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This study was performed to evaluate the subjective and objective functional outcomes of patients who had undergone submandibular gland-sparing neck dissection. All data were obtained from patients treated in a single hospital. Seventy-seven patients who had undergone complete submandibular gland sparing (CSGS) were included in the study. Cancer prognosis items were recorded. The subjective outcomes included patient self-evaluation of mouth dryness and the evaluation of the presence of saliva secretion following the application of digital pressure. Saliva scintigraphy served as the objective test. Self-reported xerostomia was compared between the CSGS patients and a control group of patients who had undergone unilateral submandibular gland removal (USGR; n = 74). In the CSGS group, local recurrence occurred in 3.8% of the 80 cancer sites, and neck recurrence occurred in 5.9% of neck dissection sites. Regarding the subjective measurements, 7.0% of the CSGS patients reported xerostomia and 91.9% demonstrated saliva secretion by digital pressure. Scintigraphy revealed actively secreting glands, with 42.9% of them showing normal gland function; none of the patients had severe xerostomia. The relative risk of dry mouth was significantly higher in the USGR patients than in the CSGS patients (P < 0.001). Submandibular gland sparing during neck dissection was found to result in satisfactory saliva secretion, with a relatively small risk of local or neck recurrence., (Copyright © 2022 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Smartphone overuse can have detrimental impacts on youth mental health. How it may be longitudinally associated with depressive symptoms and functioning, and with daily momentary affect, remains to be investigated. A total of 3,033 young people were consecutively recruited from a large-scale epidemiological youth mental health study in Hong Kong. A subsample (n = 936) was followed-up after 1 year, with experience sampling data collected from 177 participants. Separate multivariable logistic regression models were applied to examine the prospective associations between smartphone overuse and depressive symptoms, with multilevel models fitted to examine its associations with momentary affect. The prevalence of smartphone overuse in the Hong Kong youth population was 29.3%. Smartphone overuse was significantly associated with more depressive symptoms and functional impairments both cross-sectionally and longitudinally. The associations between smartphone overuse and 1-year depressive symptoms were significant, even when accounting for baseline symptoms, social media use, and other risk and protective factors. Baseline depressive symptoms, in contrast, were not associated with 1-year smartphone overuse after adjusting for baseline smartphone overuse. Smartphone overuse was also significantly associated with higher levels of momentary negative affect, even when accounting for depressive symptoms. Strategies to mitigate the impact of smartphone overuse can have important long-term implications., Competing Interests: Declaration of Competing Interest E.Y.H.C. has received speaker honoraria from Otsuka and DSK BioPharma, research funding from Otsuka, participated in paid advisory boards for Janssen and DSK BioPharma, and received funding to attend conferences from Otsuka and DSK BioPharma. All other authors declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Restrictive COVID-19 measures can have significant mental health impacts, particularly on young people. How such measures may influence day-to-day momentary affect, nonetheless, remains to be explored. Experience sampling data were collected from 165 young people (aged 15-24) as part of a larger epidemiological youth mental health study in Hong Kong. We examined the impact of one of the most stringent COVID-19 measures - dine-in restrictions - on momentary positive and negative affect and current contexts and activities of these young people. The effects of a milder form of COVID-19 measure - school suspension - were separately examined. Multilevel analysis revealed that those in the dine-in ban group, compared to dining-as-usual, showed significantly reduced momentary positive affect ( β  = -0.17, SE  = 0.06, p  = 0.003). Its effect remained significant even when accounting for baseline depressive and anxiety symptoms and socioeconomic status ( β  = -0.15, SE  = 0.05, p  = 0.008). The effect of dine-in ban on reduced momentary positive affect was found specifically when participants were in indoor locations (e.g., home, office), alone, and engaged in passive leisure activities. This pattern was not observed when participants were at school or at other outdoor locations, with friends, or engaged in active leisure activities. No significant effect of school suspension on momentary affect was observed. More severe COVID-19 measures, such as dine-in ban, can have significant impacts on the momentary positive affect of young people. Certain contexts and activities may offer protection against the consequences of COVID-19 measures. The current findings may help to inform future designs of mental health interventions and public health policies., Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03183-y., Competing Interests: Conflict of InterestNone to declare., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)

Background: Short or long sleep duration has been associated with some major chronic diseases, but whether disease-related blood biomarkers vary according to habitual sleep duration is unclear. This cross-sectional study aimed to assess blood biomarker levels in relation to total sleep duration., Methods: The analysis includes 459,796 white British adults aged 40-69 during 2006-2010 in UK Biobank. At recruitment, blood samples and self-reported information on total sleep duration were collected from participants. A panel of blood biomarkers were measured. Using linear regression, we estimated geometric mean concentrations of blood biomarkers and mean ratio of ApoB/ApoA1 by sleep duration adjusted for sex, age at data collection, time of blood collection, and lifestyle covariates., Results: Percentage differences in the concentrations of most biomarkers by sleep duration were modest. The largest differences were for C-reactive protein (CRP, an inflammatory biomarker) and gamma glutamyltransferase (GGT, a liver function biomarker), and the differences were markedly attenuated after multivariable-adjustment. The multivariable-adjusted geometric means of CRP and of GGT were 14% and 14% higher in <6 h vs 7-8 h of sleep; and 22% and 12% higher in >9 h vs 7-8 h of sleep, respectively., Conclusion: In white British adults, most blood biomarker levels varied only modestly with sleep duration and the remaining associations may be due to residual confounding., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Most oral squamous cell carcinoma (OSCC) tumors arise from oral premalignant lesions. Oral submucous fibrosis (OSF), usually occurring in male chewers of betel quid, is a premalignant stromal disease characterized by a high malignant transformation rate and high prevalence. Although a relationship between the inhabited microbiome and carcinogenesis has been proposed, no detailed information regarding the oral microbiome of patients with OSF exists; the changes of the salivary microbiome during cancer formation remain unclear. This study compared the salivary microbiomes of male patients with OSCC and a predisposing OSF background (OSCC-OSF group) and those with OSF only (OSF group). The results of high-throughput sequencing of the bacterial 16S rRNA gene indicated that OSF-related carcinogenesis and smoking status significantly contributed to phylogenetic composition variations in the salivary microbiome, leading to considerable reductions in species richness and phylogenetic diversity. The microbiome profile of OSF-related malignancy was associated with increased microbial stochastic fluctuation, which dominated the salivary microbiome assembly and caused species co-occurrence network collapse. Artificial intelligence selection algorithms consistently identified 5 key species in the OSCC-OSF group: Porphyromonas catoniae, Prevotella multisaccharivorax, Prevotella sp. HMT-300, Mitsuokella sp. HMT-131, and Treponema sp. HMT-927. Robust accuracy in predicting oral carcinogenesis was obtained with our exploratory and validation data sets. In functional analysis, the microbiome of the OSCC-OSF group had greater potential for S -adenosyl-l-methionine and norspermidine synthesis but lower potential for l-ornithine and pyrimidine deoxyribonucleotide synthesis and formaldehyde metabolism. These findings indicated that the salivary microbiome plays important roles in modulating microbial metabolites during oral carcinogenesis. In conclusion, our results provided new insights into salivary microbiome alterations during the malignant transformation of OSF.

