Publications by authors named "Ching-Yu Cheng"

528 Publications

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes.

Nat Commun 2021 06 9;12(1):3505. Epub 2021 Jun 9.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias.
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http://dx.doi.org/10.1038/s41467-021-23556-4DOI Listing
June 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 Jun 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

COVID-19 awareness, knowledge and perception towards digital health in an urban multi-ethnic Asian population.

Sci Rep 2021 05 24;11(1):10795. Epub 2021 May 24.

Singapore Eye Research Institute, Singapore National Eye Centre, The Academia, 20 College Road, Discovery Tower Level 6, Singapore, 169856, Singapore.

This study aimed to determine COVID-19-related awareness, knowledge, impact and preparedness among elderly Asians; and to evaluate their acceptance towards digital health services amidst the pandemic. 523 participants (177 Malays, 171 Indians, 175 Chinese) were recruited and underwent standardised phone interview during Singapore's lockdown period (07 April till 01 June 2020). Multivariable logistic regression models were performed to evaluate the associations between demographic, socio-economic, lifestyle, and systemic factors, with COVID-19 awareness, knowledge, preparedness, well-being and digital health service acceptance. The average perception score on the seriousness of COVID-19 was 7.6 ± 2.4 (out of 10). 75.5% of participants were aware that COVID-19 carriers can be asymptomatic. Nearly all (≥ 90%) were aware of major prevention methods for COVID-19 (i.e. wearing of mask, social distancing). 66.2% felt prepared for the pandemic, and 86.8% felt confident with government's handling and measures. 78.4% felt their daily routine was impacted. 98.1% reported no prior experience in using digital health services, but 52.2% felt these services would be helpful to reduce non-essential contact. 77.8% were uncomfortable with artificial intelligence software interpreting their medical results. In multivariable analyses, Chinese participants felt less prepared, and more likely felt impacted by COVID-19. Older and lower income participants were less likely to use digital health services. In conclusion, we observed a high level of awareness and knowledge on COVID-19. However, acceptance towards digital health service was low. These findings are valuable for examining the effectiveness of COVID-19 communication in Singapore, and the remaining gaps in digital health adoption among elderly.
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http://dx.doi.org/10.1038/s41598-021-90098-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144201PMC
May 2021

Men's perception and understanding of male-factor infertility in the UK.

Br J Nurs 2021 May;30(9):S8-S16

Consultant Urologist, Newcastle Fertility Centre, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne.

Male-factor infertility is a common but stigmatised issue, and men often do not receive the emotional support and the information they need. This study sought to understand awareness of male fertility issues compared to female fertility among the UK general male public, and also what were perceived as being the optimum methods for providing support for affected men, emotionally and through information. Men feel that male infertility is not discussed by the public as much as female infertility. Lifestyle issues that affect male fertility are not well understood, and men affected by infertility desire more support, including online, from health professionals and through peer support. Health professionals, including those in public health, could offer evidence-based programmes to reduce stigma and increase public knowledge about infertility, as well as offer emotional support to men with infertility problems.
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http://dx.doi.org/10.12968/bjon.2021.30.9.S8DOI Listing
May 2021

Visual Impairment, Major Eye Diseases and Mortality in a multi-ethnic Asian population and a Meta-analysis of Prospective Studies.

Am J Ophthalmol 2021 May 6. Epub 2021 May 6.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore. Electronic address:

Purpose: Vision impairment (VI) is associated with poor quality of life and increased risk of falls. Few prospective data are available on the impact of VI and the major eye diseases on mortality risk in Asians.

Design: Prospective cohort study with meta-analysis METHODS: We conducted a multi-ethnic prospective study of adults (40-80 years) in the Singapore Epidemiology of Eye Diseases Study (baseline 2004-11). All-cause mortality was obtained from the National Death Registry until May 2017. VI was defined by best-corrected visual acuity (BCVA) <20/40 in the better eye. Major eye diseases were assessed using standard protocols. We examined associations using multivariable-adjusted Cox proportional-hazards regression models. Finally, we conducted a meta-analysis on the associations between VI and mortality.

Results: Of 9,986 participants, 1210 deaths occurred (12.1%) over a median follow-up of 8.8 years. Compared to those with normal vision, persons with VI had increased risk of mortality (hazards ratio 1.53, 95% confidence interval [1.30-1.81] in multivariable models. In ethnicity-specific analyses, this association was significant across Chinese (1.63 [1.08-2.48]), Malays (1.31 [1.06-1.62]), and Indians (2.25[1.61-3.15]). Cataract, under-corrected refractive errors (URE) and diabetic retinopathy (DR) were significantly associated with mortality (HRs: 1.30, 1.22 and 1.54 respectively). In a meta-analysis of 12 studies including 58034 persons, VI was associated with 30% increased risk of mortality (1.3, [1.2-1.5]).

Conclusions: In this multi-ethnic Asian population, VI and preventable eye conditions (cataract, URE and DR) were associated with mortality, emphasizing the need for early detection and intervention to prevent and treat VI and major eye diseases.
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http://dx.doi.org/10.1016/j.ajo.2021.04.026DOI Listing
May 2021

Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis.

Ophthalmology 2021 May 1. Epub 2021 May 1.

Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Republic of Singapore; Duke-NUS Medical School, Singapore, Republic of Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore. Electronic address:

Topic: To provide updated estimates on the global prevalence and number of people with diabetic retinopathy (DR) through 2045.

Clinical Relevance: The International Diabetes Federation (IDF) estimated the global population with diabetes mellitus (DM) to be 463 million in 2019 and 700 million in 2045. Diabetic retinopathy remains a common complication of DM and a leading cause of preventable blindness in the adult working population.

Methods: We conducted a systematic review using PubMed, Medline, Web of Science, and Scopus for population-based studies published up to March 2020. Random effect meta-analysis with logit transformation was performed to estimate global and regional prevalence of DR, vision-threatening DR (VTDR), and clinically significant macular edema (CSME). Projections of DR, VTDR, and CSME burden were based on population data from the IDF Atlas 2019.

