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Primary diabetes care and diabetic retinopathy (DR) screening persist as major public health challenges due to a shortage of trained primary care physicians (PCPs), particularly in low-resource settings. Here, to bridge the gaps, we developed an integrated image–language system (DeepDR-LLM), combining a large language model (LLM module) and image-based deep learning (DeepDR-Transformer), to provide individualized diabetes management recommendations to PCPs. In a retrospective evaluation, the LLM module demonstrated comparable performance to PCPs and endocrinology residents when tested in English and outperformed PCPs and had comparable performance to endocrinology residents in Chinese. For identifying referable DR, the average PCP’s accuracy was 81.0% unassisted and 92.3% assisted by DeepDR-Transformer. Furthermore, we performed a single-center real-world prospective study, deploying DeepDR-LLM. We compared diabetes management adherence of patients under the unassisted PCP arm (n= 397) with those under the PCP+DeepDR-LLM arm (n= 372). Patients with newly diagnosed diabetes in the PCP+DeepDR-LLM arm showed better self-management behaviors throughout follow-up (P< 0.05). For patients with referral DR, those in the PCP+DeepDR-LLM arm were more likely to adhere to DR referrals (P< 0.01). Additionally, DeepDR-LLM deployment improved the quality and empathy level of management recommendations. Given its multifaceted performance, DeepDR-LLM holds promise as a digital solution for enhancing primary diabetes care and DR screening.

IMPORTANCE: Effects of genetic variants on primary angle-closure disease remained uncertain. OBJECTIVE: To systematically review the associations of common single-nucleotide variants (SNVs) and rare coding variants with primary angle-closure disease, its subtypes (including primary angle-closure glaucoma, primary angle-closure suspect, and primary angle-closure) and progression. DATA SOURCES: Eligible studies from PubMed, Embase, and Web of Science were retrieved up to April 3, 2023. SNV information was extracted from eligible reports and 2 genome-wide association studies summary statistics, UK BioBank and FinnGen. STUDY SELECTION: Studies providing analyzable genotype or allele data in a case-control design for primary angle-closure disease association and longitudinal case-only design for primary angle-closure disease progression. DATA EXTRACTION AND SYNTHESIS: PRISMA guidelines were used for literature screening and the Newcastle Ottawa Scale for data quality assessment. Pooled effect size with 95% CIs of SNV associations were calculated using fixed- or random-effect models according to I2 statistics. MAIN OUTCOMES AND MEASURES: SNVs reported in 2 or more studies were meta-analyzed to generate pooled odds ratios and P values. Common and rare coding variants from single reports were summarized. RESULTS: Sixty-nine citations were eligible for meta-analysis on overall primary angle-closure disease, involving 206 SNVs in 64 genes or loci. Seventeen SNVs in 15 genes or loci showed associations with primary angle-closure disease, and 15 SNVs in 13 genes or loci showed associations with primary angle-closure glaucoma. Two SNVs, ABCA1 rs2422493 and ZNRF3 rs3178915, were associated only with primary angle-closure disease. Two SNVs, PCMTD1-ST18 rs1015213 and COL11A1 rs3753841, were associated with primary angle-closure suspect, and 1 SNV, MMP9 rs3918249, was associated with primary angle-closure. This systematic review and meta-analysis newly confirmed 7 genes or loci associated with primary angle-closure glaucoma: ATOH7, CALCRL, FBN1, IL6, LOXL1, MMP19, and VAV3. Common and rare coding variants in 16 genes or loci that have been associated with primary angle-closure disease were cataloged. Stratification analysis revealed different primary angle-closure disease–associated genes in different ethnic populations. Only 1 study regarding the genetic association of primary angle-closure glaucoma progression was identified. CONCLUSIONS AND RELEVANCE: This study revealed the genetic complexity of primary angle-closure disease, involving common SNVs and rare coding variants in more than 30 genes or loci, with ethnic and phenotypic diversities. Further replication, genotype-phenotype correlation, and pathway analyses are warranted.

To compare the anatomic and functional outcomes of half-dose photodynamic therapy (PDT) and yellow 577-nm subthreshold micropulse laser (SMLT) in treating patients with chronic central serous chorioretinopathy (CSCR).

AimsTo compare and rank the myopia control effects of different light wavelengths in children using a systematic review and Bayesian network meta-analysis (Bayesian NMA).MethodsThe review protocol was registered with PROSPERO. We searched PubMed, EMBASE and MEDLINE for relevant clinical and animal studies published as of 2 February 2023. We included studies comparing red, violet or full-spectrum light with controls. Data extracted included descriptive statistics and study outcomes (axial length (AL) elongation and progression of spherical equivalent (SE) refraction). After quality assessment, estimates of treatment effect outcomes (mean differences (MDs) and 95% CIs) were first pooled for the animal and clinical studies in a traditional meta-analysis. To compare and rank the different light wavelengths, the Bayesian NMA was then conducted for all the included clinical studies (12 studies) and separately for only randomised controlled trials (8 studies). MDs, 95% credible intervals (CrIs) and ranks of the various light wavelengths were estimated in the Bayesian NMA.ResultsWhen all clinical studies were included in the Bayesian NMA (12 studies), only red-light significantly slowed AL elongation, MD (95% CrI), −0.38 mm (−0.59 mm to −0.16 mm)/year and SE refraction progression, 0.72D (0.35D to 1.10D)/year compared with controls. It remained the only significant intervention when effect sizes from only RCTs (eight studies) were separately combined, (−0.28 mm (−0.40 mm to −0.15 mm)/year and 0.57D (0.22D to 0.92D)/year, for AL and SE refraction, respectively).ConclusionMyopia control efficacy varied among different wavelengths of light, with red light ranked as the most effective.PROSPERO registration numberClinical studies: CRD42022368998; animal studies: CRD42022368671.

In this study, we developed an efficient method for the synthesis of aryl amides from sodium thiosulfate pentahydrate, organic anhydrides, and aryl azides. Sodium thiosulfate may be used as the sulfur source, which reacts with anhydrides to generate acyl-Bunte salt; this salt reacts with aryl azides viathe in situgeneration of thiocarboxylate. Using our method, we successfully synthesized a key bioactive compound. The advantages of one-pot two-step reactions include operational simplicity, structurally diverse products with favorable yields, use of less toxic odorless reagents, and easy applicability to large-scale operations.

Objectives: To evaluate result of early pars plana vitrectomy (PPV) within 24 hours of presentation for acute postoperative endophthalmitis after cataract operation, and to determine factors that predict visual outcome. Methods: Consecutive patients who developed acute postoperative endophthalmitis within 6 weeks after cataract operation were reviewed. Patients were divided into two groups for analysis: (1) those receiving PPV within 24 hours of presentation (early PPV group), and (2) those receiving initial intravitreal antibiotics only without PPV within 24 hours of presentation (IVA group). Results: Out of 41,411 cataract operations, 22 eyes developed acute postoperative endophthalmitis. Presenting VA was hand-movement or worse in 72.7%. The most common organisms were Staphylococcus (40.9%), Streptococcus (13.6%) and Enterococcus (13.6%). 22.7% of eyes had good final VA ≥ 20/30 and 27.3% had poor final VA &lt; 20/400. Early PPV group had significantly lower rate of requiring additional treatments to control infection (25% versus 80%, P= 0.030), higher rate of retinal detachment (25% versus 0%, P= 0.221) and similar final logMAR VA (1.08 ± 1.08 versus 0.80 ± 0.80, P= 0.489) compared to IVA. Multivariate linear regression analysis showed that worse final VA was significantly associated with Streptococcus (ß= 1.92, P= 0.007) and retinal detachment (ß= 1.72, P= 0.005) but not with early PPV (P= 0.225). Conclusion: Early PPV was superior to initial intravitreal antibiotics alone as it required fewer additional treatments to control infection. Visual outcome was similar between early PPV and initial intravitreal antibiotics alone despite high number of poor presenting VA of light-perception in early PPV group. Streptococcal infection and retinal detachment were major poor prognostic factors for vision.

