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2.
Age Ageing ; 51(4)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35363255

RESUMO

BACKGROUND: ageing is an important risk factor for a variety of human pathologies. Biological age (BA) may better capture ageing-related physiological changes compared with chronological age (CA). OBJECTIVE: we developed a deep learning (DL) algorithm to predict BA based on retinal photographs and evaluated the performance of our new ageing marker in the risk stratification of mortality and major morbidity in general populations. METHODS: we first trained a DL algorithm using 129,236 retinal photographs from 40,480 participants in the Korean Health Screening study to predict the probability of age being ≥65 years ('RetiAGE') and then evaluated the ability of RetiAGE to stratify the risk of mortality and major morbidity among 56,301 participants in the UK Biobank. Cox proportional hazards model was used to estimate the hazard ratios (HRs). RESULTS: in the UK Biobank, over a 10-year follow up, 2,236 (4.0%) died; of them, 636 (28.4%) were due to cardiovascular diseases (CVDs) and 1,276 (57.1%) due to cancers. Compared with the participants in the RetiAGE first quartile, those in the RetiAGE fourth quartile had a 67% higher risk of 10-year all-cause mortality (HR = 1.67 [1.42-1.95]), a 142% higher risk of CVD mortality (HR = 2.42 [1.69-3.48]) and a 60% higher risk of cancer mortality (HR = 1.60 [1.31-1.96]), independent of CA and established ageing phenotypic biomarkers. Likewise, compared with the first quartile group, the risk of CVD and cancer events in the fourth quartile group increased by 39% (HR = 1.39 [1.14-1.69]) and 18% (HR = 1.18 [1.10-1.26]), respectively. The best discrimination ability for RetiAGE alone was found for CVD mortality (c-index = 0.70, sensitivity = 0.76, specificity = 0.55). Furthermore, adding RetiAGE increased the discrimination ability of the model beyond CA and phenotypic biomarkers (increment in c-index between 1 and 2%). CONCLUSIONS: the DL-derived RetiAGE provides a novel, alternative approach to measure ageing.


Assuntos
Aprendizado Profundo , Idoso , Envelhecimento/fisiologia , Humanos , Morbidade , Modelos de Riscos Proporcionais , Fatores de Risco
3.
Commun Biol ; 5(1): 329, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35393509

RESUMO

South Asians are at high risk of developing type 2 diabetes (T2D). We carried out a genome-wide association meta-analysis with South Asian T2D cases (n = 16,677) and controls (n = 33,856), followed by combined analyses with Europeans (neff = 231,420). We identify 21 novel genetic loci for significant association with T2D (P = 4.7 × 10-8 to 5.2 × 10-12), to the best of our knowledge at the point of analysis. The loci are enriched for regulatory features, including DNA methylation and gene expression in relevant tissues, and highlight CHMP4B, PDHB, LRIG1 and other genes linked to adiposity and glucose metabolism. A polygenic risk score based on South Asian-derived summary statistics shows ~4-fold higher risk for T2D between the top and bottom quartile. Our results provide further insights into the genetic mechanisms underlying T2D, and highlight the opportunities for discovery from joint analysis of data from across ancestral populations.


Assuntos
Diabetes Mellitus Tipo 2 , Estudo de Associação Genômica Ampla , /genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único
4.
Artigo em Inglês | MEDLINE | ID: mdl-35390150

RESUMO

CONTEXT: While Asians have a higher risk of type 2 diabetes (T2D) than Europeans for a given BMI, it remains unclear whether the same markers of metabolic pathways are associated with diabetes. OBJECTIVE: We evaluated associations between metabolic biomarkers and incident T2D in three major Asian ethnic groups (Chinese, Malay, and Indian) and a European population. METHODS: We analyzed data from adult males and females of two cohorts from Singapore (n = 6,393) consisting of Chinese, Malays and Indians, and three cohorts of European-origin participants from Finland (n = 14,558). We used nuclear magnetic resonance to quantify 154 circulating metabolic biomarkers at baseline and performed logistic regression to assess associations with T2D risk adjusted for age, sex, BMI and glycaemic markers. RESULTS: Of the 154 metabolic biomarkers, 59 were associated with higher risk of T2D in both Asians and Europeans (P < 0.0003; Bonferroni-corrected). These included branched-chain and aromatic amino acids, the inflammatory marker glycoprotein acetyls, total fatty acids, monounsaturated fatty acids, apolipoprotein B, larger very low-density lipoprotein particle sizes, and triglycerides. In addition, 13 metabolites were associated with a lower T2D risk in both populations including omega-6 polyunsaturated fatty acids and larger high-density lipoprotein particle sizes. Associations were consistent within the Asian ethnic groups (all Phet ≥ 0.05) and largely consistent for the Asian and European populations (Phet ≥ 0.05 for 128 of 154 metabolic biomarkers). CONCLUSION: Metabolic biomarkers across several biological pathways were consistently associated with T2D risk in Asians and Europeans.

