Low Intensity Laser Therapy Science and Clinical Applications Slava Kim, MD Clinic Director Meditech International Inc. 415 Horner Avenue, Toronto, Ontario.

Low Intensity Laser Therapy

Science and Clinical ApplicationsSlava Kim, MD

Clinic Director

Meditech International Inc.415 Horner Avenue, Toronto, Ontario M8W 4W3

Tel: (416) 251-1005Toll Free: (888) 557-4004

[email protected]

Copyright © 2008 Meditech International Incorporated. ALL RIGHTS RESERVED.

Lasers – What comes to mind?

Sun Gods

Belenus Celtic Sun God

Ra Egyptian Sun God

Temple of ApolloGreek Sun God

Healing with light is a common concept in many cultures

Light as a healing force

Heliotherapy – Sunlight Therapy

Samuel and Nettie Bowne Hospital Poughkeepsie, New York.

Circa 1935

University of Virginia Medical CenterCharlotteville, Virginia

Circa 1929

Absence of Light on Human Body - SAD

Seasonal Affective Disorder (SAD)

– Bright Light Phototherapy has been shown to effectively treat seasonal affective disorder (SAD).

– Non thermal and does not require specialized cells

Endre Mester - The Father of Laser Therapy

May 29, 1966• Endre Mester working at

Semmelweiss hospital in Budapest, Hungary publishes the first paper on the stimulatory effects of ruby laser light on the skin of rats

Biological Photoacceptor Molecules

Plants– Chlorophyll– Carotenoids

Humans– Rhodopsin (vision)– Hemoglobin (blood)– Myoglobin (muscle)– Cytochrome (all cells)

The Electromagnetic Spectrum

Decrease in wavelength = Increase in energy in a smaller area

Damage with Electromagnetic Radiation

Two ways to cause damage1. Ionizing radiation

• Able to break bonds (i.e. DNA causing mutations)

2. Intensity• Thermal heating of tissue (i.e. microwave

heating food)

Wavelengths in the BioFlex Systems

• Red light at 660nm• Infrared light at 840nm and 830nm

Cytochrome C Oxidase Absorption

M. Cope thesis data modified by M. Patterson

Red light at 660nm and Infrared light at 830/840nm

Published Absorption Spectra

Desmet et. al., Photomed. Laser Surg. 24(2):121-128, 2006

Red light at 660nm and Infrared light at 830/840nm

Published Action Spectra

Karu and Afanasyeva, DAN 392(5):693, 1995

Red light at 660nm and Infrared light at 830/840nm

Wavelength, nm

620 nm

820 nm

760 nm

CuA redCuB red

oxid

oxid

CuA

CuB680 nm

0.0000

0.0500

0.1000

0.1500

0.2000

450 550 650 750 850 950 1050

Wavelength (nm)

