On "is low-level laser therapy effective ..." Maher S. Phys Ther. 2006;86:1161-1167.

The assessment of low-level laser therapy (LLLT) in lateral epicondylitis by Maher (1) in the August issue of Physical Therapy's Evidence in Practice section needs some commentary. The negative conclusion is not surprising based on the few studies the author was able to retrieve; however, the conclusion may still be wrong for a number of reasons:

(1) The reviews the author retrieved do not address the question of proper dose and treatment procedure.

(2) More trials and reviews could have been found if the search had included the Cochrane Library and CINAHL databases. For instance, our review of location-specific LLLT doses in tendinopathy was not included. (2) In this review, we found a distinct dose-response pattern, and the results of later trials (3,4) do not alter the positive overall result in which adequate doses of LLLT were 32% more effective than placebo. For updated guidelines on location-specific LLLT doses, see the World Association of Laser Therapy Web site. (5)

(3) To my knowledge, the fact that studies are "old" has never been a valid criterion for exclusion.

(4) Maher bases her clinical decision on the studies by Papadopoulos et al (6) (0.714 mW/[cm.sup.2] and 30 J/[cm.sup.2]) and by Basford et al (7) (204 mW/[cm.sup.2] and 12.24 J/[cm.sup.2]), which use power densities that are too high. Both treatment regimens will inhibit fibroblast activity and impair collagen production in injured superficial tendons such as the extensor carpi radialis brevis tendon in the lateral elbow (which is usually partially ruptured in patients who are middle-aged). The depth of this tendon is only 1.9 mm from the skin surface, and thus the upper power density threshold (30 mW/ [cm.sup.2]) for fibroblast stimulation is probably surpassed. (8) In the study by Papadopoulos et al, (6) the LLLT dose probably inhibits collagen production, resulting in less improvement than in the placebo control group.

(5) A number of studies with negative results in lateral elbow tendinopathy (9,10) state that they included patients who received steroid injections shortly before randomization. A number of LLLT trials have not specified whether such treatment had been given, which may seriously confound the results. Our research group (11,12) has shown that the anti-inflammatory effect of LLLT is erased by steroids and down-regulated cortisol receptors. In addition, it has been shown that a group that received steroid injections had significantly poorer outcomes than a control group on a waiting list after 6 months. (13)

Several laboratories are currently working to elucidate the mechanisms behind LLLT. (14) Based on the results from 19 out of 22 controlled trials, we are fairly certain that certain doses of LLLT can modulate inflammation. (3) Low-level laser therapy also can temporarily increase or decrease collagen production from fibroblast cells (31 out of 34 controlled studies). (15) I trust that we will see another face of LLLT in the literature when this new knowledge about LLLT doses is implemented in clinical research.

It is a bit frustrating to see yet another commentary about how ineffective laser is, when in fact it may be very effective when used properly for this condition. The insufficient evidence to support the use of LLLT provided by the manufacturers that the author describes is another problem, and I urge physical therapists to seek LLLT information from the published literature, laser Web sites such as http://www.laser.nu, and their colleagues.

Jan M Bjordal

JM Bjordal, PT, PhD, is Associate Professor, University of Bergen, Bergen University College, Bergen, Norway; Scientific Secretary, World Association of Laser Therapy ([e-mail]).

References

(1) Maher S. Is low-level laser therapy effective in the management of lateral epicondylitis? [Evidence in Practice.] Phys Ther. 2006;86:1161-1167.

(2) Bjordal J, Couppe C, Ljunggren A. Low level laser therapy for tendinopathy: evidence of a dose-response pattern. Physical Therapy Reviews. 2001;6(2):91-99.

(3) Bjordal JM, Lopes-Martins RA, Iversen VV. A randomised, placebo controlled trial of low level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendinous prostaglandin E2 concentrations. Br J Sports Med. 2006;40:76-80; discussion 76-80.

(4) Stergioulas A. Effects of a 904 nm GaAs laser versus placebo in the treatment of patellar tendonitis. Laser & Technology. 2003;13(1-2):21-23.