5.
Int J Stroke ; : 17474930221097737, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35450485

RESUMO

BACKGROUND: Quantitative changes in retinal vessels and thinning of optic nerves have been associated with subclinical (atherosclerosis, inflammation) and clinical age-related brain pathologies (stroke and neurodegeneration). However, data on the association between both retinal vascular and neuronal parameters with cortical cerebral microinfarcts (CMIs) and how these factors jointly influence cognition are lacking. AIM: We investigated the association of retinal vascular and neuronal changes with CMIs on 3 T MRI and explored their interaction with cognitive impairment in a memory-clinic population. METHODS: A total of 538 participants were included. Retinal vascular parameters (caliber, tortuosity, and fractal dimension) were measured from retinal fundus photographs using a semi-automated computer-assisted program. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thicknesses were obtained from optical coherence tomography. Cortical CMIs were defined as hypointense on T1-weighted MRI, <5 mm in diameter and restricted to the cortex. Cognition was assessed using Clinical Dementia Rating Sum-of-Boxes (CDR-SoB) score and detailed neuropsychological test. Multivariable regression analysis was conducted adjusting for age, sex, hypertension, hyperlipidemia, diabetes mellitus, smoking, diagnosis, white matter hyperintensities volume, lacunes, and cerebral microbleeds. RESULTS: Larger venular caliber (Rate ratios (RR): 1.15, 95% CI: 1.01-1.38, p = 0.014), increased venular fractal dimension (RR: 1.58, 95% CI: 1.31-1.91, p ⩽ 0.001), increased venular tortuosity (RR: 1.54, 95% CI: 1.35-1.75, p ⩽ 0.001), and thinner GC-IPL (RR: 1.24, 95% CI: 1.13-1.36, p ⩽ 0.001) were associated with CMI counts. Among individuals in highest tertile of retinal parameters, a significant interaction was observed between venular tortuosity (RR: 1.12, 95% CI: 1.02-1.22, p-interaction = 0.014) and GC-IPL (RR: 1.05, 95% CI: 1.01-1.11, p-interaction < 0.001) with CMIs on CDR-SoB. CONCLUSION: Retinal vascular and neuronal parameters are associated with cortical CMIs, and persons with both pathologies are likely to have cognitive impairment. Further studies may be warranted to evaluate the clinical utility of retinal parameters and CMI in risk prediction for cognitive dysfunction.

6.
Ophthalmology ; 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35306094

RESUMO

PURPOSE: To determine the incidence and risk factors of primary angle-closure disease (PACD) over 6 years in a multi-ethnic Asian population. DESIGN: Population-based, longitudinal study. PARTICIPANTS: The Singapore Epidemiology of Eye Diseases study is a population-based cohort study conducted among adults aged 40 years or more. The baseline examination was conducted between 2004 and 2010, and the 6-year follow-up visit was conducted between 2011 and 2017. Of 6762 participants who attended the follow-up examination, 5298 at risk for primary angle-closure glaucoma (PACG) and 5060 at risk for PACD were included for analyses. METHODS: Standardized examinations including slit-lamp biomicroscopy, indentation gonioscopy, intraocular pressure (IOP) measurement, and static automated perimetry were performed. In this study, PACD includes primary angle-closure suspect (PACS), primary angle-closure (PAC), and PACG. MAIN OUTCOME MEASURES: The 6-year PACD incidence was evaluated among an at-risk population excluding adults with baseline glaucoma, PACS, PAC, pseudophakia at baseline or follow-up, or laser peripheral iridotomy or iridectomy at baseline visit. Logistic regression analysis adjusting for age, gender, and ethnicity was performed to evaluate associations between PACD development and demographic or ocular characteristics. Forward selection based on the Quasi-likelihood Information Criterion was used in multivariable analysis to reduce potential multicollinearity. RESULTS: The 6-year age-adjusted PACD incidence was 3.50% (95% confidence interval [CI], 2.94-4.16). In multivariable analysis, increasing age per decade (odds ratio [OR], 1.35; 95% CI, 1.15-1.59), higher IOP (OR, 1.04; 95% CI, 1.00-1.08), and shallower anterior chamber depth (OR, 1.11; 95% CI, 1.08-1.14) at baseline were associated with higher odds of PACD, whereas late posterior subcapsular cataract (PSC) (OR, 0.60; 95% CI, 0.48-0.76) was associated with lower odds of PACD. The 6-year age-adjusted incidences of PACG, PAC, and PACS were 0.29% (95% CI, 0.14-0.55), 0.46% (95% CI, 0.29-0.75), and 2.54% (95% CI, 2.07-3.12), respectively. CONCLUSIONS: Our study showed that the 6-year incidence of PACD was 3.50%. Increasing age, higher IOP, and shallower anterior chamber were associated with a higher risk of incident PACD, whereas late PSC was associated with a lower odds of PACD. These findings can aid in future projections and formulation of health care policies for screening of at-risk individuals for timely intervention.

