Photobiomodulation with low-level laser (LLLT) in the treatment of wounds

Photobiomodulation is a term used to describe treatments with lasers or other LEDs. A common method in the field of photobiomodulation is low-level laser or low-level laser therapy (LLLT). Wound healing was one of the first areas where low-power lasers were tested, but the method has also been used to reduce pain, inflammation and swelling.

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SBU Enquiry Service

Consists of structured literature searches to highlight studies that can address questions received by the SBU Enquiry Service from Swedish healthcare or social service providers. We assess the risk of bias in systematic reviews and when needed also quality and transferability of results in health economic studies. Relevant references are compiled by an SBU staff member, in consultation with an external expert when needed.

Question

What systematic reviews are there on the effect of low-level laser therapy?

Identified literature

Table 1. Systematic reviews with low/medium risk of bias
RCT = Randomised controlled trial; LLLT = Low level laser therapy; nm = Nanometre; cm2 = Square centimetres; J = Joule; W = Watt; SMD = Standardized mean difference; CI = Confidence interval; SD = Standard deviation; RR = Risk ratio
Included studies Population/Intervention Outcome and Results
Huang et al, 2021, [1]
Study design: Randomized controlled trials (RCTs).
Included: n=13 RCTs
Countries: India (n=2), Iran (n=2), Israel (n=1), Brazil (n=2), Colombia (n=1), and China (n=5).
Risk for bias:Moderaterisk of bias		 Population: Patients with diabetic foot ulcers. Five on type 2 diabetes.
Severity of ulcer from Wagner I to Wagner III
Mean age: 48.33 to 68.50 years

Intervention: LLLT

Setting: Not specified		 Complete healing rate (9 RCTs, n=278):
RR 2.10 (95% CI, 1.56 to 2.83)
GRADE: Very Low

Ulcer area reduction percentage (5 RCTs, n=166):
SMD 3.52 (95% CI, 1.65 to 5.38)

Mean healing time (2 RCTs, n=80):
SMD –1.40 (95% CI, –1.90 to –0.91)

Adverse effect:
None observed in 7 studies
Data not available from 6 studies
Authors' conclusion:
“This meta-analysis demonstrates that LLT is a promising and effective treatment for DFUs. Further evidence from larger samples and higher quality RCTs is needed to prove the effect of LLLT and to determine the most appropriate parameters for the healing of DFUs.”
Zhou et al, 2021, [2]
Study design: Randomized controlled trials (RCTs).
Control was either usual care with or without placebo lights.
Included: n=12 RCTs
Countries: India (n=3), Iran (n=2), Brazil (n=2), Slovenia (n=1), Israel (n=1), Malaysia (n=1), Colombia (n=1), and China (n=1).
Risk for bias: Low risk for bias		 Population: Patients with diabetic foot ulcers.
Mean age: 45 to 64.85 years

Intervention: LLLT. Defined as wavelengths ranging from 500 to 1100 nm, energy densities between 0.1 and 10 J/cm2 and power ranging from 0.01 to 0.5 W/cm2.

Setting: At hospital (n=11), at home (n=1).
Mean initial ulcer size: 1.83 to 62.9 cm2.
Mean duration of ulcer: 5 days to 95.5 months.		 Reduction (%) of wound ulcer size (6 RCTs, n=235)
30.89% (95% CI, 15.60 to 46.18), p<0.001
Hedges’ g=2.81
SMD: 2.80 SD higher (95% CI, 1.09 to 4.51 higher)
GRADE: Very low (Symbol for very low certainty of evidence).
Reduction (cm2) of wound ulcer size (5 RCTs, n=232)
4.20 cm2 (95% CI, 0.41 to 7.99), p=0.03)
Hedges’ g: 1.37
SMD: 1.37 SD higher (95% CI, 0.30 to 2.44 higher)
GRADE: Very low (Symbol for very low certainty of evidence).
Complete wound healing rate (5 RCTs, n=221)
RR: 4.65 (95% CI, 1.89 to 11.46)
GRADE: Low (Symbol for low certainty of evidence).
Authors' conclusion:
“Low-level light therapy had shown promising results for diabetic foot ulcers in accelerated ulcer healing and effectively reduced ulcer sizes. Subgroup findings revealed the high efficacy of low-level light therapy on diabetic foot ulcers of different sizes. However, due to the limited body of evidence in terms of sample size in this meta-analysis, results were interpreted with caution. Low-level light therapy can be used as an adjunct therapy. Future investigation could explore optimal conditions, settings, and regimes of therapy for diabetic foot ulcers. This review also urges researchers to adhere to the CONSORT guidelines in future studies to strengthen the quality of trials.”
Lucas et al, 2000, [3]
Study design: Randomized controlled trials (RCTs).
Control was either placebo or ultrasound/ultraviolet treatment.
Included: n=4 RCT

Countries: Canada, Sweden, Israel, Australia.

