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Plastic Surgeon Dr. Michele Koo’s Blog | St. Louis | Kansas City FOREHEAD CREASES

Posts Tagged ‘FOREHEAD CREASES’

What is a good age to start BOTOX and filler, is 25 too early, 65 too late?

Tuesday, October 6th, 2009

The advantage of something like BOTOX and Juvederm is that it only takes 20-30 minutes in your plastic surgeon’s office. The disadvantage of course is the cost and you must maintain the BOTOX every 3-5 months and the filler every 12-18 months. However, if you start BOTOX before the lines and creases become deep and relatively permanent, your skin will stay quite a bit more smooth and youthful appearing as you age.

The animation muscles of your face have worked all of your life, your skin is much more resilient during the first 25 years and therefore you see no lines and creases. As you incur sun damage along with age, your skin begins to show the results of that muscle action and sun exposure as well as exposure to toxins such as nicotine from cigarettes if you are a smoker.

It is better to start with the BOTOX in the mid to late 20’s to prevent the deep creases from ever beginning. There really is no age limit on the other end except that the BOTOX and fillers are not as effective if there are so many creases and they are so deep. Same thing for the fillers in that you will need so much more filler if your wrinkles are extremely deep and you in fact may need to have the skin redraped with surgery in addition to the filler to regain softness and volume to your face.

The following exerpt continues the information from the study by Dr Mary Lupo published in Plastic and Reconstructive Surgery, January 2008. Dr Michele Koo hopes that this is helpful and that you understand that outcomes and effects are continually being studied and monitored by plastic surgeons throughout the country to ensure the safety of the products we use for WRINKLE REDUCTION.

Dr Koo is extremely respectful of your time and money and will only use what she feels is the best product for you and will not use any more than you need to address your concerns. She truly believes that often, “less is more” and that subtlety is the key to looking better without looking done.  Why should anyone know what your secret is. Dr Koo will be your best kept secret on the War Against Wrinkles.

With the baby boomer generation firmly ensconced in middle age, there is increasing interest in maintaining a youthful appearance to match this energetic generation. After the 2002 U.S. Food and Drug Administration approval of botulinum toxin type A (Botox Cosmetic; Allergan, Inc., Santa Barbara, Calif.) for treatment of glabellar lines, nonsurgical correction of wrinkles became a possibility. With Botox management of dynamic wrinkles, a plethora of new dermal fillers are vying to address static wrinkles, providing an overall rejuvenation of the aging face.

Among these promising new treatments is the family of Juvéderm hyaluronic acid dermal fillers (Allergan), approved in the United States in 2006 for treatment of facial wrinkles and folds. Juvéderm Ultra Plus Injectable Gel has a high degree of cross-linking, which makes it particularly well suited for volumizing and correcting deeper folds and wrinkles.2 Patients with deep facial wrinkles and folds are generally at a disadvantage when it comes to cosmetic correction, as they require a large volume of dermal filler and their correction may not be sustained; thus, a filler that is specifically designed to treat severe wrinkles is an important advancement.

Results from the randomized, controlled study of three Juvéderm formulations compared with bovine collagen have been published previously.3 We sought to further characterize the clinical characteristics of Juvéderm Ultra Plus treatment (and to compare this to bovine collagen treatment) among subjects who had severe nasolabial folds before treatment.

A multicenter, double-blind, randomized, within-subject, controlled study was conducted as part of a submission for approval by the U.S. Food and Drug Administration. This study compared three different formulations of Juvéderm against bovine collagen (Zyplast; Allergan). One-third of subjects were randomly assigned to receive treatment with Juvéderm Ultra Plus, containing 24 mg/ml of cross-linked hyaluronic acid, in one nasolabial fold and Zyplast in the other. Results presented here are limited to those subjects who received Juvéderm Ultra Plus and had severe folds at baseline.

Blog to be Continued in What age is good to start BOTOX…

The True Facts about BOTOX…

Wednesday, September 23rd, 2009

DR MICHELE KOO, MD, FACS, BOARD CERTIFIED PLASTIC SURGEON, ST LOUIS, MISSOURI 314-984-8331 WANTS YOU TO KNOW THAT BOTOX INJECTIONS FOR FACIAL LINES AND WRINKLES ARE EXTREMELY SAFE AND EFFECTIVE. IF YOU DON’T LIKE THE LINES OF YOUR FOREHEAD, “11″ WRINKLES BETWEEN YOUR EYEBROWS, YOUR CROWS FEET, OR YOUR “SMOKERS WRINKLES” AROUND YOUR MOUTH, YOU NEED TO CALL DR KOO AT 314-984-8331 AND SEE FOR YOURSELF IN 30 MINUTES WHAT YOU CAN AFFORDABLY ACHIEVE WITH NO DOWN TIME.

DR KOO IS EXTREMELY PRECISE ABOUT WHICH MUSCLES SHE INJECTS AND CAREFUL NOT TO USE ANY MORE THAN NECESSARY SAVING YOU COST AND MINIMIZING YOUR POSSIBLE COMPLICATIONS. IF YOU THOUGHT ALL THOSE MEDIA PERSONALITIES HAVE PERFECT FLAWLESS SKIN WITHOUT WRINKLES BECAUSE OF THEIR GENETICS OR GOOD LUCK, THINK AGAIN. THEY ALL HAVE THEIR FAVORITE PLASTIC SURGEONS, AND DR KOO WANTS TO BE YOURS.

THE FOLLOWING IS AN ARTICLE THAT SHE HOPES IS HELPFUL FOR YOUR EDUCATION ABOUT BOTOX AND ITS POSSIBILITIES OF SMOOTHING YOUR FACE WITHOUT SURGERY.

BOTOX (R) Injections to Improve Facial Aesthetics

Author: Pramit S Malhotra, MD, MS, Director, Malhotra Center for Plastic Surgery, PC
Coauthor(s): Daniel G Danahey, MD, PhD, Consulting Staff, Michiana Eye Center and Facial Plastic Surgery; Peter Hilger, MD, Professor, Department of Otolaryngology, University of Minnesota Medical School

Introduction

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 blepharospasm, strabismus, cervical dystonia, and the aesthetic improvement of glabellar rhytides.

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, plastic surgeons only had surgical options in their armamentarium, including excision or implantation of fat, collagen, or silicone. 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.

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 musculature to avoid upper lid ptosis.

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 5 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.

Indications

Current indications for BOTOX® injections include the following:

  • Hyperfunctional lines (eg, glabellar, forehead, crow’s feet, platysma, nasolabial lines)
  • Hemifacial spasm
  • Post–Bell palsy synkinesis
  • Blepharospasm
  • Spasmodic dysphonia
  • Strabismus
  • Cervical dystonia
  • Frey syndrome
  • Achalasia
  • Hyperhidrosis
  • Sialorrhea
  • Migraines

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)

Treatment

Patient Selection

Several prospective studies by Blitzer et al and Pribitkin et al have examined the effectiveness of botulinum injections for hyperfunctional lines. 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 are often taken by the individual surgeons’ photography studio. 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. 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 are 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. 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.

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

  • 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.
  • 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.
    • 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. 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.
  • 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. Once again, the BOTOX® must be placed outside the orbital rim to avoid intraorbital complications.
  • 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

Many authors have 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. However, EMG-guided injections remain a useful adjunct in patients who have residual function after their initial injection.

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.

Complications

The most feared complication is temporary paralysis of nearby facial musculature. Approximately 1-3% 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.6 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.

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.

DR MICHELE KOO, MD, FACS, BOARD CERTIFIED PLASTIC SURGEON , ST LOUIS, MISSOURI hopes that this is helpful information. She will only suggest Botox for you if she feels it will be helpful and worthwhile for you based on your cosmetic goals for your face.

Can you still look normal and get BOTOX and filler for your face?

Thursday, May 28th, 2009

Before Juvederm by Dr Michele Koo

After Juvederm by Dr Michele Koo

Dr Michele Koo, MD, FACS

Board Certified Plastic Surgeon, St Louis, Missouri

314-984-8331

Dr Michele Koo feels that it is very safe to use BOTOX for facial wrinkles in the forehead, between the eyebrows, crowsfeet area, in the upper and lower lip and even in the neck bands.