Study Question: Can the priorities for future research in infertility be identified?, Summary Answer: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care for people with fertility problems were identified., What Is Known Already: Many fundamental questions regarding the prevention, management, and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems., Study Design, Size, Duration: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines, and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care., Participants/materials, Setting, Methods: Healthcare professionals, people with fertility problems, and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance., Main Results and the Role of Chance: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties were entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities, and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI, and IVF), and ethics, access, and organization of care, were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment, and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings, and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research, and population science., Limitations, Reasons for Caution: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgement, and arbitrary consensus definitions., Wider Implications of the Findings: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems, and others, will help research funding organizations and researchers to develop their future research agenda., Study Funding/ Competing Interest(s): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand, and Maurice and Phyllis Paykel Trust. Geoffrey Adamson reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies, and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. Hans Evers reports being the Editor Emeritus of Human Reproduction. Andrew Horne reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research, and Wellbeing of Women and consultancy fees from Abbvie, Ferring, Nordic Pharma, and Roche Diagnostics. M. Louise Hull reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. Neil Johnson reports research sponsorship from Abb-Vie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics, and Vifor Pharma. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Ernest Ng reports research sponsorship from Merck. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Jane Stewart reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring, and being a clinical subeditor of Human Fertility. Annika Strandell reports consultancy fees from Guerbet. Jack Wilkinson reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. Andy Vail reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from HFEA for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form., Trial Registration Number: Not applicable., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Question: Can the priorities for future research in infertility be identified?, Summary Answer: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified., What Is Known Already: Many fundamental questions regarding the prevention, management and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems., Study Design, Size, Duration: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care., Participants/materials, Setting, Methods: Healthcare professionals, people with fertility problems and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance., Main Results and the Role of Chance: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties was entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI and IVF) and ethics, access and organization of care were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research and population science., Limitations, Reasons for Caution: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgment and arbitrary consensus definitions., Wider Implications of the Findings: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, will help research funding organizations and researchers to develop their future research agenda., Study Funding/competing Interest(s): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand and Maurice and Phyllis Paykel Trust. G.D.A. reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. A.W.H. reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research and Wellbeing of Women and consultancy fees from AbbVie, Ferring, Nordic Pharma and Roche Diagnostics. M.L.H. reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. N.P.J. reports research sponsorship from AbbVie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics and Vifor Pharma. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from AbbVie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. E.H.Y.N. reports research sponsorship from Merck. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring and retains a financial interest in NexHand. J.S. reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring and being a clinical subeditor of Human Fertility. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form., Trial Registration Number: N/A., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Contingency-theorists have put forth differing accounts of evolutionary contingency. The bulk of these accounts abstractly refer to certain causal structures in which an evolutionarily contingent outcome is supposedly embedded. For example, an outcome is evolutionarily contingent if it is at the end of a 'path-dependent' or 'causally dependent' causal chain. However, this paper argues that many of these proposals fail to include a desideratum - the notion of biological evitability or that evolutionary outcomes could have been otherwise - that for good theoretical reasons ought to be part of an account of evolutionary contingency. Although an inclusion of this desideratum might seem obvious enough, under some existing accounts, an outcome can be contingent yet inevitable all the same. In my diagnosis of this issue, I develop the idea of trajectory propensity to highlight the fact that there are plausible biological scenarios in which causal structures, alone, fail to exhaustively determine the biological evitability of evolutionary forms. In the second half of the paper, I present two additional desiderata of an account of evolutionary contingency and, subsequently, proffer a novel account of evolutionary contingency as non-trivial objective probability, which overcomes the shortcomings of some previous proposals. According to this outcome-based account, contingency claims are probabilistic statements about an evolutionary outcome's objective probability of evolution within a specifically defined modal range: an outcome, O, is evolutionarily contingent in modal range, R, to the degree of objective probability, P (where P is in between 1 and 0)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The Centre for Health Protection of the Department of Health has convened the Advisory Group on Antibiotic Stewardship Programme in Primary Care (the Advisory Group) to formulate guidance notes and strategies for optimising judicious use of antibiotics and enhancing the Antibiotic Stewardship Programme in Primary Care. Acute pharyngitis is one of the most common conditions among out-patients in primary care in Hong Kong. Practical recommendations on the diagnosis and antibiotic treatment of acute streptococcal pharyngitis are made by the Advisory Group based on the best available clinical evidence, local prevalence of pathogens and associated antibiotic susceptibility profiles, and common local practice., Competing Interests: As editors of this journal, DVK Chao and MCS Wong were not involved in the peer review process of this article. All other authors have no conflicts of interest to disclose.

Transoral vertical ramus osteotomy (VRO) has been condemned because the condyle has the potential to sag, and because it needs lengthy maxillomandibular fixation. We have therefore introduced a simple method of fixation, and examined its effectiveness and complications. After the osteotomy, the proximal and distal segments are trimmed to adapt to each other. Four Kirschner (K) pins 0.9mm in diameter are inserted percutaneously from the proximal to the distal segment while the condyle is positioned in the glenoid fossa. This is followed by a brief period of maxillomandibular fixation. We have reviewed the records of 95 patients who had unilateral or bilateral vertical ramus osteotomy fixed with K pins, after which the mean (SD) period of fixation was 19 (11) days. Fixation failed in two patients because excursion of the jaw was either too heavy or too early. The fixations were redone. All other fixations remained stable, including the 20 dual-jaw procedures in which VRO preceded maxillary osteotomy. The mean (SD) maximal mouth opening at final follow-up was 44 (7) mm, and in only one patient was it less than 30mm. Numbness of the lip or chin developed in seven patients, five of whom had other anterior mandibular procedures. Four patients had discomfort on palpation of the site of the pins, and one required removal. The new method was effective, and resulted in few complications within its limitations., (Copyright © 2018. Published by Elsevier Ltd.)

Aims: Tear cytokine levels indicate severity of ocular surface inflammation. Previous reports of cytokine concentrations were based on hospital-based studies or non-Chinese populations. We determine the range of tear concentration of cytokines in a representative adult Chinese population., Methods: Thirty-nine participants were recruited from a population-based study of Chinese adults in Singapore, and standardized clinical ocular surface/eyelid features evaluated. Tear was extracted from Schirmer strips and analysed using a multiplex bead-based assay., Results: Tear concentrations of 14 cytokines were investigated and quantifiable in each participant. Eight cytokines increased with increasing age, and 4 cytokines (IL-4, IL-12, IL-10 and IFN-γ) were increased in people with increased frequency of ocular discomfort. Three cytokines (MCP-1, IP-10 and IL-13) had increased levels in people with lower Schirmer tests, while 9 other cytokines were increased in patients with eyelid crusting (TNF-α, IL-1β, IL-17α, IL-2, IL-4, IL-6, IL-12, IL-10 and IFN-γ). Twelve percent of participants had eyelid crusting., Conclusion: Using a convenient collection technique that is a routine clinical test, 14 tear cytokines could be quantifiable even in Singapore Chinese adults without a dry eye diagnosis. Elevation of different tear cytokines may be linked to subclinical aqueous tear deficiency or eyelid inflammation even in asymptomatic people., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The retinal microcirculation provides a unique view of microvessel structure by means of non-invasive, retinal image analysis. The aim of the study was to compare the retinal vessel caliber at delivery and one-year post-partum between women who have had pre-eclampsia during pregnancy to a normotensive control group., Methods: Digital photos of the eye were taken at delivery and one-year post-partum. Retinal vessels were analysed and summarised as the corrected central retinal arteriolar equivalent and corrected central retinal venular equivalent., Results: The corrected central retinal arteriolar equivalent and corrected central retinal venular equivalent were significantly lower in the pre-eclamptic group compared to the control group both at delivery and one-year post-partum ( p  < 0.001)., Conclusion: Retinal artery and venular caliber changes that occur during pregnancies affected by pre-eclampsia persist for up to one-year post-partum. These changes may reflect a permanent, long-term microvascular dysfunction and may be useful as a biomarker of future vascular risk.

Introduction: A point prevalence survey was conducted to study the epidemiology of and risk factors associated with multidrug-resistant organism carriage among residents in residential care homes for the elderly (RCHEs)., Methods: A total of 20 RCHEs in Hong Kong were selected by stratified single-stage cluster sampling. All consenting residents aged ≥65 years from the selected RCHEs were surveyed by collection of nasal swab, axillary swab, rectal swab or stool on one single day for each home. Specimens were cultured and analysed for methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Acinetobacter (MDRA, defined as concomitant resistant to fluoroquinolones, carbapenems, aminoglycosides, cephalosporins and beta-lactam with or without beta-lactamase inhibitors), vancomycin-resistant Enterococcus (VRE), and carbapenemase-producing Enterobacteriaceae (CPE). One third of the MRSA-positive samples were selected at random for molecular typing; all positive MDRA, VRE and CPE samples were tested for molecular typing. Demographic and health information of residents including medical history, history of hospitalisation, antimicrobial usage, and use of indwelling catheters were collected to determine any associated risk factors., Results: Samples of 1028 residents from 20 RCHEs were collected. Prevalence of MRSA was estimated as 30.1% (95% confidence interval [CI]=25.1%-35.6%) and MDRA 0.6% (95% CI=0.1%-4.1%). No residents carried VRE nor CPE. Residents living in privately run RCHEs were associated with MRSA carriage. Non-Chinese residents were associated with MRSA carriage with borderline significance., Conclusions: This survey provided information about multidrug-resistant organism carriage among RCHE residents. This information will enable us to formulate targeted surveillance and control strategies for multidrug-resistant organisms.

