Investigations into the potential effectiveness of new and existing corneal cross-linking therapies

The studies comprising this thesis were conducted to examine the potential of a range of cross-linking therapies; in particular, to investigate the effect of a novel cross-linking therapy (involving a bacteriochlorophyll derivative and near-infra red illumination (WST-D/NIR)) on the structure of the cornea, and to develop a trans-epithelial riboflavin/Ultraviolet-A (UVA) corneal cross-linking protocol that was equally effective to that of the standard protocol (SCXL), without the need for epithelium removal. A number of laboratory techniques were used to investigate changes in the structure of the cornea and its biochemical and biomechanical properties following cross-linking. X-ray scattering and electron microscopy data provided evidence that treatment with WST-D/NIR resulted in no change in corneal collagen organisation and confirmed its potential as an alternative to riboflavin/UVA cross-linking for stiffening diseased or surgically weakened corneas. Enzyme digestion studies and strip extensometry were performed to compare the effectiveness of newly developed riboflavin/UVA protocols to that of the SCXL protocol in terms of their ability to increase the enzymatic resistance and stiffness of the cornea. The studies indicated that the intensity and distribution of cross-links formed within the cornea vary with different protocols, and that the outcome of trans-epithelial riboflavin/UVA cross-linking may be significantly enhanced through the use of higher concentrations of riboflavin, a longer duration of iontophoresis and the use of pulsed and higher energy dose UVA. Although the precise amount of CXL required to prevent the disease progression is still unidentified, the full stromal depth of CXL post SCXL treatment might not be needed, therefore, modified trans-epithelial protocols identified in this thesis may be sufficient to prevent disease progression. Further clinical studies, especially randomized prospective trials, are, however, required to confirm the encouraging results of these modified procedures