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BOTOX (R) Injections to Improve Facial Aesthetics

  • Author: Pramit S Malhotra, MD, MS; Chief Editor: Arlen D Meyers, MD, MBA  more...
 
Updated: Sep 17, 2015
 

Overview

History

Botulinum toxin is best known to clinicians as a deadly poison produced by the Clostridium botulinum bacterium. Only within the past 2 decades have clinical applications for this toxin surfaced. Originally, applicability was found for botulinum toxin in the treatment of strabismus; however, this single indication has now grown into many. Currently, the Food and Drug Administration (FDA) has approved botulinum toxin A for several indications, including blepharospasm, strabismus, cervical dystonia, chronic migraines, axillary hyperhidrosis, upper limb spasticity, urinary incontinence, and the aesthetic improvement of glabellar rhytides. The list of indications continues to grow, including off-label use of this product. See an example illustrated below.

Frontalis muscle injections. Frontalis muscle injections.

Common clinical uses

Currently, botulinum toxin is most commonly used in the management of hyperfunctional lines. Previously, hyperfunctional lines were the source of much consternation for those affected by them. These lines often caused patients to be misinterpreted as angry, anxious, fearful, or fatigued. In the past, facial plastic surgeons only had surgical options in their armamentarium. These procedures often provided minimal improvement and exposed patients to the risks associated with surgery. Injections of botulinum toxin A provide an opportunity to manage these hyperfunctional lines with minimal morbidity. The 3 most common sites for injection are the glabella, periorbital crow's feet, and forehead areas.

For patient education resources, see the Procedures Center, as well as BOTOX® Injections.

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Pathophysiology

Etiology of hyperfunctional lines

Hyperfunctional lines result from the contraction of the underlying facial musculature. The forehead is a complex of the frontalis muscle with insertions onto fibers of the procerus, corrugator, depressor supercilii, and orbicularis muscles. The frontalis muscle, responsible for the surprised appearance when acting unopposed, mediates elevation of the brow and is primarily responsible for horizontal wrinkles. Soft tissue laxity of the forehead and periorbital area causes brow ptosis and reflex contraction of the frontalis muscle to restore brow position, exacerbating forehead rhytides. Treatment of these rhytides with BOTOX® can increase brow ptosis.

The frontalis muscle can also be responsible for the appearance of scowling. However, the main agent responsible for the appearance of scowling is the corrugator muscle. The normal function of the corrugator is as a brow adductor, bringing the eyebrow medial and inferior. Chronic contraction of the corrugator results in deep vertical hyperfunctional lines between the eyes, sometimes referred to as a glabellar crease. The depressor supercilii muscle pulls the medial brow inferior and medially. The last muscle in this group is the procerus muscle, which overlies the nasal root. Contraction of the procerus results in a snout-nose appearance and a horizontal rhytid at the nasal root.

The anatomy of hyperfunctional lines in the orbit is intricate. Contraction of the orbicularis oculi muscle is primarily responsible for the clinically observed periorbital crow's feet. The orbicularis oculi muscle is bordered superolaterally by fibers of the frontalis muscle and medially by the levator palpebrae muscle. Injection of this area requires special cognizance of adjacent peri-orbital veins to avoid bruising.

Pharmacology

The Clostridium botulinum bacterium produces 7 distinct toxins lettered A through G. All 7 toxins are antigenically distinct; however, toxin A is most familiar to clinicians. Botulinum toxin A (BOTOX®) causes paralysis by inhibiting acetylcholine release at the neuromuscular junction. This is accomplished in 3 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 byproducts 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 may require as many as 7 days for the full effect to be observed. The dose of the toxin is measured as 1 standard unit, which is equal to the amount necessary to kill 50% of Swiss-Webster mice injected with that dose.

The effect of botulinum toxin lasts 8-12 weeks. Typically, at the 10-week mark, patients begin to note a gradual disappearance of the injection effect.

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Indications

Current indications for BOTOX® injections include the following:

  • Hyperfunctional lines
  • Hemifacial spasm
  • Post–Bell palsy synkinesis
  • Blepharospasm
  • Strabismus
  • Cervical dystonia
  • Frey syndrome
  • Achalasia
  • Hyperhidrosis
  • Sialorrhea
  • Urinary incontinence
  • Limb spasticity
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Contraindications

Contraindications to BOTOX® injections include the following:

  • Pregnancy
  • Lactation
  • History of reaction to toxin or albumin
  • Preexisting motor neuron disease (eg, myasthenia gravis, Eaton-Lambert syndrome, neuropathies)
  • Age younger than 12 years
  • Infection at the injection site
  • Coincident administration of aminoglycosides can potentiate paralysis (relative contraindication)
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Treatment & Management

Patient selection

Several prospective studies by Blitzer et al and Pribitkin et al have examined the effectiveness of botulinum injections for hyperfunctional lines.[1, 2] From these studies, certain characteristics of successfully treated patients have been identified. The ideal patients have thin skin, fine wrinkles, lines that are exacerbated by muscle contraction, and hyperfunctional lines that can be spread out with their fingers. Blitzer et al describe a "glabellar spread test" in which the physician is able to spread out the hyperfunctional glabellar lines to project the maximum benefit that a paralytic injection could achieve.

