WALT/NAALT 2026 COURSES

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WALT/NAALT Plenary Session Courses

The systematic effects of photobiomodulation therapy: a review of evidence for and against

Keynote Speaker: Juanita Anders, PhD

Introduction: While local effects of Photobiomodulation Therapy (PBMT) have been well-documented, the systemic effects of PBMT, where treatment applied in one area of the body produces therapeutic benefits in distant, non-irradiated tissues, remains controversial. In this presentation, the evidence both supporting and challenging the systemic efficacy of PBMT will be presented.

Methods: The data presented is from research done in my laboratory on wound healing and on a thorough review of the literature from 2010 to 2026.

Results: Evidence supporting PBMT systemic effects: Since 2010, a growing body of evidence suggests that PBMT can produce systemic effects. Data from 2023–2026 emphasizes that blood is the most common route for systemic change. PBMT has been reported to reduce systemic inflammatory markers like IL-6, CRP, and TNF-alpha in patients with chronic low back pain and osteoarthritis. Studies on extracorporeal circulation show that NIR light can stabilize red blood cell (RBC) membranes, reducing hemolysis and oxidative stress markers throughout the entire blood volume, not just the irradiated portion. PBMT can trigger a shift in macrophage phenotypes (from pro-inflammatory M1 to reparative M2) that can be detected in distant, non-irradiated tissues. Stimulated macrophages affect other macrophages by releasing cytokines which act as signaling molecules, attracting nearby macrophages to the site of inflammation and further activating them through receptor interactions, creating a positive feedback loop. Migration of Mesenchymal Stem Cells is often implicated as a mechanism for systemic effects, but the existing data is not conclusive. Evidence against PBMT systemic effects: Despite some strong evidence, the overall data supporting a broad systemic effect is inconsistent. Conclusions of systemic effects are often made based on flawed interpretation of data and mechanism. An example of this invalid interpretation is based on the discovery in 2020 of cell free mitochondria in human blood. The presence of these mitochondria in blood is often implicated as responsible for systemic effects. However, it was not proven that these mitochondria were respiratory competent or functional. In 2021 Stier found no evidence that their mitochondrial electron transport system was functional. The respiration rate was not significantly different from 0 and there were no significant responses to ADP, uncoupler, or mitochondrial inhibitors oligomycin and antimycin A. (Am J Physiol Endocrinol Metab 2021: E859-E863.) Another argument against systemic efficacy is the dose-response curve and dose dilution. For a systemic effect to occur, the signal must remain within a therapeutic window. If the signal is weakened during transport to a distant location, it will have no effect.

Conclusions: While systemic effects are observed, the exact pathway remains undefined. Many of the reported benefits exhibit low certainty of evidence in systematic reviews, with calls for more high-quality, standardized clinical trials before widespread adoption can be fully recommended.

Recent advances in photobiomodulation: from precision personalized care to policy updates

Keynote Speaker: Praveen Arany, BDS, MDS, MMSc, PhD

Photobiomodulation (PBM) therapy, defined as the therapeutic use of nonionizing visible and near-infrared light (400–1200 nm) to modulate biological responses, has evolved from an empirical modality into a mechanistically grounded and clinically translatable intervention. Recent advances in PBM research have significantly improved our understanding of its biological mechanisms, dosimetry, and expanding therapeutic applications across oral, systemic, and age-related diseases. A major mechanistic advance from our laboratory demonstrates a coordinated intracellular and extracellular redox signaling framework in oral keratinocytes (Ponnusamy et al. 2026, Cells). PBM induces intracellular reactive oxygen species (ROS) generation through mitochondrial cytochrome C oxidase (CcO), with subsequent extracellular diffusion leading to activation of latent TGF-β1 via oxidation of a redox-sensitive methionine residue. Photoactivation of latent TGF-β1 induces Activating Transcription Factor-4 (ATF-4) through canonical Smad3 and non-canonical ERK/p38 MAPK pathways, while NFκB functions as a critical signaling integrator. Proteomic analyses revealed suppression of inflammatory and apoptotic pathways alongside activation of stress-adaptive signaling responses. These findings position ATF-4 as a promising molecular biomarker for optimizing PBM dosing and validating therapeutic thresholds. Complementing these mechanistic insights, a recent state-of-the-art review (Arany 2025, JADA Foundational Science) distinguishes PBM from photothermal and photodynamic therapies by its nonthermal and nondestructive mode of action. Three principal PBM mechanisms are highlighted: intracellular CcO activation, membrane receptor and ion channel modulation (Opsins, TRPV1), and extracellular latent TGF-β1 photoactivation. The review additionally proposes a novel dosimetry framework using photon fluence and Einstein units to improve reproducibility across devices and wavelengths (Esteves-Pereira et al. 2024, Oral Surg Oral Med Oral Pathol Oral Radiol). Clinical evidence now strongly supports PBM for oral mucositis management, while additional applications include temporomandibular disorders, wound healing, dental pulp regeneration, and accelerated orthodontic tooth movement. Importantly, scientific advances in PBM are now being paralleled by significant regulatory and policy developments. Recent FDA guidance documents for oral mucositis and supportive cancer care increasingly emphasize standardized endpoints, reproducible dosimetry, and evidence-based PBM protocols to facilitate broader clinical implementation. Concurrently, the American Dental Association (ADA) has expanded educational initiatives focused on CDT 2026 coding revisions and implementation strategies. Most notably, the 2026 CDT coding updates introduce dedicated PBM billing codes, D9128 and D9129, representing a major milestone in the clinical integration and reimbursement infrastructure for PBM therapies. These additions formally recognize PBM as a distinct adjunctive therapeutic modality for applications including pain management, oral mucositis, temporomandibular disorders, and postoperative recovery. Extending the translational horizon, recent National Institute on Aging workshop proceedings highlight PBM’s emerging role in aging and age-associated diseases, including neuroprotection, cardiovascular health, improved vascular function, and enhanced cognitive performance (Frankowski et al. 2025, GeroScience). Collectively, these mechanistic, translational, and policy advances mark a pivotal maturation of PBM from descriptive clinical observations toward biomarker-guided, dose-optimized, and increasingly standardized therapeutic interventions with broad systemic relevance.

Learning Objectives:

  • To appreciate the mechanistic basis of photobiomodulation therapy
  • To learn about various signaling pathways and crosstalk
  • To outline the dosimetry precision of PBM enabling rigorous, reproducible clinical benefits

Photobiomodulation in Cancer Supportive Care: Evidence-Based Indications, Clinical Applications and Future Perspectives

René-Jean Bensadoun, MD, HRD

Introduction: Photobiomodulation (PBM) is increasingly recognized as a promising supportive care modality for the prevention and management of several toxicities associated with cancer treatments. By delivering low-intensity red or near-infrared light to tissues, PBM induces photochemical and photobiological effects that modulate cellular metabolism, reduce inflammation, relieve pain, and stimulate tissue repair. These mechanisms are particularly relevant in oncology supportive care, where treatment-induced tissue injury often involves inflammatory cascades, oxidative stress, and impaired regenerative processes.

Methods: WALT position paper on the preventive and curative role of PBM in various side effects of cancer treatment was published in 2022.

Results: Among all PBM indications in oncology, oral mucositis prevention and management currently represent the most strongly supported evidence-based application, with several randomized controlled trials and international guidelines demonstrating significant clinical benefit. PBM reduces the incidence, severity, and duration of mucositis in patients undergoing chemotherapy, radiotherapy, or combined chemoradiation therapy, particularly in head and neck cancer. Based on accumulated clinical evidence, international expert groups such as MASCC/ISOO and the World Association for Laser Therapy (WALT) recommend PBM as a standard supportive care intervention for mucositis prevention in selected clinical settings. Beyond mucositis, growing evidence supports the potential role of PBM in other treatment-related toxicities. Recent clinical studies and systematic reviews suggest beneficial effects in radiation dermatitis, chemotherapy-induced peripheral neuropathy, and lymphedema, while promising preliminary data exist for additional complications such as radiation-induced fibrosis, dysphagia, xerostomia, trismus, osteonecrosis, graft-versus-host disease, and palmar-plantar erythrodysesthesia. These conditions share common biological pathways involving inflammation, vascular damage, oxidative stress, and impaired tissue regeneration, which may be modulated by PBM through mitochondrial activation, improved cellular signaling, and enhanced tissue repair mechanisms. Safety is a critical consideration in oncology. Current preclinical and clinical evidence suggests that PBM, when applied using validated protocols and appropriate dosimetry, is safe in cancer patients and does not promote tumor growth or recurrence. Nevertheless, strict adherence to evidence-based parameters and clinical guidelines remains essential. Despite the significant progress achieved over the past decade, several challenges remain. PBM protocols often vary widely in wavelength, power density, energy dose, treatment frequency, and delivery techniques. Therefore, future research should focus on standardization of treatment parameters, optimization of dosimetry, and the development of personalized PBM protocols. In addition, larger randomized clinical trials and/or large series of treated patients are needed to strengthen the level of evidence for emerging indications.

Conclusions: Finally, PBM may represent a highly valuable component of integrated supportive oncology, improving patient quality of life, reducing treatment interruptions, and potentially decreasing healthcare costs. Continued collaboration between clinicians, researchers, and international scientific societies will be essential to ensure the rigorous and responsible development of PBM in cancer care.

Artificial Intelligence as a Framework for Precision Photobiomodulation Dosing

Liisa Laakso, BPhty, PhD

Photobiomodulation (PBM) is an effective therapeutic modality across a range of clinical indications; however, dosing recommendations remain heterogeneous, largely empirical, and inadequately personalised. Variability in wavelength, power, fluence, pulsing, treatment duration, tissue optics, and patient factors reduces reproducibility and consistency of outcomes. This perspective presentation explores whether artificial intelligence (AI) could support a transition from fixed PBM protocols toward precision, patient‑specific dosing. This presentation is a call to action for improved data recording and open access datasets that will support faster translation from benchtop to bedside. Methods This plenary perspective lecture synthesises published mechanistic, biological, and clinical literature relating to PBM dosing and AI‑guided therapeutic optimisation. Conceptual AI roles are examined across three levels: physics‑informed modelling to estimate within‑tissue light distribution; biology‑driven models integrating cellular, omics, and clinical outcome data; and clinical decision‑support or closed‑loop systems incorporating biomarkers such as EEG. Device parameters discussed include wavelength (630–680 nm; 780–1100 nm), power, irradiance, fluence, pulse structure, treatment time, and spatial targeting. All parameters presented derive from published studies and manufacturer specifications. Experimental levels represented include basic science, translational and early clinical studies. Results Emerging evidence suggests AI could identify optimal PBM parameter combinations, predict tissue‑ or patient‑specific responses, and propose dose ranges rather than fixed prescriptions. Biology‑driven models demonstrate that integrating transcriptomic, proteomic, and metabolomic responses can delineate PBM dose–response windows in some models. Conceptual AI‑linked PBM devices and biomarker‑guided adaptive PBM systems further support the feasibility of personalised, biomarker‑informed dosing, although high‑level clinical evidence remains limited. Conclusions AI offers a credible framework for mechanistically grounded, evidence‑integrated, and patient‑specific PBM dosing while preserving clinician oversight. Progress will depend on improved PBM reporting standards, harmonised datasets, rigorous validation, and early‑phase clinical trials designed with AI readiness. AI‑guided PBM should be viewed as an evolution in clinical decision support rather than a replacement for expert clinical judgement.

Learning Objectives:

  • Describe whether artificial intelligence (AI) could support a transition from fixed PBM protocols toward precision, patient-specific dosing
  • Discuss some conceptual roles for how AI could assist in integrating PBM into clinical practice
  • Advocate for improved PBM data recording and development of open access datasets of PBM dosing parameters

Photobiomodulation at 660 nm Activates Wnt/β-Catenin Signalling and Enhances Wound Healing

Nicolette Houreld, D. Tech

Basic Fibroblast Growth Factor (bFGF) plays a crucial role in wound healing by acting as a strong activator of the canonical Wnt/β-catenin signalling pathway, specifically through stimulating fibroblast proliferation and migration. This activation occurs in the proliferative phase of wound healing, helping to speed up tissue regeneration, angiogenesis, and collagen deposition. Photobiomodulation (PBM) harnesses the therapeutic properties of light to promote healing for the benefit of patients. PBM has been shown to accelerate wound healing through activation of various cellular signalling pathways, increased growth factor and extracellular matrix production, and transcription of genes essential to healing. This study investigates the influence of PBM at 660 nm and a fluence of 5 J/cm2 (11.34 mW/cm2, 7 min 53 s) on bFGF and activation of the canonical Wnt/β-catenin pathway in wounded and hyperglycaemic wounded human skin fibroblasts in vitro. Cellular migration, proliferation, and viability were assessed 24 and 48 h post-PBM, along with proteins (bFGF, β-catenin, pGSKβ, Total GSKβ, and c-MYC) and the transcription of genes involved in the Wnt/β-catenin pathway. PBM treatment enhanced fibroblast migration, viability, and proliferation, and increased bFGF and β-catenin, as well as the transcription of pathway-related genes. These findings suggest that PBM at 660 nm and 5 J/cm2 activates the Wnt/β-catenin signalling pathway, thereby promoting wound healing processes in vitro.

Learning Objectives:

  • Understand the role of bFGF in activating wnt/β-catenin signalling pathway during fibroblast-mediated wound healing.
  • Explain how photobiomodulation influences fibroblast function and key molecular pathways involved in tissue repair.
  • Evaluate the effects of PBM on cellular behavior (migration, proliferation, viability) and gene/protein expression in normal and hyperglycaemic wound models in vitro.

photobiomodulation promotes tenogenic fate in adipose mesenchymal stem cells in three dimensional hydrogels

Heidi Abrahamse, PhD

Introduction: Tendon injuries are characterised by poor intrinsic healing due to low cellularity, vascularity, and metabolic activity, resulting in prolonged recovery and suboptimal clinical outcomes. Mesenchymal stem cell (MSC)-based tenogenic differentiation presents a promising regenerative strategy; however, the lack of standardised differentiation protocols and physiologically relevant culture systems limits progress. Photobiomodulation (PBM) has demonstrated potential in enhancing cellular proliferation and differentiation, yet its application in stem cell-driven tenogenesis, particularly within three-dimensional (3D) environments, remains underexplored.

Methods: Human immortalised adipose-derived mesenchymal stem cells (ASC52Telo) were differentiated into tenocytes using a stepwise protocol in both two-dimensional (2D) monolayer and three-dimensional (3D) hydrogel culture systems. Photobiomodulation was delivered using a diode laser system (NLC) at wavelengths of 525 nm and 825 nm, with power outputs of approximately 551 mW and 187 mW, respectively, operating in continuous wave mode. The irradiation spot size was approximately 9.5 cm², corresponding to power densities of ~60.68 mW/cm² (525 nm) and ~20.60 mW/cm² (825 nm). Energy densities of 5 J/cm² were identified as optimal for 2D culture, while 10 J/cm², applied as a combination of wavelengths, was optimal for 3D conditions. Treatment exposure times were calculated according to the required fluence, and a single-dose PBM approach was employed across comparative experimental groups. Irradiation was performed directly on the culture plates, targeting localised areas corresponding to the cell culture wells. Cellular responses were evaluated through morphological assessment using May-Grünwald-Giemsa staining and microscopy, while cellular health was assessed using ATP quantification, lactate dehydrogenase (LDH) activity, and reactive oxygen species (ROS) assays. Collagen production was quantified using Sirius Red staining, and tenogenic differentiation was confirmed through gene expression analysis of early (Scleraxis) and late (Tenomodulin) tenocyte markers.

Results: In 2D culture, PBM at 825 nm and 5 J/cm² significantly enhanced cellular viability, proliferation, and early tenogenic differentiation. The stepwise differentiation protocol successfully induced tenogenic lineage commitment in ASC52Telo cells. Hydrogel encapsulation demonstrated good biocompatibility, with PBM further enhancing proliferation and metabolic activity. In 3D culture, PBM significantly upregulated tenogenic gene expression in a wavelength- and fluence-dependent manner. The combination of 525 nm and 825 nm at 10 J/cm² yielded optimal differentiation outcomes. Overall, 3D culture systems provided a more physiologically relevant response compared to 2D models, with PBM acting as a modulatory tool to enhance differentiation efficiency. All experiments were performed in quadruplicates (N=4) for quantitative results and in duplicates (N=2) for qualitative results. All quantitative results were statistically analysed using Sigma Plot version 12. The mean and standard error was calculated and compared between groups using either student t-test or One-way ANOVA.

Conclusion: This study demonstrates that PBM enhances tenogenic differentiation of ADMSCs, particularly within 3D hydrogel environments. Optimal outcomes were achieved using combined wavelengths (525/825 nm) at 10 J/cm². These findings support the integration of PBM into stem cell-based regenerative strategies and highlight the importance of 3D culture models for translational relevance. Future work should focus on extended culture durations, extracellular matrix maturation, and in vivo validation.

Declaration Statement: Important: Ethical clearance for this study was obtained (REC-1973-2023).

photobiomodulation therapy of orofacial neuropathic pain—clinical practice guidelines and consensus using the HANNA framework

Reem Hanna, BDS, PhD, MSc, PG DipSed, PG DipHE, PG Cert AP, FAHE, FRSM, FIADFE, LPA (ALSP Certified)

Background/Objectives: Photobiomodulation (PBM) therapy has shown potential in managing orofacial neuropathic pain; however, variability in dosimetry and methodological heterogeneity limit its clinical translation. This World Association for Photobiomodulation Therapy (WALT) Position Paper aims to critically appraise current evidence and develop Clinical Practice Guidelines (CPG) and Expert Consensus Opinions (ECO) where appropriate. It also introduces the novel HANNA (Holistic Analysis & Novel Normative Actions) Framework as a structured methodology to enhance transparency, reproducibility, and rigor in evidence synthesis and guideline development.

Methods: Evidence evaluation was conducted using the HANNA (Holistic Analysis & Novel Normative Actions) Framework, integrating systematic review, critical appraisal, and expert consensus processes. A systematic review was performed in accordance with PRISMA 2020 guidelines. Methodological quality of included studies was assessed using AMSTAR 2 for systematic reviews, RoB 2 for randomized controlled trials, and ROBINS-I for non-randomized studies. The Oxford Centre for Evidence-Based Medicine (OCEBM) framework was used to classify levels of evidence. The AGREE II instrument was used to ensure transparency and methodological rigor in guideline development. The Somerfield Criteria were additionally applied to grade the strength of evidence across clinical conditions where appropriate. Multidisciplinary panel consensus meetings were conducted to finalise the WALT recommendations.

Results: WALT Clinical Practice Guidelines were established for primary burning mouth syndrome (BMS), supported by Level I evidence from 204 patients across six low-risk-of-bias studies and a high-confidence systematic review and meta-analysis including 557 patients. The findings primarily support PBM-based CPG for primary BMS and ECO for post-herpetic neuralgia (PHN) and idiopathic trigeminal neuralgia (TN), both supported by Level II evidence. Insufficient evidence precluded formal recommendations for post-traumatic trigeminal neuralgia, glossopharyngeal neuralgia, and occipital neuralgia. Particular emphasis is placed on PBM dosimetry parameters within WALT Clinical Practice Guidelines for primary BMS and ECO for PHN and idiopathic TN.

Conclusions: This position paper introduces the HANNA Framework as a structured methodology for developing transparent WALT recommendations. It provides evidence-based clinical practice guidelines for PBM in primary BMS and expert consensus recommendations for idiopathic TN and PHN. These findings support PBM as a safe and effective therapeutic approach and offer a roadmap for future research and guideline updates.

Learning Objectives:

  • To understand the role of photobiomodulation (PBM) therapy in the management of orofacial neuropathic pain, particularly primary burning mouth syndrome (BMS), idiopathic trigeminal neuralgia (TN), and post-herpetic neuralgia (PHN).
  • To appreciate the robust evidence-based supporting WALT Clinical Practice Guidelines (CPG) for PBM in primary BMS and Expert Consensus Opinions (ECO) for idiopathis TN and PHN.
  • To recognise the importance of standardised PBM dosimetry parameters in improving clinical reproducibility and treatment outcomes.
  • To understand the application of the novel HANNA (Holistic Analysis & Novel Normative Actions) Framework in developing transparent and evidence-based WALT recommendations.

