Low-Level Laser Therapy - CAM 20156HB

Description:
Low-level laser therapy (LLLT), also called photobiomodulation, is being evaluated to treat various conditions, including, among others, oral mucositis, myofascial pain, joint pain, lymphedema, and chronic wounds.

Oral Mucositis
For individuals who have increased risk of oral mucositis due to some cancer treatments (e.g., chemotherapy, radiotherapy) and/or hematopoietic cell transplantation who receive LLLT, the evidence includes randomized controlled trials (RCTs) and systematic reviews. Relevant outcomes are symptoms, morbid events, quality of life, and treatment-related morbidity. A 2014 systematic review included 18 RCTs and found better outcomes with LLLT used to prevent oral mucositis than with control treatments. RCTs published after the systematic review had similar findings.

Musculoskeletal and Neurologic Disorders
For individuals who have carpal tunnel syndrome who receive LLLT, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Both a 2016 systematic review and a TEC Assessment (2010) did not find sufficient evidence from RCTs that LLLT improves outcomes. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have neck pain who receive LLLT, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. A 2013 systematic review identified 17 trials, most of which were considered low quality. Only 2 trials were considered moderate quality, and they found that LLLT led to better outcomes than placebo for chronic neck pain. A TEC Assessment (2010) found conflicting evidence. Additionally, laser types, application dosages, and treatment schedules vary in the available evidence and require further study. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have subacromial impingement syndrome who receive LLLT, the evidence includes RCTs. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Most trials did not show a significant benefit of LLLT compared with sham treatment or with an alternative intervention (e.g., exercise). The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have adhesive capsulitis who receive LLLT, the evidence includes RCTs and a systematic review. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. A Cochrane review evaluating treatments for adhesive capsulitis identified 2 RCTs assessing LLLT. Due to the small number of trials and study limitations, reviewers concluded that the evidence was insufficient to permit conclusions about the effectiveness of LLLT for adhesive capsulitis. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have temporomandibular joint pain who receive LLLT, the evidence includes RCTs and several systematic reviews. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Meta-analyses of RCTs had mixed findings. A 2015 meta-analysis, which included 14 placebo-controlled randomized trials, did not find a statistically significant impact of LLLT on pain, but did find that LLLT significantly improved functional outcomes (e.g., mouth opening). RCTs have not compared the impact of LLLT with physical therapy. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have low back pain who receive LLLT, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Meta-analyses of RCTs found that LLLT resulted in a significantly greater reduction in pain scores and global assessment scores than a placebo control in the immediate post-treatment setting. Meta-analyses also found that other outcomes (e.g., disability index, range of motion) were significantly better immediately after treatment with active rather than placebo LLLT, but not at longer term follow-up. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have osteoarthritic knee pain who receive LLLT, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. A 2015 systematic review, which pooled study findings, did not find that LLLT significantly reduced pain or improved function outcomes compared with a sham intervention. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have heel pain (i.e., Achilles tendinopathy, plantar fasciitis) who receive LLLT, the evidence includes RCTs. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Findings of 2 sham-controlled randomized trials were inconsistent, and while an RCT compared LLLT with standard care lacked long-term follow-up. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have rheumatoid arthritis who receive LLLT, the evidence includes RCTs and a systematic review. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. A systematic review of RCTs found inconsistent benefit of LLLT for a range of outcomes. A 2010 RCT, published after the systematic review, did not find that LLLT was significantly better than a placebo treatment on most outcomes. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have Bell palsy who receive LLLT, the evidence includes 2 RCTs. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. The RCT found significant short-term benefit of LLLT over exercise. Longer term outcomes (> 6 weeks) were not available. Because Bell palsy often improves within weeks and may completely resolve within months, it is difficult to isolate specific improvements from laser therapy over the natural resolution of the illness. Also, no sham-controlled trials are available. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have fibromyalgia who receive LLLT, the evidence includes RCTs. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. The RCTs evaluating LLLT for treatment of fibromyalgia are small (i.e., < 25 patients each). One RCT (N = 20 patients) found significantly better outcomes with LLLT than with sham, while another (N = 20 patients) did not find statistically significant between-group differences for similar outcomes. Additional RCTs with sufficient numbers of patients are needed to establish the efficacy of LLLT for fibromyalgia. The evidence is insufficient to determine the effects of the technology on health outcomes.

Wound Care and Lymphedema
For individuals who have chronic nonhealing wounds who receive LLLT, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. The few existing RCTs tend to have small sample sizes and potential risk of bias. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have lymphedema who receive LLLT, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Two systematic reviews detected methodologic flaws in the available studies and did not consistently find better outcomes for patients receiving LLLT than those receiving a control condition for treatment of lymphedema. The evidence is insufficient to determine the effects of the technology on health outcomes.

Background
Treatment
Treatment planning may also need to be modified due to dose-limiting toxicity. There are a number of interventions for oral mucositis that may partially control symptoms but none is considered a criterion standard treatment. When uncomplicated by infection, oral mucositis is self-limited and usually heals within 2 to 4 weeks after cessation of cytotoxic chemotherapy. Low-level laser therapy (LLLT) has been used in cancer therapy-induced oral mucositis in individuals treated with radiotherapy and/or chemotherapy and hematopoietic cell transplantation.

Musculoskeletal and Neurologic Disorders
Musculoskeletal disorder describes a variety of conditions leading to chronic pain and decreased quality of life. Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and the most commonly performed surgery of the hand. The syndrome is related to the bony anatomy of the wrist. The carpal tunnel is bound dorsally and laterally by the carpal bones and ventrally by the transverse carpal ligament. Through this contained space run the 9 flexor tendons and the median nerve. Therefore, any space-occupying lesion can compress the median nerve and produce the typical symptoms of CTS pain, numbness, and tingling in the distribution of the median nerve. Symptoms of more severe cases include hypesthesia, clumsiness, loss of dexterity, and weakness of pinch. In the most severe cases, individuals experience marked sensory loss and significant functional impairment with thenar atrophy.

Treatment
Several modalities of treatment are used in the management of musculoskeletal pain including medications, immobilization, and physical therapy. The use of LLLT has been investigated for use in musculoskeletal pain conditions. In the case of CTS, mild-to-moderate cases are usually first treated conservatively with splinting and cessation of aggravating activities. Other conservative therapies include oral steroids, diuretics, nonsteroidal anti-inflammatory drugs, and steroid injections into the carpal tunnel itself. Individuals who do not respond to conservative therapy or who present with severe CTS with thenar atrophy may be considered candidates for surgical release of the carpal ligament, using either an open or endoscopic approach. Low-level laser therapy is also used to treat CTS.

Wound Care and Lymphedema
Chronic wounds are wounds that do not improve after 4 weeks or heal within 8 weeks. These include diabetic foot ulcers, venous-related ulcerations, non-healing surgical wounds, and pressure ulcers. They are often found on the feet, ankles, heels, and calves, and on the hips, thighs, and buttocks of those who cannot walk.

Lymphedema is described as swelling in at least 1 leg and/or arm. It is commonly caused by the removal of a lymph node. The resulting blockage of the lymphatic system prevents lymph fluid from draining well, leading to fluid build-up and swelling. Other symptoms can include heaviness or tightness in the affected limb, restricted range of motion, aching or discomfort, recurring infections, and dermal fibrosis. Risk factors for developing lymphedema after cancer from cancer treatment or from other secondary causes can include older age, obesity, and rheumatoid or psoriatic arthritis.

Treatment
Chronic wound management involves ensuring adequate blood flow to the area, preventing the wound from drying, controlling infections, debriding scarred and necrotic tissue, and managing pain. The standard of care for diabetic foot ulcers includes debridement, dressings, offloading of pressure, infection management, and glycemic control. Lymphedema is typically managed with pneumatic compression, exercise, or complete decompression therapy. Use of LLLT has been investigated for the management of both chronic wounds and lymphedema.

Low-Level Laser Therapy
Low-level laser therapy is the use of red-beam or near-infrared lasers with a wavelength between 600 and 1000 nm and power between 5 and 500 MW. By comparison, lasers used in surgery typically use 300 W. When applied to the skin, LLLT produces no sensation and does not burn the skin. Because of the low absorption by human skin, it is hypothesized that the laser light can penetrate deeply into the tissues where it has a photobiostimulative effect. The exact mechanism of its effect on tissue healing is unknown; hypotheses have included improved cellular repair and stimulation of the immune, lymphatic, and vascular systems.

Low-level laser therapy is being evaluated to treat a wide variety of conditions, including soft tissue injuries, myofascial pain, tendinopathies, nerve injuries, joint pain, and lymphedema.

Regulatory Status

Table 1. Selected Low-Level Laser Therapy Devices Cleared by the U.S. Food and Drug Administration

Device	Manufacturer	Date Cleared	510(k) No.	Indication
FX-635	Erchonia Corporation	6/01/2019	K190572	For adjunctive use in whole body musculoskeletal pain therapy
Super Pulsed Laser Technology	Multi Radiance Medical	01/13/2018	K171354	Providing temporary relief of minor chronic neck and shoulder pain of musculoskeletal origin
Lightstream Low-Level Laser	SOLICA CORPORATION	04/03/2009	K081166	For adjunctive use in the temporary relief of pain associated with knee disorders with standard chiropractic practice
GRT LITE, MODEL 8-A	GRT SOLUTIONS, INC.	02/03/2006	K050668	Use in providing temporary relief of minor chronic neck and shoulder pain of musculoskeletal origin
MICROLIGHT 830 LASER SYSTEM	MICROLIGHT CORPORATION OF AMERICA	02/06/2002	K010175	Use in pain therapy or related indication

A number of low-level lasers have been cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process for the treatment of pain. Data submitted for the MicroLight 830^® Laser consisted of the application of the laser over the carpal tunnel 3 times a week for 5 weeks. The labeling states that the "MicroLight 830 Laser is indicated for adjunctive use in the temporary relief of hand and wrist pain associated with Carpal Tunnel Syndrome." In 2006, GRT LITE™ was cleared for marketing, listing the TUCO Erchonia PL3000, the Excalibur System, the MicroLight 830^® Laser, and the Acculaser Pro as predicate devices. Indications of the GRTLITE™ for CTS are similar to the predicate devices: "adjunctive use in providing temporary relief of minor chronic pain." In 2009, the LightStream™ LLL device was cleared for marketing by the FDA through the 510(k) process for adjunctive use in the temporary relief of pain associated with knee disorders treated in standard chiropractic practice. A number of clinical trials of LLLT are underway in the U.S., including studies of wound healing. Since 2009, many more similar LLLT devices have received 510(k) clearance from the FDA.

Policy:
Low-level laser therapy is investigational and /or unproven and therefore considered NOT MEDICALLY NECESSARY for all indications including, but not limited to, treatment of carpal tunnel syndrome.

Policy Guidelines
Other protocols have used low-level laser energy applied to acupuncture points on the fingers and hand. This technique may be referred to as "laser acupuncture." Laser acupuncture is not reviewed in this policy.

There is no specific CPT code for low-level laser therapy. However, providers may elect to use CPT code 97026 (application of a modality; infrared), since the laser emits light in the infrared spectrum. In January 2004, a HCPCS code (S8948) was added that is specific to this therapy.

Benefit Application
BlueCard^®/National Account Issues
MicroLight Corporation has published a list of providers offering low-level laser therapy; the vast majority of providers are chiropractors. Given that the therapy typically requires up to 15 treatments, contractual or benefit restrictions on chiropractic visits for an individual diagnosis may apply.

State or federal mandates (e.g., FEP) may dictate that all devices approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational, and thus these devices may be assessed only on the basis of their medical necessity.

Rationale
This evidence review was created in April 2003 and has been updated regularly with a search of the PubMed database. The most recent literature update was performed through April 25, 2022.

Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life (QOL), and ability to function including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens, and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, two domains are examined: the relevance and quality and credibility. To be relevant, studies must represent 1 or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. Randomized controlled trials are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Carpal Tunnel Syndrome
Clinical Context and Therapy Purpose
The purpose of LLLT in patients who have carpal tunnel syndrome (CTS) is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of LLLT improve the net health outcome in patients with CTS?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with CTS, a common condition that causes pain, numbness, and tingling in the hand and arm. It is due to excess pressure in the wrist and on the median nerve, often caused by inflammation. Repeated motion of the wrist can contribute to the syndrome such as any repeated movement that overextends the wrist.

Women are more likely to have CTS than men, and it is frequently diagnosed between the ages of 30 and 60 years. Certain conditions can also increase the risk of developing CTS, including diabetes mellitus, high blood pressure, and arthritis.

Interventions
The therapy being considered is LLLT. Possible mechanisms of the benefits of LLLT include anti-inflammatory effects, selective inhibition of nociceptive activation at peripheral nerves, increased adenosine triphosphate (ATP) production and cellular respiration, and improvement of blood circulation to remove algesic substances.

Comparators
The following practice is currently being used to treat CTS: conservative therapy (e.g., physical therapy, wrist splints) and medication for pain and inflammation. Surgery may also be performed, during which the transverse carpal ligament is cut often under local anesthetic.

Outcomes
The general outcomes of interest are improvements in functional outcomes and QOL and a reduction in treatment-related morbidity. The effects of LLLT to promote healing are expected to occur from weeks to months. Pain can be measured on a VAS score.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Reviews
A TEC Assessment (2010) evaluated LLLT for CTS and chronic neck pain. For inclusion in the assessment, studies had to meet the following criteria: be published in a peer-reviewed journal, be a randomized, sham-controlled trial, and, if adjunctive therapies were used, they had to have been applied to both groups, and measure outcomes at least 2 weeks beyond the end of the treatment period. Four RCTs met the inclusion criteria. Reviewers concluded that the studies had serious limitations, including small sample sizes and limited follow-up, and no study was so methodologically sound as to provide definitive results.

A 2016 Cochrane report assessed the benefits and harms of LLLT compared with placebo and compared with other non-surgical interventions in the management of CTS.⁷ Twenty-two RCTs with 1153 participants were included. The authors concluded the quality of evidence was very low and found no data to support a clinical effect of LLLT in treating CTS.

Li et al. (2016) published a meta-analysis of RCTs on LLLT for CTS.⁸ Reviewers identified 7 RCTs. Meta-analyses evaluated outcomes for hand grip strength, pain measured by a VAS, symptom severity scores, and functional status scores. Short-term follow-up was defined as less than 6 weeks after treatment and long-term follow-up as at least 12 weeks after treatment. For 6 of the 8 meta-analyses, there were no statistically significant between-group differences in outcomes. They included short-term assessment of hand grip, short-term assessment of pain (VAS), and short- and long-term assessment of symptom severity and functional status scores. Meta-analyses found stronger hand grip (3 studies) and greater improvement in VAS scores (2 studies) at the long-term follow-up in the LLLT group than in the control. Most data for these 2 positive analyses were driven by a single RCT (Fusakul et al. [2014]⁹). Reviewers concluded that additional high-quality trials with similar LLLT protocols would be needed to confirm that the intervention significantly improves health outcomes.

Section Summary: Carpal Tunnel Syndrome
A number of RCTs and several systematic reviews have been published. The most recent systematic review (2016) identified 7 RCTs. Meta-analyses did not find a significant benefit of LLLT compared with a control condition for most of the outcome measures (6 of 8). Previously, a TEC Assessment (2010) had concluded that the evidence from sham-controlled randomized trials was insufficient. More recent RCTs have not found that LLLT significantly improves outcomes.

Neck Pain
Clinical Context and Therapy Purpose
The purpose of LLLT in patients who have neck pain is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of LLLT improve the net health outcome in individuals with neck pain?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with neck pain. Accompanying symptoms can include muscle tightness and spasms, decreased mobility, and headache. It can be caused by muscle strain, worn joints, nerve compression, injuries, or disease.

Interventions
The therapy being considered is LLLT, which uses laser irradiation to help repair tissue and relieve pain.

Comparators
The following practice is currently being used to treat neck pain: conservative therapy (e.g., physical therapy), medication and surgery.

Outcomes
The general outcomes of interest are improvements in functional outcomes and QOL and a reduction in symptoms and treatment-related morbidity. The effects of LLLT to promote healing are expected to occur from weeks to months. Pain can be measured on a VAS score.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic review
The TEC Assessment (2010), which included 6 trials of LLLT for chronic neck pain, found inconsistent results.¹⁰ In the largest study (Chow et al. [2006]), 90 patients were randomized to active LLLT or sham treatment.¹¹ Five weeks after the 7-week treatment period, patients in the active treatment group reported a 2.7-point improvement in VAS pain score versus 0.3-point worsening for the sham group. A calculated mean improvement of 43.8% was reported for the active LLLT group while the sham-treated group improved by 2.1%. The Assessment noted that baseline VAS pain scores were significantly higher in the active treatment group, possibly biasing results in favor of LLLT. Overall, reviewers concluded that the trials were characterized by small sample sizes, limited statistical power, and limited long-term follow-up, and thus the evidence was insufficient.

In a systematic review and meta-regression, Gross et al. (2013) evaluated 17 trials on LLLT for neck pain.¹² Ten trials demonstrated a high-risk of bias. Two trials (n = 109 subjects) were considered of moderate quality and found LLLT produced better outcomes than placebo for chronic neck pain treatment. Other trials showed improved outcomes with LLLT compared with placebo for acute neck pain, acute radiculopathy, and cervical osteoarthritis, but they were considered to be low-quality. There was conflicting evidence on chronic myofascial neck pain.

Section Summary: Neck Pain
A number of RCTs and several systematic reviews have been published. A 2013 systematic review identified 17 trials. Only 2 trials considered of moderate quality found that LLLT led to better outcomes than placebo for chronic neck pain. Other trials were considered low-quality. A 2010 TEC Assessment found conflicting evidence. While some studies showed positive benefits with LLLT over placebo, others did not. Additionally, laser types, dosages, and treatment schedules varied in the available evidence.

Subacromial Impingement Syndrome
Clinical Context and Therapy Purpose
The purpose of LLLT in patients with subacromial impingement syndrome is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of LLLT improve the net health outcome in those who have subacromial impingement syndrome?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with subacromial impingement syndrome, involving tendonitis of the rotator cuff muscles as they pass through the subacromial space. It can result in pain, weakness, and loss of movement at the shoulder.

Interventions
The therapy being considered is LLLT.

Comparators
The following practice is currently being used to treat subacromial impingement syndrome: conservative therapy (e.g., physical therapy, rest, cessation of painful activity), medication (such as corticosteroids and local anesthetics), and surgery. Surgery can be done arthroscopically or as open surgery.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Randomized Controlled Trials
Several RCTs evaluating LLLT for the treatment of subacromial impingement syndrome have been published. Two sham-controlled studies, by Yeldan et al. (2009)¹³ and by Dogan et al. (2010)¹⁴ did not find statistically significantly better pain or functional outcomes with active treatment than with sham. A third RCT, by Abrisham et al. (2011), compared exercise plus pulsed LLLT with sham laser 5 times a week for 2 weeks in 80 patients who had a subacromial syndrome (rotator cuff and biceps tendinitis).¹⁵ At the end of treatment, while both groups had improved VAS scores for pain and shoulder range of motion (ROM), the improvements were significantly better for the active LLLT group than for the sham laser group for pain (VAS score, 4.4 vs. 2.9) and all measures of ROM (active and passive flexion, abduction, external rotation). The durability of this effect was not assessed.

Other RCTs have not shown statistically significant benefits of LLLT versus conservative treatment. In a study designed to assess the effectiveness of LLLT in patients with subacromial impingement syndrome, Bal et al. (2009) randomized 44 patients to a 12-week home exercise program with or without LLLT.¹⁶ Outcome measures of night pain, SPADI , and University of California-Los Angeles shoulder pain end-result scores were assessed at weeks 2 and 12 of the intervention. No distinct advantage was demonstrated by LLLT over exercise alone. Both groups showed significant reductions in night pain and SPADI scores at 2- and 12-week assessments, but the differences between groups were not statistically significant.

Calis et al. (2011) randomized 52 patients with subacromial impingement syndrome to LLLT, ultrasound, or exercise.¹⁷ Patients were treated 5 days a week for 3 weeks with hot pack plus ultrasound plus exercise, hot pack plus LLLT plus exercise, or hot pack plus exercise. All 3 groups showed improvements from baseline to posttreatment in pain at rest, ROM, and function, but between-group improvements with LLLT were not statistically significant.

Alfredo et al. (2020) randomized 122 patients to LLLT plus exercise (n = 44; 42 included in analysis), LLLT alone (n = 42), or exercise alone (n = 42) for 8 weeks.¹⁸ Therapy was given 3 times a week for 8 weeks. Between-group comparison showed that patients in the LLLT plus exercise group had a significantly greater improvement in SPADI compared to other groups; however, no between-group comparison was performed exclusively for patients receiving LLLT alone and exercise alone.

Badil Güloğlu (2021) randomized 64 patients with a recent diagnosis of subacromial impingement syndrome without treatment in the preceding 4 weeks to 15 sessions of LLLT (n = 34) every weekday for 3 weeks or to weekly sessions of extracorporeal shock wave treatment (ESWT; n = 30) for 3 weeks.¹⁹ In both groups, all range of motion measurements, visual analogue scale pain scores, and SPADI scores showed significant improvements both at the end of treatment and at the third month after treatment (p < .05). There was no significant difference in abduction between the groups except the change at the end of treatment (p > .05). The ESWT group showed greater improvements in terms of SPADI disability and total scores at the end of treatment compared to LLLT. The improvements in VAS pain scores and SPADI scores at the third month after treatment was significantly more evident in the ESWT group (p < .05). Tables 2 and 3 provide RCT characteristics and results for evaluation of treatment of subacromial impingement syndrome.

Table 2. Summary of Key Randomized Controlled Trial Characteristics

Study	Countries	Sites	Dates	Participants	Interventions
					Active	Comparator
Yeldan et al. (2009)¹³	Turkey	1	NR	Patients with SAIS	LLLT (n = 34)	Placebo (n = 33)
Bal et al. (2009)¹⁶	Turkey	1	NR	Newly-diagnosed SAIS patients	LLLT + 12-wk home exercise program (n = 22)	12-wk home exercise program (n = 22)
Dogan et al. (2010)¹⁴	Turkey	NR	NR	Patients with SAIS	LLLT (n = 30)	Placebo (n = 22)
Abrisham et al. (2011)¹⁵	Iran	1	NR	Patients with SAIS (rotator cuff and biceps tendinitis)	LLLT (n = 40)	Placebo (n = 40)
Calis et al. (2011)¹⁷	Turkey	NR	NR	Patients with SAIS	LLLT + moist heat + exercise (n = 15)	Comparator 1: Moist heat + ultrasound + exercise (n = 21) Comparator 2: Moist heat + exercise (n = 16)
Alfredo et al. (2020)¹⁸	Brazil	1	2015 – 2016	Patients with SAIS, aged 50 to 70 years	LLLT + exercise (n = 42); LLLT alone (n = 36)	Exercise only (n = 42)
Badil Güloğlu (2021)¹⁹	Turkey	1	2019	Patients with newly diagnosed SAIS, aged 18 to 65 years	LLLT (n = 34)	ESWT (n = 30)

ESWT: extracorporeal shock wave therapy; LLLT: low-level laser therapy; NR: not reported; SAIS: subacromial impingement syndrome.

