Persistence of Upper Blepharoptosis After Cosmetic Botulinum Toxin Type A Kenneth D. Steinsapir, MD, Michael J. Groth, MD, and Cynthia A. Boxrud, MD*
BACKGROUND Upper eyelid ptosis after cosmetic botulinum toxin is generally considered short-lived and responsive to apraclonidine ophthalmic drops. The authors present a series with persistent ptosis. OBJECTIVE
To report a series of patients with persistent upper eyelid ptosis after cosmetic botulinum toxin.
MATERIALS AND METHODS A retrospective case review series of 7 patients referred for management after developing visually significant upper eyelid ptosis after cosmetic botulinum toxin type A treatment. RESULTS Patients in this series experienced persistent visually significant ptosis after cosmetic botulinum toxin lasting from 6 weeks to 13 months. Six of the 7 patients were treated with apraclonidine ophthalmic solution. Apraclonidine drops appeared to be clinically effective within 4 to 6 weeks of the resolution of ptosis. CONCLUSION Upper eyelid ptosis after cosmetic botulinum toxin can persist for many months after treatment. Based on this series, the authors propose that apraclonidine drops can be used at the time of initial assessment to predict the relative longevity of ptosis after cosmetic botulinum toxin treatment (Level 4 evidence recommendation). After a 1-week trial, responders can be advised that ptosis is likely to resolve in 4 to 6 weeks. Nonresponders should be counseled that resolution may take longer than 6 weeks. The authors have indicated no significant interest with commercial supporters.
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osmetic applications of botulinum toxin type A have become one of the most common physicianperformed aesthetic services in the United States and the World. One source has estimated that over 6 million aesthetic botulinum toxin type A treatments were performed in the United States in 2013.1 Among the reasons accounting for the popularity of treatment are the relative ease with which the service can be provided and a very low incidence of complications. When complications do occur, they include brow ptosis, upper eyelid ptosis, diplopia, dry eye, unwanted weakness of the lip elevators, and orbicularis oris incompetence. The true incidence of upper eyelid ptosis is unknown but appears to be less than 5% of periocular treatments. Published reports of this complication imply that the induced blepharoptosis is relatively
short-lived.2 A variety of treatments have been proposed to address blepharoptosis after cosmetic botulinum toxin type A, including alpha-adrenergic agonists,3,4 anticholinesterases,5 and physical treatment including massage, electrostimulation,3 and laser irradiation.6 Apraclonidine is the predominantly prescribed alpha adrenergic and is used on a twice-a-day basis. Naphazoline is a sympathomimetic with strong alpha-adrenergic effects that is found in a number of ophthalmic decongestant products. With the exception of alphaadrenergic agonists, which stimulate the sympathetically innervated Mueller muscle of the upper eyelid to help open the eyelid, there is no evidence that any of these other methods are of any clinical benefit.7 The authors have treated a series of patients referred for management of upper eyelid ptosis after cosmetic botulinum toxin type A. These patients share in
*All the authors are affiliated with the Division of Ophthalmic Plastic and Reconstructive Surgery, Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California © 2015 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1076-0512 Dermatol Surg 2015;41:833–840 DOI: 10.1097/DSS.0000000000000386
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common profound upper eyelid ptosis that lasted 6 or more weeks. In 1 case, complete resolution did not occur for 13 months. It is the intent of this case series report to make physicians and surgeons aware that upper eyelid ptosis after cosmetic botulinum toxin treatment can persist, so that patients presenting with this complication receive accurate information regarding their possible time course for recovery. Discussion is also provided regarding steps that may minimize the risk of this rare but foreseeable complication.
Materials and Methods This study is a retrospective case series reporting the histories of patients seeking treatment at the respective private practices of the authors. As such, the study was conducted at sites without a formal institutional review board. The authors have complied with the principles of the Declaration of Helsinki and the privacy standards described by the Health Insurance Portability and Accountability Act (HIPAA). Cases were collected from December 2005 through December 2013. To be included in the study, patients needed to report a recent aesthetic botulinum toxin type A treatment preceding the sudden onset of upper eyelid ptosis. Cases of brow ptosis in the absence of actual blepharoptosis were excluded. The authors personally examined and followed each patient until the upper eyelid ptosis resolved. The distance from the central corneal light reflex to the
upper eyelid margin (MRD1) was measured, and only patients with an MRD1 of 2 mm or less (normal 4.0 mm) were included in this study. In cases with brow ptosis, the brow was lifted and supported at the superior orbital rim before measuring the upper eyelid margin to central light reflex distance (MRD1). Levator function with brow fixation was also recorded. There was no standard treatment protocol, and the patients were managed according to the clinical judgment of the respective authors. Patients were questioned regarding their history of botulinum toxin type A treatment and knowledge of their treatment dose. Patients were questioned to determine if they had any insight regarding the treatment that resulted in upper eyelid ptosis and how it might have differed from past treatments. The medical records of the original treating physicians were also requested and reviewed.
Results Seven patients were identified who met the criteria: 6 women and 1 man. The age range was 38 to 60 years, and the mean age was 50 years. The medical records contain dosage information in only 2 of the 7 cases. In all cases, the medical records indicated that the botulinum toxin product used was onabotulinum toxin A (Botox; Allergan, Inc., Irvine, CA). No unusual treatment events were noted in the medical records. Patient data are briefly summarized in Table 1. Below are more detailed descriptions summarizing the pertinent data for each case.
TABLE 1. Patient Data Case
Age
Sex
Dose of BTA*
Eyelid
MRD1
RX†
Duration of Ptosis, Months 13
1
49
F
NK
LE
1.0
+
2
57
M
NK
LE
2.0
+
4
3
46
F
40 U
LE
1.5
No
5
4
49
F
NK
RE
22.0
+
3
5 6
60 38
F F
NK 25 U
RE RE
23.0 22.0
+ +
3 5
7
54
F
NK
Both
1.0
+
3
*NK indicates that the dose of botulinum toxin A (BTA) was unknown. †RX: + indicates that the patient was prescribed apraclonidine. RE, right eye; LE, left eye.
