To evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the ...Consortium of Refractive Error and Myopia (CREAM).
A candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. Fifty loci with the strongest associations with myopia were chosen from a previous published GWAS study. Highly myopic (spherical equivalent SE ≤ -5.0 diopters D) cases with MMD (N = 348), and two sets of controls were enrolled: (1) the first set included 16,275 emmetropes (SE ≤ -0.5 D); and (2) second set included 898 highly myopic subjects (SE ≤ -5.0 D) without MMD. MMD was classified based on the International photographic classification for pathologic myopia (META-PM).
In the first analysis, comprising highly myopic cases with MMD (N = 348) versus emmetropic controls without MMD (N = 16,275), two SNPs were significantly associated with high myopia in adults with HM and MMD: (1) rs10824518 (P = 6.20E-07) in KCNMA1, which is highly expressed in human retinal and scleral tissues; and (2) rs524952 (P = 2.32E-16) near GJD2. In the second analysis, comprising highly myopic cases with MMD (N = 348) versus highly myopic controls without MMD (N = 898), none of the SNPs studied reached Bonferroni-corrected significance.
Of the 50 myopia-associated loci, we did not find any variant specifically associated with MMD, but the KCNMA1 and GJD2 loci were significantly associated with HM in highly myopic subjects with MMD, compared to emmetropes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The retinal vasculature allows direct noninvasive visualization of the body’s mircrovasculature. Because the retina and other end organs (brain and kidney) share similar anatomical features and ...physiological properties, the retinal vessels offer a unique and easily accessible window to study the health and disease of the human microcirculation. Advanced retinal vascular imaging technologies have been developed to allow a more objective and precise assessment of retinal vascular changes. The changes in the retinal vasculature associated with hypertension can be broadly divided into 3 groups(1) classic retinal vascular changes in response to blood pressure (referred to as hypertensive retinopathy signs), (2) changes in retinal vascular caliber, and (3) changes in more global geometrical patterns of the retina. In this review, we summarize the current understanding of the relationship between retinal vascular changes and blood pressure, the evidence for the retinal vasculature as a biological model to study the manifestation and early pathogenic correlates of hypertension, the latest advances in retinal vascular imaging technologies, and the future opportunities and challenges of retinal vascular imaging. We suggest that further development of retinal vascular analyses and standardized measurement protocols, evaluation of the clinical use of retinal vascular imaging in assessing cardiovascular risk prediction, and using retinal vascular imaging to test antihypertensive treatments will allow the translation of retinal vascular imaging as a tool to improve the diagnosis, prognosis, and management of hypertension in clinical practice.
To describe the relationship of retinal arteriolar and venular caliber with cardiovascular risk factors, including inflammatory biomarkers, in a multiethnic population of whites, blacks, Hispanics, ...and Chinese.
A cross-sectional study comprising 5979 persons aged 45 to 84 years residing in six U.S. communities. Retinal vascular caliber was measured and summarized from digital retinal photographs. Standard cardiovascular risk factors, including biomarkers of inflammation (e.g., high-sensitivity C-reactive protein hsCRP, interleukin IL-6, and plasma fibrinogen) and endothelial dysfunction (e.g., soluble intercellular adhesion molecule sICAM-1 , plasminogen activator inhibitor PAI-1) were assessed.
Mean retinal arteriolar caliber was 144.1+/-14.4 (SD) microm, and venular caliber 214.0+/-22.2 microm. In models controlling for age, gender, race-ethnicity, and center, smaller retinal arteriolar caliber was related to higher systolic and diastolic blood pressure, hypertension status, current alcohol consumption, greater body mass index, and higher levels of total homocysteine; larger retinal arteriolar caliber was related to diabetes, current cigarette smoking, and higher levels of plasma fibrinogen; and larger retinal venular caliber was related to diabetes, current cigarette smoking, greater body mass index and waist-hip ratio, higher levels of serum glucose, plasma triglyceride, plasma LDL-cholesterol, hsCRP, plasma fibrinogen, IL6, sICAM-1, and PAI-1 and lower levels of HDL-cholesterol. In multivariate analyses, blacks and Hispanics had larger retinal arteriolar and venular calibers than did whites and Chinese.
Retinal arteriolar and venular caliber is associated with a range of cardiovascular risk factors, including hypertension, diabetes, measures of obesity, and dyslipidemia. Venular caliber is also associated with systemic inflammation.
