Photobiomodulation Clinical Evidence

RESEARCH OVERVIEW PHOTOBIOMODULATION THERAPY

This interactive presentation gives an overview of published research on PBMT

Get started

CONFIDENTIAL

Make your choice

BASIC SCIENCE (How) does photobiomodulation work?

CLINICAL EVIDENCE High Power Laser Therapy in multiple indications

CONFIDENTIAL

Basic Science

(How) Does Photobiomodulation Work?

Karu, 2010

Karu, 1989

Mitochondria & ATP

Holanda, 2017

Analgesia mechanisms

Ketz, 2017

Chow, 2016

Chow, 2011

Anti-inflammatory

Naterstad, 2018

Pallotta, 2012

Bomfim 2024

Bjordal, 2010

Gao, 2009

Chen, 2009

Tissue repair - Cell proliferation

Alves, 2014

Luo, 2013

Terena, 2018

Tissue repair – Muscle/Tendon

Tissue repair - Cartilage

Torricelli, 2001

Morrone, 2000

Yellow border = study with LiteCure device

Karu 2010 | Mitochondria, ATP

Back to overview

Karu T. Mitochondrial mechanisms of photobiomodulation in context of new data about multiple roles of ATP. Photomed Laser Surg. 2010 Apr;28(2):159-60.

- Mitochondria are the initial site of light action in cells, and cytochrome c oxidase (the terminal enzyme of the mitochondrial respiratory chain) is the responsible molecule. - Mixed-valence copper components of cytochrome c oxidase , CuA and CuB, are believed to be the photo-acceptors. - The excitation of the photo-acceptor molecule sets in motion cellular metabolism through cascades of reactions called cellular signalling or retrograde mitochondrial signalling. - At least two reactions are starting points for monitoring cellular- signalling reactions after light action on the cytochrome c oxidase molecule. - One of them is dissociation of NO from the catalytic center of cytochrome c oxidase. - Another signalling pathway starting from the mitochondria is connected with ATP .

This article summarizes the literature that investigated the cellular responses to laser irradiation. It highlights the importance of - Mitochondria and Cytochrome C - ATP

iEnovis

Pubmed

CONFIDENTIAL

Karu 1989 | Mitochondria, ATP

Back to overview

Karu T. Photobiology of low-power laser effects. Health Phys. 1989 May;56(5):691-704.

- Laser biostimulation is a photobiological phenomenon - Primary photo-acceptors are components of the respiratory chain. This explains the universality of low-power laser effects. - The respiratory chain components can be the photoacceptors in the case of cellular metabolism stimulation, as well as inhibition depending on the dose of light. At low doses, irradiation causes redox regulation of cellular metabiolism; at high doses photodynamic damage prevails. - Light quantum is only a trigger for cellular metabolism regulation. This explainsthe low doses and intensities needed. - The magnitude of the biostimulation effect depends on the physiological state of the cell before irradiation. This explains why biostimulation effect isnot always possible. - The therapeutic effects of low-power laser irradiation can be explained by an increase of proliferation of G 0 and G 1 cellsor by changes in the physiological activity of excitable cells.

This article discusses the biological processes of photobiomodulation. - Respiratory chain components are discussed as primary photo- acceptors. - The possible ways for photo-signal transduction and amplification are discussed. - It is proposed that enhanced wound healing due to irradiation with low- intensity visible laser light is due to increasing proliferation of cells.

Pubmed

iEnovis

CONFIDENTIAL

Ketz 2017 | Analgesia

Back to overview

Kobiela Ketz A, Byrnes KR, Grunberg NE, Kasper CE, Osborne L, Pryor B, Tosini NL, Wu X, Anders JJ. Characterization of Macrophage/Microglial Activation and Effect of Photobiomodulation in the Spared Nerve Injury Model of Neuropathic Pain. Pain Med. 2017 May 1;18(5):932-946.

Animal laboratorystudy -

Subjects : 33 Sprague-Dawley rats - Sham surgery (n=13) - SNI surgery (n=13) - SNI surgery + LiteCure PBM treatment (n=7) - PBM (980 nm) protocol :

- Affected hind paw: 1 W, 20 s, 41cm above skin, dose 20 J - Dorsal root ganglia: 4.5W, 19s, skin contact, dose 85.5 J - Spinal cord regions 1.5 W, 19s, skin contact, dose 28.5 J - Every other day from day 7-30 post-operatively.

Results : - Injured groups demonstrated mechanical hypersensitivity 1-30 days post- operatively. - Photobiomodulation-treated animals began to recover after two treatments; at day 26, mechanical sensitivity reached baseline. - Peripheral nerve injury caused region-specific macrophages/ microglia activation along spinothalamic and dorsal-columnmedial lemniscus pathways. - A pro-inflammatorymicroglial marker was expressed in the spinal cord of injured rats compared to photobiomodulation-treated and sham group. - Photobiomodulation-treated dorsal root ganglion macrophages expressed anti-inflammatory markers.

KEY MESSAGE: Photobiomodulation effectively reduced mechanical hypersensitivity, potentially through modulating macrophage/microglial activation to an anti-inflammatory phenotype

iEnovis

Pubmed

CONFIDENTIAL

Holanda 2017 | Analgesia

Back to overview

Holanda VM, Chavantes MC, Wu X, Anders JJ. The mechanistic basis for photobiomodulation therapy of neuropathic pain by near infrared laser light. Lasers Surg Med. 2017 Jul;49(5):516-524.