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Case Reports Case 1 A 49-year-old woman developed left blepharoptosis 3 days after botulinum toxin type A treatment. She reported that treatment was performed along the eyebrow. Medical records from the treating surgeon did not disclose the total dosage of botulinum toxin type A administered. At her initial examination, her MRD1 was 3.5 mm in the right eye and 1.0 mm in the left eye. The levator function measured 14 mm in the right eye and 11 mm in the left eye. Her external examination was also remarkable for a relatively hollow upper eyelid sulcus bilaterally. She was unresponsive to apraclonidine drops. Her left MDR1 was noted to be 2.0 mm at a 6-week follow-up visit and remained unchanged for 13 months. At that time, she was scheduled for left upper eyelid ptosis surgery. However, when she returned for surgery 6 weeks later, her MRD1 on the left had recovered to 3.5 mm with a levator function of 14 mm. Surgery was canceled. Case 2 A 57-year-old man was treated with botulinum toxin type A by a nurse. He was examined 2 weeks later after developing increasing heaviness of the left upper eyelid. His initial examination demonstrated an MRD1 of 4.0 mm in the right eye and 2.0 mm in the left eye. The levator functions measured 14 mm in the right eye and 11 mm in the left eye. At his 3-month examination, he was found to have no change in the MRD1 or levator measurements but reported mild benefit from prescribed apraclonidine drops. He was seen again 2 months later and reported a gradual improvement of the left eyelid position over the proceeding few weeks, was no longer using the apraclonidine drops, and had MRD1 of 4.0 mm in the right eye and 4.0 mm in the left eye. Levator function was also the same in each eye, measuring 14 mm. Case 3 A 46-year-old woman was treated in the forehead and low on the eyebrow with 40 units of botulinum toxin type A by a surgeon. One week later, she was referred for consultation because of an evolving ptosis of the left upper eyelid. Her initial measurements were MRD1 3.5 mm in the right eye and 2.0 mm in the left
eye, with a levator function of 15 mm in the right eye and 13 mm in the left eye. She was reassessed 1 month after her treatment, and the MRD1 was 3.5 mm in the right eye and 1.5 mm in the left eye, with no change in the levator function. She was seen again 5 months after the treatment and the MDR1 was 3.5 mm in the right eye and 2.0 mm in the left eye. She was seen 4 months later and reported that the left eyelid seemed to have recovered to normal a few weeks after her last visit. At that time, the MRD1 measured 3.5 mm in the right eye and 3.0 mm in the left eye. The levator function measured 15 mm in the right eye and 14 mm in the left eye. Case 4 A 49-year-old woman developed marked ptosis of the right eye 3 days after botulinum toxin type A treatment by her doctor. She was initially seen in an emergency department, and her workup included an unremarkable computed tomography of the brain. She complained that her right eye felt numb but denied diplopia. She was seen in consultation 6 days after her treatment. There was no record of the total dose of botulinum toxin that she received, although she noted it was limited to the glabellar and periocular areas. Her MRD1 was 22.0 mm in the right eye and 4.0 mm in the left eye, with a levator function of 14 mm bilaterally (Figure 1). The patient was prescribed apraclonidine ophthalmic solution, to which she reported a mild benefit for about 45 minutes. She also ordered acetylcholine pills from an Internet merchant. These pills are advertised to help the condition, and she felt this made a difference. At her 1-month follow-up visit, the MRD1 was 2.0 mm in the right eye and 4.0 mm in the
Figure 1. Case 4: A 49-year-old woman who developed marked blepharoptosis of the right upper eyelid 3 days after botulinum toxin type A treatment by her doctor. She was initially seen in an emergency department, and her workup included an unremarkable computed tomography of the brain.
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left eye. She missed her 8-week follow-up visit but reported by telephone that the ptosis on the right side had resolved and she was no longer using the apraclonidine drops or the acetylcholine pills. Case 5 A 60-year-old woman was treated by a cosmetic surgeon with botulinum toxin type A. She did not know the dose, and her treating physician was also unable to provide this information. Three days after the treatment, she developed ptosis of the right upper eyelid and was seen on that day. There was no diplopia. Her MRD1 was 23.0 mm in the right eye and 3.5 mm in the left eye. Levator function measured 12 mm in the right eye and 16 mm in the left eye. A prescription for apraclonidine ophthalmic solution was provided. She did not feel drops made much of a difference. She was reassessed 3 weeks later, and the MDR1 was 0 mm in the right eye and 2.5 mm in the left eye, with levator function of 11 mm in the right eye and 14 mm in the left eye. She was reexamined 2 months after her treatment, and the MRD1 was 1.0 mm in the right eye and 3.0 mm in the left eye, with a levator function of 14 mm bilaterally. She called 1 month later to report that the upper eyelid ptosis had fully resolved. Case 6 A 38-year-old woman was injected with 25 units of botulinum toxin type A in the forehead and low along the eyebrow. Patient reported that she felt a “jet” of cold extending into the right eyelid during the injections along the eyebrow. Two days later, the right eye started to droop. She had been previously treated by this doctor with no problems. She was prescribed apraclonidine ophthalmic drops but did not find them effective. She self-referred for a second opinion and was seen 6 days after her treatment. The MRD1 was 22.0 mm in the right eye and 4.0 mm in the left eye, with a levator function of 14 mm in the right eye and 16 mm in the left eye (Figure 2A). She was reassessed at 4 months. She stopped using the apraclonidine 2 weeks before her visit to “encourage the muscle to work.” She found that for the month before that the apraclonidine seemed to be making a difference. On that visit, the MRD1 was 1 mm in the right eye and 2 mm in the left eye (Figure 2B). Levator function measured 14 mm bilaterally. She was seen again 9 months
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Figure 2. Case 6: (A) A 38-year-old woman 6 days after treatment with 25 units of botulinum toxin type A in the forehead and along the eyebrow. (B) At the 4-month follow-up visit, the position of the right eye has improved and the eyelid position is responsive to apraclonidine. (C) At the 9-month follow-up visit, the MDR1 on each side is 2.5 mm, but her appearance is consistent with a slight residual ptosis on the right.
after her botulinum toxin treatment. Her MRD1 was 2.5 mm in the right eye and 2.5 mm in the left eye, with a levator function of 17 mm (Figure 2C). Subjectively, she felt there was a slight residual ptosis that was bothersome at night. Case 7 A 54-year-old woman was seen in aesthetic consultation but elected to have cosmetic treatment elsewhere that day (Figure 3A). One week after her treatment with an unknown amount of botulinum toxin type A and under eye filler, she returned for consultation. Her botulinum toxin type A treatment was limited to the forehead. Approximately 4 to 5 days later, she developed strain in her eyes and intermittent eyelid spasms. The patient felt that the eyes and forehead were very heavy. She also reported feeling emotionally dysphoric. There was no frontals function. The MDR1 was 1 mm with levator function of 13 mm, bilaterally
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one of the most popular office-based aesthetic services on a scale that is historically unprecedented.8 A large measure of this success is related to the ease of treatment, its effectiveness, and its relative safety, with a low incidence of adverse treatment effects.
Figure 3. Case 7: (A) A 54-year-old woman presented for cosmetic consultation but elected to have botulinum toxin A and filler with another office later on the same day. (B) One week later, she returned after developing bilateral blepharoptosis after her treatment. (C) At her 3-month visit, the blepharoptosis has resolved.
(Figure 3B). She was advised to use artificial tears, and a prescription for apraclonidine ophthalmic solution was provided. However, she found the prescription ineffective. One month later, she was still experiencing ptosis but reported that at 2 months after treatment, the apraclonidine was helping open the eyelids. She was reassessed 3 months after treatment having been off the apraclonidine for 10 days, and her ptosis was noted to be resolved (Figure 3C).
