Unexpected findings: loss of corneal endothelial cells in Uygur patients with exfoliation syndrome.

PURPOSE: This study aimed to investigate anterior segment parameters in patients with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). METHODS: The study adopted a retrospective case series design, involving a total of 56 patients (112 eyes) with unrelated XFS/XFG (XFS: 26 patients/60 eyes; XFG: 30 patients/44 eyes) and 100 age-related cataract cases as the control group (200 eyes). The participants were evaluated at the ophthalmology department of the First Affiliated Hospital of Xinjiang Medical University. Clinical data, including eye axial length, anterior chamber depth, white-to-white distance, central corneal thickness, and corneal endothelial cell density (ECD), were collected for statistical analysis. RESULTS: ECD exhibited a significant difference between the XFS/XFG and age-related cataract groups (P < 0.001), while the remaining indexes did not show statistical differences (P > 0.05). Ocular parameters in patients with XFS and XFG were distinct from those in age-related cataract cases, with consistent results. Notably, there were no statistically significant differences between XFS and XFG patients. CONCLUSIONS: ECD is reduced in XFS/XFG patients compared with age-related cataract subjects. It is crucial to remain vigilant to enhance surgical safety in XFS/XFG patients and prevent complications proactively.

Prevalence and risk factors for myopia and high myopia: A cross-sectional study among Han and Uyghur students in Xinjiang, China.

PURPOSE: This study aimed to investigate the prevalence and risk factors for myopia and high myopia among Han and Uyghur students in Xinjiang, China. METHODS: This cross-sectional study with a multistage, stratified cluster sampling method was completed in Xinjiang, China. Visual acuity and noncycloplegic refraction were measured. The crude and sex- and age-adjusted prevalence of myopia and high myopia in Han and Uyghur students were compared. Multivariate logistic regression analyses were applied to identify risk factors associated with myopia and high myopia. RESULTS: In total, 84,033 participants were included in the final analysis, comprising 64,110 Han and 19,923 Uyghur participants. The overall age- and sex-adjusted prevalence of myopia and high myopia were 47.70% (95% CI: 47.67-47.74) and 2.55% (95% CI: 2.54-2.56), respectively. Compared to the Uyghur population, the Han population had a higher prevalence of myopia (63.59% vs. 21.34%, p < 0.0001) and high myopia (4.68% vs. 0.6%, p < 0.0001). Han ethnicity, age, female sex, higher education level and living in urban areas were found to be positively associated with myopia and high myopia. Living in northern Xinjiang was found to be positively associated with myopia but negatively associated with high myopia. CONCLUSIONS: Our study investigated the prevalence of myopia and high myopia among Han and Uyghur students aged 4-23 years in Xinjiang, China. The Han population had a higher prevalence of myopia and high myopia than the Uyghur population. However, the prevalence of myopia among the Uyghur population showed a more remarkable increasing trend than that among the Han population in Xinjiang.

Predictive models of aging of the human eye based on ocular anterior segment morphology.

Aging is a major risk factor for various eye diseases, such as cataract, glaucoma, and age-related macular degeneration. Age-related changes are observed in almost all structures of the human eye. Considerable individual variations exist within a group of similarly aged individuals, indicating the need for more informative biomarkers for assessing the aging of the eyes. The morphology of the ocular anterior segment has been reported to vary across age groups, focusing on only a few corneal parameters, such as keratometry and thickness of the cornea, which could not provide accurate estimation of age. Thus, the association between eye aging and the morphology of the anterior segment remains elusive. In this study, we aimed to develop a predictive model of age based on a large number of anterior segment morphology-related features, measured via the high-resolution ocular anterior segment analysis system (Pentacam). This approach allows for an integrated assessment of age-related changes in corneal morphology, and the identification of important morphological features associated with different eye aging patterns. Three machine learning methods (neural networks, Lasso regression and extreme gradient boosting) were employed to build predictive models using 276 anterior segment features of 63,753 participants from 10 ophthalmic centers in 10 different cities of China. The best performing age prediction model achieved a median absolute error of 2.80 years and a mean absolute error of 3.89 years in the validation set. An external cohort of 100 volunteers was used to test the performance of the prediction model. The developed neural network model achieved a median absolute error of 3.03 years and a mean absolute error of 3.40 years in the external cohort. In summary, our study revealed that the anterior segment morphology of the human eye may be an informative and non-invasive indicator of eye aging. This could prompt doctors to focus on age-related medical interventions on ocular health.

