Time Outdoors in Reducing Myopia: A School-Based Cluster Randomized Trial with Objective Monitoring of Outdoor Time and Light Intensity.

PURPOSE: To evaluate the efficacy of time outdoors per school day over 2 years on myopia onset and shift. DESIGN: A prospective, cluster-randomized, examiner-masked, 3-arm trial. PARTICIPANTS: A total of 6295 students aged 6 to 9 years from 24 primary schools in Shanghai, China, stratified and randomized by school in a 1:1:1 ratio to control (n = 2037), test I (n = 2329), or test II (n = 1929) group. METHODS: An additional 40 or 80 minutes of outdoor time was allocated to each school day for test I and II groups. Children in the control group continued their habitual outdoor time. Objective monitoring of outdoor and indoor time and light intensity each day was measured with a wrist-worn wearable during the second-year follow-up. MAIN OUTCOME MEASURES: The 2-year cumulative incidence of myopia (defined as cycloplegic spherical equivalent [SE] of ≤-0.5 diopters [D] in the right eye) among the students without myopia at baseline and changes in SE and axial length (AL) after 2 years. RESULTS: The unadjusted 2-year cumulative incidence of myopia was 24.9%, 20.6%, and 23.8% for control, test I, and II groups, respectively. The adjusted incidence decreased by 16% (incidence risk ratio [IRR], 0.84; 95% confidence interval [CI], 0.72-0.99; P = 0.035) in test I and 11% (IRR = 0.89; 95% CI, 0.79-0.99; P = 0.041) in test II when compared with the control group. The test groups showed less myopic shift and axial elongation compared with the control group (test I: -0.84 D and 0.55 mm, test II: -0.91 D and 0.57 mm, control: -1.04 D and 0.65 mm). There was no significant difference in the adjusted incidence of myopia and myopic shift between the 2 test groups. The test groups had similar outdoor time and light intensity (test I: 127 ± 30 minutes/day and 3557 ± 970 lux/minute; test II: 127 ± 26 minutes/day and 3662 ± 803 lux/minute) but significantly more outdoor time and higher light intensity compared with the control group (106 ± 27 minutes/day and 2984 ± 806 lux/minute). Daily outdoor time of 120 to 150 minutes at 5000 lux/minutes or cumulative outdoor light intensity of 600 000 to 750 000 lux significantly reduced the IRR by 15%～ 24%. CONCLUSIONS: Increasing outdoor time reduced the risk of myopia onset and myopic shifts, especially in nonmyopic children. The protective effect of outdoor time was related to the duration of exposure and light intensity. The dose-response effect between test I and test II was not observed probably because of insufficient outdoor time achieved in the test groups, which suggests that proper monitoring on the compliance on outdoor intervention is critical if one wants to see the protective effect.

Gonadotropin Therapy Once a Week for Spermatogenesis in Hypogonadotropic Hypogonadism.

OBJECTIVE: Hypogonadotropic hypogonadism (HH) can be caused by congenital HH (CHH), pituitary stalk interruption syndrome (PSIS), and pituitary injury (acquired HH). Gonadotropin therapy, typically administered every other day or twice a week, is commonly used to promote spermatogenesis. The aim of this retrospective study was to evaluate the efficacy of weekly gonadotropin therapy on spermatogenesis in patients with HH (n = 160). METHODS: The patients' diagnoses include Kallmann syndrome (KS) (n = 61), normosmic CHH (nCHH) (n = 34), PSIS (n = 48), and acquired HH (n = 17). The rate of successful spermatogenesis and median time to achieve spermatogenesis among these 4 subgroups were compared as well as between a weekly group (n = 95) and a twice-a-week group (n = 223) of CHH patients. RESULTS: Once-a-week gonadotropin therapy resulted in 74% (119/160) of HH patients achieving spermatogenesis with significantly increased testicular volume and total testosterone levels (P < .001). The median period of spermatogenesis was 13 (interquartile range[IQR] 11.4-14.6) months. Larger basal testicular volume (P = .0142) was an independent predictor for earlier sperm appearance. Six spontaneous pregnancies occurred. Compared with the twice-a-week regimen for spermatogenesis, the weekly injection group had a similar median time of sperm appearance (14 [IQR, 11.6-16.4] vs 15 [IQR, 13.5-16.5] months), success rate (78% [74/95] vs 64% [143/223]), sperm concentration (20.9 [IQR, 5.0-46.3] vs 11.7 [IQR, 2.1-24.4] million/mL), and progressive sperm motility (40.8 ± 27.3% vs 36.9% ± 20.2%). CONCLUSION: Weekly gonadotropin therapy is effective in inducing spermatogenesis, similar to that of twice-a-week therapy. A larger basal testicular size was a favorable indicator for earlier spermatogenesis.