Risk for bias: Moderate risk for bias		 Population: Patients with topical ulcerations or wounds.

Intervention: Infrared LLLT, defined as 820 to 950 nm.		 Patients with poor outcome (wound still open at study end)
RR 0.76 (95% CI, 0.41 to 1.40)
Authors' conclusion:
“At present, we conclude that there are no scientific arguments for routine application of low level (infrared) laser therapy on wound healing in patients with decubitus ulcers, venous leg ulcers (ulcus cruris) or other chronic wounds”

 

Table 2. Relevant studies which were identified through the reviews with high risk for bias.
Author
Year
Reference		 Population Wavelength (nm) Comparison
Vitoriano et al
2019
[4]		 DFU 830 & 850 LLLT vs other laser
Tantawy et al
2018
[5]		 DFU 632 & 904 LLLT vs other laser
Maiya et al
2018
[6]		 DFU 660, 633 & 850 LLLT, without control
Srilestari et al
2017
[7]		 DFU 630 LLLT vs placebo
Afify et al
2017
[8]		 DFU 904 LLLT vs alternative
Salvi et al
2017
[9]		 DFU 415, 633 & 830 LLLT on DFU vs healthy control
Carvalho et al
2016
[10]		 DFU 658 LLLT vs alternative
Feitosa et al
2015
[11]		 DFU 632.8 LLLT vs usual care
Taradaj et al
2013
[12]		 PU 980, 808 & 658 LLLT vs placebo
Shojaei et al
008
[13]		 PU 940, 808 & 658 LLLT vs placebo
Taly et al
2004
[14]		 PU 820 LLLT vs placebo
Lucas et al
2003
[15]		 PU 904 LLLT vs usual care
DFU = Diabetic foot ulcer; PU = Pressure Ulcer

