Factors contributing to the development of myopia: From epidemiology study of school myopia to molecular genetic study of severe myopia

Studies in this thesis aim to evaluate environmental and genetic factors attributing to the development of two important forms of myopia: school myopia (commonest form) and high myopia (strong genetic basis).; For school myopia, a large-scale epidemiology study was conducted on 7,560 randomly selected primary school children aged 5 to 16 years (mean = 9.33). The relative risk of myopia in children with one myopic parent was 1.82 and both myopic parents 3.23, when compared with children without myopic parents. It was also confirmed that pre-myopic eye is not 'abnormally' elongated but myopic progression and axial length growth were associated with the number of myopic parents. These are in support of the hypothesis that destined myopic eyes are initially normal in size but have faster growth rate. Increase in visual task was associated with increase risk of myopia (Odds Ratio = 1.31; 95% confidence interval, 1.29--1.33). Children with astigmatism were more myopic than children without astigmatism (p < 0.0001). This study has provided evidence for genetic susceptibility of myopia and quantified some environmental risk factors. Accordingly, preventive measures may be possible to reduce its incidence in school children.; One family linkage and two candidate gene studies were conducted in high myopes. In the linkage study, we tried to confirm whether linkage exists in a previously reported 7.6-cM region of linkage on chromosome 18p11.31. Two-point linkage analysis confirmed trends toward linkage with markers D18S476 and D18S62 with a high myopia locus on chromosome 18p. The maximum LOD score obtained at D18S476 by further multi-point linkage analysis was 2.4, which did not demonstrate a statistically significant (LOD > 3) linkage. There is therefore a possibility of a high myopia locus on chromosome 18p and simultaneously a strong contribution from environmental factors. The transforming growth factor beta-interacting factor (TGIF) and the aggrecan VNTR genotype were screened for sequence alterations in case control manner. SNPs with significant difference in distributions between myopia cases and controls were identified in TGIF but not aggrecan indicating that TGIF but not aggrecan may be a candidate gene for high myopia.; Results of the above studies have thrown light onto environment and genetic causes of myopia.