Abstract
In this issue of the Journal, Jenkins and Carroll 5 present tabulations of treatment parameters and equipment-related parameters that could significantly enhance reproducibility of research reports, if complied with by research investigators and others. Certainly, this is a step in the right direction. Indeed, it warrants further amplification. Whereas much has been written about inadequate and incorrect reporting of irradiation parameters by authors in this field, barely scrutinized are equipment manufacturers who have further complicated the matter with devices that are, at times, labeled with inaccurate parameters and sold with manuals that offer misleading treatment guidelines. Because of the obvious implication that reliance on such equipment parameters and guidelines may yield distorted results, there is a need for research investigators to carefully scrutinize each type of equipment, its purported parameters, and suggested guidelines before conducting and reporting their findings with such devices.
Furthermore, there is now clear evidence that standard parameters—such as dose expressed as Joules per square centimeter (J/cm2), which for decades has been the gold standard for reporting the dosage of each treatment—may be just one of several relevant parameters that should be documented with each case. This emerging fact and related factors prompted the World Association for Laser Therapy (WALT) to issue its recommended guideline for treating a variety of conditions, and suggesting parameters that should be reported in each paper. 6 For example, the significance of two parameters—total energy and total cumulative dose—which hitherto were either ignored or unaccounted for, is vividly illustrated by a recent report 7 involving what was considered to be “placebo” phototherapy.
In this example, the investigators had two identical treatment applicators; the only difference being that all but 1 of the 36 diodes in the “placebo” applicator were disabled, reducing the irradiance to <1.0 mW/cm2; whereas the output of the real treatment applicator was kept at 100 mW/cm2. As expected, treatment with the real applicator prompted faster healing of treated ulcers from the very beginning of therapy. Overall, it gave better results than the “placebo” treatment. However, the small amount of light emitted by the placebo applicator was not totally ineffective as was anticipated. Indeed, after the initial 45 days of treatment during which placebo-treated ulcers worsened, the ulcers began to heal virtually as nicely as those in the real treatment group did from the very beginning. This finding suggests that once the total amount of energy, that is, energy delivered at each treatment session multiplied by the total number of treatments, reached a certain threshold, the so-called “placebo” treatment began to engender positive healing.
As noted by the authors, 7 “… the small amount of light emitted by the ‘placebo’ probe had a cumulative effect that eventually reversed the trend toward worsening of the ulcers.” The lesson here is that there may be no such thing as “placebo” phototherapy; <1 mW/cm2 irradiance is not so minute that it could not possibly stimulate healing of ulcers—in this case, ulcers that failed to respond to any other form of treatment. Had the treatment been stopped within 45 days, the cumulative positive effect of the “placebo” treatment would not have been noticed.
Given the relevance of total cumulative energy, it can be inferred that the applicable threshold of cumulative energy would have been attained sooner if the placebo applicator had been a 5 or 10 mW/cm2 device instead of <1 mW/cm2. In other words, the beneficial effect of the 5 or 10 mW/cm2 would have manifested sooner than the 45 days reported for the <1 mW/cm2 “placebo” treatment. Herein lies the importance of a second treatment parameter that is rarely reported— total cumulative dose— that is, dose per treatment multiplied by the total number of treatments. The overall implication here is that the threshold for stimulating tissue response may well be determined by total cumulative energy measured in Joules (J), whereas the timeline for observing such response may be a function of total cumulative dose measured in Joules per square centimeter (J/cm2). It would appear that within certain limitations, and as long as the applicable dose (J/cm2) lies within the therapeutic range, the higher the dose per treatment session the quicker the threshold cumulative energy will be attained, and the sooner the positive effect of treatment will become evident, assuming treatment is indeed positive.
Therefore, three related factors should be seriously considered and carefully computed to accurately account for treatment. First is the need to report all relevant parameters as clearly presented by Jenkins and Carroll. 5 Second is to independently confirm the specifications of the equipment being used without following the guidelines offered by equipment manufacturers blindly. Third is to accurately measure the multitude of parameters tabulated by Jenkins and Carroll 5 , compare them across treatment groups when possible, and report their individual effects on the outcome measure. As successful treatment outcomes hinge squarely on correct dosimetry and informed selection of treatment parameters, such disciplined approach to phototherapy research could uncover more facts than have been reported hitherto.