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The gut microbiota has emerged as an independent risk factor for diabetes and its complications. This research aimed to delve into the intricate relationship between the gut microbiome and diabetic retinopathy (DR) through a dual approach of cross-sectional and prospective cohort studies. In our cross-sectional study cross-sectional investigation involving ninety-nine individuals with diabetes, distinct microbial signatures associated with DR were identified. Specifically, gut microbiome profiling revealed decreased levels of Butyricicoccus and Ruminococcus torques group, alongside upregulated methanogenesis pathways among DR patients. These individuals concurrently exhibited lower concentrations of short-chain fatty acids in their plasma. Leveraging machine learning models, including random forest classifiers, we constructed a panel of microbial genera and genes that robustly differentiated DR cases. Importantly, these genera also demonstrated significant correlations with dietary patterns and the molecular profiles of peripheral blood mononuclear cells. Building upon these findings, our prospective cohort study followed 62 diabetes patients over a 2-year period to assess the predictive value of these microbial markers. The results underlined the panel's efficacy in predicting DR incidence. By stratifying patients based on the predictive genera and metabolites identified in the cross-sectional phase, we established significant associations between reduced levels of Butyricicoccus, plasma acetate, and increased susceptibility to DR. This investigation not only deepens our understanding of how gut microbiota influences DR but also underscores the potential of microbial markers as early indicators of disease risk. These insights hold promise for developing targeted interventions aimed at mitigating the impact of diabetic complications. Key points: • Microbial signatures are differed in diabetic patients with and without retinopathy • DR-related taxa are linked to dietary habits and transcriptomic profiles • Lower abundances of Butyricicoccus and acetate were prospectively associated with DR [ABSTRACT FROM AUTHOR]

Purpose: To evaluate longitudinal changes in optical coherence tomography angiography (OCTA) metrics in children and adolescents with type 1 diabetes (T1D). Methods: This prospective observational cohort study included thirty-two eyes from thirty T1D children with no history of diabetic retinopathy (DR) who were followed up for 4 years. Participants underwent OCTA examinations at baseline and during follow-up. Quantitative OCTA metrics were measured using a customized MATLAB algorithm. Generalized mixed-effect models were used to determine their relationship with DR development. Systemic parameters and OCTA metrics were screened using least absolute shrinkage and selection operator to identify predictors for visual function. Results: Over the 4-year period, seven of the included eyes developed DR, and most OCTA metrics decreased with diabetes duration. Higher peripapillary and parafoveal nasal quadrant vessel area density (VAD) in the superficial capillary plexus (SCP) and vessel skeleton density (VSD) in both the SCP and the deep capillary plexus (DCP) were associated with a lower risk of DR in T1D. Parafoveal DCP VSD and VAD in the temporal and inferior quadrants were anticorrelated with changes in best corrected visual acuity. Conclusions: OCTA metrics dynamically change over the duration of diabetes and can be used as biomarkers to improve the risk evaluation of DR development and visual function in T1D children and adolescents. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effectiveness and cutoffs of axial length/corneal radius (AL/CR) ratio for myopia detection in children by age. Methods: Totally, 21 kindergartens and schools were enrolled. Non-cycloplegic autorefraction (NCAR), axial length (AL), horizontal and vertical meridian of corneal radius (CR1, CR2), and cycloplegic autorefraction were measured. Receiver operating characteristic (ROC) curve was used to obtain the effectiveness and cutoff for myopia detection. Results: Finally, 7803 participants aged 3–18 years with mean AL/CR ratio of 2.99 ± 0.16 were included. Area under the ROC curve (AUC) of AL/CR ratio for myopia detection (0.958 for AL/CR1, 0.956 for AL/CR2, 0.961 for AL/CR) was significantly larger than that of AL (0.919, all P < 0.001), while AUCs of the three were similar with different cutoffs (> 2.98, > 3.05, and > 3.02). When divided by age, the ROC curves of AL/CR ratio in 3- to 5-year-olds showed no significance or low accuracy (AUCs ≤ 0.823) in both genders. In ≥ 6-year-olds, the accuracies were promising (AUCs ≥ 0.883, all P < 0.001), the cutoffs basically increased with age (from > 2.93 in 6-year-olds to > 3.07 in 18-year-olds among girls, and from > 2.96 in 6-year-olds to > 3.07 in 18-year-olds among boys). In addition, boys presented slightly larger cutoffs than girls in all ages except for 16 and 18 years old. For children aged 3–5 years, AL/CR ratio or AL combined with NCAR increased AUC to > 0.900. Conclusion: AL/CR ratio provided the best prediction of myopia with age-dependent cutoff values for all but preschool children, and the cutoffs of boys were slightly larger than those of girls. For preschool children, AL/CR ratio or AL combined with NCAR is recommended to achieve satisfactory accuracy. AL/CR ratio calculated by two meridians showed similar predictive power but with different cutoffs. [ABSTRACT FROM AUTHOR]

