13.1 Are all the negative lllt studies really negative?

The authors of this book have performed an analysis of a number of frequently cited studies on the effects of low-power-laser therapy. In many of these studies, analysis uncovered one or more reasons for the negative findings reported, the most common being the use of extremely low doses. Other reasons are: faulty inclusion criteria, inaccurate control group definition, ineffective methods of therapy, inadequate attention to systemic effects and tissue condition, and low power density. A weakness often encountered in these studies is their failure to provide sufficient data on laser parameters. Since negatively inclined studies such as these are often quoted as "proof" of the ineffectiveness of LLLT, it is important that they be subjected to a proper critical analysis. 1.400 articles were reviewed for this analysis, the emphasis being on double-blind studies. Of the 135 localised double-blind studies, 85 reported positive findings.

Though important, the critical examination of scientific literature is decidedly unglamorous. It involves hours and days of searching through a wide variety of different sources, and by no means all information is yet available on-line. There are numerous pitfalls, too, especially for those who opt to read abstracts only - criticism of sources is impossible unless an article can be studied in its entirety. Basing an opinion from abstracts obtained from e.g. Medline is risky. In addition, only a minority of the early LLLT research reports are available from the major databases.

In the following analysis of the available literature, we have chosen to analyse those studies unable to demonstrate the effectiveness of LLLT. Although priority was given to double-blind studies, non-double-blind studies were also included in certain typical cases. Certain studies were also included merely on the grounds that they are among the most frequently cited. The 1.400 articles reviewed for this analysis are now being stored in computerised form.

"I heard it through the grapewine"

Positive from negative

Negative from negative

LLLT is a relatively young science that has only just emerged from its Sturm und Drang period, and it might perhaps be unfair to criticise the earlier negative studies. Many medical researchers then had - and indeed still have - a rather diffuse knowledge of physics, and qualified books on the physics of laser therapy were long in appearing. In many cases, the only information available to researchers on doses, methods of treatment and suitable indications came from the manufacturers or agents, while over-optimistic, ignorant salesmen often laid traps that would ensnare both themselves and the researchers.

Many studies will come in for criticism in the following paragraphs, although the researchers involved need not always take this to heart. As often as not they pioneered new territory, seeking either to retain an open mind towards the examination of new methods or reacting to what they perceived as a lack of objectivity. The purpose of our criticism is described in the Introduction - we wish to draw the reader's attention to the fact that many negative studies are poorly structured and are therefore largely irrelevant, even though they constantly feature in bibliographies and reading lists and are cited as "evidence" that LLLT does not work. Few people appear to have actually read them. As we see it, it is high time they were weeded out so that they can no longer function as traveller's tales in the future.

Important parameters

C. Power density
Power density, indicating the degree of concentration of the power output, has also increasingly proved to play a major role. It is measured in watts per square centimetre (W/cm2). If, for example, a circular area having a diameter of 5 mm (approx. 0.2 cm2) is illuminated with a laser operating at a power output of 100 mW, the biological effects are quite different from those produced by illuminating a circular area of 5 cm diameter (approx. 20 cm2) with the same laser. In the first case, the power density is 100 times greater than the second. Some studies have concluded that the power density may be of even greater significance than the dose. This parameter is very seldom indicated in the articles we have studied. It must also be remembered that the power density varies within the area illuminated - normally, it will be greatest at the centre.

Typical traditional laser instruments
Whenever possible, we also reviewed the brochure or brochures describing the instrument used for the study. The power output of the first commercial therapeutic lasers was very low. HeNe instruments often achieved an output of 1 - 2 mW at the laser tube, while the losses sustained in the optical fibres were frequently 50% or more. Further-more, the laser was sometimes pulsed (usually switched to produce a duty cycle of about 50%), thereby reducing the power/mean output power sent to the tissue by another half.
Brochures describing GaAs lasers often only specify the maximum pulse power, whereas the mean output power, which is of the greatest significance for LLLT, is often not named at all.
In the following we were often obliged to make a number of assumptions, since it was only very seldom that all the parameters were indicated in the studies. For example, unless otherwise stated, we have assumed that the fibre incurred a 50% loss; if the light was pulsed we assumed a duty cycle of 50%; and, unless otherwise indicated, we assumed that the mW values quoted envisage power output at the laser rather than at the fibre opening. For GaAs lasers, we sometimes had to make several assumptions at once, since here there are more parameters to be taken into account and they were often incompletely reported.
During the eighties, considerable discrepancies between actual outputs and those stated in manufacturers' brochures were not unusual. Only a handful of authors stated whether they themselves measured actual output at the tissue or whether they merely relied on the figure quoted in the brochure. Clearly, we must expect the dark figure to be quite large here.

