Cosmetic Improvement of Acne With Lasers David J. Goldberg, MD, JD - - PDF document

Cosmetic Improvement of Acne With Lasers

David J. Goldberg, MD, JD Skin Laser & Surgery Specialists of NY/NJ

Disclosures

• Research Grants: Sebacia, Sienna Labs, Aerolase

1. Hypercornification of pilosebaceous duct 2. Ductal colonization by P. acnes 3. Inflammation 4. Increased sebum production

• Bolongia. Dermatology ed. 3. Ch. 36

1 2 3

Why use energy based devices?

• Don’t require patient compliance
• Don’t require systemic medications
• Patients may have adverse reactions
• Many patients don’t want to ingest medications
• The energy is targeted to the affected area
• They Work!

Intense Pulsed Light (IPL)

• Photoactivates porphyrins stored by P.

acnes resulting in production of singlet

• xygen which destroy sebaceous

glands.

• Destruction of sebaceous glands lead

to decreased sebum.

• Excellent for inflammatory and non‐

inflammatory acne.

• Effective and safe up to skin type V
• Pneumatic models exist boost efficacy

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Lowest reported reduction Greatest reported reduction

Intense Pulsed Light

IPL IPL + Pneumatic

Infrared lasers (IR)

• Near infrared (700‐1064nm),

penetrates deeper into dermis than light

• Target is water in sebaceous gland,

decreases sebum output

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Lowest reported reduction Greatest reported reduction

Infrared Lasers, Inflammatory lesion reduction

890 nm 1320 nm Nd:YAG 1450 nm Nd:YAG

4 5 6

1320 nm

1450nm

BEFORE AND AFTER: ACNE -1064nm -650 microsecond

Before 13 Months After 5 Tx Photos Courtesy of Michael Gold, MD

7 8 9

Before

Acne on Skin of Color

After 3rd Treatment

650usec, 1064nm laser vs Sham

• 20 subjects
• Moderate to severe acne
• 3 txs – 2 weeks apart
• Evaluated inflammatory lesions, comedones, porphyrin score and

sebum score

10 11 12

650usec, 1064nm laser vs Sham

• Inflammatory and comedonal lesions (62% more improvement in

laser treated group vs. sham)

• Porphyrin score (92% more improvement in laser treated group vs.

sham)

• Sebum score (100% more improvement in laser treated group vs.

sham)

Sham Tx

Baseline Post 3 Treatments

(6 weeks after the baseline visit)

Sham Tx

Baseline End of Study

13 14 15

Active Tx

Baseline Post Treatment 1

(2 weeks after the baseline visit)

Active Tx

Baseline End of Study

(6 weeks after the baseline visit)

Active Tx

Baseline Post Treatment 2 Post Treatment 3 End of Study

(6 weeks after the baseline visit) (8 weeks after the baseline visit)

16 17 18

Active Tx

Baseline Post Treatment 3

Active Tx

Post Treatment 1 Baseline Post Treatment 2

(2 weeks after the baseline visit) (4 weeks after the baseline visit)

Active Tx

Baseline Post Treatment 1 Post Treatment 2 Post Treatment 3

(2 weeks after the baseline visit) (4 weeks after the baseline visit) (6 weeks after the baseline visit)

19 20 21

Pulsed Dye Laser Pulsed Dye Laser (PDL)

• 595 nm
• Usually for vascular lesions
• Evaluated after only 1 treatment
• Mechanism of action in acne unknown

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Lowest reported reduction Greatest reported reduction

PDL

PDL

Potassium titanyl phosphate laser (KTP)

• 535 nm
• Traditionally for rosacea and

telangiectasias

• Studies showed similar results if 1 or 2

times per week treatment for 2‐4 weeks

• Mechanism may result from

destruction of blood vessels

• Increased efficacy if area pre‐treated

with 5‐aminolevlinic acid (ALA)

0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% 80.00% 90.00% 100.00% Lowerst reduction reported Greatest reported reduction

KTP 532nm

KTP 532nm

22 23 24

Radiofrequency (RF)

• RF produces a thermal injury
• RF coagulates sebaceous glands
• Addition of microneedling

increases efficacy for both inflammatory and non‐ inflammatory acne

0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% 80.00% 90.00% 100.00% Greatest Reduction Reported

