Rufus R. Noble Laser therapy, which is low-level (light) treatment (LLLT), is a rapidly growing technology used to treat many diseases requiring a rediscovery of the healing process, reduction of inflammation and pain, and regaining function. Even though the skin is an organ exposed to the light spectrum more than all other tissues, the skin responds well to near-infrared and red wavelengths. Mitochondrial chromophores within skin cells absorb the photons. This results in electron transport, adenosine tripolyphosphate (ATP) release of nitric Oxide and blood flow, reactive oxygen species rise, and a variety of signaling pathways are activated. Stem cells may be activated, resulting in increased healing and repair of tissues.
Regarding dermatology, LLLT is beneficial for acne scars, wrinkles, hypertrophic scars, and the healing process of burns. LLLT may reduce UV damage as a treatment or an anti-inflammatory. For pigmentary disorders like Vitiligo, LLLT may increase the amount of pigment in your skin by stimulating melanocyte proliferation. It can also decrease depigmentation by reducing autoimmunity. Psoriasis, an inflammation-related disease, and acne also can benefit. The non-invasive nature and almost non-existent side effects encourage further dermatology investigation.
Keywords Acne Herpes, dermatology, laser LT Low-level laser therapy, Phototherapy for skin disease, Skin Rejuvenation Pigmentation Vitiligo
More and more non-invasive treatments for skin conditions and rejuvenation are being used, particularly in Western countries where comparatively high disposable incomes are coupled with the desire to achieve an ideal look fueled by social pressures. Even though the skin is an organ that is the most naturally subject to sunlight, the skin responds well to near-infrared and red wavelengths when delivered according to the appropriate conditions with a therapeutic purpose. Laser therapy at low levels (LLLT) was first discovered in the late 1960s; however, only recently has it been extensively used in dermatology. The advent of LED (LED) technology has alleviated some of the problems that used to be related to lasers, like cost as well as safety issues and the requirement for skilled personnel to manage the devices. In reality, most LED devices are made to be used at home and are readily available online. This article will discuss the usage of LLLT as the most likely treatment method for the skin.
Low-Level Laser (Light) Therapy and Its Mechanism of Action
Photobiomodulation, also known as LLLT, is the term used to describe the use of photons that emit non-thermal radiation to alter biological activity. LLLT uses coherent sources of light (lasers) and non-coherent light sources made up of filters on lamps or light-emitting diodes (LED), or occasionally; it is a mixture of the two. The most important medical uses of LLLT are to reduce inflammation and pain, enhance the healing process of tissues and encourage regeneration of various nerves and tissues, and protect against tissue damage in instances that are likely to happen. 1, 2 In the last couple of decades, Non-ablative laser treatments have been increasingly used for the cosmetic treatment of wrinkles, fine lines, or scars, as well as photoaged skin and scars, also called photorejuvenation ( Table 1). Recently, this technique is also used to treat inflammatory acne ( Table 1). 3 LLLT is the practice of the exposure of tissues or cells to low levels of red and near-infrared (NIR) radiation. The process is known as ‘low-level’ due to the fact that the power or energy density used is minimal compared to other types of laser therapy like cutting, ablation, or thermally coagulating tissues. Medical treatment using LT at different intensities was found to inhibit or stimulate the various cell process. 4
Dynatronics (Salt Lake City, UT) Synergie LT2 660 500 mW (total power) 6. J/treatment area Firmness and anti-aging properties of the skin wrinkles the skin’s tone, texture, and color for the face and neck
The mechanism that is involved in the photobiostimulation of cells by LLLT has yet to be completely realized. Based on observations, it is evident that LT has a broad range of effects on the molecular, cell, and tissue levels. The fundamental biological reason that is responsible for these effects is that LT is believed to occur due to the absorption of NIR and red light by mitochondrial chlorophytes, particularly cytochrome C oxidase (CCO), which is found in the respiratory chain in mitochondria 5,5 – 7, and perhaps by photoreceptors located in the plasma membranes of cells. In the end, a sequence of events occurs within mitochondria, leading to the biostimulation of various processes (Figure 1).8 The absorption spectrum for CCO in various oxidation states was analyzed and found to be like the spectra of action for biological responses to light.5 It is speculated that the absorbance of energy from light might result in photodissociation and dissociation of inhibitory nitric Oxide from CCO9, which could increase enzyme activity, electron transport, mitochondrial respiration, as well as adenosine Triphosphate (ATP) manufacturing (Figure 1).12-14 Then, LT alters the cellular chemical redox status, which triggers the activation of a variety of intracellular signaling pathways and affects the affinities of transcription factors that are involved in cell growth, survival, regeneration, and repair (Figure 1).2,5,6,15,16
Mechanism of operation of LLLT.
