Difficulties with differentiating botulinum toxin treatment effects in essential blepharospasm

Abstract

Blepharospasm is a focal dystonia in which the extraocular muscles contract repetitively, leading to excessive blinking and forced eyelid closure. Botulinum toxin type A (BoNTA) is the primary symptomatic treatment for blepharospasm and its effects have been evaluated using numerous rating scales. The main scales in use today were initially used to determine whether BoNTA treatment was superior to placebo, and most controlled trials have confirmed this. More recently, these scales have been used to determine whether there are efficacy differences between different BoNTs in blepharospasm. However, although the scales used in these trials are able to differentiate the effects of BoNT from placebo, they may not be sensitive enough to differentiate between BoNTs. Most of the scales include only four possible points for each item, which would necessitate a 25% greater improvement in one group than the other to detect any differences. Current scales are also relatively insensitive to patients with mild disability who may experience mainly psychosocial problems related to their blepharospasm. Clinical trials comparing BoNTs that include substantial numbers of mildly affected patients may be unlikely to find differences because the scales do not adequately measure mild symptoms. Additional challenges with evaluating blepharospasm include the lack of precision and objectivity of current measures, symptom variability, the need to evaluate aspects of the disorder that are most important to patients, and the different types of blepharospasm. Although no single scale may be able to capture all relevant aspects of blepharospasm, more sensitive and patient-centered scales are needed.

Botulinum toxin in hemifacial spasm: the challenge to assess the effect of treatment

“…In contrast to the Jankovic rating scale, which has become the most widely used current clinical scale for blepharospasm (Wabbels et al 2011) there is no established rating scale for hemifacial spasm. Due to the lack of a disease-specific instrument, some research groups simply applied clinical scales, which have been historically developed for blepharospasm (e.g., the Elston functional scale or the Fahn rating scale).…”

“…However, it has already been discussed in a previous review focusing on blepharospasm that clinical scales in the form of ordinal, numeric ratings have some disadvantages (Wabbels et al 2011). A significant drawback is the lack of sensitivity due to the limited number of possible ratings.…”

“…In accordance with a previous review of rating scales to assess blepharospasm (Wabbels et al 2011), these scales for hemifacial spasm can be classified into three general categories (1) clinical scales, (2) activities of daily living/functional ability status scales, and (3) global rating scales. In this section the different types of rating scales are described considering their advantages and disadvantages.…”

“…Interestingly none of the randomized controlled studies or those enrolling at least 50 patients summarized in Table 1 used the Jancovic rating scale (Jankovic and Orman 1987), which is probably the most adequate clinical scale to assess the severity and frequency of blepharospasm (Wabbels et al 2011).…”

“…In contrast to blepharospasm (Wabbels et al 2011) there is no consensus on main clinical rating scales for hemifacial spasm. Duration of effect and global rather than disease-specific rating scales have been used to assess the outcome in most of the studies with BoNT.…”