Botulinum toxin is an injectable neuromodulator derived from neurotoxins produced by Clostridium botulinum, the bacterium responsible for botulism.
As a result of the ability of the toxin to inhibit neurotransmission between peripheral nerves and muscle tissue, botulinum toxin is an effective treatment for aesthetic and medical concerns that are exacerbated by muscle contraction. Although US Food and Drug Administration (FDA) approval for the cosmetic use of onabotulinumtoxinA is limited to glabellar lines, lateral canthal lines (crow’s feet), and forehead lines and FDA approval for incobotulinumtoxinA and abobotulinumtoxinA remains limited to the treatment of glabellar lines, injectable botulinum toxin is widely used for other cosmetic indications.
The human face is composed of a complex array of muscles that act in concert to create facial expressions and fulfill vital functions. Clinicians with a thorough understanding of facial anatomy and the functional relationships between muscles in the face and neck can safely use botulinum toxin to selectively weaken specific muscles, resulting in favourable cosmetic results.
Appropriate candidates for botulinum toxin injection are patients with specific cosmetic concerns that can be alleviated by local muscle weakening and who lack contraindications to therapy. Patients between the ages of 30 and 50 years often achieve the most benefit from treatment; a greater proportion of rhytides in older patients may be due to loss of skin elasticity, which is not alleviated by botulinum toxin. Surgical revision may be more appropriate in these cases.
Once patients have been determined to be good candidates for botulinum toxin therapy, care must be taken to ensure that the anatomic placement of injections is correct and that the doses used are appropriate based upon the treatment site and patient-specific characteristics (eg, anatomic variation, patient sex, and preferences regarding the magnitude of effect). Conservative treatment is preferred; improper placement of injections or an excessive dose of botulinum toxin can result in cosmetic or functional defects that persist for months.
There are seven serotypes of botulinum toxin, two of which are available for clinical use (botulinum toxin type A and botulinum toxin type B). Botulinum toxin type A has been the most extensively studied for cosmetic indications and is the serotype that will be discussed here. A variety of formulations of botulinum toxin type A are available for clinical use worldwide; the agents most commonly used include onabotulinumtoxinA (Botox, Botox Cosmetic), incobotulinumtoxinA (Xeomin, Bocouture), and abobotulinumtoxinA (Dysport).
The muscles of movement and expression in the upper face include the frontalis, a large quadrilateral muscle that raises the eyebrows and skin over the root of the nose and draws the scalp forward, and the glabellar complex, a group of brow-associated muscles (corrugator supercilii, procerus, depressor supercilii, and orbicularis oculi muscles) used primarily for expression, especially anger, displeasure, or concern.
Hyperactivity or repetitive use of these muscles over time leads to the formation of skin lines that are exacerbated during muscle contraction (dynamic rhytides). Weakening of the responsible muscles with botulinum toxin can smooth vertical glabellar rhytides (related to the contraction of muscles in the glabellar complex), horizontal forehead rhytides (induced by frontalis muscle contraction), and periorbital lateral canthal rhytides (associated with contraction of the lateral orbicularis oculi muscle).
The first report of the use of botulinum toxin for a cosmetic purpose focused on the treatment of glabellar rhytides. Glabellar lines are caused by contraction of the corrugator supercilii and orbicularis oculi muscles, which move the brow medially, and the procerus and depressor supercilii muscles, which pull the brow inferiorly. The corrugator supercilii and procerus muscles are typically targeted during treatment. Beneficial effects from injection last for at least three months in most patients.
Although the precise placement and number of injections is influenced by anatomical differences among patients, five injection sites are commonly used to weaken the brow depressors in the treatment of glabellar rhytides All injections should be placed above the supraorbital rim to reduce the risk of upper eyelid ptosis. Mr Andi typicaly injects into the corrugator supercilii muscles above the inner canthi bilaterally (30 percent of total dose per injection) followed by a third medial injection into the procerus (20 percent of total dose). These injections are placed 1 cm above the supraorbital rim in the mid-pupillary line (10 percent of total dose per injection), but can also be sited above the lateral canthus, above the bony rim.
