Senolytic and senomorphic agent procyanidin C1 alleviates structural and functional decline in the aged retina.

Increased cellular senescence burden contributes in part to age-related organ dysfunction and pathologies. In our study, using mouse models of natural aging, we observed structural and functional decline in the aged retina, which was accompanied by the accumulation of senescent cells and senescence-associated secretory phenotype factors. We further validated the senolytic and senomorphic properties of procyanidin C1 (PCC1) both in vitro and in vivo, the long-term treatment of which ameliorated age-related retinal impairment. Through high-throughput single-cell RNA sequencing (scRNA-seq), we comprehensively characterized the retinal landscape after PCC1 administration and deciphered the molecular basis underlying the senescence burden increment and elimination. By exploring the scRNA-seq database of age-related retinal disorders, we revealed the role of cellular senescence and the therapeutic potential of PCC1 in these pathologies. Overall, these results indicate the therapeutic effects of PCC1 on the aged retina and its potential use for treating age-related retinal disorders.

Causal relationship between central corneal thickness and open-angle glaucoma: Evidence from Mendelian randomization.

Glaucoma is the leading cause of irreversible blindness worldwide. Previous observational studies have suggested a relationship between central corneal thickness (CCT) and glaucoma; however, the results are inconsistent. This study aimed to investigate whether CCT is associated with a risk for developing open-angle glaucoma (OAG). We employed two-sample Mendelian randomization to assess the relationship between CCT and OAG, namely, primary open-angle glaucoma (POAG) and suspected glaucoma. Genetic instruments composed of variants associated with CCT at genome-wide significance (P < 5 × 10-8) were obtained from published genome-wide association studies from Iglesias et al. for discovery and Bonnemaijer et al. for replication. Summary-level statistics for these instruments for the OAG were obtained from the FinnGen Project (Release 10). Inverse-variance-weighted regression of genetic susceptibility predicted that increased CCT was positively associated with an increased risk for POAG (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.008; P = 0.001) and suspected glaucoma (OR, 1.006; 95% CI, 1.003-1.009; P < 0.001). In the replication sample of CCT, increased CCT was also positively associated with an increased risk for POAG (OR, 1.004; 95% CI, 1.000-1.008; P = 0.029) and suspected glaucoma (OR, 1.005; 95% CI, 1.001-1.008; P = 0.013). We found genetic evidence supporting a potential causal association between increased CCT and the risk of POAG and suspected glaucoma in the European population. This findings indicates the clinical significance of CCT in the diagnosis and treatment of glaucoma. Further studies are needed to elucidate the underlying mechanisms of this causal relationship.

Metabolomics unveil key pathways underlying the synergistic activities of aztreonam and avibactam against multidrug-resistant Escherichia coli.

PURPOSE: Aztreonam/avibactam is effective against serious infections caused by Gram-negative bacteria including Enterobacterales harboring metallo-ß-lactamases. While the utility of this combination has been established in vitro and in clinical trials, the purpose of this study is to enhance our understanding of the underlying mechanism responsible for their activities through metabolomic profiling of a multidrug-resistant Escherichia coli clinical isolate. METHODS: Metabolomic analyses of time-dependent changes in endogenous bacterial metabolites in a clinical isolate of a multidrug-resistant E. coli treated with aztreonam and avibactam were performed. E. coli metabolomes were compared at 15 min, 1 h and 24 h following treatments with either avibactam (4 mg/L), aztreonam (4 mg/L), or aztreonam (4 mg/L) + avibactam (4 mg/L). RESULTS: Drug treatment affected 326 metabolites with magnitude changes of at least 2-fold, most of which are involved primarily in peptidoglycan biosynthesis, nucleotide metabolism, and lipid metabolism. The feedstocks for peptidoglycan synthesis were depleted by aztreonam/avibactam combination; a significant downstream increase in nucleotide metabolites and a release of lipids were observed at the three timepoints. CONCLUSION: The findings indicate that the aztreonam/avibactam combination accelerates structural damage to the bacterial membrane structure and their actions were immediate and sustained compared to aztreonam or avibactam alone. By inhibiting the production of crucial cell wall precursors, the combination may have inflicted damages on bacterial DNA.

Visual impairment burden in retinopathy of prematurity: trends, inequalities, and improvement gaps.

Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment, and the increase in number and survival of premature infants may inflate its burden globally. We aimed to comprehensively assess the trends and inequalities in the burden of ROP-related visual impairment and to identify improvement gaps to facilitate appropriate actions in neonatal care systems. We obtained ROP data from the Global Burden of Disease 2019 study. We employed joinpoint regression analysis to assess the trends of the burden of ROP-related visual impairment, measured by age-standardised prevalence rates, health equity analysis methods to evaluate cross-country burden inequalities, and data envelopment and stochastic frontier analyses to identify improvement gaps based on the development status, i.e., sociodemographic index (SDI). Between 1990 and 2019, the age-standardised prevalence rates of ROP-related visual impairment significantly increased worldwide (average annual percentage change: 0.23 [95% confidence interval, 0.21-0.26] among males and 0.26 [0.25-0.27] among females), primarily in developed regions. Although significant SDI-related cross-country inequalities were identified, these reduced over time (slope index of inequality: -57.74 [-66.22 to -49.25] in 1990 to -29.68 [-38.39 to -20.97] in 2019; health concentration index: -0.11 [-0.13 to -0.09] in 1990 to -0.07 [-0.09 to -0.06] in 2019). Notably, some less-developed countries exhibited superior performance despite limited resources, whereas others with a higher SDI delivered lagging performance.  Conclusion: The global burden of ROP-related visual impairment has steadily increased between 1990 and 2019, with disproportionate burden concentration among less-developed countries, requiring appropriate preventive and intervention measures. What is Known: • Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment. • The prevalence of ROP is anticipated to increase due to the growing number of extremely premature infants. What is New: • The prevalence of ROP-related visual impairment has increased worldwide, primarily in developed regions, with declining but persisting cross-country inequalities. • The increasing burden of ROP-related visual impairment should be considered as part of global and national health agendas, requiring interventions with proven efficacy.

Internal reuse of methanol-to-olefin wastewater based on micro-channel separation coupling hydrocyclone regeneration.

Methanol-to-olefin (MTO) is a typical new coal chemical industry example. Due to the large volume of generated wastewater, complex composition including catalysts, aromatics and various oxygen-containing compounds, and serious environmental hazard, wastewater recycling is critical for sustainable industrial development and ecological protection. Herein, a swirl regenerating micro-channel separation (SRMS) technology was proposed to integrate deep filtration and hydrocyclone-enhanced regeneration. A small-scale experimental investigation was first conducted to verify the feasibility of the MTO wastewater treatment. A pilot SRMS device with a treatment capacity of 20 m3/h was constructed, and the device's continuous operation effect and stability were comprehensively evaluated. The separation performance of the SRMS device at different solution pH values and the impact of the hydrocyclone-enhanced regeneration of separation media were discussed in detail. At low solution pH values (<7), the SRMS device exhibits an average separation efficiency of 92.0% for fine particulate matter in wastewater, and the median particle size, d50, decreases from 1.55 to 0.6 µm. As the solution pH increases, the repulsive energy barrier for the medium-contaminant and contaminant-contaminant increases, inhibiting the deposition behavior of particulate pollutants. In addition, hydrocyclone desorbs contaminants deposited on the separation media and the average contaminant residual rate decreases from 3.3 to 0.2 wt%. We propose an industrial application for treating and reusing MTO wastewater (200 m3/h) using the SRMS technology based on the experimental results. The costs of the wastewater treatment process are as low as 0.25 CNY/m3, and the wastewater reuse rate is over 97% without chemical consumption. This work can provide an environmentally friendly and economically sustainable approach to the source management of MTO wastewater.

Cooperative physical separation of oil and suspended solids from methanol-to-olefin wastewater: A pilot study.

Methanol-to-olefin (MTO) is an important non-petroleum chemical process for the preparation of light olefins. However, the MTO process consumes copious amounts of water and produces large amounts of untreated effluent. Therefore, the realization of efficient wastewater treatment and recycling is key to the green low-carbon development of MTO. Here, a cooperative process combining swirl regenerating micro-channel separation (SRMS) and combined fibrous coalescence (CFC) technologies was proposed to separate high contents of oil and suspended matter in MTO wastewater. Using a pilot device with a treatment capacity of 1 m3/h, the average oil content in MTO wastewater decreased from 750 mg/L to <30 mg/L, while the average content of suspended matter decreased from 108 mg/L to <15 mg/L. Compared with a commercial MTO wastewater treatment process (olefin production capacity of 0.6 million tons per annum), the proposed method could reduce wastewater discharges and costs by 57% and US$ 0.23 million per annum respectively. Equipment costs and operational energy consumption were also reduced by 30% and >95% respectively. The combined process may provide the basis for the green and sustainable treatment of MTO wastewater and its recycling.

