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Low Level Laser Therapy (LLLT) as an Effective

Therapeutic Modality for Delayed Wound Healing

Article  in  Annals of the New York Academy of Sciences · December 2005

DOI: 10.1196/annals.1352.040 · Source: PubMed

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Low Level Laser Therapy (LLLT) as an
Effective Therapeutic Modality for Delayed
Wound Healing
D. HAWKINS, N. HOURELD, AND H. ABRAHAMSE
Faculty of Health, University of Johannesburg, Johannesburg, 2028, South Africa

ABSTRACT: Low level laser therapy (LLLT) is a form of phototherapy that

involves the application of low power monochromatic and coherent light to
injuries and lesions. It has been used successfully to induce wound healing in
nonhealing defects.1 Other wounds treated with lasers include burns, amputa-
tion injuries, skin grafts, infected wounds, and trapping injuries.2 The unique
properties of lasers create an enormous potential for specific therapy of skin
diseases. As with any new device, the most efficacious and appropriate use
requires an understanding of the mechanisms of light interaction with tissue as
well as the properties of the laser itself.3

KEYWORDS: low level laser therapy (LLLT); wound healing; diabetes;

stimulation

INTRODUCTION

Low level laser therapy (LLLT) or more simply known as soft laser therapy, is a
dramatic therapy that has become progressively more popular in the management of
a wide variety of medical conditions, such as soft tissue injuries (including sports
injuries), low back pain, arthritis, and skin traumas.2 Unlike the higher powered
lasers employed in medicine, these low level lasers do not deliver enough power to
damage tissue, but they do deliver enough energy to stimulate a response from the
body tissues to initiate healing. Laser radiation has a wavelength-dependent capabil-
ity to alter cellular behavior in the absence of significant heating. Light radiation
must be absorbed to provide a biological response. The visible red and infrared por-
tions of the spectrum have been shown to have highly absorbent and unique thera-
peutic effects in living tissues.

BASIC PRINCIPLES OF LLLT

Low level laser therapy applications include: acceleration of wound healing,

enhanced remodeling and repair of bone, restoration of normal neural function

Address for correspondence: Heidi Abrahamse (PhD), Senior Research Fellow, University of
Johannesburg, P.O. Box 17011, Doornfontein, 2028, Gauteng, South Africa. Voice: +27 11 406-
8145; fax: +27 11 406-8202.
heidi@twr.ac.za

Ann. N.Y. Acad. Sci. 1056: 486–493 (2005). © 2005 New York Academy of Sciences.
doi: 10.1196/annals.1352.040