Circulating Rather Than Alveolar Extracellular Deoxyribonucleic Acid Levels Predict Outcomes in Influenza.

BACKGROUND: High levels of circulating neutrophil extracellular traps (NETs) are associated with a poor prognosis in influenza A infection. It remains unclear whether NETs in the plasma or bronchoalveolar lavage fluid (BALF) can predict clinical outcomes in influenza. METHODS: One hundred eighteen patients who were diagnosed with H1N1 influenza in 2017-2018 were recruited. The NETs were assessed in plasma and BALF samples by quantifying cell-free deoxyribonucleic acid (cfDNA) and protein-DNA complexes. Predictions of severe illness and 60-day mortality were analyzed with receiver operating characteristic curves. RESULTS: The NET levels were significantly elevated in the BALF and contributed to the pathology of lungs, yet it was not associated with disease severity or mortality in patients severely infected with H1N1. Plasma NET levels were significantly increased in the patients with severe influenza and positively correlated with the oxygen index and sequential organ failure assessment scores. High levels of plasma cfDNA (>286.6 ng/mL) or histone-bound DNA (>9.4 ng/mL) discriminated severe influenza from mild, and even higher levels of cfDNA (>306.3 ng/mL) or histone-bound DNA (>23.1 ng/mL) predicted fatal outcomes in severely ill patients. CONCLUSIONS: The cfDNA and histone-bound DNA in plasma represent early predictive biomarkers for the prognosis of influenza.

Shanghai Time Outside to Reduce Myopia trial: design and baseline data.

IMPORTANCE: Myopia is a major public health concern worldwide, while outdoor time is indicated to be protective against the onset of myopia. BACKGROUND: To describe the methodology and baseline data of the Shanghai Time Outside to Reduce Myopia (STORM) trial. DESIGN: A 2-year, school-based, prospective, cluster randomized trial. PARTICIPANTS: Children from grade I and II classes of 24 schools from eight districts in Shanghai, China, were randomized to either a control group, a test group I (40-min outdoor time/day) or test group II (80-min outdoor time/day). METHODS: At baseline and annual intervals, cycloplegic autorefraction and axial length measurement will be performed. Time outdoors and light exposure will be monitored via parent/carer questionnaires and a wearable device. MAIN OUTCOME MEASURES: Spherical equivalent, prevalence of myopia and time outdoors in each group. RESULTS: A total of 6295 eligible children (age 7.2 ± 0.7 y [6-9 y]) were randomized to control (n = 2037), test group I (n = 2329) and test group II (n = 1929). At baseline, spherical equivalent was +0.98 ± 1.02D, +1.02 ± 1.02D and +1.00 ± 0.99D (P = 0.708), myopia prevalence was 8.9, 7.7 and 7.8% (P = 0.270) and time outdoors was 58.5 ± 35.8, 59.8 ± 34.7 and 58.5 ± 35.3 min/d (P = 0.886) for control, test groups I and II, respectively. CONCLUSIONS AND RELEVANCE: Myopia prevalence was high at nearly 8 to 9% in school children aged 7 years in Shanghai, China. The current trial will help evaluate if increased time outdoors has a role to play in reducing the incidence of myopia and/or slow the progression of myopia.

Comparison of Refractive Measures of Three Autorefractors in Children and Adolescents.

