Cutaneous effects of photobiomodulation with 1072 nm light.

Photobiomodulation, also known as low-level light therapy, has gained popularity in treating a variety of dermatologic and non-dermatologic conditions. The near-infrared (NIR) portion ranging from 700 to 1440 nm has a broad spectrum but most current research focuses on relatively shorter wavelengths. To date, clinical research regarding the application of 1072 NIR is limited to treatments for infections and photorejuvenation treatment in females. However, 1072 NIR light therapy may benefit male patients. This theoretical application is based on the biological properties of this subgroup having increased cutaneous density and thickness and the physical properties of 1072 NIR allowing it to penetrate increased depth. 1072 NIR can reach more cells throughout the epidermis and dermis compared to other parts of the electromagnetic spectrum traditionally used in phototherapy to provide unique and targeted benefits. 1072 NIR light-emitting diodes are commercially available and therefore hold tremendous potential to become accessible, affordable treatment options. Given the increased demand and market size for aesthetics for men that remains untapped, there is opportunity for future research to elucidate the potential for this wavelength as a safe and effective treatment.

Red Light Phototherapy Using Light-Emitting Diodes Inhibits Melanoma Proliferation and Alters Tumor Microenvironments.

Background: Total annual cancer rates have decreased due to improved treatment and prevention. However, the incidence of melanoma is rising, and not all patients respond to immune and targeted approaches. Therefore, we sought to determine the efficacy of red light (RL) phototherapy in preclinical models of melanoma. Methods: Melanoma cells (A375, B16F10, MNT-1) were irradiated with RL. Melanoma proliferation, apoptosis, oxidative stress, and p53 phosphorylation were measured in vitro. In C57BL/6 mice, phototherapy safety, B16F10 tumor growth, and immunocyte infiltration were assessed following RL. Results: In vitro, 640 J/cm2 RL decreased cellular proliferation without increasing apoptosis, while 1280 J/cm2 increased apoptosis. RL increased intracellular reactive oxygen species generation and p53 phosphorylation. In animal models, 2560 J/cm2 RL significantly prevented melanoma growth and increased the expression of CD103+ dendritic cells. 1280 and 1920 J/cm2 RL decreased tumor volume, but not significantly. RL did not cause skin inflammation or erythema in normal skin. Conclusion: RL represents a potentially safe and effective melanoma therapeutic. RL prevented tumor growth and increased the expression of immune markers, such as CD103, that are associated with favorable melanoma outcomes. Further research is needed to determine the optimal clinical treatment regimen for melanoma using RL.

Home-based devices in dermatology: a systematic review of safety and efficacy.

There is increasing demand for home-based devices for the treatment of dermatologic conditions and cosmesis. Commercially available devices include intense pulsed light, laser diodes, radiofrequency, light-emitting diodes, and ultraviolet B phototherapy. The objective of this report is to evaluate the current evidence regarding the efficacy and safety of home-based devices for the treatment of skin conditions. A systematic search of PubMed, Embase, and Cinahl was conducted on November 9, 2020 using PRISMA guidelines. Original research articles that investigated the efficacy and safety of home-based devices for dermatologic use were included. Bibliographies were screened for additional relevant articles. Strength of evidence was graded using the Oxford Centre for Evidence-Based Medicine guidelines. Clinical recommendations were then made based on the quality of the existing literature. After review, 37 clinical trials were included-19 were randomized controlled trials, 16 were case series, and 2 were non-randomized controlled trials. Ultimately, from our analysis, we recommend the home-based use of intense pulsed light for hair removal, laser diodes for androgenic alopecia, low power radiofrequency for rhytides and wrinkles, and light-emitting diodes for acne vulgaris. Trials investigating ultraviolet B phototherapy for psoriasis revealed mixed evidence for home treatments compared to clinic treatments. All devices had favorable safety profiles with few significant adverse events. Limitations to our review include a limited number of randomized controlled trials as well as a lack of data on the long-term efficacy and safety of each device.

Transcriptome analysis of human dermal fibroblasts following red light phototherapy.