486
HAWKINS et al.: LOW LEVEL LASER THERAPY (LLLT) 487

following injury, pain attenuation, and modulation of the immune system.4 Laser
therapy increases both the rate and the quality of healing, and studies show that as
the healing rate increases, bacterial cultures decrease, suggesting a bioinhibitory ef-
fect upon wound infection.2 Nussbaum et al.5 analyzed the interactions between
wavelength and bacterial growth of Pseudomonas aeruginosa, Escherichia coli, and
Staphylococcus aureus and reported that irradiation with 1–20 J/cm2 at a wavelength
of 630 nm appeared to be commonly associated with bacterial growth inhibition,
which is of considerable importance for wound healing.5 Reports of LLLT applied to
soft tissues in vitro and in vivo suggest stimulation of specific metabolic processes
in healing wounds. Whereas low doses of LLLT are stimulatory, high doses of laser
radiation are suppressive.5
Low level laser therapy irradiation includes wavelengths of between 500 and
1100 nm and typically involves the delivery of 1–4 J/cm2 to treatment sites with
lasers having output powers between 10 and 90 mW. Low-intensity radiation can
inhibit as well as stimulate cellular activity as light irradiation appears to upregulate
cellular metabolism and proliferation. Visible red light has long been known to
promote healing in the body’s cells and tissues.6 Irradiating mitochondria with red
light causes them to produce cytochromes, which increases their efficiency, and re-
search has shown that fibroblasts and muscle cells grow five times faster when treat-
ed with red light. By decreasing the healing time of open wounds, laser therapy
significantly reduces the risk of infection and other complications. It also produces
a stronger repair with less unattractive scar tissue.
The effects of LLLT are photochemical, not thermal. To produce an effect, the
photons must be absorbed, and different substances absorb light of different wave-
lengths like the cells of injured skin are more sensitive than those of intact tissue.
Once the target cells have absorbed the photons, a cascade of biochemical events
occurs whose ultimate result is accelerated wound healing.8 Laser therapy is thought
to work through a variety of mechanisms:
(1) Photons from a laser probe are absorbed into the mitochondria and cell
membranes of the target cells.
(2) After a cell absorbs photons the energy is incorporated into the molecule to
increase chemical energy, activate or deactivate enzymes, or alter physical
or chemical properties of main macromolecules.9 Photonic energy is con-
verted to chemical energy within the cell, in the form of denosine triphos-
phate (ATP), which leads to normalization of cell function, pain relief, and
healing.
(3) Single oxygen molecules build up, which influences the formation of ATP,
which in turn leads to replication of DNA.
(4) Increased DNA leads to increased neurotransmission.
(5) A cascade of metabolic effects results in various physiological changes,
which results in improved tissue repair, faster resolution of the inflamma-
tory response, and reduction in pain.
Infra red laser light at approximately 632 nm appears to be the most effective and
stimulatory frequency of laser at a cellular level with a skin penetration depth of 0.5–
1 cm. A typical example of a laser used in LLLT is the helium-neon (He-Ne) laser,
which can penetrate as deep as 0.5 mm into freshly excised human skin, which is
regarded as sufficient for the induction of wound healing because most of the rele-
488 ANNALS NEW YORK ACADEMY OF SCIENCES

vant target cells of low level laser irradiation are located within the epidermis and
upper dermis.5 Studies have found that laser irradiation stimulates fibroblast growth
in vitro and also facilitates ulcer healing in the clinical situation.7
Karu8 found that infrared laser (620 nm) stimulated the bacterial cell growth rate,
DNA and RNA synthesis rates, enzyme activity, and cAMP levels. It is postulated
that the respiratory chain is stimulated, activating ATP turnover, increasing H+, and
ultimately triggering an increase in cell proliferation. The stimulating effects of light
appear to occur in “sluggish” cell cultures or during decreased activity such as
trophic ulcers and indolent wounds, when low tissue oxygen concentration and pH
inhibit cell growth. Conversely, where maximum regeneration is occurring naturally,
laser did not appear to enhance the process.8

LOW LEVEL LASER THERAPY FOR WOUND HEALING

LLLT, when used appropriately, can stimulate the healing of injured tissues such
as those of the dermis.9 Investigations into the mechanisms involved have shown that
many of the types of cells whose interaction results in dermal repair can be affected
in a therapeutically advantageous manner by treatment with LLLT both in vitro and
in vivo. Mast cells and macrophages can be stimulated to release growth factors and
other substances, whereas the proliferation of fibroblasts, endothelial cells, and
keratinocytes maintained in adverse conditions can also be stimulated. The develop-
ment of granulation tissue is mainly controlled by growth factors released from mac-
rophages.9
Wound healing involves the following phases:
• Hemostasis: platelets, endothelial cells, fibrin, and fibronectin act through
growth factors and cytokines.
• Inflammation: blood clots form, bacteria are attacked, and there is an orderly
recruitment of key cells into the wound site.
• Proliferation: cells necessary for wound closure multiply at the wound site to
make new tissue and blood vessels.
• Remodeling: the wound is healed and the initial scar tissue is restructured.

Any device that can accelerate any of these processes (transition from hematoma
to fibroplasias, development of new blood vessels, production of collagen, or even
the remodelling process) could accelerate the healing process of wounds.9 Early
laser studies were confined to in vitro studies because little was known about the side
effects of laser irradiation.10
Wound healing studies have focused on several types of cells including fibro-
blasts, lymphocytes, monocytes, macrophages, epithelial cells, and endothelial cells.
The wide diversity of experimental protocols and parameters such as cell line, dose,
waveform, treatment time, penetration distance, treatment area, and treatment
frequency make comparison of these studies difficult. Literature indicates that laser
photobioactivation accelerates inflammation, modulates the level of prostaglandin,
enhances the action of macrophages, promotes fibroblast proliferation, facilitates
collagen synthesis, fosters immunity, and even accelerates the healing process.9
Using the He-Ne laser, Van Breugel and Bar11 concluded that laser exposure time
HAWKINS et al.: LOW LEVEL LASER THERAPY (LLLT) 489

