For members with benefit contracts or Plans with Primary Coverage Criteria, Low Level Light (Laser) Therapy is not covered because it fails to meet the Primary Coverage Criteria (“The Criteria”) of the applicable benefit certificate or health plan (The Criteria require, among other things, that there be scientific evidence of effectiveness, as defined in The Criteria. The Criteria exclude coverage of treatments, such as low level light (laser) therapy because of lack of scientific evidence of effectiveness.

 

For members with member benefit contracts or Plans with explicit exclusion language for experimental or investigational services, Low Level Light (Laser) Therapy is not covered because it is considered experimental or investigational treatment, as defined in the applicable benefit contract or health plan, which excludes coverage of experimental or investigational treatment or services.

 

Infrared light therapy involves the treatment of damaged tissues with light from a low intensity infrared laser or light-emitting diode. Since this is a noninvasive treatment, the applied light must travel through the skin and any other overlying  tissues to reach the site of damage. The infrared light must then be absorbed to cause a biostimulatory, healing effect. Although the mechanism or mechanisms by which infrared light therapy might reduce pain and promote healing have not been established, this modality has been investigated as a treatment for a wide range of neuropathies, arthritis, and musculoskeletal disorders, including: diabetic neuropathy, osteoarthritis, rheumatoid arthritis, ankle sprains, plantar fasciitis, chondromalacia patellae, myofascial pain, musculoskeletal pain, fibromyalgia, tendonitis, epicondylitis, and temporomandibular joint disorder. Potential benefits of infrared light therapy include its safety profile and its noninvasive, nonpharmacological nature.

 

Definitive patient selection criteria have not been established for infrared light therapy for musculoskeletal pain or neuropathy.

 

Infrared light therapy treatment protocols vary in many respects. One significant aspect of variation is the light source, which is usually a single-beam infrared laser. The light source could also be a cluster of laser sources or an array of infrared light-emitting diodes. When performed with an array of light-emitting diodes, this procedure has been referred to as monochromatic near-infrared photoenergy (MIRE) therapy. These light sources usually emit light at a single wavelength. The reviewed studies involved infrared light of 820, 830, 860,890, 904, and 1060 nm, some as continuous beams and some as pulsed beams.   Variations in protocols in studies include preparation of the treatment site, placement of the laser - static or sweeping exposure, duration of exposure, total number of treatment and the treatment schedule.  

 

Although a number of placebo-controlled, double-blinded randomized trials of infrared light report that this therapy can reduce pain for certain types of arthritis and other musculoskeletal disorders, other equally well-designed studies report that it is ineffective. Further studies of infrared light therapy for treatment of pain are needed to determine if these conflicting results have arisen due to differences in the infrared therapy applied or differences in the populations of patients who underwent treatment. Efforts to determine effective treatment parameters may be assisted by studies of the fundamental biological effects of low-intensity infrared light. Karu et al. (2004) have reported that infrared light promotes cellular attachment in vitro and have postulated that this effect occurs due to metabolic changes initiated by mitochondrial light absorption. Other potential benefits have been documented by Reddy (2003), who examined the effects of infrared laser light in an animal model and found that this treatment promotes collagen synthesis and wound healing. A thorough evaluation of the wavelengths and intensities of infrared light that stimulate biological activities in experimental systems may guide investigators to discovering the optimal parameters for clinical treatment.

 

Hayes, Inc., has issued a technology assessment on Low Level Laser Light Therapy with the following conclusion: A rating of Investigational or experimental is assigned to LLLT for treatment of pain and disability due to knee osteoarthritis and hand osteoarthritis. The hand rating is based on limited evidence of no benefit. A rating of investigational or experimental is assigned LLLT for treatment of 1) osteoarthritis in joints other than the knee or hand; 2) pain and disability due to rheumatoid arthritis in the hand and foot; and 3) pain and disability due to rheumatoid arthritis in joints other than the hand or foot.  A rating of investigational or experimental is assigned LLLT for treatment of chondromalacia patellae based on very weak evidence of only slight benefit. A rating of investigational or experimental is assigned to LLLT for based on limited evidence of no benefit. A rating of investigational or experimental is also assigned to patient-administered LLLT due to the lack of evidence pertaining to the efficacy and safety of LLLT used outside of healthcare settings.

