Efficacy and Safety of Letibotulinum Toxin A for the Treatment of Essential Blepharospasm

PURPOSE: To evaluate the efficacy and safety of BOTULAX® in subjects with essential blepharospasm.METHODS: In this study, a total of 250 subjects with essential blepharospasm were enrolled at 15 investigational sites and a total of 220 subjects completed the study. The efficacy and safety were evaluated at weeks 4 and 16 after treatment compared with baseline. In total, 240 subjects were enrolled, treated with the investigational product, and evaluable for the primary efficacy assessment at week 4 after treatment; these subjects were included in the intention-to-treat (ITT) population. With the ITT set as the main efficacy set, efficacy assessment included Jankovic rating scale (JRS), functional disability score, investigator evaluation of global response and quality of life. Safety assessment including the incidence of adverse events was also performed.RESULTS: In terms of the primary efficacy endpoint (i.e., change in JRS total score at week 4 after treatment from baseline [ITT set]), mean change indicated a statistically significant reduction (p < 0.0001) and demonstrated the non-inferiority of the test drug to similar drugs. In terms of the secondary efficacy endpoints, mean change in JRS total score at week 16 after treatment and mean change in functional disability score at weeks 4 and 16 after treatment both exhibited a statistically significant reduction compared with baseline (p < 0.0001 for all). Among the 249 subjects treated with the investigational product in this study, 44 (17.67%) experienced 76 treatment emergent adverse events but no serious adverse events were observed.CONCLUSIONS: Based on the study results, BOTULAX® is considered to be an effective and safe treatment for essential blepharospasm.

Clinical Features of Benign Essential Blepharospasm in Korean Patients

PURPOSE: To analyze the clinical features of benign essential blepharospasm in Korean patients. METHODS: Patients diagnosed with benign essential blepharospasm in Kim's Eye Hospital from November 2014 to December 2016 were evaluated using a clinical examination and questionnaire. The questionnaire reviewed personal medical history, demographic factors, risk factors for blepharospasm development, and relieving and aggravating factors. RESULTS: Of the 101 patients enrolled, 78 (77.2%) were women. The mean age was 64.9 years old. Hypertension was the most common medical disorder (42.6%), followed by diabetes mellitus. The majority of the patients were non-smokers (83.2%) and drank less than a cup of a caffeinated beverage a day (30.7%). Fifty-seven percent of patients reported no stressful events immediately prior to symptom development. Fatigue and stress were aggravating factors in more than 55% of patients; rest was the most common relieving factor (35.6%). CONCLUSIONS: Here, we report the clinical features of benign essential blepharospasm in Korean patients for the first time. The results were consistent with previous reports showing that the majority of benign essential blepharospasm patients are women and non-smokers. In contrast to previous reports though, fatigue and stress were aggravating factors, and the most common relieving factor was rest. No stressful events had immediately preceded the development of blepharospasm in 57.4% of patients. This report may aid in treating and counseling patients with benign essential blepharospasm.

Comparative Study of Hugel-tox(R) versus Botox(R) for the Treatment of Essential Blepharospasm

PURPOSE: To compare clinical efficacy and duration of Hugel-tox(R) (also known as Botulax(R)) and Botox(R) for the treatment of essential blepharospasm. METHODS: A total of 48 patients who were injected with Hugel-tox(R) (17 females, 7 males) or Botox(R) (18 females, 6 males) from February 2013 to October 2013 were enrolled in the present study. Changes in eyelid closing force and Scott grade before and after injection were analyzed. Adverse events were also evaluated. RESULTS: There were no significant differences between the Hugel-tox(R) and Botox(R) groups in clinical efficacy and duration. Before and after injection, changes in Scott grade (Hugel-tox(R): -1.17 +/- 0.70, Botox(R): -1.21 +/- 0.72, p = 0.840), changes in eyelid closing force (Hugel-tox(R): -1.38 +/- 0.58, Botox(R): -1.17 +/- 0.56, p = 0.212) and duration (Hugel-tox(R): 116.08 +/- 22.12 days, Botox(R): 126.92 +/- 38.94 days, p = 0.242) were shown. No serious adverse events were found in either group. CONCLUSIONS: Hugel-tox(R) showed nearly equal efficacy and duration compared with Botox(R).