Ab

sorp

tion

Co

eff

ieci

en

t

0.0000

0.0005

0.0010

0.0015

0.0020

0.0025

0.0030

0.0035

0.0040

0.0045

0.0050

Water

Deoxyhemoglobin

Oxyhemoglobin

Cytochrome Coxidized

Cytochrome Creduced

Biological Treatment Window

M. Cope thesis data modified by M. Patterson

Treatment Window

Laser Therapy Dosage - Arndt-Shultz Law

Phys

iolo

gica

l Act

ivity

Strength of Stimuli

A B

C

D

A. No light gives no effect

B. Small amount of light also has no effect

C. Maximal effect at the apex of the curve

D. Inhibitory amount of light inhibits healing

Control

Energy Production - Components

NADH Dehydrogenase

ATP Synthase

Cytochrome bc1 Complex

Cytochrome c Oxidase

Electron Transport Chain

H+ H+H+

H+H+

H+

ADP ATP

Effect of Red and Infrared Light

H+ H+ H+ H+ H+ H+

H+

H+

H+

ADP ATP

Put title of slide hereLaser Therapy

EffectsPrimary

– The light is absorbed by cytochrome c oxidase

Secondary– Release of NO into

endothelium of blood vessels

– Small increases in free radicals

– Increased proton gradient in mitochondria

Clinical – Wound Healing,

Acceleration of the Inflammatory Process and Pain Influence

Published Effects of Light on Cells

• Increased ATP production

• Circulation– Relaxation of smooth

muscles surrounding blood vessels

– Angiogenesis

• Increased production of:– Fibroblasts – Macrophage– Collagen

• Altered nerve conduction

• Increased metabolism of:– Endorphins– Acetylcholine– Serotonin

• Increased synthesis of:– DNA– Proteins

• Stimulation of immune response

Advantages of Laser Therapy

• Non-toxic

• Non allergic

• Non invasive

• Ease of application

• No side effects

• No complications

• Completely safe

• Cost effective

• Superior alternative to:– analgesics– NSAID’s– other medications

•Surgery may not be required

Conditions Treated I

• Acute injuries/trauma– muscle

tears/hematoma– tendon tears– ligament

strain/sprains– fractures– subluxations– sport injuries

• Musculoskeletal– repetitive stress

injuries– rotator cuff tears– carpal tunnel

syndrome– reflex sympathetic

dystrophy– fibromyalgia– tempero-mandibular

joint pathologies

Conditions Treated II

• Inflammatory conditions

– tendonitis– bursitis– myositis– fasciitis– synovitis– rheumatoid

arthritisAutoimmune disease

• Degenerative disorders– osteoarthritis– discogenic and

vertebrogenic radiculopathies

– calcifications• e.g. bone spurs

– chondromalacia patella

Conditions Treated III

• Other areas– dermatological– plastic surgery – dental (e.g.

gingivitis)– gynecological

• cervical pathologies

– Podiatry• plantar fasciitis• biomechanical

problems

• Wound management– ulcers

• venous stasis• diabetic• contact• atherosclerotic

• Veterinary– equine– companion animals

Pain Mechanisms

Reduced PGE Levels (5)

Reduced TNF Levels (2)

Reduced IL1Levels (3)

Reduced COX-2

expression (2)

Reduced Plasminogen activator Levels (3)

Reduced Edema

formation (7)

ReducedHemorrhagic formation (2)

ReducedNeutrophil

cell influx (4)

Reduced Cell apoptosis

(3)

ImprovedMicrocirculatio

n(4)

Pathways for pain relief by Red or Infrared laser therapy

Local photoradiation effects occurring in less than 24 hrs

Effects on biochemical inflammatory pathway

Effects on cells and soft tissue

Inflammation

Acute PhasePlasma derived mediators- Bradykinin - complement (C3, C5a, MAC) - coagulation (Factor XII, Plasmin, Thrombin)

Cell derived mediatorsPreformed: Lysosome granules - vasoactive amines (Histamine,

Serotonin)Synthesized on demand:

- cytokines (IFN-γ, IL-8, TNF-α, IL-1) - eicosanoids (Leukotriene B4, Prostaglandins) - Nitric oxide - Kinins

Chronic PhaseMacrophage - Epithelioid cell

- Giant cell - Granuloma

Key Effects that Apply to Diabetes

• ATP production and Membrane permeability > Accelerated Metabolism

Secondary Effects Clinical Effects• Nitric Oxide Stimulation > Angiogenesis• Endothelial Growth Factor > Angiogenesis• Endorphin Release > Pain Reduction• Elevated Immune Response > Wound Healing• Increased Cell Metabolism > Acc. Inflammation Resp.

e.g. Fibroblast activity > Increased collagen production

Primary Effects

Evaluation of the degree of effectiveness of low level light therapy on the treatment of

skin ulcers and delayed postoperative wound healing.

Iusim M, Kimchy J, Pillar T, Mendes DG. Center for Implant Surgery, Flieman Geriatric Rehabilitation Hospital,

Technion, Haifa, Israel.Orthopedics. 1992 Sep;15(9):1023-6.

Twenty-one patients with 31 postoperative delayed open wounds resistant to conventional therapy were randomly allocated to three groups.