7 In vitro experiments showed decreased mitochondrial activity and formation of varicosities and undulations in neurites of DRG neurons which is a morphological indication of microtubule disruption of the pain afferents, slowing down transmission of pain signals. This specific mechanism helps explain how pain complaints can be reduced quickly after high power treatments in superficial tissues. • In vivo experiments showed significant reduction in sensitivity to heat, cold and mechanical stimulus post-laser treatment. Laboratory study . Methods: using in vivo and in vitro experimental models, this study determined the mechanistic basis of photobiomodulation therapy (PBMT) for the treatment of neuropathic pain using a high irradiance (≥ 270 mW/cm²). Specifically, neuroplastic mechanisms that take place at peripheral sensory nerves (A δ and C-fibers) when high irradiance is applied. Results : •

KEY MESSAGE: These in vitro and in vivo studies indicate that treatment with an irradiance at 270 mW/cm2 or higher at the level of the nerve can rapidly block pain transmission. A combination therapy is proposed to treat neuropathic pain with initial high irradiance/fluence rates for fast pain relief, followed by low irradiance/fluence rates for prolonged pain relief by altering chronic inflammation.

iEnovis

Pubmed

CONFIDENTIAL

Chow 2016 | Analgesia

Back to overview

Chow RT, Armati PJ. Photobiomodulation: Implications for Anesthesia and Pain Relief. Photomed Laser Surg. 2016 Dec;34(12):599-609.

Design & purpose : Review of electrophysiological studies in humans and animal models and cell culture studies to examine neural responses to PBM. Results : - Evidence shows that PBM can inhibit nerve function in vivo, in situ, ex vivo, and in culture. - Animal studies using noxious stimuli indicate nociceptor-specific inhibition with other studies providing direct evidence of local conduction block, leading to inhibited translation of pain centrally. - Evidence of PBM disrupted neuronal physiology affecting axonal flow, cytoskeleton organization, and decreased ATP is also presented. - PBM changes are reversible with no side effects or nerve damage.

KEY MESSAGE This review provides strong evidence in neuroscience identifying inhibition of neural function as a mechanism for the clinical application of PBM in pain and anesthesia.

iEnovis

Pubmed

CONFIDENTIAL

Chow 2011 | Analgesia

Back to overview

Chow R, Armati P, Laakso EL, Bjordal JM, Baxter GD. Inhibitory effects of laser irradiation on peripheral mammalian nerves and relevance to analgesic effects: a systematic review. Photomed Laser Surg. 2011 Jun;29(6):365-81.

Systematic review . • 44 studies were suitable for inclusion, 18 human and 26 animal studies.

Results : •

Chow et al. 2011 | Analgesia

In 13 of 18 human studies, pulsed or continuous wave visible and continuous wave infrared (IR) laser irradiation slowed conduction velocity (CV) and/or reduced the amplitude of compound action potentials (CAPs). • Human studies further support the hypothesis that inhibition of conduction velocity requires higher doses of laser irradiation. • In 26 animal experiments, IR laser irradiation suppressed electrically and noxiously evoked action potentials including pro-inflammatory mediators.

KEY MESSAGE: The evidence supports the view that neural inhibition is a plausible mechanism for the relief of acute and chronic pain with LLLT. Pubmed iEnovis

CONFIDENTIAL

Bomfim 2024 | Anti-inflammatory

Back to overview

Bomfim FRCD, Gomes BS, Lanza SZ, Esquisatto MAM, Lopes-Filho GJ. Photobiomodulation effects on synovial morphology, iNOS gene, and protein expression in a model of acute inflammation. Acta Cir Bras. 2024 Mar 15;39:e392024.

Laboratory animal study. Methods: 36 female Wistar rats were assigned into 3 groups: • Control (saline, no arthritis induction, n = 12), • Sham (arthritis induction, sham photobiomodulation, n = 12), • PBM (arthritis induction and photobiomodulation, n = 12). In the PBM group, a single dose of PBM was performed 24 h after induction with a laser device. In the sham and control group the device was turned off. Results • An increase in the thickness of the synovial lining epithelium and inflammatory infiltrate in sham compared to PBM was observed. • Gene expression analysis showed higher iNOS gene expression in PBM, while iNOS protein expression decreased in PBM compared to sham. • This suggests a secondary mitochondrial stimulation that can promote an increase of antioxidant enzyme balance or decrease of neutrophils migration that can be observed in morphological analyses with higher inflammatory infiltration without treatment.

KEY MESSAGE Photobiomodulation decreased inflammation in animals with induced arthritis, upregulated iNOS gene expression, however downregulated protein expression compared to sham.

Pubmed

iEnovis

CONFIDENTIAL

Back to overview

CONFIDENTIAL

Naterstad 2018 | Anti-inflammatory

Back to overview

Naterstad IF, Rossi RP, Marcos RL, Parizzoto NA, Frigo L, Joensen J, Lopes Martins PSL, Bjordal JM, Lopes-Martins RAB. Comparison of Photobiomodulation and Anti-Inflammatory Drugs on Tissue Repair on Collagenase-Induced Achilles Tendon Inflammation in Rats. Photomed Laser Surg. 2018 Mar;36(3):137-145.

Animal laboratory study . Methods : 205 Wistar rats were randomly divided into 5 groups: • Healthy control : were given a saline injection • Injury + no treatment • Injury + LLLT (3 J, 810 nm, 100 mW) • Injury + NSAID (diclofenac 1.1 mg/kg) • Injury + dexamethasone (0.02 mg/kg) Experimental groups received a collagenase injection (100 μg /tendon) in the peritendinous Achilles to induce tendinitis. Histological analyses included an assessment of the severity of inflammation, collagen fiber content, and collagen organization. Results : • Collagenase injection induced a severe inflammatory reaction with significant reduction in collagen content for 48 h, and disorientation of collagen fibers lasting between 14 and 21 days. • Diclofenac and dexamethasone reduced inflammatory signs during the first 2 days, although there was prolongation of the inflammatory phase and slower normalization of tendon quality, particularly in the dexamethasone group.

KEY MESSAGE: LLLT showed a significant superiority over commonly used anti-inflammatory pharmaceutical agents in acute collagenase-induced tendinitis for reducing early inflammatory markers, preventing hemorrhage and preserving tendon morphology.

