Low-level Laser Light Therapy Research Articles

Current Applications and Future Perspectives of Photobiomodulation in Ocular Diseases: A Narrative Review

The present article provides an overview of photobiomodulation (PBM), also known as low-level laser light therapy (LLLT), which has garnered attention in ophthalmology for its potential therapeutic benefits in various ocular diseases. Photobiomodulation involves the use of low-intensity lasers or light-emitting diodes to stimulate biological processes in target tissues without causing thermal damage. This article discusses how PBM has been explored across various ocular conditions, including ocular surface diseases, age-related macular degeneration, diabetic retinopathy, myopia, amblyopia, and glaucoma. It summarizes findings from human studies and clinical trials demonstrating positive outcomes of PBM treatment in these areas. Moreover, the article emphasizes the importance of establishing standardized treatment protocols in terms of session duration and frequency, light type, and patients’ inclusion criteria to further validate the role of PBM in managing ocular diseases.

The Effect of Supernatant Culture Medium Isolated from 3T3-L1 Cells Subjected to Low Power 980 and 650 nm Laser Radiation on Wound Healing Process

Background: Fibroblasts are the most important cells in the healing process of wounds. The motility activity of low-level laser (light) therapy (LLLT) on fibroblast proliferation has been well-established in vitro. Laser treatment for scar removal increases the number of scars. Objectives: This method uses light therapy to remove the outer layer of the skin surface and produce new skin cells to cover the damaged skin cells. Methods: The present research is from an experimental laboratory. First, tissue fibroblast cells were cultured under appropriate conditions. Then, it was exposed to laser radiation with intensities of 650 and 980 nm, and its supernatant solution was used for wound treatment. Interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) levels were used to check the recovery. Results: The results of the MTT assay showed an increase in the viability of the cell line under laser irradiation. In addition, these evaluations showed an increase in IL-2, TNF-α, and VEGF after 650 and 980 nm laser irradiation compared to the control group after 48 hours. Conclusions: According to the present study, laser therapy has potential therapeutic potential for wound healing. However, more studies are suggested to increase the efficiency and speed up the treatment process.

Further advancements in the near infrared lightemitting diode: review

During the last decade, significant advances have been made in the application of using a near infrared LED light-emitting diode over the use of low-level laser light therapy for a wide range of healing and rehabilitation processes. Near infrared LED has been shown to represent a novel, non-invasive, and effective coadjutant therapeutic intervention for the treatment of numerous diseases. With the discovery of the use of gallium arsenate (red light), the near infrared light-emitting diode has shown to be an effective therapy in the use of wound, bone, and traumatic brain injuries. Specific applications include wound healing, dentistry, peripheral nerve injury, depression, neurological disease (including Parkinson’s Disease, depression, and dementia), aging cerebrovascular disease, and traumatic brain injury. Most recently, the application of infrared light on brain tumors (photodynamic therapy) has started to provide a positive result. More evidence-based research is required to support this growing coadjutant therapeutic intervention.

Photobiomodulation regulates adult neurogenesis in the hippocampus in a status epilepticus animal model

Status epilepticus (SE) refers to a single seizure that lasts longer than typical seizures or a series of consecutive seizures. The hippocampus, which is vulnerable to the effects of SE, has a critical role in memory storage and retrieval. The trisynaptic loop in the hippocampus connects the substructures thereof, namely the dentate gyrus (DG), CA3, and CA1. In an animal model of SE, abnormal neurogenesis in the DG and aberrant neural network formation result in sequential neural degeneration in CA3 and CA1. Photobiomodulation (PBM) therapy, previously known as low-level laser (light) therapy (LLLT), is a novel therapy for the treatment of various neurological disorders including SE. However, the effects of this novel therapeutic approach on the recovery process are poorly understood. In the present study, we found that PBM transformed SE-induced abnormal neurogenesis to normal neurogenesis. We demonstrated that PBM plays a key role in normal hippocampal neurogenesis by enhancing the migration of maturing granular cells (early neuronal cells) to the GCL, and that normal neurogenesis induced by PBM prevents SE-induced hippocampal neuronal loss in CA1. Thus, PBM is a novel approach to prevent seizure-induced neuronal degeneration, for which light devices may be developed in the future.