7.
Alzheimers Res Ther ; 14(1): 41, 2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35272711

RESUMO

BACKGROUND: Diagnostic performance of optical coherence tomography (OCT) to detect Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains limited. We assessed whether compensating the circumpapillary retinal nerve fiber layer (cpRNFL) thickness for multiple demographic and anatomical factors as well as the combination of macular layers improves the detection of MCI and AD. METHODS: This cross-sectional study of 62 AD (n = 92 eyes), 108 MCI (n = 158 eyes), and 55 cognitively normal control (n = 86 eyes) participants. Macular ganglion cell complex (mGCC) thickness was extracted. Circumpapillary retinal nerve fiber layer (cpRNFL) measurement was compensated for several ocular factors. Thickness measurements and their corresponding areas under the receiver operating characteristic curves (AUCs) were compared between the groups. The main outcome measure was OCT thickness measurements. RESULTS: Participants with MCI/AD showed significantly thinner measured and compensated cpRNFL, mGCC, and altered retinal vessel density (p < 0.05). Compensated RNFL outperformed measured RNFL for discrimination of MCI/AD (AUC = 0.74 vs 0.69; p = 0.026). Combining macular and compensated cpRNFL parameters provided the best detection of MCI/AD (AUC = 0.80 vs 0.69; p < 0.001). CONCLUSIONS AND RELEVANCE: Accounting for interindividual variations of ocular anatomical features in cpRNFL measurements and incorporating macular information may improve the identification of high-risk individuals with early cognitive impairment.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico por imagem , Biomarcadores , Disfunção Cognitiva/diagnóstico por imagem , Estudos Transversais , Humanos , Fibras Nervosas , Células Ganglionares da Retina , Tomografia de Coerência Óptica/métodos
8.
J Am Heart Assoc ; 11(6): e024226, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35253475

RESUMO

Background This study examined the associations between quantitative optical coherence tomography angiography (OCTA) parameters and myocardial abnormalities as documented on cardiovascular magnetic resonance imaging in patients with systemic hypertension. Methods and Results We conducted a cross-sectional study of 118 adults with hypertension (197 eyes). Patients underwent cardiovascular magnetic resonance imaging and OCTA (PLEX Elite 9000, Carl Zeiss Meditec). Associations between OCTA parameters (superficial and deep retinal capillary density) and adverse cardiac remodeling (left ventricular mass, remodeling index, interstitial fibrosis, global longitudinal strain, and presence of left ventricular hypertrophy) were studied using multivariable linear regression analysis with generalized estimating equations. Of the 118 patients with hypertension enrolled (65% men; median [interquartile range] age, 59 [13] years), 29% had left ventricular hypertrophy. After adjusting for age, sex, systolic blood pressure, diabetes, and signal strength of OCTA scans, patients with lower superficial capillary density had significantly higher left ventricular mass (ß=-0.150; 95% CI, -0.290 to -0.010), higher interstitial volume (ß=-0.270; 95% CI, -0.535 to -0.0015), and worse global longitudinal strain (ß=-0.109; 95% CI, -0.187 to -0.032). Lower superficial capillary density was found in patients with hypertension with replacement fibrosis versus no replacement fibrosis (16.53±0.64 mm-1 versus 16.96±0.64 mm-1; P=0.003). Conclusions We showed significant correlations between retinal capillary density and adverse cardiac remodeling markers in patients with hypertension, supporting the notion that the OCTA could provide a non-invasive index of microcirculation alteration for vascular risk stratification in people with hypertension.


Assuntos
Hipertensão , Hipertrofia Ventricular Esquerda , Adulto , Estudos Transversais , Feminino , Fibrose , Angiofluoresceinografia/métodos , Humanos , Hipertensão/complicações , Hipertensão/patologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/patologia , Masculino , Pessoa de Meia-Idade , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos , Remodelação Ventricular
9.
JAMA Ophthalmol ; 140(3): 262-268, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35142821