Our improved understanding of the pathophysiology of facial lines, wrinkles, and furrows has broadened the treatment options for a variety of facial cosmetic blemishes. The persistence or recurrence of certain facial rhytids after surgery has confirmed the lack of full comprehension of their origin. Glabellar forehead furrows (frown lines) and lateral canthal rhytids (crow’s feet) have been the most popular facial lines that have been shown to be mostly the result of regional hyperkinetic muscles, and their eradication may be more suitable, at times, to chemodenervation than to soft-tissue fillers, skin resurfacing, or surgical resection. Aesthetic surgical procedures that have yielded suboptimal results may also occur from failure to recognize other causative factors including hyperkinetic or dynamic musculature, which may contribute to etiology of the visible soft-tissue changes and lack of persistent effect after surgery. Chemodenervation with botulinum toxin A (Botox) has proven to be useful both as a primary treatment for certain facial rhytids and as an adjunctive agent for a variety of facial aesthetic procedures to obtain optimal results.

The logical approach to facial rejuvenation is facilitated when one first (through an assessment and diagnosis of the nature of the pathology) differentiates quantitative from qualitative changes in facial soft tissue. Quantitative and malpositional changes have traditionally required a surgical approach: the excision or repositioning of soft tissue (skin, muscle, and fat). Conversely, qualitative changes may require the fortification of the soft tissue by mechanical, chemo- or laserexfoliation, or augmentation of a particular soft-tissue plane. Most recently, a focus has been directed to prevention with sun protection, skin care, and improved nutrition as well as the realization of other causative risk factors that include hyperfunctional and dynamic components of facial lines.

Hyperdynamic (hyperkinetic, hyperfunctional) or long-term facial muscular animation seems to contribute to the etiology of many undesired facial rhytids and furrows. The presumption that facial lines were the result of, in part, forces generated by local muscular actions was first observed post-mortem on a microanatomic basis by Pierard and Lapiere.  Focal denervation of particular facial muscles has been shown to improve overall facial appearance not only by temporarily eliminating rhytids but also by improving malpositional changes of the overlying soft tissue and possibly the results of particular facial aesthetic surgical procedures discussed herein

The interest in chemodenervation and specifically the use of botulinum toxin as a therapeutic agent for weakening particular skeletal muscles dates back to the 1920s. Almost 30 years later, pediatric ophthalmologist Dr. Alan Scott collaborated with Dr. Edward J. Schantz in the preparation of a batch of crystalline toxin to determine its effectiveness as an injectable agent for producing transient weakness of extraocular muscles and permanent changes in ocular alignment.  This had remained the source of botulinum toxin type A until 1997 as the commercially available product, Botox (Allergan, Inc., Irvine, Calif.). After many years and experiences with this product, supplies were finally exhausted, and Botox was reformulated to what is currently used worldwide.

The toxins of Clostridium botulinum are classified into eight immunologically distinguishable exotoxins. The type A toxin is most easily produced in culture and was the first one obtained in a highly purified, stable, and crystalline form. The principal effect of muscle paralysis is caused by the inhibition of the release of acetylcholine at the neuromuscular junction. The paralytic effect of the toxin is dose related, with the peak of the effect occurring 5 to 7 days after injection.  Denervated muscle histopathology shows muscle atrophy and a mild degree of demyelinative changes at the nerve terminal.  Axonal nerve sprouting seems to be a usual response to chemodenervation and may diminish true clinical muscular atrophy (hence long-term beneficial effects in some regions). Single-fiber electromyography studies indicate abnormal neuromuscular transmission in muscles distant from the site of injection despite the absence of clinical weakness, indicating the potential for spread of the toxin that could be significant at higher doses. These observations and effects supported by some good experimental data provide a rationale for treatment protocol for the use of Botox in a variety of disorders.

Botox is presently approved for the treatment of strabismus and blepharospasm associated with dystonia (including benign essential blepharospasm or VII cranial nerve disorders) in patients 12 years of age and above.  Although not (FDA) approved for its use, many have experience with a multitude of other clinical applications of botulinum toxin, including the treatment of bruxism, stuttering, painful rigidity, lumbosacral pain and back spasms, radiculopathy with secondary muscle spasm, spastic bladder, achalasis, tremor, involuntary tics,  tension headaches, neuromuscular paralysis, lower eyelid spastic entropion, aberrant regeneration of the facial nerve (after Bell’s palsy etc.), acquired nystagmus, corneal pathology/amblyopia therapy aided by the effects of occlusion, and in periorbital reconstructive surgery.

Many experienced clinicians had noted the improvement of facial rhytids in their patients who had received Botox for a variety of facial spastic disorders. This discovery, in conjunction with a prelude to a better understanding of the anatomic basis of several facial frown lines, forced the question of the possible benefit of chemodenervation for certain facial wrinkles.

The treatment of glabellar frown lines enjoyed early attention owing to the experience of those who treated patients with benign essential blepharospasm, which typically involved injection of toxin into the medial eyebrows (corrugators). Other targeted facial hyperkinetic lines that gained early popularity included the treatment of lateral canthal rhytids (crow’s feet) and horizontal forehead furrows. More recently, the applications have extended to congenital and traumatic facial asymmetry, postsurgical eyebrow asymmetry (including dyskinesis) and facial paralysis, orbicularis hypertrophy (of the lower eyelids), perioral rhytids, hyperfunctional midfacial animation lines, soft-tissue malposition, and as an adjunct to endoscopic forehead lifts, laser skin resurfacing and injectable agents for soft-tissue augmentation.

Understanding the anatomic relationships and functional features of a variety of facial muscles to the surrounding soft tissue provides the additional necessary groundwork for the treatment rationale of chemodenervation for a variety of aesthetic displeasures.

The palpebral component of the orbicularis oculi surrounds the pretarsal and proximal septal aspects and is essentially the sphincter muscle of the eyelids responsible for blinking and gentle eyelid closure. Its direct antagonist is the levator palpebrae muscle. Forceful contraction of the orbital component of the orbicularis oculi induces concentric folds emanating from the lateral canthus. Some of the fibers of the superomedial orbital component function as depressors of the medial eyebrow. These fibers constitute the depressor supercilii.  The superolateral orbital orbicularis oculi acts, in part, as a depressor of the lateral eyebrow. The corrugator supercilii serves to draw the eyebrow inferiorly and medially, and as such produces the vertical glabellar frown lines. The procerus muscle, in part, draws the medial (head of the) eyebrows inferiorly and produces the transverse wrinkles over the bridge of the nose. The main antagonist of all of the eyebrow depressors is the frontalis muscle. The zygomaticus major muscle draws the angle of the mouth superiorly, laterally, and posteriorly with actions of laughing, smiling, and chewing. The zygomaticus minor muscle functions as one of the lip elevators and with the zygomaticus major contributes to the nasolabial fold. Forceful contraction of the zygomaticus muscles in animation (smiling) produces synergistic effects in the periorbital region, accentuated by the contraction of the orbital orbicularis and enhancing the radially oriented folds at the lateral canthus, exaggeration of the skin tension lines of the midface, and recruitment of lower eyelid soft-tissue redundancy (by elevating the cheek) that is not evident in the nonanimated state. The orbicularis oris is responsible for forceful lip closure and serves as a sphincter to the mouth. Contraction of this muscle induces folds that radiate from the vermilion border. This muscle in part is an antagonist to the lip elevators. An understanding of the basic anatomy of facial expression is essential not only for the appropriate approach to the treatment of hyperkinetic facial lines and furrows but also a methodology to avoid complications discussed later.

Botulinum toxin A is a labile but highly potent toxin. Each vial (supplied by Allergan) contains approximately 100 units of toxin in a crystalline complex. The toxin should be stored immediately upon receipt in the office freezer at -5°C or lower in this crystalline form. Toxin reconstitution should be performed just before actual injection for maximal potency. Dilution should be followed carefully with the diluent of nonpreserved saline as instructed for specific concentrations as described in the package insert; however, most clinical uses of Botox are well suited for a dilution of 2.5 units per 0.1 ml, which is easily obtained by mixing 4.0 ml of nonpreserved saline to the vial. The use of preserved saline has been suggested by some authors for hope of extending the shelf life and potency once reconstituted; however, there has been concern regarding the effect of the preservative, turbulence with dilution, and agitation in denaturing (hence reduced effect) of the delicate toxin.

