Optical Coherence Tomography Angiography in Retinal Vascular Disorders.

Traditionally, abnormalities of the retinal vasculature and perfusion in retinal vascular disorders, such as diabetic retinopathy and retinal vascular occlusions, have been visualized with dye-based fluorescein angiography (FA). Optical coherence tomography angiography (OCTA) is a newer, alternative modality for imaging the retinal vasculature, which has some advantages over FA, such as its dye-free, non-invasive nature, and depth resolution. The depth resolution of OCTA allows for characterization of the retinal microvasculature in distinct anatomic layers, and commercial OCTA platforms also provide automated quantitative vascular and perfusion metrics. Quantitative and qualitative OCTA analysis in various retinal vascular disorders has facilitated the detection of pre-clinical vascular changes, greater understanding of known clinical signs, and the development of imaging biomarkers to prognosticate and guide treatment. With further technological improvements, such as a greater field of view and better image quality processing algorithms, it is likely that OCTA will play an integral role in the study and management of retinal vascular disorders. Artificial intelligence methods-in particular, deep learning-show promise in refining the insights to be gained from the use of OCTA in retinal vascular disorders. This review aims to summarize the current literature on this imaging modality in relation to common retinal vascular disorders.

CHOROIDAL VASCULAR ALTERATIONS IN AGE-RELATED MACULAR DEGENERATION AND POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To evaluate morphologic alterations in choroidal veins in eyes with typical neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: A retrospective review of baseline indocyanine green angiography in eyes with typical nAMD and PCV. We evaluated Haller layer veins in the early-phase indocyanine green angiography (before 2 minutes) for 1) macular anastomosis, 2) dilated Haller veins, and 3) focal variation in vessel caliber by at least 50% from the narrowest to largest diameters. RESULTS: We included 70 patients with gradable indocyanine green angiography for the prespecified features in the study eye (36 typical nAMD and 34 PCV) and 59 fellow eyes. The median subfoveal choroidal thickness was 167 µm versus 219 µm, P = 0.08, in the presenting eyes in typical nAMD and PCV, respectively. Macular anastomosis was common in both typical nAMD and PCV (presenting eyes 58.3% vs. 58.8%. P = 0.97; fellow eyes 65.5% vs. 63.3%, P = 0.86). Dilated Haller veins were numerically less common in typical nAMD than PCV (presenting eyes 52.8% vs. 67.6%, P = 0.21; fellow eyes 65.5% vs. 70.0%, P = 0.71), while vascular caliber variation was numerically more common in typical nAMD than PCV (presenting eyes 72.2% vs. 63.8%, P = 0.45; fellow eyes 69.0% vs. 56.7%, P = 0.33). The presence of all three features was more common in the presenting eyes with PCV compared with typical nAMD (35.3% vs. 13.9%, P = 0.03). In a multivariable analysis, every increase of 100 µm of CT conferred a 2.75 risk of having all three features present. CONCLUSION: Choroidal vascular remodeling is common in both tAMD and PCV but may be driven by different stimuli.

Association between non-alcoholic fatty liver disease and subclinical atherosclerosis in Western and Asian cohorts: an updated meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a well-established risk factor for cardiovascular disease, with ethnic and regional differences noted. With the recent surge of research within this field, we re-examine the evidence associating NAFLD with subclinical atherosclerosis, and investigate potential regional differences. METHODS: This is a systematic review and meta-analysis. PubMed and EMBASE were systematically searched for publications from January 1967 to July 2020 using standardised criteria. Original, observational studies investigating the association between NAFLD and either carotid intima-media thickness (CIMT) and/or coronary artery calcification (CAC) were included. Key outcomes included differences in mean CIMT, the presence of increased CIMT, the presence of CAC and the development/progression of CAC. Pooled ORs and pooled standard differences in means were calculated using random-effects models. Between-study heterogeneity was quantified using the Q statistic and I². Subgroup analyses stratified by region of study (Asian vs Western) were also conducted. RESULTS: 64 studies involving a total of 172 385 participants (67 404 with NAFLD) were included. 44 studies assessed the effect of NAFLD on CIMT, with the presence of NAFLD associated with increased CIMT (OR 2.00, 95% CI 1.56 to 2.56). 22 studies assessed the effects of NAFLD on CAC score, with the presence of NAFLD associated with the presence of any coronary calcification (OR 1.21, 95% CI 1.12 to 1.32), and the development/progression of CAC (OR 1.26, 95% CI 1.04 to 1.52). When stratified by region, these associations remained consistent across both Asian and Western populations (p>0.05). The majority (n=39) of studies were classified as 'high quality', with the remaining 25 of 'moderate quality'. CONCLUSIONS: There is a significant positive association between various measures of subclinical atherosclerosis and NAFLD, seen across both Western and Asian populations. These results re-emphasise the importance of early risk evaluation and prophylactic intervention measures to preclude progression to clinical cardiovascular disease in patients with NAFLD.