RESUMO

IMPORTANCE: The retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) have been proposed as potential biomarkers for Alzheimer disease (AD). Although a number of studies have shown that knowing the thickness of RNFL and GCL can help differentiate between patients with AD and healthy controls, it is unclear whether these associations are observable earlier in life. OBJECTIVE: To examine whether RNFL and GCL thickness was associated with global cognitive performance in middle age and in childhood and with a decline in cognitive performance from childhood to adulthood and whether RNFL and GCL thickness was associated with decline in specific cognitive domains over the same period. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cohort study involved members of the Dunedin Multidisciplinary Health and Development Study, a longitudinal representative birth cohort from New Zealand (n = 1037). Participants were born in 1972 to 1973 and followed up until age 45 years, with 94% of the living cohort still participating. MAIN OUTCOMES AND MEASURES: Cognitive performance (Full Scale IQ, processing speed, perceptual reasoning, and verbal comprehension) measured at ages 7, 9, and 11 years (mean value) and age 45 years, and RNFL and GCL thickness measured via optical coherence tomography (OCT) at age 45 years. RESULTS: Data were analyzed between August 2020 and April 2021. Data from 865 participants were included in the present study (50.2% male, 49.8% female; 92.2% of the 938 study members seen at age 45 years). Of the 73 participants who were excluded, 63 were excluded because of issues with OCT scans and 10 were excluded because of diseases affecting the retina. Thinner RNFL and GCL were associated with lower Full Scale IQ in childhood and at age 45 years. Thinner RNFL was also associated with a greater decline in processing speed from childhood to adulthood. CONCLUSIONS AND RELEVANCE: RNFL and GCL thickness in middle age was associated with cognitive performance in childhood and adulthood, and thinner RNFL with a decline in processing speed between childhood and adulthood. These data emphasize the potential utility of OCT measures as biomarkers of cognitive function; however, further longitudinal studies are needed to determine whether retinal thinning precedes cognitive decline and whether other confounding factors may account for this association.


Assuntos
Doença de Alzheimer , Fibras Nervosas , Adolescente , Adulto , Criança , Cognição , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Retina , Células Ganglionares da Retina , Tomografia de Coerência Óptica/métodos , Adulto Jovem
10.
Eur Heart J ; 43(18): 1702-1711, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35195259

RESUMO

AIMS: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations. METHODS AND RESULTS: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS. CONCLUSION: The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.


Assuntos
Doença da Artéria Coronariana , China/epidemiologia , Estudos de Coortes , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Herança Multifatorial/genética , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco
11.
Ophthalmol Retina ; 2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35202889

RESUMO

PURPOSE: To develop a consensus nomenclature for reporting OCT angiography (OCTA) findings in retinal vascular disease (e.g., diabetic retinopathy, retinal vein occlusion) by international experts. DESIGN: Delphi-based survey. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Twenty-five retinal vascular disease and OCTA imaging experts. METHODS, INTERVENTION, OR TESTING: A Delphi method of consensus development was used, comprising 2 rounds of online questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-five experts in retinal vascular disease and retinal OCTA imaging were selected to constitute the OCTA Nomenclature in Delphi Study Group for retinal vascular disease. The 4 main areas of consensus were: definition of the parameters of "wide-field (WF)" OCTA, measurement of decreased vascular flow on conventional and WF-OCTA, nomenclature of OCTA findings, and OCTA in retinal vascular disease management and staging. The study end point was defined by the degree of consensus for each question: "strong consensus" was defined as ≥85% agreement, "consensus" as 80% to 84%, and "near consensus" as 70% to 79%. MAIN OUTCOME MEASURES: Consensus and near consensus on OCTA nomenclature in retinal vascular disease. RESULTS: A consensus was reached that a meaningful change in percentage of flow on WF-OCTA imaging should be an increase or decrease ≥30% of the absolute imaged area of flow signal and that a "large area" of WF-OCTA reduced flow signal should also be defined as ≥30% of the absolute imaged area. The presence of new vessels and intraretinal microvascular abnormalities, the foveal avascular zone parameters, the presence and amount of "no-flow areas," and the assessment of vessel density in various retinal layers should be added for the staging and classification of diabetic retinopathy. Decreased flow ≥30% of the absolute imaged area should define an ischemic central retinal vein occlusion. Several other items did not meet consensus requirements or were rejected in the final discussion round. CONCLUSIONS: This study provides international consensus recommendations for reporting OCTA findings in retinal vascular disease, which may help to improve the interpretability and description in clinic and clinical trials. Further validation in these settings is warranted and ongoing. Efforts are continuing to address unresolved questions.

