What’s New in Cosmetic Dermatology David J. Goldberg, MD, JD Skin Laser & Surgery Specialists of NY and New Jersey

Disclosures • Research Grants: Sebacia, Sienna Labs, Cutera, AeroLase, Allergan (Kythera), Neothetics

What’s New in Cosmetic Dermatology: Where to begin? • Energy based devices for acne • Developments in vascular lasers • Fat melting

Energy Based Devices for Acne

Acne Vulgaris • Acne is normal at any age • Affects 80% of the population • Complaint of 30% of dermatology patients • Due to inflammation of pilosebaceous unit • Classically treated by antibiotics and retinoids

1. 2. 3. 4.

Hypercornification of pilosebaceous duct Ductal colonization by P. acnes Inflammation Increased sebum production

Bolongia. Dermatology ed. 3. Ch. 36

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 oxygen which destroy sebaceous glands. • Destruction of sebaceous glands lead to decreased sebum. • Excellent for inflammatory and noninflammatory acne. • Effective and safe up to skin type V • Pneumatic models exist boost efficacy

Intense Pulsed Light 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Lowest reported reduction IPL

Greatest reported reduction

IPL + Pneumatic

Studies with IPL in Acne Vulgaris Author of Trial

Type of Study

Device

Number of Patients in study

Duration of Treatment

Liu LH et al

OL

IPL

50

6 ±2.15 treatments

% Reduction in Lesions, inflammatory (Inf) or Noninflammatory (NI) >90% (Inf)

Shamban et al.

Retrospective

IPL + pneumatic

56

4 treatments

90% (Inf)

Berger et al

OL

IPL + pneumatic

15

75% (inf)

Gold et al.

OL

IPL + pneumatic

11

1 treatment QOW x 2 sessions 4 treatments

Wanitphakdeedecha et al.

OL

IPL + pneumatic

18

4 treatments

65% (Inf)

Elman et al. Yeung CK

OL OL

IPL IPL

19 30

8 treatments 4 treatments per week at 3 week intervals for 12 weeks

85% (Inf) 87% (NI) 22% (inf) 44% (NI)

Baugh W et al.

OL

IPL

25

20% (Inf)

Sadick N

OL

IPL

8

2 treatments per week for 2 weeks 3 treatments spread over 12wks

Meyers P, et al.

OL

IPL

7

1 treatment every 3 weeks

70% (Inf)

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

78.8% (Inf)

32% (Inf)

New Approach • Suction Assisted Needle IPL • For all skin types

• Suction can remove the sebum and with addition of a needle for cystic acne improvement is greater than 75% after 2 treatments.

High-intensity 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) • 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

LED for inflammatory acne 100 90 80 70 60 50 40 30 20 10 0 Lowest reported reduction

NB Blue LED

NB Red LED

Greatest reported reduction

Blue-Red LED

Studies with Low Level LED and Laser Light in Acne Vulgaris Author of Trial

Type of Study

Device

Number of Patients in study

Duration or # of Treatment

% Reduction in inflammatory (Inf) or Noninflammatory (NI)

Liu LH et al. Kwon HH et al.

OL DBRCT

Blue-red LED Blue-red LED

50 35

9±3.34 treatments 2.5 min bid for 4 weeks

>90% in 44% of subjects 77% (inf); 54% (NI)

Goldberg DJ et al.

OL

Blue-red LED + microderm abrasion

24

2 treatments per week for a total of 8 sessions

81% (inf)

Lee SY et al.

OL

Blue-red LED

24

2 per week for 4 weeks

77.8% (inf); 34.3% (NI)

Gold MH et al.

SBRCT

Blue LED

30

Twice daily for 2 days

77% (Inf)

Akaraphanth et al.

OL

Blue LED

20

Once per week for 4 weeks

56.7% (inf)

Wheeland RG et al.

OL

Blue LED

31

Twice daily for 8 weeks

60% (inf)

Gold MH et al.

OL

Blue-violet LED

17

Twice per week for 4 weeks

36.4% complete clearance

Na JI et al.

SBRCT split-face

Red LED

28

Twice daily for 8 weeks

66% (inf); 59% (NI)

Aziz-Jalali MH et al.

SBRCT split-face

Red LLLT+ 2% topical clindamycin

28

Twice per week for 12 sessions

26% (Inf)

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

Infrared lasers (IR)

Infrared Lasers, Inflammatory lesion reduction 100%

• Near infrared (700-1000nm), penetrates deeper into dermis than light • Near infrared laser is not significantly better then LED • Targets is water in sebaceous gland, decreases sebum output • Nd:YAG is most effective • Nd:YAG can be enhanced by PDL

90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Lowest reported reduction 890 nm

1320 nm Nd:YAG

Greatest reported reduction 1450 nm Nd:YAG

Studies with IR 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)

Aziz-Jalali MH et al.