SIGNIFICANCE: Our study found a good agreement between three autorefractors. Not only will readers benefit as they can now compare data measured with either device in different studies but the three devices can be used in the same study to generate one pool of data, which can be analyzed together. PURPOSE: The present study aims to evaluate the agreement of three commonly used autorefractors in children and adolescents, and the potential for their interchangeable application in a large-scale study. METHODS: Participants from seven schools were enrolled using cluster sampling. Refractive errors were measured using the following three autorefractors under cycloplegic conditions in random sequence: Topcon KR-8900, Nidek ARK-510A, and Huvitz HRK-7000A. Refractive errors were compared in terms of spherical equivalent refraction (SER), cylinder power, and the J0 and J45 by repeated-measures analysis of variance (RM-ANOVA) and Bland-Altman 95% limits of agreement (95% LoA). RESULTS: A total of 2072 participants aged from 4 to 18 years were included. The mean ± SD and 95% LoA of the differences in SER between Topcon and Nidek, Topcon and Huvitz, and Nidek and Huvitz were 0.01 ± 0.24D (-0.46 to 0.48), -0.06 ± 0.31D (-0.66 to 0.54), and -0.07 ± 0.26D (-0.58 to 0.44), and those for the differences in cylinder power were -0.07 ± 0.26D (-0.57 to 0.44), 0.01 ± 0.32D (-0.63 to 0.64), and 0.07 ± 0.28D (-0.48 to 0.62), respectively (RM-ANOVA, P < .001). Further, the mean differences in J0 and J45 between each refractor pair ranged from -0.03 to 0.01, and the 95% LoA were -0.78 to 0.74, -0.79 to 0.74, and -0.73 to 0.72 for J0 and -0.86 to 0.87, -0.86 to 0.88, and -0.83 to 0.84 for J45, respectively. CONCLUSIONS: Our study will allow for use of these three autorefractors interchangeably in large screening studies.

An analysis on intersectional collaboration on non-communicable chronic disease prevention and control in China: a cross-sectional survey on main officials of community health service institutions.

BACKGROUND: Our study aimed to design a tool of evaluating intersectional collaboration on Non-communicable Chronic Disease (NCD) prevention and control, and further to understand the current status of intersectional collaboration in community health service institutions of China. METHODS: We surveyed 444 main officials of community health service institutions in Beijing, Tianjin, Hubei and Ningxia regions of China in 2014 by using a questionnaire. A model of collaboration measurement, including four relational dimensions of governance, shared goals and vision, formalization and internalization, was used to compare the scores of evaluation scale in NCD management procedures across community healthcare institutions and other ones. Reliability and validity of the evaluation tool on inter-organizational collaboration on NCD prevention and control were verified. RESULTS: The test on tool evaluating inter-organizational collaboration in community NCD management revealed a good reliability and validity (Cronbach's Alpha = 0.89,split-half reliability = 0.84, the variance contribution rate of an extracted principal component = 49.70%). The results of inter-organizational collaboration of different departments and management segments showed there were statistically significant differences in formalization dimension for physical examination (p = 0.01).There was statistically significant difference in governance dimension, formalization dimension and total score of the collaboration scale for health record sector (p = 0.01,0.00,0.00). Statistical differences were found in the formalization dimension for exercise and nutrition health education segment (p = 0.01). There were no statistically significant difference in formalization dimension of medication guidance for psychological consultation, medical referral service and rehabilitation guidance (all p > 0.05). CONCLUSION: The multi-department collaboration mechanism of NCD prevention and control has been rudimentarily established. Community management institutions and general hospitals are more active in participating in community NCD management with better collaboration score, whereas the CDC shows relatively poor collaboration in China. Xing-ming Li and Alon Rasooly have the same contribution to the paper. Xing-ming Li and Alon Rasooly listed as the same first author.

[The option of neuroprotective therapeutics for glaucoma].

Glaucoma is the second common cause of irreversible blindness worldwide associated with a progressive neurodegenerative disease of retinal ganglion cells (RGC). The major hypothetical mechanisms of the apoptosis of RGCs includes deprivation of neurotrophic factors, excitotoxicity mediated by the interaction of glutamate with NMDAR. This article reviewed current development of three kinds of neuroprotective drugs for glaucoma management such as small-molecule therapeutics, recombinant therapeutic proteins and small-molecule bioactive peptides. Particularly, small peptides, which show high target specificity, high potency and low toxicity compared with small molecules, possession of the advantages of low immunogenicity and high cost-effectiveness over recombinant therapeutics, may become most important choice for neuroprotection against glaucoma of next generation.