The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed healthcare services, faced with the twin challenges in acutely meeting the medical needs of patients with COVID-19 while continuing ...essential services for non-COVID-19 illnesses. The need to re-invent, re-organize and transform healthcare and co-ordinate clinical services at a population level is urgent as countries that controlled initial outbreaks start to experience resurgences. A wide range of digital health solutions have been proposed, although the extent of successful real-world applications of these technologies is unclear. This study aims to review applications of artificial intelligence (AI), telehealth, and other relevant digital health solutions for public health responses in the healthcare operating environment amidst the COVID-19 pandemic. A systematic scoping review was performed to identify potentially relevant reports. Key findings include a large body of evidence for various clinical and operational applications of telehealth (40.1%, n = 99/247). Although a large quantity of reports investigated applications of artificial intelligence (AI) (44.9%, n = 111/247) and big data analytics (36.0%, n = 89/247), weaknesses in study design limit generalizability and translation, highlighting the need for more pragmatic real-world investigations. There were also few descriptions of applications for the internet of things (IoT) (2.0%, n = 5/247), digital platforms for communication (DC) (10.9%, 27/247), digital solutions for data management (DM) (1.6%, n = 4/247), and digital structural screening (DS) (8.9%, n = 22/247); representing gaps and opportunities for digital public health. Finally, the performance of digital health technology for operational applications related to population surveillance and points of entry have not been adequately evaluated.
Purpose To review clinical and experimental data for fenofibrate as a possible systemic treatment for diabetic retinopathy. Design Perspective. Methods Review of clinical studies focused on 2 major ...randomized controlled trials: the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) and ACCORD (Action to Control Cardiovascular Risk in Diabetes)-Eye studies. Progression was defined in FIELD as laser treatment for proliferative retinopathy or macular edema or increase by ≥2 steps on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, and in ACCORD-Eye as ≥3 steps (ETDRS scale) or proliferative disease requiring laser or vitrectomy treatment. Experimental studies investigating the mode of action of fenofibrate were reviewed. Results The 2 trials included 11 388 patients with type 2 diabetes mellitus, of whom 5701 were treated with fenofibrate (± statin) for up to 5 years. Fenofibrate reduced first laser treatment by 31% ( P = .0002), and progression of diabetic retinopathy with absolute reductions of 5.0% over 5 years ( P = .022, FIELD) and 3.7% over 4 years ( P = .006, ACCORD-Eye). There was greater benefit in patients with than without preexisting retinopathy. The putative mechanisms implicated in the mode of action of fenofibrate involve lipid and nonlipid pathways, including beneficial effects on apoptosis, oxidative stress, inflammation, blood-retinal barrier breakdown, and neuroprotection. Conclusions There are now robust and consistent clinical data to recommend fenofibrate as an adjunctive treatment for early diabetic retinopathy in patients with type 2 diabetes mellitus, taking into account the risks vs benefits of therapy. Further elucidating its mode of action will help to refine how best to use fenofibrate in the management of diabetic retinopathy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To examine the relationship of retinal vascular tortuosity to age, blood pressure, and other cardiovascular risk factors.
Population-based, cross-sectional study.
A total of 3280 participants aged 40 ...to 80 years from the Singapore Malay Eye Study (78.7% response rate).
Retinal arteriolar and venular (vascular) tortuosity were quantitatively measured from fundus images using a computer-assisted program. Retinal vascular tortuosity was defined as the integral of the curvature square along the path of the vessel, normalized by the total path length. Data on blood pressure and major cardiovascular disease (CVD) risk factors were collected from all participants.
Retinal arteriolar and venular tortuosity.
A total of 2915 participants contributed data to this study. The mean (standard deviation) and median were 2.99 (1.40) and 2.73 for retinal arteriolar tortuosity (×10(4)), and 4.64 (2.39) and 4.19 for retinal venular tortuosity (×10(4)), respectively. Retinal venules were significantly more tortuous than retinal arterioles (P<0.001). In multivariable-adjusted linear regression models, less arteriolar tortuosity was independently associated with older age, higher blood pressure, higher body mass index (BMI), and narrower retinal arteriolar caliber (all P<0.05); greater venular tortuosity was independently associated with younger age, higher blood pressure, lower high-density lipoprotein (HDL) cholesterol level, and wider retinal venular caliber (all P<0.05).