 

A literature search was performed for the period of 2003 through October 2005. No published studies were identified that would prompt reconsideration of the policy statement, which remains unchanged. Irvine and colleagues reported on the results of a small double-blinded study of 15 patients with carpal tunnel syndrome who were randomized to receive either low-level laser therapy or sham laser therapy. There was a significant improvement in both groups, but there was no significant difference between the groups. Bakhtiary and Rashidy-Pour reported on the outcomes of 50 consecutive patients with carpal tunnel syndrome who were randomized to receive either ultrasound therapy or low-level laser therapy. Improvement was significantly better in those randomized to ultrasound.

 

A search of the MEDLINE database was performed for the period of August 2005 through December 2006. A single publication was found for this period, which was a review of the studies discussed above.  No additional published studies were identified. Therefore, the policy statement is unchanged.

 

A search of the MEDLINE database for the period of January 2007 through February 2008 identified 2 studies, both from Turkish University Medical Centers. One double-blinded randomized sham-controlled trial with 81 patients (141 hands) found slight pre- to post-treatment improvements in sensory (0.2 msn) and distal (0.3 msn) latencies for the laser group, while sensory nerve velocity improved (by 2.7 and 2.1 m/sn) in both groups (a wrist splint was used at night in both groups).  Other measures of nerve conduction were not affected by treatment. There were no differences between the groups in visual analogue scales (VAS) for pain or in symptom severity scores. A second small, double-blinded randomized controlled trial (19 patients with rheumatoid arthritis and carpal tunnel syndrome) found slight improvement in subjective scales of pain and function (e.g., 27-point improvement vs. 13-point improvement on VAS) compared with sham laser therapy, but no differences between groups in objective functional measures (e.g., grip strength, 0.3 vs. 0.3) or in measures of nerve conduction (e.g., motor nerve conduction velocity, 55 vs. 55). Existing literature has not shown laser therapy to be as effective as established treatments for the treatment of carpal tunnel syndrome. Therefore, low-level laser therapy is considered investigational.

 

A review of the published literature through December 2009 identified studies and systematic reviews for Low-Level Laser Therapy for the treatment of various indications including, carpal tunnel syndrome, elbow, knee, shoulder and low back pain, Achilles tendinopathy, rheumatoid arthritis, temporal mandibular joint pain, fibromyalgia and wound healing.  

 

For the most part, studies of LLLT for treatment of pain compare laser treatment with a sham treatment only, rather than comparison with treatments known to be effective. With very few exceptions, the studies are from centers outside the US. A 2009 systematic review included controlled trials of LLLT as primary intervention for any tendinopathy (Tumilty, 2009).  Twenty-five trials were included, with conflicting findings for each indication studied. Twelve studies showed positive effects and 13 were inconclusive or showed no effect. Thirteen studies investigated LLLT for epicondylitis, six of them showing positive results. The largest of these trials had only 58 subjects. Two of the positive studies were of poor quality. Four studies examined LLLT for tendinopathy in the shoulder, four of them of high quality. The largest of these trials had just 30 subjects. Three of these trials found a positive effect of LLLT. Two of the positive studies had placebo controls and the third compared LLLT with ultrasound or placebo. Of the 5 trials of LLLT for Achilles tendinitis included in the review, 2 demonstrated a benefit of LLLT. One of the positive and one of the negative studies of LLLT for Achilles tendinitis received the highest quality rating. One of the negative studies was the largest study (n=89) included in the review but scored only 5 of 10 possible points for study quality. Three studies included subjects with a variety of indications; all reported inconclusive or no effect of LLLT. The authors reported that dosages used in the positive trials suggested that there is an effective dosage window, however the only parameter reported for all studies was wavelength. Power density and dose were not provided or there was too little information provided in the studies to calculate the dose. Studies of LLLT for specific joints with at least 20 subjects are summarized below.