Enhancement of PM2.5 Cyclone Separation by Droplet Capture and Particle Sorting.

Fine particulate matter (PM2.5) is one of the most serious environmental pollutants worldwide, and efficient separation technologies are crucial to the control of PM2.5 emission from industrial sources. We developed a novel method to enhance PM2.5 cyclone separation by droplet capture and particle sorting using a vertical reverse rotation cyclone (VRR-C, inlet particle-sorting cyclone). The separation performances of common cyclone (CM-C) without droplets, CM-C with droplets, and VRR-C with droplets were compared in terms of energy consumption, overall separation efficiency, particle grade efficiency, outlet particle concentration, and outlet particle size distribution. The results show that the highest overall separation efficiencies were 51.7%, 89.9%, and 94.5% for CM-C without droplets, CM-C with droplets, and VRR-C with droplets, respectively, when the mean diameter of the inlet particles was 3.2 µm and the inlet particle concentration was 500 mg/m3. The PM2.5 grade efficiency of VRR-C with droplets was as high as 89.8%, which was 6.2% and 49.9% higher than those of CM-C with droplets and CM-C without droplets, respectively. This novel method was first successfully applied to the deep purification of product gas in the methanol-to-olefin (MTO) industry, for which the separation efficiency of fine catalyst particles was considerably improved.

Age-period-cohort analysis of the global burden of visual impairment according to major causes: an analysis of the Global Burden of Disease Study 2019.

BACKGROUND: Cataract, glaucoma and age-related macular degeneration (AMD) are major causes of visual impairment. As these are age-related conditions, the prevalence of associated visual impairment is anticipated to increase as the population ages. However, age-period-cohort effects on the disease burden have not been investigated. METHODS: This was a population-based study using aggregated data from the Global Burden of Disease Study 2019. Age-period-cohort analysis was conducted using age-standardised prevalence rates (ASPRs) of visual impairment caused by cataract, glaucoma and AMD as disease burden indicator. RESULTS: In 2019, the estimated global ASPRs of visual impairment due to cataract, glaucoma and AMD were 1207.9, 94.7 and 96.8 per 100 000 people, respectively. Between 1990 and 2019, the global visual impairment ASPRs for glaucoma and AMD declined by 15.4% and 2.0%, respectively, whereas that for cataract increased by 5.0%. Wide heterogeneity was observed in age-period-cohort effects on ASPRs across different Sociodemographic Index (SDI) regions. Low-middle SDI regions had the largest ASPR reductions for all three eye diseases and showed improvement in both period and cohort effects. In contrast, in high-middle SDI regions, visual impairment ASPRs significantly increased during the study period with unfavourable patterns. CONCLUSIONS: The wide heterogeneity in age-period-cohort effects reflects different stages of societal transition and vision health. The unfavourable trends in age-period-cohort effects on disease prevalence identified in specific groups provide key information that may be used to identify priority groups in need of treatment and prevention.

Diffusion Models for Imperceptible and Transferable Adversarial Attack.

Many existing adversarial attacks generate Lp-norm perturbations on image RGB space. Despite some achievements in transferability and attack success rate, the crafted adversarial examples are easily perceived by human eyes. Towards visual imperceptibility, some recent works explore unrestricted attacks without Lp-norm constraints, yet lacking transferability of attacking black-box models. In this work, we propose a novel imperceptible and transferable attack by leveraging both the generative and discriminative power of diffusion models. Specifically, instead of direct manipulation in pixel space, we craft perturbations in the latent space of diffusion models. Combined with well-designed content-preserving structures, we can generate human-insensitive perturbations embedded with semantic clues. For better transferability, we further "deceive" the diffusion model which can be viewed as an implicit recognition surrogate, by distracting its attention away from the target regions. To our knowledge, our proposed method, DiffAttack, is the first that introduces diffusion models into the adversarial attack field. Extensive experiments conducted across diverse model architectures (CNNs, Transformers, and MLPs), datasets (ImageNet, CUB-200, and Standford Cars), and defense mechanisms underscore the superiority of our attack over existing methods such as iterative attacks, GAN-based attacks, and ensemble attacks. Furthermore, we provide a comprehensive discussion on future research avenues in diffusion-based adversarial attacks, aiming to chart a course for this burgeoning field.

Carrageenan-ferrocene-eicosapentaenoic acid composite hydrogel induce ferroptosis and apoptosis for anti-tumor recurrence and metastasis.