Once reconstituted, the toxin should be used as quickly as feasible. The package insert suggests that the product be used within 4 hours; however, many users have noted reasonable effects with the use of the product for up to 30 days.  In Dr Fagien’s experience, a notable decline in clinical potency occurs after 48 hours of reconstitution that may affect depth of focal paralysis and longevity of effect. Further, the relative stability of the reconstituted toxin is felt to be best maintained by refrigeration (not freezing), and it is suggested that the product be kept cool at every opportunity. To the best of my knowledge, however, there have been no studies to substantiate or refute claims of the duration of potency of the toxin after reconstitution.

Early investigators had suggested up to 10 to 20 units or more per site to affect the targeted muscles of facial expression.  However, one can achieve effects with far less toxin (2.5 units per site) and maintain longevity of effect for comparable periods of time. In my experience, this dose is effective for an average of 4 to 6 months. These lower doses in smaller volumes also serve to reduce unwanted effects and complications (see below). Concentrations much less that 2.5 units per 0.1 ml can induce a weakening effect on the targeted muscle but seem to do so for a much shorter duration. Additionally, men (or even women with clinically evident large hypertrophic target muscles-particularly corrugators or frontalis muscles) seem to require a slightly higher dose per injection site (up to 5.0 units per site), otherwise resulting in only mild to moderate improvement of hyperfunctional rhytids with shorter duration of effects. Diluted toxin should be drawn up into 1.0 ml (T.B. syringes) through an 18-gauge needle to minimize physical trauma to the toxin.

As in all procedures, patients desire maximum benefit with minimal side effects and morbidity. It may therefore be advisable that patients temporarily discontinue aspirin and other drugs that can affect bleeding time before Botox injection, similar to how you might instruct your patients before surgery. This, however, is not mandatory but may reduce or eliminate facial bruising that can last for several weeks. If minimal to no bruising occurs after injection of Botox, patients can typically return to work unnoticed less than 1 hour after treatment.

After the toxin is drawn up by 18-gauge needles into 1.0-ml syringes, the needle is then replaced by a short, 30-gauge needle for injection. The use of local anesthesia is relatively contraindicated and unnecessary. Alcohol may be applied to the injection sites but should be allowed to dry fully before injection of toxin owing to toxin lability. I currently do not employ the use of electromyographic guidance, as I find this cumbersome and unnecessary. Electromyographic guidance may, however, be useful when getting started with chemodenervation for general orientation. Some of the literature on the cosmetic applications of botulinum toxin A describes and illustrates sites for injection with reference points targeted at the actual wrinkle line rather than the causative muscle.

Skin demarcations and sites of eventual injections of toxin can be made over the presumed belly or muscle mass of the regional muscle of facial expression and not typically at the site of the maximal dermal depression, which at times may be quite distant from the mass of the effecting muscle. For the larger, deeper muscles such as the corrugator supercilii, it is most useful and efficacious to inject toxin deep to the overlying muscles (frontalis and orbicularis) or directly into the belly of the targeted muscle. Typically, four or five injection sites at a dose of 2.5 to 5.0 units per site are satisfactory in eliminating focal muscle tone and voluntary contraction of the corrugators. More superficial application may affect the more superficial muscles, predominantly, without achieving the desired effect. This is most easily facilitated by familiarization with the pertinent facial soft-tissue anatomy and observing the dermal and muscular effects of the frown line on command. I have found it helpful to isolate the area by placing the thumb of the nondominant hand beneath the eyebrow and superior orbital rim. This serves to steady the patient’s head and target region, orient the injector to the supraorbital notch and neurovascular bundle, and avoid inadvertent injection into the orbit. The needle is inserted to the presumed level of the muscle mass of the corrugators followed by injection of the toxin. The thinner, orbicularis muscle (and even the procerus muscle) responds favorably to a more superficial, subcutaneous injection of Botox.

Unlike the other larger muscles of facial expression that may require direct contact of the toxin to the majority of the muscle mass, hence requiring injection more directly into the muscle, the relatively thin orbicularis muscle (and isolated procerus) seems to be satisfactorily affected by injecting the toxin into the subcutaneous space overlying the muscle. This not only reduces the chance of significant ecchymoses but may therefore maintain the potency that could be reduced by bleeding. Additionally, injection into the subcutaneous space may allow for more local (even) diffusion over the targeted muscle and provide an additional safety barrier to structures deep to the muscle. For lateral canthal rhytids (crow’s feet), three or four injections are given with particular avoidance of the pretarsal orbicularis of the upper and lower eyelid. This is achieved by directing needle insertion temporal to the lateral canthus near the lateral orbital rim and distant to the eyelid margin. The procerus muscle can be injected at one or two sites just beneath the (skin) transverse wrinkle at the nasal bridge. This superficial plane also avoids orbital injection. Hyperkinetic horizontal forehead furrows seem to respond favorably to either subcutaneous or intramuscular injection of the toxin, presumably since the frontalis is the only active muscle in this region. Weakening, rather than complete frontalis denervation, may also be preferable in some individuals to avoid brow ptosis. These injections are most effective by administering a uniform grid, whereby approximately nine or more sites are injected across the forehead. Three or more sites over each side are positioned in a vertical line above the mid-eyebrow. Additional sites are positioned vertically in the mid-forehead region. This affords focal frontalis muscle weakening at the medial aspects of each muscle group. A more homogeneous treatment of the forehead avoids focal areas of residual function that can become quite noticeable in lieu of complete absence of adjacent furrows. Typically, 2.5 units (0.1 ml) are administered at each site. Injections over the lateral eyebrow are minimized or avoided to reduce the potential for lateral eyebrow ptosis. Contrary to much of the reported concern regarding staying upright or avoiding physical activity for several hours after the injections,  I have not found it necessary to instruct patients on this. Cosmetics may be applied immediately after injection.

Although, theoretically, the effect of the toxin is described as occurring between 3 and 7 days after injection, I have noted consistently an earlier onset of effect compared with those patients who experience Botox for the treatment of eyelid and facial spastic disorders such as benign essential blepharospasm and hemifacial spasm. Occasionally, a patient-recipient of Botox for hyperkinetic facial lines experiences the effects within several hours for reasons not well understood. Although the immediate treatment benefits reflect the toxins’ ability to temporarily weaken or paralyze those muscles responsible for the muscular component of the hyperkinetic facial lines, the theoretic suggestion (not yet proven) is that repeated injections into the same muscles over time could produce a sort of disuse atrophy that would limit the development of certain facial lines in younger individuals and possibly eliminate or reduce (over time) established facial lines and furrows.

However, because of the entity of axonal sprouting  (discussed earlier) and the fact that patients typically return for additional treatment after the muscles have regained near complete clinical function (i.e., the wrinkle has returned), true long-term muscular atrophy may not be the only possible cause for long-term improvement in some individuals that may also reflect (in part) alteration in facial animation patterns and remodeling of the overlying soft tissue.

Botulinum toxin A also has been shown to be useful for a variety of other facial cosmetic problems. I have found it useful in even subtle cases of aberrant regeneration of the facial (seventh cranial) nerve (for instance after recovery of a Bell’s palsy), which although it may not induce a significant visual impairment, poses significant embarrassment to some. At times, very low doses are quite effective such as 1.0 unit or less per site administered over the pretarsal orbicularis in the same manner given for the treatment of (benign essential) blepharospasm. Botox can also be used to achieve symmetry in congenital and acquired unilateral facial paralysis by weakening the contralateral side.

Eyebrow asymmetry can be seen in a variety of scenarios including facial nerve trauma after brow lifts, other surgically induced facial paralysis, habit in those with long-standing (even post-corrected) ipsilateral blepharoptosis, asymmetric nonpathologic facial expression, etc. As an alternative to brow lifting the more ptotic eyebrow, one could consider eyebrow (focal frontalis muscle) chemodenervation to enhance symmetry for those who are unwilling to undergo surgery but who desire a more symmetric appearance. The sites and number of injections depend on where the effect is desired and usually are administered into (or overlying) frontalis muscle approximately 1.0 cm above the eyebrow to avoid the brow depressors.

