Modifications of Eyebrow Position with Botulinum Exotoxin A

ORIGINAL ARTICLE Modifications of Eyebrow Position With Botulinum Exotoxin A

Mimi S. Kokoska, MD; Jason B. Amato, MD; Christopher S. Hollenbeak, PhD; Dee Anna Glaser, MD

Objective: To determine if clinically used botulinum Results: In 29 patients at rest, we found no significant exotoxin A (Botox) injections to the forehead and gla- (P value range, .17 to .97) change in eyebrow position, bellar and crow’s-feet regions result in modifications of except for a point depression at the right lateral eye- eyebrow position. brow. The 15 patients who received injections into the forehead and glabella, with or without treatment of the Design: Prospective study. crow’s-feet, had no significant (P value range, .11 to .84) change in eyebrow position, except for a point of depres- Setting: Academic medical center in St Louis, Mo. sion at the left medial eyebrow. Both groups exhibited eyebrow depression in the active state (eyebrow maxi- Subjects: Twenty-nine adult patients treated with botu- mally elevated). linum exotoxin A injections for rhytids. Conclusions: Botulinum exotoxin A injections into the Intervention: The eyebrow position at 13 different sites forehead and glabellar, and crow’s-feet regions did not was measured before injection and 2 weeks after treat- significantly change the resting eyebrow position. How- ment. The areas injected were based on patient prefer- ever, forehead injections contributed to eyebrow depres- ence and physician assessment. Of the 29 patients, 14 re- sion in the active state. ceived injections into the glabella only and 15 received injections into the glabella and forehead, with or without treatment of the crow’s-feet. Arch Facial Plast Surg. 2002;4:244-247

SE OF botulinum exo- of the face were enrolled into our study, and toxin A (Botox; Allergan, informed consent was obtained. There were 2 Inc, Irvine, Calif) has been male and 27 female patients (age range, 28-73 well described for the cos- years). Fourteen of these patients received metic treatment of hyper- injections into the glabella only, and 15 received injections into the glabella and the fore- functional facial rhytids.1-3 For the upper U head, with or without injection into the crow’s- third of the face, the drug is commonly used feet region. Selection of treated areas was based to paralyze muscles causing glabellar frown on patient preference, along with physician rec- lines, horizontal forehead furrows, and lat- ommendations. Measurements were taken be- eral orbital crow’s-feet. Reversing the age- fore injection and 2 weeks after injection. associated ptosis of the eyebrow, tradition- Thirteen measurements were taken with ally done using a surgical approach, gives the eyelids closed and the eyebrow relaxed, and a youthful result that is cosmetically desir- again in the active state, with the eyebrow maxi- able. Other articles4-6 that have examined the mally elevated (Figure 1). Vertical measure- effects of botulinum exotoxin A on eyebrow ments A, B, and C were taken from the upper position imply that it is possible to create a eyelid margin to the upper eyebrow margin at chemical eyebrow-lift with selective use of the lateral canthus, the mid eyelid line, and the medial canthus, respectively. Vertical measure- From the Department of the medication. Some of the injections in Otolaryngology–Head and ments D, E, and F were taken from the upper Neck Surgery, Indiana these previous studies were purposefully eyebrow margin to the hairline at the lateral University School of Medicine, placed to produce eyebrow elevation. In this canthus, the mid pupillary line, and the me- Indianapolis (Dr Kokoska); the study,ourobjectivewastodetermineifmodi- dial canthus, respectively. The intereyebrow Department of Dermatology, ficationsineyebrowpositionoccurwithclini- distance was also measured. Subscripts R and Saint Louis University Health cally used botulinum exotoxin A injections L denote the right and left sides of the face, re- Sciences Center, St Louis, Mo for hyperfunctional facial rhytids of the fore- spectively. (Drs Amato and Glaser); and head and glabellar, and crow’s-feet regions. Botulinum exotoxin A was prepared by di- the Department of Surgery, luting a 100-U vial with 2.0 mL of sterile pre- Graduate Health METHODS servative-free isotonic sodium chloride solu- Administration Program, tion for a final concentration of 5 U/0.1 mL. A The Pennsylvania State Twenty-nine adult patients who presented to 1.0-mL tuberculin syringe and a 30-gauge University–College of Medicine, Saint Louis University Hospital for botuli- needle were used for percutaneous injections Hershey, Pa (Dr Hollenbeak). num exotoxin A injections into the upper third into the muscular layer.