The immune-suppressive microenvironment of solid tumors is a key factor limiting the effectiveness of immunotherapy, which seriously threatens human life and health. Ferroptosis and apoptosis are key cell-death pathways implicated in cancers, which can synergistically activate tumor immune responses. Here, we developed a multifunctional composite hydrogel (CE-Fc-Gel) based on the self-assembly of poloxamer 407, cystamine-linked ιota-carrageenan (CA)-eicosapentaenoic acid (EPA), and ferrocene (Fc). CE-Fc-Gel improved targeting in tumor microenvironment due to its disulfide bonds. Moreover, CE-Fc-Gel promoted lipid peroxidation, enhanced reactive oxygen species (ROS) production, and decreased glutathione peroxidase 4 (GPX4), inducing ferroptosis by the synergistic effect of Fc and EPA. CE-Fc-Gel induced apoptosis and immunogenic cell death (ICD), thereby promoting dendritic cells (DCs) maturation and T cell infiltration. As a result, CE-Fc-Gel significantly inhibited primary and metastatic tumors in vivo. Our findings provide a novel strategy for enhancing tumor immunotherapy by combining apoptosis, ferroptosis, and ICD.

[Effect of Land Use on the Stability of Soil Organic Carbon in a Karst Region].

The composition of soil organic carbon and its stability mechanism are the key to understanding the terrestrial carbon sink capacity. The stability of soil organic carbon in a karst ecosystem greatly affects the soil carbon fixation capacity. In order to understand the impact of human activities on the stability of soil organic carbon in karst areas, the karst valley area of Zhongliang Mountain in Chongqing was selected as an example, and soil samples of four typical land use modes (mixed forest, bamboo forest, grassland, and cultivated land) were collected in layers to analyze the total organic carbon (TOC) and heavy fraction organic carbon (HFOC). The distribution characteristics of light fraction organic carbon (LFOC), labile organic carbon (LOC), and recalcitrant organic carbon (ROC) were analyzed quantitatively by using a structural equation model to provide basic data for soil carbon sink assessment and soil quality protection in karst areas. The results showed that the organic carbon components under different land use patterns in karst areas had obvious surface accumulation, and the content of organic carbon components in the surface layer was 1.2 times that in the bottom layer. Except for LFOC, the content of other organic carbon components was the highest in the mixed forest, followed by that in the bamboo forest and wasteland, with the lowest in cultivated land. Mixed forest ω(TOC) content was the highest, 42.5 g·kg-1, followed by that of bamboo forest (36.6 g·kg-1) and grassland (18.7 g·kg-1), and cultivated land content was the lowest, 13.4 g·kg-1. The soil organic carbon content of cultivated land was 68.5%, 63.5%, and 28.3% lower than that of mixed forest, bamboo forest, and grassland, respectively. Mixed forest had the highest content of ω(HFOC), 21 g·kg-1, followed by those of bamboo forest (20.9 g·kg-1), grassland (18.2 g·kg-1), and cultivated land (13.5 g·kg-1). The mixed forest ω(LOC) content was the highest, 16.3 g·kg-1, followed by those of bamboo forest (14.9 g·kg-1), grassland (11.5 g·kg-1), and cultivated land (5.3 g·kg-1). Mixed forest ω (ROC) content was the highest, 25.7 g·kg-1, followed by those of bamboo forest (21.6 g·kg-1), grassland (15.9 g·kg-1), and cultivated land (10.3 g·kg-1). The bamboo forest land ω(LFOC) content was 15.9 g·kg-1, followed by those of mixed forest (13.9 g·kg-1), grassland (7.3 g·kg-1), and cultivated land (4.9 g·kg-1). The recalcitrant organic carbon index (ROCI) was used to indicate the stability of soil organic carbon. The variation range of ROCI was 33.9%-64.5%, of which the highest was mixed forest (64.5%-66.3%), and the lowest was cultivated land (33.8%-39.6%). The ROCI of mixed forest, bamboo forest, and grassland were 1.8 times, 1.6 times, and 1.4 times that of cultivated land, respectively. Karst area ω (inert organic carbon) content and ROCI showed that human agricultural activities caused the reduction in soil organic carbon content and the destruction of soil physical structure, resulting in the accelerated decomposition and turnover rate of soil organic matter. The most important factor affecting soil stability in karst areas was soil pH. Tillage activities caused soil pH to rise, reduced soil microbial activity, and were not conducive to the accumulation of the inert organic carbon and soil organic carbon pool in the soil.