Macular and peripapillary Choroidal Vascularity Index in children with different refractive status.

OBJECTIVES: To characterize choroidal vascular changes in children with different refractive status. METHODS: A study including 5864 children aged 6-9 years was performed to investigate the choroidal vascular index (CVI) in myopic, emmetropic and hyperopic eyes. Each participant had a comprehensive ocular examination with cycloplegic autorefraction performed, axial length (AL) measured and Swept Source-Optical Coherence Tomography (SS-OCT) scans acquired. Choroidal thickness (ChT) was measured by built-in software, and CVI was calculated using a previously validated self-developed algorithm. RESULTS: The mean ChT and CVI were 275.88 ± 53.34 µm and 34.91 ± 3.83 in the macula region, and 191.96 ± 46.28 µm and 32.35 ± 4.21 in the peripapillary region. CVI was significantly lowest for myopes, followed by emmetropes and hyperopes (P < 0.001). CVI varied between different sectors separated by the Early Treatment of Diabetic Retinopathy Study (ETDRS) grid (P < 0.001). Macular CVI decreased horizontally from nasal to temporal quadrant with lowest in center fovea, and vertically from superior to inferior quadrants. Peripapillary CVI was highest in the nasal and lowest in the inferior sector. Multiple regression showed that spherical equivalent (SE), AL, intraocular pressure (IOP), ChT, age, and gender were significantly related to CVI (P < 0.05). CONCLUSIONS: In children, the distribution of CVI in the posterior pole is not uniform. A decreased CVI was observed from hyperopia to myopia and was associated with decreased SE, elongated AL, and choroidal thinning. Further study of changes in CVI during myopia onset and progression is required to better understand the role of the choroidal vasculature in myopia development.

Higher-order aberrations and their association with axial elongation in highly myopic children and adolescents.

BACKGROUND: Vision-dependent mechanisms play a role in myopia progression in childhood. Thus, we investigated the distribution of ocular and corneal higher-order aberrations (HOAs) in highly myopic Chinese children and adolescents and the relationship between HOA components and 1-year axial eye growth. METHODS: Baseline cycloplegic ocular and corneal HOAs, axial length (AL), spherical equivalent (SE), astigmatism and interpupillary distance (IPD) were determined for the right eyes of 458 highly myopic (SE ≤-5.0D) subjects. HOAs were compared among baseline age groups (≤12 years, 13-15 years and 16-18 years). Ninety-nine subjects completed the 1-year follow-up. Linear mixed model analyses were applied to determine the association between HOA components, other known confounding variables (age, gender, SE, astigmatism and IPD) and axial growth. A comparison with data from an early study of moderate myopia were conducted. RESULTS: Almost all ocular HOAs and few corneal HOAs exhibited significant differences between different age groups (all p<0.05). After 1 year, only ocular HOA components was significantly negative associated with a longer AL, including secondary horizontal comatic aberration (p=0.019), primary spherical aberration (p<0.001) and spherical HOA (p=0.026). Comparing with the moderate myopia data, the association of comatic aberration with AL growth was only found in high myopia. CONCLUSION: In highly myopic children and adolescents, lower levels of annual ocular secondary horizontal comatic aberration changes, besides spherical aberrations, were associated with axial elongation. This suggests that ocular HOA plays a potential role in refractive development in high myopia.

Normative data and percentile curves for axial length and axial length/corneal curvature in Chinese children and adolescents aged 4-18 years.