Regenerative Biotechnologies in Plastic Surgery: A Multicentric, Retrospective, Case-Series Study on the Use of Micro-Needling with Low-Level Light/Laser Therapy as a Hair Growth Boost in Patients Affected by Androgenetic Alopecia

A new biotechnology based on micro-needling (MND) with low-level light/laser therapy (LLLT) that is used for hair re-growth (HR-G) needs to be standardized. The study aims to report the clinical outcomes resulting from a multicentric, retrospective, observational, case-series study in which MND with LLLT was used on patients affected by androgenic alopecia (AGA). Twenty-six patients were initially enrolled of which 15 males were classified as stages I–III of vertex by the Norwood–Hamilton scale, and 11 females was classified in stages I–II by the Ludwig scale. Twenty patients (10 females and 10 males) were analyzed after their screening (the exclusion and inclusion criteria evaluation). The HR-G assessment was evaluated with photography, as well as the physician’s and patient’s global assessment scales, in addition to standardized phototrichograms, during a short follow-up at T0-baseline, T1-16 weeks. Encouraging results represented by a hair density increase of 12 ± 2 hairs/cm2 at T1 after 16 weeks (16 weeks vs. 0 weeks) in the targeted area, compared with the baseline results (59 ± 2 hairs/cm2 at T1 versus 47 ± 2 hairs/cm2 at baseline), were observed using computerized trichograms with a statistically significant difference in hair re-growth (p = 0.0238). The effectiveness of MND with LLLT use has been demonstrated in mild to moderate AGA patients.

A systematic review on the treatment of pediatric severe alopecia areata by topical immunotherapy or Anthralin (contact sensitization) or low-level light/laser therapy (LLLT): focus on efficacy, safety, treatment duration, recurrence, and follow-up based on clinical studies.

Alopecia areata (AA) in its extensive and severe forms is treatment-challenging, especially in pediatrics. A PRISMA-compliant systematic review of seven electronic databases was searched by the terms "alopecia areata," "pediatric," "topical immunotherapy," "Anthralin," and "light therapy" from inception until March 2021. All the alternative names of the disease and therapies have been included in the search terms. 790 articles went to title abstract review by two independent reviewers. In the subsequent level, a review of the full text of studies was conducted. Finally, 10 relevant articles in terms of content structure, subject coverage, and purpose, were selected for further review. The highest percentages of complete hair regrowth were 79.6% and 63.61% by SADBE (topical immunotherapy) and laser therapy. By Anthralin (contact sensitization), the complete response rate was below 50% (between 30 and 35%). Regarding average response, the most effective methods were local immunotherapy (with an average effectiveness of 53.8%), laser therapy (52.55%), and the use of Anthralin-induced contact dermatitis (30.86%), respectively. However, recurrence rate-after treatment with induced contact dermatitis by topical medications like Anthralin (contact sensitization)-was lower (mean 43.53%) in comparison with local immunotherapy (57%). In topical immunotherapy, light base therapy, and contact sensitization, the highest percentage of complete hair regrowth and the average response rate were (63.61% and 52.55%), (79.6% and 53.8%) and (32% and 30.8%), respectively. These methods are considered safe in children. A high and more than 50% efficacy in hair regrowth could be expected by topical immunotherapy and light/laser therapy method. No serious side effects have been observed by these methods that are well tolerated in children. Therefore, a combination of local immunotherapy and light/laser therapy could be suggested for the treatment of extensive AA in children. The use of Anthralin could be associated with a lower but more durable response. These points are important for patient selection in individualized situations.

The Effectiveness of Low-Level Light/Laser Therapy on Hair Loss.

