History

Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan compound, which is highly hydrophilic, and lacks variance among dissimilar species. It forms as a largely water-soluble linear polysaccharide comprised by repeating units of N-acetylglucosamine and D-glucuronic acid. HA serves as a major structural component of extracellular space within the skin, binding water to maintain volume and viscoelasticity.

There are two categories of HAs commercially available as dermal fillers. The first is animal derived (e.g. Hylaform Gel, Genzyme Corp., Cambridge, MA), and procured from the combs of specially bred roosters, while the second is biosynthesized from fermentation cultures of Streptococcus bacteria e.g. Restylane, (Medicis, Scottsdale, AZ) and Juvaderm (Allergan Inc., Irvine, CA). Unlike collagen, species and tissue homogeny makes the potential for immunological reactions with this biopolymer significantly less likely. Skin testing is therefore not routinely performed. Regardless of how it is obtained, unbound HA undergoes rapid degradation in the body, with a typical half-life of 24 to 48 hours. To provide clinical efficacy, HA must be “stabilized” by cross-linking the molecule to maintain durability within the skin and other tissues, without compromising biocompatibility. It is by this distinctive process of cross-linking that HA develops its characteristic persistence in vivo, making it well-suited for soft tissue augmentation.

In 1996, non-animal stabilized hyaluronic acid (NASHA) was placed on the European market under the trade name Restylane and was well received due to its increased longevity over collagen fillers. In a randomized study reported in 2003, Restylane was compared to Zyplast (bovine collagen; Inamed Aesthetics, Inc. Santa Barbara, CA.). The study indicated “superiority” of Restylane over Zyplast employing the Wrinkle Severity Rating Scale (WSRS) “at all time points and at 6 months” (Narins et al., 2003). This research also demonstrated a comparable safety profile and was instrumental for FDA approval within the United States later that year. According to a statistical analysis by the American Society of Aesthetic Plastic Surgery, there were 1,593,554 HA injection procedures performed in the United States during 2006, making it the second most popular cosmetic procedure within our specialty. Currently, both NASHA as well as animal-derived HA are marketed by multiple sources throughout the world. Individual products vary in regard to particle size, concentration of HA as well as the degree of cross-linking. These attributes correlate with the product’s corrective abilities, flow characteristics, and, presumably, duration (Table 74.1).

Physical evaluation

Anatomy

Facial aging is commonly characterized by the loss of cutaneous and subcutaneous volume. This is attributable to resorption of the facial skeleton and atrophy of subcutaneous fat. In addition, there is thinning of the dermis with pronounced elastosis and a progressive reduction of HA. These factors combine to produce the aesthetically recognizable stigmata of the aged face, such as sagging and wrinkling of the skin, as well as increased prominence of the bony landmarks and vascular structures (Fig. 74.1).

Fig. 74.1 Youthful vs. aged face.

As the malar fat pads descend with age, pleats of skin and subcutaneous tissue develop and progressively gain prominence, emphasizing the nasolabial folds. Similarly, the labiomental folds or “marionette lines” form as the soft tissues of the lower face, migrate inferomedially, creating a relative sulcus in the prejowl area. Brow ptosis brings about a compensatory resting contraction of the frontalis muscle, which results in dynamic and persisting transverse rhytides of the forehead. Additionally, repeated animation of the corrugator and procerus muscles eventually give rise to the telltale vertical rhytides of the glabellar complex.

The nasojugal fold or “tear trough,” is created by a triangular gap located between the orbicularis oculi muscle and the angular head of quadratus labii superioris. These structures combine to form a depression along the orbital rim. In senescence, there is a progressive hollowing of this area created by the attachments of the orbital septum to the inferomedial aspect of the orbital rim. The effect of these anatomical changes is generally exacerbated in individuals with a congenital underdevelopment of the suborbital malar complex, and may be associated with pseudoherniation of the orbital fat pads, which serves to further highlight this defect.

As a focal point of the face, the lips, when full and well proportioned, have historically been associated with youth and sensuality. With advancing age, fat and muscular atrophy combined with bony resorption within the mandible and maxilla result in a generalized involution of the perioral structures. There is a ptosis of the commissures with increased show of the lower dentition. These features are underscored by the actions of the depressor anguli oris and depressor labii inferioris, which function to draw down the lower lip and corners of the mouth, producing a somber and uninviting appearance.

Traditionally, these anatomical changes were most commonly corrected via exclusively surgical modalities (e.g. rhytidectomy), and we truly believe the surgical facelift remains the gold standard for addressing lax and aged skin of the face. More recently, however, a “synergistic” approach addressing skin laxity and excess, as well as the loss of volume is becoming favorable. It is within this philosophy of volumetric restoration that HA fillers have found a well-defined niche. In addition, injectable therapies offer a treatment option for patients who are not candidates for, or are unwilling to undergo elective aesthetic surgery.