Fibrosis occurs when collagen deposition and fibroblast proliferation replace healthy tissue. Red light (RL) may improve skin fibrosis via photobiomodulation, the process by which photosensitive chromophores in cells absorb visible or near-infrared light and undergo photophysical reactions. Our previous research demonstrated that high fluence RL reduces fibroblast proliferation, collagen deposition, and migration. Despite the identification of several cellular mechanisms underpinning RL phototherapy, little is known about the transcriptional changes that lead to anti-fibrotic cellular responses. Herein, RNA sequencing was performed on human dermal fibroblasts treated with RL phototherapy. Pathway enrichment and transcription factor analysis revealed regulation of extracellular matrices, proliferation, and cellular responses to oxygen-containing compounds following RL phototherapy. Specifically, RL phototherapy increased the expression of MMP1, which codes for matrix metalloproteinase-1 (MMP-1) and is responsible for remodeling extracellular collagen. Differential regulation of MMP1 was confirmed with RT-qPCR and ELISA. Additionally, RL upregulated PRSS35, which has not been previously associated with skin activity, but has known anti-fibrotic functions. Our results suggest that RL may benefit patients by altering fibrotic gene expression.

Visible light. Part I: Properties and cutaneous effects of visible light.

Approximately 50% of the sunlight reaching the Earth's surface is visible light (400-700 nm). Other sources of visible light include lasers, light-emitting diodes, and flash lamps. Photons from visible light are absorbed by photoreceptive chromophores (e.g., melanin, heme, and opsins), altering skin function by activating and imparting energy to chromophores. Additionally, visible light can penetrate the full thickness of the skin and induce pigmentation and erythema. Clinically, lasers and light devices are used to treat skin conditions by utilizing specific wavelengths and treatment parameters. Red and blue light from light-emitting diodes and intense pulsed light have been studied as antimicrobial and anti-inflammatory treatments for acne. Pulsed dye lasers are used to treat vascular lesions in adults and infants. Further research is necessary to determine the functional significance of visible light on skin health without confounding the influence of ultraviolet and infrared wavelengths.

The Vascular Component of Melasma: A Systematic Review of Laboratory, Diagnostic, and Therapeutic Evidence.

BACKGROUND: Melasma is a common acquired disorder of hyperpigmentation, classically manifesting as symmetric brown patches on the face. Although the exact pathogenesis is not fully understood, vascular abnormalities have been implicated in melasma. OBJECTIVE: To evaluate the laboratory and clinical evidence regarding the safety and efficacy of antivascular agents for the treatment of melasma. METHODS: A systematic review of PubMed, EMBASE, and Cochrane was conducted on May 13, 2020, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Original research articles investigating the role of vascularity and/or evaluating the use of antivascular therapeutics in melasma were included. Clinical recommendations were based on the American College of Physicians guidelines. RESULTS: A total of 34 original research articles as follows were identified: 4 laboratory studies, 15 diagnostic studies, and 15 therapeutic studies. CONCLUSION: There is promising evidence supporting the use of tranexamic acid and laser/light therapies to treat the vascular component of melasma, and more rigorous clinical trials are needed to validate their efficacy. Clinicians may consider treatment with one or more antivascular therapeutics in patients with melasma. Further research is warranted to characterize the role of cutaneous vascularization in melasma and may provide insights for novel therapies.

Safety of light emitting diode-red light on human skin: Two randomized controlled trials.

Therapeutic applications of light emitting diode-red light (LED-RL) are expanding, yet data on its clinical effects are lacking. Our goal was to evaluate the safety of high fluence LED-RL (≥160 J/cm2 ). In two phase I, single-blind, dose escalation, randomized controlled trials, healthy subjects received LED-RL or mock irradiation to the forearm thrice weekly for 3 weeks at fluences of 160-640 J/cm2 for all skin types (STARS 1, n = 60) and at 480-640 J/cm2 for non-Hispanic Caucasians (STARS 2, n = 55). The primary outcome was the incidence of adverse events (AEs). The maximum tolerated dose was the highest fluence that did not elicit predefined AEs. Dose-limiting AEs, including blistering and prolonged erythema, occurred at 480 J/cm2 in STARS 1 (n = 1) and 640 J/cm2 in STARS 2 (n = 2). AEs of transient erythema and hyperpigmentation were mild. No serious AEs occurred. We determined that LED-RL is safe up to 320 J/cm2 for skin of color and 480 J/cm2 for non-Hispanic Caucasian individuals. LED-RL may exert differential cutaneous effects depending on race and ethnicity, with darker skin being more photosensitive. These findings may guide future studies to evaluate the efficacy of LED-RL for the treatment of various diseases.