The standard doses recommended by the manufacturers of onabotulinumtoxinA (Botox Cosmetic), incobotulinumtoxinA (Xeomin), and abobotulinumtoxinA (Dysport) are total doses 20 units, 20 units, and 50 units, respectively. However, the doses required to achieve desired results vary among patients due to differences in muscle mass or muscle activity. Males typically have greater muscle mass in the brow than females, and thus require higher doses to achieve satisfactory results. We found the following results in two randomized dose-finding trials of 80 patients with glabellar rhytides:
●A dose of 10 units of onabotulinumtoxinA was significantly less effective than 20, 30, or 40 units for the treatment of glabellar lines in women and was associated with a higher risk of relapse after four months.
●Among male patients, doses of 40, 60, or 80 units of onabotulinumtoxinA were more effective and induced longer lasting benefit than treatment with 20 units.
The incidence of adverse effects was similar among treatment groups in both trials. Treatment-related adverse effects were transient and mild to moderate, and included symptoms such as headache, symptoms of tension or heaviness in the forehead or brow, ptosis of the brow, and muscle spasms in the forehead.
Mr Andi typically initiates treatment with approximately 30 units of onabotulinumtoxinA in women and 60 units in men, with subsequent increases in dose up to 50 or 100 units, respectively, based upon response. Lower initial doses (10 to 30 units for women and 20 to 40 units for men) have also been used for glabellar rhytides. For treatment with abobotulinumtoxinA, dose ranges of 30 to 70 units in women and 50 to 80 units in men have been suggested by some authors.
Mr Andi has found that some patients benefit from a total of seven injections, with the additional two injections placed into the lateral orbicularis oculi muscle. These injections are performed above the lateral canthus or into the lateral end of the eyebrow, and can result in further reductions in the glabellar lines and improved positioning of the lateral brow. Mr Andi typically uses 4 to 8 units of onabotulinumtoxinA in these sites.
Horizontal forehead rhytides
Contraction of the frontalis muscle eventually leads to the formation of horizontal creases in the forehead that are exacerbated during brow elevation. Botulinum toxin injection can reduce the appearance of these lines both during muscle contraction and at rest. In my experience, the beneficial effects of treatment in this area typically last between three and six months.
The goal of treatment is to weaken but not completely paralyze the frontalis muscle. Patients with favorable responses have reduced forehead rhytides and remain able to elevate the brows, albeit to a lesser extent. Treatment of the frontalis muscle for horizontal rhytides should always be performed in conjunction with treatment of the brow depressors. Weakening of the frontalis muscle without corresponding inhibition of the brow depressors can result in unopposed action of the depressors and a lowered, angry-looking brow.
In a randomized, dose-finding trial that investigated the efficacy of treatment with onaboutlinumtoxinA in 59 women with moderate to severe forehead rhytides, total doses of 16, 32, and 48 units injected into the brow elevators and depressors (frontalis, procerus, and lateral orbicularis oculi muscles) (8, 16, and 24 units injected into the frontalis) all were effective for achieving improvement. Of note, a statistically significant trend towards longer durations of response was observed with increasing doses. Sixteen weeks after treatment, wrinkle severity at maximum muscle contraction and repose had returned to baseline in 75, 58, and 35 percent of patients in the 16, 32, and 48 unit treatment groups, respectively. The number of adverse effects was similar among treatment groups and no serious adverse effects occurred during the course of the trial.
As in the glabellar area, patient-specific characteristics influence botulinum toxin administration. We typically perform five injections in patients with broad foreheads (greater than 12 cm between the temporal fusion lines at the mid-brow) and four injections in patients with narrower foreheads, using a slightly lower total dose in the latter. The total amount of onabotulinumtoxin we inject into the frontalis muscle usually ranges between 10 and 15 units. Treatment with 40 units (range 20 to 60 units) of abobotulinumtoxinA in four injection sites has been utilized by some authors.