One can induce creative changes in the eyebrow shape and position. For instance, it is well known that with injection of Botox for glabellar frown lines into the medial eyebrow, the adjacent medial frontalis muscle can at times be affected (by a higher injection that weakens the frontalis muscle focally), inducing a mild relative medial brow ptosis and at times effecting a more pleasing contour to the eyebrow (especially in flat brows). Brow contour can be even more accentuated by effecting a mild lateral brow elevation by injecting the lateral (sub-brow) orbital component of the orbicularis muscle, enhancing the effect of the antagonist lateral frontalis muscle. This method can be employed when injecting for crow’s feet with extension of the lateral canthal area injections (2.5 units/0.1 ml) into the lateral sub-brow region.

Orbicularis (oculi) muscle hypertrophy of the lower eyelids may also be effectively treated using very low concentrations (1.0 unit/0.05 ml) of toxin into or overlying the visibly hypertrophic (thickened) muscle. Low doses may still cause a mild but often acceptable degree of lower eyelid retraction. Two or three injections are administered at the central lower eyelid and lateral canthus overlying the affected areas. Higher concentrations, however, may induce significant paralytic eyelid retraction or ectropion and may also impair the nasolacrimal pumping action of the orbicularis muscle, inducing epiphora.

Similar caution and consideration can be applied to tone down the effects of the zygomaticus major and minor muscles. The zygomaticus major muscle not only affects the elevation of the corner of the mouth with smiling but in doing this recruits the enhancement of crow’s feet, which can be quite exaggerated in some individuals. The zygomaticus minor muscle originates similarly to the zygomaticus major muscle and inserts more medially into the upper lip. Both of these muscles, in part, when active, deepen the nasolabial fold. By using low dosages (2.5 units/0.2 ml) in the proximal aspects (far from the mouth) near the areas of origin, with efforts made to inject toxin mostly at the level of the edge of the inferior aspect of the orbicularis of the lower eyelid , one can soften their additive effect on the lateral canthal rhytids and nasolabial folds. One or two injections administered over the mid to lateral malar eminence are usually satisfactory in obtaining the desired effect without incurring complications, particularly paralysis of the ipsilateral upper lip.

Finally, Botox has been shown to be useful as a primary treatment in reducing fine perioral rhytids (lip stick lines).  Approximately 1.0 to 1.5 units of toxin is injected adjacent to the fine vertical rhytids overlying the orbicularis oris muscle close to the vermilion ridge. An added noted aesthetic effect at times with this treatment is the appearance of fuller (pseudo-augmented) lips because the sphincter muscle is weakened along the vermilion border to assume a more everted position.

Those experienced with CO2 laser abrasion have noted the first recurrent rhytids in the lower eyelid and lateral canthus. At times, in patients where there is significant hyperdynamics especially at the lateral canthus and perioral region, the rhytids can actually appear worse after laser skin resurfacing by any method . Pretreatment with Botox may improve the smoothing effect of the new remodeled/resurfaced skin long enough to effect more permanent eradication of wrinkles.

Similarly, this approach may be beneficial in pretreatment for those individuals who will undergo brow lifting procedures by enhancing results from weakening the inferior vector force (lateral orbital orbicularis oculi muscle, the antagonist to the frontalis muscle and eyebrow elevation), which would promote and provide maintenance of the elevated eyebrow position.

Reinforcement during lateral canthal suspension procedures such as the lateral tarsal strip or the lateral retinacular suspension  can be aided by injecting Botox (2.5 units/0.1 ml) around the lateral canthus as in the method described for the treatment of lateral canthal rhytids that not only diminished the regional rhytids but also reduced local orbicularis oculi function that, in part, may compromise the position and security of the lateral canthus with repeated muscular contraction.

Another very useful application of Botox has been in patients with soft-tissue contour abnormalities or atrophy that benefit from the coincident use of both modalities. Preceding the injection or surgical placement of the soft-tissue augmentation material by approximately 1 week, Botox is administered for focal weakness or paralysis. Injection of the dermal filler, subdermal fat, or surgical implantation (of alloplastic or allogeneic material) is then given into the paralyzed or muscularly weakened area. The denervation serves at least three purposes. First, it eliminates or reduces the dynamic/muscular component of rhytid formation. Second, there is some theoretic suggestion that it may increase the longevity of the dermal implant by reducing the supposed mechanical inflammatory influence on atrophy of the implant. Third, it may also simply reduce the immediate microextrusion at the injection sites by repetitive muscular action, etc. This can be seen by weakening the medial brow depressors before administering collagen or fat to the glabella or injecting Botox to the lip elevators and depressors before soft-tissue augmentation of the nasolabial folds and in lip augmentation, respectively. Dosages to the glabella are similar to those used in the primary treatment to any particular region. Lower dosages (1.25 units/0.1 ml) may be applied to the lips before augmentation. The combination of chemodenervation and soft-tissue augmentation (particularly autologous collagen) in these areas has been shown to be highly synergistic.

Other Observations

Not uncommonly, patients after receiving Botox (not necessarily particular to one facial region but more prevalent in those injected in or around the eyebrows and forehead) note a generalized (almost euphoric) feeling of improved sense of well being. I have assumed that this could be related to the relief of muscular contraction (tension) etc., similar to that in the classic muscular contraction or tension headaches. This finding has been consistent and possibly suggests even more expanded uses for the toxin. Most effects for the various cosmetic applications of Botox last (as in the functional/spastic disorders) between 4 and 6 months. Patients must be counseled and aware of the typical (transient) effects of chemodenervation on their hyperfunctional lines and the likely need for maintenance treatment.

Complications

Reported adverse reactions with the general use of Botox for all approved applications include blepharoptosis, diplopia, globe perforations, retrobulbar hemorrhage, Adies pupil, worsening of dry eye symptoms, lagophthalmos, photophobia, epiphora, ectropion, and exposure keratitis.  Complications that have arisen with the cosmetic applications of Botox have included most of the above-noted reactions and additional unwanted temporary effects including ecchymoses, eyebrow ptosis and asymmetry, and mouth drop. Unwanted side effects, such as blepharoptosis and mild lower eyelid retraction , typically last only a few weeks at most as the dose of migrated toxin to the affected muscle is usually significantly reduced. The temporary use of over the counter ocular decongestants (eyedrops) that contain adrenergic agents (with coincidental side effects of the eyedrops that include temporary contraction of Muller’s muscle and an elevated upper eyelid margin position) for allergy/congestion (Naphcon A, Vasocon A, Opcon A) may prove beneficial to those patients who are significantly symptomatic from the transient blepharoptosis.

The use of Botox for the treatment of hyperkinetic facial lines and furrows is merely another effective primary or adjunctive therapy to offer your cosmetic patients in the spectrum of treatment options for full facial rejuvenation. Unwanted side effects can be minimized and beneficial effects maximized with a thorough understanding of the facial soft-tissue anatomy, proper patient selection, and administration of the lowest effective dosages with minimal volume of delivery. It most often does not replace surgery, skin resurfacing, soft-tissue augmentation, or skin care. However, it has been shown to be quite useful when used alone or in conjunction with the variety of treatment options to give your selected patients the most effective and comprehensive solutions for a more youthful appearance

Once reconstituted, the toxin should be used as quickly as feasible. The package insert suggests that the product be used within 4 hours; however, many users have noted reasonable effects with the use of the product for up to 30 days.  In Dr Fagien’s experience, a notable decline in clinical potency occurs after 48 hours of reconstitution that may affect depth of focal paralysis and longevity of effect. Further, the relative stability of the reconstituted toxin is felt to be best maintained by refrigeration (not freezing), and it is suggested that the product be kept cool at every opportunity. To the best of my knowledge, however, there have been no studies to substantiate or refute claims of the duration of potency of the toxin after reconstitution.

Early investigators had suggested up to 10 to 20 units or more per site to affect the targeted muscles of facial expression.  However, one can achieve effects with far less toxin (2.5 units per site) and maintain longevity of effect for comparable periods of time. In my experience, this dose is effective for an average of 4 to 6 months. These lower doses in smaller volumes also serve to reduce unwanted effects and complications (see below). Concentrations much less that 2.5 units per 0.1 ml can induce a weakening effect on the targeted muscle but seem to do so for a much shorter duration. Additionally, men (or even women with clinically evident large hypertrophic target muscles-particularly corrugators or frontalis muscles) seem to require a slightly higher dose per injection site (up to 5.0 units per site), otherwise resulting in only mild to moderate improvement of hyperfunctional rhytids with shorter duration of effects. Diluted toxin should be drawn up into 1.0 ml (T.B. syringes) through an 18-gauge needle to minimize physical trauma to the toxin.

