There are a large variety of facial injectables, each serving a different purpose. A brief summary of the most commonly used facial injectables with a delineation of their advantages and disadvantages will be highlighted.
Botulinum toxin A (BOTOX® [Allergan, Irvine, CA] and Dysport [Medicis, Scottsdale, AZ]) decreases facial lines and wrinkles at sites of skin pleating caused by hyperfunctioning mimetic muscles. Botulinum toxin A is FDA approved for treatment of the glabella. Off-label uses have included periorbital lines (crow's feet) platysmal bands, the forehead, and nasolabial and melolabial lines. Botulinum toxin A is also used for hyperhydrosis of the palms and armpits.
Botulinum toxin A causes paralysis by inhibiting acetylcholine release at the neuromuscular junction. This is accomplished in three steps. First, the toxin binds the nerve. Second, the toxin is internalized into the nerve. Third, the toxin is cleaved by internal proteolytic enzymes, and the degradation by-products interfere with the normal process of vesicle fusion to the plasma membrane. This results in the inhibition of the exocytosis of acetylcholine.
The toxin requires 24–72 hours to take effect, reflecting the time necessary to disrupt the synaptosomal process. In very rare circumstances, some individuals require as many as 5 days for the full effect to be observed. The effects of botulinum toxin last from 2 to 6 months.
The dose of the toxin is measured as one standard unit, which is equal to the amount necessary to kill 50% of Swiss–Webster mice injected with that dose. Extrapolating the data from mouse experimentation, Meyer and Eddie estimated that a 104 kg adult male would sustain a lethal dose of botulinum toxin type A at amounts exceeding 3500 units, a dose that far surpasses any dosing regimen in the cosmetic treatment of the aging face.
Botulinum toxin is contraindicated in patients with peripheral motor neuropathic diseases or neuromuscular functional disorders such as Eaton–Lambert syndrome and myasthenia gravis. Similarly, botulinum toxin type A is contraindicated in pregnant patients and those who are lactating, although unintentional administration has not resulted in birth defects or pregnancy issues. Finally, caution should be taken when injecting botulinum toxin type A to those taking aminoglycoside antibiotics or other agents that interfere with neuromuscular transmission, since these agents may potentiate the effects of botulinum toxin both locally and regionally.
Hyaluronic Acid Derivatives
Hyaluronic acid derivatives (Restylane [Medicis Aesthetics, Scottsdale, AZ], Captique [Allergan, Irvine, CA] Juvederm [Allergan, Irvine, CA]) are glycosaminoglycan biopolymers, similar to the substance found in the intercellular layers of the dermis of the skin, and are very biocompatible. They are used primarily for lip and nasolabial fold augmentation and for fine wrinkles. Some recent uses of hyaluronic acid derivatives include nonsurgical rhinoplasty and volumetric filling in senile earlobe repair. Rare cases of hypersensitivity have been reported, but preinjection skin testing is generally not advocated. Volume enhancement with hyaluronic acid derivatives lasts 4–6 months, with some reports of material lasting for up to 16 months. Newer formulations of hyaluronic acid containing preincorporated 3% lidocaine have been shown to have equivalent product longevity.
Complications are relatively uncommon with hyaluronic acid derivatives. In cases of overaugmentation, hyaluronidase can be used to decrease the amount of dermal filling. Caution should be taken when injecting superior to the Frankfort horizontal line. Peter describes a case of retinal artery occlusion through retrograde flow through a peripheral branch of the ophthalmic artery. Skin necrosis is rare (a report of two cases of 400,000).
Poly-l-lactic acid (Sculptra) is a volumetric filler currently FDA approved for the treatment of lipoatrophy in HIV patients. Lipoatrophy in HIV is due to a number of factors including reverse transcriptase inhibitors and the disease process itself. Recently, poly-l-lactic acid has been used in an off-label capacity as a non-HIV facial filler. The main complication is nodule formation. This can be avoided by injecting deep to subcutaneous tissues and not in areas of significant muscle motion such as the lips. The duration of augmentation with poly-l-lactic acid is up to 3 years.
Calcium hydroxylapatite (Radiance FN, Bioform, Inc, Franksville, WI) is a major mineral constituent of bone. It has an off-label use for soft tissue augmentation in the face, primarily for reduction of nasolabial folds. Calcium hydroxylapatite should be injected subdermally to avoid nodule formation. In addition, the injection of radiesse should be avoided in the lips. The true longevity of calcium hydroxylapatite is not known.
Bovine collagen (Zyderm and Zyplast; McGhan Medical Corporation, Fremont, CA) is composed of 95% type I collagen and is most commonly used to augment lips and nasolabial folds. Zyplast is cross-linked with glutaraldehyde (creates a longer lasting effect) but must be injected into the deep dermis. Zyderm is injected into the superficial dermis. Hypersensitivity reactions occur in about 3% of patients; therefore, skin testing and even secondary skin testing are advocated. Bovine collagen augmentation lasts 2–4 months.
Human-derived collagen (Cosmoderm and Cosmoplast, Inamed Corporation, Santa Barbara, CA) is used for the treatment of facial rhytids and lip augmentation. In contrast to bovine-derived collagen, human-derived collagen carries essentially no risk of hypersensitivity reactions, obviating the necessity for pretreatment skin testing. Typically, injections maintain augmentation similar to that of bovine collagen. Adverse reactions may occur in patients with known allergy to bovine collagen.
