Blue Light Therapy in the Management of Chronic Wounds

Abstract and Introduction

Abstract

Introduction: Chronic wounds are a significant problem worldwide, with substantial cost to health care systems; thus, a minimally invasive and well-tolerated treatment is attractive. Blue light has shown promise in wound healing through the principle of photobiomodulation.

Objective: This review examines the physiological effects of blue light on tissue and the hypothesis that appropriate application of blue light in conjunction with SOC improves wound healing compared with SOC alone.

Methods: The authors searched in PubMed, Google Scholar, and the Cochrane Library to identify literature on the mechanism of action of blue light and then examined the clinical evidence.

Results: Key physiological pathways of blue light include generation of ROS and nitric oxide, resulting in promotion of angiogenesis, reduced inflammation, and direct antimicrobial effects. These reactions are seen only at low doses; in fact, higher doses may be harmful to tissue. The only primary study with statistical analyses demonstrated wound area reduction of 51% (P =.007) in blue light–irradiated wounds compared with SOC alone.

Conclusions: Blue light applied following a strict protocol is safe and shows promise in the management of chronic wounds. The current evidence is poor, however, and randomized trials are required to confirm its clinical utility.

Introduction

Chronic wounds are a common problem worldwide. In Australia, it is estimated that 420 000 chronic wounds are managed each year, at an annual cost of approximately 3 billion Australian dollars.^[1] Assessment of the underlying etiology is essential to optimize treatment. The most common wounds are pressure ulcers, venous ulcers, diabetic ulcers, and arterial ulcers;^[1] often, patients present with several such wounds. The average wound duration is 12 to 13 months, and wounds recur in 60% to 70% of patients.^[2] Some chronic wounds are refractory to standard treatment, including offloading, compression, revascularization, skin grafting, and dressings. Malignancy must be excluded, and rarer wound types such as dermatologic and vasculitic wounds require specialized treatment.

One well-established adjunct in the treatment of wounds of various etiologies is phototherapy, that is, the use of light ranging from UV, visible spectrum blue to red, and infrared light to promote wound healing.^[3,4] While extensive research supports the use of red or near-infrared light (wavelength 600 nm–1100 nm) for wound healing,^[3–5] the use of blue light (wavelength 400 nm–450 nm) has not been as well studied, potentially owing to its proximity to UV light and its associated risks.^[5,6] As more alternative therapies are explored, blue light has seen a resurgence in evidence and support. Recently published clinical results on the management of wounds using blue light have been promising, albeit only in a few case series and trials with a low level of evidence. The most prominent publication as of the time of this writing, the Blue Light for Ulcer Reduction (BLUR) study, demonstrated a 33.5% reduction in wound size in the treatment group compared with SOC alone.^[7]

To the knowledge of the current authors, this is the first review to consolidate the literature on the physiological basis of blue light therapy and evaluate the published clinical evidence to determine if blue light along with SOC results in improved wound healing compared with SOC alone.

Table. Summary of Evidence on Human Applications of Blue Light Therapy Identified in Literature Review
SOURCE	NO. OF PATIENTS	PATIENT AGE (y)	PATIENT AND WOUND CHARACTERISTICS	WOUND AREA ASSESSMENT METHOD	LIGHT WAVELENGTH (nm)^a	DURATION OF TREATMENT (wk)	OBSERVED OUTCOMES
Fraccalvieri et al,⁷ 2021	90	>70	SOC-resistant wounds (avg duration, 67.83 mo) of various etiologies (63.02% venous, 21.0% mixed arterial, 16.98% other)^b	Digital imaging for both treatment and control areas	400–430	10	Avg residual wound area 42.1% of baseline after blue light therapy plus SOC (treatment) vs 63.4% of baseline after SOC alone (control) Avg 3.5-point decrease in pain score (on a scale of 0–10, with 10 being the most severe pain) Healing probability rate of 0.238 in treatment group vs 0.176 in control group (P=.16) In venous subgroup, 33.3% residual wound area in treatment group vs 60.1% in control group
Khoo et al,⁴⁸ 2021	2	Case 1: 7¹ Case 2: 77	SOC-resistant recurrent venous ulcers of the lower extremity	Clinical	400–430	Case 1: 5 Case 2: 3	Case 1: 67% wound area reduction at 5 wk Case 2: 37.8% wound area reduction at 3 wk
Marchelli et al,⁴⁹ 2019	19	Avg, 75	SOC-resistant chronic ulcers of ≥2 mo duration and of various etiologies (47.4% venous, 21.1% traumatic, 10.5% PAD, 15.8% vasculitic, 5.3% wound dehiscence)	Clinical	400–430	10	6 wounds achieved ≥80% reepithelialization, 5 wounds achieved 50%-80% reepithelialization, 5 wounds achieved ≤50% reepithelialization, 3 wounds non-responsive
Nair and Sulong,⁵⁰ 2021	5	Range, 54–76	Chronic DFU (avg duration, 62 wk [range, 1–104 wk]) in patients with diabetes and hypertension	Clinical	400–430	10	Complete wound closure in 2 cases, 90% wound closure in 1 case, 94% wound closure in 1 case, and 30% wound closure in 1 case
Aliquò et al,⁵¹ 2021	11	Range, 53–84	SOC-resistant chronic ulcers of various etiologies (NR) in patients with diabetes	Clinical	400–430	10	7 wounds achieved complete wound closure, 1 wound achieved 90% closure, 1 wound achieved 80% closure, 1 wound achieved 50% closure, 1 wound achieved 30% wound closure
Dini et al,⁵² 2021	20	Avg, 67 (range, 46–86)	Treatment-resistant ulcers (avg duration, 24 mo [range, 6–60 mo]) of various etiologies (60% venous, 30% vasculitic, 10% traumatic)	Digital analysis	400–430	4	Complete wound closure in 2 wounds, wound area reduction in 16 wounds, no improvement in 2 wounds Avg 3.4-point increase in wound bed score (on a scale of 0–16, with 16 being the best score possible) Avg 2.35-point decrease in pain score (on a scale of 0–10, with 0 being no pain)

