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Background: Community-based telemedicine screening for diabetic retinopathy (DR) has been highly recommended worldwide. However, evidence from low- and middle-income countries (LMICs) on the choice between artificial intelligence (AI)-based and manual grading-based telemedicine screening is inadequate for policy making., Objective: The aim of this study was to test whether the AI model is more worthwhile than manual grading in community-based telemedicine screening for DR in the context of labor costs in urban China., Methods: We conducted cost-effectiveness and cost-utility analyses by using decision-analytic Markov models with 30 one-year cycles from a societal perspective to compare the cost, effectiveness, and utility of 2 scenarios in telemedicine screening for DR: manual grading and an AI model. Sensitivity analyses were performed. Real-world data were obtained mainly from the Shanghai Digital Eye Disease Screening Program. The main outcomes were the incremental cost-effectiveness ratio (ICER) and the incremental cost-utility ratio (ICUR). The ICUR thresholds were set as 1 and 3 times the local gross domestic product per capita., Results: The total expected costs for a 65-year-old resident were US $3182.50 and US $3265.40, while the total expected years without blindness were 9.80 years and 9.83 years, and the utilities were 6.748 quality-adjusted life years (QALYs) and 6.753 QALYs in the AI model and manual grading, respectively. The ICER for the AI-assisted model was US $2553.39 per year without blindness, and the ICUR was US $15,216.96 per QALY, which indicated that AI-assisted model was not cost-effective. The sensitivity analysis suggested that if there is an increase in compliance with referrals after the adoption of AI by 7.5%, an increase in on-site screening costs in manual grading by 50%, or a decrease in on-site screening costs in the AI model by 50%, then the AI model could be the dominant strategy., Conclusions: Our study may provide a reference for policy making in planning community-based telemedicine screening for DR in LMICs. Our findings indicate that unless the referral compliance of patients with suspected DR increases, the adoption of the AI model may not improve the value of telemedicine screening compared to that of manual grading in LMICs. The main reason is that in the context of the low labor costs in LMICs, the direct health care costs saved by replacing manual grading with AI are less, and the screening effectiveness (QALYs and years without blindness) decreases. Our study suggests that the magnitude of the value generated by this technology replacement depends primarily on 2 aspects. The first is the extent of direct health care costs reduced by AI, and the second is the change in health care service utilization caused by AI. Therefore, our research can also provide analytical ideas for other health care sectors in their decision to use AI., (©Senlin Lin, Yingyan Ma, Yi Xu, Lina Lu, Jiangnan He, Jianfeng Zhu, Yajun Peng, Tao Yu, Nathan Congdon, Haidong Zou. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 23.02.2023.)

Background: This study aimed to determine the epigenetic biomarkers of diabetic retinopathy (DR) in subjects with type 2 diabetes mellitus (T2DM). This retrospective study is based on the Shanghai Xinjing community prevention and treatment administrative system of chronic diseases. The subjects enrolled herein were T2DM patients who had undergone long-term follow-up evaluation in the system. Two consecutive studies were conducted. In the discovery cohort, among 19 subjects who had developed DR with a DM duration < 3 years and 21 subjects without DR > 30 years after being diagnosed with DM, an Infinium Human Methylation 850 Beadchip was used to identify differential methylation regions (DMRs) and differential methylation sites (DMSs). The function of the genes was assessed through KEGG enrichment analysis, Gene Ontology (GO) analysis, and pathway network analysis. In the replication cohort, 87 DR patients with a short DM duration and 89 patients without DR over a DM duration > 20 years were compared to assess the association between DMSs and DR upon pyrosequencing., Results: A total of 34 DMRs were identified. Genes containing DMSs with the top 5 highest beta value differences between DR and non-DR participants were located on chromosome 1 and were present in the S100A13 gene, which was associated with 71 GO terms. Two S100A13 gene sites, i.e., cg02873163 and cg11343894, displayed a good correlation with DR on pyrosequencing., Conclusions: DMSs in the S100A13 gene may be potential biomarkers of DR.