PURPOSE: To develop age-specific and gender-specific reference percentile charts for axial length (AL) and AL/corneal radius of curvature (AL/CR) and, to use percentiles to determine probability of myopia and estimate refractive error (RE). METHODS: Analysis of AL, cycloplegic RE and CR of 14 127 Chinese participants aged 4-18 years from 3 studies. AL and AL/CR percentiles estimated using Lambda-Mu-Sigma method and compared for agreement using intraclass correlation (ICC). Logistic regression was used to model risk of myopia based on age, gender, AL and AL/CR percentiles. Accuracy of AL progression and RE estimated using percentiles was validated using an independent sample of 5742 eyes of children aged 7-10 years. RESULTS: Age-specific and gender-specific AL and AL/CR (3rd, 5th, 10th, 25th, 50th, 75th, 90th and 95th) percentiles are presented. Concordance between AL and AL/CR percentiles improved with age (0.13 at 4 years to >0.75 from 13 years) and a year-to-year change was observed for all except <10th percentile from 15 years. Increasing age, AL and AL/CR was associated with a more myopic RE (r2=0.45,0.70 and 0.83, respectively). The sensitivity and specificity of the model to estimate probability of myopia was 86.0% and 84.5%, respectively. Estimation of 1-year change in AL using percentiles correlated highly with actual AL (ICC=0.98). Concordance of estimated to actual RE was high (ICC=0.80) and within ±0.50D and ±1.0D of actual RE for 47.4% and 78.9% of eyes, respectively. CONCLUSION: Age-specific and gender-specific AL and AL/CR percentiles provide reference data, aid in identifying and monitoring individuals at risk of myopia and have utility in screening for myopia. AL/CR percentiles were more accurate in estimating probability of myopia in younger children.

Accelerated loss of crystalline lens power initiating from emmetropia among young school children: a 2-year longitudinal study.

PURPOSE: To determine the characteristics of crystalline lens with varying refractive errors and relationship with axial elongation in young school children. METHODS: A total of 1465 children aged 6-8 years were examined annually for 2 years. Each participant underwent a series of ophthalmic examinations, including cycloplegic autorefraction, crystalline lens and axial length measurement. Crystalline lens power was determined, and factors associated with different refractive statuses were investigated. RESULTS: Crystalline lens power decreased with time; reduction in lens power in Year 1 was greater in children with emmetropia (-0.69 ± 0.59 dioptre [D]) than in those with hyperopia (-0.49 ± 0.56 D) or myopia (-0.45 ± 0.55 D) (p < 0.001). Among the emmetropes, there were no differences in loss of crystalline lens power between those who remained emmetropic (-0.63 ± 0.59 D) and those who became myopic at Year 1 (-0.74 ± 0.61 D) and Year 2 (-0.77 ± 0.57 D, p > 0.05) visits. Among myopes at Year 1 visit, there was a greater reduction at Year 2 in those who had baseline emmetropia (-0.61 ± 0.51 D) than those who had baseline myopia (-0.26 ± 0.49 D, p < 0.001). The trend was similar among children of the same age. There was a significant correlation between changes in lens power and axial elongation in non-myopia (ß = -0.954, p < 0.001) and new myopia (ß = -1.178, p < 0.001), but not in established myopia (ß = -0.001, p = 0.539). CONCLUSIONS: There is accelerated loss of lens power in emmetropia and early stage of myopia. However, this loss is retarded when myopia persists and is accompanied by disappearance of the compensatory effect of lens power against axial elongation. These findings provide new insights into human refractive development.

Effect of Ocular Magnification on Macular Choroidal Thickness Measurements Made Using Optical Coherence Tomography in Children.

PURPOSE: To evaluate the relationship between ocular magnification correction and macular choroidal thickness (ChT) measurements in children, and to demonstrate when ocular magnification correction is necessary. METHODS: Chinese children aged 6-9 years with various refractive statuses were included. Swept-source optical coherence tomography was used to measure macular ChT. A self-designed program was adopted to simulate ChT changes in each sector of the ETDRS grid in the macula under various simulated axial lengths (ALs). RESULTS: ChT measurements were not affected for all simulated ALs in over 95% of the individuals in the central fovea. In the inferior, superior, and temporal parafoveal sectors, the extent of AL that may include 95% of the individuals narrowed from approximately 22.0 mm to 27.2 mm. In the nasal parafoveal sector and inferior, superior, and temporal perifoveal sectors, the extent of AL that may include 95% of the individuals became even narrower, from approximately 22.8 mm to 26.0 mm. The narrowest extent was observed in the perifoveal nasal sector, ranging from 23.3 mm to 25.5 mm. The effect of ocular magnification was more significant in hyperopes than in myopes in the inferior parafoveal sector and temporal, superior, and nasal perifoveal sectors. CONCLUSION: During macular ChT measurements, ocular magnification correction is not necessary in the central fovea. However, ocular magnification should be corrected normally in the nasal perifoveal region and in individuals with ALs shorter than 22.8 mm or longer than 26.0 mm in the remaining macular regions.