(5) World Association of Laser Therapy Web site. Recommended dosage. Available at: http://www.walt.nu/dose/index.html. Accessed November 13, 2006.

(6) Papadopoulos ES, Smith RW, Cawley MID, Mani R. Low level laser therapy does not aid in the management of tennis elbow. Clin Rehabil. 1996;10:9-11.

(7) Basford JR, Sheffield CG, Cieslak KR. Laser therapy: a randomized, controlled trial of the effects of low intensity Nd:YAG laser irradiation on lateral epicondylitis. Arch Phys Med Rehabil. 2000;81:1504-1510.

(8) Bjordal J, Demmink J, Ljunggren A. Tendon thickness and depth: an ultrasonography study on healthy subjects. Physiotherapy. 2003;89(6):375-383.

(9) Lundeberg T, Haker E, Thomas M. Effect of laser versus placebo in tennis elbow. Scand J Rehabil Med. 1987;19:135-138.

(10) Haker E, Lundeberg T. Laser treatment applied to acupuncture points in lateral humeral epicondylagia: a double-blind study. Pain. 1990;43:243-247.

(11) Albertini R, Aimbire FS, Correa FI, et al. Effects of different protocol doses of low power gallium-aluminum-arsenate (Ga-Al-As) laser radiation (650 nm) on carrageenan induced rat paw ooedema. J Photochem Photobiol B. 2004;74:101-107.

(12) Lopes-Martins RA, Albertini R, Lopes-Martins PS, et al. Steroid receptor antagonist mifepristone inhibits the anti-inflammatory effects of photoradiation. Photomed Laser Surg. 2006;24(2):197-201.

(13) Smidt N, van Der Windt DA, Assendelft WJ, et al. Physiotherapy or a wait-and-see policy were best long-term treatment options for lateral epicondylitis [Evidence-based orthopedics]. J Bone Joint Surg Am. 2002;84:1487.

(14) Bjordal JM, Johnson MI, Iversen V, et al. Photoradiation in acute pain: a systematic review of possible mechanisms of action and clinical effects in randomized placebo-controlled trials. Photomed Laser Surg. 2006;24:158-168.

(15) Bjordal JM, Couppe C, Chow RT, et al. A systematic review of low level laser therapy with location-specific doses for pain from chronic joint disorders. Aust J Physiother 2003;49:107-116.

[DOI: 10.2522/ptj.2007.87.2.224]

Author Response:

I thank Bjordal for his reflective comments on my Evidence in Practice article. In many ways, I am thankful to have the opportunity to respond to his comments. His insights have increased my own knowledge base about LLLT and have piqued a desire to conduct my Own clinical trial using this intervention. I hope other clinicians and researchers will be encouraged to do the same.

Bjordal raises several interesting points regarding low-level laser therapy (LLLT), points that do not conflict with my own findings. First, he has identified that LLLT manufacturers often provide insufficient evidence to support the use of this intervention. In fact, many clinical trials are conducted using dosing as recommended by the manufacturer. (1) Second, he states that laser "may yet be very effective when used properly for this condition." This statement reflects 2 of the points I tried to reinforce strongly in my article:

(1) The use of the word "may" suggests that the absolute effects of the treatment intervention are not well documented in the literature;

(2) The phrase "properly used for this condition" brings up the question: What is" proper usage"?

Bjordal et al identify that the "rationale behind the selection of application technique and treatment parameters, such as power density, size of exposure, timing or treatment frequency, often remains unclear." (1) My own Evidence in Practice article arrived at this same conclusion: "The most effective method of treatment ... needs to be established before the efficacy of LLLT can be determined." (2(p1166))

I would like to respond to 2 of Bjordal's comments on the selection of my search criteria and the selection of appropriate dose and treatment procedure for LLLT.