1,25-Dihydroxyvitamin D3 Deficiency is Involved in the Pathogenesis of Diabetic Retinopathy in the Uygur Population of China.

1,25-Dihydroxyvitamin D3 [1,25(OH)2 D3 ] has recently been shown to have immunomodulatory property. This study aimed to investigate the expression and potential role of 1,25(OH)2 D3 in the pathogenesis of diabetic retinopathy (DR) in the Uygur population. Blood samples were obtained from 22 patients with proliferative DR (PDR), 29 patients with nonproliferative DR (NPDR), and 24 normal controls. ELISA was performed to estimate the serum levels of 1,25(OH)2 D3 . Peripheral blood mononuclear cells (PBMCs) were cultured with or without 1,25(OH)2 D3 in the presence of anti-CD3 and anti-CD28 antibodies to detect the secretion of cytokines and cell proliferation. The FACS cytometric bead array system was used to analyze cytokine levels in the serum and culture supernatants. The Cell Counting Kit was used to determine the rate of cell proliferation. In this study, we found that the patients with PDR showed a decreased serum level of 1,25(OH)2 D3 and increased production of IFN-γ, TNF-α, IL-6, and IL-17A, by anti-CD3 and anti-CD28 antibodies activated PBMCs. Furthermore, 1,25(OH)2 D3 significantly inhibited the proliferation of PBMCs, as well as the secretion of IFN-γ, TNF-α, IL-6, and IL-17A. Overall, our findings suggest a potential protective effect of 1,25(OH)2 D3 in DR, whereas supplementation with 1,25(OH)2 D3 might be an effective strategy for preventing the development of DR. © 2016 IUBMB Life, 68(6):445-451, 2016.

Exome sequencing reveals PPEF2 variant associated with high myopia.

High myopia (HM) is a serious blinding eye disease, and genetic factors play an important role in the development of HM. In this study, whole exome sequencing (WES) was used to identify a novel variant c.A875G of the PPEF2 for a large Uyghur family with nonsyndromic HM. The variant was verified to cosegregate with HM in the family using Sanger sequencing. Another novel variant c.1959C > G in PPEF2 was identified in one of 100 sporadic cases of HM by multiplex PCR targeted amplicon sequencing (MTA-seq). The Ppef2 was verified that mainly expressed in the retinal pigment epithelium (RPE), choroid and retina tissues. Immunofluorescence (IF) and immunohistochemistry (IHC) assays showed that the PPEF2 was strongly expressed in the inner segment layer formed by photoreceptor protrusions, as well as in the outer nuclear layer. Compared with the wild-type, the c.A875G resulted in reduced protein levels but had no effect on protein subcellular localization in cells. In addition, the c.A875G variant resulted in a decreased migratory and proliferative capacity but promoted apoptosis in cells. In summary, PPEF2 was identified as a novel HM-causing gene, and this variant in PPEF2 might cause HM by regulating the migration, proliferation and apoptosis of myopia-related cells.

Systemic Inflammatory Mediator Levels in Non-Proliferative Diabetic Retinopathy Patients with Diabetic Macular Edema.

