A genome-wide association study of corneal astigmatism: The CREAM Consortium.

Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. Results: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). Conclusions: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.

An active pursuit of reassurance-coping strategies of fathers with infants in the Neonatal Intensive Care Unit.

OBJECTIVE: This study aims to explore coping strategies of fathers of very low birth weight (VLBW) infants in the neonatal intensive care unit (NICU). STUDY DESIGN: A qualitative descriptive study among fathers of VLBW babies. Semi-structured interviews were conducted with 15 fathers until data saturation was achieved. The Consolidated Criteria for Reporting Qualitative Studies (COREQ) checklist was used for reporting. RESULTS: The overarching theme was an active pursuit of reassurance. Coping strategies revolved around identifying specific stressors and then making deliberate efforts to address them. Based on the main stressors identified, three subthemes were derived: pursuing information amidst uncertainty, bonding with the infant for normalcy and seeking emotional support in the midst of anxiety. Fathers took on a predominantly problem-focused approach. CONCLUSIONS: Empowering fathers with knowledge and emotional support, facilitating bonding with the infant and addressing their concerns are important in supporting them while having an infant in the NICU.

Case control study of risk factors and ophthalmological outcomes of very low birth weight infants with Type 1 retinopathy of prematurity.

INTRODUCTION: We evaluated the risk factors associated with Type 1 retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants and compared ophthalmologic outcomes between cases with Type 1 ROP who received treatment and gestational age-matched controls with mild or no ROP not requiring treatment. METHODS: This was a retrospective case-control study of VLBW infants born in National University Hospital, Singapore, from January 2001 to December 2013. 17 cases with Type 1 ROP were each matched for gestational age with controls who had either mild (below Stage 2) or no ROP. Antenatal, perinatal and postnatal variables, as well as childhood ophthalmologic outcomes, were collected from their clinical records and analysed. RESULTS: The number of packed cell transfusions and highest fraction of inspired oxygen given at weeks 7-10 were found to be statistically significant on multivariate analysis (p = 0.045 and p = 0.049, respectively). None of the infants had blindness or retinal detachment, and there were no significant differences in refractive errors between the groups at 1-4 years of age. Strabismus at four years of age was more common in the group with Type 1 ROP (p = 0.023). CONCLUSION: Increased episodes of blood transfusions and chronic lung disease requiring high oxygen supplementation at 7-10 weeks of life are significant risk factors associated with Type 1 ROP in VLBW infants in our study. Strabismus at four years is more common in this group of patients. This study highlights the importance of long-term ophthalmologic surveillance for these high-risk children.

MRI of posterior eye shape and its associations with myopia and ethnicity.

PURPOSE: To evaluate posterior eye shape variations across a wide refractive error range using brain MRI in a multiethnic cohort. METHODS: Adult subjects in the multiethnic Singapore Epidemiology of Eye Disease study were included. Spherical equivalent (SE) was measured using subjective refraction, and axial length (AL) was measured using optical biometry. MRI was performed using a 3-Tesla whole body scanner with a 32-channel head coil. The radii and asphericity based on fitting of the posterior two-thirds of the eye (240°) were calculated. The refractive error status was categorised as myopic (SE<-0.5 D) or non-myopic (SE≥-0.5 D). RESULTS: A total of 450 adult participants (mean age 64.2±6.5 years old) were included. Less oblate asphericity was associated with more myopic SE, longer AL and with a refractive error categorisation of myopia (p<0.001 for all). Asphericity values were less oblate in myopic compared with non-myopic eyes (p<0.001). Multivariate analysis showed that Chinese subjects had less oblate eyes than Malay and Indian subjects, especially in non-myopic eyes. CONCLUSIONS: A less oblate posterior eye shape was associated with myopic eyes. Chinese eyes have less oblate shapes than Malay and Indian eyes, especially in non-myopic eyes.

Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium.

PURPOSE: To evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the Consortium of Refractive Error and Myopia (CREAM). METHODS: A candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. Fifty loci with the strongest associations with myopia were chosen from a previous published GWAS study. Highly myopic (spherical equivalent [SE] ≤ -5.0 diopters [D]) cases with MMD (N = 348), and two sets of controls were enrolled: (1) the first set included 16,275 emmetropes (SE ≤ -0.5 D); and (2) second set included 898 highly myopic subjects (SE ≤ -5.0 D) without MMD. MMD was classified based on the International photographic classification for pathologic myopia (META-PM). RESULTS: In the first analysis, comprising highly myopic cases with MMD (N = 348) versus emmetropic controls without MMD (N = 16,275), two SNPs were significantly associated with high myopia in adults with HM and MMD: (1) rs10824518 (P = 6.20E-07) in KCNMA1, which is highly expressed in human retinal and scleral tissues; and (2) rs524952 (P = 2.32E-16) near GJD2. In the second analysis, comprising highly myopic cases with MMD (N = 348) versus highly myopic controls without MMD (N = 898), none of the SNPs studied reached Bonferroni-corrected significance. CONCLUSIONS: Of the 50 myopia-associated loci, we did not find any variant specifically associated with MMD, but the KCNMA1 and GJD2 loci were significantly associated with HM in highly myopic subjects with MMD, compared to emmetropes.

