Cosmetic Uses of Cosmetic Uses of Botulinum ToxinBotulinum Toxin

IntroductionIntroduction

Surgical procedures continue to trend towards Surgical procedures continue to trend towards minimally invasive techniques. minimally invasive techniques.

Cosmetic alterations to combat the effects of aging are Cosmetic alterations to combat the effects of aging are no exception to this trend. Patients, more and more, are no exception to this trend. Patients, more and more, are demanding cosmetic procedures that leave no scar and demanding cosmetic procedures that leave no scar and allow them to return to normal activity quicker. allow them to return to normal activity quicker.

Though traditional rhytidectomy and brow lift remain Though traditional rhytidectomy and brow lift remain in the armamentarium of the facial cosmetic surgeon, in the armamentarium of the facial cosmetic surgeon, minimally invasive procedures such as botox treatment minimally invasive procedures such as botox treatment can often achieve satisfactory results for patients. can often achieve satisfactory results for patients.

Mechanism of ActionMechanism of Action

Botulinum toxin exerts its effects by paralyzing Botulinum toxin exerts its effects by paralyzing skeletal muscle. skeletal muscle.

The pharmacological site of action is at the The pharmacological site of action is at the neuromuscular synapse. neuromuscular synapse.

The presynaptic neuromuscular nerve ending The presynaptic neuromuscular nerve ending contains membranous vesicles prepared to release contains membranous vesicles prepared to release its stored neurotransmitter, acetylcholine. its stored neurotransmitter, acetylcholine.

Mechanism of ActionMechanism of Action

Neuronal stimulation initiates a cascade of events Neuronal stimulation initiates a cascade of events that leads to the fusion of the neurotransmitter-that leads to the fusion of the neurotransmitter-containing vesicle with the nerve membrane. containing vesicle with the nerve membrane.

This process is facilitated by a group of proteins This process is facilitated by a group of proteins comprising the SNARE complex. comprising the SNARE complex.

The membrane fusion results in the release of The membrane fusion results in the release of acetylcholine into the synaptic cleft by a process of acetylcholine into the synaptic cleft by a process of exocytosis. exocytosis.

The acetylcholine diffuses and eventually binds to The acetylcholine diffuses and eventually binds to receptors on the muscle, leading to muscle receptors on the muscle, leading to muscle contraction. contraction.

Mechanism of ActionMechanism of Action Botulinumtoxin A (BOTOX) consists of a heavy Botulinumtoxin A (BOTOX) consists of a heavy

chain of 100-kilodalton and a light chain of 50-chain of 100-kilodalton and a light chain of 50-kilodalton making up the 150-kilodalton core type A kilodalton making up the 150-kilodalton core type A molecule. molecule.

The BOTOX core molecule enters the nerve cell by a The BOTOX core molecule enters the nerve cell by a process of receptor-mediated endocytosis, mediated process of receptor-mediated endocytosis, mediated by the heavy chain.by the heavy chain.

The light chain is released into the cytoplasm of the The light chain is released into the cytoplasm of the nerve terminal where it begins to cleave one of the nerve terminal where it begins to cleave one of the SNARE proteins.SNARE proteins.

Mechanism of ActionMechanism of Action

In motor neurons, the light chain of the In motor neurons, the light chain of the BOTOX core molecule blocks the release of BOTOX core molecule blocks the release of acetylcholine by cleaving SNAP-25, which is acetylcholine by cleaving SNAP-25, which is an essential component of the SNARE an essential component of the SNARE complex. When acetylcholine cannot be complex. When acetylcholine cannot be released, muscle contraction cannot occur.released, muscle contraction cannot occur.

The toxin does not appear to affect the The toxin does not appear to affect the conduction of electrical signals along the conduction of electrical signals along the nerve fiber or the synthesis or storage of nerve fiber or the synthesis or storage of acetylcholine.acetylcholine.

ApplicationsApplications

The cosmetic use of botulinum toxin is well-The cosmetic use of botulinum toxin is well-studied for the treatment of glabellar frown studied for the treatment of glabellar frown lines, horizontal forehead rhytids, and lateral lines, horizontal forehead rhytids, and lateral canthal lines (crow’s feet).canthal lines (crow’s feet).