Background: Evidence suggests that autism and schizophrenia share similarities in genetic, neuropsychological and behavioural aspects. Although both disorders are associated with theory of mind (ToM) impairments, a few studies have directly compared ToM between autism patients and schizophrenia patients. This study aimed to investigate to what extent high-functioning autism patients and schizophrenia patients share and differ in ToM performance., Methods: Thirty high-functioning autism patients, 30 schizophrenia patients and 30 healthy individuals were recruited. Participants were matched in age, gender and estimated intelligence quotient. The verbal-based Faux Pas Task and the visual-based Yoni Task were utilised to examine first- and higher-order, affective and cognitive ToM. The task/item difficulty of two paradigms was examined using mixed model analyses of variance (ANOVAs). Multiple ANOVAs and mixed model ANOVAs were used to examine group differences in ToM., Results: The Faux Pas Task was more difficult than the Yoni Task. High-functioning autism patients showed more severely impaired verbal-based ToM in the Faux Pas Task, but shared similar visual-based ToM impairments in the Yoni Task with schizophrenia patients., Conclusions: The findings that individuals with high-functioning autism shared similar but more severe impairments in verbal ToM than individuals with schizophrenia support the autism-schizophrenia continuum. The finding that verbal-based but not visual-based ToM was more impaired in high-functioning autism patients than schizophrenia patients could be attributable to the varied task/item difficulty between the two paradigms.

Background: The relationship between vitamin D insufficiency and cognitive impairment remains equivocal in Asians. We examined the association between circulating 25-hydroxyvitamin D (25OHD) concentration and cognitive performance in a large multi-ethnic Singaporean population-based study. We also conducted a meta-analysis of 25OHD concentrations amongst cognitively impaired older adults in Asia., Methods: Our population-based cross-sectional study included 2273 persons ≥60 years of age from the Singapore Epidemiology of Eye Diseases (SEED) study (mean ± SD age 70.4 ± 6.2 years; 44.7% female), who were categorized according to 25OHD concentration (i.e. ≤10, 10.1-20 and >20 ng mL(-1) ). The 25OHD concentration was measured and adjusted to reflect a deseasonalized value. Cognition was assessed using the total and domain scores of the Abbreviated Mental Test (AMT). Global cognitive impairment was defined as AMT score of ≤6 if 0-6 years of education and AMT score of ≤8 if >7 years of education. Fully adjusted multivariate models were used. We included seven studies in a meta-analysis of 25OHD and cognition in Asia (6068 participants; 1179 cognitively impaired cases)., Results: Participants with 25OHD levels >20 ng mL(-1) (n = 1302) had higher AMT total scores (mean ± SD 8.5 ± 1.9) and were less likely to have cognitive impairment (14.1%) than participants with lower 25OHD levels (overall P < 0.001, P-trend < 0.001). Deseasonalized 25OHD concentration was associated with AMT score (β = 0.10 per 10 ng mL(-1) , P = 0.035). Vitamin D insufficiency (25OHD ≤20 ng mL(-1) ) was associated with global cognitive impairment (OR 1.56, P = 0.028). Specifically, 25OHD concentration correlated with semantic memory (r = 0.08, P = 0.009) and orientation in time (r = 0.09, P = 0.003). In the meta-analysis, the pooled mean 25OHD difference was -6.83 ng mL(-1) (95% confidence interval -11.36; -2.30), indicating lower 25OHD concentrations amongst cognitively impaired compared to cognitively healthy participants in Asia., Conclusion: Vitamin D insufficiency is associated with a greater likelihood of and more severe cognitive impairment in Asian populations., (© 2016 The Association for the Publication of the Journal of Internal Medicine.)

Most previous studies on facial asymmetry have not specifically differentiated mandible deviation from structural asymmetry of the mandible. The purpose of this study was to assess the symmetry of the mandible by examining its contour in a cohort of patients with significant facial asymmetry. Eleven cases of facial asymmetry with chin deviation ≥10mm were enrolled. A voxel-paired median plane (optimal symmetry plane, OSP) and two landmark-based median planes were generated. The OSP was created by computing the best pairing of the bony voxels on the two sides. One side of the mandibular contour was mirrored onto the other side using the test plane. The contour differences were measured by distance and by area ratio. They were examined both in frontal and frontal downward inclined view. The contour symmetry of the mandible was that revealed by the plane that presented the best symmetry. The results showed that the OSP worked best in bisecting the contour into two symmetrical halves. Contour analysis showed relatively small discrepancies between the two sides. In conclusion, the mandibles retained an acceptable contour symmetry despite the presence of significant mandibular deviations. It is suggested that proper mandibular alignment be the primary objective in the correction of facial asymmetry., (Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

The International Agency for Research on Cancer lists the principal component of betel quid (BQ), the areca nut, and that of cigarette smoke, benzo[a]pyrene (BaP), as Group 1 carcinogens. Epidemiological studies have shown that coexposure of BQ and cigarette smoke markedly increases the risk of cancer. We previously demonstrated that arecoline, the most abundant alkaloid in the areca nut, inhibits nucleotide excision repair through the repression of p53 activity. To investigate the combined potency of arecoline and BaP in carcinogenesis, we treated human epithelial HEp-2 cells with subcytotoxic doses of arecoline and BaP, alone or in combination, and examined the effects on DNA damage and repair. When exposed for 24h, BaP enhanced DNA repair and p53 transactivation activity. However, these enhancements were suppressed through concurrent treatment of the cells with arecoline. Using a Comet assay, we found that extended exposure to arecoline and BaP caused moderate-to-severe DNA damage in 60% of the cells. Expression of the XPD helicase was transcriptionally suppressed by 1 week of treatment with BaP. Our studies have revealed potential targets in the DNA repair pathway that are affected by BQ and tobacco components, as well as the effect of these components on carcinogenesis., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To examine the associations of body fatness, metabolic and inflammatory markers with retinal vessel calibers among children., Design: We performed a population-based cohort study among 4145 school-age children. At the median age of 6.0 years (95% range 5.8, 8.0 years), we measured body mass index, total and abdominal fat mass, metabolic and inflammatory markers (blood levels of lipids, insulin and C-peptide and C-reactive protein) and retinal vascular calibers from retinal photographs., Results: We observed that compared with normal weight children, obese children had narrower retinal arteriolar caliber (difference -0.21 s.d. score (SDS; 95% confidence interval (CI) -0.35, -0.06)), but not venular caliber. Continuous analyses showed that higher body mass index and total body fat mass, but not android/gynoid fat mass ratio and pre-peritoneal fat mass, were associated with narrower retinal arteriolar caliber (P<0.05 for body mass index and total body fat mass), but not with retinal venular caliber. Lipid and insulin levels were not associated with retinal vessel calibers. Higher C-reactive protein was associated with only wider retinal venular caliber (difference 0.10 SDS (95% CI 0.06, 0.14) per SDS increase in C-reactive protein). This latter association was not influenced by body mass index., Conclusions: Higher body fatness is associated with narrower retinal arteriolar caliber, whereas increased C-reactive protein levels are associated with wider retinal venular caliber. Increased fat mass and inflammation correlate with microvascular development from school-age onwards.