Background: A systematic review on low-level light/laser therapy (LLLT) in male pattern hair loss (MPHL) and female pattern hair loss (FPHL) has been performed. Objectives: Compare the reported effectiveness of LLLT in MPHL and FPHL with any control, through randomized controlled trials (RCTs) analysis. Methods: The protocol was developed in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols guidelines. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, Clinicaltrials.gov, Scopus database, and Cochrane databases has been performed to identify articles on MPHL and/or FPHL treatment with LLLT. Results: Of the 298 articles initially identified, 136 articles focusing on MPHL and FPHL were selected and, consequently, only 36 articles focused exclusively on LLLT. Of this amount, 23 articles were clinical trials while 13 articles were systematic reviews. Systematic reviews were excluded, and only seven articles were analyzed as RCTs. Conclusions: All the articles selected and analyzed reported a positive effect of LLLT for MPHL and/or FPHL treatment without side effects.

Alternative modality in the treatment of acne vulgaris: Low level laser therapy

Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit with polymorphic manifestations. The four key elements leading to the formation of acne lesions are alteration of follicular keratinization that leads to comedones, increased and altered sebum production under androgen control, follicular colonization by  Propionibacterium acnes , and complex inflammatory mechanisms that involve both innate and acquired immunity. Phototherapy (light, lasers, and photodynamic therapy) has been proposed as an alternative therapeutic modality to treat acne vulgaris and is proposed to have less side effects compared to other treatment options. Recently, low-level laser (light) therapy (LLLT) which refers to the use of red-beam or near-infrared laser with a wave-length between 600 and 1000 nanometers and power from 5 to 500 milliwatts, starts to be used in the treatment of acne. Mechanism of action of LLLT for acne is through photochemical reaction that produces reactive free radicals and singlet oxygen species which in turn lead to bacterial destruction by blue light. Meanwhile, red light can affect the sebum secretion of sebaceous glands, change keratinocytes behavior, and modulate cytokines from macrophages and other cells that reduce inflammation. LLLT is proposed to be effective as an alternative modality for inflammatory type lesions in acne vulgaris.   Keywords : acne vulgaris, blue light, low level laser therapy, red light. Normal 0 false false false EN-US X-NONE X-NONE

Electromyography changes in assessment of functional status of muscles in subjects with knee-osteoarthritis undergoing low level laser therapy

Introduction and Aim: Knee Osteoarthritis (KOA) is a common degenerative joint disease which is one of the leading causes of disability in elderly people. Electromyography (EMG) is an electrophysiological method in evaluating skeletal muscle activity. Low-level laser (light) therapy (LLLT) is a modality of treatment used in several conditions required to suppress the pain, inflammation, stimulation of healing and restoration of function. Surface EMG parameters were studied before and after the low level laser therapy in subjects with knee osteoarthritis. 
 Materials and Methods: Subjects with knee OA participated in the study. Low level laser therapy (LLLT) was administered using a laser device with probe giving maximum power output of 10 mw with a wavelength of 810 nm. Surface electromyography (sEMG) of quadriceps muscles was recorded in all the study participants before and after the therapy. The parameters were statistically compared. 
 Results: There was a statistically significant difference between the maximum contraction and duration of contraction before and after the laser intervention in all the muscles. 
 Conclusion: It can be concluded that the muscle performance increased in the subjects with knee OA after the LLLT.

The effectiveness of combination therapies for androgenetic alopecia: A systematic review and meta-analysis.

Androgenetic alopecia (AGA) is the most common type of baldness affecting both men and women. Studies investigating combination therapies for AGA reported greater efficacy than monotherapy but without rigorous examination. The authors performed a meta-analysis and systemic review to further verify the evidence. To evaluate the effectiveness of three common combination therapies of minoxidil with finasteride, low-level laser light therapy (LLLT) or microneedling versus minoxidil monotherapy. We conducted a systematic review of randomized controlled trials (RCTs) of combination therapies consisting of topical minoxidil for AGA through April 2020. Quality assessment and data analysis were performed by Review Manager 5.3. Fifteen studies met the inclusion criteria involving a total of 1172 AGA patients. We conducted meta-analysis for three groups of combined treatment separately, and all were superior to monotherapy in terms of global photographic assessment (P < .05). Combination of LLLT or microneedling with minoxidil also showed significant increase in hair count (P < .05) compared to monotherapy. The present study suggests that combination therapy could be an effective, safe and promising option for the treatment of AGA. However, more RCTs are needed to further investigate and confirm the efficacy of combined treatment.

