Difficulties with differentiating botulinum toxin treatment effects in essential blepharospasm

Blepharospasm is a focal dystonia in which the extraocular muscles contract repetitively, leading to excessive blinking and forced eyelid closure. Botulinum toxin type A (BoNTA) is the primary symptomatic treatment for blepharospasm and its effects have been evaluated using numerous rating scales. The main scales in use today were initially used to determine whether BoNTA treatment was superior to placebo, and most controlled trials have confirmed this. More recently, these scales have been used to determine whether there are efficacy differences between different BoNTs in blepharospasm. However, although the scales used in these trials are able to differentiate the effects of BoNT from placebo, they may not be sensitive enough to differentiate between BoNTs. Most of the scales include only four possible points for each item, which would necessitate a 25% greater improvement in one group than the other to detect any differences. Current scales are also relatively insensitive to patients with mild disability who may experience mainly psychosocial problems related to their blepharospasm. Clinical trials comparing BoNTs that include substantial numbers of mildly affected patients may be unlikely to find differences because the scales do not adequately measure mild symptoms. Additional challenges with evaluating blepharospasm include the lack of precision and objectivity of current measures, symptom variability, the need to evaluate aspects of the disorder that are most important to patients, and the different types of blepharospasm. Although no single scale may be able to capture all relevant aspects of blepharospasm, more sensitive and patient-centered scales are needed

Low-dose AtropIne for Myopia Control in Children (AIM): protocol for a randomised, controlled, double-blind, multicentre, clinical trial with two parallel arms

IntroductionMyopia is a major cause of degenerative eye disease and increases the risk of secondary visual impairment. Mitigating its progression therefore has great potential of clinically relevant benefit as shown by using highly diluted atropine eye drops in children of Asian origin. However, limited evidence is available regarding the efficacy and safety of low-dose atropine therapy in non-Asian populations. Hence, the Low-dose AtropIne for Myopia Control in Children (AIM) study will test the efficacy and safety of 0.02% atropine vs placebo in a German population.Methods and analysisAIM is a national, multicentre, prospective, randomised, placebo-controlled, double-blind trial with two parallel arms. The primary objective is to assess the efficacy of atropine 0.02% eyedrops for myopia control in children of Caucasian origin. The primary outcome is the change in cycloplegic refraction after 1 year of treatment (D/year). Secondary and tertiary outcome measures comprise the change in axial length (mm/year) in children treated with 0.02% atropine compared with placebo, the myopic progression of participants treated with 0.01% compared with 0.02% atropine (D/year and mm/year), and the safety profile of both 0.02% and 0.01% atropine. Furthermore, the myopic progression 1 year after cessation of therapy with 0.02% atropine will be evaluated. Inclusion criteria are an age of 8–12 years and myopia of −1 D to −6 D with an estimated annual myopia progression of ≥0.5 D. After randomisation, patients will receive either atropine 0.02% (arm A) or placebo eye drops (arm B) in the first year of treatment. In the second year, they will continue to receive atropine 0.02% (arm A) or switch to atropine 0.01% (arm B). In the third year, they will switch to placebo (arm A) or continue with atropine 0.01% (arm B). To achieve a statistical power of 80%, the calculated sample size is 300. The trial has started in October 2021 with a planned recruitment period of 18 months.Ethics and disseminationAIM has been approved by the Central Ethics Committee of the University Medical Center Freiburg (21-1106), local ethics committees of each participating centre and the German Federal Institute for Drugs and Medical Devices (61-3910-4044659). It complies with the Declaration of Helsinki, local laws and ICH-GCP. Results and underlying data from this trial will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberNCT03865160

Botulinum Toxin Therapy in Congenital Blepharospasm

Botulinum toxin injections are the treatment of choice for the management of essential blepharospasm in adults. No cases of congenital blepharospasm have been described in the literature so far, and no cases of botulinum toxin injection in an infant have been reported. A 4-week-old girl was referred to our department with absent eye opening and spasmodically closed eyes. Pregnancy and delivery had been normal. A neuropediatric examination did not reveal useful findings. A periorbital injection of botulinum toxin was performed at the age of 2 months to prevent deprivation amblyopia. Four days later, clearly visible bilateral eye opening and commencement of eye contact were observed. At the age of 3 years, her eyelids remain open and no side effects of botulinum toxin therapy have occurred

