Treatment Of Blepharospasm Research Articles

Botulinum Toxin in Movement Disorders: An Update.

Since its initial approval in 1989 by the US Food and Drug Administration for the treatment of blepharospasm and other facial spasms, botulinum toxin (BoNT) has evolved into a therapeutic modality for a variety of neurological and non-neurological disorders. With respect to neurologic movement disorders, BoNT has been reported to be effective for the treatment of dystonia, bruxism, tremors, tics, myoclonus, restless legs syndrome, tardive dyskinesia, and a variety of symptoms associated with Parkinson’s disease. More recently, research with BoNT has expanded beyond its use as a powerful muscle relaxant and a peripherally active drug to its potential central nervous system applications in the treatment of neurodegenerative disorders. Although BoNT is the most potent biologic toxin, when it is administered by knowledgeable and experienced clinicians, it is one of the safest therapeutic agents in clinical use. The primary aim of this article is to provide an update on recent advances in BoNT research with a focus on novel applications in the treatment of movement disorders. This comprehensive review of the literature provides a critical review of evidence-based clinical trials and highlights recent innovative pilot studies.

Botulinum toxin as a treatment for blepharospasm

Botulinum toxin as a treatment for blepharospasm

Duration of effect of incobotulinumtoxinA for the treatment of blepharospasm in botulinum toxin-naïve subjects: Results from a Phase III study

Duration of effect of incobotulinumtoxinA for the treatment of blepharospasm in botulinum toxin-naïve subjects: Results from a Phase III study

IncobotulinumtoxinA for the Treatment of Blepharospasm in Toxin-Naïve Subjects: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Trial.

This study aimed to assess the efficacy/safety of incobotulinumtoxinA (Xeomin®, Merz Pharmaceuticals GmbH) in botulinum neurotoxin-naïve subjects with blepharospasm. Botulinum neurotoxin-naïve subjects (≥ 12months without botulinum neurotoxin treatment for blepharospasm) received single-dose incobotulinumtoxinA 50 U, 25U, or placebo. Subjects were followed for 6-20weeks (main period). Qualified subjects entered an open-label extension period and received another incobotulinumtoxinA injection (≤ 70 U). The primary efficacy variable was change from baseline in the Jankovic Rating Scale (JRS) severity subscore at the main period of week 6. Other efficacy variables included changes in the Blepharospasm Disability Index score and JRS frequency subscore and sumscore. Adverse events were monitored. Sixty-one subjects were randomized (main period: incobotulinumtoxinA 50 U, n = 19; incobotulinumtoxinA 25 U, n = 22; placebo, n = 20); 39 entered the open-label extension period (9, 14, and 16 subjects from the incobotulinumtoxinA 50 U, incobotulinumtoxinA 25 U, and placebo groups [main period], respectively, changed to open-label extension period dosing). A statistically significantly greater reduction in JRS severity subscore was reported for subjects receiving incobotulinumtoxinA 50 U versus placebo (ANCOVA, least square mean difference: -1.2, p = 0.0004). Subjects receiving incobotulinumtoxinA experienced improvements in other efficacy variables versus baseline and/or placebo. Sustained clinical improvements and low adverse event rates (22.2-42.1%) were observed. This is the second placebo-controlled, double-blind study that demonstrates favorable efficacy/safety of incobotulinumtoxinA in subjects with blepharospasm. IncobotulinumtoxinA is the first botulinum neurotoxin that could fulfill the American Academy of Neurology criteria for a Level A recommendation for blepharospasm.Trial registration ClinicalTrials.gov identifier, NCT01896895.

Botulinum toxin for benign essential blepharospasm: A systematic review and an algorithmic approach.

Currently, there is no standardised approach for benign essential blepharospasm treatment with botulinum toxin, and controversies still exist regarding this subject. The objective of this systematic review is to summarise and compare all the published data regarding benign essential blepharospasm treatment with botulinum toxin. On October 3, 2018, an online search of the Medline database was conducted. All articles with a detailed description of their botulinum toxin injection technique for benign essential blepharospasm were included in this review. Five studies were selected for inclusion with a total of 854 patients. Four of the included studies used onabotulinumtoxin A and one study used abobotulinumtoxin A. All studies injected the pretarsal orbicularis occuli muscle. The preseptal orbicularis occuli was injected in four studies, and the preorbital muscle in three studies. The most commonly used method of evaluation was the Jankovic Rating Scale. Adverse events were transient, and dose related. Ptosis was more frequently encountered with the preseptal orbicularis injections. Botulinum toxin injection for benign essential blepharospasm is a non-invasive and safe procedure.The pretarsal muscle should be considered as the key component when treating benign essential blepharospasm with botulinum toxin.We developed an algorithmic approach to the treatment of benign essential blepharospasm with botulinum toxin.However,further randomised controlled trials are warranted.

