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Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring

Pinar Avci, MD, Asheesh Gupta, PhD, Magesh Sadasivam, MTech, Daniela Vecchio, PhD, Zeev Pam, MD, Nadav Pam, MD, and Michael R Hamblin, PhD - 2014 (Publication)
This study covers LLLT use on skin rejuvenation, Acne, Protoprotection, Herpes Lesions, Vitilago, Burns, Depigmentation, scars and Psoraisis
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Low-level laser (light) therapy (LLLT) is a fast-growing technology used to treat a multitude of conditions that require stimulation of healing, relief of pain and inflammation, and restoration of function. Although the skin is the organ that is naturally exposed to light more than any other organ, it still responds well to red and near-infrared wavelengths. The photons are absorbed by mitochondrial chromophores in skin cells. Consequently electron transport, adenosine triphosphate (ATP) nitric oxide release, blood flow, reactive oxygen species increase and diverse signaling pathways get activated. Stem cells can be activated allowing increased tissue repair and healing. In dermatology, LLLT has beneficial effects on wrinkles, acne scars, hypertrophic scars, and healing of burns. LLLT can reduce UV damage both as a treatment and as a prophylaxis. In pigmentary disorders such as vitiligo, LLLT can increase pigmentation by stimulating melanocyte proliferation and reduce depigmentation by inhibiting autoimmunity. Inflammatory diseases such as psoriasis and acne can also benefit. The non-invasive nature and almost complete absence of side-effects encourages further testing in dermatology.

Keywords: Acne, Dermatology, Herpes, Laser, LLLT, Low level laser therapy, Phototherapy, Skin disease, Skin Rejuvenation, Pigmentation, Vitiligo

Increasingly, non-invasive therapies for skin disease and skin rejuvenation are used, especially in Western countries where relatively high disposable incomes are combined with the desire for an ideal appearance fostered by societal pressures. Although the skin is the organ that is naturally most exposed to light, it still responds well to red and near-infrared wavelengths delivered at the correct parameters with therapeutic intent. Low-level laser therapy (LLLT) was discovered in the late 1960s, but only in recent times has it been widely applied in dermatology. The introduction of light emitting diode (LED) devices has reduced many of the concerns formerly associated with lasers, such as expense, safety concerns and the need for trained personnel to operate them. In fact, many LED devices are designed for home use and are widely sold on the internet. This review will cover the use of LLLT as possibly the ultimate non-invasive approach to treating the skin.

Low-Level Laser (Light) Therapy and Its Mechanism of Action

LLLT, phototherapy or photobiomodulation refers to the use of photons at a non-thermal irradiance to alter biological activity. LLLT uses either coherent light sources (lasers) or non-coherent light sources consisting of filtered lamps or light-emitting diodes (LED) or, on occasion, a combination of both. The main medical applications of LLLT are reducing pain and inflammation, augmenting tissue repair and promoting regeneration of different tissues and nerves, and preventing tissue damage in situations where it is likely to occur.1,2 In the last few decades, non-ablative laser therapies have been used increasingly for the aesthetic treatment of fine wrinkles, photoaged skin and scars, a process known as photorejuvenation (Table 1). More recently, this approach has also been used for inflammatory acne (Table 1).3 LLLT involves exposing cells or tissue to low-levels of red and near infrared (NIR) light. This process is referred to as ‘low-level’ because the energy or power densities employed are low compared to other forms of laser therapy such as ablation, cutting, and thermally coagulating tissue. Recently, medical treatment with LLLT at various intensities has been found to stimulate or inhibit an assortment of cellular processes.4

Table 1
Examples of LLLT Devices for Dermatological Applications

The mechanism associated with the cellular photobiostimulation by LLLT is not yet fully understood. From observation, it appears that LLLT has a wide range of effects at the molecular, cellular, and tissue levels. The basic biological mechanism behind the effects of LLLT is thought to be through absorption of red and NIR light by mitochondrial chromophores, in particular cytochrome c oxidase (CCO) which is contained in the respiratory chain located within the mitochondria,57 and perhaps also by photoacceptors in the plasma membrane of cells. Consequently a cascade of events occur in the mitochondria, leading to biostimulation of various processes (Figure 1).8 Absorption spectra obtained for CCO in different oxidation states were recorded and found to be very similar to the action spectra for biological responses to the light.5 It is hypothesized that this absorption of light energy may cause photodissociation of inhibitory nitric oxide from CCO9 leading to enhancement of enzyme activity,10 electron transport,11 mitochondrial respiration and adenosine triphosphate (ATP) production (Figure 1).1214 In turn, LLLT alters the cellular redox state which induces the activation of numerous intracellular signaling pathways, and alters the affinity of transcription factors concerned with cell proliferation, survival, tissue repair and regeneration (Figure 1).2,5,6,15,16

Figure 1
Mechanism of action of LLLT.

