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Alison YY Chan,1,2,* Jasmine C Chuang,1,2,* Victoria WY Wong1– 3 1Hong Kong Eye Hospital, Kowloon, Hong Kong; 2Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong; 3HKU Health System, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong*These authors contributed equally to this workCorrespondence: Victoria WY WongHKU Health System, Li Ka Shing Faculty of Medicine, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong KongEmail drvwong@hotmail.comPurpose: To evaluate the prevalence of meibomian gland dysfunction (MGD) among ophthalmic healthcare workers.Setting: A tertiary ophthalmic center.Design: Prospective, observational study.Methods: Forty-four volunteer ophthalmologists and ophthalmic nurses were recruited. Information including demographics, contact lens wear, history of refractive surgery and symptom score based on Standardized Patient Evaluation of Eye Dryness (SPEED) II Questionnaire for Dry Eye Disease/Ocular Surface Disease were recorded. Lipid layer thickness (LLT), meibomian glands dropout and dilation grades, and proportion of partial blinking were evaluated using an ocular surface interferometer with dynamic meibomian imaging (LipiView, Johnson & Johnson). Based on the chance of MGD, meibomian gland dropout and dilation, selected subjects also underwent treatment with a thermal pulsation system (LipiFlow, Johnson & Johnson) in one or both eyes.Results: Eighty-eight eyes of 44 volunteers were evaluated during the study period. The mean LLT was 60.0nm. Twenty-seven (61.4%) subjects had a 90% or high chance of MGD and their mean lower lid meibomian gland dropout and dilation grades were 1.2 and 1.7, respectively. Twenty-eight eyes of 16 volunteers received treatment with the thermal pulsation system. Following treatment, the mean LLT improved from 50.3nm to 61.0nm (Wilcoxon’s signed rank test, p=0.001).Conclusion: Despite being more knowledgeable to MGD and more accessible to treatment, MGD is a highly prevalent condition among ophthalmic healthcare workers, with a 61.4% prevalence among the recruited subjects. This is similar to reported prevalence in Asian populations of up to 74.5%. Targeted therapy based on dynamic meibomian imaging is effective in improving both objective and subjective measures of MGD.Keywords: meibomian gland dysfunction, lipid layer thickness, dynamic meibomian imaging, thermal pulsation system

Objectives: The aim of this research was to compare the penetration ability of calcium silicate-based sealers (iRoot SP and TotalFill BC HiFlow) and an epoxy resin-based sealer (AH Plus) into the lateral canals using the single-cone (SC) or continuous wave compaction (CW) obturation techniques., Methods: Ninety single-rooted human teeth received canal instrumentation and diaphanisation before artificial lateral canals were created at 3 different root levels. The specimens were randomly allocated into 6 groups based on the combination of obturation technique and sealer used. Radiographic and photographic measurements evaluated the percentage of sealer penetration. Statistical analysis was performed to compare the penetration ability amongst different types of sealers, obturation methods, and root levels., Results: Although TotalFill BC HiFlow sealer combined with the CW technique demonstrated greater sealer penetration at the coronal level (P < .05), the overall penetration ability of iRoot SP, TotalFill BC HiFlow, and AH Plus was not significantly different. The deepest sealer penetration was observed at the apical root level., Conclusions: All sealers showed similar penetration abilities into the lateral canals using the SC or CW techniques in vitro. Calcium silicate-based sealers have comparable penetration ability into lateral canals compared to epoxy resin-based sealers using SC or CW obturation techniques., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In patients with cerebellar ataxia (CA), dual-tasking deteriorates the performance of one or both tasks., Objective: Evaluate the effects of 4 weeks of cognitive-coupled intensive balance training (CIBT) on dual-task cost, dynamic balance, disease severity, number of falls, quality of life, cognition and cost among patients with CA., Methods: This RCT compared CIBT (Group 1) to single-task training (Group 2) among 32 patients with CA. The intervention included either dual-task (CIBT) or single-task training for 4 weeks followed by 6 months of unsupervised home exercises. Dual-task timed up-and-go test (D-TUG) assessed dual-task cost of the physical and cognitive tasks. Assessment time points included baseline 1 (Week 0:T1), baseline 2 (Week 6:T2), post-intervention (Week 10:T3), and follow-up (Week 34:T4)., Results: Compared to single-task training CIBT improved the dual-task cost of physical task [MD -8.36 95% CI (-14.47 to -2.36, p < 0.01), dual-tasking ability [-6.93 (-13.16 to -0.70); p = 0.03] assessed using D-TUG, balance assessed using the scale for the assessment and rating of ataxia (SARAbal) [-2.03 (-4.04 to -0.19); p = 0.04], visual scores of the SOT (SOT-VIS) [-18.53 (-25.81 to -11.24, p ≤ 0.01] and maximal excursion [13.84 (4.65 to 23.03; p ≤ 0.01] of the Limits of Stability (LOS) in the forward direction and reaction time in both forward [-1.11 (-1.42 to -0.78); p < 0.01] and right [-0.18 (0.05 to 0.31); p < 0.01] directions following 4 weeks of training. CIBT did not have any additional benefits in reducing the number of falls, or improving disease severity, quality of life and cognition. The mean cost of intervention and healthcare costs for 7 months was HKD 33,380 for CIBT group and HKD 38,571 for single-task training group., Conclusion: We found some evidence to support the use of CIBT for improving the dual-tasking ability, dual-task cost of physical task and dynamic balance in CA. Future large fully-powered studies are needed to confirm this claim., Clinical Trial Registration: https://clinicaltrials.gov/study/NCT04648501, identifier [Ref: NCT04648501]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Winser, Chan, Whitney, Chen and Pang.)

