Interactions between genetic variants and near-work activities in incident myopia in schoolchildren: a 4-year prospective longitudinal study.

CLINICAL RELEVANCE: Knowledge of interactions between genetic variants and near-work activities at the onset of myopia can facilitate health education regarding myopia. BACKGROUND: To investigate the interactions between genetic variants (PDE10A, AREG and GABRR1) and near-work activities in the onset of myopia in southeastern Chinese school children. METHODS: A total of 458 non-myopic, grade 1 children aged 6-7 years were included in a 4-year follow-up examination; 409 children were assessed further. Manifest (non-cycloplegic) refraction and axial length (AL) were measured every year, and questionnaires were administered annually to assess information regarding the demographic characteristics of children, near-work activities, outdoor exposure and parental myopia. Oral mucosa was collected in the last year of follow-up, and Sanger sequencing was used to genotype single nucleotide polymorphisms (SNPs) in DNA. RESULTS: The cumulative change in the spherical equivalent refraction (SER) over 4 years was -1.20 ± 1.00 D, and the proportion of children with incident myopia was 42.9%. Multivariate logistic regression analysis showed that an increased amount of time spent doing homework (>2 h/d) was an independent risk factor for incident myopia. The PDE10A rs12206610CT genotype and spending > 5 h/d on near-work activities showed an interaction for incident myopia (OR = 4.29, 95% CI: 1.27-14.53; Pinteraction = 0.02); moreover, the rs12206610CT genotype carriers who used electronic devices for > 1 h/d displayed an increased risk of incident myopia (OR = 3.43, 95% CI: 1.07-11.01; Pinteraction = 0.043). CONCLUSIONS: The rs2206610CT genotype carriers with near-work activities of >5 h/d were more likely to show incident myopia, especially those who used electronic devices >1 h/d. However, interactions between the rs12206610 SNP and near-work activities require further verification in animal models and larger sample cohorts.

A comparative study of the prevalence of myopia and behavioral changes in primary school students.

OBJECTIVE: To analyze the changes in the prevalence of myopia and its relation to ocular biological parameters, and behaviors among primary school students in China, and understand the prevention and control of myopia. METHODS: Cross-sectional surveys were performed on 7-9-year-old children in the yrs. 2012 and 2019. In addition, spherical equivalent refraction (SER), axial length (AL), and AL/corneal radius ratio (AL/CR ratio) were collected without cycloplegia. Participants completed detailed questionnaires on behavior related to myopia. RESULTS: Data was collected on 623 children (8.02 ± 0.57 years old) in 2012 and 536 students in 2019 (8.09 ± 0.65 years old). The prevalence of myopia was 37.7% in 2012 and 39.9% in 2019. The SER was -0.25 (0.92) D in 2012 and -0.25 (1.25) in 2019. There was no statistical difference in the prevalence of myopia and SER over the 7 years (all P > 0.05). In 2019, the prevalence of myopia among girls demonstrated an increasing trend (33.8% vs. 37.8%), but there was no statistical difference (P > 0.05). The mean AL and AL/CR ratio of boys were decreasing (all P < 0.05). The proportion of children reading more than 2 h and using digital devices for more than 2 h per day after their classes in the 2019 group both decreased (all P < 0.05). However, the proportion of activities performed outdoors for more than 2 h./day decreased significantly (P = 0.001). CONCLUSION: Compared with 2012, the prevalence of myopia in primary school students in 2019 was under control, which may be related to the improvement of children's near-work behavior, but there was the problem of insufficient outdoor activity time. In terms of ocular biological parameters, the risk of myopia for boys in 2019 was lower.

Association of Extracellular Signal-Regulated Kinase Genes With Myopia: A Longitudinal Study of Chinese Children.