Given the high incidence and prevalence of myopia, the current healthcare system is struggling to handle the task of myopia management, which is worsened by home quarantine during the ongoing COVID-19 pandemic. The utilization of artificial intelligence (AI) in ophthalmology is thriving, yet not enough in myopia. AI can serve as a solution for the myopia pandemic, with application potential in early identification, risk stratification, progression prediction, and timely intervention. The datasets used for developing AI models are the foundation and determine the upper limit of performance. Data generated from clinical practice in managing myopia can be categorized into clinical data and imaging data, and different AI methods can be used for analysis. In this review, we comprehensively review the current application status of AI in myopia with an emphasis on data modalities used for developing AI models. We propose that establishing large public datasets with high quality, enhancing the model's capability of handling multimodal input, and exploring novel data modalities could be of great significance for the further application of AI for myopia. [ABSTRACT FROM AUTHOR]

Purpose: To describe the association of refraction development and axial length (AL) in young children and provide new insights into the progression of cylinder power. Methods: Children (2–3 grades) were enrolled from primary schools in Shanghai and followed up for two years. Cycloplegic refraction, AL, and corneal curvature radius were measured. Refraction parameters were compared among groups with different AL, AL1 (AL < 23.5 mm), AL2 (23.5 mm ≤ AL < 24.5 mm), and AL3 (AL ≥ 24.5 mm). Multiple regression analysis was used to explore risk factors of diopter of cylinder (DC) progression. Results: In total, out of 6891 enrolled children, 5961 participants (7–11 yrs) were included in the final analysis. Over the two-year period, the cylinder power significantly changed, and those with longer AL had more rapid DC progression over the two years (AL1, -0.09 ± 0.35 D; AL2, -0.15 ± 0.39 D; AL3, -0.29 ± 0.44 D) (P < 0.001). The change in DC was independently associated with AL at baseline (P < 0.001). The proportion of with-the-rule astigmatism increased from 91.3% to 92.1% in AL1 group, from 89.1% to 91.8% in AL2 group and from 87.1% to 92.0% in AL3 group. Conclusions: Young children with long AL experienced rapid progression of cylinder power. Both the control of myopia progression and attention to the correction of astigmatism are necessary in the health management of children with long AL. The significantly increased AL in participants might contribute to both the extent and direction of astigmatism. [ABSTRACT FROM AUTHOR]