Group 1 was treated with red low level narrow band (LLNB) light (660 nm);

Group 2 was treated with infrared LLNB light (940 nm); Group 3 was treated with a placebo such as the Biobeam machine (no

light irradiation).

Group 1 showed a significant improvement compared to groups 2 and 3 (t-test).

Systemic effects of low-intensity laser irradiation on skin microcirculation in patients with diabetic microangiopathy.

Low-intensity laser irradiation has been shown to induce wound healing in conditions of reduced microcirculation. We demonstrate low-intensity laser irradiation on skin blood circulation in patients with diabetic microangiopathy.

Patients are randomized; A) single helium-neon (HeNe, 632.8 nm) low-intensity laser irradiation with a dose of 30 J/cm(2) or B) sham irradiation over the forefoot region in a double-blind, placebo-controlled clinical study.

Skin blood circulation by means of temperature recordings over forefoot regions was detected by infrared thermography.

A single dose of low-intensity laser irradiation = a rise in skin temperature.

The placebo group = a drop in skin temperature occurred.

Our data show a significant increase in skin circulation due to athermic laser irradiation in patients with diabetic microangiopathy and point to the possibility of inducing systemic effects.

Healing of Bone Affections and Gangrene with Low Intensity Laser Irradiation in Diabetic Patients Suffering from Foot Infections.

Schindl M, Schindl A, Polzleitner D, Schindl L. Forsch Komplementarmed. 1998;5(5):244-247. 

OBJECTIVE: Evaluation of low-intensity laser irradiation on the healing of bone affections and gangrene in patients suffering from diabetic microangiopathy.

PATIENTS: Two consecutive diabetic male patients with gangrene, Osteomielitis, and bone fractures.

INTERVENTION: Helium-neon laser irradiation (36 J/cm2 ) 50 min/day. MAIN OUTCOME PARAMETER: Healing of gangrene and corticalis lesion as

well as remineralisation of bone affections. RESULTS: Within a mean period of 14 weeks not only a complete healing of

the diabetic gangrenes but also a radiographically determined reestablishment of corticalis and remineralisation of preexisting bone affections could be achieved.

CONCLUSION: low-intensity laser irradiation should be further tested as an additional beneficial therapeutic modality for the healing of gangrene and bone affections in diabetic patients.

Diabetes Mellitus: infected dermal ulcers

Initial:Diabetic with 3 week old ulcer, previously surgically debrided. The ulcer was deep, painful and prior to treatment, resistant to surgical and antibiotic therapy.

Interim progressHealing progressing

Final photo:Total healing achievedPatient, asymptomatic and discharged

10 treatments over 3 weeks

Diabetes Mellitus: Gangrenous Leg Dermal Ulcers

After 6 1 hour treatmentsInitial

Diabetes Mellitus: Initial

Final, after 35 treatments

Diabetes Mellitus: Amputated III toe

Diabetes MellitusPre-Gangrenous Right Foot

Initial

Intermediate

Intermediate

Final

Hemochromatosis Dermal Ulcers – 2 Years

Initial

After 1 Treatment

After 5 Treatments

After 23 Treatments

After 36 Treatments

Final

1-Year Follow-up

Study: Achilles Tendons

Laser photostimulation of collagen production in healing rabbit Achilles tendons. Reddy GK, Stehno-Bittel L, Enwemeka CS.

Following tenotomy and repair, the surgical hind limbs of the rabbits were immobilized in customized polyurethane casts. The experimental animals were treated with a 632.8 nm HeNe laser daily at 1.0 J cm(-2) for 14 days.

Results: Biochemical analyses of the tendons revealed a 26% increase in collagen concentration with laser photostimulation indicating a more rapid healing process in treated tendons compared to controls.

Page 18

Left Achilles Tendonitis

Initial 1 Month after final treatment

100% function,asymptomatic

Tenderness, Edema

and partial loss of flexion

10 treatments over 2 months

Inflammation – Achilles Tendonitis

• LLLT at a dose of 5.4 J per point can reduce inflammation (PGE2) and pain in activated Achilles tendinitis.