Injections into the frontalis muscle must be placed carefully to avoid undesirable cosmetic results. We inject horizontally across the mid-forehead, approximately 2 to 3 cm above the eyebrows. The use of excessive doses or placement of injections too close to the brow can result in inhibition of facial expression and brow ptosis.
Lateral canthal rhytides (crow’s feet)
The orbicularis oculi muscle complex plays an important role in eyelid closure. Contraction of the lateral fibers of the orbicularis oculi muscle also produces lines (also known as crow’s feet) that radiate from the lateral canthus and are exacerbated during smiling. Botulinum toxin injection into this area can reduce the appearance of these rhytides.
A dose-dependent effect of treatment has been reported. In one randomized trial in which 157 patients with moderate to severe lateral canthal rhytides were treated with varying doses of onabotulinumtoxinA or placebo, the rates of treatment response remained significantly greater than placebo for longer periods of time with higher doses than with lower doses. Patients treated with 12 or 18 units per side maintained significant improvement at maximal smile for at least 150 days after treatment, while the difference between placebo and treatment groups was no longer statistically significant in patients treated with 3 or 6 units at 60 or 150 days, respectively. The authors also commented that the magnitude of effect appeared to be higher in patients treated with the higher doses of onabotulinumtoxinA.
Because the orbicularis oculi muscle is diffusely innervated, multiple injections are required to weaken the muscle effectively. I typically inject 12 to 15 units of onabotulinumtoxinA per periocular region divided into two to four injection sites.
A separate randomized trial of abobotulinumtoxinA injections for lateral canthal rhytides found that doses of 15, 30, and 45 units per side were all effective, but detected a trend towards increased response rates with doses of 30 and 45 units. Use of a total dose of 30 units, divided into three injection points per side, has been suggested by some authors.
IncobotulinumtoxinA has also been used successfully for the treatment of periocular rhytides.
In order to minimize the risk for complications, all injections should be placed laterally to the lateral orbital rim and should be performed while the face is at rest. Medial injections or injections performed while the patient is smiling can result in eyelid droop and lip ptosis, respectively. Additionally, bruising is easily induced in the periorbital area; performing only a few superficial injections may reduce this risk. The application of manual pressure immediately after needle withdrawal may also reduce the occurrence of bruising.
Brow ptosis a common feature of aging, can result in facial features at rest that mimic angry or scowling facial expressions. Because the shape and height of the eyebrow are controlled by the opposing action of the frontalis muscle, which elevates the brow, and the muscles that depress the brow, botulinum toxin can be used to improve brow ptosis.
The nonsurgical brow lift with botulinum toxin was discovered serendipitously during treatment of glabellar frown lines, as it became evident that treated patients exhibited central and medial brow elevation. Elevation of the brow was initially thought to be due to inactivation of the medial depressor muscles. However, weakening of the lower medial frontalis muscle due to local diffusion of botulinum toxin may be responsible for improved resting tone in the rest of the frontalis musculature and subsequent brow elevation.
Typically, brow elevation is best seen when the glabellar area is treated without concurrent injection of frontalis muscle for horizontal forehead lines. Additionally, lateral eyebrow elevation has been reported after injections limited to the superolateral orbicularis oculi muscle (tail of the eyebrow).
Hypertrophic orbicularis oculi
Botulinum toxin can be used to widen the ocular aperture by weakening the orbicularis oculi muscle complex, resulting in the appearance of a wider, rounder eye during smiling and at rest.