and power density determine the effect of the laser. Dependent on exposure time and
power density, the laser can either stimulate or inhibit human fibroblasts in vitro.11
In the clinical situation, LLLT is an accepted, efficient, noninvasive, and painless
method of treating edema, inflammation, and pain and it is used to increase circula-
tion and promote wound healing.12 Wound healing experiments show acceleration
of healing, but these findings are often concentrated in the early phases of the healing
process.12 The effects of LLLT on wound healing are often attributed to increased
cell proliferation. However, the true effect of LLLT on cell proliferation is still con-
troversial, because of conflicting reports on the effects of visible laser light on cells
in culture.
The magnitude of the laser biostimulation effect depends on the physiological
state of the cell at the moment of irradiation. This explains why the effect is not
always detectable as well as the variability of the results reported in the literature. In
medicine, laser treatment appears to work in cases of severe damage or stress
(wounding), whereas the effect of light on normally regenerating wounds may also
be insignificant. Karu8 stated that light stimulates cell proliferation if the cells are
growing poorly at the time of irradiation. Thus, if a cell is fully functional, there is
nothing for laser irradiation to stimulate, and therefore no therapeutic benefit will be
observed.8
LLLT may induce positive side effects that are common also after other stimula-
tion therapies (acupuncture). In patients with difficult or longstanding problems,
LLLT can be combined very usefully with other forms of therapy (physiotherapy,
acupuncture, and manipulation), relaxation therapy (self-hypnosis and meditation),
medication (pharmacological, herbal, or homeopathic), and psychiatric or psycho-
logical counseling.16 There are no absolute contraindications for LLLT; however, it
is always better to be cautious when treating patients in high-risk categories. LLLT
should be avoided or given with special caution in the following cases: patients with
pacemakers, patients who are pregnant, patients with cancer if there is any doubt of
a recurrence of metastases, and patients with labile epilepsy. It is better to avoid
LLLT over the thyroid gland, ovaries, and testicles. Although LLLT has not induced
cancer in any of the reported studies, the precise reactions of existing tumors to
LLLT are unknown.16 Pessoa et al.17 conducted a study to investigate the effect of
LLLT on the wound healing process treated with steroid and concluded that LLLT
accelerated healing, caused by the steroid, acting as a biostimulative coadjuvant
agent, balancing the undesirable effects of cortisone on the tissue healing process.17
Manuskiatti and Fitzpatrick18 conducted a study to compare the clinical response of
keloidal and hypertrophic scars after treatment with interlesional corticosteroid
alone or combined with 5-fluorouracil (5-FU), 5-FU alone, and the 585-nm pulsed-
dye laser (PDL). There was significant improvement in keloidal and hypertrophic
scars after treatment in which scar texture and erythema responded better to PDL and
the long-term adverse sequelae (hypopigmentation, telangiectasia, and skin atrophy)
were demonstrated in corticosteroid therapy but not in PDL.18

LOW LEVEL LASER THERAPY FOR DIABETES

LLLT effectively promotes wound healing without causing burn to adjacent

tissue. The operative principle, known as photobiomodulation, is particularly useful
490 ANNALS NEW YORK ACADEMY OF SCIENCES

