For the general dentist, the use of BTA and dermal fillers confers the ability to exert control over the soft tissues surrounding the mouth to better create a harmonious smile. The injection of BTA and fillers into the facial musculature and dermis requires a level of finesse to achieve the desired outcomes. A sound understanding of the mechanisms of action and the ability to manage potential complications are also necessary, because the dentist administering BTA and dermal fillers must be competent to the same level as other providers who have traditionally been the gatekeepers of such agents.
For the general dentist, the use of BTA and dermal fillers confers the ability to exert control over the soft tissues surrounding the mouth to better create a harmonious smile.
The injection of BTA and fillers into the facial musculature and dermis requires a level of finesse to achieve the desired outcomes.
A sound understanding of the mechanisms of action and the ability to manage potential complications are also necessary, as the dentist administering BTA and dermal fillers must be competent to the same level as other providers who have traditionally been the gatekeepers of such agents.
Botulinum toxin A
Neuromodulators, or neurotoxins, have long been used by medical specialists—namely plastic surgeons and ophthalmologists. These medications alter the relationship between nerve and muscle fiber conduction. The most well-known neuromodulator, botulinum toxin type A or Botox, has only recently been added to the armamentarium of general dentists. Although numerous abbreviations exist to represent botulinum toxin type A, it is referred to as BTA throughout this article.
Before the application of BTA for therapeutic purposes, it was recognized as a lethal toxin responsible for botulism poisoning. Justinus Kerner, a German physician, was the first to report on BTA in 1817. Kerner realized that an outbreak of food poisoning was attributed to rotten sausage—hence the name “botulism,” from the Latin word botulus , meaning sausage. In 1897, Emile van Ermengem, a Belgian microbiologist, isolated the toxin from a patient who contracted botulism and named it Bacillus botulinus , a spore-forming obligate anaerobic bacterium. In 1922 the pathogen was renamed Clostridium botulinum .
In the late 1970s, Alan Scott, an ophthalmologist, was granted approval by the US Food and Drug Administration (FDA) to begin clinical trials of BTA for the treatment of strabismus. After many successful trials proved the efficacy of BTA, the FDA finally approved pharmaceutical preparations of BTA in 1989 for the treatment of strabismus and blepharospasm. Subsequently, Jean Carruthers, an oculoplastic surgeon, discovered that one of her patients had a decrease in glabellar wrinkles—in addition to being treated successfully for blepharospasm with BTA.
After extensive studies and investigations, the FDA approved BTA for additional therapeutic uses, including cervical dystonia in 2000, glabellar rhytids in 2002, and axillary hyperhidrosis in 2004.
Mechanism of Action
Thus far, 8 serologic types of botulinum toxin have been identified (designated A–H). Although the molecular configuration and function of the 8 serotypes are similar, BTA is the most potent and has the longest-lasting effect. Botulinum toxin causes paralysis at the neuromuscular junction by preventing communication between the nerve and muscle.
The toxin is composed of a 2-chain protein, consisting of a light chain polypeptide bound to a heavy chain polypeptide via a disulfide bond. The active part of the toxin is the light chain and the heavy chain mediates binding to the presynaptic nerve terminal. Through the mechanism of endocytosis, the toxin enters the nerve once it is bound to the nerve terminal. Ordinarily, a complex of SNARE proteins mediates the fusion of acetylcholine vesicles to the nerve cell membrane and the subsequent release of the neurotransmitter acetylcholine into the synaptic cleft. However, once inside the nerve cell cytoplasm, the light chain of the toxin cleaves the SNARE protein, SNAP-25, thus preventing fusion of acetylcholine vesicles to the cell membrane. With the nerve cell unable to release the neurotransmitter acetylcholine, nerve signaling is blocked, which leads to weakness or flaccid paralysis. Because of the storage vesicles of acetylcholine already in the synaptic cleft, the effect of the toxin is not manifested until the stores are depleted, which takes approximately 24 to 48 hours. The paralytic effect of the toxin lasts for 2 to 6 months—the length of time required for the generation of new axonal sprouts that restore the function of the neuromuscular junction ( Fig. 1 ).