Results: We included 59 population-based studies. Among individuals with diabetes, global prevalence was 22.27% (95% confidence interval [CI], 19.73%-25.03%) for DR, 6.17% (95% CI, 5.43%-6.98%) for VTDR, and 4.07% (95% CI, 3.42%-4.82%) for CSME. In 2020, the number of adults worldwide with DR, VTDR, and CSME was estimated to be 103.12 million, 28.54 million, and 18.83 million, respectively; by 2045, the numbers are projected to increase to 160.50 million, 44.82 million, and 28.61 million, respectively. Diabetic retinopathy prevalence was highest in Africa (35.90%) and North American and the Caribbean (33.30%) and was lowest in South and Central America (13.37%). In meta-regression models adjusting for habitation type, response rate, study year, and DR diagnostic method, Hispanics (odds ratio [OR], 2.92; 95% CI, 1.22-6.98) and Middle Easterners (OR, 2.44; 95% CI, 1.51-3.94) with diabetes were more likely to have DR compared with Asians.

Discussion: The global DR burden is expected to remain high through 2045, disproportionately affecting countries in the Middle East and North Africa and the Western Pacific. These updated estimates may guide DR screening, treatment, and public health care strategies.
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http://dx.doi.org/10.1016/j.ophtha.2021.04.027DOI Listing
May 2021

Retinal photograph-based deep learning algorithms for myopia and a blockchain platform to facilitate artificial intelligence medical research: a retrospective multicohort study.

Lancet Digit Health 2021 05;3(5):e317-e329

Peking Union Medical College Hospital, Beijing, China.

Background: By 2050, almost 5 billion people globally are projected to have myopia, of whom 20% are likely to have high myopia with clinically significant risk of sight-threatening complications such as myopic macular degeneration. These are diagnoses that typically require specialist assessment or measurement with multiple unconnected pieces of equipment. Artificial intelligence (AI) approaches might be effective for risk stratification and to identify individuals at highest risk of visual loss. However, unresolved challenges for AI medical studies remain, including paucity of transparency, auditability, and traceability.

Methods: In this retrospective multicohort study, we developed and tested retinal photograph-based deep learning algorithms for detection of myopic macular degeneration and high myopia, using a total of 226 686 retinal images. First we trained and internally validated the algorithms on datasets from Singapore, and then externally tested them on datasets from China, Taiwan, India, Russia, and the UK. We also compared the performance of the deep learning algorithms against six human experts in the grading of a randomly selected dataset of 400 images from the external datasets. As proof of concept, we used a blockchain-based AI platform to demonstrate the real-world application of secure data transfer, model transfer, and model testing across three sites in Singapore and China.

Findings: The deep learning algorithms showed robust diagnostic performance with areas under the receiver operating characteristic curves [AUC] of 0·969 (95% CI 0·959-0·977) or higher for myopic macular degeneration and 0·913 (0·906-0·920) or higher for high myopia across the external testing datasets with available data. In the randomly selected dataset, the deep learning algorithms outperformed all six expert graders in detection of each condition (AUC of 0·978 [0·957-0·994] for myopic macular degeneration and 0·973 [0·941-0·995] for high myopia). We also successfully used blockchain technology for data transfer, model transfer, and model testing between sites and across two countries.

Interpretation: Deep learning algorithms can be effective tools for risk stratification and screening of myopic macular degeneration and high myopia among the large global population with myopia. The blockchain platform developed here could potentially serve as a trusted platform for performance testing of future AI models in medicine.

Funding: None.
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http://dx.doi.org/10.1016/S2589-7500(21)00055-8DOI Listing
May 2021

Deep-learning-based cardiovascular risk stratification using coronary artery calcium scores predicted from retinal photographs.

Lancet Digit Health 2021 05;3(5):e306-e316

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore.

Background: Coronary artery calcium (CAC) score is a clinically validated marker of cardiovascular disease risk. We developed and validated a novel cardiovascular risk stratification system based on deep-learning-predicted CAC from retinal photographs.

Methods: We used 216 152 retinal photographs from five datasets from South Korea, Singapore, and the UK to train and validate the algorithms. First, using one dataset from a South Korean health-screening centre, we trained a deep-learning algorithm to predict the probability of the presence of CAC (ie, deep-learning retinal CAC score, RetiCAC). We stratified RetiCAC scores into tertiles and used Cox proportional hazards models to evaluate the ability of RetiCAC to predict cardiovascular events based on external test sets from South Korea, Singapore, and the UK Biobank. We evaluated the incremental values of RetiCAC when added to the Pooled Cohort Equation (PCE) for participants in the UK Biobank.

Findings: RetiCAC outperformed all single clinical parameter models in predicting the presence of CAC (area under the receiver operating characteristic curve of 0·742, 95% CI 0·732-0·753). Among the 527 participants in the South Korean clinical cohort, 33 (6·3%) had cardiovascular events during the 5-year follow-up. When compared with the current CAC risk stratification (0, >0-100, and >100), the three-strata RetiCAC showed comparable prognostic performance with a concordance index of 0·71. In the Singapore population-based cohort (n=8551), 310 (3·6%) participants had fatal cardiovascular events over 10 years, and the three-strata RetiCAC was significantly associated with increased risk of fatal cardiovascular events (hazard ratio [HR] trend 1·33, 95% CI 1·04-1·71). In the UK Biobank (n=47 679), 337 (0·7%) participants had fatal cardiovascular events over 10 years. When added to the PCE, the three-strata RetiCAC improved cardiovascular risk stratification in the intermediate-risk group (HR trend 1·28, 95% CI 1·07-1·54) and borderline-risk group (1·62, 1·04-2·54), and the continuous net reclassification index was 0·261 (95% CI 0·124-0·364).

Interpretation: A deep learning and retinal photograph-derived CAC score is comparable to CT scan-measured CAC in predicting cardiovascular events, and improves on current risk stratification approaches for cardiovascular disease events. These data suggest retinal photograph-based deep learning has the potential to be used as an alternative measure of CAC, especially in low-resource settings.

Funding: Yonsei University College of Medicine; Ministry of Health and Welfare, Korea Institute for Advancement of Technology, South Korea; Agency for Science, Technology, and Research; and National Medical Research Council, Singapore.
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http://dx.doi.org/10.1016/S2589-7500(21)00043-1DOI Listing
May 2021

Visual field defects and myopic macular degeneration in Singapore adults with high myopia.

Br J Ophthalmol 2021 Apr 22. Epub 2021 Apr 22.

Singapore Eye Research Institute, Singapore

Aims: To characterise the association between visual field (VF) defects and myopic macular degeneration (MMD) in highly myopic adults without glaucoma.