Correction: Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium.

[This corrects the article DOI: 10.1371/journal.pone.0220143.].

Sleep Duration in Infants Was Not Associated With Myopia at 3 Years.

PURPOSE: To investigate the association of sleep duration and quality at 12 months and myopia at 3 years. DESIGN: Cohort study. METHODS: The Growing Up in Singapore Towards Healthy Outcomes (GUSTO) birth cohort recruited pregnant women at 2 major public maternity hospitals (n = 1236). We included 376 children of Chinese, Malay, and Indian ethnicity who had completed caregiver questionnaires on the child's sleep at 12 months of age [Brief Infant Sleep Questionnaire (BISQ)] and also completed cycloplegic autorefraction and eye axial length (AL) measurement at 3 years of age. Data on total sleep duration and number of night wakings were collected by BISQ. Univariable and multivariable regression models adjusting for potential confounders (age, sex, ethnicity, parental myopia, maternal education level, outdoor time, near work, and height) were used. RESULTS: Thirteen (3.5%) participants were myopic and mean spherical equivalent (SE) was 0.89 diopters (D) (SD 0.88) at 3 years. Total sleep duration and number of night wakings at 12 months were not associated with SE at 3 years (P > 0.05). The total sleep duration (P = 0.07) and number of night wakings (P = 0.49) were not associated with AL in the multivariate model. Total sleep duration in tertile 2 was not associated with AL (P = 0.11) compared with tertile 1. Only total sleep duration in tertile 3 was associated with longer AL (P = 0.006), but there was no association with SE. CONCLUSIONS: Sleep duration and quality at 12 months of age were not associated with refractive error at 3 years.

An Ecologic Study of Trends in the Prevalence of Myopia in Chinese Adults in Singapore Born from the 1920s to 1980s.

INTRODUCTION: This study aimed to investigate secular trends in the prevalence of myopia over 6 decades (from the 1920s to 1980s) in Chinese adults in Singapore. MATERIALS AND METHODS: Parental myopia prevalence was estimated using a parent-completed questionnaire in paediatric cohorts that included: 1) The Singapore Cohort Of Risk factors for Myopia (SCORM), 2) The Strabismus, Amblyopia and Refractive Error in Singaporean Children (STARS), and 3) The Growing Up in Singapore Towards healthy Outcomes (GUSTO). Published estimates for myopia prevalence from 5 adult studies in Singapore were reviewed. Secular trends in the prevalence of myopia were correlated with changes in the education system. RESULTS: The prevalence of parental myopia in SCORM (n = 2943), STARS (n = 4938), and GUSTO (n = 1072) was 47.8%, 53.4%, and 73.4%, respectively; corresponding calendar years these parents might have started schooling were 1966, 1973, and 1983 (born in 1960, 1967, and 1977), respectively. Mean age of parents was 41.3, 40.1, and 33.4 years, respectively. Prevalence of myopia in adult studies in persons who started elementary school in 1928, 1934, 1938, 1939, 1942, 1948, 1952, 1958, 1962, 1972, 1982, and 1995 were 36.4%, 39.7%, 30.0%, 31.5%, 33.0%, 26.4%, 32.5%, 48.7%, 39.4%, 52.0%, 82.2%, and 85.9%, respectively. CONCLUSION: During the past few decades, the prevalence of myopia increased rapidly, especially in persons who started elementary school after the 1980s (born after 1970). The education system was expanded after Singapore's independence in 1965, and the new education system was introduced in 1978. These changes, together with increasing intensive schooling, may have contributed to the increase in myopia prevalence.

Pediatric Thromboembolism in Japan.

OBJECTIVES: To investigate the clinical and epidemiologic characteristics of thromboembolism in Japanese children. METHODS: Clinical data of 77 patients with thromboembolism from a national tertiary pediatric care center were reviewed. RESULTS: Incidence of thromboembolism was calculated to be 15 per 10,000 hospital admissions. Infants younger than one year of age made up the largest age group (25 patients, including nine neonates younger than 30 d). The occurrence of thromboembolism increased over the years in the index population. Thromboembolism was diagnosed as follows: portal vein thrombosis (n = 15), obstruction of central venous catheter (n = 13) and cerebral infarction (n = 9). Among the 77 patients, there were eight mortalities and six significant sequelae. CONCLUSIONS: In pediatric care, especially in intensive care, we should pay more attention to thromboembolism in order to detect it promptly.