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Botulinum toxin injection is the most commonly performed cosmetic procedure in the world. While it has many areas of application, it is frequently used to manage and treat rhytids in the aging upper face. This activity reviews the indications, contraindications, techniques, complications, and other key elements of botulinum toxin treatment and highlights the role of the interprofessional team in evaluating and treating patients with this condition. Objectives: Outline the treatment considerations for patients with an aging upper face due to rhytids. Identify the physical exam findings associated with an aging upper face due to rhytids. Summarize the common complications of treating an aging upper face due to rhytids. Review the psychosocial considerations for a patient with an aging upper face due to rhytids. Access free multiple choice questions on this topic.

Botulinum toxin injection is commonly performed to chemically denervate certain muscles of facial expression for the purposes of facial rejuvenation and anti-aging. Facial rhytids, or "wrinkles," result from repeated contracture of the muscle underlying the facial skin, which over time causes atrophy of the overlying dermis and pleating of the skin.[1][2] Selective chemodenervation of facial muscles allows for targeted treatment of dynamic rhytids, particularly in the upper face, and also allows for manipulation of eyebrow position and correction of asymmetries. Muscular targets of botulinum toxin in the upper face include the orbicularis oculi, procerus, corrugator supercilii, and frontalis muscles. Botulinum toxin prevents acetylcholine release at the presynaptic nerve terminal, blocking neurotransmission. Effects usually take up to 2 days to appear, with maximal effect in 1 week to 1 month and last up to 3 to 4 months.[3] Repeated injections of botulinum toxin may cause muscular atrophy in the injected regions, thereby extending the duration of effects. In addition, a retrospective study of 945 patients receiving at least 3 consecutive treatments showed no loss of effect with repeated treatments. After five treatment cycles, patients and providers both rated satisfaction outcomes higher than after the first cycle.[2] Botulinum toxin is created by fermentation of the bacteria Clostridium botulinum.[4] Botulinum toxin has 7 serotypes from A-G; however, types A and B are practically used for cosmetic applications. Serotype A exists in three formulations to include onabotulinumtoxinA, abobotulinumtoxinA, and incobotulinumtoxinA. Serotype B exists in one formulation, rimabotulinumtoxinB.[5] RimabotulinumtoxinB is notable for having the most rapid time to onset; however, it also has the greatest area of diffusion and shortest duration of effect. Its acidic pH (5.5-6.5) also increases the discomfort of an injection.[6] Serotype A botulinum toxins, conversely, have a longer onset to action and longer duration of effect. AbobotulinumtoxinA has a greater spread effect than onabotulinumtoxinA and incobotulinumtoxinA, and therefore dose ratios vary. In cosmetic practice, a typical dose ratio is 2.5 to 1 to 1 (abobotulinumtoxinA: onabotulinumtoxinA: incobotulinumtoxinA).[6]

Complications of botulinum toxin injections may include mild bruising (11 to 25% of patients), brow or eyelid ptosis (0.59% of patients), local hypesthesia, dry skin, allergic reaction to components, injection site pain, headache, asymmetry, and unwanted cosmetic result.[2][4] In a retrospective study of 945 patients and 4,103 injection cycles with abobotulinumtoxinA, mild bruising was the most common adverse event, occurring in only 1.25% of patients. Adverse events were not experienced in the majority of patients (90.6%) included in the study.[2] Procedural techniques to reduce bruising include careful avoidance of superficial blood vessels (which can be more easily visualized by removing makeup and having adequate lighting) and application of pressure and ice post-injection. Gentle stretching of the skin can also reveal superficial blood vessels. If a vessel is punctured, prompt digital pressure should be applied to the region.[4] Positioning the patient at 30 degrees with a stable headrest might also limit unnecessary movement during injection that can lead to bruising. Using a small gauge needle may limit bruising; however, no significant difference was found in a study comparing 30 and 32 gauge needles.[24] Post-procedure, patients can also limit bruising by avoiding sleeping face down, bending over to stretch, and exercising vigorously. Patients should ideally remain vertical for up to 3 hours post-injection to prevent diffusion of toxin and bruising.[3] Given the variation in depth along the course of the corrugator supercilii, injecting too superficially medially can lead to inadvertent injection of the frontalis muscle, causing brow ptosis rather than elevation. In addition, diffusion of toxin into the levator palpebrae superioris can lead to eyelid ptosis. The treatment for refractory ptosis caused in this manner is apraclonidine eye drops. Apraclonidine is an alpha-2 agonist and sympathomimetic that stimulates the contraction of Muller's muscle, causing eyelid elevation.[4] Apraclonidine also causes pupillary dilation.[25] Administration of apraclonidine should be reserved for severe and refractory cases, as apraclonidine can unmask underlying glaucoma.

