Botulinum Toxin

Published on 26/02/2015 by admin

Last modified 22/04/2025

Print this page

This article have been viewed 3704 times

21 Botulinum Toxin

Treatment of facial lines and wrinkles (also called rhytids) with botulinum toxin has become the most frequently performed cosmetic procedure in the United States, according to statistics from the American Society for Aesthetic Plastic Surgery.¹ It is also one of the most common entry procedures for health care professionals seeking to incorporate aesthetic procedures into their practice.²

As we age, the skin naturally thins, and repetitive contraction of the underlying facial musculature causes visible lines and wrinkles. Initially, these lines are seen only during facial expression with frowning, laughing, or smiling and are referred to as dynamic lines. Over time, however, dynamic lines may become etched into the skin, resulting in permanent or static lines. Botulinum toxin reduces unwanted dynamic lines, and to a lesser degree static lines, by relaxing hyperdynamic facial muscles and smoothing the overlying skin.

Botulinum toxin is a potent neurotoxin protein derived from the Clostridium botulinum bacterium. It reduces muscular contraction through inhibiting release of acetylcholine at the neuromuscular junction. Injection of small quantities of botulinum toxin into specifically targeted muscles causes localized, temporary chemical denervation with resultant muscle relaxation.³

Botulinum toxin has been used for more than 20 years to treat a variety of clinical conditions such as blepharospasm, strabismus, cervical dystonia, hyperhidrosis, migraines, and muscle spasticity.⁴^–⁶ Botulinum toxin is used in numerous facial aesthetic areas. However, treatment of the glabellar complex,⁷ frontalis⁸ and orbicularis oculi muscles,⁹ which contribute to formation of frown lines, horizontal forehead lines, and crow’s feet, respectively, offers the most predictable results, greatest efficacy, and fewest side effects.^10,¹¹ Botulinum toxin treatment of hyperdynamic muscles in the upper one-third of the face are a core aesthetic procedure for providers interested in incorporating aesthetic care into office practice.¹²

Cosmetic Indications

• FDA approved for the temporary improvement of moderate to severe dynamic glabellar frown lines.

• FDA approved for adults ages 18 to 65. It is commonly used in patients older than 65, but treatments may be less effective if severe static wrinkling is present.

• Other cosmetic uses include reduction of wrinkles in upper, mid and lower face, neck, and upper chest.

Alternative Therapies

Botulinum toxin is the only FDA-approved treatment for dynamic wrinkles. Static wrinkles can also be treated with chemical peels, microdermabrasion, topical products such as retinoids, nonablative lasers for soft-tissue coagulation and tightening using infrared and radio-frequency, nonablative lasers for collagen remodeling using 1320 and 1540 nm Q-switched lasers and others, and ablative and fractional ablative lasers using erbium and carbon dioxide. Limited data suggest that an acetylcholine blocker found in topical skin care products, acetyl hexapeptide-8, may reduce wrinkles.¹³ However, additional studies are necessary to support this finding.

Products Currently Available

Clostridium botulinum produces eight serotypes of botulinum toxin proteins (A, B, Cα, Cβ, D, E, F, and G). Once activated, the botulinum toxin protein cleaves a docking protein on the internal surface of the neuronal membrane, SNAP-25, thereby inhibiting fusion and release of acetylcholine vesicles in the neuromuscular junction. Botulinum toxin serotype A is the most potent and is used for cosmetic treatments; serotype B is used for therapeutic indications. As of 2011, two botulinum toxin serotype A products had been approved by the U.S. Food and Drug Administration (FDA) for cosmetic use to treat the glabellar complex muscles that form frown lines: onabotulinumtoxinA (trade name Botox^®) and abobotulinumtoxinA (trade name Dysport^®). Both of these were formerly known as botulinum toxin type A. Botulinum toxin products are not interchangeable because they vary in their formulation characteristics, dosing, response, and complications. All references in this chapter to botulinum toxin refer specifically to onabotulinumtoxinA manufactured by Allergan as Botox.