Background: To compare the prevalence of refractive (RA), corneal (CA), and internal astigmatism (IA) in Hong Kong children and adults and evaluate the role of IA in compensating for total astigmatism and its relations to myopic traits. Methods: The Hong Kong Children Eye Study is a population-based cross-sectional study. Totally 3704 school children (mean age 7.5 ± 1.0 years) and 5577 adults (mean age 41.1 ± 7.5 years), who were their parents, were recruited. Cycloplegic and non-cycloplegic refractive cylinders were obtained from children and adults, respectively. Spearman correlation was applied to detect associations between astigmatism, ocular biometrics, refraction, and lens power. Astigmatism compensation factor (CF) was derived from the power vector analysis J0 and J45. Results: The prevalence of RA (≤−1.0 D), CA (≥+1.0 D) and IA (≥+1.0 D) was 21.9%, 63.9%, and 9.9% in children, and 30.9%, 39.5%, and 23.7% in adults respectively. The mean RA, CA and IA values in children and adults were −0.69 ± 0.66 D, +1.14 ± 0.61 D, +0.62 ± 0.32 D, and −0.80 ± 0.74 D, +0.97 ± 0.69 D, and +0.76 ± 0.43 D, respectively. In adults and children, IA was negatively correlated with axial length (p&lt; 0.0001), but positively correlated with spherical values and equivalent (p&lt; 0.0001), suggesting an association of astigmatism with myopic traits. A greater proportion of children exhibited compensation by IA than adults in J0 (86.6% vs. 66.0%, p&lt; 0.0001) and J45 components (55.5% vs. 41.7%, p&lt; 0.0001). Conclusions: Chinese children in Hong Kong exhibit a higher prevalence of RA and CA than in other cities. Children displayed a greater compensation by IA than adults, suggesting an age-related attenuation of IA compensation. IA is associated with myopic traits.

Many complex forms of retinal diseases are common and pan-ethnic in occurrence. Among them, neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, and central serous choroid retinopathy involve both choroidopathy and neovascularization with multifactorial etiology. They are sight-threatening and potentially blinding. Early treatment is crucial to prevent disease progression. To understand their genetic basis, candidate gene mutational and association analyses, linkage analysis, genome-wide association studies, transcriptome analysis, next-generation sequencing, which includes targeted deep sequencing, whole-exome sequencing, and whole genome sequencing have been conducted. Advanced genomic technologies have led to the identification of many associated genes. But their etiologies are attributed to complicated interactions of multiple genetic and environmental risk factors. Onset and progression of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy are affected by aging, smoking, lifestyle, and variants in over 30 genes. Although some genetic associations have been confirmed and validated, individual genes or polygenic risk markers of clinical value have not been established. The genetic architectures of all these complex retinal diseases that involve sequence variant quantitative trait loci have not been fully delineated. Recently artificial intelligence is making an impact in the collection and advanced analysis of genetic, investigative, and lifestyle data for the establishment of predictive factors for the risk of disease onset, progression, and prognosis. This will contribute to individualized precision medicine for the management of complex retinal diseases.

PurposeAssociation of SIX1-SIX6variants with peripapillary retinal nerve fibre layer (p-RNFL) thickness had been reported in adults. This study aimed to investigate these associations in children, with further explorations by spatial, age and sex stratifications.Methods2878 school children aged between 6 and 9 years were enrolled from the Hong Kong Children Eye Study. Three single-nucleotide polymorphisms (SNPs) at the SIX1-SIX6locus were genotyped. The association of each SNP with p-RNFL thickness (including global and sectoral thickness) were evaluated using multiple linear regression.ResultsSNPs rs33912345 (p=7.7×10−4) and rs10483727 (p=0.0013) showed significant associations with temporal-inferior p-RNFL thickness. The C allele of rs33912345 was associated with a thinner temporal-inferior p-RNFL by an average of 2.44 µm, while rs10483727-T was associated with a thinner temporal-inferior p-RNFL by 2.32 µm. The association with temporal-inferior p-RNFL was the strongest in the 8–9 year-old group for rs33912345 (p=5.2×10−4) and rs10483727 (p=3.3×10−4). Both SNPs were significantly associated with temporal-inferior p-RNFL thickness in boys (p<0.0017), but not in girls (p>0.05). In contrast, rs12436579-C (β=1.66; p=0.0059), but not rs33912345-C (β=1.31; p=0.052) or rs10483727-T (β=1.19; p=0.078), was nominally associated with a thicker nasal-inferior p-RNFL.ConclusionsBoth rs33912345 and rs10483727 at SIX1-SIX6were associated with p-RNFL thickness in children, especially at the temporal-inferior sector, with age-dependent and sex-specific effects. SNP rs12436579 was associated with nasal-inferior p-RNFL thickness. Our findings suggested a role of SIX1-SIX6in RNFL variation during neural retina development in childhood.

AimsTo explore the prevalence and risk factors for myopia and uncorrected myopia in schoolchildren in southern China.MethodsThe government-led Shantou Myopia Study was conducted from September 2020 to June 2021. Non-cycloplegic refraction was performed. Uncorrected visual acuity (UCVA) was measured along with presenting visual acuity if participants wore spectacles. Spherical equivalent refraction (SER) is defined as the spherical dioptres added to half of the cylindrical dioptres. Myopia is defined as SER <−0.50 dioptre with UCVA of <20/20 in at least one eye.ResultsThis study enrolled 724 828 schoolchildren (77.8% of all schoolchildren in Shantou) from 901 schools. Data from 721 032 schoolchildren (99.5%) were analysed (mean age 11.53±3.13 years, 6–20 years, 373 230 boys and 347 802 girls). Among them, 373 459 (51.8%) had myopia: 37.1% of 465 696 children in primary schools, 75.4% of 170 164 children in junior high schools and 84.8% of 85 172 children in senior high schools. The prevalence of myopia increases non-linearly with age. Older age, female and urban living environment were independently associated with myopia prevalence and myopic SER. Among the 373 459 children with myopia, 60.0% had no refractive correction: 74.9%, 53.9% and 35.5% in primary, junior high and senior high schools, respectively.ConclusionThe overall prevalence of myopia among schoolchildren in Shantou was 51.8%, higher than the national average in China. The proportion of uncorrected myopia is high, especially in primary schools. Our results indicate the need for public education on eye care among schoolchildren even in a municipal city.

The objective of this paper is to shed light on the current landscape of genotyping practices, phenotyping practices and availability of essential vision rehabilitation management for inherited retinal diseases (IRD) in the Asia-Pacific (APAC) Region.