SBRCT split-face

890 nm LLLT + 2% topical clindamycin

28

Twice per week for 12 sessions

15% (Inf)

Sadick N

OL

830 nm LED + blue 11 LED

Two 20min sessions per week for 4 weeks

44.2+/- 23.99% (inf); 48.8 +/23.99% (NI)

Orringer J et al

SBRCT

1320 nm Nd:YAG

37

3 treatments every 3 weeks

0% (Inf); 27% (NI)

Deng H et al

OL

1320 nm Nd:YAG

35

Every other week for 12 weeks

51% (Inf); 35% (NI)

Friedman PM et al

OL

1450 nm Nd:YAG

20

Every three weeks for total of 3 sessions

70.6% (Inf)

Glaich AS et al

OL

1450 nm Nd:YAG +595 nm PDL

15

1 session every 4-6 weeks for total of 3 sessions

84% (Inf)

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

Pulsed Dye Laser

Studies with PDL in Acne Vulgaris Author of Trial

Type of Study

Device

Number of Patients in study

Duration of Treatment

Seaton et al.

DBRCT

PDL

41

1 treatment with 12 49% (inf); 40%(NI) week post treatment evaluation

Jasim et al.

OL; Split-face

PDL

10

1 treatment

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

% Reduction in inflammatory (Inf) or Non-inflammatory (NI)

30% of patients had 25%-50% improvement; 20% had >75% improvement

Pulsed Dye Laser (PDL)

PDL 100% 90%

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

80% 70%

60% 50% 40%

30% 20% 10% 0% Lowest reported reduction

Greatest reported reduction PDL

Photodynamic Therapy • Topical ALA • Almost all light based devices

Studies with PDT in Acne Vulgaris Author of Trial

Type of Study

Device

Number of Patients in study 12

Duration of Treatment

Yeung CK et al

OL

IPL + liposomal ALAPDT

Taub AF

OL

IPL + ALA-PDT

5

PDL + ALA-PDT

26

Oncer per month for 4 55.3% (Inf) months 1 treatment evaluated 12 53% (Inf) weeks post treatment

Orringer et al

SBRCT; split-face

Alexiades-Armenakas M OL

PDL + ALA-PDT

15

2.9 monthly treatments average

100% (Inf)

Rivard J, et al.

Case report

PDL + ALA-PDT

1

2 treatment, Increments not reported

“rapid improvement”

Akaraphanth R et al

OL; split-face

Blue LED + ALA-PDT

20

4 weekly sessions

71.1% (Inf)

Rivard et al.

Case series

Glycolic acid peel + Blue LED + ALA-PDT

8

1 treatment

Taub AF

OL

ALA-PDT

6

Once per month for 4 months

4 had no change; 3 minimal improvement; 1 significant improvement 55.3% (Inf)

Ma Y et al.

OL

Red LED + ALA-PDT

21

95.23% (Inf)

Liu LH et al

OL

Red LED + ALA-PDT

50

Once per month for 3 months 1 treatment

Wiegell SR et al

OL

Red LED + MAL-PDT

21

One treatment per every 2 weeks for total of 2 treatments

68% (inf)

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

Every 3 weeks for 1 month

% Reduction in inflammatory (Inf) or Non-inflammatory (NI) 65% (Inf)

>90% (Inf)

Radiofrequency (RF)

RF on inflammatory acne 100.00% 90.00%

• RF produces a thermal injury • RF coagulates sebaceous glands • Addition of microneedling increases efficacy for both inflammatory and noninflammatory acne

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

RF with microneedling

RF with Pulsed light

Studies with Radiofrequency in Acne Vulgaris Author of Trial

Type of Study Device

Number of Duration of Patients in study Treatment

OL

RF + microneedling

25

One treatment per 4 weeks, total of 3 treatments

Ruiz-Esparanza J et al

OL

RF

20

1 treatment

75% (Inf)

Prieto VG et al.

