Table 5.

Lists the RCTs identified in hemifacial spasm (HFS).

Study	Study Design and Goal	Method	Results
Xiao et al., 2018 [198]	RCT Formulation used: Chinese BoNTA (CBTXA—Lanzhou Biological Products Institute, Lanzhou, China) or onabotulinumtoxinA Evaluates if facial asymmetry improved with bilateral BoNT	19 HFS patients received unilateral BoNT (UBT) 24 HFS patients received bilateral BoNT Injected in orbicularis oculi (OOc), zygomaticus major (ZM), risorius (ris), orbicularis oris (OOr), levator labii superioris (LLS), frontalis, and glabella, respectively In patients who got bilateral injections, affected side was injected the same as UBT (1.25–4 MU) and unaffected side same muscles were injected with 1.25MU.	Bilateral facial injections reduced facial asymmetry Unilateral BoNT injections increased asymmetry BoNT duration of effect and adverse effect were similar between both groups
Lolekha et al., 2017 [34]	Double-blinded, cross RCT Formulation used: onabotulinumtoxinA Compares preseptal versus pretarsal BoNT injections in treatment of HFS and BSP	40 (31 HFS, 9 BSP) 20 patients were in each arm and then had crossover If BSP, medial and lateral segments of upper and lower eyelid with up to 10 units per eye lid. If HFS, additional dose was injected in OOc, ZM, LLS, and mentalis. Total dose was 12.5–22.5 units and 5–10 units per eye lid	Pretarsal BoNT had improved symptom control, decreased latency to improvement, and increased duration of efficacy. Adverse effects of ptosis were seen in the preseptal group only However, minor complications such as hematoma, tearing, and irritation was seen in both groups
Li et al., 2015 [199]	Randomized, double-blind, crossover trial Formulation: BoNTA Assesses differences in low (25U/mL) versus high (50 U/mL) BoNT for treatment of HFS	n = 20 2.5 to 5 U were injected in each location	Time of onset of efficacy was not significantly different The high concentration group had longer duration of efficacy 15/20 and 4/20 of high and low concentration groups, respectively, had adverse effects. The adverse effects lasted longer in the high concentration group
Prutthipongsit et al., 2015 [200]	Randomized, double-blind trial Formulation used: abobotulinumtoxinA Efficacy differences between split and nonsplit site injection of BoNT for HFS	31 HFS (16 patients in split site and 15 in nonsplit site) Nonsplit site—ZM and ris were injected in two spots in each (total four spots). Onespot in each muscle got a full dose of abobotulinumtoxinA and the other spot in each muscle got saline Split site—ZM and zygomaticus minor (Zmi) and two injections in risorius (ris). All four spots received abobotulinumtoxinA	Median onset of efficacy was 4 and 4.5 days for nonsplit and split, respectively Duration of effect was 60 days and 54.5 days for nonsplit and split, respectively The efficacy was similar between both groups
Li et al., 2012 [55]	Randomized controlled trial Formulation used: obtained from Lanzhou Institute of Biological Products Efficacy of BoNTA versus BoNTA with Carbamazepine (CBZ) was assessed	58 patients with either HFS or BSP were randomized 30 patients got BoNTA with CBZ 100 mg 3 times a day and 28 received only BoNTA 4–5 injections per eye, 2.5 to 5 U per site, and addition 3 sites in face for HFS. Up to 55 U for BSP and 75 U for HFS	Complete remission was noted in 90% and 67.9% of treatment and control groups The duration of effect was similar between the 2 groups
Kongsengdao et al., 2012 [201]	Prospective, double-blinded, randomized, crossover trial Evaluates quality of life (QoL) of Neuronox and abobotulinumtoxinA	26 HFS patients were randomly divided into Neuronox or abobotulinumtoxinA group and switched at 12 weeks Four injections around OOc and one each in upper and lower OOr with either 15 units of abobotulinumtoxinA or 3.125 units of Neuronox	The mean QoL scales (HFS-30, SF-36, AIMS) was not significantly different between 2 groups The total intensity score of HFS was significantly lower in the abobotulinumtoxinA group QoL scores were similar between abobotulinumtoxinA and Neuronox
Wu et al., 2011 [52]	Prospective, open-label and randomized Compares efficacy of CBTXA and onabotulinumtoxinA in HFS and BSP	273 patients with HFS and BSP 107 received onabotulinumtoxinA and 166 CBTXA Per injection site dose was 2.5–5 U	Both formulations have similar efficacy Response rate 97% with CBTXA and 99% with onabotulinumtoxinA Most common adverse effect was tightness in face and facial droop
Colakoglu et al., 2011 [202]	Randomized, single-blind, cross over trial Formulation: onabotulinumtoxinA Assessed efficacy of upper and lower facial versus pure upper facial BoNTA injections for HFS	23 patients with HFS were randomized to receive BoNTA in both OOc and perioral muscles versus BoNTA in OOc and physiological serum into perioral muscles 11–30 units of onabotulinumtoxinA in OOc and 3–11 units in lower facial (four points in ZM, Zmi, LLS, and ris)	When patients had more severe HFS symptoms in lower face, receiving BoNTA in perioral muscles was more effective Adverse effects of moderate/mild lower facial paresis were 13%/34.7% and 0%/13% in BoNT only group versus BoNT group
Quagliato et al., 2010 [53]	Prospective, randomized, double-blind trial Compares efficacy of Prosigne (Chinese origin BoNTA) and onabotulinumtoxinA	36 HFS and 21 BSP were randomized to receive either of the formulations BSP—30 units were injected in each OOc and procerus HFS—25 U OOc, 10 U spread among in ZM, Zmi, LLS, ris, levator anguli oris, and depressor anguli, mentalis, and platysma	Duration of effects was 11.3 weeks with both forms in BSP and 12.8/12.9 weeks onabotulinumtoxinA/Prosigne for HFS OnabotulinumtoxinA and Prosigne have similar efficacy and adverse effects
Price et al., 1997 [54]	Randomized, prospective trial Determines effectiveness of four sites of injection of BoNT with most efficacy and least side effects (for BSP and HFS)	92 (50 BSP and 42 HFS) Four different protocol of injections were studied with four spots of injections in OOc in each (standard, brow, and inner orbital or outer orbital) (HFS had addition cheek injection on affected side) 2.5 units were injected in four sites around eye	Standard treatment had longest effect in BSP, and brow treatment was preferred treatment for HFS Inner orbital had more ptosis in BSP group Outer orbital had lowest duration of benefit
Yoshimura et al., 1992 [203]	Prospective randomized placebo-controlled Formulation: Oculinum (Alan Scott, MD, Smith Kettlewell Eye research institute) Assessed efficacy of BoNT for HFS	11 HFS patients Three different doses (2.5–10 units) of Oculinum or normal saline (placebo) was injected in a random manner	84% of BoNT provided relief and 44% was substantial Side effects were facial weakness (97%), bruising (20%), double vision (13%), and drooping eye lid (7%) BoNT was safe and effective for treatment of HFS

Abbreviations: BSP—Blepharospasm; BoNT—Botulinum toxin; BoNTA—Botulinum toxin A; BoNTB—Botulinum toxin B; CBZ—Carbamazepine; CD—Cervical dystonia; CBTXA—Chinese Botulinum toxin A; EMG—Electromyography; HFS—Hemifacial spasm; LLS—Levator labii superioris; RCT—Randomized controlled trial; Ris—Risorius; UBT—Unilateral botulinum toxin; Zmi—Zygomaticus minor; ZM—Zygomaticus major.