In the United States, there are 3 FDA-approved BTA neuromodulators: Botox (onabotulinum toxin A), Dysport (abobotulinum toxin A), and Xeomin (incobotulinum toxin A). Although the 3 neuromodulators share the same therapeutic indications, they differ with respect to potency per unit and the nonprotein constituents that emerge from various manufacturing practices. To allow for convenience of dosing for the practitioner, the commercially available vials of these neuromodulators contain a certain amount of biologically active units. The literature demonstrates that Botox and Xeomin are equivalent in potency with respect to units, whereas the potency of 1 unit of Botox is equivalent to approximately 2.5 to 3 units of Dysport. The variance in potency is caused by the purification method, the strain from which BTA is isolated, and the diverse methods for measuring potency. Throughout this article, all doses refer to Botox units for the sake of consistency, with the comprehension that an equivalent dose of Xeomin or Dysport is as effective.
Botox that is unreconstituted may be stored at 2°C to 8°C for a period of 24 months in a standard refrigerator. Only 4.8 ng of BTA is contained in a standard 100-unit vial of Botox. Because the amount is so small, BTA is transported in empty glass vials consisting of a thin layer of precipitate. To maintain proper temperature, Botox is shipped on dry ice. After reconstitution with 2.5 mL preservative-free 0.9% sodium chloride for injection, it is stored under refrigeration and should be used within 24 hours. This dilution ratio allows for aspiration into 5 syringes (1 mL), each containing 0.5 mL solution of 20 units of Botox. Dilution with 2 or 4 mL of preservative-free saline may also be used depending on practitioner preference.
It is paramount to inform patients receiving BTA injections that the therapy varies in efficacy from one patient to another. After approximately 3 months from the time of BTA treatment, motor function is restored due to resprouting of nerve axons. A salient point to keep in mind is that this time frame is highly inconsistent. Some patients may require touch-up injections in just several weeks, whereas for other patients, the effects of the toxin may persist much longer than 3 months. Consistent BTA therapy causes muscular atrophy due to extended immobility, which decreases the ability of muscles to produce deep wrinkles. For patients who regularly present for follow-up repeat therapy, the treatment interval can typically be prolonged once the muscles begin to atrophy.
Albeit rare, BTA resistance has been documented. The literature demonstrates that the toxin can produce antibodies that inhibit the effects of BTA. High-dose BTA therapy during a short time period increases the risk of developing neutralizing antibodies against BTA. , Thus, it is prudent to use a dose as low as possible while simultaneously effective, and extending the time interval between repeat therapy. Patients may benefit from substituting to another form of toxin if they are immunoresistant to a specific form.
As with all procedures, a thorough discussion on the risks, benefits, and alternatives is required before administering BTA. Contraindications to the use of BTA include patients with neuromuscular disorders, such as myasthenia gravis, multiple sclerosis, and peripheral motor neuropathies, and those who have had an adverse reaction to any of the components of BTA. In addition, the effect of BTA can be potentiated with concomitant use aminoglycoside antibiotics and muscle relaxants. Pregnancy and lactation are considered relative contraindications.
The frontalis is a thin, paired muscle that moves vertically, producing horizontal wrinkles in the skin of the forehead. The fibers of the frontalis insert into the brow depressor muscles: the procerus, the corrugator supercilii, and the orbicularis oculi. The frontalis is the only forehead elevator, where contraction of the muscle raises the upper eyelid and eyebrows. Therefore, simultaneous treatment of the brow depressors is indicated to prevent an unwanted eyebrow shape and height.