Discussion In 1992, the Carruthers introduced the concept of using the temporary paralytic effects of botulinum toxin type A as a cosmetic treatment for glabellar rhytides.7 The method of improving facial features with botulinum toxin type A has grown in popularity since its introduction. FDA approved the indication of temporarily improving glabellar rhytides, in 2002. The consumer demand for these services has steadily grown. Botulinum toxin type A treatment has become
This case series focuses on unwanted upper eyelid ptosis after aesthetic botulinum toxin type A, which is generally considered among the nonserious adverse events. In the first year after FDA approval for the cosmetic indication for botulinum toxin type A, it is estimated that over 1.1 million cosmetic treatments were performed.9 These cases generated 36 serious and 995 nonserious adverse events. There were no deaths associated with the aesthetic botulinum toxin type A treatment. Serious adverse events included known complications such as flu-like syndromes, allergic reactions, and unwanted degrees of facial paralysis or weakness. One-third of the adverse serious events were related to an exacerbation of a preexisting medical condition at the time of the botulinum toxin type A treatment. Of the nonserious adverse events, 111 of the reports concerned upper eyelid ptosis (11%). Blepharoptosis after the aesthetic use of botulinum toxin type A has been described as the “most feared adverse event that can occur.”10 Although some may argue with this characterization, there can be little disagreement that blepharoptosis caused by cosmetic botulinum toxin type A treatment is an unwelcome event. The literature suggests that the effects of ptosis after aesthetic treatment are relatively short-lived, lasting on the order of 2 to 4 weeks but rarely longer before resolving.2,3,11,12 In contrast to the existing body of literature on this subject, the 7 cases presented here suggest that it is possible for blepharoptosis after cosmetic botulinum toxin type A to last much longer than previously described. Blepharoptosis reported among these cases lasted at least 6 weeks and in 1 case did not fully resolve until a year after treatment. In these cases, initial treatment with the alpha-adrenergic agonist agent, apraclonidine, was ineffective until a few weeks before the ptosis spontaneously resolved. In this series, apraclonidine was prescribed in 6 of the 7 cases. In
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each case, the agent was initially ineffective at significantly improving the eyelid position. Presumably, the alpha-adrenergic agonists are effective only when elevation of the eyelid margin from stimulation of the Mueller muscle is sufficient to make a subjective difference. This may require a certain degree of activity in both the Mueller muscle and the levator palpebra superioris muscle not present in these cases when they were first seen in consultation. The clinical effectiveness of periocular aesthetic botulinum toxin type A is reported to last approximately 3 to 6 months.13 When botulinum toxin is intentionally used to induce protective blepharoptosis, the mean duration of induced ptosis is reported to vary from 6.5 to 9.2 weeks.14–16 Botulinum toxin type A has been used to treat upper eyelid retraction in thyroid-related ophthalmopathy, with effects of a 5-unit treatment lasting up to 3 months.17 In these clinical circumstances, the goal is to intentionally inject botulinum toxin into the levator palpebrae superioris muscle. Overall, patients in this series exhibited a mean duration of symptoms of 20 weeks. A number of the patients in this series exhibited a thin upper eyelid with retraction of the upper eyelid sulcus and migration of the upper eyelid crease consistent with preexisting levator dehiscence. This anatomic alteration might contribute to the susceptibility of the patients in this series. Case 1 had small degree of residual ptosis that did not fully resolve until a full year after developing unilateral ptosis after a forehead botulinum toxin type A treatment. Muscle disuse atrophy and deconditioning in the setting of a levator dehiscence would need to be invoked to account for the duration of upper eyelid ptosis seen in this case. Excluding this one case (Case 1), the mean duration of upper eyelid ptosis in the remaining cases was 15 weeks. This is still longer than the results seen with intentional therapeutic ptosis.18 This longer duration may be due to the efficiency of orbital botulinum toxin distribution when it is accidently injected into the superior orbital foramen. Ramey and Woodward19 found that botulinum toxin inadvertently injected through the supraorbital neurovascular foramen is diffusely distributed in the orbit including as deep as the orbital apex. This wide distribution of botulinum toxin when injected into the foramen may account for the duration of effect
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exceeding even that of therapeutically induced ptosis. If this observation can be reliably reproduced, it suggests that the superior orbital foramen may be a useful approach for administering therapeutic upper eyelid ptosis with botulinum toxin. In each case, ptosis developed from 2 to 7 days after the initial treatment. Additional observation is needed to determine if the speed of onset of this side effect reflects something fundamental regarding the pathway by which the botulinum toxin reached the levator palpebrae superior muscle. Direct injection through the supraorbital foramen, relative dose, or other factors might be associated with a more rapid onset of ptosis. Six of the 7 patients in this series were prescribed the alpha-adrenergic ophthalmic solution, apraclonidine. It is commonly prescribed to improve a mild degree of upper eyelid ptosis after cosmetic botulinum toxin type A treatment. The authors believe that their series suggests another possible role for this agent. In this series, apraclonidine ophthalmic solution was relatively ineffective until approximately 4 to 6 weeks before the resolution of the blepharoptosis. They hypothesize that apraclonidine can be used to stratify patients first presenting with upper eyelid ptosis after cosmetic botulinum toxin type A. Before discussing the likely duration of ptosis after botulinum toxin type A treatment, the authors suggest that patients have a 1-week trial of apraclonidine ophthalmic solution. Those who respond can be counseled that their symptoms are likely to resolve in 4 to 6 weeks. However, those who do not respond should be counseled that their symptoms could persist more than 6 weeks and as long as 3 or 4 months and possibly longer. These conclusions are based on a small, retrospective, uncontrolled case series (Level 4 evidence recommendation), but the authors believe that these guidelines are more conservative than simply advising patients that ptosis is likely to be short-lived and that the apraclonidine drops will treat the ptosis. As this series demonstrates, there are patients for whom unwanted ptosis will persist for 6 or more weeks. They suggest that providing correct clinical information after a treatment complication is of the utmost importance, and this new observation contributes to the management of ptosis after cosmetic periocular botulinum