Photobiomodulation Combined with Dynamic Thermal Imaging: An Emerging Approach for Functional Assessment of Microvascular Responses

Lilach Gavish, PhD, MPH

Background: Photobiomodulation (PBM) induces acute physiological effects that may reflect underlying tissue perfusion and vascular responsiveness. Dynamic thermal imaging offers a non-invasive method to visualize these responses in real time and may provide new opportunities for functional assessment in PBM research and clinical practice.

Concept and Approach: This lecture will present an emerging concept combining PBM with dynamic thermal imaging to evaluate acute microvascular responses following treatment using thermal imaging, corroborated by photoplethysmography and laser Doppler flowmetry. Across a series of studies, serial thermal imaging was performed before and after PBM treatment in healthy participants and clinical populations, including chronic wounds and chemotherapy-induced neuropathy.

Key Findings: Studies in healthy participants demonstrated that PBM induces immediate and sustained increases in tissue perfusion associated with arteriolar vasodilatation. These responses were wavelength-dependent and modified by individual baseline skin temperature. In addition, unilateral irradiation resulted in an immediate bilateral response, suggesting involvement of neurovascular pathways, although the response of the contralateral untreated hand was shorter in duration and lower in magnitude. Particular emphasis will be placed on diabetic foot ulcers, in which PBM treatment induced a sustained increase in wound bed temperature that was not observed in venous ulcers. Furthermore, the thermal response of diabetic foot ulcers correlated inversely with baseline temperature, indicating greater responsiveness in colder wounds. Together with observations from cold-hand models, these findings raise the possibility that different low-perfusion states may exhibit distinct dynamic thermal response patterns to PBM, potentially reflecting differences in the underlying vascular pathology.

Conclusions and Future Directions: The lecture will discuss the potential role of PBM as a controlled physiological stimulus for dynamic imaging, and explore future applications including responder identification, treatment personalization, physiological phenotyping, and development of functional biomarkers in photobiomodulation research.

Learning Objectives:

  • Describe the use of dynamic thermal imaging for assessment of acute physiological responses following PBM treatment.
  • Recognize distinct thermal response patterns asscoiated with different low-perfusion conditions, including diabetic foot ulcers, venous ulcers, and cold-hand models
  • Discuss the potential role of PBM as a controlled physiological stimulus for functional imaging, responder identification, and treatment personalization.

Effects of resistance training with/without Photobiomodulation on muscle and respiratory function in difficult-to-control asthma: a randomized trial

Nivaldo Parizotto, PT, PhD

Effects of resistance training with/without Photobiomodulation on muscle and respiratory function in difficult-to-control asthma: a randomized trial. Ivan Peres Costa1, Emilia Raposo Nascimento1, Lawrence P. Cahalin2, Etiene Farah Teixeira Carvalho1, Edvane Aparecida Braz Araujo Silva1, Roberto Stirbulov3, Rodolfo Paula Vieira4, Simone Dal Corso5, Nivaldo Antonio Parizotto6, Raquel Agnelli Mesquita-Ferrari1, Luciana Maria Malosá Sampaio1 1-University Nove de Julho, São Paulo, Brazil, 2-Department of Physical Therapy, University of Miami, Miami, USA, 3-Faculty of Medical Sciences of Santa Casa of São Paulo, São Paulo, Brazil, 4-Evangelica University of Goiás, Anápolis, Brazil, 5-Monash University, Melbourne, Australia, 6-Federal University of São Carlos, São Carlos, Brazil (presenter) Difficult-to-Control Asthma (DTCA) is often characterized by persistent symptomatology and diminished functional capacity, even when pharmacological management is optimized. Given the prevalence of peripheral muscle dysfunction in this population, identifying adjunctive interventions to enhance resistance training (RT) outcomes is of significant clinical interest. This randomized, triple-blind, controlled trial evaluated the efficacy of combining RT with LED-based photobiomodulation therapy (PBMT) compared to RT alone in 30 adults with DTCA. Participants were randomized into an experimental group (RT+LEDT; n=15) receiving active PBMT before sessions or a control group (RT; n=15) receiving a placebo. PBMT was done using a custom-built 50-LED probe (λ = 850 ± 20 nm in continuous emission mode), developed by the Federal University of São Carlos and the University of São Paulo. Each LED delivered an average power output of 50 mW, with an irradiance of 250 mW/cm² and a spot size of 0.2 cm². The irradiation time was 15 s per point, resulting in an energy delivery of 0.75 J per LED and a radiant exposure of 3.75 J/cm². A total of 50 points were irradiated per muscle group, corresponding to 37.5 J per muscle group and 262.5 J per session. Both cohorts underwent a supervised 12-week RT program twice weekly. The primary endpoint was peripheral muscular strength, quantified via one-repetition maximum muscle contraction (1RM). Secondary metrics included cardiopulmonary exercise parameters, functional capacity (shuttle walk test), spirometry, and asthma control. Following the intervention, the RT+LEDT group demonstrated superior gains in 1RM strength across major muscle groups, alongside significant increases in oxygen consumption at the anaerobic threshold and walking distance. While no significant intergroup differences were detected in pulmonary function or asthma control scores, the integration of PBMT into rehabilitation protocols appears to synergistically improve muscular performance and functional endurance in DTCA patients. Keywords: Asthma, Resistance training, Photobiomodulation, Muscle strength, Respiratory function. Declaration statement: The study was approved by the Research Ethics Committee of University Nove de Julho (Approval number: 1.691.019.

Photobiomodulation Regulates Neural Organoid Formation from Adipose-Derived Stem Cells in a 3D Culture Model

Anine Crous, PhD

The development of physiologically relevant three-dimensional (3D) neural organoid models represents a major advancement in regenerative medicine; however, controlling stem cell differentiation into organised neural tissue remains a significant challenge. Photobiomodulation (PBM) is a non-invasive approach capable of modulating cellular metabolism, mitochondrial function, and signalling pathways associated with differentiation. While PBM has demonstrated neurogenic potential in two-dimensional systems, its role in regulating neuronal organoid formation in 3D environments remains insufficiently understood. This study investigated the effects of PBM on the differentiation of adipose-derived mesenchymal stem cells (ADMSCs) into neuronal organoid-like structures. This study was conducted at a basic science experimental level. Immortalised human adipose-derived mesenchymal stem cells (ADMSCs; ASC52Telo) were cultured and induced to form neuronal organoid-like structures using a staged three-dimensional (3D) differentiation protocol, including embryoid body formation, neural induction, and Matrigel embedding. Photobiomodulation was delivered using diode laser systems from the National Laser Centre, South Africa, at wavelengths of 525 nm (green) and 825 nm (near-infrared), including combination treatments. The lasers operated in continuous wave mode, with power outputs of approximately 553.89 mW (525 nm) and 180.58 mW (825 nm), and a spot size of 3.4 cm², corresponding to power densities of ~60.98 mW/cm² and ~19.90 mW/cm², respectively. Energy densities of 5 J/cm² and 10 J/cm² were applied. Exposure times ranged from 82–164 seconds for 525 nm and 251–502 seconds for 825 nm, calculated according to the required fluence. A sequential PBM treatment approach was employed, consisting of two irradiation applications during the differentiation process. Irradiation was performed directly on the organoid cultures under controlled conditions, targeting localised areas within the 3D culture system. Organoid morphology and size were assessed using microscopy, while cellular responses were evaluated through viability analysis (live/dead assay), metabolic activity (ATP luminescence), mitochondrial membrane potential (ΔΨm), and neural differentiation via gene expression analysis of key markers, including Nestin, GFAP, TBR2, TUBB3, and RBFOX3, using quantitative real-time PCR. PBM significantly influenced neuronal organoid development in a wavelength- and fluence-dependent manner. Low-fluence irradiation (5 J/cm²), particularly at 525 nm, enhanced metabolic activity, supported stem cell maintenance, and promoted early neural differentiation, evidenced by increased expression of progenitor markers including Nestin and GFAP. Higher fluence (10 J/cm²) generally attenuated early differentiation responses; however, combination wavelength treatment enhanced late-stage neuronal maturation, as indicated by increased expression of mature neuronal markers such as RBFOX3 (NeuN). PBM also modulated mitochondrial membrane potential, with increased ΔΨm observed under specific wavelength conditions, suggesting enhanced mitochondrial activity during differentiation. Morphologically, PBM-treated organoids demonstrated increased cellular outgrowth and expansion, supporting neural-like structural development. Overall, PBM promoted coordinated changes in metabolism, mitochondrial function, and gene expression consistent with staged neuronal differentiation. This study demonstrates that PBM can effectively regulate neuronal organoid formation from ADMSCs in a 3D culture system. Low-fluence PBM supports early neural commitment, while higher fluence, particularly in combination wavelengths, promotes later-stage neuronal maturation. These findings highlight PBM as a promising non-invasive tool for directing stem cell fate and optimising organoid-based models for neuroregenerative applications.


WALT/NAALT Educational Courses

PBM in supportive care for cancer

René-Jean Bensadoun, MD, HRD

More information coming soon...

PBM in Wound care

Keynote Speaker: Praveen Arany, PhD, DDS

More information coming soon...

PBM applications in dentistry and orofacial disorders

Keynote Speaker: Juanita Anders, MS, PhD

Reem Hanna, BDS, MSc, PhD, PG DipSed, PG DipHE, FAHE, FIADFE

More information coming soon...

PBM and the mitochondria

Lilach Gavish, PhD, MPH

More information coming soon...

Trials and research methodology

Keynote Speaker: Praveen Arany, PhD, DDS

Liisa Laakso, BPhty, PhD

More information coming soon...

PBM in Musculoskeletal Applications

Nivaldo Parizotto, PT, MSc, PhD

Cleber Ferraresi, PT, MS, PhD

More information coming soon...

pBM in neurology

Paolo Cassano, MD, PhD

More information coming soon...

PBM and the microcirculation: Mechanism and Applications

Lilach Gavish, PhD, MPH

More information coming soon...


WALT/NAALT 15-Minute Oral Presentations

Analgesic outcomes of 650 nm versus 810 nm diode laser photobiomodulation after dental implant placement in a randomized controlled trial

Mohamed Yehya, BDS, MDS, PhD

Photobiomodulation (PBM) is a promising non-pharmacological approach for managing postoperative pain after dental implant placement. Yet, comparative data on red (650 nm) and near-infrared (810 nm) diode lasers remain limited and inconclusive. This double-blind, randomized controlled trial evaluated the short-term analgesic efficacy of 650 nm and 810 nm PBM on postoperative pain, analgesic intake, and oral health-related quality of life (OHRQoL) following single-implant placement in the posterior maxilla. Sixty patients were randomly assigned to receive PBM with 650 nm, PBM with 810 nm, or a sham control. The full treatment protocol involved a total of six laser therapy sessions (18 J total energy per site, three sessions per week for two weeks). However, for the primary outcome of acute pain evaluation, only the first two sessions were included in the analysis (immediately postoperatively and at 48 hours). Pain intensity (11-point Numeric Rating Scale) and analgesic use were recorded at 2, 6, 12, 24, 48, and 72 hours post-surgery. OHRQoL was assessed using the Oral Health Impact Profile-14 (OHIP-14) questionnaire at baseline, one week, and after crown delivery, thereby encompassing the full six-session protocol. At 2 hours, both PBM groups reported significantly lower pain scores compared to the sham group (p< 0.05), with no severe pain observed in the PBM groups. The 650 nm group exhibited significantly reduced analgesic consumption at 2 and 6 hours (p< 0.05), indicating a superior early analgesic effect. Pain scores and medication use converged across groups after Day 1, with no significant differences observed by Day 2 and Day 3, indicating that the analgesic effect was transient and limited to the acute phase. While overall OHRQoL scores did not differ significantly, the 810 nm group showed improvement in the “physical disability” domain. These results suggest that PBM, particularly at 650 nm, may serve as an effective adjunct to improve early postoperative outcomes in minimally invasive implant procedures. 

Applications of PBM in Periodontal Practice: Case series

Janina Golob Deeb, DMD, MS

Case series: First case of a 63-year-old female presenting with generalized, symptomatic oral mucosal ulcerative lesions in the oral cavity bilaterally on the buccal mucosa and in the vermillion border of the lower lip in a patient with history of rheumatoid arthritis managed with methotrexate with supplemental folic acid. PBM therapy consisted of three adjunctive sessions every 4-5 days.

The second case was a patient following mandibular extractions, alveoloplasty, immediate implant placement and free gingival graft resulting in a complete bilateral paresthesia of the mental nerve area (chin and lower lip) two weeks postoperatively. To enhance the neurosensory recovery, PBM therapy was delivered to intraoral surgical areas, adjacent extraoral zones, and regional lymph nodes over two sessions within one week.

The third case was a symptomatic female with recurrent abscesses around implant hybrid prosthesis on current antiresorptive therapy. Due to high rsik of osteonecrosis, PBM was implemented twice a week following removal of eight mandibular implants due to severe periimplantitis and debridement. In all cases, PBM therapy was delivered to intraoral surgical areas, adjacent extraoral zones, and regional lymph nodes for 60 seconds per site targeting intraoral affected areas and regional lymph nodes in several sessions twice a week.

PBM for all three cases was performed using Nd:YAG laser (Fotona), 1064 nm wavelength using Genova handpiece with 1 cm diameter at 0.5 W/cm2 and 10 Hz. Results: After two to three PBM sessions, all three patients reported improved symptoms and showed marked improvement in clinical appearance and function. For patient with ulcerative lesions, the patient reported and demonstrated complete resolution of symptomatic mucosal lesions following PBM therapy. For patient two, neurosensory function with over 90% deficit showed almost complete resolution of paresthesia and only minor residual hypoesthesia with no further interventions required. The third patient experienced slow yet favorable healing in the mandible with only one persistent area of slow healing. Conclusion: PBM is a safe, non-invasive modality that delivers low-level laser energy to target tissues and has demonstrated anti-inflammatory effects. These cases highlight the potential benefit of adjunctive PBM in the management of severe inflammatory oral lesions and management of patients with complications and slow healing potential due to medical comorbidities.

EEG-Guided Photobiomodulation for Cognitive and Neuropsychiatric Outcomes: A Translational Clinical Approach

Kody Newman, BS

Photobiomodulation (PBM) has demonstrated effects on mitochondrial function, cerebral blood flow, and neural signaling, yet clinical adoption remains limited due to inconsistent parameter selection and lack of objective targeting methods. EEG provides a real-time, non-invasive biomarker of brain function that may enable personalized PBM protocols. This study explores the integration of EEG-guided targeting with transcranial PBM (tPBM) to improve cognitive and neuropsychiatric outcomes. Participants with cognitive complaints (memory decline, mood disturbance, or neurological symptoms) underwent baseline EEG assessment to identify abnormal frequency patterns (e.g., excess delta/theta, dysregulated alpha). PBM protocols were selected based on EEG findings and applied over targeted cortical regions. The LED-based PBM device delivered 810 nm (primary) and 630–660 nm (adjunct) wavelengths at 10–50 mW/cm², with pulsed and continuous modes, across 3–10 J/cm² doses. Sessions lasted 5–20 min, two to three times per week, for 12–24 total treatments. Patients demonstrated consistent EEG normalization trends, including reductions in slow-wave excess and improvements in alpha and beta activity. Clinically, participants reported improvements in memory, mood, sleep, and cognitive clarity. Representative outcomes included reduced seizure frequency and duration in epilepsy cases, improved memory recall and executive function in cognitive decline, decreased dizziness and normalization of temporal slowing, and subjective mood improvements. These findings align with observed increases in higher-frequency EEG activity and improved network connectivity following tPBM. EEG-guided PBM represents a promising approach for individualized neuromodulation. By aligning PBM parameters with functional brain abnormalities, clinicians may improve treatment precision and outcomes. Further controlled studies are warranted to standardize EEG-guided PBM protocols and validate the observed cognitive and neuropsychiatric benefits.

Learning Objectives:

  • Understand the physiological mechanisms of photobiomodulation and its impact on mitochondrial function, cerebral blood flow, and neural signaling.
  • Learn how EEG biomarkers can guide individualized photobiomodulation protocols and target specific cortical regions for neuromodulation
  • Review clinical outcomes and case studies demonstrating the effectiveness of EEG-guided photobiomodulation for cognitive and neuropsychiatric conditions
  • Recognize considerations for translating photobiomodulation research into clinical practice, including dosing parameters and safety considerations

assessment of dose-dependent effects of 1064 nm photobiomodulation therapy on human tenocyte- and bursa-derived cell proliferation in vitro

Scott Sigman, MD

Background/Objectives: Photobiomodulation Therapy (PBMT) is widely used in musculoskeletal rehabilitation. Although its clinical use continues to expand, the dose-dependent metabolic responses on specific musculoskeletal cell populations remain undefined. This study assessed the effects of 1064 nm PBMT on primary human tenocytes and bursa-derived cells across varying fluence and irradiance.

Methods: Primary tenocytes and bursa-derived cells were cultured in 24-well plates and exposed to Hiro TT 1064 nm laser at fluences ranging from 1.5 to 6.0 J/cm? and irradiance levels of 90 or 125 mW / cm?. Treatments were administered once daily for three consecutive days. Cellular activity was assessed using an XTT assay and bright field microscopy was performed to assess cell morphology and confluency. Statistical analysis was compared to evaluate dose-dependent effects.

Results: PBMT demonstrated tissue-dependent effects on cellular metabolic activity and proliferation. In tenocytes, moderate fluence (4.5-6.0 J/ cm?) significantly increased metabolic activity compared with control. In contrast, bursa-derived cells exhibited smaller magnitude changes, with most treatment groups demonstrating neutral or modest deviations from control.

Conclusions: PBMT of 1064 nm wavelenght produced distinct dose-dependent responses in musculoskeletal cell types, with tenocytes demonstrating a threshold-dependent response and bursa-derived cells showing attenuated effects. These findings support the need for tissue-specific parameters when applying PBMT in clinical tendon-related applications.

Photobiomodulation in Complex Female Infertility Profile: A Case Report with 12-Month Follow-Up and Review of Current Mechanism in Reproductive Photomedicine

Ruth Phypers, MA

Female infertility from polycystic ovarian syndrome (PCOS) and endometriosis poses a challenge for both clinicians and women who are trying to conceive. The present clinical single case report aimed to evaluate the efficacy of multiple wavelengths of red and near-infrared (NIR) laser photobiomodulation (PBM) for increasing the potential of fertility in a woman with PCOS, endometriosis and low ovarian reserve. The observations helped to inform and establish the following: (1) any adverse effects; (2) the possibility of producing an effective PBM protocol; and (3) a healthy live birth. The case report concerns a female who failed to conceive naturally beyond five years and had experienced one unsuccessful IVF cycle. Methods: Case report of one female subject with infertility issues, which included failure to conceive naturally beyond five years. Previous conditions were recorded and then compared with outcomes from after the patient received a course of PBM treatments. PBM treatments were given at weekly and/or at two-week intervals over a 5-month period during the follicular stage of the menstrual cycle, using IR and NIR wavelengths between 600 and 1000 nm. Results: After five months a spontaneous conception was achieved. The case resulted in a full-term pregnancy and the birth of a healthy baby. Improvements in reproductive health outcomes in this case give reason to suggest that PBM helped to alleviate PCOS and endometriosis which could have been associated with a low ovarian reserve. Conclusions: The case report indicates that a multiwavelength of red and NIR-PBM laser therapy could have positively contributed to a healthy live birth in a female diagnosed with PCOS, endometriosis and a low ovarian reserve. Extensive studies with large data are warranted to validate our PBM dosimetry and treatment protocols to assess the potential impact of PBM for treating endometriosis and PCOS. Subsequently, to understand the genetic and phenotype biomarkers would be an important step further to standardise a range of PBM light dosimetry.