 

The largest body of evidence for LLLT describes its use in treatment of carpal tunnel syndrome. As part of the FDA approval process, the manufacturer of the MicroLight device conducted a double-blind, placebo-controlled study of 135 patients with moderate to severe symptoms of carpal tunnel syndrome who had failed conservative therapy for at least a month. However, the results of this study have not been published in the peer-reviewed literature, and only a short summary is available in the FDA Summary of Safety and Effectiveness , which does not permit scientific conclusions. Naeser and colleagues published the results of a controlled study of 11 patients with mild to moderate carpal tunnel syndrome who received real and sham treatment of low-level laser acupuncture and TENS therapy (Naeser, 2002). This study is also too small to permit scientific conclusions. Irvine and colleagues reported on the results of a small double-blinded study of 15 patients with carpal tunnel syndrome who were randomized to receive either low-level laser therapy or sham laser therapy (Irvine, 2004).  There was a significant improvement in both groups, but there was no significant difference between the groups. A 2007 double-blinded randomized sham-controlled trial with 81 patients (141 hands) found slight pre- to post-treatment improvements in sensory (0.2 msn) and distal (0.3 msn) latencies for the laser group, while sensory nerve velocity improved (by 2.7 and 2.1 m/sn) in both groups (a wrist splint was used at night in both groups) (Evcik, 2007). Other measures of nerve conduction were not affected by treatment. There were no differences between the groups in visual analogue scales (VAS) for pain or in symptom severity scores. A second small, double-blinded randomized controlled trial (19 patients with rheumatoid arthritis and carpal tunnel syndrome) found slight improvement in subjective scales of pain and function (e.g., 27-point improvement vs. 13-point improvement on VAS) compared with sham laser therapy, but no differences between groups in objective functional measures (e.g., grip strength, 0.3 vs. 0.3) or in measures of nerve conduction (e.g., motor nerve conduction velocity, 55 vs. 55). (6) Chang and colleagues report on a randomized controlled trial (RCT) with short follow-up comparing LLLT with sham treatment in just 36 patients (Chang, 2008).  After 2 weeks of treatment and 2 weeks after the end of treatment, visual analog scores (VAS) for pain were lower in the treatment group than in the sham group (P<0.05). After 2 weeks of treatment, differences in grip strength, symptoms, and functional assessment were nonsignificant, but were significant (P<0.05) at 2-week follow-up. There were no significant between-group differences on nerve conduction studies at either time point. Another RCT with sham control, a study with 80 patients, was reported (Shooshtari, 2008) Outcomes were measured at the end of 15 treatment sessions (5x/week for 3 weeks). In this study, the treatment group showed significant improvement in clinical symptoms, hand grip, and nerve conduction studies.

 

Bakhtiary and Rashidy-Pour reported on the outcomes of 50 consecutive patients with carpal tunnel syndrome who were randomized to receive either ultrasound therapy or low-level laser therapy (Bakhtiary, 2004). Improvement was significantly better in those randomized to ultrasound. In a study from Turkey, Dincer et al. compared splinting with ultrasound (US), splinting with LLLT, and splinting alone in a RCT (Dincer, 2009).  Sixty women were randomized; 10 did not complete the study. One hundred hands (50 women), 30 in the splint with US group, 36 in the splint with LLLT group, and 34 with splint only were followed for 3 months after treatment and included in the analysis. Outcome measures were the Boston Questionnaire Symptom Severity Scale Score (BQ-SSS), the Boston Questionnaire Functional Status Scale (BQ-FSS, visual analogue scale for pain (VAS), second digit-wrist median nerve sensory velocity (SV), and median nerve motor distal latency (MDL). Splinting with US or LLLT was more effective than splinting alone on all measures 3 months after treatment. LLLT was significantly more effective than US on measures of pain on VAS, BQ-SSS (P=0.03) and SV. Patient satisfaction was higher in the US and LLT groups than the splint only group (P=0.05).