Currently, physicians are beginning to explore Currently, physicians are beginning to explore other uses in the face, such as contouring of other uses in the face, such as contouring of the jawline, the neck, and the melolabial fold. the jawline, the neck, and the melolabial fold.

Glabellar Frown LinesGlabellar Frown Lines

Glabellar frown Glabellar frown lines are the most lines are the most common reason for common reason for cosmetic injection cosmetic injection of botulinum toxin.of botulinum toxin.

TechniqueTechnique

Usually, 5 sites are injected with 4-6 units Usually, 5 sites are injected with 4-6 units each for an average total dose of each for an average total dose of approximately 25 units. approximately 25 units.

A 1998 dose/response study of 46 women A 1998 dose/response study of 46 women receiving botulinum toxin for glabellar receiving botulinum toxin for glabellar wrinkles found an effective starting dose from wrinkles found an effective starting dose from 2.5-4 units per injection site (12.5-20 U total). 2.5-4 units per injection site (12.5-20 U total).

TechniqueTechnique

One site on each side is used to inject the One site on each side is used to inject the corrugator, one site on each side is used to corrugator, one site on each side is used to inject the orbicularis oculi and depressor inject the orbicularis oculi and depressor supercilii, and one site is used to inject the supercilii, and one site is used to inject the procerus in the mid line.procerus in the mid line.

TechniqueTechnique The patient is asked initially to frown and scowl, and The patient is asked initially to frown and scowl, and

the target muscles are palpated. the target muscles are palpated. The first injection is placed into the belly of the The first injection is placed into the belly of the

corrugator muscle. corrugator muscle. The needle is inserted at the origin of the corrugator The needle is inserted at the origin of the corrugator

fibers just above the medial canthus and superciliary fibers just above the medial canthus and superciliary arch until bone is felt, and then withdraw it slightly. arch until bone is felt, and then withdraw it slightly.

The needle is then advanced within the belly of the The needle is then advanced within the belly of the muscle upward and lateral as far as the medial third muscle upward and lateral as far as the medial third of the eyebrow, 1 cm superior to the orbital rim. 4-6 of the eyebrow, 1 cm superior to the orbital rim. 4-6 units are injected as the needle is withdrawn.units are injected as the needle is withdrawn.

TechniqueTechnique

The next site is approximately 1 cm above the The next site is approximately 1 cm above the upper medial aspect of the supraorbital ridge. upper medial aspect of the supraorbital ridge. The needle is advanced slightly in a vertical The needle is advanced slightly in a vertical direction toward the hairline. 4-6 units are direction toward the hairline. 4-6 units are injected into the orbicularis oculi and injected into the orbicularis oculi and depressor supercilii as the needle is depressor supercilii as the needle is withdrawn. withdrawn.

TechniqueTechnique

The last injection is central into the belly of The last injection is central into the belly of the procerus to eliminate the horizontal lines at the procerus to eliminate the horizontal lines at the root of the nose. the root of the nose.

4-6 units are injected at a point where 2 lines 4-6 units are injected at a point where 2 lines drawn at 45° from the medial aspect of the drawn at 45° from the medial aspect of the eyebrows converge in the center of the nasal eyebrows converge in the center of the nasal root, just superior to the horizontal plane of the root, just superior to the horizontal plane of the medial canthi. medial canthi.

Horizontal Forehead LinesHorizontal Forehead Lines

Performing botulinum toxin injections to treat Performing botulinum toxin injections to treat horizontal forehead lines is relatively easy, and horizontal forehead lines is relatively easy, and the result usually is quite satisfying. the result usually is quite satisfying.

Treatment can be combined with injections Treatment can be combined with injections for glabellar frown lines when appropriate.for glabellar frown lines when appropriate.

TechniqueTechnique

Injections of the upper face and periocular Injections of the upper face and periocular region usually are performed with the patient region usually are performed with the patient seated, and the patient is asked to remain seated, and the patient is asked to remain upright for 2-3 hours to prevent spread of upright for 2-3 hours to prevent spread of toxin through the orbital septum.toxin through the orbital septum.

Lateral Canthal Lines (crow’s Lateral Canthal Lines (crow’s feet)feet)

Aging and photodamage Aging and photodamage cause much of the wrinkling cause much of the wrinkling in this area. in this area.

