.24 J/point; 0.036 cm2 LED and laser both were effective in alleviating oral mucositis scores, but LED had more pronounced effects. Ammar () [109] Comparison trial, uncontrolled Knee osteoarthritis 890 nm; 62.4 J/cm2; 180 cm2 850 nm; 100 mW; 0.76 mm2 LED and laser both appeared to be similarly effective in reducing pain and increasing physical function. Esper () [110] RCT Orthodontic pain 640 nm; 100 mW; 4 J/cm2; 70 s 660 nm; 30 mW; 4 J/cm2; 25 s LED was effective in reducing orthodontic pain while laser was not. Laser dose (radiant energy) might have been too small. Lizarelli () [111] RCT, double-blind Dentin hypersensitivity 630 nm; 25 mW; 5.4 J/cm2; 4 mm2 660 nm; 25 mW; 5.4 J/cm2; 4 mm2 LED and laser were equally effective in the treatment of dentin hypersensitivity. Lima () [112] RCT, double-blind Pain after surgery 640 nm; 70 mW; 10.1 J; 6 J/cm2; 1.77 cm2; sAs can be noted from these tables, most of the comparisons have a very high risk of bias due to differing key parameters between the LED and laser groups. In almost every study the wavelengths, power outputs and spot sizes are different between the groups, which makes is it impossible to make reliable comparisons between lasers and LEDs in photobiomodulation. Despite these notable shortcomings, most of these comparisons provisionally suggest that lasers could indeed be replaced by LEDs without significant worsening of the results.
If the experimental evidence suggests that non-coherent and non-monochromatic light from LEDs can be used for photobiomodulation, then it is reasonable to asssume that even the natural broadband light (blackbody radiation) originating from a heated object (such as a tungsten filament or the sun) could have similar biological effects. So far, there exists limited yet tentatively positive evidence related to beneficial effcts of broadband light in PBM.
The earliest writings on PBM were published in the very early 20th century, when several authors described that visible light, red and infrared wavelengths produced by incandescent lamps appeared to have beneficial effects in the treatment of many different diseases such as syphilis, smallpox, tuberculosis, chronic fatigue, diabetes and obesity (Figure 4) [49, 50].
In the early 20th century, incandescent bulbs were used as a source of therapeutic light in an &#;electric light bath&#;. Kellogg was one of the notable inventors and authors of this era. [Fuzheado / Wikimedia Commons / CC-SA-3.0]. No permission needed.
While the photobiomodulation research has mainly focused on monochromatic laser and quasimonochromatic LED lights, some research groups have also been using broadband (polychromatic) light sources in photobiomodulation research. Some commonly used wavelength ranges have been visible light (400 &#; 800 nm) or water-filtered infrared A (760 &#; nm). In a some cases the broadband light has been polarized [51]. Some of these studies are summarized in Table 7.
Broadband light research
Indication Animal Reference Arthritic joints Rat [115] Atherosclerosis Rabbit [116] Back pain Human [117] Burns Human, rat [118&#;120] Colitis Mice [121] Foot ulcer Human [53] Oral mucositis Human [52] Skin rejuvenation Human [122] Surgical wounds Human, rat [123, 124] Tennis elbow Human [125, 126] Wounds and ulcers Human, rat [54, 127&#;130] Open in a new tabVisible light irradiation has been investigated in numerous in vitro and in vivo trials as well as in small clinical trials. While the data is generally of low methodological quality, the results have been mostly positive and the treatment effectiveness appears to be comparable to laser or LED photobiomodulation [52, 53].