Contraindications

• Pregnancy or nursing

• Active infection in the treatment area (e.g., herpes simplex, pustular acne, or cellulitis)

• Hypertrophic or keloidal scarring

• Bleeding abnormality (e.g., thrombocytopenia or anticoagulant use)

• Impaired healing (e.g., due to immunosuppression)

• Skin atrophy (e.g., chronic oral steroid use or genetic syndromes such as Ehlers-Danlos syndrome)

• Dermatoses such as active psoriasis or eczema in the treatment area

• Uncontrolled systemic condition

• Sensitivity or allergy to constituents of Botox (i.e., botulinum toxin serotype A, human albumin, lactose, or sodium succinate)

• Gross motor weakness in the treatment area (e.g., due to a history of polio or Bell’s palsy)

• Neuromuscular disorder including, but not limited to, amyotrophic lateral sclerosis, myasthenia gravis, Lambert-Eaton syndrome, and myopathies

• Inability to actively contract muscles in the treatment area prior to treatment

• Periocular/ocular surgery within the previous 6 months (e.g., laser-assisted in situ keratomileusis [LASIK] or blepharoplasty)

• Medications that inhibit neuromuscular signaling and may potentiate botulinum toxin effects, such as aminoglycosides, penicillamine, quinine, and calcium channel blockers

• Body dysmorphic disorder

• Unrealistic expectations

• Dependency on facial expression for livelihood (e.g., actors, singers).

Advantages of Botulinum Toxin

• Technically straightforward with short procedure time

• Safe and effective, particularly in the upper one-third of the face

• High patient satisfaction.

Disadvantages of Botulinum Toxin

• Short duration of action relative to other cosmetic procedures, although effects are cumulative over time with recurring treatments.

Anatomy

A thorough understanding of facial anatomy in the treatment areas is essential prior to performing botulinum toxin procedures (Figure 21-1). The muscles of facial expression are unique because, unlike most muscles, which have bony attachments, they have soft tissue attachments to the skin through the superficial muscular aponeurotic system. When a muscle contracts, the overlying skin moves with it and wrinkles are formed perpendicular to the direction of the muscle contraction. Figure 21-2 shows lines and wrinkles in the upper one-third of the face and the corresponding underlying musculature.

FIGURE 21-1 Musculature of the face.

FIGURE 21-2 Musculature and wrinkles of the upper face.

Glabellar wrinkles, or frown lines, are vertical lines that occur between the medial aspects of the eyebrows. The muscles that contribute to formation of frown lines are the glabellar complex depressor muscles, which pull the brows medially and inferiorly and include the corrugator supercilii, procerus, depressor supercilii, and medial orbicularis oculi (Figures 21-1, 21-2 and 21-3).

FIGURE 21-3 Functional anatomy of the upper face.

Horizontal forehead lines result from contraction of the broad frontalis muscle, which spans the forehead between the temporal fusion lines (see Figures 21-1, 21-2 and 21-3). The muscle fibers are vertically oriented and contraction of this levator muscle raises the eyebrows. The inferior 2-cm portion has the most marked effect on eyebrow height and shape. The goal of treatment in this area is to partially inhibit activity of the frontalis muscle to reduce horizontal forehead lines while maintaining a desirable eyebrow shape and height.

Periorbital wrinkles, commonly known as crow’s feet, result from contraction of the lateral portion of the orbicularis oculi, a thin, superficial muscle that encircles the eye (see Figures 21-1, 21-2 and 21-3). Contraction of the palpebral portion of the orbicularis oculi muscle results in closure of the eyelid. The goal of treatment in this area is to focally inhibit the lateral orbicularis oculi to reduce crow’s feet without excessive orbicularis oculi muscle relaxation.

Many of the muscles of facial expression interdigitate with one another and, while providing treatment with botulinum toxin to one area in isolation will often provide adequate wrinkle reduction results, in some cases an adjacent muscle group may require concomitant treatment to achieve the desired results. For example, the glabellar complex muscles interdigitate to a greater or lesser degree with the frontalis muscle, and treatment of the frontalis in addition to treatment of the glabellar complex muscles may be required to smooth frown lines in some cases ¹⁴.

Reconstitution

Botox Cosmetic^® is supplied as a powder which is reconstituted using saline. The manufacturer recommends using nonpreserved saline for reconstitution because it is alcohol free; however, some providers used preserved saline.

