Treatment of facial spasm with botulinum toxin. An interim report

Forty-eight patients were given serial injections of botulinum toxin in their eyelids for treatment of eyelid spasm during a two-year interval. Ninety-four percent obtained relief of spasm from botulinum toxin injection. The duration of the spasm-free interval as well as the incidence of ptosis and of diplopia was dose dependent. The marked increase in the incidence of these side effects with only a small increase in the duration of the spasm-free interval, when a dose of 25 units per lid was used, leads the authors to conclude that this dose is too high and should not be used. Since diplopia was most commonly caused by paresis of the inferior oblique muscle, and since blepharospasm usually can be controlled by excising the upper lid protractors, further studies are required to determine whether lower lid injection is necessary and, if it is found to be so, whether injecting only the lateral portion of the lid would be adequate.     

Treatment of blepharospasm and facial hemispasm by injection of botulinum toxin

13 patients with hemifacial spasm and 19 patients with blepharospasm (essential blepharospasm or Meige syndrome) were treated with injection of botulinum A toxin in the eyelids. The effectiveness of this therapy is constant and the treatment offers relief to almost all patients. The response times for repeated treatment was 6 months for blepharospasm and 7 months for hemifacial spasm. Repeated injections were performed in several patients and gave the same improvement. Transient ptosis or diplopia were observed in 11 patients. Possible systemic side effects (respiratory trouble) were documented in two patients. Botulinum toxin injection is an effective treatment but the relief is usually temporary and repeated treatments are necessary.     

Anesthesia with EMLA cream for botulinum A toxin injection into eyelids

We investigated the efficacy of an eutectic mixture of local anesthetics (EMLA) in reducing the pain of a botulinum toxin injection into eyelids. 17 patients with facial dyskinesia (9 blepharospasm and 8 hemifacial spasm) who had been treated regularly with botulinum toxin injections received EMLA cream and placebo. The pain was assessed by the ophthalmologist and the patient. Injection with EMLA cream showed lower pain scores (mean 1.82 +/- 2.13, median 1) than injection with placebo (8.76 +/- 2.17; p = 0.0001). Percutaneous anesthesia induced by EMLA cream is an effective and safe method which improves the comfort in patients who need repeated botulinum toxin injections for their facial dyskinesia.     

Botulinum toxin type a for dysthyroid upper eyelid retraction

PURPOSE: To evaluate the safety and efficacy of botulinum toxin type A for treatment of eyelid retraction resulting from thyroid eye disease (TED) during the inflammatory phase of the condition. METHODS: In this prospective, nonrandomized case series, 18 patients with inflammatory eyelid retraction caused by active TED received botulinum toxin type A injection (10, 5, or 2.5 U) for treatment of upper eyelid retraction. Botulinum toxin type A (Allergan, Irvine, CA, U.S.A.) was injected transconjunctivally just above the superior tarsal border in the elevator complex of the upper eyelid. RESULTS: Seventeen of 18 patients (94%) demonstrated a reduced marginal reflex distance (MRD1) after botulinum toxin injection. The average change in MRD1 of the treated eyelid after injection was -2.35 mm (range, 0 to -8.0 mm). Of the 27 eyelids injected, 33% had a 0- to 1-mm drop in eyelid height, 30% had a 1.5- to 2-mm decrease, 22% had a 2.5- to 3-mm decrease, and 15% had a greater than 3-mm decrease in eyelid height. None of the treated eyelids were noted to increase in height. One patient showed no alteration inafter treatment. One patient had clinically MRD1 significant ptosis and one patient reported worsening of preexisting diplopia after injection. Three patients undergoing unilateral injection had relative contralateral eyelid elevation. All untoward effects resolved spontaneously without sequelae. CONCLUSIONS:: Botulinum toxin type A may be used in the inflammatory stage of thyroid eye disease to improve upper eyelid retraction. Individual response to treatment is variable, but this modality should be considered as a temporizing measure until stability for surgery is reached.     