Methods: Participants (n=106; 181 eyes) with high myopia (HM; spherical equivalent ≤-5.0 D or axial length (AL) ≥26 mm), after excluding glaucoma and glaucoma suspects, from the Singapore Epidemiology of Eye Diseases-HM study were included in this cross-sectional study. Humphrey VF (central 24-2 threshold), cup-disc ratio (CDR) and intraocular pressure (IOP) measurements were performed. Mean deviation (MD) and pattern SD (PSD), VF defects (normal or abnormal; p<0.05 in ≥3 non-edge contiguous locations) and pattern (eg, generalised sensitivity loss) were analysed. MMD presence was diagnosed from fundus photographs. Generalised estimating equations were used for analysing factors (MD, PSD, VF defects, CDR and IOP) associated with MMD.

Results: Mean age was 55.4±9.9 years and 51.9% were women (AL=26.7±1.1 mm). MMD eyes had lower MD (-3.8±2.9 dB vs -1.1±1.4 dB) and higher PSD (2.8±1.7 dB vs 1.7±0.6 dB). A higher percentage of MMD eyes (n=48) had abnormal VF (62.5% vs 28.6%; p<0.001) compared with no MMD (n=133 eyes). VF pattern in MMD eyes was significantly different from eyes without MMD (p=0.001) with greater generalised sensitivity loss (53.3% vs 10.5%) and arcuate defects (16.7% vs 10.5%). In multivariate analyses, MD (OR=1.52) and PSD (OR=1.67) were significantly (p=0.003) associated with MMD, but VF defects were not associated with MMD.

Conclusion: Highly myopic adults with MMD may have VF loss when compared with highly myopic patients without MMD even in adults without glaucoma.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318674DOI Listing
April 2021

Computer-aided detection and abnormality score for the outer retinal layer in optical coherence tomography.

Br J Ophthalmol 2021 Apr 19. Epub 2021 Apr 19.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore

Background: To develop computer-aided detection (CADe) of ORL abnormalities in the retinal pigmented epithelium, interdigitation zone and ellipsoid zone via optical coherence tomography (OCT).

Methods: In this retrospective study, healthy participants with normal ORL, and patients with abnormality of ORL including choroidal neovascularisation (CNV) or retinitis pigmentosa (RP) were included. First, an automatic segmentation deep learning (DL) algorithm, CADe, was developed for the three outer retinal layers using 120 handcraft masks of ORL. This automatic segmentation algorithm generated 4000 segmentations, which included 2000 images with normal ORL and 2000 (1000 CNV and 1000 RP) images with focal or wide defects in ORL. Second, based on the automatically generated segmentation images, a binary classifier (normal vs abnormal) was developed. Results were evaluated by area under the receiver operating characteristic curve (AUC).

Results: The DL algorithm achieved an AUC of 0.984 (95% CI 0.976 to 0.993) for individual image evaluation in the internal test set of 797 images. In addition, performance analysis of a publicly available external test set (n=968) had an AUC of 0.957 (95% CI 0.944 to 0.970) and a second clinical external test set (n=1124) had an AUC of 0.978 (95% CI 0.970 to 0.986). Moreover, the CADe highlighted well normal parts of ORL and omitted highlights in abnormal ORLs of CNV and RP.

Conclusion: The CADe can use OCT images to segment ORL and differentiate between normal ORL and abnormal ORL. The CADe classifier also performs visualisation and may aid future physician diagnosis and clinical applications.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317817DOI Listing
April 2021

The global extent of undetected glaucoma in adults: a systematic review and meta-analysis.

Ophthalmology 2021 Apr 15. Epub 2021 Apr 15.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore. Electronic address:

Topic: Glaucoma is the leading cause of irreversible blindness despite having good prognosis with early treatment. We evaluated the global extent of undetected glaucoma and the factors associated with it in this systematic review and meta-analysis of population-based epidemiological studies.

Clinical Relevance: Undetected glaucoma increases the risk of vision impairment, which leads to detrimental effects on the quality-of-life and socio-economic well-being of those affected. Detailed information on the extent and factors associated with undetected glaucoma aid in the development of public health interventions.

Methods: We conducted a systematic review and meta-analysis of population-based studies published between January 1, 1990 to June 1, 2020. Article search was conducted in online databases (PubMED, Web-of-Science), grey literatures (opengrey) and non-government organization (NGOs) reports. Our outcome measure was the proportion of glaucoma cases that were undetected previously. Manifest glaucoma included any form of glaucoma reported in the respective study and may include primary-open-angle-glaucoma (POAG), primary-angle-closure-glaucoma (PACG), and/or secondary glaucoma. Undetected glaucoma was defined as glaucoma cases that were undetected prior to diagnosis in the respective study. Random-effect meta-analysis was used to estimate the pooled proportion and factors associated with undetected glaucoma. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines in our study.

Results: We identified 61 articles from 55 population-based studies (N= 189,359 participants; N= 6,949 manifest glaucoma; N= 5,558 undetected glaucoma). Globally, more than half of all glaucoma cases were previously undetected in each geographical region. Regionally, Africa (OR 12.70, 95% CI 4.91, 32.86) and Asia (OR 3.41, 95% CI 1.63, 7.16) had higher odds of undetected glaucoma as compared to Europe. Countries with low human development index (HDI, <0.55) had higher proportion of undetected manifest glaucoma as compared to countries of medium to very high HDI (≥0.55, all P <0.001). In 2020, 43.78 million POAG cases were undetected, of which 76.7% reside in Africa and Asia.

Conclusion: Undetected glaucoma is highly prevalent across diverse communities worldwide, and more common in Africa and Asia. Strategies to improve detection are needed to prevent excess visual disability and blindness due to glaucoma.
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http://dx.doi.org/10.1016/j.ophtha.2021.04.009DOI Listing
April 2021

Evaluation of Shared Genetic Susceptibility to High and Low Myopia and Hyperopia.

JAMA Ophthalmol 2021 Jun;139(6):601-609

Cardiff University School of Optometry and Vision Sciences, Cardiff, United Kingdom.

Importance: Uncertainty currently exists about whether the same genetic variants are associated with susceptibility to low myopia (LM) and high myopia (HM) and to myopia and hyperopia. Addressing this question is fundamental to understanding the genetics of refractive error and has clinical relevance for genotype-based prediction of children at risk for HM and for identification of new therapeutic targets.

Objective: To assess whether a common set of genetic variants are associated with susceptibility to HM, LM, and hyperopia.

