Introduction

Patients frequently seek aesthetic rejuvenation of the periocular region. Age-related changes of the bony facial skeleton and soft tissue, in combination with photodamage of the overlying periorbital skin, can lead over time to eyebrow ptosis, drooping of the upper eyelids, and lateral canthal rhytides or ‘crow’s feet’, with a resultant tired or sad appearance. In fact, the periocular region is often a candid indicator of someone’s age, with crow’s feet developing early on in the aging process, often by the 3rd and 4th decades of life. The eyes serve as an integral component of facial recognition and have been considered a marker for physical attractiveness and beauty. During non-verbal communication, subtle differences in eyebrow and eyelid contour and position convey a broad range of emotions, from surprise, to fear, and happiness. By integrating the concepts of facial symmetry, sexual dimorphism, and ethnic diversity, along with a global understanding of the anatomy and aesthetics of the periocular region, the clinician can achieve successful facial rejuvenation. The overall result may emerge from a comprehensive treatment algorithm, including topical skin care, botulinum toxin injection, soft tissue augmentation, skin tightening, and cutaneous rejuvenation and resurfacing. In this chapter, we will focus on the indications and treatment guidelines for botulinum toxin in the periocular region.

Anatomy of ‘crow’s feet’ lateral orbital rhytides

A thorough understanding of the functional anatomy of the periocular region must precede treatment. Eyelid skin is elastic and among the thinnest of the body, with essentially no underlying subcutaneous fat. Crow’s feet are fine or coarse rhytides originating from the lateral ocular canthus and projecting outward, often in a partial or full fan-like distribution. Most prominent during the so-called ‘dynamic’ states of smiling or squinting, crow’s feet can be appreciated in repose, the ‘static’ posture, in certain patients. Several factors contribute to the development of crow’s feet, including sun exposure, smoking, lack of subcutaneous fat, and redundant skin.

In addition, rhytides develop in the setting of hyperkinetic muscle contractions of the orbicularis oculi, an elliptical muscle that functions in closing the eyelids and protecting the globe by acting as the sphincter of the eye. The orbicularis oculi encircles the eye, with a predominantly vertical orientation at the lateral canthus, and has three distinct subparts: the orbital, palpebral, and lacrimal portions. The lacrimal portion of the muscle runs deep to the lacrimal sac and inserts on the upper and lower eyelids at the tarsal plates. Contraction of this part of the muscle draws the eyelids against the globe and compresses the lacrimal sac, thus assisting tear flow. The palpebral portion is the innermost aspect of the muscle and passes into the eyelid superficial to the septum from the bifurcation of the medial palpebral ligament to the lateral palpebral raphe. The palpebral portion is subdivided into preseptal and pretarsal components, and each portion is superficial to the corresponding named portion of the eyelid. Contraction of the palpebral portion of the orbicularis oculi provides less forceful involuntary closure of the eyelid, as with blinking. The orbital portion represents the outermost aspect of the muscle overlying the bony orbit, with origins at the nasal process of the frontal bone, frontal process of the maxilla, and the medial palpebral ligament. This portion of the muscle blends into surrounding musculature, interdigitating at its superior aspect with the frontalis muscle, corrugator supercilii, depressor supercilii, and procerus muscles, and at its inferior margins with the levator labii superioris alaeque nasi, levator labii superioris, and zygomaticus minor and major muscles (Fig. 15.1). By providing forceful eye closure and eyebrow depression, this outer aspect of the muscle pulls on overlying skin and contributes most to the formation of lateral orbital rhytides. The outer orbicularis is typically treated with botulinum toxin, although the preseptal aspect of the inferior palpebral portion of the orbicularis oculi can be treated in some situations as well. The zygomaticus muscles, both major and minor, can also contribute to inferior periorbital rhytides, as contraction of this muscle elevates skin superiorly into the periocular region. The zygomaticus major originates deep to the orbicularis oculi muscle at the zygomatic bone just anterior to the zygomaticotemporal suture line and courses diagonally where it inserts into the modiolus, lifting the corner of the mouth. The zygomaticus minor muscle courses from the zygomatic bone and inserts into the upper lip, where it causes upward and lateral elevation of the oral commissure. The risorius muscle originates from the connective tissue and fascia overlying the parotid gland, platysma, and runs horizontally towards the oral commissure, where it inserts into the modiolus. Contraction of this muscle pulls the mouth laterally, retracting the corners of the mouth.