Spironolactone for treatment of female pattern hair loss

Spironolactone for treatment of female pattern hair loss

Treatment of Male-Pattern Alopecia with Platelet-Rich Plasma

Background: Androgenetic alopecia (AGA) affects up to 80% of men and 50% of women throughout their lifetime, causing significant discomfort. Minoxidil, finasteride, and low-level laser light therapy are the only Food and Drug Administration-approved treatments for AGA, and they have shown positive results in randomized controlled trials and meta-analyses. However, their efficacy is limited, and new therapies are needed. Injection of platelet-rich plasma (PRP), a minimally invasive technique, has been described by several authors as a promising treatment for AGA. Although many studies report beneficial effects of PRP on AGA, there is no standardized practice for PRP preparation and administration or a standard method to evaluate results. Objective: The aim of this study was to evaluate the efficacy of manually prepared PRP in the treatment of male AGA. Materials and Methods: We treated 20 male patients with AGA with 3 monthly injections of PRP and analyzed results by TrichoScan®. Results: In this study, there was no statistically significant improvement in hair count or proportion of anagen hairs. Conclusions: This lack of response could be related to any of the variables during PRP preparation described above and also to the limited number of patients in the study.

Laser Light Therapy in Inflammatory, Musculoskeletal, and Autoimmune Disease.

The goal of this review is to summarize the field to date and to discuss strengths and limitations of low-level laser (light) therapy (LLLT) for the future investigation as a treatment of inflammatory disease. LLLT is a promising therapeutic, particularly for those diseases of skin and joints because they are most accessible to treatment. Indeed, the known mechanisms of LLLT support its use for anti-inflammatory purposes, as well as stimulation of tissue growth and repair. Although the standard of care for the majority of inflammatory diseases is immunosuppressive agents such as corticosteroids with undesirable toxicities, LLLT offers a unique approach by being non-invasive and incurring minimal side effects. It is also relatively inexpensive and accessible and even has the possibility to be patient directed at home. There is evidence that LLLT is able to modulate the immune system at the skin and joint, and it has been shown to be efficacious in humans by affecting bacterial colonization as it may pertain to chronic rhinosinusitis. However, there is variability in the methods of laser application as well as a lack of evidence for laser type, dose-ranging studies, and wavelength selection that create barriers to the implementation of LLLT without further more rigorous and standardized study. The heterogeneity makes it difficult to draw strong conclusions about the efficacy of LLLT and its mechanisms.

Low-level laser therapy for the treatment of androgenetic alopecia in Thai men and women: a 24-week, randomized, double-blind, sham device-controlled trial

Low-level laser/light therapy (LLLT) has been increasingly used for promoting hair growth in androgenetic alopecia (AGA). Our institute developed a new home-use LLLT device, RAMACAP, with optimal penetrating energy, aiming to improve therapeutic efficacy and compliance. To evaluate the efficacy and safety of the new helmet-type LLLT device in the treatment of AGA, a 24-week, prospective, randomized, double-blind, sham device-controlled clinical trial was conducted. Forty subjects with AGA (20 men and 20 women) were randomized to treat with a laser helmet (RAMACAP) or a sham helmet in the home-based setting for 24 weeks. Hair density, hair diameter, and adverse events were evaluated at baseline and at weeks 8, 16, and 24. Global photographic assessment for hair regrowth after 24 weeks of treatment was performed by investigators and subjects. Thirty-six subjects (19 in the laser group and 17 in the sham group) completed the study. At week 24, the laser helmet was significantly superior to the sham device for increasing hair density and hair diameter (p = 0.002 and p = 0.009, respectively) and showed a significantly greater improvement in global photographic assessment by investigators and subjects. Reported side effects included temporary hair shedding and scalp pruritus. In conclusion, the novel helmet-type LLLT device appears to be an effective treatment option for AGA in both male and female patients with minimal adverse effects. However, the limitations of this study are small sample size, no long-term follow-up data, and use of inappropriate sham devices, which do not reflect the true negative control. Trial registration: http://clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=2061, identifier TCTR20160910003.