Although LLLT is now used to treat a wide variety of ailments, it remains somewhat controversial as a therapy for 2 principle reasons. First, there are uncertainties about the fundamental molecular and cellular mechanisms responsible for transducing signals from the photons incident on the cells to the biological effects that take place in the irradiated tissue. Second, there are significant variations in terms of dosimetry parameters: wavelength, irradiance or power density, pulse structure, coherence, polarization, energy, fluence, irradiation time, contact vs non-contact application, and repetition regimen. Lower dosimetric parameters can result in reduced effectiveness of the treatment and higher ones can lead to tissue damage.1 This illustrates the concept of the biphasic dose response that has been reported to operate in LLLT 1,18,19. Many of the published studies on LLLT include negative results. It is possibly because of an inappropriate choice of light source and dosage. It may also be due to inappropriate preparation of the patient’s skin before application of LLLT, such as: lack of removal of makeup and oily debris, which can interfere with the penetration of the light source, and failure to account for skin pigmentation.17 Inappropriate maintenance of the LLLT equipment can reduce its performance and interfere with clinical results as well. It is important to consider that there is an optimal dose of light for any particular application.

Laser radiation or non-coherent light has a wavelength and radiant exposure dependent capability to alter cellular behavior in the absence of significant heating.20 Phototherapy employs light with wavelengths between 390–1,100 nm and can be continuous wave or pulsed. In normal circumstances, it uses relatively low fluences (0.04–50 J/cm2) and 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 LLLT 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 common example of 904 nm), and gallium aluminum arsenide (GaAlAs; 612–870 nm).17 A wide range of LED semiconductors are available at lower wavelengths, whose medium contains the elements indium, phosphide and nitride. One question that has not yet been conclusively answered is whether there is any advantage to using coherent laser light over non-coherent LED light.22 While some medical practitioners treat deep tissue lesions using focused lasers in “points”, in dermatology the use of LEDs is becoming increasingly common due to the relatively large areas of tissue that require irradiation.

Figure 2
Tissue penetration depths of various wavelengths.

LLLT for Skin Rejuvenation

Skin starts showing its first signs of aging in the late 20s to early 30s and it usually presents with wrinkles, dyspigmentation, telangiectasia, and loss of elasticity. Common histologic and molecular-level features are reduction in the amount of collagen, fragmentation of collagen fibers, elastotic degeneration of elastic fibers, upregulation of matrix metalloproteinases (MMPs), especially MMP-1 and MMP-2, dilated and tortuous dermal vessels, and atrophy and disorientation of the epidermis.23,24 Both chronological and environmental influences are responsible for the aging process of skin; however photodamage seems to be one of the most important causes of these changes.

