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Purpose: To explore prevalence and associated factors of abnormalities of the posterior eye shape in dependence of axial length. Design: Population-based study. Participants: Of the participants (n = 3468) of the Beijing Eye Study, we included all eyes with an axial length of ≥25 mm, and a randomized sample of eyes with an axial length of

Abstract X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.

Background: To explore the prevalence of self-reported unintentional injuries and falls (UIFs) in medium-aged and old populations in Russia and factors associated with them. Methods: Two population-based studies (Ural Eye and Medical Study (UEMS), Ural Very Old Study (UVOS)) were carried out urban and rural areas in Bashkortostan/Russia. They consisted of 5899 individuals (age: 40+ years) and 1526 participants (age: 85+ years), respectively. We assessed previous falls as part of an interview with standardized questions, conducted in the framework of a series medical and ophthalmological assessments. Results: In the UEMS with 5894 individuals (age:59.0 ± 10.7 years), UIF prevalence was 1101/5894 (18.7 %; 95 % confidence interval (CI)CI:17.7,19.7), with 1,2,3,4,5,6,7,8,9, or 10+ UIFs reported by 766 (69.6 %),146 (13.3 %),56 (1.4 %),15 (1.4 %),19 (1.7 %),3 (0.3 %),2 (0.2 %),1 (0.01 %), and 10 (0.9 %) participants, respectively. The UIFs had occurred as outdoor incidents (n = 594; 53.8 %), at home (n = 162; 14.7 %), on the road or traffic accidents (n = 109; 9.9 %), at work (n = 77; 7.0 %), during garden work (n = 24; 2.2 %) or as falls from a higher level (n = 17; 1.5 %) or from house roofs (n = 16; 1.4 %). In 100 (1.7 % of the total study population; 9.1 % of the group with UIFs) participants, low vision was reported as a major cause for the UIF. Higher UIF prevalence was associated (multivariable analysis) with older age (odds ratio (OR):1.01; 95%CI:1.005,1.02;P

Abstract To assess prevalence and associated factors of depression, anxiety and suicidal ideas in populations from Russia, we conducted in rural and urban regions in Bashkortostan/Russia two population-based studies (Ural Eye and Medical Study (UEMS), performed from 2015 to 2017; Ural Very Old Study (UVOS), performed from 2017 to 2020) which included participants aged 40 + years and 85 + years, respectively. Depression was assessed using the questionnaire of the Center for Epidemiologic Studies Depression Scale Scoresheet, and anxiety was examined applying the State Trait Inventory Anxiety Test. Suicidal ideas were explored by the question whether suicide had previously been thought of or attempted (and if yes, for what reasons). In the statistical analysis we assessed the mean of the main outcome parameter (depression score and anxiety score) and searched for associations between these parameters and other parameters in univariable and multivariable regression analyses. In the UEMS with 5893 individuals (age: 59.0 ± 10.7 years; range 40–94 years), higher depression score and anxiety score were associated (multivariable analysis) with more marked hearing loss (beta: 0.07; P

Abstract To examine the size of the ciliary body stroma (CBS) in dependence of the morphology of the anterior chamber angle in enucleated human eyes, we histomorphometrically examined human enucleated eyes. The study included 107 eyes (with a mean axial length of 25.1 ± 2.8 mm (range 21.0–36.0 mm). The anterior chamber angle was open in 68 eyes and it was closed and endothelialized in 39 eyes. The maximal CBS width (541 ± 210 µm versus 59 ± 179 µm; P

Abstract Background Screening for hyperthyroidism using gold-standard diagnostic criteria in the general population is not cost-effective, leading to a relatively high rate of undiagnosed and untreated patients. This study aimed to establish a deep learning-based system to detect hyperthyroidism based on retinal photographs. Methods The multicenter, observational study included retinal photographs taken from participants in two hospitals and 24 health care centers throughout China. We first trained two models to identify hyperthyroidism: in model #1, the non-hyperthyroidism individuals were randomly selected, while in model #2, the non-hyperthyroidism group was matched for age and gender with the hyperthyroidism group. After internal validation, we selected the better model for further evaluation using external validation datasets. Results The study included 22,940 retinal photographs of 11,409 participants for the model development, and 3862 retinal photographs (1870 participants) which were obtained from two hospitals and four medical centers as the external validation datasets. Model #1 achieved a higher area under the receiver operator curve (AUC) than model #2 (0.907, 95% CI: 0.894–0.918 versus 0.850, 95% CI: 0.832–0.866) in the internal validation so that model #1 was used for further evaluation. In external datasets, model #1 reached AUCs ranging from 0.816 (95% CI 0.789–0.846) to 0.849 (95% CI 0.824–0.874) and achieved accuracies between 0.735 (95% CI 0.700–0.773) and 0.796 (95% CI 0.765–0.824). Heatmaps showed a focus of the DL-algorism on large fundus vessels and the optic nerve head. Conclusions Retinal fundus photographs may serve for DL systems for a cost-effective and non-invasive method to detect hyperthyroidism.

Purpose: To explore intraocular pressure (IOP) and its associated parameters in an aged population. Methods: The epidemiologic Ural Very Old Study (UVOS) conducted in Bashkortostan/Russia included 1526 participants with an age of ≥85 years. Besides a whole series of ocular and systemic examinations, IOP was determined applying non-contact tonometry. Body mass index, diastolic blood pressure and age were the factors used to estimate the cerebrospinal fluid pressure (CSFP). Results: The study consisted of 904 participants (age: 88.6 ± 2.7 years) with available IOP readings and without anti-glaucomatous therapy. Mean IOP was 14.5 ± 5.1 mmHg (median: 14 mm Hg; Q1:11; Q3:16; 95%CI:8,25) and 14.8 ± 4.6 mmHg (median: 14 mm Hg; Q1:12; Q3:17; 95%CI:8,28) in the right and left eyes, respectively. Higher IOP correlated (multivariable analysis; correlation coefficient r2:0.32) with female sex (P

Abstract Mutations in the extracellular matrix gene Fibrillin-2 (FBN2) are related to genetic macular degenerative disorders including age-related macular degeneration (AMD) and early-onset macular degeneration (EOMD). It was reported that the retinal protein expression of FBN2 was reduced in patients with AMD and EOMD. The effect of exogenously supplied fbn2 recombinant protein on fbn2-deficiency-related retinopathy was not known. Here we investigated the efficacy and molecular mechanism of intravitreally applied fibrin-2 recombinant protein in mice with fbn2-deficient retinopathy. The experimental study included groups (all n = 9) of adult C57BL/6J male mice which underwent no intervention, intravitreal injection of adeno-associated virus (AAV) empty vector or intravitreal injection of AAV-sh-fbn2 (adeno-associated virus for expressing short hairpin RNA for fibrillin-2) followed by three intravitreal injections of fbn2 recombinant protein, given in intervals of 8 days in doses of 0.30 μg, 0.75 μg, 1.50 μg, and 3.00 μg, respectively. Eyes with intravitreally applied AAV-sh-fbn2 as compared to eyes with injection of AAV-empty vector or developed an exudative retinopathy with involvement of the deep retinal layers, reduction in axial length and reduction in ERG amplitudes. After additional and repeated application of fbn2 recombinant protein, the retinopathy improved with an increase in retinal thickness and ERG amplitude, the mRNA and protein expression of transforming growth factor-beta (TGF-β1) and TGF-β binding protein (LTBP-1) increased, and axial length elongated, with the difference most marked for the dose of 0.75 μg of fbn2 recombinant protein. The observations suggest that intravitreally applied fbn2 recombinant protein reversed the retinopathy caused by an fbn2 knockdown.