Validation of a new hemifacial spasm grading questionnaire (HFS score) assessing clinical and quality of life parameters

Validation of the new hemifacial spasm (HFS) questionnaire 'HFS score' that captures both clinical (HFS clinical) and health-related quality of life (HRQOL) parameters (HFS subjective) in one tool and comparison with a global HRQOL questionnaire. Cross sectional, prospective validation study including 143 subjects (62 HFS patients and 81 healthy volunteers) from the University Eye Hospital Bonn. Patients were interviewed with the new HFS score and the SF-12 questionnaire prior to and 3 weeks after Botulinum neurotoxin A (BoNT-A) injection. All HRQOL-related questions (HFS subjective) were answered on a visual analogue scale (VAS) ranging from 0 (no complaints) to 100% (maximum complaints) by the patients themselves. Reproducibility was tested in a study extension with 10 patients by repeat interviews (telephone/personal). The new HFS score questionnaire provided a reliable clinical assessment and demonstrated that BoNT-A therapy significantly reduced frequency and severity of eye and cheek spasms (p < 0.001; Wilcoxon test). Relevant aspects of HRQOL of HFS patients were assessed with high accuracy and sensitivity. Significant improvements were achieved after BoNT-A injection in five out of eight HRQOL parameters (p ≤ 0.02; Wilcoxon test). Cronbach's alpha of 0.818 demonstrated good internal consistency. Telephone survey provided comparable results to personal interviews. This new sensitive and specific HFS score seems a reliable instrument to monitor BoNT therapy and customize it to the needs of the individual HFS patient-in clinical studies and daily clinical practice

Periorbital injections of botulinum toxin a: a novel therapeutic option for convergence spasm in neuropsychiatric disorders

Purpose!#!Convergence spasm (CS, spasm of near reflex) is characterized by transient attacks of convergence, miosis and accommodation, often associated with functional neurological disorders. To date, no simple and efficient treatment option is available for CS. This study investigates whether periorbital botulinum toxin injections as used in essential blepharospasm are also a treatment option in these patients.!##!Methods!#!All patients with convergence spasm having been treated with periorbital BoNTA injections in the department of neuro-ophthalmology were identified. Data were extracted from patient files concerning details and subjective effectiveness of botulinum toxin injections and relation to psychiatric or neurological disorders. Patients reporting with a history of closed-head trauma or organic neurologic pathologies possibly causing CS were excluded. A telephone assessment with a standardized questionnaire was performed to evaluate mental health issues as a trigger, as well as the long-term effect and satisfaction with periorbital injections.!##!Results!#!Of 16 patients treated with periorbital botulinum toxin injections for convergence spasm, 9 patients reported depression and/or anxiety disorders ongoing or in the past. A median number of 3 injections (range 1-13) was administered with a variable effect (relief of symptoms) between no effect and effect of up to more than 12 weeks. A longitudinal follow-up revealed ongoing symptoms in five patients.!##!Conclusions!#!Periorbital botulinum toxin injections are less invasive than injections in the medial rectus muscle and can be a bridging therapeutic option in patients with CS. Mental health exploration is important due to psychiatric comorbidity

Ultra-Long-Term Therapy of Benign Essential Blepharospasm with Botulinumtoxin A—30 Years of Experience in a Tertiary Care Center

