Onychomycosis are laser and light sources effective?

Review of evidence

Wojciech Francuzik, Klaus Fritz, Anna Janecka

no conflict of interests

DISCLOSURE:

Questions

• Is there a need for laser treatment ?

• Is it effective ?

• Is it proven ?

• Which parameters ?

• Is it economically reasonable ?

Review of evidence

• Is there a need for laser treatment ?

• Is it effective ?

• Is it proven ?

• Which parameters ?

• Is it economically reasonable ?

Questions

Review of evidence

Toe Fungus Alternate Treatment Options

• Poor current treatment alternatives – Daily lacquer ---10% success rate

• Requires ~1 year of application to achieve 10% success rate • Low cost but low success

– Oral medication (Lamisil & Sporanox) -- 50% success rate after 6 – 9 month program • High liver stress • Cannot repeat drug therapy if it does not work • Single active agent is not always effective in all types of fungus • Interaction with medication • Contraindicarion in many immunologic and other diseases

The need for new therapeutic options

• To minimalize side effects

• Confine only to affected area

• Treatment options for patients with liver disease and multimorbidity

• Inability to develop microbial resistance

• Lack of mutagenic and genotoxic effects

Why are lasers attractive?

Questions

• Is there a need for laser treatment ?

• Is it effective ?

• Is it proven ?

• Which parameters ?

• Is it economically reasonable ?

Review of evidence

Studies on laser treatment effectivness in onycomycosis

in vitro in vivo

Vural et al.

Manevitch et al.

Aguilar et al.

Bornstein et al.

Harris et al.

Manevitch et al.

Aguilar et al.

Kozarev et Vizintin

Hochmanet al.

Landsman et al.

Weiss

The effects of laser irradiation on Trichophyton rubrum growth.

Vural, E., et al. (2008) Lasers in medical science, 23(4), 349–353.

IN VITRO STUDY

Laser systems proven ineffective on T. rubrum growth inhibition

Laser system Wavelength (nm)

Fluence (J/cm2)

IPL (Lumenis, Vasculight) 695 - 1000 38, 45, 57

IPL (Lumenis, Vasculight) 795 - 1000 38, 45, 57

Pulsed dye laser (Candela, SleroPlus) 585 8, 11, 14

Erbium YAG laser (Sciton Model Contour) 2940 25

KTP laser (Laserscope, Aura) 532 2, 4, 6, 8

Vural, E., et al. (2008) Lasers in medical science, 23(4), 349–353.

Propably Thermal damage plays secondary role

Q-switched Nd:YAG of 532 and 1064 nm wavelengths and 4 – 8 J/cm2 fluencies

Laser systems proven effective on T. rubrum growth inhibition

CONCLUSION:

Nanosecond pulses of irradiation

Vural, E., et al. (2008) Lasers in medical science, 23(4), 349–353.

Microcavitation Acoustic shock

Thermal shock

T. rubrum cell

Xanthomeganin (absorbs 532 nm)

Melanin (absorbs 1064 nm)

The Direct Antifungal Effect of 800 nm Femtocecond Laser on T. rubrum

IN VITRO STUDY

Methods:

Strain identification

Culture samples To verify fungal infection

SEM NAIL EXAMINATION

2-4 weeks

CONTROL

Sabuard + cyclohexamide

SUBCULTURE

Manevitch, Z., et al. (2010) Photochemistry and photobiology, 86(2), 476

Laser used in Manevich et al. study:

Ti:Sapphire, femtosecond infra-red laser (MIRA 900, Coherent Radiation, Santa Clara, CA)

800 nm, 200 fsec pulses, 76 MHz frequency

– 800 nm allows to effectively transverse the nail and

is effective at any level – Good therapeutic index due to difference in fluences

• 4.8 x 1022 photons /s*m2 was effective, • 17 x 1022 photons /s*m2 was destructive

IN VITRO STUDY

Manevitch, Z., et al. (2010) Photochemistry and photobiology, 86(2), 476

CONCLUSION:

T. Rubrum colonies

Nd:YAG 1320 nm

4 J/cm2

vacuum or cooling

treatment

No Effect of vacuum and thermal shock on laser treatment of T. rubrum

IN VITRO STUDY

Aguilar et al. Proc. of SPIE Vol. 7548 754805-7

1. Laser irradiated samples showed reduced colony growth compared to untreated samples

2. Vacuum or cooling had little or no effect on previously irradiated samples

CONCLUSION:

In vitro studies

Vural et al. Q-switched Nd:YAG laser 532 nm and 1064 nm wavelengths

Inhibition of fungal colony growth

Manevitch et al. Femtosecond infrared

titanium sapphire, 800 nm

Complete clearance of T.rubrum infected

nail clippings

Aguilar et al.