PURPOSE: To study the systemic inflammatory mediator levels in non-proliferative diabetic retinopathy (NPDR) patients with diabetic macular edema (DME) and explore the correlation between systemic inflammatory mediators and DME. METHODS: In this prospective study, we included 25 patients without diabetes (control group) and 75 patients with type 2 diabetes mellitus (diabetic group). According to fundus examination, the diabetic group patients were divided into: diabetic patients without diabetic retinopathy (DR) (Non-DR group), NPDR patients without DME (Non-DME group), and NPDR patients with DME (DME group). Serum levels of a broad panel of inflammatory mediators were analysed by multiplex protein quantitative detection technology based on a flow cytometry detection system. RESULTS: The interferon-γ (IFN-γ) levels were significantly higher in DME group and Non-DME group as compared to control group (p = 0.023 and p = 0.033) and Non-DR group (p = 0.009 and p = 0.015). Significantly higher values were obtained in DME group and Non-DME group as compared to control group for the interleukin-8 (IL-8) (p = 0.003 and p = 0.003). The IL-23 levels were significantly elevated in DME group and Non-DR group than in Non-DME group (p = 0.013 and p = 0.004). The diabetic group had significantly higher serum levels of IL-8 and IL-33 (p = 0.001 and p = 0.011), and lower serum levels of tumor necrosis factor-α (TNF-α) (p = 0.027) in comparison with control group. CONCLUSIONS: The changed levels of serum inflammatory mediators suggest that the systemic inflammatory mediators are involved in the pathogenesis of NPDR patients with DME. Such effects can guide clinical monitoring, diagnostic and therapeutic approaches for DME patients at an early stage.

Development and construction of a cataract risk prediction model based on biochemical indices: the National Health and Nutrition Examination Survey, 2005-2008.

Purpose: The aim of this study is to develop and validate a novel multivariable prediction model capable of accurately estimating the probability of cataract development, utilizing parameters such as blood biochemical markers and age. Design: This population-based cross-sectional study comprised 9,566 participants drawn from the National Health and Nutrition Examination Survey (NHANES) across the 2005-2008 cycles. Methods: Demographic information and laboratory test results from the patients were collected and analyzed using LASSO regression and multivariate logistic regression to accurately capture the influence of biochemical indicators on the outcomes. The SHAP (Shapley Additive Explanations) scale was employed to assess the importance of each clinical feature, excluding age. A multivariate logistic regression model was then developed and visualized as a nomogram. To assess the model's performance, its discrimination, calibration, and clinical utility were evaluated using receiver operating characteristic (ROC) curves, 10-fold cross-validation, Hosmer-Lemeshow calibration curves, and decision curve analysis (DCA), respectively. Results: Logistic regression analysis identified age, erythrocyte folate (nmol/L), blood glucose (mmol/L), and blood urea nitrogen (mmol/L) as independent risk factors for cataract, and these variables were incorporated into a multivariate logistic regression-based nomogram for cataract risk prediction. The area under the receiver operating characteristic (ROC) curve (AUC) for cataract risk prediction was 0.917 (95% CI: 0.9067-0.9273) in the training cohort, and 0.9148 (95% CI: 0.8979-0.9316) in the validation cohort. The Hosmer-Lemeshow calibration curve demonstrated a good fit, indicating strong model calibration. Ten-fold cross-validation confirmed the logistic regression model's robust predictive performance and stability during internal validation. Decision curve analysis (DCA) demonstrated that the nomogram prediction model provided greater clinical benefit for predicting cataract risk when the patient's threshold probability ranged from 0.10 to 0.90. Conclusion: This study identified blood urea nitrogen (mmol/L), serum glucose (mmol/L), and erythrocyte folate (mmol/L) as significant risk factors for cataract. A risk prediction model was developed, demonstrating strong predictive accuracy and clinical utility, offering clinicians a reliable tool for early and effective diagnosis. Cataract development may be delayed by reducing levels of blood urea nitrogen, serum glucose, and erythrocyte folate through lifestyle improvements and dietary modifications.

Image Analysis-Based Machine Learning for the Diagnosis of Retinopathy of Prematurity: A Meta-analysis and Systematic Review.