Abstract The study aims to assess the thickness of the retinal outer nuclear layer (ONL), ellipsoid zone (EZ) and photoreceptor outer segment (POS) band in various macular regions and its associations with axial length and other parameters. Participants of the Beijing Eye Study 2011 underwent a series of examinations including spectral-domain optical coherence tomography of the macula. The current study included 2213 participants without retinal or optic nerve diseases (age: 61.7 ± 8.4 years; range 50–93 years); axial length: 23.15 ± 0.95 mm; range 18.96–29.15 mm). The ONL (fovea: 98.9 ± 8.8 µm), EZ (fovea: 24.1 ± 0.5 µm) and POS band (fovea: 24.3 ± 3.5 µm) were the thickest (P

AIM: To investigate the risk and protective factors associated with the retinal nerve fiber layer defect (RNFLD) in a Chinese adult population. METHODS: This study was a cross-sectional population-based investigation including employees and retirees of a coal mining company in Kailuan City, Hebei Province. All the study participants underwent a comprehensive systemic and ophthalmic examination. RNFLD was diagnosed on fundus photographs. Binary logistic regression was used to investigate the risk and protective factors associated with the RNFLD. RESULTS: The community-based study included 14 440 participants. There were 10 473 participants in our study, including 7120 males (68.0%) and 3353 females (32.0%). The age range was 45-108y, averaging 59.56±8.66y. Totally 568 participants had RNFLD and the prevalence rate was 5.42%. A higher prevalence of RNFLD was associated with older age [P

Purpose: To examine intraretinally migrated retinal pigment epithelium cells (iRPECs) in enucleated human eyes with various retinal conditions and corresponding intraretinal hyperreflective bodies (iHRBs) in a large cohort of patients with age-related macular degeneration (AMD) in China. Design: Population-based study and histomorphometric investigation. Participants: Participants of the population-based Beijing Eye Study and enucleated human eyes. Methods: OCT-based and fundus photography-based examination of the macula of the Beijing Eye Study participants and light-microscopical histomorphometry of enucleated human eyes. Main Outcome Measures: Presence and location of iRPECs and iHRBs. Results: In the Beijing Eye Study (6551 eyes; 3301 participants), the prevalence of intermediate AMD and late AMD was 331 (5.1%) and 44 (0.6%), respectively. All 42 eyes with intermediate AMD and macular hyperpigmentation had iHRBs at locations corresponding spatially with macular hyperpigmentation on the fundus photographs. Among all eyes with intermediate AMD (n = 331), iHRBs were detected in 262 (79.2%) eyes. The most internal location of the iHRBs was at the ellipsoid zone in 46 (13.9%) eyes, at the external limiting membrane (ELM) in 45 (13.6%) eyes, and in the outer nuclear layer in 145 (43.8%) eyes. Out of the 262 eyes with iHRBs, 186 (71.0%) eyes showed a corresponding defect in the ellipsoid zone, and 128 (48.9%) eyes showed a defect in the ELM. The eyes with an iHRB located beneath the ELM did not show an ELM defect. The iHRBs were associated with a plume-like appearance and with a smoke-like appearance in 20 (7.6%) eyes and 137 (52.3%) eyes, respectively. All iHRBs did not have a shadow on the OCT images. Similar findings were obtained in the eyes with late AMD. Among 237 eyes examined histologically, 21 globes showed iRPECs: 8 eyes in parapapillary α zone/β zone; 5 eyes with myopic patchy atrophies, and 3 eyes with AMD. The iRPECs were spatially associated with an ELM defect and were not surrounded by a basal membrane. Conclusions: Intraretinal hyperreflective bodies can be found in 3 out of 4 eyes with intermediate AMD, correlate histologically with intraretinally located (migrated) retinal pigment epithelium cells, and correspond spatially with localized defects of the ellipsoid zone and ELM. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose: To investigate the normative data of anterior chamber depth (ACD) and angle (ACA) and their associations in multiethnic cohorts spanning three generations in Russia. Methods: The study cohort included the participants of three population-based studies performed in urban and rural Bashkortostan/Russia: The Ural Eye and Medical Study (UEMS; age:40+ years), Ural Children Eye Study (UCES; age:6–18 years), and Ural Very Old Study (UVOS; age:85+ years). Using Scheimflug camera-based anterior chamber imaging, we measured ACD and ACA as part of a comprehensive ophthalmological and systemic examination. Exclusion criterion was previous cataract surgery. Results: The study included 4869 (98.7 %) children out of 4933 children of the UCES, 5426 (92.0 %) out of 5899 UEMS participants, and 268 (16.3 %) out of 1526 UVOS participants. In the UEMS, shallower ACD (mean:3.14 ± 0.37 mm) correlated (multivariable analysis; r[2] = 0.57) with older age (beta: 0.08;P

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes.Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: “Some College” (yes/no, for any education beyond high school) and “Graduated College” (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10−8) and suggestive (p < 1 × 10−6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals).Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue.Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

BackgroundSince the mechanisms underlying myopic axial elongation have remained unclear, we examined the effect of neuregulin-1 (NRG-1), an epidermal growth factor family member, on myopic axial elongation.MethodsThe guinea pigs aged two to three weeks were subjected to bilateral negative lens-induced axial elongation and received weekly intravitreal injections into their right eyes of NRG-1 antibody (doses: 5 μg, n = 8; 10 μg, n = 8, 20 μg, n = 9) or of NRG-1 (doses: 0.05 μg, n = 8; 0.01 μg, n = 9; 0.2 μg, n = 8), underwent only bilateral negative lens-induced axial elongation (myopia control group, n = 10), or underwent no intervention (control group, n = 10). The contralateral eyes received corresponding intravitreal phosphate-buffered solution injections. One week after the last injection, the guinea pigs were sacrificed, the eyeballs were removed, the thicknesses of the retina and sclera were histologically examined, the expression of NRG-1 and downstream signal transduction pathway members (ERK1/2 and PI3K/AKT) and the mRNA expression of NRG-1 in the retina was assessed.ResultsThe inter-eye difference in axial length at study end increased (p