Water-filtered infrared A has been investigated for the treatment of wound healing in humans [54] with positive results. However, some of the beneficial effects might be related to the thermal effects of infrared wavelengths, independently of athermic photobiomodulation mechanisms. It should be pointed out that in the case of longer wavelength IR light (>980 nm) where the primary photoacceptor is thought to be water, then the difference between thermal and non-thermal mechanisms tends to disappear. Santana-Blank has written extensively on this subject [55] and suggested that &#;exclusion zone (EZ) water may act as an electrolytic bio-battery, which can efficiently and selectively transfer light energy to sites expressing redox injury potentials, as found in cancer and other complex diseases&#;. Some researchers have also been arguing that some of the cellular effects of water-filtered infrared A might be harmful instead of being beneficial. Therefore it has been suggested that in addition to protecting skin from ultraviolet radiation, it would be helpful to also protect it from near-infrared radiation. However, those detrimental effects have been mostly noted in cell cultures receiving remarkably high irradiation doses of infrared A [56]
Because of the apparent success of these broadband light sources, it could be hypothesized that natural daylight or sunlight could also have health effects related to photobiomodulation. In cohort studies, sunlight exposure and low latitude have been associated with better health, eg. decreased mortality, lower cholesterol levels and lower incidence of cancer, fractures and type 2 diabetes [57&#;62].
While these findings have usually been attributed to increased vitamin D synthesis due to sunlight exposure, recent randomized clinical trials of vitamin D supplementation have been unable to substantiate those assumptions [63]. We suggest an alternative hypothesis, where vitamin D could act as a surrogate marker for photobiomodulation from sunlight exposure.
The current total evidence appears to support the idea that photobiomodulation is not dependent on lasers or coherence, but quasimonochromatic LED devices and even broad-wavelength light sources such as water-filtered infrared-A can also yield physiological effects. The comparisons between lasers and LEDs lend support to this idea. However, the quality of these comparisons is low for the most part, because of the difficulty of arranging the parameters so that the beam from a LED is identical to the beam from a laser, with regard to spot-size, band-width and power density. Nevertheless, even today the debate about the equivalence of laser and LED reamins the single most controversial topic in the PBM field.
Nevertheless, more high-quality head-to-head comparison studies should be conducted in order to figure out whether there are significant differences between the dose response or physiological effects of LED photobiomodulation and laser photobiomodulation, and whether LED-based treatments could be carried out based on the treatment parameters adopted from laser-based studies.
ESI
MRH was supported by US-NIH grants R01AI and R21AI
Conflict of Interest
The authors declare no conflict of Interest
Supplementary material (.PDF and .XLSX)
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The excel database of 350 LED photobiomodulation studies. Below are the links to the files:
https://drive.google.com/file/d/0B1ming8_i64HM3RrTGp3SUltQnB0TlMxZXRKS3NTeTBTMzY0/view?usp=sharing .PDF file
https://drive.google.com/file/d/1MMj6BNQD5_XEdhV1zXYZ_kD0FCqCB_vt/view?usp=sharing .XLSX file
This section collects any data citations, data availability statements, or supplementary materials included in this article.
ESI
Click on the row with your desired specification to open link to products.
Specs Tutorial
Tab)Specs Tutorial
Tab)Specs Tutorial
Tab)These Laser Safety Glasses provide CE certified laser radiation protection. The lenses of all glasses except for the LG11 series are made from absorptive dye encapsulated in hardened polycarbonate, which provides superior resistance to breakage and prevents minor scratches from affecting laser protection. The LG11(A) Laser Safety glasses use a Schott glass substrate.*
The optical density (OD) and LB-Rating for specific wavelength ranges are indelibly printed on the lens or frame for permanent identification without blocking the field of view&#;. For a complete list of optical densities and LB-Ratings, please click on the row corresponding to each item # in the selection guide to the right.
Thorlabs offers laser safety glasses in up to four different frame styles (see the Frame Styles tab for details).
*
can be worn over prescription glasses and features side and top shield protection from peripheral laser radiation.Each pair of laser safety glasses comes with a protective storage case, cleaning cloth, and adjustable neck strap. However, the Modern Goggle style does not come with the separate neck strap as the neckstrap for the Modern Goggles is built in.
Modern Goggle style shown with built-in neck strap and detachable inserts for prescription lenses. Click on the image to show a front and rear view.
Universal style glasses shown with included neck strap. This separate neck strap is included with Universal, Comfort, and Sport styles.