Retinal arteriolar tortuosity was associated with older age and higher levels of blood pressure and BMI, whereas venular tortuosity was also associated with lower HDL level. The quantitative assessment of retinal vascular tortuosity from retinal images may provide further information regarding effects of cardiovascular risk factors on the retinal vasculature.
IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (GWAS) loci explain only a fraction of disease risk. To identify novel ...susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations at ST6GAL1 on 3q27.3 (rs7634389, odds ratio (OR)=1.13, P=7.27 × 10(-10)), ACCS on 11p11.2 (rs2074038, OR=1.14, P=3.93 × 10(-9)) and ODF1-KLF10 on 8q22.3 (rs2033562, OR=1.13, P=1.41 × 10(-9)), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR=1.22, P=2.26 × 10(-19)), and identify three independent signals within the DEFA locus (rs2738058, P=1.15 × 10(-19); rs12716641, P=9.53 × 10(-9); rs9314614, P=4.25 × 10(-9), multivariate association). The risk variants on 3q27.3 and 11p11.2 show strong association with mRNA expression levels in blood cells while allele frequencies of the risk variants within ST6GAL1, ACCS and DEFA correlate with geographical variation in IgAN prevalence. Our findings expand our understanding on IgAN genetic susceptibility and provide novel biological insights into molecular mechanisms underlying IgAN.
Diabetic macular oedema, characterised by exudative fluid accumulation in the macula, is the most common form of sight-threatening retinopathy in people with diabetes. It affects one in 15 people ...with diabetes resulting in more than 20 million cases worldwide. Few epidemiological studies have been done to specifically investigate risk factors for diabetic macular oedema, although poor glycaemic and blood pressure control are associated with the presence and development of the disorder. The pathophysiological processes begin with chronic hyperglycaemia, and interplay between vascular endothelial growth factor (VEGF) and inflammatory mediators. Non-invasive imaging using optical coherence tomography has allowed clinicians to detect mild levels of diabetic macular oedema in order to monitor progress and guide treatment. Although focal or grid laser photocoagulation was the traditional mode of treatment, intraocular pharmacotherapy with anti-VEGF agents is now the standard of care. However, these therapies are expensive and resource intensive. Emerging therapeutic strategies include improving efficacy and duration of VEGF suppression, targeting alternative pathways such as inflammation, the kallikrein-kinin system, the angiopoietin-Tie2 system, and neurodegeneration, and using subthreshold and targeted laser therapy. Ongoing research should lead to improvements in screening, diagnosis, and management of diabetic macular oedema.
We sought to evaluate longer-term efficacy and safety of intravitreal aflibercept monotherapy (IAI) vs IAI plus rescue photodynamic therapy (rPDT) in patients with polypoidal choroidal vasculopathy ...(PCV).
This was a prospective multicenter, double-masked, sham-controlled randomized clinical study across 62 centers.
In this phase 3b/4 study, patients with PCV with best-corrected visual acuity of 73–24 Early Treatment Diabetic Retinopathy Study letters (20/40–20/320 Snellen equivalent) received IAI 2 mg every 4 weeks until week 12, when they were randomized 1:1 to receive IAI or IAI plus rPDT if rescue criteria were met. Patients not requiring rescue received IAI every 8 weeks; those requiring rescue received IAI every 4 weeks plus sham/active PDT. At week 52 (the primary endpoint), IAI was noninferior to IAI plus rPDT. After week 52, treatment intervals could be extended beyond 8 weeks at the investigators' discretion. Noninferiority of IAI vs IAI plus rPDT for mean best-corrected visual acuity change from baseline to week 96 was evaluated.
Over 96 weeks, 54 patients (17.0%) met rescue criteria. At week 96, IAI was noninferior to IAI plus rPDT in terms of Early Treatment Diabetic Retinopathy Study letters gained (+10.7 vs +9.1, P = .48). Proportions of patients with complete polyp regression (33.1% vs 29.1%) or without active polyps (82.1% vs 85.6%) were similar. In year 2, the mean number of injections was 4.6 in both arms. No new safety signals were observed.
IAI monotherapy was noninferior to IAI with rescue PDT up to 96 weeks, and functional and anatomical improvements achieved at 52 weeks were maintained. Few patients required rescue PDT, which provided no additional visual benefit.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
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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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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