Assessment of risk factors, clinical features and genes in keratoconus

© 2013 Dr. Srujana SahebjadaKeratoconus (KC) is a bilateral corneal condition characterised by progressive corneal thinning that results in corneal protrusion, irregular astigmatism and decreased vision. Despite various basic and clinical studies KC remains a poorly understood disease. This thesis aimed to better understand the risk factors, clinical characteristics and genetic aspects of KC. Two hundred and sixty KC individuals were recruited from a major public hospital, private rooms and mail outs. All subjects complete a study questionnaire, (including quality of life questionnaire) clinical examination and complete details of family history of disease. A blood/saliva sample was collected for genetic studies. The first aim was to describe the characteristics of the KC subjects and assess the risk factors for the disease aiming to identify features of early disease. The second aim of the study was to assess anterior segment parameters of eyes with KC at different stages of disease and also to evaluate the correlation of corneal curvature with other anterior segment parameters. The third aim was to assess posterior segment changes through the use of optical coherence tomography (OCT) and compare measures to a non-KC patient group. The fourth aim was to assess the impact of KC in the better eye and worse eye on vision-related quality of life. The final aim was to identify candidate gene associations with KC. The study showed that asthma presented as a significant risk factor for KC in this cohort and suggested that asthma and KC could potentially share some common genetic determinants as a basis of disease. Anterior segment evaluation showed that corneal thickness both at the center and apex are important markers for detecting subclinical KC and that there is a significant alteration in these parameters with increasing disease severity. In addition, I was also interested in biometric measures of the KC eyes as a whole and thus examined the posterior segment changes in these eyes and found that KC patients have thicker fovea and maculae and greater macular volume compared to non KC individuals. Having noticed considerable changes in various biometric measures of KC eyes; I further wished to assess the impact of the KC on vision related quality of life (VisQoL) in these patients. Using a vision-specific multi-attribute utility instrument (MAUI), this study demonstrated substantial disutility relating to KC. Worse vision in the better eye (but not the worse eye) was independently associated with a reduction in Vision and Quality of Life Index (VisQoL) utilities, suggesting that considering VisQoL utilities based on vision in the better eye to be important estimate of the impact of KC from the participant’s perspective. Finally genetic association studies of candidate genes with KC were assessed and the results implicated a single nucleotide polymorphism (SNP) variation at the hepatocyte growth factor locus with KC. Also SNPs rs1324183 in the MPDZ-NF1B and rs9938149 (between BANP and ZNF4659) were also associated with KC. These results replicate several genetic loci, confirm there to be a genetic basis to KC and implicate the involvement of a number of different genetic pathways in this disease. This study provides a complete data set on a large Australian population of KC subjects which includes a wide range of environmental parameters and ocular biometric measures. The findings presented in this thesis will allow us to better understand the etiology of KC and also assist in early diagnosis of KC so as to provide early disease management and ultimately arrest progression of this disease without the need for corneal transplantation. Also the data generated from the VisQoL questionnaire can be used to plan support needs for KC patients