Figure 15.1 The muscles of facial expression.

In an article by Kane et al, four lateral canthal rhytid patterns were identified, reflecting divergent muscle contraction patterns: (1) full-fan distribution of rhytides from the upper eyelid to the upper cheek, (2) rhytides of the lower lid / upper cheek, (3) rhytides of the upper eyelid skin down to the lateral canthus, and (4) central zone of rhytides at the lateral canthus only (Fig. 15.2). Although standard injection points can be helpful for beginner injectors, treatment should be individualized to take into account this diversity in lateral canthal rhytides, which may deviate from published patterns and require care and attention to understand, document, and address specifically. Some patients may exhibit right–left differences in the distribution and size of lateral canthal rhytides. Lateral canthal rhytides are generally classified as static, dynamic, or a combination of the two. Dynamic rhytides develop secondary to repeated muscle contractions, and remit during relaxation, and hence are most immediately amenable to treatment with botulinum toxin. Static rhytides, which are present in the absence of muscle contractions, may best be treated with soft tissue fillers or resurfacing procedures, and will be addressed later in this chapter. Alternatively, ongoing and repeated treatments with botulinum toxin may soften static rhytides over long time intervals, as reduction of coincident dynamic creases reduces the incidence of repeated microtrauma to the underlying collagen and elastin. Botulinum toxin treatments may also prevent the extension or deepening of static creases through a similar mechanism.

Figure 15.2 (A–D) Various typical crow’s feet patterns, as described by Kane et al.

The youthful eye

Eyes are critical in non-verbal communication, with eye contact considered an innate aspect of human interaction and expression. Large prominent eyes are a defining feature of beauty and facial recognition. Truthfulness, sincerity, and a genuine smile can be conveyed through minor modifications of eye position and ocular muscle constriction (see Paul Eckman and Alam et al). Although several attributes contribute to a youthful eye unit that conveys happiness and relaxation, maintenance of volume in the area framing the eye is a central component. The eyebrow should be full with enough volume to keep it elevated and away from the bony orbital rim. Laterally, the eye–eyelid complex should be delineated by a full and convex temple region. The upper eyelid area below the brow should be full rather than deeply recessed, and ideally there would be only a few millimeters of upper lid showing. A subtle but defined superior–lateral slope of the eyelids is associated with beauty. The one shadow that should be prominent is the eyelid crease over the upper lid lash line, and, in an attractive eye, this will run nearly parallel to the lash line. Starting at the tarsal insertion, the lower eyelid flows in a smooth convexity all the way down to the nasolabial fold and buccal region. In a youthful face, there is no sharp step-off or boundary between the lower eyelid and the cheek. While a slight to modest nasojugal hollow is appropriate, excessive volume loss should not be apparent. A single light reflex should be evident off the cheek and another off the lateral brow.

The aging eye

The aging process in the periocular region is characterized by volume loss, with the eyes appearing hollowed-out or sunken, surrounded by shadows and / or dark under-eye half-moon circles. Patients may complain of looking tired, sad, or malnourished. Volume loss and skin laxity, in addition to frontalis muscle weakening, can lead to lateral brow ptosis, with the eyebrow sitting flat against the orbital rim. Similarly, volume loss leads to drooping of the upper eyelid that induces folds of redundant skin and shadows in the upper lid sulcus; in elderly patients, any visibility of the upper lid may be effaced. As previously mentioned, lateral canthal rhytides and associated lateral atrophy also develop as part of the aging process. In the lower eyelid, a loss of orbital volume creates a ‘hollowing’ or depression that separates the lower eyelid from the cheek.

Preoperative assessment

A detailed medical and surgical history is often obtained prior to botulinum toxin injection. Specifically, history elements that may result in technique modification include prior facial surgery, including blepharoplasty, brow or face lift, as well as previous injection of soft tissue fillers or botulinum toxin. At the initial consultation, a comprehensive evaluation is undertaken of the periorbital complex, including eyebrows, eyelids, glabella, forehead, and lateral canthus. In order to objectively evaluate postoperative results, the clinic should document any pre-existing asymmetries photographically prior to treatment. Patients should also be made aware of these asymmetries, such as brow ptosis, upper eyelid ptosis, globe prominence due to exophthalmos or orbital hypoplasia, variation of intercanthal axis or tilt, lower eyelid position, scleral show, or differences in the malar prominence.