Background: The aim of this study was to explore the association between diabetic retinopathy (DR) and the variants of uncoupling proteins (UCPs) genes in a Chinese population of type 2 diabetes, in total and in patients of different glycemic status separately., Methods: This case-control study included a total of 3107 participants from two datasets, among which 662 were DR patients (21.31%). Eighteen tag single nucleotide polymorphisms (SNPs) of UCP1, UCP2, and UCP3 were selected as genetic markers. TaqMan probes, Sequenom MassARRAY MALDI-TOF mass spectrometry platform and Affymetrix Genome-Wide Human SNP Array were used for genotyping. Online SHEsis software was used for association analysis. Bonferroni correction was used for multiple comparisons correction., Results: Three SNPs of UCP1: rs7688743 (A allele, OR = 1.192, p = 0.013), rs3811787 (T allele, OR = 0.863, p = 0.023), and rs10011540 (G allele, OR = 1.368, p = 0.004) showed association with DR after the adjustment of glucose, but only rs10011540 was marginally significantly associated with DR when Bonferroni correction was strictly applied (p adj  = 0.048). In patients with uncontrolled glucose, rs7688743 (A allele, p = 0.012, OR = 1.309), rs10011540 (G allele, p = 0.033, OR = 1.432), and rs3811787 (T allele, p = 0.022, OR = 0.811) were associated with DR, while in participants with well controlled glucose, the rs2734827 of UCP3 was associated with DR (A allele, p = 0.017, OR = 0.532). Rs3811787 of UCP1 showed a protective effect to sight threatening DR (T allele, p = 0.007, OR = 0.490), and the association existed after the adjustment for environmental factors and the correction. In patients with uncontrolled glucose, the rs3811787 of UCP1 (T allele, p = 0.017, OR = 0.467) and the rs591758 of UCP3 (C allele, p = 0.026, OR = 0.103) were associated with STDR. While in those with well controlled glucose, only the rs7688743 of UCP1 showed a protective effect (A allele, p = 0.024, OR = 0.049). None of the associations remain significant when Bonferroni correction was strictly applied (all p < 0.05)., Conclusions: The rs10011540 and rs3811787 of the UCP1 gene was marginally significantly associated with DR in Chinese type 2 diabetes patients. There might be different mechanisms of DR development in patients with different glycemic status.

Purpose: To analyze the relationships between choroidal thickness (CT) and diabetes mellitus (DM), diabetic retinopathy (DR), and DR severity in community residents diagnosed with type 2 DM, and to explore whether CT can improve the discriminatory ability of other risk factors to predict the incidence of DR., Methods: A total of 1,250 type 2 DM residents and 1,027 healthy controls in Xinjing community of Shanghai participated a cross-sectional survey of eye diseases in 2016. CT was measured using swept-source optical coherence tomography. DR was classified according to the 2002 international clinical classification of DR. A total of 537 subjects with type 2 DM without DR at the 2016 survey were followed up in 2018 to investigate the 2-year incidence of DR. Receiver operating characteristic curve analysis was used to test the accuracy of different indicators in predicting the onset of DR., Results: The central CT of the control, no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR, and PDR groups were 223.40, 216.22, 213.57, 211.91, 178.47, and 168.15 μm, respectively (p for trend <0.001), and the average CT (ACT) were 197.83, 186.94, 182.03, 178.00, 156.91, and 136.72 μm respectively (p for trend <0.001). Body mass index (BMI), DM duration, fasting blood glucose, glycosylated hemoglobin (HbA1C), and ACT were risk factors for 2-year DR incidence. For the onset of DR, as predicted by ACT, after tenfold cross validation the average area under the curve was 0.55 (p = 0.048). Addition of ACT did not improve the discriminatory ability of DM duration, BMI, glucose and HbA1C on the incidence of DR (Z = 0.48; p = 0.63)., Conclusions: As the severity of DR increased, the CT of community type 2 DM patients showed a significant downward trend compared with the healthy controls. Thinner ACT was found to be a risk factor for DR incidence, but it did not improve the discriminatory ability of other risk factors to predict the incidence of DR., (© 2020 S. Karger AG, Basel.)