As in all procedures, patients desire maximum benefit with minimal side effects and morbidity. It may therefore be advisable that patients temporarily discontinue aspirin and other drugs that can affect bleeding time before Botox injection, similar to how you might instruct your patients before surgery. This, however, is not mandatory but may reduce or eliminate facial bruising that can last for several weeks. If minimal to no bruising occurs after injection of Botox, patients can typically return to work unnoticed less than 1 hour after treatment.

After the toxin is drawn up by 18-gauge needles into 1.0-ml syringes, the needle is then replaced by a short, 30-gauge needle for injection. The use of local anesthesia is relatively contraindicated and unnecessary. Alcohol may be applied to the injection sites but should be allowed to dry fully before injection of toxin owing to toxin lability. I currently do not employ the use of electromyographic guidance, as I find this cumbersome and unnecessary. Electromyographic guidance may, however, be useful when getting started with chemodenervation for general orientation. Some of the literature on the cosmetic applications of botulinum toxin A describes and illustrates sites for injection with reference points targeted at the actual wrinkle line rather than the causative muscle.

Skin demarcations and sites of eventual injections of toxin can be made over the presumed belly or muscle mass of the regional muscle of facial expression and not typically at the site of the maximal dermal depression, which at times may be quite distant from the mass of the effecting muscle. For the larger, deeper muscles such as the corrugator supercilii, it is most useful and efficacious to inject toxin deep to the overlying muscles (frontalis and orbicularis) or directly into the belly of the targeted muscle. Typically, four or five injection sites at a dose of 2.5 to 5.0 units per site are satisfactory in eliminating focal muscle tone and voluntary contraction of the corrugators. More superficial application may affect the more superficial muscles, predominantly, without achieving the desired effect. This is most easily facilitated by familiarization with the pertinent facial soft-tissue anatomy and observing the dermal and muscular effects of the frown line on command. I have found it helpful to isolate the area by placing the thumb of the nondominant hand beneath the eyebrow and superior orbital rim. This serves to steady the patient’s head and target region, orient the injector to the supraorbital notch and neurovascular bundle, and avoid inadvertent injection into the orbit. The needle is inserted to the presumed level of the muscle mass of the corrugators followed by injection of the toxin. The thinner, orbicularis muscle (and even the procerus muscle) responds favorably to a more superficial, subcutaneous injection of Botox.

Unlike the other larger muscles of facial expression that may require direct contact of the toxin to the majority of the muscle mass, hence requiring injection more directly into the muscle, the relatively thin orbicularis muscle (and isolated procerus) seems to be satisfactorily affected by injecting the toxin into the subcutaneous space overlying the muscle. This not only reduces the chance of significant ecchymoses but may therefore maintain the potency that could be reduced by bleeding. Additionally, injection into the subcutaneous space may allow for more local (even) diffusion over the targeted muscle and provide an additional safety barrier to structures deep to the muscle. For lateral canthal rhytids (crow’s feet), three or four injections are given with particular avoidance of the pretarsal orbicularis of the upper and lower eyelid. This is achieved by directing needle insertion temporal to the lateral canthus near the lateral orbital rim and distant to the eyelid margin. The procerus muscle can be injected at one or two sites just beneath the (skin) transverse wrinkle at the nasal bridge. This superficial plane also avoids orbital injection. Hyperkinetic horizontal forehead furrows seem to respond favorably to either subcutaneous or intramuscular injection of the toxin, presumably since the frontalis is the only active muscle in this region. Weakening, rather than complete frontalis denervation, may also be preferable in some individuals to avoid brow ptosis. These injections are most effective by administering a uniform grid, whereby approximately nine or more sites are injected across the forehead. Three or more sites over each side are positioned in a vertical line above the mid-eyebrow. Additional sites are positioned vertically in the mid-forehead region. This affords focal frontalis muscle weakening at the medial aspects of each muscle group. A more homogeneous treatment of the forehead avoids focal areas of residual function that can become quite noticeable in lieu of complete absence of adjacent furrows. Typically, 2.5 units (0.1 ml) are administered at each site. Injections over the lateral eyebrow are minimized or avoided to reduce the potential for lateral eyebrow ptosis. Contrary to much of the reported concern regarding staying upright or avoiding physical activity for several hours after the injections,  I have not found it necessary to instruct patients on this. Cosmetics may be applied immediately after injection.

Although, theoretically, the effect of the toxin is described as occurring between 3 and 7 days after injection, I have noted consistently an earlier onset of effect compared with those patients who experience Botox for the treatment of eyelid and facial spastic disorders such as benign essential blepharospasm and hemifacial spasm. Occasionally, a patient-recipient of Botox for hyperkinetic facial lines experiences the effects within several hours for reasons not well understood. Although the immediate treatment benefits reflect the toxins’ ability to temporarily weaken or paralyze those muscles responsible for the muscular component of the hyperkinetic facial lines, the theoretic suggestion (not yet proven) is that repeated injections into the same muscles over time could produce a sort of disuse atrophy that would limit the development of certain facial lines in younger individuals and possibly eliminate or reduce (over time) established facial lines and furrows.

However, because of the entity of axonal sprouting  (discussed earlier) and the fact that patients typically return for additional treatment after the muscles have regained near complete clinical function (i.e., the wrinkle has returned), true long-term muscular atrophy may not be the only possible cause for long-term improvement in some individuals that may also reflect (in part) alteration in facial animation patterns and remodeling of the overlying soft tissue.

Botulinum toxin A also has been shown to be useful for a variety of other facial cosmetic problems. I have found it useful in even subtle cases of aberrant regeneration of the facial (seventh cranial) nerve (for instance after recovery of a Bell’s palsy), which although it may not induce a significant visual impairment, poses significant embarrassment to some. At times, very low doses are quite effective such as 1.0 unit or less per site administered over the pretarsal orbicularis in the same manner given for the treatment of (benign essential) blepharospasm. Botox can also be used to achieve symmetry in congenital and acquired unilateral facial paralysis by weakening the contralateral side.

Eyebrow asymmetry can be seen in a variety of scenarios including facial nerve trauma after brow lifts, other surgically induced facial paralysis, habit in those with long-standing (even post-corrected) ipsilateral blepharoptosis, asymmetric nonpathologic facial expression, etc. As an alternative to brow lifting the more ptotic eyebrow, one could consider eyebrow (focal frontalis muscle) chemodenervation to enhance symmetry for those who are unwilling to undergo surgery but who desire a more symmetric appearance. The sites and number of injections depend on where the effect is desired and usually are administered into (or overlying) frontalis muscle approximately 1.0 cm above the eyebrow to avoid the brow depressors.

One can induce creative changes in the eyebrow shape and position. For instance, it is well known that with injection of Botox for glabellar frown lines into the medial eyebrow, the adjacent medial frontalis muscle can at times be affected (by a higher injection that weakens the frontalis muscle focally), inducing a mild relative medial brow ptosis and at times effecting a more pleasing contour to the eyebrow (especially in flat brows). Brow contour can be even more accentuated by effecting a mild lateral brow elevation by injecting the lateral (sub-brow) orbital component of the orbicularis muscle, enhancing the effect of the antagonist lateral frontalis muscle. This method can be employed when injecting for crow’s feet with extension of the lateral canthal area injections (2.5 units/0.1 ml) into the lateral sub-brow region.

Orbicularis (oculi) muscle hypertrophy of the lower eyelids may also be effectively treated using very low concentrations (1.0 unit/0.05 ml) of toxin into or overlying the visibly hypertrophic (thickened) muscle. Low doses may still cause a mild but often acceptable degree of lower eyelid retraction. Two or three injections are administered at the central lower eyelid and lateral canthus overlying the affected areas. Higher concentrations, however, may induce significant paralytic eyelid retraction or ectropion and may also impair the nasolacrimal pumping action of the orbicularis muscle, inducing epiphora.