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toxin treatment. Because of the lingering effects of botulinum toxin type A when blepharoptosis is induced, the authors believe that surgical repair of upper eyelid ptosis that persists after this complication should be approached cautiously recognizing that complete recovery might take place over a 12-month period. Botulinum toxin–related eyebrow ptosis and upper eyelid ptosis both involve an unwanted fall in soft tissue. In the case of eyebrow ptosis, there is a fall in the position of the eyebrow because of paralysis of the frontalis muscle. Upper eyelid ptosis is a fall in the position of the upper eyelid. This is caused by direct injection of the levator palpebrae superioris muscle or diffusion through the septal tissues of the upper eyelid by botulinum toxin. Brow ptosis does not cause upper eyelid ptosis. However, some patients with preexisting upper eyelid ptosis exhibit compensatory elevation of the forehead that may not at first be appreciated by the practitioner until after paralysis of the frontalis muscle by a cosmetic botulinum toxin treatment. Normally, the upper eyelid margin sits 3.5 to 4.5 mm above the center of the cornea. The distance from the upper eyelid margin to the center of the cornea is called the margin to (light) reflex distance 1 or MRD1. A second measure is also performed in the setting of ptosis, which is levator function. This is a measure of upper eyelid excursion from extreme downgaze to extreme upgaze (normal range, 12–16 mm). To control for the effect of brow lift on upper eyelid excursion, the examiner holds the eyebrow to a fixed position with the thumb when measuring upper eyelid levator function. Pan forehead botulinum toxin treatment is associated with eyebrow ptosis.20 Unwanted diffusion can be seen with glabellar treatment causing central eyebrow ptosis and occasionally lateral brow elevation from muscle recruitment.21,22 True upper eyelid ptosis after botulinum toxin treatment occurs when the botulinum toxin affects the levator palpebrae superioris muscle. In the case of therapeutic ptosis, botulinum toxin is directly injected into the upper eyelid with the goal of weakening the levator palpebrae superioris muscle.14,15 Upper eyelid ptosis after cosmetic botulinum toxin is unintended. Some authors believe the risk of
upper eyelid ptosis is increased when botulinum is injected in or below the eyebrow, especially at the midpupillary line, in the direction of the medial canthal tendon from the nasal bridge or injected with forceful preperiosteal injections along the superior arcus marginalis.20 Ramey and Woodward found anatomic evidence using a cadaveric model with injectable dye that deep injection through the body of the corrugator to the periosteum had the potential to track into the orbit. Alternatively, they found that deep injection through the body of the corrugator in the vicinity of the supraorbital foramen was associated with extensive dye staining of the superior orbit including the levator palpebrae superioris muscle. These authors suggest that superficial injections using small volumes would avoid these identified risks. This conclusion is supported by the microdroplet method described by Steinsapir and colleagues wherein the brow depressors are directly treated across the eyebrow using many small-volume injections of botulinum toxin solution placed at the junction of the dermis and the insertion the orbicularis oculi muscle at the eyebrow and in the glabella at the level of the dermis and glabellar musculature.23,24 The incidence of ptosis in their series was 0.2%. Huang and colleagues have also used a similar approach with an acceptable rate of upper eyelid ptosis.21 Upper eyelid ptosis is associated with injecting cosmetic botulinum toxin type A low and deep along the eyebrow, and this maneuver should be avoided particularly in individuals with a thin eyelid and associated hollow upper eyelid sulcus.
References 1. American Society of Plastic Surgeons. 2013 cosmetic plastic surgery statistics. Available at: http://www.plasticsurgery.org/Documents/newsresources/statistics/2013-statistics/cosmetic-procedures-national-trends2013.pdf. Accessed August 9, 2014. 2. Cavallini M, Cirillo P, Fundaro SP, Quartucci S, et al. Safety of botulinum toxin A in aesthetic treatments: a systematic review of clinical studies. Derm Surg 2014;40:525–36. 3. Ferreira MC, Salles AG, Gimenez R, Soares MFD. Complications with the use of botulinum toxin type A in facial rejuvenation: report of 8 cases. Aesth Plast Surg 2004;28:441–4. 4. Scheinfeld N. The use of apraclonidine eyedrops to treat ptosis after the administration of botulinum toxin to the upper face. Dermatol Online J 2005;11:9–14. Available at: http://escholarship.org/uc/item/ 06g8w0mc. Accessed August 10, 2014. 5. Karami M, Taheri A, Mansoori P. Treatment of botulinum toxininduced eyelid ptosis with anticholinesterases. Dermatol Surg 2007;33: 1392–4.
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6. Majlesi G. GaAs laser treatment of bilateral eyelid ptosis due to complication of botulinum toxin type A injection. Photomed Laser Surg 2008;26:507–9.
17. Ellis MF, Daniell M. An evaluation of the safety and efficacy of botulinum toxin type A (BOTOX) when used to produce a protective ptosis. Clin Exp Ophthalmol 2001;29:394–9.
7. Chalk CH, Benstead TJ, Keezer M. Medical treatment for botulism. Cochrane Database Syst Rev 2014;2:CD008123.
18. Costa PG, Saraiva FP, Pereira IC, Monteiro ML, et al. Comparative study of Botox injection treatment for upper eyelid retraction with 6month follow-up in patients with thyroid eye disease in the congestive or fibrotic stage. Eye (Lond) 2009;23:767–73.
8. Carruthers JD, Carruthers JA. Treatment of glabellar frown lines with C. botulinum-A exotoxin. J Dermatol Surg Oncol 1992;18:17–21. 9. Carruthers J, Carruthers A. The evolution of botulinum neurotoxin type A for cosmetic applications. J Cosmet Laser Ther 2007;9: 186–92. 10. Cote TR, Mohan AK, Polder JA, Walton MK, et al. Botulinum toxin type A injection: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases. J Am Acad Dermatol 2005;53:407–15. 11. Fagien S. Temporary management of upper lid ptosis, lid malposition, and eyelid fissure asymmetry with botulinum toxin type A. Plast Reconstr Surg 2004;114:1892–902. 12. Niamtu J. Botulinum Toxin A: a review of 1,085 oral and maxillofacial patient treatments. J Oral Maxillofac Surg 2003;61:317–24. 13. Klein AW. Complications and adverse reactions with the use of botulinum toxin. Dis Mon 2002;48:336–56. 14. Carruthers J, Fagien S, Matarasso L, and the Botox Consensus Group. Consensus recommendations on the use of botulinum toxin type A in facial aesthetics. Plast Reconstr Surg 2004:114(Suppl):1S–22S. 15. Naik MN, Gangopadhyay N, Fernandes M, Murthy R, et al. Anterior chemodenervation of levator palpebrae superioris with botulinum toxin type-A (BotoxÒ) to induce temporary ptosis for corneal protection. Eye (Lond) 2008;22:1132–6. 16. Adams GG, Kirkness CM, Lee JP. Botulinum toxin A induced protective ptosis. Eye (Lond) 1987;1:603–8.