Purpose: To calculate crystalline lens power and to determine the relationship between ocular biometry and diabetic retinopathy (DR) in an adult population with type 2 diabetes mellitus (T2DM)., Design: Cross-sectional, population-based study., Participants: Patients with T2DM from the Beixinjing community, Changning district, Shanghai., Methods: Random clustering sampling was used to identify adults with T2DM in the Beixinjing community. Spherical equivalent (SE) was determined by subjective refraction that achieved the best corrected vision. Axial length (AL), corneal power (CP), and anterior chamber depth (ACD) were measured using the IOLMaster. Diabetic retinopathy and diabetic macular edema (DME) were assessed according to the international DR classification., Main Outcome Measures: The crystalline lens power was calculated using the Bennett-Rabbetts formula. The AL-to-corneal radius ratio (AL/CR ratio) was defined as the axial length divided by the mean corneal radius of curvature., Results: A total of 4011 eyes of 2057 subjects with T2DM were included in the analysis. In multivariate logistic models adjusting for age, sex, duration of diabetes, glycosylated hemoglobin A1c, serum creatinine, body mass index, systolic blood pressure, and cataract, after categorizing values into quartiles, there were trend associations between lens power and any DR (P = 0.01), between AL/CR ratio and any DR (P = 0.02), and between AL and any DR (P = 0.03), between lens power and moderate DR (P = 0.02), and between AL and moderate DR (P = 0.02); eyes with higher AL/CR ratio were less likely to have any DR (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.24-0.78; P = 0.01 per 1 increase) and moderate DR (OR, 0.44; 95% CI, 0.21-0.93; P = 0.03 per 1 increase), eyes with longer AL were less likely to have any DR (OR, 0.88; 95% CI, 0.81-0.95; P = 0.002 per millimeter increase) or moderate DR (OR, 0.89; 95% CI, 0.80-0.98; P = 0.02 per millimeter increase), and eyes with higher SE were more likely to have any DR (OR, 1.08; 95% CI, 1.03-1.13; P = 0.003 per diopter increase)., Conclusions: In persons with T2DM, lens power, AL/CR ratio, and AL were associated with the presence of any DR and moderate DR. These findings suggested that globe elongation plays a major role in protective effects against DR, with contributions from lens power and other refractive components., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Diabetic macular edema (DME) is the major cause of vision loss in patients with diabetic retinopathy (DR). The purpose of this study was to assess the prevalence of DR and DME in a community in China and to analyze the characteristics of their optical coherence tomography (OCT) images. This study was an incidence survey based on data from 108,132 residents living in the Beixinjing District, Shanghai, China. Patients with DME came from the local health network. OCT was performed in 151 eyes of 100 type 2 diabetes patients with DR and 102 eyes of normal control subjects. Totally 795 cases were examined, and 215 of them were diagnosed to have DR. The average thickness of the macular fovea was 195.56 microm in 151 eyes from 100 random samples. Forty-six eyes had macular thickening. The statistical analysis showed that there was a positive correlation between the thickness of the macular fovea and -log of best-corrected visual acuity (r = 0.2869, p = 0.0004) as well as the severity of DR (p = 0.0003). However, there was no statistical significance between DME and posterior vitreous detachment. The images of OCT in DME included 3 types. Best-corrected visual acuity moderately correlated with retinal thickness. The macular thickness correlated with the severity of DR but not with posterior vitreous detachment., ((c) 2007 S. Karger AG, Basel.)

Background: Diabetic retinopathy has been shown to be directly associated with the degree and duration of hyperglycemia, and advanced glycosylation end products (AGEs) have been implicated in this pathological process. The purpose of the experiments reported here was to study the effect of AGE deposition on retinal vascular damage which leads to diabetic retinopathy., Methods: Intravenous injection of exogenous AGEs was used to treat wild-type non-diabetic Sprague-Dawley rats. One of the two retinal slides from each animal was treated using immunohistochemical staining to label retinal vascular AGE deposition, the other H&E staining for counting of capillary pericytes. The results were compared with the findings in untreated wild-type and diabetic controls and in rats treated with unmodified rat serum albumin (RSA)., Results: After 2 weeks of continuous treatment, AGEs were identified in the retinal vascular tissue of the AGE-RSA-injected group. The average number of retinal capillary pericytes per 10x100 microscope power field was 4.313+/-0.34 (mean +/- SD) in the AGE-RSA-injected group, compared with 5.798+/-0.481 in the control group ( P<0.01)., Conclusion: These experiments demonstrate that AGEs, independent of other metabolic factors, can induce vascular change resembling that of diabetic retinopathy.