Several modalities have been developed in order to reverse the dermal and epidermal signs of photo- and chronological aging. The main concept of most of these modalities is removing the epidermis and inducing a controlled form of skin wounding in order to promote collagen biosynthesis and dermal matrix 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.2527 However, these procedures require intensive post-treatment care, 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 minimum postoperative care and downtime, which in turn led to the emergence of non-ablative rejuvenation technologies.3032 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 (photothermolysis) can be achieved by other IPL sources (ie, 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 novel light source for non-thermal, non-ablative skin rejuvenation has been shown to be effective for improving wrinkles and skin laxity (Figure 3).3440 It is not a new phenomenon since the first reports of LLLT effects on increased collagen go back to 1987. Studies by Abergel et al. and Yu et al. reported an increase in production of pro-collagen, collagen, basic fibroblast growth factors (bFGF) and proliferation of fibroblasts after exposure to low-energy laser irradiation in vitro and in vivo animal models (Figure 4).41,42 Furthermore, LLLT was already known to increase microcirculation, vascular perfusion in the skin, alter platelet-derived growth factor (PDGF), transforming growth factor (TGF-β1) and inhibit apoptosis (Figure 4).1,43,44 Lee et al. investigated the histologic and ultrastructural changes following a combination of 830 nm, 55 mW/cm2, 66 J/cm2 and 633 nm, 105 mW/cm2, 126 J/cm2 LED phototherapy and observed alteration in the status of MMPs and their tissue inhibitors (TIMPs).33 Furthermore, mRNA levels of IL-1β, TNF-α, ICAM-1, and connexin 43 (Cx43) were increased following LED phototherapy whereas IL-6 levels were decreased (Figure 4) 33. Finally, an increase in the amount of collagen was demonstrated in the post-treatment specimens 33. Pro-inflammatory cytokines IL-1β and TNF-α 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 these observations are put together, it is possible that increased production of IL-1β and TNF-α might have induced MMPs in the early response to LED therapy. This may clear the photodamaged collagen fragments to enable biosynthesis of new collagen fibers. Later on, an increase in the amount of TIMPs might protect the newly synthesized collagen from proteolytic degradation by MMPs.33 Furthermore, increased expression of Cx43 may possibly enhance cell-to-cell communication between dermal components, especially the fibroblasts, and enhance the cellular responses to the photobiostimulation effects from LED treatment, in order to produce new collagen in a larger area which even includes the non-irradiated regions.33 In a clinical study performed by Weiss et al., 300 patients received LED therapy (590 nm, 0.10 J/cm2) alone, and 600 patients received LED therapy in combination with a thermal-based photorejuvenation procedure. Among patients who received LED photorejuvenation alone, 90% reported that they observed a softening of skin texture and a reduction in roughness and fine lines ranging from a significant reduction to sometimes subtle changes.36 Moreover, patients receiving a thermal photorejuvenation laser with or without additional LED photomodulation (n = 152) reported a prominent reduction in post-treatment erythema and an overall impression of increased efficacy with the additional LED treatment.36,45 This reduction in post-treatment erythema could be attributed to anti-inflammatory effects of LLLT.40 Using different pulse sequence parameters, a multicenter clinical trial was conducted, with 90 patients receiving 8 LED treatments over 4 weeks.37,4648 The outcome of this study showed very favorable results, with over 90% of patients improving by at least one Fitzpatrick photoaging category and 65% of patients demonstrating global improvement in facial texture, fine lines, background erythema, and pigmentation. The results peaked at 4 to 6 months following completion of 8 treatments. Markedly increased collagen in the papillary dermis and reduced MMP-1 were common findings. Barolet et al.’s study is also consistent with the previously mentioned studies. They used a 3-D model of tissue-engineered human reconstructed skin to investigate the potential of 660 nm, 50 mW/cm, 4 J/cm2 LED in modulating collagen and MMP-1 and results showed upregulation of collagen and down-regulation MMP-1 in vitro.40 A split-face, single-blinded clinical study was then carried out to assess the results of this light treatment on skin texture and appearance of individuals with aged/photoaged skin.40 Following 12 LED treatments, profilometry quantification demonstrated that while more than 90% of individuals had a reduction in rhytid depth and surface roughness, 87% of the individuals reported that they have experienced a reduction in the Fitzpatrick wrinkling severity score.40

Figure 3
Examples of LLLT devices in dermatology for home and clinical use.
Figure 4
Possible mechanism of actions for LLLT’s effects on skin rejuvenation.

LLLT for Acne

Pathogenesis of acne vulgaris has not yet been clarified, however current consensus is that it involves four main events: follicular hyperconification, increased sebum secretion effected by the androgenic hormone secretions, colonization of Propionibacterium acnes and inflammation.49 P. acnes plays a key role by acting on triglycerides and releasing its cytokines which in turn trigger inflammatory reactions and alter infundibular keratinization.49 Current treatments for acne vulgaris include topical and oral medications such as topical antibiotics, topical retinoids, benzoyl peroxide, alpha hydroxy acids, salicylic acid, or azaleic acid. In severe cases, systemic antibiotics such as tetracycline and doxycycline, oral retinoids, and some hormones are indicated.50 Medications work by counteracting microcomedone formation, sebum production, P. acnes, and inflammation.50 Despite many options that are available for treatment of acne vulgaris, many patients still respond inadequately to treatment or experience some adverse effects.

Phototherapy (light, lasers, and photodynamic therapy) has been proposed as an alternative therapeutic modality to treat acne vulgaris and was proposed to have less side effects compared to other treatment options.51 Exposure of sunlight was reported to be highly effective for treatment of acne with efficacy up to 70%.52 The sunlight decreases the androgenic hormones in the sebaceous gland, but the unwanted effect of exposure to UVA and UVB limits sunlight for the treatment of acne. Recently, phototherapy with visible light (mainly blue light, red light or combination of both) started being used in the treatment of acne (Figure 3).52 One mechanism of action of phototherapy for acne is through the absorption of light (specifically blue light) by porphyrins that have been produced by P. acnes as a part of its normal metabolism, and that act as endogenous photosensitizers. 49,53 This process causes a photochemical reaction and forms reactive free radicals and Singlet oxygen species which in turn lead to bacterial destruction (Figure 5).49,53 Red light is known to penetrate deeper in tissues when compared to blue light.50 It has been demonstrated that red light can affect the sebum secretion of sebaceous glands and change keratinocyte behavior.54 Furthermore, red light might also exert its effects by modulating cytokines from macrophages and other cells, which in turn could reduce inflammation.51,54

Figure 5
Illustration of acne treatment with red and blue light.