Pre-existing ocular conditions such as persistent or intermittent tearing, dry eyes, or previous LASIK surgery may be associated with increased risk of dry eyes after botulinum toxin treatment. As patients may not volunteer the use of over-the-counter medications, it may be informative to question them specifically regarding the use of eye drops for dry eyes. If there is a concern that decreased tear production may exist before treatment, a Schirmer’s test can measure tear production using calibrated strips of filter paper placed within the lower eyelid, or a rose bengal test can employ a dye to detect corneal scratches associated with dry eye. Injection treatments around the eye may be modified in the context of systemic conditions with ocular manifestations, including Graves’ disease, Hashimoto’s thyroiditis, Sjögren’s syndrome, and other collagen vascular diseases. A lower eyelid ‘snap-test’ can estimate the risk for development of ectropion or scleral show after infraorbital toxin injections. The snap is assessed by pulling gently downward and outward on the lower eyelid and then quickly releasing; a rapid return to the rest position without requiring an eyelid blink suggests a fully functional orbicularis muscle and a low risk of excessive eye rounding after botulinum toxin injections (Fig. 15.3). A positive test is defined as a slow return to baseline, with the eyelid staying in a distracted position until the patient blinks, or until several seconds elapse and the lid very slowly resumes its normal apposition against the globe.

Figure 15.3 Snap test to measure lower lid laxity can be performed by pulling the lower lid outward and downward, then allowing the eyelid to snap back against the eye.

Photoaging, including dyschromias and actinic damage, of the periorbital region is often appropriately noted prior to treatment. Before commencing cosmetic treatment with botulinum toxin, it may be useful to discuss with patients adjunctive modalities, like resurfacing and pigment lasers, that may be helpful in correcting any such photoaging; this reassures patients that all their cosmetic deficits are treatable, and also makes clear that additional procedures in addition to toxin injections may be necessary to modify skin complaints other than fine lines and wrinkles. Postponing this discussion until after toxin injections can lead patients to erroneously conclude that the toxin injections failed to achieve their full effect, and the physician is now attempting to rationalize this incomplete effect. Anticoagulant medications and those that interfere with platelet function that are not medically necessary, including aspirin, supplements such as garlic and vitamin E, in addition to alcohol, should be discontinued at least 1 week prior to injections.

An assessment of lateral canthal rhytides should be performed at rest and while the patient is making deliberate muscle contractions, as during smiling or squinting. As previously mentioned, both dynamic and static rhytides may be noted, with the latter potentially responding to a lesser extent to treatment with botulinum toxin. The presence of horizontal forehead rhytides may signify a compensatory response to eyebrow ptosis, with contraction of the frontalis muscles allowing for elevation of the eyebrow. In addition to eyebrow position, eyebrow shape should also be considered, since this may be modified by toxin injections along the upper lateral brow. While individual and ethnic differences may intrude, in general, feminine eyebrows should be high and mildly arched, whereas the male ideal is generally a lower, straight brow, perpendicular to the nose. Pretreatment eyelid ptosis should be documented so that there is no subsequent concern that this was induced by the toxin injections, and so toxin injections can be placed in a manner that does not exacerbate the baseline finding. Usually, the normal adult upper lid lies 1.5 mm below the superior corneal limbus.

Treatment

Although treatment of crow’s feet with botulinum toxin has only recently been approved for abobotulinumtoxinA and is currently pending for onabotulinumtoxinA, it is a highly effective and frequently sought after procedure. When performing injections in the periocular region, the patient is typically seated upright or slightly reclined. Although some physicians may find standing on the same side as the treatment area more natural, others may choose to stand on the opposite side so that the needle is pointed away from the eye, and yet others may stand facing the patient. To minimize the risk of ecchymoses, injections are placed as a wheal superficially into the dermis rather than deep into the muscle (Fig. 15.4). Cleansing the skin with alcohol prior to treatment, in addition to side lighting and stretching of the skin, may help to identify any superficial vessels along the treatment area (Fig. 15.5). Injections should be performed meticulously and slowly, with the needle changed frequently to prevent it from becoming blunt. The hand is typically braced to avoid inadvertent sideways motion or deeper placement, both of which may predispose to trauma and bruising. It goes without saying that the needle tip should be aimed to minimize the risk of inadvertently spearing the globe. Some injectors prefer to insert the needle head on vertically, and others insert the needle from the side, almost tangential to the skin, occasionally tenting the skin. Vertical injections are associated with a marginal higher risk of deeper than desired placement, and lateral injections course through more dermis, thus being at greater likelihood of perforating a small blood vessel. Overall, superficial injections no more than 2–3 mm deep minimize the risk of spread or direct injection into nearby lip elevators, including the zygomaticus minor and major muscles. Smaller volumes may aid with precision and prevention of migration; on the other hand, more dilute solutions may enable a wider radius of action, and reduce the number of injections needed.