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19. Ramey NA, Woodward JA. Mechanisms of blepharoptosis following cosmetic glabellar chemodenervation. Plast Reconstr Surg 2010;126: 248e–9e. 20. Alam M, Dover JS, Klein AW. Botulinum A exotoxin for hyperfunctional facial lines: where not to inject. Arch Dermatol 2002; 138:1180–5. 21. Huang L, Costin BR, Sakolsataydorn N, Perry JD. Safety of onabotulinum toxin A injection to the central upper eyelid and eyebrow regions. Ophthal Plast Reconstr Surg 2014;30:377–80. 22. Kang SM, Feneran A, Kim JK, Park O, et al. Exaggeration of wrinkles after botulinum toxin injection for forehead horizontal lines. Ann Dermatol 2011;23:217–21. 23. Steinsapir KD, Rootman D, Wulc A, Hwang C. Cosmetic microdroplet botulinum toxin A forehead lift: a new treatment paradigm. Ophthal Plast Reconstr Surg 2014. [Epub ahead of print]. DOI: 10.1097/IOP. 0000000000000282. 24. Steinsapir KD. Cosmetic use of botulinum toxin for the treatment of eyebrow and forehead ptosis, and unwanted eyebrow expression. US patent 7,846,457 B2. 2010 Dec 7.
Address correspondence and reprint requests to: Kenneth D. Steinsapir, MD, 9001 Wilshire Blvd, Suite 305, Beverly Hills, CA 90211, or e-mail: [email protected]
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BACKGROUND Upper eyelid ptosis after cosmetic botulinum toxin is generally considered short-lived and responsive to apraclonidine ophthalmic drops. The authors present a series with persistent ptosis. OBJECTIVE
To report a series of patients with persistent upper eyelid ptosis after cosmetic botulinum toxin.
MATERIALS AND METHODS A retrospective case review series of 7 patients referred for management after developing visually significant upper eyelid ptosis after cosmetic botulinum toxin type A treatment. RESULTS Patients in this series experienced persistent visually significant ptosis after cosmetic botulinum toxin lasting from 6 weeks to 13 months. Six of the 7 patients were treated with apraclonidine ophthalmic solution. Apraclonidine drops appeared to be clinically effective within 4 to 6 weeks of the resolution of ptosis. CONCLUSION Upper eyelid ptosis after cosmetic botulinum toxin can persist for many months after treatment. Based on this series, the authors propose that apraclonidine drops can be used at the time of initial assessment to predict the relative longevity of ptosis after cosmetic botulinum toxin treatment (Level 4 evidence recommendation). After a 1-week trial, responders can be advised that ptosis is likely to resolve in 4 to 6 weeks. Nonresponders should be counseled that resolution may take longer than 6 weeks. The authors have indicated no significant interest with commercial supporters.
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osmetic applications of botulinum toxin type A have become one of the most common physicianperformed aesthetic services in the United States and the World. One source has estimated that over 6 million aesthetic botulinum toxin type A treatments were performed in the United States in 2013.1 Among the reasons accounting for the popularity of treatment are the relative ease with which the service can be provided and a very low incidence of complications. When complications do occur, they include brow ptosis, upper eyelid ptosis, diplopia, dry eye, unwanted weakness of the lip elevators, and orbicularis oris incompetence. The true incidence of upper eyelid ptosis is unknown but appears to be less than 5% of periocular treatments. Published reports of this complication imply that the induced blepharoptosis is relatively
short-lived.2 A variety of treatments have been proposed to address blepharoptosis after cosmetic botulinum toxin type A, including alpha-adrenergic agonists,3,4 anticholinesterases,5 and physical treatment including massage, electrostimulation,3 and laser irradiation.6 Apraclonidine is the predominantly prescribed alpha adrenergic and is used on a twice-a-day basis. Naphazoline is a sympathomimetic with strong alpha-adrenergic effects that is found in a number of ophthalmic decongestant products. With the exception of alphaadrenergic agonists, which stimulate the sympathetically innervated Mueller muscle of the upper eyelid to help open the eyelid, there is no evidence that any of these other methods are of any clinical benefit.7 The authors have treated a series of patients referred for management of upper eyelid ptosis after cosmetic botulinum toxin type A. These patients share in
*All the authors are affiliated with the Division of Ophthalmic Plastic and Reconstructive Surgery, Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California © 2015 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1076-0512 Dermatol Surg 2015;41:833–840 DOI: 10.1097/DSS.0000000000000386
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common profound upper eyelid ptosis that lasted 6 or more weeks. In 1 case, complete resolution did not occur for 13 months. It is the intent of this case series report to make physicians and surgeons aware that upper eyelid ptosis after cosmetic botulinum toxin treatment can persist, so that patients presenting with this complication receive accurate information regarding their possible time course for recovery. Discussion is also provided regarding steps that may minimize the risk of this rare but foreseeable complication.
Materials and Methods This study is a retrospective case series reporting the histories of patients seeking treatment at the respective private practices of the authors. As such, the study was conducted at sites without a formal institutional review board. The authors have complied with the principles of the Declaration of Helsinki and the privacy standards described by the Health Insurance Portability and Accountability Act (HIPAA). Cases were collected from December 2005 through December 2013. To be included in the study, patients needed to report a recent aesthetic botulinum toxin type A treatment preceding the sudden onset of upper eyelid ptosis. Cases of brow ptosis in the absence of actual blepharoptosis were excluded. The authors personally examined and followed each patient until the upper eyelid ptosis resolved. The distance from the central corneal light reflex to the
upper eyelid margin (MRD1) was measured, and only patients with an MRD1 of 2 mm or less (normal 4.0 mm) were included in this study. In cases with brow ptosis, the brow was lifted and supported at the superior orbital rim before measuring the upper eyelid margin to central light reflex distance (MRD1). Levator function with brow fixation was also recorded. There was no standard treatment protocol, and the patients were managed according to the clinical judgment of the respective authors. Patients were questioned regarding their history of botulinum toxin type A treatment and knowledge of their treatment dose. Patients were questioned to determine if they had any insight regarding the treatment that resulted in upper eyelid ptosis and how it might have differed from past treatments. The medical records of the original treating physicians were also requested and reviewed.
Results Seven patients were identified who met the criteria: 6 women and 1 man. The age range was 38 to 60 years, and the mean age was 50 years. The medical records contain dosage information in only 2 of the 7 cases. In all cases, the medical records indicated that the botulinum toxin product used was onabotulinum toxin A (Botox; Allergan, Inc., Irvine, CA). No unusual treatment events were noted in the medical records. Patient data are briefly summarized in Table 1. Below are more detailed descriptions summarizing the pertinent data for each case.
TABLE 1. Patient Data Case
Age
Sex
Dose of BTA*
Eyelid
MRD1
RX†
Duration of Ptosis, Months 13
1
49
F
NK
LE
1.0
+
2
57
M
NK
LE
2.0
+
4
3
46
F
40 U
LE
1.5
No
5
4
49
F
NK
RE
22.0
+
3
5 6
60 38
F F
NK 25 U
RE RE
23.0 22.0
+ +
3 5
7
54
F
NK
Both
1.0
+
3
*NK indicates that the dose of botulinum toxin A (BTA) was unknown. †RX: + indicates that the patient was prescribed apraclonidine. RE, right eye; LE, left eye.