12.
Artigo em Inglês | MEDLINE | ID: mdl-35135974

RESUMO

BACKGROUND: Longitudinal evidence on retinal microvasculature and subsequent systemic inflammatory alteration is lacking. We investigated the association between retinal microvasculature and immune response among HIV/AIDS patients over a 9-month antiretroviral therapy (ART). METHODS: We conducted a prospective cohort on HIV/AIDS patients at Singapore Communicable Disease Centre (CDC) since June 2011. We recruited all eligible patients and then reviewed them every three months over a 9-month follow-up, including performing blood tests (CD4+/CD8+ T-cell counts, HIV viral load), blood pressure, anthropometry measurements, and retinal photography at each visit. We assessed retinal vascular indexes via a semi-automated computer-based program. Lastly, we applied a linear mixed model to analyze associations between baseline retinal vascular indexes and 9-month changes of CD4+/CD8+ T-cell cell counts and HIV viral load throughout study observation, after adjusting for major confounders. RESULTS: We found that narrower arteriolar caliber (per 10 µm decrease), wider venular caliber (per 10 µm increase), and larger arteriolar branching angle (per 10 degrees increase) in the retina assessed at baseline were significantly associated with 9-month reductions in CD4+ T-cell count by 52.97 cells/µl (p=0.006), 33.55 cells/µl (p=0.01), and 39.09 cells/ µl (p=0.008), accordingly. CONCLUSION: HIV/AIDS Patients with a suboptimal retinal microvascular morphology tended to fail immune restoration undertaking a 9-month ART.

13.
Retina ; 42(3): 529-539, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35188491

RESUMO

PURPOSE: To evaluate the interrelationship between macular sensitivity and retinal perfusion density (PD) in eyes with myopic macular degeneration (MMD). METHODS: One hundred and thirty-eight highly myopic eyes from 82 adult participants were recruited. Macular sensitivity was evaluated using the Microperimeter MP-3. Retinal PD was measured using the PLEX Elite 9000 swept source optical coherence tomography angiography. Macular sensitivity values between different categories of MMD and its relationship with optical coherence tomography angiography measurements were evaluated using multivariable linear mixed models, adjusting for age and axial length. RESULTS: Macular sensitivity reduced with increasing severity of MMD (ß ≤ -0.95, P < 0.001), whereas the best-corrected visual acuity was not associated with MMD severity (P > 0.04). Persons who were older (ß = -0.08, P < 0.001), with longer axial length (ß = -0.32, P = 0.005), presence of macular diffuse choroidal atrophy (ß = -2.16, P < 0.001) or worse MMD (ß = -5.70, P < 0.001), and presence of macular posterior staphyloma (ß ≤ -2.98, P < 0.001) or Fuchs spot (ß = -1.58, P = 0.04) were associated with reduced macular sensitivity. Macular sensitivity was significantly associated with deep retinal PD in MMD (ß = 0.15, P = 0.004) but not with superficial retinal PD (P = 0.62). CONCLUSION: There was a strong correlation between reduced macular sensitivity and increasing MMD severity, even in mild MMD independent of the best-corrected visual acuity. Furthermore, macular sensitivity was correlated with deep retinal PD, suggesting a vasculature-function relationship in MMD.


Assuntos
Degeneração Macular/fisiopatologia , Miopia Degenerativa/fisiopatologia , Retina/fisiologia , Vasos Retinianos/fisiopatologia , Adulto , Idoso , Comprimento Axial do Olho , Capilares/fisiopatologia , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Degeneração Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Miopia Degenerativa/diagnóstico , Refração Ocular , Sensibilidade e Especificidade , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Testes de Campo Visual , Campos Visuais/fisiologia
14.
Br J Ophthalmol ; 2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35140059

RESUMO

PURPOSE: To use optical coherence tomography angiography (OCTA) parameters from both the retinal and choroidal microvasculature to detect the presence and severity of diabetic retinopathy (DR). METHOD: This is a cross-sectional case-control study. OCTA parameters from retinal vasculature, fovea avascular zone (FAZ) and choriocapillaris were evaluated from 3×3 mm2 fovea-centred scans. Areas under the receiver operating characteristic (ROC) curve were used to compare the discriminative power on the presence of diabetes mellitus (DM), the presence of DR and need for referral: group 1 (no DM vs DM no DR), group 2 (no DR vs any DR) and group 3 (non-proliferative DR (NPDR) vs proliferative DR (PDR)). RESULTS: 35 eyes from 27 participants with no DM and 132 eyes from 75 with DM were included. DR severity was classified into three groups: no DR group (62 eyes), NPDR (51 eyes), PDR (19 eyes). All retinal vascular parameters, FAZ parameters and choriocapillaris parameters were strongly altered with DR stages (p<0.01), except for the deep plexus FAZ area (p=0.619). Choriocapillaris parameters allowed to better discriminate between no DM versus DM no DR group compared with retinal parameters (areas under the ROC curve=0.954 vs 0.821, p=0.006). A classification model including retinal and choroidal microvasculature significantly improved the discrimination between DR and no DR compared with each parameter separately (p=0.029). CONCLUSIONS: Evaluating OCTA parameters from both the retinal and choroidal microvasculature in 3×3 mm scans improves the discrimination of DM and early DR.