BackgroundThe impacts of social restrictions for COVID-19 on children’s vision and lifestyle remain unknown.AimsTo investigate myopia incidence, spherical equivalent refraction (SER) and lifestyle changes among schoolchildren during the COVID-19 pandemic.MethodsTwo separate longitudinal cohorts of children aged 6–8 years in Hong Kong were included. The COVID-19 cohort was recruited at the beginning of the COVID-19 outbreak, whereas the pre-COVID-19 cohort was recruited before the COVID-19 pandemic. All children received ocular examinations, and answered a standardised questionnaire relating to their lifestyle, including time spent on outdoor activities and near work, both at baseline and at follow-up visits.ResultsA total of 1793 subjects were recruited, of whom 709 children comprised the COVID-19 cohort with 7.89±2.30 months of follow-up, and 1084 children comprised the pre-COVID-19 cohort with 37.54±3.12 months of follow-up. The overall incidence was 19.44% in the COVID-19 cohort, and 36.57% in pre-COVID-19 cohort. During the COVID-19 pandemic, the change in SER and axial length was –0.50±0.51 D and 0.29±0.35 mm, respectively; the time spent on outdoor activities decreased from 1.27±1.12 to 0.41±0.90 hours/day (p<0.001), while screen time increased from 2.45±2.32 to 6.89±4.42 hours/day (p<0.001).ConclusionsWe showed a potential increase in myopia incidence, significant decrease in outdoor time and increase in screen time among schoolchildren in Hong Kong during the COVID-19 pandemic. Our results serve to warn eye care professionals, and also policy makers, educators and parents, that collective efforts are needed to prevent childhood myopia—a potential public health crisis as a result of COVID-19.

AimsTo identify single-nucleotide polymorphisms (SNPs) associated with central serous chorioretinopathy (CSCR) by a systematic review and meta-analysis, and to compare the association profiles between CSCR, neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV).MethodsWe searched the EMBASE, PubMed and Web of Science for genetic studies of CSCR from the starting dates of the databases to 12 September 2020. We then performed meta-analyses on all SNPs reported by more than two studies and calculated the pooled OR and 95% CIs. We also conducted sensitivity analysis and adopted the funnel plot to assess potential publication bias.ResultsTotally 415 publications were reviewed, among them 10 were eligible for meta-analysis. We found 10 SNPs that have been reported at least twice. Meta-analysis and sensitivity analysis confirmed significant associations between CSCR and six SNPs in three genes, namely age-related maculopathy susceptibility 2 (ARMS2) (rs10490924, OR=1.37; p=0.00064), complement factor H (CFH) (rs800292, OR=1.44; p=7.80×10−5; rs1061170, OR=1.34; p=0.0028; rs1329428, OR=1.40; p=0.012; and rs2284664, OR=1.36; p=0.0089) and tumour necrosis factor receptor superfamily, member 10a (TNFRSF10A) (rs13278062, OR=1.34; p=1.44×10−15). Among them, only TNFRSF10Ars13278062 showed the same trend of effect on CSCR, nAMD and PCV, while the SNPs in ARMS2and CFHshowed opposite trends in the SNP associations.ConclusionsThis study confirmed the associations of ARMS2, CFHand TNFRSF10Awith CSCR, and revealed that ARMS2, CFHand TNFRSF10Amay affect different phenotypic expressions of CSCR, nAMD and PCV.

Objective: To explore the role and underlying mechanism of GW842166X on osteoarthritis and osteoarthritis-associated abnormal catabolism. Methods: The extracted mouse chondrocytes were treated with GW842166X followed by lipopolysaccharide (LPS). The chondrocytes were divided into the control group, LPS group, LPS+50 nmol/L GW842166X group, and LPS+100 nmol/L GW842166X group. The cytotoxicity of GW842166X was tested using the CCK-8 assay. Western blot, RT-qPCR, and ELISA were applied to evaluate the expression of the inflammatory biomarkers in mouse chondrocytes. The expression of extracellular matrix molecules was detected by the Western blot, RT-qPCR, and immunofluorescence. Additionally, the activity of NF-κB was checked by the Western blot and immunofluorescence. The mouse Hulth models were generated to examine the in vivoeffects of GW842166X on osteoarthritis. Hematoxylin and eosin staining, safranin O/fast green staining, and immunohistochemistry were applied to detect the histological changes. Results: GW842166X below 200 µmol/L had no cytotoxicity on the mouse chondrocytes. LPS-induced high expression of TGF-β1, IL-10, TNF-α, and IL-6 was significantly reduced by GW842166X. In addition, GW842166X upregulated the expression of aggrecan and collagen type III, which was downregulated after the LPS stimulation. The upregulated expression of ADAMTS-5 and MMP-13 by LPS stimulation was dropped in response to the GW842166X treatment. Furthermore, LPS decreased the IκBα expression in the cytoplasm and increased the nuclear p65 expression. However, these changes were reversed by the GW842166X pretreatment. Moreover, the damages in the knees caused by the Hulth surgery in mice were restored by GW842166X. Conclusion: GW842166X impeded the LPS-mediated catabolism in mouse chondrocytes, thereby inhibiting the progression of osteoarthritis.

To evaluate the associations of the TIE2gene with diabetic retinopathy (DR) and diabetic macular edema (DME).

PurposeThe purpose of this study was to investigate the signal changes in choriocapillaris flow deficits and choroidal thickness changes using swept-source optical coherence tomography angiography (OCTA) following different treatments.DesignA double-blind, randomised controlled trial.MethodsPatients with unilateral chronic central serous chorioretinopathy (CSC) were randomised to receive subthreshold micropulse laser therapy (MLT) or half-dose photodynamic therapy (PDT). Choroidal thickness and choriocapillaris flow deficit signals were investigated.ResultsEighteen patients were randomised into the MLT group and 15 patients into the PDT group. Areas with flow deficit signals were identified in all baseline OCTA images of the choriocapillaris, with mean areas of 0.420 and 0.465 mm2in the MLT and PDT groups, respectively. These flow deficit signal areas were significantly reduced at 6 months (p=0.011) in the MLT group and at 3 months (p=0.008) in the PDT group. Patients from the PDT group were shown to have smaller flow deficit areas than patients from the MLT group at all time points after treatment (p=0.001, analyses of variance). The mean choroidal volume of the fovea showed a significant reduction at 1 month (p=0.003), 3 months (p=0.199) and 6 months (p=0.006) in the PDT group.ConclusionThe flow deficit areas identified in the choriocapillaris layer may suggest possible relative choroidal ischaemia. With measurement of choroidal volume reduction and faster rates of flow deficit area change, PDT has a stronger effect than MLT in promoting choriocapillaris recovery.