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Case Reports Case 1 A 49-year-old woman developed left blepharoptosis 3 days after botulinum toxin type A treatment. She reported that treatment was performed along the eyebrow. Medical records from the treating surgeon did not disclose the total dosage of botulinum toxin type A administered. At her initial examination, her MRD1 was 3.5 mm in the right eye and 1.0 mm in the left eye. The levator function measured 14 mm in the right eye and 11 mm in the left eye. Her external examination was also remarkable for a relatively hollow upper eyelid sulcus bilaterally. She was unresponsive to apraclonidine drops. Her left MDR1 was noted to be 2.0 mm at a 6-week follow-up visit and remained unchanged for 13 months. At that time, she was scheduled for left upper eyelid ptosis surgery. However, when she returned for surgery 6 weeks later, her MRD1 on the left had recovered to 3.5 mm with a levator function of 14 mm. Surgery was canceled. Case 2 A 57-year-old man was treated with botulinum toxin type A by a nurse. He was examined 2 weeks later after developing increasing heaviness of the left upper eyelid. His initial examination demonstrated an MRD1 of 4.0 mm in the right eye and 2.0 mm in the left eye. The levator functions measured 14 mm in the right eye and 11 mm in the left eye. At his 3-month examination, he was found to have no change in the MRD1 or levator measurements but reported mild benefit from prescribed apraclonidine drops. He was seen again 2 months later and reported a gradual improvement of the left eyelid position over the proceeding few weeks, was no longer using the apraclonidine drops, and had MRD1 of 4.0 mm in the right eye and 4.0 mm in the left eye. Levator function was also the same in each eye, measuring 14 mm. Case 3 A 46-year-old woman was treated in the forehead and low on the eyebrow with 40 units of botulinum toxin type A by a surgeon. One week later, she was referred for consultation because of an evolving ptosis of the left upper eyelid. Her initial measurements were MRD1 3.5 mm in the right eye and 2.0 mm in the left
eye, with a levator function of 15 mm in the right eye and 13 mm in the left eye. She was reassessed 1 month after her treatment, and the MRD1 was 3.5 mm in the right eye and 1.5 mm in the left eye, with no change in the levator function. She was seen again 5 months after the treatment and the MDR1 was 3.5 mm in the right eye and 2.0 mm in the left eye. She was seen 4 months later and reported that the left eyelid seemed to have recovered to normal a few weeks after her last visit. At that time, the MRD1 measured 3.5 mm in the right eye and 3.0 mm in the left eye. The levator function measured 15 mm in the right eye and 14 mm in the left eye. Case 4 A 49-year-old woman developed marked ptosis of the right eye 3 days after botulinum toxin type A treatment by her doctor. She was initially seen in an emergency department, and her workup included an unremarkable computed tomography of the brain. She complained that her right eye felt numb but denied diplopia. She was seen in consultation 6 days after her treatment. There was no record of the total dose of botulinum toxin that she received, although she noted it was limited to the glabellar and periocular areas. Her MRD1 was 22.0 mm in the right eye and 4.0 mm in the left eye, with a levator function of 14 mm bilaterally (Figure 1). The patient was prescribed apraclonidine ophthalmic solution, to which she reported a mild benefit for about 45 minutes. She also ordered acetylcholine pills from an Internet merchant. These pills are advertised to help the condition, and she felt this made a difference. At her 1-month follow-up visit, the MRD1 was 2.0 mm in the right eye and 4.0 mm in the
Figure 1. Case 4: A 49-year-old woman who developed marked blepharoptosis of the right upper eyelid 3 days after botulinum toxin type A treatment by her doctor. She was initially seen in an emergency department, and her workup included an unremarkable computed tomography of the brain.
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left eye. She missed her 8-week follow-up visit but reported by telephone that the ptosis on the right side had resolved and she was no longer using the apraclonidine drops or the acetylcholine pills. Case 5 A 60-year-old woman was treated by a cosmetic surgeon with botulinum toxin type A. She did not know the dose, and her treating physician was also unable to provide this information. Three days after the treatment, she developed ptosis of the right upper eyelid and was seen on that day. There was no diplopia. Her MRD1 was 23.0 mm in the right eye and 3.5 mm in the left eye. Levator function measured 12 mm in the right eye and 16 mm in the left eye. A prescription for apraclonidine ophthalmic solution was provided. She did not feel drops made much of a difference. She was reassessed 3 weeks later, and the MDR1 was 0 mm in the right eye and 2.5 mm in the left eye, with levator function of 11 mm in the right eye and 14 mm in the left eye. She was reexamined 2 months after her treatment, and the MRD1 was 1.0 mm in the right eye and 3.0 mm in the left eye, with a levator function of 14 mm bilaterally. She called 1 month later to report that the upper eyelid ptosis had fully resolved. Case 6 A 38-year-old woman was injected with 25 units of botulinum toxin type A in the forehead and low along the eyebrow. Patient reported that she felt a “jet” of cold extending into the right eyelid during the injections along the eyebrow. Two days later, the right eye started to droop. She had been previously treated by this doctor with no problems. She was prescribed apraclonidine ophthalmic drops but did not find them effective. She self-referred for a second opinion and was seen 6 days after her treatment. The MRD1 was 22.0 mm in the right eye and 4.0 mm in the left eye, with a levator function of 14 mm in the right eye and 16 mm in the left eye (Figure 2A). She was reassessed at 4 months. She stopped using the apraclonidine 2 weeks before her visit to “encourage the muscle to work.” She found that for the month before that the apraclonidine seemed to be making a difference. On that visit, the MRD1 was 1 mm in the right eye and 2 mm in the left eye (Figure 2B). Levator function measured 14 mm bilaterally. She was seen again 9 months
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Figure 2. Case 6: (A) A 38-year-old woman 6 days after treatment with 25 units of botulinum toxin type A in the forehead and along the eyebrow. (B) At the 4-month follow-up visit, the position of the right eye has improved and the eyelid position is responsive to apraclonidine. (C) At the 9-month follow-up visit, the MDR1 on each side is 2.5 mm, but her appearance is consistent with a slight residual ptosis on the right.
after her botulinum toxin treatment. Her MRD1 was 2.5 mm in the right eye and 2.5 mm in the left eye, with a levator function of 17 mm (Figure 2C). Subjectively, she felt there was a slight residual ptosis that was bothersome at night. Case 7 A 54-year-old woman was seen in aesthetic consultation but elected to have cosmetic treatment elsewhere that day (Figure 3A). One week after her treatment with an unknown amount of botulinum toxin type A and under eye filler, she returned for consultation. Her botulinum toxin type A treatment was limited to the forehead. Approximately 4 to 5 days later, she developed strain in her eyes and intermittent eyelid spasms. The patient felt that the eyes and forehead were very heavy. She also reported feeling emotionally dysphoric. There was no frontals function. The MDR1 was 1 mm with levator function of 13 mm, bilaterally
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one of the most popular office-based aesthetic services on a scale that is historically unprecedented.8 A large measure of this success is related to the ease of treatment, its effectiveness, and its relative safety, with a low incidence of adverse treatment effects.
