Botox (Forehead and Periorbital Rhytids and Chemical Brow Lift)
Corey S. Maas
INTRODUCTION
Botulinum toxin is a natural polypeptide neurotoxin first described for use in glabellar lines by Carruthers and Carruthers in 1992. There are seven distinct serotypes of the toxin (botulinum toxin A, B, C, D, E, F, and G), each with unique antigenicity, binding sites, and enzymatic activity. Of the subtypes, type A has proven to be most efficacious in clinical practice. The mechanism of action of the toxin takes place at the presynaptic terminal where it effectively prevents release of acetylcholine into the neuromuscular junction thereby inhibiting muscle contraction. Although it binds irreversibly, new axonal growth allows for return of muscle function within 3 to 4 months after injection.
Since approval by the Food and Drug Administration (FDA) for cosmetic use, Botox/Botox Cosmetic (onabotulinumtoxinA; Allergan Inc., Irvine, CA), in 2002, and more recently Dysport (abobotulinumtoxinA; also known as Azzalure: Ipsen, Paris, London; distributed in the United States by Medicis Corp., Scottsdale, AZ), in 2009, neurotoxins have been a mainstay in the treatment of hyperdynamic rhytids of the upper face. Xeomin (incobotulinumtoxinA; Merz Pharmaceuticals, Germany), the most recent preparation available for cosmetic use, was approved in July 2011.
All three products contain the botulinum neurotoxin type A (BoNT-A), protein which, in its simplest form, has a molecular weight of 150 kD. The protein is made up of both a heavy chain (100 kD) and a light chain (50 kD), each with its own role in the mechanism of action of the neurotoxin. Botox and Dysport contain the active 150-kD protein along with a complex of proteins that play no role in the neurotoxin’s mechanism of action. As a whole, the Botox protein complex weighs 900 kD with one active 150-kD protein per complex, while the Dysport complex, of which the biochemical composition is unknown, weighs approximately 900 kD. Xeomin contains the “naked” 150-kD protein only. Through the years, research and the widespread use of BoNT-A has shown that it has a wide margin of safety, is generally well tolerated, and has a high rate of satisfaction. Various methods of reconstitution, optimal dosage, and placement of the injections have also been described but above all a thorough understanding of the anatomy and function of the musculature of the upper face is the most important element in achieving optimal aesthetic outcomes.
RELEVANT ANATOMY
A thorough understanding of the anatomy of the upper face and muscular interactions is of utmost importance for successful treatment of hyperdynamic rhytids. For simplicity, the muscles of the upper face that are effectively treated with neuromodulators can be divided into depressors and elevators of the brow. The frontalis muscle is the sole elevator of the brow and in the classic anatomical description consists of two bellies, one on either side of the midline of the forehead. The lateral extent of the frontalis coincides with the peak of the brow, and the medial aspect of each belly lies at the medial border of the brow leaving a space devoid of muscle in the midline. More commonly, however, the muscle is found as one broad muscular band without a medial division.
Inferiorly, the frontalis interdigitates with the brow depressors and is contiguous with the galea aponeurotica superiorly. The brow depressors consist of the procerus, paired corrugators and depressor supercilii, and the medial and lateral orbicularis oculi. Medially, the procerus overlies the glabella and is flanked by the depressor supercilii, while the corrugators extend superiorly and laterally at the level of the brow. The procerus and corrugators are responsible for horizontal and vertical lines over the bridge of the nose, respectively. Although the paired nasalis muscles, which overly the upper lateral cartilages, do not contribute to brow depression, they produce horizontal lines over the lateral nasal dorsum commonly referred to when hyperactive as “bunny lines.” Overall, the lateral orbicularis oculi acts as the strongest depressor of the brow and is responsible for periorbital rhytids also known as “crow’s feet.” Knowledge of this anatomy is important in that overzealous treatment of the frontalis with the intention of correcting all visible forehead lines could lead to significant brow ptosis.
Inferiorly, the frontalis interdigitates with the brow depressors and is contiguous with the galea aponeurotica superiorly. The brow depressors consist of the procerus, paired corrugators and depressor supercilii, and the medial and lateral orbicularis oculi. Medially, the procerus overlies the glabella and is flanked by the depressor supercilii, while the corrugators extend superiorly and laterally at the level of the brow. The procerus and corrugators are responsible for horizontal and vertical lines over the bridge of the nose, respectively. Although the paired nasalis muscles, which overly the upper lateral cartilages, do not contribute to brow depression, they produce horizontal lines over the lateral nasal dorsum commonly referred to when hyperactive as “bunny lines.” Overall, the lateral orbicularis oculi acts as the strongest depressor of the brow and is responsible for periorbital rhytids also known as “crow’s feet.” Knowledge of this anatomy is important in that overzealous treatment of the frontalis with the intention of correcting all visible forehead lines could lead to significant brow ptosis.
HISTORY
A thorough history should include allergies and current medications with an emphasis on the use of anticoagulants as the procedure may need to be postponed if the patient desires minimal bruising. It is important to note previous surgical treatment of surrounding tissues as well as any past treatments with BoNT-A. Asking the patient what they liked or disliked about previous experiences with neuromodulators can be very helpful. The importance of facial expression in the patient’s occupation and daily lifestyle should also be discussed. Finally, extreme caution should be taken in treatment of patients who have known peripheral neuropathies or disorders of the neuromuscular junction since they may be at increased risk of severe systemic effects such as dysphagia and respiratory compromise.
