Innovative Medical Uses of Lasers

Transcription

1 Innovative Medical Uses of Lasers Justin Finch, MD Assistant Professor Director, Clinical Photography UConn Department of Dermatology March 3 rd, 2017

2 Disclosures No conflicts of interest for this lecture 100% of drugs and devices discussed are off-label

3 Overview 1. PDT treatment of skin cancer 2. Laser-assisted drug delivery 3. Laser management traumatic scars and fibrotic disorders

4 PDT for Skin Cancers 77 tumors (67 patients) 44 superficial BCC 5 year f/u data 2 year recurrence = 25% 5 year recurrence = 30% Superficial BCC 1. An Bras Dermatol Dec;90(6): doi: /abd

5 How to Enhance ALA Penetration? Rate-limiting step in topical drug absorption is penetration through the stratum corneum Disrupt the Stratum Corneum Topical Pre-Treatment Retinoid 5-FU Mechanical Disruption Microdermabrasion Tape-stripping Curettage Microneedling Fractional Laser Ablation

6 Ablative Fractional Resurfacing 100 um Immediately 48 hours 7 days 1 month 3 months

7 Laser-Assisted PDT Skin Surface Fluorescence After Topical Application of Methyl 5-Aminolevulinic Acid (MAL) 90 minutes 180 minutes MAL alone Fractional CO 2 laser + MAL Haedersdal et al. Lasers Surg Med Feb;42(2):

8 Laser-Assisted PDT Fluorescence 3 hours after mala application Ablative Fractional Laser Non-Ablative Fractional Laser Microneedling Dermabrasion Image adapted from Bay et al. JAMA Dermatol 2017

9 Laser-Assisted PDT Fluorescence 3 hours after mala application Ablative Fractional Laser Non-Ablative Fractional Laser Microneedling Dermabrasion 1. Bay C, Lerche CM, Ferrick B, Philipsen PA, Togsverd-Bo K, Haedersdal M. Comparison of Physical Pretreatment Regimens to Enhance Protoporphyrin IX Uptake in Photodynamic Therapy: A Randomized Clinical Trial. JAMA Dermatol Feb 1. doi: /jamadermatol [Epub ahead of print]

10 Laser-assisted PDT for nodular BCC ORIGINAL ARTICLE Er:YAG ablative fractional laser-primed PDT with mala as an alternative treatment option for patients with thin nodular BCC: 12-month follow-up results of a randomized, prospective, comparative trial S.H. Choi, K.H. Kim, K.H. Song 9 November patients randomized to either: Conventional MAL-PDT (2 sessions) Er:YAG + MAL-PDT (1 session) 3 month response rate (p=0.028) MAL-PDT: 50.0% Laser-assisted PDT 84.2% 12-month response rate MAL-PDT: 22.2% Laser-assisted PDT 78.9% J Eur Acad Dermatol Venereol May;30(5): doi: /jdv

11 Laser-Assisted Drug Delivery (LAD) Candidate Diseases and Drugs Actinic Keratoses and SCC/BCC: Photosensitizing drugs, 5-FU, imiquimod Scars, Fibrosis: Corticosteroids 1 Anesthesia: Lidocaine 2, 3 Hair Loss: Minoxidil, Latanoprost 4, Corticosteroids Atrophy: Poly-L Lactic Acid 5 Hyperpigmentation: (e.g. hydroquinone, azeleic acid) Vaccinations 6 Hypo/Depigmentation: bimatoprost 7 1) Kineston D, Kwan JM, Uebelhoer NS, Shumaker PR. Use of a fractional ablative 10.6-mum carbon dioxide laser in the treatment of a morphea-related contracture. Arch Dermatol2011;147: ) Baron ED, Harris L, Redpath WS, Shapiro H, Hetzel F, Morley G, Bar-Or D, Stevens SR. Laser-assisted penetration of topical anesthetic in adults. Arch Dermatol 2003;139: ) Yun PL, Tachihara R, Anderson RR. Efficacy of erbium:yttrium-aluminium-garnet laser-assisted delivery of topicalanesthetic. J Am Acad Dermatol 2002;47: ) Dermatol Surg Jul;38(7 Pt 1): doi: /j x. Epub 2012 Apr 27. 5) Rkein A, Ozog D, Waibel JS. Treatment of atrophic scars with fractionated CO2 laser facilitating delivery of topically applied poly-l-lactic acid. Dermatol Surg Jun;40(6): ) Lee WR, Pan TL, Wang PW, et al. Erbium:YAG laser enhances transdermal peptide delivery and skin vaccination. J Control Release 2008;128(3): ) Dermatol Surg Jul;38(7 Pt 1): doi: /j x. Epub 2012 Apr 27.