Multiple low-dose BTA injections are needed for the treatment of frontalis rhytids because of the large surface area and thin muscle mass of the frontalis. Injection points are typically spaced 20 to 30 mm apart because the diffusion of BTA from the site of injection is approximately 10 to 15 mm. Two to 5 units of Botox are administered at each injection point, with the upper end of this range being reserved for patients with larger muscle mass. If patients desire to maintain some mimetic function of the frontalis then a lower amount of Botox may be used (2–3 units), which will still soften wrinkles and permit animation. Based on patient’s desired result, a total of 10 to 30 units of Botox may be administered across the forehead. To determine the ideal location of needle placement, the practitioner should use his or her nondominant hand to stabilize the patient’s forehead during animation ( Fig. 2 ).
Patients with dermatochalasis have a subconscious habit of continually elevating their brows with the hope of masking the excess upper eyelid skin. These patients need special consideration because excess Botox for the treatment of their frontal rhytids may prevent them from retaining their usual brow position. Therefore, all patients pursuing frontalis treatment need a careful preoperative assessment to determine if they posture their brows; and, if so, the practitioner has to discuss this possibility before initiating treatment.
The brow depressors are the procerus, corrugator supercilii, and medial orbicularis oculi. These paired muscles overlap in the glabellar region and are responsible for the frown lines—commonly referred to as the 11 because they present as 2 vertical lines between the eyebrows (patients may also present with 1 or 3 lines). The procerus originates from the nasal bone and cartilage, extends laterally as its fibers run superiorly, and inserts into the skin of the forehead. The skin in this region develops rhytids through movement of the procerus. The corrugator supercilii originates from the medial aspect of the superior orbital rim, runs laterally nearly following the boundary of the rim, and inserts into the skin of the mid-brow. This muscle pulls the brow in an inferior and medial direction, which contributes to brow furrowing. The procerus and corrugator supercilii, along with the medial orbicularis oculi are primarily targeted when treating frown lines ( Fig. 3 ).
For the ordinary presentation of the 11, a centrally placed injection into the procerus with 5 units of Botox is adequate. Subsequently, 5 units are injected into each corrugator supercilii and each superior orbicularis oculi ( Fig. 4 ). If several ridges are present in the glabellar region or if the rhytids in the procerus are diverse then the central 5-unit injection is spread uniformly across them. For most patients, 20 to 30 units of Botox uniformly spread across the glabellar region are adequate. Those with deep frown lines or thick muscle may need significantly more to achieve results that they will be satisfied with. Treatment of the frown lines is the only on-label cosmetic indication for Dysport and Xeomin, and along with crow’s feet, 1 of 2 for Botox.
The patient can assist the practitioner in locating the ideal injection sites by frowning intentionally. Before injecting BTA, it is judicious to aspirate the syringe given the proximity of the supratrochlear and supraorbital vessels in the glabellar region. In addition, it is prudent to maintain a distance of 10 to 15 mm from the bony orbital rim to minimize the incidence of lid ptosis and paralysis of the extraocular muscles.
Periorbital and Midfacial Region
Lateral canthal region
A fan-shaped configuration of horizontal wrinkles that unite in the lateral canthal region is created by the lateral aspect of the orbicularis oculi muscle. These rhytids, known as crow’s feet, are commonly treated with Botox injections. Treatment in this region is highly technique sensitive and requires the practitioner to be cognizant of the numerous large, superficial blood vessels to prevent marked ecchymosis, which can persist for weeks. Botox injections for the treatment of crow’s feet are completed markedly superficial. BTA injected intradermally will diffuse to the target muscle. However, the practitioner must be extremely cautious to not inject BTA too close to the orbit as the consequences can be devastating. As mentioned earlier, a distance of 10 to 15 mm must be maintained from the bony orbital rim to avoid paralysis of the extraocular muscles and eyelid ptosis ( Fig. 5 ). If eyelid ptosis does ensue then the patient can be treated with apraclonidine (Iopidine) ophthalmic solution, which is an alpha adrenergic receptor agonist that stimulates the Mueller muscle to elevate the upper eyelid. Unfortunately, the duration of action of this drug is brief.