 

Authors of a systematic review published in 2008 grouped trials by application technique and wave lengths and reported that 7 out of the 13 included trials had a narrowly defined regimen where lasers of 904 nm wavelength with low output (5-50 mW) were used to irradiate the tendon insertion at 2-6 points on the lateral elbow (Bjordal, 2008). Positive results in these trials were consistent on outcomes of pain and function, and significance persisted for at least 3-8 weeks after the end of treatment. The authors noted that the conclusions of their review differed from conclusion of other, prior reviews of this topic.

 

A 2008 update of the Cochrane Database System Review of low level laser therapy for nonspecific low back pain concluded that “based on the heterogeneity of the populations, interventions, and comparison groups, we conclude that there are insufficient data to draw firm conclusions on the clinical effect of LLLT for low-back pain” (Yousefi-Nooraie, 2008).  Chou and colleagues assessed benefits and harms of nonpharmacological therapies including LLLT for acute and chronic low back pain in a 2007 review of evidence and did not find good evidence of efficacy for LLLT for either indication (Chou, 2007). In a study by Djavid et al., 61 patients were randomized to LLLT alone , LLLT with exercise, or sham laser treatment with exercise (Djavid, 2007).  Outcomes of pain on VAS, lumbar range of motion (ROM), and disability were measured by blinded assessors after 6 weeks of treatment, after another 6 weeks and 12 weeks without treatment. By intention-to-treat analysis, there were no between-group differences for any outcome measure immediately after the 6-week intervention. After 6 weeks without intervention, there was no difference between the LLLT alone group and the placebo laser therapy plus exercise group however, in the LLLT plus exercise group, pain had reduced by 1.8 cm (95% confidence interval [CI] 0.1 to 3.3, p=0.03), lumbar ROM increased by 0.9 cm (95% CI 0.2 to 1.8, p=<0.01) on the Shrober Test and by 15 degrees (95% CI 5-25, p<0.01) of active flexion, and disability reduced by 9.4 points (p=0.03) on the Oswestry Disability Index more than in the placebo laser therapy plus exercise group. The authors advise that larger trials are needed to detect differences between groups for some outcomes.

 

Stergioulas and colleagues randomized 52 recreational athletes with chronic Achilles tendinopathy symptoms to an 8-week (12 sessions) program eccentric exercises (EE) with LLLT or with sham LLLT (Stergioulus, 2008).  By intention-to-treat analysis, results for the primary outcome of pain during physical activity on visual analog scale (VAS) were significantly lower in the EE with LLLT group at 4 weeks, 8 weeks, and 12 weeks after randomization. Results of EE with LLLT at 4 weeks were similar to results for the EE plus sham LLLT group after 12 weeks.

 

In a study designed to assess the effectiveness of LLLT in patients with subcacromial impingement syndrome, 44 patients were randomized in equal numbers to receive a 12-week home exercise program with or without LLLT (Bal, 2009).  Outcome measures of night pain, shoulder pain and disability index (SPADI), and University of California-Lost Angeles end-result scores were assessed at the 2nd and 12th weeks of intervention. Both groups showed significant reductions in night pain and SPADI at 2- and 12-week assessments. UCLA scores improved significantly in both groups at 12 weeks. No distinct advantage was demonstrated by LLLT over exercise alone. Another RCT compared outcomes of a 3-week program of exercise with either LLLT or sham therapy for treatment of subacromial impingement (Yeldan, 2009). Both groups improved significantly, and there were no significant between-group differences on measures of pain, function, disability, and muscle strength. Sixty-three patients with frozen shoulder were included in a RCT comparing an 8-week program of LLLT or placebo (Stergioulas, 2008). Compared to the sham group, the active laser group had a significant decrease in overall, night, and activity pain scores after 4 weeks and 8 weeks of treatment, and at the end of 8 more weeks of follow-up. At the same time intervals, a significant decrease in shoulder pain, disability index (SPADI) scores, and Croft shoulder disability questionnaire scores was observed, while a significant decrease in disability of arm, shoulder, and hand questionnaire (DASH) scores was observed at 8 weeks of treatment and 16 weeks’ postrandomization; and a significant decrease in health assessment questionnaire scores was observed at 4 weeks and 8 weeks of treatment.