Several studies reported that LLLT in the red to near infrared spectral range (630–1000 nm) and nonthermal power (less than 200 mW) alone or in combination with other treatment modalities (mainly blue light), is effective for treatment of acne vulgaris.17,49,52,54,55 One of these studies demonstrated significant reduction in active acne lesions after 12 sessions of treatment using 630-nm red spectrum LLLT with a fluence of 12 J/cm2 twice a week for 12 sessions in conjunction with 2% topical clindamycin; however the same study showed no significant effects when a 890 nm laser was used.50 A few studies also showed that the combination of blue light and red light have synergistic effects in acne treatment.49,5456 It is proposed that synergistic effects of mixed light is due to synergy between the anti-bacterial and anti-inflammatory effect of blue and red light respectively (Figure 5).49,56 It is also worth mentioning that in most studies improvement in inflammatory lesions were higher than the improvement in comedones.49,56

LLLT for Photoprotection

It is widely accepted that the UV range (< 400 nm) exposure is responsible for almost all damaging photo-induced effects on human skin.5759 Some proposed mechanisms for UV induced skin damage are collagen breakdown, formation of free radicals, inhibition of DNA repair, and inhibition of the immune system.5759 Existing solutions to prevent UV induced damaging effects are based on minimizing the amount of UV irradiation that reaches the skin, which is achieved by either avoidance of sun exposure or by use of sunscreens. However sometimes sun avoidance might be hard to implement, especially for the people involved in outdoor occupations or leisure activities. On the other hand, the photoprotective efficacy of topical sunscreens have their own limitations as well, which include decreased efficacy following water exposure or perspiration, spectral limitations, possible toxic effects of nanoparticles that are contained by most sunscreens,60 user allergies, and compliance.

It has recently been suggested that infrared (IR) exposure might have protective effects against UV-induced skin damage mainly by triggering protective/repair responses to UV irradiation. In the natural environment, visible and IR solar wavelengths predominate in the morning and UVB and UVA are maximal around noon which suggest that mammalians already possess a natural mechanism which, in reaction to morning IR radiation, prepares the skin for upcoming potentially damaging UV radiation at noon.61 However, opposing views also exist, such as Krutmann’s study demonstrating IR-induced disturbance of the electron flow of the mitochondrial electron transport chain which leads to inadequate energy production in dermal fibroblasts.62 Schroeder’s report is another example stating that IR alters the collagen equilibrium of the dermal extracellular matrix by leading to an increased expression of the collagen-degrading enzyme MMP-1, and by decreasing the de novo synthesis of the collagen itself.59 As previously mentioned, the same light source may have opposite effects on the same tissue depending on the parameters used and these conflicting views are probably due to the biphasic effects of light.18,19

Menezes et al. demonstrated that non-coherent near infrared radiation (NIR) (700–2,000 nm) generated a strong cellular defense against solar UV cytotoxicity in the absence of rising skin temperature and it was assumed to be a long-lasting (at least 24 hours) and cumulative phenomenon.63 Following this study, Frank et al. proposed that IR irradiation prepares cells to resist UVB-induced damage by affecting the mitochondrial apoptotic pathway.64 IR pre-irradiation of human fibroblasts was shown to inhibit UVB activation of caspase-9 and -3, partially release of cytochrome c and Smac/Diablo, decrease pro-apoptotic (ie, Bax) and increase anti-apoptotic proteins (ie, Bcl-2 or Bcl-xL).64 The results suggested that IR inhibited UVB-induced apoptosis by modulating the Bcl2/Bax balance, pointing to a role of p53, a sensor of gene integrity involved in cell apoptosis and repair mechanisms. In a further study, Frank et al. studied more specifically the role of the p53 cell signaling pathway in the prevention of UVB toxicity.64 The response to IR irradiation was shown to be p53 dependent which further suggests that IR irradiation prepares cells to resist and/or to repair further UVB-induced DNA damage. Finally, the IR induction of defense mechanisms was supported by Applegate et al. who reported that the protective protein, ferritin, normally involved in skin repair (scavenger of Fe2+ otherwise available for oxidative reactions) was induced by IR radiation.65