Aim: To examine the relationships of serum markers of inflammation and endothelial function to diabetic retinopathy., Methods: We recruited 224 patients with diabetes (85 with Type 1 and 139 with Type 2 diabetes) aged 18-70 years. Serum markers of inflammation (high-sensitivity C-reactive protein) and endothelial function (soluble intercell adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, endothelin-1 and total nitrite) were assessed using nephelometry, immunoassays and spectroscopy. Diabetic retinopathy was graded from two-field fundus photographs according to the Airlie House Classification system and was categorized into no diabetic retinopathy, mild non-proliferative diabetic retinopathy, moderate non-proliferative diabetic retinopathy and vision-threatening diabetic retinopathy, the latter comprising severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy or clinically significant macular oedema. Multinomial logistic regression was used to assess the associations between serum markers and diabetic retinopathy., Results: In the study, 64% of patients (144/224) had diabetic retinopathy and 25% (57/244) had vision-threatening diabetic retinopathy. After controlling for age, gender, diabetes duration, HbA1c , systolic blood pressure, total and HDL cholesterol, smoking, the use of insulin or oral hypoglycaemic agents, nephropathy and cardiovascular disease, a positive association was found between increasing high-sensitivity C-reactive protein levels and the presence of vision-threatening diabetic retinopathy (odds ratio 1.26; 95% CI 1.05-1.51, per sd increase in high-sensitivity C-reactive protein). After stratifying by BMI ( ≥ 30 and < 30 kg/m(2) ), this association was found to be more pronounced in people with a BMI ≥ 30 kg/m(2) (odds ratio 2.9; P for interaction = 0.019). No associations were found between serum markers of endothelial activation and diabetic retinopathy., Conclusions: Higher C-reactive protein levels, but not markers of endothelial function, may be related to more severe diabetic retinopathy. This finding suggests that inflammatory processes are involved in severe diabetic retinopathy, particularly in patients with a BMI ≥ 30 kg/m(2) ., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

Objectives: The role of the microcirculation in the pathogenesis of osteoarthritis (OA) remains unclear. This prospective cohort study examined the association between retinal vascular calibre and incidence of knee replacement for OA., Design: 1838 participants of the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study had retinal vascular calibre measured using a nonmydriatic digital fundus camera in 1999-2000 and were aged ≥ 40 years at joint replacement data collection commencement. The incidence of knee replacement for OA during 2002-2011 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR)., Results: 77 participants underwent knee replacement for OA. They had narrower retinal arteriolar calibre compared with those without knee replacement (166.1 ± 24.8 μm vs 174.3 ± 24.5 μm, P = 0.004). For every one standard deviation reduction in retinal arteriolar calibre, the incidence of knee replacement increased by 25% (HR 1.25, 95% confidence interval (CI) 1.00-1.56). Participants in the narrower two-thirds of arteriolar calibre had twice the risk of knee replacement compared with those in the widest one-third (HR 2.00, 95% CI 1.07-3.74, P = 0.03) after adjustment for sex, body mass index (BMI), physical activity and HbA1c. There was no association for retinal venular calibre., Conclusions: Retinal arteriolar narrowing is associated with increased risk of knee replacement for OA suggesting that further work is warranted to determine the role of the microcirculation in the pathogenesis of knee OA., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Previous studies examining the association between genetic variations in prostaglandin pathway and risk of head and neck cancer (HNC) have only included polymorphisms in the PTGS2 (COX2) gene. This study investigated the association between genetic polymorphisms of six prostaglandin pathway genes (PGDS, PTGDS, PTGES, PTGIS, PTGS1 and PTGS2), and risk of HNC., Methods: Interviews regarding the consumption of alcohol, betel quid, and cigarette were conducted with 222 HNC cases and 214 controls. Genotyping was performed for 48 tag and functional single-nucleotide polymorphisms (SNPs)., Results: Two tag SNPs of PTGIS showed a significant association with HNC risk [rs522962: log-additive odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.01-1.99 and dominant OR = 1.58, 95% CI: 1.02-2.47; rs6125671: log-additive OR = 1.49, 95% CI: 1.08-2.05 and dominant OR = 1.96, 95% CI: 1.16-3.32]. In addition, a region in PTGIS tagged by rs927068 and rs6019902 was significantly associated with risk of HNC (global P = 0.007). Finally, several SNPs interacted with betel quid and cigarette to influence the risk of HNC., Conclusions: Genetic variations in prostaglandin pathway genes are associated with risk of HNC and may modify the relationship between use of betel quid or cigarette and development of HNC., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Age-related macular degeneration (AMD) is a common vision-threatening condition affecting the elderly. AMD shares common risk factors and processes, including vascular and inflammatory pathways, with many systemic disorders. Associations have been reported between AMD and hypertension, cardiovascular disease, cerebrovascular disease, dyslipidaemia, chronic kidney disease and neurodegenerative disorders. An increasing amount of evidence suggests that individuals with AMD are also at risk of systemic diseases such as stroke. In this review, we summarize the latest evidence to support the notion that AMD is an ocular manifestation of systemic disease processes, and discuss the potential systemic side effects of ocular AMD therapy of which general physicians should be aware. Recent genetic discoveries and understanding of the pathogenic pathways in AMD in relation to systemic disorders are also highlighted., (© 2014 The Association for the Publication of the Journal of Internal Medicine.)

The Ministry of Health (MOH) have updated the clinical practice guidelines on Diabetes Mellitus to provide doctors and patients in Singapore with evidence-based treatment for diabetes mellitus. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Diabetes Mellitus, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh&#95;web/healthprofessionalsportal/doctors/guidelines/cpg&#95;medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Background: To assess prevalence and causes of vision impairment in Southeast Asia and Oceania in 1990 and 2010., Methods: Based on a systematic review of medical literature, prevalence of moderate and severe vision impairment (MSVI; presenting visual acuity <6/18 but ≥3/60 in the better eye) and blindness (presenting visual acuity <3/60) was estimated for 1990 and 2010., Results: In Oceania, the age-standardised prevalence of blindness and MSVI did not decrease significantly (1.3% to 0.8% and 6.6% to 5.1%) respectively, but in Southeast Asia, blindness decreased significantly from 1.4% to 0.8%, a 43% decrease. There were significantly more women blind (2.18 million) compared with men (1.28 million) in the Southeast Asian population in 2010, but no significant gender differences in MSVI in either subregion. Cataract was the most frequent cause of blindness in Southeast Asia and Oceania in 1990 and 2010. Uncorrected refractive error, followed by cataract, macular degeneration, glaucoma and diabetic retinopathy were the most common causes for MSVI in 1990 and 2010. With the increasing size of the older population, there have been relatively small increases in the number of blind (2%), and with MSVI (14%) in Southeast Asia, whereas increases have been greater in Oceania of 14% for blindness and of 31% for MSVI., Conclusions: The prevalence of blindness has reduced significantly from 1990 to 2010, with moderate but non-significant lowering of MSVI. Cataract and uncorrected refractive error are the main causes of vision impairment and blindness; cataract continues as the main cause of blindness, but at lower proportions.

Systemic lupus erythematosus (SLE) associated with antiphospholipid syndrome can have ocular complications. We report a 44-year-old Chinese lady with recurrent relapses of SLE and antiphospholipid syndrome with high disease activity, presenting with visual distortion in her right eye for 2 months. There was subretinal hemorrhage in her right eye, confirmed on investigations to be choroidal neovascularization secondary to a variant of age-related macular degeneration known as polypoidal choroidal vasculopathy (PCV). Anti-vascular endothelial growth factor therapy resolved her eye condition. SLE could be associated with PCV via common mechanisms, including complement pathway activation and vasculitis involving the choroidal circulation.

