No abstract

Refractive error is the most common eye disorder worldwide, and a prominent cause of blindness. Myopia affects over 30% of Western populations, and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses including 37,382 individuals from 27 studies of European ancestry, and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in subjects of European ancestry, of which 8 were shared with Asians. Combined analysis revealed 8 additional loci. The new loci include genes with functions in neurotransmission (GRIA4), ion channels (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2, BMP2), and eye development (SIX6, PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for subjects with the highest genetic load. Our results, accumulated across independent multi-ethnic studies, considerably advance understanding of mechanisms involved in refractive error and myopia.

Time spent outdoors was predictive of incident myopia independently of physical activity level. The greater association observed for time outdoors suggests that the previously reported link between "sports/outdoor activity" and incident myopia is due mainly to its capture of information relating to time outdoors rather than physical activity.

Rates of cesarean section have increased in the past 2 to 3 decades in the United Kingdom and elsewhere. Apart from immediate maternal and infant complications, there appears to be an increased risk of placenta previa, placental abruption, and uterine rupture during labor in subsequent pregnancies. Recent studies suggest an increased risk of stillbirth in pregnancies following cesarean delivery. The investigators attempted to clarify this risk in a retrospective cohort study of 81,784 singleton deliveries taking place in the UK in the years 1968-1989. Excluding those caused by congenital anomalies there were 290 stillbirths, 113 of which were classified as explained, and 177 as unexplained. Mothers having a previous cesarean delivery tended to be older than the others, to have lower parity, to be of higher social class, and to have had previous adverse pregnancy outcomes.Unadjusted hazard ratios for all stillbirths, those that were explained, and those unexplained were, respectively, 1.54 (95% confidence interval [CI], 1.04-2.29), 2.13 (95% CI, 1.22-3.72), and 1.19 (95% CI, 0.68-2.09). After adjusting for maternal age, parity, social class, previous adverse pregnancy outcomes, body mass index, and smoking status, the respective hazard ratios were 1.58 (95% CI, 0.95-2.63), 2.08 (95% CI, 1.00-4.31), and 1.24 (95% CI, 0.60-2.56). Stillbirths following a previous cesarean section were more likely than in the "unexposed" group to be explained, and they were likelier to be associated with abruption/hemorrhage or mechanical causes. It was estimated, using a hazard ratio of 1.58 to approximate the adjusted relative risk in a population with a section rate of 7.1% and an average stillbirth rate of 0.35%, that approximately 4% of all stillbirths in the population may be ascribed to previous cesarean delivery.These findings affirm an increased risk of stillbirth in women previously having a cesarean section. The risk is most evident in cases of explained stillbirth. Further research is needed to determine whether this association is causal and, if so, what mechanisms might be involved.

Although strabismus has decreased in the UK, it and amblyopia remain common problems. Children from less advantaged backgrounds were more at risk of hypermetropia and to a lesser extent of amblyopia and convergent strabismus. Children's eye-care services may need to take account of this socio-economic gradient in prevalence to avoid inequity in access to care.