Care Instructions
When not being used, the laser safety glasses should be stored in their protective case and in an area where the temperature does not exceed 80 °F (26.6 °C). The cleaning cloth included with each pair of laser safety glasses can be used for removing dust from the surface of the lens. Products used for cleaning prescription eyeglasses are safe to use with our laser safety glasses. For disinfection of the glasses, we recommend mild detergent or soap and hot water or a dilution of isopropyl alcohol (up to 70% solution). We do not recommend any highly caustic solutions. The laser safety rating will not be affected by any of the above cleaning procedures.
Picking the Appropriate Laser Safety Glasses
Since the correct choice of laser safety eyewear depends upon many local factors that cannot be evaluated remotely, including the beam path, laser parameters, and lab environment, Thorlabs cannot recommend specific eyewear for your application. We would recommend discussing your needs with your organization's laser safety officer.
*The LG11 and LG11A are made using Schott glass, and therefore use a different frame design than our other Universal style laser glasses. Fit over prescription glasses may be affected (see the Frame Styles tab for details). To ensure CE compliance, only two styles are offered. OD and LB-Rating specifications for the LG11 and LG11A are printed on the frame.
&#;For maxmimum protection, our laser safety glasses should not be used more than five years from the production date. All of our laser safety glasses except for the LG11 and LG11A are inscribed with a production date code on the bottom-right corner of the right lens, as can be seen here. The date code is represented as a five-digit number, with the first two digits defining the year and the last three defining the day of the year. Thorlabs will not ship glasses with less than three years of usable life remaining.
OD = Optical DensityT = Transmission (decimal)
Modern Goggle Style
Sport Style
Comfort Style
Universal Style
LG1 Universal Style Laser Glasses on 1 x 1 cm Grid for Measuring Interior Dimensions
Each pair of glasses and goggles comes with a protective carrying case, cleaning cloth, and adjustable neck strap (separate neck strap not included with Modern Goggles).
Universal Style
Universal Style laser safety glasses feature a large (145 mm x 53 mm) frame that can be worn comfortably on top of prescription glasses. They are equipped with lensed side shields and solid top shields to protect the user's eyes from laser radiation while maintaining peripheral vision. The frame has adjustable arm lengths to accommodate different temple sizes. Laser safety ratings are indelibly printed on the lenses to indicate the level of protection provided for specific wavelength ranges.
The LG11 is composed of a Schott Glass substrate, and uses a different frame than other universal style laser glasses that features side shields made from solid plastic providing full laser protection but at the expense of peripheral vision. These laser glasses may not fit over prescription glasses. Laser ratings on the LG11 are indelibly printed on the left side shield, not on the lenses.
Comfort Style
Comfort Style glasses feature a medium (145 mm x 47 mm) frame with solid side shields for full protection from peripheral laser radiation. While these laser safety glasses cannot be worn over prescription glasses, each pair includes a detachable insert for prescription lenses (seen by clicking on the the image to the right). Contact your doctor to fit lenses for the inserts. These frames are equipped with an extended nosepiece that allows the glasses to sit more comfortably on the noses of users who have a low nose bridge. Laser safety ratings are indelibly printed on the lenses (LG11A laser ratings are printed on the frame) to indicate the level of protection provided for specific wavelength ranges.
Sport Style
The Sport Style glasses have a compact (134 mm x 48 mm) frame designed for full laser safety coverage without the need for side shields and provide the user with a wide field of view. Glasses with this frame style have arms that feature adjustable lengths and an adjustable joint (seen by clicking on the image to the right) to customize the fit for different head shapes and sizes. These sport style glasses cannot be worn over prescription glasses and do not include inserts for prescription lenses. Laser safety ratings are indelibly printed on the lenses to indicate the level of protection provided for specific wavelength ranges.