References

  1. Huang J, Chen J, Xiong S, Huang J, Liu Z. The effect of low-level laser therapy on diabetic foot ulcers: A meta-analysis of randomised controlled trials. Int Wound J 2021.
  2. Zhou Y, Chia HWA, Tang HWK, Lim SYJ, Toh WY, Lim XL, et al. Efficacy of low-level light therapy for improving healing of diabetic foot ulcers: A systematic review and meta-analysis of randomized controlled trials. Wound Repair Regen 2021;29:34-44.
  3. Lucas C, Stanborough RW, Freeman CL, De Haan RJ. Efficacy of Low-Level Laser Therapy on Wound Healing in Human Subjects: A Systematic Review. Lasers Med Sci 2000;15:84-93.
  4. Vitoriano NAM, Mont'Alverne DGB, Martins MIS, Silva PS, Martins CA, Teixeira HD, et al. Comparative study on laser and LED influence on tissue repair and improvement of neuropathic symptoms during the treatment of diabetic ulcers. Lasers Med Sci 2019;34:1365-1371.
  5. Tantawy SA, Abdelbasset WK, Kamel DM, Alrawaili SM. A randomized controlled trial comparing helium-neon laser therapy and infrared laser therapy in patients with diabetic foot ulcer. Lasers Med Sci 2018;33:1901-1906.
  6. Maiya AG, Kumar AS, Hazari A, Jadhav R, Ramachandra L, Hande HM, et al. Photobiomodulation therapy in neuroischaemic diabetic foot ulcers: a novel method of limb salvage. J Wound Care 2018;27:837-842.
  7. Srilestari A, Nareswari I, Simadibrata CL, Tarigan TJE. Effectiveness of combined laser-puncture and conventional wound care to accelerate diabetic foot ulcer healing. Medical Journal of Indonesia 2017;26:26-34.
  8. Afify N, Rasheed A, Fekry N, Hamada H, El Khatib A. Pulsed electromagnetic fields versus laser therapy on enhancing recovery of diabetic foot ulcer- A single blind randomized controlled trial. Biomedical Research 2017;28.
  9. Salvi M, Rimini D, Molinari F, Bestente G, Bruno A. Effect of low-level light therapy on diabetic foot ulcers: a near-infrared spectroscopy study. J Biomed Opt 2017;22:38001.
  10. Carvalho AF, Feitosa MC, Coelho NP, Rebelo VC, Castro JG, Sousa PR, et al. Low-level laser therapy and Calendula officinalis in repairing diabetic foot ulcers. Rev Esc Enferm USP 2016;50:628-634.
  11. Feitosa MC, Carvalho AF, Feitosa VC, Coelho IM, Oliveira RA, Arisawa EA. Effects of the Low-Level Laser Therapy (LLLT) in the process of healing diabetic foot ulcers. Acta Cir Bras 2015;30:852-7.
  12. Taradaj J, Halski T, Kucharzewski M, Urbanek T, Halska U, Kucio C. Effect of Laser Irradiation at Different Wavelengths (940, 808, and 658 nm) on Pressure Ulcer Healing: Results from a Clinical Study. Evid Based Complement Alternat Med 2013;2013:960240.
  13. Shojaei H, Sokhangoei Y, Soroush M. Low level laser therapy in the treatment of pressure ulcers in spinal cord handicapped veterans living in Tehran. 2008;33:44-48.
  14. Taly AB, Sivaraman Nair KP, Murali T, John A. Efficacy of multiwavelength light therapy in the treatment of pressure ulcers in subjects with disorders of the spinal cord: A randomized double-blind controlled trial. Arch Phys Med Rehabil 2004;85:1657-61.
  15. Lucas C, van Gemert MJ, de Haan RJ. Efficacy of low-level laser therapy in the management of stage III decubitus ulcers: a prospective, observer-blinded multicentre randomised clinical trial. Lasers Med Sci 2003;18:72-7.
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Published: Report no: ut202125 Registration no: SBU 2021/300
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Literature search

CINAHL via EBSCO 2021-09-13

Photobiomodulation with low-level laser (LLLT) in the treatment of wounds
The final search result, usually found at the end of the documentation, forms the list of abstracts.