Background: Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the earliest and most specific prodromes of the α-synucleinopathies including Parkinson's disease (PD). It remains uncertain whether RBD occurring in the context of psychiatric disorders (psy-RBD), although very common, is merely a benign epiphenomenon of antidepressant treatment, or whether it harbours an underlying α-synucleinopathy. We hypothesised that patients with psy-RBD demonstrate a familial predisposition to an α-synucleinopathy., Methods: In this case-control-family study, a combination of family history and family study method was used to measure the α-synucleinopathy spectrum features, which included RBD, neurodegenerative prodromal markers and clinical diagnoses of neurodegenerative disorders. We compared the risk of α-synucleinopathy spectrum features in the first-degree relatives (FDRs) of patients with psy-RBD, psychiatric controls and healthy controls., Results: There was an increase of α-synucleinopathy spectrum features in the psy-RBD-FDRs, including possible and provisional RBD (adjusted HR (aHR)=2.02 and 6.05, respectively), definite RBD (adjusted OR=11.53) and REM-related phasic electromyographic activities, prodromal markers including depression (aHR=4.74) and probable subtle parkinsonism, risk of prodromal PD and clinical diagnosis of PD/dementia (aHR=5.50), as compared with healthy-control-FDRs. When compared with psychiatric-control-FDRs, psy-RBD-FDRs consistently presented with a higher risk for the diagnosis and electromyographic features of RBD, diagnosis of PD/dementia (aHR=3.91) and risk of prodromal PD. In contrast, psychiatric controls only presented with a familial aggregation of depression., Conclusion: Patients with psy-RBD are familially predisposed to α-synucleinopathy. The occurrence of RBD with major depression may signify a subtype of major depressive disorders with underlying α-synucleinopathy neurodegeneration., Trial Registration Number: NCT03595475., Competing Interests: Competing interests: JW: Supported by the Faculty Postdoctoral Fellowship Scheme of the Chinese University of Hong Kong and the International Postdoctoral Exchange Fellowship Program (YJ20220085). She is currently a Principal Investigator, funded by the China Postdoctoral Science Foundation (2022M720913). The Chinese University of Hong Kong reimbursed the airfare and registration fee for attending an international academic conference in 2019. BH: Supported by the Faculty Postdoctoral Fellowship Scheme of the Chinese University of Hong Kong. The Chinese University of Hong Kong reimbursed the airfare and registration fee for attending an international academic conference in 2019. YL: Reported being as Principal Investigator, funded by the Health and Medical Research Fund from Food and Health Bureau, but not related to this manuscript. Received presentation fee from the Chinese Sleep Research Society, but not related to this study. JWYC: Reported grants from General Research Fund of University Grants Committee and Health and Medical Research Fund-Food and Health Bureau, Hong Kong SAR, which are outside of this study, and personal fees for joining an expert panel meeting from Eisai. YKW: Received consultation fee and personal fees from Eisai for lecture, and travel support from Lundbeck HK Limited, which are outside the submitted work. CHS: Received a personal fee from Eisai for a one-time lecture., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Balance deficits are common in cerebellar ataxia. Determining which balance outcome measures are psychometrically strong for this population remains an unmet need., Objective: To evaluate the validity and responsiveness of two clinic-based balance measures (Berg Balance Scale [BBS] and balance sub-component of the Scale for the Assessment and Rating of Ataxia [SARA-bal]) and two laboratory-based balance measures (Sensory Organization Test [SOT] and Limits of Stability [LOS]) in cerebellar ataxia., Design: Prospective cohort study., Setting: Institutional study assessing 40 participants with cerebellar ataxia at baseline, and 6 and 12 months., Main Outcome Measures: Balance was assessed using the BBS, SARA-bal, SOT, and LOS; disease severity was assessed using the SARA; and Patients' Global Impression of Change (PGIC) was used to estimate responsiveness to disease progress at 6 and 12 months., Results: BBS and SARA-bal (Spearman's correlation coefficient, ρS = -0.89, p < .01) demonstrated strong criterion validity. Convergent validity was moderate to high (ρS range: -0.75 to 0.92) and external validity was low (ρS range: -0.75 to 0.11). Composite SOT scores (SOT-COM; ρS = 0.29, p < .01) and