Design, Setting, And Participants: This genetic association study assessed unrelated UK Biobank participants 40 to 69 years of age of European and Asian ancestry. Participants 40 to 69 years of age living in the United Kingdom were recruited from January 1, 2006, to October 31, 2010. Of the total sample of 502 682 participants, 117 279 (23.3%) underwent an ophthalmic assessment. Data analysis was performed from December 12, 2019, to June 23, 2020.

Exposures: Four refractive error groups were defined: HM, -6.00 diopters (D) or less; LM, -3.00 to -1.00 D; hyperopia, +2.00 D or greater; and emmetropia, 0.00 to +1.00 D. Four genome-wide association study (GWAS) analyses were performed in participants of European ancestry: (1) HM vs emmetropia, (2) LM vs emmetropia, (3) hyperopia vs emmetropia, and (4) LM vs hyperopia. Polygenic risk scores were generated from GWAS summary statistics, yielding 4 sets of polygenic risk scores. Performance was assessed in independent replication samples of European and Asian ancestry.

Main Outcomes And Measures: Odds ratios (ORs) of polygenic risk scores in replication samples.

Results: A total of 51 841 unrelated individuals of European ancestry and 2165 unrelated individuals of Asian ancestry were assigned to a specific refractive error group and included in our analyses. Polygenic risk scores derived from all 4 GWAS analyses were predictive of all categories of refractive error in both European and Asian replication samples. For example, the polygenic risk score derived from the HM vs emmetropia GWAS was predictive in the European sample of HM vs emmetropia (OR, 1.58; 95% CI, 1.41-1.77; P = 1.54 × 10-15) as well as LM vs emmetropia (OR, 1.15; 95% CI, 1.07-1.23; P = 8.14 × 10-5), hyperopia vs emmetropia (OR, 0.83; 95% CI, 0.77-0.89; P = 4.18 × 10-7), and LM vs hyperopia (OR, 1.45; 95% CI, 1.33-1.59; P = 1.43 × 10-16).

Conclusions And Relevance: Genetic risk variants were shared across HM, LM, and hyperopia and across European and Asian samples. Individuals with HM inherited a higher number of variants from among the same set of myopia-predisposing alleles and not different risk alleles compared with individuals with LM. These findings suggest that treatment interventions targeting common genetic risk variants associated with refractive error could be effective against both LM and HM.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.0497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033508PMC
June 2021

New digital models of care in ophthalmology, during and beyond the COVID-19 pandemic.

Br J Ophthalmol 2021 Mar 22. Epub 2021 Mar 22.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore

COVID-19 has led to massive disruptions in societal, economic and healthcare systems globally. While COVID-19 has sparked a surge and expansion of new digital business models in different industries, healthcare has been slower to adapt to digital solutions. The majority of ophthalmology clinical practices are still operating through a traditional model of 'brick-and-mortar' facilities and 'face-to-face' patient-physician interaction. In the current climate of COVID-19, there is a need to fuel implementation of digital health models for ophthalmology. In this article, we highlight the current limitations in traditional clinical models as we confront COVID-19, review the current lack of digital initiatives in ophthalmology sphere despite the presence of COVID-19, propose new digital models of care for ophthalmology and discuss potential barriers that need to be considered for sustainable transformation to take place.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317683DOI Listing
March 2021

Incidence and progression of diabetic retinopathy in a multi-ethnic US cohort: the Multi-Ethnic Study of Atherosclerosis.

Br J Ophthalmol 2021 Mar 19. Epub 2021 Mar 19.

Singapore Eye Research Insitute and Singapore National Eye Centre, Singapore.

Aim: To provide contemporary longitudinal data on the incidence and progression of diabetic retinopathy (DR) in a multi-ethnic population of whites, African Americans, Chinese and Hispanics in the United States.

Methods: A prospective, multi-region, multi-ethnic population-based cohort study that included 498 participants with diabetes, aged 45-84 years at baseline, from the Multi-Ethnic Study of Atherosclerosis with retinal images obtained twice, on average 8 years apart. Presence and severity of DR were graded from these retinal images according to the modified Airlie House classification system. Main outcome measures were 8-year incidence, progression and improvement of DR, and their associated risk factors.

Results: Over the 8 years, the cumulative rates were 19.2% for incident DR, 17.3% for DR progression, 23.3% for DR improvement, 2.7% for incident vision-threatening DR, 1.8% for incident proliferative DR and 2.2% for incident macular oedema. In multivariate analysis, significant risk factors associated with incident DR were higher glycosylated haemoglobin (relative risk (RR) 1.28; 95% CI: 1.16 to 1.41) and higher systolic blood pressure (RR 1.14; 95% CI: 1.04 to 1.25). Significant factors associated with DR progression were higher glycosylated haemoglobin (RR 1.20; 95% CI: 1.00 to 1.43) and higher low-density lipoprotein cholesterol (RR 1.01; 95% CI: 1.00 to 1.03).

Conclusion: Over an 8-year period, approximately one in five participants with diabetes developed DR, while almost a quarter of those with DR at baseline showed improvement, possibly reflecting the positive impact of clinical and public health efforts in improving diabetes care in the United States over the last two decades.
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http://dx.doi.org/10.1136/bjophthalmol-2021-318992DOI Listing
March 2021

Referral for disease-related visual impairment using retinal photograph-based deep learning: a proof-of-concept, model development study.

Lancet Digit Health 2021 01;3(1):e29-e40

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Duke-NUS Medical School, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Background: In current approaches to vision screening in the community, a simple and efficient process is needed to identify individuals who should be referred to tertiary eye care centres for vision loss related to eye diseases. The emergence of deep learning technology offers new opportunities to revolutionise this clinical referral pathway. We aimed to assess the performance of a newly developed deep learning algorithm for detection of disease-related visual impairment.

Methods: In this proof-of-concept study, using retinal fundus images from 15 175 eyes with complete data related to best-corrected visual acuity or pinhole visual acuity from the Singapore Epidemiology of Eye Diseases Study, we first developed a single-modality deep learning algorithm based on retinal photographs alone for detection of any disease-related visual impairment (defined as eyes from patients with major eye diseases and best-corrected visual acuity of <20/40), and moderate or worse disease-related visual impairment (eyes with disease and best-corrected visual acuity of <20/60). After development of the algorithm, we tested it internally, using a new set of 3803 eyes from the Singapore Epidemiology of Eye Diseases Study. We then tested it externally using three population-based studies (the Beijing Eye study [6239 eyes], Central India Eye and Medical study [6526 eyes], and Blue Mountains Eye Study [2002 eyes]), and two clinical studies (the Chinese University of Hong Kong's Sight Threatening Diabetic Retinopathy study [971 eyes] and the Outram Polyclinic Study [1225 eyes]). The algorithm's performance in each dataset was assessed on the basis of the area under the receiver operating characteristic curve (AUC).