BackgroundThis study aims to investigate the association between an elevated bilateral pulse wave velocity difference (BPWVD) and cardiovascular diseases (CVDs) and all-cause mortality.MethodsThis study included a total of 38,356 participants. A multivariable Cox proportional hazards regression was used to assess the association between high BPWVD and the increased risk of CVDs and all-cause mortality by calculating hazard ratios (HRs) with 95% confidence intervals.ResultsA total of 1,213 cases of CVDs were identified over a mean duration of 6.19 years, including 886 cases of cerebral infarction (CI), 105 cases of intracerebral hemorrhage (ICH), and 222 cases of myocardial infarction (MI), along with 1,182 cases of all-cause mortality. The median BPWVD was 42 cm/s (19–80 cm/s). After adjusting for all confounders and baseline brachial-ankle PWV (baPWV), our analysis revealed a significant correlation between a higher risk of CVDs, MI, and all-cause mortality with an increase in BPWVD per standard deviation. HRs (95% confidence interval) were found to be 1.06 (1.01–1.11), 1.11 (1.02–1.21), and 1.07 (1.04–1.10), respectively. Among the participants with higher baPWV on the left side, the HRs (95% confidence interval) were 1.08 (1.02–1.14) for CVDs, 1.27 (1.10–1.46) for incident ICH, 1.16 (1.00–1.24) for incident MI, and 1.10 (1.07–1.15) for all-cause mortality, for per standard deviation increase in BPWVD.ConclusionsOur findings reveal a significant correlation between elevated BPWVD and the risks of developing CVDs and all-cause mortality. This highlights the importance of thoroughly evaluating BPWVD as a means of detecting individuals at risk for CVDs and mortality.

Summary: Background: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38).

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Abstract The purpose of the study was to examine peculiarities of the inner limiting membrane (ILM) in axially elongated eyes. The histomorphometric study included human globes enucleated due to reasons such as painful secondary angle-closure glaucoma or malignant uveal melanomas. Using light microscopy, we searched for regions with ILM-specific features in association with a marked axial elongation. Out of 279 eyes (279 patients) (mean age: 61.8 ± 13.9 years; axial length: 25.5 ± 3.1 mm (range: 20.0–37.0 mm)), two eyes (axial length: 30 mm and 34 mm, respectively) showed one region and two regions, respectively, characterized by ILM presence and absence of all other retinal layers, retinal pigment epithelium, Bruch´s membrane (BM) and choroid. The length of these regions, called ILM-bridges, was 1.06 mm, 0.73 mm, and 0.62 mm, respectively. All ILM-bridges were spatially associated with a larger, underlying BM defect and with localized scleral thinning without a staphylomatous scleral configuration. The distance between the ILM-bridges and the optic disc ranged between 1.92 mm and 4.21 mm. In univariable analysis, ILM-bridge number increased with longer axial length (beta: 0.19; P = 0.002) and higher BM defect prevalence (beta: 0.21; P = 0.001), while in multivariable analysis, the ILM-bridges number remained to be significantly correlated only with a higher prevalence of BM defect (beta: 0.15; P = 0.048). ILM-bridges occur in eyes with pathologic myopia in spatial association with underlying, larger BM defects. They may be due to an axial elongation-associated local stretching and rupture of all other retinal layers, caused by the BM defect-related enlargement of the retinal undersurface. Future studies may explore whether these histologic observations support the notion of the ILM having a relatively high biomechanical strength against myopic stretching-associated forces.

Abstract The purpose of the study was to examine the density of retinal photoreceptors and retinal pigment epithelium (RPE) cells in relation to myopic axial elongation in human eyes. Using light microscopy, we assessed the density of photoreceptors and RPE cells at the ora serrata, equator, and midperiphery (equator/posterior pole midpoint), and the RPE cell density additionally at the posterior pole, in enucleated human globes. The study included 78 eyes (mean age: 59.2 ± 15.6 years; range: 32–85 years) with a mean axial length of 27.3 ± 3.6 mm (range: 21.5–37.0 mm). Close to the ora serrata, at the equator and midperiphery, photoreceptor and RPE cell density was 246 ± 183, 605 ± 299 and 1089 ± 441 photoreceptors/mm and 56.1 ± 13.7, 45.2 ± 15.1, and 48.8 ± 15.6 RPE cells/mm, respectively. Densities of both cell types in all three regions were positively correlated with each other (all P

Abstract To assess the prevalence of dry eye disease (DED) and Meibomian gland dysfunction (MGD) in a population in Russia. The population-based Ural Eye and Medical Study was conducted in an urban and rural region in Bashkortostan/Russia and included 5899 (80.5%) out of 7328 eligible persons, aged 40 + years. DED and MGD were assessed by Schirmer´s test, slit-lamp based examination of the Meibomian glands, and an interview with DED-related questions. The study included 5153 (87.4%) individuals with DED and MGD assessments (mean age: 58.5 ± 10.5 years). The mean Schirmer´s test result was 11.8 ± 6.8 mm and 12.5 ± 7.1 mm for the right/left eye, with a result of ≤ 5 mm measured in 1098 (21.3%; 95% confidence intervals (CI) 20.2, 22.4) of the worse eyes. The mean subjective dry eye symptoms score was 1.37 ± 1.82. MGD grade 1 (telangiectasia at the lid margin), 2, 3, 4 or any grade in the worse eye was diagnosed in 901 (21.1%), 1161 (27.1%), 158 (3.7%), 32 (0.7%), and 2252 (52.6%; 95% CI 51.1, 54.1) eyes respectively. The prevalence of DED diagnosis #1, #2 and #3 (Schirmer´s test ≤ 5 mm, and dry eye score ≥ 1, ≥ 2, and ≥ 3, respectively), #4 (dry eye score ≥ 1, Schirmer test ≤ 5 mm, MGD grade 1 +), and #5 (dry eye score ≥ 1, Schirmer test ≤ 5 mm, MGD grade 2 +) were 598/5142 (11.6%), 426/5153 (8.3%), 273/5142 (5.3%), 335/5142 (6.5%), and 186/5142 (3.6%), respectively. Mean depression score as applied was 5.1 ± 3.8. Higher DED prevalence (definition #4) was associated (multivariable analysis) with female sex (odds ratio (OR) 1.71; 95% CI 1.31, 2.22; P