We evaluated the use of onabotulinumtoxinA for this indication in a randomized, split-face trial of 15 women. Injection of 2 units of botulinum toxin subdermally into the lower eyelid, 3 mm below the ciliary margin, increased palpebral aperture in 40 percent of patients (average increase in palpebral aperture was 0.5 mm at rest and 1.3 mm at maximum smile). Similar injections on the contralateral side given in combination with 12 units of onabotulinumtoxinA into the lateral orbital area enhanced the effect; increases in palpebral aperture occurred in 86 percent of patients (mean increase in palpebral aperture of 1.8 mm at rest and 2.9 mm at full smile). Both treatment regimens were well tolerated.
Doses of more than 4 units of botulinum toxin in the lower eyelid are not recommended, due to an increased risk for adverse effects. Poor candidates for this procedure include patients who respond poorly to a preinjection snap test (lower eyelid does not return quickly to the globe after abrupt release from manual downward retraction), patients who are susceptible to lower lid puffiness, patients who have had ablative laser resurfacing of the lower eyelid, or patients who have had lower lid blepharoplasty without concomitant canthopexy to support the normal eyelid position.
Botulinum toxin injection is useful for the treatment of several cosmetic concerns in the mid-facial area. Injection into the upper nasalis muscle can soften wrinkling on the dorsal or lateral nose (also known as “bunny lines”). I typically utilize 2 to 4 units of onabotulinumtoxinA per side; doses of 10 to 20 units of abobotulinumtoxinA have also been used for this purpose.
In our practice, we have found that injection of 5 to 10 units of onabotulinumtoxinA into the lower nasalis is useful for reducing nostril flare. A small amount of onabutlinumtoxinA (2 to 3 units) into the depressor septi nasi muscle can also be used to slightly elevate the nasal tip.
Prominent nasolabial folds, which extend from the lateral nasal alae to the skin lateral to the mouth, are common cosmetic concerns that are often managed with injectable soft tissue fillers and laser resurfacing. Very small amounts of botulinum toxin (eg, 1 unit of onabotulinumtoxinA) into each lip elevator complex above the nasofacial groove can collapse the upper nasolabial fold. However, this procedure may also vertically lengthen the upper lip, a feature associated with aging. Thus, I only consider this procedure in patients with naturally short upper lips. Treatment may be most effective when combined with soft tissue fillers or laser resurfacing.
Care should be taken to select patients who are most likely to benefit cosmetically from this procedure and to avoid overtreatment; in my experience, the effects of botulinum toxin injection in this site can last for up to six months. Injections should not be placed directly into the nasolabial fold, as this may result in an asymmetrical smile or lip ptosis.
Botulinum toxin injection in the lower face is commonly performed. However, injections must be given with caution. Improper injection in the perioral area may result in a flaccid cheek, an incompetent mouth, or an asymmetrical smile. In addition, perioral injections generally are not recommended for singers or musicians who play wind instruments, or others who require intense use of the perioral musculature.
Perioral lip rhytides
Vertical perioral rhytides are common cosmetic concerns that may be induced by repetitive contraction of the orbicularis oris muscle, volume loss, photodamage, and other factors. Cosmetic fillers or laser resurfacing are often used to treat perioral rhytides. However, the results of these procedures are temporary, and normal perioral animation likely contributes to the fairly rapid recurrence of rhytides.
The muscular contribution to perioral rhytides can be treated with the injection of small doses of botulinum toxin adjacent to the vermillion border in the areas of rhytides lateral to the Cupid’s bow area of the lip. In a series of 18 patients treated with varying doses of onabotulinumtoxinA, smoothing of perioral rhytides and favorable eversion of the upper lip were detected after treatment.
I often inject 2 units of onabotulinumtoxinA per lip quadrant, divided into two injection sites within each quadrant. Doses of abobotulinumtoxinA suggested by other authors include 8 units divided into four injection points for the upper lip and 4 units divided into two injection points in the lower lip . Combination treatment with soft tissue fillers may result in improved efficacy.