OL

RF + Pulsed light

25

Twice weekly for 4 weeks

47% (Inf)

Kim ST et al

% Reduction in inflammatory (Inf) or Non-inflammatory (NI) 90.11% (Inf); 76.46% (NI)

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

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

silica-gold nanoshell + 800 nm diode laser 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Efficacy with 2 passes silica-gold nanoshell + 800 nm diode laser

Studies with Particle-assisted Laser Treatment in Acne Vulgaris Author of Trial

Type of Study

Device

Paithankar DY et al Trial 1

SBRCT

Paithankar DY et al Trial 2

SBRCT

Number of Patients in study

Duration of Treatment

% Reduction in inflammatory (Inf) or Noninflammatory (NI)

Silica-gold 48 nanoshells + 800 nm diode laser

Once with 2 laser passes

61% (inf)

Silica-gold 51 nanoshells + 800 nm diode laser

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

Plasmon Resonance: Strong absorption at 800 nm

Light, e.m. wave

particle heated particle

Particle: silica core: gold shell, 0.150 mm diameter, engineered for surface plasmon resonance at 800 nm wavelength (hair removal wavelength) Light causes electrons-oscillation and conversion to heat 25

Selective Photothermolysis of Sebaceous Follicles with Externally Added Gold Chromophore Penetration assist

•

• • •

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

Laser

Particles Formulation

Preferential heating and inactivation of sebaceous follicle

26

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

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

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

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.

28

Energy Based Device Acne Treatment • Alternative to systemic treatments • Alterative to patient non-compliance • Effective • Minimal adverse events • Exciting newer approaches

Innovations in Vascular Lasers

A Look at Wavelength and Pulse Duration

Vascular Lasers 





To be effective, vascular lasers/light sources must be preferentially absorbed by blood vessels Absorption normally by oxyhemoglobin and reduced hemoglobin Major absorption peaks around 532, 595 and 1064nm

Absorption Spectra

http://www.laserandhealthacademy.com/en/public/lasers_medicine /

Clinical Applications for Vascular Lasers 

   

Capillary malformations (PWS) Hemangiomas Venous malformations Telangiectasias Radiation dermatitis

Clinical Applications for Vascular Lasers 

    

Rosacea Facial erythema Cherry angiomas Venous lakes Poikiloderma of Civatte Others: adenoma sebacea, hypertrophic and erythematous scars, striae distensae, warts

Pulsed Dye Lasers (595nm)  

Vbeam Perfecta (595 nm) Cynosure Cynergy

KTP Lasers (532nm)   

 

Versapulse Aura Verilyte Genesis Excel V

Typical KTP Laser • 100u-2 mm spot size • No cooling • Low Energy Delivery Systems

• Fluence: 1.8 - 42 J/cm2 • Spot Size: 2 – 12mm

• Pulse Duration: 1.5 – 40 ms • Repetition Rate: 0 to 4 Hz

• Treatment Spot: 101 Spot Options (2 to 12 mm) • Epidermal Cooling: 16mm Sapphire Window • High power

Intelligent Delivery

Excellent Visibility • • •

Unique cut-out design Large diameter sapphire window Visibility throughout treatment

Adjustable Spot Size • • •

On-the-fly adjustments 2mm to 12mm Real time calibration

Parallel Cooling • • •

Variable temperature sapphire window Superior cooling before, during, and after each pulse 5º C to 20º C

Vascular Lasers 



Newest lasers are all pulsed to avoid problems with nonspecific thermal heating Wavelengths and pulse durations now optomized to decrease complications and increase efficacy

Fat Melting Injectables

Deoxycholic acid Injection

42

42

• Clinical Results With KYBELLA™ (deoxycholic acid) Injection

Clinical Program

WITH

CLINICAL STUDIES have been conducted

OF WHICH

PATIENTS WORLDWIDE

HAVE BEEN TREATED WITH KYBELLA™

Clinical Results

In Pivotal Phase III Clinical Trials: Treatments OF SUBJECTS TREATED WITH KYBELLA™ were responders compared to 20.5% of placebo treated subjects based upon validated physician and patient measurements

Many patients experienced VISIBLE RESULTS IN TWO TO FOUR TREATMENT SESSIONSb spaced at least one month apart

of patients treated with KYBELLA™ reported SATISFACTION WITH THEIR APPEARANCE in association with their face and chinc

43

• Clinical Results With KYBELLA™ (deoxycholic acid) Injection

Most Adverse Reactions:

Were Primarily Associated with the Treatment Area

Were Reported as Mild or Moderate in Severity

The most common adverse reactions* were injection site:

81% were mild

• • • • • •

Edema/swelling Hematoma/bruising Pain Numbness Erythema Induration

Resolved by End of Study

0.9% of adverse reactions had not resolved by end of study

17.4% were moderate 1.6% were severe

*

44

LIPO-202 (Salmeterol Xinafoate for Injection, 0.42 mcg)

Treatment for Central Abdominal Bulging in Non-Obese Patients

45

Well Understood, Targeted Mechanism of Action • Triggers body’s natural process of triglyceride metabolism (lipolysis) • Affects only fat cells; does not affect other structures in the tissue

LIPO-202 shrinks fat cells without killing them

46

What’s New in Cosmetic Dermatology David J. Goldberg, MD, JD Skin Laser & Surgery Specialists of NY and New Jersey