Effect of eyelid botulinum toxin injection on lacrimal drainage

PURPOSE: To determine the effect of eyelid botulinum toxin injection on the lacrimal drainage and to assess the use of botulinum toxin in dry eye conditions. METHODS: Prospectively, three test groups were examined and one lacrimal system investigated in each person in each group. Botulinum toxin A (3.75 IU) was injected into the medial part of 13 lower eyelids of 13 normal test subjects and the medial part of nine lower eyelids in nine patients with dry eyes. A dose of 2.5 IU was injected into the medial part of 10 lower eyelids and the medial part of 10 upper eyelids of 10 patients with dry eyes. The drop test was used to determine the lacrimal drainage capacity and the blink output, before and after the injection. The subjective effect of the botulinum toxin injection on eye comfort was investigated. RESULTS: Three weeks after lower eyelid botulinum toxin injection, the mean blink output was reduced to 64% (1.19 of 1.87; P <.001) and 70% (0.94 of 1.35; P <.001) of the baseline values in the groups of normal subjects and patients, respectively. After injection in both the upper and lower eyelid, the mean blink output was reduced to 38% (0.54 of 1.41; P <.001) of the baseline value. The patients with dry eyes reported an improved eye comfort in six of nine cases after injection in the lower eyelid and in seven of 10 cases after injection in both the upper and lower eyelid. Adverse effects included one case of increased discomfort for 3 weeks after injection. CONCLUSION: Injection of botulinum toxin into the medial part of the eyelids decreased the lacrimal drainage, suggesting a new way to treat dry eye conditions. Further studies are required to assess the clinical value of this treatment.     

The use of botulinum toxin in blepharospasm

Twenty-two patients, 17 with benign essential blepharospasm and five with hemifacial spasm, received botulinum toxin by subcutaneous injections in the eyelids and eyebrows. All 22 patients received a standard treatment of 12.5 units of botulinum toxin per side at each injection session. The orbicularis oculi muscle showed pronounced weakness after injection and the spasms decreased. Spasms often recurred despite persistent orbicularis oculi muscle weakness. Side effects were minimal. All patients received some relief, which generally lasted six to 12 weeks.     

Clinical doxorubicin chemomyectomy. An experimental treatment for benign essential blepharospasm and hemifacial spasm

Doxorubicin (DXR) was injected as a treatment for benign essential blepharospasm and hemifacial spasm. The other eyelids were treated concurrently with botulinum toxin (BT). No DXR-treated eyelid has maintained 0 strength (commonly achieved with BT). Two patients with benign essential blepharospasm and four patients with hemifacial spasm have achieved major improvement, sustained for more than 6 months. Eyelids have been swollen and inflamed for up to 3 months. No spontaneously irreversible complication has occurred. A single injection at the maximum safe dose (1 mg in the upper lid and 1.5 mg in the lower lid) has not proven sufficient to produce cure. Treatment of each lower eyelid of a muscular male with severe blepharospasm may require cumulative doses of up to 4.0 mg, delivered in three injection events separated by at least 2 months, with each injection no greater than 1.5 mg DXR per site. At the present time, there is no assurance that a permanent cure will result.     

Treatment selections of 239 patients with blepharospasm and Meige syndrome over 11 years.

BACKGROUND: A retrospective review of 239 patients with benign essential blepharospasm and Meige syndrome was performed in order to determine patients' long term treatment preferences. METHODS: Of 239 patients evaluated, 228 received local injections of botulinum toxin, type A, into the eyelid and facial musculature over 11 years. RESULTS: Of 228 patients, 202 (72.1%) were still treated with botulinum toxin, type A. Eighteen patients (6.9%) no longer received botulinum toxin injections and sought no other treatment. Five patients (2.2%) had apparent remission of their disease after injection. Three patients (1.3%) ultimately obtained relief from orbicularis muscle extirpative surgery and required no additional treatment. Two of the 11 patients (4.6%) who chose not to receive botulinum toxin injections were successfully treated with other modalities: psychotherapy (one patient) and oral haloperidol (one patient). CONCLUSION: While botulinum toxin is the most highly effective treatment for benign essential blepharospasm and Meige syndrome over a long period of time, adjunctive oral drug therapy, including minor tranquillisers as well as eyelid surgery, may augment its effectiveness.     

Effects of eyelid protractor excision for the treatment of benign essential blepharospasm.

