Cosmetic Applications of Botulinum Toxin in Oculoplastics

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 by Cat Nguyen Burkat, MD FACS on August 29, 2023.


Botulinum toxin has played several roles throughout history. In the 1700s, the first written accounts in Germany linked it to food poisonings by blood sausages.[1] Later on, during World War 2, scientists attempted to weaponize its paralytic effects for biological warfare.[2] During the late twentieth century, scientists began experimenting with its therapeutic potential in medicine.

Botulinum toxin was first tested in 1973 as an experimental treatment for strabismus and was approved in 1989 to treat strabismus, blepharospasm, and hemifacial spasm.[3][4] In 2002, the FDA approved its cosmetic usage to treat glabellar wrinkles, which was the launching point for a multibillion-dollar industry that continues to thrive today.[5][6] Over the years, several companies have utilized differing methods of preparation to develop commercial formulations of botulinum toxin, including Botox (OnabotulinumtoxinA), Dysort (AbobotulinumtoxinA), Xeomin (IncobotulinumtoxinA), Jeuveau (PrabotulinumtoxinA), and Daxxify (DaxibotulinumtoxinA). There are high rates of patient-reported satisfaction with botulinum toxin therapy across disorders, suggesting a high impact on quality of life.[7] In oculoplastics, the most common cosmetic applications of botulinum toxin are for reducing forehead and glabellar wrinkles, eyebrow repositioning, and soften periorbital wrinkles.[8][9][10]


The gram-positive, anaerobic bacillus Clostridium botulinum produces seven different antigenic serotypes (A-G).[11] These toxins are 150-kd polypeptides composed of a 100-kd heavy chain and 50-kd light chain linked together by disulfide bonds.[12] They act by binding irreversibly to presynaptic cholinergic receptors, upon which these molecules are endocytosed.[13][14] They then cleave and deactivate SNARE proteins, which are normally responsible for the fusion of acetylcholine vesicles with the cell membrane.[15] By blocking the release of presynaptic acetylcholine vesicles, botulinum toxin thereby causes muscle paralysis.[16]

The most common commercial formulations of botulinum toxin derive from toxin serotype A. The onset of action of botulinum toxin A is 24-72 hours and the maximum effect will occur within 7-14 days.[11] The duration of action on striated muscle is 3-4 months.

The different commercial formulations of botulinum toxin differ by their method of preparation and their potency.[8][17] Their preparations differ by the nontoxic accessory proteins attached to the 150-kd active toxin A.[18] Botox, Dysport, and Xeomin have been used commercially for a longer period of time and are consequently more researched in the literature. They have been used to treat glabellar and forehead lines, eyebrow repositioning, and periorbital wrinkles, among other uses.[19][20][21][22][23][24][25][26] Jeuveau and Daxxify are more recent on the market and have mainly been used to treat glabellar lines.[27][28][29] There is no significant difference in efficacy or safety profile among the different formulations.[18][30][31] The most recent research trials suggest that Daxxify may be useful for long-lasting treatment with a median duration of efficacy of 6 months, while most other botulinum toxin formulations have a shorter duration of efficacy of 3 months.[28]

Trade name (proprietary name) Manufacturer Onset of action Length of therapeutic effect Units per vial Molecular weight (kDa) Conversion ratio of product to Botox FDA approved uses
Botox (OnabotulinumtoxinA) Allergan Inc., Irvine, CA, USA 3-5 days 3-6 months 50 or 100 900 1:1 Glabellar lines (2002), periorbital wrinkles (2013), forehead lines (2017)
Dysport (AbobotulinumtoxinA) Slough Berkshire, UK 24 hours 3-6 months 300 or 500 500-900 3:1 Glabellar lines (2009)
Xeomin (IncobotulinumtoxinA) Merz Pharmaceuticals, Frankfurt, Germany 5-7 days 3-6 months 100 150 1:1 Glabellar lines (2011)
Jeuveau (PrabotulinumtoxinA) Daewoong Pharmaceutical, Seoul, South Korea 3-5 days 3-6 months 50 or 100 900 1:1 Glabellar lines (2019)
Daxxify (DaxibotulinumtoxinA) Revance Therapeutics, Inc., Newark, CA 1-2 days 6-9 months 50 or 100 150 2:1 Glabellar lines (2022)