TOPIC: To evaluate the performance of machine learning (ML) in the diagnosis of retinopathy of prematurity (ROP) and to assess whether it can be an effective automated diagnostic tool for clinical applications. CLINICAL RELEVANCE: Early detection of ROP is crucial for preventing tractional retinal detachment and blindness in preterm infants, which has significant clinical relevance. METHODS: Web of Science, PubMed, Embase, IEEE Xplore, and Cochrane Library were searched for published studies on image-based ML for diagnosis of ROP or classification of clinical subtypes from inception to October 1, 2022. The quality assessment tool for artificial intelligence-centered diagnostic test accuracy studies was used to determine the risk of bias (RoB) of the included original studies. A bivariate mixed effects model was used for quantitative analysis of the data, and the Deek's test was used for calculating publication bias. Quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Twenty-two studies were included in the systematic review; 4 studies had high or unclear RoB. In the area of indicator test items, only 2 studies had high or unclear RoB because they did not establish predefined thresholds. In the area of reference standards, 3 studies had high or unclear RoB. Regarding applicability, only 1 study was considered to have high or unclear applicability in terms of patient selection. The sensitivity and specificity of image-based ML for the diagnosis of ROP were 93% (95% confidence interval [CI]: 0.90-0.94) and 95% (95% CI: 0.94-0.97), respectively. The area under the receiver operating characteristic curve (AUC) was 0.98 (95% CI: 0.97-0.99). For the classification of clinical subtypes of ROP, the sensitivity and specificity were 93% (95% CI: 0.89-0.96) and 93% (95% CI: 0.89-0.95), respectively, and the AUC was 0.97 (95% CI: 0.96-0.98). The classification results were highly similar to those of clinical experts (Spearman's R = 0.879). CONCLUSIONS: Machine learning algorithms are no less accurate than human experts and hold considerable potential as automated diagnostic tools for ROP. However, given the quality and high heterogeneity of the available evidence, these algorithms should be considered as supplementary tools to assist clinicians in diagnosing ROP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A deep learning system for myopia onset prediction and intervention effectiveness evaluation in children.

The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p < 0.001) in both test sets. In an emulated randomized controlled trial (eRCT) on the Shanghai outdoor cohort (n = 3303) where DeepMyopia showed effectiveness in myopia prevention compared to NonCyc-based model, with an adjusted relative reduction (ARR) of -17.8%, 95% CI: -29.4%, -6.4%. DeepMyopia-assisted interventions attained quality-adjusted life years (QALYs) of 0.75 (95% CI: 0.53, 1.04) per person and avoided blindness years of 13.54 (95% CI: 9.57, 18.83) per 1 million persons compared to natural lifestyle with no active intervention. Our findings demonstrated DeepMyopia as a reliable and efficient AI-based decision support system for intervention guidance for children.

Prediction of outpatients with conjunctivitis in Xinjiang based on LSTM and GRU models.

BACKGROUND: Reasonable and accurate forecasting of outpatient visits helps hospital managers optimize the allocation of medical resources, facilitates fine hospital management, and is of great significance in improving hospital efficiency and treatment capacity. METHODS: Based on conjunctivitis outpatient data from the First Affiliated Hospital of Xinjiang Medical University Ophthalmology from 2017/1/1 to 2019/12/31, this paper built and evaluated Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU) models for outpatient visits prediction. RESULTS: In predicting the number of conjunctivitis visits over the next 31 days, the LSTM model had a root mean square error (RMSE) of 2.86 and a mean absolute error (MAE) of 2.39, the GRU model has an RMSE of 2.60 and an MAE of 1.99. CONCLUSIONS: The GRU method can better predict trends in hospital outpatient flow over time, thus providing decision support for medical staff and outpatient management.

Long-term effects of meteorological factors and extreme weather on daily outpatient visits for conjunctivitis from 2013 to 2020: a time-series study in Urumqi, China.