in treating decubitus ulcers, typical of persons with diabetes and frail elderly patients
who spend long hours in bed. Some wounds, such as decubitus ulcers, heal slowly
or not at all in persons with diabetes or the frail elderly.13 Diabetes is a chronic
metabolic disorder in which utilization of carbohydrate is impaired and that of lipid
and protein enhanced. It is caused by an absolute or relative deficiency of insulin.
Long-term complications include neuropathy, retinopathy, generalized degenerative
changes in large and small blood vessels, and increased susceptibility to infection.
The consequences of leaving diabetes untreated are dialysis, heart failure, paralysis,
loss of limbs, and early death. Use of a low level laser can start the healing process.
Even if a wound such as a leg ulcer will not heal in all cases, pain relief is usually
immediate and is the most important benefit. Stimulation of the circulation may be
the primary reason that pain relief occurs after the application of LLLT to chronic
wounds.13 Laser treatment increases blood flow and raises local temperature, and no
evidence has been found that laser therapy could aggravate diabetic symptoms.
In general terms, in the treatment of a chronic ulcer, a higher dose such as 3–4 J/
cm2 will be used on points along the periphery of the wound followed by a lower
dose of 0.5 J/cm2 over the open wound. The open wound needs a lower dosage than
the skin-covered periphery as the laser light is not reflected or scattered but rather
absorbed by the skin in the unprotected wound because it hits the uncovered cells
directly.13 Laser therapy should be recommended as an additional treatment modal-
ity for diabetic foot problems according to Kleinman et al.14 However, not all results
have been positive, and some studies do not support or refute the use of laser therapy
as an effective therapeutic modality for diabetic ulcers (TABLE 1).
Diabetic patients have a 22-fold higher risk of nontraumatic foot amputation
compared with the nondiabetic population,15 and according to the World Health
Organization, the number of patients with diabetes mellitus will double to 250 mil-
lion by the year 2050. Attempts have been made to use helium neon, CO2, and KTP
lasers to encourage wound healing in diabetics. Results were inconclusive, so that
further research is needed to assess the effectiveness of biostimulation for diabetic
wound healing. Stadler et al.16 reported that low-power laser irradiation at 830 nm
significantly enhanced cutaneous wound tensile strength in a murine diabetic model,
whereas Schindl et al.6 reported a beneficial effect on a recalcitrant diabetic neuro-
pathic foot ulcer. Yu et al.17 used diabetic mice to compare the effect of basic fibro-
blast growth factor (bFGF), laser irradiation at 660 nm, and a combination of growth
factor and laser therapy. Wound closure was significantly enhanced with light ther-
apy alone or most effectively in combination with topical application of bFGF.17
LLLT is effective in enhancing wound contraction of partial-thickness abrasions. It
also facilitates wound contraction of untreated wounds, suggesting an indirect effect
on surrounding tissues; however, the exact mechanism by which LLLT facilitates
wound healing is largely unknown, and further investigation of the mechanism of
LLLT in primary wound healing is warranted.16

CONCLUSION

Early laser studies were confined to in vitro studies because little was known
about the side effects of laser irradiation.18 More studies have therefore been per-
formed in the area of wound healing than in any other. The majority of studies have
HAWKINS et al.: LOW LEVEL LASER THERAPY (LLLT) 491