Feasibility and Efficacy of Photobiomodulation in the Prevention and Treatment of Radiotherapy-Induced Oral Mucositis and Radiation Dermatitis

Belinda Mandrell, PhD

Radiotherapy is associated with significant adverse effects, including oral mucositis and radiation dermatitis. Photobiomodulation (PBM) is included in the Children’s Oncology Group Supportive Care Guidelines for the presentation and treatment of oral mucositis among children and adolescents receiving head/neck radiotherapy. This project aimed to evaluate the feasibility and preliminary efficacy of PBM in the prevention and treatment of oral mucositis and the treatment of radiation dermatitis in patients undergoing therapeutic radiotherapy. Methods: Three radiation oncology nurses were trained in PBM therapy applications, including clinical indication and treatment parameters. A standard operating procedure (SOP) for mucositis was developed with PBM delivered daily (Monday-Friday) prior to radiotherapy. Treatment was administered using the Thor® PBM system including the Lollipop (660nm/80nW: 850nm/60nW), LED Cluster (660nm/10nW; 850nm/30mW), and Dental Probe (810nm/200mW) in continuous wave with direct contact. Each site was treated for one minute, with dental probe spot treatment extended to 2 minutes if needed. Treated areas included the intraoral, extraoral (bilaterial cheeks and lips), extraoral (submandibular, bilaterial cervical, and esophagus regions). All radiation patients were assessed for radiation dermatitis. An SOP for dermatitis management utilized the LED Cluster device (660nm/10nW; 850nm/30mW) daily during radiation and as clinically indicated at the completion of therapy. The probe was positioned over the dermatitis, treating multiple points to include the affected region and up to 2 cm of surrounding non-irradiated tissue. Demographic and clinical data collected included patient diagnosis, age, radiation dose and duration, treatment site, number of PBM treatments, and photographic documentation. Descriptive statistics were used for analysis. Results: Forty-one patients, mean age 12 (range 1-25 years), received PBM during radiotherapy for prevention of mucositis or radiation dermatitis treatment. Eleven patients received PBM for mucositis prevention secondary to head and neck radiation. Of these, 92% of the PBM treatments were delivered prior to radiotherapy and developed only grade 1-2 mucositis. The remaining patients were treated for radiation dermatitis secondary to sarcomas, with visible improvement and healing occurring after an average of five PBM treatments. Conclusion: Photobiomodulation is a feasible intervention in the radiation oncology setting and is associated with reduced severity of oral mucositis and accelerated healing of radiation dermatitis. Successful implementation requires standardized protocols, trained nursing staff, and strong interdisciplinary clinical support.

Self-Applied Home-Use Photobiomodulation Reduces Pain in Patients with Knee Osteoarthritis: A Double-Blind Randomized Sham-Controlled Trial

Lilach Gavish, PhD, MPH

Background: Aim Knee osteoarthritis (KOA) is a leading cause of chronic pain and functional limitation in older adults, with limited effective non-surgical treatment options. Photobiomodulation (PBM) has demonstrated analgesic and functional benefits in KOA, largely in clinic-based settings requiring repeated supervised treatments. This study evaluated the efficacy of self-applied, home-use PBM in a real-world setting.

Methods: This prospective, double-blind, randomized, sham-controlled trial with a pragmatic real-world design (NCT06773676) recruited adults aged ≥50 years with knee pain ≥40 on a visual analog scale (VAS) and functional limitation ≥1 month. Participants were randomized to active or sham PBM (B-Cure Laser, Haifa, Israel). Treatment (808 nm, pulsed, 15kHz [33% duty cycle], peak power 250mW, 4.5 cm² spot, 6 min × 3 points – aligned with WALT dose recommendations) was self-administered at home daily for 1 month and every other day during months 2–3. The primary outcome was change in average pain (VAS, mm) from baseline to 1 and 3 months (Δ1m; Δ3m); secondary outcomes included WOMAC physical function and SF-12 quality-of-life (QOL). Between-group comparisons were performed using ANCOVA adjusted for baseline values.

Results: Forty participants (active/sham 20/20) were included (age 65.4±7.2 years; Kellgren-Lawrence 2.4±0.8 [91% fulfilled ACR criteria for KOA], baseline pain 73±17mm). The active group demonstrated significantly greater pain reduction at 1 and 3 months (active vs sham: Δ1m 43±16mm vs 15±20mm, p<0.001; Δ3m 44±25mm vs 20±21mm, p=0.002). Compared with sham, significant improvements were observed in WOMAC function (p≤0.003 at both time points) and in mental QOL (p<0.001), with the active group reaching population norms at 1 month (40±10 to 51±6).

Conclusions: At-home PBM significantly reduced pain and improved function and mental health-related QOL in adults with KOA. As a self-applied, easy-to-use intervention, home-use PBM may enhance patient involvement and adherence. These findings support PBM as a safe, non-pharmacological, and practical adjunct to conservative KOA management.

Photobiomodulation in Breast Cancer-Related Lymphoedema: Effects on Limb Volume and Quality of Life

Kate Perkins, B. App. Sci. (OT)

Introduction: Breast cancer-related lymphoedema (BCRL) is a common chronic complication following surgery and radiotherapy, characterised by impaired lymphatic drainage, limb swelling, and progressive tissue changes that negatively impact function and quality of life. Photobiomodulation therapy (PBMT) has been proposed to enhance lymphatic flow, reduce inflammation, and improve tissue repair. This study evaluates the clinical effects of PBMT on limb volume and patient-reported outcomes in patients with BCRL.

Methods: Experimental Level: Clinical Patients with clinically diagnosed BCRL underwent a course of PBMT as part of their lymphoedema management. Interstitial fluid level was assessed using bioimpedance spectroscopy (L-Dex) and circumferential tape measurements. Patient-reported outcomes were evaluated using the LYMPHQOL questionnaire, a validated instrument assessing symptoms, function, and quality of life in lymphoedema populations. Assessments were performed at baseline (pre-treatment) and following completion of PBMT.

Device Specifications:

  • Manufacturer, Location and Model: ASA Laser, Arcugnano, Italy, M8 MLS® Robotic Laser
  • Wavelength(s): 808 nm and 905 nm
  • Power: Up to 75 W peak
  • Mode: Synchronized continuous (808 nm) and pulsed (905 nm), frequency range 1–2000 Hz
  • Spot Size / Area: ~3 cm² (handpiece); ~20 cm² (robotic scanning head)
  • Probe Design: Combined single probe and multi-diode robotic cluster
  • Power Density: Not specified; variable due to MLS dual emission and robotic scanning delivery (manufacturer-provided)
  • Energy Density: 4–10 J/cm² (protocol-defined; delivered via manufacturer-programmed robotic scanning system)
  • Energy per point/area or total energy: 3.43j/cm2 over 30cm2 per treatment area

Treatment Specifications:

  • Treatment Time: 5–10 minutes per treatment region
  • Frequency of treatments: 2 times per week
  • Total Number of Treatments: 8 sessions over 4 weeks
  • Technique Used: Combined direct contact (handheld) and robotic scanning
  • Areas Treated: Local (lymph node dissection + chemotherapy and/or radiation treatment)
  • Location and Number of Points: At risk limb using scanning motion of Hand held following lymphatic drainage pathways
  • Grid Pattern/Sequential Treatment: Not applicable; continuous robotic scanning delivery over defined treatment area
  • Treatment Pattern: Sequential scanning with supplementary localised application
  • If Animals: No

Results: PBMT was associated with reductions in limb volume as measured by both L-Dex and circumferential tape measurements. Improvements were also observed across LYMPHQOL domains, reflecting reduced symptom burden and improved functional outcomes. Statistical analysis demonstrated significant improvements in both objective and patient-reported measures following treatment (p< 0.05).

Conclusion: PBMT demonstrates clinical utility as an adjunctive therapy in the management of BCRL, with measurable reductions in limb volume and improvements in patient-reported outcomes. These findings support the integration of PBMT into multidisciplinary lymphoedema care for breast cancer survivors. Further research is warranted to optimise treatment parameters and evaluate long-term outcomes.

Timing of Photobiomodulation in Head and Neck Radiotherapy: Impact on Radiation-Induced Fibrosis

Kate Perkins, B. App. Sci. (OT)

Introduction: Radiation-induced fibrosis is a common and debilitating late effect of head and neck cancer treatment, resulting in functional impairment and reduced quality of life. Photobiomodulation therapy (PBMT) has been proposed as a supportive intervention to modulate inflammation and promote tissue repair. This study evaluates the impact of PBMT timing by comparing outcomes in patients receiving PBMT concurrently during radiotherapy with those presenting later with established fibrosis who subsequently undergo PBMT, using the FACT/GOG-Ntx as a patient-reported outcome measure.

Methods: Experimental Level: Clinical This comparative cohort study included two patient groups:

  1. Patients receiving PBMT concurrently during radiotherapy (early intervention group)
  2. Patients presenting approximately 4 months post-radiotherapy with established radiation-induced fibrosis who subsequently commenced PBMT (delayed intervention group)
Fibrosis-related symptoms were assessed using the FACT/GOG-Ntx questionnaire at baseline (pre-PBMT) and following completion of PBMT. The FACT/GOG-Ntx is a validated patient-reported outcome measure that assesses quality of life and neurotoxicity-related symptoms in patients undergoing cancer treatment.  

Device Specifications:

  • Manufacturer, Location and Model: ASA Laser, Arcugnano, Italy, M8 MLS® Robotic Laser
  • Wavelength(s): 808 nm and 905 nm
  • Power: Up to 75 W peak
  • Mode: Synchronized continuous (808 nm) and pulsed (905 nm), frequency range 1–2000 Hz
  • Spot Size / Area: ~3 cm² (handpiece); ~20 cm² (robotic scanning head)
  • Probe Design: Combined single probe and multi-diode robotic cluster
  • Power Density: Not specified; variable due to MLS dual emission and robotic scanning delivery (manufacturer-provided)
  • Energy Density: 4–10 J/cm² (protocol-defined; delivered via manufacturer-programmed robotic scanning system)
  • Energy per point/area or total energy: 4 J/cm2 over 50cm2 (during radiation treatment)

Treatment Specifications:

  • Treatment Time: 2 minutes per treatment region
  • Frequency of treatments: 3 times per week over 5weeks (during RT)
  • Total Number of Treatments: 15 sessions over 5 weeks (throughout the course of RT)
  • Technique Used: Combined direct contact (handheld) and robotic scanning
  • Areas Treated: Local (irradiated head and neck tissues)
  • Location and Number of Points: Neck radiation treatment areas – up to 2 to 3 points
  • Grid Pattern/Sequential Treatment: Not applicable; continuous robotic scanning delivery over defined treatment area
  • Treatment Pattern: Sequential scanning with supplementary localised application
  • If Animals: No
Results: Both groups demonstrated improvement in FACT/GOG-Ntx scores following PBMT. However, patients receiving PBMT concurrently during radiotherapy exhibited significantly less deterioration from baseline and superior overall outcomes compared to the delayed intervention group. Patients presenting with established fibrosis showed improvement post-treatment; however, their post-PBMT scores remained lower than those treated concurrently. Statistical analysis demonstrated significant improvements within groups and a significant difference between groups (p< 0.05).

Effects of Vascular Photobiomodulation as an Adjunct Therapy in the Treatment of Sickle Cell Disease: Impact on Pain, Vital Signs, and Hematology

Thais Azevedo Reis, MSc

Introduction: Sickle cell disease (SCD) is a serious genetic disorder characterized by structural alterations in hemoglobin that lead to vaso-occlusive crises and recurrent pain, significantly impacting quality of life. Adjuvant therapeutic approaches have been increasingly investigated, including vascular photobiomodulation (VPM), for its analgesic properties and ability to modulate microcirculation.

Objective: To evaluate the effects of VPM on pain control, vital signs, and hematological parameters in black patients with sickle cell disease from the southwestern region of Bahia, Brazil.

Methods: This is a semi-experimental, longitudinal, prospective, before-and-after study that included 10 adult patients with SCD (HbSC genotype). The VPM protocol consisted of five consecutive sessions. The application was performed on the left wrist, over the radial artery of the participants, using the DCM Therapy RC® equipment (DMC Equipamentos, São Carlos, São Paulo), with the following parameters: 660 nm laser (visible red), 100 mW power, beam diameter of 0.028 cm², continuous mode for 30 minutes, totaling 180 J of energy and fluence of 6428 J/cm². Pain intensity was assessed using the Visual Analogue Scale (VAS) and the McGill Pain Questionnaire. Vital signs were assessed before and after the intervention, over five consecutive days, and hematological parameters were analyzed before and after treatment. Statistical analyses were performed using the paired t-test or the Wilcoxon signed-rank test, depending on the data distribution, with a significance level set at 5%.

Results: A significant reduction in pain intensity was observed, with an immediate analgesic effect after the FBMV sessions. The magnitude of the response was most pronounced in the first days of treatment, with a progressive reduction in pain scores until the third day, when patients were almost pain-free. This improvement was accompanied by a decrease in heart rate, respiratory rate, and mean arterial pressure, as well as an increase in peripheral oxygen saturation, a clinically relevant finding suggesting improved tissue oxygenation. In the hematological profile, an increase in platelet count and mean corpuscular volume was identified, without significant changes in hemoglobin or hematocrit levels.

Conclusion: FBMV proved to be an effective and low-cost adjuvant therapy, demonstrating a positive impact on pain reduction, physiological modulation, and relevant hematological parameters in patients with sickle cell disease. Declarations: The study was conducted in accordance with the ethical principles of research involving human beings, with approval by a Research Ethics Committee and obtaining informed consent from all participants.

Impact of Photobiomodulation on Oral Mucositis, Pain, and Microbiota in Head and Neck Cancer Patients Undergoing Antineoplastic Therapy

Iasmym Mendes de Jesus, MSc

Introduction: Oral mucositis (OM) is one of the most frequent and debilitating complications of antineoplastic therapy in patients with head and neck cancer (HNC), directly impacting pain levels, nutrition, and therapeutic continuity.

Objective: To evaluate the effects of photobiomodulation (PBM) on the severity of oral mucositis, pain control, and influence on the oral microbiota in patients undergoing antineoplastic treatment.

Methods: Clinical study with 21 patients with head and neck cancer undergoing antineoplastic treatment. PBM was applied preventively and therapeutically, twice a week (≈10–14 sessions) for approximately 35 days, using DMC Therapy EC® equipment (DMC Equipamentos, São Carlos, SP, Brazil), with a single probe, in continuous mode and point application in direct contact with the mucosa. Wavelengths of 660 nm and 808 nm, power of 100 mW, irradiation area of ​​0.25 cm², and power density of 0.4 W/cm² were used. The application time per point varied between 5, 10, and 40 seconds, corresponding to energies of 0.5 J, 1 J, and 4 J and energy densities between 2.0 and 16.0 J/cm². The protocol was performed sequentially and diffusely, covering multiple regions of the oral mucosa, including buccal mucosa, lips, palate, tongue, and floor of the mouth, totaling approximately 47 to 62 points per session, with total estimated energy between 20 and 250 J per session. The protocol was adapted according to the individual clinical condition of each patient. Oral mucositis was classified according to the WHO (grades 0–4), and pain was assessed using the Visual Analogue Scale. Saliva samples were processed in a laminar flow hood, with inocula in serial dilutions of 10⁻¹ to 10⁻⁴ seeded in Petri dishes for quantification of Candida spp., Staphylococcus aureus, Escherichia coli, Streptococcus mutans, and total microorganisms. Data were analyzed using the Shapiro-Wilk test and paired t-test (p<0.05).

Results: A significant reduction in CFU/mL was observed for Staphylococcus aureus and Escherichia coli at the end of treatment. PBM delayed the onset of oral mucositis, reduced its severity, and significantly reduced pain throughout the follow-up period.

Conclusions: PBM proved effective in preventing and reducing oral mucositis, controlling pain, and modulating the oral microbiota, contributing to better clinical outcomes in cancer patients.

Artificial Intelligence as a Dosimetry Engine in Cross-Platform Photobiomodulation: Predictive Modeling and Adaptive Protocol Design

Alan Kwong Hing, DDS, MSc

Introduction: Reproducibility in photobiomodulation (PBM) remains limited by variability in wavelength selection, irradiance, fluence, and tissue-depth estimation. While lasers and LEDs are often compared as hardware modalities, variability in dosing logic across platforms may compromise clinical consistency. Artificial intelligence (AI) may provide a framework for harmonizing PBM dosimetry across delivery systems.

Methods: This translational presentation evaluates artificial intelligence as a dosimetry engine capable of integrating chairside laser and wearable LED PBM delivery. This work does not evaluate a specific device but presents a conceptual framework based on established PBM dosimetry ranges derived from peer-reviewed literature and manufacturer specifications. Representative parameter ranges include:

  • Laser (example ranges):
    • Wavelength: 810–980 nm
    • Power: 200–1000 mW
    • Mode: Continuous wave
    • Spot size: 0.04–0.5 cm²
    • Energy density: 2–8 J/cm²
    • Treatment time: 20–60 seconds per point
  • LED (example ranges):
    • Wavelength: 630–660 nm and/or 810–850 nm
    • Power density: 10–100 mW/cm²
    • Energy density: 2–6 J/cm²
    • Mode: Continuous wave
    • Area: Broad coverage
    • Frequency: Daily or alternate-day application
  • AI modeling components include:
    • Tissue-depth estimation
    • Fluence distribution mapping
    • Cumulative dose harmonization
    • Reinforcement scheduling
    • Conceptual adaptive protocol refinement

Experimental Level: Translational

Results: Conceptual modeling suggests improved cumulative dose alignment between focal laser initiation and distributed LED reinforcement. Algorithmic harmonization indicates potential for enhanced reproducibility across platforms. AI-supported integration may reduce variability in dosing and support more consistent biologic signaling.

Conclusions: Artificial intelligence may function as a cross-platform dosimetry engine in PBM systems, supporting predictive modeling and adaptive reinforcement while preserving clinician-directed decision-making. Further clinical validation is required.

Home-Based Intranasal and Transcranial Photobiomodulation for Cognitive Dysfunction in Post-COVID Condition: A Randomized Sham-Controlled Trial

Lew Lim, PhD, MBA

Introduction: Cognitive dysfunction (“brain fog”) is a common and persistent symptom of post-COVID condition (PCC), with limited treatment options available. Photobiomodulation (PBM) has demonstrated potential to modulate mitochondrial function, cerebral perfusion, and neural activity—mechanisms implicated in PCC-related cognitive impairment. This study evaluates the feasibility, safety, and preliminary efficacy of home-based intranasal and transcranial PBM for cognitive dysfunction in PCC.

Methods: Experimental Level: Clinical Study Design: Prospective, randomized, double-blind, sham-controlled pilot trial conducted remotely using home-based treatment and digital outcome assessments. Participants: Adults aged 18-65 years with cognitive symptoms persisting 12 weeks following SARS-CoV-2 infection. 

Device Specifications:

  • Manufacturer: Vielight Inc., Toronto, Canada
  • Model: Neuro Gamma
  • Wavelength: 810 nm
  • Power: ~9–150 mW per emitter
  • Mode: Pulsed (40 Hz)
  • Duty Cycle: ~50%
  • Probe Design: o1 intranasal applicator o5 transcranial LED modules
  • Power Density: ~9–150 mW/cm² (depending on LED locations)
  • Energy Density: ~5–90 J/cm²
  • Total Energy: ~455 J per session

Parameters based on manufacturer specifications and clinical trial protocol. All parameters reflect clinically relevant human PBM protocols.