The dioxin-degrading bacterium strain NSYSU (NSYSU strain) has been isolated from dioxin-contaminated soil by selective enrichment techniques. In the present study, the NSYSU strain was investigated for its capability to biodegrade polychlorinated dibenzo--dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) under aerobic and anaerobic conditions. High-resolution gas chromatography-mass spectrometry and a chemically activated luciferase gene expression bioassay were performed to determine the presence of dioxin compounds. The results indicate that the NSYSU strain could degrade PCDDs and PCDFs under anaerobic conditions in liquid cultures. The main intermediates of the dechlorination process were identified. The results of the bioreactor test indicate that the NSYSU strain could also degrade PCDDs and PCDFs effectively in soil slurries under aerobic conditions. Results from the bioreactor experiment show that approximately 98 and 97% of octachlorodibenzofuran and OCDD were degraded, respectively. The dioxin concentrations in soil slurry decreased from 5823 to 1198 pg toxic equivalency g, resulting in total dioxin removal of 79%. These first findings suggest that the NSYSU strain has the potential to be an effective tool for the bioremediation of soils contaminated with highly recalcitrant organic compounds., (Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)

We assessed the associations between body mass index (BMI) and blood pressure (BP) with the retinal microvasculature among preschool-aged children. Three hundred and seventy-nine children aged 3-<6 years old had gradable retinal photographs, and quantifiable retinal vascular caliber using validated computer-based methods. Weight, height, BMI, waist circumference and BP were obtained using standardized protocols. Mean (±s.d.) BMI and systolic BP in preschool-aged children were 16.0 (±1.8) kg m(-2) and 93.2 (±9.9) mm Hg, respectively. After multivariable adjustment, each kg m(-2) increase in BMI was associated with a 1.06 μm narrowing of retinal arteriolar caliber (P=0.01) and 1.12 μm widening of retinal venular caliber (P=0.02). Children in the 95th percentile (obese) compared with those in the <85th percentile (healthy weight) had narrower retinal arteriolar caliber (∼6.1 μm, Ptrend=0.01) and wider retinal venular caliber (∼6.4 μm, Ptrend=0.01). Each 10 mm Hg increase in systolic BP was associated with a 1.70 μm narrower retinal arteriolar caliber (multivariable-adjusted P=0.02). We show that BMI and systolic BP have inverse linear associations with retinal arteriolar caliber, and BMI has a positive linear association with retinal venular caliber during early childhood. These findings suggests that the influence of BP and BMI on small vessels are continuous and commence early in life.

Aims/hypothesis: Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians., Methods: We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations., Results: We identified CDKN2A/B and four novel type 2 diabetes association signals with p < 1 × 10(-5) from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (p meta = 2.6 × 10(-8); OR [95% CI] 1.18 [1.11, 1.25]). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (p meta = 2.3 × 10(-10)) and a population of European descent (p = 8.6 × 10(-3)). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians., Conclusions/interpretation: Our study identifies rs10229583 near PAX4 as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.

Objective: Type 2 diabetes and associated complications adversely affect health-related quality of life (HRQoL). However, it is unclear whether different complications have the same or different associations with HRQoL. We examined associations between retinopathy, nephropathy, peripheral neuropathy (microvascular), coronary heart disease, stroke and peripheral arterial disease (macrovascular) in diabetes and HRQoL., Design: This study was a follow-up examination between 2004 and 2007 of participants from four previous cross-sectional population-based studies in Singapore., Methods: Health-related quality of life was assessed through self-administered SF-36 health survey version 2. Diabetes and complications status were assessed through self-report, clinical and laboratory examinations. About 2601 individuals, 2205 healthy and 396 with diabetes, were studied., Results: Lower physical component scores (PCS) were associated with microvascular (2.96 points, P < 0.001) and both macro- and microvascular complications (4.67 points, P < 0.001), but not diabetes alone. Coronary heart disease (3.86 points, P = 0.007), peripheral neuropathy (11.46 points, P < 0.001) and severe retinopathy (4.46 points, P < 0.001) were associated with lower PCS. The greatest reduction in scores was seen in peripheral neuropathy., Conclusions: Quality of life in patients with diabetes is affected mainly by presence of complications, and not diabetes per se. Peripheral neuropathy was associated with the greatest reduction in quality of life. Improved management to prevent or delay onset of complications may reduce the effect on quality of life in patients with diabetes., (© 2012 John Wiley & Sons Ltd.)

Few previous studies in Western populations have reported an association between C-reactive protein (CRP) and prehypertension. However, no previous study has examined this association in Asians. We examined individuals who were free of hypertension from two independent population-based studies in Singapore: the Singapore Prospective Study Programme (SP2, n=2843 Chinese, Malay and Indians aged 24 years) and the Singapore Malay Eye Study (SiMES, n=957 Malays, aged 40-80 years). Prehypertension was defined as systolic blood pressure (BP) 120-139 mm Hg or diastolic BP 80-89 mm Hg. CRP was analyzed as categories (<1, 1-3, >3 mg l(-1)). The prevalence of prehypertension increased with increasing categories of CRP in both cohorts (P for trend <0.05 in both cohorts). After adjusting for potential confounders including body mass index (BMI), smoking and diabetes, persons with higher levels of CRP were more likely to have prehypertension in both SP2 (compared with CRP <1 mg l(-1), odds ratio (OR) 1.23, 95% confidence interval (CI) 1.03-1.48 for CRP 1-3 and OR 1.67, 95% CI 1.32-2.10 for >3 mg l(-1)) and SiMES (OR 1.45, 95% CI 1.04-2.01 and OR 1.56, 95% CI 1.07-2.27) respectively. In conclusion, data from two population-based Asian cohorts suggest that elevated serum CRP levels are associated with prehypertension.

Aim: To investigate the frequency and risk factors of non-retinopathy ocular conditions in persons with diabetes., Methods: A population-based cross-sectional study of 3176 Malay persons aged between 40 and 79 years in Singapore was conducted. Cataract, glaucoma, refractive errors, age-related macular degeneration, dry eye, epiretinal membrane, ocular hypertension and retinal conditions were assessed based on standardized interviews, clinical examinations and laboratory investigations., Results: A total of 768 participants (24.2%) had diabetes. People with diabetes were more likely to have cortical cataract (52.1 vs. 37.3%, P < 0.001), ocular hypertension (10.9 vs. 7.4%, P = 0.002) and epiretinal membrane (17.2 vs. 10.1%, P < 0.001) compared with those without diabetes. The odds of having cortical cataract (odds ratio 1.63, 95% CI 1.20-2.20) and epiretinal membrane (among those with previous cataract surgery: odds ratio 1.63, 95% CI 1.20-2.20) were significantly higher in people with diabetes compared with those without. The population attributable risks for cortical cataract and epiretinal membrane because of diabetes were 8.7 and 9.0%, respectively. In persons with diabetes, hypertension and high cholesterol were the major risk factors associated with non-retinopathy eye complications such as ocular hypertension (odds ratio 1.18, 95% CI 1.04-1.33) and retinal emboli (odds ratio 1.99, 95% CI 1.05-3.80)., Conclusion: Our results allow clinicians to better inform patients with diabetes that they are more likely to have cortical cataract and epiretinal membranes (those with previous cataract surgery) in addition to diabetic retinopathy. Two modifiable risk factors-blood pressure and cholesterol associated with ocular hypertension and retinal emboli, respectively-are also risk factors for non-retinopathy ocular conditions in persons with diabetes., (© 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.)

Large-artery stiffness is a risk factor for stroke, including cerebral small-vessel disease. Retinal microvascular changes are thought to mirror those in cerebral microvessels. We investigated the relationship between aortic stiffness and retinal microvascular changes in Asian ischemic stroke patients. We studied 145 acute ischemic stroke patients in Singapore who had aortic stiffness measurements using carotid-femoral pulse wave velocity (cPWV). Retinal photographs were assessed for retinal microvessel caliber and qualitative signs of focal arteriolar narrowing, arteriovenous nicking and enhanced arteriolar light reflex. Aortic stiffening was associated with retinal arteriolar changes. Retinal arteriolar caliber decreased with increasing cPWV (r=-0.207, P=0.014). After adjusting for age, gender, hypertension, diabetes, mean arterial pressure and small-vessel stroke subtype, patients within the highest cPWV quartile were more likely to have generalized retinal arteriolar narrowing defined as lowest caliber tertile (odds ratio (OR) 6.84, 95% confidence interval (CI) 1.45-32.30), focal arteriolar narrowing (OR 13.85, CI 1.82-105.67), arteriovenous nicking (OR 5.08, CI 1.12-23.00) and enhanced arteriolar light reflex (OR 3.83, CI 0.89-16.48), compared with those within the lowest quartile. In ischemic stroke patients, aortic stiffening is associated with retinal arteriolar luminal narrowing as well as features of retinal arteriolosclerosis.