Injectors reconstitute Botox with differing amounts of saline and there is no standardized reconstitution protocol. Botox efficacy is based on the number of units injected rather than the dilution. However, diffusion and the risk of complications are related to greater dilution volumes.¹⁵ The author’s reconstitution technique is outlined below.

Reconstitute a 100-unit vial of Botox with 4.0 mL of 0.9% nonpreserved sterile saline. Using an 18-gauge needle with a 5.0-mL syringe, draw up 4.0 mL of saline. Insert the needle at a 45-degree angle into the Botox vial and inject saline slowly, maintaining upward plunger pressure so that the diluent runs down the sides of the vial. Gently swirl the reconstituted Botox vial and record the date and time of reconstitution on the vial. Note that alcohol can denature botulinum toxin and, therefore, bottle stoppers must be fully dry. Reconstitution of Botox powder using 4.0 mL of saline results in a concentration of 100 units of botulinum toxin per 4 mL (100 units/4 mL) or 2.5 units botulinum toxin per 0.1 mL increment on the 1.0-mL treatment syringe.

Handling and Storage

Botox is shipped frozen, on dry ice. Prior to and after reconstitution it should be stored in the refrigerator at a temperature of 2 to 8°C (35.6 to 46.4°F). Prior to reconstitution it may be stored for 24 months. While the manufacturer recommends using Botox within 24 hours of reconstitution, the American Society for Plastic Surgery Botox Consensus Panel recommends using Botox within 6 weeks and notes no loss of potency during that time.^3,¹⁶

Procedure Preparation

1. Perform an aesthetic consultation and review the patient’s medical history (see Chapter 19, Aesthetic Principles and Consultation).

2. Formulate a cosmetic treatment plan and record in the chart (see Chapter 19).

3. Obtain informed consent (see Chapter 19; also see Appendix A for an informed consent form and patient information handout titled Botulinum Toxin Treatments).

4. Take pretreatment photographs with the patient actively contracting the muscles in the intended treatment area and with the muscles at rest.

5. Document and discuss any notable asymmetries prior to treatment.

6. Minimize bruising by discontinuation of aspirin, vitamin E, St. John’s wort, and other dietary supplements including ginkgo biloba, evening primrose oil, garlic, feverfew, and ginseng for 2 weeks prior to treatment. Discontinue other nonsteroidal anti-inflammatory medications and alcohol consumption 2 days prior to treatment.

7. Position the patient comfortably in a reclined position for the procedure, at about 65 degrees.

8. Cleanse the treatment areas with alcohol prior to injection and allow the alcohol to dry.

9. Anesthesia is not typically required for botulinum toxin treatments. If necessary, ice may be used prior to injections in all treatment areas except the crow’s feet, because this makes identification and avoidance of veins more difficult.

Botulinum Toxin: Steps and Principles

General Treatment Technique

1. Injections are made into the “hill” of the contracted muscle.

2. Botulinum toxin is injected as the needle is withdrawn and should flow very easily, requiring only a light touch. If resistance is encountered, fully withdraw the needle and reinsert.

3. Avoid intravascular injection. Intravascular injection is apparent when the surrounding skin blanches during injection. If this occurs, withdraw the needle partially from the blanched site, reposition, and inject.

4. Avoid hitting the periosteum, particularly with frontalis muscle treatments, because this is painful and dulls the needle.

5. If bleeding occurs, apply firm pressure directed away from the eye and achieve hemostasis before proceeding to subsequent injection points.

Frown Lines

Frown lines often convey anger, frustration, and irritation, and reduction of frown lines is a common aesthetic request. Botulinum toxin treatment of the glabellar complex muscles offers dramatic improvements in frown lines.

Botulinum toxin is placed within the Glabellar Complex Safety Zone. This region is bounded by two vertical lines at the lateral limbus that extend superiorly from the supraorbital ridge to the hair line. The lateral-most injection point for corrugator muscle injections should be 1 cm or above the supraorbital ridge at the lateral limbus line (Figure 21-4) to minimize the risk of blepharoptosis (droopy upper eyelid).

FIGURE 21-4 Glabellar Complex Safety Zone.

(Copyright Rebecca Small, MD.)