Efficacy of a Non-invasive Cosmetic Forcible Trick Treatment for Blepharospasm: Increase in Quality of Life Due to Use of Ultra-thin Adhesive Tape

Efficacy of a Non-invasive Cosmetic Forcible Trick Treatment for Blepharospasm: Increase in Quality of Life Due to Use of Ultra-thin Adhesive Tape

FDA Approvals and Consensus Guidelines for Botulinum Toxins in the Treatment of Dystonia.

In 2016, the American Academy of Neurology (AAN) published practice guidelines for botulinum toxin (BoNT) in the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache. This article, focusing on dystonia, provides context for these guidelines through literature review. Studies that led to Food and Drug Administration (FDA) approval of each toxin for dystonia indications are reviewed, in addition to several studies highlighted by the AAN guidelines. The AAN guidelines for the use of BoNT in dystonia are compared with those of the European Federation of the Neurological Societies (EFNS), and common off-label uses for BoNT in dystonia are discussed. Toxins not currently FDA-approved for the treatment of dystonia are additionally reviewed. In the future, additional toxins may become FDA-approved for the treatment of dystonia given expanding research in this area.

Treatment of Blepharospasm and Oromandibular Dystonia with Botulinum Toxins.

Blepharospasm and oromandibular dystonia are focal dystonias characterized by involuntary and often patterned, repetitive muscle contractions. There is a long history of medical and surgical therapies, with the current first-line therapy, botulinum neurotoxin (BoNT), becoming standard of care in 1989. This comprehensive review utilized MEDLINE and PubMed and provides an overview of the history of these focal dystonias, BoNT, and the use of toxin to treat them. We present the levels of clinical evidence for each toxin for both, focal dystonias and offer guidance for muscle and site selection as well as dosing.

Specificity of using botulinic toxin type A for blepharospasm treatment

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.

Long-term treatment of blepharospasm with botulinum toxin A: a service-based study over a 16-year follow-up in southern China.

To elucidate the effect of long-term treatment with botulinum toxin A (BTX-A) for blepharospasm. Prevalence data and clinical features in southern China and influencing factors for selecting BTX-A treatment were explored. We collected data retrospectively from 338 consecutive patients diagnosed with blepharospasm over 16 years to assess prevalence data and clinical features. Thereafter, all patients were classified into BTX-A (n = 135) or non-BTX-A (n = 203) treatment groups according to the patients' requests in order to explore the factors influencing whether BTX-A treatment was chosen. Furthermore, dynamic follow-up data were analyzed to evaluate the long-term efficacy in the BTX-A group. The prevalence was 23.3 per million, with an onset age of 50.3 ± 12.3 years and a female:male ratio of 2.4:1; the most common symptom was excessive blinking (91.2%). The symptom severity and psychological assessment scores were significantly decreased by treatment with BTX-A (p < 0.01), and there was no significant difference in response duration with the prolongation of BTX-A injections. Adverse events occurred 52 times (5.0%) among 1038 injections. The symptom severity and psychological assessment scores and the occurrence of eye-opening difficulty were higher, and medical expenses and the symptom tolerability rate were lower in the BTX-A group than in the non-BTX-A group (p < 0.05). The onset age was earlier than that in Western countries. However, starting BTX-A treatment early is justified, even though a higher dosage was needed to maintain reliable long-term efficacy. Additionally, symptom severity and medical expenses are the primary factors affecting whether patients select BTX-A treatment.