[Effects of Land Use Change on Soil Aggregate Stability and Soil Aggregate Organic Carbon in Karst Area of Southwest China].

Investigating the relationship of soil aggregate stability with the organic carbon in the aggregate and its response to land use change is conducive to the estimation of soil carbon sink potential, improvement of rocky desertification, and rational land use in karst areas of Southwest China. In order to explore the effects of land use change on the composition and stability of soil aggregate stability as well as the content of aggregate organic carbon, the soil (0-30 cm) of five land use types (secondary forest, pomelo forest, paddy field, pepper forest, and dry land) was selected as the research object. The characteristics and correlation of soil aggregate components and organic carbon under different land use patterns were obtained, and the contribution of soil aggregates to the change in organic carbon after land use change was calculated. The results showed that the macroaggregates in the surface soil (0-15 cm) of the secondary forest, pomelo forest, and paddy field were 63.32%, 52.38%, and 47.77%, respectively, which were significantly higher than that of dry land (23.70%), as was also seen in the lower layer (15-30 cm). The geometric mean diameter (GMD) and mean weight diameter (MWD) of soil aggregates in the secondary forest, pomelo forest, and paddy field were significantly higher than those in dry land. In the surface soil, the organic carbon of the secondary forest and paddy field was significantly higher than that of other land use patterns. By contrast, in the lower soil layer, only the organic carbon of the paddy field was significantly higher than that of the others. Under different land use patterns, the organic carbon content of aggregates followed the same order of macroaggregates > microaggregates > silt and clay, indicating that macroaggregates allowed soil organic carbon to accumulate, whereas silt and clay did the opposite. According to correlation analysis, the content of soil macroaggregates was significantly positively correlated with GMD, MWD, and soil aggregate organic carbon, suggesting that the increase in soil macroaggregates could improve the stability of soil aggregates and store more soil organic carbon. Further, as land use change may have significantly affected the soil aggregate, moderate development of forestry and paddy cultivation is suggested to improve the soil carbon sequestration potential in the karst area of Southwest China.

Temporal trends and projection of blindness and vision loss prevalence in older adults in BRICS countries.

BACKGROUND: Blindness and vision loss (BVL) is a major global health issue affecting older adults, but its burden in transition countries has received limited attention. Therefore, we aimed to assess the trends in the burden of BVL among older adults between 1990 and 2019 across Brazil, Russia, India, China, and South Africa (BRICS), and predict the burden by 2040. METHODS: Data on BVL and its related causes were obtained from the Global Burden of Disease 2019 study. We investigated the temporal trends by calculating the average annual percentage change using joinpoint regression analysis. Subsequently, we performed Bayesian age-period-cohort modeling to estimate the burden of BVL and its related causes by 2040. RESULTS: Most BRICS countries experienced a significant decline (p < 0.05) in age-standardized prevalence rates, and the decreasing trends tend to continue. However, by 2040, the number of BVL cases is expected to increase by approximately 50% across BRICS, with an estimated approximately 192, 170, 25, 17, and 7 million cases in China, India, Russia, Brazil, and South Africa, respectively. The related ranks of BVL causes are also estimated to change in the future, particularly in India. CONCLUSIONS: The different burdens and trends of BVL across BRICS reflected the different stages of population health transition. Effective eye disease prevention requires appropriate public health interventions. Developing effective health policies and services for older adults is urgently needed in BRICS countries.

Quantitative assessment of colour fundus photography in hyperopia children based on artificial intelligence.

OBJECTIVES: This study aimed to quantitatively evaluate optic nerve head and retinal vascular parameters in children with hyperopia in relation to age and spherical equivalent refraction (SER) using artificial intelligence (AI)-based analysis of colour fundus photographs (CFP). METHODS AND ANALYSIS: This cross-sectional study included 324 children with hyperopia aged 3-12 years. Participants were divided into low hyperopia (SER+0.5 D to+2.0 D) and moderate-to-high hyperopia (SER≥+2.0 D) groups. Fundus parameters, such as optic disc area and mean vessel diameter, were automatically and quantitatively detected using AI. Significant variables (p<0.05) in the univariate analysis were included in a stepwise multiple linear regression. RESULTS: Overall, 324 children were included, 172 with low and 152 with moderate-to-high hyperopia. The median optic disc area and vessel diameter were 1.42 mm2 and 65.09 µm, respectively. Children with high hyperopia had larger superior neuroretinal rim (NRR) width and larger vessel diameter than those with low and moderate hyperopia. In the univariate analysis, axial length was significantly associated with smaller superior NRR width (ß=-3.030, p<0.001), smaller temporal NRR width (ß=-1.469, p=0.020) and smaller vessel diameter (ß=-0.076, p<0.001). A mild inverse correlation was observed between the optic disc area and vertical disc diameter with age. CONCLUSION: AI-based CFP analysis showed that children with high hyperopia had larger mean vessel diameter but smaller vertical cup-to-disc ratio than those with low hyperopia. This suggests that AI can provide quantitative data on fundus parameters in children with hyperopia.

