What is low and what is high?

By Jan Tunér

Let us first be clear about one thing – science is not to be based upon what we already know. To use “inappropriate” methods in a study is not wrong. It may be a waste of time in the end, but many discoveries are serendipitous.

In LLLT a lot is now known about the limits within which we can expect reasonable expected biological results. For musculoskeletal indications these are summarized by the World Association for Laser Therapy. For many indications the optimal parameters are still not known.

However, paying attention to what has been discovered during the 40 odd years of published papers about the use of the suitable energies (Joule) and energy densities (Joule/cm^2) ought to be some sort of a guideline for new research. It is sometimes surprising to see all the efforts put down into a study which is doomed to fail from the start, due to an inadequate choice of parameters.

Our first example is:

Santos JD, Oliveira SM, Nobre MR, Aranha AC, Alvarenga MB. A randomised clinical trial of the effect of low-level laser therapy for perineal pain and healing after episiotomy: A pilot study. Midwifery. 2011 Oct 5. [Epub ahead of print].

OBJECTIVE: to evaluate the effects of low-level laser therapy for perineal pain and healing after episiotomy.

DESIGN: a double-blind, randomised, controlled clinical trial comparing perineal pain scores and episiotomy healing in women treated with low-level laser therapy (LLLT) and with the simulation of the treatment.

PARTICIPANTS: fifty-two postpartum women who had had mediolateral episiotomies during their first normal delivery were randomly divided into two groups of 26: an experimental group and a control group.

INTERVENTION:  in the experimental group, the women were treated with LLLT. Irradiation was applied at three points directly on the episiotomy after the suture and in three postpartum sessions: up to 2hrs postpartum, between 20 and 24hrs postpartum and between 40 and 48hrs postpartum. The LLLT was performed with diode laser, with a wavelength of 660nm (red light), spot size of 0.04cm^2, energy density of 3.8J/cm^2, radiant power of 15mW and 10s per point, which resulted in an energy of 0.15J per point and a total energy of 0.45J per session. The control group participants also underwent three treatment sessions, but without the emission of radiation (simulation group), to assess the possible effects of placebo treatment.

MAIN OUTCOMES:  perineal pain scores, rated on a scale from 0 to 10, were evaluated before and immediately after the irradiation in the three sessions. The healing process was assessed using the REEDA scale (Redness, Edema, Echymosis, Discharge Aproximation) before each laser therapy session and 15 and 20 days after the women’s discharge.

FINDINGS:  comparing the pain scores before and after the LLLT sessions, the experimental group presented a significant within-group reduction in mean pain scores after the second and third sessions (p=0.003 and p<0.001, respectively), and the control group showed a significant reduction after the first treatment simulation (p=0.043). However, the comparison of the perineal pain scores between the experimental and control groups indicated no statistical difference at any of the evaluated time points. There was no significant difference in perineal healing scores between the groups. All postpartum women approved of the low-level laser therapy.

CONCLUSIONS:  this pilot study showed that LLLT did not accelerate episiotomy healing. Although there was a reduction in perineal pain mean scores in the experimental group, we cannot conclude that the laser relieved perineal pain. This study led to the suggestion of a new research proposal involving another irradiation protocol to evaluate LLLT’s effect on perineal pain relief.

The authors have provided sufficient information about the irradiation parameters and indeed at the end state that a different irradiation protocol might have a better outcome. And indeed so! 0.15 J on three points, in total 0.45 J to stimulate healing of an incision wound and reduce postop pain is in fact homeopathic. The question is: why did the researchers use these parameters and who gave them advice?

Another striking example of homeopathic energies is:

Lai SM, Zee KY, Lai MK, Corbet EF. Clinical and radiographic investigation of the adjunctive effects of a low-power He-Ne laser in the treatment of moderate to advanced periodontal disease: a pilot study. Photomed Laser Surg. 2009;27(2):287-293.

