Clinical and genetic studies of keratoconus: A case control study

Jenny, Parameshvara Deva and Nee Ng, Gek Pheng (2023) Clinical and genetic studies of keratoconus: A case control study. PhD thesis, UTAR.

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Abstract

Keratoconus (KC) was initially described about 150 years ago, but still remains an enigmatic disease. International research is still pursuing the wide ranging genetic and environmental factors which play an important role in aetiopathogenesis. The complexity of Keratoconus makes it difficult to investigate and conclusively find a solution to treat it clinically and genetically. The first objective of this study is to analyse the risk factors associated with keratoconus. The main contribution of this study, shows that eye rubbing and severe rubbing in KC were more significantly present (78.6%) as a habit than in the control Family (50%) and Normal (58.3%) groups. Eye rubbing is 4.85 times increased risk compared to normal controls. Eye itchiness seems to be 4.39 times more a risk in KC. Eye wateriness is 19.8 times more associated with KC compared with normal controls. The second objectives is to assess the clinical keratoconus, with diagnostic methods such as topography, and the use of Crosslinking for the biomechanical stabilization and treatment of KC patients. We find that the visual acuity of post- CXL KC patients improved to above 90%, achieving optimized normal vision. This study has shown, that progression can be halted and the cornea can be remolded and vision rehabilitated with Rigid Gas Permeable contact lenses or INTACS. Crosslinking definitely improves the corneal biomechanical strength, but does not fully correct, so that some cases need a second crosslinking a few years later. Research to date has not identified any single major gene associated with the aetiology of KC, though in some families, the inheritance pattern does suggest such a model. It is clear that Keratoconus is a complex disease, and multifactorial issues complicate its aetiology and even its genetic heritage. The third objective of this study is to assess the role of the three candidate genes, VSX1exon3, SOD1exon2, and COL4A3exon17 in the aetiopathogenesis of KC. Results through PCR sequencing and Exome sequencing are encouraging but inconclusive. Multivariate analysis with Odds Ratio, Linkage Disequilibrium and Haploview Software have only partially confirmed the association between the VSX1 gene variants, A182A, P237P and R217H. Further genomic research using Next Generational Sequencing (NGS) and GWAS possibly and hopefully will uncover the keratoconus mystery!

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