Wl Ho

Efficacy of selective laser trabeculoplasty for normal tension glaucoma: 1 year results

BackgroundNormal tension glaucoma (NTG) is commonly treated with anti-glaucoma medications. Recently, selective laser trabeculoplasty (SLT) has been demonstrated to lower the intraocular pressure (IOP) and medication use in NTG. The purpose of this study was to investigate the efficacy of a single session of SLT for NTG at 1 year.MethodsThis prospective cohort study recruited NTG patients taking anti-glaucoma medication. Potential subjects were excluded if they had had previous glaucoma surgery or laser and also if intraocular surgery or additional SLT procedures were performed after the first treatment. All subjects underwent a 1-month washout. A 30% IOP reduction was set as the target IOP. A single session of SLT was performed to 360 degrees of the trabecular meshwork. At 1-month after SLT, medication was resumed to achieve the target IOP. The IOP was measured every 3 months, and the number of medications was recorded at 3, 6, and 12 months. Only the right eye was used for statistical analysis.ResultsIn 41 right eyes, the mean pre-study IOP was 14.3 ± 3.4 mmHg while on 1.5 ± 0.8 eye drops. The post-washout IOP was 16.2 ± 2.2 mmHg. A mean of 191.1 ± 26.3 SLT shots at 1.0 ± 0.07 mJ were applied. There was significant IOP reduction at all time intervals following SLT when compared to the post-washout IOP (P < 0.0001). The number of medications was significantly reduced at all time intervals following SLT when compared to the pre-study level (P < 0.0001). At 12 months, the mean IOP was 12.2 ± 2.2 mmHg while on 1.1 ± 0.9 eye drops.ConclusionsA single session of SLT for NTG achieved an additional 15% IOP reduction while using 27% less medication at 1 year compared to pre-study levels.Trial registrationThe Clinical Trials Register of the University of Hong Kong HKCTR1847The European Clinical Trials Database 2014-003305-15 (August 11, 2014) (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-003305-15)

Hepatic Actinomycosis Presenting as a Liver Tumour: Case Report and Literature Review

Hepatic actinomycosis poses a difficult problem in both diagnosis and management. We report the management of a patient with isolated hepatic actinomycosis, and review the clinical features and management of patients with hepatic actinomycosis mimicking liver tumour.

The ophthalmological complications of targeted agents in cancer therapy: what do we need to know as ophthalmologists?

Recently, there has been an increase in the use of targeted therapies for cancer treatments. Nevertheless, the ocular side‐effects of the commonly used targeted agents are generally under‐reported and not well studied in the literature. We conducted multiple searches in databases, including Medline, EMBASE, Cochrane Library and conference proceedings, using the following strings: ‘name of targeted therapeutic agent (both generic and commercial names)’ AND ‘eye OR ocular OR vision OR ophthalmological’. Various targeted agents have been found to be associated with ocular side‐effects due to their specific targeting of activities in the eye. Imatinib commonly causes periorbital oedema, epiphora and occasionally conjunctival haemorrhage. Cetuximab causes corneal lesions, meibomian gland dysfunction, periorbital and lid dermatitis, blepharitis and conjunctivitis. Erlotinib is related to various ocular toxicities, mainly on the ocular surface, and perifosine has been reported to be associated with severe keratitis. Bevacizumab could potentially disrupt intrinsic ocular circulation and lead to the development of thromboembolic events; there are rare reported cases of optic neuritis or optic neuropathy. Other targeted agents, such as trastuzumab, sunitinib and crizotinib, also have specific ocular toxicities. In conclusion, ocular effects of targeted agents are not uncommon in cancer patients receiving targeted therapy. Ophthalmologists should have high indexes of suspicion to diagnose and treat these complications promptly.

Investigating degeneration of the retina in young and aged tau P301L mice

AIMS Tau is a microtubule-binding protein facilitating the stability of the cytoskeleton. It is important for neurons as several neurodegenerative diseases involve hyperphosphorylation and aggregation of tau. It is known that mutated tau P301L results in aggregation of tau proteins, leading to neuronal loss in the brain. The aim of this study was to investigate the effect of tau mutation on the retina using a transgenic tau P301L mouse model. MAIN METHODS Morphometric analysis was utilized to quantify the neurodegenerative changes, including the thickness of the inner nuclear layer (INL), and the density and size of retinal ganglion cells (RGCs). Sections of retina tissue stained by hematoxylin and eosin (H&E) and immunohistochemistry were analyzed. Comparisons were made between the tau P301L mice and control mice, as well as between different age groups. KEY FINDINGS A significant decrease in the thickness of the INL in tau P301L mice was found when compared with that of control mice. The effect was more pronounced in the peripheral area, and the effect increased with age. Regarding density of RGCs, tau P301L mice showed a similar age-related decline as in control mice. Furthermore, the RGCs from tau P301L mice increased in size with age, and the RGCs from control mice decreased in size with age. SIGNIFICANCE Tau may be an age-independent factor of accelerated neurodegeneration, with effects differing by types of neurons and regions of the retina.

