Hyaluronic acid (HA) is a collagen replacement product that comes in a variety of chemically similar but structurally different forms. HA is a naturally occurring glycosaminoglycan that is a major component of all connective tissue and exhibits no species or tissue specificity [22]. HA is a nonanimal product, and thus, there is no potential for an adverse immunologic reaction to HA. Therefore, no preinjection allergic testing is required. In addition, HA plays an important role in dermal hydration; decreases in HA with age result in reduced dermal thickness, increased skin wrinkling, and folding.

HAs are the most popular soft tissue filler in the United States and comprised 85 % of filler treatments in 2010 [23]. Restylane/Perlane (Medicis Aesthetics, Scottsdale, AZ) and Juvéderm Ultra/Ultraplus (Allergan, Irvine, CA) are the most popular HA products used as effective dermal fillers for cosmetic and reconstructive purposes. Patients who lack a severe degree of aging-associated facial volume loss may be candidates for HA injection. In addition, HA can be reversed within 12–24 h following injection of hyaluronidase. Juvéderm is FDA approved for 12 months on initial treatment and 18 months with retreatment for Restylane. However, anecdotally, both HAs can persist well beyond a year with documented occurrences of Restylane persisting for 5 years [24]. A 2007 report demonstrated that HA can stimulate collagen production [25] and perhaps this contributes to its extended correction. If placed in large quantities or if an early retreatment is given, the product seems to last longer and can persist at 36 months [26]. However, while the currently marketed soft tissue fillers are often thought of interchangeably, each HA has unique properties that should be considered when evaluating candidates for injection [27].

Juvéderm is marketed as the “smoother filler” with a gel-like 24 mg/mL concentration of HA and hydrophilic properties six times that of Restylane [28]. In contrast, Restylane is over six times more resistant to deformation than Juvéderm as defined by its rheological properties G’ [28]. It is the differences between Restylane and Juvéderm that the senior author frequently relies upon when selecting an HA for a specific indication. Juvéderm-corrected areas tend to lead to a fuller and more diffuse augmentation as water is absorbed. Moreover, the results of Juvéderm augmentation are more likely to be affected by the body’s current level of hydration. Consequently, knowledge of its greater hydrophilicity should be considered when injecting. In particular, Juvéderm, with its highly hydrophilic nature, tends to attract more fluid and, therefore, results in a diffuse filling effect.

For the buccal cheek space, the diffuse filling properties inherent to Juvéderm have shown to be more beneficial. However, in the infraorbital tear trough, Restylane is preferred. The differences between Restylane and Juvéderm are extremely apparent when placed into the loose areolar tissues surrounding the orbital region. When treating this area, the senior author prefers Restylane to Juvéderm as the latter will attract water, swell, and result in dark puffy under-eye circles representative of a tired unflattering appearance. While this can occur with both Juvéderm and Restylane when placed under the eyes, it—the Tyndall effect, in which the optical chamber of HA and fluid reflects blue light—is more commonly associated with Juvéderm. In patients with thin, translucent skin, the blueness is distracting and obvious.

Perlane and Juvéderm Ultraplus are HA products of a larger particle size. While both Perlane and Juvéderm Ultraplus are at the same concentration of HA as their smaller particle-sized counterparts, the large particle size provides a more robust alternative intended for deeper placement into the soft tissues with potential for greater product longevity [29]. However, clinically appreciable differences are not as apparent and rarely offset the greater cost of the product.

In addition to the current HA fillers available, the large particle Allergan Voluma and Restylane SubQ offer potential advances in facial shaping. Additionally, Belotero (Merz Aesthetics, San Mateo, CA) is a smooth consistency monophasic HA and is reported to provide correction without risk for a Tyndall effect due to its trademark cohesive polydensified matrix properties. This may prove to be a superior product for treating the tear trough.