Pubmed

iEnovis

• LLLT prevented hemorrhage, reduced inflammation severity, and preserved tendon morphology compared with the other groups.

CONFIDENTIAL

Pallotta 2012 | Anti-inflammatory

Back to overview

Pallotta RC, Bjordal JM, Frigo L, Leal Junior EC, Teixeira S, Marcos RL, Ramos L, Messias Fde M, Lopes-Martins RA. Infrared (810-nm) low-level laser therapy on rat experimental knee inflammation. Lasers Med Sci. 2012 Jan;27(1):71-8.

- Design : animal laboratory study (30 Whistar rats) - Methods : knee joint inflammation was induced with - Results : - Significant reduction of the number of leucocytes and neutrophils in the joint cavity - Significant reduction of pro-inflammatory mediators (IL-1, IL-6) implicated in cartilage degeneration

KEY MESSAGE: The results suggest that laser radiation could be acting to modulate the inflammatory process and possibly to stimulate the production of anti-inflammatory mediators.

Pubmed

iEnovis

Fig. 1 Analysis of articular wash 3 and 6 h after induced inflammation. a Total number of leukocytes in articular lavage fluid after 3 h in the control group and after LLLT (n=6 animals per group (*p<0.05) (**p<0.001). b Total number of leukocytes in articular lavage fluid after 6 h in the control group and after LLLT (n=6 animals per group arthritis group (AT); the arthritis group treated with diclofenac (Diclof); the arthritis group treated with 1 J LLLT (AT+ 1 J); the arthritis group treated with 3 J LLLT (AT+3 J); the arthritis group treated with 6 J LLLT (AT+6 J); the arthritis group treated with 10 J LLLT (AT+10 J). Results are expressed as mean (±SEM)

CONFIDENTIAL

Bjordal 2010 | Anti-inflammatory

Back to overview

Bjordal JM, Lopes-Martins RA, Joensen J, Iversen VV. The anti-inflammatory mechanism of low level laser therapy and its relevance for clinical use in physiotherapy. Physical Therapy Reviews 2010;15(4):286-293.

Systematic review Studies : 11 cell studies and 27 animals studies met all inclusion criteria, and another 6 animal studies met the inclusion criteria for drug comparisons and LLLT interactions. Results : - There is strong evidence of an anti-inflammatory effect from LLLT, which is consistent across all 12 tested laboratory models and phases of inflammation and wavelengths between 633 and 904 nm. - The magnitude of the anti-inflammatory effect is not significantly different from that of non-steroidal anti- inflammatory drugs (NSAIDs), but it is slightly less than glucocorticoid steroids. - There is moderate evidence that concomitant use of glucocorticoid steroid has a negative effect on LLLT mechanisms and should be avoided.

KEY MESSAGE: There is strong evidence that red and infrared LLLT has a dose-dependent anti-inflammatory effect in animals, and scant evidence that the anti-inflammatory effect also occurs after LLLT in humans. The magnitude of the effect is not significantly different from NSAIDs

iEnovis

Journal link

CONFIDENTIAL

Gao 2009 | Tissue repair

Back to overview

Gao X, Xing D. Molecular mechanisms of cell proliferation induced by low power laser irradiation. J Biomed Sci. 2009; 16(1): 4.

This study discusses the discovered mitochondrial photoacceptors and nonmitochondrial photoacceptors, and then reviews the studies on the molecular mechanisms of LPLI-induced proliferation since January 1999, which will serve as a reference for the researchers in this field - A number of signalling proteinsare involved with laser-induced cell proliferation. - Laser irradiation can regulate cell cycle progression by by the activation or elevated expressions of cell cycle-specific proteins. - Laser irradiation reduces signal molecules involved in inflammatory response and enhances immunomodulatory effects. - Laser irradiation induces expression and secretion of growth factors, interleukins, inflammatory cytokines and small molecules (such as ATP, ROS, intracellular Ca 2+ ).

Molecular mechanisms of LPLI induced cell proliferation involve a number of signalling proteins, cell cycle-specific proteins and other molecules such as growth factors, interleukins, inflammatory cytokines and other small molecules.

iEnovis

Pubmed

CONFIDENTIAL

Chen 2009 | Tissue repair

Back to overview

Chen CH, Tsai JL, Wang YH, Lee CL, Chen JK, Huang MH. Low-level laser irradiation promotes cell proliferation and mRNA expression of type I collagen and decorin in porcine Achilles tendon fibroblasts in vitro. J Orthop Res. 2009 May;27(5):646-50.

Laboratory study Methods : 4 groups of identically cultured fibroblasts were exposed to LLLI and harvested after 24 h. • Group 1 (control group) received no LLLI.

• Group 2 received 1 J/cm2 LLLI • Group 3 received 2 J/cm2 LLLI • Group 4 received 3 J/cm2 LLLI Results :

• When compared to the control group, the cell proliferation of irradiated AT fibroblasts in the other 3 groups increased significantly by 13% (Group 2), 30% (Group 3), and 12% (Group 4) respectively. • The mRNA expressions of decorin and type I collagen in fibroblasts with LLLI were significantly higher than in the control condition (p < 0.05).

Low level laser irradiation promotes cell proliferation and production of mRNA for type I collagen and decorin synthesis.

iEnovis

Pubmed

CONFIDENTIAL

Terena 2018 | Tissue Repair

Back to overview

Terena SML, Fernandes KPS, Bussadori SK, Brugnera Junior A, de Fátima Teixeira da Silva D, Magalhães EMR, Ferrari RAM. Infrared Laser Improves Collagen Organization in Muscle and Tendon Tissue During the Process of Compensatory Overload. Photomed Laser Surg. 2018 Mar;36(3):130-136.