Similar caution and consideration can be applied to tone down the effects of the zygomaticus major and minor muscles. The zygomaticus major muscle not only affects the elevation of the corner of the mouth with smiling but in doing this recruits the enhancement of crow’s feet, which can be quite exaggerated in some individuals. The zygomaticus minor muscle originates similarly to the zygomaticus major muscle and inserts more medially into the upper lip. Both of these muscles, in part, when active, deepen the nasolabial fold. By using low dosages (2.5 units/0.2 ml) in the proximal aspects (far from the mouth) near the areas of origin, with efforts made to inject toxin mostly at the level of the edge of the inferior aspect of the orbicularis of the lower eyelid , one can soften their additive effect on the lateral canthal rhytids and nasolabial folds. One or two injections administered over the mid to lateral malar eminence are usually satisfactory in obtaining the desired effect without incurring complications, particularly paralysis of the ipsilateral upper lip.

Finally, Botox has been shown to be useful as a primary treatment in reducing fine perioral rhytids (lip stick lines).  Approximately 1.0 to 1.5 units of toxin is injected adjacent to the fine vertical rhytids overlying the orbicularis oris muscle close to the vermilion ridge. An added noted aesthetic effect at times with this treatment is the appearance of fuller (pseudo-augmented) lips because the sphincter muscle is weakened along the vermilion border to assume a more everted position.

Those experienced with CO2 laser abrasion have noted the first recurrent rhytids in the lower eyelid and lateral canthus. At times, in patients where there is significant hyperdynamics especially at the lateral canthus and perioral region, the rhytids can actually appear worse after laser skin resurfacing by any method . Pretreatment with Botox may improve the smoothing effect of the new remodeled/resurfaced skin long enough to effect more permanent eradication of wrinkles.

Similarly, this approach may be beneficial in pretreatment for those individuals who will undergo brow lifting procedures by enhancing results from weakening the inferior vector force (lateral orbital orbicularis oculi muscle, the antagonist to the frontalis muscle and eyebrow elevation), which would promote and provide maintenance of the elevated eyebrow position.

Reinforcement during lateral canthal suspension procedures such as the lateral tarsal strip or the lateral retinacular suspension  can be aided by injecting Botox (2.5 units/0.1 ml) around the lateral canthus as in the method described for the treatment of lateral canthal rhytids that not only diminished the regional rhytids but also reduced local orbicularis oculi function that, in part, may compromise the position and security of the lateral canthus with repeated muscular contraction.

Another very useful application of Botox has been in patients with soft-tissue contour abnormalities or atrophy that benefit from the coincident use of both modalities. Preceding the injection or surgical placement of the soft-tissue augmentation material by approximately 1 week, Botox is administered for focal weakness or paralysis. Injection of the dermal filler, subdermal fat, or surgical implantation (of alloplastic or allogeneic material) is then given into the paralyzed or muscularly weakened area. The denervation serves at least three purposes. First, it eliminates or reduces the dynamic/muscular component of rhytid formation. Second, there is some theoretic suggestion that it may increase the longevity of the dermal implant by reducing the supposed mechanical inflammatory influence on atrophy of the implant. Third, it may also simply reduce the immediate microextrusion at the injection sites by repetitive muscular action, etc. This can be seen by weakening the medial brow depressors before administering collagen or fat to the glabella or injecting Botox to the lip elevators and depressors before soft-tissue augmentation of the nasolabial folds and in lip augmentation, respectively. Dosages to the glabella are similar to those used in the primary treatment to any particular region. Lower dosages (1.25 units/0.1 ml) may be applied to the lips before augmentation. The combination of chemodenervation and soft-tissue augmentation (particularly autologous collagen) in these areas has been shown to be highly synergistic.

Other Observations

Not uncommonly, patients after receiving Botox (not necessarily particular to one facial region but more prevalent in those injected in or around the eyebrows and forehead) note a generalized (almost euphoric) feeling of improved sense of well being. I have assumed that this could be related to the relief of muscular contraction (tension) etc., similar to that in the classic muscular contraction or tension headaches. This finding has been consistent and possibly suggests even more expanded uses for the toxin. Most effects for the various cosmetic applications of Botox last (as in the functional/spastic disorders) between 4 and 6 months. Patients must be counseled and aware of the typical (transient) effects of chemodenervation on their hyperfunctional lines and the likely need for maintenance treatment.

Complications

Reported adverse reactions with the general use of Botox for all approved applications include blepharoptosis, diplopia, globe perforations, retrobulbar hemorrhage, Adies pupil, worsening of dry eye symptoms, lagophthalmos, photophobia, epiphora, ectropion, and exposure keratitis.  Complications that have arisen with the cosmetic applications of Botox have included most of the above-noted reactions and additional unwanted temporary effects including ecchymoses, eyebrow ptosis and asymmetry, and mouth drop. Unwanted side effects, such as blepharoptosis and mild lower eyelid retraction , typically last only a few weeks at most as the dose of migrated toxin to the affected muscle is usually significantly reduced. The temporary use of over the counter ocular decongestants (eyedrops) that contain adrenergic agents (with coincidental side effects of the eyedrops that include temporary contraction of Muller’s muscle and an elevated upper eyelid margin position) for allergy/congestion (Naphcon A, Vasocon A, Opcon A) may prove beneficial to those patients who are significantly symptomatic from the transient blepharoptosis.

The use of Botox for the treatment of hyperkinetic facial lines and furrows is merely another effective primary or adjunctive therapy to offer your cosmetic patients in the spectrum of treatment options for full facial rejuvenation. Unwanted side effects can be minimized and beneficial effects maximized with a thorough understanding of the facial soft-tissue anatomy, proper patient selection, and administration of the lowest effective dosages with minimal volume of delivery. It most often does not replace surgery, skin resurfacing, soft-tissue augmentation, or skin care. However, it has been shown to be quite useful when used alone or in conjunction with the variety of treatment options to give your selected patients the most effective and comprehensive solutions for a more youthful appearance

Once reconstituted, the toxin should be used as quickly as feasible. The package insert suggests that the product be used within 4 hours; however, many users have noted reasonable effects with the use of the product for up to 30 days.  In Dr Fagien’s experience, a notable decline in clinical potency occurs after 48 hours of reconstitution that may affect depth of focal paralysis and longevity of effect. Further, the relative stability of the reconstituted toxin is felt to be best maintained by refrigeration (not freezing), and it is suggested that the product be kept cool at every opportunity. To the best of my knowledge, however, there have been no studies to substantiate or refute claims of the duration of potency of the toxin after reconstitution.

Early investigators had suggested up to 10 to 20 units or more per site to affect the targeted muscles of facial expression.  However, one can achieve effects with far less toxin (2.5 units per site) and maintain longevity of effect for comparable periods of time. In my experience, this dose is effective for an average of 4 to 6 months. These lower doses in smaller volumes also serve to reduce unwanted effects and complications (see below). Concentrations much less that 2.5 units per 0.1 ml can induce a weakening effect on the targeted muscle but seem to do so for a much shorter duration. Additionally, men (or even women with clinically evident large hypertrophic target muscles-particularly corrugators or frontalis muscles) seem to require a slightly higher dose per injection site (up to 5.0 units per site), otherwise resulting in only mild to moderate improvement of hyperfunctional rhytids with shorter duration of effects. Diluted toxin should be drawn up into 1.0 ml (T.B. syringes) through an 18-gauge needle to minimize physical trauma to the toxin.

As in all procedures, patients desire maximum benefit with minimal side effects and morbidity. It may therefore be advisable that patients temporarily discontinue aspirin and other drugs that can affect bleeding time before Botox injection, similar to how you might instruct your patients before surgery. This, however, is not mandatory but may reduce or eliminate facial bruising that can last for several weeks. If minimal to no bruising occurs after injection of Botox, patients can typically return to work unnoticed less than 1 hour after treatment.

After the toxin is drawn up by 18-gauge needles into 1.0-ml syringes, the needle is then replaced by a short, 30-gauge needle for injection. The use of local anesthesia is relatively contraindicated and unnecessary. Alcohol may be applied to the injection sites but should be allowed to dry fully before injection of toxin owing to toxin lability. I currently do not employ the use of electromyographic guidance, as I find this cumbersome and unnecessary. Electromyographic guidance may, however, be useful when getting started with chemodenervation for general orientation. Some of the literature on the cosmetic applications of botulinum toxin A describes and illustrates sites for injection with reference points targeted at the actual wrinkle line rather than the causative muscle.