However, the component of However, the component of hyperfunctional contraction hyperfunctional contraction of the lateral aspect of the of the lateral aspect of the orbicularis oculi is targeted orbicularis oculi is targeted for improvement with for improvement with botulinum toxin injections.botulinum toxin injections.

TechniqueTechnique

3 or 4 subcutaneous injections are applied 3 or 4 subcutaneous injections are applied approximately 1 cm lateral to the lateral orbital approximately 1 cm lateral to the lateral orbital rim using 2-3 units per injection site (for a rim using 2-3 units per injection site (for a total of 6-12 U per side). total of 6-12 U per side).

Sites are spaced 0.5-1 cm apart in a vertical Sites are spaced 0.5-1 cm apart in a vertical line or slightly curving arch. Doses that are too line or slightly curving arch. Doses that are too high or injections that are too medial can lead high or injections that are too medial can lead to eyelid ptosis or diplopia.to eyelid ptosis or diplopia.

ContraindicationsContraindications

Pregnancy or active nursing Pregnancy or active nursing Preexisting neuromuscular conditions, such as Preexisting neuromuscular conditions, such as

myasthenia gravis or Eaton-Lambert syndromemyasthenia gravis or Eaton-Lambert syndrome Some medications such as aminoglycosides, Some medications such as aminoglycosides,

penicillamine, quinine, and calcium channel penicillamine, quinine, and calcium channel blockers can potentiate the effects of botox blockers can potentiate the effects of botox and should not be used concomitantlyand should not be used concomitantly

Adverse EffectsAdverse Effects

Generalized reactions that have occurred from Generalized reactions that have occurred from botox injections include nausea, fatigue, botox injections include nausea, fatigue, malaise, flulike symptoms, and rashes at sites malaise, flulike symptoms, and rashes at sites distant from the injection. distant from the injection.

In addition, there were no symptoms of In addition, there were no symptoms of weakness remote to the injection site or related weakness remote to the injection site or related to the central nervous system.to the central nervous system.

Adverse EffectsAdverse Effects Sequelae that can occur at any site due to percutaneous Sequelae that can occur at any site due to percutaneous

injection of botox include pain, edema, erythema, injection of botox include pain, edema, erythema, ecchymosis, headache.ecchymosis, headache.

Discomfort can be decreased by use of topical anesthetics such Discomfort can be decreased by use of topical anesthetics such as EMLA cream before injection, and the use of smaller-gauge as EMLA cream before injection, and the use of smaller-gauge needles. needles.

A 2005 single-center, double-blind, randomized study A 2005 single-center, double-blind, randomized study demonstrated a statistically significant reduction in subject-demonstrated a statistically significant reduction in subject-reported procedural pain in participants pretreated with reported procedural pain in participants pretreated with lidocaine 4%. lidocaine 4%.

Adverse EffectsAdverse Effects

Pinching the skin and the underlying muscle, Pinching the skin and the underlying muscle, slowly inserting the needle bevel up through slowly inserting the needle bevel up through the opening of a pilosebaceous unit, and the opening of a pilosebaceous unit, and slowly injecting the solution will also help to slowly injecting the solution will also help to diminish discomfort. diminish discomfort.

Ice applied immediately after injection will Ice applied immediately after injection will further reduce the pain as well as the edema further reduce the pain as well as the edema and erythema associated with an IM injection. and erythema associated with an IM injection.

Adverse EffectsAdverse Effects

Ecchymosis can be minimized by avoiding Ecchymosis can be minimized by avoiding aspirin, aspirin-containing products, and aspirin, aspirin-containing products, and NSAIDs for 7 to 10 days before injection. NSAIDs for 7 to 10 days before injection.

Bruising occurs most frequently in older Bruising occurs most frequently in older patients taking aspirin and in middle-aged patients taking aspirin and in middle-aged persons taking vitamin E. persons taking vitamin E.

Limiting the number of injections and Limiting the number of injections and applyingapplying postinjection digital pressure without postinjection digital pressure without manipulation will also assist in reducing manipulation will also assist in reducing bruising. bruising.