Abstract To determine the prevalence of osteoarthritis and its associated factors in populations from Russia. The population-based Ural Eye and Medical Study (UEMS) and the population-based Ural Very Old Study (UVOS) were conducted in a rural and urban region in Bashkortostan/Russia and included participants aged 40+ and 85+ years, respectively. As part of a detailed systematic examination, we assessed the osteoarthritis prevalence in an interview including questions on the self-reported presence of osteoarthritis, the joints affected and osteoarthritis-related pain-relieving therapy taken. Out of 5898 participants of the UEMS, 1636 individuals had osteoarthritis [prevalence: 27.7%; 95% confidence interval (CI) 26.7, 28.7], with 816 individuals (13.8%; 95% CI 12.8, 14.8) taking pain-relieving medication. A higher osteoarthritis prevalence was associated (multivariable analysis) with older age [odds ratio (OR 1.04; 95% confidence interval (CI) 1.03, 1.05], urban region of residence (OR 1.25; 95% CI 1.07, 1.45), higher body mass index (BMI) (OR 1.04; 95% CI 1.03, 1.06), lower monthly income (OR 0.78; 95% CI 0.68, 0.90), higher physical activity score (OR 1.02, 95% CI 1.01, 1.03), higher prevalence of a history of cardiovascular disease including stroke (OR 1.55; 95% CI 1.33, 1.81), previous bone fractures (OR 1.20; 95% CI 1.04, 1.40) and previous falls (OR 1.22; 95% CI 1.03, 1.45), higher hearing loss score (OR 1.01; 95% CI 1.01, 1.02), and less alcohol consumption (OR 0.78; 95% CI 0.65, 0.93). Out of 1526 UVOS participants, 567 individuals had osteoarthritis (prevalence: 37.2%; 95% CI 35.0, 40.0), with 195 (12.8%; 95% CI 11.3, 14.3) individuals taking pain-relieving medication. Higher osteoarthritis prevalence was associated with rural region of habitation (OR 1.69; 95% CI 1.20, 2.38), lower monthly income (OR 0.62; 95% CI 0.46, 0.84), higher prevalence of cardiovascular disease (OR 1.75; 95% CI 1.30, 2.36), and higher anxiety score (OR 1.04; 95% CI 1.03, 1.06). Osteoarthritis and use of pain-relieving medication are common in these populations in Russia. Main associated factors were older age and lower monthly income in both study populations, female sex, higher BMI, urban region, and previous falls and bone fractures in the UEMS population, and rural region and a higher anxiety score in the UVOS study population.

Abstract To assess safety and tolerability of intraocularly applied cetuximab as epidermal growth factor receptor antibody, we conducted the experimental study which consisted of groups of adult rabbits (body weight: 2.4 kg) and young rabbits (body weight: 1.6 kg). All animals received three intravitreal injections of 0.5 mg cetuximab (Erbitux) (0.10 mL; 5 mg cetuximab/mL) into their right eyes in 4-week intervals, while the contralateral eyes received intravitreal injections of Ringer's solution. All animals underwent regular ophthalmological examinations at baseline and two-week intervals. Four weeks after the last injection, the animals were sacrificed, and the eyes were enucleated, fixed and examined by light microscopy. The study included 10 adult rabbits (age: 18 weeks; range: 17–19 weeks) and 8 young rabbits (age: 8 weeks; range: 7–10 weeks). Biometric measurements of axial length, anterior chamber depth and lens thickness and intraocular pressure readings did not differ significantly (all P > 0.05, Bonferroni corrected) between the right (study) eyes and the left (control) eyes, neither in the young nor in the adult rabbit group. Signs of intraocular inflammation or fundus peculiarities were not detected. Thickness of the outer nuclear layer, inner nuclear layer, combined outer and inner nuclear layer and outer plexiform layer, and total retina, measured at the posterior pole, posterior pole/equator midpoint, equator, and ora serrata region, did not vary significantly between study eyes and control eyes (all P > 0.05, Bonferroni corrected). The results suggest that repeated intravitreal application of cetuximab did not result in any detected intraocular toxic or destructive effect in young and adult rabbits, concurring with the notion of an intraocular tolerability of cetuximab.

A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease.

Abstract Information about prevalence and associated factors of non-alcoholic fatty liver disease (NAFLD) has been scarce for the Russian, Eastern European and Central Asian world region. We assessed prevalence and associated factors of NAFLD in two population-based studies (Ural Eye and Medical Study (UEMS), Ural Very Old Study (UVOS)), which were conducted in rural and urban regions in Bashkortostan/Russia and included participants aged 40 + years and 85 + years, respectively. Defining NAFLD by an absence of regular alcohol consumption, and by abnormally high alanine transaminase (ALT) and aspartate transaminase (AST) concentrations or an AST/ALT ratio of > 1.0, 2341 out of 5852 UEMS participants (40.0%; 95% confidence intervals (CI) 38.8, 41.3) had NAFLD. A higher NAFLD prevalence correlated (multivariable analysis) with older age (odds ratio (OR) 1.02; 95%CI 1.01, 1.03; P

Abstract Background Injury remains a major concern to public health in the European region. Previous iterations of the Global Burden of Disease (GBD) study showed wide variation in injury death and disability adjusted life year (DALY) rates across Europe, indicating injury inequality gaps between sub-regions and countries. The objectives of this study were to: 1) compare GBD 2019 estimates on injury mortality and DALYs across European sub-regions and countries by cause-of-injury category and sex; 2) examine changes in injury DALY rates over a 20 year-period by cause-of-injury category, sub-region and country; and 3) assess inequalities in injury mortality and DALY rates across the countries. Methods We performed a secondary database descriptive study using the GBD 2019 results on injuries in 44 European countries from 2000 to 2019. Inequality in DALY rates between these countries was assessed by calculating the DALY rate ratio between the highest-ranking country and lowest-ranking country in each year. Results In 2019, in Eastern Europe 80 [95% uncertainty interval (UI): 71 to 89] people per 100,000 died from injuries; twice as high compared to Central Europe (38 injury deaths per 100,000; 95% UI 34 to 42) and three times as high compared to Western Europe (27 injury deaths per 100,000; 95%UI 25 to 28). The injury DALY rates showed less pronounced differences between Eastern (5129 DALYs per 100,000; 95% UI: 4547 to 5864), Central (2940 DALYs per 100,000; 95% UI: 2452 to 3546) and Western Europe (1782 DALYs per 100,000; 95% UI: 1523 to 2115). Injury DALY rate was lowest in Italy (1489 DALYs per 100,000) and highest in Ukraine (5553 DALYs per 100,000). The difference in injury DALY rates by country was larger for males compared to females. The DALY rate ratio was highest in 2005, with DALY rate in the lowest-ranking country (Russian Federation) 6.0 times higher compared to the highest-ranking country (Malta). After 2005, the DALY rate ratio between the lowest- and the highest-ranking country gradually decreased to 3.7 in 2019. Conclusions Injury mortality and DALY rates were highest in Eastern Europe and lowest in Western Europe, although differences in injury DALY rates declined rapidly, particularly in the past decade. The injury DALY rate ratio of highest- and lowest-ranking country declined from 2005 onwards, indicating declining inequalities in injuries between European countries.