In contrast to the HA products previously discussed, Radiesse (Merz Aesthetics, San Mateo, CA) is a synthetic injectable implant composed of smooth calcium hydroxylapatite (CaHA) microspheres suspended in a sodium carboxymethylcellulose gel carrier. It is a more substantial facial filler than HA and thus tends to be more effective in treating more deep lines and furrows [30]. The body slowly degrades the CaHA microspheres after injection, whose treatment effect is estimated to last between 6 and 12 months. It is FDA approved for the correction of moderate to severe facial folds and wrinkles, as well as lipodystrophy. Like the HA products previously described, Radiesse does not contain animal products, so no allergic testing is required prior to its use. CaHA is particularly useful in highlighting bony prominences such as the malar area in patients with thicker skin. In contrast to HAs, CaHA has minimal hydrophilic properties and it is important to avoid placing the filler thinly or diffusely. CaHA is metabolized by enzymatic breakdown with absorption of microspheres evident at 9 months [31]. The senior author has experienced CaHA to predictably and routinely persist from nine to 12 months, regardless of the patient.

Poly-l-lactic acid (Sculptra, Sanofi Aventis, Bridgewater, NJ) is a product that relies on its controlled foreign body biostimulatory properties and is preferred by many physicians and patients for its subtle and progressive augmentation. However, too robust of a response can be problematic, resulting in nodules and, rarely, granulomas [32]. This product is primarily for patients requesting global facial volumization where autologous fat is not available. Poly-l-lactic acid is likely degraded by hydrolysis and extracellular enzymes and subsequently broken down by macrophages [31]. It can be expected to last from 12 to 18 months following a series of three treatments.

Other fillers that are used less often include the permanent silicone (Silikon 1000 purified polydimethylsiloxane, Alcon Laboratories, Fort Worth, TX) and polymethylmethacrylate (PMMA) (Artefill, Suneva, San Diego, CA). The firm nature of these products is advantageous for filling in the fine rhytides of the upper lip, scars, and deep etched-in dermal rhytides, but are not appropriate in periorbital augmentation.

Autologous fat is not generally used in the clinic setting, but is very effective when high volumes are required for volume registration and tends to have a more long-lasting effect than HA dermal fillers. Additionally, autologous fat transfer to the head and neck region has been recently linked with promising ancillary benefits in addition to volume restoration, including overlying skin rejuvenation. It is unclear at this time to what this regenerative effect may be attributed, although there is good evidence that the regenerative effect of adipose-derived mesenchymal stem cells is responsible [33].

Collagen (Zyderm, Inamed, Santa Barbara, CA) was the first FDA-approved bovine filler for cosmetic use and was injected into the deep dermis to fill in fine wrinkles. However, hypersensitivity testing and limited duration ultimately led to the demise of collagen when Restylane garnered FDA approval in 2003. There was a brief resurgence in collagen popularity with the June 2008 FDA approval for porcine-derived collagen product Evolence (Johnson & Johnson, New Brunswick, NJ). Skin testing was unnecessary and a 12-month cosmetically appealing correction of an NLF could be expected. Unfortunately, the product did not achieve its business objectives and was discontinued in 2009.

Botulinum toxin is commonly used as an adjunct therapy to soft tissue fillers and, as such, deserves special mention here. For example, after toxin is used to treat dynamic rhytids in the forehead region, fillers may be employed to address the static rhytids that remain. When soft tissue filler techniques, with or without concomitant neurotoxin therapy, are used judiciously, they can effect subtle yet drastic improvements in facial appearance.

Soft tissue fillers have an overall excellent patient safety profile. However, complications can and do occur, and as the number of patients treated with soft tissue fillers increases commensurate with the demand for more minimally invasive facial rejuvenation procedures, so will the number of complications. As such, it is important that physicians interested in providing this service to patients be adequately informed regarding injection techniques and, perhaps more importantly, principles of facial analysis guiding the decision whether or not to employ these techniques. And, if so, where to place such injections to affect a particular desired change.

When evaluating a patient who presents for facial rejuvenation procedures, it is best to start the evaluation as you would in another patient encounter, namely, by taking a history and focusing on elicting the patient’s major concerns about their appearance. Particular attention should be paid to their general concerns about their face and any specific aspects of their appearance they would like altered. This may include anything from depressed scars to rosacea to apparently thinning lips to periorbital wrinkles. This is critical because what the clinician may perceive as being a major contributor to the patient’s aging appearance may not, in fact, be bothersome to the patient. In achieving an outcome that is overall satisfying to the patient, it is paramount to target their primary concerns in your treatment plan [34].