Q-switched Nd:YAG laser, 1320 nm by vacuum and

thermal shock

Inhibition of T. rubrum colony

growth

Bornstein et al. Diode, 870/930 nm 4074 – 4500 J/cm2

Complete clearance of T. rubrum and

C.albicans

OCT-

In vivo studies and clinical controls

Background - Nail Anatomy

• Fingernails grow ~ 3 mm / month

– Takes 6 months for nail to grow out

• Toenails grow ~ 1 mm / month

– Takes 12-18 months for nail to grow out

• Diseased nails tend to grow slower then normal

Treatment of nail fungus

Type of nail fungus pattern: Subungual and or nail bed Therapy by thermolysis needs maximum temperature in

fungus layers (for effectivity) and Minimal temperature in

uninvolved tissue (increases saftey , reduces

pain)

Onycho-

gryphosis

Nerves

Laser

Capillaries

Courtesy PinPointe

Temperature distribution example: CoolBreeze

Laser used: 1. COOLTOUCH

• Nd:YAG Q switched laser

• 1064 or 1320 nm wl

• 6-350 microsec

• 4mm beam diameter

• Fluence 4 J/cm2

• 50 ms pulse envelope

IN VITRO STUDY

Reaches Target Temperature • Move the hand piece over the nail in different directions until the

target temperature is reached • Real time temperature is displayed • System will deliver cryogen spray when the set target

temperature is reached • Adjust target temperature to achieve a comfortable treatment for

the patient

Number of Passes • Repeat until all the nails have been treated to the target

temperature 2 times Treatment Interval • Every 2 - 6 weeks for a total of 3 to 4 treatments,depends on

condition of the nail, clinical response to treatment and rate of nail growth

CoolBreeze 1064nm Laser Treatment

Photos courtesy of Ritchie Steed, DPM

6 weeks Post - Treatment Pre - treatment

Post Treatment, 7.5 months

CoolBreeze™ 1320nm Laser Treatment

Photos courtesy of Ritchie Steed, DPM

6 weeks Post - Treatment Pre - treatment

• Diode Laser

• Low power

• Requires the use of toe clips

• Treats 4 toes simultaniously

• Protocol requires three 6 min

procedures

Noveon (Nomir Technologies) Laser

Noveon (Nomir Technologies) Laser

Bornstein, E., et al. Photochemistry and photobiology, 85(6), 1364–74.

Study In vitro

Bornstein et al. In vivo

Landsman et al.

Laser system Noveon, diode, 870/930 nm Noveon, diode, 870/930 nm

Power output (W) 11,0 3,0

Energy fluence (J/cm2)

4500 Over 720 sec

204 + 424 Over 120 + 240 sec

Total energy used in protocol 7920 J 360 + 750 J

Outcome 100% Clearance 38% negative cultures

after 3 x 6 min Tx

Landsman, A. S., et al. (2012) JAPMA, 102(2), 169–171.

IN VIVO

STUDY

Laser treatment for toenail fungus

with PinPointe FootLaser

IN VIVO

STUDY

Harris, DM, et al. (2009) Proceedings of SPIE, 7161, 71610M–71610M–7.

3 months follow-up

79% (11/14) had over 3 mm of clear

nail growth in 90 days

L R

14 patients

NO -Tx Tx

Laser specifications

IN VIVO

STUDY

Harris, DM, et al. (2009) Proceedings of SPIE, 7161, 71610M–71610M–7.

Laser used: PinPointe FootLaser, Patholase, Nd:YAG pulse laser, 1064nm wl

Approved by FDA, CE Mark Sigle treatment required

CONCLUSION:

Small sample size, (N=14) There was no culture after treatment Effectiveness is measured by „clear” nail growth

Unique Pulse Modulation

• The PinPointe FootLaser’s unique combination of wavelength and pulse structure for targeting the fungus

• Laser pulse ends before there is damage to surrounding tissue-or pain to the patient

• Other Nd:YAG lasers can be very painful due to non-specific pulse modulation

LASER PRESETS

P1 P2 P3

PULSE ENERGY

200 mJ 200 mJ 200 mJ

REPETITION RATE

20 Hz 30 Hz 30 Hz

LASER ON TIME PER BURST

½ second ½ second 1/3 second

LASER OFF TIME PER BURST

½ second 1/6 second

1/3 second

95% of negative cultures after 3

months and 100% after 6 months.

Laser treatment for toenail fungus with Dualis (Fotona) Laser

During each treatment visit:

3 treatment visits 12 month folow-up

No sideffects

RESULTS:

IN VIVO

STUDY

Kozarev, J., & Vižintin, Z. (2010) J Laser Health Academy, 1(1), 1–8

Fotona Dualis Laser Specifications

IN VIVO

STUDY

Kozarev, J., & Vižintin, Z. (2010) J Laser Health Academy, 1(1), 1–8

CONCLUSION:

Effective but… Study lacks control group, (N=72)

The 1064 nm Nd:YAG laser was used with: 35-45 J/cm2 of fluence 30-35 msec of pulse duration 4 mm of spot size 1 Hz of frequency

• Same methodology and protocol

• Only 37.14% (N=35) negative cultures after 3 months

• Possible causes: – 30% of patients had Scytalidium diminatum infection

– 14,3% of patients had dimished peripheral circulation

– Subungual hyperkeratosis?