Table 3. Summary of Key Randomized Controlled Trial Results

Study	Pain	ROM (º)
Yeldan et al. (2009)¹³	VAS-A; VAS-R; VAS-N (Change from Baseline)	NR
LLLT	-2.20 ± 1.78; -1.47 ± 2.12; -2.85 ± 1.98
Placebo	-2.15 ± 2.11; -2.03 ± 2.45; -3.07 ± 2.81
P-value	.94;.30;.79
Bal et al. (2009)¹⁶	SPADI (Change from Baseline)	NR
LLLT	-37 ± 18.58
Exercise	-37.2 ± 21.28
P-value	.486
Dogan et al. (2010)¹⁴	VAS (Baseline; Post-treatment)	NR
LLLT	7.16 ± 1.64; 3.76 ± 1.45
Placebo	7.59 ± 1.76; 4.63 ± 2.10
P-value	.343;.216
Abrisham et al. (2011)¹⁵	VAS (Post-treatment)	Active Flexion, mean
LLLT	4.4 ± 1.2	43.1 ± 2.5
Placebo	2.9 ± 1.1	25.3 ± 2.4
P-value	.000	.000
Calis et al. (2011)¹⁷	VAS at Rest (Baseline; Post-treatment)	Flexion (Baseline; Post-treatment)
LLLT	4.00 ± 3.45; 2.56 ± 2.28	163.80 ± 10.05; 174.46 ± 6.94
Ultrasound	3.56 ± 2.49; 2.21 ± 2.09	168.33 ± 1.34; 177.04 ± 3.74
Control	4.67 ± 2.47; 3.96 ± 2.71	163.06 ± 8.57; 172.18 ± 6.93
P-value	.49;.10	.21;.05
Alfredo et al. (2020)¹⁸	SPADI (Posttreatment value [median quartile])	Flexion (Baseline; Posttreatment)
LLLT + exercise	0 (0 to 10)	132.9 ± 27.1; 161.5 ± 10.9
LLLT	16 (10.0 to 27.5)	124.9 ± 35.0; 153.5 ± 17.9
Exercise	41 (8.0 to 86.0)	118.4 ± 28.1; 137.1 ± 24.1
P-value	< .001	< .001
Badil Güloğlu (2021)¹⁹	SPADI (End of treatment; Third month after treatment)	Change in Abduction (Before Treatment to End of Treatment Difference)
LLLT	48 (range, 12 to 92); 52 (range, 12 to 80)	-10 to 100; median, 30
ESWT	35 (range, 0 to 76); 32 (range, 0 to 68)	0 to 50; median, 20
P-value	.003;.002	.018

-A: activity; ESWT: extracorporeal shock wave therapy; LLLT: low level laser therapy; -N: night; -R: rest; ROM: range of motion; SPADI: shoulder pain and disability index; VAS: visual analog scale.

Tables 4 and 5 display notable limitations identified in each study.

Table 4. Subacromial Impingement Syndrome Randomized Controlled Trial Study Relevance Limitations

Study	Population^a	Intervention^b	Comparator^c	Outcomes^d	Follow-Up^e
Yeldan et al. (2009)¹³	4. 78.3% of patients included in the analysis were female				1,2. Follow-up duration limited to 3 weeks
Bal et al. (2009)¹⁶	4. 70% of patients included in the analysis were female
Dogan et al. (2010)¹⁴					1,2. Follow-up duration not specified
Abrisham et al. (2011)¹⁵					1,2. Follow-up duration limited to 3 weeks
Calis et al. (2011)¹⁷
Alfredo et al. (2020)¹⁸	3. Detailed baseline characteristics (e.g., gender) not presented
Badil Güloğlu (2021)¹⁹	4. 70.6%, of patients in the LLLT group were female		2., 3. ESWT efficacy not completely established.

LLLT: low-level laser therapy
The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
^a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.
^b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4. Not the intervention of interest.
^c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.
^d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.
^e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Table 5. Subacromial Impingement Syndrome Randomized Controlled Trial Study Design and Conduct Limitations

Study	Allocation^a	Blinding^b	Selective Reporting^c	Follow-Up^d	Power^e	Statistical^f
Yeldan et al. (2009)¹³	2. Allocation not concealed	2. Blinding unclear
Bal et al. (2009)¹⁶	3. Allocation concealment unclear	1,2,3. Blinding unclear
Dogan et al. (2010)¹⁴	3. Allocation concealment unclear
Abrisham et al. (2011)¹⁵	3. Allocation concealment unclear	1,2,3. Blinding not described
Calis et al. (2011)¹⁷	3. Allocation concealment unclear	1,2,3. Not blinded
Alfredo et al. (2020)¹⁸		1, 2, 3. Not blinded		6. Per protocol analysis performed; however, only 2 patients were excluded from this analysis		4. No comparative analysis performed to compare LLLT only group with exercise only group
Badil Güloğlu (2021)¹⁹		1,2,3. Not blinded		6. Per protocol analysis performed (7 patients excluded from analysis)

LLLT: low-level laser therapy
The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
^a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.
^b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.
^c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.
^d Follow-Up key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).
^e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.
^f Statistical key: 1. Intervention is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Intervention is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4.Comparative treatment effects not calculated.

Section Summary: Subacromial Impingement Syndrome
The literature on LLLT for subacromial impingement syndrome consists of several RCTs. Most trials failed to show a significant benefit of LLLT compared with sham treatments or alternative interventions (e.g., exercise).

Adhesive Capsulitis
Clinical Context and Therapy Purpose
The purpose of LLLT in patients with adhesive capsulitis is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of LLLT improve the net health outcome in those who have adhesive capsulitis?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with adhesive capsulitis, also known as frozen shoulder. In this condition, the connective tissue surrounding the glenohumeral joint, becoming inflamed, stiff, and painful.

Risk factors for adhesive capsulitis include tonic seizures, diabetes mellitus, stroke, and lung, heart, and thyroid diseases. It occurs most frequently in women aged 40 to 65 years.

Interventions
The therapy being considered is LLLT.

Comparators
The following practice is currently being use to treat adhesive capsulitis: conservative therapy (e.g., physical therapy), medication, and surgery.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Review
A Cochrane review by Page et al. (2014) evaluated LLLT and other electrotherapy modalities for adhesive capsulitis (i.e., frozen shoulder).²⁰ Reviewers found limited evidence on which to conclude whether electrotherapy modalities are effective for frozen shoulder. Only 1 RCT (N = 40 patients) compared LLLT with placebo. That trial administered LLLT for 6 days. On day 6, patients receiving LLLT showed some improvements on a global assessment of treatment success compared with patients receiving a placebo. However, this trial was considered low-quality, and its small sample size and short follow-up limited interpretation of results. Another RCT on LLLT discussed in the 2014 Cochrane review was assessed as moderate quality. In that RCT, Stergioulas et al. (2008) randomized 63 patients with frozen shoulder to an 8-week program of LLLT (n = 31) or placebo (n = 32).²¹ Both groups also participated in exercise therapy. Compared with the sham group, the active laser group had a significant decrease in overall, night, and activity pain scores after 4 and 8 weeks of treatment and at the end of 8 more weeks of follow-up. At the same assessment intervals, significant decreases in SPADI and Croft Shoulder Disability Questionnaire scores were observed, while significant decreases in Disability of Arm, Shoulder, and Hand Questionnaire scores were observed at 8 weeks of treatment and 16 weeks post-randomization; significant decreases in Health Assessment Questionnaire scores were observed at 4 weeks and 8 weeks of treatment.

Section Summary: Adhesive Capsulitis
A Cochrane review evaluating treatments for adhesive capsulitis identified 2 RCTs on LLLT for adhesive capsulitis and, due to the small number of trials and study limitations, concluded that the evidence was insufficient to conclude whether LLLT is effective for adhesive capsulitis.

Temporomandibular Joint Pain
Clinical Context and Therapy Purpose
The purpose of LLLT in patients who have temporomandibular joint (TMJ) pain is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of LLLT improve the net health outcome in those who have TMJ pain?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with TMJ pain.

Interventions
The therapy being considered is LLLT.

Comparators
The following practice is currently being used to treat TMJ pain: conservative therapy (e.g., physical therapy), medication, and surgery.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Reviews
Several meta-analyses of RCTs on LLLT for TMJ pain have been published. A meta-analysis by Chen et al. (2015) assessed pain and functional outcomes after LLLT for TMJ pain.²² Fourteen placebo-controlled randomized trials were identified. Ten trials provided data on pain, as measured by a VAS. Pooled analysis of these studies found no significant differences between active treatment and placebo for VAS scores at final follow-up (WMD, -19.39; 95% CI, -40.80 to 2.03; p = .08). However, meta-analyses did find significantly better functional outcomes (i.e., maximum active mouth opening, maximum passive mouth opening) favoring LLLT. For example, the mean difference (MD) in maximum active mouth opening for active treatment versus placebo was 4.18 (95% CI, 0.73 to 7.63).

Chang et al. (2014) published a meta-analysis of 7 RCTs on LLLT for TMJ pain.²³ Single- or double-blind RCTs included in the review compared LLLT with no treatment or placebo. The primary outcome of interest was pain measured by a VAS. Six studies (N = 223 patients) were eligible for inclusion in the meta-analysis. In a meta-analysis, reduction in VAS scores after treatment was significantly greater in the LLLT group than in the control group (pooled effect size, -0.6 ; 95% CI, -0.47 to -0.73).

Hanna et al. (2021) recently published the largest systematic review including 44 RCTs of LLLT for TMJ pain to date.²⁴ All included trials were at low risk for reporting missing outcome data. Seventy percent of the included trials were at low risk, 28% were at high risk, and 2% had some concerns in terms of reporting outcome measurement. Of the RCTs included, 98% were at low risk of bias for selective reporting of the results. Overall, 38% of studies reported a low risk of bias, 46% were at high risk, and 16% had some concerns. Comparators across RCTs included sham placebo, drug therapy and physiotherapy. The primary outcome of interest was was change in pain intensity reduction from baseline, measured by a VAS. Thirty-three studies (n = 1163) were eligible for inclusion in the meta-analysis. In a meta-analysis, pooled change in VAS score from baseline to final follow-up evaluation demonstrated a significantly greater reduction with LLLT compared to comparator groups (pooled SMD, -0.55; 95% CI, -0.82 to -0.27; p < .0001), however, heterogeneity was high (I2 = 78%).

Tables 6 through 8 provide further details of these systematic reviews.