The fundamental biological process behind these effects of LT is believed to occur by the absorption of NIR and red light by mitochondrial chromophores, particularly cytochrome c oxygenase (CCO) which is found within the respiratory chain within mitochondria 55 – 7. It is speculated that this photon absorption could result in the photodissociation of inhibitory Nitric oxide from CCO 9, leading to a boost in enzyme activity, electron transport 11, mitochondrial respiration, and the production of ATP between 12-14. In turn, LLLT, by altering the cellular redox state, can induce the activation of numerous intracellular signaling pathways; change the affinity of transcription factors concerned with cell proliferation, survival, tissue repair, and regeneration2,5,6,15,16.
While LT is currently used for treating a range of diseases, it is unpopular as a treatment because of two primary reasons. The first is that there are questions about the fundamental molecular and cell mechanisms that are which are responsible for the transmission of signals generated by the photons that strike onto cells to biological reactions that occur within the tissues that have been exposed to radiation. There are also significant variations in dosimetry parameters like wavelength, irradiance or density and coherence, pulse shape and polarization, energy, rate of radiation as well as contact vs. non-contact application, and repetition. Dosimetric parameters that are lower may result in a lower effectiveness of treatment, while higher ones can cause tissue damage.1 This demonstrates the concept of biphasic dose responses that are reported to be present during LLLT 1,18,19. A lot of studies published on LLLT have negative results. This could be due to an inadvertent selection of the source of light and dosage. It could also be due to improper treatment of the patient’s skin prior to applying LT, like not getting rid of oily and makeup debris that can hinder the absorption into the source of light and the inability to take into account the pigmentation of the skin. 17 A lack of proper maintenance on the LLLT equipment may hinder its effectiveness and affect the results of clinical tests too. It is essential to think about whether there is a suitable dosage of light for a particular procedure.
Laser radiation or non-coherent lighting has a wavelength as well as an exposure-dependent ability to alter cellular behavior without substantial heating. 20 Phototherapy uses light with frequencies ranging from 390-1100 nm. These may be continuous or pulsed. In normal conditions, the procedure uses comparatively low levels of fluence (0.04-50 J/cm2) and high power densities (< 100 mW/cm2).21 Wavelengths in the range of 390 nm to 600 nm are used to treat superficial tissue, and longer wavelengths in the range of 600nm to 1,100nm, which penetrate further, are used to treat deeper-seated tissues (Figure 2).4 Wavelengths in the range 700 nm to 750 nm have been found to have limited biochemical activity and are therefore not often used.1 Various light sources used in LT include inert gas lasers and semiconductor laser diodes such as helium-neon (HeNe; 633 nm), ruby (694 nm), argon (488 and 514 nm), krypton (521, 530, 568, 647 nm), gallium arsenide (GaAs; > 760 nm with a standard example of 904 nanometers) and gallium aluminum arsenide (GaAlAs 612-870 nm).17 A variety of LED semiconductors are accessible with lower wavelengths. Their media contains elements like indium, phosphide and. Another question that still needs to be definitively answered is whether there is an advantage to making use of coherent laser light versus the non-coherent lighting of LEDs. 22 While some physicians treat deep tissue lesions with targeted lasers within “points,” in dermatology, lasers are increasing because of the vast tissues which require irradiation.
LT for Skin Rejuvenation
Skin begins showing the early signs of aging around the 20s to the early 30s and typically shows signs of wrinkles, discoloration, telangiectasia, and loss of elasticity. Common molecular and histologic signs are a reduction in the quantity of collagen, the fragmentation of collagen fibers, elastotic degradation of elastic fibers and upregulation of matrix metalloproteinases (MMPs), specifically MMP-1 and MMP-2, dilation and tortuous dermal veins and disorientation and atrophy of skin’s epidermis. 23, 24 Environmental and chronological factors can be responsible for the process of aging in the skin. However, photodamage is believed to be among the leading causes of these changes.