Clinical Outcomes of Individualized Botulinum Neurotoxin Type A Injection Techniques in Patients with Essential Blepharospasm

PURPOSE: To assess the clinical outcomes following botulinum neurotoxin type A (BoNT-A) treatment with an individualized injection technique based on the types of spasms and to compare the results of the individualized injection technique with those of the conventional injection technique in the same patients. METHODS: From November 2011 to July 2013, 77 BoNT-A injections were performed in 38 patients. Eighteen patients were treated with conventional BoNT-A injections before 2011, and 20 patients were referred to our hospital for unsatisfactory results after a conventional injection technique. We classified the patients by spasm-dominant sites: the lateral orbital area, representing the orbital orbicularis-dominant group (ODG); the glabella, representing the corrugator-dominant group (CDG); and the ptosis, representing the palpebral part of the orbicularis-dominant group (PDG). We increased the injection dose into the spasm-dominant sites of the blepharospasm groups. We assessed subjective symptom scores (functional disability score, FDS) after treatment. RESULTS: This study included 38 patients (26 women, 12 men; mean age, 60.6 +/- 10.9 years). There were 21 patients in the ODG, 10 patients in the CDG, and 7 patients in the PDG. Mean ages were 59.7 +/- 12.6, 59.8 +/- 8.5, and 66.8 +/- 9.0 years, and mean BoNT-A injection dose was 38.8 +/- 11.2, 38.8 +/- 11.2, and 38.8 +/- 10.8 U in each group, respectively (p = 0.44, 0.82 Kruskal-Wallis test). Mean FDS after injection was 1.7 +/- 0.7 in the ODG, 1.4 +/- 0.8 in the CDG, and 1.2 +/- 0.3 in the PDG. There were significant differences in reading and job scale among the three groups. In a comparison between the conventional and individualized injection techniques, there was a significant improvement in mean FDS and in the reading scale in the PDG with the individualized injection technique. The success rate was 92.1% in the conventional injection group and 94.1% in the individualized injection group. CONCLUSIONS: The individualized injection technique of BoNT-A according to the spasm-dominant site is an effective and safe treatment method for essential blepharospasm patients.

Cognitive Function Evaluation by Mini-Mental State Examination-Korea in Essential Blepharospasm

PURPOSE: The present study evaluated cognitive functions of Korean patients with essential blepharospasm by the Mini Mental State Examination - Korea (MMSE-K). METHODS: Atotal of 33 patients diagnosedwith essential blepharospasm were evaluated. Using the K-MMSEcognitive functions such as orientation, registration and recall, attention and calculation, language, comprehension, and decision were evaluated. RESULTS: All patients were alert and orientedwith an average K-MMSEscore of 25.2 +/- 4.0 points. The normal group scores were above 24 points in 25 patients (75%), suspected dementia scores were from 20 to 23 points in 5 patients (15%), and definite dementia scores were from 15 to 19 points in 3 patients (9%). Neurologic and brain imaging evaluation was performed in the 8 patients with suspected dementia or definite dementia. Among these patients, 2 were diagnosed with Parkinson's disease, 2 were shown to have a specific brain lesion on magnetic resonance imaging, and 1 was diagnosed with a stroke and treated with antiplatelet therapy. CONCLUSIONS: The K-MMSE can be a helpful tool for the early detection of cognitive dysfunction in outpatients with essential blepharospasm.

Las distonías craneales en oftalmología / Cranial dystonias in ophthalmology

Las distonías craneales y craneocervicales son enfermedades neurológicas que periódicamente constituyen motivo de consulta en oftalmología, principalmente el blefaroespasmo esencial benigno. Esta afección se caracteriza por contracciones bilaterales, espasmódicas e involuntarias de los párpados. Dentro de las frecuentes manifestaciones oculares asociadas, el síndrome de ojo seco es la más habitual. Estudios recientes sugieren que esta condición pudiera estar implicada en la etiopatogenia de la enfermedad. El manejo de los síntomas y signos provocados por alteración de la superficie ocular es requerido incluso luego de la quimiodenervación con toxina botulínica, que constituye el tratamiento de elección. El beneficio final para los pacientes, derivado de un enfoque multidisciplinario es evidente, por lo que la incorporación activa del oftalmólogo a esta área de trabajo es cada día más necesaria.