Data were analyzed from 37 patients with essential blepharospasm who had undergone upper eyelid protractor excision with brow suspension, and who had a median follow-up of 40 months (range, 12 to 83.5 months) after surgery. Of the 37 patients, 15 (40.5%) had sufficient relief of their spasms at their last follow-up; 22 patients (59.5%) had functionally significant recurrent or residual spasms after upper eyelid surgery. Of these 22 patients, 12 (55%) had recurrences more than six months after surgery, and four patients (18%) had recurrences more than one year after surgery. Patients with Meige syndrome were no more likely to experience recurrent spasms after upper eyelid surgery than patients who lacked a lower facial spasm component. Recurrence of symptoms was primarily the result of lower eyelid spasms in 11 patients (50%), upper eyelid spasms in one patient (5%), and all eyelids in six patients (27%). The location of recurrent spasms could not be ascertained in four patients (18%), with whom we had only telephone contact. Seven of 12 patients (58%) undergoing secondary procedures had relief from their spasms at the end of this study. Excluding those patients who chose to decline further surgery, 22 of 27 patients (81.5%) received satisfactory relief of symptoms after upper eyelid and, if needed, lower eyelid and repeat upper eyelid protractor excision. These long-term results are comparable to those reported previously for differential section of the facial nerve. Because the side effects of eyelid protractor excision are generally more acceptable, we recommend that when surgery is determined to be necessary for essential blepharospasm, upper eyelid protractor excision is the preferred surgical approach.     

Pain relief in patients receiving periocular botulinum toxin A

PURPOSE: We hypothesized that patients with benign essential blepharospasm and hemifacial spasm experience relief of headache and eye pain after botulinum toxin injections. METHODS: A retrospective chart review of 85 patients who had received botulinum toxin injections at the University of Minnesota for treatment of benign essential blepharospasm and hemifacial spasm was conducted. A prospective telephone questionnaire was used to ascertain details regarding improvement of headache and eye pain. RESULTS: Of the 85 patients (34 men, 51 women), 20 patients (23.5%) had headaches and 29 (34.1%) had eye pain. Ten of 20 (50.0%) headache-positive patients and 24 of 29 patients (82.8%) with eye pain had reduction in their pain after botulinum toxin injections. CONCLUSION: The findings of this study support the use of botulinum toxin for headache and eye pain relief in patients with benign essential blepharospasm and hemifacial pain. In addition, with the expanding uses of botulinum toxin, the results support its antinociceptive effects. Further investigation should continue in the mechanism of botulinum toxin's effects on pain.     

Treatment of blepharospasm with medication, surgery and type A botulinum toxin

A total of 39 patients with essential blepharospasm and 2 patients with hemifacial spasm were treated with one or more forms of therapy. All patients underwent neurologic and ophthalmic assessment to rule out ocular causes of blepharospasm. Thirty-six patients were given a trial of various medications. Only one patient was successfully treated: her condition was markedly improved with pimozide after benztropine mesylate, clonazepam and amantadine hydrochloride had failed to help. Patients who did not respond to drug therapy were offered the option of undergoing eyebrow-eyelid muscle stripping surgery. The six patients who underwent surgery showed considerable improvement; however, side effects such as frontal anesthesia, exposure keratitis, lagophthalmus, scarring and eyelid malposition occurred, and three of the six had residual spasm. At this point type A botulinum toxin became available. A total of 27 patients (26 who did not respond to drug therapy, including the 3 with residual spasm after surgery, and 1 previously untreated patient) received type A botulinum toxin injections. Most experienced rapid relief from their spasms. The beneficial effects lasted weeks to months, and there were no major side effects. Treatment with type A botulinum toxin appears to be a safe and effective means of temporarily relieving blepharospasm. The long-term results with repeated injections are yet to be determined.     

Innervation zone of orbicularis oculi muscle and implications for botulinum A toxin therapy.

Motor points (areas of maximal sensitivity to electrical stimulation) were found in constant locations over orbicularis oculi when measured in both eyes of six normal subjects. All subjects had a motor point at the lateral terminus of the upper lid crease and the medial extent of the lower lid crease. A study of the innervation zone [distribution of neuromuscular junctions (NMJ)] was conducted on strips of pretarsal and preseptal portions of the upper eyelid orbicularis that had been removed routinely during involutional ptosis surgery. There was no significant difference in NMJ concentration between the medial and lateral sections, as determined by cholinesterase staining. Therefore, we concluded that the innervation zone is diffuse for the orbicularis muscle within this portion of the upper eyelid. Single-point injections of botulinum toxin were then compared to the conventional multiple injection sites on separate eyes in 10 patients with benign essential blepharospasm. Eight of the 10 patients reported greater relief on the side given injections into multiple points; the other two patients experienced no difference between the two methods. Both histologic data and clinical observation of response to botulinum toxin injection suggest the innervation zone for the upper orbicularis is diffuse. Thus, we conclude that multiple injections are superior to the injection of a single motor point.     

