Treatment of Blepharospasm

ABSTRACTIntroduction: Blepharospasm is a focal dystonia manifested by repetitive spasms of eyelid muscles, resulting in involuntary eye closure, often accompanied by other facial and neck muscle sustained contractions (cranial–cervical dystonia). Abnormalities in multiple pathways involving the basal ganglia, and aberrant dopaminergic, GABAergic, serotonergic and cholinergic systems have been implicated in blepharospasm and considered as potential targets for pharmacological intervention.Areas covered: Literature was reviewed for relevant case reports, case series, review articles, and update reports on blepharospasm and treatment of blepharospasm including articles on botulinum toxin and other pharmacological interventions.Expert commentary: Botulinum neurotoxin (BoNT) is the first line and mainstay of treatment for blepharospasm. Oral medications for the treatment of blepharospasm may be considered in tardive syndromes, parkinsonian conditions, and as adjunct to BoNT in patients with inadequate symptom control. Dopaminergic agents including levodopa and dopamine agonists, GABAergic agents such as benzodiazepines and baclofen, and anticholinergics such as trihexyphenidyl have been used in patients with blepharospasm with varying benefits. Dopamine-depleting agents including tetrabenazine, deutetrabenazine, and valbenazine have a role in the treatment of secondary blepharospasm due to tardive syndromes.

Crotoxin is the main neurotoxin of South American rattlesnake Crotalus durissus terrificus. The neurotoxic action is characterized by a presynaptic blockade. The purpose of this research is to assess the ability of crotoxin to induce temporary paralysis of extraocular and facial muscles in humans. Doses of crotoxin used ranged from 2 to 5 units (U), each unit corresponding to one LD50. We first applied 2U of crotoxin in one of the extraocular muscles of 3 amaurotic individuals to be submitted to ocular evisceration. In the second stage, we applied crotoxin in 12 extraocular muscles of 9 patients with strabismic amblyopia. In the last stage, crotoxin was used in the treatment of blepharospasm in another 3 patients. No patient showed any systemic side effect or change in vision or any eye structure problem after the procedure. The only local side effects observed were slight conjunctival hyperemia, which recovered spontaneously. In 2 patients there was no change in ocular deviation after 2U crotoxin application. Limitation of the muscle action was observed in 8 of the 12 applications. The change in ocular deviation after application of 2U of crotoxin (9 injections) was in average 15.7 prism diopters (PD). When the dose was 4U (2 applications) the change was in average 37.5 PD and a single application of 5U produced a change of 16 PD in ocular deviation. This effect lasted from 1 to 3 months. Two of the 3 patients with blepharospasm had the hemifacial spasm improved with crotoxin, which returned after 2 months. This study provides data suggesting that crotoxin may be a useful new therapeutic option for the treatment of strabismus and blepharospasm. We expect that with further studies crotoxin could be an option for many other medical areas.

Combination of Pretarsal and Preseptal Botulinum Toxin Injections in the Treatment of Blepharospasm: A Prospective Nonrandomized Clinical Trial

Objective To investigate the clinical effect of subcutaneous injecting the compound anisodine besides the superficial temporal artery combined with danhong iontophoresis in treatment of blepharospasm with dry eye. Methods The clinical data of 64 patients (75 eyes) with blepharospasm and dry eye treated in The Second People′s Hospital of Lianyungang were collected from September 2014 to June 2016. According to the digital table method, the patients were randomly divided into control group and treatment group. Among them, there were 30 cases (34 eyes) in the control group and 34 cases (41 eyes) in the treatment group. 30 cases (34 eyes) enrolled in the control group were treated with oral mecobalamin capsule and sodium hyaluronate eye drops. On the basis of the control group′s treatments, 34 cases (41 eyes) enrolled in the treatment group were treated by injecting the compound anisodine besides the superficial temporal artery combined with Danhong iontophoresis. Before and after treatment, two groups of patients were examined in classification of blepharospasm, SchirmerⅠtest (SIt), breakup time (BUT), and corneal fluorescent staining, respectively. SIt wetted length, BUT, and corneal fluorescein staining scores were presented as mean ± standard deviation(±s), and compared by independent samples t-test between two groups, and compared by paired samples t-test before and after treatment. The intensity of blepharospasm was divided into four grades, and the results were compared by Kruskal-Wallis H rank sum test. The therapeutic effect of blepharospasm was expressed as the number of cases and percentage (%), and the total effective rate was compared by chi square test. Results Before the treatment, the results of SIt, BUT and corneal fluorescent staining in the control group were (2.43±1.17) mm/5 min, (2.67±1.03) s and (5.10±1.71) points; after treatment, they were (10.00±2.99) mm/5 min, (9.10±2.44) s and (1.67±1.15) points, respectively. The results of SIt, BUT and corneal fluorescent staining were compared in the control group before and after treatment, and the differences were statistically significant (t=9.12, 10.26, 5.48; P 0.05). However, comparing the results of SIt, BUT and corneal fluorescent staining between the treatment group and control group, after the treatment, and the differences were statistically significant (t=3.88, 5.00, 2.25; P 0.05). But after the treatment, there was statistical difference in the total effective rate which was 94.12% in the treatment group and 80.00% in the control group (χ2=6.94, P<0.05). Conclusion Subcutaneous injecting the compound anisodine besides the superficial temporal artery combined with Danhong iontophoresis is efficient in the treatment of blepharospasm and dry eye. Key words: Blepharospasm; Dry eye; Compound anisodine; Iontophoresis