Table. Summary of Evidence on Human Applications of Blue Light Therapy Identified in Literature Review

SOURCE

NO. OF PATIENTS

PATIENT AGE (y)

PATIENT AND WOUND CHARACTERISTICS

WOUND AREA ASSESSMENT METHOD

LIGHT WAVELENGTH (nm)^a

DURATION OF TREATMENT (wk)

OBSERVED OUTCOMES

Fraccalvieri et al,⁷ 2021

>70

SOC-resistant wounds (avg duration, 67.83 mo) of various etiologies (63.02% venous, 21.0% mixed arterial, 16.98% other)^b

Digital imaging for both treatment and control areas

400–430

Avg residual wound area 42.1% of baseline after blue light therapy plus SOC (treatment) vs 63.4% of baseline after SOC alone (control)
Avg 3.5-point decrease in pain score (on a scale of 0–10, with 10 being the most severe pain)
Healing probability rate of 0.238 in treatment group vs 0.176 in control group (P=.16) In venous subgroup, 33.3% residual wound area in treatment group vs 60.1% in control group

Khoo et al,⁴⁸ 2021

Case 1: 7¹
Case 2: 77

SOC-resistant recurrent venous ulcers of the lower extremity

Clinical

400–430

Case 1: 5
Case 2: 3

Case 1: 67% wound area reduction at 5 wk
Case 2: 37.8% wound area reduction at 3 wk

Marchelli et al,⁴⁹ 2019

Avg, 75

SOC-resistant chronic ulcers of ≥2 mo duration and of various etiologies (47.4% venous, 21.1% traumatic, 10.5% PAD, 15.8% vasculitic, 5.3% wound dehiscence)

Clinical

400–430

6 wounds achieved ≥80% reepithelialization, 5 wounds achieved 50%-80% reepithelialization, 5 wounds achieved ≤50% reepithelialization, 3 wounds non-responsive

Nair and Sulong,⁵⁰ 2021

Range, 54–76

Chronic DFU (avg duration, 62 wk [range, 1–104 wk]) in patients with diabetes and hypertension

Clinical

400–430

Complete wound closure in 2 cases, 90% wound closure in 1 case, 94% wound closure in 1 case, and 30% wound closure in 1 case

Aliquò et al,⁵¹ 2021

Range, 53–84

SOC-resistant chronic ulcers of various etiologies (NR) in patients with diabetes

Clinical

400–430

7 wounds achieved complete wound closure, 1 wound achieved 90% closure, 1 wound achieved 80% closure, 1 wound achieved 50% closure, 1 wound achieved 30% wound closure

Dini et al,⁵² 2021

Avg, 67 (range, 46–86)

Treatment-resistant ulcers (avg duration, 24 mo [range, 6–60 mo]) of various etiologies (60% venous, 30% vasculitic, 10% traumatic)

Digital analysis

400–430

Complete wound closure in 2 wounds, wound area reduction in 16 wounds, no improvement in 2 wounds
Avg 3.4-point increase in wound bed score (on a scale of 0–16, with 16 being the best score possible)
Avg 2.35-point decrease in pain score (on a scale of 0–10, with 0 being no pain)