(REPRINTED) ARCH FACIAL PLAST SURG/ VOL 4, OCT-DEC 2002 WWW.ARCHFACIAL.COM 244

AR BR CR CL BL AL

Figure 1. Measurements taken in the relaxed position and then with maximal Figure 3. All 29 patients at rest, showing no change except for a right lateral eyebrow elevation. Vertical measurements A, B, and C were taken from the eyebrow elevation (arrow). upper eyelid margin to the upper eyebrow margin at the lateral canthus, the mid eyelid line, and the medial canthus, respectively. Vertical measurements D, E, and F were taken from the upper eyebrow margin to the hairline at the lateral canthus, the mid pupillary line, and the medial canthus, respectively. Subscripts R and L denote the right and left sides of the face, respectively.

Figure 4. The 15 patients who received injections into the forehead and glabella had only a left medial eyebrow depression (arrow).

Figure 2. Standardized injection sites (diamonds). RESULTS We first tested whether modifications in eyebrow posi- Botulinum exotoxin A injection doses and sites were se- tion could be detected for resting positions. In all 29 pa- lected based on the typical injections used for treatment of the tients at rest, only the right lateral eyebrow elevation (po- upper third of the face in our practice (Figure 2). For treatment of the forehead, 5 injection sites were used, with4Uper sition AR in Figure 1) was significant (mean, −1.34 mm; injection, for a total of 20 U. Three 5-U injections were used P=.006) (Figure 3). There was no significant (P value to treat the glabella, for a total of 15 U. Each lateral orbital re- range, .17 to .97) change in intereyebrow or other eye- gion was injected at 2 sites, with 4 U each, for a total of 16 U to brow distances. In the subsample of 15 patients who re- treat the bilateral crow’s-feet regions. ceived injections into the forehead and glabella, with or with- Statistical analyses were performed using SAS statistical soft- out treatment of the crow’s-feet, the left medial eyebrow ware, version 6.12 (SAS Institute Inc, Cary, NC). Observations (position FL in Figure 1) was significantly depressed (mean, were paired measurements of the distance before and after treat- −1.87 mm; P=.03) (Figure 4). No other significant (P value ment with botulinum exotoxin A; therefore, we used a paired t 7 range, .11 to .84) changes were found in other eyebrow po- test in our statistical analysis. Posttreatment measurements were sitions or in the intereyebrow distance. A separate analy- subtracted from pretreatment measurements, and the average difference was tested using a null hypothesis that the average dif- sis of the 14 patients who received glabellar injections with- ference was 0. We performed one statistical test for each of the out forehead injections produced no significant (P value 13 sites for the entire sample and for the subsample of 15 pa- range, .18 to .73) changes in eyebrow position. tients who received injections into the forehead and the glabella. We did find significant (P value range, Ͻ.001 to .01) Results were considered significant if PϽ.05. changes in eyebrow position for the active state, with the