Table 6. Comparison of Trials/Studies Included in Systematic Reviews & Meta-Analysis

Study	Chen et al. (2015)²²	Chang et al. (2014)²³	Hanna et al. (2021)²⁴
Conti et al. (1997)²⁵	⚫
Kulekcioglu et al. (2003)²⁶	⚫
Venancio et al. (2005)²⁷	⚫	⚫	⚫
Cetiner et al. (2006)²⁸		⚫	⚫
Fikackova et al. (2007)²⁹		⚫	⚫
Mazzetto et al. (2007)³⁰	⚫	⚫	⚫
Frare et al. (2008)³¹			⚫
Da Cunha et al. (2008)³²	⚫	⚫	⚫
Lassemi et al. (2008)³³			⚫
Carrasco et al. (2008)³⁴	⚫	⚫	⚫
Emshoff et al. (2008)³⁵	⚫	⚫	⚫
Carrasco et al. (2009)³⁶			⚫
Shirani et al. (2009)³⁷	⚫		⚫
Venezian et al. (2010)³⁸			⚫
Oz et al. (2010)³⁹			⚫
Marini et al. (2010)⁴⁰	⚫		⚫
Rohlig et al. (2011)⁴¹			⚫
Sattayut et al. (2012)⁴²	⚫		⚫
de Carli et al. (2012)⁴³			⚫
da Silva et al. (2012)⁴⁴	⚫		⚫
Panhoca et al. (2013)⁴⁵			⚫
Uemoto et al. (2013)⁴⁶			⚫
Ferreira et al. (2013)⁴⁷	⚫
Demirkol et al. (2014)⁴⁸	⚫
Ahrari et al. (2014)⁴⁹	⚫		⚫
Pereira et al. (2014)⁵⁰			⚫
Maia et al. (2014)⁵¹			⚫
Sancakli et al. (2015)⁵²			⚫
De Oliveira et al. (2017)⁵³			⚫
Costa et al. (2017)⁵⁴			⚫
Seifi et al. (2017)⁵⁵			⚫
Shobha et al. (2017)⁵⁶			⚫
Rezazadeh et al. (2017)⁵⁷			⚫
Varma et al. (2018)⁵⁸			⚫
Borges et al. (2018)⁵⁹			⚫
Brochado et al. (2018)⁶⁰			⚫
Rodrigues et al. (2018)⁶¹			⚫
Peimani et al. (2018)⁶²			⚫
Nadershah et al. (2019)⁶³			⚫
Magri et al. (2019)⁶⁴			⚫
Al-Quisi et al. (2019)⁶⁵			⚫
Herpich et al. (2019)⁶⁶			⚫
Khairnar et al. (2019)⁶⁷			⚫
Sobral et al. (2020)⁶⁸			⚫
Maracci et al. (2020)⁶⁹			⚫
Chellappa et al. (2020)⁷⁰			⚫
Monteiro et al. (2020)⁷¹			⚫

Table 7. Systematic Reviews & Meta-Analysis Characteristics

Study	Dates	Trials	Participants	N (Range)	Design	Duration
Chen et al. (2015)²²	2003 – 2014	14	Patients suffering from TMDs	454 (NR)	RCT	NR
Chang et al. (2014)²³	2006 – 2008	7	Patients suffering from TMDs	NR (NR)	RCT	NR
Hanna et al. (2021)²⁴	2005 – 2021	44	Patients with TMDs	1163 (10 to > 50)	RCT	4 days to 8 weeks

NR: not reported; RCT: randomized controlled trial; TMD: temporomandibular disorders.

Table 8. Systematic Reviews & Meta-Analysis Results

Study	Pain (VAS)	MAVO	MPVO
Chen et al. (2015)²²
WMD	-19.39	4.18	6.73
95% CI	-40.80 to 2.03	0.73 to 7.63	1.34 to 12.13
P-value	< .001	.006	.06
Chang et al. (2014)²³
ES (95% CI)	-0.60 (-0.47 to -0.73)	NR	NR
Hanna et al. (2021)²⁴
SMD (95% CI)	-0.55 (-0.83 to -0.28)	-0.40 (-0.61 to -0.20)	NR
P-value	< .0001	.0001
I² (p)	78% (< .0001)	0% (.56)

CI: confidence interval; ES: effect size; MAVO: maximum active vertical opening; MPVO: maximum passive vertical opening; SMD: standard mean difference; VAS: visual analog scale; WMD: weighted mean difference.

Randomized Controlled Trials
Several RCTs have been published since the meta-analyses, showing inconsistent results.

Del Vecchio et al. (2021) randomized 90 patients between the ages of 18 and 73 years old with TMJ disorders to home LLLT (808 nm, 5 J/min, 250 mW, 15 KHz for 8 minutes twice daily), sham control, or standard conventional drugs (nimesulide 100 mg daily with 5-days of cyclobenzaprine 10 mg daily) for 1 week.⁷² Pain was measured using a 100-mm VAS, and the examiner was blinded. At the end of treatment, the reduction in VAS was greater in the LLLT group (MD, 13.030; p = .036) and the drug group (MD, 14.409; p = .17) compared to the sham group. However, no significant difference in pain reduction was observed between the LLLT group and the drug group (MD, 1.379; p = 1). This study evaluated a specific at-home LLLT protocol and can not be generalized to other LLLT regimens.

Aisaiti et al. (2021) randomized 78 patients with TMJ pain to receive LLLT (810 nm, 6 J/cm2, applied at 5 points for 30 seconds) or placebo once daily for 7 consecutive days.⁷³ Pain was measured on a 0 to 10 numerical rating scale and pressure pain thresholds. Only 50 patients, 25 per group, remained in the study to contribute data to analysis. Greater reduction in numerical rating scale pain scores were seen with LLLT than with placebo (p = .014), but no significant interaction between time and intervention was found (p = .35). For pressure pain thresholds, there was no significant difference found between interventions or interaction between time and intervention.

Section Summary: Temporomandibular Joint Pain
A number of RCTs and several systematic reviews have evaluated LLLT for TMJ pain. Meta-analyses of these trials had mixed findings. The largest and most recent meta-analysis, using 33 randomized trials, found a statistically significant impact of LLLT on pain reduction and functional outcomes (e.g., mouth opening) compared to sham laser or other therapies including drug therapy; however heterogeneity was high amongst included trials. Randomized controlled trials have not compared the impact of LLLT with physical therapy on health outcomes.

Low Back Pain
Clinical Context and Therapy Purpose
The purpose of LLLT in patients with low back pain is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of LLLT improve the net health outcome in those who have low back pain?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with low back pain. It can be the result of an injury, such as muscle strains, or disease.

Interventions
The therapy being considered is LLLT.

Comparators
The following practices are currently being used to treat low back pain: conservative therapy (e.g., physical therapy), medication, and surgery. These medications can include muscle relaxants and nonsteroidal anti-inflammatory drugs.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Reviews
A number of RCTs and several systematic reviews of RCTs have assessed LLLT for low back pain. For example, Glazov et al. (2016) published a meta-analysis of blinded sham-controlled trials evaluating LLLT for treatment of chronic low back pain.⁷⁴ Fifteen RCTs (N = 1,039 patients) met reviewers' eligibility criteria. Reviewers found that 3 of the 15 trials were at higher risk of bias (using a modified Cochrane risk of bias tool), mainly due to lack of blinding. The primary outcomes of interest to reviewers were pain measured by a VAS or a numeric rating scale, and a global assessment measure evaluating overall improvement and/or satisfaction with the intervention. Outcomes were reported immediately posttreatment (< 1 week) and at short-term (1 to 12 weeks) follow-up. Longer-term outcomes (i.e., at 6 and 12 months) were secondary measures. For the pain outcomes, a meta-analysis of 10 trials found a significantly greater reduction in pain scores in the LLLT group at immediate follow-up (WMD, -0.79 cm; 95% CI, -1.22 to 0.36 cm). In a meta-analysis of 6 trials, there was no significant difference in pain reduction at short-term follow-up. However, in subgroup analyses, there was a significantly greater reduction in pain with LLLT in trials that used a higher dose (> 3 J/point), but not a lower dose, and in trials that included patients with a short duration of back pain (5 to 27 months) but not long duration (49 months to 13 years). Decisions on the cutoff to use for laser dose and duration of back pain were made post hoc and considered review findings. Findings were similar for the global assessment outcome. Meta-analyses found significantly higher global assessment scores at immediate follow-up (5 trials) but not at short-term follow-up (3 trials). Only 2 trials reported pain or global assessment at 6 and 12 months, and neither found statistically significant differences between the LLLT and sham groups.

Huang et al. (2015) published a systematic review of RCTs on LLLT for treating nonspecific chronic low back pain.⁷⁵ Reviewers included trials comparing LLLT with placebo that reported pain and/or functional outcomes and a Physiotherapy Evidence Database (PEDro) quality score. Seven trials (N = 394 patients; 202 assigned to LLLT, 192 assigned to placebo) were included. Six of the 7 trials were considered high-quality (i.e., a PEDro score ³7; maximum score, 11 points). Primary outcomes of interest were posttreatment pain measured by VAS score and disability measured by the Oswestry Disability Index (ODI) score. Change in pain and ROM scores were secondary outcomes. In pooled analyses, reviewers found a statistically significant benefit of LLLT on pain outcomes but not disability or ROM. For the primary outcome (posttreatment pain scores) in a meta-analysis of all 7 trials, mean VAS scores were significantly lower in the LLLT group than in the placebo group (WMD, -13.57; 95% CI, -17.42 to -9.72). In a meta-analysis of 4 studies reporting the other primary outcome (ODI score), there was no statistically significant difference between the LLLT and the placebo groups (WMD, -2.89; 95% CI, -7.88 to 2.29). Outcomes were only reported immediately after treatment.

Chen et al. (2022) published a systematic review of RCTs on LLLT for treating nonspecific chronic low back pain compared to placebo.⁷⁶ Eleven trials were included that compared LLLT to placebo (N = 836 patients); seven of these trials assessed LLLT alone compared to placebo and 4 trials assessed LLLT plus acupuncture compared to placebo. For the overall risk of bias in LLLT trials, 8 were identified as low risk, 2 as having some concerns, and 1 as high risk. The primary outcomes of interest were changes from baseline in pain scores, measured by VAS, and disability measured by the ODI score. In pooled analyses, reviewers found a significant reduction in pain scores with all LLLT interventions compared to placebo posttreatment (SMD, -0.22; 95% CI, -0.38 to -0.05) and in disability scores for trials comparing LLLT therapy alone compared to placebo (SMD, -0.50; 95% CI, -0.79 to -0.21). In trials comparing LLLT plus acupuncture to placebo, there was no significant difference in disability scores post-treatment (SMD, 0.10; 95% CI, -0.15 to 0.35).

Table 9. Comparison of Trials/Studies Included in Systematic Reviews and Meta-Analysis for Low Back Pain

Study	Glazov et al. (2016)⁷⁴	Huang et al. (2015)⁷⁵	Chen et al. (2022)⁷⁶
Alayat et al. (2014)⁷⁷	⚫
Ay et al. (2010)⁷⁸	⚫		⚫
Basford et al. (1999)⁷⁹	⚫	⚫	⚫
Djavid et al. (2007)⁸⁰	⚫	⚫	⚫
Glazov et al. (2009)⁸¹	⚫		⚫
Glazov et al. (2014)⁸²	⚫		⚫
Klein et al. (1990)⁸³	⚫	⚫
Konstantinovic et al. (2011)⁸⁴	⚫
Lin et al. (2012)⁸⁵	⚫		⚫
Okamoto et al. (1989)⁸⁶	⚫
Ruth et al. (2010)⁸⁷	⚫
Soriano et al. (1998)⁸⁸	⚫	⚫
Umegaki et al. (1989)⁸⁹	⚫
Vallone et al. (2014)⁹⁰	⚫	⚫
Wallace et al. (1996)⁹¹	⚫
Gur et al. (2003)⁹²		⚫	⚫
Hsieh et al. (2014)⁹³		⚫
de Carvalho et al. (2016)⁹⁴			⚫
Tantawy et al. (2019)⁹⁵			⚫
Nambi et al. (2018)⁹⁶			⚫
Shin et al. (2015)⁹⁷			⚫

Table 10. Systematic Reviews and Meta-Analysis Characteristics for Low Back Pain

Study	Dates	Trials	Participants	N (Range)	Design	Duration
Glazov et al. (2016)⁷⁴	1989 – 2014	15	Non-pregnant adults with CLBP	1039 (20 – 144)	RCT	NR
Huang et al. (2015)⁷⁵	1990 – 2014	7	Patients with nonspecific CLBP	394 (20 – 100)	RCT	NR
Chen et al. (2022)⁷⁶	1999 – 2020	11	Patients with nonspecific CLBP	836 (30 – 220)	RCT	NR

CLBP: chronic low back pain; NR: not reported; RCT: randomized controlled trial.

Table 11. Systematic Reviews & Meta-Analysis Results for Low Back Pain

Study	Pain	Disability Score
Glazov et al. (2016)⁷⁴	VAS (LLLT vs. Control)	NR
WMD	-0.79
95% CI	-1.22 to -0.36
I²	70%
Huang et al. (2015)⁷⁵	VAS (LLLT vs. Control)	ODI (LLLT vs. Control)
WMD	-13.57	-12.0
95% CI	-17.42 to -9.72	-2.02 to -21.98
I²	0%	77.6%
Chen et al. (2022)⁷⁶	VAS (LLLT + acupuncture vs. Control)	ODI (LLLT vs. Control; LLLL + acupuncture vs. Control)
SMD	-0.22	-0.50; 0.10
95% CI	-0.38 to -0.05	-0.79 to -0.21; -0.15 to 0.35
P-value	.009	.0007;.44
I²	24%	11%; 0%

CI: confidence interval; LLLT: low-level laser therapy; NR: not reported; ODI: Oswestry Disability Index; SMD: standard mean difference; VAS: visual analog scale; WMD: weighted mean difference.

