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

Abstract and Background

Abstract

Background: Recent reviews have indicated that low level level laser therapy (LLLT) is ineffective in lateral elbow tendinopathy (LET) without assessing validity of treatment procedures and doses or the influence of prior steroid injections.
Methods: Systematic review with meta-analysis, with primary outcome measures of pain relief and/or global improvement and subgroup analyses of methodological quality, wavelengths and treatment procedures.
Results: 18 randomised placebo-controlled trials (RCTs) were identified with 13 RCTs (730 patients) meeting the criteria for meta-analysis. 12 RCTs satisfied half or more of the methodological criteria. Publication bias was detected by Egger's graphical test, which showed a negative direction of bias. Ten of the trials included patients with poor prognosis caused by failed steroid injections or other treatment failures, or long symptom duration or severe baseline pain. The weighted mean difference (WMD) for pain relief was 10.2 mm [95% CI: 3.0 to 17.5] and the RR for global improvement was 1.36 [1.16 to 1.60]. Trials which targeted acupuncture points reported negative results, as did trials with wavelengths 820, 830 and 1064 nm. In a subgroup of five trials with 904 nm lasers and one trial with 632 nm wavelength where the lateral elbow tendon insertions were directly irradiated, WMD for pain relief was 17.2 mm [95% CI: 8.5 to 25.9] and 14.0 mm [95% CI: 7.4 to 20.6] respectively, while RR for global pain improvement was only reported for 904 nm at 1.53 [95% CI: 1.28 to 1.83]. LLLT doses in this subgroup ranged between 0.5 and 7.2 Joules. Secondary outcome measures of painfree grip strength, pain pressure threshold, sick leave and follow-up data from 3 to 8 weeks after the end of treatment, showed consistently significant results in favour of the same LLLT subgroup (p <0.02). No serious side-effects were reported.
Conclusion: LLLT administered with optimal doses of 904 nm and possibly 632 nm wavelengths directly to the lateral elbow tendon insertions, seem to offer short-term pain relief and less disability in LET, both alone and in conjunction with an exercise regimen. This finding contradicts the conclusions of previous reviews which failed to assess treatment procedures, wavelengths and optimal doses.

Background

Lateral elbow tendinopathy (LET) or "tennis elbow" is a common disorder with a prevalence of at least 1.7%,^[1] and occuring most often between the third and sixth decades of life. Physical strain may play a part in the development of LET, as the dominant arm is significantly more often affected than the non-dominant arm. The condition is largely self-limiting, and symptoms seem to resolve between 6 and 24 months in most patients.^[2]

A number of interventions have been suggested for LET. Steroid injections, non-steroidal anti-inflammatory drugs or a regimen of physiotherapy with various modalities, seem to be the most commonly applied treatments.^[3] However, treatment effect sizes seem to be rather small, and recommendations have varied over the years. In several systematic reviews over the last decade,^[4,5] glucocorticoid steroid injections have been deemed effective, at least in the short-term. But in later well-designed trials evidence is found that intermediate and long-term effects of steroid injections groups yield consistently and significantly poorer outcomes than placebo injection groups, and physiotherapy or wait-and-see groups.^[6,7] Nevertheless, steroid injections have been considered as the most thoroughly investigated intervention, with 13 randomized controlled trials comparing steroid injections to either placebo/local anaesthetic or another type of intervention.^[5] Non-steroidal anti-inflammatory drugs (NSAIDs) have been found to achieve smaller short-term effect sizes than steroid injections,^[8] and topical application seems to be the best medication administration route^[8] For oral administration of NSAIDs for LET, evidence is inconclusive from two heterogeneous trials only.^[9] The positive short-term results of anti-inflammatory therapies in LET appear to partly contradict the recent paradigm in tendinopathy research, where LET is thought to be mainly a degenerative disorder with minimal inflammation.^[10,11]