Puberty could regulate the effects of outdoor time on refractive development in Chinese children and adolescents.

AIM: To explore the impact of puberty on refractive development and its interaction with outdoor time in children and adolescents. METHODS: In this 2-year observational study, students aged 7-13 years were selected with cluster sampling. All participants underwent cycloplegic refraction and axial length measurements once every year. Information of related factors was acquired through proper questionnaire or inquiry. The level of testosterone/estradiol was detected from the saliva of the subjects using the ELISA kit. Multiple linear regression and generalised estimating equation (GEE) were used to analyse the relationship among puberty, outdoor activities and refractive indicators. RESULTS: A total of 776 children and adolescents were included, with an average baseline age of 9.64±1.54 years and 53.6% boys. There were 350 myopes (55.2% of the 634 cyclopleged subjects) at baseline. There was a significant difference in the mean axial length changes and outdoor time among different puberty groups (for axial length: p=0.017, for outdoor time: p=0.015). Myopic parents, less outdoor time and more changes in estradiol were associated with greater changes in axial length and spherical equivalent (SE) (axial length changes: parental myopia ß=0.230, outdoor time ß=-0.250, changes in estradiol ß=0.261; SE changes: parental myopia ß=-0.267, outdoor time ß=0.256, changes in estradiol ß=-0.297). In the GEE model, the interaction between outdoor time and puberty was significantly associated with axial length (p=0.024, ß=1.199). CONCLUSIONS: This study implies puberty may play a regulating role on the relationship between outdoor time and refractive development among Chinese children and adolescents, which provides clues for in-depth mechanism interpretation and efficient intervention strategies.

Protective effects of peptide FK18 against neuro-excitotoxicity in SH-SY5Y cells.

Excitotoxic neuronal injury is associated with numerous acute and chronic neurological disorders, such as Alzheimer's disease and glaucoma. Neuroprotection is a direct and effective therapeutic approach, with small-molecule bioactive peptides displaying certain advantages, including high membrane permeability, low immunogenicity and convenient synthesis and modification. FK18 is a novel peptide derived from basic fibroblast growth factor, which is a protein with neuroprotective effects. The present study aims to evaluate the neuroprotective effect of FK18 against excitotoxic injury. For this purpose, cell viability was determined by the MTS assay, cell apoptosis was assessed by flow cytometry and the TUNEL assay; expression of antiapoptotic proteins Bcl-2, proapoptotic protein Bax and caspase-3 as well as the phosphorylation of Akt and Erk was estimated by western blotting. The results of the present study demonstrated that FK18 effectively increased the viability of, and attenuated glutamate-induced apoptosis of SH-SY5Y cells. In addition, FK18 significantly increased Akt phosphorylation and decreased Erk phosphorylation in SH-SY5Y cells. FK18 also increased the Bcl-2/Bax ratio and decreased the level of cleaved-caspase-3 in SY5Y cells, which was reversed by the Akt pathway inhibitor LY294002, but not by the Erk pathway inhibitor U0126. The findings of the present study suggested that FK18 may be a promising therapeutic agent for the inhibition of neuronal cell death in multiple neurological diseases involving excitotoxicity.

COVID-19 Home Quarantine Accelerated the Progression of Myopia in Children Aged 7 to 12 Years in China.

Purpose: To investigate the effect of home quarantine during the COVID-19 pandemic on myopia progression in children and its associated factors. Methods: Myopic children aged 7 to 12 years with regular follow-up visits every half a year from April 2019 to May 2020 were included. Cycloplegic refraction was measured at baseline and at two follow-up visits. The first follow-up visit (visit 1) was conducted before the COVID-19 home quarantine, whereas the second (visit 2) was four months after the home quarantine. Myopia progression at visits 1 and 2 were compared. Factors associated with changes in myopia progression were tested with a multiple regression analysis. Results: In total, 201 myopic children were enrolled. There was a significantly greater change in spherical equivalent at visit 2 (-0.98 ± 0.52 D) than at visit 1 (-0.39 ± 0.58 D; P < 0.001). Students were reported to have spent more time on digital devices for online learning (P < 0.001) and less time on outdoor activities (P < 0.001) at visit 2 than at visit 1. Children using television and projectors had significantly less myopic shift than those using tablets and mobile phones (P < 0.001). More time spent on digital screens (ß = 0.211, P < 0.001), but not less time on outdoor activities (ß = -0.106, P = 0.110), was associated with greater myopia progression at visit 2. Conclusions: Changes in behavior and myopic progression were found during the COVID-19 home quarantine. Myopic progression was associated with digital screen use for online learning, but not time spent on outdoor activities. The projector and television could be better choices for online learning.