Upper eyelid myectomy in blepharospasm with associated apraxia of lid opening

PURPOSE: To assess the impact of upper eyelid myectomy surgery on blepharospasm with associated apraxia of lid opening (ALO), dry eye, photophobia, and daily functioning in patients who are refractory to botulinum toxin treatment. DESIGN: Noncomparative, consecutive, interventional case series. METHODS: A retrospective chart review was performed to identify 100 consecutive patients beginning on January 1, 2000, who underwent upper eyelid myectomy surgery for blepharospasm and fulfilled the inclusion criteria. A survey was sent to all patients. Data were entered in an anonymous manner into a spreadsheet and analysis was performed using the Student t test with significance set at P<.05. RESULTS: Forty-five (88%) patients experienced ALO before surgery, among which 15 (33%) patients stated they were completely cured and 20 (44%) others had more than 50% improvement in ALO with surgery. In 20 of 30 patients who continued botulinum toxin treatment after surgery, the effect lasted longer. Twelve (29%) of 42 patients who experienced dry eyes before surgery improved. Eighteen (41%) of the 44 patients who experienced light sensitivity before surgery improved. Thirty-seven (82%) patients noted their cosmetic appearance to be better after surgery. The cumulative preoperative disability score was 14.11+/-5.78 (59%), whereas the cumulative postoperative disability score was 5.20+/-8.25 (22%; P<.01). CONCLUSIONS: Upper eyelid myectomy surgery appears to be effective in treating blepharospasm with associated ALO in most patients who are refractory to botulinum toxin injections and can provide improvement in the quality of life.     

Treatment of upper eyelid retraction associated with thyroid eye disease with subconjunctival botulinum toxin injection

OBJECTIVE: To study the effectiveness of botulinum toxin injections, via a subconjunctival approach, in the management of upper eyelid retraction associated with thyroid eye disease. DESIGN: Prospective, non-comparative, interventional case series. PARTICIPANTS: Eleven patients with upper scleral exposure associated with thyroid eye disease who declined conservative or conventional surgical management. INTERVENTION: One or more treatments with injections of botulinum toxin into the subconjunctival space at the superior margin of the tarsal plate, via a conjunctival approach. MAIN OUTCOME MEASURES: Upper eyelid position in relation to the upper limbus, patient satisfaction, and complications. RESULTS: All patients experienced some improvement in the amount of lid retraction after injections. The amount of lid lowering varied between patients and lasted between 1 and 40 months. A lid position acceptable to the patient was obtained in 10 patients. Four patients had ptosis lasting from 1 to 3 weeks, and three patients had transient diplopia lasting 1 day to 3 weeks. CONCLUSIONS: This subconjunctival method of botulinum toxin injection provides an effective treatment for upper eyelid retraction associated with thyroid eye disease that is easy to administer and well tolerated by patients with few side effects.     

Treatment of blepharospasm with botulinum toxin

In 43 patients (81 eyes) with blepharospasm resistant to other forms of therapy, 149 outpatient injections of botulinum A toxin were given into the orbicularis oculi muscle. Subsequent follow-up periods ranged from ten to 210 days. Orbicularis oculi spasm, eyelid forced closure, and eyebrow spasm all decreased substantially over the first ten days following the initial injection. Patients with essential blepharospasm, hemifacial spasm, or previous surgery all responded in a similar fashion. This beneficial effect was transient, however, and additional treatment was required for sustained relief. Twenty-five patients received multiple injections with a mean interval of 65 days. Results of second and third injections were similar to the first in rapidity of onset and duration of effect. Complications were local, mild, and transient, and no systemic side effects were noted.     

Thyroid associated ophthalmopathy: botulinum toxin A in the treatment of upper eyelid retraction--a pilot study.