OBJECTIVE:  To evaluate the adjunctive effect of a low-power He-Ne laser in the non-surgical periodontal treatment of patients with moderate to advanced chronic periodontitis. Background Data: Laser applications in dental treatment are now more common in the literature. However, limited data are available on the potential effects of the low-power laser as an adjunct to non-surgical periodontal therapy for managing patients with moderate to advanced periodontal disease.

MATERIALS AND METHODS:  Sixteen patients with probing pocket depth (PPD) > or =5 mm and comparable bone defects on both sides of the mouth were recruited. Supragingival plaque (PL), bleeding on probing (BOP), PPD, and probing attachment level (PAL) were recorded at baseline and at 3, 6, 9, and 12 mo, while gingival crevicular fluid (GCF) samples and standardized intra-oral radiographs for digital subtraction radiography were taken at baseline and at 1, 3, 6, 9, and 12 mo. After non-surgical mechanical periodontal treatment, the test sites were selected randomly and irradiated with a low-power He-Ne laser (output power 0.2 mW) for 10 min for a total of eight times in the first 3-mo period, while the control sites received no additional treatment.

RESULTS:  PL percentage (83-16%) and BOP percentage (95-34%) decreased significantly after 12 mo. Statistically significant changes in reductions of PPD and GCF volume, gain in PAL, and increase in recession were seen in both test and control sites when compared to baseline (p < 0.05). No statistically significant differences in any clinical parameters or radiographic findings were found between the test and control sites. Changes in GCF volume were significant only at 3 mo in the test sites.

CONCLUSION:  Within the limits of this pilot study, the use of the low-power He-Ne laser as an adjunct to non-surgical periodontal therapy in patients with moderate to advanced chronic periodontitis did not seem to provide additional clinical benefit.

Looking closer in the published paper, this additional information is given:

The procedure was performed for test sites immediately after non-surgical therapy, for a total of 10 min, and the treatment was repeated at each review appointment over the following 3 mo. A total of eight laser irradiation sessions were performed on the test sites. The dose delivered at each application was 1.7 J/cm^2 (2.83 mW/cm^2), and the total dosage for the entire course of treatment was 13.6 J/cm^2.

The first commercially available LLLT units in the mid-80s were HeNe lasers with an approximate output of 0.9 mW. With the poor results in mind, it is surprising to find a recent study using even less. It is true that low power and long time is better than the opposite, but there is a limit! With 0.2 mW for 10 minutes gives a total energy of 0.06 J per each of the two test sites. The author indicates that the dose delivered at each application was 1.7 J/cm^2 (2.83 mW/cm^2), and the total dosage for the entire course of treatment was 13.6 J/cm^2. Again, this illustrates the confusion between J and J/cm^2. A high value of J/cm^2 is depending on the method of calculating the dose (yes, there are unfortunately two quite different ones!) and the size of the laser eye. Both energy and dose have to be within the therapeutic window.Indeed, recent studies indicate that low power and long time are optimal for tissue the anti-inflammatory effect. (See Biphasic dose responses in low level light therapy  3.7 MB PDF). But where is the lower limit? And what is clinically useful?

Studies like these are problematic from several points of view. One is that research capital is wasted and researchers disappointed and not receiving new grants. Even worse is that people checking PubMed for studies within a particular area only read the PubMed abstracts. Too often these abstracts do not state the laser parameters or only given them briefly. The novices in LLLT will then find many negative outcomes of LLLT, not being able to estimate the background. The studies quoted above gave enough information in the abstracts to make anybody with a reasonable knowledge about LLLT see the reason behind the failure, fair enough. But too many medical professionals are unable to understand the importance of the parameters, even if stated reasonably. Reviewers and editors of non-specialised journals frequently do not understand this problem, and quite unfortunately even specialised laser journals now and then fail to require a sufficient reporting of laser parameters. This further leads to confusing discussions in other papers where, unknowingly, apples and oranges are being compared.