Development of a Patient-Centered Outcome Tool for Blepharospasm: A Stepwise Modified Delphi Study

Abstract

Blepharospasm (BSP) is characterized by excessive orbicularis oculi muscle activity leading to abnormal blinking and involuntary eyelid closure. Botulinum neurotoxin (BoNT) injections are the main treatment for BSP, but they only partially and transiently relieve symptoms, leading to a waxing and waning therapeutic response. A patient-centered outcome (PCO) tool that measures BSP symptoms in a simple and efficient way could inform the development of better treatments. Using a stepwise modified Delphi approach, potential PCO items were first identified using the Dystonia Coalition Database with data from over 200 individuals with BSP who had provided responses to existing clinical assessment scales. These items were then analyzed for contribution to overall severity using a Random Forests approach, and redundant items were merged and revised in a series of iterative meetings with a specialist panel along with input from patient advocacy group representatives and focus groups. An online survey was conducted with 330 individuals with BSP to validate and verify the items' relevance. Finally, the specialist panel provided content validity ratio, which was repeated until it showed good agreement for relevance and clarity of all items. In the end, an easy-to-use PCO tool designed for smartphones and tablets containing 17 items covering three symptom domains (motor, disability, and psychosocial/quality of life) was created. This novel PCO tool for BSP may be used to characterize the cyclical response that an individual patient experiences from BoNT treatments and provide a vital tool for future investigations of longer-acting BoNT preparations or adjunctive therapies.

Keywords: blepharospasm; botulinum neurotoxin; patient-centered outcomes; self-assessments; symptom monitoring; treatment tracking.

Figure 1

Flow diagram for the development of the blepharospasm (BSP) patient-centered outcome (PCO)—MOTOR domain. Item selection, revision, and finalization went through three stages of the process for the MOTOR domain (see Supplemental Materials for flow diagrams of DISABILITY and PSYCHOSOCIAL domains). Stage 1 involved content development and item generation, Stage 2 was focused on item improvement and revision of items, and Stage 3 involved a content validity rating (CVR) process to ensure content validity.

Figure 2

Patient-centered outcome total MOTOR scores for two randomly selected individuals with blepharospasm. Scores were obtained weekly over three 12-week botulinum neurotoxin treatment (BoNT) treatment cycles. The total MOTOR scores for both individuals decrease after the BoNT treatment cycles, with the greatest benefit observed around 6–8 weeks after the injection and wearing-off of treatment effect observed around 10–12 weeks after the injection.

Figure 3

Percent change from assessments at time of botulinum neurotoxin (BoNT) injections to peak effect (typically 6–8 weeks after injection). Results are shown for five individuals in a pilot project assessment (A) with data from two individuals shown separately (B) to highlight individual differences across the different rating measures. Change in the positive direction indicates improvement in symptoms from injection to peak effect. Congruence largely seen with clinician ratings (CGI-C: Clinical Global Impression of change) and patient ratings (PGI-C: Patient Global Impression of change) as well as with total patient-centered outcome (PCO) MOTOR domain score change. Less congruence was seen with percent changes in the total PCO DISABILITY and PSYCHOSOCIAL domain scores.