Joseph L. Lin, MD, Jane J. Olson, MD, Norwalk, Conn.

Facial aging is characterized by skin quality changes, volume deflation of soft tissues, and descent of the facial muscles and fascia. The result is a change from a youthful heart-shaped face to a rectangular or pear-shaped face.1 Much of this volumetric change is due to atrophy of facial fat deposits. Additionally, the descent of soft tissues can be perceived as a forward drift from the malar region into the nasolabial area and jowl.2
Accompanying this soft tissue movement is remodeling of the underlying bone. These changes result in the features commonly associated with aging, including dynamic and static facial lines, temporal and cheek concavities, and an unmasking and protrusion of facial musculature.


Current Treatments

Current aesthetic treatments are aimed at restoring a youthful appearance. Skin quality may be enhanced by treatment such as chemical peels and CO2 laser resurfacing. Traditional surgical "face-lifting" addresses skin excess and perceived facial descent. Tightening of the face, however, may cause an unnatural two-dimensional flattening of the cheeks that is not seen in youth. The development of safe, effective, long-lasting filler products, the recent Food and Drug Adminstration approval of Sculptra Aesthetic for cosmetic volume augmentation, and the increased pricing pressures on traditional aesthetic surgery due to the economic downturn have highlighted the role of facial fillers in nonsurgical facial rejuvenation.

Facial fillers help restore youthful appearance by ameliorating soft-tissue deflation and gravitational effects. The evolving paradigm in injectable facial rejuvenation has been combination therapy. Chemodenervation with botulinum toxin type A (Botox and Dysport, now both FDA approved) achieves facial shaping by movement control, dermal fillers soften wrinkles, and deep fillers recontour and restore volume to the face.3,4,5 This recent prevailing view is a three-dimensional understanding of facial aging that emphasizes volume loss.6 Even in the lay press, public perception now embraces a conception of beauty that is focused on restoring a natural youthful appearance through multifaceted facial rejuvenation.7

Facial volume placement now emphasizes restoring the heart-shaped or upside-down egg-shaped face by injecting fillers in the upper face (i.e., malar, lateral zygomal, preauricular, subtemporalis, sub-brow, tear trough and upper eyelid sulcus areas) in addition to the traditionally emphasized lower facial areas. Volume enhancement and widening of the upper face contributes to the lifting effect of the nasolabial and melomental folds and jowls. Many FDA studies focus on filler effectiveness at the nasolabial folds due to ease of testing and administration. However, in our opinion, total ablation of the nasolabial folds looks odd and can produce a simian appearance.

The new role of dermal and deep fillers in facial rejuvenation is attracting considerable attention by aesthetic practitioners. However, filler treatment is just one component of a comprehensive facial rejuvenation. The overall aesthetic goal is to use fillers synergistically with surgery, laser- and light-based skin treatment, topical skin care, and botulinum toxin type A treatment.

The Layers of the Skin

In order to choose the appropriate dermal filler and inject accurately, it is important to understand the layers of the skin. Human skin consists of three layers: epidermis, dermis and subcutaneous fat. The outer layer of skin, or epidermis, serves the major barrier function of skin. Underneath the epidermis is the dermis. The dermis is largely acellular with a matrix of extracellular connective tissues and is made up principally of collagen.
Additionally, in the dermal space, there is a filling material that is most commonly composed of the glycosaminoglycans hyaluronic acid and dermatan sulfate.8 Under the dermis, subcutaneous fat cushions the skin and provides volume.

When choosing a filler, the aesthetic surgeon has a range of options. Fillers are useful in many facial areas and depths, including the forehead, glabella, temporalis, eyelids, nasal tip or dorsum, cheeks, nasolabial folds, melolabial folds (marionette lines), jawline, preauricular, earlobes, chin and lips. The site and depth of desired placement must be determined in order to choose the appropriate filler. Use in the eyelid can improve both superior sulcus deformity of the upper eyelid and tear trough deformity of the lower eyelid. Perioral applications include reduction of perioral lines, reduction of nasolabial folds and marionette lines, and lip augmentation and shaping. Novel applications of filling agents use their volume-occupying properties to replace lost subdermal fat and the decreased volume of remodeled maxillary and mandibular bones.9


