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

1. Dermabrasion

2. Laser Resurfacing

3. Chemical Peels

4. 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

LaserResurfacing

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 Lasers1. Nd:YAG Laser (1,064nm)

• Infrared, invisible, oxyhemaglobin, deep penetration• Good for port-wine stains, telangiectasias, hemangiomas

2. KTP (532nm)• Visible, oxyhemaglobin absorption• Good for cutaneous lesions

3. Argon (193nm)• Visible, broad blue band, oxyhemaglobin• Penetrates between CO2 and Nd:YAG• Same indications as Nd:YAG

4. 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

1. Xenografts

2. Homografts

3. Autografts

4. 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)1. 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)

2. 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

• 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

1. Collagen ingrowth by fibroblasts2. 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 daysadd intralesional

steroid injection to avoid resistant granuloma – Still no responsebiopsy 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

References1. S. Friedman and J. Lippitz, Chemical Peels, Dermabrasion, and Laser Therapy. Dis Mon 55(4);2009: 223-2352. J.M. Stuzin, Phenol peeling and the history of phenol peeling, Clin Plast Surg 25 (1998), p. 1 3. F. Blanco-Davila, Beauty and the body: the origins of cosmetics, J Am Soc Plast Reconstruct Surg 105 (3) (2000), pp. 1196–1204 4. J. Golan and N. Hai, JetPeel: a new technology for facial rejuvenation, Ann Plast Surg 54 (4) (2005), pp. 369–374

5. 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

6. S. Brooke and J. Griffiths, Interventions for photodamaged skin, Cochrane Database Syst Rev 1 (2005) CD001782

7. Athre RS. Facial filler agents. Operative Techniques in Otolaryngology 2007; 18: 243-247.8. G. Monheit, Chemical peels, Skin Ther Lett 9 (2) (2004), pp. 6–11 9. B.M. Freedman, E. Rueda-Pedraza and S.P. Waddell, The epidermal and dermal changes associated with microdermabrasion,

Dermatol Surg 27 (12) (2001), pp. 1031–1033 10. Karimipour DJ, Karimipour G, Orringer JS. Microdermabrasion: An Evidence-Based Review. Plast Reconstr Surg. 2010 125(1):372-

377 11. 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 12. Bisson MA, Grover R, Grobbelaar AO. Long-term results of facial rejuvenation by carbon dioxide laser resurfacing using a

quantitative method of assessment. Br J Plast Surg 2002;55(8):652–656.13. Trelles MA, Pardo L, Ayliffe P, et al. Patients' answers to a postoperative questionnaire related to laser resurfacing. Facial Plast Surg

2001;17(3):187–19214. J. Chew, I. Gin and K. Rau et al., Treatment of upper lip wrinkles: a comparison of 950 usec dwell time carbon dioxide laser with

unoccluded baker's phenol chemical peel, Dermatol Surg 25 (4) (1999), pp. 262–266 15. 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 16. K. Holmkvist and G. Rogers, A comparison of dermabrasion and superpulsed carbon dioxide laser, Arch Dermatol 136 (2000), pp.

725–731 17. S. Gilbert, Improving the outcome of facial resurfacing—prevention of herpes simplex virus type 1 reactivation, J Antimicrob

Chemother 47 (2001), pp. 29–34 18. Hinman CD, Maibach H. Effects of air exposure and occlusion on skin wounds. Nature 1963;200:37719. Farrior RT. Dermabrasion in facial surgery. Laryngoscope 1985;95:53420. Stegman SS. Avoid dermabrasion soon after Accutane therapy. Schoch Lett 1984;34:44

References21. T.L. Roberts, C. Weinstein and J.K. Alexandidies et al., Aesthetic CO2 laser surgery: evaluation of 907 patients, Aesthet Surg J 17 (1997), pp.

293–303 22. H.J. Brody, Chemical Peeling and Resurfacing (2nd ed.), Mosby-Year Book, St. Louis, MO (1997) 23. M. Landau, Exogenous factors in skin aging, Curr Probl Dermatol 35 (2007), pp. 1–13 24. Neuber F. Fettransplantation. Chir Kongr Verhandl Dsch Gesellch Chir 22;66:189325. Klein A, Elson M. The history of substances for soft tissue augmentation. Dermatol Surg 26(12);1096:2000

26. C.A. Murray, D. Zloty and L. Warshawski, The evolution of soft tissue fillers in clinical practice, Dermatol Clin 23 (2005), pp. 343–363

27. Framer FM, Churukium MM. Clinical use of injectable collagen: a three-year retrospective review. Arch Otolaryngol 1984;110:93–9828. Cooperman LS, Mackinnon V, Bechler G, et al. Injectable collagen: a six-year clinical investigation. Aesthetic Plast Surg 1985;9:145–15129. Hanke CW, Hingley HR, Jolivette DM, et al. Abscess formation and local necrosis after treatment with Zyderm or Zyplast collagen implant. J Am

Acad Dermatol 1991;25:319–32630. Overholt MA, Tschar JA, Font RL. Granulomatous reaction to collagen implant: light and electron microscopic observations. Cutis 1993;51:95–98

31. J.M. Owens, Soft tissue implants and fillers, Otolaryngol Clin N Am 38 (2005), pp. 361–369

32. S.L. Matarasso, J.D. Carruthers, M.L. Jewell and Restylane Consensus Group, Consensus recommendations for soft-tissue augmentation with nonanimal stabilized hyaluronic acid (Restylane), Plast Reconstr Surg 117 (suppl) (2006), pp. 3S–34S

33. J. Rao, G.C. Chi and M.P. Goldman, Clinical comparison between two hyaluronic acid-derived fillers in the treatment of nasolabial folds: Hylaform versus restylane, Dermatol Surg 31 (2005), pp. 1587–1590

34. R.S. Narins and P.H. Bowman, Injectable skin fillers, Clin Plast Surg 32 (2005), pp. 151–162

35. Watson D, Keller GS, Lacombe V, et al. Autologous fibroblasts for treatment of facial rhytids and dermal depressions. Arch Facial Plast Surg 1999;1:165–170

36. Webster RC, Fuleihan NS, Gaunt JM, et al. Injectable silicone for small augmentations: twenty year experience in humans. Am J Cosmet Surg 1984;1(4):1–10

37. Ellenbogen R, Ellenbogen R, Rubin L. Injectable fluid silicone therapy: human morbidity and mortality. JAMA 1975;234:308–30938. Ficarra G, Mosqueda-Taylor A, Carlos R. Silicone granuloma of the facial tissues: a report of seven cases. Oral Surg Oral Med Oral Pathol Oral

Radiol Endod 2002;94(1):65–7339. Pearl RM, Laub DR, Kaplan EN. Complications following silicone injections for augmentation of the contours of the face. Plast Reconstr Surg

1978;61:888–891

40. P. Flaharty, Radiance, Facial Plast Surg 20 (2004), pp. 165–169

41. Tzikas TL. Evaluation of the radiance FN soft tissue filler for facial soft tissue augmentation. Arch Facial Plast Surg 2004;6:234–23942. Sclafani AP, Fagien S. Treatment of Injectable Soft Tissue Filler Complications. Dermatol Surg. 2009 Oct;35 Suppl 2:1672-80