In an in vitro study, it was reported that an increase dermal fibroblast procollagen secretion reduces metalloproteinases (MMP) or collagenase production following non-thermal non-coherent deep red visible LED exposures (660 nm, sequential pulsing mode).40 These results correlated with significant clinical improvement of rhytids in vivo.40 In a subsequent in vivo pilot study, effect of this wavelength in 3 healthy subjects using a minimal erythemal dose (MED) method adapted from sunscreen SPF determination has been investigated.61 The results showed that LED therapy was effective, achieving a significant response in the reduction of the erythema induced by UVB.61 Following this pilot study a further investigation has been performed to find out in vivo aspects of this phenomenon. Effects of non-thermal, non-coherent 660 nm LED pulsed treatments in providing enhanced skin resistance prior to upcoming UV damage was investigated in a group of subjects with normal fair skin and patients presenting polymorphous light eruption (PLE). Results suggested that LED based therapy prior to UV exposure provided significant dose-related protection against UVB induced erythema. A significant reduction in UVB induced erythema reaction was observed in at least one occasion in 85% of subjects as well as in the patients suffering from PLE. Furthermore, a sun protection factor SPF-15-like effect and a reduction in post-inflammatory hyperpigmentation were observed. An in vitro study by Yu et al. revealed that HeNe laser irradiation stimulated an increase in nerve growth factor (NGF) release from cultured keratinocytes and its gene expression.66 NGF is a major paracrine maintenance factor for melanocyte survival in skin.67 It was shown that NGF can protect melanocytes from UV-induced apoptosis by upregulating BCL-2 levels in the cells.68 Therefore, an increase in NGF production induced by HeNe laser treatment may provide another explanation for the photoprotective effects of LLLT.

LLLT for Herpes Virus Lesions

One of the most common virus infections is caused by herpes simplex virus (HSV). HSV is chronic and lasts one’s entire life. The exposure of the host to several kinds of physical or emotional stresses such as fever, exposure to UV light, and immune suppression causes virus reactivation and migration through sensory nerves to skin and mucosa, localizing particularly on the basal epithelium of the lips and the perioral area.69 Up to 60% of sufferers will experience a prodromic stage, after which the lesions develop through stages of erythema, papule, vesicle, ulcer and crust, until healing is achieved. It is accompanied by pain, burning, itching, or tingling at the site where the blisters form. Immune responses to HSV infection involve: macrophages, Langerhans cells, natural killer cells, lymphocyte-mediated delayed-type hypersensitivity, and cytotoxicity.70

While several anti-viral drugs such as acyclovir and valacyclovir are used to control recurrent herpes outbreaks, only limited reduction in the lesions’ healing time has been observed.69 Furthermore, development of drug-resistant HSV strains is of increasing significance especially in immunocompromised patients.70 Therefore, new therapy modalities that can shorten the recurrent episodes and cause prominent reduction of related pain and inflammation are necessary.

LLLT has been suggested as an alternative to current medications for accelerated healing, reducing symptoms and influencing the length of the recurrence period.69,71,72 Among 50 patients with recurrent perioral herpes simplex infection (at least once per month for more than 6 months), when LLLT (690 nm, 80 mW/cm2, 48 J/cm2) was applied daily for 2 weeks during recurrence-free periods it was shown to decrease the frequency of herpes labialis episodes.73 In another study with similar irradiation parameters (647 nm, 50 mW/cm2, 4.5 J/cm2), investigators achieved a significant prolongation of remission intervals from 30 to 73 days in patients with recurrent herpes simplex infection.74 Interestingly, patients with labial herpes infection showed better results than those with genital infection. However, irradiation did not effect established HSV latency in a murine model.75

Even though mechanism of action is still not clear, an indirect effect of LLLT on cellular and humoral components of the immune system involved in antiviral responses rather than a direct virus-inactivating effect was proposed.76 Inoue et al. investigated tuberculin reactions at the bilateral sites of the backs of sensitized guinea pigs. They applied a single low-power laser irradiation dose at a fluence of 3.6 J per cm2on one side and compared it to contralateral non-irradiated sites.77 Interestingly, following irradiation, tuberculin reaction was suppressed not only at the irradiated site but also at the contralateral nonirradiated site. It is worth to note that this phenomenon was observed when mononuclear cells were dominant in the perivascular cellular infiltration. Based on their results, they have suggested a possible systemic inhibitory effect of LLLT on delayed hypersensitivity reactions.77 Activation and proliferation of lymphocytes7881 and macrophages82 as well as the synthesis and expression of cytokines83,84 following low intensities of red and NIR light have been reported by several investigators. The question of whether these effects of LLLT have any influence on HSV infection remains to be determined.