Efficacy and Safety of a Low-Level Light Therapy for Androgenetic Alopecia: A 24-Week, Randomized, Double-Blind, Self-Comparison, Sham Device-Controlled Trial.

Previous studies have reported the benefits of low-level/light laser therapy (LLLT) for the promotion of hair regrowth. However, the effectiveness of LLLT for the treatment of androgenetic alopecia (AGA) is still a topic of debate. To investigate the efficacy and safety of LLLT on hair regrowth in patients with AGA. This 24-week, randomized, double-blind, self-comparison, sham device-controlled trial enrolled 100 patients with AGA. All participants were randomly assigned to receive the investigational LLLT on one side of the head and sham light treatment on the contralateral side, 3 times weekly for 30 minutes each, over a 24-week period. Global scalp photography, phototrichogram assessment, the investigator's global assessment (IGA) of hair regrowth, and the subject's assessment of the treatment satisfaction were used for evaluation. After 24 weeks of treatment, the LLLT-treated scalp exhibited significantly greater hair coverage than the sham light-treated side (14.2% vs. 11.8%, p < .001). A significantly greater improvement from baseline in hair thickness, hair count, hair coverage, and IGA were also observed in the LLLT-treated side than in the sham light-treated side at the 12- and 24-week visits. No serious adverse events were observed. The use of LLLT might be an effective, safe, well-tolerated treatment for AGA.

Photobiomodulation for Global Cerebral Ischemia: Targeting Mitochondrial Dynamics and Functions.

Hypothermia is currently the only approved therapy for global cerebral ischemia (GCI) after cardiac arrest; however, it unfortunately has multiple adverse effects. As a noninvasive procedure, photobiomodulation (PBM) therapy has emerged as a potential novel treatment for brain injury. PBM involves the use of low-level laser light therapy to influence cell behavior. In this study, we evaluated the therapeutic effects of PBM treatment with an 808-nm diode laser initiated 6h after GCI. It was noted that PBM dose-dependently protected against GCI-induced neuronal death in the vulnerable hippocampal CA1 subregion. Functional assessments demonstrated that PBM markedly preserved both short-term (a week) and long-term (6months) spatial learning and memory function following GCI. Further mechanistic studies revealed that PBM post-treatment (a) preserved healthy mitochondrial dynamics and suppressed substantial mitochondrial fragmentation of CA1 neurons, by reducing the detrimental Drp1 GTPase activity and its interactions with adaptor proteins Mff and Fis1 and by balancing mitochondrial targeting fission and fusion protein levels; (b) reduced mitochondrial oxidative damage and excessive mitophagy and restored mitochondrial overall health status and preserved mitochondrial function; and (c) suppressed mitochondria-dependent apoptosome formation/caspase-3/9 apoptosis-processing activities. Additionally, we validated, in an in vitro ischemia model, that cytochrome c oxidase served as a key PBM target for mitochondrial function preservation and neuroprotection. Our findings suggest that PBM serves as a promising therapeutic strategy for the functional recovery after GCI, with mechanisms involving PBM's preservation on mitochondrial dynamics and functions and the inhibition of delayed apoptotic neuronal death in GCI.

Photobiomodulation Optimization for Spinal Cord Injury Rat Phantom Model.

Spinal Cord Injury (SCI) causes interruption along the severed axonal tract(s) resulting in complete or partial loss of sensation and motor function. SCI can cause tetraplegia or paraplegia. Both these conditions can have lifelong excessive medical costs, as well as can reduce life expectancy. Preclinical research showed that Photobiomodulation therapy (PBMT), also known as Low-level laser (light) therapy (LLLT), possesses reparative and regenerative capabilities that have the potential to be used as a complimentary or supplementary SCI therapy. Despite the promising effects of PBMT, there are still no standardized irradiation parameters (i.e. different wavelengths, power, fluence, irradiance, beam type, beam diameters, and irradiation time) and there is also a lack of standardized experimental protocol(s), which makes it difficult to compare different studies. It is, nonetheless, essential to standardize such irradiation parameters in order to provide better PBMTs. The aim of this study, therefore, is to evaluate the delivery of light in a 3D voxelated SCI rat model for PBMT using different irradiation parameters (wavelengths: 660, 810, and 980 nm; beam types: Gaussian and Flat beam; and beam diameters: 0.04-1.2 cm) using Monte Carlo simulation. This study also aids in providing standardization for preclinical research for PBMT, which will eventually translate into clinical standardization upon clinical research studies and results.