Findings: In the internal test dataset, the AUC for detection of any disease-related visual impairment was 94·2% (95% CI 93·0-95·3; sensitivity 90·7% [87·0-93·6]; specificity 86·8% [85·6-87·9]). The AUC for moderate or worse disease-related visual impairment was 93·9% (95% CI 92·2-95·6; sensitivity 94·6% [89·6-97·6]; specificity 81·3% [80·0-82·5]). Across the five external test datasets (16 993 eyes), the algorithm achieved AUCs ranging between 86·6% (83·4-89·7; sensitivity 87·5% [80·7-92·5]; specificity 70·0% [66·7-73·1]) and 93·6% (92·4-94·8; sensitivity 87·8% [84·1-90·9]; specificity 87·1% [86·2-88·0]) for any disease-related visual impairment, and the AUCs for moderate or worse disease-related visual impairment ranged between 85·9% (81·8-90·1; sensitivity 84·7% [73·0-92·8]; specificity 74·4% [71·4-77·2]) and 93·5% (91·7-95·3; sensitivity 90·3% [84·2-94·6]; specificity 84·2% [83·2-85·1]).

Interpretation: This proof-of-concept study shows the potential of a single-modality, function-focused tool in identifying visual impairment related to major eye diseases, providing more timely and pinpointed referral of patients with disease-related visual impairment from the community to tertiary eye hospitals.

Funding: National Medical Research Council, Singapore.
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http://dx.doi.org/10.1016/S2589-7500(20)30271-5DOI Listing
January 2021

Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color.

Sci Adv 2021 Mar 10;7(11). Epub 2021 Mar 10.

Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.

Human eye color is highly heritable, but its genetic architecture is not yet fully understood. We report the results of the largest genome-wide association study for eye color to date, involving up to 192,986 European participants from 10 populations. We identify 124 independent associations arising from 61 discrete genomic regions, including 50 previously unidentified. We find evidence for genes involved in melanin pigmentation, but we also find associations with genes involved in iris morphology and structure. Further analyses in 1636 Asian participants from two populations suggest that iris pigmentation variation in Asians is genetically similar to Europeans, albeit with smaller effect sizes. Our findings collectively explain 53.2% (95% confidence interval, 45.4 to 61.0%) of eye color variation using common single-nucleotide polymorphisms. Overall, our study outcomes demonstrate that the genetic complexity of human eye color considerably exceeds previous knowledge and expectations, highlighting eye color as a genetically highly complex human trait.
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http://dx.doi.org/10.1126/sciadv.abd1239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946369PMC
March 2021

Rare clinical manifestations of primary peritoneal serous carcinoma presenting as colorectal cancer: A report of two cases.

Taiwan J Obstet Gynecol 2021 Mar;60(2):363-366

Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

Objective: To report two cases of for primary peritoneal serous carcinoma (PPSC) to present with gastrointestinal manifestations that mimic colorectal cancer.

Case Report: There were two patients with initial presentations of fatigue with iron deficiency anemia, and tenesmus with bloody stool. Tumors of the ascending colon and rectum were detected by colonofiberoscope, and pathologic reports of tumor biopsies revealed adenocarcinoma of suspected gynecologic origin. Both patients underwent optimal debulking surgery without macroscopic residual tumor, and then received adjuvant carboplatin and paclitaxel chemotherapy with bevacizumab.

Conclusions: PPSC can clinically present like primary colorectal carcinoma. The differential diagnosis requires special staining of several markers for tumor tissues.
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http://dx.doi.org/10.1016/j.tjog.2021.01.018DOI Listing
March 2021

Retinal microvascular signs and risk of diabetic kidney disease in asian and white populations.

Sci Rep 2021 Mar 1;11(1):4898. Epub 2021 Mar 1.

Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore, 168751, Singapore.

The objective was to examine prospectively the association between retinal microvascular signs and development of diabetic kidney disease (DKD) in Asian and White populations. We analysed two population-based cohorts, composing of 1,221 Asians (SEED) and 703 White (WESDR) adults with diabetes. Retinal microvascular signs at baseline included vascular caliber (arteriolar-CRAE, and venular-CRVE) and diabetic retinopathy (DR). Incident cases of DKD were identified after ~ 6-year. Incident cases were defined based on eGFR in SEED and proteinuria or history of renal dialysis in WESDR. The incidence of DKD were 11.8% in SEED and 14.0% in WESDR. Wider CRAE in SEED (OR = 1.58 [1.02, 2.45]) and wider CRVE (OR = 1.69 [1.02, 2.80)) in WESDR were associated with increased risk of DKD. Presence of DR was associated with an increased risk of DKD in both cohorts (SEED: OR = 1.91 [1.21, 3.01] in SEED, WESDR: OR = 1.99 [1.18, 3.35]). Adding DR and retinal vascular calibers in the model beyond traditional risk factors led to an improvement of predictive performance of DKD risk between 1.1 and 2.4%; and improved classification (NRI 3 between 9%). Microvascular changes in the retina are longitudinally associated with risk of DKD.
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http://dx.doi.org/10.1038/s41598-021-84464-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921402PMC
March 2021

Impact of incident age-related macular degeneration and associated vision loss on vision-related quality of life.

Br J Ophthalmol 2021 Feb 26. Epub 2021 Feb 26.

Singapore Eye Research Institute, Singapore

Background: We examined the associations between the 6-year incidence of age-related macular degeneration (AMD) and vision-related quality of life (VRQoL), and the contribution of presenting visual acuity (VA), in an Asian population.

Methods: Fundus images from the Singapore Chinese Eye Study, a population-based cohort study (baseline: 2009-2011; follow-up: 2015-2017), were graded using a modified Wisconsin age-related maculopathy grading system. Incident AMD was defined as no baseline AMD in both eyes and early/late AMD in the worse eye at follow-up. Presenting VA was assessed using the logarithm of the minimum angle of resolution chart at 4 m under standard lighting conditions with habitual correction. Multiple linear regression models determined the associations between AMD incidence with changes in the Rasch-transformed scores of the Reading, Mobility and Emotional VRQoL domains of the 32-item Impact of Visual Impairment (IVI-32) questionnaire, adjusted for traditional confounders. The contribution of presenting VA to changes in VRQoL was also estimated.