Animal laboratory study. Methods : 22 Wistar rats were submitted to bilateral partial removal of the synergists - gastrocnemius and soleus - of the plantar muscle, thereby overloading the plantar muscle, and divided in 3 groups: • Control (no hypertrophy, no LLLT) • Hypertrophy program without LLLT • Hypertrophy program + LLLT : 780 nm, 40 mW, 9.6 J/cm2 and 10 s/point, 8 points, total energy 3.2 J, daily

Results : Infrared laser irradiation induces an improvement in collagen organization in tendons, increased space between the muscle fascicles and a reduction in the total area of collagen in muscles during compensatory atrophy following the ablation of synergist muscles, all of which are beneficial to tissue adaptation.

KEY MESSAGE: Better collagen fiber deposition and organization in both muscle and tendon tissue with LLLT during compensatory hypertrophy reflects the better quality in the muscle hypertrophy process that contributes significantly to this tissue in terms of functional performance and protection against recurrence of injury.

iEnovis

Pubmed

CONFIDENTIAL

Alves 2014 | Muscle repair

Back to overview

Alves AN, Fernandes KP, Deana AM, Bussadori SK, Mesquita-Ferrari RA. Effects of low-level laser therapy on skeletal muscle repair: a systematic review. Am J Phys Med Rehabil. 2014 Dec;93(12):1073-85.

Systematic review of 17 studies on the use of LLLT for the repair of skeletal muscle in any animal model. Results : • LLLT has been shown to be an extremely efficient therapeutic resource for the modulation of the inflammatory process and the attenuation of oxidative damage after muscle injury. • LLLT has shown promise in modulating MRFs (myogenic regulatory factors). • LLLT has been shown to be effective in modulating the formation of fibrotic tissue during the repair of injured muscle tissue. It has been shown to be effective in reducing the gene expression of TGF- β which plays a key role in the initiation of fibrotic cascades and the differentiation of satellite cells into myofibroblasts in injured muscle. • LLLT is extremely effective in modulating the expression of VEGF mRNA and the consequent formation of new blood vessels during the repair of injured skeletal muscle.

The main effects of LLLT in muscle injuries were a reduction in the inflammatory process, the modulation of growth factors and myogenic regulatory factors, remodelling of extracellular matrix, and increased angiogenesis.

iEnovis

Pubmed

CONFIDENTIAL

Luo 2013 | Muscle repair

Back to overview

Luo L, Sun Z, Zhang L, Li X, Dong Y, Liu TC. Effects of low-level laser therapy on ROS homeostasis and expression of IGF-1 and TGF- β1 in skeletal muscle during the repair process. Lasers Med Sci. 2013 May;28(3):725-34.

Animal laboratory study Methods : Adult male Sprague-Dawley rats (n=96) were randomly divided into three groups: control group (no lesion, untreated, n=6), contusion group (n=48), and contusion-plus-LLLT group (n=42). Muscle remodelling was evaluated at 0 h and 1, 2, 3, 7, 14, 21, and 28 days after injury. Results : • LLLT markedly promoted the regeneration of muscle and reduced scar formation. • LLLT also significantly enhanced muscle SOD (muscle superoxide dismutase) activity and significantly decreased muscle MDA (malondialdehyde) levels 1, 2, and 3 days after injury. • LLLT increased the expression of IGF-1 2, 3, and 7 days after injury and decreased the expression of IGF-1 21 and 28 days after injury. • LLLT decreased the expression of TGF- β1 3 and 28 days after injury but increased expression at 7 and 14 days after injury.

This study showed that LLLT could modulate the homeostasis of ROS (reactive oxygen species) and of the growth factors IGF-1 and TGF- β 1, which are known to play important roles in the repair process. This may constitute a new preventive approach to muscular fibrosis.

iEnovis

Pubmed

CONFIDENTIAL

Torricelli et al. 2001 | Cartilage repair

Back to overview

Torricelli P, Giavaresi G, Fini M, Guzzardella GA, Morrone G, Carpi A, Giardino R. Laser biostimulation of cartilage: in vitro evaluation. Biomed Pharmacother. 2001 Mar;55(2):117-20.

In vitro study . Methods : Chondrocyte cultures were derived from rabbit and human cartilage. • These cells were exposed to laser treatment for 5 days, using the following parameters: 300 joules, 1 watt, 100 (treatment A) or 300 (treatment B) hertz, pulsating emission for 10 minutes, under a sterile laminar flow. • Control cultures (no treatment) received the same treatment with the laser device off. Outcome : Cell viability was measured by MTT assay at the end of the laser treatment and then after 5 days. Results: • Neither rabbit nor human cultured chondrocytes showed any damage under a light microscope and immunostaining control following laser treatment. • The MTT test results indicated a positive biostimulation effect on cell proliferation with respect to the control group. • The increase in viability of irradiated chondrocytes was maintained for five days following the end of the laser treatment.

Laser irradiation had a positive biostimulation effect on chondrocyte cell proliferation which was maintained for five days following the laser treatment.

iEnovis

Pubmed

CONFIDENTIAL

Morrone 2000 | Cartilage repair

Back to overview

Morrone G, Guzzardella GA, Tigani D, Torricelli P, Fini M, Giardino R. Biostimulation of human chondrocytes with Ga-Al-As diode laser: 'in vitro' research. Artif Cells Blood Substit Immobil Biotechnol. 2000 Mar;28(2):193-201.

In vitro study . Methods : The cartilage sample used for the biostimulation treatment was taken from the right knee of a 19-year-old patient. After the chondrocytes were isolated and suspended for cultivation, the cultures were incubated for 10 days. The cultures were divided into four groups. • Groups I, II, III were subject to biostimulation with the following laser parameters: 300 J, 1 W, 100 Hz, 10 min. exposure, pulsating emission; 300 J, 1 W, 300 Hz, 10 min. exposure, pulsating emission; and 300 J, 1 W, 500 Hz, 10 min. exposure, pulsating emission, respectively. • Group IV did not receive any treatment. The laser biostimulation was conducted for five consecutive days. Outcomes : At the end of the treatment, the Calcium, Alkaline Phosphate, MTT tests and proteoglycan were performed to assess cell metabolism and toxicity level. Results The data showed good results in terms of cell viability and levels of Ca and Alkaline Phosphate in the groups treated with laser biostimulation compared to the untreated group.