maximal excursion (MXE-LOS) in the forward (F) and right (R) directions of the LOS (ρS = 0.18, p < .01) demonstrated moderate to low criterion and convergent validity. The area under the receiver-operating characteristic curve (AUC ROC ) and its effect size (standard response mean [SRM]) for categorizing "stable" and "worsened" patients at 6 and 12 months were satisfactory for the BBS (AUC ROC : 0.75; SRM-Stable: 1.06; SRM-Worsened: 1.16), SARA-bal (AUC ROC : 0.76; SRM-Stable: 0.86; SRM-Worsened: 0.85), and MXE-LOS(R) (AUC ROC : 0.29; SRM-Stable: 0.41; SRM-Worsened: 1.39)., Conclusion: BBS and SARA-bal have moderate to strong criterion and convergent validity and adequate responsiveness to balance changes. Both laboratory-based measures (SOT and LOS) demonstrated a high floor effect. The SOT-COM and MXE-LOS(R) demonstrated moderate to low criterion validity, with only the MXE-LOS(R) displaying adequate responsiveness to balance changes after 6 and 12 months., (© 2022 The Authors. PM&R published by Wiley Periodicals LLC on behalf of American Academy of Physical Medicine and Rehabilitation.)

Objectives: The predisposition of intracranial atherosclerotic disease (ICAD) to East Asians over Caucasians infers a genetic basis which, however, remains largely unknown. Higher prevalence of vascular risk factors (VRFs) in Chinese over Caucasian patients who had a stroke, and shared risk factors of ICAD with other stroke subtypes indicate genes related to VRFs and/or other stroke subtypes may also contribute to ICAD., Methods: Unrelated symptomatic patients with ICAD were recruited for genome sequencing (GS, 60-fold). Rare and potentially deleterious single-nucleotide variants (SNVs) and small insertions/deletions (InDels) were detected in genome-wide and correlated to genes related to VRFs and/or other stroke subtypes. Rare aneuploidies, copy number variants (CNVs) and chromosomal structural rearrangements were also investigated. Lastly, candidate genes were used for pathway and gene ontology enrichment analysis., Results: Among 92 patients (mean age at stroke onset 61.0±9.3 years), GS identified likely ICAD-associated rare genomic variants in 54.3% (50/92) of patients. Forty-eight patients (52.2%, 48/92) had 59 rare SNVs/InDels reported or predicted to be deleterious in genes related to VRFs and/or other stroke subtypes. None of the 59 rare variants were identified in local subjects without ICAD (n=126). 31 SNVs/InDels were related to conventional VRFs, and 28 were discovered in genes related to other stroke subtypes. Our study also showed that rare CNVs (n=7) and structural rearrangement (a balanced translocation) were potentially related to ICAD in 8.7% (8/92) of patients. Lastly, candidate genes were significantly enriched in pathways related to lipoprotein metabolism and cellular lipid catabolic process., Conclusions: Our GS study suggests a role of rare genomic variants with various variant types contributing to the development of ICAD in Chinese patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Silicone oil insertion is a common modality in vitreoretinal surgeries. The purpose of this study is to conduct a systematic review to summarize the uncommon complication of extraocular silicone oil migration., Methods: Following the PRISMA guidelines, a systematic review of the literature was performed on January 11, 2020, using PubMed and EMBASE with the following terms: "silicone oil," "eye," and "migrat*.", Results: A total of 69 patients-68 patients from 59 articles and one case from our institution-were included in the final analysis. The median age was 54 years (range, 9-92) and 40 patients (57.9%) were men. Orbital migration was reported in 34 patients, and retrolaminar migration (including optic nerve, optic chiasm, suprasellar, subarachnoid space, intraventricular spaces) was reported in 35 patients. Orbital migration group had more aphakics (p = 0.007), implanted glaucoma drainage device (p = 0.005), scleral buckle (p = 0.000), history of trauma-related indications for pars plana vitrectomy (p = 0.000), shorter silicone oil endotamponade time (p = 0.008), more symptomatic (p = 0.000), and requiring surgical intervention (p = 0.000). Retrolaminar migration group had older patients (p = 0.016) and more diabetics (p = 0.041)., Conclusion: Systematic review sheds light on plausible risk factors on site of silicone oil migration. Majority of orbital cases are symptomatic and require intervention while retrolaminar cases are incidental and can be managed conservatively. Awareness of this complication can help guide clinicians predict which patients would likely need surgical intervention. Graphical abstract.