LLLT for Vitiligo

Vitiligo is an acquired pigmentary disorder characterized by depigmentation of the skin and hair. The underlying mechanism of how the functional melanocytes disappear from the involved skin is still under investigation. However, findings suggest that regardless of the pathogenetic mechanism involved, keratinocytes, fibroblasts, melanoblasts and melanocytes may all be involved in both the depigmentation and also the repigmentation processes of vitiligo.66,8589 Therefore, stimulation of these epidermal and dermal cells may be a possible treatment option. Due to the obscure pathogenesis of the disease, treatment of vitiligo has generally been unsatisfactory. Current existing therapies that induce varying degrees of repigmentation in patients with vitiligo are topical corticosteroids, phototherapy, and photochemotherapy (PUVA).89 In 1982, a group of investigators found that low energy laser irradiation had effects on defective biosynthesis of catecholamine in certain dermatological conditions including scleroderma and vitiligo.90,91 Later on, one of the investigators from the same group reported that after 6–8 months of treating 18 vitiglio patients with low-energy HeNe laser (632 nm, 25 mW/cm2 ) therapy, marked repigmentation was observed in 64% of the patients and some follicular repigmentation was observed in the remaining 34%.91 Since then, LLLT has been suggested as an alternative effective treatment option for patients with vitiligo.66,88,89

Segmental-type vitiligo is associated with a dysfunction of the sympathetic nerves in the affected skin and it is relatively resistant to conventional therapies.66 Based on the previous reports stating that HeNe laser irradiation leads to improvement in nerve injury9294 and LLLT induces repigmentation responses,95,96 it was proposed that the HeNe laser might be a potential treatment modality for treatment of segmental type vitiligo. 66 When the HeNe laser light was administered locally (3 J/cm2, 1.0 mW, 632.8 nm), marked perilesional and perifollicular repigmentation (> 50%) was observed in 60% of patients with successive treatments. Both NGF and bFGF stimulate melanocyte migration and deficiencies of these mediators may participate in the development of vitiligo.86,97,98 In the same study, when cultured keratinocytes and fibroblasts were irradiated with 0.5–1.5 J per cm2 HeNe laser, significant increase in bFGF release both from keratinocytes and fibroblasts as well as a significant increase in NGF release from keratinocytes was reported. 66 Additionally, the medium from HeNe laser irradiated keratinocytes stimulated [3H]thymidine uptake and proliferation of cultured melanocytes. Another study by Lan et al. demonstrated that the HeNe laser (632.8 nm, 1 J/cm2 and 10 mW) stimulates melanocyte proliferation through enhanced α2β1 integrin expression88 and induces melanocyte growth through upregulation of the expression of phosphorylated cyclic-AMP response element binding protein (CREB) which is an important regulator of melanocyte growth.88 ECM molecules are also important elements of the pigmentation process due to their regulatory roles for physiological functions of pigment cells including morphology, migration, tyrosinase activity and proliferation.

LLLT for Producing Depigmentation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126803/


Comparison of Red and Infrared Low-level Laser Therapy in the Treatment of Acne Vulgaris.

Aziz-Jalali MH1, Tabaie SM, Djavid GE. - Indian J Dermatol. 2012 Mar;57(2):128-30. doi: 10.4103/0019-5154.94283. (Publication)
This study found that RED laser (660nm) provided a signicant decrease in vulgaris while 890nm did not show an improvement
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Intro: Acne vulgaris is a very prevalent skin disorder and remains a main problem in practice. Recently, phototherapy with various light spectrums for acne has been used. There are some evidences that low-level laser therapy (LLLT) has beneficial effect in the treatment of acne lesions. In this study, two different wavelengths of LLLT (630 and 890 nm) were evaluated in treatment of acne vulgaris.

Background: Acne vulgaris is a very prevalent skin disorder and remains a main problem in practice. Recently, phototherapy with various light spectrums for acne has been used. There are some evidences that low-level laser therapy (LLLT) has beneficial effect in the treatment of acne lesions. In this study, two different wavelengths of LLLT (630 and 890 nm) were evaluated in treatment of acne vulgaris.

Abstract: Abstract BACKGROUND/PURPOSE: Acne vulgaris is a very prevalent skin disorder and remains a main problem in practice. Recently, phototherapy with various light spectrums for acne has been used. There are some evidences that low-level laser therapy (LLLT) has beneficial effect in the treatment of acne lesions. In this study, two different wavelengths of LLLT (630 and 890 nm) were evaluated in treatment of acne vulgaris. MATERIALS AND METHODS: This study was a single-blind randomized clinical trial. Patients with mild to moderate acne vulgaris and age above 18 years and included were treated with red LLLT (630 nm) and infrared LLLT (890 nm) on the right and left sides of the face respectively, twice in a week for 12 sessions, and clinically assessed at baseline and weeks 2, 4, 6, and 8. RESULTS: Twenty-eight patients were participated in this study. Ten weeks after treatment acne lesion were significantly decreased in the side treated by 630 nm LLLT (27.7±12.7 to 6.3±1.9) (P<0.001), but this decrease was not significant in the site treated by 890 nm LLLT (26.9±12.4 to 22.2±8.5) (P>0.05). CONCLUSION: Red wavelength is safe and effective to be used to treat acne vulgaris by LLLT compared to infrared wavelength.