Skin demarcations and sites of eventual injections of toxin can be made over the presumed belly or muscle mass of the regional muscle of facial expression and not typically at the site of the maximal dermal depression, which at times may be quite distant from the mass of the effecting muscle. For the larger, deeper muscles such as the corrugator supercilii, it is most useful and efficacious to inject toxin deep to the overlying muscles (frontalis and orbicularis) or directly into the belly of the targeted muscle. Typically, four or five injection sites at a dose of 2.5 to 5.0 units per site are satisfactory in eliminating focal muscle tone and voluntary contraction of the corrugators. More superficial application may affect the more superficial muscles, predominantly, without achieving the desired effect. This is most easily facilitated by familiarization with the pertinent facial soft-tissue anatomy and observing the dermal and muscular effects of the frown line on command. I have found it helpful to isolate the area by placing the thumb of the nondominant hand beneath the eyebrow and superior orbital rim. This serves to steady the patient’s head and target region, orient the injector to the supraorbital notch and neurovascular bundle, and avoid inadvertent injection into the orbit. The needle is inserted to the presumed level of the muscle mass of the corrugators followed by injection of the toxin. The thinner, orbicularis muscle (and even the procerus muscle) responds favorably to a more superficial, subcutaneous injection of Botox.

Unlike the other larger muscles of facial expression that may require direct contact of the toxin to the majority of the muscle mass, hence requiring injection more directly into the muscle, the relatively thin orbicularis muscle (and isolated procerus) seems to be satisfactorily affected by injecting the toxin into the subcutaneous space overlying the muscle. This not only reduces the chance of significant ecchymoses but may therefore maintain the potency that could be reduced by bleeding. Additionally, injection into the subcutaneous space may allow for more local (even) diffusion over the targeted muscle and provide an additional safety barrier to structures deep to the muscle. For lateral canthal rhytids (crow’s feet), three or four injections are given with particular avoidance of the pretarsal orbicularis of the upper and lower eyelid. This is achieved by directing needle insertion temporal to the lateral canthus near the lateral orbital rim and distant to the eyelid margin. The procerus muscle can be injected at one or two sites just beneath the (skin) transverse wrinkle at the nasal bridge. This superficial plane also avoids orbital injection. Hyperkinetic horizontal forehead furrows seem to respond favorably to either subcutaneous or intramuscular injection of the toxin, presumably since the frontalis is the only active muscle in this region. Weakening, rather than complete frontalis denervation, may also be preferable in some individuals to avoid brow ptosis. These injections are most effective by administering a uniform grid, whereby approximately nine or more sites are injected across the forehead. Three or more sites over each side are positioned in a vertical line above the mid-eyebrow. Additional sites are positioned vertically in the mid-forehead region. This affords focal frontalis muscle weakening at the medial aspects of each muscle group. A more homogeneous treatment of the forehead avoids focal areas of residual function that can become quite noticeable in lieu of complete absence of adjacent furrows. Typically, 2.5 units (0.1 ml) are administered at each site. Injections over the lateral eyebrow are minimized or avoided to reduce the potential for lateral eyebrow ptosis. Contrary to much of the reported concern regarding staying upright or avoiding physical activity for several hours after the injections,  I have not found it necessary to instruct patients on this. Cosmetics may be applied immediately after injection.

Although, theoretically, the effect of the toxin is described as occurring between 3 and 7 days after injection, I have noted consistently an earlier onset of effect compared with those patients who experience Botox for the treatment of eyelid and facial spastic disorders such as benign essential blepharospasm and hemifacial spasm. Occasionally, a patient-recipient of Botox for hyperkinetic facial lines experiences the effects within several hours for reasons not well understood. Although the immediate treatment benefits reflect the toxins’ ability to temporarily weaken or paralyze those muscles responsible for the muscular component of the hyperkinetic facial lines, the theoretic suggestion (not yet proven) is that repeated injections into the same muscles over time could produce a sort of disuse atrophy that would limit the development of certain facial lines in younger individuals and possibly eliminate or reduce (over time) established facial lines and furrows.

However, because of the entity of axonal sprouting  (discussed earlier) and the fact that patients typically return for additional treatment after the muscles have regained near complete clinical function (i.e., the wrinkle has returned), true long-term muscular atrophy may not be the only possible cause for long-term improvement in some individuals that may also reflect (in part) alteration in facial animation patterns and remodeling of the overlying soft tissue.

Botulinum toxin A also has been shown to be useful for a variety of other facial cosmetic problems. I have found it useful in even subtle cases of aberrant regeneration of the facial (seventh cranial) nerve (for instance after recovery of a Bell’s palsy), which although it may not induce a significant visual impairment, poses significant embarrassment to some. At times, very low doses are quite effective such as 1.0 unit or less per site administered over the pretarsal orbicularis in the same manner given for the treatment of (benign essential) blepharospasm. Botox can also be used to achieve symmetry in congenital and acquired unilateral facial paralysis by weakening the contralateral side.

Eyebrow asymmetry can be seen in a variety of scenarios including facial nerve trauma after brow lifts, other surgically induced facial paralysis, habit in those with long-standing (even post-corrected) ipsilateral blepharoptosis, asymmetric nonpathologic facial expression, etc. As an alternative to brow lifting the more ptotic eyebrow, one could consider eyebrow (focal frontalis muscle) chemodenervation to enhance symmetry for those who are unwilling to undergo surgery but who desire a more symmetric appearance. The sites and number of injections depend on where the effect is desired and usually are administered into (or overlying) frontalis muscle approximately 1.0 cm above the eyebrow to avoid the brow depressors.

One can induce creative changes in the eyebrow shape and position. For instance, it is well known that with injection of Botox for glabellar frown lines into the medial eyebrow, the adjacent medial frontalis muscle can at times be affected (by a higher injection that weakens the frontalis muscle focally), inducing a mild relative medial brow ptosis and at times effecting a more pleasing contour to the eyebrow (especially in flat brows). Brow contour can be even more accentuated by effecting a mild lateral brow elevation by injecting the lateral (sub-brow) orbital component of the orbicularis muscle, enhancing the effect of the antagonist lateral frontalis muscle. This method can be employed when injecting for crow’s feet with extension of the lateral canthal area injections (2.5 units/0.1 ml) into the lateral sub-brow region.

Orbicularis (oculi) muscle hypertrophy of the lower eyelids may also be effectively treated using very low concentrations (1.0 unit/0.05 ml) of toxin into or overlying the visibly hypertrophic (thickened) muscle. Low doses may still cause a mild but often acceptable degree of lower eyelid retraction. Two or three injections are administered at the central lower eyelid and lateral canthus overlying the affected areas. Higher concentrations, however, may induce significant paralytic eyelid retraction or ectropion and may also impair the nasolacrimal pumping action of the orbicularis muscle, inducing epiphora.

Similar caution and consideration can be applied to tone down the effects of the zygomaticus major and minor muscles. The zygomaticus major muscle not only affects the elevation of the corner of the mouth with smiling but in doing this recruits the enhancement of crow’s feet, which can be quite exaggerated in some individuals. The zygomaticus minor muscle originates similarly to the zygomaticus major muscle and inserts more medially into the upper lip. Both of these muscles, in part, when active, deepen the nasolabial fold. By using low dosages (2.5 units/0.2 ml) in the proximal aspects (far from the mouth) near the areas of origin, with efforts made to inject toxin mostly at the level of the edge of the inferior aspect of the orbicularis of the lower eyelid , one can soften their additive effect on the lateral canthal rhytids and nasolabial folds. One or two injections administered over the mid to lateral malar eminence are usually satisfactory in obtaining the desired effect without incurring complications, particularly paralysis of the ipsilateral upper lip.

Finally, Botox has been shown to be useful as a primary treatment in reducing fine perioral rhytids (lip stick lines).  Approximately 1.0 to 1.5 units of toxin is injected adjacent to the fine vertical rhytids overlying the orbicularis oris muscle close to the vermilion ridge. An added noted aesthetic effect at times with this treatment is the appearance of fuller (pseudo-augmented) lips because the sphincter muscle is weakened along the vermilion border to assume a more everted position.