Optimize Illumination Parameter of Low-Level Laser Therapy for Hemorrhagic Stroke by Monte Carlo Simulation on Visible Human Dataset

Stroke is the second leading cause of death and disability worldwide. The incidence of hemorrhagic stroke increases dramatically with the increasingly aging population. Recently, technology of low-level light/laser therapy (LLLT) is emerging as a novel noninvasive therapeutic approach to treat stroke based on effective photobiomodulation. To obtain optimal therapeutic effects, several LLLT illumination parameters such as beam size and beam type need to be optimized. However, the quantitative optimization of LLLT illumination parameters for stroke therapeutics is impractical to test directly on human subjects. In this paper, we employed a precise voxelized three-dimensional Monte Carlo method (MCVM) to simulate photon propagation within Visible Chinese human (VCH) head at different level of stroke with varied parameters of beams. By evaluation with criteria of the total fluence flux in lesion region and the maximal penetration depth, we found that Gaussian beam with larger or the same size of hemorrhagic region generates the highest and relative homogeneous therapeutic outcomes, while the Top-hat beam performed better when hemorrhagic region is much bigger than beam size. These results demonstrate the great potential of using VCH and MCVM in optimizing LLLT treatment parameters for stroke and in guiding future instrumentation of LLLT on hemorrhagic stroke.

Cooling-controlled and reliable driving module for low-level light therapy LED helmet

Stroke is a horrible disease of high incidence, which is the second leading cause of disability worldwide. Thousands of people are suffering from stroke sequelae. Therefore, how to rehabilitate from stroke sequela is an urgent research field benefiting human beings. The traditional and experience-based treatment methods not only have an uncertain treatment effect, but were also unsuitable to be widely used due to its unstable therapeutic effect. Transcranial low level light/laser therapy (LLLT) of neurological diseases and brain trauma has gained momentum due to the character of high-efficient, safe and non-invasive in the past decade. In this study, we developed a LLLT helmet with cooling-controlled and reliable driving module for treating stroke depending on near-infrared light. An application of integrated constant-current driving solution under high power is introduced in this paper. In order to reduce the large heat release of instrument and voltage drift of reference source, the major factors of current fluctuation, we proposed an integral thermal cooling solution and a multi-element parallel reference sources with temperature compensation to enhance the stability and robustness of the LLLT helmet. A series of experiments were performed to quantitatively testify the robustness and stability of our instrument.

Analgesic effects of preinjection low-level laser/light therapy (LLLT) before third molar surgery: a double-blind randomized controlled trial

The aim of this study was to evaluate the analgesic effects of low-level laser therapy (LLLT) on preinjection sites in patients scheduled for third molar removal. This double-blind randomized controlled trial included 163 healthy patients undergoing third molar extractions. The study participants were randomly divided into an LLLT and a placebo group. Objective and subjective data sets were obtained from physiologic feedback (heart rate and sweat response) and a questionnaire, respectively. In the LLLT group, each targeted injection site was irradiated twice with 198mW continuous wave for 30seconds with a 0.088cm2 focal spot at an applied energy of 5.94J and fluence of 67.50J/cm2. Measurements were recorded from 4 time-points during data acquisition. There was no significant difference between the LLLT and placebo groups in pain experience scores associated with the injected sites for maxillary or mandibular third molar extractions. Mean heart rates before and during injection were lower in the LLLT group than in the placebo group for both maxillary and mandibular regions. No statistically significant differences were observed for any remaining parameters. The present data indicated that preinjection LLLT did not effectively decrease the pain felt during local anesthetic injections before third molar surgery.