Figure 15.4 (A) Injection wheals illustrating the superficial injection technique of botulinum toxin around the periocular region. (B) Placement of botulinum toxin into the dermis rather than the underlying muscle or at the level of periosteum.

Figure 15.5 Stretching of the skin and side lighting can aid in identifying and then avoiding blood vessels during botulinum toxin injection.

For standard treatment of periorbital rhytides, injections are commonly placed 1.5 cm from the lateral canthus or 1 cm lateral to the bony orbital rim. Some injectors place the injection on or even inside the orbital rim with equal effect and no increase in side effects. The injected dose and pattern is adjusted to account for individual patient preference, as well as the strength and size of the orbicularis oculi muscle (Figs 15.6, 15.7). In general, 6–18 units of onabotulinumtoxinA (Botox^®) are injected per side as three to four injections along a 90–180° arc, spaced at 1–1.5 cm intervals, as recommended in the studies by Matarasso & Matarasso and by Lowe et al. In the latter study, evaluating the safety and efficacy of 6, 12, and 18 units of onabotulinumtoxinA (Botox^®) in the treatment of crow’s feet, there was no statistically significant difference in the efficacy or safety profile among the tested doses. In the trials by Lowe and co-workers, at 4 weeks post-treatment 89% of patients in the 6-unit group and 95% of patients in the 12- and 18-unit group had an improvement of at least 1 point from baseline on the Facial Wrinkle Scale; these authors also noted that a second injection of the same dose resulted in a longer duration of action compared with the first injection, with up to half of the patients still one grade above baseline 16 weeks after the second injection. Notably, like many such small, relatively underpowered studies, this research was susceptible to type II error, i.e. the failure to detect small real differences that may have been statistically and clinically significant. In general, smaller doses may be sufficient for women with minimal movement of the lateral canthal rhytides, whereas certain men, patients with stronger muscles, and those with larger faces may need higher cumulative doses. In patients with protuberant globes, lowering the dose may reduce the risk for ectropion or incomplete eyelid closure. When injecting lower malar crow’s feet, especially those that blend into the diagonal rhytides of the mid and lateral cheeks, extreme caution should be exercised as direct injection or spread into the zygomaticus major and minor muscles can cause ipsilateral facial paralysis and lip ptosis. In order to prevent such complications, injections below the level of the superior zygomatic arch should be avoided. Again, discussing with patients why far lower infraorbital rhytides cannot be safely injected with toxin may reduce their disappointment when these persist after treatment.

Figure 15.6 (A–F) Representative botulinum toxin injection sites of the lateral canthus, with variations appropriate for different muscle strengths and locations across individuals. Quantities are of onabotulinumtoxin A.

Figure 15.7 (A) Before and (B) after pictures of botulinum toxin injection into lateral crow’s feet. Note static rhytides may persist and even some dynamic rhytides may respond only partially.

With regards to abobotulinumtoxinA (Dysport^®), a study by Ascher et al evaluated the efficacy and safety of 15-, 30-, and 45-unit injections per side in the treatment of crow’s feet. At week 4, response rates at maximum smile were 42% in the 15-unit group, 60% in the 30-unit group, and 57% in the 45-unit group, with response defined as an improvement in crow’s feet severity of at least one grade from baseline on both sides. This improvement in rhytides was maintained for up to 8 weeks in the 15-unit group and for up to 12 weeks in the 30- and 45-unit groups. While a statistically significant difference in efficacy was not appreciated when comparing the 30- and 45-unit groups, one patient in the 45-unit group did develop eyelid ptosis, which resolved by day 31. Beyond this, no difference in the safety profile between the tested doses was noted. This study also documented a trend towards improved response in subjects 50 years of age or younger compared with those over 50 years of age.