Purpose: To examine histologic characteristics of macular Bruchś membrane defects (BMD) in axially elongated eyes. Design: Histomorphometric study. Methods: Using light microscopy, we examined enucleated human globes for BMDs. Results: In 247 eyes, BMDs were detected in 15 (6.1%) eyes (axial length:27.0–36.0 mm), in 10 of them in the macular region. Prevalence and size of BMDs (mean:1.93 ± 1.62 mm; range:0.22mm–6.24 mm) correlated with longer axial length (OR:1.52; 95%CI:1.19,1.94; P = 0.001) and higher prevalence of scleral staphylomas (OR:16.3; 95%CI:2.67,99.3; P 0.05) between the BDM border and adjacent areas. In the BMD, choriocapillaris and RPE were absent. The sclera was thinner in the BDM area than in adjacent areas (0.28 ± 0.19 mm versus 0.36 ± 0.13 mm; P = 0.006). Conclusions: BMDs as hallmarks of myopic macular degeneration are characterized by longer gaps in the RPE and smaller gaps in the outer nuclear layer and inner nuclear layer, by localized scleral thinning, and by a spatial association with scleral staphylomas. Thickness of the choriocapillaris and density of the RPE cell layer, both absent within the BDMs, do not vary between the BMD border and adjacent regions. The results suggest an association between BDMs and absolute scotomas, stretching of the adjacent retinal nerve fiver layer, and an axial elongation-associated stretching effect on BM as etiology of the BDMs.

Abstract Background Myopic axial elongation may be due to an equatorial enlargement of Bruch’s membrane (BM), leading to a prolate eye shape and increasing strain with BM and the retinal pigment epithelium (RPE) layer at the posterior pole. The increased BM strain may cause an enlargement of Bruch’s membrane opening (BMO) of the optic nerve head, with the subsequent development and enlargement of parapapillary gamma zone as BM-free parapapillary zone. The increased strain within BM and RPE may also cause lacquer cracks (LCs) as linear breaks in the RPE and / or BM. Studies suggested that a more marked gamma zone enlargement is associated with lower prevalence of LCs or macular BM defects. Here report on the disappearance of a LC during a 10-year follow-up of a highly myopic eye, concurrent with a marked increase in gamma zone. Case presentation A 56-year-old woman showed in her right eye (axial length measured 30.69 mm) a LC, vertically oval optic disc, and parapapillary gamma zone in 2001. When re-examined in 2006, gamma zone had enlarged, while the LC was no longer detectable. In 2011, the LC was not visible neither upon ophthalmoscopy and or upon optical coherence tomography (OCT), while gamma zone had further enlarged. The gamma zone enlargement occurred in a direction perpendicular to the direction of the former LC. Conclusions The observation suggest that a LC can decrease in width, in temporal association with an enlargement of gamma zone. It fits with the notion that an enlargement of the BMO (i.e., enlarging gamma zone) may lead to a relaxation of the BM strain and subsequently to a decrease in the width of the LC.

Abstract To assess the histological correlate of neovascular or exudative myopic macular degeneration (nMMD) in highly myopic human eyes, we examined histomorphometrically histologic sections of enucleated eyes of Caucasian patients. The study included 284 eyes (age: 61.9 ± 13.7 years; range: 24–89 years; axial length: 25.5 ± 3.1 mm; range: 20–37 mm). An nMMD was detected in 5 eyes (axial length: 29.6 ± 2.6 mm; range: 26.0–31.0 mm). All these eyes showed within or close to the nMMD a macular Bruch’s membrane (BM) defect, fibrous tissue with erythrocyte-filled blood vessels, and proliferations of irregularly pigmented and irregularly piled-up retinal pigment epithelium (RPE) cells each of which was connected with a curled-up, PAS (Periodic-Acid-Shiff)-positive membrane. The nMMD lesions were covered by proliferated RPE cells. RPE cells were not detected within the retina. In binary regression analysis, a higher nMMD prevalence was associated with a higher prevalence of macular BM defects (odds ratio: > 1000; P

Abstract To assess the distribution of axial length as surrogate for myopia and its determinants in an old population, we performed the Ural Very Old Study as a population-based cohort study. Out of 1882 eligible individuals aged 85 + years, the Ural Very Old Study performed in an urban and rural region in Bashkortostan/Russia included 1526 (81.1%) individuals undergoing ophthalmological and medical examinations with sonographic axial length measurement. Biometric data were available for 717 (47.0%) individuals with a mean age of 88.0 ± 2.6 years (range 85–98 years; 25%). Mean axial length was 23.1 ± 1.1 mm (range 19.37–28.89 mm). Prevalences of moderate myopia (axial length 24.5–

Abstract The aim of the study was to assess longitudinal changes in the spatial relationship of the choroidal vasculature to retinal vasculature in myopic eyes. In the population-based longitudinal Beijing Eye Study in 2001/2011, we examined all highly myopic eyes with assessable fundus photographs and a randomized group of non-highly myopic. Using fundus photographs, we qualitatively assessed changes in the location of major choroidal vessels in relationship to retinal vessels. The study consisted of 85 highly myopic eyes (58 participants;age:64.8 ± 9.4 years) and 85 randomly selected non-highly myopic eyes. A choroidal shift in relationship to the retinal vessels was detected more often in the highly myopic group than the non-highly myopic group (47/85 (55%) vs 6/85 (7%); P

BackgroundDespite its marked importance in public health, the prevalence of cognitive impairment (CI) and its associated factors have only rarely been examined in old populations in general or in Russia at all.ObjectiveTo assess CI prevalence and its determinants in a very elderly population in Russia.Materials and methodsThe population-based Ural Very Old Study, conducted in rural and urban region in Bashkortostan/Russia, included 1,526 (81.1%) out of 1,882 eligible individuals aged 85+ years. A series of medical examinations including the Mini-Mental State Examination (MMSE) for the assessment of CI was performed.ResultsMini-Mental State Examination data were available for 1,442 (94.5%) individuals (mean age: 88.3 ± 2.9 years; range: 85–103 years). The median MMSE score was 24 (interquartile range: 19, 27). Prevalence of any CI (MMSE score < 24 points) was 701/1,442 [48.6%; 95% confidence interval (CI): 46.0, 51.2]. Prevalence of mild, moderate and severe CI (MMSE score 19–23 points, 10–18 points, and ≤9 points, respectively) was 357/1,442 (24.8%; 95% CI: 22.5, 27.0), 246/1,442 (17.1%; 95% CI: 15.1, 19.0), and 98/1,442 (6.8%; 95% CI: 5.5, 8.1), resp. A lower MMSE score correlated (regression coefficient r2: 0.31) with older age (beta: −0.13; P < 0.001), rural region of habitation (beta: 0.15; P < 0.001), lower level of education (beta: 0.19; P < 0.001), higher depression score (beta: −0.33; P < 0.001) (or alternatively, higher prevalence of hearing loss (beta: −0.10; P = 0.001), worse visual acuity (beta: −0.10; P = 0.001), and lower physical activity (beta: 0.06; P = 0.04).ConclusionIn this elderly study population from rural and urban Russia, prevalence of any, mild, moderate and severe CI was 48.6, 24.8, 17.1, and 6.8%, resp. Besides medical and lifestyle factors, vision and hearing impairment were major factors associated with CI.