Laser irradiation provides biostimulation to chondrocytes without cell damage

iEnovis

Pubmed

CONFIDENTIAL

Clinical Evidence

CLINICAL STUDIES with LiteCure/LightForce

SYSTEMATIC REVIEWS

Arroyo-Fernández 2023

General

Alayat, 2022

Neck Pain

Xie 2023

De la Barra Ortiz, 2024

Frozen shoulder

De la Barra Ortiz, 2023

Karlekar, 2015

Postop pain sternotomy

Fibromyalgia

Panton, 2013

Low Back Pain

Abdildin 2023

Epicondylitis

Roberts, 2013

Qceps Muscle Recovery

Borsa, 2019

Verma, 2022

Hamstring Tendinopathy

Ahmad, 2022

Cai, 2023

Song 2020

Knee OA

Tumilty, 2016

Achilles Tendinopathy

Diabetic Neuropathy

Chatterjee, 2020

Ketz, 2024

Plantar Fasciitis

Important notice, please read

Notice:

Please note that:

• Publications with Litecure/LightForce devices may be on a previous model that may not be available in the EU. • The results/ findings/ indications evaluated in the studies are not necessarily applicable or included in the intended use of the Chattanooga devices available in the EU and off-label use is discouraged.

CONFIDENTIAL

Arroyo-Fernández 2023 | General MSD

Back to overview

Arroyo-Fernández R, Aceituno-Gómez J, Serrano-Muñoz D, Avendaño-Coy J. High-Intensity Laser Therapy for Musculoskeletal Disorders: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Clin Med. 2023 Feb 13;12(4):1479.

Systematic review with Meta-analysis. • In total, 48 RCTs (total of 3107 participants) were included in the qualitative synthesis and 44 RCTs in the quantitative meta-analysis The main outcome measures were pain (VAS) and functionality. Secondary outcomes were range of motion (ROM), muscle strength, and quality of life of participants, as well as the safety of the treatment. Results • HILT showed a decrease on the pain VAS (mean difference (MD) = -1.3 cm) and an improvement in functionality (standardized mean difference (SMD) = -1.0), with low and moderate quality of evidence, respectively. • Best results for functionality improvement were obtained for knee and shoulder, and with dosages between 10 - 50 mJ/cm². • HILT was also effective for improving ROM and QoL, but not for muscle strength improvement. • HILT could be considered a safe technique due to the absence of adverse effects reported by the authors and the similar number of abandonments in the experimental and control groups. • An important limitation of this review is the large heterogeneity in the results of the assessed variables, which lowered the certainty of evidence.

KEY MESSAGE HILT is an effective treatment for improving pain, functionality, range of motion, and quality of life in people with MSD without side effects, although these findings must be treated with caution due to the high risk of bias in the studies.

iEnovis

Pubmed

CONFIDENTIAL

De la Barra Ortiz 2024| Neck pain

Back to overview

de la Barra Ortiz HA, Arias M, Liebano RE. A systematic review and meta-analysis of randomized controlled trials on the effectiveness of high-intensity laser therapy in the management of neck pain. Lasers Med Sci. 2024 May 6;39(1):124.

Systematic review and meta-analysis including 20 RCTs. Results

• A statistically significant difference was found for pain at rest (MD=-14.05 mm) and during movement (MD = -16.4 mm), and this advantage was sustained at the three-month follow-up (MD = -12.17 mm). • A statistical significance in favor of HILT was found for movements of extension, right and left side bending, and right and left rotation, with a pooled effect in terms of MDs of 3.93°, 2.63°, 3.19°, 3.47°, and 2.73° respectively. • A statistically significant difference of -8.3% was found in favor of HILT for disability . • Only the results for pain intensity are in line with the minimal clinically important differences (MCID) reported in the literature. • Subgroup analysis showed that the most favorable results are obtained when HILT is employed to address myofascial pain, cervical radiculopathy and chronic neck pain.

KEY MESSAGE HILT has a positive effect on reducing pain and disability in a variety of neck disorders.

iEnovis

PubMed

Figures

CONFIDENTIAL

Back to overview

Pain intensity at rest post-treatment

Pain intensityat during movement post-treatment

Pain intensity at 3m follow-up

CONFIDENTIAL

Xie 2023 | Neck pain

Back to overview

Xie YH, Liao MX, Lam FMH, Gu YM, Hewith A Fernando WC, Liao LR, Pang MYC. The effectiveness of high-intensity laser therapy in individuals with neck pain: a systematic review and meta-analysis. Physiotherapy. 2023 Dec;121:23-36.

Systematic review and meta-analysis including 8 RCTs (total 603 subjects) with moderate to high PEDRO scores for methodological quality. The included RCTs recruited participants diagnosed with cervical spondylosis, cervical disc herniation, chronic neck pain, cervical radicular syndrome, myofascial pain syndrome of the trapezius or cervical myofascial pain syndrome. The duration of treatment ranged from 2 to 6 weeks. Results • Compared with placebo, HILT was effective in improving pain intensity (moderate quality evidence), cervical flexion ( moderate quality evidence), extension (moderate quality evidence), right lateral flexion (low-quality evidence) ROM . • There was a trend of better outcome in functional activity after HILT (low quality evidence).

