Botulinum toxin type A therapy for blepharospasm.

BACKGROUND: Blepharospasm is a focal dystonia characterized by chronic intermittent or persistent involuntary eyelid closure due to spasmodic contractions of the orbicularis oculi muscles. Other facial and neck muscles are also frequently involved. Most cases are idiopathic and blepharospasm is generally a life-long disorder. Its severity can range from repeated frequent blinking to persistent forceful closure of the eyelids with functional blindness. Botulinum toxin type A (BtA) is the current first line therapy.

OBJECTIVES: To determine whether botulinum toxin (BtA) is an effective and safe treatment for blepharospasm.

SEARCH STRATEGY: We identified studies for inclusion in the review using the Cochrane Movement Disorders Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, handsearches of the Movement Disorders Journal and abstracts of international congresses on movement disorders and botulinum toxin, communication with other researchers in the field, reference lists of papers found using above search strategies, and contact with authors and drug manufacturers.

SELECTION CRITERIA: Studies were eligible for inclusion in the review if they evaluated the efficacy of BtA for the treatment of blepharospasm. They must have been randomised and placebo-controlled.

DATA COLLECTION AND ANALYSIS: We used a paper pro-forma to collect data from the included studies using double extraction by two independent reviewers. The two reviewers separately assessed each trial for internal validity and they settled differences between them by discussion. The outcome measures used included adverse events, improvement in symptomatic rating scales, subjective evaluation by patients and clinicians, and changes in quality of life assessments.

MAIN RESULTS: We found few controlled trials. They were of short duration and enrolled small numbers of patients. Because of their poor internal validity, the characteristics of the populations studied, and the types of interventions and outcomes, none of the trials fitted our criteria for inclusion. However, all these trials found BtA to be superior to placebo as did large case-control and cohort studies, which reported that around 90% of patients benefited.

AUTHORS' CONCLUSIONS: There are no high quality, randomised, controlled efficacy data to support the use of Bt for blepharospasm. Despite this, other studies suggest that BtA is highly effective and safe for treating blepharospasm and support its use. The effect size (90% of patients benefit) seen in open studies makes it very difficult and probably unethical to perform new placebo-controlled trials of efficacy of BtA for blepharospasm. Future trials should explore technical factors such as the optimum treatment intervals, different injection techniques, doses, Bt types and formulations. Other issues include service delivery, quality of life, long-term efficacy, safety, and immunogenicity.