Those experienced with CO2 laser abrasion have noted the first recurrent rhytids in the lower eyelid and lateral canthus. At times, in patients where there is significant hyperdynamics especially at the lateral canthus and perioral region, the rhytids can actually appear worse after laser skin resurfacing by any method . Pretreatment with Botox may improve the smoothing effect of the new remodeled/resurfaced skin long enough to effect more permanent eradication of wrinkles.

Similarly, this approach may be beneficial in pretreatment for those individuals who will undergo brow lifting procedures by enhancing results from weakening the inferior vector force (lateral orbital orbicularis oculi muscle, the antagonist to the frontalis muscle and eyebrow elevation), which would promote and provide maintenance of the elevated eyebrow position.

Reinforcement during lateral canthal suspension procedures such as the lateral tarsal strip or the lateral retinacular suspension  can be aided by injecting Botox (2.5 units/0.1 ml) around the lateral canthus as in the method described for the treatment of lateral canthal rhytids that not only diminished the regional rhytids but also reduced local orbicularis oculi function that, in part, may compromise the position and security of the lateral canthus with repeated muscular contraction.

Another very useful application of Botox has been in patients with soft-tissue contour abnormalities or atrophy that benefit from the coincident use of both modalities. Preceding the injection or surgical placement of the soft-tissue augmentation material by approximately 1 week, Botox is administered for focal weakness or paralysis. Injection of the dermal filler, subdermal fat, or surgical implantation (of alloplastic or allogeneic material) is then given into the paralyzed or muscularly weakened area. The denervation serves at least three purposes. First, it eliminates or reduces the dynamic/muscular component of rhytid formation. Second, there is some theoretic suggestion that it may increase the longevity of the dermal implant by reducing the supposed mechanical inflammatory influence on atrophy of the implant. Third, it may also simply reduce the immediate microextrusion at the injection sites by repetitive muscular action, etc. This can be seen by weakening the medial brow depressors before administering collagen or fat to the glabella or injecting Botox to the lip elevators and depressors before soft-tissue augmentation of the nasolabial folds and in lip augmentation, respectively. Dosages to the glabella are similar to those used in the primary treatment to any particular region. Lower dosages (1.25 units/0.1 ml) may be applied to the lips before augmentation. The combination of chemodenervation and soft-tissue augmentation (particularly autologous collagen) in these areas has been shown to be highly synergistic.

Other Observations

Not uncommonly, patients after receiving Botox (not necessarily particular to one facial region but more prevalent in those injected in or around the eyebrows and forehead) note a generalized (almost euphoric) feeling of improved sense of well being. I have assumed that this could be related to the relief of muscular contraction (tension) etc., similar to that in the classic muscular contraction or tension headaches. This finding has been consistent and possibly suggests even more expanded uses for the toxin. Most effects for the various cosmetic applications of Botox last (as in the functional/spastic disorders) between 4 and 6 months. Patients must be counseled and aware of the typical (transient) effects of chemodenervation on their hyperfunctional lines and the likely need for maintenance treatment.

Complications

Reported adverse reactions with the general use of Botox for all approved applications include blepharoptosis, diplopia, globe perforations, retrobulbar hemorrhage, Adies pupil, worsening of dry eye symptoms, lagophthalmos, photophobia, epiphora, ectropion, and exposure keratitis.  Complications that have arisen with the cosmetic applications of Botox have included most of the above-noted reactions and additional unwanted temporary effects including ecchymoses, eyebrow ptosis and asymmetry, and mouth drop. Unwanted side effects, such as blepharoptosis and mild lower eyelid retraction , typically last only a few weeks at most as the dose of migrated toxin to the affected muscle is usually significantly reduced. The temporary use of over the counter ocular decongestants (eyedrops) that contain adrenergic agents (with coincidental side effects of the eyedrops that include temporary contraction of Muller’s muscle and an elevated upper eyelid margin position) for allergy/congestion (Naphcon A, Vasocon A, Opcon A) may prove beneficial to those patients who are significantly symptomatic from the transient blepharoptosis.

The use of Botox for the treatment of hyperkinetic facial lines and furrows is merely another effective primary or adjunctive therapy to offer your cosmetic patients in the spectrum of treatment options for full facial rejuvenation. Unwanted side effects can be minimized and beneficial effects maximized with a thorough understanding of the facial soft-tissue anatomy, proper patient selection, and administration of the lowest effective dosages with minimal volume of delivery. It most often does not replace surgery, skin resurfacing, soft-tissue augmentation, or skin care. However, it has been shown to be quite useful when used alone or in conjunction with the variety of treatment options to give your selected patients the most effective and comprehensive solutions for a more youthful appearance

BOTOX FACTS AND NUMBERS

Monday, September 8th, 2008

BOTOX® Cosmetic and BOTOX® (Botulinum Toxin Type A) By the Numbers

• 3,181,592: Number of BOTOX® Cosmetic treatments administered in the United States in 2006
alone

• 1,000,000s: People who received treatment with BOTOX® for medical and aesthetic purposes
around the world

• 300,000: Number of men who received treatment with BOTOX® Cosmetic in 2006

• 10,000: People in clinical trials

• 3,000: Publications on Botulinum Toxin Type A in scientific and medical journals

• 100: Years of study into botulinum neurotoxins

• 97: Percentage of people satisfied with their BOTOX® Cosmetic treatment based on a survey of
   approximately 1,000 patients

• 75: Countries around the world who have approved use of BOTOX®

• 20: BOTOX® indications approved by regulatory authorities around the world, including the aesthetic 
   indication

• 18: Years since U.S. Food and Drug Administration (FDA) approved BOTOX® to treat excessive eye 
   blinking and crossed eyes

• 11: Descriptor for the glabellar (vertical) lines between the brows which can be treated with BOTOX®
   Cosmetic, that can help improve one’s overall facial appearance

• 8: Years since FDA approval of BOTOX® for the treatment of cervical dystonia (painful neck twisting
   condition) in adults

• 6: Years since FDA approval of BOTOX® Cosmetic for the treatment of the moderate to severe
   glabellar (vertical) lines between the brows in adults 18 to 65

• 4: Years since FDA approval of BOTOX® for the treatment of severe primary hyperhidrosis (excessive
   underarm sweating) inadequately managed with topical agents

• 1: Rank of BOTOX® Cosmetic on list of “Top 5 Surgical & Nonsurgical Physician Administered
   Cosmetic Procedures,” according to American Society for Aesthetic Plastic Surgery

About BOTOX® (Botulinum Toxin Type A)

BOTOX® is a medical product that contains tiny amounts of highly purified botulinum toxin protein refined from a bacterium. The product is administered in small therapeutic doses by injection directly into the affected area, and works by blocking the release of acetylcholine (a neurotransmitter that signals the
muscles to contract) at the neuromuscular junction.

BOTOX® neurotoxin therapy was granted approval by the FDA in 1989 for the treatment of strabismus
(crossed eyes) and blepharospasm (uncontrollable eye blinking) associated with dystonia, including benign essential blepharospasm or VII nerve disorders in patients 12 years of age and above. The efficacy of BOTOX® treatment in deviations over 50 prism diopters, in restrictive strabismus, in Duane’s syndrome with lateral rectus weakness, and in secondary strabismus caused by prior surgical over-recession of the
antagonist has not been established. BOTOX® is ineffective in chronic paralytic strabismus except when
used in conjunction with surgical repair to reduce antagonist contracture.

BOTOX® neurotoxin has since received approval in December 2000 for the treatment of cervical dystonia in adults to decrease the severity of abnormal head position and neck pain associated with cervical dystonia.

In 2002, with dosing specific to treat frown lines between the eyebrows, the product was approved by the FDA for the temporary improvement in the appearance of moderate to severe glabellar lines (the vertical “frown lines” between the eyebrows) in adult men and women aged 65 and younger, under the name BOTOX® Cosmetic. More recently, in July 2004, BOTOX® was granted FDA approval for the treatment of
severe primary axillary hyperhidrosis (excessive underarm sweating) that is inadequately managed with
topical agents.


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