Purpose: To assess retinal vascular calibre changes in eyes with neovascular age-related macular degeneration (AMD), treated with intravitreal anti-vascular endothelial growth factor agents, over a 1-year period and compare any such changes to untreated fellow eyes., Methods: Treatment naïve patients with neovascular AMD received three consecutive intravitreal injections of ranibizumab, followed by a pro re nata dosing regimen up to 1 year, with the aim of maintaining a 'fluid-free' macula. Retinal arteriolar and venular calibre was measured from digital fundus photographs at baseline and at three monthly intervals to 1 year, and summarised as central retinal artery equivalent (CRAE) and central retinal venular equivalent (CRVE), respectively., Results: A total of 53 injected eyes and 41 fellow, non-injected eyes were analysed. At baseline, there were no differences in retinal vascular calibre between injected and non-injected eyes (mean CRAE (SD) 144.93 (14.07) vs 145.74 (13.10) μm, P=0.80 and mean CRVE (SD) 216.23 (25.93) vs 219.91 (22.82) μm, P=0.53). Over a 12-month period, retinal venular calibre dilatation occurred in injected eyes (mean CRVE change +5.71 (14.71) μm, P=0.007), with no change in retinal arterioles, +0.69 (14.71) μm, P=0.68. In non-injected eyes, arteriolar narrowing occurred as a whole, mean CRAE change -4.20 (7.00) μm, P=0.001, over 12 months, with a trend for narrowing in venules, -2.16 (11.56) μm, P=0.28. In injected eyes, after controlling for covariates, the changes in CRVE over 12 months mirrored improvements in macular thickness, -0.06 (-0.005, -0.11) μm, P=0.04, and visual acuity, +9.66 (-0.30, +19.32) μm, P=0.06., Conclusion: Intravitreal ranibizumab significantly dilated retinal venules after a 1-year period.

Introduction: Early recognition of preeclampsia (PE) is crucial for better obstetric care. Clinical risk factors are easier to identify than biochemical markers and may be useful in the prediction of PE., Objectives: To evaluate which risk factors provide the best prediction for PE in a group at high-risk for developing PE., Methods: A prospective cohort study of 100 pregnant women was performed. During the first trimester we included pregnant women who had at least one of the following risk factors for PE: previous history of PE, previous history of HELLP, pre-existing hypertension, diabetes mellitus, multiple pregnancy, obesity or autoimmune diseases. These women were monitored during their pregnancy and their medical data were used to set up a database. We focused on baseline characteristics (parity, maternal age, maternal smoking, ethnic origin, blood pressure at booking, risk factors mentioned above and medication use). Differences between groups were analysed using the Student's t test or the Mann-Whitney U test as applicable. Categorical data were analysed with χ(2) statistics. Subsequently, multivariable logistic regression analysis with a stepwise backward selection procedure of predictors was performed to identify independent risk factors for PE., Results: Of the 100 women 22 (22.0%) developed PE and 13 (13.0%) developed gestational hypertension (GH). More women in the group with progression to PE had a history of PE (50.0% versus 26.2%, p=0.039), while less women had a multiple pregnancy (4.5% versus 27.7%, p=0.023) as compared with the group not progressing to either PE or GH. In the group of GH, no women were using antihypertensive medication while in the group of women not progressing to either PE or GH 32.3% were using antihypertensive medication (p=0.017). Multivariable logistic regression revealed that singleton pregnancy was the only independent predictor of PE (OR 8.04, 95% CI 1.01 - 64.3, p=0.045)., Conclusion: In this prospective cohort study we evaluated clinical risk factors for the development of PE in pregnant high-risk women based on obstetric history and comorbidity. We found that a singleton pregnancy was the only independent predictor for PE in this group of high-risk women. The other risk factors for which the women were included were not strong enough to act as a predictor for PE in this relatively small cohort. Nonetheless, it is important to be alert for PE in this group of pregnant women with high-risk for PE, especially because most of them have more than one risk factor., (Copyright © 2012. Published by Elsevier B.V.)

Aims: To compare methods to measure time outdoor and light levels, two possible predictors of myopia, in Singapore children., Methods: Outdoor time from a diary and portable light meter over a 1-week period was compared in 117 Singapore children aged 6-12 years with and without myopia. All children wore a (HOBO Pendant temp/light Part # UA-002-64) light meter for 1 week and the parents filled the 7-day outdoor diary to track the outdoor activity., Results: Mean outdoor time from diary and time with light levels was 5.44 hours per week and 7.91 hours per week, respectively, during school term and school holidays. Time spent with light levels of >1000 Lux from the light meter were 7.08 h per week and 9.81 h per week, respectively, during school term and school holidays. The intraclass correlation coefficients were 0.21 and 0.28 for outdoor time from the diary and light meter (1000 Lux cut-off) during the school term and holidays, respectively. The correlation coefficient was 0.34 (95% CI 0.05, 0.58) for a weekday during school holidays, 0.17 (-0.14, 0.45) for a weekday during school term, 0.07 (-0.16, 0.29) for a weekday during school term, and 0.25 (0.02, 0.46) for a weekend during school term., Conclusions: The agreement between the light meter and 1-week diary was poor to fair. Both instruments measure different parameters, time outdoors and light intensity, and could therefore capture different aspects of risk in future myopia studies.

Introduction: Visualisation of the microcirculation through retinal imaging can provide information on the health of systemic vasculature. Characterisation of the retinal vasculature throughout pregnancy using retinal imaging is a novel approach to examine physiological changes to the cardiovascular system, and may be useful to predict early pathophysiological signs of adverse maternal outcomes., Objectives: To characterise the retinal vascular and blood pressure (BP) changes that occur throughout a healthy pregnancy., Methods: Data was collected from women recruited at 13±2 weeks of gestation from Royal Prince Alfred Hospital, a major tertiary referral hospital in Sydney, Australia. Retinal images centred on the optic disc and BP readings were collected throughout pregnancy. Postnatal data was collected from medical records, and women with hypertensive disorders of pregnancy and gestational diabetes mellitus were excluded. This left a final group of 19 women. Retinal images from 13±2, 19±2, 29±2 and 38±2 weeks gestation were graded using semi-automated retinal vascular calibre measurement (IVAN) software and the central retinal arteriolar equivalent (CRAE), and central retinal venular equivalent (CRVE). BP data was collected at the same time points as the retinal images. Analysis of data was performed using paired t-tests and repeated measures analysis of variance (ANOVA). Women with missing data points were excluded from the analysis at the relevant time points., Results: Over the course of pregnancy, there was a significant dilatation of retinal arterioles between 13±2 and 19±2weeks (from 166.4 to 172.7μm, SE: 3.7μm, n=19, p=0.01), corresponding to a significant fall in diastolic BP during this time (from 64.6 to 60.2mmHg, SE: 1.5mmHg, p=0.01). No significant changes in venular diameter or systolic BP were noted. Between 19±2 and 29±2weeks (n=4), no significant changes to retinal arteriolar or venular diameter were seen although there were significant increases in both systolic and diastolic BP (SBP: from 100.3 to 109.9mmHg, SE: 1.9mmHg, p=0.01; DBP: from 59.3 to 64.6mmHg, SE: 6.9mmHg, p=0.01). Between 29±2 and 38±2weeks (n=3), no significant changes in retinal arteriolar, and venular diameter or BP were observed., Conclusion: An increase in retinal arteriolar diameter between 13±2 and 19±2 weeks gestation was observed, which corresponded to a decrease in both systolic and diastolic BP. However, between 19±2 and 29±2 weeks there was no change in vasculature, even though there was a significant increase in BP. By characterising the changes to retinal vessels that occur throughout a healthy pregnancy, we can further our understanding of the response of the systemic vasculature to pregnancy, which may provide clues to early vascular disease of pregnancies., (Copyright © 2012. Published by Elsevier B.V.)