Overview of hereditary breast and ovarian cancer (HBOC) guidelines across Europe.

Hereditary breast and ovarian cancer (HBOC) is a syndrome defined by an increased risk of developing breast and/or ovarian cancer most commonly due to germline disease-causing variants in the BRCA1 and BRCA2 genes, but also other causative genes such as PALB2, ATM and CHEK2. As genetic testing becomes more prevalent and new clinical data emerge, updates of national guidelines are required to incorporate these advances in our knowledge. The aim of this work is to review the guidelines for HBOC genetic testing and clinical surveillance across European countries, mostly affiliated to the European Reference Network (ERN) for Genetic Tumor Risk Syndroms (GENTURIS). Young onset breast cancer (BC), triple negative phenotype, or bilateral BC are considered as criteria for genetic testing in all, with differences in age limits. Testing of invasive epithelial non-mucinous ovarian cancer is also universally accepted. While breast magnetic resonance imaging (MRI) is consistently recommended in high-risk individuals, age of onset for mammograms differ between 30 and 40 years. Risk-reducing mastectomy is commonly offered as an option, while risk-reducing salpingo-oophorectomy is universally recommended. The largest differences are observed with respect to ovarian surveillance prior to risk-reducing salpingo-oophorectomy and in breast surveillance for carriers of non-BRCA1/2 genes. These differences in national guidelines reflect the variations in clinical consensus that may be reached in the absence of consistent evidence for some recommendations.

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

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.

Impact of Age and Sex on Subclinical Coronary Atherosclerosis in a Healthy Asian Population.

Background: The influence of age and sex on clinical atherosclerotic cardiovascular disease is well reported, but literature remains sparse on whether these extend to the disease in its preclinical stage. Objectives: The purpose of this study was to report the prevalence, risk factors, and impact of age and sex on the burden of subclinical coronary atherosclerosis in a healthy Asian population. Methods: Healthy subjects age 30 to 69 years, with no history of cardiovascular disease or diabetes were recruited from the general population. Subclinical coronary atherosclerosis was quantified via the coronary artery calcium score (CAC) with CAC of 0 indicating absence of calcified plaque, 1 to 10 minimal plaque, 11 to 100 mild plaque, and >100 moderate to severe plaque. Results: A total of 663 individuals (mean age 49.4 ± 9.2 years; 44.8% men) were included. The prevalence of any CAC was 29.3%, with 9% having CAC >100. The prevalence was significantly higher in men than women (43.1% vs 18.0%; P < 0.001). Multivariable analysis revealed significant associations of increasing age, male sex, higher blood pressure, increased glucose levels, and higher low-density lipoprotein cholesterol levels with the presence of any CAC. Low-density lipoprotein cholesterol was more significantly associated with CAC in women compared with men (P interaction = 0.022). Conclusions: The prevalence of preclinical atherosclerosis increased with age, and was higher in men, with sex-specific differences in associated risk factors. These results will better inform individualized future risk management strategies to prevent the development and progression of coronary artery disease within healthy individuals.

Interethnic differences in neuroimaging markers and cognition in Asians, a population-based study.

We examined interethnic differences in the prevalence of neuroimaging markers of cerebrovascular and neurodegenerative disease in 3 major Asian ethnicities (Chinese, Malays, and Indians), as well as their role in cognitive impairment. 3T MRI brain scans were acquired from 792 subjects (mean age: 70.0 ± 6.5years, 52.1% women) in the multi-ethnic Epidemiology of Dementia In Singapore study. Markers of cerebrovascular disease and neurodegeneration were identified. Cognitive performance was evaluated using Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and a neuropsychological assessment. Compared to Chinese, Malays had a higher burden of intracranial stenosis (OR: 2.28. 95%CI: 1.23-4.20) and cortical atrophy (ß: -0.60. 95%CI: -0.78, -0.41), while Indians had a higher burden of subcortical atrophy (ß: -0.23. 95%CI: -0.40, -0.06). Moreover, Malay and Indian ethnicities were likely to be cognitively impaired (OR for Malays: 3.79. 95%CI: 2.29-6.26; OR for Indians: 2.87. 95%CI: 1.74-4.74) and showed worse performance in global cognition (ß for Malays: -0.51. 95%CI: -0.66, -0.37; and Indians: -0.32. 95%CI: -0.47, -0.17). A higher burden of cerebrovascular and neurodegenerative markers were found in Malays and Indians when compared to Chinese. Further research is required to fully elucidate the factors and pathways that contribute to these observed differences.

Prevalence and Risk Factors for Cognitive Impairment and Dementia in Indians: A Multiethnic Perspective from a Singaporean Study.