KEY MESSAGE HILT studies show moderate level evidence to support its use for treating neck pain to improve pain intensity and cervical range of movement.

iEnovis

PubMed

Figures

CONFIDENTIAL

Back to overview

CONFIDENTIAL

Alayat 2022 | Myofascial Pain Syndrome

Back to overview

Alayat MSM, Battecha KH, Elsodany AM, Alzahrani OA, Alqurashi AKA, Jawa AT, Alharthi YS. Effectiveness of Photobiomodulation Therapy in the Treatment of Myofascial Pain Syndrome of the Upper Trapezius Muscle: A Systematic Review and Meta-Analysis. Photobiomodul Photomed Laser Surg. 2022 Oct;40(10):661-674.

Systematic review with meta-analysis Methods: 17 studies included in the review • 16 includedin the meta-analysis • 3 HILT studies • 12 high quality studies (PEDRO)

• 8 studies (441 patients) compared ‘PBMT alone ’ with control treatment (placebo /medication /other PT / manual therapy). • 7 studies (421 patients) compared ‘PBMT + Exercise ’ with control treatment. Results: • PBMT and PBMT+Ex were significantly more effective than control or comparator groups post-treatment and at follow-up for pain reduction and increase of PPT (pain pressure threshold)

KEY MESSAGE: PBMT is an effective treatment modality for myofascial pain syndrome with significant effects compared to controls.

• PBMT: medium effect size • PBMT+Ex: large effect size

iEnovis

PubMed

CONFIDENTIAL

De la Barra Ortiz 2021 | Frozen shoulder

Back to overview

de la Barra Ortiz HA, Parizotto N, Arias M, Liebano R. Effectiveness of high-intensity laser therapy in the treatment of patients with frozen shoulder: a systematic review and meta-analysis. Lasers Med Sci. 2023 Nov 20;38(1):266.

Systematic review and meta-analysis including 5 RCTs comparing HILT with other physical therapy interventions in patients with frozen shoulders, with or without sham HILT. - Outcomes: Pain (VAS), houlder pain and disability index (SPADI), ROM - Results - Statistically and clinically significant effect in favour of HILT compared to conventional PT on pain (MD = - 2.23 cm) and SPADI (MD = - 10.1%) at the end of treatment. - At 3m follow-up results were still in favour of HILT, but the difference was not statistically significant anymore. - No significant difference between groups for shoulder ROM.

KEY MESSAGE: Improvements in pain and disability were significantly greater - both clinically and statistically - with HILT compared to other PT interventions and sham treatment.

iEnovis

Pubmed

Figures

CONFIDENTIAL

Back to overview

CONFIDENTIAL

Panton2013 | Fibromyalgia

Back to overview

Panton L, Simonavice E, Williams K, Mojock C, Kim JS, Kingsley JD, McMillan V, Mathis R. Effects of Class IV laser therapy on fibromyalgia impact and function in women with fibromyalgia. J Altern Complement Med. 2013 May;19(5):445-52.

Double-blind randomised placebo controlled trial - Subjects : 38 women with fibromyalgia - Laser heat therapy: HILT + warm air (n=20) - Placebo: warm air only (n=18) - Device : Litecure LCT-1000 - HILT Protocol : - 10.63 J/cm² , total dose per session 4200J

- Grid scanning technique over 7 tender points located across the neck, shoulders and back - 2 sessions/week for 4 weeks (total 8 sessions) Results : - Pain decreased with 12.7% in the HILT group (signif.) versus 5.1% in the control group (not signif.) - Fibromyalgia Impact score improved with 9.5% in the HILT group (signif.) versus no change in the control group. - Function scores improved with 19.5% in the HILT group (signif.) versus 8.2% in the control group (signif.) - Upper body flexibility improved with 9.9% in the HILT group (signif.) versus no change in the control group.

KEY MESSAGE: HILT may be a beneficial modality for women with fibromyalgia. It produced significantly greater improvements in pain and upper- body flexibility than placebo treatment, ultimately reducing the impact of fibromyalgia.

iEnovis

Pubmed

CONFIDENTIAL

Karlekar 2015 | Postop Sternotomy Pain

Back to overview

Karlekar A, Bharati S, Saxena R, Mehta K. Assessment of feasibility and efficacy of Class IV laser therapy for postoperative pain relief in off-pump coronary artery bypass surgery patients: A pilot study. Ann Card Anaesth. 2015 Jul-Sep;18(3):317-22.

Observational study Methods : 100 sternotomy patients received one or two sessions of high power laser treatment in addition to the standard institutional pain management protocol. • LiteCure LCT-1000 • ED 10J/cm², total dose 1500 J Results : • Mean VRS (Verbal Rating Scale) Pain score decreased significantly 1h and 24h after one laser treatment on postop day 1. • A second laser treatment on the next day produced complete resolution of pain.

KEY MESSAGE: High Power Laser therapy provides significant additional pain relief when included in a multimodal analgesic treatment protocol.

iEnovis

PubMed

Figure

CONFIDENTIAL

Back to overview

CONFIDENTIAL

Abdildin 2023 | Low Back pain

Back to overview

Abdildin Y, Tapinova K, Jyeniskhan N, Viderman D. High-intensity laser therapy in low back pain management: a systematic review with meta-analysis. Lasers Med Sci. 2023 Jul 26;38(1):166.

Systematic Review and Meta-Analysis including 3 RCTs (200 patients) comparing HILT with sham therapy or LLLT. • Two of the three studies were graded as having a high risk of bias due to their single-blinded nature. • The methodological quality of the studies was graded as acceptable (3 out of 5) on the Oxford quality assessment system (JADAD scale). • Using GRADE approach, the certainty of outcomes Pain intensity and the Roland disability index were assessed as having high certainty, while the Oswestry disability index was evaluated as having moderate certainty. Results The results significantly favor the HILT group over the control group in terms of: • Pain intensity. Certainty of evidence: High. • Oswestry disability. Certainty of evidence: Moderate. • Roland disability index. Certainty of evidence: High. The studies also showed improved flexibility compared to controls at 12 weeks.