Introduction: Hypertensive disorders of pregnancy (HDP) are characterised by vascular dysfunction. Retinal vascular imaging is a novel, non-invasive way to characterise early microvascular changes in pregnancy, and as a result has the potential to be used to predict the onset of HDP., Objectives: To characterise retinal vascular changes that occur in HDP, and compare these changes to those in healthy pregnancies., Methods: Women were recruited at 13±2 weeks of gestation from Royal Prince Alfred Hospital, a major metropolitan tertiary referral hospital in Sydney, Australia. Retinal images centred on the optic disc and blood pressure (BP) readings were collected at 13±2, 19±2, 29±2 and 38±2 weeks gestation. Retinal images were graded using semi-automated retinal vascular calibre measurement software (IVAN) and the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were calculated. Within and between subject repeat measures analysis was performed on images from each trimester, using paired t-tests and repeated measures analysis of variance (ANOVA). Multiple linear regressions were used to model the average arteriole diameter adjusted for age, tobacco consumption and body mass index (BMI). All tests were two-sided using a 5% level of significance. A clinical diagnosis of HDP was obtained from postnatal medical record data. Women with missing data points were excluded from the analysis at that time point., Results: Of the 39 women included in the study, 6 (15%) were diagnosed with HDP. In the HDP cohort, repeated measures ANOVA revealed no significant changes in arteriolar or venular diameter measurements throughout pregnancy. Paired t-tests indicated no significant differences in any of the outcome measures between HDP and healthy pregnancies at 13±2 (n=36) and 19±2 (n=39)weeks. At 29±2weeks (n=39), there was a significantly smaller venular diameter in HDP pregnancies (220.4±6.9μm vs 239.1± 5.4μm in healthy pregnancies, p=0.03). At 38±2weeks (n=39), arteriolar diameter was significantly smaller in HDP pregnancies (148.6±6.0μm vs 164.1±4.6μm in healthy pregnancies, p=0.04). Similar results persisted following adjustments for cardiovascular risk factors (age, tobacco use and BMI)., Conclusion: Significant differences in the retinal vasculature develop in HDP as compared to healthy pregnancies. These differences appear at29±2weeks gestation and persist throughout the rest of the pregnancy. Retinal vascular imaging is a promising tool for the detection of the early microvascular changes in HDP, prior to diagnosis., (Copyright © 2012. Published by Elsevier B.V.)

Very few studies have explored links between physical activity, sedentary behaviours and blood pressure (BP) in early adolescence. We aimed to assess the association between a range of sedentary activities (screen time, television (TV) viewing, computer usage, video game usage and time spent in homework or reading) and BP in schoolchildren. Eligible year-7 students (2353/3144, mean age 12.7 years) from a random cluster sample of 21 Sydney schools were examined during 2003-2005. Parents and children completed detailed questionnaires of activity. BP was measured using a standard protocol and high BP was defined using published guidelines. Height and weight were measured, and body mass index (BMI) calculated. After adjusting for age, sex, ethnicity, parental education, height, BMI and time spent in physical activity, each hour per day spent in screen time, watching TV and playing video games was associated with a significant increase in diastolic BP of 0.44 (P=0.0001), 0.99 (P<0.0001) and 0.64 mm Hg (P=0.04), respectively. In contrast, each hour per day spent reading was associated with a decrease of 0.91 (P=0.01) and 0.69 mm Hg (P=0.02) in systolic and diastolic BP, respectively. Our results indicate that addressing different types of sedentary activities could be a potentially important strategy to reduce the prevalence of elevated BP in children.

Purpose: To determine the influence of diabetes, diabetic retinopathy (DR), and other factors on macular thickness, measured using optical coherence tomography (OCT), in a population-based sample., Methods: Data from the population-based Singapore Indian Eye Study were analyzed. We measured macular thickness using Stratus OCT Fast Macular Thickness scan protocol in 228 participants with diabetes mellitus (including 167 without DR, 44 with mild DR, 17 with moderate or severe DR) and 72 non-diabetic controls without macular oedema or other macular lesions. Analysis was done on right eyes., Results: The mean age of participants was 60.1 ± 10.1 years, with 53.8% men. Macular thickness measurements did not differ significantly between diabetic participants with no or mild DR and non-diabetic participants. Diabetic participants with moderate or severe DR had greater foveal and temporal outer macula thickness compared with those with no or mild DR (P=0.003). In a multivariate linear regression model, older age (P=0.009), male gender (P=0.005), and lower spherical equivalent (P=0.001) were other factors associated with greater foveal thickness in all participants after controlling for body mass index, glycosylated haemoglobin, total cholesterol, and mean systolic blood pressure., Conclusion: This population-based study showed that diabetic participants with moderate or severe DR had thicker foveal measurements, even in the absence of diabetic macula oedema, than non-diabetic controls. Other factors that influenced macular thickness measurements were age, gender, and spherical equivalent. These data may aid the interpretation of OCT findings in persons with diabetes and DR.

Understanding the impact of a condition from the patient's perspective is important, and different types of patient-reported outcomes or instruments are available to help with this. This review article summarises the current evidence on the impact of diabetic retinopathy (DR) and its associated vision impairment on patient-reported outcomes. We have included research that has used a range of outcome measures to assess the impact of DR on generic health-related quality of life, utility, vision-functioning and vision-specific quality of life. This review also offers clarification on frequently misused psychometric terminologies to help clinicians and researchers better understand the literature associated with patient-reported outcome research. Overall, the evidence suggests that DR, particularly in its vision-threatening stages, has a substantial, negative impact on the patient. However, our understanding of the impact of DR is currently restricted due to limitations inherent in currently available patient-reported outcome measures. We conclude by discussing potential directions for future research in this area, such as item banking and computer adaptive testing.

Aims/hypothesis: To explore the relative contribution of novel and traditional risk markers for diabetic retinopathy (DR)., Methods: A clinic-based study of 224 diabetic patients (85 type 1, 139 type 2) from a diabetes clinic was performed. DR was graded from fundus photographs according to the Airlie House Classification system and classified as absent or present (at least ETDRS level 14). Novel risk markers assessed included serum apolipoprotein (Apo) AI and B, skin microvascular responses to acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) iontophoresis, flicker-light-induced retinal vasodilation and retinal vascular tortuosity. Relative contribution was determined by semi-partial correlation coefficient generated from a logistic regression model containing all traditional and novel risk markers simultaneously., Results: There were 144 (64.3%) participants with DR. Of the novel markers, ApoAI, flicker-light-induced vasodilation and retinal arteriolar tortuosity were significantly associated with DR, independently of traditional measures (all p < 0.03). Diabetes duration contributed most (51%) to the risk of DR, followed by ApoAI (16%), systolic blood pressure (13%), retinal arteriolar tortuosity (8%) and flicker-light-induced venular and arteriolar dilation (3% and 0.5%, respectively)., Conclusions/interpretation: ApoAI and retinal arteriolar tortuosity made considerable contributions to DR risk, independently of traditional risk markers. Findings from this study suggest that serum ApoAI and retinal arteriolar tortuosity may be novel and independent risk markers of DR.

Hypertension has profound effects on various parts of the eye. Classically, elevated blood pressure results in a series of retinal microvascular changes called hypertensive retinopathy, comprising of generalized and focal retinal arteriolar narrowing, arteriovenous nicking, retinal hemorrhages, microaneurysms and, in severe cases, optic disc and macular edema. Studies have shown that mild hypertensive retinopathy signs are common and seen in nearly 10% of the general adult non-diabetic population. Hypertensive retinopathy signs are associated with other indicators of end-organ damage (for example, left ventricular hypertrophy, renal impairment) and may be a risk marker of future clinical events, such as stroke, congestive heart failure and cardiovascular mortality. Furthermore, hypertension is one of the major risk factors for development and progression of diabetic retinopathy, and control of blood pressure has been shown in large clinical trials to prevent visual loss from diabetic retinopathy. In addition, several retinal diseases such as retinal vascular occlusion (artery and vein occlusion), retinal arteriolar emboli, macroaneurysm, ischemic optic neuropathy and age-related macular degeneration may also be related to hypertension; however, there is as yet no evidence that treatment of hypertension prevents vision loss from these conditions. In management of patients with hypertension, physicians should be aware of the full spectrum of the relationship of blood pressure and the eye.

Introduction: This study highlights the key epidemiological findings from the Singapore Malay Eye Study (SiMES-1)., Methods: SiMES-1 was a cross-sectional, population-based epidemiological study on eye diseases. It was performed on 3,280 randomly selected Malay adults living in the south-western part of Singapore. All study participants underwent various validated questionnaires and detailed eye examinations. A review of all papers published from SiMES-1 was performed., Results: A total of 24.6% of the study population had myopia, while 35.3% had hyperopia and 39.4% had astigmatism. 20.4% of the population had under-corrected refractive error. 1,338 (45.7%) participants were diagnosed to have cataracts in at least one eye. 8.6% of the study population had undergone cataract surgery in either eye, while 4.7% had bilateral cataract surgery. 150 (4.6%) participants were diagnosed to have glaucoma, of which primary open angle glaucoma was the most common type (3.2% of the study population), followed by secondary glaucoma (0.8%) and primary angle closure glaucoma (0.2%). Pterygium was diagnosed in 508 out of 3,266 study participants, giving a prevalence rate of 15.6%. The presence of diabetic retinopathy was observed in 421 (12.9%) out of 3,265 study participants. 183 (5.6%) study participants had some degree of age-related macular degeneration (AMD), of which 23 (0.7%) were classified as having late AMD., Conclusion: This paper provides a summary of the prevalence of common eye diseases among the Singaporean adult Malay population and provides data useful for public health education and disease prevention.