Aim of this study was to investigate the long-term results of botulinum toxin A (BoNT-A) injections for the treatment of benign essential blepharospasm (BEB) and to report our experience with (ultra-)long-term treatment with onabotulinumtoxin-A. We conducted a retrospective cross-sectional analysis at a university hospital. Patients with BEB and BoNT-A treatment were assigned to the Total Blepharospasm Group, patients with ≥21 onabotulinumtoxin-A injections to the Ona Long-Term Group. The Total Blepharospasm Group (n = 1940) included 33,933 BoNT-A injections. The age of patients at symptom onset was (mean ± SD) 58.0 ± 13.1 years, and 70.4% were female. The Ona long-term group (n = 234) included 10,632 onabotulinumtoxin-A injections. In this group, patients received 45.4 ± 22.9 injections with a mean dose of 22.2 IU ± 0.5. The duration of treatment was 12.6 ± 5.4 years, ranging from 2.9 to 30.0 years. The effect–duration–dose quotient did not change during long-term treatment. The observed side effects were comparable in type and frequency to other studies, even with the (ultra-)long treatment with onabotulinumtoxin-A. Our results, based on one of the largest patient populations and a treatment duration of up to 30 years, impressively demonstrate that onabotulinumtoxin-A is a safe and effective therapy for essential blepharospasm, even in the ultra-long term

Implementing strabismus-specific psychosocial questionnaires in everyday clinical practice: mental health and quality of life in the context of strabismus surgery

Background Strabismus can have a great negative impact on the quality of life and the well-being of affected patients. In the past, these aspects were often neglected and, compared with somatic functioning, placed in the background. The aim of our study is to elicit factors influencing satisfaction with strabismus surgery, quality of life and expectations of surgery in order to better predict who will benefit the most and who may need further support.Methods We made a selection of suitable questionnaires to assess psychosocial aspects of strabismus and decided for Adult Strabismus 20 Questionnaire, Amblyopia and Strabismus Questionnaire, Diplopia Questionnaire, Expectations of Strabismus Surgery Questionnaire and Hospital Anxiety and Depression Scale. We then translated these measures (if not available in German). The patients filled out these forms as part of their preoperative orthoptic and ophthalmological assessment as well as approximately 3 months after strabismus surgery.Results We enrolled 59 patients in this study. Postoperative strabismus-related quality of life was higher after surgery and anxiety and depression levels were lower. Satisfaction with surgery was lower with higher postoperative angle and diplopia; the latter was also a determinant of lower postoperative quality of life. Higher expectations of strabismus surgery were present with higher depression levels and higher preoperative strabismus angle.Conclusion Our data indicate that strabismus surgery may cause a significant improvement in several psychosocial domains. There is evidence that psychosocial factors can have significant impact on expectations with surgery. Hence, it is important to consider mental health aspects of this disease in order to treat patients in the best possible way

Depression in blepharospasm: a question of facial feedback?

Depression is the most important nonmotor symptom in blepharospasm (BL). As facial expression influences emotional perception, summarized as the facial feedback hypothesis, we investigated if patients report fewer depressive symptoms if injections of botulinum neurotoxin (BoNT) include the "grief muscles" of the glabellar region, compared to treatment of orbicularis oculi muscles alone. Ninety BL patients were included, half of whom had BoNT treatment including the frown lines. While treatment pattern did not predict depressive symptoms overall, subgroup analysis revealed that in male BL patients, BoNT injections into the frown lines were associated with remarkably less depressive symptoms. We hypothesize that in BL patients presenting with dystonia of the eyebrow region, BoNT therapy should include frown line application whenever justified, to optimize nonmotor effects of BoNT denervation

Depression in blepharospasm: a question of facial feedback?

Depression is the most important nonmotor symptom in blepharospasm (BL). As facial expression influences emotional perception, summarized as the facial feedback hypothesis, we investigated if patients report fewer depressive symptoms if injections of botulinum neurotoxin (BoNT) include the "grief muscles" of the glabellar region, compared to treatment of orbicularis oculi muscles alone. Ninety BL patients were included, half of whom had BoNT treatment including the frown lines. While treatment pattern did not predict depressive symptoms overall, subgroup analysis revealed that in male BL patients, BoNT injections into the frown lines were associated with remarkably less depressive symptoms. We hypothesize that in BL patients presenting with dystonia of the eyebrow region, BoNT therapy should include frown line application whenever justified, to optimize nonmotor effects of BoNT denervation