Given the variation in depth along the course of the corrugator supercilii, injecting too superficially medially can lead to inadvertent injection of the frontalis muscle, causing brow ptosis rather than elevation. In addition, diffusion of toxin into the levator palpebrae superioris can lead to eyelid ptosis. The treatment for refractory ptosis caused in this manner is apraclonidine eye drops. Apraclonidine is an alpha-2 agonist and sympathomimetic that stimulates the contraction of Muller's muscle, causing eyelid elevation.[4] Apraclonidine also causes pupillary dilation.[25] Administration of apraclonidine should be reserved for severe and refractory cases, as apraclonidine can unmask underlying glaucoma. Inadvertent injection deep to the procerus and into the frontalis muscle can cause skin drooping between the eyebrows. This is best avoided by superficial injection in the glabellar area when targeting the procerus.[8] Frontalis injection can lead to ptotic eyebrow position in multiple ways, including injecting too inferiorly, injecting too superficially when attempting to address the medial corrugator, neglecting to inject the opposing orbicularis oculi and glabellar muscles, and administering too large a unit volume compared to the opposing musculature. Blepharoptosis can also occur if there is a pre-existing LPS weakness that is unmasked. As mentioned previously, overcorrection of the medial versus the lateral frontalis can lead to "Mephisto" or "Spock" deformity. It may occur if frontalis injections are only performed between the mid-pupillary lines and can be corrected with the careful injection of the lateral frontalis, with care not to overcorrect and cause brow ptosis laterally.[14]

Frontalis injection can lead to ptotic eyebrow position in multiple ways, including injecting too inferiorly, injecting too superficially when attempting to address the medial corrugator, neglecting to inject the opposing orbicularis oculi and glabellar muscles, and administering too large a unit volume compared to the opposing musculature. Blepharoptosis can also occur if there is a pre-existing LPS weakness that is unmasked. As mentioned previously, overcorrection of the medial versus the lateral frontalis can lead to "Mephisto" or "Spock" deformity. It may occur if frontalis injections are only performed between the mid-pupillary lines and can be corrected with the careful injection of the lateral frontalis, with care not to overcorrect and cause brow ptosis laterally.[14] Unintended outcomes of orbicularis oculi injection may occur if the injection is carried out too medially and inferiorly. If this occurs, the zygomaticus major and minor muscles may be inadvertently injected. These muscles are important in smiling function, and therefore injection can lead to an asymmetric smile. An aggressive medial/inferior OO injection may also create the appearance of a "shelf" at the lid/cheek junction, where the cheeks elevate during smiling, but there is no movement of the periorbital skin.[7] Similarly, aggressive lateral/superior OO injection in a male patient may cause undesirable lateral eyebrow elevation. Excessive injection near the canthus or eyelids may cause lagophthalmos or ectropion, strabismus or diplopia, and worsening orbital fat pad pseudogenization.[4] Lastly, injection in the periorbital area may lead to temporary periorbital edema, possibly due to a lack of muscular pump mechanism integral to local lymphatic drainage.[26] Asymmetry can occur if botulinum toxin is dosed or administered unequally between sides of the face. This is best avoided by careful attention to injection quantity and consistent dilution technique.

All healthcare team members performing botulinum toxin injection should be familiar with its indications, contraindications, techniques, complications, and psychosocial implications. Botulinum toxin injection may be performed by a broad range of specialties and disciplines, including dermatology, plastic surgery, facial plastic surgery, otolaryngology, ophthalmology, neurology, and oral maxillofacial surgery. Practitioners may work with a nurse or medical assistant who reconstitutes the botulinum toxin, but botulinum toxin injection must be performed by a licensed healthcare practitioner, such as a physician, physician assistant, dentist, or registered nurse. Provider and patient communication and expectation setting are paramount in the management of patients seeking cosmetic procedures. Careful planning, discussion of cosmetic goals, and pre-procedure documentation are vital. The provider may desire pre- and post-procedure photography to accurately document desired and undesired outcomes, pre-existing facial features, as well for teaching trainees. The photography should be standardized and reproducible.[29] It may be wise for the provider to work closely with a nurse, physician assistant, medical assistant, or technician trained specifically in medical photography related to facial plastic surgery. This individual may also be responsible for obtaining patient consent to use "before and after" photos for training, patient recruitment, and/or technique publication purposes. In addition, the provider should screen for comorbid psychiatric conditions (such as body dysmorphic disorder) and may require the patient to be screened by a mental health professional before any interventions.[30] [Level 4]