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    • Nonoperative Facial Rejuvenation Andrew Coughlin M.D. Raghu Athre M.D. University of Texas Medical Branch Department of Otolaryngology Grand Rounds Presentation February 25, 2010
    • Objectives
      • Discuss the history of cosmetic facial rejuvenation
      • Discuss Aging and Photodamage to the skin
      • Discuss treatment options for adynamic facial conditions and their associated complications
    • History of Facial Rejuvenation
      • 3000 BCE Egyptians
        • Manicures, Make-up, Tattoos of the face (1)
      • 1500 BCE Egyptians
        • Used sandpaper for scars as early form of dermabrasion (2)
      • 100 BCE Roman poet Ovid: The Art of Love
        • Facial mask of barley, bean, eggs, hartshorn, narcissus bulbs, balsam, Tuscany seed, honey (3)
      • 200 CE Jewish Talmud
        • Husband must provide 10 dinars for his wife’s cosmetic needs
      • 900 CE Arabic Physicians
        • Crushed rice, seashells, marble, crystal, limes, eggs, beans, ground lentils (dermabrasion)
    • History of Facial Rejuvenation
      • 1905 Kromayer
        • Mechanical dermabrasion with wheels and rasps (4)
      • 1960’s Facial Peels
      • 1990’s CO2 Laser Resurfacing
      • Most recently filler agents have become increasingly popular
      • **Modern techniques are reminiscent of ancient techniques
    • Layers of the Skin
    • Epidermis
      • Stratum Corneum
        • Keratinized cells to be sloughed off
      • Stratum Lucidum
      • Stratum Granulosum
      • Stratum Spinosum
      • Stratum Basale
        • Basal regenerative cells and melanocytes
        • Regeneration every 12-14 days (1)
    • Epidermis
    • Dermal Layers
      • Papillary Dermis
        • Meshwork of fine type III collagen fibers
        • Anchors epidermis down to dermis
      • Reticular Dermis
        • Thick type I collagen bundles
        • Elastic fibers for resiliency
        • Glycosaminoglycans (GAG’s)
          • Ground substance between fibers
          • Can hold up to 1000x their weight in water (5)
        • Hair, sebaceous/sweat glands, nerve receptors and blood vessels
    • Papillary and Reticular Dermis
    • Hypodermis
      • Connects skin and underlying bone/muscle
      • Loose connective tissue and elastin
      • Predominant Cells
        • Fibroblasts
        • Macrophages
        • Adipocytes
    • Damage to the Dermis
      • Age
        • Decreased ratio of Type I : Type III collagen
      • Photodamage and Tobacco Smoke (6)
        • Increase tissue collagenases and gelatinases
        • Further decrease collagen in the dermis
        • Decrease capillary and blood flow to skin
        • Decreased skin integrity
      • **Ultimately leads to decreased skin turgor and elasticity forming wrinkles and sagging skin (7)
    • Initial Evaluation
      • Patient selection is key
        • Unrealistic
        • Psychiatric history or multiple physician visits
        • Smokers have 12 times increased skin sloughing and scarring
      • Must perform proper:
        • Education
        • Counselling
        • Consistent procedural skills
    • Physical Exam
      • Are rhytids dynamic vs adynamic
        • Traction of skin in antagonistic direction
      • Hypo- or Hyperpigmented skin
      • Associated skin conditions
      • Active infection
      • Thickness of skin
      • Glogau System
    • Glogau System (8)
      • Stratifies patients based on amount of aging and skin damage
      • Category I
        • Photoaging down to stratum granulosum or papillary dermis with minimal wrinkles
        • Dermabrasion or superficial chemical peeling
      • Category II
        • Photodamage down to upper reticular dermis and wrinkles with facial gestures
        • Medium depth chemical peeling
      • Category III
        • Photodamage down to upper reticular dermis and wrinkles at rest
        • Medium depth peels
      • Category IV
        • Photodamage to mid reticular dermis, wrinkles, skin discoloration
        • Deep peel required
    • Treatment Options
      • Dermabrasion
      • Laser Resurfacing
      • Chemical Peels
      • Facial Fillers
    • Dermabrasion
      • Purpose is to level the skin and promote re-epithelialization with new collagen deposition.