Relationships between Frailty and the Risk of Glaucoma in Middle-aged and Older Adults.

PURPOSE: Increased frailty in older individuals increases health risks, but its relationship with glaucoma, the leading cause of irreversible blindness in middle-aged and older adults, is unclear. We investigated the association between frailty and glaucoma in a large-scale representative sample and explored possible causal relationships. DESIGN: Combined cross-sectional and Mendelian randomization (MR) study. PARTICIPANTS: In the cross-sectional analysis, we included 5744 participants of the US National Health and Nutrition Examination Surveys 2005-2008 aged ≥40. For the MR analysis, frailty genome-wide association study (GWAS) data were sourced from a UK Biobank and TwinGen meta-analysis, and GWAS data on glaucoma subtypes were derived from FinnGen. METHODS: According to the 49-item frailty index, we classified participants into nonfrail (≤0.10), prefrail (0.10-0.21), and frail (>0.21) groups. Using survey-weighted logistic regression models adjusted for multiple covariates, we explored the association between frailty and glaucoma. We further assessed causation using MR. MAIN OUTCOME MEASURES: The associations between different levels of frailty (nonfrail, prefrail, and frail) and glaucoma, as well as causal relationships between genetically predicted frailty and various subtypes of glaucoma (primary open-angle glaucoma, primary angle-closure glaucoma, normotensive glaucoma, exfoliation glaucoma, and suspected glaucoma). RESULTS: After adjusting for covariates, higher frailty levels were significantly associated with glaucoma in frail individuals (odds ratio [OR]=1.83, 95% confidence interval [CI]=1.05-3.19, P=0.036) but not prefrail (OR=1.90, 95% CI=0.99-3.64, P=0.052). The association was significantly stronger among male participants (P interaction=0.042). The variation in the association between frailty and glaucoma did not reach statistical significance across age groups (P interaction=0.575) or race groups (P interaction=0.092). MR revealed that genetically predicted frailty was linked to greater risks for primary open-angle glaucoma (OR=1.67, 95% CI=1.24-2.25, P=0.001), primary angle-closure glaucoma (OR=2.78, 95% CI=1.48-5.20, P=0.001), exfoliation glaucoma (OR=1.70, 95% CI=1.18-2.43, P=0.004), and suspected glaucoma (OR=1.74, 95% CI=1.30-2.34, P<0.001), but not for normotensive glaucoma (OR=1.01, 95% CI=0.61-1.68, P=0.956). CONCLUSIONS: Our study revealed an association between frailty and increased glaucoma risk and emphasized the significance of glaucoma screening in frail individuals. Targeted healthcare strategies can help prevent or delay irreversible blindness among middle-aged and older adults.

Quantitative Assessment of Fundus Tessellated Density in Highly Myopic Glaucoma Using Deep Learning.

Purpose: To characterize the fundus tessellated density (FTD) in highly myopic glaucoma (HMG) and high myopia (HM) for discovering early signs and diagnostic markers. Methods: This retrospective cross-sectional study included hospital in-patients with HM (133 eyes) and HMG (73 eyes) with an axial length ≥26 mm at Zhongshan Ophthalmic Center. Using deep learning, FTD was quantified as the average exposed choroid area per unit area on fundus photographs in the global, macular, and disc regions. FTD-associated factors were assessed using partial correlation. Diagnostic efficacy was analyzed using the area under the curve (AUC). Results: HMG patients had lower global (0.20 ± 0.12 versus 0.36 ± 0.09) and macular FTD (0.25 ± 0.14 vs. 0.40 ± 0.09) but larger disc FTD (0.24 ± 0.11 vs. 0.19 ± 0.07) than HM patients in the tessellated fundus (all P < 0.001). In the macular region, nasal FTD was lowest in the HM (0.26 ± 0.13) but highest in the HMG (0.32 ± 0.13) compared with the superior, inferior, and temporal subregions (all P < 0.05). A fundus with a macular region nasal/temporal (NT) FTD ratio > 0.96 (AUC = 0.909) was 15.7 times more indicative of HMG than HM. A higher macular region NT ratio with a lower horizontal parapapillary atrophy/disc ratio indicated a higher possibility of HMG than HM (AUC = 0.932). Conclusions: FTD differs in degree and distribution between HMG and HM. A higher macular NT alone or with a lower horizontal parapapillary atrophy/disc ratio may help differentiate HMG. Translational Relevance: Deep learning-based FTD measurement could potentially assist glaucoma diagnosis in HM.