AimsTo assess the association of single-nucleotide polymorphisms (SNPs) with myopia progression for polygenic risk prediction in children.MethodsSix SNPs (ZC3H11Brs4373767, ZFHX1Brs13382811, KCNQ5rs7744813, METrs2073560, SNTB1rs7839488 and GJD2rs524952) were analysed in 1043 school children, who completed 3-year follow-up, using TaqMan genotyping assays. SNP associations with progression in spherical equivalent (SE) were analysed by logistic regression. Polygenic risk scores (PRS) were applied for computing the sum of the risk alleles of multiple SNPs corresponding to myopia progression, weighted by the effect sizes of corresponding SNPs.ResultsGJD2rs524952 showed significant association with fast progression (OR=1.32, 95% CI 1.10 to 1.59; p=0.003) and KCNQ5rs7744813 had nominal association (OR=1.32, 95% CI 1.04 to 1.67; p=0.02). In quantitative traits locus analysis, GJD2rs524952 and KCNQ5rs7744813 were associated with progression in SE (β=−0.038 D/year, p=0.008 and β=−0.042 D/year, p=0.02) and axial elongation (β=0.016 mm/year, p=0.01 and β=0.017 mm/year, p=0.027). ZFHX1Brs13382811 also showed nominal association with faster progression in SE (β=−0.041 D/year, p=0.02). PRS analysis showed that children with the highest PRS defined by rs13382811, rs7744813 and rs524952 had a 2.26-fold of increased risk of fast myopia progression (p=4.61×10−5). PRS was also significantly associated with SE progression (R2=1.6%, p=3.15×10−5) and axial elongation (R2=1.2%, p=2.6×10−4).ConclusionsIn this study, multi-tiered evidence suggested SNPs in ZFHX1B, KCNQ5and GJD2as risk factors for myopia progression in children. Additional attention and appropriate interventions should be given for myopic children with high-risk PRS as defined by GJD2rs524952, KCNQ5rs7744813 and ZFHX1Brs13382811.

AimsTo determine the prevalence and predictors of myopic macular degeneration (MMD) in a consortium of Asian studies.MethodsIndividual-level data from 19 885 participants from four population-based studies, and 1379 highly myopic participants (defined as axial length (AL) >26.0 mm) from three clinic-based/school-based studies of the Asian Eye Epidemiology Consortium were pooled. MMD was graded from fundus photographs following the meta-analysis for pathologic myopia classification and defined as the presence of diffuse choroidal atrophy, patchy chorioretinal atrophy, macular atrophy, with or without ‘plus’ lesion (lacquer crack, choroidal neovascularisation or Fuchs’ spot). Area under the curve (AUC) evaluation for predictors was performed for the population-based studies.ResultsThe prevalence of MMD was 0.4%, 0.5%, 1.5% and 5.2% among Asians in rural India, Beijing, Russia and Singapore, respectively. In the population-based studies, older age (per year; OR=1.13), female (OR=2.0), spherical equivalent (SE; per negative diopter; OR=1.7), longer AL (per mm; OR=3.1) and lower education (OR=1.9) were associated with MMD after multivariable adjustment (all p<0.001). Similarly, in the clinic-based/school-based studies, older age (OR=1.07; p<0.001), female (OR=2.1; p<0.001), longer AL (OR=2.1; p<0.001) and lower education (OR=1.7; p=0.005) were associated with MMD after multivariable adjustment. SE had the highest AUC of 0.92, followed by AL (AUC=0.87). The combination of SE, age, education and gender had a marginally higher AUC (0.94).ConclusionIn this pooled analysis of multiple Asian studies, older age, female, lower education, greater myopia severity and longer AL were risk factors of MMD, and myopic SE was the strongest single predictor of MMD.

ObjectiveTo investigate the associations of multiple single-nucleotide polymorphisms (SNPs) with the severities and endophenotypes of myopia in children.MethodsA total of 3300 children aged 5–10 years were recruited: 137 moderate and high myopia (SE≤−3.0D), 670 mild myopia (−3.0D−0.5D). 13 SNPs in 13 genes/loci were selected for genotyping in all subjects using TaqMan assays. Associations between each SNP with myopia severities and ocular traits (spherical equivalent (SE), axial length (AL) and corneal radius (CR)) were analysed.ResultsWhen compared with controls, SNPs ZC3H11Brs4373767 (OR=1.15, p=0.038), BICC1rs7084402 (OR=1.18, p=0.005) and GJD2rs524952 (OR=1.14, p=0.025) showed nominal associations with overall myopia. ZC3H11Brs4373767 and BICC1rs7084402 showed stronger associations with moderate and high myopia (rs4373767: OR=1.42, p=0.018; rs7084402: OR=1.33, p=0.025), while GJD2rs524952 had a stronger association with mild myopia (OR=1.14, p=0.025). GJD2rs524952 also showed a difference between emmetropia and hyperopia (p=0.018). In quantitative trait locus analysis, ZC3H11Brs4373767, KCNQ5rs7744813 and GJD2rs524952 were correlated with both myopic SE (β=−0.09, p=0.03; β=−0.12, p=0.007; β=−0.13, p=0.0006, respectively) and AL (β=0.07, p=0.002; β=0.09, p=0.0008; β=0.07, p=0.0003, respectively). SNTB1rs7839488 was correlated with both AL (β=0.07, p=0.005) and CR (β=0.02, p=0.006). Moreover, ZC3H11Brs4373767-T (β=0.006; p=0.018), KCNQ5rs7744813-A (β=0.007; p=0.015) and GJD2rs524952-T (β=0.009; p=0.0006) were correlated with AL-CR ratio.Conclusions and RelevanceZC3H11Band BICC1are genetic risk factors for moderate and high myopia, while ZC3H11B, KCNQ5, SNTB1and GJD2confer risk to excessive AL in children.

PurposeThe endothelial and cell-specific angiopoietin-Tie pathway plays an important regulatory role in angiogenesis. In this study, we investigated the associations of the TIE2(tyrosine kinase, endothelial, TEK) gene with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), using haplotype-tagging single-nucleotide polymorphisms (SNPs) analysis.MethodsThis study involved totally 2343 subjects, including a Hong Kong Chinese cohort (214 nAMD patients, 236 PCV patients and 433 control subjects), a Shantou Chinese cohort (189 nAMD patients, 187 PCV patients and 531 control subjects) and an Osaka Japanese cohort (192 nAMD patients, 204 PCV patients and 157 control subjects). Thirty haplotype-tagging SNPs in TIE2were genotyped in the Hong Kong cohort using TaqMan technology. Two SNPs (rs625767 and rs2273717) showing association in the Hong Kong cohort were genotyped in the Shantou and Osaka cohorts. The SNP-disease association of individual and pooled cohorts were analysed.ResultsTwo SNPs (rs625767 and rs2273717) showed suggestive association with both nAMD and PCV in the Hong Kong cohort. In the meta-analysis involving all the three cohorts, rs625767 showed significant associations with nAMD (p=0.01; OR=0.82, 95% CI 0.70 to 0.96; I2=0%), PCV (p=0.02; OR=0.83, 95% CI 0.71 to 0.97; I2=27%) and pooled nAMD and PCV (p=0.002; OR=0.82, 95% CI 0.72 to 0.93; I2=0%), with low inter-cohort heterogeneities.ConclusionThis study revealed TIE2as a novel susceptibility gene for nAMD and PCV in Japanese and Chinese. Further studies in other populations are warranted to confirm its role.