OBJECTIVE: The present study was designed to investigate whether the extracellular signal-regulated kinase (ERK) signaling pathway, a downstream component of dopamine signaling, is involved in myopia among Chinese children. METHODS: During a 3.5-year follow-up, 488 primary school students were enrolled in this study. Non-cycloplegic spherical equivalent refraction (SE) and other ocular parameters were assessed. Four variants of four genes in the ERK signaling pathway were selected: RASGRF1 rs6495367, PTPN5 rs1550870, PTPRR rs11178469, and PDGFRA rs6554163. SNPscan was used to genotype single-nucleotide polymorphisms (SNPs). PLINK software was used to assess the associations of the genetic variants with the occurrence or development of myopia, SE, and other ocular parameters. We created a protein-protein interaction (PPI) network and microRNA (miRNA)-gene network using String and Cytoscape and conducted enrichment analyses on the genes in these networks. RESULTS: In total, 426 children (baseline age: 7.28 ± 0.26 years; 236 (55.4%) boys and 190 girls) wereenrolled. After adjusting for confounding factors with 10,000 permutations, children with the CT or TT genotype of PTPN5 rs1550870 were more susceptible to myopia than those with the CC genotype (adjusted p = 0.011). Additionally, PTPN5 rs1550870 was correlated with significant myopic shift and increasing axial length (AL) and lens thickness (LT) but had a negative effect on central corneal thickness (CCT). RASGRF1 rs6495367 was negatively associated with myopic shift (additive: adjusted p = 0.034; dominant: adjusted p = 0.020), myopic SE and AL. PDGFRA rs6554163 TA or AA was negatively associated with increasing LT (adjusted p = 0.033). Evaluation of the effects of SNP-SNP combinations on incident myopia revealed a statistically significant one-locus model: PTPN5 rs1550870 [cross-validation consistency (CVC) = 10/10, adjusted p = 0.0107]. The genes in the PPI and miRNA-gene interaction networks were subjected to enrichment analyses, which suggested that these genes are involved mainly in eye development and dopaminergic synapse-related processes. CONCLUSION: We identified genetic variants of crucial ERK signaling pathway genes that were significantly correlated with myopia and ocular parameter alterations in Chinese children. A combination of gene and miRNA functional analyses with enrichment analyses highlights the regulatory effects associated with ocular development and dopamine biological functions. This study offers novel clues to understand the role of dopamine in the molecular mechanisms of myopia.

Association of Myopia and Genetic Variants of TGFB2-AS1 and TGFBR1 in the TGF-ß Signaling Pathway: A Longitudinal Study in Chinese School-Aged Children.

BACKGROUND: Myopia is a complex multifactorial condition which involves several overlapping signaling pathways mediated by distinct genes. This prospective cohort study evaluated the associations of two genetic variants in the TGF-ß signaling pathway with the onset and progression of myopia and ocular biometric parameters in Chinese school-aged children. METHODS: A total of 556 second grade children were examined and followed up for 3.5 years. Non-cycloplegic refraction and ocular biometric parameters were measured annually. Multivariate regression analysis was used to assess the effect of the TGFBR1 rs10760673 and TGFB2-AS1 rs7550232 variants on the occurrence and progression of myopia. A 10,000 permutations test was used to correct for multiple testing. Functional annotation of single nucleotide polymorphisms (SNPs) was performed using RegulomeDB, HaploReg, and rVarBase. RESULTS: A total of 448 children were included in the analysis. After adjustments for gender, age, near work time and outdoor time with 10,000 permutations, the results indicated that the C allele and the AC or CC genotypes of rs7550232 adjacent to TGFB2-AS1 were associated with a significantly increased risk of the onset of myopia in two genetic models (additive: P' = 0.022; dominant: P' = 0.025). Additionally, the A allele and the AA or AG genotypes of rs10760673 of TGFBR1 were associated with a significant myopic shift (additive: P' = 0.008; dominant: P' = 0.028; recessive: P' = 0.027). Furthermore, rs10760673 was associated with an increase in axial length (AL) (P' = 0.013, ß = 0.03) and a change in the ratio of AL to the corneal radius of curvature (AL/CRC) (P' = 0.031, ß = 0.003). Analysis using RegulomeDB, HaploReg, and rVarBase indicated that rs7550232 is likely to affect transcription factor binding, any motif, DNase footprint, and DNase peak. CONCLUSION: The present study indicated that rs10760673 and rs7550232 may represent susceptibility loci for the progression and onset of myopia, respectively, in school-aged children. Associations of the variants of the TGFBR1 and TGFB2-AS1 genes with myopia may be mediated by the TGF-ß signaling pathway; this hypothesis requires validation in functional studies. This trial was registered as ChiCTR1900020584 at www.Chictr.org.cn.