 

In 2007, Bjordal et al. published a systematic review of placebo-controlled RCTs to determine the shortterm efficacy of physical interventions for osteoarthritic knee pain (Bjordal, 2007). They concluded that transcutaneous electrical stimulation (TENS) (including interferential currents), and LLLT offered clinically relevant pain relieving effects on VAS compared to placebo control. Follow-up data up to 121 weeks were sparse, but positive effects seemed to persist for at least 4 weeks after the course of treatment.

 

A 2005 Cochrane Review included 5 placebo-controlled RCTs and found that relative to a separate control group, LLLT reduced pain by 1.10 points on visual analogue scale compared to placebo, reduced morning stiffness duration by 27.5 minutes, and increased tip-to-palm flexibility by 1.3 cm (Brosseau, 2005).  Other outcomes, such as functional assessment, range of motion and local swelling, did not differ between groups. For RA, relative to a control group using the opposite hand (one study), there was no difference observed between the control and treatment hand for morning stiffness duration and no significant improvement in pain relief. The authors noted that “despite some positive findings, this meta-analysis lacked data on how LLLT effectiveness is affected by four important factors: wavelength, treatment duration of LLLT, dosage and site application over nerves instead of joints.”

 

Outcomes of trials of LLLT for TMJ pain are inconsistent. In a study from Brazil, 40 patients with TMJ were treated with LLLT or placebo (da Cunha, 2008).  After 4 weeks of weekly treatment, patients were evaluated on pain on visual analog scale (VAS) and the Craniomandibular Index (CMI). Both groups improved on both measures (p<0.05) and there were no significant differences between groups. Emshoff et al. evaluated LLLT in the management of TMJ in a double-blinded RCT with 52 patients randomized equally to LLLT or sham treatment (Emshoff, 2008).  After 8 weeks of 2-3 treatments/week, both groups showed improvements in pain during function. Between-group differences were not significant. Fikácková and colleagues treated 61 patients TMJ or myofascial pain with LLLT at one of 2 densities (10 J/cm2 or 15 J/cm2) and 19 patients with sham LLLT (0.1 J/cm2) (Fikácková, 2007). Outcomes were measured by self administered questionnaire. The authors report significantly better outcomes in patients treated with 10 j/cm2 or 15 J/cm2 than in patients given sham treatment. There were no differences in outcomes between patients with TMJ and myofascial pain.

 

Matsutani and colleagues randomized 20 patients with fibromyalgia to receive laser treatment and stretching exercises or stretching alone (Matsutani, 2007).  Outcome measures were visual analog scale of pain (VAS) and dolorimetry at tender points, quality of life on the Fibromyalgia Impact Questionnaire (FIQ), and the 36-item Short-Form Health Survey (SF-36). At the end of treatment, both groups demonstrated pain reduction, higher pain threshold at tender points (all p<0.01), lower mean FIQ scores, and higher SF-36 mean scores (all p<0.05). No significant differences were found between groups.

 

A 2004 evidence report on vacuum assisted and low-level laser wound therapies for treatment of chronic non-healing wounds prepared for the Agency for Healthcare Research and Quality was based on 11 studies of LLLT (Samson, 2004). It stated that “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 to 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”. No newer studies were identified in the literature search. Clinical trials are underway.

 

In summary, the available literature has not shown laser therapy to be as effective as established treatments for the treatment of various musculoskeletal conditions, including carpal tunnel syndrome, or for wound healing. Outcomes of studies comparing LLLT with sham laser therapy for treatment of pain are inconsistent and generally involve small numbers of participants. There is some evidence of a dose dependent effect in the treatment of tendinopathies. Randomized controlled trials involving larger numbers of patients comparing low-lever laser therapy with established treatments and reporting complete dosage information are required. Evidence for LLLT for many conditions including chronic wounds and nerve damage is extremely limited and FDA clearance has not been given for use of LLLT   for these indications.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