Purpose: Due to pubertal development and crystalline lens compensation, axial length (AL) continues to increase among non-progressive myopic children (absolute annual spherical equivalent (SE) progression less than 0.25 diopter), but the amount is unknown. This study was to investigate the cutoff of AL change to accurately differentiate between progressive and non-progressive myopes. Methods: A total of 8,546 myopic and treatment-naive children aged 6–10 years were enrolled from two cohort studies. AL with optical biometer and cycloplegic SE with auto refraction were evaluated at baseline and annually. Annual AL change was calculated, and the percentiles of annual axial elongation among progressive and non-progressive myopes were estimated by quantile regression with restricted cubic spline. Area under receiver-operating characteristic (ROC) curve (AUROC), positive predictive value (PPV), and negative predictive value (NPV) were applied to evaluate the accuracy of predicting progressive and non-progressive myopes. Results: Among 8,546 myopic children, 603 (7.06%) were non-progressive myopes. Annual AL changes among non-progressive myopes remained stable with the median annual change being 0.25 mm, while the median for progressive myopes decreased with age from 0.58 to 0.42 mm. AUROC for distinguishing between non-progressive and progressive myopes was 0.88 and was > 0.85 for each age group. Annual AL change, the cutoff of 0.20 mm/year, had significantly high PPV and NPV in predicting progressive myopes with high proportion of progressive myopes and non-progressive myopes with low proportions of progressive myopes. Conclusion: Myopic children with non-progressive status had markedly less axial elongation than progressive ones. AL changes with cutoff of 0.20 mm/year could differentiate between non-progressive and progressive status and may be an alternative for evaluating progressive status. [ABSTRACT FROM AUTHOR]

As innate immune cells of the central nervous system (CNS), microglia are involved in the physiological processes of the CNS, including neural development and maintenance of homeostasis, and in the occurrence and development of most CNS diseases. Lipoxygenases (LOXs) are a family of non-heme, iron-containing enzymes that generate lipid mediators that regulate cellular inflammation by catalyzing the oxidation of polyunsaturated fatty acids. Many previous studies have demonstrated the indispensable role of the LOX pathway in microglia-mediated neuroinflammation, especially the 5-LOX and 12/15-LOX pathways. Emerging evidence indicates that the LOX pathway is also implicated in physiological processes, such as synaptic pruning and synaptic phagocytosis mediated by microglia, and that deficiency can contribute to neurodevelopmental disorders. The present review summarizes the impact of the LOX pathway on microglia-related physiological and pathological processes in the CNS and describes the potential for inhibition of the LOX pathway as a future strategy for the treatment of CNS diseases. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relationship between serum 12-Hydroxyeicosatetraenoic acid (12-HETE) and diabetic retinopathy (DR) in children with type 1 diabetes mellitus (T1DM) and adults with type 2 diabetes mellitus (T2DM). Methods: Children from the Shanghai Children and Adolescent Diabetes Eye (SCADE) study and adults from the Shanghai Cohort Study of Diabetic Eye Disease (SCODE) were examined in 2021. Serum 12-HETE levels were detected and compared. Multivariate logistic regression was used to analyze the relationship between 12-HETE and the rate of DR in diabetic patients. Results: The child study included 4 patients with new-onset DR and 24 patients with T1DM without DR. In children with T1DM, the 12-HETE level was significantly higher in those with DR (P = 0.003). The adult study had two sets, for testing and verification. The test set included 28 patients with new-onset DR and 24 T2DM patients with a course of ≥ 20 years who had never developed DR. The verification set included 41 patients with DR, 50 patients without DR and 50 healthy controls. In the adult test set, the 12-HETE level was significantly higher in patients with DR than in those with T2DM without DR (P = 0.003). In the verification set, the 12-HETE level of patients with DR was significantly higher than that of patients without DR (P < 0.0001) and the healthy controls (P < 0.0001). Multivariate logistic regression indicated that 12-HETE was independently associated with DR in both children (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.00–1.13, P = 0.041) and adults (test set [OR 9.26, 95% CI 1.77–48.59, P = 0.008], verification set [OR 10.49, 95% CI 3.23–34.05, P < 0.001]). Conclusion: Higher serum 12-HETE levels are positively correlated with an increased risk of DR in children with T1DM and adults with T2DM. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the association between microvascular changes in the iris and refractive errors. Methods: A cross-sectional case study. Seventy eyes from 70 patients with refractive errors were enrolled. Iris microvasculature was analyzed using optical coherence tomography angiography (OCTA). We divided the iris images into three regions and calculated the vessel area density (VAD) and vessel skeleton density (VSD) of the inner one-third, inner two-thirds, and the entirety of the iris. Results: The VADs and VSDs of the different regions were significantly different. The VAD and VSD of the inner one-third of the iris were higher than those of the other regions. The iris blood vessels were denser near the pupil margin, and blood vessels from the iris root to the pupil edge were radially distributed. The VAD and VSD of patients with mild hyperopia and emmetropia were higher than those of patients with moderate and high myopia. As the spherical equivalent increased, the VAD and VSD of the iris increased. Neither age nor sex contributed to significant differences in VAD and VSD. Conclusion: Quantitative changes in iris microvasculature may indicate the development of myopia. [ABSTRACT FROM AUTHOR]