IncobotulinumtoxinA (Xeomin^®), which was FDA-approved in 2011 for the treatment of glabellar frown lines, cervical dystonia, and blepharospasm, is differentiated from onabotulinumtoxinA (Botox^®) based on the lack of complexing proteins in the former. In a randomized, double-blind, split-face design study by Prager and colleagues, of 21 patients comparing 12 units of incobotulinumtoxinA (Xeomin^®) and 12 units of onabotulinumtoxinA (Botox^®) in the treatment of crow’s feet, no statistically significant difference in response rates over a 4-month study period was observed. At 1 month, a 95% response rate was noted on the side treated with incobotulinumtoxinA (Xeomin^®), compared with a 90% response rate on the side treated with onabotulinumtoxinA (Botox^®), with response defined as an improvement of at least 1 point on the Facial Wrinkle Scale.

Adjunctive treatments

Although botulinum toxin injections are highly effective in reducing the appearance of dynamic lateral canthal rhytides, patients presenting with advanced facial aging, including static rhytides, photodamage, skin laxity, and volume loss, may benefit from adjunctive treatment modalities. Several non-invasive procedures including soft tissue augmentation, laser resurfacing, and skin tightening can be employed to optimize aesthetic outcomes and improve patient satisfaction. Conversely, the outcomes of some of these other procedures are enhanced secondary to toxin treatment, and synergies are possible.

For instance, botulinum toxin pretreatment of the periorbital region has been shown to impede recurrence and severity of dynamic rhytides after laser resurfacing. In a prospective, randomized, placebo-controlled study by Yamauchi et al, of 33 patients receiving either 18 units of onabotulinumtoxinA (Botox^®) or saline into the periorbital region followed 2–6 weeks later by erbium–YAG resurfacing, patients receiving onabotulinumtoxinA (Botox^®) demonstrated a more significant reduction in periorbital rhytides as well as textural and pigmentary changes. In a separate study by Zimbler et al, in which 10 patients were pre-treated on one side of the face with onabotulinumtoxinA (Botox^®) 1 week prior to laser resurfacing, the greatest improvement in facial rhytides was observed in the crow’s feet region that had been pre-treated with onabotulinumtoxinA (Botox^®). Ideally, pre-treating patients with botulinum toxin and then repeating treatment well into the postoperative period could enhance and prolong the aesthetic effects of laser resurfacing. In the same manner, the effects of soft tissue augmentation in the periorbital region may last longer when muscle activity is inhibited with botulinum toxin. Prominent periorbital hollows may disappear after volume replacement with hyaluronic acids fillers, thus contributing to global facial rejuvenation and the beneficial effect of rhytid reduction induced by toxin injections (Fig. 15.8). Given that areas of volume loss often develop in regions with greater movement, a comprehensive strategy that combines soft tissue augmentation and chemodenervation may optimize patient outcomes.

Figure 15.8 Areas of volume loss or hollowing in the infraorbital (tear trough and nasojugal fold) and lateral canthal regions, which may be amenable to treatment with soft tissue augmentation.

Case Study 1

A patient presents to you requesting treatment of her crow’s feet (Fig. 15.9). How do you counsel this patient?

Figure 15.10 Upper lip ptosis secondary to direct injection or diffusion of botulinum toxin into zygomaticus major, zygomaticus minor, levator labii superioris alaeque nasi, or levator labii superioris muscles.

In evaluating this patient, you should appreciate that her crow’s feet are quite broad, extending from the lateral canthus inferiorly down the cheek. Caution should be exercised in injecting the inferior border of these rhytides. In general, injections below the level of the superior zygomatic arch should be avoided. Drooping of the upper lateral lip can occur if botulinum toxin spreads or is injected directly into the zygomaticus major, zygomaticus minor, levator labii superioris alaeque nasi, or levator labii superioris muscles. The patient should thus be educated that eradication of all rhytides is not possible without risk of lip ptosis.

Complications

While complications secondary to botulinum toxin injections in the periocular region can occur, they are usually mild, self-limited, and quickly resolving. Even when the rare instance of brow or eyelid ptosis occurs, this generally results in only a temporary deficiency in anatomical function, which tends to return to baseline in a matter of weeks, long before the end of the 3-month longevity period of toxin injections. As with all cutaneous injections, the first adverse effect of toxin injections is injection pain upon delivery. Injection discomfort can be ameliorated by using very small needles, injecting slowly, gently rubbing or tickling nearby skin with the injector’s finger, pre-treating with ice and topical anesthetic preparations, or with forced cold air during the procedure, and reconstituting the toxin in preserved rather than unpreserved saline.

