With the increase in minimally invasive cosmetic surgical techniques and the rising popularity of non-surgical interventions such as dermal fillers and botulinum toxins, it is no surprise that the demand for facial rejuvenation procedures are more popular than ever. The aesthetic uses of botulinum toxin may have been discovered incidentally, but they have dramatically changed the landscape of facial rejuvenation.
The purpose of this article is to explore botulinum toxin as a medication, as well as the various indications, techniques and complications associated with its uses in facial aesthetics.
Botulinum toxin
Botulinum toxin is the exotoxin of Clostridium botulinum, which is a spore-forming, gram-positive anaerobic bacterium (Kedlaya, 2010). In total, seven different serotypes are produced by Clostridium botulinum, namely A, B, C (C1, C2), D, E, F and G. Although structurally similar, each serotype varies in size and cellular mechanism, and also in its clinical usefulness. All serotypes bind to the same receptors, but target different proteins within the synapse. Additionally, each serotype differs in its potency and duration of effect.
To date, botulinum toxin type A (BTXA) is the longest lasting toxin type, and is also the most potent. It is for this reason that botulinum toxin type A is the most commonly used serotype in medicine. Generally, types E and F are short-acting, and may be of some clinical value following surgery or post-trauma (Carruthers and Carruthers, 2003a). Only toxin types A and B are commercially available for use in clinical practice.
In 2009, the US Food and Drug Administration (FDA) implemented changes to the established drug names of types A and B of botulinum toxin. The purpose of this was to ensure that differences between the botulinum toxins were recognisable by practitioners and safe use was maintained.
Botulinum toxins A and B were renamed as follows:
- OnabotulinumtoxinA (Botox)
- AbobotulinumtoxinA (Dysport)
- IncobotulinumtoxinA (Xeomin)
- Rimabotulinumtoxin B (Neurobloc) (Foster, 2014).
BTXA is a neurotoxin that works within cholinergic synapses present at neuromuscular endplates, preventing the transmission of neurotransmitters, such as acetylcholine, from nerves to muscles. Normally, when a muscle is required to contract, a nerve sends a signal to the muscle and this signal reaches the neuromuscular junction. At this point, acetylcholine is released from the nerve side of the junction and binds to the muscle side, causing contraction of the muscle. When BTXA is injected into the muscle, acetylcholine is unable to bind to its receptor on the muscle. This interference with nerve impulses leads to the muscles being temporarily weakened (paralysis) (Nigam and Nigam, 2010). BTXA is approved by the FDA for many indications, including strabismus, cervical dystonia, hyperhidrosis, upper and lower limb spasticity and chronic migraine prevention, as well as the cosmetic treatment for wrinkles in three areas. The first area to receive approval was the glabella in 2002, followed by crow's feet in 2013 and then the forehead in 2017 (BOTOX®, 2017).
Botulinum toxin is a neurotoxin that prevents the transmission of neurotransmitters from nerves to muscles
Botulinum toxin in clinical practice
Paralysis and a near-complete loss of motor end plate potentials occur within a few hours of BTXA injection (Jankovic, 1991); however, the full clinical effect is not evident until 14 days post treatment, and, in the majority of cases, this is the point at which the injector will review the patient and their results. The latency to clinical effect may be caused by spontaneous, non-vesicle-associated release of acetylcholine at the neuromuscular junction (Stanley, 1983). The neuromuscular blockade from BTXA administration is irreversible, with axonal sprouting and the formation of new neuromuscular junctions being responsible for the gradual easing of clinical effects over time (Pamphlett, 1989).
The average duration of toxin effect is 3–4 months, depending on factors such as dose, concentration, technique and patients' individual immune response (Gart and Gutowski, 2016).
Indications
There are many uses for BTXA in the face, and patient satisfaction following these treatments is very high, with significant improvements in wrinkles reported by patients (Fagien, 2008). The process of weakening the facial muscles is effective in improving the appearance of dynamic lines created during facial expression, rather than having an effect on static lines. Over time, there seems to have been a shift in the goals of treatment, from the completely inactive ‘frozen’ look, to a softer, more expressive dampening of muscle activity (Gart and Gutowski, 2016). BTXA is a prescription-only medication, and a full consultation should be carried out prior to treatment to ascertain the patient's desired outcome, conduct a thorough medical history and for the patient to be counselled regarding the anticipated outcome, side effects and the limitations of BTXA.