Dry eye syndrome in benign essential blepharospasm

To determine the significance of dry eye syndrome in benign essential blepharospasm. Retrospective consecutive case series. One hundred and forty-four patients (288 eyes) with benign essential blepharospasm. All subjects had Schirmer I tear tests. Those scores were analysed as a function of patient age, sex, and blepharospasm severity. Individual Schirmer-test scores in both eyes of all patients. A total of 144 eligible subjects (mean age±SD: 68.3±11.5 years; 76% females) were evaluated. Benign essential blepharospasm was significantly associated with female sex (P=0.0044). The mean Schirmer-test value was 5.9±7.5 (median: 2.5) mm; it was <15mm for 86.8% of the patients and <10mm for 75%, with no difference observed between men and women (P=0.27). Dry-eye syndrome severity was not correlated with age at diagnosis, for men (r=-0.22, P=0.22) or women (r=-0.067, P=0.49), or benign essential blepharospasm severity (P=0.15), but was strongly associated with benign essential blepharospasm independently of age, sex or blepharospasm intensity. Dry-eye syndrome and benign essential blepharospasm are strongly linked, independently of age, sex or BEB severity, and should be considered for the diagnosis of benign essential blepharospasm. The useful symptomatic treatment of dry eye will not cure the blepharospasm or the ocular pain, and specific treatment for blepharospasm is required, i.e., quarterly injections of botulinum toxin A into the orbicularis oculi muscle.

Treatment of blepharospasm and Meige's syndrome with abo- and onabotulinumtoxinA: long-term safety and efficacy in daily clinical practice.

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 trial of a mechanical device for the treatment of blepharospasm.

Idiopathic blepharospasm (IB) is a rare but well-characterised adult onset focal dystonia that may cause severe visual disability. The most effective treatment is with periodic injections of botulinum toxin (BTX) into the pre-tarsal and/or pre-septal orbicularis oculi muscles bilaterally. However, even with treatment, practical visual function often remains compromised. A subset of IB sufferers find that eye opening improves with a focal unilateral digital pressure usually on a specific point on the temple. This is known as a 'sensory trick'. We have developed a spectacle mounted device ('Pressop') to apply continuous individually localised focal pressure on the temple to mimic the effect of finger pressure. The aim of the study was to determine if the 'sensory trick' could be replicated by Pressop and if the interval between BTX treatments could thereby be extended. Study participants had three clinic visits-an initial screening assessment, a visit 2 weeks before the next injection was due when the device was fitted, and one 2 weeks later to assess the response to Pressop. A CDQ 24 and device-specific feedback questionnaire were completed and comparison photographs were taken. Repeat BTX injections were administered at the third visit. Of 58 patients with typical IB recruited to the trial, 39 reported an effective focal finger pressure sensory trick. 56 completed the trial, more than 50% of whom reported some benefit using Pressop; 18% had substantial improvement, sustained for up to 5 years. Improvement could occur in those without an effective sensory trick, therefore there was no significant correlation between using a sensory trick and benefiting from 'Pressop'. There was a trend towards the responders having greater improvement in CDQ24 total score than non-responders but this was not statistically significant. We recommend a trial of this simple safe device as a means of augmenting visual function in all IB patients.

Long-term Safety and Efficacy of IncobotulinumtoxinA for the Treatment of Blepharospasm in Botulinum Toxin-naïve Subjects: Results of a Phase III Study (S28.005)

Long-term Safety and Efficacy of IncobotulinumtoxinA for the Treatment of Blepharospasm in Botulinum Toxin-naïve Subjects: Results of a Phase III Study (S28.005)

Efficacy of EMLA Cream in Pain Reduction during Botulinum Toxin Injections for Facial Dystonias

Purpose: To determine the efficacy of EMLA cream (Eutectic Mixture of Local Anesthetics) in pain reduction while injecting botulinum toxin in patients with hemifacial spasm and blepharospasm. Study Design: Quasi Experimental Study. Place &amp; Duration of Study: Yaqin Vision Eye center from January 2015 to December, 2018. Material &amp; Methods: Patients undergoing routine treatment of Blepharospasm and Hemifacial spasm since 2010 were offered pre-injection EMLA cream application to reduce the pain during injections. A total of 74 Botulinum A toxin injections were given for blepharospam and hemifacial spasm, half of which were administered without the use of any topical analgesia while other half were given to same patient on next visit using EMLA cream 15 minutes prior to injection. Pain was assessed as mild, moderate and severe in all the patients by the consultant administering the medication. Results: Among 37 cases of facial dystonias, 17 (45.9%) were males and 20 (54.1%) were females. It was observed that when EMLA was not used, severe pain was observed during 8 injections (21.6%), moderate pain in 17 (45.9%), and mild pain in 12 (32.4%) sessions. However when EMLA was used mild pain was observed during 33 (89.2%) injections, moderate pain in 3 injections and severe pain in 1 (2.7%) case. There was a statistically significant difference in pain control during the sessions involving use of EMLA. Conclusion: Use of topical EMLA cream dramatically reduces the pain and makes the administration of botulinum toxin A injection easier in patients with hemifacial spasm and blepharospasm. Keywords: Topical anesthetia, Blepharospasm, Hemifacial spasm, Botulinum Toxin.