Conjunctivitis is a common multifactorial inflammatory ocular surface disease characterized by symptoms such as congestion, edema, and increased secretion of conjunctival tissue, and the potential effects of meteorological factors as well as extreme meteorological factors on conjunctivitis and their lagging effects have not been fully evaluated. We obtained the electronic case information of 59,731 outpatients with conjunctivitis from the Ophthalmology Department of the First Affiliated Hospital of Xinjiang Medical University (Urumqi, Xinjiang, China) for the period from January 1, 2013, to December 31, 2020. Meteorological data for daily mean temperature (°C), daily relative humidity (%), daily average wind speed (m/s), and atmospheric pressure (hPa) were obtained from the China Meteorological Data Sharing Service. The air pollutant data were obtained from 11 standard urban background fixed air quality monitors. A time-series analysis design and a quasi-Poisson generalized linear regression model combined with a distributed lagged nonlinear model (DLNM) were used to fit the effects of exposure to different meteorological factors and extreme weather on conjunctivitis outpatient visits. Subgroup analyses were performed on gender, age and season, and type of conjunctivitis. Univariate and multifactorial model results indicated that each 10-unit increase in mean temperature and relative humidity was associated with an increased risk of conjunctivitis outpatient visits, while each 10-unit increase in atmospheric pressure was associated with a decreased risk. The results of the extreme weather analysis suggested that extremely low levels of atmospheric pressure and relative humidity as well as extreme levels of temperature were associated with an increased risk of outpatient conjunctivitis visits, and extreme wind speeds were associated with a decreased risk. The results of the subgroup analysis suggested gender, age, and seasonal differences. We conducted the first large sample size time-series analysis in the large city furthest from the ocean in the world and confirmed for the first time that elevated mean temperature and extreme low levels of relative humidity in Urumqi were risk factors for local conjunctivitis outpatient visits, while elevated atmospheric pressure and extreme low levels of wind speed were protective factors, and there were lagged effects of temperature and atmospheric pressure. Multicenter studies with larger sample sizes are needed.

Short-term effect of meteorological factors and extreme weather events on daily outpatient visits for dry eye disease between 2013 and 2020: a time-series study in Urumqi, China.

Dry eye disease (DED) is a common disorder of tear secretion on the ocular surface caused by multiple factors with dry eyes as the main symptom, but until now studies focusing on relationship between local meteorological factors and ocular surface diseases in Urumqi are very limited. Besides, the effects of long-term and extreme meteorological factors on DED and the lag effect have not been fully evaluated. Electronic case information of 9970 DED outpatients from the Ophthalmology Department of the First Affiliated Hospital of Xinjiang Medical University (Urumqi, Xinjiang, China) between January 1, 2013, and December 31, 2020, was screened and analyzed. We used a time-series analysis design and a quasi-Poisson generalized linear regression model combined with a distributed lagged nonlinear model (DLNM) to fit the effects of exposure to different meteorological factors and extreme weather on DED outpatient visits. Subgroup analyses were further performed for gender, age, and season. The results showed that exposure to extremely low mean temperature (P1:RR = 1.18), atmospheric pressure (P1:RR = 1.11), and extremely high relative humidity (P99:RR = 1.35) were the risk factors, while extremely high atmospheric pressure (P90:RR = 0.883) and extremely low humidity (P10:RR = 0.856) appeared to have a positive effect on reduced risk of DED. Relative humidity exhibited a 1-day lag effect (RR = 1.06). Increased mean temperature positively affected female DED patients (RR = 0.761) with similar effects in the cold season (RR = 0.926). However, elevated relative humidity had a negative effect on female patients (RR = 1.14). We conducted the first large sample size time-series analysis study in this major city at the farthest distance from the ocean in the world and in northwest China, confirming the association of DED outpatient visits with the remaining three meteorological factors except wind speed in Urumqi, and a larger sample size multi-center epidemiological study with a longer duration is still needed.

Short-term exposure to air pollution and outpatient visits for conjunctivitis: a time-series analysis in Urumqi, China.