Many modalities have been devised to reverse epidermal and dermal signs resulting from chronological and photo-induced aging. The principle behind most of these treatments is to remove the epidermis and create a controlled process of skin wounds in order to stimulate the biosynthesis of collagen and tissue remodeling. The most commonly used interventions as of today are retinoic acid (a vitamin A derivative), dermabrasion, chemical peels, and ablative laser resurfacing with carbon dioxide (CO2) or erbium: yttrium-aluminum-garnet (Er: YAG) lasers or a combination of these wavelengths.25-27 However, these procedures require intensive post-treatment care and prolonged downtime and may lead to complications such as long-lasting erythema, pain, infection, bleedings, oozing, burns, hyper- or hypopigmentation, and scarring.28,29 These limitations created a need for the development of alternative rejuvenation procedures that were safer, more effective, had fewer side effects, and had minimum postoperative care and downtime, leading to non-ablative rejuvenation technologies.30-32 Non-ablative skin rejuvenation aims to improve photoaged and aging skin without destroying the epidermis.31,32 Irregular pigmentation and telangiectasia can be treated with intense pulsed light sources (IPL), 532 nm potassium-titanyl-phosphate lasers (KTP), and high-dose 585/595 nm pulsed dye lasers (PDL)33. Wrinkle reduction and skin tightening through thermal injury to the dermis (photo thermolysis) can be achieved by other IPL sources (i.e., low-dose 589/595 nm PDLs, 1064 & 1320 nm neodymium:yttrium-aluminum-garnet lasers, (Nd: YAG) 1450 nm diode lasers, and 1540 nm erbium fiber lasers).33
LED, which is a unique light source that can be used for non-thermal, not-ablative skin rejuvenation, has been demonstrated to be effective in improving wrinkles and laxity of the skin ( Figure 3). 3434 – 40 It’s a concept that has been introduced previously, as the first studies about LLLT’s effects on collagen production were from 1987. The research conducted by Abergel et al. and Yu et al. observed an increase in the production of collagen, pro-collagen, and essential collagen, fibroblast-growth and growth factors (bFGF), and the proliferation of fibroblasts upon exposure to low-energy lasers in vivo and in vitro animals (Figure 4).41,42 In addition, LT was already known to improve microcirculation and blood flow to the skin, modify platelet-derived growth factor (PDGF) as well as transformative growth factor (TGF-b1), and also inhibits the process of apoptosis (Figure 4).1,43,44 Lee et al. examined the histologic as well as ultrastructural changes resulting from an 830 nm 55 mW/cm2, 56 J/cm2 and 633 nanometers, with 105 mW/cm2, 126J/cm2 LED Phototherapy, and observed alteration in the state of MMPs along with their tissues inhibitors (TIMPs).33 Additionally, the levels of mRNA for IL-1b, ICAM-1, TNF-a, and connexin43 (Cx43) were raised after LED Phototherapy, whereas the levels of IL-6 decreased (Figure 4).) 33. In addition, the increase in the quantity of collagen was observed in post-treatment specimens 34. Pro-inflammatory cytokines IL-1b and TNF-a are thought to be recruited to heal the intentionally formed photothermally-mediated wounds associated with laser treatments, and this cascade of wound healing consequently contributes to new collagen synthesis.33 LED therapy may induce this wound healing process through non-thermal and atraumatic induction of a subclinical ‘quasi-wound,’ even without any actual thermal damage, which could cause complications as in some other laser treatments.33 TIMPs inhibit MMP activities, so another possible mechanism for the increased collagen could be through the induction of TIMPs (Figure 4). When all these data are put together, an increase in the production of TNF and IL-1band TNF-a a may have stimulated MMPs during the initial response to LED treatment. This could help clear damaged collagen fragments, allowing the production of collagen fibers. In the future, an increase in the quantity of TIMPs may protect newly produced collagen from destruction by MPs. 33 Additionally, the increased expression of Cx43 could enhance cell-to-cell communication between dermal constituents, specifically the fibroblasts. It could also enhance the cell’s response to the effects of photobiostimulation resulting from LED treatments, enabling them to create new collagen over more significant areas that include non-irradiated parts. 33 In a clinical trial conducted by Weiss and Co., 300 patients received LED treatment (590 millimeters, 0.10 J/cm2) alone, as well as 600 who received LED therapy in conjunction with a photorejuvenation treatment based on thermal energy. In the case of patients receiving LED photorejuvenation on its own, the majority reported the skin’s texture softening and a decrease in fine lines and roughness, which ranged from a substantial decrease to, at times, subtle changes.36 Additionally, patients who received thermal photorejuvenation in combination with or without LED photo modulation (n = 152)) saw a notable reduction in erythema after treatment and a general impression of improved efficacy due to the addition of LED treatment.36,45 This decrease in erythema post-treatment could be due to the anti-inflammatory properties of LLLT.40 A multicenter clinical trial was conducted With different parameters for the sequence of pulses, with 90 participants receiving eight LED treatments over four weeks.37,46-48 The results of this study demonstrated favorable results, with nearly 90percent of the patients being improved by at minimum one Fitzpatrick photoaging class and the majority of patients displaying overall improvement in facial contour lines, wrinkles, and erythema of the background pigmentation. The results were most impressive between 4 and six months after completing eight treatments. Significantly increased collagen within the dermis of papillary as well as decreased MMP-1 were typical findings. Barolet and al.’s study is in line with previous studies. They utilized a 3D model of human tissue-engineered skin to study the possibility of the 660 nm, 50MW/cm 4J/cm 2 LED to alter collagen and MMP-1. Results revealed an increase in collagen production and decreased MMP-1 levels in the laboratory. 40 A split-face, single-blinded study was carried out to examine the effect of this treatment on the appearance and texture of people with photoaged/aged skin.