AB = Abstract; AU = Author; DE = Term from the thesaurus; MH = Exact Subject Heading from CINAHL Subject Headings; MM = Major Concept; TI = Title; TX = All Text. Performs a keyword search of all the database's searchable fields; ZC = Methodology Index; * = Truncation; “ “ = Citation Marks; searches for an exact phrase; N = Near Operator (N) finds the words if they are a maximum of x words apart from one another, regardless of the order in which they appear.; W = Within Operator (W) finds the words if they are within x words of one another, in the order in which you entered them.
  Search terms Items found
Population:
1. Exp ”Wound healing” OR ((TI "Wound heal*" OR AB "Wound heal*") OR (TI "wound care" OR AB "wound care") OR (TI "tissue repair" OR AB "tissue repair") OR (TI “tissue regeneration” OR AB “tissue regeneration”) 22 712
2. Exp ”diabetic foot” OR exp ”foot ulcer” OR (((TI foot OR AB foot) N2 (TI ulcer* OR AB ulcer*)) OR (TI "diabetic foot" OR AB "diabetic foot") OR (TI "diabetic feet" OR AB "diabetic feet")) 7 282
3. Exp ”Pressure Ulcer” OR  ((TI "pressure ulcer" OR AB "pressure ulcer") OR (TI "pressure ulcers" OR AB "pressure ulcers") OR (TI bedsore* OR AB bedsore*) OR (TI "bed sore" OR AB "bed sore") OR (TI "bed sores" OR AB "bed sores") OR (TI "pressure sore" OR AB "pressure sore") OR (TI "pressure sores" OR AB "pressure sores") OR (TI decubitus OR AB decubitus)) 11 756
4. Exp ”burns” OR ((TI burn* OR AB burn*) OR ((TI therm* OR AB therm*) N2 ((TI wound* OR AB wound*) OR (TI ulcer OR AB ulcer)))) 37 808
5. Exp ”leg ulcer" OR ((TI "leg ulcer" OR AB "leg ulcer") OR (TI "lower extremity ulcer" OR AB "lower extremity ulcer") OR (TI "vascular ulcer" OR AB "vascular ulcer") OR (TI "venous ulcer" OR AB "venous ulcer") OR (TI "arterial ulcer" OR AB "arterial ulcer") OR (TI "lower extremity arterial ulcer" OR AB "lower extremity arterial ulcer") OR (TI "arterial insufficiency ulcer" OR AB "arterial insufficiency ulcer") OR (TI "atrophie blanche" OR AB "atrophie blanche")) 1 807
6. OR 1-4 76 866
Intervention:
7. Exp ”Low-Level Light Therapy” OR (((TI low-level OR AB low-level) OR (TI low-power OR AB low-power) OR (TI lowlevel OR AB lowlevel) OR (TI Low-reactive OR AB Low-reactive) OR (TI low-energy OR AB low-energy) OR (TI low-intensity OR AB low-intensity)) N3 ((TI Laser OR AB Laser) OR (TI light OR AB light))) 1 814
8. ((TI Photobiomodulation* OR AB Photobiomodulation*) OR (TI photo-biomodulation OR AB photo-biomodulation) OR (TI biostimulation OR AB biostimulation) OR (TI photo-biotherap* OR AB photo-biotherap*)) 619
9. ((TI LLLT OR AB LLLT) OR (TI LPLT OR AB LPLT) OR (TI LILT OR AB LILT) OR (TI MIRE OR AB MIRE) OR (TI PBM OR AB PBM)) 1 390
10. ((TI "soft-laser therap*" OR AB "soft-laser therap*") OR (TI "cold laser therap*" OR AB "cold laser therap*") OR (((TI monochromatic OR AB monochromatic) OR (TI red OR AB red) OR (TI infrared OR AB infrared) OR (TI infra-red OR AB infra-red)) N2 ((TI laser OR AB laser) OR (TI therap* OR AB therap*) OR (TI light OR AB light)))) 1 408
11. ((TI "Laser therap*" OR AB "Laser therap*") OR (TI "laser treatment*" OR AB "laser treatment*") OR (TI "therapeutic laser" OR AB "therapeutic laser")) 4 172
12. OR 6-10 6 759
Study types:
13. Exp ”Systematic review” OR exp ”meta-analysis” OR (((TI Systematic* OR AB Systematic*) N3 (TI review* OR AB review*)) OR (TI Meta-analysis OR AB Meta-analysis)) 156 234
Final 5 AND 11 AND 12 40

Embase via embase.com 2021-09-13

Photobiomodulation with low-level laser (LLLT) in the treatment of wounds
The final search result, usually found at the end of the documentation, forms the list of abstracts.

/de = Term from the EMTREE controlled vocabulary; /exp = Includes terms found below this term in the EMTREE hierarchy; /mj = Major Topic; :ab = Abstract; :au = Author; :ti = Article Title; :ti,ab = Title or abstract; * = Truncation; ' ' = Citation Marks; searches for an exact phrase; NEAR/n = Requests terms that are within 'n' words of each other in either direction; NEXT/n = Requests terms that are within 'n' words of each other in the order specified
  Search terms Items found
Population:
1. 'Wound healing’/exp OR ('Wound heal*' OR 'wound care’ OR 'tissue repair’ OR “tissue regeneration”):ti,ab 240 495
2. 'diabetic foot'/exp OR 'foot ulcer'/exp OR ((foot NEAR/2 ulcer*) OR 'diabetic foot’ OR 'diabetic feet’):ti,ab 23 512
3. 'decubitus'/exp OR (‘pressure ulcer’ OR ‘pressure ulcers’ OR bedsore* OR 'bed sore' OR ‘bed sores’ OR 'pressure sore’ OR ‘pressure sores’ OR decubitus):ti,ab 30 723
4. 'burn'/exp OR (burn* OR (therm* NEAR/2 (wound* OR ulcer))):ti,ab 167 873
5. 'leg ulcer'/exp OR (‘leg ulcer’ OR 'lower extremity ulcer’ OR ‘vascular ulcer’ OR ‘venous ulcer’ OR ‘arterial ulcer’ OR 'lower extremity arterial ulcer’ OR ‘arterial insufficiency ulcer’ OR ‘atrophie blanche’):ti,ab 17 406
6. OR 1.5 450 865
Intervention:
7. 'laser therapy'/exp OR ((low-level OR low-power OR lowlevel OR Low-reactive OR low-energy OR low-intensity) NEAR/3 (Laser OR light)):ti,ab,kw 31 168
8. (Photobiomodulation* OR “photo-biomodulation” OR biostimulation OR “photo-biotherap*”):ti,ab,kw 3 646
9. (LLLT OR LPLT OR LILT OR MIRE OR PBM):ti,ab,kw 7 247
10. (“soft-laser therap*” OR “cold laser therap*” OR ((monochromatic OR red OR infrared OR “infra-red”) NEAR/2 (laser OR therap* OR light))):ti,ab,kw 21 704
11. (“Laser therap*” OR “laser treatment*” OR “therapeutic laser”):ti,ab,kw 26 072
12. OR 7-11 68 950
Study types:
13. ‘Systematic review’/exp OR ‘meta-analysis’/exp OR ((Systematic* NEAR/3 review*) OR ‘Meta-analysis’):ti,ab,kw 528 942
Final 6 AND 12 AND 13 238