(REPRINTED) ARCH FACIAL PLAST SURG/ VOL 4, OCT-DEC 2002 WWW.ARCHFACIAL.COM 245

©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 This results in an improved cosmetic appearance.8 The pri- mary functional upper facial rhytids include the glabellar frown lines, the horizontal forehead furrows, and the crow’s- feet. The medial frontalis, the procerus, the corrugator supercilii, and the medial orbicularis oculi muscles contribute to the glabellar frown lines. Contraction of the frontalis muscle causes the horizontal forehead furrows, and contraction of the lateral orbital portion of the orbicularis oculi muscles results in the crow’s-feet rhytids.9 Eyebrow position is determined by underlying skel- etal shape, resting muscular tone, and overlying skin tone. It is generally accepted that the eyebrow is elevated by the frontalis muscle and depressed by the procerus, the corrugator supercilii, and the orbicularis oculi muscles.1 In their retrospective study of 29 patients injected with 20 U of botulinum exotoxin A into the procerus and corrugator supercilii muscles, Frankel and Kamer5 found Figure 5. All 29 patients with maximal elevation, showing a depression of that 8 (32%) of 25 patients had an elevation of the me- the medial two thirds of the eyebrow (arrows). dial eyebrow, 12 (48%) of 25 patients had an elevation at the mid pupillary eyebrow, and 17 (59%) of the 29 patients had an increase in intereyebrow distance with measurements from standardized photographs. A subjec- tive comparison of the photographs by blinded observers found that 18 (62%) of the 29 patients have a higher medial eyebrow. Although this is not stated in their article, further interpretation of their results suggests that 17 (68%) of their 25 patients had either a depression or no change in medial eyebrow position, 13 (52%) of the 25 patients had either a depression or no change in mid pupillary eyebrow position, and 12 (41%) of the 29 patients had either a depression or no change in intereyebrow distance. Huilgol et al4 reported that 5 of 7 women showed an eyebrow elevation of 1 to 3 mm with selective botulinum exotoxin A treatment of the eyebrow depressors. They injected a total of 10 to 14 U into the glabellar region and the supralateral eyebrow, and measured from the mid pupillary line to the lowest portion of the eyebrow to make this determination. One difference Figure 6. The 15 patients who received injections into the forehead and glabella in the active position had a depression of the entire eyebrow from the present study is that the subjects in the study (arrows), except at the right lateral eyebrow position. by Huilgol et al received lateral eyebrow injections. No statistical analysis was performed in either of these studies; therefore, the results should be interpreted with this eyebrow maximally elevated. For the 29 patients in the in mind. active position, the medial two thirds of the eyebrow (po- Ahn et al6 examined subjects with only injections sitions B, C, E, and F in Figure 1) were depressed to the supralateral eyebrow. The purpose of the injec- (Figure 5). The numbers were bilaterally consistent, with tions was to produce an eyebrow-lift, not to treat rhytids. absolute means ranging from 1.93 to 7.86 and P values No injections were performed in the crow’s-feet area in- ranging from .01 to Ͻ.001. The subsample of 15 pa- ferior to the lateral canthus. There was significant lat- tients also had a depression of the entire eyebrow in the eral and mid eyebrow elevation after supralateral eye- active position at all sites shown in Figure 1, except site brow injection. The injection sites differ significantly from AR (Figure 6). Again, the effects were bilaterally con- those in the present study; therefore, no direct compari- sistent, with absolute means ranging from 2.93 to 11.53 sons can be made. mm (P value range, Ͻ.001 to Ͻ.01). In our study, eyebrow position was assessed after injections of botulinum exotoxin A for cosmetic treat- COMMENT ment of hyperfunctional facial rhytids on the upper third of the face. The 29 patients at rest had no statistically sig- Functional facial rhytids result from tension of the under- nificant change in eyebrow position after injection, ex- lying mimetic facial musculature on the overlying skin. cept in the right lateral eyebrow measurement. These same Botulinum exotoxin A acts as a peripheral neuromuscular patients had a depression of the medial two thirds of the blockade and, thus, weakens the underlying muscles of fa- eyebrow in the active position. This change can be ex- cial expression, causing a flattening of the overlying skin. plained by the toxin’s effect on the frontalis muscle, the