KEY MESSAGE High-intensity laser therapy may decrease pain scores and disability in chronic low back pain patients, as well as improve flexibility at 12 weeks after treatment.

iEnovis

Pubmed

Figures

CONFIDENTIAL

Back to overview

CONFIDENTIAL

Roberts et al. 2013 | Epicondylitis

Back to overview

Roberts DB, Kruse RJ, Stoll SF. The effectiveness of therapeutic class IV (10 W) laser treatment for epicondylitis. Lasers Surg Med. 2013 Jul;45(5):311-7.

Randomized placebo-controlled double-blinded clinical trial. - Subjects : 16 patients with epicondylitis - Group 1: HILT - Group 2: Placebo laser - Device : LiteCure 10W HPL device - HILT Protocol : - 6.6 J/cm², total dose per session 3000 J - 8 sessions over 18 days Results: HILT group improvements at 3, 6, and 12 months respectively : • Handgrip strength: 17%, 52%, and 66% • Function: 44%, 71%, and 82% • Pain with resistance to extension of the middle finger was reduced by 50%, 93%, and 100% In contrast, NO CHANGES WERE SEEN UNTIL 12 MONTHS FOLLOWING SHAM TREATMENT. No adverse effects were reported at any time.

KEY MESSAGE: Faster reductions in pain and return of strength and function in the HP laser treatment group than in the sham group, with improvement continuing up to 1 year post-treatment.

Figures

Pubmed

iEnovis

CONFIDENTIAL

Back to overview

CONFIDENTIAL

Verma 2022 |Hamstring Tendinopathy

Back to overview

Verma S, Esht V, Chahal A, Kapoor G, Sharma S, Alghadir AH, Khan M, Kashoo FZ, Shaphe MA. Effectiveness of High Power Laser Therapy on Pain and Isokinetic Peak Torque in Athletes with Proximal Hamstring Tendinopathy: A Randomized Trial. Biomed Res Int. 2022 May 20;2022:4133883.

- Design : Randomized comparative study. - Subjects : 36 athletes with proximal hamstring tendinopathy

- Experimental group received HILT as monotherapy. - 50J/cm² - total energy per session was 1800 J. - Conventional group received conventional PT. - US, moist heat pack, home exercises - Both groups were treated 3 days / week for 3 weeks - Device : Litecure LCT-1000 (810/980 nm) - Results - Significant decrease of pain (by 61%) and increase of hamstring isokin. strength (by 13%) in HILT group - In conventional group, only pain decreased significantly (by 41%) while strength increase was only 1.5% and n.s. - Difference in pain decrease between groups (61% vs. 41%) was significant: significantly greater pain relief with HILT.

KEY MESSAGE: HPLT was effective for significantly improving pain and increasing hamstring muscle strength in athletes with PHT. Pain relief was significantly greater than with conventional PT.

iEnovis

Pubmed

CONFIDENTIAL

Back to overview

Isokin Peak Torque (Nm)

NPRS Pain (points)

+13%

300

250

200

-41%

150

-61%

100

HILT

Conv

HILT

Conv

PRE POST

CONFIDENTIAL

Borsa 2019 |Muscle Recovery

Back to overview

Borsa PA, Dale RB, Levine D and Crow JA. Muscular Preconditioning using Phototherapy Improves the Physical Work Capacity of the Quadriceps when applied between Repeated bouts of resistance Exercise. J Athl Enhanc 2019, Vol: 8 Issue: 1

Triple-blind, repeated measures, placebo controlled, cross-over study - Subjects : 20 healthy individuals, 2 conditions - HILT during recovery - Sham-laser during recovery - Procedure: - Subjects performed quadriceps fatiguing protocol consisting of 4 high intensity exercise bouts - HILT or sham laser was applied during the recovery in between exercise bouts

- HILT Device : LiteCure LT-1000 810/980 nm HPL device - HILT protocol: 10 J/cm²; total dose per session 1600-2400 J - Result

KEY MESSAGE: HILT appears to reduce Quadriceps muscle fatigue for athletes requiring high levels of endurance. Preconditioning skeletal muscle with phototherapy intermittently during recovery intervals may be a beneficial, non-invasive and safe ergogenic aid for athletes that require high levels of muscular endurance.

- HILT group was able to produce higher quadriceps torque and showed less decline of muscle performance throughout the bouts.

Figures

iEnovis

Journal link

CONFIDENTIAL

Back to overview

CONFIDENTIAL

Cai 2023 | Knee OA

Back to overview

Cai P, Wei X, Wang W, Cai C, Li H. High-intensity laser therapy on pain relief in symptomatic knee osteoarthritis: A systematic review and meta-analysis. J Back Musculoskelet Rehabil. 2023;36(5):1011-1021.

Systematic review and meta-analysis. 9 RCTs investigating the effectiveness of HILT compared to other laser therapies, conventional therapies or exercises on knee OA pain were included. 7 studies had good to excellent methodological quality. Results All studies reported positive effects of High-Intensity Laser therapy on knee osteoarthritis pain. • 2 studies (136 people) showed HILT was more effective for pain relief than sham laser therapy in a short-term treatment (MD, -2.04, 95% CI, -2.12 to -1.96; Z= 51.01, P< 0.01). • 4 studies (160 people) showed that HILT was more effective for decreasing VAS score than conventional physiotherapies (MD, -0.98, 95% CI, -1.19 to -0.76; Z= 9.02, P< 0.01).

KEY MESSAGE High-Intensity Laser therapy could be a promising and recommended modality in alleviating knee osteoarthritis pain, especially when it was implemented in combination with exercises.

• 3 studies (123 people) demonstrated that HILT combined with exercises was more effective than placebo laser or lower-intensity laser combined with exercises in alleviating pain in patients with knee osteoarthritis (MD, -1.54, 95% CI, -1.84 to -1.24; Z= 10.06, P< 0.01).