Ecchymoses can develop both during and after injections, and have been reported (in a 2005 study by Lowe and co-workers) to occur in up to 25% of patients receiving injections for crow’s feet. Although this is not surprising given the thin nature of periorbital skin, several strategies can be employed to reduce the risk of ecchymoses. Completely removing all make-up by washing the face and then using alcohol pads can help in identifying and avoiding vessels. Similarly, stretching the skin and side lighting, injecting superficially in the dermal plane with only the needle tip inserted, and using a 31- or 32-gauge needle may also minimize the likelihood of a bruise. If bleeding does occur upon injection, pressure should be applied immediately for up to 5 minutes to mitigate the risk of ecchymoses.

Although rare, lip ptosis can occur after botulinum toxin injections for crow’s feet (Fig. 15.10). This can result either from direct intramuscular injection or spread of toxin into the zygomaticus major, zygomaticus minor, levator labii superioris alaeque nasi, or levator labii superioris muscles, all of which have fibers that blend with the orbicularis oculi muscle. Lip ptosis has been estimated to occur in far less than 1% of treated patients and is characterized by an inability to elevate the corner of the mouth. Patients who have undergone facial surgery prior to treatment may be at increased risk of inadvertent injection or diffusion into the lip elevators due to aberrant muscle fiber realignment or planes of dissection. Although there is no treatment for this complication, Lowe et al reported in 2002 that muscle function should normalize by 6 weeks post-injection, much sooner than the recurrence of periorbital rhytides, but when the injection is placed too far inferior or deeply and the bulk of toxin is injected into the zygomaticus major the ill effects can last as long as 4 months.

Figure 15.9 Case study: evaluation of crow’s feet.

Some patients also describe a bunching of skin or a new fold beneath the eye or along the malar prominence that is noticeable after effacement of inferior canthal rhytides. This is thought to arise secondary to contraction of the zygomaticus muscle and subsequent elevation of the cheek into a now-flattened infraorbital / nasojugal region. This post-treatment difference in contour may be relatively more prominent during smiling. It appears more common in young women with prominent zygomatic arches or prominent malar prominence. Thus, caution should be exercised, with the inferior injection site omitted or lower doses considered in this subset of patients.

Rarely, eyelid ptosis can occur as a result of migration of toxin into the levator palpebrae superioris muscle, which functions to elevate the upper eyelid. Fortunately, this complication can be treated with alpha-adrenergic drops, such as Iopidine^® (apraclonidine 0.5%), which stimulates the Müller muscles to contract quickly and raise the upper eyelid. One to two drops three times daily can be used until ptosis resolves. It is important to recognize that both eyelid and, more commonly, eyebrow ptosis can also occur secondary to inadvertent weakening of the frontalis muscle, which can no longer compensate for a sagging eyelid or eyebrow. This most often occurs secondary to diffusion of toxin when performing forehead injections too close to the eyebrow or from injections in the periocular region. To prevent this complication, injections should be performed at least 1 cm above the eyebrow. Furthermore, patients should be warned against vigorous massaging after botulinum toxin injections in the periocular region. Some botulinum toxin A formulations, such as abobotulinumtoxinA, may spread slightly further from the point of injection at equivalent dilutions per unit of potency; if these are used, it may be prudent to inject slightly higher than 1 cm above the mid brow.

Conclusion

In conclusion, treatment of crow’s feet with botulinum toxin injections is safe and effective. Appropriate patient selection and preoperative assessment increase the likelihood of an optimal result. Injection technique is now well defined, and some variation is possible based on the patient’s functional anatomy and the injector’s preference. Adverse events are rare and, without exception, self-limited and spontaneously resolving. Annoying rare outcomes like eyelid ptosis and dry eye, or an excessively rounded eye, usually remit within weeks to months. Botulinum toxin injections at the crow’s feet are routinely performed in conjunction with other modalities, like laser or light treatment of sun-induced dyspigmentation, laser resurfacing, and hyaluronic acid fillers, for more comprehensive rejuvenation of the periocular space. At present there is little reliable data to differentiate between the utility and safety of the several FDA-approved botulinum A toxins in treating the periorbital region.