Upper face
In comparison to the middle and lower thirds of the face, the upper face has a lot less volume loss as it ages, and the majority of signs of ageing are related to the increased presence of lines and wrinkles. It is for this reason that BTXA produces such good results in this area.
»The patient is asked to contract the platysma muscle, which allows the practitioner to grasp the band between their thumb and forefinger … injections are directed into the band in a suggested three to five sites at 1 cm intervals«
Transverse forehead lines
Licensed in 2017, treatment of transverse forehead lines with BTXA produces excellent results and is commonly sought after by patients due to its high levels of satisfaction in correctly selected people. The frontalis is an elevator muscle that lifts the forehead and eyebrows and is responsible for the transverse forehead lines that patients so often want to eliminate. The frontalis originates in the galea aponeurotica and inserts into the subcutaneous tissues and deep dermis of the skin overlaying the supercillary arch. In the majority of individuals, the two bellies of the frontalis are divided in the middle of the forehead by a central, tendinous aponeurosis, composed of little or no muscle fibres.
Individual assessment of each patient should be made, with attention to muscle strength and orientation, brow height and any current asymmetry, which should be discussed with the patient before treatment. Forehead treatment can be highly variable due to the frontalis muscle and characteristics of the patients' individual animation patterns. For example, some patients have multiple fine transverse lines, whereas others have one or two deep transverse creases. Patients should be assessed both at rest and on forceful elevation of the eyebrows to assess the strength of muscle contraction and positioning of dynamic lines. There are a number of injection patterns that can be used across the frontalis; however, care should be taken to stay at least 1–2 cm above the supraorbital rim to avoid brow or eyelid ptosis (Carruthers et al, 2004).
Glabellar lines
Treatment of glabellar lines was the first aesthetic use of BTXA that was approved by the FDA in 2002. As well as being shown to improve both quality of life (Jandhyala, 2013) and negative mood (Lewis and Bowler, 2009), treatment of the glabella region also produces high levels of patient satisfaction as well as improved self-perception for up to 4 months after treatment (Molina et al, 2015).
The glabellar occupies a relatively central position and, as such, draws attention when looking at the face. Lines can vary from a fine appearance to deep creases, and can give the impression of anger, anxiousness, fear and/or advanced age. The glabellar complex, consisting of the central procerus muscle and paired corrugator supercilii muscles, depresses the medial brow. Originating on the frontal bone medially, the corrugators interlock into the medial preorbital orbicularis oculi and insert into the dermis of the forehead, just above the eyebrows at the mid-pupillary line (Gant, 2016). Hyperactivity of these muscles contributes to vertical glabellar lines. Originating from the soft tissues overlaying the nasal bone and inserting into the skin of the lower central forehead, the vertically orientated procerus produces transverse horizontal lines at the nasal root on contraction.
Muscle location, strength and size can be assessed by asking the patient to frown as deeply as possible. Any asymmetry noted should be evaluated and discussed with the patient during the consultation. The recommended dosage in this area is 20 iu split between injections; however, in clinical practice, this may vary between individual patients. Injections should also be kept to a minimum of 1 cm above the orbital rim to avoid diffusion into the levator palpabrae superioris muscle, causing iatrogenic ptosis.
Lateral orbital region
Commonly, one of the first regions to age are the lateral canthal lines (Gart and Gutowski, 2016). The result of hyperkinetic orbicularis occuli muscles, crow's feet respond well to treatment with BTXA (Ghalamkarpour et al, 2010). Orbicularis oculli is a circular muscle that allows forceful closure of the eye. Its bony origin is near the inner canthus, via the medial palpebral ligament (MPL), with many superficial insertions all around the dermis surrounding the eye. This muscle is considered in three parts: pretarsal, preseptal and preorbital. The main focus of BTXA treatment is the most lateral fibres peripherally located preorbital section. When treating the orbicularis, it is important not to cause such an effect that important eye functions and closure are affected.