In this paper, a risk cloud model (RCM) based on cloud model theory is proposed for evaluating risks in the nautical navigational environment (NNEt). To validate the method, the proposed strategy is applied to a risk evaluation of NNEt of the waters around the Hangzhou Bay Sea-Crossing Bridge and the results are compared with those of a conventional fuzzy theory-based evaluation approach. The results show that risk evaluations based on the proposed RCM are robust, can accommodate uncertainty, can leverage multi-channel information, and provide a full-featured analysis of NNEt. In addition, plots of the RCM droplets provide an intuitive depiction of the risk level, which is extremely beneficial in analyses of the results. Thus, the proposed RCM and implementation method is well-suited for use in conducting risk evaluation of NNEt.

ObjectiveTo investigate the associations of single-nucleotide polymorphisms (SNPs) in the ZC3H11B, ZFHX1B, VIPR2, SNTB1and MIPEPgenes with severities of myopia in Chinese populations.MethodsBased on previous myopia genome-wide association studies, five SNPs (ZC3H11Brs4373767, ZFHX1Brs13382811, VIPR2rs2730260, SNTB1rs7839488 and MIPEPrs9318086) were selected for genotyping in a Chinese cohort of 2079 subjects: 252 extreme myopia, 277 high myopia, 393 moderate myopia, 366 mild myopia and 791 non-myopic controls. Genotyping was performed by TaqMan assays. Allelic frequencies of the SNPs were compared with myopia severities and ophthalmic biometric measurements.ResultsThe risk allele T of ZC3H11BSNP rs4373767 was significantly associated with high myopia (OR=1.39, p=0.007) and extreme myopia (OR=1.34, p=0.013) when compared with controls, whereas ZFHX1Brs13382811 (allele T, OR=1.33, p=0.018) and SNTB1rs7839488 (allele G, OR=1.71, p=8.44E-05) were significantly associated with extreme myopia only. In contrast, there was no significant association of these SNPs with moderate or mild myopia. When compared with mild myopia, subjects carrying T allele of rs4373767 had a risk of progressing to high myopia (spherical equivalent ≤−6 dioptres) (OR=1.29, p=0.017). Similarly, the T allele of rs13382811 also imposed a significant risk to high myopia (OR=1.36, p=0.007). In quantitative traits analysis, SNPs rs4373767, rs13382811 and rs7839488 were correlated with axial length and refractive errors.ConclusionsWe confirmed ZC3H11Bas a susceptibility gene for high and extreme myopia, and ZFHX1Band SNTBfor extreme myopia in Chinese populations. Instead of myopia onset, these three genes were more likely to impose risks of progressing to high and extreme myopia.

There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region.

To evaluate the genetic associations of different subtypes of central serous chorioretinopathy (CSCR), neovascular age-related macular degeneration (nAMD), and polypoidal choroidal vasculopathy (PCV).

Retinoblastoma (RB), originating from the developing retina, is an aggressive intraocular malignant neoplasm in childhood. Biallelic loss of RB1is conventionally considered a prerequisite for initiating RB development in most RB cases. Additional genetic mutations arising from genome instability following RB1mutations are proposed to be required to promote RB development. Recent advancements in high throughput sequencing technologies allow a deeper and more comprehensive understanding of the etiology of RB that additional genetic alterations following RB1biallelic loss are rare, yet epigenetic changes driven by RB1loss emerge as a critical contributor promoting RB tumorigenesis. Multiple epigenetic regulators have been found to be dysregulated and to contribute to RB development, including noncoding RNAs, DNA methylations, RNA modifications, chromatin conformations, and histone modifications. A full understanding of the roles of genetic and epigenetic alterations in RB formation is crucial in facilitating the translation of these findings into effective treatment strategies for RB. In this review, we summarize current knowledge concerning genetic defects and epigenetic dysregulations in RB, aiming to help understand their links and roles in RB tumorigenesis.

IMPORTANCE: Secondhand smoking is a risk to adult ocular health, but its effect on children’s ocular development is not known. OBJECTIVE: To assess the association between choroidal thickness and secondhand smoking exposure in children. DESIGN, SETTING, AND PARTICIPANTS: Children aged 6 to 8 years were consecutively recruited from January 2016 to July 2017 from the population-based Hong Kong Children Eye Study at the Chinese University of Hong Kong Eye Centre. All participants underwent detailed ophthalmic investigations. Choroidal thickness was measured by swept-source optical coherence tomography, with built-in software that automatically segmented the choroid layer to analyze its terrain imagery. History of secondhand smoking was obtained from a questionnaire. Multiple linear regression analyses were performed to assess the correlation between choroidal thickness and secondhand exposure when controlling for confounding factors. Analysis began July 2018 and ended in April 2019. MAIN OUTCOMES AND MEASUREMENTS: The association between children’s choroidal thickness and their exposure to secondhand smoking. RESULTS: Of 1400 children, 941 (67.2%) had no exposure to secondhand smoking, and 459 (32.8%) had exposure to secondhand smoking. The mean (SD) age was 7.65 (1.09) years for children in the nonexposure group and 7.54 (1.11) years for children in the exposure group. After adjustment for age, sex, body mass index, axial length, and birth weight, exposure to secondhand smoking was associated with a thinner choroid by 8.3 μm in the central subfield, 7.2 μm in the inner inferior, 6.4 μm in the outer inferior, 6.4 μm in the inner temporal, and 7.3 μm in the outer temporal. Choroidal thinning with also associated with increased number of family smokers and increased quantity of secondhand smoking. An increase of 1 family smoker was associated with choroidal thinning by 7.86 μm in the central subfield, 4.51 μm in the outer superior, 6.23 μm in the inner inferior, 5.59 μm in the outer inferior, 6.06 μm in the inner nasal, and 6.55 μm in the outer nasal. An increase of exposure to 1 secondhand cigarette smoke per day was associated with choroidal thinning by 0.54 μm in the central subfield, 0.42 μm in the inner temporal, and 0.47 μm in the outer temporal. CONCLUSIONS AND RELEVANCE: This investigation showed that exposure to secondhand smoking in children was associated with choroidal thinning along with a dose-dependent effect. These results support evidence regarding the potential hazards of secondhand smoking to children.

In order to investigate the high-temperature fatigue and fatigue–creep behavior of 15CrNbTi ferritic stainless steel at 800 °C, fatigue tests without holding time in laboratory air and with 10 s holding time induced at maximum cyclic stress under argon atmosphere were conducted on an electrohydraulic servo fatigue testing machine. In addition, the morphologies of fatigue fracture surfaces were observed, and the precipitates and dislocation substructures were characterized. The experimental results show that the fatigue limit of 15CrNbTi ferritic stainless steel is 30 MPa at 800 °C. The fatigue life of the experimental steel obviously decreases if holding time of 10 s is introduced at maximum cyclic stress. Under two test conditions, the fatigue cracks transgranularly initiate at the free surface of fatigue specimens and then propagate in a transgranular mode. It is demonstrated that three kinds of precipitates including (Nb, Ti)C phase, Fe2Nb phase and Fe3Nb3C phase can be observed in 15CrNbTi ferritic stainless steel, and the Fe2Nb and Fe3Nb3C phases are mainly precipitated during the fatigue tests. In the fatigue deformation area, both dislocation tangles and dislocation arrays are observed. Furthermore, the sub-grains which form during the cycling deformation with holding time of 10 s are also found. Moreover, the formation of sub-grains leads to the deterioration of the fatigue life of 15CrNbTi steel.

