Table 1.

Lists randomized controlled trials (RCTs) associated with blepharospasm.

Study	Study Design and Goal	Sample Size and Method	Results
Lungu et al., 2013 [56]	Double-blind placebo controlled randomized trial Formulation: onabotulinumtoxinA or rimabotulinumtoxinB B Assessed topical use of acetyl hexapeptide-8 (AH8), competitive SNAP25 inhibitor as new therapy for BSP	n = 24 Injections into OOc palpebral portion and 3/4 also received in the orbital portion/procerus/corrugator Topical application of AH8 or placebo started on Day 1 of BoNT	Time for symptom return to baseline was 3.7 and 3 months in active and placebo groups, respectively AH8 is safe and may be useful in increasing duration of effect
Wabbels et al., 2011 [57]	Double-blind, randomized trial Goal: compares incobotulinumtoxinA (Merz, BoNTA) to onabotulinumtoxinA	65 BSP patients received either incobotulinumtoxinA or onabotulinumtoxinA 20–40 U/eye Mean dose was 29 U/eye and 27 U/eye for onabotulinumtoxinA and incobotulinumtoxinA	Though there was no significant difference between the two formulations, however, there was a greater tendency to improve at 4 and 8 weeks with onabotulinumtoxinA BDSI score mean change was −0.42 in onabotulinumtoxinA and −0.21 in incobotulinumtoxinA No significant differences in side effects
Boyle et al., 2009 [58]	Prospective, randomized trial Study looks at differences between low (10 U/mL) and high (100 U/mL) concentrations of BoNTA	16 patients 10–30 units per side. Left and right sides were randomized	62% had equal relief of both sides No difference in efficacy Bruising and redness similar between groups
Truong et al., 2008 [59]	Randomized trial, double-blind, placebo controlled Studied safety and efficacy of abobotulinumtoxinA versus placebo in BSP	10, 23, 25, and 27 patients completed placebo, abobotulinumtoxinA 40, 80, and 120 U/eye, respectively	25%, 87%, 97%, and 94% of patients found placebo, 40 U/eye, 80 U/eye, and 120 U/eye to be effective Ptosis occurred in 4%, 13%, 39%, and 58% in placebo, 40 U/eye, 80 U/eye, and 120 U/eye, respectively Blurred vision occurred in 4%, 23%, 19%, and 42% in placebo, 40 U/eye, 80 U/eye, and 120 U/eye, respectively 80 U/eye provided the most efficacy while balancing for adverse effects.
Roggenkamper et al., 2006 [60]	Double-blind, randomized trial Assessed NT201(Merz Pharmaceuticals GmbH, Germany) new formulation of BoNTA compared to onabotulinumtoxinA	148 patients received NT201 and 152 patients received onabotulinumtoxinA Mean total dose in NT201 was 39.6 units and onabotulinumtoxinA 40.8 units	Mean change in Jankovic rating scale was −2.67 and −2.90 for onabotulinumtoxinA and NT201, respectively. NT201 is safe and efficacious for BSP treatment Ptosis, xerophthalmia, and abnormal vision occurred at 6.1%, 2%, and 1.4% in NT 201 Ptosis, xerophthalmia, and abnormal vision occurred in 4.5%, 0%, and 3.2% in the onabotulinumtoxinA group, respectively.
Mezaki et al., 1999 [61]	Double-blind trial Assesses effectiveness of type A versus type F versus combination of A+F	54 patients had 5 units each of A+F on one side and on the other side had A or F Patient were randomly given either type A or F on one side and the mixture in the other side	There was no difference between the groups when comparing the AF side The peak effect was similar among the three groups Duration of action of AF group was less than that of A and more than that of F alone.
Nussgens Z et al., 1997 [62]	Double-blind trial Studies onabotulinumtoxinA versus abobotulinumtoxinA	212 BSP patients received either onabotulinumtoxinA or abobotulinumtoxinA the first time and the other BoNT during second session OnabotulinumtoxinA average dose was 45.4 IU and abobotulinumtoxinA was 182 IU	OnabotulinumtoxinA and abobotulinumtoxinA lasted 7.98 ± 3.8 weeks and 8.03 ± 4.6 weeks, respectively Adverse effects such as ptosis, blurred vision, diplopia, hematoma, and tearing occurred in 17% and 24.1% of onabotulinumtoxinA and abobotulinumtoxinA, respectively (p < 0.01) Bioequivalence of onabotulinumtoxinA:abobotulinumtoxinA is 1:4 in this trial
Jankovic et al., 1988 [63]	Randomized double-blind placebo-controlled trial (after initial open-label phase) Assessed BoNTA for management of various focal dystonia including BSP	22 patients with focal dystonia received either BoNTA or saline	All 12 BSP patients had relief of symptoms with BoNT and none who received saline improved Mean beneficial effect lasted 12.5 weeks
Mitsikostas et al., 2020 [64]	Randomized double-blind placebo-controlled trial (following which there was an open-label phase) Assessed incobotulinumtoxinA for management of BSP	61 BSP patients were randomized to receive either 50 U or 25 U of incobotulinumtoxinA or placebo	A statistically significant improvement was noted in Jankovic rating scale in the 50U group compared to the placebo group Low adverse event rate of 22.2–42.1 was noted.
Sane et al., 2019 [65]	Triple masked randomized controlled trial Assessed efficacy of onabotulinumtoxinA versus Neuronox in BSP	24 patients with BSP were randomized to receive either formulation	Mean duration of improvement was 3.78 months Neuronox and onabotulinumtoxinA were similar in safety and efficacy

Abbreviations: BSP—Blepharospasm; BoNT—Botulinum toxin; BoNTA—Botulinum toxin A; OOc—Orbicularis oculi.