Adjunctive and Anti-Aging Therapies
By Marisa Lawrence

The skin, soft tissues, and structural support of the human face are all affected by the aging process.  Successful treatment of facial rejuvenation requires combination therapies that address visible aging changes and their underlying causes.  Facial contour changes associated with aging are the result of soft tissue descent, skeletal remodeling, and atrophy of fat.  A rhytidectomy, or “facelift,” is only part of the answer for most patients with facial aging.  Botulinum toxin injections, dermal fillers, and skin tightening devices are playing an important role in both enhancing surgical results as well as reversing signs of aging in patients who wish to avoid larger procedures and the associated downtime.

Botox Cosmetic (Allergan, Inc., Irvine, CA), or Botulinum Toxin Type A, is a complex structure composed of a 150 kd pure neurotoxin and non-active proteins that protect the neurotoxin from degradation.  Botox Cosmetic works at the neuromuscular junction by inactivating SNAP-25, thereby preventing acetylcholine vesicles from binding to the axonal plasma membrane.(1)  This cholinergic inhibition effectively eliminates the action potential and subsequent contractions of the small muscles of interest to eliminate facial wrinkles.  (Figure 1)  Botox Cosmetic is currently only FDA-approved for the glabella area.  Any other cosmetic use –periorbital and perioral regions, transverse forehead lines – is considered off-label.  Results take several days to one week to take effect and last an average of 4-6 months.  Regular treatments are required to maintain results.  Side effects such as blepharoptosis, lower eyelid ectropion, and diplopia have been reported with the use of Botox Cosmetic.(2) Botox Cosmetic injections can be used in combination with dermal fillers to prolong and enhance results.  Pricing per Botox Cosmetic treatment varies from one physician’s office to another.  Presently, Allergan charges $485 for 100 units of Botox Cosmetic.

Dermal fillers are used for soft tissue augmentation in plastic surgery, laryngology, urinary incontinence, vesicourethral reflux, gastroesophageal reflux, and fecal incontinence.  The ideal filler is biocompatible with human tissue, inert, durable, and easy to inject.  Historically these agents were limited to fat transplantation, collagen, and off-label materials with variable success and numerous complications. (3)  The recognition of the importance of soft tissue volume loss as a component of facial aging has led to a renewed interest in reliable soft tissue augmentation.  Within the last several years, there has been an explosion in the introduction of new fillers from a variety of sources for both permanent and nonpermanent use.

Fillers are classified into four major types: synthetic, xenogenic, homogeneic, and autogenic. (4)  Synthetic fillers include silicone, calcium hydroxylapatite, and poly-methylmethacrylate beads (PMMA).   Xenograft fillers, donor and recipient from different species, include bovine collagen and hyaluronic acid derivatives.  Homogeneic fillers, donor and recipient from the same species, include agents derived from accredited tissue bank human cadaveric tissue.  Autogeneic materials, donor and recipient from the same individual, include autologous fat, autologous collagen, and dermal fibroblasts.

Liquid silicone injections have had the longest history of clinical application and the greatest amount of controversy.  Silicone is a generic name for a group of polymers which are based on the element silicon and which range in viscosity from fluids to solids.  Currently there are two FDA-approved, medical grade liquid injectable silicone devices for ophthalmologic use to tamponade retinal detachments: Adatosil 5000 (Bausch & Lomb Surgical, Claremont, CA) and Silikon 1000 (Alcon Laboratories, Inc. Fort Worth, TX).  The use of liquid silicone for soft tissue augmentation is off-label.  Liquid injectable silicone is a permanent filler.  Potential adverse reactions include chronic inflammation, persistent foreign body reaction, and granulomas, which may occur 1 month to 25 years after treatment. (5)    

