Identifying, Characterising and Modifying the Natural History and Progression of Keratoconus in New Zealand/ Aotearoa

Abstract

Keratoconus, the focus of this thesis, is a progressive ectasia (thinning/bowing) of the cornea thought to be more prevalent in New Zealand with a predilection for Maori and Pacific populations. Keratoconus occurs due to a combination of genetic and environmental factors. Typically, diagnosis of keratoconus is made on the basis of clinical and corneal topographic/tomographic signs. A large population of advanced keratoconics was analysed for tomographic and phenotypic variations between subjects with differing aetiological risk factors. This study specifically identified phenotypic differences occurring between subjects with, and without, a family history. The results confirmed over-representation of Maori and Pacific ethnicities in the New Zealand keratoconic population and identified largely asymmetric corneal disease by tomographic classification. The Ocular Response Analyser (ORA) was employed to investigate the intrinsic biomechanical properties of the normal and keratoconic cornea. Significant correlations were observed between posterior corneal elevation and corneal resistance factor in the keratoconic cohort. However, no single ORA value was identified as a discriminator of keratoconus, nonetheless, combining these factors may increase their diagnostic sensitivity. Corneal collagen cross-linking aims to halt, or slow, the progression of keratoconus. This novel therapy involves utilising ultra violet light (UVA) and the photosensitiser riboflavin to stimulate formation of covalent bonds between corneal collagen fibrils. This improves the mechanical rigidity of the cornea and increases resistance to the ectatic process. In a large randomised contolled trial (RCT) of collagen cross-linking for keratoconus in New Zealand, corneal keratometry reduced (improved) in the majority of treated eyes, while visual acuity and refraction remained stable. In contrast, control, untreated, contralateral eyes showed continued progression in both keratometric and refractive indices. A unique quantitative study by in vivo confocal microscopy revealed significant reduction in the sub-basal nerve plexus and anterior keratocyte density following cross-linking in keratoconus. These effects persisted over 12 months post-operatively. Dense hyperreflective bands developed in the corneal mid-stroma following treatment that reduced in intensity over 24 months post cross-linking. These inter-related studies provide new data on keratoconus in New Zealand, on the application of diagnostic techniques, and the safety and effectiveness of collagen crosslinking for keratoconus in a large RCT.