Methods: This study was a single-blind randomized clinical trial. Patients with mild to moderate acne vulgaris and age above 18 years and included were treated with red LLLT (630 nm) and infrared LLLT (890 nm) on the right and left sides of the face respectively, twice in a week for 12 sessions, and clinically assessed at baseline and weeks 2, 4, 6, and 8.

Results: Twenty-eight patients were participated in this study. Ten weeks after treatment acne lesion were significantly decreased in the side treated by 630 nm LLLT (27.7±12.7 to 6.3±1.9) (P<0.001), but this decrease was not significant in the site treated by 890 nm LLLT (26.9±12.4 to 22.2±8.5) (P>0.05).

Conclusions: Red wavelength is safe and effective to be used to treat acne vulgaris by LLLT compared to infrared wavelength.

Original Source: http://www.ncbi.nlm.nih.gov/pubmed/22615511

Effects of monopolar radiofrequency treatment over soft-tissue fillers in an animal model.

England LJ1, Tan MH, Shumaker PR, Egbert BM, Pittelko K, Orentreich D, Pope K. - Lasers Surg Med. 2005 Dec;37(5):356-65. ()
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Intro: Monopolar radiofrequency (RF) treatment is used by physicians to tighten and contour the skin of their patients. In many cases, patients have received prior treatment with other aesthetic modalities such as soft-tissue augmentation or they may wish to receive these treatment modalities simultaneously. Together, soft-tissue augmentation and monopolar RF treatment have the potential to restore tissue volume and improve facial laxity. To date, no published studies have documented the effects of RF treatment directly over soft-tissue fillers.

Background: Monopolar radiofrequency (RF) treatment is used by physicians to tighten and contour the skin of their patients. In many cases, patients have received prior treatment with other aesthetic modalities such as soft-tissue augmentation or they may wish to receive these treatment modalities simultaneously. Together, soft-tissue augmentation and monopolar RF treatment have the potential to restore tissue volume and improve facial laxity. To date, no published studies have documented the effects of RF treatment directly over soft-tissue fillers.

Abstract: Abstract BACKGROUND AND OBJECTIVES: Monopolar radiofrequency (RF) treatment is used by physicians to tighten and contour the skin of their patients. In many cases, patients have received prior treatment with other aesthetic modalities such as soft-tissue augmentation or they may wish to receive these treatment modalities simultaneously. Together, soft-tissue augmentation and monopolar RF treatment have the potential to restore tissue volume and improve facial laxity. To date, no published studies have documented the effects of RF treatment directly over soft-tissue fillers. STUDY DESIGN/MATERIALS AND METHODS: We examined the tissue interactions of monopolar RF heating with five commonly injected fillers in a juvenile pig model. This is the first part of a two-part study. In this study, the interaction of monopolar RF and filler substances was examined over a period of 4 months. The five soft-tissue fillers examined were cross-linked human collagen (Cosmoplast), hyaluronic acid (Restylane), calcium hydroxylapatite (Radiesse), polylactic acid (Sculptra), and liquid injectable silicone (Silikon 1000). RESULTS: There was no apparent increase in the risk of local burns and no observable effect of RF treatment on filler persistence in the tissue. With monopolar RF treatment, an increase in fibroplasia and collagen deposition surrounding Restylane, Radiesse, and Sculptra was observed. When scored in a blinded fashion, the increase in collagen deposition was statistically significant for Radiesse. CONCLUSIONS: In this animal study, RF treatment had no observed adverse effect on filler collagen responses or persistence. Filler presence did not increase the risk of undesirable thermal effects with monopolar RF treatment. Further clinical studies are required to evaluate the effect of monopolar RF treatment over dermal fillers with respect to aesthetic outcome. (c) 2005 Wiley-Liss, Inc.

Methods: We examined the tissue interactions of monopolar RF heating with five commonly injected fillers in a juvenile pig model. This is the first part of a two-part study. In this study, the interaction of monopolar RF and filler substances was examined over a period of 4 months. The five soft-tissue fillers examined were cross-linked human collagen (Cosmoplast), hyaluronic acid (Restylane), calcium hydroxylapatite (Radiesse), polylactic acid (Sculptra), and liquid injectable silicone (Silikon 1000).

Results: There was no apparent increase in the risk of local burns and no observable effect of RF treatment on filler persistence in the tissue. With monopolar RF treatment, an increase in fibroplasia and collagen deposition surrounding Restylane, Radiesse, and Sculptra was observed. When scored in a blinded fashion, the increase in collagen deposition was statistically significant for Radiesse.

