Personalizing Photobiomodulation Therapy

Some of the earliest work in the field of laser photobiomodulation (PBM) therapy ¹ highlighted the need to consider tissue and treatment reactions as part of dosing principles, and to incorporate such knowledge as part of a rigorous history and physical examination of patients. Kert and Rose ¹ discussed “the unique sensitivity to laser treatment of each individual patient” (p. 60). More recently, others have espoused the reasonable proposition “that individual patient's response to LLLT is not uniform.” ² As healthcare moves toward individualized care, it is time to consider how we might harness our current knowledge of laser PBM dosing, and better target PBM therapy for a personalized medicine approach.

How do we apply a personalized approach to PBM therapy? Is there a genetically derived determinant for PBM outcomes, and can this be evaluated before making the decision to apply PBM therapy? And how can we combine a personalized/precision medicine approach with evidence based on randomized controlled trials in which trial participant characteristics are homogenized because of strict trial designs and restrictive inclusion and exclusion criteria? Does a new approach to translating research findings into practice need to be considered for PBM therapies?

It is now increasingly clear that the quantity and quality of appropriately designed PBM clinical trials have resulted in robust evidence for the use of laser and light PBM therapy for a range of musculoskeletal conditions. The WALT Dosage Recommendations (http://waltza.co.za/documentation-links/recommendations) are a clear demonstration of how the peer-reviewed literature has contributed to distilling research outcomes into clinically applicable guidelines for time-poor clinicians. In general, the WALT recommendations have significant utility, yet not all patients benefit. For instance, the WALT guidelines do not yet include the entirety of published conditions that have been treated with PBM therapy nor the range of wavelengths that are now available in the market.

The PBM community is a broad church, including scientists, clinicians across many fields, physicists, and so on. Although the basic and laboratory PBM sciences have been ascendant for the better part of the past two decades, it would seem that now more than ever, we must bring together the laboratory scientists and clinical researchers to enact the vision of precision medicine espoused by Sonis et al. ² How might this challenge be approached in a noncompetitive and cohesive way?

It is clear that globally, there are many nodes of exceptional research being carried out within the PBM community. This author proposes that the first step to filling some of the gaps in our existing knowledge of PBM therapy is by a stocktake of existing publications, and of research currently being conducted. A vast amount of this information already exists as part of PBM-specific journals and PBM societies, but the work cannot be left to isolated pockets or a few passionate individuals. A concerted effort would be required through national and international networks to collate information. Such a stocktake could be carried out by developing a one-stop online system similar to clinical trials research registers.

A stocktake would identify where international expertise resides and would aid in connecting researchers with common interests and complementary skills. Multi-national collaborative groups would subsequently be able to leverage from the work of each other, applying for scarce research funds as international teams, and would be able to continue the task of filling gaps and pursuing valuable avenues of translational research to answer some of the most pressing health needs of our time. The proposed database and network of teams would assist in preventing unnecessary duplication of effort, and of replicating findings where important to do so, thus assisting in facilitating cost-effective clinical trials. This author contends that some of the most pressing gaps in translational research include those in which the greatest quantity of data derived from biological effects on cell studies in animals and in vitro could be selectively distilled for application in clinical trials. Moreover, clinical trials need to include multi-center, international collaborations so that further information may be gleaned regarding matters such as genetic variations that occur in different regions of the world.

Sonis et al. ² have recently drawn some attention to potential genomic determinants that may be associated with PBM therapy for chemotherapy-induced mucositis. The notion of evaluating individual genetic markers as a method for identifying responders and nonresponders to PBM is a realistic opportunity for bringing laboratory scientists together with clinicians. Wound healing is a good example of where such an approach would be valuable and potentially viable. Evidence for the use of laser PBM therapy in stimulating human and animal cell proliferation in vitro is relatively robust ³ and there is supporting evidence from animal studies, ⁴ yet it has not been possible to translate the evidence into clinical trials of healing of chronic wounds. ⁵ Individual patient variation, difficulties in recruiting participants with specific wound types, and the plethora of PBM parameters are some of the reasons for the inability to fill this research gap. Ramirez et al. ⁶ used microRNA profiling to investigate cellular and molecular differences in human diabetic foot skin. Their findings were suggestive of subtle changes in gene expression between human foot skin from diabetics and those without diabetes mellitus. Given that PBM therapy has been shown to have selective effects on gene expression, for example, ⁷ it would seem prudent to be collecting and archiving such data from all clinical trials to better understand how PBM therapy can be individualized.

This author proposes the development of a biological data register within which deidentified data from multi-center, international PBM trials, for example, wound healing, pain treatment, and exercise preconditioning, could be located and would include gene expression profiling data. Information maintained in such a register would contain big data sets that could be interrogated for matches in clinical outcomes with laser parameters, and include the ability to identify the most likely genetic markers for positive responses to PBM therapy. Further, where nonresponders are identified, other PBM options might be investigated and developed.

In the meantime, two initiatives are required. First, those with laboratory skills should continue to pursue answers to questions regarding dosing parameters so that translation of outcomes can continue to refine the clinical application of PBM therapy. Importantly, such efforts should be coordinated where the expertise exists in a way similar to that proposed for clinical trials. An example would be the excellent work on bone regeneration being carried out by Renno, Parizotto, and colleagues in Brazil.

Second, clinicians in diverse fields such as physiotherapy, dentistry, and medicine need to continue to understand the appropriate technical aspects of clinically applying PBM therapy, and specifically where it can be applied safely for greatest efficacy in different conditions. In recent yet-to-be-published work, our team has been investigating optimization of clinical musculoskeletal outcomes from laser PBM. We have identified that selective targeting of specific vascular structures around the elbow may result not only in augmented physiological responses but also improved pain outcomes for individuals with lateral epicondylalgia.

It is only through the insights provided by clinicians that the translational work of applying results from meta-analyses, systematic reviews, and laboratory studies can lead to positive individual clinical outcomes. It is highly likely that the accurate placement of photons at specific anatomical sites may assist in optimizing individual outcomes, resulting in the precision medicine that has recently become so topical. After all, when our cars need gas, we put the fuel in the petrol tank. We do not pour the gas all over the vehicle and expect that it will leak in somewhere to ignite the engine.