Topical Treatments for Melasma: A Systematic Review of Randomized Controlled Trials

Background: Melasma is an acquired skin disease characterized by symmetric hyperpigmentation on sun-exposed areas, particularly on the face. Recently, there has been tremendous scientific interest in novel, safe, and effective topical agents to manage melasma. Objective: To evaluate topical treatments for melasma and provide evidence-based recommendations for clinical use and further research. Methods: We performed a systematic review of randomized controlled trials (RCTs) on topical agents for the treatment of melasma on March 4th, 2019 using PRISMA guidelines. Clinical recommendations were based on the American College of Physicians guidelines. Results: After screening, we identified 35 original RCTs using azelaic acid, cysteamine, epidermal growth factor, hydroquinone (liposomal-delivered), lignin peroxidase, mulberry extract, niacinamide, Rumex occidentalis, triple combination therapy, tranexamic acid, 4-n-butylresorcinol, glycolic acid, kojic acid, aloe vera, ascorbic acid, dioic acid, ellagic acid and arbutin, flutamide, parsley, or zinc sulfate for melasma. Conclusions: Cysteamine, triple combination therapy, and tranexamic acid received strong clinical recommendations for the treatment of melasma. Cysteamine has excellent efficacy and is reported to have anti-cancer properties, but has not been directly compared with hydroquinone. Triple combination agents and tranexamic acid are effective, but carry theoretical risks for ochronosis and thrombosis, respectively. Natural compounds are associated with low risk for adverse events, but more research is needed to determine the efficacy, optimal formulation, and appropriate concentration of novel treatments. J Drugs Dermatol. 2019;18(11):1156-1171.

A single-blind, dose-escalation, phase I study of high-fluence light-emitting diode-red light on Caucasian non-Hispanic skin: study protocol for a randomized controlled trial.

BACKGROUND: Visible light (400 to 700 nm) is common in our environment, comprising 44% of total solar radiation and a large component of environmental light exposure. The effects of visible light on skin remain undefined. The red light portion of the visible spectrum (600 to 700 nm) may be used to treat skin diseases as a monotherapeutic modality or in combination with other agents. Light-emitting diode-red light (LED-RL) phototherapy may represent an important advance in light-based treatment modalities because it is non-invasive, inexpensive, portable, and easily combinable with other therapies. We previously determined the maximum tolerated dose (MTD) of high-fluence LED-RL (HF-LED-RL) in skin of color individuals to be 320 J/cm2. To the best of our knowledge, no clinical trials have been performed to determine the safety of higher doses of HF-LED-RL in Caucasian non-Hispanic individuals. The aim of this study is to investigate the safety of HF-LED-RL at doses of 480 and 640 J/cm2 in healthy Caucasian non-Hispanic individuals. METHODS: This is a single-blind, dose-escalation, randomized, controlled, phase I trial titled Safety Trial Assessing Red-light on Skin (STARS) 2. Healthy subjects will be randomly assigned to groups of five (three subjects randomly assigned to HF-LED-RL phototherapy and two subjects randomly assigned to mock therapy). Subjects in group 1 will receive HF-LED-RL or mock irradiation at the starting dose of 480 J/cm2, and the dose will be escalated in the subsequent group (group 2) to 640 J/cm2. The MTD is defined as the dose level below the dose at which two or more subjects (>20% of the cohort) experience a dose-limiting toxicity (DLT). After either the MTD is established or the study endpoint of 640 J/cm2 is achieved, additional HF-LED-RL phototherapy subjects and mock therapy subjects will be enrolled at that fluence (group 3) for a total number of up to 60 subjects. Each subject will receive a total of nine irradiation sessions, three times per week for three consecutive weeks. DISCUSSION: This follow-up study aims to provide important knowledge about safety and cutaneous effects of HF-LED-RL phototherapy of 480 and 640 J/cm2 in Caucasian non-Hispanic subjects. The importance of this clinical trial is that it may establish new treatment paradigms and a safety profile for LED-RL based on race and ethnicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03433222 . Registered on February 1, 2018 - Retrospectively registered. Protocol date and version: January 12, 2018; version 1.