15.
Br J Ophthalmol ; 106(2): 267-274, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33208351

RESUMO

AIMS: To use machine learning (ML) to determine the relative contributions of modifiable and non-modifiable clinical, metabolic, genetic, lifestyle and socioeconomic factors on the risk of major eye diseases. METHODS: We conducted analyses in a cross-sectional multi-ethnic population-based study (n=10 033 participants) and determined a range of modifiable and non-modifiable risk factors of common eye diseases, including diabetic retinopathy (DR), non-diabetic-related retinopathy (NDR); early and late age-related macular degeneration (AMD); nuclear, cortical and posterior subcapsular (PSC) cataract; and primary open-angle (POAG) and primary angle-closure glaucoma (PACG). Risk factors included individual characteristics, metabolic profiles, genetic background, lifestyle patterns and socioeconomic status (n~100 risk factors). We used gradient boosting machine to estimate the relative influence (RI) of each risk factor. RESULTS: Among the range of risk factors studied, the highest contributions were duration of diabetes for DR (RI=22.1%), and alcohol consumption for NDR (RI=6.4%). For early and late AMD, genetic background (RI~20%) and age (RI~15%) contributed the most. Axial length was the main risk factor of PSC (RI=30.8%). For PACG, socioeconomic factor (mainly educational level) had the highest influence (20%). POAG was the disease with the highest contribution of modifiable risk factors (cumulative RI~35%), followed by PACG (cumulative RI ~30%), retinopathy (cumulative RI between 20% and 30%) and late AMD (cumulative RI ~20%). CONCLUSION: This study illustrates the utility of ML in identifying factors with the highest contributions. Risk factors possibly amenable to interventions were intraocular pressure (IOP) and Body Mass Index (BMI) for glaucoma, alcohol consumption for NDR and levels of HbA1c for DR.


Assuntos
Catarata , Retinopatia Diabética , Oftalmopatias , Glaucoma de Ângulo Fechado , Glaucoma de Ângulo Aberto , Degeneração Macular , Estudos Transversais , Retinopatia Diabética/epidemiologia , Humanos , Pressão Intraocular , Aprendizado de Máquina , Degeneração Macular/epidemiologia , Degeneração Macular/etiologia , Fatores de Risco
16.
Ophthalmology ; 129(3): 285-294, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34592243

RESUMO

PURPOSE: We hypothesized that the effect of blood lipid-related metabolites on primary open-angle glaucoma (POAG) would differ according to specific lipoprotein particles and lipid sub-fractions. We investigated the associations of blood levels of lipoprotein particles and lipid sub-fractions with POAG. DESIGN: Cross-sectional study. PARTICIPANTS: Individuals recruited for the baseline visit of the population-based Singapore Epidemiology of Eye Disease study (n = 8503). METHODS: All participants underwent detailed standardized ocular and systemic examinations. A total of 130 blood lipid-related metabolites were quantified using a nuclear magnetic resonance metabolomics platform. The analyses were conducted in 2 stages. First, we investigated whether and which lipid-related metabolites were directly associated with POAG using regression analyses followed by Bayesian network modeling. Second, we investigated if any causal relationship exists between the identified lipid-related metabolites, if any, and POAG using 2-sample Mendelian randomization (MR) analysis. We performed genome-wide association studies (GWAS) on high-density lipoprotein (HDL) 3 cholesterol (after inverse normal transformation) and used the top variants associated with HLD3 cholesterol as instrumental variables (IVs) in the MR analysis. MAIN OUTCOME MEASURE: Primary open-angle glaucoma. RESULTS: Of the participants, 175 (2.1%) had POAG. First, a logistic regression model showed that total HDL3 cholesterol (negatively) and phospholipids in very large HDL (positively) were associated with POAG. Further analyses using a Bayesian network analysis showed that only total HDL3 cholesterol was directly associated with POAG (odds ratio [OR], 0.72 per 1 standard deviation increase in HDL3 cholesterol; 95% confidence interval [CI], 0.61-0.84), independently of age, gender, intraocular pressure (IOP), body mass index (BMI), education level, systolic blood pressure, axial length, and statin medication. Using 5 IVs identified from the GWAS and with the inverse variance weighted MR method, we found that higher levels of HDL3 cholesterol were associated with a decreased odds of POAG (OR, 0.91; 95% CI, 0.84-0.99, P = 0.021). Other MR methods, including weighted median, mode-based estimator, and contamination mixture methods, derived consistent OR estimates. None of the routine lipids (blood total, HDL, or low-density lipoprotein [LDL] cholesterol) were associated with POAG. CONCLUSIONS: Overall, these results suggest that the relationship between HDL3 cholesterol and POAG might be causal and specific, and that dysregulation of cholesterol transport may play a role in the pathogenesis of POAG.