Conjunctivitis is an inflammatory disease of the conjunctival tissue caused by a variety of causes; despite the conjunctiva being directly exposed to the external atmospheric environment, the important role of air pollution is not fully evaluated, especially in areas with poor air quality undergoing rapid economic and industrial development. Information on 59,731 outpatient conjunctivitis visits from 1 January 2013 to 31 December 2020 was obtained from the Ophthalmology Department of the First Affiliated Hospital of Xinjiang Medical University (Urumqi, Xinjiang, China), and data on six air pollutants including particulate matter with a median aerometric diameter of less than 10 and 2.5 mm (PM10 and PM2.5, respectively), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) from eleven standard urban background fixed air quality monitors were also recorded. A time-series analysis design and a quasi-Poisson generalized linear regression model combined with a distributed lagged nonlinear model (DLNM) were used to fit the effect of exposure to air pollutants on the risk of conjunctivitis outpatient visits. Further subgroup analyses were conducted for gender, age, and season, as well as the type of conjunctivitis. Single and multi-pollutant models showed that exposure to PM2.5, PM10, NO2, CO, and O3 was associated with increased risk of outpatient conjunctivitis visits on the lag 0 day and various other lag days. Variations in the effect estimates on direction and magnitude were found in different subgroup analyses. We conducted the first time-series analysis with the longest duration as well as the largest sample size in Northwest China, which provides evidence that outpatient conjunctivitis visits is significantly associated with air pollution in Urumqi, China. Meanwhile, our results demonstrate the effectiveness of SO2 reduction in reducing the risk of outpatient conjunctivitis visits in the Urumqi region and reaffirm the need to implement special air pollution control measures.

DNA Polymorphism of the LOXL1 Promoter Region in Exfoliation Syndrome in Uygur Individuals in XinJiang, China.

Purpose: On the basis of our previously reported work, the association of lysyl oxidase-like 1 (LOXL1) promoter region gene polymorphism with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) in Uygur individuals was examined. Methods: This was a case-control association trial. A total of 242 unrelated XFS/G and 310 control cases were assessed. The genotypes of 6 single nucleotide polymorphisms (SNPs) of the LOXL1 promoter (rs4886761, rs4886467, rs4558370, rs4461027, rs16958477, and rs12914489) were examined via direct sequencing. Results: Each of the above SNPs had significant associations with XFS and XFG. The T allele of rs4886761 (OR (95% CI): 2.204 (1.711-2.838)), G of rs4886467 (OR (95% CI): 1.946 (1.513-2.503)), T of rs4461027 (OR (95% CI): 2.26 (1.773-2.881)), A of rs16958477 (OR (95% CI): 1.792 (1.399-2.297)), and G of rs12914489 (OR (95% CI): 1.103 (0.631-1.929)) independently predicted XFS/G. The genotypes TT and CC of rs4886761 (OR (95% CI): 5.655 (3.000-10.660) and 2.241 (1.473-3.408), respectively), TT and GG of rs4886467 (OR (95% CI): 4.026 (2.162-7.497) and 1.631 (1.08-2.463), respectively), CC and TT of rs4461027 (OR (95% CI): 5.245 (3.037-9.058) and 2.210 (1.37-3.564), respectively), CC and AA of rs16958477 (OR (95% CI): 3.530 (1.968-6.334) and 1.740 (1.145-2.646), respectively) also independently predicted XFS/G. The GGT and GTG haplotypes of rs12914489, rs4886467, and rs4558370 and TC and CT of rs4461027 and rs4886761 showed significant associations with XFS/G. Conclusions: These results confirmed LOXL1 as a susceptibility gene in XFS/XFG among Uygur individuals. The new SNPs of rs4886761, rs4886467, rs4461027, and rs16958477 polymorphisms are involved in the pathogenetic mechanism of XFS/G.

Comparison of wavefront aberrations in the object and image spaces using wide-field individual eye models.

Wavefront aberrations in the image space are critical for visual perception, though the clinical available instruments usually give the wavefront aberrations in the object space. This study aims to compare the aberrations in the object and image spaces. With the measured wavefront aberrations over the horizontal and vertical ±15° visual fields, the in-going and out-going wide-field individual myopic eye models were constructed to obtain the wavefront aberrations in the object and image spaces of the same eye over ±45° horizontal and vertical visual fields. The average differences in the mean sphere and astigmatism were below 0.25 D between the object and image spaces over the horizontal and vertical ±45° visual fields under 3 mm and 6 mm pupil diameter. The wavefront aberrations in the object space are a proper representation of the aberrations in the image space at least for horizontal visual fields ranging from -35°to +35° and vertical visual fields ranging from -15°to +15°.

Decreased 1,25-Dihydroxyvitamin D3 level is involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease.