Novel Peptide NT/K-CRS Derived from Kringle Structure of Neurotrypsin Inhibits Neovascularization In Vitro and In Vivo.

Purpose: To assess the anti-neovascularization effect of a novel peptide NT/K-CRS derived from the kringle domain of neurotrypsin in vitro and in vivo. Methods: Primary human umbilical vein endothelial cells (HUVECs) were treated with vascular endothelial growth factor (VEGF) in advance. Cell migration, lumen formation, and cell proliferation assays were performed to determine the anti-neovascularization effect of NT/K-CRS in HUVECs. TUNEL and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium tests were conducted to evaluate cell viability. Chick chorioallantoic membrane and oxygen-induced retinopathy model were established to assess the anti-angiogenic role of NT/K-CRS in vivo. Results: The in vitro results showed that NT/K-CRS effectively decreased VEGF-induced cell migration and endothelial tube formation, with no significant effect on cell proliferation and cell viability. In addition, NT/K-CRS showed great efficacy in angiogenesis inhibition in chicken embryos. The cytokine release syndrome (CRS) peptide also inhibited retinal neovascularization and improved retinal blood perfusion in oxygen-treated mouse pups through intravitreal injection. Conclusions: NT/K-CRS peptide derived from the kringle domain of neurotrypsin can strongly inhibit neovascularization in vitro and vivo. This novel peptide may become a promising therapeutic agent for neovascular-related ocular diseases.

Novel Peptide NT/K-CFY Derived from Kringle Structure of Neurotrypsin Inhibits Neovascularization.

Purpose: To assess the anti-neovascularization effect of a novel peptide NT/K-CFY derived from the kringle domain of neurotrypsin.Materials and Methods: Cell migration, lumen formation and cell proliferation assays were performed to determine the anti-neovascularization effect of NT/K-CFY in primary human umbilical vein endothelial cells (HUVECs). Chick chorioallantoic membrane (CAM) and oxygen-induced retinopathy (OIR) models were established to assess the anti-angiogenic role of NT/K-CFY in vivo. The retinal expression of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) was examined by western blot and real-time PCR in OIR model.Results: The in vitro results showed that NT/K-CFY effectively and safely decreased VEGF-induced cell migration, cell proliferation and tube formation in HUVECs. In addition, NT/K-CFY showed certain efficacy in angiogenesis inhibition in chicken embryos and oxygen-treated mouse pups. Moreover, the CFY peptide also improved retinal blood perfusion and reversed the abnormal expression of VEGF and PEDF in OIR mouse model.Conclusion: NT/K-CFY peptide strongly inhibits neovascularization in vitro and vivo. This novel peptide may become a promising therapeutic agent for ocular angiogenesis-related diseases.

Prevalence of myopia and high myopia, and the association with education: Shanghai Child and Adolescent Large-scale Eye Study (SCALE): a cross-sectional study.

OBJECTIVES: To report on: (a) overall myopia and high myopia prevalence, and (b) the impact of education on the spherical equivalent refractive error in children across Shanghai. DESIGN: Cross-sectional study. SETTING: Across all 17 districts of Shanghai. PARTICIPANTS: 910 245 children aged 4-14 years from a school-based survey conducted between 2012 and 2013. MAIN OUTCOME MEASURES: Data of children with non-cycloplegic autorefraction, visual acuity assessment and questionnaire were analysed (67%, n=6 06 476). Prevalence of myopia (≤-1.0 D) and high myopia (≤-5.0 D) was determined. We used a regression discontinuity design to determine the impact of school entry cut-off date (1 September) by comparing refractive errors at each age, for children born pre-September to post-1 September, and performed a multivariate analysis to explore risk factors associated with myopia. Data analysis was performed in 2017-2018. RESULTS: Prevalence rates of myopia and high myopia were 32.9% (95% CI: 32.8% to 33.1%) and 4.2% (95% CI: 4.1% to 4.2%), respectively. From 6 years of age onwards, children born pre-September were more myopic compared with those born post-1 September (ahead in school by 1 year, discontinuity at 6 years: -0.19 D (95% CI: -0.09 to -0.30 D); 14 years: -0.67 D (95% CI: -0.21 to -1.14 D)). CONCLUSIONS: Our findings suggest that myopia is associated with education, that is primarily focused on near-based activities. Efforts to reduce the burden should be directed to public awareness, reform of education and health systems.