Thirty years after their approval, botulinum toxin injections still are the first-line therapy for blepharospasm. The aim of our study was to analyze long-term data concerning safety and efficacy in a large cohort over decades. Treatment data of all patients with blepharospasm and Meige´s syndrome in our outpatient clinic having undergone at least three subsequent treatment sessions with current onabotulinumtoxinA or abobotulinumtoxin A were analyzed with respect to the course of dose, effect duration, side effects, patients´ satisfaction and occurrence/reasons for treatment discontinuation. The observation period was up to 18years for onabotulinumtoxinA and 29 years for abobotulinumtoxinA with a total of 1778 and 9319 treatment sessions in 69 patients with onabotulinumtoxinA, 281 with abobotulinumtoxin A and 2 of these having used both products. The dose increased in the first years followed by a stable dose in the following years. The mean dose was 39.1/198.7 mouse units (onabotulinumtoxinA/abobotulinumtoxinA). In over 25% of all sessions, inhibition of the eyelid opening was effectively treated with pretarsal injections. The most common adverse events included ptosis (4%/5%), epiphora/sicca (4%/5%), double vision (1%/1%) and facial asymmetry (1%/1%). Reasons for therapy discontinuation were change to a nearby doctor, age, other diseases, spontaneous improvement, side effects or possible treatment failure. Only one patient was tested positive for neutralizing antibodies against botulinum toxin A. The treatment of blepharospasm and Meige's syndrome with onabotulinumtoxinA and abobotulinumtoxinA is safe and effective, also over a long observation period of up to 29years.

A cross-sectional structured survey of patients receiving botulinum toxin type A treatment for blepharospasm

PurposeTo compare the efficacies and safeties of Meditoxin® (Medy-Tox, Korea) and Botox® in the treatment of essential blepharospasm.MethodsWe performed a double-blind, randomized, comparative trial comparing Meditoxin® and Botox® for treatment of blepharospasm in 60 patients from the intention-to-treat (ITT) population and 52 patients from the per-protocol (PP) population. We analyzed the improvements in severity of spasm (SS) at four weeks post-injection as a primary efficacy outcome. Changes in eyelid closing force (CF) and functional visual status (FVS) after injection were analyzed for secondary efficacy outcomes, and adverse effects were demonstrated for the safety evaluation.ResultsImprovement in SS was noted in 90.3% of the Meditoxin® group and 86.2% of the Botox® group. There were no significant differences between treatment groups in the changes of CF and FVS post-injection (p>0.05). Since the lower limit of the 95% confidence interval (-1.76% for ITT, -1.64% for PP) was over the -15% threshold, we determined that Meditoxin® was not inferior to Botox® in either the ITT or PP populations. Adverse effects developed in 16.1% of the Meditoxin® group and 27.6% of the Botox® group, but no serious adverse events were found in either group.ConclusionsMeditoxin® and Botox® were comparable in efficacy and safety in the treatment of essential blepharospasm.

To evaluate the long-term effect of botulinum toxin type A (BTX) in the treatment of blepharospasm, a retrospective analysis was conducted from the patients seen at the Movement Disorders Clinic of the Department of Neurology, Hospital das Clínicas, University of São Paulo School of Medicine from 1993 to 2003. A total of 379 treatments with BTX were administered to 30 patients with blepharospasm. Sixty six per cent of the subjects had used oral medication for dystonia and only 15% of them reported satisfactory response to this treatment. Ninety three per cent of the patients showed significant improvement after the first BTX injection. There was no decrement in response when compared the first and the last injection recorded. Adverse effects, mostly minor, developed at least once in 53% of patients. Six patients (20%) discontinued the treatment but there was no case of secondary resistance.