Clinical applications

Forehead lines

Figure 1

Forehead wrinkles are formed by repeated upward pulling of the frontal muscle, especially of the medial fibers. Botox can be applied to the lines that form when the patient engages in maximal contraction of the frontal muscle, at typically 6-8 injection sites with a dosage of 10-15 U Botox or 20-30 U Dysport divided among all sites.[10][27] When treating the upper forehead, it may be sufficient to inject only the medial frontal muscle. Before addressing forehead wrinkles, it is important to assess the presence of brow ptosis to prevent exacerbation.

Figure 2

Glabellar lines

Glabellar lines are frown lines between the eyebrows that form due to repeated downward pulling of the procerus and depressor, as well as medially movement of the corrugator supercilii muscles (the latter are known colloquially as “11’s”). While Botox and Dysport have been traditionally used to treat glabellar lines, Jeuveau and Daxxify are more recent drugs with comparable efficacy and safety profiles.[29][31] Female patients are commonly treated with 20 U Botox or 50 U Dysport divided among 5 injection sites, while men may need a higher dosage of at least 40 U Botox and 60 U Dysport.[32][33][34]

Eyebrow repositioning

Figure 3

While brow position and shape preferences vary across cultures and facial shapes, an arched eyebrow with the highest point over the lateral canthus is generally viewed to be aesthetically pleasing.[35][36][37] With aging, the lateral brow tends to be the first to experience descent, while the medial brow may descend with gravity or rise due to compensatory upward pull of the frontalis muscle.[38] Botox injected below the lateral brow at the orbicularis oculi can weaken the depressor muscle and provide a temporary and small lateral brow lift for patients, who do not want to undergo brow-enhancing surgery.[39][40] Typically a dosage of 10-15 U Botox or 30-40 U Dysport is divided among three sites inferior to the lateral third of the brow (see image).[10] Although it is unpredictable how much lateral brow elevation will be achieved with an injection, it has been reported that this procedure can cause as much as a brow elevation of 5 mm above the lateral canthus.[39] Since it is imperative to prevent diffusion of the toxin to adjacent orbital muscles, a conservative dose should be given with follow-up injections if desired.

Periorbital wrinkles

Figure 4

Periorbital wrinkles result from repeated radial movement of the orbicularis oculi muscle, resulting in wrinkles along the lateral corner of the eye (known colloquially as “crows feet”) . Neurotoxin of 12 U Botox, 30 U Dysport, or 12 U Xeomin divided among 3 injection sites 1 cm from the lateral orbital rim can weaken the sphincter function of this muscle and soften wrinkle lines.[10][41][42] Care must be taken to avoid the zygomaticus major and levator labii superioris muscles, which fuse with the deep surface of the orbicularis oculi muscle, as this may result in lip ptosis.[43]

Complications and side effects

One issue that may arise with repeated or escalating doses of botulinum toxin treatment is that patients may develop resistance to the toxin. It is reported, however, that fewer than 2% of patients undergoing botulinum toxin therapy will develop neutralizing antibodies over the long-term.[44] To avoid immunologic resistance, patients should be injected with the lowest dose possible for achieving clinical effect and avoid reinjection within one month.[11]

Cosmetic usage of botulinum toxin has a low incidence of adverse effects and most complications are temporary.[45] General side effects may include nausea, fatigue, flu-like symptoms, rashes, and headache.[46] Side effects localized to the injection site may include muscle weakness, pain, edema, ptosis, ecchymosis, headache, and hypesthesia.[45][47] Side effects may also include diplopia, ectropion, drooping lower eyelid, and asymmetric smile.[45][48]

The following conditions are among the exclusion criteria for botulinum toxin usage: pregnancy or breastfeeding, neuromuscular conditions such as myasthenia-gravis and Lambert-Eaton syndrome, and medications that may interact with botulinum toxin such as aminoglycosides, penicillamine, quinine, and calcium channel blockers.[45] While Botox has not been associated with teratogenic events so far, it has not been definitely established as safe during pregnancy.[49][50]


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