Bilateral neovascular age-related macular degeneration (AMD) causes much more handicaps for patients than unilateral neovascular AMD. Although several AMD-susceptibility genes have been evaluated for ...their associations to bilaterality, genome-wide association study (GWAS) on bilaterality has been rarely reported. In the present study, we performed GWAS using neovascular AMD cases in East Asian. The discovery stage compared 581,252 single nucleotide polymorphisms (SNPs) between 803 unilateral and 321 bilateral Japanese cases but no SNP showed genome-wide significance, while SNPs at six regions showed P-value < 1.0 × 10
, STON1-GTF2A1L/LHCGR/FSHR, PLXNA1, CTNNA3, ARMS2/HTRA1, LHFP, and FLJ38725. The first replication study for these six regions comparing 36 bilateral and 132 unilateral Japanese cases confirmed significant associations of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR), rs2284665 (ARMS2/HTRA1), and rs8002574 (LHFP) to bilaterality. In the second replication study comparing 24 bilateral and 78 unilateral cases from Singapore, rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) only showed significant association. Meta-analysis of discovery and replication studies confirmed genome-wide level significant association (P = 2.61 × 10
) of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) and strong associations (P = 5.76 × 10
and 9.73 × 10
, respectively) of rs2284665 (ARMS2/HTRA1) and rs8002574 (LHFP). Our GWAS for neovascular AMD bilaterality found new genetic loci STON1-GTF2A1L/LHCGR/FSHR and confirmed the previously reported association of ARMS2/HTRA1.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To examine the relationship of central corneal thickness (CCT) with optic disc parameters measured by confocal scanning laser ophthalmoloscopy in a Malay population.
This was a population-based ...cross-sectional study of Asian Malay adults aged 40-80 years living in Singapore. Participants had a standardized interview, examination, and imaging at a study clinic. CCT was measured with an ultrasound pachymeter. Confocal scanning laser imaging was performed on all participants to obtain optic disc parameters. Multivariate regression analyses controlling for age, sex, intraocular pressure, and other potentially confounding factors were conducted separately for disc area, rim area, cup-to-disc ratio, and mean cup depth.
Of the 3280 participants in the study, 2525 (77.0%) right eyes with reliable confocal scanning laser tomography images were included in this analysis, with 48 eyes defined to have primary open-angle glaucoma (POAG). In POAG subjects, CCT was positively correlated with rim area (regression coefficient of 0.372 mm(2) per 100 μm CCT increase; P = 0.035) and negatively correlated with cup-to-disc area ratio (-0.160 per 100 μm CCT increase; P = 0.024). There was no relationship between CCT and disc size (P = 0.088). In the 2468 subjects without glaucoma, there were no associations between CCT and confocal scanning laser tomography parameters.
In this population-based study, decreased CCT was associated with lower rim area and greater cup-to-disc area in subjects with POAG, but not in subjects without glaucoma.
Retinal microvascular caliber is a risk marker for cardiovascular disease. The authors examined the relation between high-sensitivity C-reactive protein (hsCRP) and retinal microvascular caliber in a ...multiethnic Asian population (n = 3,583) of Chinese, Malays, and Indians aged 24–95 years residing in Singapore (2003–2007). Retinal arteriolar and venular diameters were measured and summarized as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE), respectively. Persons with higher levels of hsCRP had wider CRVE (Ptrend < 0.001). In subgroup analysis stratified for different cardiovascular disease risk factors, the association between hsCRP and CRVE was seen in persons without diabetes (Ptrend < 0.001) but was absent in persons with diabetes (Ptrend = 0.200; Pinteraction = 0.004). No significant interaction between race/ethnicity and hsCRP in relation to retinal vascular caliber was observed. These data suggest that retinal venular caliber is associated with higher levels of hsCRP in Asians, which is consistent with studies in white Caucasian populations, further supporting the concept that retinal venular caliber may be a marker for low-grade systemic inflammation.
The goal of this study was to describe the development and validation of an artificial intelligence-based, deep learning algorithm (DLA) for the detection of referable diabetic retinopathy (DR).