Blepharospasm and hemifacial spasm are the two most common movement disorders that affect the facial muscles. Despite having different pathophysiological mechanisms, both disorders produce involuntary eyelid closure due to contractions of the orbicularis oculi muscle. The treatment of blepharospasm and hemifacial spasm most often involves the use of botulinum toxin. Although only a few double-blind, placebo-controlled studies exist, botulinum toxin injections have been accepted as a safe and efficacious treatment modality for these disorders. Complications include ptosis, blurred vision, diplopia, facial weakness and other minor side effects that usually improve in days to weeks. A large body of evidence supports the use of botulinum toxin as a first-line treatment for blepharospasm and hemifacial spasm. This review aims to present an update on the treatment of blepharospasm and hemifacial spasm with botulinum toxin type A. (Archives of Neuropsychiatry 2010; 47 Supplement: 6-10)

In this chapter a case series is described of the use of botulinum A toxin for the treatment of blepharospasm in thirty-nine patients with blepharospasm due to various causes—essential, Meige’s syndrome, hand apraxia, cerebrovascular disease, and parkinsonism. A reduction of abnormal movement occurred in all patients, lasting up to 170 days. Both the amount and the duration of effect were dose dependent. Tearing, dry-eye symptoms, or transient ptosis occurred in 20% of injections, especially in patients who had had previous eyelid surgery. Botulinum A toxin injection into the orbicularis oculi muscle was found to be a safe, simple, and symptomatically helpful treatment for blepharospasm that can be repeated at intervals as required.

Studies on focal dystonia showed that the formulations of botulinum toxin type A, incobotulinumtoxin-A (Inco-BTA) and onabotulinumtoxin-A (Ona-BTA), have equivalent efficacy and safety. To carry-out a cost-utility analysis of Inco-BTA administered on flexible intervals vs. Ona-BTA on a fixed interval, in the treatment of blepharospasm and cervical dystonia. A probabilistic Markov model was designed to estimate costs (euros, 2017) and benefits (quality-adjusted life years, QALY), from the Spanish National Health Service perspective and on a 5-year time horizon, of treatment of blepharospasm and cervical dystonia with Inco-BTA (6-12 month flexible intervals) versus Ona-BTA (12-month fixed intervals). It is assumed that symptoms will re-emerge some time later in both options. Result was expressed as incremental cost-utility ratio (ICUR). Inco-BTA and Ona-BTA costs were 3,742 and 3,366 euros respectively, in blepharospasm, and 6,673 and 6,419 euros in cervical dystonia. Patients treated with Inco-BTA remained asymptomatic for 22.12, and 21.34 more weeks than those treated with Ona-BTA, leading in 3.040 and 3.012 QALY, respectively, in blepharospasm, and 3.471 and 3.401 QALY, respectively, in cervical dystonia. Differences showed statistical significance in all cases. ICUR was estimated as 13,576 and 4,158 euros/QALY in blepharospasm and cervical dystonia, respectively. Treatment of blepharospasm and cervical dystonia with Inco-BTA is a cost-effective therapeutic alternative in Spain, based on the flexibility of their administration.

To observe the efficacy of the combined treatment of carbamazepine and botulinum toxin A for blepharospasm and hemifacial spasm. Fifty-eight patients with either blepharospasm or hemifacial spasm were randomly divided into treatment and control groups. In the treatment group, 30 patients were administered with local intramuscular injections of botulinum toxin A and oral carbamazepine 100 mg/time, 3 times a day for 60 days. Twenty-eight subjects in the control group underwent local intramuscular injections of botulinum toxin A only. After combined treatment, the complete remission rate was 90%, which was significantly higher than that of the of the control group (67.9%, P<0.05, X2=4.733). However, no statistical significance was noted regarding the duration of therapeutic effects between the treatment group (range 14~40 weeks; 19.2 weeks on average) and control group (range 12~36 weeks; 18 weeks on average). The combined therapy of carbamazepine and topical injections of botulinum toxin A had increased efficacy in the treatment of blepharospasm or hemifacial spasm, but had no significant effect in terms of the duration of the therapeutic effect.