Randomized Controlled Trials
In a double-blind RCT, Koldas Dogan et al. (2017) compared the effectiveness of 2 laser therapy regimens on pain, lumbar ROM, and functional capacity in patients with chronic low back pain.⁹⁸ This trial assessed 49 patients with chronic low back pain who were randomized to a hot pack and the 2 different laser therapies for a total of 15 sessions. A series of assessments were conducted before and after treatment, including a modified Schober test, right and left lateral flexion measurements, VAS, and a modified ODI. After treatment, both groups saw a significant improvement in VAS, ODI, and lumbar ROM (p < .05). However, group 2 saw significantly better results in lateral flexion measurements and ODI scores (p < .05). Trial limitations included: (1) the short duration of follow-up; and (2) use of hot packs, which might have biased the pain measurements. No superiority was found for 1 laser treatment over the other regarding pain relief; however, regarding functionality, patients might find the Helium-Neon laser to be superior.

Section Summary: Low Back Pain
The literature on LLLT for low back pain consists of RCTs and several systematic reviews of RCTs. Meta-analyses found that LLLT resulted in significantly greater reductions in pain scores and global assessment scores than a placebo control in the immediate post-treatment setting. Meta-analyses also found that other outcomes (e.g., disability index, ROM) were significantly better immediately after treatment with active versus placebo LLLT, though not at longer-term follow-up.

Osteoarthritic Knee Pain
Clinical Context and Therapy Purpose
The purpose of LLLT in patients who have osteoarthritic knee pain is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of LLLT improve the net health outcome in those who have osteoarthritic knee pain?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is those who have osteoarthritic knee pain. Also called degenerative arthritis, osteoarthritis (OA) is the most common type of arthritis, which occurs when the cartilage in the knee deteriorates with use and age.

Interventions
The therapy being considered is LLLT.

Comparators
The following practices are currently being used to treat osteoarthritic knee pain: conservative therapy (e.g., physical therapy), medication, and surgery.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Review
Several RCTs and systematic reviews of RCTs have evaluated LLLT for treatment of knee OA, coming to inconsistent conclusions.^99,100 The most inclusive and up-to-date of these was published by Stausholm et al. (2019) and compared LLLT with placebo for knee OA patients.¹⁰¹ To be eligible for inclusion, trials had to report pain, disability, or QOL. A total of 22 trials (N = 1063) met the eligibility criteria. Interventions included between 5 to 16 sessions of LLLT or sham LLLT. A total of 9 included studies used a non-recommended dose of LLLT, which had a mean treatment duration of 3.7 weeks. The mean treatment duration was 3.53 weeks in studies using appropriate dosing. The primary outcome was posttreatment pain measured by a 0 to 100 mm VAS score at end of treatment and follow-up (1 to 12 weeks). The mean difference in VAS score was statistically significant favoring LLLT over placebo at end of treatment (14.23 mm; 95% CI, 7.31 to 21.14; I2 = 93%) and at follow up (15.92 mm; 95% CI, 6.47 to 25.37; I2 = 93%). There was high heterogeneity for the primary outcome, possibly due to differences in the follow-up time period. Risk of bias appeared low. Only 1 study included QOL data, and therefore no QOL meta-analysis was performed.

Table 12. Trials/Studies Included in Systematic Reviews & Meta-Analysis for Osteoarthritic Knee Pain

Study	Stausholm et al. (2019)¹⁰¹
Al Rashoud et al. (2014)¹⁰²	⚫
Alfredo et al. (2011, 2018)^103,¹⁰⁴	⚫
Alghadir et al. (2014)¹⁰⁵	⚫
Bagheri et al. (2011)¹⁰⁶	⚫
Bülow et al. (1994)¹⁰⁷	⚫
Delkhosh et al. (2018)¹⁰⁸	⚫
Fukuda et al. (2011)¹⁰⁹	⚫
Guret et al. (2003)¹¹⁰	⚫
Gur and Oktayoglu (unpublished)	⚫
Gworys et al. (2012)¹¹¹	⚫
Hegedűs et al. (2009)¹¹²	⚫
Helianthi et al. (2016)¹¹³	⚫
Hinman et al. (2014)¹¹⁴	⚫
Jensen et al. (1987)¹¹⁵	⚫
Kheshie et al. (2014)¹¹⁶	⚫
Koutenaei et al. (2017)¹¹⁷	⚫
Mohammed et al. (2018)¹¹⁸	⚫
Nambi et al. (2016)¹¹⁹	⚫
Nivbrant et al. (1992)¹²⁰	⚫
Rayegani et al. (2012)¹²¹	⚫
Tascioglu et al. (2004)¹²²	⚫
Youssef et al. (2016)¹²³	⚫

Table 13. Systematic Reviews & Meta-Analysis Characteristics for Osteoarthritic Knee Pain

Study	Dates	Trials	Participants	N (Range)	Design	Duration
Stausholm et al. (2019)¹⁰¹	1987 – 2018	22	Patients with OA knee pain	1063 (12 – 71)	RCT	1 – 12 weeks

OA: osteoarthritis; RCT: randomized controlled trial.

Table 14. Systematic Reviews & Meta-Analysis Results for Osteoarthritic Knee Pain

Study	VAS (LLLT vs. placebo)	Disability (LLLT vs. placebo)
Stausholm et al. (2019)¹⁰¹
At end of therapy
n	816	617
MD	14.23 mm	0.59
95% CI	7.31 to 21.14	0.23 to 0.86
I² (%)	93	57
At follow-up (week 1 – 12)
n	581	289
MD	15.92 mm	0.66
95% CI	6.47 to 25.37	0.23 to 1.09
I²	93	67

CI:confidence interval; LLLT: low level laser therapy; MD: mean difference; VAS: visual analogue scale

Section Summary: Osteoarthritic Knee Pain
The literature on LLLT for OA includes RCTs and multiple systematic reviews of RCTs. One of the more recent systematic reviews, which pooled study findings, did find that LLLT significantly reduced pain and improved disability compared with a sham intervention; however, there was high heterogeneity between studies, and individual studies are limited by small sample size and inconsistent timing of follow-up.

Heel Pain
Clinical Context and Therapy Purpose
The purpose of LLLT in patients who have heel pain (i.e., Achilles tendinopathy, plantar fasciitis) is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of LLLT improve the net health outcome in those who have heel pain (i.e., Achilles tendinopathy, plantar fasciitis)?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals who have heel pain, which can include Achilles tendinopathy, plantar fasciitis, and heel bursitis, etc.

Interventions
The therapy being considered is LLLT.

Comparators
The following practice is currently being used to treat heel pain: conservative therapy (e.g., physical therapy), medication, and surgery.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded

Review of Evidence
Achilles Tendinopathy
Randomized Controlled Trials
Stergioulas et al. (2008) randomized 52 recreational athletes with chronic Achilles tendinopathy symptoms to an 8-week (12-session) program of eccentric exercises with LLLT or sham LLLT.²¹ By intention-to-treat analysis, results for the primary outcome of pain during physical activity assessed on a VAS were significantly lower in the exercise with LLLT group at 4 (p < .001), 8 (p < .001), and 12 weeks (p = .007) after randomization.

Tumilty et al. (2012) reported on a randomized, double-blinded, sham-controlled trial of LLLT as an adjunct to 3 months of exercise training in 40 patients with Achilles tendinopathy.¹²⁴ Active or sham LLLT was administered 3 times a week for 4 weeks, and exercises performed twice daily for 12 weeks. The primary outcome was the Victorian Institute of Sport Assessment-Achilles Questionnaire at 12 weeks. The only significant difference between groups using intention-to-treat analysis was at 4 weeks for the Victorian Institute of Sport Assessment-Achilles Questionnaire scores, and that difference favored the sham control group. The Victorian Institute of Sport Assessment-Achilles Questionnaire and pain numeric rating scale scores did not differ significantly between the active and the sham groups at 12-week or 1-year follow-ups.

Plantar Fasciitis
Systematic Reviews
Wang et al. (2019) published a systematic review and meta-analysis of 6 RCTs comparing LLLT (alone or combined with other interventions) and controls (placebo or other interventions).¹²⁵ A total of 315 adults with plantar heel pain or plantar fasciitis were included in the analysis. Compared with controls, VAS was significantly reduced after treatment (SMD, -0.95; 95% CI -1.20 to -0.70; p < .001), as well as remaining significantly better at 3 months (SMD, -1.13; 95% CI -1.53 to -0.72; p < .001). The meta-analysis was limited by the small number of studies included, small sample size, and insufficient data for longer-term outcomes.

Guimaraes et al. (2022) published a systematic review and meta-analysis of 14 studies (N = 817) comparing LLLT (alone or combined with other interventions) and controls (placebo and other interventions).¹²⁶ Compared to the placebo group, LLLT improved pain in the short term of 0 to 6 weeks (4 studies, n = 234; moderate-quality evidence; MD, -2.28; 95% CI, -2.58 to -1.97;p < .00001; I2 = 0%). No significant difference in short-term disability was found for individuals in the LLLT group compared to the placebo group. Compared to the conventional rehabilitation alone group, LLLT combined with conventional rehabilitation improved pain in the short term of 0 to 6 weeks (2 studies, n = 90; moderate-quality evidence; MD, -2.01; 95% CI, -2.89 to -1.13; p < .00001; I2 = 0%). However, compared to ESWT, LLLT did not significantly reduce pain intensity in the short term (4 studies, n = 175; low-quality evidence; MD, 0.45; 95% CI, -2.0 to 2.9; p = .72; I2 = 94%). The meta-analysis was limited by insufficient data for longer-term outcomes, the lack of multicenter studies, and lack of a large sample. Additionally, the quality of evidence for the outcome disability were determined to be low.

Randomized Controlled Trials
A double-blind RCT by Macias et al. (2015) assessed 69 patients with unilateral chronic plantar fasciitis and chronic heel pain of 3 months or longer that was unresponsive to conservative treatments (e.g., rest, stretching, physical therapy).¹²⁷ Patients were randomized to twice weekly treatment for 3 weeks of LLLT or sham treatment. The primary efficacy outcome (reduction of heel pain pre- to posttreatment) differed significantly between groups (p < .001). Mean VAS scores decreased from 69.1 to 39.5 in the LLLT group and from 67.6 to 62.3 in the sham group. The difference in Foot Function Index scores did not differ significantly between groups.

An RCT on LLLT for plantar fasciitis was reported by Kiritsi et al. (2010).¹²⁸ The trial was double-blind and sham-controlled and assessed 30 patients. Twenty-five (83%) patients completed the trial, with treatment 3 times a week over 6 weeks. At baseline, plantar fascia thickness, measured by ultrasound, was significantly greater in symptomatic feet (5.3 mm) compared with asymptomatic feet (3.0 mm). Plantar fascia thickness decreased in both the LLLT and the sham groups during the trial. Although plantar fascia thickness after 6 weeks of treatment did not differ significantly between groups (3.6 mm in LLLT vs. 4.4 mm in sham), there was a significant between-group difference in the reduction in thickness (1.7 mm LLLT vs. 0.9 mm sham). After night rest or daily activities, VAS scores improved significantly more in the LLLT group (59% improvement) than in the sham group (26% improvement). At baseline, pain after daily activities were rated as 67 out of 100 by both groups. At the end of treatment, VAS scores for daily activities were rated as 28 out of 100 for LLLT and 50 out of 100 for sham.