Bjordal et al. Br J Sports Med. 40(1):76-80,

2006.

• Low-level laser therapy accelerates clinical recovery from chronic Achilles tendinopathy when added to an Eccentric Exercise regimen. For the LLLT group, the results at 4 weeks were similar to the placebo LLLT group results after 12 weeks.

Stergioulas et al. American J. Sports Med. 36(5):881,

2008.

Muscle Tear/Hematoma

3 treatments over 5 days

Hamstring Tear/Hematoma

4 treatments over 7 days

Post-Traumatic Hematoma

Initial After 4 Treatments After 5 Treatments

Lateral Epicondylitis (tennis elbow)

• A systematic review with procedural assessments and meta-analysis of low level laser therapy in lateral elbow tendinopathy was recently performed because other reviews had found laser therapy to be ineffective.

• LLLT administered with optimal doses of 904 nm and possibly 632 nm wavelengths directly to the lateral elbow tendon insertions, seem to offer short-term pain relief and less disability in LET, both alone and in conjunction with an exercise regimen.

Bjordal et. al. BMC Musculoskelet Disord. 29(9): 75. 2008

Subacromial Impingement Syndrome

• A meta-analysis of the literature in Subacromial Impingement Syndrome (SAIS) found that laser therapy is an effective single intervention when compared with placebo treatments, but adding laser treatment to therapeutic exercise did not improve treatment efficacy.

• The overall results of this meta analysis found that exercise, joint mobilization, and laser therapy are effective physical interventions for decreasing pain and functional loss or disability for patients with SAIS. The current evidence does not support the use of ultrasound.

Sauers. J Athletic Training. 40(3): 221-223, 2005.

Muscle Fatigue

• Recently published study was aimed to investigate the effect of low-level laser therapy (LLLT) (830 nm wavelength, 100 mW output, spot size 0.0028 cm(2), 200 s total irradiation time) on skeletal muscle fatigue.

• Concluded that 830 nm LLLT can delay the onset of skeletal muscle fatigue in high-intensity exercises, in spite of increased blood lactate levels.

Leal Junior et. al. Lasers Med Sci. Jul 23, 2008.

Joint Disorders

• A systematic review on the effects of laser therapy in chronic joint disorders found “Low level laser therapy with the suggested dose range significantly reduces pain and improves health status in chronic joint disorders.”

Bjordal et al. Aust J Physio. 49:107-116, 2003.

Osteoarthritis

• Efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomized placebo-controlled trials.

• LLLT administered with optimal doses in an intensive 2-4 week treatment regimen, seem to offer clinically relevant short-term pain relief for osteoarthritis of the knee.

Bjordal et. al. BMC Musculoskelet Disord. 22(8):51, 2007.

Thermal Burn (Heat)

5 Treatments Over 8 Days

Thermal Burn (Heat)

19 treatments over 2 months

Burns

LLLT of deep second-degree cutaneous burns significantly

increased the number of intact mast cells during the inflammatory and proliferative phases of healing, and decreased the total number of mast cells during the

remodeling phase.Kaviani et. al. Lasers in Med. Sci. 21: 90, 2006.

• A small pilot study used 400mW laser at 670 nm laser twice a week over 8 weeks on 19 patients with burn scars who were requesting laser therapy

• Seventeen out of 19 lesions showed macroscopic improvement after the treatment (expressed in points on the Vancouver Scar Scale) with no scars becoming worse

Gaida et. al. Burns. 30: 362, 2004.

Fracture. R-Humerus.Age: 66/M

Initial Intermediate Final

10/29/2006 11/04/2006 11/29/2006

10/25/2006 11/01/2006 12/06/2006

Bone Healing

• A study performed in human osteoblast cells found “low-level laser therapy has a biostimulatory effect on human osteoblast-like cells during the first 72 h after irradiation.”

Stein et. al. Wien Klin Wochenschr. 120(3-4): 112-117, 2008.