RF on inflammatory acne

RF RF with microneedling RF with Pulsed light

Before After 4 Treatments Before After 4 Treatments

Photodynamic Therapy

• Photo‐oxidation and cytotoxicity via a

sensitizing substance

25 26 27

Photodynamic Therapy (PDT)

Photosensitizing Compound + Light

• Administer a photosensitizing agent
• Allow it to accumulate in target cells
• Activate it by irradiation with visible light
• Facilitate destruction of target cells through activated

photosensitizer

PDT with various energy devices

• Activation of protoporphyrin IX can

be achieved by many energy modalities

• Many devices work very well

0% 20% 40% 60% 80% 100% 120% Greatest reduction reported

PDT with various energy devices

IPL PDL Blue LED Red LED

28 29 30

12 wks after 4 treatments Before

Photos courtesy Michael H. Gold, MD

Clinical Experience – ALA PDT + IPL

31 32 33

ALA‐PDT Photodynamic acne treatment

Before After

34 35 36

Photodynamic acne treatment

Before After 12 months

Particle‐assisted Laser Treatment

• Exogenous chromophore is placed into

sebaceous unit

• Laser or light heats particle destroying the

proximal sebaceous gland

• Silica‐gold nanoshells with 800 nm diode

has demonstrated reduction of inflammatory lesions by 61% with one treatment

• Well tolerated by patients

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Efficacy with 2 passes

silica‐gold nanoshell + 800 nm diode laser

silica‐gold nanoshell + 800 nm diode laser

37 38 39

Studies with Particle‐assisted Laser Treatment in Acne Vulgaris Author of Trial Type of Study Device Number of Patients in study Duration of Treatment % Reduction in inflammatory (Inf) or Non‐ inflammatory (NI) Paithankar DY et al Trial 1 SBRCT Silica‐gold nanoshells + 800 nm diode laser 48 Once with 2 laser passes 61% (inf) Paithankar DY et al Trial 2 SBRCT Silica‐gold nanoshells + 800 nm diode laser 51 1 treatment every 2 weeks for 3 total treatments 53% (inf)

SBRCT = Single blinded randomized controlled; DBRCT = Double blinded randomized controlled; OL = Open label; RSB = Randomized single‐blinded

Metallic Microparticles

• Sebacia‐gold
• Sienna ‐silver

Plasmon Resonance: Strong absorption at 800 nm

Particle: silica core: gold shell, 0.150 m diameter, engineered for surface plasmon resonance at 800 nm wavelength (hair removal wavelength) Light causes electrons‐oscillation and conversion to heat

Light, e.m. wave particle

42

heated particle

40 41 42

Selective Photothermolysis of Sebaceous Follicles with Externally Added Gold Chromophore

Laser Preferential heating and inactivation of sebaceous follicle Penetration assist Particles Formulation

• Apply particle suspension to skin;

deliver to sebaceous follicle

• Wipe off surface particles
• Laser tuned to absorption peak
• Key: selectivity into follicle

– Not in epidermis/dermis – Low pain – No collateral or epidermal damage

43 J Invest Dermatol. 2015 Jul;135(7):1727-34.

Pre‐ and post‐auricular histology showing consistent sebaceous follicle photothermal damage

Scale bar: 100 microns; arrows delineate areas of photothermal damage

Topical Application of Microparticles followed by wiping

• ff of surface particles

45

43 44 45

Laser Treatment after infusing particles to sebaceous follicles

46

Mean inflammatory lesion count change vs baseline, Treated versus Sham

Statistically significant change between Tx and Sham at 8, 12, 16 wks Standard errors of mean and p‐values are shown.

47

01‐51‐KC‐D

SEB ‐ 003

Baseline

IGA: 4

Inflammatory: 69

12 Weeks Δ from baseline: ‐80%

IGA: 2

48

46 47 48

01‐56‐MB‐D

SEB ‐ 003

Baseline

IGA: 3

Inflammatory: 52

12 Weeks

Δ from baseline: ‐87%

IGA: 1

49

• Contained in a topical pre‐treatment solution
• Activation by a pulse of laser light causes a burst of energy
• Targeted thermal tissue injury for clinical applications

Heat Near-IR Light E-field Oscillations of Electrons

Silv Silver er pl plasmonic nanop anopla lates are ul ultra eff efficient, near near in infr frared lig light abs absorber rbers SN SNA‐001: 001: Li Light Ab Abso sorp rptio tion a