BackgroundIn 2021, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) validated a new equation for estimated glomerular filtration rate (eGFR). However, this new equation is not ethnic-specific, and prevalence of CKD in Asians is known to differ from other ethnicities. This study evaluates the impact of the 2009 and 2021 creatinine-based eGFR equations on the prevalence of CKD in multiple Asian cohorts.MethodsEight population-based studies from China, India, Russia (Asian), Singapore and South Korea provided individual-level data (n = 67,233). GFR was estimated using both the 2009 CKD-EPI equation developed using creatinine, age, sex, and race (eGFRcr [2009, ASR]) and the 2021 CKD-EPI equation developed without race (eGFRcr [2021, AS]). CKD was defined as an estimated glomerular filtration rate (eGFR)

This study aimed to investigate the prevalence of age-related macular degeneration (AMD) in patients with diabetes mellitus (DM) and diabetic retinopathy (DR) and analyze whether DR is a risk factor for AMD. This population-based epidemiological study included 14,440 people from the Kailuan Eye Study in 2016, of whom 1,618 were patients with type 2 DM aged over 50 years, and 409 had DM with DR. We analyzed whether there were differences in the prevalence of AMD between DM with DR and DM without DR, and conducted a hierarchical statistical analysis according to different stages of DR. Using variable regression analysis, we explored whether DR constituted a risk factor for AMD. In the DM population, the prevalence of wet AMD in patients with DM with and without DR was 0. 3 and 0.2%, respectively, with no significant difference (P = 0.607). Meanwhile, the prevalence of dry AMD in patients with DM with and without DR was 20.8 and 16.0%, respectively, with a significant difference. In the subgroup analysis of dry AMD, the prevalence of early, middle, and late dry AMD in DM with DR was 14.4, 5.9, and 0.5%, respectively. In DM without DR, the prevalence of early, middle, and late dry AMD was 10.5, 4.8, and 0.7%, respectively (P = 0.031). In the subgroup analysis of DR staging, statistical analysis could not be performed because of the limited number of patients with PDR. In the variable regression analysis of risk factors for dry AMD, after adjusting for age, sex, body mass index, hypertension, and dyslipidemia, DR constituted the risk factor for dry AMD. In conclusion, DM did not constitute a risk factor for AMD, and the prevalence of wet AMD and dry AMD in patients with DM and DR was higher than that in patients with DM without DR (among which dry AMD was statistically significant). Multivariate regression analysis confirmed that DR is an independent risk factor for dry AMD. Reasonable control of DM and slowing down the occurrence and development of DR may effectively reduce the prevalence of AMD in patients with DM.

PurposeTo compare optic nerve head (ONH) ovality index and rotation angle measurements based on semi-automated delineation of the clinical ONH margin derived from photographs and automated BMO configuration derived from optical coherence tomography (OCT) images in healthy and glaucomatous eyes with high-, mild- and no axial myopia.MethodsOne hundred seventy-five healthy and glaucomatous eyes of 146 study participants enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with optic disc photographs and Spectralis OCT ONH scans acquired on the same day were stratified by level of axial myopia (non-myopic [n = 56, axial length (AL) 26 mm]. The clinical disc margin of each photograph was manually annotated, and semi-automated measurements were recorded of the ovality index and rotation angle based on a best-fit ellipse generated using ImageJ software. These semi-automated photograph-based measurements were compared to ovality index and rotation angle generated from custom automated BMO-based analysis using segmented OCT ONH volumes. R2 values from linear mixed effects models were used to describe the associations between semi-automated, photograph-based and automated OCT-based measurements.ResultsAverage (95% CI) axial length was 23.3 (23.0, 23.3) mm, 24.8 (24.7, 25.0) mm and 26.8 (26.6, 27.0) mm in non-myopic, mild-myopic and high-myopic eyes, respectively (ANOVA, p ≤ 0.001 for all). The R2 association (95% CI) between semi-automated photograph-based and automated OCT-based assessment of ONH OI for all eyes was [0.26 (0.16, 0.36); p < 0.001]. This association was weakest in non-myopic eyes [0.09 (0.01, 0.26); p = 0.02], followed by mild-myopic eyes [0.13 (0.02, 0.29); p = 0.004] and strongest in high-myopic eyes [0.40 (0.19, 0.60); p < 0.001]. No significant associations were found between photography- and OCT-based assessment of rotation angle with R2 values ranging from 0.00 (0.00, 0.08) in non-myopic eyes to 0.03 (0.00, 0.21) in high-myopic eyes (all associations p ≥ 0.33).ConclusionsAgreement between photograph-based and automated OCT-based ONH morphology measurements is limited, suggesting that these methods cannot be used interchangeably for characterizing myopic changes in the ONH.

Purpose: To examine prevalence and associated factors of the metabolic syndrome (MS) in populations in Russia. Methods: Two population-based studies (Ural Eye and Medical Study (UEMS), Ural Very Old Study (UVOS)) were conducted in rural and urban regions in Bashkortostan/Russia and included participants aged 40+ years and 85+ years, respectively. Results: Out of 5895 UEMS participants, 1572 individuals had MS (prevalence:26.7%; 95% confidence interval (CI):25.5,27.8). The criteria of waist circumference, blood pressure, hyperglycemia, serum high-density lipoprotein concentration and serum triglyceride concentration were fulfilled by 4269 (72.4%; 95%CI:71.3,73.6), 3168 (53.7%; 95%CI:52.5,55.1), 1375 (23.3%; 95%CI:22.4,24.6), 712 (13.3%; 95%CI:12.4,14.2), and 1527 (28.6%; 95%CI:27.4,29.8) individuals, respectively. Higher MS prevalence was associated with older age (odds ratio (OR):1.03; 95%CI:1.02,1.04;P

Abstract To assess changes in the disc-fovea distance (DFD) in highly myopic eyes in a 10-year population-based follow-up study. The case control study included all highly myopic eyes (myopic refractive error ≥ − 6.0 diopters or axial length ≥ 26.0 mm) and a randomized group of non-highly myopic eyes examined in the population-based Beijing Eye Study 2001 and 2011. Using fundus photographs and optical coherence tomographic images, we assessed changes in DFD, parapapillary gamma zone, angle kappa (angle between the temporal arterial arcades), and course of papillo-macular retinal vessels. The study included 89 highly myopic eyes and 86 non-highly myopic eyes. DFD elongation, gamma zone widening, angle kappa decrease and straightening of papillo-macular retinal vessels were detected more often (all P

Abstract This study characterizes differences in glaucomatous eyes with and without high axial myopia using custom automated analysis of OCT images. 452 eyes of 277 glaucoma patients were stratified into non (n = 145 eyes), mild (n = 214 eyes), and high axial myopia (axial length (AL) > 26 mm, n = 93 eyes). Optic disc ovality index, tilt and rotation angle of Bruch´s membrane opening (BMO) and peripapillary choroidal thickness (PCT) were calculated using automated and deep learning strategies. High myopic optic discs were more oval and had larger BMO tilt than mild and non-myopic discs (both p