Purpose: To investigate the prevalence and associated factors of fundus tessellation in highly myopic children and adolescents. Methods: A total of 513 high myopes (spherical equivalent [SE] ≤ −5.0 D, 4–19 years of age) without any advanced pathological myopic lesions were enrolled. Fundus photographs and choroidal thickness (ChT) data were collected by SS‐OCT. A novel grading approach was adopted to classify fundus tessellation into four categories on colour fundus photography, referring to the location of tessellation divided by an Early Treatment Diabetic Retinopathy Study grid centred on the fovea, through which closer to the fovea represents higher grades of fundus tessellation. Peripapillary atrophy (PPA) area and ovality index were also measured. Results: Among the participants, with a mean age of 13.47 ± 3.13 years and mean SE of − 8.34 ± 1.91 D, there were 29 (5.7%), 95 (18.5%), 233 (45.4%) and 156 (30.4%) participants with grade 0 to grade 3 fundus tessellation, respectively. The ChT in both the macular and peripapillary area was negatively correlated with the fundus tessellation grade (R = −0.763 and −0.537, respectively, all p < 0.001). Higher grades of fundus tessellation were independently associated with thinner macular ChT (OR = 1.734, 95% CI: 1.621–1.856, p < 0.001), longer axial length (OR = 1.368, 95% CI: 1.105–1.695, p = 0.004), larger PPA area (OR = 1.391, 95% CI: 1.073–1.802, p = 0.013) and the female sex (OR = 1.605, 95% CI: 1.092–2.359, p = 0.016). Conclusion: The fundus tessellation grade could reflect the ChT, representing the severity of myopic maculopathy among young high myopes who rarely had any advanced lesions of pathological myopia. Fundus tessellation grade might be a potential index for assessing early‐stage myopic maculopathy in children and adolescents. [ABSTRACT FROM AUTHOR]

Background: This study was performed to evaluate the prevalence and clinical characteristics of dry eye disease (DED) in community-based type 2 diabetic patients and to identify the associated factors related with DED.Methods: A total of 1360 type 2 diabetic patients in the Beixinjing community were randomly selected. All participants were given a questionnaire that assessed basic information and subjective symptoms.DED was diagnosed using the revised Japanese DED diagnostic criteria. All subjects underwent a routine ophthalmic examination, corneal sensitivity test, tear film break-up time(BUT) test, Schirmer I test, fluorescein and lissamine green staining(FL) and fundus photography. Diabetic retinopathy (DR) was graded according to the International severity scale of diabetic retinopathy and diabetic macular edema.Results: Of the 1360 subjects, 238 (17.5%) were diagnosed with DED. There was a significant association between the presence of DED and higher blood glucose (P < 0.001, OR1.240) as well as higher levels of glycosylated hemoglobin HbA1c (P < 0.001, OR1.108). Corneal sensitivity was negatively correlated with the prevalence of DED (P = 0.02, OR0.973).Conclusions: The prevalence of DED in this community-based study was 17.5%, which was lower than that observed in hospital-based studies. Diabetic patients with poor metabolic control were more likely to present with DED. A dry eye examination should be added to the routine screening of diabetes. [ABSTRACT FROM AUTHOR]

Background: To investigate the prevalence and risk factors of undercorrected refractive error (URE) among people with diabetes in the Baoshan District of Shanghai, where data for undercorrected refractive error are limited.Methods: The study was a population-based survey of 649 persons (aged 60 years or older) with diabetes in Baoshan, Shanghai in 2009. One copy of the questionnaire was completed for each subject. Examinations included a standardized refraction and measurement of presenting and best-corrected visual acuity (BCVA), tonometry, slit lamp biomicroscopy, and fundus photography.Results: The calculated age-standardized prevalence rate of URE was 16.63% (95% confidence interval [CI] 13.76-19.49). For visual impairment subjects (presenting vision worse than 20/40 in the better eye), the prevalence of URE was up to 61.11%, and 75.93% of subjects could achieve visual acuity improvement by at least one line using appropriate spectacles. Under multiple logistic regression analysis, older age, female gender, non-farmer, increasing degree of myopia, lens opacities status, diabetic retinopathy (DR), body mass index (BMI) index lower than normal, and poor glycaemic control were associated with higher URE levels. Wearing distance eyeglasses was a protective factor for URE.Conclusion: The undercorrected refractive error in diabetic adults was high in Shanghai. Health education and regular refractive assessment are needed for diabetic adults. Persons with diabetes should be more aware that poor vision is often correctable, especially for those with risk factors. [ABSTRACT FROM AUTHOR]