Patients may also present with more general complaints of feeling or looking “older” and seek your opinion regarding procedures that may be helpful in improving their overall appearance. It is with these patients that a holistic approach to facial analysis is even more salient than among those presenting to address a single, specific concern. In taking a holistic approach to facial analysis, one has the ability to examine a patient for opportunities to “rejuvenate” the face by making minor changes to restore a more youthful appearance to the face. This is done by keeping the general effects of aging on the face in mind that have been previously mentioned—namely, increased tissue laxity, “sagging,” and (dermal and fat) volume loss [18]. To this effect, minor changes using a combination of neurotoxin and fillers can have subtle yet noticeably positive effects on patients.

Dayan and Arkins presented a case of a 37-year-old otherwise healthy Caucasian female who presented for evaluation desiring a more youthful appearance (Fig. 6.2a, b) [17]. Facial analysis was significant for mild malar volume loss and moderate forehead, glabellar, and periorbital rhytids. Following the philosophy that one’s attention is drawn first to the eyes, attention was paid to this region. Specifically, volume was restored to the periorbital and malar areas using HA, resulting in the appearance of an inverted, and less square-like, orientation of the face. This created a more overall youthful feminine look. A combination of onabotulinumtoxinA and soft tissue filler was used to treat rhytids in the forehead/temple area. Details of the technique of this injection may be found in the next section of the chapter.

One of the most important aspects to periorbital rejuvenation is more rooted in the ability to understand what makes someone feel attractive. This analysis is often more important than the selection of a particular product and one’s injection technique. It is imperative to understand that at its core, beauty can serve as a subliminal indicator of our evolutionary fitness that is used to depict our health and vitality. Neural pathways in the posterior cingulated cortex and amygdala process facial characteristics [35] and determine an emotional response that allows humans to make personality judgments [35–37] within 39–100 ms [36, 37].

Moreover, an essential element to any cosmetic enhancement is that the alteration must appear natural and remain in the subconscious. Once elevated to the realm of the conscious, the pleasure-eliciting effects of beauty are greatly diminished [38]. The slightest evidence of cosmetic alteration can tip off the primitive subconscious that something has been done and that a possible genetic weakness may exist under the façade. It is the same reason that women are perceived more favorably when makeup is placed in moderation and more negatively when placed in excess [39].

As previously discussed, the eyes are the feature that is most commonly examined first [5, 40]. However, historically, periorbital rejuvenation has not been a primary focus when treating with soft tissue fillers. Likely driven by its FDA indications, soft tissue fillers have long been used in the treatment of the nasolabial fold region. However, augmenting treating this region is not always advisable. Filling the nasolabial fold augments and draws more attention to the lower third of the face. This may result in the chin appearing larger and the jaw appearing more square-like. It is the senior author’s opinion that this visual effect is masculinizing—even simian-like—and should be avoided among females. In contrast, applying fillers to the upper and middle thirds has the ability to feminize the face through mitigation of lower eyelid contour defects, raising the cheek lid pedestal, and rejuvenating the brows. In doing so, one may directly address the atrophy, fat loss, and skeletal changes brought on by the aging process with filler augmentation.

When treating the periorbital region, one should attempt to make the eyes appear as large as possible—in part because the more childlike the eyes appear, the more attractive a female’s face is perceived. Infantile eyes are large, light colored, and slightly further apart than those of an adult. A lateral outside corner of the eye that lies 2 mm above the inside corner of the eye is also considered highly attractive. In addition to this slight slant, eyes that are farther apart have been shown to be more attractive, regardless of culture [41].

In addition to treating within the larger context of subliminally influenced beauty, the use of blunt-tip cannulas instead of needles for injecting fillers allows for immediate results with minimal morbidity. Using the cannulas, the provider is able to place the fillers deep, resulting in a procedure that is less focused on the filling of superficial rhytids and is able to avoid the ecchymosis, discomfort, and edema often associated with treatments that are more superficial. Moreover, the cannulas allow the injector to dissect underlying soft tissue to select a precise plane for product placement. Importantly, using a blunt-tip cannula instead of a sharp needle in theory reduces the chance of inadvertent intravascular injection of filler, a disastrous complication.