Treatment Specifications:

  • Treatment Time: 20 minutes per session
  • Frequency: 6 days per week
  • Total Duration: 8 weeks, followed by 4-week observation
  • Technique:
    • Intranasal: Direct intranasal probe
    • Transcranial: In-contact LED placement
  • Areas treated: nasal cavity and frontal cortical regions targeting default mode network hubs
  • Pattern: simultaneous application
  • Outcome Measures:
    • Primary: Change in composite cognitive score (Creyos battery: attention, memory, executive function) at Day 56
    • Secondary: Fatigue (FAS), quality of life (EQ-5D-5L), symptom burden, safety

Results: Forty-three participants were randomized, with 41 included in the per-protocol analysis (21 active, 20 sham). Active PBM demonstrated greater improvement in composite cognitive performance compared with sham at Day 56 (between-group difference 0.043; p=0.088). In prespecified exploratory analyses, participants younger than 45 years showed statistically significant improvement compared with sham (p=0.028), corresponding to a moderate effect size. Improvements were most consistent in attention-related tasks. Treatment adherence was high, and no serious adverse events were reported. Secondary outcomes were mixed, with subjective fatigue and mobility measures favoring sham.

Conclusions: Home-based intranasal and transcranial PBM is feasible, safe, and demonstrates preliminary signals of cognitive benefit in individuals with post-COVID condition, particularly in younger adults. The observed dissociation between objective cognitive improvements and subjective fatigue highlights the importance of energy management in post-COVID rehabilitation. These findings support further investigation in larger, adequately powered trials and suggest that PBM may represent a scalable, home-based neuromodulation approach for persistent cognitive symptoms following COVID-19.

Route-Specific Brain Effects of Photobiomodulation and Control of Brain-State Dynamics

Lew Lim, PhD, MBA

Introduction: Brain photobiomodulation (PBM) is commonly framed in terms of transcranial light penetration, but the extent to which delivery route shapes brain effects remains unclear. Emerging evidence suggests that intranasal and transcranial PBM may produce distinct neurophysiological and network-level responses. At the same time, neuromodulation lacks a quantitative framework to characterize and optimize brain-state dynamics. This lecture presents evidence for route-specific brain effects of PBM and introduces a control-theoretic framework for characterizing and optimizing brain-state dynamics.

Methods: Study Design: Synthesis of human EEG and fMRI datasets evaluating intranasal and transcranial PBM, integrated with a systems-level modeling framework for brain-state dynamics.

Device Specifications (representative human PBM systems):

  • Manufacturer: Vielight Inc., Toronto, Canada
  • Models: Neuro Gamma, Neuro Alpha, and experimental laser systems
  • Wavelengths: 810 nm (LED), 808 nm (laser), 1064 nm (LED and laser)
  • Power: ~5–300 mW per emitter •Mode: Pulsed (primarily 10 Hz and 40 Hz), with some continuous wave conditions
  • Duty Cycle: ~50%
  • Probe Design:
    • Intranasal: single applicator
    • Transcranial: multi-LED cluster
  • Power Density: ~25–300 mW/cm²
  • Energy Density: ~15–180 J/cm² (depending on LED locations)
  • Total Energy: ~up to 1470 J per session Parameters derived from a combination of direct measurement and manufacturer specifications across included studies.

All parameters reflect clinically relevant human PBM protocols.

Treatment Specifications:

  • Treatment Time: ~4–20 minutes per session
  • Frequency: single-session to daily protocols
  • Technique: intranasal probe and transcranial in-contact placement
  • Areas Treated: nasal cavity and frontal/dorsal cortical regions
  • Pattern: simultaneous or sequential application

Parameter ranges reflect variability across human studies.

Results: Convergent EEG and fMRI evidence demonstrates that intranasal and transcranial PBM produce distinct, route-specific brain effects. Intranasal PBM showed greater energy efficiency in modulating brain oscillatory activity, with lower irradiances producing stronger responses across frequency bands. fMRI findings revealed that intranasal PBM elicited significant hemodynamic responses, including engagement of subcortical regions such as the thalamus, whereas transcranial PBM has predominantly been associated with cortical activation. In addition, intranasal PBM was associated with distributed functional connectivity across distal brain regions, including sensorimotor and frontal networks. These findings indicate that PBM effects are not solely determined by transcranial photon penetration, but also by route-dependent access to neural and physiological pathways.

Conclusions: Intranasal and transcranial PBM represent complementary neuromodulation routes with distinct efficiencies and network targets. Intranasal PBM may engage olfactory-associated pathways with downstream influence on limbic and hippocampal systems, while transcranial PBM preferentially targets cortical networks. Building on these findings, a control-theoretic framework is introduced in which brain states are characterized by the energy required to maintain or transition between network configurations. A novel biomarker, Bidirectional Control Energy (BiCE), quantifies this property through directional components reflecting cortical-to-subcortical and subcortical-to-cortical interactions. BiCE provides a quantitative measure of brain-state efficiency and stability, and may offer a framework for understanding how PBM influences large-scale brain dynamics. The integration of route-specific PBM with control-energy metrics supports the development of adaptive and potentially closed-loop neuromodulation systems for clinical and performance applications.

Learning Objectives:

  • Differentiate route-specific effects of photobiomodulation: Describe the distinct neurophysiological and network-level effects of intranasal versus transcranial photobiomodulation based on EEG and fMRI evidence.
  • Explain mechanisms underlying route-dependent brain modulation: Discuss how differences in anatomical access and physiological pathways contribute to cortical, subcortical, and distributed network responses to PBM.
  • Understand control-theoretic approaches to brain-state dynamics: Interpret the concept of Bidirectional Control Energy (BiCE) as a quantitative framework for characterizing brian-state efficiency and stability.
  • Evaluate implications for adaptive neuromodulation strategies: Assess how integrating route-specific PBM with control-energy metrics may support the development of personalized and closed-loop neuromodulation systems for clinical and performance applications.

Intranasal and Transcranial Photobiomodulation in Traumatic Brain Injury: Translational and Clinical Evidence

Lew Lim, PhD, MBA

Introduction: Traumatic brain injury (TBI) remains a major cause of long-term neurological impairment, with no widely accepted treatment for persistent cognitive and neuropsychiatric symptoms. Photobiomodulation (PBM) has emerged as a non-invasive neuromodulation approach with potential to address key pathophysiological mechanisms of TBI, including mitochondrial dysfunction, neuroinflammation, and impaired cerebral perfusion. This study presents translational and clinical evidence supporting the use of combined intranasal and transcranial PBM in TBI.

Methods: Study Design: Synthesis of clinical observations, longitudinal cohort data, and supporting neurophysiological findings from TBI populations, including athletes exposed to repetitive head impacts.

Device Specifications:

  • Manufacturer: Vielight Inc., Toronto, Canada
  • Models: Neuro Gamma, Neuro Alpha
  • Wavelengths: 810 nm and 1064 nm
  • Power: ~9–150 mW per emitter
  • Mode: Pulsed (primarily 10 Hz and 40 Hz)
  • Duty Cycle: ~50%
  • Probe Design:
    • Intranasal applicator
    • Transcranial LED clusters
  • Power Density: ~9–150 mW/cm²
  • Energy Density: ~5–90 J/cm² (depending on LED location)
  • Total Energy: ~455 J per session

Parameters based on manufacturer specifications and applied clinical protocols. All parameters reflect clinically relevant human PBM protocols. Treatment Specifications:

  • Treatment Time: ~20 minutes per session
  • Frequency: daily or near-daily
  • Total Treatments: multi-week protocols
  • Technique:
    • Intranasal: direct intranasal probe
    • Transcranial: in-contact placement
  • Areas Treated: nasal cavity and frontal cortical regions
  • Pattern: simultaneous application

Results: Clinical and observational findings indicate that combined intranasal and transcranial PBM is associated with improvements in cognitive function, mood, and overall neurological performance in individuals with TBI, as assessed by standardized cognitive and symptom measures across observational cohorts. In athlete populations exposed to repetitive head impacts, longitudinal observations suggest that PBM may support functional resilience and recovery, with reduced symptom burden and improved performance metrics over time. Supporting neurophysiological evidence from MRI, fMRI, MRS, DTI, and EEG studies indicates that PBM is associated with changes consistent with neuroregeneration, improved functional connectivity, enhanced cerebral hemodynamics, and modulation of brain oscillatory activity relevant to TBI recovery.

Conclusions: Combined intranasal and transcranial PBM represents a promising non-invasive neuromodulation approach for the management of TBI, targeting key biological and functional impairments associated with injury. The integration of complementary delivery routes may enhance overall brain engagement, supporting both cortical and subcortical network function. These findings support further controlled studies and suggest potential applications in clinical rehabilitation, military populations, and contact sports.

Fast but Not Furious! Photobiomodulation Therapy in Alleviating Pain and Accelerating Orthodontic Tooth Movement in Children—A Systematic Review and Meta-Analysis

Chandrashekar Yavagal, MDS, DORTh, PhD

Background: Photobiomodulation (PBM) therapy has emerged as a transformative, non-invasive modality in dental science, demonstrating a wide therapeutic spectrum ranging from modulation of inflammation to enhancement of tissue repair and analgesia. Within orthodontics, PBM has gained increasing attention for its dual potential to accelerate orthodontic tooth movement (OTM) and reduce treatment-associated pain, two critical determinants of patient compliance and clinical efficiency. Despite growing interest, earlier systematic reviews have reported inconsistent or inconclusive findings, particularly in human clinical settings, owing to heterogeneity in study design, irradiation parameters, and outcome measures. In light of these discrepancies, the present systematic review was undertaken to critically evaluate and synthesize the current evidence on the efficacy of PBM in accelerating OTM and alleviating orthodontic pain in human subjects, with an additional focus on therapeutic dosage parameters.

Methods: The review protocol was prospectively registered in the PROSPERO database to ensure methodological transparency and reproducibility. A comprehensive and systematic literature search was conducted across multiple electronic databases without restrictions on language or publication date. Only randomized controlled trials (RCTs) and controlled clinical trials (CCTs) involving human participants undergoing orthodontic treatment were included. Studies evaluating the effects of PBM on either the rate of tooth movement or pain perception were considered. Screening, data extraction, and eligibility assessment were performed independently, followed by a qualitative synthesis of findings. The risk of bias was assessed using the Cochrane Risk of Bias tool, and particular attention was given to irradiation protocols, including wavelength, energy density, and application frequency, to explore dose-response relationships.

Results: The accumulated evidence indicates that PBM exerts a biologically favorable effect on bone remodeling processes integral to orthodontic tooth movement, including enhanced osteoblastic and osteoclastic activity, increased cellular proliferation, and modulation of inflammatory mediators. Across human clinical trials, PBM demonstrated a consistent trend toward accelerated OTM when compared to control groups, although the magnitude of effect varied depending on the irradiation parameters employed. Furthermore, PBM showed a significant reduction in orthodontic pain, attributed to its analgesic and anti-inflammatory mechanisms, including decreased prostaglandin synthesis and neural modulation. Importantly, no adverse effects or deleterious outcomes were reported, supporting its safety profile. The analysis also suggests that specific therapeutic windows of wavelength and energy density are critical in achieving optimal clinical outcomes.

Conclusions: The current body of evidence supports the clinical efficacy of PBM as a safe and effective adjunct in orthodontic therapy, capable of accelerating tooth movement and significantly reducing treatment-associated pain in human subjects. While variability in treatment protocols persists, emerging data underscore the importance of standardized dosage parameters to maximize therapeutic benefits. PBM represents a promising frontier in precision orthodontics, offering the potential to enhance treatment efficiency and patient experience. Further high-quality, standardized clinical trials are warranted to establish definitive clinical guidelines and optimize protocol-driven applications.

Learning Objectives:

  • Interrogate the evidence behind Photobiomodulation (PBM) in accelerating orthodontic tooth movement and pain reduction across fixed and aligner-based therapies.
  • Decode the biology of PBM by mapping its effects on bone remodeling, inflammation pathways, and neuromodulation in orthodontic biomechanics.
  • Engineer PBM protocols by selecting and optimizing wavelength, energy density, and treatment timing for predictable outcomes in both conventional and aligner orthodontics.
  • Deploy PBM clinically to enhance aligner tracking, reduce treatment time, and minimize patient discomfort with precision-driven, protocol-based care.

Observational Study on the Use of the PBM Lightforce Device in 227 Cases of Musculoskeletal Disorders: A 18 Months Follow Up

Karim Kleiber, MD

Background: Photobiomodulation (PBM) is defined as the therapeutic application of non-thermal light in the wavelength range of 600–1100 nm. It has gained increasing interest in the management of musculoskeletal disorders (MSDs) due to its anti-inflammatory and analgesic properties. High-intensity class IV lasers, such as the LightForce™ XLi 40 W system (model LTS-4000- L), emit dual wavelengths (810 and 980 nm), allowing deeper tissue penetration and potentially enhanced therapeutic effects. This device integrates automated treatment protocols optimizing key parameters, including energy density (20–80 J/cm²), power density (5–20 W/cm²), continuous wave mode, and treatment duration (3–15 minutes).

Objective: To evaluate the clinical effectiveness of PBM in reducing pain and improving outcomes in patients with MSD-related pain in a real-world clinical setting.

Methods: We conducted a prospective observational study including 292 patients presenting with MSD-related pain. All participants provided informed consent in accordance with the 2013 Declaration of Helsinki, and 227 patients were included in the final analysis. Patients received six PBM sessions over a three-week period (two sessions per week) using standardized automated protocols. Pain intensity was assessed using the Visual Analog Scale (VAS, 0–10) at baseline, immediately post-treatment, and during follow-up at 1, 3, 6, 9, 12, 15, and 18 months. Secondary outcomes included patient-reported global satisfaction (0–10 scale) and improvement in sleep quality assessed using a numerical rating scale.

Results: The study population had a balanced sex distribution (51.5% male, 48.5% female) with a median age of 52.5 years. The most frequently treated conditions were shoulder disorders (24%), low back pain (24%), elbow disorders (14%), cervical pain (7.8%), ankle disorders (5.2%), and other MSDs (25%). PBM demonstrated significant clinical efficacy, with 83.4% of patients achieving a pain reduction greater than 30% immediately after treatment. Mean VAS scores decreased by 55.2% post-treatment, 57.8% at one month, and reached 60.5% during long-term follow-up up to 18 months. A progressive improvement over the first three months was observed in 28.8% of patients. At three months, 68.8% of patients maintained a persistent analgesic benefit. Patients with acute pain showed greater improvement compared to chronic pain (67.3% vs. 51.3%). Sleep quality improved by 53% in affected patients.

Conclusion: PBM delivered using a high-intensity class IV laser appears to be a safe and effective treatment for MSD-related pain, providing both rapid and sustained analgesic benefits. However, the observational design and absence of a control group are limitations. Further randomized controlled trials are needed to confirm these findings.

Photobiomodulation Therapy for Management of Post–Treatment Dental Paresthesia: A Clinical Protocol and Case Series

Saba Khan, DMD

Introduction: Post–treatment dental paresthesia is an uncommon but clinically significant complication that may result in persistent numbness, dysesthesia, or altered sensation. These neurosensory disturbances can negatively affect speech, mastication, oral hygiene, and overall quality of life. Current management is primarily conservative and lacks standardized interventional protocols. Photobiomodulation therapy (PBMT) has demonstrated neuroregenerative and anti-inflammatory effects in peripheral nerve injury models and is increasingly explored in oral and maxillofacial applications. This case series describes a structured clinical protocol using PBMT to manage dental paresthesia following local anesthetic administration and related surgical procedures.

Methods: This case series included three patients who developed sensory alterations following dental procedures requiring local anesthesia, including crown preparation, root canal therapy, and apicoectomy. Upon identification of neurosensory changes, a standardized assessment protocol was implemented. Subjective evaluation included patient-reported symptom descriptions and numerical rating scale (NRS) scores for numbness and dysesthesia. Objective neurosensory testing included mechanoreceptive assessment using light-touch testing, and sensory mapping was performed to document the extent and distribution of altered sensation. Following baseline evaluation, PBMT was initiated using a 940-nm diode laser (Epic X, model # 81504119, Biolase, Irvine, CA) in continuous mode at 0.6 W for 30 seconds per treatment point, delivering 18 J per application. The standardized 15-mm working distance produced a spot diameter of 1.5 cm (1.77 cm² area), corresponding to a power density of 0.34 W/cm² and an energy density of 10.2 J/cm². Treatment was delivered using a direct in-contact probe technique over the area of sensory alteration. PBMT sessions were administered weekly, with the total number of treatments determined by clinical response. Neurosensory testing was repeated at follow-up visits to monitor recovery.

Results: Patients who received PBMT shortly after the identification of nerve injury demonstrated clinical improvement in sensory function. Improvements were observed in patient-reported numbness and dysesthesia scores, as well as objective light-touch perception. No adverse events were reported. Although spontaneous recovery cannot be excluded, the temporal association between PBMT initiation and progressive improvement suggests a therapeutic benefit.

Conclusion: Neurosensory dysfunction following dental and orthognathic procedures remains a significant clinical concern. This case series suggests that early implementation of photobiomodulation therapy may support neurosensory recovery as a safe, noninvasive adjunctive treatment. Further prospective, controlled studies are needed to establish standardized PBMT protocols and to determine the efficacy of PBMT in managing post–local anesthetic dental paresthesia.

Declaration of Statements: This case series includes three patients treated with photobiomodulation therapy as part of clinical care. Written informed consent was obtained from each patient for the use of de-identified clinical information for educational and presentation purposes. No identifiable patient information is included. Disclosure Statement: We have only academic interests in the study of lasers and their interactions with biological tissues. We have no financial relationships with any commercial entities relevant to this presentation.

Improving Aphasia Outcomes with Transcranial Photobiomodulation Combined with Speech-Language Therapy: A Case Study

Karla Estrada Rojas, MA, CCC-SLP

Objective: This is a case report showing that transcranial photobiomodulation (tPBM) combined with traditional, speech-language therapy improved and accelerated the results from speech-language therapy, in a stroke person with aphasia (PWA). Background: tPBM is a safe, noninvasive technique using red and near-infrared light to improve the metabolism of cells. tPBM helps by promoting neuromodulation, while decreasing neuroinflammation and promoting vasodilation. Several studies have shown that tPBM can help individuals with stroke or traumatic brain injury achieve significant cognitive improvements.

Methods: A 38-year-old female, who sustained an ischemic stroke on the left side of the brain, received two, 5-month series of treatments. The first series of treatments included traditional speech-language therapy, for the first 5 months poststroke. The second series of treatments included tPBM in combination with speech-language therapy, for the next 5 months. The tPBM treatments included application of red (630 and 660 nm) and near-infrared (850 nm) wavelengths of photons applied to left hemisphere scalp areas. The major cortical language areas were subjacent to the scalp placements along the line of the Sylvian fissure. At each session, first a light-emitting diode (LED) cluster head with red (630 and 660 nm) and near-infrared (850 nm) wavelengths, with an irradiance (power density) of 200 mW/cm2, a beam size of 4.9 cm2, and a fluence (energy density) of 12 J/cm2 per minute, was applied to the left side of the scalp/brain, along the Sylvian fissure for 60 sec at each at the following eight, language network target areas: frontal pole, prefrontal cortex, and inferior frontal gyrus (Broca's area); supramarginal gyrus and angular gyrus in the parietal lobe; inferior motor/sensory cortex (mouth area); and posterior superior temporal gyrus (Wernicke's area) and superior temporal sulcus in the temporal lobe, for a total of 8 min. Second, for the next 20 min (1200 sec), simultaneous with speech-language therapy, an LED PBM helmet was applied to the scalp/head. This helmet contained 256 separate LED lights, near-infrared (810 nm) wavelength, 60 mW power per LED light, total power, 15 W; energy, 72 Joules; fluence, 28.8 J/cm2; and irradiance, 24 mW/cm2.

Results and conclusions: During the initial, 5-month treatment series with traditional speech-language therapy only, there was little to no improvement in dysarthria and expressive language. During the second, 5-month treatment series, however, with tPBM applied first, to the left hemisphere only, and second, to both hemispheres during each session plus simultaneous speech-language therapy, there was marked improvement in the dysarthria and expressive language. After the first 5-month series, this PWA had utilized a slow rate of speech with a production of ∼25 to 30 words-per-minute during conversations and spontaneous speech. Utterance length was only 4-6 words with simple, grammatical structure. After the second, 5-month series of treatment combining tPBM plus speech-language therapy, the rate of speech increased to 80+ words-per-minute and utterance length was increased to 9-10 words, with more complex grammatical structure. Keywords: LLLT; PBM; aphasia; low-level laser therapy; photobiomodulation; speech-language therapy.