Objective: To evaluate the efficacy and safety of nerve loop blocking in the treatment of blepharospasm caused by Meige syndrome. Methods: It was a retrospective case series study. Patients with Meige syndrome characterized by blepharospasm or blepharospasm-oromandibular dystonia who underwent nerve loop blocking in the Ophthalmology Department of Henan No. 3 Provincial People's Hospital from April 2018 to January 2020 were included. Before and after surgery, blepharospasm was graded, and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to score the symptoms of ocular and oral dystonia. The improvement rate of ocular spasm was calculated after surgery according to the scores. The postoperative complications were observed. The Wilcoxon rank test was used to compare the BFMDRS movement subscale scores before and after surgery. The independent sample Mann-Whitney U test was used to compare the improvement rates of eye spasm between male and female patients and between patients with and without combined oromandibular dystonia. Results: Among the 199 patients included, 64 (32.2%) were males, and 135 (67.8%) were females, aged 58 (51, 64) years (22-79 years). The postoperative follow-up period was 24 (21, 28) months. Preoperatively, blepharospasm was graded as grade 3 in 12 patients (6.0%) and grade 4 in 187 patients (94.0%), while the postoperative blepharospasm grades were grade 0 in 100 patients (50.3%), grade 1 in 64 patients (32.2%), grade 2 in 31 patients (15.6%), and grade 3 in 4 patients (2.0%). There was statistically significant difference in the BFMDRS scores of ocular dystonia before and after surgery [8.0 (8.0, 8.0) vs. 0.0 (0.0, 1.0); Z=-12.41, P<0.001]. The improvement rate of blepharospasm in all patients was 100% (87.5%, 100%), ranging from 43.8% to 100%, with no statistically significant difference between patients of different genders and between patients with and without combined oral dystonia (both P>0.05). Statistically significant difference existed in the scores of oral dystonia before and after surgery [2.0 (0.5, 4.5) vs. 1.0 (0.5, 2.0); Z=-4.38, P<0.001], with 25 of 65 patients (38.5%) having their oral symptoms improved. Postoperative complications included eyelid valgus (7.5%, 15/199), frontal numbness (100%, 199/199) and tearing (89.9%, 179/199). Conclusion: Nerve loop blocking is a relatively safe and effective method in the treatment of blepharospasm symptoms of Meige syndrome.

Blepharospasm (BS) is one of the diseases characterized exclusively by involuntary face movements (facial hyperkinesis). Typical clinical manifestations include squinting or increased blinking. Among frequent patients’ complains at the disease onset are unpleasant irritations, a foreign body sensation, itching, dry eyes, and frequent blinking. Dynamism is a typical BS feature: 1) it increases during emotional stress, in stressful situations, during fatigue, eye strain (reading), in bright light; 2) disappears while sleeping; 3) decreases after waking up; 4) «corrective gestures», such as touching skin of the eyelids, paraorbital regions and glabellar region, wearing glasses, chewing or absorbing sweets, other arbitrary movements, affect BS. Botulinum therapy (botulinum toxin type A (BtA) injections, in particular using Relatox, the effectiveness of which has been demonstrated in clinical studies) is considered the «gold standard» in BS treatment. BtA is injected mainly into the orbicular muscle of eye, superficially, into the upper, lower eyelids and outer eye corner. The clinical effect occurs quickly, already in the first week after injection and lasts 3 months or more. Cases of botulinum therapy inefficiency in treating BS and other facial hyperkinesis are extremely rare.The article describes BS main clinical aspects, BtA injection schemes as well as adverse events during the therapy. Electromyography is not mandatory to assess BtA effectiveness in BS treatment, but it is necessary in cases of inefficient therapy, adverse events or the therapy complications. It is particularly important to strictly comply with recommended BtA doses, and that the drug is injected by a certified specialist only. Botulinum therapy for BS patients is a highly effective and, in most cases, the only treatment with a good safety profile.

Objective To observe the treatment efficacy of blepharospasm in children. Methods The data of 240 eyes of 120 cases with blepharospasm from May 2016 to Apr.2017 were collected. The optical history, symptom, visual acuity, refraction, Schirmer Ⅰtest(SIT), fluorescent staining(FL) and break-up time(BUT) were observed.All cases received application of recombinant bovine basic fibroblast growth factor(r-bFGF) eye-gel combined with warm compress to the lid.Compound tropicamide eye drops was applied to children with myopia.The followed up time was half a year. Results According to the degree of blepharospasm, 13 cases were grade Ⅰ, grade Ⅱ in 88 cases, and grade Ⅲ in 19 cases. There were 60 cases with myopia, 6 cases with astigmatism, and 3 cases with amblyopia. SIT were≤10 mm in 77 cases, BUT were<10 s in 73 cases, and FL were positive in 23 cases.After treatment, 91 cases had complete remission, 29 cases had partial remission, and the efficiency rate was 100%. Conclusion Dioptroscopy should be performed on children with blepharospasm, and half of the children with ametropia. Application of r-bFGF eye-gel combined with warm compress to the lid for the treatment of children with blepharospasm are effective. Key words: Blepharospasm, children; r-bFGF eye-gel; Ametropia; Treatment