Significant lip weakening is a risk of this procedure; when performed appropriately, some patients may have altered lip proprioception after treatment, but functions such as eating, drinking, and singing should not be affected. Placing injections superficially and utilizing conservative dosing may help to minimize the risks of treatment. However, avoidance of this procedure should be considered in patients who require intense use of the perioral musculature, such as professional singers and orators or musicians who play wind instruments.
Injection of the oral commissures (corners of the lip) and the midline area should be avoided, as it may result in a drooping lateral lip and flattening of the Cupid’s bow, respectively.
Mouth frown and melomental folds
The depressor anguli oris (DAO) muscle pulls the corner of the mouth downward in opposition to the action of the zygomaticus major and zygomaticus minor muscles. When the lateral corners of the mouth angle downward, the mouth takes on a frowning, unpleasant expression. Botulinum toxin can be used to weaken the DAO and subtly reset muscular balance, allowing the zygomaticus to elevate the corners of the mouth and return them to a horizontal position. As with perioral lip rhytides, treatment of this area is not recommended in patients in whom intense use of the perioral musculature is essential (eg, professional singers and wind instrument musicians).
In order to avoid unintentional weakening of the nearby depressor labii inferioris muscle during the treatment of mouth frown, we inject at the posterior margin of the DAO muscle, close to the anterior margin of the masseter. We usually utilize 2 to 3 units of onabotulinumtoxinA per side. Because the upward pull of the mentalis muscle also contributes to mouth frown, I perform additional 3 unit injections into each insertion point of the mentalis muscle.
Contraction of the DAO muscle also exacerbates the melomental folds (also known as marionette lines). Melomental folds have traditionally been corrected with soft tissue filling agents, but the benefit from treatment is generally short-lived. Treatment with botulinum toxin may potentiate the results of soft tissue filler injections by reducing the mobility of the underlying musculature. In one split-face randomized trial of 22 patients with melomental folds, photographic assessments revealed longer durations of effect after combination therapy than after treatment with a filling agent alone (median time to return to baseline of 39 weeks versus 32.5 weeks). However, the difference in the rate of relapse was not significant on live clinician assessment. Additional studies are necessary to explore the value of combination therapy in this setting.
For the treatment of melomental folds, we inject small amounts (2 to 5 units) of onabotulinumtoxinA into the posterior margin of each DAO immediately above the mandible. Injections placed too anterior or too high can cause ipsilateral weakness of the depressor labii inferioris muscle, flattening of the lower lip contour, mouth incompetence, and reduced oral sphincter function.
When using abobotulinumtoxinA for mouth frown or melomental folds, injections of 2.5 to 10 units per side into the lower one-third of the DAO have been suggested.
Mental crease and peau d’orange chin
Contraction of the mentalis muscle produces a horizontal crease between the lower lip and the prominence of the chin. In our experience, small doses of botulinum toxin injected into the mentalis muscle just anterior to the bony mentum on each side of the midline soften the indentation. I often use 3 to 5 units of onabotulinumtoxinA per side. Injection at the level of the mental crease should be avoided, as this can weaken the orbicularis oris muscle, creating mouth incompetence that can last for up to six months.
In patients with local loss of dermal collagen and subcutaneous fat on the chin due to aging, contraction of the mentalis muscle can contribute to the appearance of multiple dimpled areas on the chin (peau d’orange chin). Peau d’orange chin can also occur during or after recovery from Bell’s palsy. Botulinum toxin injection into the mentalis muscle at the prominence of the chin (distal to the orbicularis oris) with or without soft tissue fillers can ameliorate the peau d’orange chin. I typically use 5 to 10 units of onabotulinumtoxinA as one or two injections. Doses of 5 to 20 units of abobotulinumtoxinA divided into two injections into the mentalis muscle also have been used for this purpose.
Excessive hypertrophy of the masseter muscle, caused by bruxism (teeth grinding), temporomandibular joint disorders, misaligned jaws, or genetic background, leads to a square appearance to the jaw that may or may not be asymmetrical. Historically, persistent masseteric hypertrophy was treated surgically.