(2014) reported correlation coefficients (R2) of 0.573 (p=0.03) and 0.510 (p=0.02) for associations between WBC and neutrophil counts, respectively. (Nishikawa, 2014).  In this study, ATP levels in 5 patients who developed viral infections in the early post-transplantation period (<50 days) were within normal limits. Methodological limitations prevented any conclusion about the association of ATP levels with infections in 8 patients in the late post-transplantation period (>120 days). In a study of 306 patients at a single U.S. center, Sageshima et al (2014) reported a correlation coefficients (R2) of 0.264 (p<0.001) for the association between ATP production and WBC (Sageshima, 2014). In this study, mean (SE) ATP production in patients with biopsy-proven rejection (389 [56] ng/ml) and borderline/clinical rejection (254 [41] mg/mL) were not statistically higher compared with ATP production in patients without rejection (not reported).

 

Subsequent studies in kidney transplant recipients have demonstrated no association between ATP production and risk of acute rejection or viral infections using manufacturer-recommended cutoffs for ImmuKnow®  (Libri, 2013; Myslik, 2014) have suggested an alternative approach to determining optimal cutoff values (Quaglia, 2014; Wang, 2014). In a prospective cohort study of 55 patients followed for 3 years, Libri et al (2014) observed that ATP production was often lower in patients with acute rejection compared with patients without acute rejection, and was often greater in patients with infection compared with patients without infection. Using labelled cutoffs for ImmuKnow®, AUC was 0.44 (95% CI: 0.18 to 0.71) for acute rejection and 0.37 (95% CI: 0.22 to 0.53) for viral or major respiratory tract infections. In a prospective study of 67 patients undergoing kidney transplant, patients with low preoperative ATP production had statistically fewer rejection episodes than those with high preoperative ATP production (p<0.001) (Myslik, 2014). The cutoff used for this analysis was 300 ng/mL. To optimize ImmuKnow® performance, Quaglia et al (2014) and Wang et al (2014) both proposed assessing change in ATP production over time, rather than single values. In a retrospective study of 118 patients, Quaglia et al reported AUC of 0.632 (95% CI: 0.483 to 0.781) for infection risk using a cutoff of –30 ng/mL for the decrease in ATP production from month 1 to month 3 (Quaglia, 2014). In a prospective study of 140 patients, Wang et al reported AUC of 0.929 for risk of acute rejection using a cutoff of 172.55 ng/mL for the increase in ATP production from “right before” the rejection episode to the occurrence of rejection (Wang, 2014).

 

Natsuda et al (2014) assessed ATP production in 28 patients co-infected with HIV and HCV (Natsuda, 2014). These patients were all receiving anti-retroviral therapy with undetectable viral load in most, and were classified Child-Pugh class A. Results were compared with those of 24 HCV-infected liver transplant recipients and 11 healthy volunteers. Median ATP levels in the HIV/HCV co-infected group (259 ng/ML [range: 30-613]) were statistically higher compared with the HCV mono-infected group (33 ng/mL [range: 6-320]; Mann-Whitney U test, p<0.001) and significantly lower compared with healthy volunteers (446 ng/mL [range: 309-565]; Mann-Whitney U test, p=0.001). In HIV/HCV co-infected patients, ATP production was significantly correlated with CD4+ cell count (Spearman rank correlation, p=0.03) but not with CD4/CD8 ratio (Spearman rank correlation, p=0.76). The clinical significance of these findings, for either HCV mono-infected liver transplant recipients or HIV/HCV co-infected patients, is unclear.

 

Liu et al (2014) compared ATP production in 22 patients with lupus nephritis and severe infection requiring hospitalization, 74 patients with lupus nephritis and no infection, and 28 healthy controls (Liu, 2014). Mean ATP production was significantly lower in patients with lupus nephritis and severe infection compared with non-infected patients and healthy controls (p<0.01 for both comparisons). Mean ATP production in non-infected LN patients did not differ statistically from that in healthy controls. Using a cutoff of 300 ng/mL, sensitivity and specificity for severe infection were both 77%. Strength of the correlation between ATP production and severe infection (r=–0.040, p<0.001) was less than that between C-reactive protein and severe infection (r=0.962, p<0.001).