Candidates that have received minimal improvement from botulinum injections include those that failed the spread test, those with previous surgery near treated areas, those with thick skin or deep dermal scarring, and those with actinic skin changes. Facial lines resulting from the loss of dermal elasticity associated with aging are unlikely to respond to botulinum toxin injections. These areas are more appropriately treated with injectable fillers, which efface the static rhytides.

Treatment

Before the procedure is undertaken, a thorough history (including prior facial surgical procedures) and medication review are undertaken. Attention is focused on looking for those patients with contraindications as previously discussed. Preprocedure photographs can be taken but are not routinely performed. A close-up photograph that isolates the area of interest should be taken, as well as a full-face photograph. Photographs are taken at rest and during muscle contraction.

Physical examination concentrates on the identification of prior facial surgical sites, the assessment of the thickness of the skin, and the quality of the skin. Ahn et al note that thicker skinned patients often require higher doses.[3] In addition, the accentuation of hyperfunctional lines with muscle contraction is noted as well as the ability to smooth out these lines with the spread test. Patients with larger muscles, such as men, also require higher doses of BOTOX®. Follow-up photographs can be taken 3-4 weeks postinjection.

Botulinum toxin A (BOTOX®) arrives on dry ice and must be stored frozen at temperatures lower than -4°C. It comes in a 100-U bottle. One unit is defined as the median lethal dose in mice. The median lethal dose in humans is estimated at 3000 U. The toxin generally is mixed with 2.5 mL of 0.9% nonpreserved sterile saline solution, creating a concentration of 40U/mL.

Carruthers et al, in an outstanding consensus panel article, noted that panel members agreed that preserved saline could also be used.[4] An insulin syringe with a 30-gauge needle works nicely for injection. The insulin syringe does not waste any of the solution in the hub of the syringe. Some clinicians are moving to 32-gauge needles, which demonstrate better patient tolerance.

The area of injection can be covered with topical anesthetic cream (eg, eutectic mix of local anesthetics [EMLA]) or can be anesthetized using ice. The solution then lasts up to 4 hours if refrigerated between injections, according to the manufacturer. Hexsel et al conducted a blinded multi-institution study and demonstrated that reconstituted BOTOX® retained its efficacy for up to 6 weeks when stored at 4°C.[5]

Studies by Blitzer et al and Carruthers et al, and the BOTOX® Consensus Group provide some very reasonable dose suggestions, as follows:[1, 4]

  • Forehead
    • A total of 10-30 U should be sufficient for this area. The patient is instructed to contract the areas of concern to demonstrate the approximate location of the hyperfunctional muscle. The injections are divided into 2- to 4-U injections. Most authors recommend that all injections be at least 1 cm above an imaginary line drawn horizontally between the middle portions of the eyebrows to avoid brow ptosis. An imaginary vertical line is drawn passing through the pupil for a reproducible reference point.
    • The first injection of 3 U is placed 1.5 cm above the superior bony orbital rim on this imaginary line. The second injection of 3.0-3.5 U is injected at a point 1.5 cm superior and 1.5 cm lateral from the first injection. The last injection uses the same dose but is injected 1.5 cm superior and 1.5 medial to the first injection. In effect, this creates a letter V. This set of injections is repeated on the opposite side. The injections are massaged in a direction away from the orbit (see image below).
      Frontalis muscle injections. Frontalis muscle injections.
  • Glabellar region
    • This region can be divided into 2 areas. The superior-lateral region is the first area, and it is affected by the corrugator supercilii muscle. This muscle is responsible for the vertical furrow between the brows. Each muscle receives an injection of 10 U as follows: 5 U is injected into the medial portion of the muscle near its origin, and 5 U is injected in the mid portion of the muscle belly (see image below).[6]
      Corrugator muscle injections. Corrugator muscle injections.
    • The central and inferomedial regions comprise the second area, and they are affected by the procerus muscle and depressor supercilii muscle. These muscles are responsible for the horizontal furrow at the root of the nose. A 6-U injection is placed into the middle of the procerus muscle belly, which is slightly off the midline (approximately 7 mm) and at the level of the superior orbital rims. The same injection is repeated on the opposite side. Then 3 U is injected into the depressor supercilii muscle, which is approximately 1 cm above the medial canthal tendon (see image below). Finally, 3 U then is injected on the opposite side. Great care must be taken not to inject the solution too deep, which may place BOTOX® into the orbit, causing an oculomotor paresis.
      Procerus muscle injections. Procerus muscle injections.
  • Periorbital crow's feet: A total of 12 U is used per side. Injections are divided into 3 U each. Using the patient's right eye as an example, the first injection is approximately 1 cm lateral to the lateral canthus at the outermost portion of the bony orbital rim. This correlates approximately with the 10-o'clock position of the orbicularis oculi muscle (some authors feel that this injection provides a chemical brow lift of several millimeters in the lateral brow region). This is followed by an injection of 3 U at the half-past-9 position. The last 2 injections are placed at the half-past-8 and half-past-7 positions (see image below). Once again, the BOTOX® must be placed outside the orbital rim to avoid intraorbital complications.
    Orbicularis muscle/periorbital crow's feet injecti Orbicularis muscle/periorbital crow's feet injections.
  • Nasolabial: This area has been difficult to inject and offers mixed results. Electromyograph (EMG)–guided injection of 2-3 U to paralyze the levator labii superioris alaeque nasi has demonstrated some success. The authors' center does not use botulinum toxin in this area because of complications of upper lip paresis.
  • Platysma: Platysmal bands can be treated with the direct injection of botulinum toxin into the concerning band. Once the band is identified, 5 U can be injected at 1-cm to 3-cm intervals along the vertical line created by the platysma. Some authors find these areas more amenable to surgical treatment.