(REPRINTED) ARCH FACIAL PLAST SURG/ VOL 4, OCT-DEC 2002 WWW.ARCHFACIAL.COM 246

©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 only eyebrow elevator. In patients who received injec- feet (lateral orbicularis oculi), injections did not tions into the forehead and the glabella, with or without significantly change resting eyebrow positions. Fore- crow’s-feet injections, there was no significant change in head injections resulted in depression of the eyebrow in eyebrow position at rest, except for the left medial eye- the active state. This translates into a decreased ability brow measurement. These patients also had a depres- for upward excursion of the eyebrow after injection into sion of the eyebrow in the active eyebrow-raising posi- the forehead. tion 2 weeks after injection, also explained by the Our findings are important for patient counseling botulinum exotoxin A effect on the frontalis muscle. before injection with botulinum exotoxin A. While it may These results can be correlated with facial anatomi- be possible to modify the eyebrow with botulinum exo- cal features. The corrugator supercilii muscle is situated toxin A injections, the resultant modification of the eye- in a horizontal or diagonal plane. The procerus is a ver- brow position in the relaxed state is not consistently pre- tical muscle, and the orbicularis oculi is a circumferen- dictable. When treating the forehead for rhytids, the tial muscle. These eyebrow depressors, however, are rela- physician should modify the injections in a patient with tively smaller in muscle mass than the frontalis muscle a ptotic eyebrow to avoid further lowering of the eye- and, therefore, in most patients, contribute less to eyebrow in the extended position. In other words, patients brow elevation or depression than the frontalis muscle. who constantly and actively raise their eyebrows will likely The frontalis muscle inserts into the skin of the eye- be perceived as having eyebrow ptosis after botulinum brows and the nasal root.10 Therefore, botulinum exo- exotoxin A injections to the frontalis muscle, because their toxin A injections at the eyebrow level will likely affect eyebrows will be relatively depressed. It is helpful in the the most inferior portion of the frontalis muscle, in ad- pretreatment patient consultation to manually lift or de- dition to the corrugator supercilii muscles. This relation- press the patient’s eyebrows to demonstrate the possible ship may explain the lack of eyebrow elevation with in- modification in eyebrow position and the varying de- jections into the medial eyebrow area. The horizontal or grees of resultant upper eyelid skin redundancy. This pro- oblique orientation of the corrugator supercilii muscle vides the patient with a better understanding of the pos- explains its dominant role in eyebrow medialization and sible aesthetic changes in the upper third of the face after its more minor role as an eyebrow depressor, creating the botulinum exotoxin A injection. vertical wrinkles at the glabella. The 2 sites that showed This study suggests that botulinum exotoxin A in- a statistically significant change at rest, the right lateral jections to the upper third of the face do not universally eyebrow and the left medial eyebrow, may change with lift the eyebrows. Based on this study and our review of a larger sample size. the literature, botulinum exotoxin A may result in eye- We found that it was more difficult to measure from brow depression, eyebrow elevation, or no change in eye- the eyebrow to the hairline than from the eyebrow to the brow position. The resultant effect on the eyebrows is closed eyelid margin. The exact margin of the hairline likely multifactorial, including the site(s) and dosage of was sometimes ambiguous and more difficult to repro- injections, the extent of muscular paralysis, the state of duce at the 2-week follow-up. Despite this, the eyebrow- muscle activity, and individual anatomical variations. to-hairline measurements were generally confirmatory with respect to eyebrow position. Accepted for publication January 8, 2002. A subpopulation of subjects in this study (n=10) who Corresponding author: Mimi S. Kokoska, MD, Depart- were classified as hypertonic (defined in the pretreatment of Otolaryngology–Head and Neck Surgery, Indiana ment consultation as having clinically constant corru- University School of Medicine, 550 N University Blvd, Room gator and/or frontalis muscle contraction) were not sig- 3170, Indianapolis, IN 46202. nificantly different from the general population. This may be secondary to the small numbers in the subpopula- REFERENCES tion in our study. Another possible explanation is that the subjects were asked to purposefully relax the upper third of their face for the resting measurements, which 1. Carruthers A, Carruthers J. Clinical indications and injection technique for the cosmetic use of botulinum A exotoxin. Dermatol Surg. 1998;24:1189-1194. may have reduced their baseline muscular hypertonic- 2. Blitzer A, Binder WJ, Aviv JE, Keen MS, Brin MF. The management of hyperfunc- ity. Two of us (M.S.K. and D.A.G.) have clinically ob- tional facial lines with botulinum toxin: a collaborative study of 210 injection sites served subjects who are hypertonic who have more ex- in 162 patients. Arch Otolaryngol Head Neck Surg. 1997;123:389-392. aggerated eyebrow position changes after botulinum 3. Klein AW. Dilution and storage of botulinum toxin. Dermatol Surg. 1998;24: 1179-1180. exotoxin A injections. In other words, some patients who 4. Huilgol SC, Carruthers A, Carruthers JDA. Raising eyebrows with botulinum toxin. constantly raise their eyebrows, even at rest, have a dra- Dermatol Surg. 1999;25:373-376. matic depression in their resting eyebrow position after 5. Frankel AS, Kamer FM. Chemical browlift. Arch Otolaryngol Head Neck Surg. 1998; botulinum exotoxin A injection into the frontalis muscle. 124:321-323. Further study of this subpopulation is warranted. 6. Ahn MS, Catten M, Maas CS. Temporal brow lift using botulinum toxin A. Plast Reconstr Surg. 2000;105:1129-1139. 7. Daniel WW. Biostatistics. 6th ed. New York, NY: John Wiley & Sons Inc; CONCLUSIONS 1995. 8. Binder WJ, Blitzer A, Brin MF. Treatment of hyperfunctional lines of the face with We present a prospective and statistically analyzed study botulinum toxin A. Arch Otolaryngol Head Neck Surg. 1997;123:393-396. 9. Wieder JM, Moy RL. Understanding botulinum toxin. Dermatol Surg. 1998;24: of botulinum exotoxin A–induced effects on eyebrow po- 1172-1174. sition. We found that glabellar, including procerus, cor- 10. Woodburne RT. Essentials of Human Anatomy. 6th ed. New York, NY: Oxford rugator with or without depressor supercilii, and crow’s- University Press Inc; 1978:199-212.

(REPRINTED) ARCH FACIAL PLAST SURG/ VOL 4, OCT-DEC 2002 WWW.ARCHFACIAL.COM 247