FAILURE TO REPRODUCE RESULTS

Wanitphakdeedecha R, The Efficacy and Safety of 1064 nm Nd:YAG Laser in the Treatment of Onychomycosis – Thai Experiences

www.Fotona.com

IN VIVO

STUDY

=

• 2 or 3 treatments 223 J/cm2 fluence,

2mm spot size

• Results: – Negative cultures in 7/8

patients

• Conclusion: – Non comparable results

– Small sample size

0.65 milisecond Nd:YAG 1064 nm

Hochman, L. G. (2011) Journal of cosmetic and laser therapy , 13(1), 2–5

IN VIVO

STUDY

Laser: LightPod Neo, Aerolase

1 pass 2 pass ANTIFUNGAL CREAM

Visible aiming beam (coaxial with invisible treatment beam)

Visible working distance beam

Invisible Temperature

sensor

GenesisPlus (Cutera) Laser Specifications

Two aiming beams + Temp Sensor

GenesisPlus (Cutera) Laser Specifications

IN VIVO

STUDY

The 1064 nm Nd:YAG laser was used with: 16 J/cm2 fluence 0,3 msec of pulse duration 5 mm of spot size 2 Hz of frequency

Goal for effective treatment is to heat and hold tissue temperature at 43o- 46o as indicated by yellow LEDs Use 700-800 pulses / 5 toes,

GenesisPlus (Cutera) Laser Specifications

IN VIVO

STUDY

Weiss D. 3 Month Clinical Results using Sub-millisecond 1064 nm Nd : YAG Laser for the Treatment of Onychomycosis.

CONCLUSION:

70% of improvment in nail condition Study lacks control group, (N=7) No cultures post Tx

The 1064 nm Nd:YAG laser was used with: 16 J/cm2 fluence 0,3 msec of pulse duration 5 mm of spot size 2 Hz of frequency

Results base on a subjective

score of a single examiner!!!

U. Kimura et al. study

IN VIVO

STUDY

Kimura U, et al. J Drugs Dermatol. 2012 Apr;11(4):496-504

CONCLUSION:

Very similar design to previous study 51% of microscopicly negative samples

Study lacks control group, (N=13)

The 1064 nm Nd:YAG laser was used with: 14 J/cm2 fluence 0,3 msec of pulse duration 5 mm of spot size 5 Hz of frequency

Questions

Review of evidence

• Is there a need for laser treatment ?

• Is it effective ?

• Is it proven ?

• Which parameters ?

• Is it economically reasonable ?

Nail Anatomy and Types of Onychomycosis Need to be defined in order to find the best technology

Light Absorption in Tissue makes a difference

1 µm

10 µm

100 µm

1 mm

10 mm

100 mm

1 m

10 m

100 m

0.1 0.5 1 2 3 0.4 0.3 0.2

1064 Nd:YAG

Water

Wavelength

Hemoglobin

Melanin

1320 nm Nd:YAG

1320 nm is absorbed uniformly in water and tissue with little effect from melanin or hemoglobin

1 µm

10 µm

100 µm

1 mm

10 mm

100 mm

1 m

10 m

100 m

0.1 0.5 1 2 3 0.4 0.3 0.2

1064 nm Nd:YAG

Water

Wavelength

Hemoglobin

Melanin 1064 nm is not as

well absorbed in water and tissue

Melanin or hemoglobin are the dominate chromophores

Light Absorption in Tissue makes a difference

Summary and discussion

• Studies proove positive effects • Are hard to compare • Small sample sizes • Most had no control group • Some were not reproducible • Remissions: no comment

Questions

• Is there a need for laser treatment ?

• Is it effective ?

• Is it proven ?

• Which parameters ?

• Is it economically reasonable ?

Review of evidence

Is it economically reasonable ?

• Not reimbursed

• If effective 30-100 €/session

• Cost of device should not exceed 4 sessions in 100 patients = < 20 000 €

• Better : use an existing laser and adapt similar parameters for addititional pay off

What’s next

• Photodynamic phototherapy?

• A standardized reasearch protocol

• Chromophore related laser treatment

• More studies on laser can be expected to find best wavelenghth and protocol

• Studies OCT controlled?

OCT (optical coherence tomography)

may be useful in effectivity studies

OCT

The Nail in OCT

Papillary Dermis

Naiel

Matrix

Eponychium

Courtesy PD Dr Messmer , Munich, Germanyou

OCT: nail fungus

Courtesy PD Dr Messmer , Munich, Germanyou

Hematoma

Courtesy PD Dr Messmer , Munich, Germanyou

Thank You for Your attention

WHERE POZNAN MEETS PRAGUE

Wojciech Francuzik, Klaus Fritz, Anna Janecka