Relationship between Myopia Progression and School Entrance Age: A 2.5-Year Longitudinal Study.

OBJECTIVE: To investigate the association between myopia progression and school entrance age among Chinese schoolchildren and to suggest a more appropriate school age. METHODS: 1,463 children aged six to nine years from Wenzhou, China, were examined and followed up for two and a half consecutive years. Their noncycloplegic refraction was measured twice each year by using an automatic refractometer; axial length (AL) and corneal radius of curvature (CRC) were tested annually by using the IOLMaster for 2.5 years. The questionnaires were completed by the children to collect detailed information regarding risk factors. Here, myopia is defined as a spherical equivalent less than -1.0D. RESULTS: The changes in spherical equivalent (SE) of 7-year-old children in grade 1 and grade 2 were -0.45D and -0.56D, while changes in AL were 0.59 mm and 0.62 mm, respectively. The SE changes of 8-year-old children in grade 2 and grade 3 were -0.54D and -0.75D; meanwhile, the AL changes were 0.57 mm and 0.61 mm, respectively. Significant statistical differences were observed in ocular biological structure parameters, except for corneal radius of curvature (CRC) or anterior chamber depth (ACD), among children with the same age in different grades during this study. The prevalence of myopia was also significantly higher in higher grades for children with same age. CONCLUSIONS: Myopia is related to children's school entrance age. Children who start school in an earlier age are more likely to suffer from myopia, and the progression of myopia can be considerably faster. Therefore, it is recommended to enter school after the age of 7.

Longitudinal association between myopia and parental myopia and outdoor time among students in Wenzhou: a 2.5-year longitudinal cohort study.

BACKGROUND: To evaluate the impact of parental myopia and outdoor time on myopia among students in Wenzhou. METHODS: We examined 1388 primary students from first grade to third grade in Wenzhou from September 2012 to March 2015. We performed noncycloplegic refractometry on each student every six months and axial length (AL) measurements every year. At the commencement of our study, children were asked to complete a questionnaire regarding near work activity and outdoor activity, whereas parents were asked to complete a self-administered questionnaire regarding their background circumstances and their history of myopia. RESULTS: A total of 1294 students (93.2%) returned for follow-up examinations. Children with initial and final no myopia spent more time on outdoor activities than those with new onset myopia (1.92 vs. 1.81 h/d, p = 0.022), and elongation of AL in children with a high level (> 2.5 h/day) of outdoor time (0.22 ± 0.13 mm/Y) was less than those with a low level (≤ 1.5 h/day) of outdoor time (0.24 ± 0.14 mm/Y, p = 0.045). The proportion of rapid myopia progression (≤-0.5D/Y) was 16.7%, 20.2% and 31.5% among the children with no myopic parent, one myopic parent and two myopic parents, respectively (X2 = 28.076, p < 0.001), and the elongation of AL in children among different numbers of myopic parents was significantly different (p < 0.001). A high level of outdoor time was a protective factor for children with one myopic parent (HR 0.49, 95% CI 0.27-0.88; p = 0.018). CONCLUSIONS: In this sample, parental myopia and outdoor time were associated with myopia in children. A high level of outdoor time was a protective factor for children with one myopic parent.

Genome-Wide Association of Genetic Variants With Refraction, Axial Length, and Corneal Curvature: A Longitudinal Study of Chinese Schoolchildren.