Figure 3. Case 7: (A) A 54-year-old woman presented for cosmetic consultation but elected to have botulinum toxin A and filler with another office later on the same day. (B) One week later, she returned after developing bilateral blepharoptosis after her treatment. (C) At her 3-month visit, the blepharoptosis has resolved.
(Figure 3B). She was advised to use artificial tears, and a prescription for apraclonidine ophthalmic solution was provided. However, she found the prescription ineffective. One month later, she was still experiencing ptosis but reported that at 2 months after treatment, the apraclonidine was helping open the eyelids. She was reassessed 3 months after treatment having been off the apraclonidine for 10 days, and her ptosis was noted to be resolved (Figure 3C).
Discussion In 1992, the Carruthers introduced the concept of using the temporary paralytic effects of botulinum toxin type A as a cosmetic treatment for glabellar rhytides.7 The method of improving facial features with botulinum toxin type A has grown in popularity since its introduction. FDA approved the indication of temporarily improving glabellar rhytides, in 2002. The consumer demand for these services has steadily grown. Botulinum toxin type A treatment has become
This case series focuses on unwanted upper eyelid ptosis after aesthetic botulinum toxin type A, which is generally considered among the nonserious adverse events. In the first year after FDA approval for the cosmetic indication for botulinum toxin type A, it is estimated that over 1.1 million cosmetic treatments were performed.9 These cases generated 36 serious and 995 nonserious adverse events. There were no deaths associated with the aesthetic botulinum toxin type A treatment. Serious adverse events included known complications such as flu-like syndromes, allergic reactions, and unwanted degrees of facial paralysis or weakness. One-third of the adverse serious events were related to an exacerbation of a preexisting medical condition at the time of the botulinum toxin type A treatment. Of the nonserious adverse events, 111 of the reports concerned upper eyelid ptosis (11%). Blepharoptosis after the aesthetic use of botulinum toxin type A has been described as the “most feared adverse event that can occur.”10 Although some may argue with this characterization, there can be little disagreement that blepharoptosis caused by cosmetic botulinum toxin type A treatment is an unwelcome event. The literature suggests that the effects of ptosis after aesthetic treatment are relatively short-lived, lasting on the order of 2 to 4 weeks but rarely longer before resolving.2,3,11,12 In contrast to the existing body of literature on this subject, the 7 cases presented here suggest that it is possible for blepharoptosis after cosmetic botulinum toxin type A to last much longer than previously described. Blepharoptosis reported among these cases lasted at least 6 weeks and in 1 case did not fully resolve until a year after treatment. In these cases, initial treatment with the alpha-adrenergic agonist agent, apraclonidine, was ineffective until a few weeks before the ptosis spontaneously resolved. In this series, apraclonidine was prescribed in 6 of the 7 cases. In
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each case, the agent was initially ineffective at significantly improving the eyelid position. Presumably, the alpha-adrenergic agonists are effective only when elevation of the eyelid margin from stimulation of the Mueller muscle is sufficient to make a subjective difference. This may require a certain degree of activity in both the Mueller muscle and the levator palpebra superioris muscle not present in these cases when they were first seen in consultation. The clinical effectiveness of periocular aesthetic botulinum toxin type A is reported to last approximately 3 to 6 months.13 When botulinum toxin is intentionally used to induce protective blepharoptosis, the mean duration of induced ptosis is reported to vary from 6.5 to 9.2 weeks.14–16 Botulinum toxin type A has been used to treat upper eyelid retraction in thyroid-related ophthalmopathy, with effects of a 5-unit treatment lasting up to 3 months.17 In these clinical circumstances, the goal is to intentionally inject botulinum toxin into the levator palpebrae superioris muscle. Overall, patients in this series exhibited a mean duration of symptoms of 20 weeks. A number of the patients in this series exhibited a thin upper eyelid with retraction of the upper eyelid sulcus and migration of the upper eyelid crease consistent with preexisting levator dehiscence. This anatomic alteration might contribute to the susceptibility of the patients in this series. Case 1 had small degree of residual ptosis that did not fully resolve until a full year after developing unilateral ptosis after a forehead botulinum toxin type A treatment. Muscle disuse atrophy and deconditioning in the setting of a levator dehiscence would need to be invoked to account for the duration of upper eyelid ptosis seen in this case. Excluding this one case (Case 1), the mean duration of upper eyelid ptosis in the remaining cases was 15 weeks. This is still longer than the results seen with intentional therapeutic ptosis.18 This longer duration may be due to the efficiency of orbital botulinum toxin distribution when it is accidently injected into the superior orbital foramen. Ramey and Woodward19 found that botulinum toxin inadvertently injected through the supraorbital neurovascular foramen is diffusely distributed in the orbit including as deep as the orbital apex. This wide distribution of botulinum toxin when injected into the foramen may account for the duration of effect
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exceeding even that of therapeutically induced ptosis. If this observation can be reliably reproduced, it suggests that the superior orbital foramen may be a useful approach for administering therapeutic upper eyelid ptosis with botulinum toxin. In each case, ptosis developed from 2 to 7 days after the initial treatment. Additional observation is needed to determine if the speed of onset of this side effect reflects something fundamental regarding the pathway by which the botulinum toxin reached the levator palpebrae superior muscle. Direct injection through the supraorbital foramen, relative dose, or other factors might be associated with a more rapid onset of ptosis. Six of the 7 patients in this series were prescribed the alpha-adrenergic ophthalmic solution, apraclonidine. It is commonly prescribed to improve a mild degree of upper eyelid ptosis after cosmetic botulinum toxin type A treatment. The authors believe that their series suggests another possible role for this agent. In this series, apraclonidine ophthalmic solution was relatively ineffective until approximately 4 to 6 weeks before the resolution of the blepharoptosis. They hypothesize that apraclonidine can be used to stratify patients first presenting with upper eyelid ptosis after cosmetic botulinum toxin type A. Before discussing the likely duration of ptosis after botulinum toxin type A treatment, the authors suggest that patients have a 1-week trial of apraclonidine ophthalmic solution. Those who respond can be counseled that their symptoms are likely to resolve in 4 to 6 weeks. However, those who do not respond should be counseled that their symptoms could persist more than 6 weeks and as long as 3 or 4 months and possibly longer. These conclusions are based on a small, retrospective, uncontrolled case series (Level 4 evidence recommendation), but the authors believe that these guidelines are more conservative than simply advising patients that ptosis is likely to be short-lived and that the apraclonidine drops will treat the ptosis. As this series demonstrates, there are patients for whom unwanted ptosis will persist for 6 or more weeks. They suggest that providing correct clinical information after a treatment complication is of the utmost importance, and this new observation contributes to the management of ptosis after cosmetic periocular botulinum