Abstract Glaucoma is a common neurodegenerative disease and a leading cause of irreversible blindness worldwide. Retinal microglia-mediated neuroinflammation is involved in the process of optic nerve damage, but the mechanisms driving this microglial activation remain mostly elusive. Previous investigations reported that microRNAs are associated with the retinal microglial reaction and neural apoptosis. In the present study, we found that microRNA-93-5p (miR-93) played a key role in the reaction of retinal microglial cells in vivo and in vitro. The miR-93 level was significantly reduced in the retinae of rat acute ocular hypertension (AOH) models, which were accompanied by retinal microglial activation, overproduction of inflammatory cytokines, and subsequent retinal ganglion cells (RGCs) death, versus the retinae of controls. The induction of miR-93 overexpression significantly reduced microglial proliferation, migration and cytokine release, inhibited the expression of the target gene signal transducer and activator of transcription 3 (STAT3) and p-STAT3, and was associated with a reduced loss of RGCs. Treatment with a STAT3 inhibitor also decreased retinal microglial activation after AOH injury. Taken together, these results suggest that the miR-93/STAT3 pathway is directly related to the downregulation of retinal microglia-mediated neuro-inflammation and showed a neuroprotective effect. Regulating microglial activation through miR-93 may serve as a target for neuroprotective therapy in pathological ocular hypertension.

Here, the authors report a multi-ethnic genome wide association meta-analysis of 12 studies from the International Cataract Genetics Consortium. They find six new loci associated with age-related nuclear cataract, in addition to replicating the association at CRYAA, and suggest a strong genetic link between age-related nuclear and congenital cataracts.

Summary: Background: Mental health is a public health issue for European young people, with great heterogeneity in resource allocation. Representative population-based studies are needed. The Global Burden of Disease (GBD) Study 2019 provides internationally comparable information on trends in the health status of populations and changes in the leading causes of disease burden over time. Methods: Prevalence, incidence, Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) from mental disorders (MDs), substance use disorders (SUDs) and self-harm were estimated for young people aged 10-24 years in 31 European countries. Rates per 100,000 population, percentage changes in 1990-2019, 95% Uncertainty Intervals (UIs), and correlations with Sociodemographic Index (SDI), were estimated. Findings: In 2019, rates per 100,000 population were 16,983 (95% UI 12,823 – 21,630) for MDs, 3,891 (3,020 - 4,905) for SUDs, and 89·1 (63·8 - 123·1) for self-harm. In terms of disability, anxiety contributed to 647·3 (432–912·3) YLDs, while in terms of premature death, self-harm contributed to 319·6 (248·9–412·8) YLLs, per 100,000 population. Over the 30 years studied, YLDs increased in eating disorders (14·9%;9·4-20·1) and drug use disorders (16·9%;8·9-26·3), and decreased in idiopathic developmental intellectual disability (–29·1%;23·8-38·5). YLLs decreased in self-harm (–27·9%;38·3-18·7). Variations were found by sex, age-group and country. The burden of SUDs and self-harm was higher in countries with lower SDI, MDs were associated with SUDs. Interpretation: Mental health conditions represent an important burden among young people living in Europe. National policies should strengthen mental health, with a specific focus on young people. Funding: The Bill and Melinda Gates Foundation

Abstract Background Currently, whether and when intraocular pressure (IOP)-lowering medication should be used in glaucoma suspects with high myopia (GSHM) remains unknown. Glaucoma suspects are visual field (VF) defects that cannot be explained by myopic macular changes or other retinal and neurologic conditions. Glaucoma progression is defined by VF deterioration. Here we describe the rationale, design, and methodology of a randomized controlled trial (RCT) designed to evaluate the effects of medically lowering IOP in GSHM (GSHM study). Methods The GSHM study is an open-label, single-center, RCT for GSHM. Overall, 264 newly diagnosed participants, aged 35 to 65 years, will be recruited at the Zhongshan Ophthalmic Center, Sun Yat-sen University, between 2020 and 2021. Participants will be randomly divided into two arms at a 1:1 ratio. Participants in the intervention arm will receive IOP-lowering medication, while participants in the control arm will be followed up without treatment for 36 months or until they reach the end point. Only one eye per participant will be eligible for the study. If both eyes are eligible, the eye with the worse VF will be recruited. The primary outcome is the incidence of glaucoma suspect progression by VF testing over 36 months. The secondary outcomes include the incidence of changes in the optic nerve head morphology including the retinal nerve fiber layer, and retinal ganglion cell-inner plexiform layer loss, progression of myopic maculopathy, visual function loss, and change in the quality of life. Statistical analyses will include baseline characteristics comparison between the intervention and control groups using a two-sample t-test and Wilcoxon rank sum test; generalized linear models with Poisson regression for the primary outcome; Kaplan-Meier curve and log-rank test for the incidence of the secondary outcome; and longitudinal analyses to assess trends in outcomes across time. Discussion To the best of our knowledge, the GSHM study is the first RCT to investigate the impact of medically lowering IOP in GSHM. The results will have implications for the clinical management of GSHM. Trial registration ClinicalTrials.gov NCT04296916 . Registered on 4 March 2020

Abstract Background The goal of this review is to summarize structural and anatomical changes associated with high myopia. Main text Axial elongation in myopic eyes is associated with retinal thinning and a reduced density of retinal pigment epithelium (RPE) cells in the equatorial region. Thickness of the retina and choriocapillaris and RPE cell density in the macula are independent of axial length. Choroidal and scleral thickness decrease with longer axial length in the posterior hemisphere of the eye, most marked at the posterior pole. In any eye region, thickness of Bruch’s membrane (BM) is independent of axial length. BM opening, as the inner layer of the optic nerve head layers, is shifted in temporal direction in moderately elongated eyes (axial length 26.5 mm), BM opening enlarges with longer axial length. It leads to a circular gamma zone. In a parallel manner, the peripapillary scleral flange and the lamina cribrosa get longer and thinner with longer axial length in highly myopic eyes. The elongated peripapillary scleral flange forms the equivalent of parapapillary delta zone, and the elongated lamina cribrosa is the equivalent of the myopic secondary macrodisc. The prevalence of BM defects in the macular region increases with longer axial length in highly myopic eyes. Scleral staphylomas are characterized by marked scleral thinning and spatially correlated BM defects, while thickness and density of the choriocapillaris, RPE and BM do not differ markedly between staphylomatous versus non-staphylomatous eyes in the respective regions. Conclusions High axial myopia is associated with a thinning of the sclera and choroid posteriorly and thinning of the retina and RPE density in the equatorial region, while BM thickness is independent of axial length. The histological changes may point towards BM having a role in the process of axial elongation.