TABLE 1. Studies of low level laser therapy (LLLT) on open diabetic wounds
Patient
Study characteristics Therapy Outcomes Comments
Shuttleworth et al.20 n
= 14; age, 76.3 yr Control group: Control group: all Results of this study
Prospective com- Control group: conventional patients showed neither support
parative study of n = 8; 1 diabetic wound care and improvement nor refute the use
laser and conven- patient dressings in of LLLT in
tional wound Laser group: n = 6; accordance with Laser group: 3 wound manage-
therapy (non- 2 diabetic local wound man- patients improved ment; further
randomized) patients (3 agement policy or healed and 3 studies should
patients received deteriorated incorporate a
both laser and Laser group: each larger sample
conventional laser therapy ses- size and actively
treatment) sion was a maxi- control or elimi-
Leg ulcers caused mum of 4 min nate variables
by a variety of using HeNe at such as size of
conditions 632.8 nm and wounds
Study period: 15 infrared laser at
wk/patient 904 nm. 4 J/cm2;
patients received
treatment and
dressings twice a
week
Landau et al.21 n = 50 (patients Hyperbaric oxygen All patients contin- Topical hyperbaric
Noncontrolled had chronic (HBO) ued medication, oxygen alone or
clinical series diabetic foot HBO group: 15 and antibiotic combined with a
ulcers and had patients treatment was low level energy
not responded HBO and laser administered laser for treat-
to conventional group: 35 according to the ment of patients
therapy) patients sensitivity of the with chronic dia-
Age: 59 yr (±11 yr) Unilaser Scan 60, micro-organism betic foot ulcers
Diabetes: two sources of were valuable
Type 1: n = 14 laser: HeNe at No significant dif- adjuvants to con-
Type 2: n = 35 632.8 nm and ference between ventional therapy
Ulcer duration: infrared laser at groups
9 ± 6.6 mo 904 nm 4 J/cm 2
Range: 2–70 mo Treatment HBO: 2–
5 h, laser 20 min,
2–3×/ wk
No of treatments: 25
± 13
Range: 7– 70
Duration: 3 ± 1.8
mo
Range: 1–8 mo
Gupta et al.22 n=9 Control group: Unhealed ulcers in Low level laser
Double-blind, (12 venous ulcers) placebo treatment control group: therapy was
placebo- Control group: received sham 87.6% effective modal-
controlled study Age, 64.7 (±9.4 yr) therapy from Decrease in ulcer ity for treatment
Ulcer duration: identical appear- area compared to of venous leg
36.0 ± 21.6 wk ing light sources, baseline: 14.7 ulcers
Intervention from same deliv- mm2
group: ery system Unhealed ulcers in No adverse effects
Age: 61.0 (±7.8 yr) Intervention intervention
Ulcer duration: group: 2 mono- group: 24.4%
105.8 ± 36.0 wk chromatic opti- Decrease in ulcer
cal sources: 1 area compared to
(red-light) source baseline: 193.0
660 nm used over mm2
ulcer for 180 s; 1
(infra-red) source
990 nm used on
periphery for
ulcer for 30 s;
treatments were
3/wk for 10 wk
492 ANNALS NEW YORK ACADEMY OF SCIENCES

shown beneficial effects, and most of the work has been performed using the helium
neon (He-Ne) 632.8 nm laser.10 Research studies on the effects of low energy laser
irradiation on biologic function are growing in number and scope. Although many
experiments show alleviation of pain, the quality of the investigations, the number
of subjects, and the varied techniques frequently preclude statistical verification.
Currently, no universally accepted theory has explained the mechanism of either
“laser analgesia” or “laser biostimulation.” Modification of current lasers and inno-
vative advances with biomedical laser instrumentation may eventually allow the
physician to match optimally the laser and the treatment procedure with the lesion.3
Low level laser therapy is still very controversial, and there are still studies that
present conflicting results. However, as knowledge and techniques improve, a scien-
tific explanation may provide an understanding of the cellular and molecular effects
of LLLT.19