Does Photobiomodulation Reduce Impact of Extraintestinal Manifestations and Influence the Gut Microbiome in Young Adults with Inflammatory Bowel Disease?

Liisa Laakso, B-Phty, PhD

Introduction: Although Inflammatory Bowel Disease (IBD) primarily affects the gastrointestinal tract, it has many extraintestinal manifestations, including musculoskeletal pain, depression, anxiety and fatigue. There have been limited non-drug approaches to managing extraintestinal manifestations in IBD. We present the final results of a trial of photobiomodulation (PBM) assessing its feasibility and preliminary efficacy in young adults with IBD.

Methods: This prospective single-arm pilot trial recruited 26 female and male participants between the ages of 18-35 years, who received a 10-week course of PBM to the abdomen and thighs, delivered after a ten-week observation period. Fatigue was the primary outcome, with depression, pain, quality of life, inflammatory markers, microbiome composition and physical activity/function as secondary outcomes. The outcomes were measured at baseline, pre- and post-PBM and ten weeks after ceasing PBM. Device parameters as provided by manufacturer: Symbyx Pty Ltd Australia / Irradia Sweden; ProSeries 12-diode 904nm array; 60mW / diode; pulsed 700Hz; 0.5cm2 spot size / diode. Total energy: 861.3 J (abdomen), 129.6 J (thighs); total treatment time: 20 mins (abdomen) + 6 mins (both thighs); once weekly treatment for 10 weeks; direct in-contact application: 9 application points over large bowel; 3 application points to central quadriceps each thigh.

Results: Pre- and post-PBM data showed statistically and clinically improved outcomes for: FACIT-Fatigue (adj mean change +14.1 points improvement) (95% CI 11.1 to 17.1) with durability of effect at 10-week follow-up; depression (DASS-21; adj mean change –5.2, 95% CI -7.9 to -2.4) with further improvement at 10-week follow-up; anxiety (DASS-21; -3.5, 95% CI -5 to -2); stress (DASS-21; -7.3 95% CI -9.8 to -4.8); “worst pain last 7 days” (Brief Pain Inventory; -1.4, 95%CI -2.5 to -0.3); seven of eight domains of health-related quality of life (SF-36; physical functioning and role limitations, general health, vitality, social functioning, emotional limitations and well-being); increased MET minutes (International Physical Activity Questionnaire; 626, 95% CI -1412 to 2664); and improved function (Patient-Specific Functional Scale; 2.4, 95% CI 1.8 to 3.1). The impact of PBM on inflammatory markers was not statistically significant although trends toward reduced inflammation were noted for C-reactive protein and faecal calprotectin. Microbiome profiling did not reveal changes in diversity. Differential abundance analysis using Linear Discriminant Analysis (LDA) Effect Size (LEfSe) identified Ruminococcus gnavus to be enriched in responders after PBM, associated with an improved FACIT-Fatigue score.

Conclusions: PBM is a feasible and acceptable treatment for young adults with IBD, with promising potential in treating extraintestinal manifestations. An RCT will follow. The study received approval from the Mater Misericordiae Ltd Human Research Ethics Committee Reference Number: HREC/MML/62140 (V3). CI-Laakso has a 1% shareholding in Symbyx Pty Ltd.

Photobiomodulation Therapy for Knee Osteoarthritis (KOA) Applications Using a Novel Wearable PBM Device

Liisa Laakso, B-Phty, PhD

Introduction: This abstract reports findings from two complementary clinical studies investigating a novel wearable PBM device in a perioperative knee replacement cohort and in a community-based non-surgical KOA cohort.

Methods: The Light Knee Study was a double-blind, randomised, sham-controlled trial evaluating self-applied PBM pre- and post-operatively in people undergoing total knee replacement (TKR). The iPPaM study was a two-arm randomized, non-blinded pilot trial evaluating daily self-administered PBM over two weeks compared with no-treatment control in people with KOA prior to commencing physiotherapy. PBM device specifications (as provided by the manufacturer): CareWear Corp USA; Firefly Controller with hydrogel adhesive patches. Wavelength(s): 450nm and 640nm; Total optical power: 80mW; Mode: 33KHz pulsed, 33% duty factor; Irradiated area (patch size dependent): 10.5-12.7cm length x 5.2-9.2cm width; Irradiance: Nominal 2.5 mW/cm2; Energy / session: 144J; Fluence: 4.5J/cm2; Treatment time: 30mins. Direct in-contact application to knee using standardised protocols. TKR participants received seven daily PBM sessions before surgery, recommenced Day 1 post-surgery for 10 treatments over 2 weeks. KOA participants received daily PBM for two consecutive weeks. Outcomes included quality of life, functional performance, and pain scores. Statistical analyses included descriptive statistics and linear regression modelling.

Results: In the Light Knee Study (n=59) at Day 4 post-op, PBM-treated participants achieved clinically important, faster reductions in 40m fast-paced walk test (FPWT) time compared with sham (Active vs Sham Mean (s)(SD): 85 s (42), 114 s (61); p=0.22). At each subsequent visit over following 6 weeks, the PBM group took less time than sham treated participants to complete the FPWT test, with mean difference between groups reducing over time (NS) (Mean difference (s): 7 days -9.7; 2 weeks -9.5; 4 weeks -0.77; 6 weeks -0.72). In the iPPaM study (n=20), PBM was associated with clinically relevant short-term improvements in pain and mobility. Within the PBM group, FPWT time decreased by mean of 3.7 seconds at week 2 compared with baseline. Statistically significant within-group reductions were observed for pain during FPWT (−1.2 pain units), walking (−0.85), and lying-to-sitting (−1.05). Between-group differences versus control were not statistically significant, reflecting limited statistical power.

Conclusions: Across two clinical studies, PBM using a novel wearable device was associated with improvements in pain and function, in people with KOA and those undergoing TKR. Although between-group differences were not consistently statistically significant, clinically meaningful trends—particularly in functional recovery trajectories for walking—support further investigation. PBM appears to be a safe adjunct therapy with potential functional and symptomatic benefits. Large adequately powered trials using the novel device in KOA are warranted to confirm efficacy and optimise treatment parameters.

Declaration Statements: The studies received approvals from the Mater Misericordiae Ltd Human Research Ethics Committee Reference Number - Light Knee study: HREC/AM/MML/79175; iPPaM study: HREC/AM/MML/89297.

Disclosure Statement: The authors declare no conflicts of interest related to this study although CI-Laakso has a 1% shareholding in another company (Symbyx Pty Ltd)

Optimizing Photobiomodulation to Enhance Smooth Muscle Differentiation of Adipose-Derived Stem Cells in a 2D Model

Blassan George, PhD

Smooth muscle dysfunction underlies numerous pathological conditions, including atherosclerosis, where current treatments fail to restore functional contractility. Adipose-derived stem cells (ADSCs) offer a promising regenerative approach due to their accessibility and multipotency. However, efficient and controlled differentiation into smooth muscle cells (SMCs) remains a challenge. While biochemical induction using transforming growth factor beta (TGF-β) and retinoic acid (RA) is well established, the integration of non-invasive stimuli such as photobiomodulation (PBM) to enhance differentiation outcomes remains insufficiently explored. This study aimed to optimise PBM parameters to modulate ADSC behaviour and improve SMC differentiation in a two-dimensional model. This study was conducted at a basic science experimental level. Immortalised human adipose-derived stem cells (ASC52Telo) were cultured and induced to differentiate into smooth muscle cells (SMCs) using smooth muscle induction medium supplemented with TGF-β (1 ng/mL) and RA (0.1 µM). Photobiomodulation was delivered using diode laser systems from the National Laser Centre, South Africa, at wavelengths of 525 nm (green) and 825 nm (near-infrared), including combination treatments. The lasers operated in continuous wave mode, with power outputs of 128 mW (525 nm) and 516 mW (825 nm), and a spot size of 9.62 cm², corresponding to power densities of 14.09 mW/cm² and 56.83 mW/cm². Energy densities of 5 J/cm² and 10 J/cm² were applied. Exposure times ranged from 354-709 seconds for 525 nm and 87-175 seconds for 825 nm, calculated according to the required fluence. A single irradiation protocol was used, with direct irradiation of culture plates performed under dark conditions, targeting localised areas corresponding to the cell culture wells. Cellular responses were evaluated at 24 hours, 7 days, and 14 days post-treatment. Assessments included morphological analysis using Giemsa staining, proliferation via ATP quantification, cytotoxicity using lactate dehydrogenase (LDH) assays, mitochondrial membrane potential (MMP) analysis, collagen production using Sirius Red staining, migration through scratch assays, and smooth muscle differentiation through immunofluorescent detection of SMC markers including SMAα, desmin, calponin, and smooth muscle myosin heavy chain (SMMHC). PBM induced a clear fluence-dependent biphasic response in ADSCs. At 5 J/cm², PBM significantly enhanced cellular proliferation, mitochondrial activity, extracellular matrix production, and expression of smooth muscle markers, supporting progression toward a contractile phenotype. In contrast, 10 J/cm² reduced metabolic activity, suppressed early differentiation markers, and significantly increased cellular migration, indicative of a synthetic or stress-modulated phenotype. Green light (525 nm) at 5 J/cm² consistently demonstrated the most favourable outcomes, showing enhanced collagen deposition, organised cytoskeletal development, and strong expression of late-stage SMC markers. Combination treatments did not outperform single-wavelength irradiation. Overall, PBM at lower fluence promoted contractile SMC differentiation, whereas higher fluence favoured phenotypic modulation toward a migratory state. This study demonstrates that PBM effectively modulates ADSC differentiation into SMCs in a fluence-dependent manner. A dose of 5 J/cm², particularly at 525 nm, optimally supports differentiation toward a contractile phenotype, while higher fluences promote a synthetic phenotype. These findings highlight the importance of precise PBM parameter optimisation and support its application as a non-invasive tool in smooth muscle tissue engineering and regenerative medicine

Photobiomodulation in Chronic Autoimune Thyroiditis: Novel Glutathione Modulation in Early Disease and Clinical Outcomes

Venera Berisha-Muharremi, Prof. assoc., MD, PhD

Introduction: Chronic autoimmune thyroiditis (CAT) is the most prevalent autoimmune endocrine disorder, characterized by progressive thyroid destruction, immune dysregulation, and oxidative stress. Standard therapy corrects hormonal imbalance but does not address underlying autoimmune or redox mechanisms. Photobiomodulation therapy (PBM) has demonstrated anti-inflammatory and mitochondrial effects, suggesting a potential disease-modifying role. This study compering serum glutathione level before and after PBM treatment, introduces a novel redox-based effect of PBM as stand alone therapy in early-stage of CAT.

Methods: An pilot study evaluating PBM as standalone therapy in newly diagnosed euthyroid female CAT patients without other pharmacological or supplemental intervention. Comparing glutathione levels as redox biomarker, before treatment, right after 6 treatment sessions and after three months. Pilot Study Endpoint: Primary outcome: systemic glutathione levels.

Results: The study included 25 females (mean age 30.04±4.63 years) with a mean BMI of 30.54±3.72 kg/m² and waist-to-hip ratio of 0.88±0.06. Glutathione levels increased significantly right after 6 treatment sessions (263.00±48.13 mg/L) and remained elevated at 3 months (245.96 ± 56.50 mg/L) compared to baseline (223.40±60.83 mg/L) (p<0.001). The proportion of participants with glutathione levels<200 mg/L decreased from 12 at baseline to 0 after treatment and 5 at 3-month follow-up. The treatment also resulted in statistically significant reductions in TSH, anti-TPO, anti-TG, and waist-to-hip ratio, alongside increases in FT4, FT3, and BMI decrease (p<0.001). Results demonstrate that PBM monotherapy increases systemic glutathione levels in untreated euthyroid CAT patients, indicating direct modulation of oxidative stress independent of adjunct therapies.

Conclusion: PBM demonstrates clinically relevant functional, immunological, and anthropometric benefits in CAT. Importantly, this study introduces PBM as a standalone early intervention targeting redox homeostasis, with glutathione as a potential biomarker of treatment response. This supports a paradigm shift toward disease-modifying, non-pharmacological management in autoimmune endocrinology. Further randomized controlled trials are warranted.

Declaration Statement: Procedures were conducted in accordance with ethical standards. Informed consent was obtained from participants. Institutional review board approval was obtained. No conflicts of interest to declare.

Disclosure Statement: The authors declare no financial relationships with manufacturers of PBM devices.

Effect of Photobiomodulation Therapy on Disability and Function in Low Back Pain: A Randomized, Double-Blind, Sham-Controlled Crossover Trial

Cleuton Landre, MSc

Introduction: Few conditions impact global health like low back pain (LBP), a leading cause of global disability. Photobiomodulation (PBM) holds promise due to its non-invasive nature and proposed cellular mechanisms, including mitochondrial stimulation, enhanced ATP production, and reduced oxidative stress, contributing to its potential anti-inflammatory and analgesic effects. Despite this theoretical appeal, robust evidence for its efficacy in functional disability and optimal dosing remains limited, particularly concerning rigorous crossover designs. This investigation aimed to assess whether two PBM doses (50J – 1.25J/cm² or 500J – 12.5J/cm2) could offer a superior effect compared to a sham on functional disability in individuals with LBP.

Methods: A randomized, double-blind, sham-controlled crossover design enrolled 10 participants with chronic LBP (duration >3 months) and pain ≥4/10 (VAS). The sample (N=10) had a mean age of 36.8±9.8 years (5 females, 5 males). A non-commercial prototype LED cluster (69 LEDs: 35 red at 630 ± 10nm [50 mW/cm2], 34 Infrared at 830 ± 20 nm [150 mW/cm2]) was used. This device delivered 50 J (Red: 3.6 p.J/cm2, 0.8 Einstein; Infrared: 8.2 p.J/cm2, 1.8 Einstein) or 500 J (Red: 36 p.J/cm2, 8 Einstein; infrared: 82 p.J/cm2, 18 Einstein) or sham (0 p.Jcm2, 0 Einstein) from 1,370mW total power (continuous mode), 40 cm², 34.25 mW/cm2, calibrated using a power and energy meter (PM100D, Thorlabs) fitted with sensor S130C. Treatments were applied directly to the skin, at 90° with light pressure, targeting the L2 dorsal root ganglion bilaterally. Each participant experienced three conditions: 50 J (37s), 500 J (365s), and sham (365s, 0 J), with a 45-day washout between treatments, with assessments at baseline (pre-treatment) and 24h after each intervention (post-treatment). Functional disability was assessed using the Roland Morris Disability Index (RMDI) and Oswestry Disability Index (ODI). Data analysis used Repeated Measures ANOVA with time (pre vs. post) and dose (sham, 50 J, 500 J) as factors.

Results: Repeated Measures ANOVA revealed significant time effects for both instruments. RMDI decreased significantly (F(2,27) =19.41, p<0.001) from 6.46 ± 0.77 points (pre) to 4.43 ± 0.64 points (post). ODI improved significantly (F(2,27) =24.33, p<0.001) from 18.82% ± 1.88 (pre) to 14.14% ± 1.49 (post). Only 50 J and 500 J groups significantly decreased RMDI (7 ± 1.33 to 4.6 ± 1.11, p=0.005; and 6 ± 1.33 to 3.8 ± 1.11, p=0.014, respectively) and ODI (18.68 ± 3.26 to 14.15 ± 2.58, p=0.010; and 18.97 ± 3.26 to 11.88 ± 2.58, p<0.001, respectively) within-group comparisons.

Conclusions: PBM significantly reduced functional disability at the L2 dorsal root ganglion irradiation. However, improvements were not dose-dependent. Further studies with larger sample sizes are warranted to validate and strengthen these findings.

Declaration Statement: The study was approved by USC Ethics Committee under the code 62920516.6.0000.5502 and individuals signed the informed patient consent.

Disclosure Statement: This study was supported by the São Paulo Research Foundation (FAPESP, grant 2017/18722-3) and partially supported by the Coordination for the Improvement of Higher Education Personnel (CAPES, code 001).

Acute Effects of Whole-Body Photobiomodulation on Blood Pressure in Individuals with Hypertension: A Randomized, Double-blind Controlled Trial

Lara Maria Bataglia Espósito, MSc, PT

Introduction: Hypertension is a global health issue that affects 1.28 billion adults. This disease has low control rates, and around 10.8 million deaths could be prevented by blood pressure (BP) control. Recent studies suggest that photobiomodulation (PBM) could reduce BP. However, there is an insufficient number of well-designed clinical trials, and whole-body PBM, a promising strategy, has not been investigated for this purpose yet. The aim of the study was to assess the acute effect of whole-body PBM on BP in people with hypertension.

Methods: This was a randomized, double-blind and sham-controlled trial. Twenty-one participants (blinded) were included and secretly randomized to one of two groups: PBM Group (n=10) or Sham PBM Group (n=11). Individuals of both sexes, aged 40 to 65 years old with a diagnosis of hypertension, in medication use, and with reported difficulty to control BP were included. Participants were assessed by a blinded evaluator for systolic (SBP) and diastolic BP (DBP) both pre- and post-intervention with the Sphygmocor® equipment (Sphygmo-Cor, AtCor Medical, Sydney, Australia). Whole-body PBM with a red wavelength was applied in one session through a low-level LED panel from the Joovv Elite system (Joovv, Inc.), composed by six panels of 76 red LEDs (660 ± 10 nm; 450 mW each) and 74 infrared LEDs (850 ± 10 nm; 350 mW each – turned off), totalling 900 LEDs distributed over a 12,193 cm² area. Participants remained in orthostatic position wearing swimwear at 20 cm from the device, and the irradiation time (continuous mode) was of 20 minutes (600s front + 600s back). The active dose of PBM applied to each region (front and back) was 25.34 J/cm² with an irradiance of 42.24 mW/cm², total energy of 16,180 J, photon fluence of 47.38 p.J/cm2, and Einstein dose of 10.52 Einstein. Parameters were measured using a power and optical energy meter (PM100D Thorlabs®) equipped with an S130C sensor. Procedures were maintained the same for the sham group; however, the device did not emit therapeutic light, and a standard red LED light attached to the panel was switched on. Groups were compared with ANOVA Two-way with Fisher LSD post hoc test, and deltas were compared with Mann-Whitney’s test. A p<0.05 was considered significant.

Results: PBM Group presented a significant decrease on SBP from 144.30 ± 10.48 to 134.60 ± 9.99 mmHg (p=0.0062), while the Sham PBM Group had no significant difference (133.70 ± 11.84 to 131.20 ± 14.74 mmHg) (p=0.4075). Between-group values were not statistically significant, but deltas of change were significant when comparing both groups (Δ -9.70 ± 8.29 vs -2.54 ± 11.26 mmHg) (p=0.0407). No significant differences were found for DBP (p>0.05). PBM Group presented a DBP from 89.80 ± 9.94 to 85.30 ± 8.48 mmHg, while Sham PBM Group presented a DBP from 83.64 ± 11.27 to 80.55 ± 9.94 mmHg (Δ -4.50 ± 4.90 vs -3.07 ± 9.19 mmHg).

Conclusions: Whole-body PBM with a red wavelength was able to acutely reduce peripheral SBP in people with hypertension, being a promising strategy for BP control.

Declaration Statement: The study was approved by UFSCar’s Ethics Committee under the code 75138323.6.0000.5504 and individuals signed the informed patient consent.

Disclosure Statement: This study was supported by the São Paulo Research Foundation (FAPESP, grant 2023/11652-0) and partially supported by the Coordination for the Improvement of Higher Education Personnel (CAPES, code 001).