Most patients desire little to no movement of the glabellar complex muscles, however, this should be discussed with the patient prior to treatment. An overview of botulinum toxin injection points and starting doses for treatment of frown lines is shown in Figure 21-5. The starting dose for women is 20 units (0.8 mL of Botox reconstituted to 100 units/4 mL) and for men 25 units (1.0 mL of Botox reconstituted to 100 units/4 mL).

FIGURE 21-5 Glabellar complex botulinum toxin injection points and doses.

(Copyright Rebecca Small, MD.)

Performing Botulinum Toxin Injections for Frown Lines

1. The glabellar muscles require deep intramuscular injection and a 30-gauge 1-inch needle is used.

2. The first injection point is at the lateral margin of the corrugator within the Glabellar Complex Safety Zone. Identify the lateral margin of the corrugator by directing the patient to actively frown. Inject 2.5 units of botulinum toxin 1 cm above the supraorbital ridge, at the visible margin of the corrugator. Insert the needle to one-half depth.

CAUTION: Injection interior to the Safety Zone at the lateral limbus line increases the risk of blepharoptosis.

CAUTION: Injection lateral to the Safety Zone increases the risk of eyebrow ptosis (droopy upper eyelid).

3. The second injection point is in the body of the corrugator, approximately 1 cm medial and inferior to the first injection point, closer to the eyebrow. Direct the needle toward the procerus muscle, inserting the needle to the hub, and inject 5 units of botulinum toxin. Repeat corrugator muscle injections for the contralateral side of the face.

4. The third injection point is in the procerus muscle. The procerus is approached inferiorly with the needle directed toward the forehead. While the patient frowns, insert the needle into the procerus to one-half depth and inject 2.5 to 5 units of botulinum toxin.

Horizontal Forehead Lines

Treatment of the frontalis muscle with botulinum toxin reduces horizontal forehead lines and can also affect eyebrow shape and height. Patients are assessed prior to treatment for the presence of eyebrow ptosis and dermatochalasis (upper eyelid laxity) with the frontalis muscle at rest. Frontalis muscle contraction is often compensatory to elevate low-set eyebrows or alleviate upper eyelid skin laxity, and treatment should be avoided in patients with these characteristics.

Botulinum toxin is placed within the Frontalis Safety Zone to minimize the risk of eyebrow ptosis and preserve eyebrow shape and height. The Frontalis Safety Zone is bounded by two vertical lines at the lateral limbus, and includes the area 2 cm above the supraorbital ridge to the hair line, as well as a small area lateral to the vertical lines approximately 2 cm inferior to the hair line (Figure 21-6).

FIGURE 21-6 Frontalis Safety Zone.

(Copyright Rebecca Small, MD.)

The goal of frontalis muscle treatment is to reduce horizontal forehead lines while maintaining a desirable eyebrow shape. In women, high arched eyebrows are often desired and minimizing botulinum toxin placement in the lateral frontalis muscle will help preserve the arch. In men, a flat eyebrow shape is usually preferable, and can be achieved by placement of botulinum toxin more inferiorly in the lateral frontalis, taking care to avoid eyebrow ptosis.

An overview of botulinum toxin injection points and starting doses for treatment of horizontal forehead lines is shown in Figure 21-7. The starting dose for women is 15 to 22.5 units (0.6 to 0.9 mL of Botox reconstituted to 100 units/4 mL) and for men 20 to 25 units (0.8 to 1.0 mL of Botox reconstituted to 100 units/4 mL).

FIGURE 21-7 Frontalis muscle botulinum toxin injection points and doses.

(Copyright Rebecca Small, MD.)

Performing Botulinum Toxin Injections for Horizontal Forehead Lines

1. Identify the horizontal ridges of the frontalis muscle by directing the patient to actively raise the eyebrows as if surprised. While standing in front of the patient, insert a 30-gauge 0.5-inch needle at a 30-degree angle to the forehead, into the “hill” of the contracted muscle. Inject 2.5 units of botulinum toxin to raise a wheal.

CAUTION: Avoid injecting too deeply and hitting the periosteum.

2. Continue laterally along each horizontal ridge of frontalis muscle within the Frontalis Safety Zone lines, injecting 2.5 units of botulinum toxin approximately 1 cm apart. Perform botulinum toxin injections evenly across the forehead to achieve symmetry.