Modern Goggle Style
The Modern Goggle Style features an adjustable strap, a gasket to create a seal around the eyes, as well as vents to prevent fogging. The interior dimensions of these laser goggles are
133 mm x 51 mm. The lenses have a diagonal length of 66 mm. Laser Safety Goggles are equipped with detachable inserts for prescription lenses (please consult your doctor to fit prescription lenses for the insert). Laser safety ratings are indelibly printed on the lenses to indicate the level of protection provided for specific wavelength ranges.
*** This guide is not intended as a substitute for reading and understanding the ANSI Z136 or EN 207 or EN 208 Laser Safety Standards. It is only meant to provide an introductory overview to understanding the markings on the lenses of the LG series of laser glasses. ***
Indelibly printed on the laser safety glasses are two sets of numbers: Optical Density (OD) and LB-Rating, which are both used to indicate the level of protection provided for specific wavelength ranges. The OD numbers indelibly printed on the laser safety glasses can be used to determine if the glasses meet the ANSI Z136 standards of laser safety protection for a given laser product. In addition, the OD can be used to calculate the transmission (T) of light through the laser safety glasses.
The European EN 207 standard for laser safety glasses requires that the protective eyewear be labeled with the CE mark and that the LB-Rating specifications are indelibly printed on the lens. In addition, the lenses and frames must be able to provide the stated level of protection for 10 seconds or 100 pulses depending on the mode of the laser. The LB-Rating is composed of 3 components: a wavelength range, a laser mode designation, and a scale number. The wavelength range engraved on the laser safety glasses is given in nm and is extremely important since the level of protection provided by the laser safety glasses is wavelength dependent. The laser mode designation is based on the duration of laser pulse emitted by the laser.
The scale number (LBn) is intended to be used in conjunction with the wavelength range and the laser mode designation in order to determine if the laser safety glasses meets the minimum required level of protection for a given laser; see the table below. If one component of the LB-Rating is shared, a plus sign is used to separate multiple wavelength ranges or laser modes and scale numbers in order to save space. In addition, a greater than, >, sign preceding a wavelength range indicates that the mode and scale number ratings for that wavelength range are valid for wavelengths of light greater than the bottom number in the range up to and including the top number in the range. For example, if the glasses were rated as 330-370 D LB2 and >370-500 D LB3 then at 370 nm the rating would be D LB2 and for all wavelengths greater than 370 nm up to and including 500 nm would be rated at D LB3.
There are two ways to use the table above: start with the scale number and calculate the maximum safe power density or start with a power density and calculate the minimum safe scale number. This is demonstrated by the two examples below.
Example 1: The LG3 laser safety glasses have an LB-Rating line that reads "180-315 D LB7 + IR LB4". So if the LG3 glasses are being used with a 10 µs pulsed 280 nm light source the table above can be referenced to find that, E=3x10n+1 J/m2, where in this example the scale number is LB4 so n=4. As a result, when the LG3 laser safety glasses are being used in this situation the maximum power density of the light source should not exceed 3x105 J/m2.
Example2: A CW Krypton Ion laser lasing at 647.1 nm has a maximum power density of 2.2x104 W/m2. Using the table above, the scale number can be calculated using LBn=log10(P)-1, which results in a rounded up scale number of 4. The LG4 laser safety glasses meet the safety specifications of the European EN 207 standard for this example.
The LG13 and LG14 series of glasses are rated for laser alignment applications. This rating allows the lens to transmit a portion of the light for alignment purposes, while attenuating the light to eye-safe power levels in the event of accidental direct exposure to a beam. The rating is given as RB# where # is replaced by the minimum optical density at the specified wavelength or wavelength range (in nm). Along with this RB value is the maximum allowable power and energy of the laser over a Ø7 mm aperture. Power is given for pulses greater than 0.2 ms, while energy is specified for pulses from 1 ns to 0.2 ms. When using a pulsed laser, a correction factor of N1/4 must be multiplied by the maximum energy rating, replacing N with the number of pulses the laser produces in a 10 s interval.