Abstract Background Intraocular pressure (IOP) is an important physiological measure of the eye and is associated with some ocular disorders. We aimed to assess the influence of topical beta blocker-induced IOP reduction on lens-induced axial elongation in young guinea pigs. Methods The experimental study included 20 pigmented guinea pigs (age: 2–3 weeks). Myopia was induced in the right eyes for 5 weeks with − 10 diopter lenses. The right eyes additionally received either one drop of carteolol 2% (study group, n = 10) or one drop of artificial tears daily (control group, n = 10), while the contralateral eyes of all animals remained untouched. The outcome parameter was axial elongation during the follow-up period. The mean of all IOP measurements taken during the study was referred to as mean IOP. Results Greater axial elongation was associated with a shorter axial length at baseline (P 0.25). Conclusions In young guinea pigs with or without lens-induced axial elongation, neither the physiological IOP nor the IOP reduced by carteolol, a topical beta-blocker, was associated with the magnitude of axial elongation. These results suggest that IOP, regardless of whether it is influenced by carteolol, does not play a major role in axial elongation in young guinea pigs.

Abstract Background To examine the prevalence of chronic kidney disease (CKD) and its associations in a Russian population. Methods Out of 7328 eligible individuals, the population-based cross-sectional Ural Eye and Medical Study included 5899 (80.5%) individuals aged 40+ years and undergoing a detailed medical examination. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic-Kidney-Disease-Epidemiology-Collaboration (CKD-EPI) equation. Results The mean eGFR was 72.3 ± 19.1 mL/min/1.73m2 (median:70.3 mL/min/1.73m2). Prevalence of CKD stage 3a (eGFR 45 mL/min/1.73m2), CKD stage 3b (eGFR 30 mL/min/1.73m2) and CKD stage 4+ (eGFR

Abstract Background Back pain and neck pain are leading causes of the burden of disease worldwide, while information about their prevalence in Russia is missing. Methods The population-based Ural Eye and Medical Study was conducted in a rural and urban region in Bashkortostan/Russia. As part of a detailed systematic examination, we assessed the prevalence of low back pain, thoracic spine pain and neck pain in an interview with standardized questions in 5397 study participants (mean age:58.6 ± 10.6 years;range:40–94 years). Results The mean prevalence of low back pain, thoracic spine pain and neck pain was 2912/5397 (54.0%;95% confidence interval (CI):52.6,55.3), 1271/5397 (23.6%;95%CI:22.4,24.7), and 1570/5397 (29.1%;95%CI:27.9,30.3), respectively. A higher prevalence of low back pain was associated with females (P = 0.04;odds ratio (OR):1.14;95%CI:1.004,1.30), younger age (P

Abstract Background Diagnosis and follow-up of retinal diseases may be improved if the thickness of the various retinal layers, in addition to the total retinal thickness, is taken into account. Here we measured the thickness of the macular retinal layers in a population-based study group to assess the normative values and their associations. Methods Using spectral-domain optical coherence tomographic images (Spectralis®, wavelength: 870 nm; Heidelberg Engineering Co, Heidelberg, Germany), we measured the thickness of the macular retinal layers in participants of the population-based Beijing Eye Study without ocular diseases and without systematic diseases, such as arterial hypertension, hyperlipidemia, diabetes mellitus, cardiovascular diseases, previous myocardial infarction, cerebral trauma and stroke. Segmentation and measurement of the retinal layers was performed automatically in each of the horizontal scans. Results The study included 384 subjects (mean age:60.0 ± 8.0 years). The mean thickness of the whole retina, outer plexiform layer, outer nuclear layer,retinal pigment epithelium, inner retinal layer and photoreceptor layer was 259.8 ± 18.9 μm, 19.4 ± 3.9 μm, 93.4 ± 9.6 μm, 17.6 ± 1.9 μm, 169.8 ± 18.6 μm, and 90.0 ± 4.2 μm, respectively. In multivariable analysis, the thickness of the foveola and of all retinal layers in the foveal, parafoveal and perifoveal region decreased with older age (all P

Purpose: To evaluate the feasibility of in-vivo imaging of the retina and choroid using spectral domain optical coherence tomography (OCT) in guinea pigs.Methods: The study included 19 pigmented guinea pigs (age: 3–4 weeks) which underwent sonographic axial length measurements and OCT imaging. At study end, the animals were sacrificed and histomorphometric examinations of the retina and choroid were performed. We assessed the reproducibility of the OCT measurements and compared in-vivo measurements to histomorphometric data.Results: The mean thickness of the retina and choroid near the optic nerve head was 175.6 ± 25.8 and 63.4 ± 16.5 μm, respectively, and mean Bruch's membrane opening (BMO) diameter was 831 ± 121 μm. The intra-observer comparison of measurements of retinal thickness (intraclass correlation coefficient (ICC) = 0.92, 95% CI: 0.86–0.96; P < 0.001), choroidal thickness (ICC = 0.92, 95% CI: 0.86–0.96; P < 0.001), and BMO diameter (ICC = 0.92, 95% CI: 0.86–0.96; P < 0.001) showed a high correlation. A high agreement was present also for the inter-observer reproducibility of the measurements of retinal thickness (Pearson correlation coefficient (R) = 0.98; P < 0.001), choroidal thickness (R = 0.96; P < 0.001), and BMO diameter (R = 0.98; P < 0.001). The Bland-Altman plots showed that 2.6% (1/38), 5.3% (2/38), and 7.9% (3/38) of the measurement points of retinal thickness, choroidal thickness and BMO diameter, respectively, were located outside of the 95% limits of agreement. The OCT-based thickness measurements of retina and choroid were significantly higher than those measured by histomorphometry (both P-values

Aims: To examine the prevalence of primary epiretinal membranes (ERMs) and associated systemic factors.Methods: The cross-sectional, community-based Tongren Health Care Study enrolled participants who received regular health examinations in the Beijing Tongren Hospital from 2017 to 2019. Using fundus photographs, retinal specialists assessed the presence of ERMs and their systemic associations.Results: Primary ERMs were detected in 841/22820 individuals, with a prevalence of 3.7% [95% confidence intervals (CI): 3.4–3.9%] in the total study population (mean age: 44.5 ± 13.8 years) and 6.5% (95% CI: 6.1–7.0%) in individuals aged 40+ years. In multivariable analysis, a higher ERMs prevalence was associated with older age [odds ratio (OR): 1.10; P < 0.001], higher serum cholesterol concentration (OR: 1.14; P = 0.003) and higher serum sodium concentration (SSC) (OR: 1.12; P < 0.001). In women, a higher SSC, even within the normal range, was associated with an increased risk of ERMs (OR: 1.19; P < 0.001). Female participants with an SSC of 144–145mmol/L as compared with those with an SSC of 135–137 mmol/L had a 5-fold increased odds of having ERMs (All women: OR: 5.33; P < 0.001; Women aged 40+years: OR: 4.63; P < 0.001).Conclusion: Besides older age and higher serum cholesterol concentration, a higher SSC, even if within the normal range, was independently associated with a higher ERM prevalence in women.