AimTo determine the association between dementia and age-related macular degeneration (AMD) using meta-analysis.MethodsWe searched in the MEDLINE, EMBASE, Web of Knowledge, PsycInfo and Cochrane database of systematic reviews for studies published from March 1959 to March 2018. We included cross-sectional, case–control and cohort studies that evaluated the association of dementia/Alzheimer's disease (AD) with AMD (as outcome) and the association of AMD with dementia/AD (as outcome). Studies that compared cognitive functions between AMD and controls were also included. The summary outcomes, namely odds ratio (OR), relative risk, mean differences and corresponding 95% CIs, were estimated using random effects models. We performed sensitivity analysis based on study quality and individual study effect to control for potential biases.ResultsAmong 2159 citation records, we identified 21 studies consisting of 7 876 499 study subjects for meta-analysis. Patients with dementia (padjusted≤0.017, OR≥1.24, I2≤9%) or AD (p=0.001, ORunadjusted=2.22, I2=50%) were at risk for AMD, particularly for late AMD (padjusted<0.001, OR=1.37, I2=0). AMD was also significantly associated with increased risk of AD/cognitive impairment (padjusted=0.037, OR=2.42, I2=38%). Moreover, patients with AMD had poorer cognitive functions when compared with controls, including Mini-Mental State Examination (p<0.001, I2≤79%) and Trail Making Test A (p<0.001, I2=0). Sensitivity analysis and Egger’s test indicated our results were less likely biased.ConclusionsA significant association between dementia/AD and AMD calls for greater clinical awareness. The cost-effectiveness of routine screening for the other condition in patients with primary diagnosis of dementia/AD or AMD requires further study.

AimsTo evaluate the distributions of quantitative optical coherence tomography angiography (OCT-A) metrics and its associated factors in children.Methods1059 children aged 6–8 years were recruited from the Hong Kong Children Eye Study. All the participants underwent OCT-A with a swept-source OCT. Retinal microvasculature on superficial capillary plexus was assessed and quantified by a customised automated image analysis programme. Univariable and multiple linear regression analyses were performed to determine systemic (body mass index (BMI), waist circumference, head circumference and blood pressure), demographic and ocular (axial length (AL), macular thickness and volume, retinal nerve fibre layer (RNFL) thickness and visual acuity) variables (independent variables) associated with OCT-A metrics (dependent variables).ResultsIn multiple linear regression analyses, enlarged foveal avascular zone area was associated with female gender (β=0.110, p<0.001), decreased AL (β=−0.097, p<0.001) and decreased central macular thickness (β=−0.008, p<0.001). Decreased vessel density was associated with increased BMI (β=−4.12×10−4, p=0.006), decreased AL (β=0.003, p<0.001) and decreased central macular thickness (β=7.87×10−5, p=0.001). Increased vessel diameter index was associated with female gender (β=0.020, p=0.007) and decreased AL (β=−0.020, p<0.001). Decreased fractal dimension was associated with older age (β=−0.001, p=0.008). There were no significant correlations between OCT-A metrics with visual acuity, RNFL thickness, central corneal thickness, waist circumference, head circumference and blood pressure (all p>0.05).ConclusionOur findings provides new information on baseline morphology of retinal microvasculature and its associated factors in school children, which will be useful for interpreting OCT-A metrics and for identifying and characterising pathological changes in retinal microvasculature.

ObjectiveTo conduct a systematic review and meta-analysis of the association of blood vitamin D (25-hydroxyvitamin D, 25(OH)D) concentration and vitamin D pathway genes with myopia.MethodsWe searched the MEDLINE and EMBASE databases for studies published up to 29 January 2018. Cross-sectional or cohort studies which evaluated the blood 25(OH)D concentration, blood 25(OH)D3 concentration or vitamin D pathway genes, in relation to risk of myopia or refractive errors were included. Standard mean difference (SMD) of blood 25(OH)D concentrations between the myopia and non-myopia groups was calculated. The associations of blood 25(OH)D concentrations and polymorphisms in vitamin D pathway genes with myopia using summary ORs were evaluated.ResultsWe summarised seven studies involving 25 008 individuals in the meta-analysis. The myopia group had lower 25(OH)D concentration than the non-myopia group (SMD=−0.27 nmol/L, p=0.001). In the full analysis, the risk of myopia was inversely associated with blood 25(OH)D concentration after adjusting for sunlight exposure or time spent outdoors (adjusted odds ratio (AOR)=0.92 per 10 nmol/L, p<0.0001). However, the association was not statistically significant for the <18 years subgroup (AOR=0.91 per 10 nmol/L, p=0.13) and was significant only for 25(OH)D3 (likely to be mainly sunlight derived), but not total 25(OH)D (AOR=0.93 per 10 nmol/L, p=0.00007; AOR=0.91 per 10 nmol/L, p=0.15). We analysed four single nucleotide polymorphisms in the VDR gene from two studies; there was no significant association with myopia.ConclusionsLower 25(OH)D is associated with increased risk of myopia; the lack of a genetic association suggests that 25(OH)D level may be acting as a proxy for time outdoors.

AimsTo investigate the association of the paired box gene 6(PAX6) with different severities of myopia.MethodsA total of four haplotype-tagging single-nucleotide polymorphisms (SNPs; rs2071754, rs3026354, rs3026390 and rs628224) and two previously reported SNPs (rs644242 and rs662702) in the PAX6gene were analysed in a Hong Kong Chinese cohort of 1288 myopia subjects (including 252 extreme myopia, 277 high myopia, 393 moderate myopia and 366 mild myopia) and 791 no myopia controls. Allelic association analyses were performed for individual SNPs in different subgroups of myopia and in combined myopia, followed by a meta-analysis of our current data with reported data on PAX6in myopia.ResultsThe association of tagging SNPs rs2071754 and rs644242 with extreme myopia could not withstand multiple correction (rs2071754: OR=1.25, P value=0.031; rs644242: OR=1.33, P value=0.032). In the meta-analysis, rs644242 showed an enhanced, significant association with extreme myopia (OR=1.27, 95% CI 1.10 to 1.46, P value=0.001; I2=0%). In contrast, there was no significant association between the PAX6SNPs and high, moderate or mild myopia. No linear correlation was found between the PAX6SNPs and axial length.ConclusionThis study provides additional evidence suggesting that the PAX6SNP rs644242 is associated with extreme myopia but not lower grade myopia. Thus, PAX6may be implicated in the development or progression into severe myopia. Further longitudinal studies are warranted.