Fat transplantation has the advantage of being an autologous substance. Fat transplantation is used as a volumetric filler. The concept of loss of facial volume is recent, and surgeons recontour the face, the nasolabial folds, temporal fossa, prejowl sulcus, and perioral and periorbital areas.
Most commonly, fat is harvested from the lateral thigh or abdominal region. Fat is then either strained or centrifuged, and injected into areas requiring volume. Technique in handling fat is crucial in maintaining adipocyte viability. Fat transplantation often requires multiple treatment sessions and has variable degrees of resorption. Fat can be frozen with minimal loss in fat viability and reinjected at a future date.
Disadvantages of fat harvest include donor site morbidity, potential for prolonged facial swelling, and unpredictable resorption. In addition, fat can lead to granulomas that can be treated with triamcinolone injections or direct excision. Advantages of fat transplantation include a potentially permanent natural facial filler that can serve as an adjunctive or stand-alone procedure.
Butterwick KJ, Bevin AA, Iyer S. Fat transplantation using fresh versus frozen fat: a side-by-side two-hand comparison pilot study. Dermatol Surg.
(This pilot study supports the use of autologous frozen fat or equivalent to improve results regarding longevity and aesthetic appearance versus fresh fat at 1, 3, and 5 months for fat augmentation of aging hands.)
Carruthers J, Fagien S, Matarasso, and the Botox Consensus Group. Consensus recommendations on the use of botulinum toxin type A in facial aesthetics. Plast Reconstr Surg.
(The review of each area encompasses the relevant anatomy, specifics on injection locations and techniques, starting doses (total and per injection point), the influence of other variables, such as gender, and assessment and retreatment issues by a consensus panel on botulinum toxin.)
Castor SA, To WC, Papay FA. Lip augmentation with AlloDerm acellular allogenic dermal graft and fat autograft: a comparison with autologous fat injection alone. Aesthetic Plast Surg.
(Authors concluded that AlloDerm in conjunction with autologous fat injection constitutes a safe, reliable, and lasting method of lip augmentation, providing increased vermilion show compared with that with autologous fat injection alone.)
Coleman SR. Facial recontouring with lipostructure. Clin Plast Surg.
(Landmark article describing the use of fat transplantation.)
Elson ML. The role of skin testing in the use of collagen
injectable materials. J Dermatol Surg Oncol.
(Skin testing can identify those patients with an allergic reaction, compromising approximately 2–3% of all patients.)
Friedman PM, Mafong EA, Kauvar ANB et al. Safety data of injectable nonanimal stabilized hyaluronic acid gel for soft tissue augmentation. Dermatol Surg.
(According to the reported worldwide adverse events data, hypersensitivity to nonanimal hyaluronic acid gel is the major adverse event and is most likely secondary to impurities of bacterial fermentation.)
Han SK, Shin SH, Kang HJ et al. Augmentation rhinoplasty using injectable tissue-engineered soft tissue: a pilot study. Ann Plast Surg.
(Description of a novel use of Restylane as a material for augmentation in rhinoplasty.)
Matarasso SL, Herwick R. Hypersensitivity reaction to nonanimal stabilized hyaluronic acid. J Am Acad Dermatol.
(First report of a reaction to NASHA [nonanimal stabilized hyaluronic acid].)
Peter S, Mennel S. Retinal branch artery occlusion following injection of hyaluronic acid (Restylane). Clin Exp Ophthalmol.
(Report of a retinal branch artery occlusion after facial injection of dermal filler. The superior temporal artery showed occlusion due to a clearly visible long and fragmented embolus suggestive of gel and clearly distinguishable from calcific or cholesterol emboli.)
Raspaldo H, De Boulle K, Levy PM. Longevity of effects of hyaluronic acid plus lidocaine
facial filler. J Cosmet Dermatol.
(Comparison of hyaluronic acid fillers versus those with lidocaine
to determine longevity of effects)
Sattler G. Long-lasting results with polylactic acid. J Drugs Dermatol.
(Review article demonstrating benefits of polylactic acid as a facial filler.)
Shoshani O, Ullmann Y, Shupak A, et al. The role of frozen storage in preserving adipose tissue obtained by suction-assisted lipectomy for repeated fat injection procedures. Dermatologic Surgery, 27(7): 645–647, 2001.
Sklar JA, White SM. Radiance FN. A new soft tissue filler. Dermatol Surg.
(Retrospective review demonstrating favorable results with Radiance FN.)
Tzikas TL. A 52-month summary of results using calcium hydroxylapatie for facial soft tissue augmenation. Dermatol Surg.
(A clinical review of the results of 1000 patients injected over a 52-month span, with recommendation to avoid injection into the lips)
Vartanian AJ, Frankel AS, Rubin MG. Injected hyaluronidase
reduces Restylane-mediated cutaneous augmentation. Arch Facial Plast Surg.
injections can be used to reduce dermal augmentation from previously injected Restylane. A small dose of hyaluronidase
equivalent to 5–10 U may be injected initially.)