Skin Temperature Changes Following Whole-Body Photobiomodulation in Individuals with Hypertension: A Randomized, Double-blind Controlled Pilot Trial

Lara Maria Bataglia Espósito, MSc, PT

Introduction: Whole-body photobiomodulation (PBM) has gained attention in research and clinical settings, showing promising results. However, the large body surface area exposed during whole-body PBM may lead to heat accumulation at the skin surface, a response that remains underexplored. To the best of our knowledge, no studies have quantified body surface temperature responses to whole-body PBM. This pilot study aimed to investigate skin temperature responses to whole-body PBM in individuals with hypertension.

Methods: This randomized, double-blind, sham-controlled pilot trial included 14 hypertensive participants (7 per group), aged 40–65 years, of both sexes. Participants were randomly allocated to either a PBM group or a sham PBM group, with all procedures and analyses performed under blinding. Thermographic assessments were performed by a blinded evaluator using a thermographic camera (Model T-420, FLIR Systems Inc.) immediately before and after the intervention. Images were acquired in an orthostatic position under standardized lighting and background conditions. Temperature analyses were carried out using FLIR software (Version 5.2.15036.1001, 2015), for predefined regions: abdomen, upper and lower limbs, and sacral area. Whole-body PBM with a red wavelength was applied in a single 20-minute session (600s front, 600s back) in a temperature-controlled room using a low-level LED panel (Joovv Elite system, Joovv, Inc.), consisting of six panels of 76 red LEDs each (660±10 nm; 450 mW per LED) and 74 infrared LEDs (850±10 nm; 350 mW each, turned off), totaling 900 LEDs distributed over 12,193 cm². Participants stood 20 cm from the device wearing swimwear. The applied dose was 25.34 J/cm² per region (front and back), with an irradiance of 42.24 mW/cm², total energy of 16,180 J, photon fluence of 47.38 p.J/cm2, and Einstein dose of 10.52 Einstein. Parameters were measured using a power and optical energy meter (PM100D Thorlabs®) with an S130C sensor. The sham group followed identical procedures, except the device did not emit light, and a standard red LED light attached to the panel was switched on. Statistical analyses used two-way ANOVA with Fisher’s LSD post hoc test, and deltas were compared using an unpaired t-test (p<0.05).

Results: In the PBM Group, four participants had skin phototype III and three IV, whereas the sham group included five with phototype III, one IV, and one V. Whole-body PBM significantly increased body surface temperature in the abdomen (31.50±1.20 to 32.90±1.25 °C), quadriceps femoris (30.91±1.02 to 32.03±0.83 °C), and hamstrings (31.99±0.83 to 33.26 ± 0.82 °C) when comparing pre- and post-intervention. Delta comparisons between PBM and sham groups were significantly different for abdomen (1.40±1.42 vs -1.06±1.34 °C), quadriceps femoris (1.11±0.87 vs -0.97±1.38 °C), sacral region (1.47±1.90 vs 0.04±1.72 °C), and hamstrings (1.27±0.91 vs -0.62±0.95), while no changes were found in upper limbs.

Conclusions: Whole-body PBM with red wavelength at a 20 cm distance significantly increases skin surface temperature. These findings highlight the need for further investigations exploring the influence of skin phototype and personalized dosing on thermal responses to PBM.

Declaration Statement: The study was approved by UFSCar’s Ethics Committee under the code 75138323.6.0000.5504 and individuals signed the informed patient consent.

Transcranial 1064 nm Laser Photobiomodulation Improves Prefrontal Hemodynamic Response and Cognitive Function in Adults with ADHD

Farzad Salehpour

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition with an estimated prevalence of 6% among U.S. adults. Neuroimaging studies demonstrate reduced hemodynamic responses in the right prefrontal cortex (PFC) during tasks requiring inhibitory control in individuals with ADHD. Transcranial photobiomodulation (tPBM) is a non-invasive neuromodulation technique shown to enhance prefrontal metabolic activity. This study was a single-blind, randomized, sham-controlled trial designed to investigate the cognitive and hemodynamic effects of tPBM in adults with ADHD.

Methods: Eligible participants were adults aged 18 years or older with a verified clinical diagnosis of ADHD, either receiving stable pharmacological treatment or unmedicated. A total of 52 participants were randomly assigned to either active tPBM or sham stimulation. Participants received a single session of tPBM targeting the right PFC using a continuous-wave 1064 nm laser with top-hat beam profile (HD Laser, Cell Gen Therapeutics LLC, Dallas, USA) with a 4.16 cm diameter aperture (13.6 cm² spot size). The protocol consisted of eight 1-minute irradiations alternating between two sites medial and lateral to the EEG Fp2 location, delivered using a non-contact distance of 20 cm. The laser had an output power of 3.4 W, corresponding to an irradiance of 250 mW/cm² and a fluence of 60 J/cm² (816 J per site). Sham stimulation followed the same procedure without emission of therapeutic light. Laser parameters were based on manufacturer specifications, with key values independently verified prior to the experiment. Cognitive performance was assessed before and after the intervention using the continuous performance test (CPT) and a 2-back working memory task. Prefrontal hemodynamic responses were concurrently measured using functional near-infrared spectroscopy (fNIRS).

Results: A significant phase × treatment × medication interaction was observed for CPT total correct rejections (p = 0.049, η²p = 0.083, a moderate-to-large effect size), indicating greater improvement following active tPBM among medicated participants. Active tPBM also resulted in significant improvements in 2-back performance, including increased correct rejections (p = 0.04) and reduced false alarms (p = 0.028), reflecting enhanced working memory and inhibitory control. fNIRS analyses demonstrated increased PFC oxygenation following active tPBM, with higher oxyhemoglobin (p = 0.011, Cohen’s d = 0.73) and total hemoglobin (p = 0.038, Cohen’s d = 0.59) compared to sham. No adverse events were reported.

Conclusions: A single session of tPBM applied to the right PFC improved attention and impulse control in adults with ADHD. These findings provide evidence of acute cognitive and neurophysiological effects and support future longitudinal studies to evaluate the sustained clinical benefits of repeated tPBM sessions.

Declaration Statement: All participants provided written informed consent to participate in the study, which was approved by the Institutional Review Board (IRB) of The University of Texas at Austin. The protocol complied with all applicable IRB, federal, and NIH guidelines. The authors have no conflicts of interest to disclose. The laser device was purchased commercially, and we confirm that no author holds financial interests related to the equipment.

Disclosure Statement: The Oskar Fischer Project and Elhapa Foundation grants to FGL funded the research and production of this manuscript.

Effects of Photobiomodulation as Adjunctive Therapy on Pressure Ulcer Healing: A Randomized Clinical Study

Magda Souza Viana, MSc

Photobiomodulation has been investigated as a non-invasive adjunctive approach to improve the healing of pressure ulcers, which are chronic lesions caused by prolonged tissue compression, resulting in ischemia, delayed repair, and high morbidity. This study aimed to evaluate the effectiveness of photobiomodulation associated with conventional treatment in the healing of pressure ulcers. A randomized clinical experimental study was conducted with 20 patients presenting pressure ulcers, who were divided into two groups: a control group receiving conventional treatment with saline cleaning and calcium alginate dressing, and a treatment group receiving conventional care associated with photobiomodulation. The therapy was performed using a red visible laser with a wavelength of 660 nm, power of 40 mW, continuous emission mode, and spot size of 0.04 cm². The energy density was 10 J/cm², with irradiance of 1 W/cm² and energy delivered per point of 0.4 J. The treatment was applied in direct contact mode at the wound edges, with an irradiation time of 10 seconds per point, twice weekly, over a follow-up period of 20 weeks. The number of sessions varied according to patient follow-up duration. Wound healing progression was assessed through digital image analysis, measuring ulcer area over time. Statistical analysis was performed using ANOVA (5%) to compare differences between groups. Both groups showed reduction in ulcer area over time; however, the treatment group demonstrated significantly greater healing, with approximately 86.5% reduction in ulcer area compared to 41% in the control group after 20 weeks (p = 0.013). No complete healing was observed in the control group, while some patients in the treatment group achieved complete wound closure. These results indicate that photobiomodulation significantly enhances pressure ulcer healing when used as an adjunct to conventional treatment, supporting its clinical application as a non-invasive strategy to improve outcomes in patients with chronic wounds. All participants provided informed consent prior to inclusion in the study, and no funding sources or conflicts of interest were reported in the original study

Acute Effects of Whole-Body Photobiomodulation on Glycaemic Control in Individuals with Diabetes Type 2: A Randomized, Double-blind Controlled Trial

Cleber Ferraresi, Prof.

Introduction: Type 2 diabetes mellitus (T2DM) is a major global public health problem, characterized by chronic hyperglycemia, inflammation, oxidative stress, and mitochondrial alterations. Photobiomodulation (PBM) has been proposed as a non-pharmacological adjuvant therapy with modulatory effects on glucose metabolism. This study assessed acute time–response effects of whole-body PBM on plasma glucose in men with T2DM.

Methods: This randomized, double-blind, sham-controlled trial included 14 men (50–70 years), diagnosed with T2DM, without oral hypoglycemic medicine or insulin, randomized to PBM Group (n=7) or Sham PBM Group (n=7). Participants were assessed by a blinded evaluator for capillary glucose at pre- and post-prandial (standardized meal, 260 kcal) and at 1, 3, 6, 12, and 24h after PBM. Standardized meals were repeated at 3 and 6h, and participants resumed daily activities without exercise. Whole-body PBM was applied in one session using a Joovv Elite LED panel (six panels, 76 red LEDs, 660±10 nm, 450 mW each – turned off; 74 infrared LEDs, 850±10 nm, 350 mW each; total 900 LEDs; 12.193 cm²). Participants stood 20 cm from the device, wearing swimwear, irradiated 30 min (900s front + 900s back). Active dose: 32.50 J/cm², irradiance 36.13 mW/cm², total energy 20,211 J, photon fluence 47.14 p.J/cm², Einstein dose 10.47. Parameters measured with PM100D Thorlabs® and S130C sensor. Sham group followed identical procedures without light emission. Groups were compared at 1, 3, 6, 12, and 24h using independent samples t-test for glycemic variation (baseline: pre-prandial). Area under the curve (AUC) from 1–24h was calculated. A p<0.05 was considered significant.

Results: Compared to sham, PBM significantly decreased plasma glucose at 1h (MD: -31.0±9.6 mg/dL, p=0.007), 3h (MD: -25.1±8.71 mg/dL, p=0.014), 12h (MD: -43.6±9.12 mg/dL, p=0.042), and AUC (MD: -607.9±245.50 mg/dL, p=0.029). Differences at 6 and 24h were not significant.

Conclusions: Whole-body PBM with infrared wavelength acutely reduced plasma glucose in men with T2DM, mainly at 1–3h, lasting up to 24h, suggesting a promising strategy for glycemic control.

Declaration Statement: Approved by UFSCar’s Ethics Committee (code 80093724.9.0000.5504); informed consent obtained.

Disclosure Statement: Partially supported by CAPES (code 001).

Whole-Body Photobiomodulation in Individuals with Type 2 Diabetes Mellitus and Hypertension: Randomized, Double-Blind, Sham-Controlled Clinical Trial

Cleber Ferraresi, Prof.

Introduction: Type 2 diabetes mellitus (T2DM) is a chronic condition that can lead to cardiovascular complications and double the likelihood of increased blood pressure. In this context, photobiomodulation therapy (PBMT) has been investigated as treatment for T2DM and blood pressure control. The aim of this study was to analyze the effects of photobiomodulation (PBM) on blood pressure in individuals with T2DM through ambulatory blood pressure monitoring (ABPM).

Methodology: Systolic (SBP) and diastolic blood pressure (DBP) and mean arterial pressure (MAP) were analyzed over 21h following whole-body PBM irradiation. The study included 16 individuals (50-70 years), diagnosed with T2DM and hypertension, who were randomly assigned to two groups: SHM (7) and PBM (9). Participants underwent 6 PBM sessions over 2 weeks, with 3 sessions per week on non-consecutive days. Blood pressure measurements were taken before and after the PBM intervention. Whole-body PBM was applied using a Joovv Elite LED panel (six panels, 76 red LEDs, 660±10 nm, 450 mW each – turned off; 74 infrared LEDs, 850±10 nm, 350 mW each; total 900 LEDs; 12.193 cm²). Participants stood 20 cm from the device, wearing swimwear, irradiated 20 min (600s front + 600s back). Active dose: 21.67 J/cm², irradiance 36.13 mW/cm², total energy 13,474 J, photon fluence 31.43 p.J/cm², Einstein dose 6.98. Parameters measured with PM100D Thorlabs® and S130C sensor. SHM group followed identical procedures without light emission. Groups were compared with ANOVA Two-way with Fisher post hoc test, and p<0.05 was considered significant

Results: On the first PBM session, a significant difference between groups was found only in MAP (p=0.04 , PBM 92.8±10.6mmHg, SHM 95.1±10.6mmHg). On the fourth PBM session, there was no statistical difference between groups (p>0.05). On the sixth PBM session, significant differences were observed in SBP (p=0.028, PBM 98,5±8.3mmHg, SHM 118±47.7), DBP (p=0.002, PBM 72.2±9.9mmHg, SHM 94.7±23.5mmHg), and MAP (p=0.012, PBM 92.2±14,2mmHg, SHM 113±26.9mmHg).

Conclusion: Whole-Body PBM reduced blood pressure in patients with T2DM and hypertension after irradiation, especially on the last day of irradiation, suggesting a cumulative effect.

Declaration Statement: The study was approved by UFSCar’s Ethics Committee under the code 63020822.6.0000.5504 and individuals signed the informed patient consent.

Disclosure Statement: This study was partially supported by the Coordination for the Improvement of Higher Education Personnel (CAPES, code 001).

Transcranial Photobiomodulation as an Adjunctive Therapy for Drug-Resistant Epilepsy in a Dog: A Five-Year Case Report

Alain Lecat, DVM

Epilepsy is one of the most prevalent neurological disorders in dogs, and approximately 30% of affected individuals remain poorly controlled despite appropriate diagnosis, antiepileptic drug (AED) therapy, and dietary management. Severe seizure phenotypes, such as cluster seizures (CS) and status epilepticus (SE), are associated with cumulative neuronal injury, neuroinflammation, and progressive deterioration of quality of life (QOL). Current AEDs primarily target seizure suppression and do not directly address the neurodegenerative and post-ictal processes underlying disease progression. Transcranial photobiomodulation (tPBM) has demonstrated neuroprotective and neurorestorative effects in several human and experimental neurological conditions by modulating mitochondrial function, oxidative stress, inflammation, and synaptic plasticity. Given the shared pathophysiological mechanisms between human and canine epilepsy, tPBM may represent a promising adjunctive therapy in veterinary neurology. This case report describes a five-year clinical follow-up of a dog with drug-resistant epilepsy characterized by recurrent SE and CS, treated with standard AEDs in combination with tPBM. After initiation of tPBM, a marked reduction in seizure frequency, staging, and intensity was observed, together with a substantial improvement in functional performance and owner-reported QOL. Although limited to a single case, these observations suggest that tPBM may beneficially modulate both ictal and post-ictal pathophysiology and support its potential role as a complementary treatment in canine epilepsy.

Laser-Stimulated Human Gingival Fibroblasts: Alterations in Migration, Secretome Production, and Induction of Reactive Oxygen Species

Marggie Grajales-Ramirez, DDS, MSc

Introduction: This study aimed to investigate the effects of low-level laser irradiation on human gingival fibroblasts, specifically examining changes in proliferation, morphology, migration, and reactive oxygen species (ROS) production. Additionally, we assessed the impact of the secretome from irradiated fibroblasts on non-irradiated cell proliferation and migration.

Methods: Human gingival fibroblasts were exposed to 650 and 940 nm CW laser irradiation, 0.1 W for 50 s. Cell proliferation was quantified using resazurin, while migration was evaluated through a wound generation assay and by treating non-irradiated cells with the secretome from irradiated fibroblasts. We also analysed changes in type I collagen (COL1A1) expression, ROS production, and mitochondrial membrane potential (ΔΨm).

Results: Both 650 nm and 940 nm laser treatments induced morphological changes and significantly enhanced cell proliferation, observed 10 days post-irradiation, without causing cell detachment or death. Non-irradiated cells treated with the secretome from 940 nm-irradiated fibroblasts exhibited increased cell density at five and 10 days post-irradiation. Laser treatment at both wavelengths significantly stimulated cell migration. Cells irradiated with the 650 nm laser showed increased COL1A1 expression at five days, while those treated with 940 nm demonstrated a marked increase at 10 days. Low-level laser treatment led to significant increases in both ROS production and ΔΨm.

Conclusion: Low-level laser treatment induced morphological changes and increased proliferation, cell migration, and COL1A1 expression in gingival fibroblasts. Treatment with laser-stimulated cell secretome significantly enhanced gingival fibroblast proliferation. The 940 nm laser treatment elicited the most pronounced cellular changes, particularly in relation to increased ROS production and ΔΨm.

Disclosure statement: Authors declare no competing interests.

Photobiomodulation with 976 nm Diode Laser Enhances Osteoblastic Differentiation of Seos-2 Cells Cultured on Collagen Membranes

Marggie Grajales-Ramirez, DDS, MSc

Introduction: This study aimed to investigate the effects of low-level laser irradiation on human gingival fibroblasts, specifically examining changes in proliferation, morphology, migration, and reactive oxygen species (ROS) production. Additionally, we assessed the impact of the secretome from irradiated fibroblasts on non-irradiated cell proliferation and migration.

Methods: Human gingival fibroblasts were exposed to 650 and 940 nm CW laser irradiation, 0.1 W for 50 s. Cell proliferation was quantified using resazurin, while migration was evaluated through a wound generation assay and by treating non-irradiated cells with the secretome from irradiated fibroblasts. We also analysed changes in type I collagen (COL1A1) expression, ROS production, and mitochondrial membrane potential (ΔΨm).

Results: Both 650 nm and 940 nm laser treatments induced morphological changes and significantly enhanced cell proliferation, observed 10 days post-irradiation, without causing cell detachment or death. Non-irradiated cells treated with the secretome from 940 nm-irradiated fibroblasts exhibited increased cell density at five and 10 days post-irradiation. Laser treatment at both wavelengths significantly stimulated cell migration. Cells irradiated with the 650 nm laser showed increased COL1A1 expression at five days, while those treated with 940 nm demonstrated a marked increase at 10 days. Low-level laser treatment led to significant increases in both ROS production and ΔΨm.

Conclusion: Low-level laser treatment induced morphological changes and increased proliferation, cell migration, and COL1A1 expression in gingival fibroblasts. Treatment with laser-stimulated cell secretome significantly enhanced gingival fibroblast proliferation. The 940 nm laser treatment elicited the most pronounced cellular changes, particularly in relation to increased ROS production and ΔΨm.

Disclosure statement: Authors declare no competing interests.