PURPOSE: Eyelid retraction in patients with thyroid associated ophthalmopathy is a common cause of eye discomfort and a disfigured facial appearance. The aim of this pilot study was to evaluate the effects and safety of inducing a temporary partial ptosis of the eyelid through injection of botulinum toxin A into the levator palpebrae superioris muscle. METHODS: Nine patients were treated. They were followed up with ophthalmologic examinations and self-assessment questionnaires until the point at which they either required renewed treatment or had no residual effect of the first injection. Maximum follow-up time was twenty weeks. RESULTS: In all eyes but one there was a lowering of the eyelid position one week after treatment and all these patients reported an improvement of eye appearance and symptoms. There was variability in the degree of lowering of the eyelid with the same dose of injected botulinum toxin A. It was also difficult to predict the time interval needed for re-treatment. Ptosis impairing visual acuity was not a consequence of the treatment in any of the patients. One week after treatment two patients experienced increased diplopia but only one showed transient change in Lees screen measurement of eye motility. CONCLUSION: Botulinum toxin A injection may be used to lower the upper eyelid position in patients awaiting eyelid surgery. The treatment safely relieved symptoms and improved eye appearance. However, treatment was short term and difficult to predict. There is also an inherent risk of transient diplopia.     

Use of botulinum toxin in blepharospasm and other facial spasms

Essential blepharospasm is an involuntary spasmodic closure of the eyelids. It frequently makes normal social human life such as reading, driving and even walking almost impossible. Botulinum toxin has been approved for investigational use for treatment of blepharospasm. We report the results and side-effects of botulinum A toxin treatment of the first 13 patients in Finland. Temporary control of spasms was achieved in all patients varying from 1 to 38 weeks with a mean of 11 weeks after the first injection. Most patients needed re-treatment after varying intervals. All complications were transient.     

Essential blepharospasm and related dystonias

Essential blepharospasm is an idiopathic disorder of progressive involuntary spasms of the orbicularis oculi and upper facial (corrugator, procerus) muscles. Blepharospasm literally means spasm of the eyelids; however, most patients with blepharospasm also have or will develop squeezing in the lower face and neck muscles (Meige's syndrome, orofacial dystonia, or oromandibular dystonia). Some patients develop dystonic, uncontrolled movements in areas outside the facial nerve distribution (segmental cranial dystonia or craniocervical dystonia). Chronic, forceful squeezing by the periocular muscles becomes debilitating for the patient and leads to functional and cosmetic eyelid deformities. Treatment has included a variety of modalities and oral medications that are of limited efficacy. Botulinum-A toxin injections have delivered the best temporary relief from this disorder, while the periorbital myectomy operation has been shown to give the best long-term results.     

Differential section of the seventh nerve as a tertiary procedure for the treatment of benign essential blepharospasm

PURPOSE: To examine the efficacy of differential section of the seventh nerve in treatment of patients with blepharospasm refractory to botulinum toxin and eyelid protractor myectomy. METHODS: A retrospective noncomparative interventional case series consisting of a cohort of 228 patients with benign essential blepharospasm followed from 1987 to 1997 in a university ophthalmic plastic surgery referral practice. Patients were treated with botulinum toxin injections, eyelid protractor myectomy, and differential section of the seventh nerve in stepwise fashion as needed for symptomatic control. RESULTS: Thirty-four patients (15% of total) underwent eyelid protractor myectomy during this period. Eyelid protractor myectomy failed to control blepharospasm in 7 (21%) of these 34 patients, who then underwent differential section of the seventh nerve an average of 2 years after myectomy. Patients were followed up for an average of 36 months, with a success rate of 42% (3 of 7). The remaining 4 patients had repeat differential section of the seventh nerve with a 50% success rate, which brought the overall success rate from differential section of the seventh nerve to 71%. Lower eyelid ectropion requiring surgical repair complicated 27% of differential section of the seventh nerve procedures. CONCLUSIONS: Differential section of the seventh nerve is a reasonable alternative in the treatment of patients who have persistent disability despite treatment with botulinum toxin injections and eyelid protractor myectomy.     

Use of botulinum toxin in the treatment of one hundred patients with facial dyskinesias

One hundred patients with involuntary eyelid and facial spasms resulting from essential blepharospasm, Meige syndrome, and hemifacial spasm continued to respond to repeated injections of botulinum toxin at expected time intervals during a 30-month period. This series of more than 372 injections done by one of us (JAM) supports the finding of earlier, smaller series that tolerance to the toxin does not develop. The drug had a greater duration of effect in patients with hemifacial spasm than in patients with blepharospasm; the duration of effect was 17.25 weeks in the former group and 12.6 weeks in the latter. Eighteen percent of patients required a higher than standard dose for a therapeutic response. Fourteen of 15 patients with lower facial spasms and one patient with torticollis had significant relief. Dry eye may be managed by titrating the lower lid dose.