REFERENCES

1. YUJI, Y. & Y. KUNIHIKO. 2001. Cutaneous wound healing: an update. J. Dermatol. 28:
521–534.
2. NELSON, J.S. 1993. Lasers: state of the art in dermatology. Dermatol. Clin. 11: 15-26.
3. WALSH, L.J. 1997. The current status of low level laser therapy in dentistry. Part 1. Soft
tissue applications. Aus. Dent. J. 42: 247–254.
4. CABRERO, M.V., J.M.G. FAILDE & O.M. MAYORDOMO. 1985. Laser therapy as a regen-
erator for healing wound tisues. Int. Congr. Laser Med. Surg. June 27-28, 187–192.
5. NUSSBAUM, E.L., L. LILGE & T. MAZZULLI. 2002. Effects of 630-, 660-, 810-, and 905-
nm laser irradiation delivering radiant exposure of 1-50 J/cm2 on three species of
bacteria in vitro. J. Clin. Laser Med. Surg. 20: 325–333.
6. SCHINDL, A., M. SCHINDL, H. PERNERSTORFER-SCHON & L. SCHINDL. 2000. Low inten-
sity laser therapy: a review. J. Invest. Med. 48: 312–326.
7. SCHINDL A., M. SCHINDL, H. PERNERSTORFER-SCHON, et al. 1999. Diabetic neuropathic
foot ulcer: successful treatment by low intensity laser therapy. Dermatology 198:
314–317.
8. NELSON, J.S. 1993. Lasers: state of the art in dermatology. Dermatol Clin. 11: 15-26.
9. MATIC, M. et al. 2003. Low level laser irradiation and its effect on repair processes in
the skin. Med. Pregl. 56: 137–141.
10. BOSATRA, M., A. JUCCI & P. OLLIANO. 1984. In vitro fibroblast and dermis fibroblast
activation by laser irradiation at low energy. Dermatologica 168: 157–162.
11. KARU, T. 1989. Photobiological fundamentals of low power laser therapy. Journal of
Quant. Electr. 23: 1703–1717.
12. DYSON, M. 1991. Cellular and sub-cellular aspects of low level laser therapy (LLLT).
In Progress in Laser Therapy: Selected papers from the October 1990 ILTA Con-
gress. :221,222. Wiley & Sons, Inc. New York and Brisbane.
13. ENWEMEKA, C.S. 1988. Laser biostimulation of healing wounds: specific effects and
mechanisms of action. J. Orthopaed. Sports Physiother. 9: 333–338.
14. VAN BREUGEL, H.H. & P.R. BAR. 1992. Power density and exposure time of he-Ne laser
irradiation are more important than total energy dose in photo-biomodulation of
human fibroblasts in vitro. Lasers Surg. Med. 12: 528–537.
15. BASFORD, J.R. 1995. Low intensity laser therapy: still not an established clinical tool.
Lasers Surg. Med. 16: 331–342.
16. PONTINEN, P.J. 1992. Guidelines for LLLT. Low Level Laser Therapy as a Medical
Treatment Modality: A Manual for Physicians, Dentists, Physiotherapists and Veteri-
nary Surgeons. P.J. Pontinen, Ed. :148. Art Urpo Ltd. Tampere, Finland.
17. PESSOA, E.S et el. 2004. A histologic assessment of the influence of low intensity laser
therapy on wound healing in steroid treated animals. Photomed. Laser Surg. 22: 199–
204.
 HAWKINS et al.: LOW LEVEL LASER THERAPY (LLLT) 493

18. MANUSKIATTI, W. & R.E. FITZPATRICK. 2002. Treatment response of keloidal and
hypertrophic sternotomy scars: comparison among intralesional corticosteroid, 5–
fluorouracil, and 585nm flashlamp pumped pulsed dye laser treatments. Arch. Der-
matol. 138: 1149–1155.
19. TUNER, J. & L. HODE. 2002. Laser Therapy: Clinical Practice and Scientific Back-
ground. Prima Books AD. Grangesberg, Sweden. ISBN 91-631-1344-9.
20. KLEINMAN, K., S. SIMMER & Y. BRAKSMA. 1996. Low power laser therapy in patients
with diabetic foot ulcers: early and long term outcome. Laser Ther. 8: 205–208.
21. KARU, T.I. 1988. Molecular mechanisms of the therapeutic effects of low intensity
laser radiation. Lasers Life Sci. 2: 53–74.
22. STADLER, I., R.J. LANZAFAME, R. EVANS, et al. 2001. 830-nm irradiation increases the
wound tensile strength in a diabetic murine model. Lasers Surg. Med. 28: 220-226.
23. YU, W., J.O. NAIM & R.J. LANZAFAME. 1997. Effects of photostimulation on wound
healing in diabetic mice. Laser Surg. Med. 20: 56–63.
24. ENWEMEKA, C.S. 1988. Laser biostimulation of healing wounds: specific effects and
mechanisms of action. J. Orthopaed. Sports Physiother. 9: 333–338.
25. PINHEIRO, A.L.B., S.C. NASCIMENTO, A.L. VIEIRA, et al. 2002. Effects of Low level
laser therapy on malignant cells: in vitro study. J. Clin. Laser Med. Surg. 20: 23–26.
26. SHUTTLEWORTH, E. & K. BANFIELD. 1997. Wound care. light relief, low-power laser
therapy. Nursing Times 93: 74–78.
27. LANDAU, Z. 1998. Topical hyperbaric oxygen and low energy laser for the treatment of
diabetic foot ulcers. Arch. Orthopaed. Trauma Surg. 117: 156–158.
28. GUPTA, A.K., N. FILONENKO & N. SALANSKY. 1998. The use of low energy photon ther-
apy (LEPT) in venous leg ulcers: a double-blind, placebo-controlled study. Derm.
Surg. 24: 1383–1386.

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