      • Used for:
        • Scar revision
        • Acne scarring
        • Rhinophyma
        • Facial rhytids
      • Contraindicated for Keloids and Hypertrophic Scars
      • Must only injure only the papillary dermis
        • Preserves adnexal structures for re-epithelialization
        • Damage through the reticular dermis (Fat visualized) leads to adverse scarring
    • Dermabrasion
      • Performed with high speed diamond fraise or wire brush.
      • Local anesthesia +/- IV sedation
      • Broad surfaces are frozen to maintain rigid tissue (malar region)
      • Brush strokes are made at right angles to the brush rotation to avoid loss of control and damage to normal tissue
      • Feathering : Edges are slightly brushed for blending
    • Dermabrasion
      • Upper layers of skin are removed resulting in partial thickness wounds
      • Small pinpoint bleeding of the wound
      • Heal by re-epithelialization in 7-10 days
      • Recovery is 2-3 weeks
    • Microdermabrasion
      • Alternative to dermabrasion that attacks just the upper layer of skin
      • Disadvantages
        • Only good for early photodamage and superficial wrinkles
        • Not useful for dermal pathology
      • Uses Aluminum oxide microcrystals
      • Advantages
        • Repeated at short intervals
        • Painless requiring no anesthesia
        • Minimal erythema and side effects
    • Microdermabrasion
      • Freedman 2001 (9)
        • 10 patients treated with 6 treatments
        • Physical exam and tissue biopsy
        • Thickened epidermis and dermis with newly deposited collagen
      • Karimipour 2010 PRSJ (10)
        • Very good for skin contour irregularities such as rhytids
        • Less effective with dyschromias than glycolic acid peels
        • No RCT to evaluate uses in acne but decision should be based on patients expectations
    • Picture of Debridment Instrument
    • Dermabrasion Results
    • Laser Resurfacing
    • Laser Resurfacing
      • Works by targeting chromophores
      • Each laser has a different chromophore:
        • Water, oxyhemoglobin, melanin, etc.
      • Chromophore absorbs the laser heat destroys cells harboring that chromophore
      • Amount of chromophore in a cell is proportional to absorption/destruction
      • Lasers have opened the door for treatment of periocular skin where dermabrasion cannot reach
    • Ablative Lasers
      • Carbon Dioxide (10,600nm)
        • Used with the same indications as dermabrasion
        • Wavelength selectively targets water in soft tissue
        • More collagen production and prolonged redness due to dispersed thermal injury
      • Other advantages
        • Hemostatic properties
        • Depth of treatment is more precise with laser
          • Skin tightening is immediate
          • Skin irregularities are improved immediately
    • Ablative Lasers
      • Erbium:YAG (2,940nm)
        • Reduced thermal damage
          • Less post-therapy redness
          • Less collagen production
      • Newman et al. 1999 (11)
        • Compared Er:YAG and CO2 laser
        • 21 patients with half the upper lip treated by each laser
        • Er:YAG had less days of crusting 3.4 compared to 7.7
        • 63% vs 54% improvement at 2 months favoring CO2
    • Other Lasers
      • Nd:YAG Laser (1,064nm)
        • Infrared, invisible, oxyhemaglobin, deep penetration
        • Good for port-wine stains, telangiectasias, hemangiomas
      • KTP (532nm)
        • Visible, oxyhemaglobin absorption
        • Good for cutaneous lesions
      • Argon (193nm)
        • Visible, broad blue band, oxyhemaglobin
        • Penetrates between CO2 and Nd:YAG
        • Same indications as Nd:YAG
      • Flashlamp Excited Pulsed Dye (595 nm)
        • Visible, yellow light, vascular sensitive
        • Less scarring and hypopigmentation than Nd:YAG & Argon
        • Cutaneous vascular lesions
    • Effectiveness of Lasers
      • Bisson in 2002 evaluated 31 patients (12)
        • At 6 weeks wrinkle depth reduction of 91%
        • At 2 years wrinkle depth reduction of 87%
      • 2001 Lasers are falling out of favor (13)
        • 88% of patients considered post-therapy results very good.
        • 77% would not be willing to have procedure again.