ObjectiveTo investigate the associations between 16 single-nucleotide polymorphisms (SNPs) in 14 genetic loci and keratoconus in an independent Chinese cohort.MethodsThis cross-sectional, case-control association study included a Chinese cohort of 133 patients with keratoconus and 371 control subjects. In a recent meta-analysis study, we identified association of 16 SNPs in 14 gene loci with keratoconus. In this study, we genotyped these 16 SNPs in all the patients and controls and analysed their association with keratoconus, its clinical severities and progression profiles. We also analysed the genotype-phenotype correlation between individual SNPs and steep keratometry, flat keratometry (Kf), average keratometry (Avg K) and best-fit sphere diameter (BFS) of the anterior and posterior corneal surface.ResultsAmong the 16 selected SNPs, rs1324183 in the MPDZ-NF1Blocus showed a significant association with keratoconus (OR=2.22; 95% CI 1.42 to 3.45, p=4.30×10–4), especially severe keratoconus (OR=5.10, 95% CI 1.63 to 15.93, p=0.005). The rs1324183 A allele was positively associated with anterior Kf (p=0.008), anterior Avg K (p=0.017), posterior Kf (p=0.01) and negatively associated with apex pachymetry (p=0.007) and anterior BFS (p=0.023) in keratoconus. The other 15 SNPs had no significant association with keratoconus or genotype-phenotype correlations.ConclusionsThis study confirmed the association of SNP rs1324183 in MPDZ-NF1Bwith keratoconus and revealed the association of this SNP with keratoconus severity and corneal parameters. It is thus a putative genetic marker for monitoring the progression of keratoconus to a severe form and facilitating early intervention.

ABSTRACTWith the increment for liquefied natural gas (LNG) demand, LNG carriers are becoming larger in size. The operational safety of the carriers and the associated terminals is increasingly attracting attention. This is particularly true when a large LNG vessel approaches a terminal, requiring a detailed investigation of ship handling in port waters, especially in certain unusual cases. A full mission simulator provides an effective tool for research and training in operations of both port terminals and ships. This paper presents an experimental design methodology of the full mission simulation. The details as to how the simulation is achieved are described, and the simulation strategies applicable to LNG ships are specified. A typical case study is used to demonstrate and verify the proposed design methodology. The proposed methodology of the full mission simulation provides guidance for port safety research, risk evaluation and seafarer training.

BackgroundRetinopathy of prematurity (ROP) is one of the leading causes of childhood blindness. Use of antenatal steroid can reduce neonatal morbidity and mortality in preterm births, but its effect on ROP remained controversial. We aim to determine the association between antenatal steroid and risk of ROP by a systematic review and meta-analysis.MethodsReported studies on the association between antenatal steroid and risk of ROP or severe ROP were identified from MEDLINE and Embase databases from their inception to November 2016. Outcome measures were ORs with 95% CIs. Extracted data were pooled using a random-effect model or fixed-effect model where appropriate. Heterogeneity was assessed, and sensitivity analysis was performed.ResultsA total of 434 relevant studies were identified, and 28 studies were eligible for the meta-analysis, involving 20 731 neonates with 4202 cases of ROP. Among the 28 studies included, 13 studies provided data evaluating the association between antenatal steroid use and severe ROP, involving 4999 neonates with 792 cases of severe ROP. Antenatal steroid administration was associated with a reduced risk of ROP development (ORunadjusted=0.82, 95% CI 0.68 to 0.98; ORadjusted=0.67, 95% CI 0.47 to 0.94) and progression to severe ROP (ORunadjusted=0.58, 95% CI 0.40 to 0.86).ConclusionAntenatal steroid administration is associated with a reduced risk of ROP development and progression to severe ROP. Our results strengthened the indications of antenatal steroid therapy to high-risk mothers giving preterm births, especially in low-income and middle-income countries where antenatal steroid are not yet widely used.

Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD) more frequently seen in East Asians, has both common and distinct clinical manifestations with typical neovascular AMD (tAMD). We aim to examine the extent to which common genetic variants are shared between these two subtypes. We performed the meta-analysis of association in a total of 1062 PCV patients, 1157 tAMD patients and 5275 controls of East Asian descent from the Genetics of AMD in Asians Consortium at the 34 known AMD loci. A total of eight loci were significantly associated with PCV, including age-related maculopathy susceptibility 2 (ARMS2)-HtrA serine peptidase 1 (HTRA1), complement factor H (CFH), C2-CFB-SKIV2L, CETP, VEGFA, ADAMTS9-AS2and TGFBR1(P<5 × 10−4) from the single-nucleotide polymorphism-based test and COL4A3from the gene-based tests (Pgene=2.02 × 10−4). PCV and tAMD are genetically highly correlated (rg=0.69, P=4.68 × 10−3), with AMD known loci accounting for up to 36% variation. Weaker association for PCV was observed at ARMS2-HTRA1(Pdif=4.39 × 10−4) and KMT2E-SRPK2(Pdif=4.43 × 10−3), compared with tAMD. Variants at CFH, CETPand VEGFAexhibited different association signals in East Asians, in contrast to those in European individuals. Our data suggest a substantially shared genetic susceptibility for PCV and tAMD, while also highlight the unique associations for PCV, which is useful in understanding the pathogenesis of PCV.

Age-related macular degeneration (AMD) is a leading cause of visual impairment and irreversible blindness in most developed countries, affecting about 50 million elderly people worldwide. Retinal pigment epithelial (RPE) cell degeneration is the pathophysiological cause of AMD, leading to geographic atrophy and choroidal neovascularization. We and others have previously identified several polymorphisms on chromosome 10q26 (HTRA1rs11200638 as well as LOC387715rs10490924 and c.372_815del443ins54) associated with AMD. In this study, we confirmed the association of our previously identified HTRA1insertion–deletion (indel) variant (c.34delCinsTCCT) in 195 exudative AMD patients and 390 controls from the Hong Kong Chinese cohort with additional 168 patients and 210 controls from the Chengdu Chinese cohort and followed by studying its biological functions in RPE cells. Genetic analysis verified the higher prevalence of c.34delCinsTCCT allele in control subjects (8.0%) than in AMD patients (1.9%; P=7.87 × 10−5, odds ratio=0.229). This protective effect was validated as the haplotype of the c.34delCinsTCCT allele existed independent of the risk haplotype (P=1.17 × 10−5). In vitrostudies showed that recombinant HTRA1 c.34delCinsTCCT variant protein was more localized in the endoplasmic reticulum of RPE cells compared with the wild-type protein, and its secretion was delayed. Moreover, ARPE-19 cells expressing HTRA1 c.34delCinsTCCT variant had higher cell viability, lower cell apoptosis and were less responsive to anoikis, supporting its protective role. We revealed a protective AMD-associated HTRA1variant in Chinese populations and the biological role of HTRA1 in RPE cell degeneration, indicating its involvement in AMD pathogenesis.

Age-related macular degeneration (AMD) is a leading cause of visual impairment and irreversible blindness in most developed countries, affecting about 50 million elderly people worldwide. Retinal pigment epithelial (RPE) cell degeneration is the pathophysiological cause of AMD, leading to geographic atrophy and choroidal neovascularization. We and others have previously identified several polymorphisms on chromosome 10q26 (HTRA1 rs11200638 as well as LOC387715 rs10490924 and c.372_815del443ins54) associated with AMD. In this study, we confirmed the association of our previously identified HTRA1 insertion–deletion (indel) variant (c.34delCinsTCCT) in 195 exudative AMD patients and 390 controls from the Hong Kong Chinese cohort with additional 168 patients and 210 controls from the Chengdu Chinese cohort and followed by studying its biological functions in RPE cells. Genetic analysis verified the higher prevalence of c.34delCinsTCCT allele in control subjects (8.0%) than in AMD patients (1.9%; P=7.87 × 10−5, odds ratio=0.229). This protective effect was validated as the haplotype of the c.34delCinsTCCT allele existed independent of the risk haplotype (P=1.17 × 10−5). In vitro studies showed that recombinant HTRA1 c.34delCinsTCCT variant protein was more localized in the endoplasmic reticulum of RPE cells compared with the wild-type protein, and its secretion was delayed. Moreover, ARPE-19 cells expressing HTRA1 c.34delCinsTCCT variant had higher cell viability, lower cell apoptosis and were less responsive to anoikis, supporting its protective role. We revealed a protective AMD-associated HTRA1 variant in Chinese populations and the biological role of HTRA1 in RPE cell degeneration, indicating its involvement in AMD pathogenesis.