Exercise therapy and stretching exercises have been used either alone or in conjunction with manipulation techniques or physical interventions. Although the sparse evidence makes it difficult to assess the separate effect of active exercises or stretching,^[12] four studies have found that either exercises alone,^[13] or in conjunction with a physiotherapy package, are more effective than placebo ultrasound therapy or wait-and-see controls. Also exercise therapy, particularly eccentric exercises, have been found effective in the intermediate term in tendinopathies of the Achilles, patellar or shoulder tendons.^[14-17] There is some evidence suggesting that joint manipulation or mobilisation techniques either of the wrist, elbow or cervical spine may contribute to short-term effects in LET.^[18-20]

Among the physical interventions, ultrasound therapy has been considered to offer a small benefit over placebo from two small trials,^[12] but a well-designed and more recent trial did not find significant effects of ultrasound therapy in LET.^[21] Reviewers have arrived at different conclusions for the effect of acupuncture.^[22,23] In reviews of physical interventions for LET, conclusions may vary between reviews because of differences in the treatment procedures. A good example of this is the negative conclusion of the LET review for extracorporeal shockwave therapy (ESWT) by Buchbinder et al.,^[24] where a later review with in-depth assessments of treatment intervention protocols,^[25] found that a subgroup of trials with proper treatment procedures and adequate timing of outcomes gave a positive result.

Low level laser therapy (LLLT) has been available for nearly three decades, and scattered positive results have been countered by numerous negative trial results. Several systematic reviews have found no significant effects from LLLT, in musculoskeletal disorders in general,^[26] and in LET in particular.^[12,23,27] In this perspective it may seem futile to perform yet another systematic review in this area. But none of these reviews evaluated the results separately for the different LLLT treatment procedures, laser wavelengths or doses involved. Neither did they implement evidence of the newly discovered biomodulatory mechanisms which are involved when LLLT is applied. During the last 5–6 years the annual number of published LLLT reports in Medline has increased from 25 to around 200. We recently made a review of this literature, and concluded that LLLT has an anti-inflammatory effect in 21 out of 24 controlled laboratory trials, and a biostimulatory effect on collagen production in 31 out of 36 trials.^[28] Both of these effects were dose-dependent and could be induced by all wavelengths between 630 and 1064 nm with slight variations in therapeutic dose-ranges according to the wavelength used. The anti-inflammatory effect was seen in higher therapeutic dose-ranges than the biomodulatory effect on fibroblast cells and collagen fibre production. Diagnostic ultrasonography of tendinopathies has revealed that partial ruptures and tendon matrix degeneration are underdiagnosed if only physical examinations are made. Consequently, the stimulatory LLLT-effect on collagen fibre production should probably be beneficial for tendon repair. Another interesting feature was that LLLT with too high power densities or doses (above 100 mW/cm²), seemed to inhibit fibroblast activity^[29] and collagen fibre production.^[30] Six years ago we showed in a systematic review of tendinopathy, that the effect of LLLT is dose-dependent.^[31] At the time, the accompanying editoral suggested that the advanced review design could become the new standard for reviewing empirical therapies with unknown optimal doses and procedural differences.^[32] Steroids induce a down-regulation of cortisol receptors, and we recently discovered that the cortisol antagonist mifepristone completely diminished the anti-inflammatory effect of LLLT.^[33] All these recent findings from the LLLT literature, prompted the World Association for Laser Therapy (WALT) to publish dosage recommendations and standards for the conductance of systematic reviews and meta-analyses last year.^[34] One of the issues that has lacked attention is the validity of LLLT-application procedures in tendinopathy. To our knowledge there are only three valid irradiation techniques for LLLT in tendinopathies: a) direct irradiation of the tendon, b) irradiation of trigger points and c) irradiation of acupuncture points.

In this perspective and as our previous tendinopathy review^[31] is becoming outdated, there seems to be a need for a new in-depth review of the effects of LLLT in LET where possible confounders are analyzed and subgroup analyses are performed.