This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai, China. A total of 173 235 patients with type 2 diabetes in 2017 were included in the analysis. Profiles of risk factors and intermediate outcomes were determined. The patients had a mean age of 66.43 ± 8.12 (standard deviation (SD)) years and a mean diabetes duration of 7.95 ± 5.53 (SD) years. The percentage of patients who achieved the target level for HbA1c (< 7.0%) was 48.6%. Patients who achieved the target levels for blood pressure (BP) < 130/80 mmHg and low-density lipoprotein-cholesterol (LDL-c) < 2.6 mmol/L reached 17.5% and 34.0%, respectively. A total of 3.8% achieved all three target levels, and the value increased to 6.8% with an adaptation of the BP target level (< 140/90 mmHg) for those over 65 years. Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels: male, young age, short diabetes duration, low body mass index, macrovascular complications, no microvascular complications, prescribed with lipid-lowering medication, and no prescription of antihypertensive medication. In conclusion, nearly 50% and one-third of the patients with diabetes met the target levels for HbA1c and LDL-c, respectively, with a low percentage achieving the BP target level. The percentage of patients who achieved all three target levels needs significant improvement. [ABSTRACT FROM AUTHOR]

Purpose: To investigate morphological differences between two types of Bruch's membrane (BM) defects—patchy atrophy (PA) and CNV-related macular atrophy (CNV-MA) Methods: Eyes presenting with PA or CNV-MA were included. Scleral thickness (ST), choroidal thickness (CT), and scleral morphological characteristics were obtained by swept-source optical coherence tomography (SS-OCT). Fundus photographs were performed to measure the size of PA and CNV-MA lesions. Results: Among a total of 167 eyes evaluated, 106 eyes had PA and 61 eyes had CNV-MA. In addition, dome-shaped macula (DSM) was identified in 20 (18.87%) and 10 (16.39%) eyes among PA and CNV-MA, respectively. The eyes of CNV-MA without DSM showed a thicker subfoveal ST (278.61 ± 56.17 vs 231.58 ± 66.09 mm, P < 0.001), a thinner subfoveal CT, and a higher rate of scleral perforating vessels (70.6% vs 50.0%, P = 0.021) when compared with those of PA without DSM. The size of PA/CNV-MA lesions was associated with CT in eyes without DSM. However, it was only associated with bulge height in eyes with DSM (r = 0.5, P = 0.013). Conclusions: The eyes with CNV-MA had a thicker sclera than those with PA, which add another evidence to indicate the absence of the progressive relationship between two types of BM defects. The enlargement of lesions in BM defects between eyes with and without DSM may be caused by different mechanical forces. SS-OCT, which focuses on scleral and choroid morphology, may be necessary for more accurate classification of pathologic myopia. [ABSTRACT FROM AUTHOR]