As with all BTXA treatments, patients should be counselled on the treatment being effective for dynamic lines, rather than static lines, and given realistic expectations for the area of treatment. While effective on lateral lines, patients should be advised that lines that extend under the eye, although potentially caused by an active inferiolateral orbicularis oculli, are often caused by the movement of cheeks rising, and therefore their origins are zygomatic. These muscles should not be injected, as paresis of the zygomaticus muscles will affect perioral movement and smile.
For safety purposes, injection points should be at least 1 cm from the orbital rim
For safety purposes, injection points should be at least 1 cm from the orbital rim to avoid inadvertent diffusion to the lid retractors or extraocular muscles.
Mid-face
Treatment of both the mid- and lower face with BTXA will have a much more limited role, as the changes associated with ageing in these areas are more commonly caused by relative volume loss and descent.
Oblique nasal sidewall lines
Sometimes referred to as ‘bunny lines’, oblique nasal sidewall lines are caused by hyperactivity of the transverse portion of the nasalis muscle. The nasalis muscle is a paired structure consisting of an alar and transverse portion. The transverse nasalis muscle originates on the maxilla near the medial canthus, meeting in the medial aponeurosis that overlies the nasal dorsum. Contraction of these muscles results in the oblique lines due to superomedial elevation of the nasal sidewall skin.
Treatment with BTXA can either be carried out with two injections—one in each muscle belly—or with a single central injection. Injections should be kept high and superficial to avoid paralysis of levator labii superioris and alaeque nasi. Deactivation of these important upper lip elevators may lead to upper lip ptosis.
Vertical perioral lines
Vertical perioral lines, also referred to as lip lines or smoker's lines, are a common complaint among people seeking facial rejuvenation. Although predominantly a result of age-related volume loss, these lines can also be exacerbated by smoking and sun exposure. While dermal filler is most often used to improve static lines, the use of BTXA has been found to improve lip contour, eversion and fullness (Wu et al, 2015).
The primary function of the orbicularis oris muscle is as a sphincter to aid in oral competence and speech. Originating from the modiolus complex and inserting into the skin and subcutaneous tissues of the upper lip, the muscle encircles the upper and lower lips.
During consultation, patients should be advised that, following treatment, they may have difficulty with activities that involve pursing of the lips, such as whistling, drinking though a straw and pronunciation of certain plosives. With injection of this area, it is safer to risk undertreatment and subsequent retreatment than to overtreat and risk excessive paresis of the perioral musculature.
Lower face
Despite the age-related changes of the lower face being predominantly related to volume loss and the resuspension of descended tissue, there are a number of areas of the lower face than can benefit from treatment with BTXA.
Mentalis
Overactivity of the mentalis muscle can create the appearance of wrinkling or ‘orange peel’ dimpling of the skin overlying the chin. BTXA can be used to relax the underlying mentalis muscle. Arising from the incisive fossa on the anterior mandible and inserting into the subcutis of the chin on either side of the lower lip frenulum, this paired muscle is the primary elevator of the lower lip, also serving to elevate the skin of the chin (Hur et al, 2013). The mentalis lies deep, and interlocks with the fibres of the orbicularis oris and depressor labil inferioris (Hur et al, 2013).
Treatment can be as a single injection at the origin of both bellies or, more commonly, with an injection into both bellies. Injections should be kept deep to avoid inadvertent spread to the overlying orbicularis oris and depressor labil inferioris (Hur et al, 2013).
Masseteric hypertrophy
Hypertrophy of the masseter can lead to a squareness of the lower face and give the unwanted impression of heaviness or a masculine appearance to the female face. The treatment with BTXA to reduce hypertrophy in this area of the face is the same regardless of if the cause is genetic or habitual (Lee et al, 2014).
The masseter, a primary muscle of mastication, is a powerful, superficial quadrangular muscle with two divisions: superficial and deep. The superficial portion of the masseter muscle originates from a thick aponeurosis on the temporal process of the zygomatic bone and the anterior two-thirds of the inferior border of the zygomatic arch. The superficial masseter muscle has a quadrangular-shaped appearance due to its origins and insertions. The deep portion of the masseter muscle originates from the entire surface of the zygomatic arch. Anteriorly, the deep portion is covered by the superior portion of the masseter, while posteriorly, the parotid gland covers the deep portion.