Results: Of the 2251 participants without AMD at baseline (mean age (SD): 57.7 (9) years, 51.4% women), 101 (4.5%) and 11 (0.5%) developed incident early and late AMD at follow-up, respectively. Incident late AMD was associated with significant 30.3%, 32.5% and 30.9% decrements in Reading, Mobility and Emotional IVI scores, respectively. The contribution of presenting VA ranged between 1.62% and 4.35% of the observed decrements. No significant associations were noted with incident early AMD.

Conclusion: Incident late AMD had a substantial impact on all aspects of VRQoL, with presenting VA contributing only minimally to this longitudinal relationship.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318269DOI Listing
February 2021

Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries.

Nat Commun 2021 02 24;12(1):1258. Epub 2021 Feb 24.

Faculty of Medicine, University of Southampton, Southampton, UK.

Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.
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http://dx.doi.org/10.1038/s41467-020-20851-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904932PMC
February 2021

Association between body mass index and diabetic retinopathy in Asians: the Asian Eye Epidemiology Consortium (AEEC) study.

Br J Ophthalmol 2021 Feb 23. Epub 2021 Feb 23.

Beijing Institute of Ophthalmology, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Background/aims: Obesity is a well-known risk factor for diabetes, but its association with diabetic retinopathy (DR) is inconclusive, in particular in Asians. We aimed to assess whether body mass index (BMI) is associated with the presence and severity of DR in Asian populations with diabetes.

Methods: Pooled analysis of individual-level cross-sectional data from 10 010 adults with diabetes who participated in 12 population-based studies conducted in China, India, Japan, Russia (Asian), Singapore and South Korea that were part of the Asian Eye Epidemiology Consortium (AEEC). BMI was calculated as weight in kilograms divided by height in square metres and categorised into normal (<25 kg/m, reference), overweight (25-29.9 kg/m) and obese (≥30 kg/m). Any-DR (n=1669) and vision-threatening DR (VTDR, n=489) were assessed from digital retinal photographs and graded according to standard protocols. Each study was analysed separately using multivariable logistic regression models adjusted for age, sex, haemoglobin A1c%, systolic blood pressure and diabetes duration, and the estimated odds ratios (ORs) and 95% confidence interval (CIs) from all studies were then combined using random-effects models.

Results: In multivariable models, obesity showed a significant inverse association with any-DR (pooled OR (95% CI) =0.74 (0.59 to 0.91)) and VTDR (0.75 (0.60 to 0.93)). Similarly, in continuous analysis, BMI showed a significant inverse association with both any-DR (0.93 (0.87 to 0.99)) and VTDR (0.79 (0.68 to 0.92) per SD increase). Overweight did not show a significant association with any-DR.

Conclusions: Among Asian adults with diabetes, both BMI and obesity showed an inverse association with DR. These findings warrant confirmation in further longitudinal studies.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318208DOI Listing
February 2021

Deep Learning Approach for Automated Detection of Myopic Maculopathy and Pathologic Myopia in Fundus Images.

Ophthalmol Retina 2021 Feb 18. Epub 2021 Feb 18.

Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address:

Purpose: To determine whether eyes with pathologic myopia can be identified and whether each type of myopic maculopathy lesion on fundus photographs can be diagnosed by deep learning (DL) algorithms.

Design: A DL algorithm was developed to recognize myopic maculopathy features and to categorize the myopic maculopathy automatically.

Participants: We examined 7020 fundus images from 4432 highly myopic eyes obtained from the Advanced Clinical Center for Myopia.

Methods: Deep learning (DL) algorithms were developed to recognize the key features of myopic maculopathy with 5176 fundus images. These algorithms were also used to develop a Meta-analysis for Pathologic Myopia (META-PM) study categorizing system (CS) by adding a specific processing layer. Models and the system were evaluated by 1844 fundus image. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to determine the performance of each DL algorithm. The rate of correct predictions was used to determine the performance of the META-PM study CS.

Main Outcome Measures: Four trained DL models were able to recognize the lesions of myopic maculopathy accurately with high sensitivity and specificity. The META-PM study CS also showed a high accuracy and was qualified to be used in a semiautomated way during screening for myopic maculopathy in highly myopic eyes.

Results: The sensitivity of the DL models was 84.44% for diffuse atrophy, 87.22% for patchy atrophy, 85.10% for macular atrophy, and 37.07% for choroidal neovascularization, and the AUC values were 0.970, 0.978, 0.982, and 0.881, respectively. The rate of total correct predictions from the META-PM study CS was 87.53%, with rates of 90.18%, 95.28%, 97.50%, and 91.14%, respectively, for each type of lesion. The META-PM study CS showed an overall rate of 92.08% in detecting pathologic myopia correctly, which was defined as having myopic maculopathy equal to or more serious than diffuse atrophy.

Conclusions: The novel DL models and system can achieve high sensitivity and specificity in identifying the different types of lesions of myopic maculopathy. These results will assist in the screening for pathologic myopia and subsequent protection of patients against low vision and blindness caused by myopic maculopathy.
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http://dx.doi.org/10.1016/j.oret.2021.02.006DOI Listing
February 2021

Telehealth Demand Trends During the COVID-19 Pandemic in the Top 50 Most Affected Countries: Infodemiological Evaluation.

JMIR Public Health Surveill 2021 02 19;7(2):e24445. Epub 2021 Feb 19.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.

Background: The COVID-19 pandemic has led to urgent calls for the adoption of telehealth solutions. However, public interest and demand for telehealth during the pandemic remain unknown.

Objective: We used an infodemiological approach to estimate the worldwide demand for telehealth services during COVID-19, focusing on the 50 most affected countries and comparing the demand for such services with the level of information and communications technology (ICT) infrastructure available.

Methods: We used Google Trends, the Baidu Index (China), and Yandex Keyword Statistics (Russia) to extract data on worldwide and individual countries' telehealth-related internet searches from January 1 to July 7, 2020, presented as relative search volumes (RSV; range 0-100). Daily COVID-19 cases and deaths were retrieved from the World Health Organization. Individual countries' ICT infrastructure profiles were retrieved from the World Economic Forum Report.