Types of Fillers

    • Hyaluronic acid. Hyaluronic acid is a major component of the connective tissue matrix in the dermis. It can be found in skin, connective, epithelial and neural tissues. It is ubiquitous across all species and does not require skin allergy testing prior to injection, which makes it very convenient for daily use. This glycosaminoglycan has the ability to bind 1,000 times its volume in water, which makes it the perfect substance for adding volume to the skin. The hydrophilic nature of hyaluronic acid attracts and maintains water within the extracellular space, which affects dermal volume and compressibility. Older skin has been shown to have lower levels of hyaluronic acid than younger skin; the theory is that the loss of hyaluronic acid leads to loss of tissue hydration.10 An interesting property of the hyaluronic acid fillers is that as the molecules of hyaluronic acid degrade, the remaining molecules are able to bind more water and the overall volume remains unchanged.11 The result is that as the filler degrades, the volume remains relatively steady leading to a safe, stable effect.

Restylane (Q-Medical) became the first FDA-approved hyaluronic acid filler in the United States in December 2003. The filler is produced from cultures of Streptococcus equi. Restylane is most often used for facial wrinkles such as frown lines, downturned lip lines and the under-eye area or "tear trough."

A recent report also demonstrated the safe, effective use of hyaluronic acids for reinflation of medial/generalized upper eyelid hollowing or significant postblepharoplasty upper eyelid show.12 In our experience, injection in the superior sulcus and sub-brow areas can be effective in restoring deflated volume. It should, however, be placed gradually in small amounts, and avoided in the ptotic eyelid. When injecting the inferior orbital rim hollows and tear trough, the needle tip is placed at the supraperiosteal preseptal location, aspirated to avoid intravascular injection, and then slow injection of the product followed by molding is performed. We avoid attempting to fill wrinkles in the eyelid skin due to the thin dermis. Restylane effects can be expected to last up to 18 months with a single retreatment between 4.5 to nine months.13 Perlane (Q-Medical) is another hyaluronic acid filler that is administered at the same concentration but consists of larger injectable gel-particles. Used commonly to add volume to the cheek, jawline near the ears and nasolabial folds, the effects last about one year.

Juvéderm (Allergan) was approved by the FDA in June 2006 for the correction of moderate to severe facial wrinkles and folds. Juvéderm comes in multiple formulations, which include Juvéderm Ultra and Juvéderm Ultra Plus. The latter has differing proportions of crosslinked hyaluronic acid, which makes the product more viscous.
Overall, Juvéderm Ultra Plus is often used for correcting moderate to deeper facial grooves and furrows, and contour defects, particularly in enhancing the cheeks, nasolabial folds and jawline. Depending on the treatment location and product formulation, Juvederm is generally injected mid-dermis or slightly deeper for Ultra, and subdermal to supraperiosteally for Ultra Plus. Juvéderm Ultra is useful for shaping the pink and white areas of the lip as well as similar periorbital areas described for Restylane.
Effects generally last six to 12 months. However, all of the hyaluronic acid fillers' durations vary between patients and placement location.

• Poly-L-lactic acid. Sculptra Aesthetic (Dermik Laboratories) is injectable poly-L-lactic acid that was FDA-approved in August 2004 for correction of HIV-related facial lipoatrophy. Sculptra was FDA approved in July 2009 for cosmetic soft-tissue augmentation. Sculptra works by stimulating new collagen production, leading to a volume effect. There is a transient filling effect after the initial sterile water injection, followed by the slower, new collagen effect over a few months. For this reason, it is important to avoid over-injection of the filler. It is a synthetic, non-animal product, and allergy testing is not required.