Myopia is a major cause of visual impairment worldwide. In particular, high myopia is associated with serious blinding complications, including retinal detachment, chorioretinal degeneration, and choroidal neovascularization. Myopia is multifactorial in etiology, resulting from the interaction of environmental and genetic risk factors. During the past 2 decades, a large number of gene loci and variants have been identified for myopia. There are more than 20 myopia-associated loci spanning all chromosomes. Earlier findings were obtained mainly from family linkage analyses and candidate gene studies, and more recent results are principally from genome-wide association studies and exome sequencing. Some genetic associations have been successfully validated and replicated in populations of different geographic localities and ethnicities, but some have not. Compared with Whites, Asian populations—in particular Japanese, Korean, and Chinese—have a much higher prevalence of myopia, especially high myopia. Both genetic and environmental factors contribute to such ethnic variations. This review attempts to summarize and compare the allelic frequencies of gene variants known to be associated with myopia in different ethnic groups, especially in the Asia-Pacific region.

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10−15), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10−16), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10−14), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10−11), and DPM2–FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10−12). We also confirmed significant association at three previously described loci (P < 5 × 10−8for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1–ST18), providing new insights into the biology of PACG.

To explore the effect of strain rate on the high temperature deformation characteristics of ultrafine-grained materials, the deformation and damage features as well as microstructures of ECAP-treated pure Al at different temperatures Tand strain rates were systematically studied through compression tests and microscopic observations. The increase in eliminates strain softening at T≤473 K, and largely enhances the yield strength and flow stress at 473–573 K. The shear deformation dominates the plastic deformation of ECAP-treated Al. Many cracks along shear bands (SBs) are formed at T≥473 K and secondary SBs basically disappear at 1×10−3s−1; however, at 1×10−2s−1, cracks are only observed at temperature below 473 K, and secondary SBs become clearer at T≥473 K. The microstructures of ECAP-treated Al mainly consist of sub-grains (SGs). The increase in inhibits the SG growth, thus leading to the increases both in yield strength and flow stress at high temperatures.

A systematic review was performed to evaluate the safety and efficacy of topical 0.05% cyclosporine in treating patients with dry eye syndrome (DES). Twelve qualified randomized-controlled trials incorporating 1367 patients were analyzed. In comparison to controls, patients who were on topical 0.05% cyclosporine eye drops had lower Ocular Surface Disease Index scores (mean difference [MD]=4.10, 95% CI: 0.25-7.96, P=.04), longer tear film breakup time (MD=2.30 seconds, 95% CI: 0.75-3.86, P=.004), improved Schirmer I scores (MD=2.77 mm/5min, 95% CI: 1.63-3.91, P=.00001), reduced corneal fluorescein staining (standardized mean difference [SMD]=0.61, 95% CI: 0.07-1.15, P=.03), and higher goblet cell densities (SMD=1.68, 95% CI: 0.54-2.81, P=.004). However, there were more adverse effects in the cyclosporine patient group (odds ratio=1.64, 95% CI: 1.17-2.30, P=.004). Topical 0.05% cyclosporine eye drops twice daily significantly improved both the objective and subjective outcomes in DES patients. The study limitations in the clinical, methodological and statistical heterogeneities are discussed.

In this study, equilibrium lattice parameters, heat of formation and cohesive energy of four kinds of typical phases with different structure intermetallic compound in Al-Cu-Mg alloy were investigated by first-principles calculations based on density functional theory via CASTEP software. The calculation results are analyzed and show that ternary strengthening phase Al2CuMg generated first when Mg content is higher, while binary strengthening phase Al2Cu or Al3Cu2 first generated and more stable when Mg content is low in Al-Cu-Mg alloy which indicates that element Cu and Al alloying capacity significantly higher than that of Mg and Al element.

Cr/CrN multilayer coatings with bilayer periods in the range from 1351 to 260 nm were prepared on 304 stainless steel substrates by arc ion plating to study the microstructure and properties of multilayer coatings and stimulate their application. SEM results confirm the clear periodicity of the Cr/CrN multilayer coatings and the clear interface between individual layers. XRD patterns reveal that these multilayer coatings contain Cr, CrN and Cr2N phases. Because Cr layer is softer than its nitride layer, the hardness decreases with the shortening of the bilayer period (or increasing volume fraction of Cr layer). The Cr/CrN multilayer coating with 862 nm period possesses the highest indentation toughness due to a proper individual Cr and nitride layer thickness. However, for the Cr/CrN multilayer with the bilayer period of 1351 nm, it possesses the lowest toughness due to more nitride phase. The indentation toughness of Cr/CrN multilayer coatings is related with their bilayer period. A coating with a proper individual Cr and nitride layer thickness possesses the highest indentation toughness.

Renewable energy is an ideal source of power, with advantages such as low pollution, low energy consumption, sustainability, and an inexhaustible supply of energy. The method of importance-performance analysis (IPA) is frequently applied to measure satisfaction and to improve competitive strategies. In this study, we perform a complete analysis of the operational performance of Taiwanese renewable energy industries. A wind power company was recruited as a case study, and IPA was employed to survey and evaluate the company’s competitive performance. Subsequently, the results were used as a guide to improve the performance of the company.

The low-cycle fatigue behaviors of as-extruded and T6 treated Al-6Zn-2.5Mg-2Cu-0.1Zr-0.1Sc alloys at room temperature have been investigated under those total-strain amplitudes ranged from 0.3% to 1.0%, and the influence of T6 treatment on the low-cycle fatigue properties of Al-6Zn-2.5Mg-2Cu-0.1Zr-0.1Sc alloy was clarified. The experimental results show that during fatigue deformation, the significant cyclic strain hardening and stable cyclic stress response can be noted for both as-extruded and T6 treated Al-6Zn-2.5Mg-2Cu-0.1Zr-0.1Sc alloys. The fatigue life of as-extruded Al-6Zn-2.5Mg-2Cu-0.1Zr-0.1Sc alloy at all strain amplitudes is longer than that of the alloy subjected to T6 aging treatment. The relationship between both elastic and plastic strain amplitudes with reversals to failure shows a monotonic linear behavior, and can be described by the Basquin and Coffin-Manson equations, respectively. The T6 treatment can significantly increase the cyclic strain hardening exponent and cyclic strength coefficient of extruded Al-6Zn-2.5Mg-2Cu-0.1Zr-0.1Sc alloy.

The combination of atomization and smelting fabricated high strength Al-6Zn-2Mg-2Cu alloy. Microstructure was observed and analyzed by optical microscopy and SEM. The alloy featured with refined grains and even distribution. After being solution treated at 475°C for 1.5h, following multi-pass rolling with total reduction of 33% and aging at 120°C for 40h, the yield strength was 592MPa, peak stress of 597MPa and elongation of 12.2%.