Global, Regional, and National Epidemiology of Visual Impairment in Working-Age Individuals, 1990-2019.

Importance: Visual impairment in working-age individuals can affect their general health and employment prospects, leading to decreased social and economic productivity and increased poverty rates. Nonetheless, investigations in this population appear to be limited. Objective: To investigate the trends of visual impairment prevalence and disability-adjusted life-years (DALYs) in working-age individuals from 1990 to 2019. Design, Setting, and Participants: This cross-sectional, population-based study used data for individuals of working age (15-64 years) from 204 countries and territories obtained from the Global Burden of Disease 2019 study. The data analysis was performed between May 1 and 10, 2023. Exposure: Visual impairment, defined as visual acuity of less than 6/18 (20/60) or near visual acuity of less than 6/12 (20/40) distance equivalent as determined by Snellen chart. Main Outcomes and Measures: Trends of visual impairment prevalence, DALYs, and corresponding estimated annual percent changes (EAPCs) from 1990 to 2019 were stratified according to region, nation, and sociodemographic index (SDI). Results: There were 437 539 484 (95% uncertainty interval [UI], 325 463 851-575 573 588) prevalent cases of visual impairment globally (53.12% female and 46.88% male) in 2019, representing an increase of 91.46% from 1990 (prevalent cases, 228 530 964; 95% UI, 172 515 833-297 118 596). Over 3 decades, visual impairment-associated DALYs increased from 7 601 852 (95% UI, 5 047 030-11 107 897) to 12 563 276 (95% UI, 8 278 866-18 961 723). Among the 5 SDI groups, the low-SDI group had the largest increase in DALYs (898 167 [95% UI, 597 161-1 301 931] in 1990 to 1 634 122 [95% UI, 1 079 102-2 444 381] in 2019). Regionally, the greatest increase in prevalence was observed in Eastern Europe (EAPC, 0.10; 95% CI, 0.02-0.19). Among all countries and territories, Nepal had the highest national prevalence of visual impairment per 100 000 population in 2019 (26 008.45; 95% UI, 19 987.35-32 482.09), while South Sudan had the highest DALY rate per 100 000 population (480.59; 95% UI, 316.06-697.06). Conclusions and Relevance: Despite the mild decrease in visual impairment prevalence rates in less-developed countries, these findings suggest that the number of prevalent cases globally has increased substantially, with discernible unfavorable patterns in developed regions. The findings support the notion that visual impairment in working-age individuals is a growing global health challenge. A better understanding of its epidemiology may facilitate the development of appropriate measures for prevention and treatment from both medical and social perspectives.

Global, regional, and national burden of retinoblastoma in infants and young children: findings from the global burden of disease study 1990-2021.

Background: Retinoblastoma is considered a lethal but curable malignancy often presenting in childhood. We investigated its global, regional, and national burden among infants and young children from 1990 to 2021. Methods: We obtained data on retinoblastoma incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021. Trends were analysed using joinpoint regression to calculate annual percentage changes. Spearman's rank correlation and locally estimated scatterplot smoothing regression were used to assess the relationship between retinoblastoma burden and sociodemographic index. Findings: In 2021, the global incidence, prevalence, mortality, and DALYs of retinoblastoma were 0.82 (95% uncertainty interval [UI], 0.48-1.10), 7.46 (95% UI, 4.42-10.08), 0.37 (95% UI, 0.22-0.51), and 32.81 (95% UI, 19.9-45.21), respectively. From 1990 to 2021, the global incidence and prevalence rates of retinoblastoma increased, with average annual percentage changes (AAPCs) of 0.67 (95% confidence interval [CI], 0.49-0.85] and 0.68 (95% CI, 0.50-0.86), respectively. Conversely, those of related mortality and DALYs decreased, with AAPCs of -0.64 (95% CI, -0.79 to -0.49) and -0.63 (95% CI, -0.78 to -0.48), respectively. Children aged 2-4 years and those in low-income regions exhibited the highest burden. Negative correlations were found between sociodemographic index and retinoblastoma burden. Interpretation: Advancements in retinoblastoma detection and treatment have increased its reported incidence and prevalence while reducing its mortality and DALYs. Nonetheless, substantial socioeconomic and geographic disparities persist. In low-income countries, the incidence has decreased, possibly reflecting challenges such as limited healthcare access and underreporting, necessitating targeted interventions and improved healthcare access. Funding: National Key R&D Project of China (2020YFA0112701), Natural Science Foundation of Guangdong Province (2024A1515013058), and Science and Technology Program of Guangzhou, China (202206080005).