      • **Several studies have shown equivalent results of CO2 lasers compared to dermabrasion (14-16)
    • Laser Resurfacing Results
    • Complications of Dermabrasion/Laser Resurfacing
      • Infection (17)
        • Bacterial infection rates 4.3 to 12%
        • Fungal infection rates 1.8 to 2.2%
      • Hypo/Hyperpigmentary mismatches
        • Dark Skinned Patients
        • Melasma or Cholasma associated with OCP’s
        • Photosensitivity post-procedure should be prevented with UV blocking lotions for 2 months (18-19)
      • Scarring Risk
        • Must stop 13-cis-retinoic acid (Accutane) for 6-12 months prior to therapy (20)
      • Milia Formation
        • Small epidermal cysts common after dermabrasion
        • Can be prevented with occlusive ointments or dressings for 1-2 weeks
        • Can be treated with abrasive cleansers or scalpel
      • Herpes Simplex Risk
        • Roberts et al 1997 (21)
          • Studied 907 patients with CO2 laser treatment and found that HSV infection of 3% was reduced to 1% with acyclovir prophylaxis
          • Therefore patients treated with antivirals for 2-3 days prior and 7-10 days post procedure
    • Laser Resurfacing Redness
    • Melasma/Chloasma
    • Milia
    • Chemoexfoliation
      • Controlled wounding of skin to induce regeneration and a more youthful appearance
      • Most commonly used for photodamage that leads to
        • Thickened Stratum Corneum
        • Thinned Stratum Spinosum
        • Disorganized maturation and elastin
        • Decreased dermal collagen and GAG’s
        • Irregular melanin dispersion
      • Skin is rough, wrinkled and mottled
    • Damaging Levels
      • Stratum Corneum
        • Skin feels smoother
      • Epidermal Basement Membrane
        • Melanocytes live here
        • Lighter and evenly pigmented
      • Upper Reticular Dermis
        • Smoother and lighter skin
        • Deposition of new collagen, elastin, GAG’s
        • Subsequent reduction of fine wrinkles
      • Middle Reticular Dermis
        • More collagen production with reduction of deeper wrinkles
      • Deep Reticular Dermis
        • Collagen production can produce a scar
    • Factors that increase solution penetration
      • Solution Concentration
      • Condition of Skin
        • Pre-treatment tretinoin, electrolysis, surgery, waxing.
      • Pre-peel degreasing with alcohol or acetone
      • Application (brush, swab, sponge)
      • Rubbing
      • Time of contact
      • Occlusion with tape or petroleum jelly
    • Individual Results
      • Some argue that test patching is important because each person reacts so differently to each type of peel
        • Depth of penetration
        • Wrinkling response
        • Scarring
      • Post-therapy care should include ointment to promote healing, sun avoidance, and proper wound care to prevent infection
    • Patient Selection
      • Post-therapy appearance can be frightening
      • Make sure patients are:
        • Psychologically stable
        • Compliant with post-therapy care
        • Willing to stay out of the sun
        • Willing to wear makeup
      • Be sure to perform proper informed consent and document it appropriately
    • Topical Retin-A
      • First line therapy
      • Advantages
        • Reverses all the previously discussed findings of sun damage
        • Also decreases fine wrinkles, evens pigmentary differences, smoothes the skin
      • Disadvantages
        • Photosensitivity
        • Dries the skin out making moisturizers necessary
        • Class C pregnancy media
      • Can be combined with alpha hydroxy acids which are less effective but potentiate tretinoin preparations
    • Process of Skin Peeling
      • Cleansing
        • Septisol and acetone to decrease oil and scaliness of the skin
        • Jessner’s or 70% glycolic solution can be used first to break initial barriers and allow TCA to penetrate deeper (8)
      • Application
        • Superficial  blotchy white and red frost
        • Medium  white frost with surrounding erythema
        • Deep  solid white with no erythema
      • Healing
        • Cool saline presses to decrease inflammation
        • Vinegar soaks Q2 hours while awake for 5-7 days
        • Regular follow up to look for infection
    • Superficial Peels
      • Glycolic Acid
      • Trichloroacetic Acid 10%
      • Jessner Solution (lactate+salicylate+resorcinol+ethanol)
        • Apply for a few minutes then rinse with water or neutralize with bicarbonate solution
        • Stinging sensation and slight flush
        • Smooth glowing skin with no activity restrictions
        • Repeated doses Q week/2 weeks/4 weeks
      • If you want to peels down to the basement membrane
        • Slightly stronger concentration of solution
        • desquamation for 2-3 days
    • Superficial Peel Results
    • Medium Depth Peel
      • Amount of collagen depends on depth of peel and individual variations