Conclusions: In this animal study, RF treatment had no observed adverse effect on filler collagen responses or persistence. Filler presence did not increase the risk of undesirable thermal effects with monopolar RF treatment. Further clinical studies are required to evaluate the effect of monopolar RF treatment over dermal fillers with respect to aesthetic outcome.

Original Source: http://www.ncbi.nlm.nih.gov/pubmed/16240419

Abstracts of COSMOderm2/LASERderm1. August 31-September 3, 2002. Trieste, Italy.

[No authors listed] - J Cosmet Laser Ther. 2002 Jun;4(2):51-65. ()
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Abstract: Publication Types, MeSH Terms Publication Types Congresses Overall MeSH Terms Animals Dermatology/methods* Humans Laser Therapy, Low-Level/methods Phototherapy/methods* Surgery, Plastic/methods*

Original Source: http://www.ncbi.nlm.nih.gov/pubmed/12470515

Home Search Introduction

Ken Teegardin - (Video)
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Welcome to the laser-therapy.us research tool. This tool is a searchable collection of technical publications, books, videos and other resources about the use of lasers for photobiomodulation. This tool includes almost the entire U.S. library of medicine research papers on LLLT, videos from Youtube associated with therapy lasers and the tables of contents from laser therapy books. This allows users to search for a keyword or condition and see resources about using lasers to treat that condition. All the resources include links to the original source so we are not making any statement about the use of lasers for treating non-FDA cleared application, we are simple summarizing what others have said.  Where every possible, we have included a link to the orginal publication.

Here are some of our favorite queries:

This tool uses a broad match query so:

  • It does not correct spelling and searches only cold laser related subjects so do not use LLLT, cold or laser in the search bar
  • It works better with shorter search terms or even parts of search terms
  • It searches all the available fields so you can enter a body part, author, condition or laser brand.
  • Where ever possible, the detailed section about the resource will link to the sources.
  • This system is only for photobiomodulation or cold laser therapy research (including LLLT, laser acupuncture and high power laser therapy) only. It does NOT include photodynamic laser therapy (where the laser is used to react with a pharmaceutical), hot surgery lasers or cosmetic lasers. It does include some resources on weight loss and smoking cessation.

The results of the search are sorted based on 3 quality factors on a scale of 1 to 10 with 10 being the best score. Originally all the resources were given a 5-5-5 until they could be individually evaluated. These scores are purely opinion and are only used to simplify the rank of the results from more valuable to least valuable. This should not be considered a critique of any work. This system was created to help researchers (including ourselves) find the most usable resources for any cold laser therapy research. The resources are assigned values based on the following 3 factors:

  • Efficacy: The resource (especially research papers) should show a significant improvement in the condition being treated. Resources that show better results are given a higher quality score.
  • Detail: The source must give enough information that the results can be duplicated. If a resource lacks too many details that it cannot be recreated, it is given a lower detail score.
  • Lack of Bias: Many resources are created to try and show that one device is superior to its competition. Many manufacturers have staff that crank out biased papers on a regular basis on the hope that this will make their product look superior. If the author of the resource is paid by a manufacturer of the resource appears to be biased towards one device and not one technology, the resource has much less value.

Over the past few years of working with research, we found that a majority of the published resources are lacking in one of these three ranking factors.
The original goal of this research tool was to tie published resources to the protocols in the laser-therapy.us library. This connection allows users to trace each protocol back to a list of resources so the protocol can be researched and improved.

General Comments


POWER
When many of the first research papers were published, the most power laser available for therapy were less than 100mW and many systems had to be pulsed to keep the laser from burning out too quickly. Today, system are available that will deliver up to 60,000mW of continuous output. Because of these power limitation, many early studies were limited to extremely low dosages by today’s standards. It takes a 50mW system 17 minutes to deliver 50 joules at the surface of the skin. If this was spread over a large area of damage or was treating a deeper problem, the actual dosages were much less than 1J/cm2.  Today, we know that these dosages typically produce very little or no results.
WAVELENGTH
About 80% of the resources in this database are in the near infrared wavelength. There is also some interest in the red wavelength (600 to 660nm) . Other wavelengths like blue, purple, and green have very little scientific research behind them and have not gotten much traction in the core therapy market with the exception of some fringe consumer products.
Legal Disclaimer
This research tool is free to use but we make no claims about the accuracy of the information. It is an aggregation of existing published resources and it is up to the user to determine if the source of the resources has any value. The information provided through this web site should not be used for diagnosing or treating a health problem or disease. If you have or suspect you may have a health problem, you should consult your local health care provider.



The query result(s) can be shared using the following direct link. Anyone who clicks on this link in an email or on a web site will be shown the current results for the query.
https://www.laser-therapy.us/research/index.cfm?researchinput=cosmo