PURPOSE: 1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] has recently been found to be involved in the development of autoimmune diseases. This study was to investigate the expression and potential role of 1,25(OH)(2)D(3) in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. METHODS: Blood samples were obtained from VKH patients and healthy individuals. Serum 1,25(OH)(2)D(3) levels were measured using ELISA. Peripheral blood mononuclear cells (PBMCs) or cluster of differentiation (CD) 4(+) T cells were cultured with or without 1,25(OH)(2)D(3) in the presence of anti-CD3 and anti-CD28 for the measurement of cell proliferation and cytokines. The cell proliferation was detected using the Cell Counting Kit. The levels of interleukin (IL)-17 and interferon (IFN)-γ levels in the supernatants of PBMCs or CD4(+) T cells were detected by ELISA. RESULTS: 1,25(OH)(2)D(3) was significantly decreased in the serum of active VKH patients as compared with inactive VKH patients and controls. It significantly inhibited PBMCs proliferation and CD4(+) T cell proliferation. It was also able to significantly inhibit the production of IL-17 and IFN-γ by both PBMCs and CD4(+) T cells from VKH patients and controls. CONCLUSIONS: These findings suggest that decreased expression of 1,25(OH)(2)D(3) may be involved in the development of VKH disease. 1,25(OH)(2)D(3) may be potentially used in the treatment of this disease.

Changes in Corneal Morphology with Age in Asian Population: A Multicenter Study of 30,618 Cases.

INTRODUCTION: To evaluate normal reference ranges for corneal morphological parameters and investigate age-related changes in these parameters in Asian subjects with healthy eyes in order to provide reference data for preoperative evaluation of corneal refractive surgery and the early differential diagnosis of subclinical and asymptomatic keratoconus. METHODS: This cross-sectional, multicenter, observational study was conducted in five provinces of China, from January 2014 through October 2019. It is a retrospective analysis. Examiner-blinded clinical measurements were performed after stratification of the subjects into the following age groups: < 18, 18-30, 31-40, 41-50. We evaluated 30,618 healthy eyes of Chinese subjects who exhibited a normal corneal morphology, had no history of eye surgery or trauma, stopped wearing soft contact lenses for at least 2 weeks (rigid contact lenses for at least 4 weeks), and underwent topographic studies for both eyes on the same day. RESULTS: While the anterior and posterior corneal curvatures (K1 and K2) increased with age, corneal astigmatism of the anterior and posterior surfaces (ΔK) and central, minimum, and overall corneal thicknesses decreased with age. Age-related decrease of the overall corneal thickness was more obvious toward the periphery. The anterior and posterior corneal surface heights exhibited a decrease and an increase, respectively. Both index of height asymmetry (IHA) and index of vertical asymmetry (IVA) exhibited an increase with age. CONCLUSIONS: The cornea exhibits overall thinning with age and gradually changes from a flat ellipse to an elongated ellipse in Asian individuals with healthy eyes. However, the anterior and posterior surfaces become smoother with age. Owing to the very large number of cases, these small differences are statistically significant. The results obtained are consistent with the hypothesis that a normal cornea seems to withstand quite well the effect of IOP, external pressures, and the natural cross-linking.

Associations Between Regional Environment and Cornea-Related Morphology of the Eye in Young Adults: A Large-Scale Multicenter Cross-Sectional Study.

Purpose: To investigate environmental factors associated with corneal morphologic changes. Methods: A cross-sectional study was conducted, which enrolled adults of the Han ethnicity aged 18 to 44 years from 20 cities. The cornea-related morphology was measured using an ocular anterior segment analysis system. The geographic indexes of each city and meteorological indexes of daily city-level data from the past 40 years (1980-2019) were obtained. Correlation analyses at the city level and multilevel model analyses at the eye level were performed. Results: In total, 114,067 eyes were used for analysis. In the correlation analyses at the city level, the corneal thickness was positively correlated with the mean values of precipitation (highest r [correlation coefficient]: >0.700), temperature, and relative humidity (RH), as well as the amount of annual variation in precipitation (r: 0.548 to 0.721), and negatively correlated with the mean daily difference in the temperature (DIF T), duration of sunshine, and variance in RH (r: -0.694 to 0.495). In contrast, the anterior chamber (AC) volume was negatively correlated with the mean values of precipitation, temperature, RH, and the amount of annual variation in precipitation (r: -0.672 to -0.448), and positively associated with the mean DIF T (r = 0.570) and variance in temperature (r = 0.507). In total 19,988 eyes were analyzed at the eye level. After adjusting for age, precipitation was the major explanatory factor among the environmental factors for the variability in corneal thickness and AC volume. Conclusions: Individuals who were raised in warm and wet environments had thicker corneas and smaller AC volumes than those from cold and dry ambient environments. Our findings demonstrate the role of local environmental factors in corneal-related morphology.