Technical steps

There are numerous techniques that can be used for injection of HA products. These methods vary depending upon the area being addressed, as well as the preferences of the injector. Most commonly, “serial puncture” or a “linear threading” technique are employed, especially when treating the nasolabial folds, specific rhytides or the lip border. By fully inserting the needle and injecting while it is being withdrawn, as in threading, we have the added benefit of fewer puncture sites. We often combine both methods in a “serial threading” approach, which also requires less injection points, yet allows precise placement of the filler product (Figs 74.2, 74.3). By always keeping the needle moving during injection, a smooth and predictable deposition of product is achieved.

Fig. 74.2 Serial puncture injection technique.

Fig. 74.3 Linear threading injection technique.

For larger flat areas such as the malar prominence or cheek, a “fanning” pattern of injection is often beneficial. As in threading, the needle is inserted fully, and the filler is extruded upon withdrawal. Prior to removal from the injection site, the trajectory is redirected in a radial pattern and repeated, not unlike the cannula movements in a suction lipectomy procedure. This configuration may be overlaid at 90 degrees, in a variation of the “cross-hatch” technique, providing volumization in a uniform manner (Figs 74.4, 74.5).

Fig. 74.4 Fanning pattern injection technique.

Fig. 74.5 Cross-hatch injection technique.

The most commonly treated areas for soft tissue augmentation with HA are the nasolabial folds, which is currently the only site specifically approved and labeled for injection by the FDA. This is also a reasonable area for the novice injector to gain experience in the use of HA fillers, as it is fairly forgiving. Correction is typically achieved with 1–3 mL injected bilaterally, depending upon severity. Often, there is a asymmetry in these folds, which must be addressed in the treatment plan in order to optimize results. Overcorrection, however, is discouraged, as it may produce an unnatural appearance which is accentuated with muscular contraction. It is of key importance that the product be placed in the deep dermis to avoid being visible and is injected slightly inferomedial to the folds themselves to prevent exacerbation of the deformity. An overlaid fanning technique works well in the superior aspects for this application, where the most volume is generally required (Figs 74.6–74.9).

Figs 74.6 & 74.7 Plan for injection of tear troughs, bilateral inframalar hollows and nasolabial folds in a 38-year-old woman who complains of volume deficiency of her face.

Figs 74.6 & 74.7 Plan for injection of tear troughs, bilateral inframalar hollows and nasolabial folds in a 38-year-old woman who complains of volume deficiency of her face.

Fig. 74.8 Immediately following injection of 1.0 mL of Restylane to bilateral nasolabial folds (0.5 mL per fold), 1.5 mL per inframalar hollow and 0.6 mL per tear trough.

Fig. 74.9 Three months following procedure.

It is common for patients to request correction of the labiomental folds or “marionette lines” in conjunction with the nasolabial regions. Generally, 1–2 mL is sufficient volume to correct both sides. Just as with the prior techniques mentioned, the key points are to stay deep within the dermis and inferomedial to the folds. When correction is directed at the base of the folds, along the mandible the restoration of volume to the prejowl sulcus often results in a quite rejuvenating effect. It is consequently very helpful in ameliorating the appearance of a “witch’s chin”, and in certain patients may even aid in the modest redraping of submental skin.

The superior aspect of the labiomental folds is intimately associated with the oral commissures, and thus, the lips themselves. When injecting this area, a “fanning” pattern directed toward the vermillion border bolsters and aids in elevating the oral commissures.

Often a voracious site for injectables, the relatively modest area below the oral commissures may require substantial volumes (1 mL bilateral total) in order to achieve the endpoint of therapy. In terms of injecting the lips themselves patients may desire restoration of lost volume, augmentation, or in some other fashion, reshaping of the lip contours. When seeking treatment of this area, patients often voice concerns about looking “like a fish”. In this regard, communication with the patient to establish the goals of treatment cannot be over-emphasized.

Augmentation of the lip is well achieved by injecting along the mucosal border, while volumizing the vermilion not only aids in defining the lips but also is also efficacious in minimizing the vertical rhytides commonly referred to as “smoker’s lines”. This approach is usually preferable to individual treatment of each vertical rhytid, and the lip border is an ideal area to apply one of the threading techniques discussed previously. Soft tissue augmentation of the upper lip as well as the immediately superior structures is additionally useful in reducing the aesthetic deformity of maxillary hypoplasia (Figs 74.10, 74.11). The Cupid’s bow, philtral columns and commissures are very commonly addressed, and can be modified as desired, again keeping in mind that the aesthetic ideal of the lips may have numerous interpretations (Figs 74.12–74.20).