Importance: Large-scale genome-wide association studies in the European population have identified 90 risk variants associated with Parkinson disease (PD); however, there are limited studies in the largest population worldwide (ie, Asian)., Objectives: To identify novel genome-wide significant loci for PD in Asian individuals and to compare genetic risk between Asian and European cohorts., Design Setting, and Participants: Genome-wide association data generated from PD cases and controls in an Asian population (ie, Singapore/Malaysia, Hong Kong, Taiwan, mainland China, and South Korea) were collected from January 1, 2016, to December 31, 2018, as part of an ongoing study. Results were combined with inverse variance meta-analysis, and replication of top loci in European and Japanese samples was performed. Discovery samples of 31 575 individuals passing quality control of 35 994 recruited were used, with a greater than 90% participation rate. A replication cohort of 1 926 361 European-ancestry and 3509 Japanese samples was analyzed. Parkinson disease was diagnosed using UK Parkinson's Disease Society Brain Bank Criteria., Main Outcomes and Measures: Genotypes of common variants, association with disease status, and polygenic risk scores., Results: Of 31 575 samples identified, 6724 PD cases (mean [SD] age, 64.3 [10] years; age at onset, 58.8 [10.6] years; 3472 [53.2%] men) and 24 851 controls (age, 59.4 [11.4] years; 11 030 [45.0%] men) were analyzed in the discovery study. Eleven genome-wide significant loci were identified; 2 of these loci were novel (SV2C and WBSCR17) and 9 were previously found in Europeans. Replication in European-ancestry and Japanese samples showed robust association for SV2C (rs246814; odds ratio, 1.16; 95% CI, 1.11-1.21; P = 1.17 × 10-10 in meta-analysis of discovery and replication samples) but showed potential genetic heterogeneity at WBSCR17 (rs9638616; I2=67.1%; P = 3.40 × 10-3 for hetereogeneity). Polygenic risk score models including variants at these 11 loci were associated with a significant improvement in area under the curve over the model based on 78 European loci alone (63.1% vs 60.2%; P = 6.81 × 10-12)., Conclusions and Relevance: This study identified 2 apparently novel gene loci and found 9 previously identified European loci to be associated with PD in this large, meta-genome-wide association study in a worldwide population of Asian individuals and reports similarities and differences in genetic risk factors between Asian and European individuals in the risk for PD. These findings may lead to improved stratification of Asian patients and controls based on polygenic risk scores. Our findings have potential academic and clinical importance for risk stratification and precision medicine in Asia.