Cinar et al. (2018) conducted a prospective single-blinded RCT investigating combination therapy consisting of LLLT plus exercise and orthotic care versus orthotic care alone in persons with plantar fasciitis.¹²⁹ Forty-nine individuals were randomized to LLLT (n = 27) or a control therapy (n = 22). Each person performed a home exercise routine and received orthotic care; persons in the LLLT group received treatment 3 times a week for a total of 10 sessions. The function subscale of the American Orthopedic Foot and Ankle Society Score, a VAS, and the 12-minute walk test were used to measure progress. Scores were recorded at baseline, 3 weeks, and 3 months after treatment. At week 3, both groups saw a significant improvement in American Orthopedic Foot and Ankle Society total score (LLLT, p < .001; control, p = .002). However, at the 3-month follow-up, only the LLLT group progressed as assessed on the American Orthopedic Foot and Ankle Society total score (p = .04). At all check-ins, the group scores for the 12-minute walk test were comparable. Both groups showed significant pain reductions at the 3-month follow-up (LLLT, p < .001; control, p = .01); however, the LLLT group had a more significant reduction in pain at month 3 (p = .03). Thus, reviewers concluded that combination therapy plus LLLT was more effective in reducing pain and improving function for patients with plantar fasciitis than orthotic care alone. Limitations included a lack of a control group, which would have accounted for the natural progression of recovery in patients with plantar fasciitis.

Table 15. Summary of Key Randomized Controlled Trial Characteristics

Study; Trial	Countries	Sites	Dates	Participants	Interventions
					Active	Comparator
Kiritsi et al. (2010)¹²⁸	Greece	NR	2006 – 2007	Patients with unilateral idiopathic PF	LLLT (n = 15)	Placebo (n = 15)
Macias et al. (2015)¹²⁷	US	NR	2011 – 2013	Patients unilateral chronic PF	LLLT (n = 37)	Placebo (n = 32)
Cinar et al. (2018)¹²⁹	Turkey	NR	2012 – 2013	Patients with PF	LLLT (n = 27)	Control (n = 22)

LLLT: low-level laser therapy; NR: not reported; PF: plantar fasciitis.

Table 16. Summary of Key Randomized Controlled Trial Results

Study	Pain	Plantar Fascia Thickness	AOFAS-F [95%CI]
Kiritsi et al. (2010)¹²⁸	VAS (Difference from Baseline)	mm (Difference from Baseline)	NR
LLLT	40 ± 20.3	1.667 ± 0.547
Placebo	18 ± 8.9	0.920 ± 0.220
P-value	.001	.007
Macias et al. (2015)¹²⁷	FFI scores (Baseline; Endpoint)	NR	NR
LLLT	111.9 ± 34.2; 82.0 ± 43.6
Placebo	110.8 ± 32.3; 86.1 ± 43.2
P-value	.89;.70
Cinar et al. (2018)¹²⁹	VAS (Baseline; 3 months) [95% CI]	NR
LLLT	6.13; 1.72 [5.41 to 6.85; 0.78 to 2.67]		44.16; 49.95 [42.58 to 45.74; 48.45 to 51.45]
Placebo	5.49; 3.67 [4.67 to 6.31; 2.56 to 4.77]		45.55; 47.78 [43.75 to –47.34; 46.07 to 49.49]

AOFAS: American Orthopedic Foot and Ankle Society Score; CI: confidence interval; FFI: foot function index; LLLT: low-level laser therapy; NR: not reported; VAS: visual analog scale.

Table 17 displays notable limitations identified in each study.

Table 17. Study Design and Conduct Limitations

Study	Allocation^a	Blinding^b	Selective Reporting^c	Follow-Up^d	Power^e	Statistical^f
Kiritsi et al. (2010)¹²⁸	3. Allocation concealment unclear	3. Blinding of outcome assessment unclear
Macias et al. (2015)¹²⁷
Cinar et al. (2018)¹²⁹		3. Blinding of outcome assessment unclear

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
^a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.
^b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.
^c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.
^d Follow-Up key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).
^e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.
^f Statistical key: 1. Intervention is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Intervention is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4.Comparative treatment effects not calculated.

Section Summary: Heel Pain
Multiple sham-controlled randomized trials have evaluated LLLT for heel pain (Achilles tendinopathy, plantar fasciitis) but findings were inconsistent. One RCT compared LLLT plus therapy with orthotic care alone, and while a significant advantage was observed in LLLT treatment, LLLT treatment was used as a combination therapy. Findings from meta-analyses were conflicting. A meta-analysis of Achilles tendinopathy trials found no benefit in pain reduction with LLLT with the exception of at 2 months of follow-up reported in a single trial. A second meta-analysis did find short-term (0 to 6 week) pain improvement in patients receiving LLLT compared to placebo or in combination with conventional rehabilitation, but did not find pain improvement with LLLT compared to ESWT. None of the studies presented long-term follow-up data. Given all factors, further studies are needed to validate the technology.

Rheumatoid Arthritis
Clinical Context and Therapy Purpose
The purpose of LLLT in patients who have rheumatoid arthritis (RA) is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of LLLT improve the net health outcome in those who have RA?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with RA, a debilitating autoimmune condition that can affect most joints in the body.

Interventions
The therapy being considered is LLLT.

Comparators
The following practices are currently being used to treat RA: conservative therapy (e.g., exercise) and medication, including nonsteroidal anti-inflammatory drugs, steroids, disease-modifying antirheumatic drugs, and biologic agents.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Review
A Cochrane review by Brosseau et al. (2005) included 5 placebo-controlled randomized trials and found that, relative to a separate control group, LLLT reduced pain by 1.10 points on a VAS compared with placebo, reduced morning stiffness duration by 27.5 minutes, and increased tip-to-palm flexibility by 1.3 cm.¹³⁰ Other outcomes, such as functional assessment, ROM, and local swelling, did not differ between groups. For RA, relative to a control group using the opposite hand (1 study), no difference was observed between the control and treatment hand for morning stiffness duration, and no significant improvement was reported in pain relief. Reviewers noted that "despite some positive findings, this meta-analysis lacked data on how LLLT effectiveness is affected by 4 important factors: wavelength, treatment duration of LLLT, dosage, and site application over nerves instead of joints."

A randomized, double-blind, placebo-controlled trial assessing outcomes for pain reduction and improvement in hand function in 82 patients with RA treated with LLLT or placebo laser was reported by Meireles et al. (2010).¹³¹ There were no statistically significant differences between groups for most outcome measurements, including the primary variables, though a few measures significantly favored either the active or placebo treatment. Reviewers concluded that LLLT at the dosage used in the trial was ineffective for treating RA.

Section Summary: Rheumatoid Arthritis
A Cochrane review of 5 placebo-controlled randomized trials found statistically significant improvement of LLLT on some outcomes (e.g., VAS) but not others (e.g., functional assessment). A 2010 RCT, published after the Cochrane review, did not find that LLLT was significantly better than a placebo treatment for most outcomes.

Bell Palsy (Facial Nerve Palsy)
Clinical Context and Therapy Purpose
The purpose of LLLT in patients who have Bell palsy is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of LLLT improve the net health outcome in patients with Bell palsy?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with Bell palsy, a condition in which the muscles on 1 side of the face become weak or paralyzed caused by trauma to the seventh cranial nerve.

Interventions
The therapy being considered is LLLT.

Comparators
The following practices are currently being used to treat Bell palsy: conservative therapy (e.g., exercise) and medications, including corticosteroids and antiviral drugs.

Outcomes
General outcomes of interest are improvements in functional outcomes and QOL and a reduction in symptoms and treatment-related morbidity. The effects of LLLT to promote healing are expected to occur from weeks to months. Outcomes are assessed using the Facial Disability Index and the House-Brackmann Scale.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Randomized Controlled Trials
Alayat et al. (2014) reported on a randomized, double-blind, placebo-controlled trial of laser therapy for the treatment of 48 patients with Bell palsy.¹³² Facial exercises and massage were given to all patients. Patients were randomized to 1 of 3 groups: high-intensity laser therapy, LLLT, or exercise only. Laser treatment was given 3 times a week to 8 points on the affected side for 6 weeks. At 3 and 6 weeks posttreatment, outcomes were assessed using the Facial Disability Index and the House-Brackmann Scale. Significant improvements in recovery were seen in both laser therapy groups over exercise alone, with the greatest improvement seen with a high-intensity laser.

Ordahan and Karahan (2017) investigated the efficacy of LLLT when used in combination with traditional facial exercises to treat facial paralysis.¹³³ Forty-six patients with Bell palsy were randomized to 2 groups: 1 group underwent LLLT plus facial exercise therapy (n = 23); the other group underwent facial exercise therapy alone (n = 23). Laser therapy was administered 3 times a week for 6 weeks. Patients were evaluated during the treatment and at 3 and 6 weeks posttreatment. The Facial Disability Index was used to evaluate progress. No significant improvement was observed at week 3 in the facial exercise therapy-alone treatment group (p < .05), but significant improvement was noted at week 6 (p < .001). In the LLLT plus facial exercise therapy group, significant improvement was noted at 3 and 6 weeks (p < .001); moreover, improvements in the Facial Disability Index scores in the LLLT plus facial exercise therapy group were significantly greater than those of the facial exercise therapy-alone treatment group at week 3 and week 6 (p < .05). Study limitations included lack of long-term follow-up and the use of combination therapy, which obscures the contribution of LLLT.

Section Summary: Bell Palsy
One RCT found a significant short-term benefit of LLLT over exercise, but long-term outcomes were not available. Another RCT found significant short-term benefit with facial exercise therapy plus LLLT over facial exercise therapy alone, but again, no long-term data were available. The limited evidence on laser therapy for Bell palsy is insufficient to draw conclusions. Because Bell palsy often improves within weeks and may resolve completely within months, it is difficult to isolate specific improvements from laser therapy over the natural resolution of the illness. Also, no sham-controlled trials are available.

Fibromyalgia
Clinical Context and Therapy Purpose
The purpose of LLLT in patients who have fibromyalgia is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of LLLT improve the net health outcome in patients with fibromyalgia?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with fibromyalgia, a disorder characterized by widespread musculoskeletal pain often accompanied by fatigue, sleep, memory, and mood issues. Symptoms can begin after a physical trauma, surgery, or infection or, in some cases, gradually accumulate over time without a single triggering event.

Often, fibromyalgia co-exists with other conditions, including irritable bowel syndrome, migraine, interstitial cystitis, and TMJ disorders.

Interventions
The therapy being considered is LLLT.

Comparators
The following practice is currently being used to treat fibromyalgia: conservative therapy (e.g., exercise) and medications, including pain relievers, antidepressants, and anti-seizure drugs.

Outcomes
General outcomes of interest are improvements in functional outcomes and QOL and a reduction in symptoms and treatment-related morbidity. The effects of LLLT to promote healing are expected to occur from weeks to months. Outcomes are measured with the Fibromyalgia Impact Questionnaire (FIQ), the McGill Pain Questionnaire, and a pain VAS.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Review
Honda et al. (2018) published a systematic review and meta-analysis of RCTs evaluating pain relief modalities for fibromyalgia.¹³⁴ Eleven studies with a total of 498 patients (range, 20 to 80) were included; 5 studies evaluated LLLT and the remainder covered other treatment modalities. Compared with control, LLLT was not associated with a reduction of VAS-measured pain (MD, -4.0; 95% CI, -23.4 to 15.4; p = .69). LLLT showed a significant reduction in tender points compared with control (MD, -2.21; 95% CI, -3.51 to -0.92; I2 = 42%; p = .0008) and in the FIQ score (MD, -4.35; 95% CI, -6.69 to -2.01; I2 = 62%; p = .03). The analysis was limited by its inclusion criteria limited to a pure control group or placebo group for a specific intervention and exclusion of those that used another intervention as a comparator. Several treatment modalities were evaluated and individual pooled results for each intervention had a high degree of heterogeneity.