Fig. 74.10 Profile view of a 25-year-old woman with thin lips and horizontal maxillary deficiency.

Fig. 74.11 An example of how a relatively small amount of HA filler (0.7 mL) in the upper lip can help address maxillary deficiency (immediately following injection).

Fig. 74.12 Preprocedural photo displaying deficiency in proportion of upper to lower lip.

Fig. 74.13 Five weeks after injection of 1.0 mL of Restylane to upper lip and lateral aspects of lower lip/oral commissures.

Figs 74.14, 74.15 & 74.16 Preprocedural photos of a woman requesting lip augmentation, with a history of previous injections.

Figs 74.14, 74.15 & 74.16 Preprocedural photos of a woman requesting lip augmentation, with a history of previous injections.

Figs 74.14, 74.15 & 74.16 Preprocedural photos of a woman requesting lip augmentation, with a history of previous injections.

Fig. 74.17 Immediately following injection of 1.0 mL total Restylane (0.5 mL per lip).

Figs 74.18, 74.19 & 74.20 Four weeks following procedure of lip injection. One week after injection of 1.0 mL Radiesse to bilateral nasolabial folds.

Figs 74.18, 74.19 & 74.20 Four weeks following procedure of lip injection. One week after injection of 1.0 mL Radiesse to bilateral nasolabial folds.

Figs 74.18, 74.19 & 74.20 Four weeks following procedure of lip injection. One week after injection of 1.0 mL Radiesse to bilateral nasolabial folds.

While restoring volume to diminish dynamic lines in the perioral area, one ought to consider adjuvant therapy with Botox (Allergan Inc., Irvine, CA). Botulinum toxin lessens the force with which the orbicularis oris contracts, and can be engaged independently of fillers to evert the lip and reduce vertical rhytides. Employed in conjunction with HAs, it provides an added benefit of curtailing migration of the filler product as a result of intense animation, hence prolonging its duration. When using Botox in this region, a conservative approach is key to preventing oral incontinence. Generally injected along the vermilion border, two units at each peak of the upper lip, and one unit directly below the lateral aspect of the piriform aperture is sufficient to complement the effect of an HA filler.

Similarly, the rhytides of the brow, glabella and “crow’s feet” are primarily associated with muscular contraction and therefore respond well to chemodenervation. Once the dynamic aspect of muscular activity has been appropriately addressed, any residual creasing of the skin may be attended to with filler materials. Again, it is important to remember that without reducing muscular contraction with Botox, the aesthetic effect may be diminished with only filler injection to the glabellar wrinkles.

Perhaps one of the most challenging areas to address with HA products is the nasojugal groove or tear trough. As discussed earlier, the anatomical changes brought on by the aging process result in a widening depression along the orbital rim. Younger patients have an advantage in requiring less volume for restoration, as well as possessing more substantial tissues. In older patients, however, as the defect extends laterally, they typically require larger amounts of filler material to achieve their aesthetic goals, and the thinner tissues are prone to displaying virtually any imperfections.

The main concept to remember when treating this area is that a deeper injection is strongly recommended. This being said, several experienced practitioners have reported success injecting more superficially in multiple passes, using a 32 Ga needle to mechanically decrease particle size. Superficial placement of HA fillers, especially in areas of thin transparent skin, however, may produce irregularities as well as a Tyndall effect, which is a bluish discoloration brought about by the optical properties of HA gels. To minimize the risk of these issues the product may be placed in small parcels along the orbital rim, at the supraperiosteal level, or at least deep to the orbicularis muscle. An anterograde injection technique works well to displace vascular structures and avoid their disturbance (Figs 74.21–74.24). As most patients are unable to tolerate this procedure with only a topical anesthetic, an infraorbital nerve block incorporating epinephrine works well to provide comfort and reduce ecchymosis, which can be prolonged in the periocular region.

Figs 74.21 & 74.22 Preprocedural photo of a woman who desires softening of the tear troughs.

Figs 74.21 & 74.22 Preprocedural photo of a woman who desires softening of the tear troughs.

Figs 74.23 & 74.24 Immediately following injection of 1.2 mL of total Restylane (0.6 mL per trough).

Figs 74.23 & 74.24 Immediately following injection of 1.2 mL of total Restylane (0.6 mL per trough).

HAs work exceptionally well for “sculpting” fine detail. Discrete segments may be built up producing a very natural appearance in areas such as nasal tips, and irregularities following rhinoplasty. HA products have additionally found a successful application in the improvement of depressed scars, and subincision may be performed with the injection needle to undermine minimally adherent tissues. For more cicatricial depressions, the tip of a 22 Ga needle may be bent at 90 degrees with a sterile needle driver and inserted into the defect. By employing a reciprocal “twirling” motion the scar may be released from the underlying tissues in a rounded pattern. The treatment area may then be injected with filler material to full correction.

