The SA Journal Diabetes & Vascular Disease Vol 14 No 1 (July 2017)

VOLUME 14 NUMBER 1 • JULY 2017

SA JOURNAL OF DIABETES & VASCULAR DISEASE

REVIEW

of endothelial cells and fibroblasts, accelerating the development

of granulation tissue over which epidermal cells migrate and so

enhance wound healing.

Despite the fact that LLLT is not an established treatment

modality for ulceration in South Africa, a number of studies, case

reports and clinical trials with humans have shown good ulcer

healing outcomes using LLLT. Beckmann and colleagues conducted

a systemic review in 2014 of the relevant literature on LLLT for the

treatment of DFUs and found that several clinical studies had been

published between 1998 and 2011, suggesting that LLLT promotes

wound healing of diabetic ulceration.

A summary of these clinical

trials is presented in Table 2.

such as methicillin-resistant

Staphylococcus aureus

(MRSA),

Propionibacterium acne

and

Pseudomonas aeruginosa

Enwemeka

et al.

found that blue light (470 nm) was able to kill MRSA

in vitro

Lipovsky

et al

. suggested that high-intensity visible light in the

range of 400–1 000 nm is bactericidal to

S aureus

P aeruginosa

and

Escherichia coli

, to name a few.

Irradiation at a wavelength of

408nm was proposed by Ankri and colleagues in treating infected

wounds to clear an infection, followed by irradiation at 730nm to

speed up the healing process.

According to the literature, red as well as blue light lasers improve

perfusion by releasing nitric oxide (NO) from nitrosyl complexes

with haemoglobin, enhanced epithelialisation and elevated

keratin-10 mRNA levels.

It has been discovered that the activity

of cytochrome c oxidase is inhibited by NO and this was initially

seen as an imperfection.

However blue light also facilitates the

recovery of mitochondria inhibited by NO gas by releasing NO from

the mitochondrial complexes. Therefore improved wound healing

via the NO pathway induces endothelial cell migration by activating

growth factors, resulting in an increase in keratin expression.

This

shows that a combination of red and blue light lasers can be used

to treat infection to promote and enhance the healing process of

infected DFUs, since infection plays a role in delaying the wound

healing process.

Table 2.

Clinical trials on lower-limb ulcer treatment with LLT in diabetic ulcers

Study

Study design

Participants

Intervention

Outcome

Kazemi-Khoo

(2006)

Prospective

cohort study

7 type 2 diabetes

patients with grades

2 and 3 diabetic foot

ulcers

Red light (660 nm; power: 25 MW; 0.6–1 J/cm

)

and ulcer margins with infra-red laser (980

nm; power: 200 MW; 4–6 J/cm

) along with

intravenous laser irradiation with red light laser

(650 nm; power: 1.5 MW) for 15–20 min, in

addition to laser acupuncture with infrared laser

(1 J/cm

). Sessions were every other day for 10–15

sessions (route 1) and then continuing the course

twice weekly (route 2) until complete recovery

was achieved

Complete recovery was achieved in

all cases and there was no relapse

after an average of about 19

sessions. Only 1 case took a total of

26 sessions (route 1).

Minatel

et al

(2009)

Randomised,

placebo-controlled,

double-blinded

trial

14 patients with 23

chronic diabetic ulcers

LLLT: 660nm and 890nm, 3J/cm

, 30sec/5cm

twice a week for 90 days/until healed

LLLT group had more granulation

(day 30: 56%) and faster healing

(day 30: 79.2%), 58.3% healed fully

(1 ulcer placebo group); 75% ulcer

healed 90–100% day 90 (1 ulcer

placebo group)

Mokmeli

et al.

(2010)

Prospective

cohort study

74 DFUs

LLLT: 650 nm and 860-nm laser, with total

energy density of 3.6 J/cm² plus intravenous laser

therapy (IVL) with 2.5-MW, 650-nm laser used for

30 minutes

Excluding the wounds that were

found to be in stage 5, more than

80% of each categorised stage

were found to have been almost

completely healed (by more than

50%) within a 2-month period

Kajagar

et al.

(2012)

Randomised

controlled trial

patients

with

chronic DFUs (grade 1)

Daily treatment for 15 days, 2–4-J/cm

power,

60-mW frequency, 5kHz

Significant reduction of percentage

of ulcer area in the LLLT group

Key message:

Phototherapy can enhance wound healing of

DFUs, since it exhibits bactericidal effects as well as stimulating

cellular repair and growth.

Conclusion

Diabetic foot ulceration still proves to be a difficult condition to

manage and generally has a negative impact on the patient’s

Key message:

Once acute inflammation has been induced in

DFUs by mechanical or sharp debridement, the healing process

can be further promoted by LLLT, which stimulates cellular

proliferation and wound healing.

Phototherapy, bactericidal effects and cellular repair enhance

wound healing

Various wavelengths are used for different applications in

phototherapy as they have different depths of penetration into

human tissue. Visible red, infra-red and near infra-red have

been demonstrated to penetrate deep tissue and are absorbed

by cytochrome c oxidase, compared to violet and blue spectrum

lasers.

39,43

When blue laser light is absorbed by flavins (flavoproteins)

and porphyrins that lack transition metal coordinating, these

molecules have been shown to have bactericidal effects through the

production of reactive free radicals, which destroy bacteria.

35,37-39

A number of studies have found that, at different wavelengths,

blue light laser is bactericidal to different infectious organisms,