• The results of a study carried out in laboratory mice indicates “that the use of low-intensity laser promotes better repair of bone injury”.

De Souza Merli et. al. Photomed Laser Surg. 23(2): 212-215, 2005.

• A more recent study in rabbits found that LILT “may accelerate the process of fracture repair or cause increases in callus volume and BMD, especially in the early stages of absorbing the hematoma and bone remodeling”

Liu et. al. Photomed Laser Surg. 25(6): 487-494, 2007.

Pain

Laser therapy in acute pain: a systematic review of possible

mechanisms of action and clinical effects in randomizedplacebo-controlled trials.

• The goal of the study was to review the biological and clinical short-term effects of laser therapy in acute pain from soft-tissue injury.

• Laser therapy can modulate inflammatory processes in a dose-dependent manner and can be titrated to significantly reduce acute inflammatory pain in clinical settings.

Bjordal et al. Photomed Laser Surg. 24(2):158-168. 2006

Case Study: Pain Reduction

Low level laser therapy with trigger points technique: A clinical study on 243 patients.

(HeNe 632.8 nm visible red or infrared 820-830 nm continuous wave and 904 nm pulsed emission.There are very promising "trigger points" (TPs), i.e., myofascial zones of particular sensibility and of highest projection of focal pain points, due to ischemic conditions. Headaches and facial pain, skeletomuscular ailments, myogenic neck pain, shoulder and arm pain, epicondylitis humery, tenosynovitis, low back and radicular pain, Achilles tendinitis) to whom the "trigger points"

Results: rigidity decreases, the mobility is restored (functional recovery), and the spontaneous or induced pain decreases or even disappears, by movement, too. LLLT improves local microcirculation and it can also improve oxygen supply to hypoxic cells in the TP areas and at the same time it can remove the collected waste products.

Results measured according to VAS/VRS/PTM: in acute pain, diminished more than 70%; in chronic pain more than 60%. Clinical effectiveness (success or failure) depends on the correctly applied energy dose--over/underdosage produces opposite, negative effects on cellular metabolism. The use of analgesic drugs could be reduced or completely excluded. LLLT suggests that the laser beam can be used as monotherapy for pain treatment.

Page 29

Pain Reduction - Mechanism

• 830 nm laser irradiation induces varicosity formation, reduces mitochondrial membrane potential and blocks fast axonal flow in small and medium diameter rat dorsal root ganglion neurons: implications for the analgesic effects of laser.

• Laser-induced neural blockade is suggested as a primary candidate for the mechanism of laser-induced pain relief.

Chow et al. J Peripher Nerv Syst. 12(1): 28-39, 2007.

Peripheral-Arterial Occlusive Disease(Frostbite 1992) – 86 yr. old podiatrist

InitialAfter 5 Consecutive Days of Treatment

11/29/2006

Acute for 6 months

Buergers Disease. Thromboangitis Obliterans

Initial:

Interim (4-5)2 days after initiating treatments, foot no longer in jeopardy.Improved arterial circulation and venous filling.

Final photo:June 11, color normal, one ulcertotally healed, 2nd ulcer almost healed, foot warm to the touch, ready for weight bearing.

12 treatments over 3 weeks

Venous Stasis Dermal Ulceration

5 Treatments Over 9 Days

Chronic Lymphedema

After 10 Treatments • Cyanosis and induration

gone• Good venous filling• Mid-calf diameter same as

left

Neck Pain

• A randomized, double-blind, placebo-controlled study of low-level laser therapy (LLLT) in 90 subjects with chronic neck pain was conducted with the aim of determining the efficacy of 300 mW, 830 nm laser in the management of chronic neck pain.

• Low-level laser therapy (LLLT), at the parameters used in this study, was efficacious in providing pain relief for patients with chronic neck pain over a period of 3 months.

Chow et al. Pain. 124: 201-210, 2006

The Patients

Laser Therapy Publications

Intellectual Property

Technology

Regulatory

Technology

Thank You!

Questions?