Assuntos
HDL-Colesterol/sangue , Glaucoma de Ângulo Aberto/sangue , Análise da Randomização Mendeliana , Metabolômica , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Estudo de Associação Genômica Ampla , Glaucoma de Ângulo Aberto/diagnóstico , Gonioscopia , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Microscopia com Lâmpada de Fenda , Tonometria Ocular
17.
Qual Life Res ; 31(4): 1237-1246, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34562188

RESUMO

PURPOSE: We are developing an age-related macular degeneration (AMD) health-related quality of life (HRQoL) item bank, applicable to Western and Asian populations. We report primarily on content generation and refinement, but also compare the HRQoL issues reported in our study with Western studies and current AMD-HRQoL questionnaires. METHODS: In this cross-sectional, qualitative study of AMD patients attending the Singapore National Eye Centre (May-December 2019), items/domains were generated from: (1) AMD-specific questionnaires; (2) published articles; (3) focus groups/semi-structured interviews with AMD patients (n = 27); and (4) written feedback from retinal experts. Following thematic analysis, items were systematically refined to a minimally representative set and pre-tested using cognitive interviews with 16 AMD patients. RESULTS: Of the 27 patients (mean ± standard deviation age 67.9 ± 7.0; 59.2% male), 18 (66.7%), two (7.4%), and seven (25.9%) had no, early-intermediate, and late/advanced AMD (better eye), respectively. Whilst some HRQoL issues, e.g. activity limitation, mobility, lighting, and concerns were similarly reported by Western patients and covered by other questionnaires, others like anxiety about intravitreal injections, work tasks, and financial dependency were novel. Overall, 462 items within seven independent HRQoL domains were identified: Activity limitation, Lighting, Mobility, Emotional, Concerns, AMD management, and Work. Following item refinement, items were reduced to 219, with 31 items undergoing amendment. CONCLUSION: Our 7-domain, 219-item AMD-specific HRQoL instrument will undergo psychometric testing and calibration for computerized adaptive testing. The future instrument will enable users to precisely, rapidly, and comprehensively quantify the HRQoL impact of AMD and associated treatments, with item coverage relevant across several populations.


Assuntos
Degeneração Macular , Qualidade de Vida , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Qualidade de Vida/psicologia , Inquéritos e Questionários
18.
Atherosclerosis ; 341: 63-70, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34756728

RESUMO

BACKGROUND AND AIMS: Endothelial dysfunction is a precursor to atherosclerosis and is implicated in the coexistence between cardiovascular disease (CVD) and chronic kidney disease (CKD). We examined whether retinal microvascular dysfunction is present in subjects with renal impairment and predictive of long-term CKD progression in patients with CVD. METHODS: In a single centre prospective observational study, 253 subjects with coronary artery disease and CVD risk factors underwent dynamic retinal vessel analysis. Retinal microvascular dysfunction was quantified by measuring retinal arteriolar and venular dilatation in response to flicker light stimulation. Serial renal function assessment was performed over a median period of 9.3 years using estimated GFR (eGFR). RESULTS: Flicker light-induced retinal arteriolar dilatation (FI-RAD) was attenuated in patients with baseline eGFR <90 mL/min/1.73 m2, compared to those with normal renal function (eGFR ≥90 mL/min/1.73 m2) (1.0 [0.4-2.1]% vs. 2.0 [0.8-3.6]%; p < 0.01). In patients with normal renal function, subjects with the lowest FI-RAD responses exhibited the greatest annual decline in eGFR. In uni- and multivariable analysis, among subjects with normal renal function, a 1% decrease in FI-RAD was associated with an accelerated decline in eGFR of 0.10 (0.01, 0.15; p = 0.03) and 0.07 mL/min/1.73 m2 per year (0.00, 0.14; p = 0.06), respectively. FI-RAD was not predictive of CKD progression in subjects with baseline eGFR <90 mL/min/1.73 m2. CONCLUSIONS: Retinal arteriolar endothelial dysfunction is present in patients with CVD who have early-stage CKD, and serves as an indicator of long-term CKD progression in those with normal renal function.