Frequent falls in people with cerebellar ataxia (CA) is a significant problem Therefore, an intervention that could improve balance and reduce the number of falls is of paramount importance from the patients' perspective. Combining cognitive training with physical training to improve balance is a new approach for reducing the risk of falls in patient populations who are at risk for falls. To determine if adding structured cognitive demands to conventional balance and coordination training we designed the Cognitive-coupled Intensive Balance Training (CIBT) program. We found that the more intensive and focused CIBT intervention reduced dual-task cost, improved balance, and reduced the number of falls in a sample of individuals with CA. We hypothesize that (1) CIBT will improve balance and reduce falls; and (2) CIBT will be a cost-effective treatment option for improving balance and reduce falls. To test these hypotheses, we propose conducting a randomized controlled trial (RCT) with economic evaluation . This paper reports the findings of our study testing the feasibility of the CIBT program, rationale for testing our hypothesis and an overview of our future study design to test the effectiveness and cost-effectiveness of the CIBT program., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Recent whole-exome sequencing studies in European patients with Parkinson's disease (PD) have identified potential risk variants across 33 novel PD candidate genes. We aim to determine if these reported candidate genes are similarly implicated in Asians by assessing common, rare, and novel nonsynonymous coding variants by sequencing all 33 genes in 198 Chinese samples and genotyping coding variants in an independent set of 9756 Chinese samples. We carried out further targeted sequencing of CD36 in an additional 576 Chinese and Korean samples. We found that only 8 of 43 reported risk variants were polymorphic in our Chinese samples. We identified several heterozygotes for rare loss-of-function mutations, including the reported CD36 p.Gln74Ter variant, in both cases and controls. We also observed 2 potential compound heterozygotes among PD cases for rare loss-of-function mutations in CD36 and SSPO. The other reported variants were common in East Asians and not associated with PD, completely absent, or only found in controls. Therefore, the 33 reported candidate genes and associated variants are unlikely to confer significant PD risk in the East Asian population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Balance problems and frequent falls are common among clients with Cerebellar Ataxia (CA). CA is not a disease by itself but a collection of symptoms due to the involvement of cerebellum or its pathways. Presently the treatment for balance problems for CA is not standardized. Interventions available to improve balance are not specific to symptoms presentation. Functionally the cerebellum is divided into the spinocerebellum, vestibulocerebellum and corticocerebellum. Each functional zone has a distinct role in maintaining balance. Therefore, the presentation of symptoms will vary according to the functional zone involved. Pre-screening clients with CA for identifying the part of cerebellum involved will facilitate clinicians to provide tailor-made interventions for targeting specific symptoms for better outcomes. Pre-screening clients with CA according to the part of cerebellum involved is not in practice and our study will introduce this concept. We hypothesize pre-screening participants with spinocerebellar ataxia (SCA) for the involvement vestibulocerebellum followed by prescribing vestibulocerebellum targeted exercises will have better outcomes when compared to conventional balance training. We plan to conduct two related studies. In study 1 we will screen participants with CA for the involvement of vestibulocerebellum. In study 2, the effects of vestibulocerebellum targeted balance exercises on balance will be studied. We will assess the Subjective Visual Vertical (SVV) deviation and postural sway pattern to screen participants into people with and without vestibulocerebellar involvement. SVV deviation will be estimated using a computerized Subjective Visual Vertical (cSVV) device and postural sway pattern will be assessed using the limits of stability program of the Bertec© Balance system. The obtained SVV deviation scores will be used to derive at cut-off scores to discriminate clients with and without vestibulocerebellar involvement. The second study will test the treatment effects of conventional exercises plus vestibulocerebellum targeted exercises to improve balance by correcting SVV deviation in SCA with vestibulocerebellar involvement. The intervention is planned as 12 one-to-one sessions over three months period. Participants will be reassessed after the intervention and 3 months post-intervention. The findings of this cutting-edge research are extremely important to the clinicians, researchers and clients with SCA., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The Montreal Cognitive Assessment (MoCA) is psychometrically superior over the Mini-mental State Examination (MMSE) for cognitive screening in stroke or transient ischemic attack (TIA). It is free for clinical and research use. The objective of this study is to convert scores from the MMSE to MoCA and MoCA-5-minute protocol (MoCA-5 min) and to examine the ability of the converted scores in detecting cognitive impairment after stroke or TIA., Methods: A total of 904 patients were randomly divided into training (n = 623) and validation (n = 281) samples matched for demography and cognition. MMSE scores were converted to MoCA and MoCA-5 min using (1) equipercentile method with log-linear smoothing and (2) Poisson regression adjusting for age and education. Receiver operating characteristics curve analysis was used to examine the ability of the converted scores in differentiating patients with cognitive impairment., Results: The mean education was 5.8 (SD = 4.6; ranged 0-20) years. The entire spectrum of MMSE scores was converted to MoCA and MoCA-5 min using equipercentile method. Relationship between MMSE and MoCA scores was confounded by age and education, and a conversion equation with adjustment for age and education was derived. In the validation sample, the converted scores differentiated cognitively impaired patients with area under receiver operating characteristics curve 0.826 to 0.859., Conclusion: We provided 2 methods to convert scores from the MMSE to MoCA and MoCA-5 min based on a large sample of patients with stroke or TIA having a wide range of education and cognitive levels. The converted scores differentiated patients with cognitive impairment after stroke or TIA with high accuracy., (Copyright © 2018 John Wiley & Sons, Ltd.)

Introduction: Patients surviving stroke without immediate dementia are at high risk of delayed-onset dementia. Mechanisms underlying delayed-onset dementia are complex and may involve vascular and/or neurodegenerative diseases., Methods: Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA., Results: Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of ≥3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD., Discussion: Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group., (Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)