Background/aims: In persons with diabetes, retinal microvascular abnormalities are associated with chronic kidney disease (CKD). However, it is not clear if the same relationship applies in persons without diabetes., Methods: We examined 2,971 participants from a population-based study (240 with, 2,731 without diabetes). Retinal photographs were masked graded for retinal microvascular signs, and CKD was defined as estimated glomerular filtration rate (eGFR(MDRD)) <60 ml/min/1.73 m(2)., Results: Retinal microvascular signs were more frequent in persons with CKD. After adjusting for age, gender, systolic blood pressure and fasting plasma glucose, CKD was associated with both presence of retinopathy (odds ratio, OR, 1.2, 95% confidence interval, CI 1.0-1.5) and venular dilation (OR 1.2, 95% CI 1.0-1.5). These associations were similar in persons with and without diabetes. There was a significant trend for increasing magnitude of associations of retinopathy with increasing severity levels of CKD (p for trend 0.03)., Conclusions: Retinal microvascular signs, namely retinopathy lesions and venular dilation, are associated with CKD both in persons with, and without diabetes. This supports the concept that retinal microvascular signs are indicators of generalized microvascular disease even in the absence of diabetes, and reinforces the link between retinal and renal microcirculations., (Copyright © 2012 S. Karger AG, Basel.)

Objective: Recent genome-wide association studies (GWAS) have identified 38 obesity-associated loci among European populations. However, their contribution to obesity in other ethnicities is largely unknown., Methods: We utilised five GWAS (N=10 482) from Chinese (three cohorts, including one with type 2 diabetes and another one of children), Malay and Indian ethnic groups from Singapore. Data sets were analysed individually and subsequently in combined meta-analysis for Z-score body-mass index (BMI) associations., Results: Variants at the FTO locus showed the strongest associations with BMI Z-score after meta-analysis (P-values 1.16 × 10(-7)-7.95 × 10(-7)). We further detected associations with nine other index obesity variants close to the MC4R, GNPDA2, TMEM18, QPCTL/GIPR, BDNF, ETV5, MAP2K5/SKOR1, SEC16B and TNKS/MSRA loci (meta-analysis P-values ranging from 3.58 × 10(-4)-1.44 × 10(-2)). Three other single-nucleotide polymorphisms (SNPs) from CADM2, PTBP2 and FAIM2 were associated with BMI (P-value ≤ 0.0418) in at least one dataset. The neurotrophin/TRK pathway (P-value=0.029) was highlighted by pathway-based analysis of loci that had statistically significant associations among Singaporean populations., Conclusion: Our data confirm the role of FTO in obesity predisposition among Chinese, Malays and Indians, the three major Asian ethnic groups. We additionally detected associations for 12 obesity-associated SNPs among Singaporeans. Thus, it is likely that Europeans and Asians share some of the genetic predisposition to obesity. Furthermore, the neurotrophin/TRK signalling may have a central role for common obesity among Asians.

Purpose: To determine the prevalence rates of refractive errors and pattern of ocular biometry in a multi-ethnic elderly Asian population., Methods: A population-based study of 1835 residents aged 55-85 years, evaluating the refractive error and ocular biometry parameters, including axial length (AL) and anterior chamber depth., Results: The age-standardized prevalence of myopia, hyperopia, astigmatism, and anisometropia were 30.0% (95% confidence interval (CI): 29.6, 30.4), 41.5% (95% CI: 41.1, 41.9), 43.5% (95% CI: 43.1, 44.0), and 22.1% (95% CI: 21.7, 22.4), respectively. Male gender (P=0.02), age ≥ 75 years (P=0.033), and higher educational level (P<0.001) were significantly associated with higher rates of myopia in multivariate analyses. The prevalence of astigmatism was higher in persons with diabetes (odds ratio (OR) 1.4, 95% CI: 1.03, 1.90, P=0.031). AL was longer in Chinese than other ethnic groups (23.7 vs 23.4 mm, P=0.018), and in men compared with women (24.2 vs 23.4 mm, P<0.001). AL was associated with increasing height (AL increased by 0.3 mm for every 10 cm increase in height, P<0.001)., Conclusion: There is a high prevalence of myopia in elderly Singaporeans, consistent with trends seen in younger populations in Asia. Male gender and higher education were independent risk factors for myopia. These data suggest that higher rates of myopia in East Asians compared with Caucasians may not be a recent phenomenon.

Aim/hypothesis: The aim of this hypothesis was to examine the association of retinal vessel tortuosity with diabetes and diabetic retinopathy (DR)., Methods: A clinic-based study of 327 participants (224 with diabetes and 103 non-diabetic controls) aged ≥ 18 years. DR was graded from fundus photographs according to the modified Airlie House Classification system and categorised into mild non-proliferative DR (NPDR), moderate NPDR and vision-threatening DR (VTDR). Retinal vessel tortuosity was measured from disc-centred retinal photographs. Measurements were taken, using a semi-automated computer program by a single grader, of arterioles and venules within 0.5 to 2 disc diameters away from the optic disc., Results: There were 114 (44%) participants with DR. In the multivariate analysis, retinal arteriolar and venular tortuosity were increased in participants with diabetes without DR (mean difference 12.4 × 10(-5) and 13.3 × 10(-5), respectively; both p < 0.05) and in those with DR (mean difference 15.4 × 10(-5) and 15.0 × 10(-5), respectively; both p < 0.01) compared with non-diabetic participants. Among participants with diabetes, increased arteriolar tortuosity was significantly associated with mild NPDR (OR 1.53, 95% CI 1.03-2.05, per SD increase in arteriolar tortuosity) and moderate NPDR (OR 1.67, 95% CI 1.10-2.55) but not VTDR (OR 0.91, 95% CI 0.54-1.54). No association with DR was found for venular tortuosity., Conclusions/interpretation: Persons with diabetes had more tortuous retinal vasculature than persons without diabetes. In persons with diabetes, increased arteriolar tortuosity was associated with mild and moderate stages of DR. This suggests that retinal vascular tortuosity might be an early indicator of microvascular damage in diabetes; thus, further investigation is indicated.

Objectives: Retinal microvasculature changes are associated with vascular events including stroke in healthy populations. It is not known whether retinal microvascular changes predict recurrent vascular events after ischemic stroke. We examined the relationship between retinal microvascular signs and subsequent vascular events in a prospective cohort of 652 acute ischemic stroke patients admitted to a tertiary hospital in Singapore from 2005 to 2007., Methods: Retinal photographs taken within 1 week of stroke onset were assessed in a masked manner for quantitative and qualitative measures. Follow-up data over 2-4 years were obtained by standardized telephone interview and then were verified from medical records. Predictors of recurrent vascular events (cerebrovascular, coronary, vascular death, and composite vascular events) were determined using Cox regression models., Results: Follow-up data over a median of 29 months were obtained for 89% (652 patients) of the cohort. After adjustment for covariates including traditional risk factors and index stroke etiology, patients with severe arteriovenous nicking (AVN) were more likely to have a recurrent cerebrovascular event (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.20-4.33) compared with those without AVN. Patients with severe focal arteriolar narrowing (FAN) were more likely to have a recurrent cerebrovascular event (HR 2.75, 95% CI 1.14-6.63) or subsequent composite vascular event (HR 2.77, 95% CI 1.31-5.86) compared to those without FAN., Conclusions: Retinal microvascular changes predicted subsequent vascular events after ischemic stroke, independent of traditional risk factors and stroke subtype. Thus, retinal imaging has a potential role in predicting the risk of recurrent vascular events after ischemic stroke and in understanding novel vascular risk factors.