Medline via Ovid 2021-09-13

Photobiomodulation with low-level laser (LLLT) in the treatment of wounds
The final search result, usually found at the end of the documentation, forms the list of abstracts.

.ab. = Abstract; .ab,ti. = Abstract or title; .af. = All fields; Exp = Term from the Medline controlled vocabulary, including terms found below this term in the MeSH hierarchy; .sh. = Term from the Medline controlled vocabulary; .ti. = Title; / = Term from the Medline controlled vocabulary, but does not include terms found below this term in the MeSH hierarchy; * = Focus (if found in front of a MeSH-term); * or $ = Truncation (if found at the end of a free text term); .mp = Text, heading word, subject area node, title; “ “ = Citation Marks; searches for an exact phrase; ADJn = Positional operator that lets you retrieve records that contain your terms (in any order) within a specified number (n) of words of each other
  Search terms Items found
Population:
1. Exp ”Wound healing” OR (”Wound heal*” OR ”wound care” OR ”tissue repair” OR “tissue regeneration”).ti,ab 201 680
2. Exp ”diabetic foot” OR exp ”foot ulcer” OR ((foot ADJ2 ulcer*) OR ”diabetic foot” OR ”diabetic feet”).ti,ab 15 195
3. Exp ”Pressure Ulcer” OR (”pressure ulcer” OR ”pressure ulcers” OR bedsore* OR ”bed sore” OR ”bed sores” OR ”pressure sore” OR ”pressure sores” OR decubitus).ti,ab 20 374
4. Exp ”burns” OR (burn* OR (therm* ADJ2 (wound* OR ulcer))).ti,ab 124 728
5. Exp ”leg ulcer” OR (”leg ulcer” OR ”lower extremity ulcer” OR ”vascular ulcer” OR ”venous ulcer” OR ”arterial ulcer” OR ”lower extremity arterial ulcer” OR ”arterial insufficiency ulcer” OR ”atrophie blanche”).ti,ab 24 400
6. OR 1-5 352 933
Intervention:
7. Exp ”Low-Level Light Therapy” OR ((low-level OR low-power OR lowlevel OR Low-reactive OR low-energy OR low-intensity) ADJ3 (Laser OR light)).ti,ab,kw 10538
8. (Photobiomodulation* OR “photo-biomodulation” OR biostimulation OR “photo-biotherap*”).ti,ab,kw 2930
9. (LLLT OR LPLT OR LILT OR MIRE OR PBM).ti,ab,kw 5 176
10. (“soft-laser therap*” OR “cold laser therap*” OR ((monochromatic OR red OR infrared OR “infra-red”) ADJ2 (laser OR therap* OR light))).ti,ab,kw 21 388
11. (“Laser therap*” OR “laser treatment*” OR “therapeutic laser”).ti,ab,kw 19 002
12. OR 7-11 49 361
Study types:
13. Exp ”Systematic review” OR exp ”meta-analysis” OR ((Systematic* ADJ3 review*) OR ”Meta-analysis”).ti,ab,kw 357 127
Final 6 AND 12 AND 13 132
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