Evidence in Practice articles were designed to illustrate how working clinicians can efficiently use literature to make decisions regarding patient care. For this reason, the search criteria for these articles are often narrowed in order to meet the time constraints of the clinician. Bjordal argues that the age of a study is not a valid criterion for exclusion. Portney and Watkins, (3) however, have identified that it is generally practical to limit the review of older articles, so as to not review every historical document in the field. If not confined in some manner, a review of literature can go on indefinitely. (3)

For this reason, I selected a parameter of 10 years, with the assumption that the more recent articles would include an analysis of older research. For example, the systematic review by Trudel et al (4) was retrieved in my search for evidence. This systematic review examined a variety of interventions for lateral epicondylitis. In particular, 9 studies were relevant to laser therapy and LLLT. The authors reported at least level 2b evidence (based on the Sackett system (5)) that showed laser therapy to be ineffective in the treatment of lateral epicondylitis. Of the 9 studies examined by Trudel et al, 7 were conducted more than 10 years ago.

Bjordal also raises the question of using the Cochrane Library and CINAHL database. The CINAHL database, unlike MEDLINE, is not available for free to the public. For clinicians without complimentary access to CINAHL, the cost may prohibit the use of the database. * In addition, MEDLINE has a large database of indexed journals. In fact, it indexes all but 1 journal included as references in Bjordal's letter to the editor. On the other hand, CINAHL does not index Laser & Technology, Pain, Photomedicine and Laser Surgery, or the Journal of Photochemistry and Photobiology. Although the Cochrane Library does provide free access to abstracts, costs are associated with access to full-text articles. Once again, the cost for full articles, currently $25, may prohibit use of this tool by clinicians. MEDLINE, on the other hand, provides access to the full text of many journals at no additional cost to the user.

As my final point regarding my search criteria, I was interested only in studies relevant to the lateral epicondylitis. This is the location of 25% to 40% of injuries seen in my clinical practice and was the diagnosis in which I was most interested regarding LLLT. Because I wanted to compare "apples to apples," I limited my selection of articles to only those pertinent to "lateral elbow."

This approach was further validated after reading the 2001 systematic review by Bjordal et al. (1) This review highlights that treatment varies for different tendons based on laser type, distance from the skin surface, and volume of injured tissue.

For this reason, different treatments need to be provided for tendon injuries in different locations. In contrast, the articles referenced by Bjordal in his letter to the editor covered topics, injuries, or diagnoses that were not pertinent to my patient population: Achilles tendinitis, (6) patellar tendinitis, (7) ultrasonographic research on tendon thickness and depth, (8) edema, (9) the effect of steroids on laser therapy, and chronic joint disorders. (11) Journal articles about these injuries or diagnoses would not efficiently help to answer a clinical question about the efficacy of LLLT in the treatment of lateral epicondylitis, although they may be pertinent for other research or Evidence in Practice articles.

I concur with Bjordal that reviews of articles in the literature do not answer the question of proper dose or treatment procedure. In a study not identified by my own literature review, Bjordal et al (11) attempted to identify a dose-response pattern for several types of tendinopathy: epicondylitis, rotator cuff tendinopathy, patellar tendinopathy, Achilles tendinopathy, and plantar fasciitis. They conducted a systematic review of trials using LLLT published after 1980. The search was conducted on MEDLINE, EMBASE, and the Cochrane Library, in addition to a hand search of physical therapy journals in English and Scandinavian languages. Twenty trials were identified with the keyword "tendinopathy." Of those 20 trials, 13 met the inclusion criteria. When all studies were taken as a whole, the authors found a 22% effect in favor of LLLT over placebo. However, when the authors eliminated the studies that they determined did not utilize "optimal dosage," the effect increased to 32% in favor of LLLT over placebo.

Of the 13 included trials, only 7 were relevant to epicondylitis. The authors did not differentiate the results of epicondylitis from other tendinopathies.

In addition, the authors did not separate the diagnosis of medial and lateral epicondylitis, conditions that may involve application of treatment to tendons at different depths, with different cross-sectional diameters, and so on. The use of optimal dosage in the review is a "suggested optimal range" determined by the authors. The optimal ranges were developed from the results of 5 in vitro studies examining increases in collagen production and estimations of tendon characteristics (depth, cross-sectional diameter, and area). Although in vitro studies are useful for developing guidelines for treatment, future studies should be conducted with live subjects. Human tissues can significantly vary in distance from the skin surface to the target tissue, in vascularity, and in amount of tissue injury.