Randomized Controlled Trials
Several small RCTs evaluating LLLT for fibromyalgia have been published. Ruaro et al. (2014) reported on 20 patients randomized to LLLT or sham treatment 3 times a week for 4 weeks (12 total treatments).¹³⁵ Outcomes included scores in the FIQ , which measures physical function, ability to work, pain, fatigue, and depression; the McGill Pain Questionnaire; and a pain VAS. All 3 outcomes were significantly better with active than with sham LLLT posttreatment. Mean overall FIQ scores were 18.6 in the LLLT group and 5.2 in the sham group (p = .003). Mean change scores also differed significantly between groups for McGill Pain Questionnaire score (p = .008) and VAS score (p = .002).

Matsutani et al. (2007) randomized 20 patients with fibromyalgia to laser treatment plus stretching exercises or stretching alone.¹³⁶ Outcome measures were VAS scores and dolorimetry at tender points, QOL on the FIQ, and the 36-Item Short-Form Health Survey scores. At the end of treatment, both groups demonstrated pain reductions, higher pain thresholds at tender points (all p < .01), lower mean FIQ scores, and higher 36-Item Short-Form Health Survey mean scores (all p < .05). No significant differences were found between groups.

Section Summary: Fibromyalgia
Few RCTs evaluating LLLT for fibromyalgia are available, which have been included in a systematic review and meta-analysis; the existing trials are small (i.e., < 25 patients each). One RCT (N = 20 patients) found significantly better outcomes with LLLT than with sham, and another RCT (N = 20 patients) did not find statistically significant between-group differences for similar outcomes. Additional RCTs with sufficient numbers of patients are needed.

Chronic Nonhealing Wounds
Clinical Context and Therapy Purpose
The purpose of LLLT in patients with chronic non-healing wounds is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of LLLT improve the net health outcome in patients with chronic non-healing wounds?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with chronic non-healing wounds: wounds that do not improve after 4 weeks or heal in 8 weeks. These include diabetic foot ulcers, venous-related ulcerations, non-healing surgical wounds, and pressure ulcers. They are often found on the feet, ankles, heels, calves, and on the hips, thighs, and buttocks of those who cannot walk.

Interventions
The therapy being considered is LLLT.

Comparators
The following practice is currently being used to treat chronic nonhealing wounds: standard wound care, including wound debridement, compression therapy, and antibacterial treatment.

Outcomes
The outcome of interest is complete healing or healing to a degree that permits a procedure that results in complete healing. The effects of LLLT to promote healing are expected to occur from weeks to months.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Reviews
An evidence assessment by Samson et al. (2004), which evaluated vacuum-assisted and low-level laser wound therapies for the treatment of chronic nonhealing wounds and was prepared for the Agency for Healthcare Research and Quality, was based on 11 studies of LLLT.¹³⁷ It stated: "The best available trial [of low-level laser wound therapy] did not show a higher probability of complete healing at 6 weeks with the addition of low-level laser compared with sham laser treatment added to standard care. Study weaknesses were unlikely to have concealed existing effects. Future studies may determine whether different dosing parameters or other laser types may lead to different results."

A Cochrane review by Chen et al. (2014) evaluated RCTs on light therapy, including phototherapy, ultraviolet, and laser, for pressure ulcers.¹³⁸ The few trials available for analysis were of small size and very low quality. Reviewers found the available evidence overall insufficient to conclude whether light therapy is effective on pressure ulcers.

Machado et al. (2017) also published a systematic review evaluating the treatment of pressure ulcers with LLLT.¹³⁹ Reviewers identified 4 studies meeting eligibility requirements (N = 210 patients). Outcomes were the ulcer area, healing rate, and overall healing rate. Two of the 4 studies used LLLT with a single wavelength^140,141; and the other 2 used LLLT with probe cluster, which employs the simultaneous assimilation of different types of diodes and wavelengths.^142,143 In the study that employed the 658 nm wavelength, reviewers found that particular frequency reduced pressure ulcers by 71%. The other wavelengths did not produce any significant findings related to the study outcome; moreover, the studies using the probe cluster technique were also not successful in producing significant findings. While studies should be conducted to investigate further the success found in single wavelength at 658 nm, at this time there is insufficient evidence to suggest LLLT can significantly benefit patients with pressure ulcers.

Li et al. (2018) published a systematic review and meta-analysis of 7 RCTs (N = 194) evaluating LLLT as a treatment for a diabetic foot ulcer.¹⁴⁴ Ulcer area was significantly reduced with LLLT compared with control (WMD, 34.18; 95% CI, 19.38 to 48.99; p < .001), and the complete healing rate significantly improved with LLLT (odds ratio [OR], 6.72; 95% CI, 1.99 to 22.64; p = .002). The analysis was limited by the number of studies included and small sample size, and by each study having different parameters, demographic information, ulcer characteristics, follow-up time, and treatment period.

Section Summary: Chronic Nonhealing Wounds
Multiple systematic reviews of the literature did not find sufficient evidence from controlled studies demonstrating that LLLT is effective for wound healing.

Lymphedema
Clinical Context and Therapy Purpose
The purpose of LLLT in patients with lymphedema is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of LLLT improve the net health outcome in patients with lymphedema?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with lymphedema or swelling in 1 or both arms and legs. It is commonly caused by the removal of a lymph node. The resulting blockage of the lymphatic system prevents lymph fluid from draining well, leading to fluid build-up and swelling. Other symptoms can include heaviness or tightness in the affected limb, restricted range of motion, aching or discomfort, recurring infections, and dermal fibrosis. Risk factors for developing lymphedema after cancer from cancer treatment or from other secondary causes can include older age, obesity, and rheumatoid or psoriatic arthritis.

Interventions
The therapy being considered is LLLT.

Comparators
The following practice is currently being used to treat lymphedema: conservative care (e.g., exercise), pneumatic compression, and complete decongestive therapy.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Reviews
Several systematic reviews of RCTs and observational studies have been published. For example, Smoot et al. (2015) published a systematic review of studies on the effect of LLLT on symptoms in women with breast cancer-related lymphedema.¹⁴⁵ Reviewers identified 9 studies, 7 RCTs, and 2 single-group studies. Three studies had a sham control group, 1 used a waitlist control, and 3 compared LLLT with an alternative intervention (e.g., intermittent compression). Only 3 studies had blinded outcomes assessments, and in 3 studies, participants were blinded. A pooled analysis of 4 studies found significantly greater reductions in upper-extremity volume with LLLT than with the control condition (pooled effect size, -0.62; 95% CI, -0.97 to -0.28). Only 2 studies were suitable for a pooled analysis of the effect of LLLT on pain. This analysis did not find a significant difference in pain levels between LLLT and control (pooled effect size, -1.21; 95% CI, -4.51 to 2.10).

Omar et al. (2012) published a qualitative systematic review of LLLT for the management of breast cancer-related lymphedema.¹⁴⁶ They selected 8 studies (N = 230 patients) for their review. Five studies were graded as Sackett evidence level II (small randomized trial with high false-positive or false-negative errors), 2 were graded as level III (nonrandomized comparative study), and 1 study was graded as level V evidence (case series). Reviewers noted major methodologic flaws and little uniformity in trial designs.

Randomized Controlled Trial
One of the larger double-blind RCTs was published by Omar et al. (2011); it reported on 50 patients with postmastectomy lymphedema.¹⁴⁶ The average length of time that patients had swelling was 14 months (range, 12 to 36 months). They were treated with active or sham laser 3 times a week for 12 weeks over the axillary and arm areas. Also, all participants were instructed to perform daily arm exercises and to wear a pressure garment. Limb circumference, shoulder mobility, and grip strength were measured before treatment and at 4, 8, and 12 weeks. Limb circumference declined over time in both groups, with significantly greater reductions in the active laser group at 8 (20.0 cm vs. 16.4 cm), 12 (29 cm vs. 21.8 cm), and 16 (31 cm vs. 2 cm) weeks. Shoulder flexion and abduction were significantly better in the active laser group at 8 and 12 weeks. Grip strength was significantly better in the active laser group after 12 weeks (26.2 kg vs. 22.4 kg). The durability of these effects was not assessed.

Section Summary: Lymphedema
Several systematic reviews of RCTs and observational studies found methodologic flaws in the available studies and collectively these studies did not consistently report better outcomes in patients receiving LLLT versus a control condition for treatment of lymphedema.

Summary of Evidence
Musculoskeletal and Neurologic Disorders
For individuals who have CTS who receive LLLT, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms, functional outcomes, QOL, and treatment-related morbidity. Both a 2016 systematic review and a TEC Assessment (2010) did not find sufficient evidence from RCTs that LLLT improves outcomes. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have neck pain who receive LLLT, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms, functional outcomes, QOL, and treatment-related morbidity. A 2013 systematic review identified 17 trials, most of which were considered low-quality. Only 2 trials were considered moderate quality, and they found that LLLT led to better outcomes than placebo for chronic neck pain. A TEC Assessment (2010) found conflicting evidence. Additionally, laser types, application dosages, and treatment schedules vary in the available evidence and require further study. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have subacromial impingement syndrome who receive LLLT, the evidence includes RCTs. Relevant outcomes are symptoms, functional outcomes, QOL, and treatment-related morbidity. Most trials did not show a significant benefit of LLLT compared with sham treatment or with an alternative intervention (e.g., exercise). The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have adhesive capsulitis who receive LLLT, the evidence includes RCTs and a systematic review. Relevant outcomes are symptoms, functional outcomes, QOL, and treatment-related morbidity. A Cochrane review evaluating treatments for adhesive capsulitis identified 2 RCTs assessing LLLT. Due to the small number of trials and study limitations, reviewers concluded that the evidence was insufficient to permit conclusions about the effectiveness of LLLT for adhesive capsulitis. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have TMJ pain who receive LLLT, the evidence includes RCTs and several systematic reviews. Relevant outcomes are symptoms, functional outcomes, QOL, and treatment-related morbidity. Meta-analyses of RCTs had mixed findings. A 2021 meta-analysis, which included 33 placebo-controlled randomized trials, found a statistically significant impact of LLLT on pain scores and improved functional outcomes (e.g., mouth opening); however, heterogeneity was high among included trials. Furthermore, RCTs have not compared the impact of LLLT with physical therapy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have low back pain who receive LLLT, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms, functional outcomes, QOL, and treatment-related morbidity. Meta-analyses of RCTs found that LLLT resulted in a significantly greater reduction in pain scores and global assessment scores than a placebo control in the immediate posttreatment setting. Meta-analyses also found that other outcomes (e.g., disability index, range of motion) were significantly better immediately after treatment with active rather than placebo LLLT but not at longer-term follow-up. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have OA knee pain who receive LLLT, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms, functional outcomes, QOL, and treatment-related morbidity. A 2020 systematic review, which pooled study findings, did find that LLLT significantly reduced pain or improved functional outcomes compared with a sham intervention; however, the study was limited by high heterogeneity and inconsistency between regimens and follow-up duration. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have heel pain (i.e., Achilles tendinopathy, plantar fasciitis) who receive LLLT, the evidence includes RCTs and 2 systematic reviews. Relevant outcomes are symptoms, functional outcomes, QOL, and treatment-related morbidity. Findings of sham-controlled randomized trials were inconsistent, and RCTs lacked long term follow up. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have RA who receive LLLT, the evidence includes RCTs and a systematic review. Relevant outcomes are symptoms, functional outcomes, QOL, and treatment-related morbidity. A systematic review of RCTs found an inconsistent benefit of LLLT for a range of outcomes. A 2010 RCT, published after the systematic review, did not find that LLLT was significantly better than a placebo treatment on most outcomes. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have Bell palsy who receive LLLT, the evidence includes a systematic review of 4 RCTs, with 2 RCTs reported in English. Relevant outcomes are symptoms, functional outcomes, QOL, and treatment-related morbidity. One RCT found a significant short-term benefit of LLLT over exercise. Longer-term outcomes (> 6 weeks) were not available. Because Bell palsy often improves within weeks and may completely resolve within months, it is difficult to isolate specific improvements from laser therapy over the natural resolution of the illness. Also, no sham-controlled trials are available. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have fibromyalgia who receive LLLT, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms, functional outcomes, QOL, and treatment-related morbidity. The RCTs evaluating LLLT for treatment of fibromyalgia are small (i.e., < 25 patients each). One RCT (N = 20 patients) found significantly better outcomes with LLLT than with sham, while another (N = 20 patients) did not find statistically significant between-group differences for similar outcomes. Additional RCTs with sufficient numbers of patients are needed to establish the efficacy of LLLT for fibromyalgia. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Wound Care and Lymphedema
For individuals who have chronic nonhealing wounds who receive LLLT, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms, functional outcomes, QOL, and treatment-related morbidity. The few existing RCTs tend to have small sample sizes and potential risk of bias. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have lymphedema who receive LLLT, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms, functional outcomes, QOL, and treatment-related morbidity. Multiple systematic reviews detected methodologic flaws in the available studies and did not consistently find better outcomes for patients receiving LLLT than those receiving a control condition for the treatment of lymphedema. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Practice Guidelines and Position Statements
Guidelines or position statements will be considered for inclusion in Supplemental Information if they were issued by, or jointly by, a U.S. professional society, an international society with U.S. representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology
In 2017, the Mucositis Prevention Guideline Development Group published guidelines on preventing oral and oropharyngeal mucositis in children undergoing hematopoietic cell transplantation.¹⁴⁷ The guidelines were based on an evidence review consisting of randomized controlled trials that evaluated interventions such as cryotherapy and low-level laser therapy (LLLT). The guidelines suggested that LLLT could be offered to children but classified this recommendation as weak.