Treatment of the masseter, unlike other areas of the face, is primarily indicated to induce muscle atrophy, rather than to limit muscle contraction to prevent the appearance of lines. Care must be taken to avoid excessive paralysis, which can lead to complications such as weakened mastication, asymmetry, changes in facial expression, dysgeusia (distortion of taste) and transient muscle bulging (Liew and Dart, 2008).
To avoid altering the angle of mouth movement or causing facial asymmetry, knowledge of the underlying facial anatomy is essential when treating the masseters. Ensuring that injections are deep into the required muscle bellies will reduce unwanted diffusion.
Gummy smile
The smile is seen as a form of communication and socialisation that expresses many feelings. As such, it is seen as aesthetically pleasing when the lips, teeth and gums are disposed in suitable proportion, and the exposure of gingival tissue is limited to 3 mm. Exposure of more than 3 mm is known as a gummy smile.
BTXA has been successful in treating gummy smiles when it is injected into the hyperactive muscles of the upper lip. Treatment results in a reduction in lip elevation, and therefore less exposure of gingiva. BTXA is commonly injected into the three lip elevator muscles that converge on the lateral side of the ala of the nose: the levator labii superioris, the levator labii superioris alaeque nasi and the zygomaticus minor (Dinker et al, 2014).
Platysmal bands
There are many components to an ageing neck, with the majority of cases requiring surgical intervention. However, there is a place for non-surgical neck rejuvenation with BTXA for vertical platysmal banding and horizontal lines (Rohrich et al, 2006). Patients seeking improved contouring and jawline definition have also successfully been treated with BTXA.
Platysma is a broad, thin muscle originating in the deltapectoral fascia and extending upwards to insert along the inferior border of the mandible and the superficial musculoaponeurotic system of the lower face. These insertions make the platysma a powerful depressor of the lower face and mandible. Injection into the platysma bands is both safe and effective in correctly selected candidates.
The patient is asked to contract the platysma muscle, which allows the practitioner to grasp the band between their thumb and forefinger. Injections are directed into the band in a suggested three to five sites at 1 cm intervals. Care must be taken to inject specifically into the deep dermal layer of the bands to avoid diffusion in the strap muscles or deeper muscles of the neck, which could result in dysphagia, dysphonia, dysarthria or life-threatening breathing difficulties (Carruthers and Carruthers, 2003b). A technique that has gained popularity is the Nefertiti lift, in which injections are placed into the platysma along the mandible and posterior platysmal bands to better define the mandible-neck junction and elongate the appearance of the neck (Levy, 2015).
Conclusion
There are a number of treatment options for each section of the face, and although this article has solely discussed the benefits of BTXA, each patient should always be assessed holistically as an individual. Patients should be selected carefully for BTXA, and all other options for treatment, both alone and in combination, should be considered. Although there are clinical guidelines, some of which have been presented in this article, variations in patient anatomy, behaviours and dosing patterns will occur. If a patient is selected for BTXA treatment, then their treatment plans should be considered individually with regard to treatment areas and dosing. If a patient is receiving treatment on an area that is considered to be off-license, then they should be made aware of this and the implications at the time of consultation.
Key Points
- If a patient is selected for treatment, their treatment plan should be considered individually in regard to treatment areas and dosing
- Botulinum toxin is a neurotoxin that works within cholinergic synapses present at neuromuscular endplates, preventing the transmission acetylcholine, from nerves to muscles. This interference leads to the muscles being temporarily weakened
- The process of weakening the facial muscles is effective in improving the appearance of dynamic lines created during facial expression, rather than having an effect on static lines
- In comparison to the middle and lower thirds of the face, the upper face has a lot less volume loss as it ages, and the majority of the signs of ageing are related to the increased presence of lines and wrinkles. It is for this reason that botulinum toxin A produces such good results in this area.
CPD reflective questions
- How does Botox work and how would you counsel the patient on this?
- What signs of ageing does botulinum toxin help with, and how does this change in the upper, mid- and lower face?
- What are the key safety points for injection location in each treatment area?