Although the study by Bjordal et al is the first study I have reviewed that identified actual dose ranges, I would like to see additional studies that validate or refute "optimal dosage" as determined by Bjordal et al. They found only 7 studies that met inclusion criteria for epicondylitis. Of those 7 studies, only 4 met the "suggested" optimal power density and dose ranges as determined by the authors. Validation of the use of laser in epicondylitis, therefore, was determined by 4 articles. The systematic review by Trudel et al, (4) although not dose specific, analyzed 9 studies and found laser to be ineffective.

I believe that identifying a need for additional research regarding LLLT is not a negative conclusion. Instead, it challenges those who manufacture lasers, those who use lasers, and those interested in new treatment options to continue to design high-quality research studies to either validate or refute the benefits of this intervention. I thank Bjordal for his insightful comments about my article. I look forward to continuing my own research on this intervention and hope other clinicians and researchers will conduct studies as well.

Sara Maher

S Maher, PT, DScPT, OMPT, is Assistant Professor, Oakland University, Oakland, Mich, and Physical Therapist, Michigan Rehabilitation Specialists, Hamburg, Mich ([e-mail]).

References

(1) Bjordal JM, Couppe C, Ljunggren A. Low level laser therapy for tendinopathy: evidence of a dose-response pattern. Physical Therapy Reviews. 2001;6(2):91-99.

(2) Maher S. Is low-level laser therapy effective in the management of lateral epicondylitis? [Evidence in Practice.] Phys Ther. 2006;86:1161-1167.

(3) Portney LG, Watkins MP. Foundations of Clinical Research: Applications to Practice. 2nd ed. Upper Saddle River, NJ: Prentice Hall Health; 2000:128.

(4) Trudel D, Duley J, Zastrow I, et al. Rehabilitation for patients with lateral epicondylitis: a systematic review. J Hand Ther 2004;17:243-266.

(5) Sackett DL, Straus SE, Richardson WS, et al. Evidence-Based Medicine: How to Teach and Practice EBM. 2nd ed. Edinburgh, United Kingdom: Churchill Livingston Inc; 2000.

(6) Bjordal JM, Lopes-Martins RA, Iversen VV. A randomised, placebo controlled trial of low level laser therapy for activated Achilles tendonitis with microdialysis measurement of peritendinous prostaglandin E2 concentrations. Br J Sports Med. 2006;40:76-80.

(7) Stergioulas A. Effects of a 904 nm GaAs laser versus placebo in the treatment of patellar tendonitis. Laser & Technology. 2003;13(1-2):21-23.

(8) Bjordal JM, Demmink J, Ljunggren A. Tendon thickness and depth: an ultrasonography study on healthy subjects. Physiotherapy. 2003;89(6):375-383.

(9) Albertini R, Aimbire FS, Correa FI, et al. Effects of different protocol doses of low power gallium-aluminum-arsenate (Ga-Al-As) laser radiation (650 nm) on carrageenan induced rat paw ooedema. J Photochem Photobiol B. 2004;74:101-107.

(10) Lopes-Martins RA, Albertini R, Lopes-Martins PS, et al. Steroid receptor antagonist mifepristone inhibits the anti-inflammatory effects of photoradiation. Photomed Laser Surg. 2006;24(2):197-201.

(11) Bjordal JM, Couppe C, Chow RT, et al. A systematic review of low level laser therapy with location-specific doses for pain from chronic joint disorders. Aust J Physiother. 2003;49:107-116.

[DOI: 10.2522/ptj.2007.87.2.225]

* Editor's note: APTA members now have free access to the CINAHL, ProQuest Health & Medical Complete, and ProQuest Nursing and Allied Health Source databases through Open Door (http://www.apta.org/opendoor). This free access was not available at the time the Evidence in Practice article was written.