Distribution and Trends in Corneal Thickness Parameters in a Large Population-Based Multicenter Study of Young Chinese Adults.

Purpose: The purpose of this study was to characterize corneal thickness from multiple regions and determine accurate reference values in young adults for diagnosis and treatment. Methods: This cross-sectional observational study was conducted from January 2008 through October 2016 using examiner-blinded clinical measurements and included 37,375 healthy eyes from young adults who exhibited normal corneal morphology, had no history of eye surgery or trauma, had stopped wearing soft contact lenses for ≥2 weeks (rigid contact lenses for ≥4 weeks), and had undergone topographies of both eyes on same day. Keratoconus and subclinical keratoconus were excluded. This multicenter study was conducted in four provinces of China: Tianjin, Shandong, Hubei, and Xinjiang. Results: Central corneal, corneal vertex, and thinnest corneal thicknesses were higher in eyes from Hubei than other provinces. The left eye was thicker than the right in patients from Shandong, Tianjin, and Hubei, but not Xinjiang. Overall corneal thickness was higher in eyes from Hubei than from other provinces. Changing trend of the whole-cornea thickness in eyes from Xinjiang differed from eyes from other provinces. Trends in maximum and minimum axial for change of corneal thickness were similar between eyes from Hubei and Xinjiang and between Shandong and Tianjin. Conclusions: Corneal thickness differs among eyes from different regions. Corneal thickness parameters are influenced by ethnicity and geographical location, as increasing proximity to the equator was related to increasing corneal thickness. Design of refractive surgery and diagnosis of related diseases in patients of a certain area should be based on reference values from its population.

FGFR1OP tagSNP but not CCR6 polymorphisms are associated with Vogt-Koyanagi-Harada syndrome in Chinese Han.

BACKGROUND: Polymorphisms of the CC chemokine receptor 6 (CCR6) and FGFR10P tagSNP (locus close to CCR6) at 6q27 have recently been reported to be associated with the susceptibility to several immune-related diseases. This study was designed to determine the association of CCR6 and FGFR10P (tag)SNPs with Vogt-Koyanagi-Harada (VKH) syndrome, an autoimmune disease directed against melanocytes, in two independent Chinese Han populations. METHODOLOGY/PRINCIPAL FINDINGS: A total of 601 VKH patients and 725 healthy controls from two Chinese Han populations were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. Hardy-Weinberg equilibrium was tested using the χ(2) test. Genotype frequencies were estimated by direct counting. Allele and genotype frequencies were compared between patients and controls using the χ(2) test. The frequency of the A allele of rs2301436 was significantly higher both in Cohort 1 and Cohort 2 as compared with two separate controls (P = 0.044; P = 0.049, respectively). The significance was lost after Bonferroni correction in both cohorts (Pc = 0.516; Pc = 0.392, respectively). The frequency of the A allele was significantly higher in the combined patient group as compared with all controls before and after Bonferroni correction (P = 0.005, Pc = 0.025). The genotype and allele frequencies of rs3093024, rs6902119, rs3093023 and rs968334 were not different between patients with VKH and healthy controls based on analysis either for both cohorts or for the patients and controls in total. Analysis according to extra ocular clinical findings including headache, alopecia and poliosis, vitiligo and tinnitus did not show any association of the five polymorphisms with these parameters. CONCLUSION: These results suggest that the rs2301436 tagSNP of FGFR10P is positively associated with susceptibility to VKH syndrome in the tested Chinese Han populations. No association was found for the tested CCR6 SNPs.