Electromyograph monitoring

Historically, some authors had chosen to perform their injections under the guidance of EMG monitoring. This technique involves using a 27-gauge (1.5 in) polytef-coated EMG needle connected to an EMG recorder by an alligator clip on its shaft. The patient is asked to contract the muscle in question. The injection is placed where the maximal EMG recording can be found within the muscle. This technique ensures that the injection is at the portion of the muscle that is contributing most to the hyperfunctional facial line. As these injections have become routine, many centers have obtained satisfactory results without EMG guidance. Many physicians use a readily available 30-gauge insulin syringe instead.

Reinjection

If a patient feels that little benefit was derived from the original injection, reinjection can be performed 1 week postinjection. However, 2-3 weeks postinjection is probably a more practical time for a return clinic visit. Generally, 2.5-5 U are used for reinjection. Reinjection strategies are still evolving. Once the patient has a satisfactory result, the next visit is at 2-3 months or when the patient requests another treatment.

A randomized, double-blind study by Carruthers et al supported the efficacy of repeated botulinum toxin A treatments in reducing crow’s feet, as measured via the Facial Winkle Scale and patient-reported outcomes. Among patients who received the drug for treatment and then, in a 5-month extension of the original 7-month study, retreatment of crow’s feet alone or of crow’s feet and glabellar lines, the response rates were 56.5% and 63.6%, respectively, compared with just 1.1% for patients who received placebo.[7]

A study by Lee et al indicated that in lower facial contouring via bilateral injections of botulinum toxin A to the masseter muscle, better aesthetic results are achieved if the patient undergoes two injection sessions instead of just one. In the study, which involved 20 patients, individuals in the two-injection group received the doses 4 months apart.[8]

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Complications

The most feared complication is temporary paralysis of nearby facial musculature. Approximately 1% of patients may experience a temporary upper lid or brow ptosis; the most troublesome complication to the patient is upper lid ptosis. This results from migration of the botulinum toxin to the levator palpebrae superioris muscle. The ptosis usually lasts 2-6 weeks. It can be treated with apraclonidine (Iopidine, Alcon). This is an alpha-adrenergic agent that stimulates the Müller muscle and immediately elevates the upper eyelid. This treatment can usually raise the eyelid 1-3 mm. The treatment of 1-2 drops 3 times per day continues until the ptosis resolves.

Bruising can occur, particularly if a small vein is lacerated or a patient is taking aspirin, vitamin E, or NSAIDs. Ideally, patients should stop taking these products 2 weeks before the procedure. Headaches can occur after BOTOX® injections; however, in one study by Carruthers et al, this did not exceed the placebo group.[9] This is thought to be due to the trauma of the injection and not something inherent in the toxin. In fact, botulinum toxin injections are extremely safe. To date, no significant long-term hazards of botulinum toxin injections have been identified in excess of placebo groups.

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Future

Future

The popularity of BOTOX® is unmatched in cosmetic surgery. The use and scope of botulinum toxin increases every year. Patients have shown a high degree of satisfaction with the procedure. Current research focuses on using BOTOX® as an adjunct to a myriad of surgical and ablative procedures.

Botulinum toxin A now has been used in significant numbers for 20 years. Its injection has proved to be an extremely safe strategy for selectively inducing muscle paralysis.