Retinal screening contributes to early detection of diabetic retinopathy and timely treatment. To facilitate the screening process, we develop a deep learning system, named DeepDR, that can detect early-to-late stages of diabetic retinopathy. DeepDR is trained for real-time image quality assessment, lesion detection and grading using 466,247 fundus images from 121,342 patients with diabetes. Evaluation is performed on a local dataset with 200,136 fundus images from 52,004 patients and three external datasets with a total of 209,322 images. The area under the receiver operating characteristic curves for detecting microaneurysms, cotton-wool spots, hard exudates and hemorrhages are 0.901, 0.941, 0.954 and 0.967, respectively. The grading of diabetic retinopathy as mild, moderate, severe and proliferative achieves area under the curves of 0.943, 0.955, 0.960 and 0.972, respectively. In external validations, the area under the curves for grading range from 0.916 to 0.970, which further supports the system is efficient for diabetic retinopathy grading. As the leading cause of vision loss in working-age adults, diabetic retinopathy requires routinely retinal screening. Here the authors develop a deep learning system that can facilitate the screening by providing real-time image quality assessment, lesions detection, and grades across the disease spectrum. [ABSTRACT FROM AUTHOR]

Purpose: To determine which utility value assessment method is more suitable to evaluate changes in the quality of life due to dry eye symptoms.Methods: Dry eye outpatients with a presenting visual acuity of 20/25 or better in the worse-seeing eye were recruited. Presenting distance visual acuity, tear film break-up time, Schirmer I test and fluorescein were assessed. The severity of dry eye symptoms was assessed using the Ocular Surface Disease Index (OSDI), and utility values were measured using the time trade-off (TTO), standard gamble (SG1 and SG2) and rating scale (RS) methods. Different utility values were compared with each other. The most appropriate utility value method to evaluate quality-of-life changes solely due to dry eye symptoms is determined by calculating the correlation between the OSDI score and different utility values.Results: A total of 104 patients were enrolled. The three sections of OSDI in the order of high to low scores were as follows: "environmental trigger," "eye discomfort" and "visual function." The utility scores measured with TTO, SG1, SG2 and RS were 0.95 ± 0.11, 0.96 ± 0.10, 0.99 ± 0.07 and 0.89 ± 0.10, respectively. The utility scores evaluated by the TTO, SG1, SG2 and RS methods were significantly different from each other (p < 0.05). Only the utility scores measured with RS were significantly correlated with the composite OSDI score, "environmental trigger" and "eye discomfort" section scores (p < 0.05).Conclusions: RS is more sensitive than TTO and SG for the evaluation of altered quality of life due to dry eye symptoms. [ABSTRACT FROM AUTHOR]

Breast cancer survival was associated with higher frequencies of CD8 T cytotoxic T cells in infiltrating lymphocytes. On the other hand, the frequency of CD4CD25FoxP3 regulatory T cells was inversely correlated with clinical outcomes of breast cancer. The regulation and interaction of different types of tumor-infiltrating T cells in different stages of breast cancer patients are still unclear. In this study, we examined the functions and regulations of CD8 T cells and CD4CD25FoxP3 T cells from resected tumors from 12 stage I, 24 stage II, and 20 stage III untreated breast cancer patients. We found that tumor-infiltrating CD8 T cells from stage III patients were more refractory to T cell receptor (TCR) stimulation than those from stage I and stage II patients in terms of interferon gamma (IFN-γ) production and proliferation. On the other hand, tumor-infiltrating CD4CD25FoxP3 T cells had higher proliferation in stage III tumors than in stage I and stage II tumors. In addition, we found that tumor-infiltrating CD4CD25 T cells can suppress CD8 T cell inflammation ex vivo. Altogether, our data demonstrated that stage III tumors in breast cancer patients had a more immunosuppressive microenvironment. [ABSTRACT FROM AUTHOR]

