A Systematic Review With Procedural Assessments and Meta-analysis of Low Level Laser Therapy in Lateral Elbow Tendinopathy (Tennis Elbow): Discussion

Discussion

In this review, we found that most RCTs of LLLT for LET were of acceptable methodological quality. This finding is in line with previous reviews,^[12,23,27] although there were some differences between reviewers in methodological scores for individual trials. RCTs of LLLT are of similar methodological quality and include similar sample sizes as RCTS included in recent reviews of corticosteroid injections^[5] and topical or oral NSAIDs.^[8] Two of the previous reviews of LLLT for LET found only six RCTs,^[12,23] whereas an earlier review found ten RCTs,^[27] and excluded one RCT for methodological shortcomings.^[43] We used broader searching criteria in our review and had no language restrictions. This resulted in 18 potentially eligible RCTs. We excluded one RCT for not meeting the inclusion criteria of specific endpoints^[43] and another two RCTs for complete lack of blinding^[44] and a lack of an LET control group.^[42] None of the previous LET reviews assessed the LLLT regimen for procedural errors, while our procedural assessments resulted in exclusion of another two RCTs with grave procedural errors, such as leaving the tendon insertion and acupoints unirradiated^[40] and giving adequate LLLT to the placebo group.^[61] These exclusions resulted in 13 RCTs being eligible for our review which is twice the number of RCTs included in two of the previously published reviews.^[12,23]

Previous LET-reviews of LLLT^[12,23,27] and pharmacological interventions like NSAID^[8] or corticosteroid injections^[5] have not assessed possible bias from for-profit funding sources or publication bias. Our analysis revealed that bias from for-profit funding was largely absent in the available LLLT material and that trials were performed by independent research groups receiving funding from internal sources or non-profit organisations. This feature of the LLLT literature is definitely different from pharmacological pain treatments where up to 83% of trials may be industry-funded.^[62] A second feature of the LLLT-literature is that publication bias seems to go in a negative direction. This is distinctly different from the drug trials^[63,64] where positive results have been found to account for up to 85% of the published trials in single journals,^[63] although this bias seems to be lesser or absent in high impact journals.^[64] Our review suggests that LLLT trials reporting negative results are more likely to be published than trials with positive results. To our knowledge we are the first to demonstrate such bias, but such negative publishing bias is probably not unique to LLLT, and it may also be present for other electrophysical agents including TENS and acupuncture. We were surprised to see how large well-designed positive trials of LLLT^[51,50] were published in unlisted journals or journals with low-impact factor, and how small negative trials,^[46] often with grave methodological^[42] or procedural flaws^[40] were published in higher ranking journals. This may reflect a predominance of RCTs designed using drug-research methodology paradigms without due consideration given to adequacy of the technique used in delivering LLLT, leading to under dosing and negative outcome bias.^[65] In addition, it has been that documented drug sponsorship of research activities may influence guideline panels, journal editors and referees^[66,67] leading to negative views on non-drug treatments such as LLLT as reflected in editorials in pain journals^[68] and national medical journals.^[69]

Despite these concerns, we believe that the positive overall results of this review need to interpreted with some caution. They arise from a subgroup of 7 out of the 13 included trials.^{[48-51,55-57]} These 7 trials had a narrowly defined LLLT regimen where lasers of 904 nm wavelength with low output (5–50 mW) were used to irradiate the tendon insertion at the lateral elbow using 2–6 points or an area of 5 cm² and doses of 0.25–1.2 Joules per point/area. The positive results for this subgroup of trials were consistent across outcomes of pain and function, and significance persisted for at least 3–8 weeks after the end of treatment, in spite of several factors which may have deflated effect sizes.

For the red 632 nm wavelength which has a poorer skin penetration ability,^[70] a single trial^[60] with a higher dose (6 Joules) seemed to be equally effective as the lower doses of 904 nm used in the seven positive trials. These LLLT-doses are well within the therapeutic windows for reducing inflammation, increasing fibroblast activity and collagen fibre synthesis, and the dosage recommendations suggested by WALT.^[71]

The negative results for the 830 nm GaAlAs and 1064 nm NdYag lasers can be attributed to several factors such as too high doses, too high power density or the inclusion of patients with poor prognosis from long symptom duration and prior steroid injections. These wavelengths have previously been found effective in some tendon animal studies and in other locations such as shoulder tendinopathies.^[72,73] At this time it is not possible to draw firm conclusions about the clinical suitability of wavelengths 820, 830 and 1064 nm in LET treatment, but the lack of evidence of effects indicates that they cannot be recommended as LET treatment before new research findings have established their possible effectiveness. The lack of effect for these lasers may also serve as a reminder that higher doses is not always best. We have been witnessing a tendency where newly developed lasers with these wavelengths are being marketed with ever-increasing power and power densities. This may be inappropriate because current knowledge about LLLT mechanisms and dose-response patterns at higher powers is inconsistent or lacking.

The positive results for combining LLLT of 904 nm wavelength with an exercise regimen, are encouraging. We would have thought that exercise therapy could have erased possible positive effects of LLLT, but the results showed an added value in terms of a more rapid recovery when LLLT was used in conjunction with an exercise regimen. This may indicate that exercise therapy can be more effective when inflammation is kept under control. Adding LLLT to regimens with eccentric and stretching exercises reduced recovery time by 4 and 8 weeks in two trials.^[48,56] For this reason, LLLT should be considered as an adjunct, not an alternative, to exercise therapy and stretching.

Based on the above findings, LLLT should be considered as an alternative therapy to commonly used pharmacological agents in LET management. Cochrane-based reviews of NSAIDs^[8] and corticosteroid injections^[5] have found evidence of short-term effects within 4 and 6 weeks, respectively. The short-term reduction in pain intensity after corticosteroid injections may appear to have a more rapid onset and may also be larger in effect size than after LLLT. But on the other hand, the available LLLT-material is confounded by factors capable of deflating effect sizes. In this perspective, there is a need for more high quality trials with head-to-head comparison of short-term effects between LLLT and corticosteroid injections. In the longer term, NSAIDs seems to be ineffective and corticosteroid injections seem to be harmful both at 26 and at 52 weeks.^[6] For LLLT there are some significant long-term effects found at 8, 12 and 24 weeks after the end of treatment.