Crystalline Lens Power and Associated Factors in Highly Myopic Children and Adolescents Aged 4 to 19 Years.

PURPOSE: To investigate the distribution characteristics of lens power in highly myopic Chinese children and adolescents and its association with age, axial length (AL), and spherical equivalent (SE). DESIGN: Cross-sectional study. METHODS: A total of 459 highly myopic (SE ≤-5 diopter [D]) children and adolescents aged 4-19 years were included in the study. Participants underwent a series of ophthalmic examinations, which included AL, cycloplegic refraction, and Pentacam measurements. Lens power was calculated using Bennett's formula with its distribution described by age, AL, and SE. Multiple regression was conducted to analyze the associated factors of lens power. RESULTS: Greater lens power was independently associated with younger age, girls, shorter AL, and thicker lens thickness (standardized ß = -0.203, 0.214, -0.379 and 0.492, respectively; all P < .001). However, a significant difference in lens power with age was only found in participants younger than 9 years, after which it reached a plateau (mean difference of 1.23 and 0.084 D per age group, respectively). Lens power was negatively associated with AL only in participants with AL <27 mm. No correlation was observed between lens power and SE. CONCLUSION: Among highly myopic children and adolescents, differences in lens power with age declined significantly after 9 years of age, which was 1 year earlier than non-high myopic patients in previous studies, which implied differences in pathophysiological process between non-high myopia and high myopia. The decoupling of lens power and AL in eyes >27 mm might represent the limited influence of AL on lens power.

Design and Pilot data of the high myopia registration study: Shanghai Child and Adolescent Large-scale Eye Study (SCALE-HM).

PURPOSE: To describe the methodology and pilot data of the Shanghai Child and Adolescent Large-scale Eye Study (SCALE-HM). METHODS: This is a population-based, prospective, examiner-masked study with annual follow-up. Patients are 4- to 18-year-olds with high myopia. The participants will fill out questionnaires and then undergo visual acuity, axial length (AL), intraocular pressure, ophthalmologist assessment, microperimetry, cycloplegic refraction, Pentacam, wavefront aberration, fundus, blood and saliva examinations. To describe the pilot data, intergroup differences were assessed with t-tests or analysis of variance and a logistic regression model was used to determine the independent factors associated with peripapillary atrophy (PPA). RESULTS: Overall, 134 eyes of 79 participants met the pilot study recruitment criteria. The mean AL and spherical equivalent were 26.91 ± 1.07 mm and -9.40 ± 1.77 D, respectively. Peripapillary atrophy (PPA) (N = 112) and tessellated fundus (N = 67) were the most common fundus changes. The mean AL was significantly longer in PPA (27.08 ± 0.93 mm) than in non-PPA eyes (26.06 ± 1.31 mm; p < 0.001). Axial length (AL) (p = 0.041) was the only independent factor associated with PPA. Axial length (AL) was significantly longer in eyes with diffuse chorioretinal atrophy (N = 11; 28.02 ± 1.31 mm) than without myopic retinal lesions (N = 56; 26.48 ± 0.91 mm, p < 0.001) or with tessellated fundus (N = 67; 27.09 ± 0.97 mm, p = 0.012). The myopic degree was higher in eyes with diffuse chorioretinal atrophy than without myopic retinal lesions (-10.51 ± 2.76 D versus -9.06 ± 1.58 D, p = 0.039). CONCLUSION: Peripapillary atrophy and tessellated fundus were common in children and adolescents with high myopia. Results from this prospective study will help to understand the mechanisms, development and prognosis of these changes and can guide early myopia screening.