TIP: Changing needles after six or more injections will maintain a sharp needle and minimize discomfort.

3. The last injection is placed at the maximal point of eyebrow elevation, typically located just lateral to the Safety Zone line, about 2 cm below the hairline, and 1.25 units of botulinum toxin are injected. Repeat for the contralateral side.

TIP: Omission of this injection may result in a peaked eyebrow shape and subsequently require a touch-up procedure.

TIP: As a general rule, injections are placed above the lowest forehead wrinkle to minimize effects on eyebrow height and to concentrate botulinum toxin only in the frontalis muscle.

Crow’s Feet

Botulinum toxin can dramatically reduce the appearance of periocular lines, or crow’s feet by relaxing the lateral portion of the orbicularis oculi muscles. The pattern of crow’s feet varies, with some extending superiorly toward the eyebrow and others extending inferiorly toward the cheek. Optimal results with botulinum toxin treatments in the crow’s feet area are achieved by adapting the injection technique outlined below to the patient’s pattern of crow’s feet.

Botulinum toxin is placed within the Crow’s Feet Safety Zone to minimize the risk of globe trauma and upper lip ptosis. The Crow’s Feet Safety Zone is 1 cm outside of the orbital rim, above the level of the zygoma; it extends under the eyebrow to the lateral limbus line (Figures 21-8A and B). Botulinum toxin is concentrated within the Central Crow’s Feet Safety Zone, but injections may be placed in the Extended Safety Zone according to the patient’s anatomy.

FIGURE 21-8 (A, B) Crow’s Feet Safety Zone.

(Copyright Rebecca Small, MD.)

The goal of treatment in the lateral orbicularis oculi muscle is to reduce crow’s feet lines and elevate the lateral eyebrow. An overview of botulinum toxin injection points and doses for treatment of crow’s feet is shown in Figure 21-9. The total (bilateral) starting dose for women is 15 to 20 units (0.6 to 0.8 mL of Botox reconstituted to 100 units/4 mL) and for men 20 to 25 units (0.8 to 1.0 mL of Botox reconstituted to 100 units/4 mL).

FIGURE 21-9 Orbicularis oculi muscle botulinum toxin injection points and doses.

(Copyright Rebecca Small, MD.)

Performing Botulinum Toxin Injections for Crow’s Feet

1. The orbicularis oculi muscle is a thin, superficial muscle, and botulinum toxin is placed subdermally using a 30- or 32-gauge 0.5-inch needle to raise a wheal at each injection point. After each injection, apply firm pressure away from the eye to compress the wheal.

2. The first injection point is at the lateral canthal line, 1 cm outside of the orbital rim. Direct the patient to first smile and then squint to elicit contraction of the orbicularis oculi muscle. Inject 2.5 units of botulinum toxin subdermally into the “hill” of the contracted muscle.

3. The second injection point is approximately 0.5 cm superior to the first injection point and 2.5 units of botulinum should be injected.

4. The third injection point is approximately 0.5 cm inferior to the first injection point. The needle should be angled inferiorly and threaded superficially to the hub, and 2.5 units of botulinum toxin injected as the needle is withdrawn. Repeat injections for the contralateral orbicularis oculi muscle.

TIP: Bruising is the most common side effect of the crow’s feet procedure. Look for and avoid veins, which are best seen with oblique lighting.

CAUTION: Avoid injecting too deeply and too inferiorly below the level of the zygoma, to avoid the zygomatic muscles. Relaxation of these muscles may result in cheek and lip ptosis.

Results and Follow-Up

Partial reduction in muscle function is typically seen by the third day after botulinum toxin treatment. Maximal reduction in function of the targeted muscles is visible 1 to 2 weeks after treatment. Botulinum toxin effects are most noticeable for treatment of dynamic lines. Static lines are slower to respond, usually requiring two or three consecutive botulinum toxin treatments. Deep, static lines, particularly in the glabellar complex area may not fully respond even after multiple treatments, and combination treatment with dermal fillers may be necessary to achieve reduction of these severe frown lines.

If excessive muscle activity persists in the treated area, a touch-up procedure may be performed 2 weeks after the initial treatment. The touch-up dose is based on the degree of movement remaining in the treated muscle and may range from 2.5 to 10 units. Reassess the treatment area 2 weeks after the touch-up procedure. Photographs are taken at each visit for documentation.