Results: Across the 50 countries, the mean RSV was 18.5 (SD 23.2), and the mean ICT index was 62.1 (SD 15.0). An overall spike in worldwide telehealth-related RSVs was observed from March 11, 2020 (RSV peaked to 76.0), which then tailed off in June-July 2020 (mean RSV for the period was 25.8), but remained higher than pre-March RSVs (mean 7.29). By country, 42 (84%) manifested increased RSVs over the evaluation period, with the highest observed in Canada (RSV=100) and the United States (RSV=96). When evaluating associations between RSV and the ICT index, both the United States and Canada demonstrated high RSVs and ICT scores (≥70.3). In contrast, European countries had relatively lower RSVs (range 3.4-19.5) despite high ICT index scores (mean 70.3). Several Latin American (Brazil, Chile, Colombia) and South Asian (India, Bangladesh, Pakistan) countries demonstrated relatively higher RSVs (range 13.8-73.3) but low ICT index scores (mean 44.6), indicating that the telehealth demand outstrips the current ICT infrastructure.

Conclusions: There is generally increased interest and demand for telehealth services across the 50 countries most affected by COVID-19, highlighting the need to scale up telehealth capabilities, during and beyond the pandemic.
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http://dx.doi.org/10.2196/24445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899203PMC
February 2021

Utilisation of poor-quality optical coherence tomography scans: adjustment algorithm from the Singapore Epidemiology of Eye Diseases (SEED) study.

Br J Ophthalmol 2021 Feb 15. Epub 2021 Feb 15.

Singapore Eye Research Institute, Singapore

Purpose: To evaluate the effect of signal strength (SS) on optical coherence tomography (OCT) parameters, and devise an algorithm to adjust the effect, when acceptable SS cannot be obtained.

Methods: 5085 individuals (9582 eyes), aged ≥40 years from the Singapore Epidemiology of Eye Diseases population-based study were included. Everyone underwent a standardised ocular examination and imaging with Cirrus HD-OCT. Effect of SS was evaluated using multiple structural breaks linear mixed-effect models. Expected change for increment in SS between 4 and 10 for individual parameter was calculated. Subsequently we devised and evaluated an algorithm to adjust OCT parameters to higher SS.

Results: Average retinal nerve fibre layer (RNFL) thickness showed shift of 4.11 µm from SS of 5 to 6. Above 6, it increased by 1.72 and 3.35 µm to 7 and 8; and by 1.09 µm (per unit increase) above 8 SS. Average ganglion cell-inner plexiform layer (GCIPL) thickness shifted 5.15 µm from SS of 5 to 6. Above 6, increased by 0.94 µm from 7 to 8; and by 0.16 µm (per unit increase) above 8 SS. When compared with reference in an independent test set, the algorithm produced less systemic bias. Algorithm-adjusted average RNFL was 0.549 µm thinner than the reference, while the unadjusted one was 2.841 µm thinner (p<0.001). Algorithm-adjusted and unadjusted average GCIPL was 1.102 µm and 2.228 µm thinner (p<0.001).

Conclusions: OCT parameters can be adjusted for poor SS using an algorithm. This can potentially assist in diagnosis and monitoring of glaucoma when scans with acceptable SS cannot be acquired from patients in clinics.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317756DOI Listing
February 2021

White matter network damage mediates association between cerebrovascular disease and cognition.

J Cereb Blood Flow Metab 2021 Feb 2:271678X21990980. Epub 2021 Feb 2.

Department of Medicine, Center for Sleep and Cognition, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

To determine whether white matter network disruption mediates the association between MRI markers of cerebrovascular disease (CeVD) and cognitive impairment. Participants (n = 253, aged ≥60 years) from the Epidemiology of Dementia in Singapore study underwent neuropsychological assessments and MRI. CeVD markers were defined as lacunes, white matter hyperintensities (WMH), microbleeds, cortical microinfarcts, cortical infarcts and intracranial stenosis (ICS). White matter microstructure damage was measured as fractional anisotropy and mean diffusivity by tract based spatial statistics from diffusion tensor imaging. Cognitive function was summarized as domain-specific Z-scores.Lacunar counts, WMH volume and ICS were associated with worse performance in executive function, attention, language, verbal and visual memory. These three CeVD markers were also associated with white matter microstructural damage in the projection, commissural, association, and limbic fibers. Path analyses showed that lacunar counts, higher WMH volume and ICS were associated with executive and verbal memory impairment via white matter disruption in commissural fibers whereas impairment in the attention, visual memory and language were mediated through projection fibers.Our study shows that the abnormalities in white matter connectivity may underlie the relationship between CeVD and cognition. Further longitudinal studies are needed to understand the cause-effect relationship between CeVD, white matter damage and cognition.
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http://dx.doi.org/10.1177/0271678X21990980DOI Listing
February 2021

Vision, vision-specific functioning and mobility, and their relationship with clinically assessed cognitive impairment.

Age Ageing 2021 Jan 22. Epub 2021 Jan 22.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.

Background: The relationship between self-reported visual disability and cognitive impairment in older individuals is unclear.

Objective: To determine the relationship of vision-specific functioning (VSF), vision-specific mobility (VSM) and visual acuity (VA) with clinically assessed cognitive impairment in the Epidemiology of Dementia in Singapore study.

Design: Cross-sectional.

Setting: Population-based.

Subjects: Eight hundred and seventy-four adults aged ≥60 years at higher risk of possible cognitive impairment by the Abbreviated Mental Test and progressive forgetfulness question.

Methods: VSF and VSM were measured using Rasch-transformed continuous scores of two Impact of Vision Impairment questionnaire domains. Cognitive impairment was objectively determined using detailed neuropsychological testing and defined as no cognitive impairment (NCI), mild cognitive impairment-no dementia (CIND), moderate CIND only and moderate CIND or dementia. Associations were assessed using multinomial logistic regression models.

Results: Of the 874 participants (49.0% males, mean age (SD) 65.5 (7.0) years), 277, 281 and 316 had NCI, mild CIND and moderate CIND or dementia, respectively. Compared to NCI, the odds of moderate CIND, and moderate CIND or dementia increased for every SD worsening in VSF (OR: 1.44, 95% CI 1.14-1.82, and OR: 1.52, 95%CI 1.19-1.94, respectively) and VSM (OR: 1.42, 95%CI 1.11-1.81, and OR: 1.50, 95%CI 1.15-1.95). Similarly, the odds of mild CIND (OR: 1.62, 95%CI 1.19-2.22), moderate CIND (OR: 1.93, 95%CI 1.45-2.58), and moderate CIND or dementia (OR: 2.25, 95%CI 1.62-3.11) increased significantly with every SD worsening of VA.