Neurological illnesses like cranial and craniocervical dystonias are often cause of consultation in ophthalmology, basically benign essential blepharospasm. This illness is characterized by bilateral involuntary spasmodic contraction of eyelids. Among the common associated ocular manifestations, the dry eye syndrome is the most frequent. Current studies suggest that this condition could be connected with the etiopathogeny of the disease. Most of patients require the treatment of signs and symptoms stemmed from disturbances in the eye surface after the use of chemical denervation with botulinum toxin, which is the therapical choice. It is increasingly clear that the opthalmologist must be part of the multidisciplinary medical team in order to achieve the greatest benefit for these patients.

Double-Blind, Randomized, Comparative Study of Meditoxin(R) Versus Botox(R) in the Treatment of Essential Blepharospasm

PURPOSE: To compare the efficacies and safeties of Meditoxin(R) (Medy-Tox, Korea) and Botox(R) in the treatment of essential blepharospasm. METHODS: We performed a double-blind, randomized, comparative trial comparing Meditoxin(R) and Botox(R) 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. RESULTS: Improvement in SS was noted in 90.3% of the Meditoxin(R) group and 86.2% of the Botox(R) 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(R) was not inferior to Botox(R) in either the ITT or PP populations. Adverse effects developed in 16.1% of the Meditoxin(R) group and 27.6% of the Botox(R) group, but no serious adverse events were found in either group. CONCLUSIONS: Meditoxin(R) and Botox(R) were comparable in efficacy and safety in the treatment of essential blepharospasm.

Clinical Comparability of Dysport and Botox in Essential Blepharospasm

PURPOSE: To compare the clinical efficacy, duration of effect, and safety of Dysport and Botox for patients with essential blepharospasm using functional disability scale. METHODS: Patients with a confirmed diagnosis of essential blepharospasm who had received Botox (Allergan, USA) from September 2006 to May 2007 were enrolled in this study. We switched from Botox to Dysport (Ipsen, UK) after the botulinum effect of previous injection had disappeared and compared the clinical efficacy of two drugs. We used a 2.5:1 Dysport:Botox conversion ratio. The clinical efficacy of the drugs treatment was evaluated using a functional disability scale. We compared the duration of the effect and the safety of the two drugs. RESULTS: The study included 48 patients (43 women, 5 men). There was no significant difference in mean functional disability scores or in any item of the functional disability scale. There was no significant difference in duration of effect between Botox (100.2+/-37.34 days) and Dysport (99.1+/-39.7days). There was also no significant difference in frequency of adverse reaction between Botox (13%) and Dysport (10%). CONCLUSIONS: When a dose conversion of 2.5:1 Dysport:Botox was used for essential blepharospasm patients, the two drugs displayed almost identical clinical efficacy, duration of effect, and safety.

Management of Essential Blepharospasm: Botulinum Toxin A Treatment and Orbicularis Myectomy Operation

To investigate results of treatment with essential blepharospasm, patients were evaluated by results of treatment with botulinum toxin A and myectomy operation. Seventy patients of the essential blepharospasm who received local injection of botulinum toxin or orbicularis muscle extirpative surgery were evaluated according to results and complications of the treatment modality over a 7-year period. Fifty-six patients[80%] were primarily treated with botulinum toxin and 14 patients[20%] underwent myectomy operation as the primary treatment. Of the 56 patients, 8[14.3%] were treated later with myectomy operation. In botulinum toxin treatment, the mean subjective improvement was found in 89.2% of the patients, and the mean effective durations of essential blepharospasm were 12.7 weeks. Severity and frequency grades in eyelid spasm were significantly lower after injection[P=.000]. Tearing, dry eye, and headche were the most frequent complications and ptosis was observed in 2 cases[2.0%]. In the orbicularis myectomy operation, 13 patients[59.1%] were carried out through a brow incisions, 1[4.5%] through a blepharoplasty incisions, and 8[36.4%] through both. Fourteen patients[63.6%] had acceptable control of blepharospasm throughout follow-up after the upper lid orbicularis stripping procedure alone. We believe that botulinum toxin is the treatment of first choice because of its higher acceptance rate. Surgery is reserved for botulinum toxin failure. In otherwise fit patients, myectomy is the treatment of first choice.