      • Scarring occurs with any subepidermal wound but is unpredictable
      • TCA >50% have higher incidence of scarring (22-24)
      • TCA 35% in combo with Jessner or glycolic solution first help with penetration
      • Post treatment
        • Skin turns dark brown
        • Exfoliates for 4-7 days
        • Socially incapacitated for 7 days
        • New skin is very pink
    • Medium Peel Results
    • Deep Peels
      • Baker-Gordon Peel
        • Formulation
          • 3cc 88% phenol
          • 2cc water
          • 8 drops of septisol
          • 3 drops croton oil
        • Treatment
          • Agitate solution prior to usage
          • Cotton tip application to 1 section of face at a time
          • Slow application to regional subunits
            • Prevents systemic absorption and arrhythmias
        • Post Treatment
          • Frosting of skin is immediate
          • Swelling intense and release of epithelium over 1-2 days
          • Re-epithelialization takes over 1 week
          • Constant serous exudate hourly
          • Very red skin for months
          • Hypopigmentation expected
        • Results
          • Robust collagen formation is long-lasting
          • Fine and deep wrinkles respond well
    • Baker’s Peel Progression
    • Complications
      • Landau 2007 (23)
        • 181 patients with full face peels
        • 10-15 minutes between each face section
        • 6.6% arrhythmias
        • Increased with Diabetes, HTN, depression
      • Prevention
        • Sedation
        • IV hydration
        • EKG, LFT’s, Kidney function prior to therapy
        • Monitoring with close follow up
    • Complications
      • Infection
        • Usually result of poor post-procedural care
        • Bacterial, Fungal, or Herpetic
        • Prophylactic antivirals
        • Post-procedure antibiotics
        • Vinegar washes very important
        • Culture any non-healing wounds
    • Complications
      • Hyperpigmentation
        • Dark skin, OCP’s and pregnancy
        • Prophylaxis with hydroquinone
        • Treatment with Tretinoin, alpha hydroxy acid, and steroid cream
        • Sun avoidance before and after treatment plus sunscreen
        • Repeeling is an option if poor results occur
    • Complications
      • Scarring
        • Post-therapy infection
        • Use of oral accutane
          • Healing is by re-epithelialization from pilosebaceous units
          • Accutane destroys sebaceous units
        • Recently radiated skin
        • Recently operated skin (undermining)
        • History of keloids
    • Complications
      • Hypopigmentation
        • Occurs after deep peeling
        • More apparent in very dark or very light skin
        • Feathering of the peel with dermabrasion can camouflage the edges
    • Soft Tissue Augmentation
    • Soft-Tissue Augmentation History
      • Began in 1893 Neuber harvested arm fat and injected it into the patients facial defects (24)
      • Fillers now used for
        • Scars from trauma and acne
        • Static or dynamic rhytids
        • Lip augmentations
        • Melolabial fold augmentation
      • 1900s paraffin injection used but fell out of favor due to paraffinomas (granulomatous reactions)
      • 40-50’s Silicone introduced
        • Granulomatous reactions and scarring limited its use
      • 1970’s Stanford used human and animal collagen
        • Still in use today in bovine form (25)
    • Modern Injectable Fillers
      • Research is huge in this area for the ideal filler
        • Inert, long lasting, abundant, low cost, no allergy, not carcinogenic, fixable
      • Patient demand high
        • Outpatient injection
        • No surgery
        • Minimal recovery 48-72 hours
        • Lower short term cost
      • Dermis is the #1 place of injection
        • Fibroblasts that produce type 1 collagen are most abundant in this region
    • Types of Fillers
      • Xenografts
      • Homografts
      • Autografts
      • Synthetics
    • Xenografts
      • Bovine Collagen
      • Most widely used and is the “Gold Standard”
      • All are dissolved in saline and lidocaine and Pepsin proteolysis to decrease antigenicity
        • Zyderm I (35mg/mL)
          • Injected into upper dermis
          • Poor long term effect because of low concentration
          • Overcorrection necessary 100% (26)
        • Zyderm II (65mg/mL)
          • Injected into mid dermis
          • Longer effect with higher concentration
          • Overcorrection necessary 50% (26)
        • Zyplast (35mg/mL)
          • Cross linked with glutaraldehyde to decrease degredation
          • Injected into reticular dermis for longer duration/less resorption
          • No overcorrection recommended
    • Bovine Collagen Complications
      • Hypersensitivity reaction
        • Tenderness
        • Induration
        • Erythema
        • Pruritis
      • Skin testing before definitive use