 

 

In 2015, Barbosa and colleagues evaluated the efficacy of orthoses and patient education with or without the addition of LLLT in patients with mild and moderate carpal tunnel syndrome (Barbosa, 2015). Laser treatment was provided twice a week for 6 weeks. Forty-eight patients were randomized and 30 (63%) completed the study protocol. Compared with baseline, outcomes (eg, scores on the Boston Carpal Tunnel Questionnaire and its domains) did not differ significantly between groups after treatment. The study is limited by the high dropout rate.

 

 

A 2015 qualitative systematic review by Doeuk and colleagues addressed literature on LLLT for patients undergoing maxillofacial surgery (Doeuk, 2015). The authors identified a total of 45 studies that included more than 10 patients. Three RCTs on treatment of oral mucositis in patients with head and neck cancer were identified and these found significantly better outcomes (eg, pain, symptoms, quality of life) in patients receiving active LLLT versus sham treatment. Overall, the authors conduced that LLT “seems to be effective” for treating oral mucositis after head and neck cancer therapy, but that LLLT cannot be considered a valid treatment option for patients undergoing other types of maxillofacial surgery. The systematic review did not address prophylactic LLLT.

 

In 2015, 3 relatively small (ie, <50 patients), double-blind, sham-controlled RCTs on prevention of oral mucositis in patients undergoing cancer treatment were published. Gautam and colleagues reported on 46 patients with head and neck cancer scheduled for radiotherapy and found significant reductions in the incidence and duration of severe oral mucositis (p=0.0016) and severe pain (p=0.023) after LLLT versus sham (Gautam, 2015). Oton-Leiter reported on 30 head and neck cancer patients undergoing chemoradiation and found that the oral mucositis grade was significantly lower in the LLLT group than the control group at the week 1, 3, and 5 evaluations (Oton-Leite, 2015). For example, at the last clinical evaluation (week 5), the rate of grade 3 oral mucositis was 25% in the LLLT group and 54% in the control group. The third RCT, by Ferreira and colleagues, included 36 patients with hematologic cancer undergoing HSCT (Ferreira, 2016). The overall incidence of oral mucositis did not differ significantly between the groups (p=0.146). However, the rate of severe oral mucositis (grade 3 or 4) was significantly lower in the laser group (18%) than the control group (61%; p=0.015).

 

 

Several systematic reviews and meta-analyses of RCTs on LLLT for temporomandibular joint (TMJ) pain have been published. A 2015 systematic review by Chen and colleagues published a meta-analysis of pain and functional outcomes after LLLT for TMJ pain (Chen, 2015). Fourteen placebo-controlled RCTs were identified. Ten trials provided data on pain, measured by a visual analog scale (VAS). A pooled analysis of these studies found no significant difference between active treatment and placebo on the VAS at final follow-up (weighted mean difference [WMD], -19.39; 95% CI, -40.80 to 2.03; p=0.08). However, meta-analyses did find significantly better functional outcomes (ie, maximum active mouth opening, maximum passive mouth opening). For example, the mean difference in maximum active mouth opening, active treatment versus placebo, at final follow-up was a mean difference (MD) of 4.18 (95% CI, 0.73 to 7.63).

 

 

A number of RCTs and several systematic reviews of RCTs have been published. In 2015, Huang and colleagues published a systematic review of RCTs on LLLT for treatment of nonspecific chronic low back pain (Huang, 2015a). The review included trials comparing LLLT and placebo that reported pain and/or functional outcomes and reported a PEDro quality score. Seven trials with a total of 394 patients were included (202 assigned to LLLT and 192 assigned to placebo). Six of the 7 trials were considered high quality (ie, a PEDro score of at least 7 out of 11 possible points). Primary outcomes of interest were posttreatment pain measured by VAS and disability measured by the Oswestry Disability Index (ODI). Range of motion and change in pain scores were secondary outcomes. In pooled analyses of study data, the authors found a statistically significant benefit of LLLT on pain outcomes, but not disability or range of motion. For the primary outcome posttreatment pain scores, in a meta-analysis of all 7 trials, mean VAS was significantly lower in the LLLT compared with 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, there was not a statistically significant difference between LLLT and placebo groups (WMD = -2.89; 95% CI, -7.88 to 2.29).