PHYSICAL EXAMINATION
During evaluation, it is important to assess the patient’s goals of treatment. Evaluation of the face for any preexisting asymmetries should be performed and documented, and a thorough discussion of irregularities should take place with the patient. The patient should be asked to actively contract the glabellar, frontalis, and orbicularis oculi muscles in order to discern the amount of improvement that can be reasonably expected to guide your discussion and treatment plan.
INDICATIONS
Botulinum toxin is generally indicated for the treatment of hyperdynamic lines or furrows of the upper face that are of concern to the patient including glabellar frown lines, horizontal forehead creases, periorbital “crow’s feet,” and lateral nasal “bunny lines.” Also, if necessary, treatment can be extended to include infraorbital lines. Though most patients present with lines or wrinkles that they wish to have treated, neuromodulators can also be used as a preventive measure prior to formation of lines in younger patients who tend to overuse their upper facial musculature. Some patients may request elevation of the lateral brow, and BoNT-A can be placed with good results into the lateral orbicularis oculi to produce what has been described as a chemical brow lift. In addition, BoNT-A can be used prior to procedures such as lower eyelid reconstruction, brow lift, scar revision, and repair of lacerations to help promote favorable wound healing. Patients may also present to the office having had a recent injection using an improper technique causing asymmetries. With a thorough understanding of the upper facial musculature, these unfortunate irregularities can be treated with small amounts of neuromodulator injected at the proper anatomical location.
CONTRAINDICATIONS
BoNT-A treatment is contraindicated in patients with active infection at planned injection sites as well as in those with known allergy or hypersensitivity to any of the formulation ingredients (botulinum toxin type A, sodium chloride, human albumin). The neurotoxin is listed as a category C drug in pregnancy meaning no adequate well-controlled studies of use in pregnant women exist, and it is unknown whether the toxin is excreted during lactation. Therefore, any patient who is pregnant or breast-feeding should not undergo treatment. It should be noted, however, that the literature contains a small number of reports of patients who underwent treatment with BoNT-A while unknowingly pregnant. Of these, one study surveyed 396 physicians of which 12 reported having injected women who were not aware they were pregnant. In this study, one miscarriage was reported in a woman with a history of previous miscarriages, but no fetal abnormalities or other adverse events have been linked to the neurotoxin.
Patients should be made aware, if present, of preexisting lid or brow ptosis and educated on the risk of exacerbation. Although careful injection technique should minimize the risk, if the possibility of worsening ptosis is unacceptable to the patient, they should not be injected. Occasionally, a patient may present with the request for further treatment although on examination they clearly have appropriate lack of muscular activity due to a recent injection. In this case, a detailed discussion with the patient should take place focusing on minimization of hyperdynamic lines as the goal of treatment rather than complete absence of muscle activity. These patients should be made aware that further injection will only place them at risk for complications and likely provide no incremental improvement.
SURGICAL TECHNIQUE
Reconstitution of Product
Reconstitution is the correct term to use when describing the method of converting dried product into solution. Using words like “dilution” or “diluted” is not accurate and can lead to a false belief by the patient that they are receiving a less-than-quality product. The “unit” (U) of measurement for Botox Cosmetic, Dysport, and Xeomin, each measured on the LD50 mouse test, is a proprietary measurement of the individual manufacturer. In the literature, 1 U of Botox has been shown to be closely equivalent to 2.5 to 3 U of Dysport and 1 U of Xeomin. The product is packaged in vials either vacuum dried (Botox, 50 or 100 U) or lyophilized (Dysport, 300 U, and Xeomin, 100 U) and must be kept refrigerated at 0 to 8°C (except Xeomin, which can be stored up to 25°C) until just prior to use to avoid denaturization of the protein. Since the product is packaged in powder form, it must be hydrated to make it suitable for injection, and the manufacturers package insert recommends use of preservative-free saline. In my practice, a 100-U vial of Botox or Xeomin is reconstituted with 2.0 mL of preservative-free saline to produce 5 U/0.1 mL. Similarly, 300 U of Dysport is reconstituted with 1.5 mL of preservative-free saline to give 20 U/0.1 mL. Other methods of reconstitution have been described and can be found in Table 27.1. Due to the fragile nature of BoNT-A, care is taken, in the case of Botox, to allow the vacuum property of the vial to draw in the saline rather than forcefully injecting into the container. For Dysport and Xeomin vials, which have a partial vacuum seal, the amount of saline drawn in will vary, and therefore, slow injection of the remaining saline will ensure sustained quality of the product. A gentle swirl of the vial is then performed to mix the contents. Insulin syringes with a permanently attached needle, manufactured in 50 and 30 insulin-unit capacities, are then used to carefully draw up the product. With these syringes, 10 insulin-units are equivalent to 0.1 mL allowing for ease of measurement. For Botox and Xeomin, a 50 insulin-unit syringe is utilized to draw up increments of both 0.2 and 0.4 mL, which equals 10 and 20 U, respectively. Dysport is drawn up in 30 insulin-unit syringes at increments of both 0.15 and 0.3 mL to give 30 and 60 U, respectively. When drawing up the reconstituted product, it is important to ensure that the needle does not touch the floor of the glass container as this will dull the tip and make for a more painful injection.
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