        • 3-4% with positive skin test (27,28)
      • 20 to 30% may show delayed reaction
        • Must examine skin test site in 4 to 6 weeks prior to initiating therapy
      • Some argue that second skin test necessary as reactions can occur with repeated injections
      • Other complications
        • Tissue necrosis (29)
        • Foreign body reaction
        • Headache/Nausea/Arthralgias (30)
    • Homografts
      • Cosmoderm and Cosmoplast
        • Bioengineered collagen from fibroblasts
          • No antigenicity so no skin testing required
        • Packaged and concentrated analogously to Zyderm I and Zyplast respectively
          • Cosmoderm for superficial wrinkles
          • Cosmoplast for deeper scars and grooves
        • On average they last 3-6 months but duration is less than bovine equivalents (26)
    • Homografts
      • Alloderm (Cymetra = injectable form)
        • Acellular dermal graft from cadaveric skin
        • Freeze drying process removes cells but leaves collagen IV, VII, proteoglycans and elastin
        • Requires reconstitution with lidocaine prior to injection
        • No skin testing required
        • Duration of 3 to 6 months (31)
    • Xenografts
      • Hyaluronic Acid
        • A Glycosaminoglycans (GAG)
        • Can hold 1000x its weight in water leading to increased skin turgor
        • Overcorrection not required
        • Identical in all species leading to minimal immunogenicity
        • <1% chance of hypersensitivity
        • Correction achieved for 6-9 months with HA (32)
        • Hylaform (500 micron, 5.5mg/mL)
          • Purified from rooster combs
          • Few reports of local or systemic reactions from avian protein
          • Shortened lifespan due to lower concentration (33)
        • Restylane (400 micron, 20mg/mL)
          • Bacterial cultures of Equine steptococci
          • Cross linked with epoxides
          • Also has “Fine Lines” and “Perlane” formulations with diffent particle sizes
      • Isovolumetric contraction where matrix does not disperse water until all hyaluronic acid particles are degraded leading to prolonged effects (34)
    • HA Pitfalls
      • Must inject intradermally
        • Injection too deep
          • Decreased duration of action
        • Injection too superficial
          • Unappealing bumps
      • **Undesirable injections can be corrected with hyaluronidase injection.
    • Autografts
      • Fat
        • Very abundant
        • No antigenic potential
        • Requires additional procedure for harvesting
          • Liposuction
        • Questions regarding how much is reabsorbed
        • Adynamic melolabial folds have prolonged duration of action compared to dynamic glabella (26)
    • Autografts
      • Isolagen (Fibroblasts)
        • Postauricular punch biopsy of patients skin
        • Cultured in vitro with growth factors for 4-6 weeks
        • Overnight delivery for injection the following day
        • Several Treatments required for desired outcome
        • Cost and time considerations make it impractial
        • 6 month histologic evaluation showed integration of fibroblasts but is on hold by FDA due to growth factors and further studies (35)
    • Synthetic Material
      • Silicone
        • Been used for over 50 years
        • Requires multiple microdroplet injections over 4 weeks
        • Injections performed into deep dermis 1 to 3mm apart
        • No overcorrection because innate reaction to the product was part of the process
        • Webster studied 235 pts over 2800 injections (36)
          • Good results and few complications
        • Others have shown extensive reactions (37-39)
          • Chronic inflammation
          • Migration
          • Extrusion ulceration
          • Skin necrosis
          • Granulomatous hepatitis
          • Pulmonary emboli
          • Silicosis (pneumonitis)
      • FDA declared it illegal in 1991 but recent use for retinal detachment is bringing off label use back
      • American Academy of Dermatology (1993) (7)
      • “ There is a wealth of clinical experience in dermatology with the use of liquid injectable silicone by the micro-droplet technique which shows its efficacy and safety in many individuals over many years.”
    • Synthetic Material
      • ArteFill
        • Combined 20% polymethylmethacrylate and 80% bovine collagen
        • Skin testing required
        • As collagen is degraded (4 months) the PMMA is encapsulated to maintain augmentation
        • Injected into the subdermis to prevent persistent painful nodule
        • Individual results are unpredictable so multiple injections are required over 3-4 months with 50 to 75% permanent correction (25)
        • Overcorrection not recommended because each result is different
      • Lemperle (Bailey 37 ) showed good results with minimal complications
      • Others report granulomatous reactions and scarring (Bailey 38 ).
