Researchers have tested the effects of low-level light therapy (LLLT) using low-power lasers or non-coherent, non-collimated light therapy from light-emitting diodes (LEDs) on wounds for decades, exploring the efficacy of phototherapy treatments for chronic¹ and acute² wounds. Low-level light therapy has received device clearance in the United States for cosmetic improvement of aging or sun-damaged skin, acne, actinic keratoses, non-melanoma skin cancer, improving circulation, and decreasing pain as well as stiffness and muscle spasm. ³ It has been used for dental, dermatologic, neurologic, and chiropractic conditions in Canada, Europe, and Asia for several years.⁴ There are few adequately powered, double-blind randomized clinical trials (RCTs) carefully evaluating energy dose-response of each color or wavelength of LLLT. Typical ranges of LLLT include infrared light waves (800–1200 nm, penetrating 5–10 mm of tissue), red (630–700 nm, penetrating 2–3 mm), yellow (570–590 nm, penetrating 0.5–2 mm), and blue to ultraviolet (400–170 nm, penetrating < 1 mm).³ Low-level light therapy is delivered at various power densities (W/cm²), time durations, and duty cycles, accumulating as energy absorbed over time, called fluence (J/cm²). The variety of wound outcomes in response to differing LLLT parameters used to stimulate various aspects, depths, and types of tissue injury can be confusing. In this installment of Evidence Corner, a systematic review⁵ of LED effects on dermatologic conditions and wounds and a second on LLLT effects on diabetic foot ulcers (DFUs)¹ add clarity to LLLT effects on some aspects of wound management.

Reference: Jagdeo J, Austin E, Mamalis A, Wong C, Ho D, Siegel DM. Light-emitting diodes in dermatology: a systematic review of randomized controlled trials. Lasers Surg Med. 2018;50(6):613–628. doi:10.1002/lsm.22791

Rationale: PubMed-indexed articles on medical uses of LEDs have more than doubled each year since 2010, providing growing evidence of efficacy and safety of therapeutic uses of non-ionizing LED light.

Objective: This systematic review critically analyzed published evidence of safety and efficacy of LEDs used in dermatology and provided evidence-based recommendations for this use.

Methods: Two authors and a research librarian searched the PubMed, Cochrane, EMBASE, and Web of Science databases through 2016 to identify and analyze any RCT that compared at least 1 LED therapeutic arm with any other topical treatment of patients with skin wounds or conditions. Preclinical, non-clinical, and ultraviolet light studies reviewed elsewhere were excluded. Results were tabulated separately for US Food & Drug Administration (FDA)-cleared and for non-FDA-cleared indications. Resulting evidence was graded according to the Oxford Centre for Evidence-based Medicine—Levels of Evidence⁶ and then used to support related recommendations, which were graded according to statistical consistency (P < .05) of effects supporting dermatologic use of LEDs. Grade A was defined as consistent support by a systematic review of RCTs or high-quality RCT; Grade B was consistent low-quality RCT and/or cohort study and/or case-control systematic review support; Grade C was consistent support from case series and extrapolations from cohort and/or low-quality RCTs; and Grade D was troubling, inconclusive, or inconsistent support from case reports, expert opinion, or bench studies.

Results: Of the 3844 articles screened for inclusion, 31 qualified for inclusion as RCT evidence exploring the effects of LEDs on skin. There were no Grade A recommendations, largely due to limited capacity to conduct double-blind studies of colored light-based interventions, small sample sizes, and variations in stimulation parameters, including distance from source, power density, orientation, and fluence. Grade B recommendations were supported by (1) eight RCTs on 456 patients exposed to red (8–100 mW/cm²) or blue (6–40 mW/cm²) LED for 20 minutes twice weekly to reduce inflammation or counts of acne vulgaris lesions; (2) three RCTs on 147 patients exposed to near infrared (830 nm at 55 mW/cm² for 10 minutes 4 times over 10 days) to reduce healing time and scarring of herpes simplex and zoster lesions; or (3) five RCTs on 99 patients receiving 2 minutes of daily exposure to yellow (5 mW/cm²) or 20 minutes of daily exposure to near infrared (about 50 mW/cm²) LED to reduce acute wound erythema or healing time. Of indications with Grade B recommendations, only acne vulgaris and herpes simplex and zoster were FDA-cleared. The FDA-cleared skin rejuvenation received a Grade C recommendation for daily treatment with near infrared (55 mW) or red light (55 mW/cm²) combined or alone for up to 20 minutes per day for 8 to 10 weeks to improve skin wrinkles (6 RCTs of 328 patients with 42 withdrawn). Non-FDA-cleared daily treatment of psoriasis with blue light (50 mW/cm²) received a Grade C recommendation based on 3 RCTs (114 patients) for reducing inflammatory aspects of psoriasis. Indications receiving Grade D recommendations not cleared by the FDA were chronic wound healing (2 RCTs on 97 patients), oral mucositis(1 RCT on 80 patients), radiation dermatitis (1 RCT on 33 patients), or cellulite reduction (1 RCT on 9 patients). 