Radiesse (Bioform Inc, Franksville, WI), formerly known as Radiance, is comprised of calcium hydroxylapatite microspheres suspended in a carboxymethylcellulose gel carrier.  It is biocompatible as the calcium and phosphate ions are identical to the mineral portion of bone.  Metabolism of the product occurs via the macrophage phagocytosis system similar to degradation of small bone fragments. (6)  The longevity of Radiesse has been reported to be 11-13 months for facial soft tissue augmentation.  Radiesse is an ideal filler for deeper rhytids along the oral commissures, marionette lines, and nasolabial folds. (Figure 2)  In the lips there is a potential for nodule formation secondary to extravasation of material with lip movement.  Radiesse is currently FDA cleared for radiographic tissue marking, vocal fold augmentation, and oral maxillofacial defects, but its use in soft tissue augmentation is still considered off-label.  Cost to the patient per 1.3cc syringe of Radiesse is about $1000.00.

ArteFill (Artes Medical, San Diego, CA) is being promoted as a permanent injectable that is expected to receive final FDA approval early this year.  ArteFill, known as Artecoll in Europe and Canada, is composed of homogeneous PMMA microspheres suspended in 3.5% purified bovine collagen.  Once injected, Artefill stimulates the body’s own production of collagen, which encapsulates each microsphere and thus builds volume to correct wrinkles. (7)  Results with Artecoll can be seen at 3 years post- injection and beyond. (7)  PMMA microspheres are nonbiodegradable but too large to be phagocytized or migrate.  Artecoll has been manufactured and marketed by an independent European distributor since 1994 and used in more than 200,000 patients worldwide with a reported complication rate of 0.01%. (8)

The collagen-based dermal fillers were first introduced in 1982 for the correction of facial lines. The bovine-derived products Zyderm and Zyplast (Inamed Aesthetics, Santa Barbara, CA) required a skin test prior to use and were soon replaced by the human-derived CosmoDerm and CosmoPlast (Inamed Aesthetics, Santa Barbara, CA).  CosmoDerm is indicated as a dermal filler for fine lines.  CosmoPlast is cross-linked with glutaraldehyde for a thicker consistency and is more appropriate for deeper wrinkles.  Injected collagen is fairly rapidly resorbed with loss of clinical effect and histological presence by 3-6 months.  Most physicians price collagen at $450.00-500.00 per 1.0 syringe.

Hyaluronic acid (HA) is a polysaccharide naturally found in the extracellular space of human dermis.  HA fillers are composed of linear molecules that, once injected, coil to form a unique three-dimensional structure that can retain water molecules (9).  Restylane (Medicis Aesthetics, Inc., Scottsdale, AZ) is biosynthetically produced by bacterial fermentation and was FDA approved for dermal implantation in 2003. Correction with Restylane lasts an average of 6-9 months (Figure 3).  The cost of Restylane is about $450.00-500.00 per 1cc syringe.  Hylaform, Hylaform Plus, and Captique (Inamed Aesthetics, Santa Barbara, CA) are HA fillers composed of Hylan B gel that are FDA approved for injection into the nasolabial folds. The Hylaform products are derived from a highly purified avian source; Captique is derived from a bacterial source.  These products have been reported to last 4-6 months.  Pricing for Hylaform and Captique are similar to Restylane.  Newer products being marketed include Puragen (Mentor Corp., Santa Barbara, CA) with double cross-linked HA molecules for longer lasting results, and Juvederm (Inamed Aesthetics, Santa Barbara, CA) derived from bacterial fermentation for improved resistance to enzymatic degradation.

Sculptra (Dermik Laboratories, Berwyn, PA) is FDA approved for treatment of facial lipoatrophy in persons with HIV infection.  This product, a poly-L-lactic acid (PLLA) material, is also being used by some physicians off-label as a volume restorer for cosmetic enhancement of non-HIV patients.  Poly-L-lactic acid is a biocompatible, biodegradable polymer used in resorbable sutures and facial implants.   It is injected subdermally and provides immediate benefit due to volume filling and some post-treatment edema. As the polymer slowly begins to degrade over a period of weeks, collagen remodeling occurs to augment volume and maintain the treatment effect for up to 2 years.  Patients typically receive a series of two to four injections that are administered at intervals of two to four weeks. (10)