Development and pilot-testing of patient decision aid for use among Chinese patients with primary open-angle glaucoma

Background A patient decision aid (PDA) is a tool for shared decision making (SDM), which emphasises patient empowerment. It is useful in chronic diseases and when there are multiple, no best single treatment option. Although SDM is prevalent in Western countries, its use is limited in Chinese societies, where the adoption of a paternalistic approach is strong. Here, we report the development, acceptance and pilot test results of a PDA targeted at Chinese patients with primary open-angle glaucoma (POAG). Methods We developed a PDA designed for use in Chinese patients with POAG. Recruited subjects were given our PDA. Baseline evaluation included decision conflict scale (DCS), validated glaucoma adherence questionnaires and glaucoma knowledge questionnaire. Subjects were briefed through the PDA and instructed to read it that day. Three to four weeks later, follow-up questionnaire as described above were conducted with the addition of acceptance questionnaires. Results Data from 65 subjects were available. The PDA was well received among subjects. DCS improved from 48.9±20.4 at baseline to 34.3±20.3 during follow-up, with P<0.01. Validated medication adherence questionnaires and knowledge showed improvement from baseline, which was statistically significant. Conclusions The use of PDA among Chinese subjects with POAG demonstrated positive reception and acceptance. Evaluation of its initial effects shows improvement in DCS, medication adherence and glaucoma knowledge. The implementation of SDM and PDA among Chinese subjects with POAG is encouraged. Future studies with randomised design and later evaluation time points can further reveal the impacts of PDA among Chinese subjects with POAG.

Defective ubiquitinated mitochondria accumulation in aged parkinsonian LRRK2 R1441G knockin mice

This free journal suppl. entitled: Supplement: Abstracts of the Twentieth International Congress of Parkinsons Disease and Movement DisordersObjective: To investigate the possible disease-association and pathogenic mechanisms of heterozygous PINK1 mutations from a genetic, functional, and structural perspective. Background: It has been postulated that heterozygous mutations in recessive PD genes may increase disease risk. In particular, the PINK1 p.G411S mutation has been reported in families with dominant inheritance patterns, suggesting that it might confer a sizeable disease risk. Methods: We performed a pedigree analysis of seven patients with a heterozygous PINK1 p.G411S mutation with at least one additional affected family member. We screened five case-control series and performed a meta-analysis of previous studies that had examined the variant. For functional cell-based analyses, we used patients skin fibroblast from PINK1 p.G411S or p.Q456X heterozygotes and investigated endogenous protein levels and kinase activity by biochemistry and imaging. For structural analyses, we performed molecular modeling and generated monomeric and dimeric forms of wild type (WT) and mutant PINK1 protein. Using molecular dynamics simulations, we analyzed effects of the p.G411S mutation on WT PINK1 in a heterodimeric complex over time. Results: Our analyses revealed a genetic association of heterozygous PINK1 p.G411S mutation with an increased risk for PD and a possible dominant inheritance with incomplete co-segregation. In patients skin fibroblasts, we establish a dominant negative mode for heterozygous p.G411S mutations under endogenous conditions. While total PINK1 protein levels were similar to controls upon mitochondrial stress, cellular PINK1 kinase activity was significantly reduced in p.G411S heterozygotes compared to WT and importantly to p.Q456X heterozygotes, which resulted in 50% reduction of PINK1 protein levels. Structural analyses supported our hypothesis that the p.G411S mutation can poison PINK1 WT in a heterodimeric complex and thus effectively reduce cellular PINK1 kinase activity. This in turn impairs the protective functions of the PINK1/PARKIN-mediated mitochondrial quality control. Conclusions: Our study uncovers increased disease risk and molecular mechanisms of a particular heterozygous mutation in a recessive PD gene. Based on genetic and clinical evaluation as well as functional and structural characterization, we established PINK1 p.G411S as a rare genetic risk factor with a relatively large effect size conferred by a dominant negative function phenotype. (Less)Objective: The aim of this study is to develop and evaluate methods for quantifying motor symptoms in Parkinson’s disease (PD) using combined upper limb motor test data collected during tapping and ...20th International Congress of Parkinson’s disease and Movement Disorders, Berlin, Germany, 19-23 June, 2016Upper limb motor tests are related to clinical ratings of motor function in advanced Parkinsons disease