In addition to these commonly treated areas, several innovative practitioners have reported the successful use of HA fillers for large volume correction of facial lipoatrophy. The utilization of HA fillers in the hands and feet has also been described in the literature. Although a detailed discussion of these uses is beyond the scope of this chapter, it is important to note that when treating relatively large areas with high volume injections, the frequent maintenance and financial cost of short-term correction may present an obstacle to patient retention. This is of particular consideration since the products appear to be metabolized more quickly when deposited into the subcutaneous tissues. For this reason, although feasible with HA products autologous fat or perhaps one of the longer duration fillers may be a more appropriate choice in these applications until advances in technology produce significantly longer acting HAs.

Postoperative care

Postprocedurally, the physician gently massages the treatment site to assess for irregularities and simultaneously corrects them by means of digital pressure. This manipulation does not denature or eliminate the material, but rather modifies the contours of the correction. Following this, a cold pack is used to minimize both swelling and the potential for bruising. Patients are instructed to apply intermittent cold compresses as often as possible, and avoid manipulation of the treatment site for the next six hours. Also, they are discouraged from engaging in any strenuous activity or consuming alcoholic beverages during this time frame to minimize vasodilatation. Typically, edema and erythema resolve in less than seven days, during which period, exposure to heat or sunlight should be deferred. A follow-up is generally scheduled for two weeks to evaluate the results and perform any “touch-ups” if required. As always, the patient is advised to contact the office prior to the next scheduled appointment if they have any questions or concerns.

Complications

The most common reactions to implantation of HAs are erythema, edema, and discomfort, which usually resolve on their own within several days. HA gels, unlike traditional collagen-based fillers, provide minimal hemostasis and are therefore more likely to result in bruising (Fig. 74.25). Liberal icing following the procedure may be of benefit in this regard. As with other procedures in aesthetic surgery, patient satisfaction is closely associated with proper patient selection, and management of expectations. It is crucial that prospective patients understand the risks, benefits and alternatives of injection with HA products, and are willing to accept the requisite down-time as well as potential complications. Preprocedural photographs should be taken for medical-legal purposes as well as to evaluate the correction upon follow-up.

Fig. 74.25 Hematoma following injection with an HA filler and over zealous pressure/massage in an attempt to “smooth” materials.

HA fillers may occasionally provide suboptimal aesthetic results due to improper placement. Over correction or lumps may respond to massage, but in some cases requires extraction using an 18 Ga needle or #11 blade. Some physicians inject hyaluronidase preparations such as Vitrase (ISTA Pharmaceuticals, Irvine, CA) to dissolve excess HA material, and report variable doses of 10 to 30 U as efficacious (Matarasso et al., 2006). Please keep in mind that this is an off label use of the product and that it is ovine derived, so skin testing is advised. In general, the short-term duration of these fillers often makes patience the best intervention by far.

Bacterial infections are very infrequent, but herpetic flare-ups may also involve the injection site if they occur. These are treated with antivirals; however, they must be recognized early on to avoid significant complications. Many practitioners prophylactically pretreat patients with a history of cold sores, to reduce the risk of an outbreak following injection. This can be accomplished with a course of famciclovir 500 mg given orally twice per day. The patient is generally started on the medication one day prior to the procedure, and is maintained on the regimen for 5–7 days.

Finally, a rare but potentially devastating complication associated with dermal fillers is vascular embolization. When injecting these products with a sharp needle, it is possible to deposit material into an artery and obstruct blood flow. In severe cases, this has resulted in full thickness necrosis and loss of skin. Additionally, there have been reports of stroke and permanent loss of vision as a consequence of arterial occlusion (Coleman, 2006) (Fig. 74.26). Unfortunately, it is impossible to completely eliminate these risks when performing facial injections without forgoing treatment altogether, but keeping the needle moving during injection reduces the risk of depositing a clinically significant bolus if a vessel is entered. Also, syringe aspiration prior to injection is always advisable, especially in the periorbital area. If planning to inject in the subcutaneous tissues, a blunt cannula may be of additional benefit to avoid perforation of vessels within the subdermal plexus.

Fig. 74.26 A bolus inadvertently injected into the supraorbital or supratrochlear artery may be displaced posteriorly, thus potentially occluding the ophthalmic or internal carotid artery.

The long-term sequelae of dermal implantation with HA injectables are not fully known at this time. Although uncommon, persistent inflammatory reactions to stabilized HAs products have been reported which has caused some to question their lack of immunogenicity. Additionally, as stabilization of HA is accomplished by continually newer methods of cross-linking, we cannot be certain of the properties that such molecular alterations may have over time. We must therefore be committed to continued data collection and research in order to enhance patient safety and satisfaction over the coming years.