• SNA‐001 silver nanoplates are tuned to

specific wavelengths

• 1,000 – 10,000X greater absorbance than

melanin

• 4X greater absorbance than gold

nanoshells

aData on file. Sienna Biopharmaceuticals, Inc. bAbsorbance normalized to 1% wt/wt metal (Au, Ag) or melanin cGold nanoshells

Near Infrared Light Visible Light

400 500 600 700 800 900 1000 1100 Wavelength (nm) Absorbance (cm-1)b 400 200 600 800 1000 1200

SNA-001.755 Goldc Melanin SNA-001.810 SNA-001.1064 755nm Alexandrite 810nm Diode 1064nm Nd:YAG

49 50 51

Sign Signific icant re reduction of

• f ac

acne ne le lesions in in sil silver pl plasm asmonic th therapy feas asib ibil ility ity st study udya

• Evaluator blinded, controlled study (N = 5)
• Randomized, split‐back design
• Laser alone or Laser + SNA‐001
• 810 nm diode
• 4 treatments, one week apart
• Acceptable safety profile

Baseline 12 weeks post Tx Laser + SNA-001

aData on file, Sienna Biopharmaceuticals, Inc. Interim analysis results.

• 2

4 6 8 10 12

• 55%**
• 75%*

Mean lesion counts (95% CI)b Laser Laser + SNA-001 Baseline 12 wks post Tx

Change in lesion counts

Low Level Light

PHOTOMODULATION PHOTOMODULATION PHOTOTHERMOLYSIS PHOTOTHERMOLYSIS

Photomodulation Photobiochemical Photomodulation Photobiochemical “Very Low Level” “Very Low Level” Non‐Ablative Non‐Ablative “Lower Level Energy” “Lower Level Energy” Non‐ablative Photothermal Non‐ablative Photothermal Non‐Ablative Non‐Ablative Selective Photothermal Selective Photothermal Non‐ Selective Photothermal Non‐ Selective Photothermal “Higher Level Energy” “Higher Level Energy” Ablative Ablative

52 53 54

RE R Ri L y Mi G C C M Nu

IR energy is absorbed in the membranes Visible light energy passes through the cell membrane and is absorbed in the intracellular

• rganelles

Primary photophysical reaction… Secondary photochemical cascade Primary photochemical cascade

Low Level Light

• LED known to reduce inflammatory acne
• May decrease inflammatory immune response
• May destroy P. acnes
• LED targets keratinocyte inflammation and slow keratinocyte

proliferation.

• Safe in all skin types

Light Emitting Diode (LED)

10 20 30 40 50 60 70 80 90 100 Lowest reported reduction Greatest reported reduction

LED for inflammatory acne

NB Blue LED NB Red LED Blue‐Red LED

• Blue and red light stimulates protoporphyrin

IX in P. acnes, creating an oxygen singlet, toxic to P. acnes.

• Red light (620‐660 nm) as LED or low level

laser

• Blue light (400‐500nm)
• Blue‐red light is most effective for

inflammatory and non‐inflammatory

• Blue‐red is more effective than 5% BPO alone
• LED may used with photodynamic therapy for

best results

55 56 57

• Blue – Antimicrobial
• Red – Anti‐microbial and anti‐inflammatory

Light readily penetrates skin to trigger multiple responses

Omnilux Device

• 8x treatments in 4 weeks
• Blue 4 x 20 min 415 @ 40 mW/cm2  48 J/cm2
• Red 4 x 20 min 633 @ 80 mW/cm2  96 J/cm2
• Assess at 0, 2, 4, 8, 12 wk
• 10‐20% full clearance
• N=30
• Dramatic reduction in lesion count

Percentage reduction of inflamed lesions at 1, 4, and 8 weeks post treatment

Low‐level Light and Acne

• Combination blue and red LED therapy appears to have excellent potential in the treatment of

mild to severe acne.

• Treatment appears to be both pain‐ and side effect‐free.

Low‐level Light and Acne

58 59 60

IlluMask Handhelds In Home Devices

Low‐level Light Therapy Cosmetic Improvement of Acne With Lasers

• Alternative to systemic treatments
• Alterative to patient non‐compliance
• Effective
• Minimal adverse events
• Exciting newer approaches

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