Patient-reported outcomes in lasers and light therapy.

As the prevalence of lasers and light devices to treat dermatologic conditions increases, patient reported outcomes (PROs) will be an essential component of evaluating clinical efficacy and patient satisfaction. PROs may be used to identify patients' values, weigh risks and benefits of various therapies, identify barriers to treatment and help guide the development of new therapies. Utilizing patient and physician assessments may help determine if a new treatment is objectively better than currently available therapies. In creating a patient-centered treatment plan using laser and light modalities, it is critical to evaluate side effects using PROs. Determining and resolving barriers to treatment has benefits at the individual level and the population level. Many PRO measures (PROMs) are available to use for general and specific dermatologic conditions. The Dermatologic Life Quality Index, Skindex, and FACE-Q are PROMs that have been used in laser and light therapy studies. Selecting the proper instrument should be based on study aims to yield high quality data. Herein, we assess PROs use in laser and light treatment protocols to improve patient care, increase patient satisfaction and reduce barriers to care, and review dermatology PRO measures (PROMs) used in published laser and light clinical studies.

Light-emitting diodes in dermatology: A systematic review of randomized controlled trials.

OBJECTIVE: In dermatology, patient and physician adoption of light-emitting diode (LED) medical technology continues to grow as research indicates that LEDs may be used to treat skin conditions. The goal of this systematic review is to critically analyze published randomized controlled trials (RCTs) and provide evidence-based recommendations on the therapeutic uses of LEDs in dermatology based on published efficacy and safety data. METHODS: A systematic review of the published literature on the use of LED treatments for skin conditions was performed on September 13th 2017. RESULTS: Thirty-one original RCTs were suitable for review. CONCLUSIONS: LEDs represent an emerging modality to alter skin biology and change the paradigm of managing skin conditions. Acne vulgaris, herpes simplex and zoster, and acute wound healing received grade of recommendation B. Other skin conditions received grade of recommendation C or D. Limitations of some studies include small patient sample sizes (n < 20), absent blinding, no sham placebo, and varied treatment parameters. Due to few incidences of adverse events, affordability, and encouraging clinical results, we recommend that physicians use LEDs in clinical practice and researchers continue to explore the use of LEDs to treat skin conditions. Lasers Surg. Med. 9999:1-16, 2018. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Laser and light-based therapy for cutaneous and soft-tissue metastases of malignant melanoma: a systematic review.

Invasive cutaneous melanoma is a growing health concern. Although surgical excision can effectively treat in situ tumors, use for metastatic melanoma is limited. Laser and light-based therapies may be a valuable palliative treatment option for patients with stage III and stage IV cutaneous metastatic melanoma. Our goal is to review the published literature and provide evidence-based recommendations on laser and light-based palliative therapies for metastatic melanoma. A search of the databases Pubmed, EMBASE, Web of Science, and CINAHL was performed on March 10, 2016. Key search terms were related to melanoma, laser, and light-based modalities. Our search initially identified 13,923 articles and 27 original articles met inclusion criteria for our review. Grade of recommendation: C for non-fractionated carbon dioxide laser, Grade of recommendation: D for fractionated carbon dioxide laser, ruby laser, neodymium laser, near-infrared diode laser, and photodynamic therapy. Non-fractionated carbon dioxide laser had the best palliative efficacy of the reviewed laser and light-based therapies, while other treatment modalities may have potential as adjunctive therapy to standard of care.