In our experience, Sculptra is useful as a diffuse volume enhancer rather than a filler of specific wrinkles. For this reason, Sculptra is often used in conjunction with more immediate fillers to build a longer-lasting architecture to the face. It is injected just subdermally or supraperiosteally. Supraperiosteal placement of product builds deep volume to contour and augment the skeletal structure. Deep volume augmentation can be thought of as a non-surgical facial implant that can be placed in the chin, jawline, subtemporalis area or cheek.14 It is important to avoid intramuscular injection into areas of active muscle contraction (e.g., periorbital or perioral areas), which can localize product resulting in palpable and sometimes visible bumps of resultant collagen. Sculptra should not be used for lip augmentation due to the significant incidence of submucosal nodule formation. The product may be technically more difficult to inject because of the frequent occlusion with smaller needles and frequency of hematomas with larger ones.15
Higher dilution volumes (8 c.c. sterile injectable water/vial) and reconstitution a couple days in advance of injection have made injection smoother with collagen bumps less likely. Sculptra comes as a lyophilized powder that must be reconstituted in sterile water.
Some injectors add lidocaine during product reconstitution to decrease the pain of injection. Manual massage by the injector and patient post-treatment gives an even distribution of the product and pan-facial volume augmentation may be achieved.

A complete treatment with Sculptra generally requires a series of several injections of one to two vials, spaced four to six weeks apart. Treatments have been shown to stimulate new collagen for six to 12 months, with the volume effect lasting at least two years. Many injectors believe that the volume effects last longer than two years with the thought that new intrinsic collagen is unlikely to breakdown during this period. Patients should be warned that there will be delayed gratification, given that the predominant effect is from new collagen production.

   • Calcium hydroxyapatite. Radiesse, formerly known as Radiance or Radiance FN (BioFormMedical), is soft-tissue filler comprising calcium hydroxyapatite spheres suspended in an aqueous gel with glycerin and sodium hydroxycellulose. It was FDA-approved in December 2006 for facial lipoatrophy and nasolabial folds. Besides these aesthetic indications, it is also FDA-approved for oral/maxillofacial defects, vocal-cord insufficiency and radiographic tissue marking.

Hydroxyapatite is the mineral component of bone, so it is considered extremely biocompatible, and no allergy testing is required. After Radiesse injection, the hydroxyapatite acts as a scaffold for collagen ingrowth. Radiesse is highly viscous, and after injection it may be palpable for two to three months. The effects may last up to a year with the collagen stimulation effects likely lasting longer.

Radiesse can be used to treat deep folds, furrows and creases, to augment and lift cheeks, to emphasize cheekbones, to fill in hollows in the preauricular and temporal areas, and to bolster the jawline. Like Sculptra, product injection should be subdermal or deeper while avoiding areas of active muscle contraction or thin skin. Additionally, Radiesse should not be used in the lip due to of the risk of submucosal nodule formation.

• Collagen. Bovine collagen was considered the "gold standard" in dermal fillers because of the ease of use, availability, affordability and convenience. However, the risk of allergic reactions and the shorter duration of effect have limited its use.17 Currently, the most popular collagens are bioengineered human collagen products. CosmoDerm and CosmoPlast (Inamed Aesthetics) are approved for cosmetic use in the United States and are commonly used to fill moderate creases, fine wrinkles and depressed scars. Both products are also effective in enhancing lips and defining the lip border. They are believed to have a reduced allergy profile. The brief, several-month duration limits the use of collagens, but they can be useful for a quick touch-up with less bruising. Of note, a newly FDA-approved collagen called Evolence was recently discontinued by a division of Johnson & Johnson, Ortho Dermatologics, given poor market performance.

Dermal and deep fillers in combination treatment with botulinum toxin type A, are the mainstay of minimally invasive facial rejuvenation or "liquid face lift," and taken together account for over half of all nonsurgical aesthetic procedures performed in the United States.18 Additionally, the shift in treatment paradigms from simply treating wrinkles to restoring volume and facial contouring will likely increase the use of layering combinations of fillers going forward. The most comprehensive facial rejuvenation is achieved by vertical integration of surgical tissue repositioning or resection, laser- and light-based skin treatment, topical skin care, and botulinum toxin type A treatment in conjunction with dermal and volumizing fillers. Given the increasing popularity of filler use, ophthalmologists should become familiar with these products.

Dr. Lin is an ophthalmology resident in the Department of Ophthalmology and Visual Science at the Yale University School of Medicine. Dr. Olson is an ophthalmic facial plastic surgeon with private practices in Norwalk, Conn. and Baton Rouge, La. She is an associate clinical professor at Yale University School of Medicine. Contact her at: 148 East Ave., Ste. 1A, Norwalk Conn. 06851, phone: (203) 857-0115.


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