12 LAD Repigmentation with Bimatoprost Hypopigmented scars 1 79% of patients had >50% improvement after 2-10 treatments with a nonablative fractional laser protocol Vitiligo Chemical Burn s/p 5 treatments Facial Plast Surg Clin North Am Feb;25(1): ) Dermatol Surg Jul;38(7 Pt 1): doi: /j x. Epub 2012 Apr 27.

13 LAD Vaccination In vivo mouse study Mouse skin treated with fractional Er:YAG laser Skin vaccination with a lysozyme antigen 129 amino acid molecule Too large to penetrate stratum corneum Production of antibodies in the serum by 3x Lee WR, Pan TL, Wang PW, et al. Erbium:YAG laser enhances transdermal peptide delivery and skin vaccination. J Control Release 2008;128(3):200 8.

14 LAD of stem cells resulting in functional chimeric mouse Immunosuppressed mice received radiation to ablate their bone marrow Skin was subsequently treated with AFR and donor stem cells Three weeks after this single treatment, post-procedure fluorescence-activated sorting demonstrated engraftment of the donor cells, along with functional recovery. Waibel J, Davis S, Badiavas E. A pilot study of laser assisted delivery of allogeneic mesenchymal cutaneous stem cells resulting in functional chimeric mouse model. Lasers Surg Med 2012;44:37. Rodriguez-Menocal L, Salgado M, Davis S, Waibel J, Shabbir A, Cox A, Badiavas EV. Percutaneous bone marrow transplantation using fractional ablative Erbium:YAG laser. PLoS One Mar 25;9(3):e doi: /journal.pone ecollection 2014.

15 Future Directions for LAD 1) Depth Would expect deeper channels to give greater absorption However, data inconsistent 2) Density Higher density is not always better At very high densities dermal vasculature gets wiped out and drug absorption decreases 3) Coagulation Laser-induced thermal coagulation enhances skin uptake CO2 is best b/c it has a coag zone Er:YAG intermediate Microneedle holes offer the least penetration No-coag may be better for systemic delivery Depth Density Coagulation ~200um ~100 channels / cm 2 CO 2 Er:YAG Microneedle

16 Advances in Laser Treatment of Traumatic Scars and Sclerotic Disorders

17 Scar Contractures Scar contractures across joints impair functional mobility Non-healing erosions can be painful and a source for infection May impede prosthetic rehabilitation Surgical interventions may be required for refractory or severe contractures incision and release, skin grafting, flaps, and long-term splinting unpredictable efficacy, high recurrence rates, and additional morbidity.

18 Scar Contractures 43 y.o. male Iraq war veteran with scar contracture of left knee after IED injury Scheduled for surgery to have scar release and skin grafting 3 days after 1 st AFR procedure, had 12 increased ROM, resolution of non-healing erosion By 2 year f/u (after 2 AFR), had regained normal ROM Pre-treatment 3 days after first treatment 2 years Shumaker et al. J Trauma Acute Care Surg Aug;73(2 Suppl 1):S

19 Linear Morphea 27 y.o. Hispanic woman, avid runner Treated with topical calcipotriene, intralesional triamcinolone injections, UVA phototherapy No response, contracture worsening Bandlike sclerotic plaque extends across the left ankle to the mediodorsal foot, restricting patient ambulation Arch Dermatol. 2011;147(10): doi: /archdermatol

20 Linear Morphea Pretreatment 4 month followup Restricted plantar flexion of the left foot (45 from neutral) 65 of plantar flexion from neutral Arch Dermatol. 2011;147(10): doi: /archdermatol

21 Microstomia of Systemic Sclerosis Intense-pulsed light Patients (n=4) treated with up to 5 monthly sessions 3 of 4 patients had 1mm in oral aperture Before IPL: 3.1 cm After 3 IPL: 3.3 cm Comstedt LR, Svensson A, Troilius A. Improvement of microstomia in scleroderma after intense pulsed light: A case series of four patients. J Cosmet Laser Ther Apr;14(2): doi: /

22 Scar Contractures Summary & Approach Start Treatment Early 2-4 months Ablative column depth should approximate full thickness of scar Low density: ~5% LAD with topical triamcinolone or 5-FU Similar efficacy TAC may have more AEs, including increased scar width and telangiectasias 3-5 sessions Lasers are not a monotherapy for traumatic scars Physical and occupational therapy should be an ongoing part of rehabilitation to optimize scar remodeling and functional enhancement May still require surgical revision

23 Fractional Laser Mechanism Fenestration? Collagen remodeling? shift from collagen I to collagen III Transepidermal elimination of elastic fibers? 1 1. Richert SM, Bridenstine J. Transepidermal elimination of elastic fibers after carbon dioxide laser resurfacing. A report of two cases. Dermatol Surg 1998; 24:

24 Justin Finch, MD Assistant Professor Director, Clinical Photography UConn Department of Dermatology Thank You