Peripapillary Retinal Nerve Fiber Layer and Macular Ganglion Cell-Inner Plexiform Layer Parameters and Their Associated Factors in Cynomolgus Macaques.

Purpose: The purpose of this study was to define the normal range of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer (mGCL), and macular inner plexiform layer (mIPL) thickness in cynomolgus macaques, and explore their inter-relationship and correlation with age, refractive errors, and axial length (AL). Methods: In this cross-sectional study, we measured biometric and refractive parameters, and pRNFL/mGCL/mIPL thickness in 357 healthy cynomolgus macaques. Monkeys were divided into groups by age and spherical equivalent (SE). Correlation and regression analyses were used to explore the relationship between pRNFL and mGCL/mIPL thickness, and their correlation with the above parameters. Results: The mean age, SE, and AL were 14.46 ± 6.70 years, -0.96 ± 3.23 diopters (D), and 18.39 ± 1.02 mm, respectively. The mean global pRNFL thickness was 95.06 ± 9.42 µm (range = 54-116 µm), with highest values in the inferior quadrant, followed by the superior, temporal, and nasal quadrants (P < 0.001). Temporal pRNFL thickness correlated positively with age (r = 0.218, P < 0.001) and AL (r = 0.364, P < 0.001), and negatively with SE (r = -0.270, P < 0.001). In other quadrants, pRNFL thickness correlated negatively with age and AL, but positively with SE. In the multivariable linear regression model, adjusted for sex and AL, age (ß = -0.350, P < 0.001), and SE (ß = 0.206, P < 0.001) showed significant associations with global pRNFL thickness. After adjusting for age, sex, SE, and AL, pRNFL thickness positively correlated with mGCL (ß = 0.433, P < 0.001) and mIPL thickness (ß = 0.465, P < 0.001). Conclusions: The pRNFL/mGCL/mIPL thickness distribution and relationship with age, AL, and SE in cynomolgus macaques were highly comparable to those in humans, suggesting that cynomolgus monkeys are valuable animal models in ophthalmic research.

Temporal trends in the visual impairment burden attributable to high fasting plasma glucose levels: a population-based study.

AIMS: Elevated fasting plasma glucose (FPG) levels have been associated with visual impairment. Recognising global patterns of high FPG level exposure can facilitate the prevention and treatment of related visual impairment. We aimed to assess the trends of the visual impairment burden attributable to high FPG levels globally, regionally, nationally, and by income level. METHODS: We obtained data on the visual impairment burden attributable to high FPG levels from the Global Burden of Disease Study 2019. We evaluated the trends of related disability-adjusted life-years (DALYs) from 1990 to 2019 through joinpoint regression analysis and calculated the annual percentage change (APC) and average APC (AAPC). Countries/territories were categorised into high-, upper-middle-, lower-middle-, and low-income groups based on the 2019 World Bank criteria. RESULTS: The age-standardised rate of DALYs due to visual impairment attributable to high FPG levels significantly increased globally, from 6.75 (95% uncertainty interval [UI], 1.55-15.79) in 1990 to 8.44 per 100,000 population (95% UI, 2.00-19.63) in 2019 (AAPC, 0.79; 95% confidence interval [CI], 0.69-0.89; p < 0.001). The largest increases were observed in high-income (AAPC, 0.73; 95% CI, 0.60-0.85) and lower-middle-income countries/territories (AAPC, 0.68; 95% CI, 0.62-0.73). In 2019, lower-middle-income countries/territories had the highest age-standardised DALY rate (18.94 per 100,000 population; 95% UI, 4.39-43.98), whereas high-income countries/territories had the lowest (2.97 per 100,000 population; 95% UI, 0.75-6.74). CONCLUSIONS: The visual impairment burden associated with elevated FPG levels has increased significantly, necessitating enhanced public health prevention measures, clinical management, and treatment to mitigate adverse outcomes.