Figures

Pubmed

iEnovis

CONFIDENTIAL

Back to overview

CONFIDENTIAL

Ahmad 2022 | Knee OA

Back to overview

Ahmad MA, A Hamid MS, Yusof A. Effects of low-level and high-intensity laser therapy as adjunctive to rehabilitation exercise on pain, stiffness and function in knee osteoarthritis: a systematic review and meta-analysis. Physiotherapy. 2022 Mar;114:85-95.

Systematic review and Meta-analysis including10 studieswith high PEDRO score for methodological quality. • 6 investigated LLLT + Exercise, • 3 on HILT + Exercise, and • 1 evaluated both. Results Based on the meta-analysis of the scores on the VAS and WOMAC subscales: • HILT + E combination demonstrated larger effects compared to control for knee pain, stiffness and function scores. • LLLT + E combination showed small effects for knee pain and function. • Comparatively, HILT + E showed a change of 2.06 points for VAS, which is clinically significant, whereas LLLT + E only achieved a change of 0.67 points for the same measures.

KEY MESSAGE: Photobiomodulation therapy, compared to control, is an effective adjunct treatment modality for improving pain, stiffness and function in knee OA, with HILT producing larger effects than LLLT.

Pubmed

iEnovis

Figures

CONFIDENTIAL

Back to overview

CONFIDENTIAL

Song 2020 | Knee OA

Back to overview

Song HJ, Seo HJ, Kim D. Effectiveness of high-intensity laser therapy in the management of patients with knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials. J Back Musculoskelet Rehabil. 2020;33(6):875-884.

Systematic review and Meta-analysis Results : • 6 randomized controlled trials (RCTs) were included in this meta-analysis. • For VAS pain , 334 patients from 4 studies showed that HILT significantly decreased pain compared to the control (MD, -1.18; 95% CI, -1.68 to -0.69). • For stiffness , 168 patients from 4 studies showed that HILT significantly improved WOMAC stiffness compared to the control (SMD -1.00; 95% CI -1.32, -0.68) • For function , 87 patients from 4 studies showed that HILT significantly improved function compared to the control(SMD, -5.36; 95% CI -7.39 to -3.34).

KEY MESSAGE: HILT can significantly improve pain, stiffness and function in Knee Osteoarthritis compared to placebo or other control interventions.

Figures

iEnovis

Pubmed

CONFIDENTIAL

Back to overview

CONFIDENTIAL

Tumilty 2016 | Achilles Tendinopathy

Back to overview

Tumilty S, Mani R, Baxter GD. Photobiomodulation and eccentric exercise for Achilles tendinopathy: a randomized controlled trial. Lasers Med Sci. 2016 Jan;31(1):127-35.

Double-blind randomised controlled trial Methods : 80 subjects were randomly assignedto • Group 1: Placebo laser + Ex Regime 1 • Group 2: Laser + Ex Regime 1 • Group 3: Placebo laser + Ex Regime 2 • Group 4: Laser + Ex Regime 2 Protocols: • Laser: ED 6.66J/cm², total dose: 450J per session, 2X/week for 4 weeks • LightForce EX device • Exercise Regime 1: 14 sessions/week (2x/day) • Exercise Regime 2: 2 sessions/week (2x/week) Results : • Significantly greater improvement of VISA-A score at 12 weeks in Group 4 compared to other groups. • Clinical relevance: • Twice-daily exercise sessions are not necessary as equivalent results can be obtained with two exercise sessions per week. • The addition of photobiomodulation as adjunct to exercise can bring added benefit.

KEY MESSAGE: In this study the best results were obtained with a combined protocol of twice a week eccentric exercise plus high power photobiomodulation therapy.

iEnovis

Pubmed

CONFIDENTIAL

Chatterjee 2019 | Diabetic Neuropathy

Back to overview

Chatterjee P, Srivastava AK, Kumar DA, Chakrawarty A, Khan MA, Ambashtha AK, Kumar V, De Taboada L, Dey AB. Effect of deep tissue laser therapy treatment on peripheral neuropathic pain in older adults with type 2 diabetes: a pilot randomized clinical trial. BMC Geriatr. 2019 Aug 12;19(1):218.

Randomized double-blind sham-controlled trial. - Subjects : 40 patients with type 2 diabetes with painful diabetic peripheral neuropathy - HILT group: HILT + standard care - Control group: sham laser + standard care - 2x/wk for 4 weeks + 1x/wk for 8 weeks (12 weeks in total) - Device : LightForce HPL device (810/980 nm) - HILT protocol: - Treatment area: plantar foot and lumbar region (DRG L4-S2) - Power: plantar 2W; lumbar 8W - Energy density: plantar 1.8-3.0 J/cm²; lumbar 13 J/cm² - Total dose: plantar 300-1800 J; lumbar 1920 J - Application technique: on contact scanning technique - Results - Signif. more pain relief in HILT group - Greater improvements of function HILT group - Signif. improvement of QoL in HILT group vs. no improvement in control group - Serum levels of inflammatory biomarkers improved more in the HILT group

KEY MESSAGE: HILT is a safe, nonpharmacological addition to the standard of care for the management of pain in older adults with painful diabetic peripheral neuropathy, offering significant improvement of their quality of life.

Figures

iEnovis

Pubmed

CONFIDENTIAL

Page 1 Page 2 Page 3 Page 4 Page 5 Page 6 Page 7 Page 8 Page 9 Page 10 Page 11 Page 12 Page 13 Page 14 Page 15 Page 16 Page 17 Page 18 Page 19 Page 20 Page 21 Page 22 Page 23 Page 24 Page 25 Page 26 Page 27 Page 28 Page 29 Page 30 Page 31 Page 32 Page 33 Page 34 Page 35 Page 36 Page 37 Page 38 Page 39 Page 40 Page 41 Page 42 Page 43 Page 44 Page 45 Page 46 Page 47 Page 48 Page 49 Page 50 Page 51 Page 52 Page 53 Page 54

Made with FlippingBook - PDF hosting