      • Not approved in US but Europe has shown long term correction of >10 years (7)
    • Synthetic Material
      • Radiesse (25 to 45 micron size)
        • 35% synthetic hydroxyapatite particles in water, glycerin, and sodium carboxymethylcellulose
        • Injeted into deep dermis or subdermally due to viscosity
        • Massage is necessary to contour product
        • Produces augmentation in 2 ways
          • Collagen ingrowth by fibroblasts
          • Encapsulation of crystals by fibroblasts to prevent degredation
        • Radiographic evidence of implant for up to 6 years (40)
        • Pitfalls
          • Injection into lips can produce painful nodules
          • Palpable implant for 2 to3 months until the product is replaced by collagen
        • Tzikas studied 90 patients and found 88% patient satisfaction at 6 months (41)
    • Post-therapy Findings
      • Post-injection pain
      • Redness
      • Ecchymosis
      • Swelling
      • Nodularity
      • Palpability
      • **Should be transient and resolve over 1-2 days
    • Complications: 0-2 days
      • Overcorrection
        • Know the properties of the injectable filler and whether to overcorrect or not
      • Implant visibility
        • HA can produce bluish nodule
        • Other fillers cause white nodule
          • Massage can help
          • Hyaluronidase or mechanical deroofing of nodule
      • Vascular compromise
        • Arterial: Immediate skin blanching with necrosis (glabella)
          • Aspiration, massage, warm compress, 2% nitropaste
          • +/- hyperbaric oxygen for impending necrosis
        • Venous: violaceous discoloration with dull ache
          • Nitropaste and warm compresses
      • **Skin breakdown treated with Abx and gentle debridment
    • Venous Injury
    • Complications: 3-14 days
      • Noninflammatory Nodules
        • Observation, gentle massage, reassurance
      • Early Inflammatory Nodules
        • Treat with antibiotics for 4-6 weeks
          • Macrolide and Tetracycline
        • I&D plus culture if fluctuance is observed
        • Close f/u visit at 48 hours
          • If no response to therapy get tissue culture
    • Tissue Infection Immediate Day 2
    • Complications: >14 days
      • Hypersensitivity
        • Bovine collagen 3-4% + skin test
        • HA <1%
      • Nodules
        • Saline injection and vigorous massage
      • Inflammatory nodules
        • Evaluate for infection and treat as necessary
        • No infection but no response at 7-10 days  add intralesional steroid injection to avoid resistant granuloma
        • Still no response  biopsy and culture
      • True Granulomas (0.01-1%)
        • Massage and Intralesional steroids
    • Summary
      • There are a variety of treatment options available
      • Proper knowledge of the product or procedure is necessary to avoid complications
      • Patient expectations, informed consent, and proper patient selection is paramount
    • References
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      • F. Blanco-Davila, Beauty and the body: the origins of cosmetics, J Am Soc Plast Reconstruct Surg 105 (3) (2000), pp. 1196–1204
      • J. Golan and N. Hai, JetPeel: a new technology for facial rejuvenation, Ann Plast Surg 54 (4) (2005), pp. 369–374
      • J. Uitto, E.F. Bernstein and J.A. McGrath, The dermis vol. 1. In: C.R. White Jr, M. Bigby and O.P. Sangueza, Editors, Cutaneous Medicine and Surgery: An Integrated Program in Dermatology , W.B. Saunders Company, Philadelphia (1996), pp. 857–881
      • S. Brooke and J. Griffiths, Interventions for photodamaged skin, Cochrane Database Syst Rev 1 (2005) CD001782
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      • J. Newman, J. Lord and K. Ash et al. , Variable pulse erbium:YAG laser skin resurfacing of perioral rhytides and side-by-side comparison with carbon dioxide laser, Lasers Surg Med 25 (2) (1999), pp. 208–214
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      • J. Kitzmiller, M. Visscher and D. Page et al. , A controlled evaluation of dermabrasion versus CO2 laser resurfacing for the treatment of perioral wrinkles, Plast Reconstruct Surg 106 (6) (2000), pp. 1366–1372
      • K. Holmkvist and G. Rogers, A comparison of dermabrasion and superpulsed carbon dioxide laser, Arch Dermatol 136 (2000), pp. 725–731
      • S. Gilbert, Improving the outcome of facial resurfacing—prevention of herpes simplex virus type 1 reactivation, J Antimicrob Chemother 47 (2001), pp. 29–34
      • Hinman CD, Maibach H. Effects of air exposure and occlusion on skin wounds. Nature 1963;200:377
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