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toxin treatment. Because of the lingering effects of botulinum toxin type A when blepharoptosis is induced, the authors believe that surgical repair of upper eyelid ptosis that persists after this complication should be approached cautiously recognizing that complete recovery might take place over a 12-month period. Botulinum toxin–related eyebrow ptosis and upper eyelid ptosis both involve an unwanted fall in soft tissue. In the case of eyebrow ptosis, there is a fall in the position of the eyebrow because of paralysis of the frontalis muscle. Upper eyelid ptosis is a fall in the position of the upper eyelid. This is caused by direct injection of the levator palpebrae superioris muscle or diffusion through the septal tissues of the upper eyelid by botulinum toxin. Brow ptosis does not cause upper eyelid ptosis. However, some patients with preexisting upper eyelid ptosis exhibit compensatory elevation of the forehead that may not at first be appreciated by the practitioner until after paralysis of the frontalis muscle by a cosmetic botulinum toxin treatment. Normally, the upper eyelid margin sits 3.5 to 4.5 mm above the center of the cornea. The distance from the upper eyelid margin to the center of the cornea is called the margin to (light) reflex distance 1 or MRD1. A second measure is also performed in the setting of ptosis, which is levator function. This is a measure of upper eyelid excursion from extreme downgaze to extreme upgaze (normal range, 12–16 mm). To control for the effect of brow lift on upper eyelid excursion, the examiner holds the eyebrow to a fixed position with the thumb when measuring upper eyelid levator function. Pan forehead botulinum toxin treatment is associated with eyebrow ptosis.20 Unwanted diffusion can be seen with glabellar treatment causing central eyebrow ptosis and occasionally lateral brow elevation from muscle recruitment.21,22 True upper eyelid ptosis after botulinum toxin treatment occurs when the botulinum toxin affects the levator palpebrae superioris muscle. In the case of therapeutic ptosis, botulinum toxin is directly injected into the upper eyelid with the goal of weakening the levator palpebrae superioris muscle.14,15 Upper eyelid ptosis after cosmetic botulinum toxin is unintended. Some authors believe the risk of
upper eyelid ptosis is increased when botulinum is injected in or below the eyebrow, especially at the midpupillary line, in the direction of the medial canthal tendon from the nasal bridge or injected with forceful preperiosteal injections along the superior arcus marginalis.20 Ramey and Woodward found anatomic evidence using a cadaveric model with injectable dye that deep injection through the body of the corrugator to the periosteum had the potential to track into the orbit. Alternatively, they found that deep injection through the body of the corrugator in the vicinity of the supraorbital foramen was associated with extensive dye staining of the superior orbit including the levator palpebrae superioris muscle. These authors suggest that superficial injections using small volumes would avoid these identified risks. This conclusion is supported by the microdroplet method described by Steinsapir and colleagues wherein the brow depressors are directly treated across the eyebrow using many small-volume injections of botulinum toxin solution placed at the junction of the dermis and the insertion the orbicularis oculi muscle at the eyebrow and in the glabella at the level of the dermis and glabellar musculature.23,24 The incidence of ptosis in their series was 0.2%. Huang and colleagues have also used a similar approach with an acceptable rate of upper eyelid ptosis.21 Upper eyelid ptosis is associated with injecting cosmetic botulinum toxin type A low and deep along the eyebrow, and this maneuver should be avoided particularly in individuals with a thin eyelid and associated hollow upper eyelid sulcus.
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6. Majlesi G. GaAs laser treatment of bilateral eyelid ptosis due to complication of botulinum toxin type A injection. Photomed Laser Surg 2008;26:507–9.
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8. Carruthers JD, Carruthers JA. Treatment of glabellar frown lines with C. botulinum-A exotoxin. J Dermatol Surg Oncol 1992;18:17–21. 9. Carruthers J, Carruthers A. The evolution of botulinum neurotoxin type A for cosmetic applications. J Cosmet Laser Ther 2007;9: 186–92. 10. Cote TR, Mohan AK, Polder JA, Walton MK, et al. Botulinum toxin type A injection: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases. J Am Acad Dermatol 2005;53:407–15. 11. Fagien S. Temporary management of upper lid ptosis, lid malposition, and eyelid fissure asymmetry with botulinum toxin type A. Plast Reconstr Surg 2004;114:1892–902. 12. Niamtu J. Botulinum Toxin A: a review of 1,085 oral and maxillofacial patient treatments. J Oral Maxillofac Surg 2003;61:317–24. 13. Klein AW. Complications and adverse reactions with the use of botulinum toxin. Dis Mon 2002;48:336–56. 14. Carruthers J, Fagien S, Matarasso L, and the Botox Consensus Group. Consensus recommendations on the use of botulinum toxin type A in facial aesthetics. Plast Reconstr Surg 2004:114(Suppl):1S–22S. 15. Naik MN, Gangopadhyay N, Fernandes M, Murthy R, et al. Anterior chemodenervation of levator palpebrae superioris with botulinum toxin type-A (BotoxÒ) to induce temporary ptosis for corneal protection. Eye (Lond) 2008;22:1132–6. 16. Adams GG, Kirkness CM, Lee JP. Botulinum toxin A induced protective ptosis. Eye (Lond) 1987;1:603–8.
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19. Ramey NA, Woodward JA. Mechanisms of blepharoptosis following cosmetic glabellar chemodenervation. Plast Reconstr Surg 2010;126: 248e–9e. 20. Alam M, Dover JS, Klein AW. Botulinum A exotoxin for hyperfunctional facial lines: where not to inject. Arch Dermatol 2002; 138:1180–5. 21. Huang L, Costin BR, Sakolsataydorn N, Perry JD. Safety of onabotulinum toxin A injection to the central upper eyelid and eyebrow regions. Ophthal Plast Reconstr Surg 2014;30:377–80. 22. Kang SM, Feneran A, Kim JK, Park O, et al. Exaggeration of wrinkles after botulinum toxin injection for forehead horizontal lines. Ann Dermatol 2011;23:217–21. 23. Steinsapir KD, Rootman D, Wulc A, Hwang C. Cosmetic microdroplet botulinum toxin A forehead lift: a new treatment paradigm. Ophthal Plast Reconstr Surg 2014. [Epub ahead of print]. DOI: 10.1097/IOP. 0000000000000282. 24. Steinsapir KD. Cosmetic use of botulinum toxin for the treatment of eyebrow and forehead ptosis, and unwanted eyebrow expression. US patent 7,846,457 B2. 2010 Dec 7.
Address correspondence and reprint requests to: Kenneth D. Steinsapir, MD, 9001 Wilshire Blvd, Suite 305, Beverly Hills, CA 90211, or e-mail: [email protected]
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