In 2020, the Multinational Association of Supportive Care in Cancer and the International Society of Oral Oncology published joint guidelines on the management of mucositis secondary to cancer therapy.¹⁴⁸

For the prevention of oral mucositis, the 2 associations recommended the following treatments, based on level 1 evidence: LLLT in patients undergoing radiotherapy with chemotherapy for head and neck cancer; LLLT in patients receiving hematopoietic cell transplantation conditioned with high-dose chemotherapy with or without total body irradiation; recombinant human keratinocyte growth factor-1 in patients receiving high-dose chemotherapy and total body irradiation, followed by autologous cell transplantation for hematologic malignancy; and benzydamine mouthwash in patients with head and neck cancer receiving moderate-dose radiotherapy without concomitant chemotherapy.

Additionally, numerous treatments were recommended for the prevention of oral mucositis based on level II evidence, including LLLT in patients undergoing radiotherapy, without concomitant chemotherapy, for head and neck cancer. Several LLLT protocols are outlined by the guideline based on cancer treatment modality, ranging in wavelength from 632.9 to 660 nm.

American Physical Therapy Association
In 2018, the American Physical Therapy Association published an updated guideline on the diagnosis and treatment of Achilles tendinitis.¹⁴⁹ The use of LLLT was given a level D recommendation, meaning that no recommendation could be made due to contradictory evidence. This is a change from the previous version of the guideline published in 2010, which gave LLLT a level B recommendation.¹⁵⁰

National Institute for Health and Care Excellence
In 2009, NICE issued guidance on early management of persistent, nonspecific low back pain and did not recommend laser treatment, citing limited evidence.¹⁵¹ The 2016 and 2020 updated guidance does not mention laser therapy.¹⁵¹

North American Spine Society
In 2020, the North American Spine Society published a guideline on the diagnosis and treatment of low back pain.¹⁵² The guideline was based on a systematic review of the literature to address key clinical questions regarding the diagnosis and treatment of adults with nonspecific low back pain.

Table 18. North American Spine Society Guideline Recommendations for Laser Therapy

Guideline Recommendation	Grade of Recommendation
"It is suggested that the combination of laser therapy (low-level or high-level) with exercise provides better short-term relief of pain than either exercise or laser therapy alone."	B
"There is conflicting evidence that the combination of laser therapy with exercise provides better short-term improvement in function compared to exercise or laser therapy alone."	I
"It is suggested that there is no short-term benefit of laser therapy (low-level or high-level) when compared with exercise alone."	B

Grade of Recommendation (levels of evidence range from Level I [high quality randomized controlled trial] to Level V [expert consensus]): A = Good evidence (Level I studies with consistent findings) for or against recommending intervention; B = Fair evidence (Level II or III studies with consistent findings) for or against recommending intervention; C = Poor quality evidence (Level IV or V studies) for or against recommending intervention; I = Insufficient or conflicting evidence not allowing a recommendation for or against intervention.

American College of Physicians
In 2017, the American College of Physicians released guidelines relating to noninvasive treatments for chronic low back pain.¹⁵³ The guidelines strongly recommended that patients with chronic low back pain should first seek nonpharmacologic treatment such as exercise, multidisciplinary rehabilitation, acupuncture, and mindfulness-based stress reduction-all based on moderate quality evidence. The recommendation also stated that patients with chronic low back pain should seek treatments such as tai chi, yoga, motor control exercise, progressive relaxation, electromyography biofeedback, LLLT, operant therapy, cognitive behavioral therapy, or spinal manipulation-all based on low-quality evidence. While the College stated that LLLT has a small effect on pain and function, it found the evidence insufficient for the use of LLLT.

In 2020, the American College of Physicians published a joint guideline on management of acute pain from non-low back musculoskeletal injuries with the American Academy of Family Physicians.¹⁵⁴ No recommendations are made specific to LLLT, but the guideline notes that laser therapy did not significantly reduce pain in 1 to 7 days compared to placebo.

American Academy of Orthopaedic Surgeons
In 2016, the American Academy of Orthopaedic Surgeons' guidelines on the management of carpal tunnel syndrome indicated the: "limited evidence supports that laser therapy might be effective compared to placebo."¹⁵⁵

U.S. Preventive Services Task Force Recommendations
Not applicable

Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed in Table 19.

Table 19. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT04784377	High Intensity Versus Low Level Laser Therapy in Treatment of Patients With Subacromial Impingement Syndrome: A Randomized, Double-blind, Controlled Trial	45	Sep 2021
NCT04287725	Additional Effects of The Association of The Photobiomodulation Therapy (904 Nm) With Exercise in Participants with Chronic Non-Specific Low Back Pain In The Long Term	130	Dec 2022
NCT04690439	Evaluating the Effectiveness of Photobiomodulation Therapy in the Management of Breast Cancer-related Lymphedema: a Randomized Controlled Trial	104	Feb 2028
NCT05242991	Comparison of Two Photobiomodulation Protocols for the Oral Mucositis and Xerostomia Prevention in Irradiated Head and Neck Cancer Patients: a Randomized, Multicenter, Single-blind Controlled Clinical Trial	132	Oct 2024
NCT04831346	Effects of Low-Level Laser Therapy Versus Soft Occlusive Splints on Mouth Opening and Surface Electromyography in Temporomandibular Disorders	100	Dec 2022
NCT04826263	Comparison of the Effectiveness of Low-level Laser Therapy and Extracorporeal Shock Wave Therapy in Plantar Fasciitis Treatment	48	May 2021
NCT04596410	Double-blind, Randomized, Multi-center, Non-inferiority Clinical Trial Comparing Two Photobiomodulation Protocols in the Analgesia of Chemotherapy-induced Oral Mucositis in Children	406	Feb 2023
NCT03945240	Evaluating Different Low-level Laser Therapies to Treat Neck Pain in Air Force Pilots and Flight Crew	296	Sep 2024
Unpublished
NCT02696408	Efficacy of Prophylactic Low Level Laser Therapy (LLLT) Performed by Nurses for Decreasing Severity of Oral Mucositis During Hematopoietic Stem Cell (HSC) Transplantation: a Randomized Double-Blind Multicenter Prospective Phase III Trial	234	Dec 2019 (completed)
NCT02682992	A Phase II Prospective Trial of Low-Level Laser Therapy for Prevention of Oral Mucositis in Patients Receiving Chemotherapy and Radiation for Head and Neck Cancer	47	Nov 2020 (completed)
NCT04682171	Effects of Low Level Laser Therapy on Knee Pain and Function in Patients With Knee Osteoarthritis	44	June 2021 (completed)

NCT: national clinical trial.
^a Denotes industry-sponsored or cosponsored trial.

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de Carvalho ME, de Carvalho RM, Marques AP, et al. Low intensity laser and LED therapies associated with lateral decubitus position and flexion exercises of the lower limbs in patients with lumbar disk herniation: clinical randomized trial. Lasers Med Sci. Sep 2016; 31(7): 1455-63. PMID 27379776
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S GN, Kamal W, George J, et al. Radiological and biochemical effects (CTX-II, MMP-3, 8, and 13) of low-level laser therapy (LLLT) in chronic osteoarthritis in Al-Kharj, Saudi Arabia. Lasers Med Sci. Feb 2017; 32(2): 297-303. PMID 27913970
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Youssef EF, Muaidi QI, Shanb AA. Effect of Laser Therapy on Chronic Osteoarthritis of the Knee in Older Subjects. J Lasers Med Sci. 2016; 7(2): 112-9. PMID 27330707
Tumilty S, McDonough S, Hurley DA, et al. Clinical effectiveness of low-level laser therapy as an adjunct to eccentric exercise for the treatment of Achilles' tendinopathy: a randomized controlled trial. Arch Phys Med Rehabil. May 2012; 93(5): 733-9. PMID 22541305
Wang W, Jiang W, Tang C, et al. Clinical efficacy of low-level laser therapy in plantar fasciitis: A systematic review and meta-analysis. Medicine (Baltimore). Jan 2019; 98(3): e14088. PMID 30653125
Guimaraes JS, Arcanjo FL, Leporace G, et al. Effect of low-level laser therapy on pain and disability in patients with plantar fasciitis: A systematic review and meta-analysis. Musculoskelet Sci Pract. Feb 2022; 57: 102478. PMID 34847470
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Alayat MS, Elsodany AM, El Fiky AA. Efficacy of high and low level laser therapy in the treatment of Bell's palsy: a randomized double blind placebo-controlled trial. Lasers Med Sci. Jan 2014; 29(1): 335-42. PMID 23709010
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Coding Section

Codes	Number	Description
CPT	0552T	Low-level laser therapy, dynamic photonic and dynamic thermokinetic energies, provided by a physician or other qualified health care professional
	97037 (effective 01/01/2024)	Low‐level laser therapy for post‐operative pain reduction
HCPCS	S8948	Application of a modality (requiring constant provider attendance) to one or more areas; low-level laser; each 15 minutes
ICD-10-CM (effective 10/01/15)		Investigational for all diagnoses
	C00-D49	Neoplasms code range
	G56.0-G56.02	Carpal tunnel syndrome
	L98.411-L98.499	Non-pressure chronic ulcer of skin, not elsewhere classified, code range
	M05.00-M05.9	Rheumatoid arthritis with rheumatoid factor code range
	M06.00-M06.9	Other rheumatoid arthritis code range
	M17.0-M17.9	Osteoarthritis of knee code range
	M25.521-M25.529	Pain in elbow code range
	M26.60-M26.69	Temporomandibular joint disorders code range
	M54.5	Low back pain
	M75.40-M75.42	Impingement syndrome of shoulder code range
	M76.60-M76.72	Achilles tendinitis code range
	M79.7	Fibromyalgia
ICD-10-PCS (effective 10/01/15)		ICD-10-PCS codes are only used for inpatient services. There is no specific ICD-10-PCS code for this procedure.
Type of Service	Medicine
Place of Service	Oupatient

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

History From 2024 Forward

01/01/2024 NEW POLICY

04/17/2024 Annual review, no changes to policy intent.

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Low-Level Laser Therapy - CAM 20156HB