Early diagnosis and modified collagen crosslinking treatment of keratoconus

Abstract

Keratoconus is a disease of the eye characterized by change in the shape of a weakened cornea. It often begins in the teenage or young adulthood and progresses gradually leading to loss of vision. Traditionally, the diagnosis of keratoconus is made by a combination of clinical history and corneal topographic findings. There have been several advances in imaging technologies in evaluating the cornea. This thesis showed that there was significant difference in posterior corneal and thickness measurement between imaging devices in keratoconus. Measurements from different imaging modalities should not be used interchangeably. Although the diagnosis of moderate to advanced keratoconus can be made readily, differentiation of early or subclinical keratoconus from normal can be difficult. Consequently, there is an emphasis on the use of non-tomographic strategies for diagnosis of keratoconus. The results of this thesis showed comparable diagnostic capability between selected tomographic and corneal dynamic response parameters in moderate to advanced keratoconus. Combined corneal tomographic and biomechanical evaluation was found to be more accurate than individual parameters for the diagnosis of subclinical keratoconus. Corneal collagen crosslinking (CXL) is the only proven treatment to halt disease progression in keratoconus. This procedure utilizing riboflavin and ultraviolet-A light can significantly increase the biomechanical strength of the cornea. The major drawback of the conventional protocol is its long treatment duration and the need of epithelial removal. Accelerated CXL is an alternative protocol with higher illumination intensity but shorter treatment duration. Transepithelial CXL is another modification that aims at reducing postoperative complications following epithelial removal. The efficacy of both accelerated and transepithelial CXL has been questioned. This thesis evaluated the application of modified CXL protocols in the management of progressive keratoconus. Accelerated CXL was demonstrated to stop keratoconus progression with a better efficacy demonstrated in advanced cases. Both accelerated and conventional CXL protocols were effective in stabilizing keratoconus progression, but a stronger topographic flattening effect was observed for the conventional technique. Long-term evaluation of clinical outcomes after accelerated CXL showed continuous corneal flattening over 5 years. Accelerated CXL was able to induce a shift in anterior corneal curvature from steepening to flattening. This was significantly different from the change observed in stable keratoconus. Corneal haze has been considered as visible CXL effect, but its relationship with corneal curvature remained unknown. This thesis showed that corneal curvature remained stable or decrease over time after resolution of corneal haze in eyes following accelerated CXL. These findings suggested that accelerated CXL has a good treatment efficacy in moderate to advanced keratoconus, and the effect persisted over long-term without impairing the transparency of cornea. As for the transepithelial CXL, results showed that disease progression can be stopped in advanced keratoconus. The advantages of keeping the corneal epithelium intact include a faster visual rehabilitation and minimal postoperative discomfort compared to epithelium-off protocols. The results of this thesis suggested that combined corneal tomographic and biomechanical assessment may enable early keratoconus detection. Furthermore, modified versions of CXL could be offered as treatment option for stopping disease progression in moderate to advanced keratoconus.