Authors’ conclusions: Based on published evidence, acne vulgaris, herpes simplex and zoster (shingles), and acute wound healing have shown improved outcomes in response to LED therapy sufficient to support Grade B recommendations. While other skin conditions have less supporting evidence, rare adverse events, affordability, and encouraging clinical results suggest the merit of further clinical research.

Reference: Tchanque-Fossuo CN, Ho D, Dahle SE, Koo E, Li CS, Isseroff RR, Jagdeo J. A systematic review of low-level light therapy for treatment of diabetic foot ulcer. Wound Repair Regen. 2016;24(2):418–426. doi:10.1111/wrr.12399

Rationale: Low-level light therapy using low-power lasers or LEDs affects cellular and molecular aspects of repair, suggesting low-level laser or LED may be used in treating DFUs.

Objective: This systematic literature review explored the efficacy of LLLT compared with standard of care on DFU healing after 12 or 20 weeks of treatment.

Methods: Three independent reviewers extracted and synthesized information found in PubMed, EMBASE, CINAHL, and Web of Science database searches from inception through September 30, 2016, for published RCTs or derivative references documenting partial or complete healing effects of DFUs receiving standard of care treatment as compared with any low-level laser or LED treatment. Risk of bias was assessed using Cochrane standards. Both non-clinical and clinical studies on wounds other than DFUs or those using photodynamic or anodyne therapies were excluded.

Results: Among the 1051 articles found, 4 RCTs qualified for review. A total of 69 patients with a DFU treated with LLLT were compared with 62 patients receiving standard of care or sham or placebo-controlled treatment. Each RCT had important limitations. Procedures, timing, and measures of healing varied across the studies, rendering meta-analysis inappropriate. Three RCTs were double-blind and placebo-controlled or sham-controlled. The fourth and largest RCT, with 32 patients receiving LLLT and 32 patients receiving standard of care, had only a 15-day duration, lacked clear allocation concealment or treatment parameters, measured a sub-standard healing outcome, and was not blinded to treatment or evaluation. Despite these limitations, each RCT reported at least 1 significant effect on DFU healing. The LLLT for DFUs was given a Grade B recommendation, with the authors noting a stronger recommendation would require more well-designed RCTs using comparable light parameters, screening periods to exclude rapid healers, larger sample sizes, and longer follow-up periods.

Authors’ conclusions: All 4 studies reviewed had improved some aspect of DFU healing when exposed to LLLT with no adverse effects, suggesting the merit of future stringent RCTs to validate LLLT treatment of DFUs. 

These 2 systematic reviews suggest the promise of LLLT for skin and acute wound care⁶ or for DFU treatment¹ while highlighting important needs for more rigorous research before any specific wavelength, power density, or fluence of LED or low-level laser light would qualify for enthusiastic recommendation for clinical use. Both reviews noted the absence of adverse effects and suggested the potential for cost-effectiveness research. Before studying cost effectiveness, it will be important to conduct rigorous RCTs that meet Cochrane and Agency for Healthcare Research and Quality evidence standards to define effective regions of wavelength, power density, and fluence for each indication studied. Results of these RCTs could be mapped on triaxial diagrams to determine the “sweet spot” of LLLT parameters for efficacy and cost-effectiveness for each indication described. Triaxial plots are valuable tools for guiding research and clinical practice in pharmacology,⁷ infection control,⁸ and other important areas exploring multifaceted phenomena and could similarly help define effective LLLT stimuli for wound care. More rigorous RCTs identifying ideal LLLT stimulation parameters will determine if the findings described by these systematic reviews^1,6 represent genuine light at the end of the LLLT evidence tunnel. 

Author: Laura Bolton, PhD

Affiliation: Adjunct Associate Professor, Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ

Disclosure: The author discloses no financial or other conflicts of interest.