Dose development
A number of early positive reports on the clinical effects of very weak HeNe lasers suggested that there was cause for some optimism - and scepticism, too. Among them are Walker (1983) [E1] (calculated at approx. 0.005 J per point) and Snyder-Mackler (1988) [E2, 3] (calculated at approx. 0.01 J per point), reporting on the effect of very weak HeNe lasers.
It must be remembered that Mester had been working with doses of around 1 J as far back as the early seventies. Later, in an article published in 1971 [E4] he recommended a dose of 1.5 J/cm2 as conducive to wound healing. The HeNe laser he used had an output of 25 mW at the laser. For a long time Mester's papers attracted little attention in the West, since they were published in relatively unknown journals. Later, in 1981, Kana [E5] published a study on the healing of open skin wounds in which he presented an analysis of the biological effect of 4, 10 and 20 J therapy.
The instrument he used was an HeNe laser producing an output of 25 mW from the laser tube. Mester's and Kana's experience of doses suitable for wound healing still hold good today. Although HeNe lasers with a power output of 25 mW were extremely expensive at the time, it cannot be held that information on suitable doses was not then available. It should be noted, too, that the treatment of pain requires larger doses than does the healing of open wounds. It seems that a large proportion of the negative studies concentrated mainly on testing the reliability of studies such as [E1, 2 and 3] without regard to existing knowledge of reasonable doses.

Pitfalls

Our comments:
Very little is known about the parameters, such as wavelength, pulsing/continous and treatment technique. The indications are plantar fasciitis, trochanteric bursitis, tendonitis, lateral epicondylitis, knee pain, cervical pain and lumbar pain. If applied in the compressive mode, 1 J/cm2 may be a reasonable dose (but of the low side) for some of the indications but certainly subclinical for indications such as cervical pain and lumbago. The list could be made much longer.

For example, Krikorian [E15] used a HeNe laser and a dose of 0.05 J/cm2 to study wound healing in rats. Zarkovic [E16] used a GaAs laser and a dose of 0.0004 J/cm2 to study pain perception in mice. Using a HeNe laser and a dose of 0.004 J/cm2, Jarvis [E17] could (naturally) find no evidence of stimulation of thermoreceptors in humans.

It is interesting to quote the abstract of the negative study by Siebert [E40] and then compare it to the analysis made by Baxter [E35].

Siebert: “The efficacy of "athermic" lasers (HeNe/GaAs) in the treatment of tendinopathies was investigated in a randomized double-blind study. On 10 consecutive days, 64 patients (32 therapy, 32 placebo) were treated for 15 minutes each with a switched-on or switched-off laser under otherwise identical conditions. The extent of movement in involved joints (neutral 0 method) and rating on a pain scale for rest in pain, movement pain, and pressure pain before treatment, after treatment, and 2 weeks after conclusion of therapy, as well as infrared thermography, served to check therapy.
After the end of therapy, a significant reduction (P = < 0.001) of 50% was shown for resting pain as well as reductions of 30% for movement an 30% for pressure pain. This result was identical in the therapy group and in the placebo group. There was also no indication of a different result of therapy between the therapy and placebo groups with regard to the thermographic control and the extent of movement.
The breakdown of the data in terms of age, sex, and duration of disease did not provide any indications of different results for placebo or therapy. It was striking that the patients who reported sensations during or after the treatment (irrespective of whether pleasant or unpleasant) had a greater reduction of pain than the patients without sensations. This laser therapy thus did not show any effect above and beyond that in the untreated group”.

Baxter: “Despite being highly critical of the standard of previous laser research, these investigators employed a non-contact technique in their trial, irradiating the patients’ skin from a distance of 10 cm. Given the beam divergence of clinical LLLT apparatus, the use of such a distance would appear to be inappropriate, producing minimal power and energy densities on the irradiated tissue. This, coupled with the apparent inaccuracies in calculation of doasge (by a factor of 10), casts serious doubts upon the reliability and validity of the reported findings”.