Leucine-rich repeat kinase-2 (LRRK2) R1441G knockin mice are more susceptible to rotenone toxicity

Objective: To explore the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug-naive Parkinson’s disease patients and to test the hypothesis that executive dysfunction in Parkinson’s disease is caused by striatal dopaminergic depletion. Background: Cognitive impairment in Parkinson’s disease is common and influences patients’ everyday functioning, but the mechanisms of early cognitive decline are not known. Understanding of these mechanisms is important for the development of methods preventing cognitive decline in Parkinson’s disease. Previous studies suggest that the dopaminergic system influences cognition in PD. Methods: Neuropsychological and cerebral dopamine transporter SPECT imaging data of 339 Parkinson’s disease patients and 158 Healthy controls of the Parkinson’s Progression Markers Initiative study were analysed. Neuropsychological evaluation consisted of standardized tests of memory, visuospatial and executive function. SPECT imaging was performed with [123I]FP-CIT and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios and cognition was performed using a cognitive composite z-score, domain z-scores and individual test scores. Multivariate general linear model regression analyses were performed including age, gender, education, and laterality as predictors and specific binding ratios as dependent variables. Results: Uncorrected analysis showed no associations between dopamine transporter imaging and memory and visuospatial domains. A small but significant positive association between specific binding ratios and the attention/executive domain was found, which was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with Parkinson’s disease were mediated by an age-moderated dopaminergic deficit in the left caudate nucleus. Conclusions: Our findings support the hypothesis that nigrostriatal dopaminergic deficit contributes to executive impairment, but not to memory or visuospatial impairment in early Parkinson’s disease.Objective: To investigate whether spirography-based objective measures of motor dysfunctions are able to discriminate between Parkinson’s disease (PD) patients with different motor states (Off and ...Objective: This study aims to determine PPN’s electrophysiological activities in rats to help future studies and to investigate the effect of subthalamic nucleus stimulation on PPN. Background: Long-duration medical treatment of Parkinson patients causes complications and morbidity. Risks in destructive surgery are releatively high, new treatment methods such as stereotactic functional surgery has been proposed recently. While sensory and behavioral processes of pedunculopontine nucleus (PPN) are well known as a locomotor center, its role on initiating and sustaining motion function in primates or rats has been also demonstrated. All functions of PPN are not fully known yet, and its DBS has been proposed as an alternative therapeutic target in treating gait problems of Parkinson’s disease recently. Methods: In this study, 14 male wistar type healthy rats with average 292 (284-317) gram weight and with the same age group were used. In the sham group, two probes were inserted, one to the STN bilaterally and the other to the right PPN to record PPN’s electrophysiological activities. In the experiment group, in addition to the same procedures used in the sham group, STN was stimulated bilaterally at 0.5 Hz, 10 Hz, 60 Hz ve 130 Hz and PPN’s electrophysiological activities were recorded before and after bilateral STN stimulations. Results: Analyzing the neural activity after the 60 Hz stimulation, it revealed that STN has a stimulus effect on PPN neurons increasing the firing rate. The PPN neurons demonstrated three different patterns of firing, burst random and regular. The majority of the neurons (68%) exhibited a regular pattern of firing in the sham group. After bilateral STN stimulation with very low (0,5 Hz and 10 Hz) and high (130 Hz) frequencies the PPN neurons maintained their firing patterns. However, after 60 Hz stimulation of STN a significant percentage of neurons (82,1 %) fired with a more regular pattern. Conclusions: The results of this study provides additional information to our understanding on PPN’s electrophysiological activities. 60 Hz STN stimulation can increase the firing rates and changes the behaviour of the PPN neurons.Objective: To analyze the relationship between the electric field and the volume of tissue activated (VTA) during model-based investigations of deep brain stimulation (DBS).Background: An important ...This journal suppl. entitled: Supplement: Abstracts of the Eighteenth International Congress of Parkinsons Disease and Movement Disorders / Poster Presentation