Botulinum-Induced Changes in Orbicularis Oculi Muscle

A 60-year-old woman who had essential blepharospasm was treated with botulinum toxin A (two injections) around her orbital regions. The patient experienced reduction of blepharospsam for one month. But involutional blepharoptosis, brow ptosis and dermatochalasis had remained, so she underwent blepharoplasty. The resected orbicularis muscle during blepharoplasty was examined histopathologically. It was suggested that nonselective atrophy of the orbicularis muscles was derived from the loss of the normal neurotrophic influence of nerve on muscle by the botulinum toxin A.

Clinieal Studies in Patients with Essential Blepharospasm and with Hemifacial Spasm

This clinical investigation was undertaken to evluate the patients who had characteristic fearutes of essential blepharospasm and hemifacial spasm during the period from July, 1987 to August, 1990 in this ophthalmological department of Chung Ang University Hospital. The results were as follows; 1) The age onset of essential blepharospasm and hemifacial spasm patients were 51.3 years and 42.7 years, respectively. 2) These patients showed lid spasm, tricks, and lid or brow ptosis as common signs and complained of foreign body sensation, photophobia, and epiphora as main symptons, which were worsened by emotional stress or fatigue. 3) The BUT(tear film break-up time)under 10 seconds were 74.1% in essential blepharospasm, 69.2% in hemifacial spasm, and 55.0% in control but there was no significant difference between these patients and control(p>0.05). The Schirmer test value under 10mm was 69.7%, 66.3%, and 35.0%, respectively and there was significant difference between them(p0.05).

Clinieal Studies in Patients with Essential Blepharospasm and with Hemifacial Spasm

This clinical investigation was undertaken to evluate the patients who had characteristic fearutes of essential blepharospasm and hemifacial spasm during the period from July, 1987 to August, 1990 in this ophthalmological department of Chung Ang University Hospital. The results were as follows; 1) The age onset of essential blepharospasm and hemifacial spasm patients were 51.3 years and 42.7 years, respectively. 2) These patients showed lid spasm, tricks, and lid or brow ptosis as common signs and complained of foreign body sensation, photophobia, and epiphora as main symptons, which were worsened by emotional stress or fatigue. 3) The BUT(tear film break-up time)under 10 seconds were 74.1% in essential blepharospasm, 69.2% in hemifacial spasm, and 55.0% in control but there was no significant difference between these patients and control(p>0.05). The Schirmer test value under 10mm was 69.7%, 66.3%, and 35.0%, respectively and there was significant difference between them(p0.05).

Surgical treatment of essential blepharospasm

Essential blepharospasm is an incurable disease for which many treatment modalities fave been tried. The author has performed the Anderson's muscle stripping procrdure involving the meticulous extirpation of all eyelid protractors and reinrorcement or the retractors in three patients with essential blerharospasm withgratifying results.

Treatment of blepharospasm with botulinum A toxin

Thirty-nine patients with blepharospasm were treated with botulinum A toxin. Twenty-six patients had essential blepharospasm, and thirteen had a hemifacial spasm. A total of 113 injections were given, and the average follow-up was 14.6 months. The mean preinjection spasm intensity was 2.9+ and the mean postinjection spasm intensity was 0.7+. The mean interval between injections was 4.4 months. The treatment was effective, although transient, in all patients with essential blepharospasm and hemifacial spasm. The toxin had a prolonged effect on the patients who had previously undergone muscle stripping procedure. The side effects were mild, transient, and local.