Purpose: The neuroprotective effect of carbamylated erythropoietin (CEPO), an erythropoietin (EPO) derivative, in diabetic retinopathy (DR) has not been clearly verified. We conducted this study to investigate the potential neuroprotective role of CEPO in a streptozotocin-induced diabetic rat model. Methods: Streptozotocin-induced diabetic rats and blank controls were treated with or without CEPO and EPO for 4 weeks. Retinal functional and histological changes were quantified by electroretinogram, light microscopy, and terminal dUTP nick end labeling assay. Gene and protein levels of colony-stimulating factor 2 receptor beta, low-affinity (CD131), EPO receptor (EPOR), THY1, glial fibrillary acidic protein (GFAP), and vascular endothelial growth factor (VEGF-A) in retinal tissues were determined by real-time PCR and western blotting, respectively. Vascular penetration was assessed by fluorescein retinal angiography. Results: Diabetic rats had decreased retinal thickness, decreased ganglion cells, and increased retinal neuron apoptosis. CEPO increased CD131 and THY1 expression, while EPO increased EPOR expression. High glucose increased GFAP expression in the diabetic group, but both CEPO and EPO attenuated the trend for increase. CEPO downregulated VEGF-A expression. The amplitudes of b-wave and oscillatory potentials were decreased in the untreated diabetic group, whereas neither parameter decreased in diabetic rats after CEPO or EPO treatment. Vascular leakage and microaneurysms in the diabetic group were significantly improved following CEPO treatment. Conclusions: CEPO has similar anti-apoptotic effects to EPO in DR, but CEPO does not induce neovascularization. CEPO may exert neuroprotective effects via its receptor CD131. [ABSTRACT FROM AUTHOR]

Purpose: To assess the time trade-off (TTO) utility values in patients with persistent visually disabling vitreous floaters (DVF) and to determine the reliability and validity of TTO methods in DVF patients. Methods: Prospective cross-sectional questionnaire survey: Eligible patients with persistent DVF referred to the Shanghai First People's Hospital outpatient service between January 2006 and February 2010, and randomly selected normal vision general population residents, were enrolled. All participants underwent TTO utility value evaluation. After 4-5 weeks, the patients were asked to undergo second TTO utility value evaluation during the follow-up interview. Results: The mean initial utility values of the 107 persistent DVF patients were 0.904 ± 0.054. Regression analyses revealed that length of education, visual acuity in the poorer-vision eye and employment status were associated with utility values (all P < 0.01). All patients took part in the follow-up interview; the intra-class correlation coefficient for TTO utility values at the initial and follow-up interviews was 0.855. In the 91 general population residents, the mean utility value was 0.923 ± 0.032, which was statistically higher than that of active study patients ( t = 3.01, P < 0.01). Conclusions: Persistent DVF can substantially diminish the patients' perception of their life, and can be measured by TTO utility values with high reliability and construct validity. [ABSTRACT FROM AUTHOR]

The purpose of the cross-sectional study is to describe the values and distribution of choroidal thickness and to explore its related factors, especially age, in Chinese children. A total of 3001 Chinese school children aged 6 to 19 years underwent comprehensive ophthalmic examinations, including axial length and cycloplegic refraction. Choroidal thickness was measured by swept-source optical coherence tomography (SS-OCT). There was a greater difference in the more central regions between the myopes and emmetropes. Multiple regression analysis was performed to determine the associated factors of choroidal thickness. The results demonstrated that age was independently positively related to choroidal thickness for emmetropes (β = 3.859, p < 0.001), and mild myopes with spherical equivalent greater than −2.00 D (−1.25 D < spherical equivalent ≤ −0.50 D: β = 3.476, p = 0.006; −2.00 D < spherical equivalent ≤ −1.25 D: β = 3.232, p = 0.020). However, no significant relationship between age and choroidal thickness was found in children with spherical equivalent ≤ −2.00 D, suggesting that the protective effect of physiologic choroidal growth with age against rapid axial elongation disappeared while axial elongation becomes the dominant determinant of choroidal thickness among children with myopia worse than −2.00 D. [ABSTRACT FROM AUTHOR]