Assuntos
Doenças Cardiovasculares , Insuficiência Renal Crônica , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Progressão da Doença , Taxa de Filtração Glomerular , Fatores de Risco de Doenças Cardíacas , Humanos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco
19.
Ophthalmology ; 129(5): 552-561, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34856231

RESUMO

PURPOSE: To evaluate ethnic variations, ocular and systemic determinants of retinal nerve fiber layer (RNFL) thickness, and neuroretinal rim area among Asians using a large consortium of population-based eye studies. DESIGN: Cross-sectional pooled analysis. PARTICIPANTS: Twenty-two thousand four hundred thirty-six participants (22 436 eyes) from 10 population-based studies (in China, Hong Kong, India, Japan, Russia, and Singapore) of the Asian Eye Epidemiology Consortium. METHODS: Participants 40 years of age or older without glaucoma were included. All participants underwent spectral-domain OCT imaging and systemic and ocular examinations. Data were pooled from each study. Multivariable regression was performed to evaluate interethnic differences, intermachine variations, and ocular and systemic factors associated with RNFL thickness and rim area, adjusting for age, gender, diabetes, intraocular pressure (IOP), spherical equivalent (SE), ethnicity, OCT model, and study group. When evaluating body mass index, smoking, and hypertension as exposures, these factors were additionally adjusted for in the model. MAIN OUTCOME MEASURES: Average RNFL thickness (in micrometers) and rim area (in square millimeters). RESULTS: Indian and Japanese eyes have thinner RNFLs than those of other Asian ethnicities (ß values range, 7.31-12.76 µm; P < 0.001 for all pairwise comparisons). Compared with measurements by Cirrus HD-OCT (Carl Zeiss Meditec, Inc), RNFL on average was 7.29 µm thicker when measured by Spectralis (Heidelberg Engineering), 12.85 µm thicker when measured by RS-3000 (NIDEK Co, Ltd), and 17.48 µm thicker when measured by iVue/RTVue (Optovue, Inc) devices (all P < 0.001). Additionally, older age (per decade, ß = -2.70), diabetes (ß = -0.72), higher IOP (per 1 mmHg, ß = -0.07), more myopic SE (per diopter, ß = -1.13), cardiovascular disease (ß = -0.94), and hypertension (ß = -0.68) were associated with thinner RNFL (all P ≤ 0.003). Similarly, older age (ß = -0.019), higher IOP (ß = -0.010), and more myopic SE (ß = -0.025) were associated with smaller rim area (all P < 0.001). CONCLUSIONS: In this large pooled analysis of Asian population studies, Indian and Japanese eyes were observed to have thinner RNFL profiles. These findings suggest the need for an ethnic-specific normative database to improve glaucoma detection.


Assuntos
Glaucoma , Hipertensão , Miopia , Estudos Transversais , Glaucoma/diagnóstico , Glaucoma/epidemiologia , Humanos , Pressão Intraocular , Fibras Nervosas , Células Ganglionares da Retina , Tomografia de Coerência Óptica/métodos
20.
Br J Ophthalmol ; 106(5): 681-688, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33397658

RESUMO

PURPOSE: To quantify retinal and choriocapillaris (CC) microvasculature in highly myopic (HM) eyes with myopic macular degeneration (MMD) using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: 162 HM eyes (spherical equivalent ≤ -6.0 dioptres or axial length (AL) ≥26.5 mm) from 98 participants were enrolled, including 60 eyes (37.0%) with tessellated fundus, 54 eyes (33.3%) with peripapillary diffuse chorioretinal atrophy (PDCA), 27 eyes (16.7%) with macular diffuse chorioretinal atrophy (MDCA) and 21 eyes (13.0%) with patchy or macular atrophy. PLEX Elite 9000 SS-OCTA was performed to obtain perfusion densities (PD) of the superficial and deep retinal capillary plexus, and CC signal voids (number, area and density). RESULTS: Retinal PD decreased with increasing severity of MMD. Multivariable analysis showed that after adjustment of age and other factors, retinal PD decreased significantly in eyes with longer AL (ß≤-0.51, p<0.001) and with an MMD severity of MDCA or worse (ß≤-1.63, p<0.001). Reduced retinal PD were significantly associated with worse vision (ß≤-0.01, p≤0.04). In terms of CC signal voids, multivariable analysis showed that longer AL (p<0.001), but not MMD severity (p≥0.12) was significantly associated with CC signal void changes in the earliest stage of MMD. CONCLUSION: We demonstrate significant OCTA alterations in the retina and CC in HM eyes with varying severities of MMD. In eyes with early-stage PDCA, lower retinal PD and more extensive CC signal voids are predominantly associated with increasing AL. In contrast, in eyes with MDCA or worse, MMD itself was associated with sparser retinal and CC circulation.


Assuntos
Degeneração Macular , Miopia Degenerativa , Angiografia , Atrofia , Corioide/patologia , Doenças da Coroide , Angiofluoresceinografia/métodos , Humanos , Degeneração Macular/complicações , Microvasos , Miopia Degenerativa/complicações , Miopia Degenerativa/diagnóstico , Retina , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos
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