Kurcz powiek – od rozpoznania do właściwego leczenia

Background: Blepharospasm is a movement disorder characterized by involuntary spasms of eye-closing muscles. This second most common adult-onset focal dystonia still raises many doubts among ophthalmologists and neurologists. Aim of the study: To present current knowledge about blepharospasm with historical background of the disease. Methods: Literature review regarding diagnosis, pathophysiology and treatment of blepharospasm. Results: Different types of eye-closing spasms, the spread of dystonia, co-occurrence of eyelid opening apraxia, enhanced blinking, sensory trick and psychiatric disorders define blepharospasm as a heterogeneous condition. Actual genetic, electrophysiological and neuroimaging studies reveal complex and multifocal involuntary movements generators defining blepharospasm and other focal dystonias as a ”communication node disorders” where botulinum toxin acting at the end of all pathways is the first-line treatment. Conclusions: The history of blepharospasm as a neurological condition that affects the eye shows that the most important discoveries regarding the diagnosis, pathophysiology and treatment of this disease have occurred owing to ophthalmologists and neurologists. Therefore, the future of blepharospasm will also depend on this cooperation.

The History of Botulinum Toxins in Medicine: A Thousand Year Journey.

Botulinum toxin is one of the most potent and deadliest substances on earth. Because of its unique mechanism of action at the synaptic junction and the ability to precisely deliver the toxin locally to where it is needed, botulinum toxin has been used as an effective treatment for a plethora of diseases from head to foot, from chronic migraine to ankle spasticity. Unlike systemic drugs, botulinum toxin is delivered by injection to the site of disease. As we will see from the history of botulinum toxin, the ability to deliver the drug locally to minimize the amount of botulinum toxin needed and thereby minimizing systemic exposure has been key to its medical utility. Botulinum toxin was first approved by the US Food and Drug Administration in 1989 for the treatment of blepharospasm and strabismus, but the history starts long before this, with outbreaks of food poisoning in the tenth century. Importantly, the development of botulinum toxins for medical use continues today with the engineering of novel toxins to treat disease.

Duration of effect of incobotulinumtoxinA for the treatment of blepharospasm in botulinum toxin–naive subjects: Results from a phase 3 study

Duration of effect of incobotulinumtoxinA for the treatment of blepharospasm in botulinum toxin–naive subjects: Results from a phase 3 study

Long-term safety and efficacy of incobotulinumtoxinA for the treatment of blepharospasm in botulinum toxin-naive subjects: results of a phase 3 study

Long-term safety and efficacy of incobotulinumtoxinA for the treatment of blepharospasm in botulinum toxin-naive subjects: results of a phase 3 study

Efficacy and Safety of Long-Term Therapy with Type A Botulinum Toxin in Patients with Blepharospasm

ABSTRACTBlepharospasm (BPS) is one of the most frequent types of facial dystonia and, at the same time, one of the most disabling, being able to trigger functional blindness if not treated. Our aim with this work was to evaluate the efficacy and safety of long-term onabotulinum A toxin (BAT) treatment in a cohort of patients with BPS.The retrospective study was conducted on consecutive patients with BPS treated with subcutaneous BAT. The selection of muscles and dose was made based on each patient’s needs. The clinical and demographic characteristics, number of sessions, dose, duration and effectiveness of treatment, and adverse events were analysed.130 patients were included in the study. The median (95% confidence interval) length of follow-up was 14 (13–15.6) years with an average of 20.5 sessions (range from 10 to 57). Regarding the efficacy of the treatment, 114 (87.7%) experienced satisfactory results with functional and aesthetics recovery. Patient evaluation of global response suggested a clear improvement without adverse events in 72 (55.4%) patients. Adverse events developed at least once during the treatment in 39% of patients, with transient ptosis and haematoma the most common reported both by physician and patient.The results of our study suggest that botulin toxin A is a safe and effective long-term treatment for blepharospasm with mild, transient and well-tolerated side effects when they appear.