The efficacy of botulinum toxin injection for facial sculpting in patients with masseteric hypertrophy is supported by case reports and uncontrolled studies. Botulinum injected into each masseter effectively sculpts the jawline, reducing muscle thickness by up to 50 percent for three to six months or longer and easing symptoms of bruxism. Mean muscle size decreases over repeated treatments, allowing for smaller doses as treatment progresses. The potential adverse effects of treatment include temporarily reduced bite strength, speech disturbances, muscle pain, facial asymmetry, and prominent zygoma.
Gingival (gummy) smile
Some patients find display of a significant portion of the upper gum during smiling undesirable. The terms “gingival smile” or “gummy smile” are used to describe exposure of more than 3 mm of the gum during smiling. Surgical and orthodontic interventions have been used to manage this condition; botulinum toxin offers a nonsurgical treatment option.
Injections of abobotulinumtoxinA into the levator labii superioris alaeque nasi muscles, zygomaticus muscles, or both areas (dependent upon smile characteristics) resulted in a decrease in gum display in all 16 patients in one uncontrolled study. Adverse effects of treatment were mild and included smile abnormalities in two patients that were corrected with subsequent injections. In a separate uncontrolled study of 30 patients, injection of 2.5 units of onabotulinumtoxinA into overlapping points of the levator labii superioris alaeque nasi and levator labii superioris muscles and the overlapping points of the levator labii superioris and zygomaticus minor muscles (total of four injections) was effective for the treatment of gummy smile. Treatment was generally well tolerated; reported adverse effects included pain at injection sites (four patients), headache (one patient), and dizziness (one patient).
Although data are limited on the use of botulinum toxin for cosmetic concerns in the neck, botulinum toxin appears to be beneficial for vertical platysmal bands in patients who do not desire or who are poor candidates for surgical intervention (platysmaplasty), or in whom residual platysmal bands remain after neck rejuvenation surgery. We have also used botulinum toxin for the treatment of patients with horizontal lines on the neck.
Platysmal bands are vertical linear bands on the anterior neck that result from the separation and protrusion of the anterior edges of the platysma. Increased prominence of platysmal bands is associated with aging and is most evident during neck animation.
Data on the efficacy of botulinum toxin for platysmal bands are limited to case series and reports of clinical experience. In a series of 1500 patients treated with varying doses of onabotulinumtoxinA for platysmal bands, the majority of patients achieved good to excellent results. The greatest benefit appeared to occur in patients with platysma muscle flaccidity, horizontal neck rhytides, and skin laxity that were graded as mild to moderate; 99 percent of patients with mild versions of these features achieved good to excellent results.
The most common adverse effect associated with the injection of platysmal bands is bruising.Oedema, erythema, muscle soreness, and neck discomfort may also occur. Neck weakness and dysphagia are rare adverse effects.
Although a wide range of doses of onabotulinumtoxinA has been utilized for the treatment of platysmal bands, we typically do not exceed 30 to 40 units of onabotulinumtoxinA in the neck per session, due to our concern for the induction of neck weakness or dysphagia with higher doses. I often use 15 units of onabotulinumtoxinA per platysmal band, divided into three injection sites separated by 1 to 1.5 cm. Doses of 30 units of abobotulinumtoxin per platysmal band have been successfully utilized by some clinicians.
Horizontal neck lines
Horizontal neck lines are caused by the attachments of superficial musculoaponeurotic system, a fibromuscular layer that envelops and connects muscles face and neck. We have had some success with softening the appearance of horizontal neck bands with botulinum toxin injection. I typically inject 10 to 20 units of onabotulinumtoxinA per session divided into multiple intradermal injections of 1 to 2 units spaced at 2 to 3 cm intervals. Injection beneath the dermis should be avoided to prevent bleeding from perforating veins and weakening of the underlying musculature utilized for swallowing.