BACKGROUND: Myopia is a common eye disorder that is approaching epidemic proportions worldwide. A genome-wide association study identified AREG (rs12511037), GABRR1 (rs13215566), and PDE10A (rs12206610) as being associated with refractive error in Asian populations. The present study investigated the associations between these three genetic variants and the occurrence and development of myopia, spherical equivalent refraction (SER), axial length (AL), and corneal curvature (CC) in a cohort of southeastern Chinese schoolchildren. METHODS: We examined and followed 550 children in grade 1 enrolled in the Wenzhou Epidemiology of Refractive Error (WERE) project. During the 4-year follow-up, non-cycloplegic refraction was evaluated twice each year, and the AL and CC were measured once every year. Age, sex, and the amounts of time spent on near work and outdoors were documented with a questionnaire. Sanger DNA sequencing was used to genotype single nucleotide polymorphisms (SNPs). SNPtest software was used to identify potential genetic variants associated with myopia, SER, AL, and CC. Ten thousand permutations were used to correct for multiple testing. RESULTS: In total, 469 children, including 249 (53.1%) boys and 220 (46.9%) girls, were included in analyses. The mean age of all the children was 6.33 ± 0.48 years. After adjusting for age, sex, time spent on near work and time spent outdoors, neither the genotypes nor the allele frequencies of the three SNPs were significantly associated with myopic shift, incident myopia or the change in SER. After adjusting for age, sex, near-work time and outdoor time with 10,000 permutations, the genotype AREG (rs12511037) was associated with an increase in AL (P'-values for the dominant, recessive, additive and general models were 0.0032, 0.0275, 0.0045, and 0.0099, respectively); the genotype PDE10A (rs12206610) was associated with a change in CC in the additive (P' = 0.0096), dominant (P' = 0.0096), and heterozygous models (P' = 0.0096). CONCLUSION: These findings preliminarily indicate that AREG SNP rs12511037 and PDE10A SNP rs12206610 are etiologically relevant for ocular traits, providing a basis for further exploration of the development of myopia and its molecular mechanism. However, elucidating the role of AREG and PDE10A in the pathogenesis of myopia requires further animal model and human genetic epidemiology studies. This trial is registered as ChiCTR1900020584 at www.Chictr.org.cn.

Epidemiology of pediatric eye injuries requiring hospitalization in rural areas of Wenzhou and Changsha, China: a 10-year retrospective study.

BACKGROUND: The aim of this study was to review the demographic and characteristic distribution data of serious rural pediatric eye injuries in Wenzhou and Changsha, located in Zhejiang Province in East China and Hunan Province in Central China. METHODS: This retrospective study included hospitalized pediatric patients aged < 18 years with eye injuries at the Eye Hospital of Wenzhou Medical University and Xiangya Hospital of Central South University from January 2008 to December 2017. Demographic data, injury types, injury causes, and initial and final visual acuity (VA) were recorded and analyzed. The ocular trauma score (OTS) was calculated to assess the severity of injury and evaluate the prognosis. All patient data were obtained from the medical record systems. RESULTS: In total, 1125 children were hospitalized during the 10-year period; 830 (73.8%) were males and 295 (26.2%) were females. The majority of the patients were aged 3 to 8 years (57.4%, n = 646). Among mechanical injuries (n = 1007), penetrating injury was the most common (68.4%, n = 689), followed by contusion (17.2%, n = 173) and rupture (8.1%, n = 82). Overall, the top three injury causes were sharp objects (n = 544, 48.4%), blunt objects (n = 209, 18.6%) and fireworks (n = 121, 10.8%). In Wenzhou, eye injuries occurred mostly in summer (n = 136, 29.1%), and sharp object-related eye injuries accounted for the highest proportion (n = 98, 72.1%). In Changsha, eye injuries occurred mostly in winter (n = 272, 41.3%), and firecracker- and fireworks-associated eye injury accounted for the highest proportion (n = 73, 26.8%). The final VA was positively correlated with the initial VA (r = 0.641, P < 0.001) and the OTS (r = 0.582, P < 0.001). CONCLUSION: The age range of the susceptible pediatric population from rural areas was 3-8 years. Most eye injuries were penetrating, and the main cause of injury was a sharp object. Notably, the differences in the characteristics of eye injuries in the two areas were related to regional features.