BACKGROUND: Dementia is the leading cause of dependency and disability among older persons worldwide. There remains, however, limited studies on dementia rates within the Asia-Pacific region, with little data on differences across major Asian ethnic groups. OBJECTIVE: To study the prevalence of cognitive impairment (CI) and dementia in community-dwelling Indians from Singapore and to examine interethnic differences among Chinese, Malays, and Indians. METHODS: Participants (>60 years) drawn from the Indian component of the multiethnic Epidemiology of Dementia in Singapore (EDIS) study were screened using the locally validated Abbreviated Mental Test and Progressive Forgetfulness Questionnaire. Screen-positive participants underwent further detailed neuropsychological assessments. CI was classified into Cognitive impairment no dementia (CIND)-mild, CIND-moderate, and dementia. RESULTS: Of 961 Indian adults, 120 (12.5%) had CIND-mild, 101 (10.5%) CIND-moderate, and 12 (1.2%) dementia. The overall age-standardized prevalence of any CI was 24.6%. The prevalence of any CI increased with age (15.7% in ages 60-64 years to 30.1% in ages≥80 years), and was higher in women than men. Multivariate analysis showed that age, lower education, and hypertension were independently associated with CI. Even after demographic and cardiovascular risk factor adjustment, Indians were more likely to be cognitively impaired compared to Chinese (odds ratio [OR], 95% CI:1.37 [1.01-1.86]) but not Malays (0.89 [0.72-1.10]). CONCLUSIONS: Among elderly Indians, the overall prevalence of any CI was 24.6%. Despite similar assessment protocols and risk factor adjustments, the prevalence of CI was higher in Indians compared to Chinese but similar to Malays. Further research is needed to unravel other factors that may underlie these ethnic differences.

The Relationship between Generalized and Abdominal Obesity with Diabetic Kidney Disease in Type 2 Diabetes: A Multiethnic Asian Study and Meta-Analysis.

This study examined the associations of body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR) and waist-height ratio (WHtR) with diabetic kidney disease (DKD) in a clinical sample of Asian patients with type 2 diabetes (T2DM); substantiated with a meta-analysis of the above associations. We recruited 405 patients with T2DM (mean (standard deviation (SD)) age: 58 (7.5) years; 277 (68.4%) male; 203 (50.1%) with DKD) from a tertiary care centre in Singapore. DKD was defined as urinary albumin-creatinine ratio >3.3 mg/mmoL and/or estimated glomerular filtration rate <60 mL/min/1.73 m². All exposures were analysed continuously and categorically (World Health Organization cut-points for BMI and WC; median for WHR and WHtR) with DKD using stepwise logistic regression models adjusted for traditional risk factors. Additionally, we synthesized the pooled odds ratio of 18 studies (N = 19,755) in a meta-analysis of the above relationships in T2DM. We found that overweight and obese persons (categorized using BMI) were more likely to have DKD compared to under/normal weight individuals, while no associations were found for abdominal obesity exposures. In meta-analyses however, all obesity parameters were associated with increased odds of DKD. The discordance in our abdominal obesity findings compared to the pooled analyses warrants further validation via longitudinal cohorts.

Is Corneal Arcus Independently Associated With Incident Cardiovascular Disease in Asians?

PURPOSE: To examine the longitudinal relationship between baseline corneal arcus (CA) and incident cardiovascular disease (CVD) in ethnic Indian and Malay adults in Singapore. DESIGN: Population-based cohort study. METHODS: Indian and Malay adults aged 40-80 years were recruited for baseline and 6-year follow-up visits between 2004-2009 and 2010-2015, respectively (follow-up response rate 73.9%). CA was assessed by ophthalmologists using slit-lamp biomicroscopy. The main outcome was self-reported incident CVD, defined as new myocardial infarction, angina pectoris, or stroke, which developed between baseline and follow-up. Multivariable logistic regression models assessed independent associations between baseline CA and incident CVD, adjusting for traditional CVD risk factors including age, sex, serum cholesterol, hypertension, diabetes, and smoking. We further conducted sex-stratified analyses to identify possible effect modifications. RESULTS: Of the total 3637 participants (overall mean [SD] age: 56 [9] years, 46% male) with available follow-up data, without history of CVD at baseline, 208 (5.7%) incident CVD cases were reported. Participants with CA were more likely to have incident CVD (7.5%) than those without (4.9%). After controlling for traditional CVD risk factors, CA was independently associated with incident CVD (odds ratio [95% confidence interval]: 1.52 [1.07-2.16]) in adjusted models. In sex-stratified models, associations between CA and incident CVD were seen in men (1.73 [1.12-2.67]) and not in women (1.05 [0.56-1.97]). CONCLUSIONS: CA is associated with incident CVD, independent of serum lipids and traditional CVD risk factors, in ethnic Malay and Indian men. Our finding suggests that CA is an additional observable indicator of CVD in men.