Conclusions: Our results emphasise the importance of interventions to prevent vision loss and improve quality of life to reduce likelihood of age-related cognitive decline.
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http://dx.doi.org/10.1093/ageing/afaa276DOI Listing
January 2021

Six-year incidence and systemic associations of retinopathy in a multi-ethnic Asian population without diabetes.

Br J Ophthalmol 2021 Jan 19. Epub 2021 Jan 19.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore

Purpose: We described the 6-year incidence and changes of retinopathy, and their associated risk factors in a multi-ethnic Asian population without diabetes.

Methods: We included 4374 participants with non-diabetes from a population-based cohort, the Singapore Epidemiology of Eye Disease Study, with gradable retinal photographs at baseline and 6-year follow-up visit. Retinopathy was assessed according to the modified Airlie House classification system.

Results: Over the 6-year period, the cumulative rates were 2.5% (106/4279) for retinopathy incidence, 1.0% (1/95) for retinopathy progression and 68.4% (65/95) for retinopathy regression. In multivariable analysis, higher diastolic blood pressure (DBP) (risk ratio (RR)=1.02; 95% CI: 1.00 to 1.04; per 10 mm Hg increase in DBP) and wider retinal arteriolar calibre (RR=1.36; 95% CI: 1.13 to 1.63; per SD increase in central retinal artery equivalent) were associated with higher risk of incident retinopathy, while higher level of high-density lipoprotein (HDL) was associated with lower risk of incident retinopathy (RR=0.56; 95% CI: 0.32 to 0.99; per mmol/L increase in HDL). Compared with Chinese, Malays were more likely to have retinopathy regression (RR=1.63; 95% CI: 1.20 to 2.22), while overweight (RR=0.47; 95% CI: 0.26 to 0.84) and higher glycosylated haemoglobin (HbA1c) level (RR=0.58; 95% CI: 0.37 to 0.93; per per cent increase in HbA1c) were associated with lower likelihood of retinopathy regression.

Conclusion: Risk of developing retinopathy in Asians without diabetes is generally low. However, regression of retinopathy over time is common, suggesting that these retinopathy signs may reflect subclinical reversible microvascular dysfunction. Several metabolic risk factors are associated with incidence or regression of retinopathy, suggesting that good metabolic control may still be important in the management of non-diabetic retinopathy.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318126DOI Listing
January 2021

Ethnic differences in the incidence of pterygium in a multi-ethnic Asian population: the Singapore Epidemiology of Eye Diseases Study.

Sci Rep 2021 Jan 12;11(1):501. Epub 2021 Jan 12.

Ocular Epidemiology, Singapore Eye Research Institute, Singapore National Eye Centre, The Academia, 20 College Road, Discovery Tower Level 6, Singapore, 169856, Singapore.

We evaluated the 6-year incidence and risk factors of pterygium in a multi-ethnic Asian population. Participants who attended the baseline visit of the Singapore Epidemiology of Eye Diseases Study (year 2004-2011) and returned six years later, were included in this study. Pterygium was diagnosed based on anterior segment photographs. Incident pterygium was defined as presence of pterygium at 6-year follow-up in either eye, among individuals without pterygium at baseline. Multivariable logistic regression models were used to determine factors associated with incident pterygium, adjusting for baseline age, gender, ethnicity, body mass index, occupation type, educational level, income status, smoking, alcohol consumption, presence of hypertension, diabetes and hyperlipidemia. The overall age-adjusted 6-year incidence of pterygium was 1.2% (95% confidence interval [CI] 1.0-1.6%); with Chinese (1.9%; 95% CI 1.4%-2.5%) having the highest incidence rate followed by Malays (1.4%; 95% CI 0.9%-2.1%) and Indians (0.3%; 95% CI 0.3-0.7%). In multivariable analysis, Chinese (compared with Indians; odds ratio [OR] = 4.21; 95% CI 2.12-9.35) and Malays (OR 3.22; 95% CI 1.52-7.45), male (OR 2.13; 95% CI 1.26-3.63), outdoor occupation (OR 2.33; 95% CI 1.16-4.38), and smoking (OR 0.41; 95% CI 0.16-0.87) were significantly associated with incident pterygium. Findings from this multi-ethnic Asian population provide useful information in identifying at-risk individuals for pterygium.
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http://dx.doi.org/10.1038/s41598-020-79920-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804407PMC
January 2021

Peripapillary sclera exhibits a v-shaped configuration that is more pronounced in glaucoma eyes.

Br J Ophthalmol 2020 Dec 17. Epub 2020 Dec 17.

Ophthalmic Engineering & Innovation Laboratory, Singapore Eye Research Institute, Singapore

Aims: To compare the shape of the anterior surface of the peripapillary sclera (PPS) between glaucoma and healthy subjects.

Methods: 88 primary open angle glaucoma (POAG), 98 primary angle closure glaucoma (PACG) and 372 age-matched and gender-matched healthy controls were recruited in this study. The optic nerve head of one randomly selected eye of each subject was imaged with spectral domain optical coherence tomography. The shape of the PPS was measured through an angle defined between a line parallel to the nasal anterior PPS boundary and one parallel to the temporal side. A negative value indicated that the PPS followed an inverted v-shaped configuration (peak pointing towards the vitreous), whereas a positive value indicated that it followed a v-shaped configuration.

Results: The mean PPS angle in normal controls (4.56±5.99°) was significantly smaller than that in POAG (6.60±6.37°, p=0.011) and PACG (7.90±6.87°, p<0.001). The v-shaped PPS was significantly associated with older age (β=1.79, p<0.001), poorer best-corrected visual acuity (β=3.31, p=0.047), central corneal thickness (β=-0.28, p=0.001), peripapillary choroidal thickness (β=-0.21, p<0.001) and presence of POAG (β=1.94, p<0.009) and PACG (β=2.96, p<0.001). The v-shaped configuration of the PPS significantly increased by 1.46° (p=0.001) in healthy controls for every 10-year increase in age, but not in glaucoma groups.

Conclusions: The v-shaped configuration of the PPS was more pronounced in glaucoma eyes than in healthy eyes. This posterior bowing of the PPS may have an impact on the biomechanical environment of the optic nerve head.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317900DOI Listing
December 2020