The use of autogenous fat to correct facial soft tissue defects has been reported in the scientific literature since the early 1900’s.  The procedure involves removing fat cells from the patient’s abdomen, thighs, or buttocks and replacing them beneath the facial skin. Duration of fat injections varies significantly from patient to patient.    Though some patients have reported results lasting a year or more, the majority of patients have at least half of the injected fullness disappear within 3-6 months. (11)

Skin toning and tightening devices fall into four types based on the energy source used to penetrate the dermis.  Current devices include nonablative lasers -pulsed-dye (585 nm, 595 nm), Nd:YAG (1064 nm, 1320 nm), diode (910 nm, 1450 nm) and fractional resurfacing (1550 nm) , or pulsed- light systems (500-1200 nm), monopolar and bipolar radiofrequency devices, LED, plasma energy and electrical stimulation. 

The Fraxel SR laser (Reliant Technologies, Inc., Mountain View, CA) is uniquely designed to create columns of microthermal treatment zones (MTZ) with pulsed energy surrounded by uninjured tissue.  These microlesions are characterized by an intact stratum corneum, coagulated epidermis that promotes rapid removal of undesirable pigment, and deep columns of denatured collagen initiating long-term dermal remodeling.  Zones of spared tissue adjacent to each MTZ provide a healthy reservoir of epidermal stem cells and dermal fibroblasts to permit rapid wound healing.   Reproducible and clinically proven outcomes indicate that results are superior to the non-ablative lasers that rely on selective photolysis alone. (12)  The FDA has approved the Fraxel Laser for skin resurfacing, soft tissue coagulation, and the treatment of pigmented lesions, periorbital rhytides and melasma.  Typical pricing for the Fraxel Laser treatment is variable but a minimum of 3-5 treatments necessary to obtain desired results.

Thermal Cool TC System (Thermage, Inc., Hayward, CA) uses monopolar radiofrequency energy to selectively heat dermal and subdermal tissue to produce modest tissue tightening through dermal collagen remodeling. The final result relies on a gradual remodeling of collagen and takes approximately 3-6 months.  A single Thermage treatment costs approximately $2500.00.  The newer Aluma Skin Renewal System (Lumenis, Santa Clara, CA) – recently cleared by the FDA for treatment of rhytids and wrinkles – uses bipolar radiofrequency with a vacuum-assisted hand piece that bypasses the epidermis and penetrates the deeper layers of skin.  According to Dr. Mitchell Goldman, associate clinical professor of dermatology  at UCSD and medical director of La Jolla Day Spa, treatment is virtually painless and a 40% reduction in wrinkles is noticed in 4-6 months.

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For a patient who desires extensive correction of multiple deep-lines, ablative laser resurfacing may be a more satisfying and economical choice. Deeper dynamic wrinkles are best treated with the CO2 laser whereas fine facial wrinkles may be treated with either the CO2 or Erbium laser.  Both of these laser treatments stimulate natural collagen production within the dermis.  Erbium laser resurfacing can be performed in an office setting with topical anesthetic.  There is typically less redness than with a CO2 laser and patients are fully recovered in 5-7 days.  CO2 laser treatment is commonly performed under sedation and requires 7-10 days for the initial healing.  Patients may experience facial erythema for up to 6 months after resurfacing.  CO2 and erbium laser treatments are not approved for all skin types and have a risk of hypopigmentation in the treatment areas.

With increasing popularity and apparent safety of non-surgical facial rejuvenation, multimodality treatment is playing an increasing role in the anti-aging and cosmetic surgery market.  Botox injections, dermal fillers, and skin tightening devices may be used alone or in combination to improve and prolong results.  Although results are often modest in comparison with aesthetic surgery techniques, these adjuvant therapies clearly allow more patients to diminish facial wrinkles, augment tissue volume, and improve facial laxity with less expense and healing time.