Example: The LG14 laser safety glasses have an alignment rating of 1 W 2 x 10-4 J 532 RB3. At 532 nm, the glasses will have an optical density between 3 and 4, correlating to transmission between 0.1% and 0.01%. The maximum power/energy over a Ø7 mm aperture that these glasses can be used with at 532 nm is 1 W for CW or pulses greater than 0.2 ms, and 2 x 10-4 J for pulses from 1 ns to 0.2 ms.
Please refer to the official EN 208 standard that can be purchased from BSI.
P(mW) = Power in mW
When working with fiber optics, light emitted directly from the endface of a fiber is diverging. Thus, the power density is decreasing as the beam spreads and the danger of damage to the eye decreases. The table to the left lists the beam area created by light exiting a fiber for fibers with numerical apertures (NA) between 0.10 and 0.50. If you know the total power emitted from the fiber, you can calculate the power density at 25.4 mm (1") from the fiber tip. This power density will allow you to determine the safe fiber-tip viewing distances.
Safe practices and proper usage of safety equipment should be taken into consideration when operating lasers. The eye is susceptible to injury, even from very low levels of laser light. Thorlabs offers a range of laser safety accessories that can be used to reduce the risk of accidents or injuries. Laser emission in the visible and near infrared spectral ranges has the greatest potential for retinal injury, as the cornea and lens are transparent to those wavelengths, and the lens can focus the laser energy onto the retina.
Lasers are categorized into different classes according to their ability to cause eye and other damage. The International Electrotechnical Commission (IEC) is a global organization that prepares and publishes international standards for all electrical, electronic, and related technologies. The IEC document -1 outlines the safety of laser products. A description of each class of laser is given below:
Class Description Warning Label 1 This class of laser is safe under all conditions of normal use, including use with optical instruments for intrabeam viewing. Lasers in this class do not emit radiation at levels that may cause injury during normal operation, and therefore the maximum permissible exposure (MPE) cannot be exceeded. Class 1 lasers can also include enclosed, high-power lasers where exposure to the radiation is not possible without opening or shutting down the laser. 1M Class 1M lasers are safe except when used in conjunction with optical components such as telescopes and microscopes. Lasers belonging to this class emit large-diameter or divergent beams, and the MPE cannot normally be exceeded unless focusing or imaging optics are used to narrow the beam. However, if the beam is refocused, the hazard may be increased and the class may be changed accordingly. 2 Class 2 lasers, which are limited to 1 mW of visible continuous-wave radiation, are safe because the blink reflex will limit the exposure in the eye to 0.25 seconds. This category only applies to visible radiation (400 - 700 nm). 2M Because of the blink reflex, this class of laser is classified as safe as long as the beam is not viewed through optical instruments. This laser class also applies to larger-diameter or diverging laser beams. 3R Class 3R lasers produce visible and invisible light that is hazardous under direct and specular-reflection viewing conditions. Eye injuries may occur if you directly view the beam, especially when using optical instruments. Lasers in this class are considered safe as long as they are handled with restricted beam viewing. The MPE can be exceeded with this class of laser; however, this presents a low risk level to injury. Visible, continuous-wave lasers in this class are limited to 5 mW of output power. 3B Class 3B lasers are hazardous to the eye if exposed directly. Diffuse reflections are usually not harmful, but may be when using higher-power Class 3B lasers. Safe handling of devices in this class includes wearing protective eyewear where direct viewing of the laser beam may occur. Lasers of this class must be equipped with a key switch and a safety interlock; moreover, laser safety signs should be used, such that the laser cannot be used without the safety light turning on. Laser products with power output near the upper range of Class 3B may also cause skin burns. 4 This class of laser may cause damage to the skin, and also to the eye, even from the viewing of diffuse reflections. These hazards may also apply to indirect or non-specular reflections of the beam, even from apparently matte surfaces. Great care must be taken when handling these lasers. They also represent a fire risk, because they may ignite combustible material. Class 4 lasers must be equipped with a key switch and a safety interlock. All class 2 lasers (and higher) must display, in addition to the corresponding sign above, this triangular warning sign.Please Give Us Your Feedback
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