A ...DLA using a convolutional neural network was developed for automated detection of vision-threatening referable DR (preproliferative DR or worse, diabetic macular edema, or both). The DLA was tested by using a set of 106,244 nonstereoscopic retinal images. A panel of ophthalmologists graded DR severity in retinal photographs included in the development and internal validation data sets (
= 71,043); a reference standard grading was assigned once three graders achieved consistent grading outcomes. For external validation, we tested our DLA using 35,201 images of 14,520 eyes (904 eyes with any DR; 401 eyes with vision-threatening referable DR) from population-based cohorts of Malays, Caucasian Australians, and Indigenous Australians.
Among the 71,043 retinal images in the training and validation data sets, 12,329 showed vision-threatening referable DR. In the internal validation data set, the area under the curve (AUC), sensitivity, and specificity of the DLA for vision-threatening referable DR were 0.989, 97.0%, and 91.4%, respectively. Testing against the independent, multiethnic data set achieved an AUC, sensitivity, and specificity of 0.955, 92.5%, and 98.5%, respectively. Among false-positive cases, 85.6% were due to a misclassification of mild or moderate DR. Undetected intraretinal microvascular abnormalities accounted for 77.3% of all false-negative cases.
This artificial intelligence-based DLA can be used with high accuracy in the detection of vision-threatening referable DR in retinal images. This technology offers potential to increase the efficiency and accessibility of DR screening programs.
Purpose. We examined the association of CKD defined by serum creatinine, serum cystatin C, and albuminuria with moderate diabetic retinopathy (DR). Methods. We examined 1,119 Indian adults with ...diabetes, aged 40–80 years, who participated in the Singapore Indian Eye Study (2007–2009), a population-based cross-sectional study. The associations of CKD defined by each of the three markers alone and in combination with moderate DR were examined using logistic regression models adjusted for potential confounding factors including duration of diabetes, smoking, body mass index, systolic blood pressure, and HbA1c. Results. The prevalence of moderate DR was significantly higher among those with CKD defined by triple markers (41.1%) compared to CKD defined separately by creatinine (26.6%), cystatin C (20.9%), and albuminuria (23.4%). People with CKD defined by triple markers had a fourteenfold higher odds of moderate DR (OR (95% CI) = 13.63 (6.08–30.54)) compared to those without CKD by any marker. Nearly half (48.7%) of participants with cystatin C ≥ 1.12 mg/L have moderate DR. Conclusions. CKD defined by a triple marker panel was strongly associated with moderate DR in this Asian population with diabetes.
Full text
Available for:
FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Declarations Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits ...unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To describe the prevalence of retinal vascular signs and their association with cardiovascular risk factors in a Japanese population.
Population-based cross-sectional study.
Adult persons aged 35 ...years or older from Funagata, Yamagata Prefecture, Japan (n = 1481).
The Funagata Study is a Japanese population-based study of persons aged 35 years or older, and included 1961 nondiabetic participants (53.3% of 3676 eligible subjects). A nonmydriatic retinal photograph was taken of 1 eye to assess retinal microvascular signs. Retinal arteriolar wall signs (focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar wall reflex) and retinopathy were assessed in 1481 participants without diabetes (40.3% of eligible persons) using a standardized protocol. Using a computer-assisted method, retinal vessel diameters were measured in 921 participants with gradable retinal image (25.1% of eligible persons).
Prevalence of retinal microvascular signs and their association with cardiovascular risk factors.
Moderate or severe focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar wall reflex, and retinopathy were found in 8.3%, 15.2%, 18.7%, and 9.0%, respectively, of the study population. Mean (+/-standard error) values for retinal arteriolar diameter were 178.6+/-21.0 mum, and mean values (+/-standard error) for venular diameter were 214.9+/-20.6 mum. Older persons were more likely to have retinal arteriolar wall signs, retinopathy, and narrower retinal vessel diameters. After adjusting for multiple factors, each 10-mmHg increase in mean arterial blood pressure was associated with a 20% to 40% increased likelihood of retinal arteriolar signs and a 2.8-mum reduction in arteriolar diameter. Retinopathy was associated with higher body mass index and both impaired glucose tolerance and impaired fasting glucose.
In nondiabetic Japanese adults, retinal arteriolar wall signs were associated with older age and increased blood pressure, whereas retinopathy was associated with older age, higher body mass index, impaired glucose tolerance, and impaired fasting glucose. These findings are comparable with data from white populations.
PDF