Return of muscle function in the treated area is gradual, typically to 4 months after treatment, based on the area treated and botulinum toxin dose. Patients should follow up for subsequent treatments when muscles in the treated areas begin to contract, prior to facial lines returning to their pretreatment appearance.¹⁷

Treatment of the glabellar complex muscles with botulinum toxin results in a dramatic improvement of dynamic frown lines, as well as marked elevation in medial eyebrow position post-treatment due to the lack of depressor muscle function (Figures 21-10A and B). The duration of botulinum toxin effects in the glabellar complex for frown lines is typically 3 to 4 months.

FIGURE 21-10 (A) Before botulinum toxin treatment with active frowning. (B) One month after botulinum toxin treatment with active frowning.

(Copyright Rebecca Small, MD.)

Patients receiving botulinum toxin treatments for horizontal forehead lines are usually seen in follow-up 2 weeks after treatment to evaluate eyebrow symmetry and shape at rest and with active elevation. Figure 21-11A shows a patient with dynamic horizontal forehead lines prior to treatment, and Figure 21-11B shows the patient 1 week after receiving 22.5 units of botulinum toxin in the frontalis muscle with mildly peaked eyebrows. A peaked eyebrow shape, or “quizzical brow” is treated with 1.25 to 2.5 units of botulinum toxin just inferior to the lateral Frontalis Safety Zone, in line with the most peaked portion of the eyebrow. Figure 21-11C shows the same patient 3 weeks after receiving 1.25 units of botulinum toxin above each peaked eyebrow and represents her final result. The duration of botulinum toxin effects in the frontalis muscle for reduction of horizontal forehead lines is typically 3 to 4 months.

FIGURE 21-11 (A) Before botulinum toxin treatment with active eyebrow elevation. (B) One week after botulinum toxin treatment demonstrating peaked eyebrows with active eyebrow elevation. (C) Three weeks after botulinum toxin touch-up treatment with active eyebrow elevation.

(Copyright Rebecca Small, MD.)

Treatment of the lateral orbicularis oculi muscle with botulinum toxin results in reduction of crow’s feet and elevates the lateral eyebrow (Figures 21-12A and B). Patients receiving botulinum toxin treatment for crow’s feet should be seen in follow-up 2 weeks after treatment to evaluate for compensatory contraction of the orbicularis oculi muscle adjacent to the treated area. Adjacent orbicularis oculi contraction is treated with 1.25 to 2.5 units of botulinum toxin in the region of orbicularis oculi muscle showing excessive activity, within the Crow’s Feet Safety Zone. The duration of botulinum toxin effects in the orbicularis oculi muscles for reduction of crow’s feet is typically to 3 months.

FIGURE 21-12 (A) Before botulinum toxin treatment with active squinting. (B) One month after botulinum toxin treatment with active squinting.

(Copyright Rebecca Small, MD.)

Aftercare

On the day of treatment, instruct the patient to avoid manipulating the treated area, lying down for 4 hours immediately after treatment and activities that cause facial flushing including application of heat to the face, alcohol consumption, exercising and tanning. Avoiding these actions will help reduce the likelihood of product migration and side effects. If bruising occurs, a soft ice pack may be applied for 10 to 15 minutes to each site, every 1 to 2 hours until resolved.

Complications

Complications and side effects can be grouped into injection-related and botulinum toxin–related issues. Complications related to botulinum toxin occur less frequently, are usually technique dependent, and the incidence declines as injector skill improves.

Injection-Related

• Numbness or dysesthesia

• Headache.