Adverse EffectsAdverse Effects The most common The most common

complication in complication in treatment of the treatment of the glabellar complex is glabellar complex is ptosis of the upper ptosis of the upper eyelid. eyelid.

This is caused by This is caused by diffusion of the toxin diffusion of the toxin through the orbital through the orbital septum, where it septum, where it affects the levator affects the levator palpebrae muscle. palpebrae muscle.

Adverse EffectsAdverse Effects To avoid ptosis, injections should not cross the To avoid ptosis, injections should not cross the

midpupillary line, and should be 1 cm above the midpupillary line, and should be 1 cm above the eyebrow. eyebrow.

Digital pressure at the border of the supraorbital ridge Digital pressure at the border of the supraorbital ridge while injecting the corrugator also reduces the while injecting the corrugator also reduces the potential for extravasation. potential for extravasation.

Patients often are instructed to remain in an upright Patients often are instructed to remain in an upright position for 3-4 hours following injection and to position for 3-4 hours following injection and to avoid manual manipulation of the area. avoid manual manipulation of the area.

Active contraction of the muscles under treatment Active contraction of the muscles under treatment may increase the uptake of toxin and decrease its may increase the uptake of toxin and decrease its diffusion. diffusion.

Adverse EffectsAdverse Effects

Ptosis can be treated with apraclonidine 0.5% Ptosis can be treated with apraclonidine 0.5% eyedrops, an alpha2-adrenergic agonist that causes eyedrops, an alpha2-adrenergic agonist that causes contraction of Müller muscles contraction of Müller muscles

Apraclonidine is contraindicated in patients with Apraclonidine is contraindicated in patients with documented hypersensitivity. documented hypersensitivity.

Phenylephrine (Neo-Synephrine) 2.5% can be used Phenylephrine (Neo-Synephrine) 2.5% can be used when apraclonidine is not available. when apraclonidine is not available.

Neo-Synephrine is contraindicated in patients with Neo-Synephrine is contraindicated in patients with narrow-angle glaucoma and in patients with narrow-angle glaucoma and in patients with aneurysms. aneurysms.

Adverse EffectsAdverse Effects

The most significant complication of treatment of the The most significant complication of treatment of the frontalis is brow ptosis. frontalis is brow ptosis.

Injections in the forehead should always be above the Injections in the forehead should always be above the lowest fold produced when the subject is asked to lowest fold produced when the subject is asked to elevate their forehead (frontalis). elevate their forehead (frontalis).

Adverse EffectsAdverse Effects An unfavorable outcome is the brow that assumes a An unfavorable outcome is the brow that assumes a

“cockeyed” appearance.“cockeyed” appearance. This occurs when the lateral fibers of the frontalis muscle have This occurs when the lateral fibers of the frontalis muscle have

not been appropriately injected. not been appropriately injected. The central brow then becomes lowered and the lateral brow is The central brow then becomes lowered and the lateral brow is

still able to contract and is pulled upward. sides of the brow. still able to contract and is pulled upward. sides of the brow. The treatment is to inject a small amount of botox into the The treatment is to inject a small amount of botox into the

fibers of the lateral forehead that are pulling upward. fibers of the lateral forehead that are pulling upward. However, only a small amount of Botox is required, as However, only a small amount of Botox is required, as

overcompensation can cause hooded brow that partially covers overcompensation can cause hooded brow that partially covers the eye. the eye.

Adverse EffectsAdverse Effects The most common reported complications in the “crow’s feet” The most common reported complications in the “crow’s feet”

area are bruising, diplopia, ectropion and an asymmetric smile area are bruising, diplopia, ectropion and an asymmetric smile due to injection of zygomaticus major. due to injection of zygomaticus major.

If severe lower lid weakness occurs, an exposure keratitis may If severe lower lid weakness occurs, an exposure keratitis may result. Treatment is symptomatic. result. Treatment is symptomatic.

These complications are avoided by injecting at least 1 cm These complications are avoided by injecting at least 1 cm outside the bony orbit or 1.5 cm lateral to the lateral canthus, outside the bony orbit or 1.5 cm lateral to the lateral canthus, not injecting medial to a vertical line through the lateral not injecting medial to a vertical line through the lateral canthus and not injecting close to the inferior margin of the canthus and not injecting close to the inferior margin of the zygoma. zygoma.