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Contributor Information and Disclosures
Author

Pramit S Malhotra, MD, MS Director, Malhotra Center for Plastic Surgery, PC

Pramit S Malhotra, MD, MS is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Medical Association, American Society of Plastic Surgeons

Disclosure: Nothing to disclose.

Coauthor(s)

Daniel G Danahey, MD, PhD Consulting Staff, Department of Otolaryngology, DuPage Medical Group

Daniel G Danahey, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Facial Plastic and Reconstructive Surgery, American Cleft Palate-Craniofacial Association, American Academy of Otolaryngology-Head and Neck Surgery, Sigma Xi

Disclosure: Nothing to disclose.

Peter Hilger, MD, MS, FACS Professor, Department of Otolaryngology, University of Minnesota Medical School

Peter Hilger, MD, MS, FACS is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, Minnesota Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Keith A LaFerriere, MD Clinical Professor, Fellowship Director, Department Otolaryngology-Head and Neck Surgery, University of Missouri-Columbia School of Medicine

Keith A LaFerriere, MD is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Medical Association, Missouri State Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan;RxRevu;SymbiaAllergySolutions<br/>Received income in an amount equal to or greater than $250 from: Symbia<br/>Received from Allergy Solutions, Inc for board membership; Received honoraria from RxRevu for chief medical editor; Received salary from Medvoy for founder and president; Received consulting fee from Corvectra for senior medical advisor; Received ownership interest from Cerescan for consulting; Received consulting fee from Essiahealth for advisor; Received consulting fee from Carespan for advisor; Received consulting fee from Covidien for consulting.

Additional Contributors

Jennifer P Porter, MD Assistant Professor, Department of Otorhinolaryngology, Division of Communicative Science, Chevy Chase Facial Plastic Surgery

Jennifer P Porter, MD is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, Texas Medical Association

Disclosure: Nothing to disclose.

References
  1. Blitzer A, Binder WJ, Aviv JE, et al. The management of hyperfunctional facial lines with botulinum toxin. A collaborative study of 210 injection sites in 162 patients. Arch Otolaryngol Head Neck Surg. 1997 Apr. 123(4):389-92. [Medline].

  2. Pribitkin EA, Greco TM, Goode RL, et al. Patient selection in the treatment of glabellar wrinkles with botulinum toxin type A injection. Arch Otolaryngol Head Neck Surg. 1997 Mar. 123(3):321-6. [Medline].

  3. Ahn KY, Park MY, Park DH, et al. Botulinum toxin A for the treatment of facial hyperkinetic wrinkle lines in Koreans. Plast Reconstr Surg. 2000 Feb. 105(2):778-84. [Medline].

  4. Carruthers J, Fagien S, Matarasso SL. Consensus recommendations on the use of botulinum toxin type a in facial aesthetics. Plast Reconstr Surg. 2004 Nov. 114(6 Suppl):1S-22S. [Medline].

  5. Hexsel DM, De Almeida AT, Rutowitsch M, et al. Multicenter, double-blind study of the efficacy of injections with botulinum toxin type A reconstituted up to six consecutive weeks before application. Dermatol Surg. 2003 May. 29(5):523-9; discussion 529. [Medline].

  6. Trindade de Almeida A, Carruthers J, Cox SE, Goldman MP, Wheeler S, Gallagher CJ. Patient satisfaction and safety with aesthetic onabotulinumtoxinA after at least 5 years: a retrospective cross-sectional analysis of 4,402 glabellar treatments. Dermatol Surg. 2015 Jan. 41 Suppl 1:S19-28. [Medline].

  7. Carruthers J, Rivkin A, Donofrio L, et al. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Repeated OnabotulinumtoxinA Treatments in Subjects With Crow's Feet Lines and Glabellar Lines. Dermatol Surg. 2015 Jun. 41 (6):702-11. [Medline].

  8. Lee HH, Kim ST, Lee KJ, Baik HS. Effect of a second injection of botulinum toxin on lower facial contouring, as evaluated using 3-dimensional laser scanning. Dermatol Surg. 2015 Apr. 41 (4):439-44. [Medline].

  9. Carruthers A, Carruthers J. Clinical indications and injection technique for the cosmetic use of botulinum A exotoxin. Dermatol Surg. 1998 Nov. 24(11):1189-94. [Medline].

  10. Carruthers JD, Lowe NJ, Menter MA, et al. Double-blind, placebo-controlled study of the safety and efficacy of botulinum toxin type A for patients with glabellar lines. Plast Reconstr Surg. 2003 Sep 15. 112(4):1089-98. [Medline].

 
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Frontalis muscle injections.
Corrugator muscle injections.
Procerus muscle injections.
Orbicularis muscle/periorbital crow's feet injections.
 
 
 
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