PBM is Not a Local Modality Applied Systemically—It is a Systemic Modality with a Local Entry Point: A Systematic Review of Remote and Systemic Biological Effects of Photobiomodulation

Mark Cronshaw, PhD, BDS, LDS, RCS (Eng), MSc

PBM is not a local modality applied systemically — it is a systemic modality with a local entry point: a systematic review of remote and systemic biological effects of photobiomodulation Cronshaw M, Parker S De Montfort University, Leicester, UK Experimental Level: Systematic review / meta-analysis Introduction Photobiomodulation (PBM) is characterised in the literature as a local intervention, yet evidence indicates this is fundamentally incomplete. Irradiated blood circulates systemically within minutes of dermal capillary exposure. Cutaneous photoreceptors activate neuroendocrine cascades without hypothalamic engagement. Photons reaching the dura activate meningeal lymphatic and glymphatic pathways. Peripheral PBM produces dose-dependent CNS responses measurable by fMRI. This systematic review tests the hypothesis that PBM is more accurately characterised as a systemic modality with a local entry point than as a local modality with occasional systemic effects. Methods A systematic review was conducted per PRISMA 2020 guidelines. Databases searched: PubMed/MEDLINE, EMBASE, Cochrane, Web of Science, and CINAHL (inception to March 2026). Inclusion criteria: studies reporting biological effects remote from the irradiation zone, or systemic changes in circulating mediators, immune cell phenotype, neuroendocrine markers, or neuroimaging parameters following PBM by any delivery route. Device parameters were extracted where reported. Risk of bias was assessed using RoB 2, ROBINS-I, and SYRCLE. Evidence was graded using GRADE across pre-specified systemic mechanism domains. Results [N] studies met inclusion criteria across six systemic mechanism domains. GRADE profiling identified: blood irradiation effects — HIGH; cutaneous neuroendocrine coupling — MODERATE-HIGH; meningeal lymphatic/glymphatic activation — MODERATE (Motsenyat et al., Brain Stimulation 2025); peripheral fMRI-confirmed CNS effects — MODERATE (Van Lankveld/Chen group, 2025–26); psychoneuroimmunological modulation — MODERATE; survival signals from mucositis trials — LOW (Antunes et al. Phase 3 RCT), a biologically coherent signal requiring powered investigation. Beam spatial profile was systematically absent from dosimetric reporting. Remote delivery routes produced systemic effects equivalent to or exceeding direct local irradiation in comparative studies. Conclusions The evidence supports a fundamental recharacterisation: PBM is a systemic modality with a local entry point, not a local modality applied systemically. Blood irradiation, neuroendocrine transduction, glymphatic activation, and remote CNS effects are mechanistically established or supported by emerging human evidence. Survival signals from mucositis trials demand properly powered follow-up. Adequate dosimetric characterisation including beam spatial profile remains systematically absent. This review provides a GRADE-assessed framework to support expanded clinical application and future trial design. Declaration: Systematic review of published literature. No patient data or primary data collection involved. No ethical approval required. Disclosure: No funding received. The authors declare no financial relationships with PBM device manufacturers or competing products.

Learning Objectives:

  • Delegates will be able to describe the principal biological mechanisms by which photobiomodulation produces systemic effects remote from the irradiation site, including blood irradiation, cutaneous neuroendocrine transduction, and meningeal lymphatic and glymphatic activation.
  • Delegates will be able to appraise the current GRADE-assessed evidence base for systemic PBM effects across six mechanism domains, distinguishing established from emerging pathways and identifying gaps requiring futher investigation.
  • Delegates will be able to apply the recharacterisation of PBM as a systemic modality with a local entry point to clinical practice, including selection of delivery route, device parameters, and treatment site to optimise systemic as well as local therapeutic outcomes.
  • Delegates will be able to identify the dosimetric resporting deficiencies—particularly absence of beam spatial profile data—that currently limit reproducibility and evidence synthesis in the systemic PBM literature, and apply best-practice dosimetric specification in their own clinical and research work.

The Effects of PBM on Heart Rate, Heart Rate Variability, VO₂max, Sleep Quality, and Implications for Longevity and Health Span

James Carroll

Over the past century, global life expectancy has risen by about 30 years. However, health span hasn’t kept pace, with many people spending their final 10-20 years in poor health, roughly equivalent to 20-25% of their lives. This contrasts sharply with 75-100 years ago, when fewer people lived long enough to develop chronic diseases. So while we’re living longer, we’re also dying longer. Improving longevity starts with a single objective: delaying death by targeting the primary drivers of mortality: atherosclerotic cardiovascular disease (including myocardial infarction, stroke, aneurysmal disease, and peripheral arterial disease), cancer, neurodegenerative disorders, and type 2 diabetes with its associated metabolic dysfunction. But what about health span? PBM has emerged as a biologically plausible and increasingly supported intervention targeting several modifiable physiological domains across various diseases associated with chronic degenerative diseases. Clinical studies show PBM improves exercise capacity, sleep quality, reduces nocturnal hypertension and alleviates systemic oxidative and inflammatory burdens. Each of these factors independently contributes to reducing cardiovascular risk, improving metabolic health, and enhancing long-term survival. Beyond these effects, PBM has been shown to improve autonomic balance as reflected by reductions in resting heart rate (HR) and increases in heart rate variability (HRV), and to increase VO₂max, a powerful and well-validated predictor of all-cause mortality. Improvements in muscular strength and recovery further support its relevance, providing a longevity framework that prioritises functional capacity alongside disease prevention. This presentation will review the mechanistic rationale and clinical evidence underpinning these observations, drawing on a combination of randomised controlled trials and high-quality non-randomised studies. The objective is not to position PBM as a panacea, but to evaluate its potential as an adjunctive, system-level intervention that addresses shared biological pathways across the major causes of age-related morbidity and mortality.

Photobiomodulation Therapy for Temporomandibular Disorders: A Randomized Double-Blind Sham-Controlled Trial Considering Skin Tone

Carlos Girasol, PhD

Introduction: Photobiomodulation therapy (PBMT) is widely used for pain management in temporomandibular disorders (TMD), although treatment response remains variable. Biological factors such as skin pigmentation may influence light–tissue interaction, as melanin can attenuate photon penetration. However, the impact of skin tone on PBMT outcomes remains poorly investigated in clinical settings. This study aimed to evaluate the effects of PBMT on pain intensity, pressure pain threshold (PPT), and pain catastrophizing in women with TMD, considering skin tone quantified by the Individual Typology Angle (ITA).

Methods: This was a double-blind randomized controlled trial including women with myofascial TMD allocated to PBMT or sham groups. Assessments were performed at baseline, during treatment, and follow-up. Pain intensity was measured using a numeric rating scale, PPT using a digital algometer, and pain catastrophizing using a validated questionnaire. Skin tone was quantified using the Individual Typology Angle (ITA). PBMT was delivered using a diode laser (Twin Flex Evolution, MMOptics, São Carlos, Brazil) with the following parameters: wavelength 780 nm, continuous mode, output power 70 mW, spot size 0.5 cm², and power density 140 mW/cm². Energy delivered was 4 J per point, totaling 28 J per session across seven points, with 57 seconds per point (399 seconds total). Treatment was applied in direct contact mode over masseter and temporomandibular joint regions, once weekly for four weeks. Sham treatment followed the same procedures without active irradiation. Data were analyzed using linear mixed-effects models including time, treatment, ITA, and pain duration as fixed effects, and participant as a random effect.

Results: Pain intensity significantly decreased over time, with no significant differences between PBMT and sham groups. A significant time-by-treatment interaction was observed at Day 2, indicating a transient early difference not sustained at later time points. Pain catastrophizing significantly decreased from pre- to post-intervention, with no between-group differences. Pressure pain threshold at the temporomandibular joint increased over time, with a significant time-by-treatment interaction, suggesting a localized treatment-related effect. ITA was not associated with pain intensity but showed a limited association with pressure pain threshold.

Conclusions: PBMT and sham interventions were associated with reduced pain intensity and catastrophizing over time, with no consistent superiority of PBMT for pain outcomes. Pressure pain threshold at the temporomandibular joint showed localized changes, including a treatment-related interaction. Skin tone, assessed by ITA, demonstrated limited influence on clinical outcomes.

Declaration Statements: Human Research Ethics Committee of FFCLRP/USP (No. 6.585.831).

Disclosure Statement: The present work was supported in part by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), No. 2023/10457-0, and in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes), Financing Code 001. The authors declare no conflicts of interest.

Accelerated Reversal of Metabolic Syndrome with Adjunct Phototherapy

Denis J. Gendron, Physics PhD

Introduction: Clinical research on natural health over the last 30 years aimed to quantify the potential of physical wellness to prevent and to reverse growing problem of chronic illnesses epidemic. Progress in epidemiology led to etiology model for metabolic syndrome informed from Lifestyle Medicine. 

Methods: Clarity on the etiology of these chronic illnesses enabled more effective reversal strategies, targeting the root cause of the metabolic syndrome problem. Leveraging advances in neurology, hematology, immunology and lipidomic, combined with previously established progress with cytochrome C, led to the nLightN method for optimization of metabolic syndrome reversal. The light therapy component of the physical wellness intervention uses a combination of three led wavelengths within the range of 405-430 nm, 620-650 nm, 835-865 nm and with variable intensity and total irradiance, that depends on the specific condition treated, and body type, and body size. The intensity remained less than 100 mW, and estimated total energy irradiated between 25 kJ and 100 kJ. Depending on the client and conditions treated, we treated patient during 4-week program duration, with weekly frequency ranging between 3 to 12 session per week, with session lasting 12-48 minutes.

Results: Addressing the root cause of the problem translated into record rate of symptoms reversal for all chronic illnesses treated. E.g. we witnessed obese men losing weight at rate of 0.5 to 1.5 lbs per day, hypertension reduction at rate of 3-12 mm-Hg/week, and rapid healing chronic illnesses at record rate of [Hb 1AC] ~ (1%-2%)/(4-weeks).

Conclusions: We claim record rate of healing chronic illnesses, via addressing directly etiology problem causing metabolic syndrome at the root cause; impaired processes of homeostasis not fully understood by mainstream medicine.

Declaration Statements: Clinical studies leverage protocol that already received acceptance by ethical review board, and all patients signed informed consent.

Learning Objectives:

  • Adjunct Phototherapy to a precise wellness program can accelerate reversal of metabolic syndrome

Optimizing Wound Healing Outcomes Utilizing Photobiomodulation Therapy

Sara Ciurca, BS Biological Sciences

Photobiomodulation therapy is a form of non-ionizing radiation that utilizes visible and near-infrared wavelengths of light to influence cellular processes involved in wound healing. These involve ATP production and interactions with reactive oxygen species and can impact the behavior of keratinocytes and fibroblasts . Despite the broad clinical applications of PBM there is a lack of standardized dosing parameters. This study aimed to evaluate PBM treatment dosing methods and investigate discrepancies in previous reported outcomes using in vitro models of wound healing. Human keratinocytes (HaCaT cells) were used to assess cell migration and outgrowth following PBM treatment. While initially a scratch assay model was used to replicate the study, technical limitations led to the implementation of an outgrowth assay model instead. In this method, approximately 35,000 cells were plated in 3 µL spots in a 96-well plate and were incubated and allowed to adhere for 5 hours. Then 100 uL of media was added and wells were exposed to PBM at wavelengths of 450 nm, 660 nm, and 810 nm under Einstein dosimetry conditions. Einstein dosing corresponds to a 60 second treatment for 450 nm, 210 seconds for 660 nm, and 300 seconds for 810 nm. Images were taken at 0, 12, 24, and 36 hours, and analysis was conducted using ImageJ to quantify the difference in cell-free area and migration distance after 36 hours. Preliminary analysis of results demonstrated that 450 nm Einstein-dosed PBM produced the greatest enhancement in cell outgrowth, followed by 810 nm and 660 nm treatments. These findings are consistent with prior work showing improved outcomes with 450 nm dosing compared to conventional dosing of 450 nm. Additionally the 810 nm wavelength did not show significant improvement compared to control despite being a popular wavelength clinically. Overall, the results support the conclusion that PBM efficacy is strongly influenced by wavelength and the method of dosing. The outgrowth assay provides a reproducible alternative to traditional wound models and may be useful for further optimization of PBM dosimetry. Further investigation is needed to refine analysis methods and to continue to study methods of improving clinical standardization.

Non-Invasive Blood Photobiomodulation Reduces ASD Symptoms in Young Children: A Pilot Study

Daiane Meneguzzo, DDS, MSc, PhD

Systemic inflammation in autistic patients, stemming from intestinal disorders or P450 polymorphism challenges, poses a significant treatment hurdle. Intravascular laser irradiation of blood (ILIB) has demonstrated favorable effects in controlling systemic oxidative stress, and its non-invasive variant (blood photobiomodulation) offers greater acceptability for autistic patients. The objective of this study was to evaluate the effectiveness of blood PBM in reducing ASD symptoms. The study, approved by the ethics committee, was conducted at a social institution in Campinas, SP, Brazil. Fifteen children under 8 years were selected: 5 in the control group and 10 for blood PBM, all receiving standard multidisciplinary treatment. Blood PBM was performed for 10 consecutive days using a wristwatch-shaped device on the wrist (ILIB 4.0, Ecco Fibras, Campinas, SP, Brazil; 100 mW, 660 nm, single diode, 0.02 cm² spot area, 15 min irradiation, 4 mm distance from skin, 90 J per session). Effectiveness was assessed using the Childhood Autism Rating Scale (CARS) before and after blood PBM. Results showed a significant reduction in ASD symptoms per CARS scores, alongside qualitative parental reports of improvements in comprehension, attention, interest in functional play, vocabulary, and language. The mean score for the 10 PBM children dropped from 40.4 at baseline to 37 post-treatment (3.4-point reduction), while the control group showed no change over 10 days. Blood PBM proved effective in reducing ASD symptoms after just 10 days of treatment, opening possibilities for even more significant improvements with longer protocols. This positions it as a plausible, non-invasive clinical tool for ASD patients.

Analysis of the Role of Dental Sleep Medicine in the Detection, Assessment, and Therapeutic Support of Patients with Obstructive Sleep Apnea

Pilar Blanco, MSc

Obstructive sleep apnea (OSA) is a multisystemic, complex, and frequent disease. It is a respiratory disorder associated with the obstruction of the upper airway during sleep, which leads to respiratory, cardiovascular, neurological, metabolic, and functional repercussions. This disease is considered to have a high impact on health, as it affects the quality of life of those who suffer from it and increases the risk of accidents, mood disturbances, cognitive dysfunction, and socioeconomic burden. The purpose of this study is to analyze the role of dental sleep medicine in the processes of detection, assessment, and therapeutic support in patients with obstructive sleep apnea. To this end, a qualitative research approach is proposed, with a descriptive-analytical scope and a documentary design based on a literature review. The study seeks to clearly and soundly understand the function of dental sleep medicine within the comprehensive management of this condition, as well as its relationship with other specialties involved in its care, such as otorhinolaryngology, neurology, and pulmonology/sleep medicine. In this way, the study is expected to make visible and highlight the academic and practical functions of dental sleep medicine, strengthen its understanding within the interdisciplinary clinical approach, and serve as a basis for future research and professional training. Keywords: obstructive sleep apnea, dental sleep medicine, clinical detection, morphofunctional assessment, interdisciplinary approach.

Learning Objectives:

  • Critically analyze the pathophysiology and multisystemic impact of obstructive sleep apnea (OSA)*, linking upper airway dysfunction with systemic inflammation, neuromuscular imbalance, and quality-of-life impairment.
  • Integrate dental sleep medicine with advanced morphofunctional assessment and emerging biophotonics-based approaches*, including photobiomodulation (PBM), the enhance early detection and support minimally invasive therapeutic strategies.
  • Design interdisciplinary, innovation-driven management frameworks for OSA*, incorporating dental sleep medicine, sleep medicine, and adjunctive light-based therapies to optimize airway function and patient-centered outcomes.

Diode Laser Assisted Facial Lifting: A New Technical and Case Report

Pilar Blanco, MSc

The facial aging process is the result of anatomical changes in the facial bones and muscles that are ultimately expressed in the elasticity of the skin. Different strategies have been proposed for the management of photoaging such as radiofrequency, fillers, ablative laser with erbium:YAG laser (Er:YAG) and carbon dioxide laser; these last methods have demonstrated benefits in the effectiveness for skin rejuvenation. The minimally invasive facial endolifting technique reported with photothermal, photochemical advantages and long-term results. Keywords: endolifting; collagenogenic; photoaging

Learning Objectives:

  • Deconstruct the biological and structural basis of facial aging to identify precise targets for laser-assisted intervention, linking extracellular matrix dynamics, collagen remodeling, and tissue laxity with clinical treatment planning.
  • Implement Dr. Pilar Blanco's diode laser endolifting technique, including specific wavelengths, fiber selection, irradiation parameters, and PBM-supported protocols, to achieve controll photothermal and photochemical effects for enhanced collagenogenesis and tissue tightening.
  • Optimize clinical outcomes through a protocol-driven, minimally invasive approach, integrating safety standards, anatomical mapping, and adjunctive LED/PBM therapies to improve efficacy, reduce complications, and ensure long-term aesthetic results.

Standardized Photobiomodulation Dosimetry Enhances Bone Regeneration in Critical-Size Calvarial Defects: Influence of Beam Profile and Bio-Oss®

Reem Hanna, BDS, PhD, MSc, PG DipSed, PG DipHE, PG Cert.AP, FAHE, FRSM, FIADFE, LPA (ALSP Certified)

Background: Photobiomodulation (PBM) has demonstrated promising potential in enhancing bone regeneration; however, optimal delivery parameters and interactions with osteoconductive scaffolds remain insufficiently defined. This preclinical study incorporates a novel pilot dosimetry evaluation to standardize 980-nm photonic energy delivery and ensure effective irradiance at the target surface of critical-size mouse calvarial defects (CSDs). Aim This translational in vivo study evaluates the efficacy of a novel 980-nm PBM laser protocol delivered via flat-top (FT) and standard Gaussian (ST) beam profiles, with and without Bio-Oss® grafting. The study addresses the following research questions: 1.PBM dosimetry accuracy: Does the 980-nm protocol deliver accurate and reproducible energy to the target tissue in vivo? 2.Beam profile effect: Does the FT beam profile enhance osteogenesis compared to the ST profile and untreated controls? 3.PBM–biomaterial synergy: Is there a synergistic effect between PBM and Bio-Oss® in promoting bone regeneration?

Objectives:

  • Validate a novel PBM dosimetry protocol for translational application
  • Compare FT versus ST beam profiles in CSD bone regeneration
  • Assess the combined effect of PBM and Bio-Oss® on osteogenesis
  • Investigate the biological mechanisms underlying PBM–biomaterial interaction
  • Evaluate osteogenic activity and bone formation at 30- and 60-days using histology and immunohistochemical biomarkers.

Methods: A total of 120 adult mice were assigned to twelve groups (n = 10/group): control, Bio-Oss® alone, PBM alone, and PBM combined with Bio-Oss®, each treated with FT or ST beam profiles and evaluated at 30 and 60 days. Pilot dosimetry quantified effective irradiance reaching the defect base under varying optical conditions. Outcomes included histological analysis (H&E, Masson’s trichrome) and immunohistochemistry (CD34, Gli1, Runx2, OCN, CTSK). Statistical analysis was performed using ANOVA with post hoc testing.

Results: Dosimetry confirmed that irradiance at the defect base was influenced by both beam profile and optical conditions, decreasing from 1.224 to 1.131 W/cm² (FT) and from 0.487 to 0.413 W/cm² (ST) following Bio-Oss® placement and membrane coverage. Histologically, controls showed minimal regeneration (<10%), while Bio-Oss® alone achieved moderate repair (20–30%). PBM significantly enhanced bone formation, exceeding 60% at 60 days, while PBM combined with Bio-Oss® resulted in >80% defect closure. The FT beam profile consistently produced more uniform and mature bone architecture. Immunohistochemical analysis revealed significant differences across all markers (CD34 F = 120.9; Gli1 F = 41.86; OCN F = 35.76; CTSK F = 41.19; all p< 0.0001). PBM-FT-particularly in combination with Bio-Oss®—demonstrated the highest expression levels, indicating enhanced progenitor activation (CD34), early signaling (Gli1), osteoblastic differentiation (OCN), and remodeling activity (CTSK). Runx2 expression qualitatively supported sustained osteogenic activation.

Conclusion: Standardized, dosimetry-driven PBM significantly enhances bone regeneration in critical-size defects. The flat-top beam profile provides more uniform energy distribution and superior biological outcomes compared to the Gaussian profile. Moreover, PBM exhibits a synergistic effect with Bio-Oss®, promoting osteogenesis and tissue remodeling. These findings support the translational potential of optimized PBM protocols for craniofacial bone regeneration.

Abdominal Photobiomodulation as Gut–Brain Axis Therapy: Mechanisms, Dosimetry, and Translational Evidence

Gabriela Guimaraes, MD

Introduction: The gut–brain axis has become a central translational framework for neurological, psychiatric, and neurodevelopmental disorders. Abdominal photobiomodulation (PBM) is an emerging non-invasive intervention that may act not only locally on intestinal tissue, but systemically through mitochondrial, epithelial, immune, vascular, vagal, and microbiome-mediated pathways.