 

 

Several RCTs and systematic review of RCTs on LLLT for treatment of knee osteoarthritis have been published. In 2015, Huang and colleagues published a systematic review of RCTs comparing at least 8 treatment sessions of LLLT and sham laser treatment in knee osteoarthritis patients (Huang, 2015b). To be eligible for inclusion in the review, trials needed to report pain and/or functional outcomes and a PEDro quality score. A total of 9 trials (total N=518 patients) met eligibility criteria. In these studies, the interventions included between 8 and 20 laser or sham sessions over 2 to 6 weeks. All 9 trials were considered high quality according to the PEDro scale (score of at least 7 out of 11 possible points). Primary outcomes of interest were post treatment pain measured by VAS and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores (pain and function). Meta-analyses did not find that LLLT led to significantly better pain scores than the sham control, either immediately after treatment or at the 3-month follow-up. For example, a meta-analysis of 5 studies that reported 12-week pain scores did not find a statistically significant between-group difference (standardized mean difference [SMD], -0.06; 95% CI, -0.30 to 0.18). Moreover, there were not statistically significant differences between active and sham laser interventions on WOMAC stiffness cores or WOMAC function scores. The secondary outcome, range of motion after therapy, also did not significantly favor LLLT over a sham intervention.

 

Previously, in 2007, Bjordal and colleagues published a systematic review of placebo-controlled RCTs to determine the short-term efficacy of physical interventions for pain associated with knee osteoarthritis (Bjordal, 2007). They included a total of 36 RCTs. The largest proportion of trials evaluated TENS (n=11), followed by 8 trials on LLLT and 7 on pulsed electromagnetic fields. Also included were trials on electroacupuncture, manual acupuncture, static magnets, and ultrasound. The authors did not report findings of pooled analyses on LLLT for knee osteoarthritis. In a qualitative analysis, they stated that all the physical interventions but 2 (manual acupuncture, ultrasound) showed better results with active treatment over placebo.

 

 

A 2015 RCT by Macias and colleagues published a double-blind RCT that 69 patients with unilateral chronic plantar fasciitis and chronic heel pain of 3 months or longer that was unresponsive to conservative treatments (eg, rest, stretching, physical therapy) (Macias, 2015). Patients were randomized to twice weekly treatment for 3 weeks of LLLT or sham treatment. The primary efficacy outcome, difference in reduction of heel pain pre- to posttreatment, differed significantly between groups (p<0.001). Mean VAS 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 scores on the Foot Function Index did not differ significantly between groups.

 

 

Several small RCTs evaluating LLLT for treating fibromyalgia have been published. In 2014, Ruaro and colleagues reported on 20 patients randomized to receive LLLT or sham treatment 3 times a week for 4 weeks (total of 12 treatments) (Ruaro, 2014). Outcomes included scores in the Fibromyalgia Impact Questionnaire (FIQ) which measures physical function, ability to work, pain, fatigue and depression, the McGill Pain Questionnaire (MPQ) and a pain VAS. All 3 outcomes were significantly better in the active compared to sham group after treatment. The mean overall FIQ score was 18.6 in the LLLT group and 5.2 in the sham group (p=0.003). Mean change scores also differed significantly between groups for MPQ score (p=0.008) and VAS score (p=0.002).

 

 

Several systematic reviews of RCTs and observational studies have been published. In 2015, Smoot and colleagues published a systematic review of studies on the effect of LLLT on symptoms in women with breast cancer‒related lymphedema (Smoot, 2015). The authors 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 to an alternative intervention (eg, intermittent compression). Only 3 studies had blinded outcome assessment and, in 3 studies, participants were blinded. A pooled analysis of 4 studies found significantly greater reduction in upper-extremity volume with LLLT versus the control condition (effect size [ES], -0.62; 05% 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 between LLLT and control (ES = -1.21; 95% CI, -4.51 to 2.10).