Age-related Cataract: Incidence, Modifiable Risk Factors and Gene-Environment Interplay

Abstract

Abstract Age-related cataract is the leading cause of blindness and visual impairment worldwide in older adults. Although risk factors for cataract have been suggested, the aetiologies of different types of cataract, namely cortical, nuclear and posterior subcapsular (PSC) cataract, remain largely unclear. In particular, there is limited knowledge of potentially modifiable risk factors, such as dietary factors, and of cataract development in Asian populations. Recently, there has been growing interest in the genetics of cataract. It is likely that combination of genetic and environmental factors contributes to the development of cataract. The aims of this thesis are: 1) to determine the incidence and associated risk factors of cataract and cataract surgery in an Asian population; 2) to evaluate associations between dietary factors and cataract; and 3) to explore possible gene-environment interactions in regard to risk of age-related cataract. This thesis used cataract phenotype data assessed by the candidate from two population-based cohort studies: the Blue Mountains Eye Study (BMES) and the Singapore Epidemiology of Eye Diseases (SEED) study. Using data from the Singapore populations, 6-year incidence of cataract and cataract surgery ranged from 8.7% to 14.1%. Important risk factors for cataract and cataract surgery in Asians were diabetes, hypertension and myopia. From the BMES, combination of adherence to dietary guidelines and healthy body weight was associated with decreased risk of nuclear cataract, while higher legume intake was associated with reduced likelihood of incident PSC cataract. Four gene-environment interactions were investigated: 1) AKR1B1 polymorphism and elevated fasting glucose in relation to cortical cataract; 2) MTHFR polymorphism and elevated homocysteine in relation to cortical cataract; 3) SLCO1B1 gene and statin use in relation to incidence of cataract; and 4) FTO polymorphism and low protein intake in relation to PSC cataract. Findings from this thesis contributes to the knowledge of lifestyle (modifiable) factors and possible gene and environment interplays in relation to the risks of age-related cataract. If modifiable risk factors identified are confirmed, therapeutic strategies could be developed to reduce the risk of cataract among older persons, and thus reduce the burden of age-related cataract.