Methods: This presentation synthesizes mechanistic and translational evidence from a recently completed systematic review of abdominal PBM and the gut–brain axis, complemented by clinical expertise in neurodevelopmental regression and a published translational pediatric case involving combined transcranial and abdominal PBM. The reviewed evidence includes preclinical and clinical studies using red and near-infrared light protocols, principally 630–904 nm in the indexed literature, and a 1064 nm LED cluster protocol in a translational case. Reported parameters include wavelength, output power, emission mode, treatment geometry, irradiance or fluence when available, abdominal target region, treatment time, frequency, and total number of sessions. Clinical examples include 904 nm laser protocols applied to nine abdominal points with cervical or cranial sites, 660/850 nm LED belt-and-helmet systems, and a 1064 nm LED cluster protocol delivering 10 minutes per site daily for 90 days.

Results: Across the systematic evidence base, nine eligible studies were identified, including five human and four animal studies. Human studies, mainly in Parkinson’s and Alzheimer’s disease, reported improvements in mobility, balance, cognition, olfaction, and microbiota-related outcomes. Animal studies reported cognitive improvement, reduced neuroinflammation, dopaminergic neuroprotection, and microbial rebalancing. Mechanistic convergence was observed around cytochrome c oxidase activation, ATP production, redox signaling, epithelial barrier support, nitric oxide-mediated perfusion, anti-inflammatory macrophage signaling, short-chain fatty acid-producing taxa, and vagal or immune-mediated gut–brain communication. A translational pediatric case of Down Syndrome Regression Disorder further illustrates how abdominal PBM may be integrated with metabolic and antimicrobial strategies when regression is accompanied by gut inflammation and dysbiosis.

Conclusions: Abdominal PBM should not be viewed merely as a local abdominal treatment, but as a peripheral neuromodulatory strategy capable of influencing systemic physiology through the gut–brain axis. However, the field remains limited by heterogeneous dosimetry, small clinical samples, combined treatment sites, and insufficient sham-controlled trials. Future research requires standardized reporting, biological target-engagement biomarkers, microbiome/SCFA profiling, inflammatory measures, and carefully designed randomized trials.

Learning Objectives:

  • Describe the biological rationale by which abdominal photobiomodulation may influence the gut-brain axis through mitochondrial, epithelial, immune, vascular, vagal, and microbiome-mediated pathways.
  • Identify the essential dosimetric and treatment parameters required for abdominal PBM reporting, including wavelength, power, irradiance, fluence, emission mode, treatment geometry, anatomical target, session duration, frequency, and total number of treatments.
  • Critically evaluate the current preclinical and clinical evidence supporting abdominal PBM as a systemic neuromodulatory strategy, including its effects on cognition, neuroinflammation, microbiota composition, motor outcomes, and mitochondrial bioenergetics.
  • Discuss future translational research strategies for abdominal PBM, including sham-controlled trials, standardized dosimetry, microbiome and SCFA profiling, inflammatory biomarkers, mitochondrial readouts, and clinically meaningful neurobehavioral outcomes.

Clinical and Economic Benefits of Photobiomodulation for Oral Mucositis: Reduced Pain, Opioid Use, Hospitalisation, and Cost

James Carroll

Oral mucositis (OM) remains one of the most frequent, severe, and costly acute toxicities associated with radiotherapy (RT), chemoradiotherapy (CRT), and hematopoietic stem cell transplantation (HSCT). Incidence rates approach 75–99% in high-risk populations, with substantial consequences for pain, nutrition, opioid use, hospital admissions, treatment interruptions, quality of life, and healthcare resource utilisation. Photobiomodulation therapy (PBM) is now endorsed by international guidelines, yet its real-world clinical, economic, and environmental impact remains underappreciated. This presentation synthesises randomised controlled trials, prospective and retrospective clinical evaluations, and large matched-cohort service implementations using THOR PBM systems across adult and pediatric oncology settings. Prophylactic PBM delivered intra- and extra-orally during RT, CRT, or HSCT conditioning consistently reduced the severity and duration of OM. Across studies, PBM was associated with delayed onset of severe OM, significant reductions in pain scores, fewer grade 3 OM days, and improved swallowing and functional outcomes. Importantly, PBM produced marked downstream effects: reductions of 45–64% in opioid prescriptions, up to 89% fewer hospital admissions, substantial reductions in total bed days, decreased reliance on PEG/TPN support, and earlier recovery trajectories. Economic analyses demonstrated large cost savings driven by avoided admissions, reduced medication use, and shorter inpatient stays, with single-centre implementations reporting annual savings ranging from $700,00 to $1.3 M per department. These clinical efficiencies also translated into meaningful environmental benefits, including reductions in carbon emissions aligned with NHS Net Zero targets. Emerging data also suggest the broader applicability of PBM in managing late effects such as radiation-induced fibrosis. Collectively, the evidence positions PBM not merely as a symptomatic intervention for OM, but as a high-value supportive oncology therapy delivering measurable patient, system, economic, and sustainability benefits when implemented as standard of care.

Why I Do Not Believe Your Dose: Beam Power, Beam Area, Irradiance, and Reproducibility in Photobiomodulation

James Carroll

Photobiomodulation (PBM) has matured into a clinically adopted therapeutic modality, supported by over 1,800 randomised controlled trials, dozens of regulatory clearances, emerging reimbursement pathways, and multiple clinical care guidelines. Despite this progress, fundamental errors in the measurement, calculation, and reporting of optical power, beam area, and dose remain widespread and continue to undermine reproducibility, interpretation, and clinical translation. As a result, many systematic reviews conclude that dose guidelines are not possible. This presentation examines sources of dosimetric error in PBM research and practice and proposes solutions. These include inconsistent beam-area measurement methods, failure to account for non-Gaussian and non-homogeneous beam profiles, misleadingly high dose figures caused by small beam areas, over-reliance on manufacturer-stated power values, and variability between different optical power meters. These errors propagate into incorrect irradiance and radiant exposure calculations, rendering many reported doses incomparable and misleading. A critical failure is the lack of appreciation of reciprocity in PBM dose. Identical radiant exposures (J/cm²) delivered at different irradiances do not produce equivalent biological effects. PBM responses are dose-rate dependent: cellular and mitochondrial processes respond to irradiance (W/cm²) rather than total energy. Experimental evidence demonstrates biphasic behaviour in which stimulation, no effect, or inhibition occurs depending on irradiance and treatment time, even when total energy is held constant. Briefly delivered high irradiance can suppress or negate responses stimulated by lower irradiance over longer durations, while low irradiance treatments may fall below biological activation thresholds. Collapsing irradiance and time into a single value (J/cm²) hides the critical irradiance information and falsely implies biological equivalence where none exists. Standards-based solutions are proposed. These include the adoption of ISO 11146 second-moment (D4σ) beam measurement for all PBM sources, treating beams below 3.5 mm diameter as a minimum biologically relevant area consistent with laser safety precedent, independent verification of delivered optical power using calibrated instruments, and reporting irradiance and exposure time separately rather than as a single J/cm² value. Addressing these foundational measurement and reporting errors is essential if PBM research is to achieve true reproducibility, dose–response clarity, and reliable clinical translation.

Targeting Oral Neuropathic Pain with Photobiomodulation: Mechanisms, Clinical Applications, and Implementation in Cancer Supportive Care

Reem Hanna, BDS, PhD, MSc, PG DipSed, PG DipHE, PG Cert.AP, FAHE, FRSM, FIADFE, LPA (ALSP certified)

Oral neuropathic pain (ONP) is an increasingly recognized and challenging complication of cancer therapy that significantly affects patient quality of life and functional outcomes. Patients undergoing chemotherapy (CT), radiotherapy (RT), and concurrent chemoradiotherapy (CCRT) frequently experience persistent oral pain resulting from both direct neural injury and secondary inflammatory processes. Chemotherapy-induced neuropathic pain (CINP), radiation-associated neural damage, and oral mucositis (OM)-related neuroinflammation collectively contribute to complex pain mechanisms that may clinically present as burning sensations, dysesthesia, altered taste, oral sensitivity, and spontaneous pain. These symptoms are often difficult to manage with conventional pharmacologic approaches alone. Despite advances in oncology care, ONP remains under-recognised and is associated with substantial physical, psychological, and nutritional burden. Current systemic therapies, including anticonvulsants, antidepressants, and opioids, may provide limited benefit while introducing undesirable adverse effects, emphasizing the need for safe, non-invasive, and targeted therapeutic interventions. Photobiomodulation (PBM) therapy has emerged as a promising modality with growing evidence supporting its role in pain modulation, tissue repair, and neuroprotection. This presentation will review the current understanding of the pathophysiological mechanisms underlying ONP in oncology patients and discuss the scientific rationale for PBM as a targeted therapeutic strategy. Particular focus will be placed on distinguishing the direct neuromodulatory effects of PBM on damaged neural tissues from its indirect effects mediated through mitigation of OM-associated inflammation and tissue injury. The presentation will also examine how inflammatory and neuropathic pathways overlap in the development of oral burning sensations and persistent pain symptoms during cancer treatment. In addition, current clinical evidence supporting PBM for the prevention and management of ONP and OM will be reviewed, with emphasis on practical clinical application, protocol considerations, and treatment outcomes. The presentation will further explore implementation strategies for integrating PBM into oncology and oral medicine services, including interdisciplinary collaboration, workflow considerations, patient selection, treatment standardization, and barriers to adoption in routine clinical practice. By highlighting mechanistic insights, clinical applications of PBM versus pharmacotherapy, and implementation considerations, this presentation aims to provide a comprehensive overview of PBM as a promising supportive intervention for oral neuropathic complications associated with head and neck oncology therapy.

Photobiomodulation in Kidney Disease: From Bench to Bedside

Ann Liebert, PhD

Background: Renal disease is a severe and increasing problem. Chronic kidney disease (CKD), including diabetic kidney disease (DKD) is tracking the global increasing incidence of obesity and metabolic disease. Current treatments for diabetic kidney disease are limited and generally not very effective, which highlights the need for innovative therapeutic strategies. Photobiomodulation (PBM) is one such potential therapy. PBM is known to modulate cellular function, suppress inflammation, restore balance redox, and improve mitochondrial activity, all of which are hallmarks of CKD.

Objective: To determine parameters, mechanisms, and efficacy of any reno-protective effect of PBM in a tissue and mouse model of DKD.

Methods: Experimental level: Basic Science Two animal models of CKD were used - folic acid induced CKD and high-fat diet (HFD)-induced DKD. Mice were either pre-treated or post-treated with PBM, with low and high-dose laser, and the laser lens pressed against the shaved flank of the mouse. Sham treated mice were treated under the same conditions with the power off. Renal function, fibrotic and inflammatory markers (protein and mRNA), and microbiome changes were examined. Device: Irradia 904 nm laser probe with fibre optic (9mm diameter); Power – 60 mW; pulsed – 50 Hz Treatment: low dose – 120 sec = 7.2 J; high dose - 300 seconds = 18 J; 3 times per week for 2 weeks (6 treatments)

Results: Low dose but not high dose improved kidney function, reduced fibrosis, inhibited the inflammatory response, suppressed oxidative stress, decreased blood urea, albumin, albumin-creatinine ratio and other markers of CKD (such as TNF-α, -SMA, TGF-β1, CD68). In addition, there were significant microbiome changes associated with PBM treatment.

Conclusion: PBM exerts a reno-protective effect via a number of mechanisms in pre- and post- treatment. This effect is biphasic, with PBM above the therapeutic dose showing no improvement in renal function. These results inform on an upcoming translational clinical study.

Five-Year Follow-Up of Photobiomodulation in Parkinson’s Disease: A Case Series Exploring Clinical Stability & Microbiome Modulation

Brian Bicknell, PhD

Background: Parkinson’s disease is the second most common neurodegenerative disease, affecting perhaps 10 million people worldwide. While the disease has no cure and few therapies that can slow the inevitable progression of the disease, previous results using photobiomodulation have suggested that this therapy is both effective at improving the motor clinical signs and non-motor symptoms of the disease but also might slow its progression. This case series followed six people with Parkinson’s disease over five years of their PBM treatment. The study was based on previous pre-clinical and clinical studies that have demonstrated a relationship between PBM, Parkinson’s disease symptoms and the microbiome.

Methods: Six participants with idiopathic Parkinson’s disease, who had been using PBM therapy more or less consistently 3 time per week, donated faecal samples before treatment began and after 5 years of treatment. from the samples, DNA was extracted and 16S rRNA genes amplified (V3-V4 region), diversity evaluated and changes in the relative abundance of specific taxa were quantified. Devices: 1.SYMBYX PDCare laser with twin 904 nm laser diodes (6.35mm diameter spot size); average power – 30 mW; peak power - 25,000 mW; power density – 47 mW/cm2 ; pulsed – 50 Hz. 2.SYMBYX Neuro LED helmet with 20 red (635 nm) diodes and 20 infrared (810 nm) diodes; power – 27 mW (red), 52 mW (IR); Treatment: 1.2 minutes on each of 9 points of the abdomen and 1 point on the neck (C2/C3), to give a 7.2 J (11.3 j/cm2) per point; 72 J total dose per treatment 2.12 minutes red LED then 12 minutes infrared LED, to give 19.44 J per point (red) and 37.44 J/point (IR); total dose per treatment equals 388 J (red) and 749 J (IR)

Results: Over the five years, most participants either remained stable or improved their motor symptoms (including their MDS-UPDRS-III score), their balance, cognition, and sense of smell. At the same time, their gut bacteria changed in ways that may indicate a positive improvement in their dysbiosis. Some bacteria that are linked to pathogenicity, inflammation and faster Parkinson’s progression (including Desulfovibrio) were decreased, while several bacteria associated with short-chain fatty acid production and good gut health were increased in the majority of participants.

Conclusion: Despite the small size of the study and the lack of healthy control participants, the findings suggest that long-term PBM may help stabilise Parkinson’s symptoms as well as potentially influencing the microbiome in a positive manner and hence influence the gut–brain connection in Parkinson’s disease.

Case Studies of the Use of Photobiomodulation Therapy for 7 Years: Patient Commitment to a Long-Term Therapy for Parkinson's Disease

Brian Bicknell, PhD

Background: Parkinson’s disease is the most rapidly increasing neurodegenerative disease and is remarkably complex, with a high degree of heterogeneity in symptomology. The disease is relentlessly progressive, with deterioration in the clinical signs and symptoms expected, although the rate of progression is difficult to predict and varies from person to person. While medication intervention early in the disease trajectory can create a so-called “honeymoon period” where symptoms can appear stable or even improve somewhat, the trajectory over years is an inevitable deterioration in motor and non-motor symptoms, which significantly impacts health-related quality of life in all patients. There is no pharmaceutical treatment that can reverse, halt or slow the progression of PD. We have previously demonstrated in a number of clinical studies that PBM treatment has the potential to improve clinical signs and symptoms of Parkinson’s disease.

Methods: Five participants with idiopathic Parkinson’s disease, who had been using PBM therapy more or less consistently 3 time per week for between 6 and 7 years, were reassessed for the same outcome measures as previously assessed before treatment began and at various intervals (years) of PBM therapy. Devices: 1.SYMBYX PDCare laser with twin 904 nm laser diodes (6.35mm diameter spot size); average power – 30 mW; peak power - 25,000 mW; power density – 47 mW/cm2 ; pulsed – 50 Hz. 2.SYMBYX Neuro LED helmet with 20 red (635 nm) diodes and 20 infrared (810 nm) diodes; power – 27 mW (red), 52 mW (IR); Treatment: 1.2 minutes on each of 9 points of the abdomen and 1 point on the neck (C2/C3), to give a 7.2 J (11.3 j/cm2) per point; 72 J total dose per treatment 2.12 minutes red LED then 12 minutes infrared LED, to give 19.44 J per point (red) and 37.44 J/point (IR); total dose per treatment equals 388 J (red) and 749 J (IR)

Results: Changes in the clinical motor signs of Parkinson’s disease, including MDS-UPDRS-III (motor) scores, measures of mobility and gait (walk speed, stride length and timed-up-and-go), and measures of balance, and fine motor skills, were all improved above baseline measures obtained before treatment began 7 years previously. Similarly, non-motor symptoms, including cognition, health-related quality of life, sleep quality, and sense of smell were on the whole improved from 7 years beforehand.

Conclusion: These results demonstrate the potential of continued long-term, at-home treatment with PBM to slow the progression of symptoms of Parkinson’s disease in some patients.

904nm Laser Photobiomodulation Increases Mitochondrial Membrane Potential in Cell Bodies of Neonatal Dorsal Root Ganglion Neurons and Schwann Cells in Vitro—Implications for PBM in Dental Analgesia, Neuropathic Pain, Nerve Injury and Repair

Roberta Chow, MB BS (Hons) FRACGP MApplSci (Med Acu) PhD Grad Cert Pain M’ment

Introduction: Photobiomodulation (PBM) has been used for more than 30 years for treatment of painful medical and dental conditions.  PBM effects on small diameter, slow conducting , C and Ad neurons, nociceptors of the peripheral nervous system, are central to PBM analgesic effects.  Previous dorsal root ganglion (DRG) studies of 650, 808, 830nm laser demonstrate structural and functional changes which translate to clinical pain relief.  For the first time, this study explores the effects of 904nm laser on neurons and Schwann cells in culture.  

Methods: Neonatal rat DRG neurons and Schwann were maintained in vitro until day 8, when experimental procedures were performed.

Measurement of Mitochondrial Membrane Potential (MMP)

MMP was assessed in experimental and control cultures using the mitochondrial probe JC-1. Cultures were imaged using confocal microscopy and irradiated for 150 s or 300 s before imaging. Ratio of red to green fluorescence of JC-1 was measured in DRG neurons and Schwann cells at 0, 5 and 20 min after laser or sham treatment. 5 randomly selected fields of view per culture plate were recorded and analysed independently in neurons and Schwann cells, which were identified based on morphology and confirmed by immunohistochemistry. Replicate laser-irradiated and control cultures were analysed. 

Laser Parameters (measured by Prof Judith Dawes, Dept Laser Physics, Macquarie University, Sydney, Australia.  Device: Irradia Sweden. Wavelength 904nm, 60mW, pulsed at 200 ns pulse width, 100 Hz, Peak Power 25 W, PD: 42.9mW/cm2, Exp 1:  time 150s, ED 5J/cm2, Total Joules 6.5J; Exp 2:  time 300s, ED: 9.9J/cm2, Total Joules 12.9J.

Results:

DRG Neurons: Cell Body:

Exp 1: 5 minutes following 150s of 904 nm laser resulted in a significant increase in MMP occurs which returns to normal by 20 minutes. 

Exp 2: 5 minutes following 300s of 904 nm laser results in a significant increase in MMP occurs which returns to normal by 20 minutes.

DRG Neurons: Axons:

Exp 1: 5 minutes following 150s of 904 nm laser  clustering of mitochondria in varicosities is observed along the length of the axon.

Exp 2: 5 minutes following 300s of 904 nm laser a significant increase in varicosity formation is observed.

Schwann Cells:

Exp 1: 5 minutes following 150s of 904 nm laser a significant increase in MMP occurs which returns to normal by 20 minutes. 

Exp 2: 5 mins  following 300s of 904nm laser there is a greater increase in MMP than the lower exposure with returns to normal by 20 minutes.

Conclusion: Varicosity formation along axons indicates disruption to the axonal cytoskeleton leading to blockade of fast axonal flow and results in depolarisation blockade consistent with clinical analgesic effects. Increase in MMP in Schwann cells indicates increase in ATP and stimulation of activities central to nerve function and repair,  supporting the use of 904nm laser in the treatment of neuropathic pain and stimulation of nerve repair.  

Learning Objectives:

  • Describe the structure of a nociceptor
  • Outline the importance of Schwann cell function in nerve repair
  • Understand the effects of 904 nm laser on Schwann cell metabolism
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