Botulinum toxin type A therapy for blepharospasm

  • Review
  • Intervention

Authors


Abstract

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 methods

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.

摘要

背景

以Botulinum toxin type A治療眼瞼痙攣

眼瞼痙攣是一種局部性肌張力障礙,主要病徵是由眼輪匝肌的痙攣性收縮造成的慢性間歇或持續性非自主眼瞼閉合。其它臉部或頸部肌肉也經常會受到牽連。大部分的案例都是原發性的,且眼瞼痙攣通常是終身的障礙。它的嚴重度從反覆頻繁的眨眼到伴隨功能性失明的永久強迫闔眼都有可能。Botulinum toxin type A (BtA)是目前的第一線治療。

目標

評估botulinum toxin (BtA)作為眼瞼痙攣的治療是否有效且安全。

搜尋策略

我們利用the Cochrane Movement Disorders Group trials register、 the Cochrane Central Register of Controlled Trials (CENTRAL)、MEDLINE、EMBASE搜尋欲收錄的研究,手動搜尋the Movement Disorders Journal及關於運動障礙和botulinum toxin的國際研討會摘要、和其他這個領域的研究者溝通、搜尋找到論文中的參考資料,以及和這些論文的作者和藥商連絡。

選擇標準

有評估BtA治療眼瞼痙攣的療效的研究是可以為本篇評論採用的。它們必須是隨機且安慰劑對照的研究。

資料收集與分析

由兩位評論者分別使用預先制定的格式,從收錄的研究中以二次擷取的方式收集資料。這兩位作者分別評估每個試驗的內部確效,意見分歧的部分經過討論取的共識。利用不良反應、症狀評分量表改善、病人和醫師的主觀評估及生活品質改善作為結果量測。

主要結論

我們找到了一些對照試驗。它們都是短期、病人數很少的試驗。由於這些試驗的內部確效、樣本數、介入方式和結果都不夠好,沒有任何試驗符合我們收錄的標準。然而,所有的試驗都發現BtA比安慰劑有效,和回報有90%的病患受會的個案對照及世代研究的結果是一致的。

作者結論

目前沒有高品質、隨機、對照的療效數據能支持用Bt治療眼瞼痙攣。儘管如此,其他研究認為BtA用於治療眼瞼痙攣是有效且安全的,並且支持它的使用。從1個開方性研究取得的療效程度(90%病患受惠),使得以BtA治療眼瞼痙攣的安慰劑對照試驗很難進行,甚至可能很不合乎道德。進一步的試驗應該探討技術因子,例如最佳治療間隔、各種注射方式、劑量、Bt的種類及劑型。其他議題,包括服務、生活品質、長期的療效、安全性和免疫原性。

翻譯人

本摘要由朱奕蓁翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

以Botulinum toxin type A局部注射作為眼瞼痙攣或非自主性眼瞼閉合的治療。眼瞼痙攣是眼瞼的功能異常,是由眼部肌肉痙攣性收縮造成的非自主性眼瞼閉合。其它臉部及頸部肌肉也時常受到牽連。它通常在晚年發病,嚴重度從反覆性頻繁的眨眼到永久強迫闔眼及功能性失明都有可能。治療方式有手術、心理治療、生物回饋療法及藥物。Botulinum toxin type A (BtA)是目前常用的治療方式。目前沒有有足夠病患數目的隨機對照試驗符合本評論的收錄標準。我們找到的試驗顯示BtA比安慰劑有效,案例對照及世代研究也有想同的結果,其中大約有90%的病人受惠。最常見的不良反應是對於眼睛的影響且很短暫。

Plain language summary

Botulinum toxin type A local injection therapy for blepharospasm or involuntary eyelid closure

Blepharospasm is a dysfunction of the eyelids showing as involuntary eyelid closure due to spasmodic contractions of eye muscles. Other facial and neck muscles are also frequently involved. It often begins late in life with the severity ranging from repeated frequent blinking of both eyelids to persistent forceful closure and functional blindness. Treatment has included surgery, psychological approaches, biofeedback and drugs. Botulinum toxin type A (BtA) is the current treatment. No randomised controlled trials with sufficient numbers of patients fitted the review criteria. Trials identified found BtA to be superior to placebo as did large case-control and cohort studies, with around 90% of patients benefiting. The most common adverse effects affected the eyes and were short lived.