Botulinum Toxin–Related

• Localized burning or stinging pain during injection

• Facial asymmetry

• Blepharoptosis (eyelid droop), 1% to 5%

• Diplopia, blurry vision

• Eyebrow ptosis (eyebrow droop)

• Oral incompetence with crow’s feet treatment

• Ectropion

• Autoantibodies against botulinum toxin may be present or develop after treatments rendering treatments ineffective (1% to 2% of patients treated for cosmetic indications per Allergan)

• Poor aesthetic result

• Extremely rare, immediate hypersensitivity reaction with signs of urticaria, edema, and a remote possibility of anaphylaxis

• Case reports of side effects due to distant spread from the site of injection have been reported with large doses of botulinum toxin, including generalized muscle weakness, ptosis, dysphagia, dysarthria, urinary incontinence, respiratory difficulties, and death due to respiratory compromise.¹⁸

Temporary blepharoptosis can occur as a complication with treatment of the glabellar complex muscles for frown lines, particularly if botulinum toxin is injected inferior to the Glabellar Complex Safety Zone, too close to the supraorbital ridge at the lateral limbus. Figure 21-13 shows a patient 3 weeks after botulinum toxin treatment (not by the author) in the glabellar complex muscles with a profound right-sided blepharoptosis and mild right eyebrow ptosis. Blepharoptosis is infrequent (1% to 5%)⁷ and is almost always unilateral. It results from migration of botulinum toxin through the orbital septum fascia to the upper eyelid levator muscle, levator palpebrae superioris. At the bony supraorbital margin in the mid-eyebrow, some of the levator palpebrae superioris muscle fibers pass up through the orbital septum, and botulinum toxin can more easily migrate into and relax the levator palpebrae superioris from this site. Blepharoptosis is typically seen as a 2- to 3-mm lowering of the affected eyelid, which is most marked at the end of the day with muscle fatigue. It usually resolves spontaneously within 6 weeks.

FIGURE 21-13 Right-sided blepharoptosis 3 weeks after botulinum toxin treatment for frown lines (not performed by the author).

(Copyright Rebecca Small, MD.)

Blepharoptosis can be treated using over-the-counter alpha-adrenergic eye drops such as Naphcon-A, 1 drop four times per day in the affected eye, or prescription Iopidine (apraclonidine), 0.5% solution, 1 to 2 drops three times per day. Both of these medications cause contraction of Mueller’s muscle, an adrenergic levator muscle of the upper eyelid, which results in elevation of the upper eyelid. Iopidine should be used with caution because it can exacerbate or unmask underlying glaucoma and is reserved for refractory cases.¹⁹

Severe complications resulting from distant spread of botulinum toxin from the site of injection such as generalized muscle weakness, ptosis, dysphagia, dysarthria, urinary incontinence, respiratory difficulties, and death due to respiratory compromise have been reported in patients receiving very large doses of botulinum toxin (e.g., 300 units in the calves ²⁰) and have not been reported with cosmetic use of botulinum toxin at the labeled dose of 20 units (for glabellar lines) or 100 units (for severe primary axillary hyperhidrosis). These symptoms have been reported hours to weeks after injection. The risk of symptoms is presumed to be greatest in children treated for clinical conditions such as spasticity, particularly in patients with compromised baseline respiratory function.

Learning the Techniques

Begin with conservative doses and ensure botulinum toxin injection is within the defined Safety Zones. Additional botulinum toxin can be added if required at subsequent visits. Marking injection sites initially using a marker or soft white eyeliner pencil is helpful with placement, but lengthens the visit time.

Consider performing initial treatments on staff and family as feedback will be available and the evolution of botulinum toxin effects may be closely observed and touch-up procedures may be performed if necessary. Receiving a treatment is one of the best ways to gain knowledge about botulinum toxin treatments.

Current Developments

AbobotulinumtoxinA (trade name Dysport^®, see the Resources section below) was FDA approved in 2009 for cosmetic use to treat glabellar frown lines. It is estimated that Dysport requires 2.5 to 3 times the number of units to achieve effects equivalent to Botox,²¹ but may have a more rapid onset of action.²²

Several new botulinum toxin products for cosmetic use are in clinical trials or in the FDA approval process. PurTox (Mentor Corporation) and Xeomin (Merz Pharmaceuticals) are injectable botulinum toxin formulations that are under investigation for cosmetic use and in clinical trials for approval in the United States.

A physician-applied topical botulinum toxin by ReVance Therapeutics shows promise for the treatment of axillary hyperhidrosis ²³ and is under investigation for cosmetic applications including treatment of crow’s feet. The company claims to have a novel method of delivery of topical products (TransMTS™) that allows for macromolecules such as botulinum toxin to penetrate beneath the skin and reach the neuromuscular junction.