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Understanding the structural basis of corneal refractive function and its modification via novel therapeutic approaches

Morgan, Sian 2014. Understanding the structural basis of corneal refractive function and its modification via novel therapeutic approaches. PhD Thesis, Cardiff University.
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Abstract

The studies comprising this thesis were conducted to further understand how structural changes to the corneal extracellular matrix can affect the cornea’s unique properties, with the ultimate goal of improving novel treatments and their outcomes. Following refractive surgery, changes in matrix structure can cause loss of structural integrity and transparency, which may adversely affect the surgical outcome. The first objective was to define what governs corneal shape and ultrastructural organisation by analysing the abnormal post-hatch corneal collagen arrangement in an avian model (beg). Structural information was also obtained post-in vivo microwave keratoplasty to assess the treatment as a suitable alternative to more invasive correction procedures. In addition, modifying the resident cell type as a means of improving post-treatment wound healing following LASIK was also investigated using corneal stromal stem cells. Finally, the efficiency of transepithelial riboflavin/UVA collagen cross-linking in terms of riboflavin uptake and post-treatment corneal stiffness, was evaluated. X-ray scattering studies revealed that corneal flattening in beg chickens is related to biomechanical changes brought about by an alteration in collagen arrangement at the corneal periphery. This highlights the importance of the limbal fibril annulus in corneal shape preservation. X-ray studies also revealed that microwave keratoplasty may impact on peripheral vision by introducing spatial disruption of stromal collagen, resulting in localised corneal opacity in the treatment area. Loss of fibrillar structure and order could also have further implications for corneal biomechanics and shape. The application of human corneal stromal stem cells under LASIK-like flaps was revealed to be a promising approach for increasing flap adherence strength whilst maintaining corneal clarity. Introducing these cells in the early stages of flap-healing appears to improve the repair process, conceivably through an embryonic-like mechanism. Lastly, stress-strain and riboflavin uptake results for transepithelial riboflavin delivery during corneal cross-linking were encouraging, however refinements to the testing procedure are required to fully assess the treatment efficacy. Collectively these findings accentuate the importance of the precise stromal collagen fibril arrangement and composition for maintaining corneal transparency, shape and general functionality. All these factors must be taken into consideration when implementing novel correction procedures or modifying existing treatments for corneal defects.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Optometry and Vision Sciences
Subjects: R Medicine > RE Ophthalmology
Uncontrolled Keywords: Cornea; Refractive surgery; Cross-linking; Collagen; X-ray scattering; Wound healing
Date of First Compliant Deposit: 30 March 2016
Last Modified: 09 Jan 2024 15:31
URI: https://orca.cardiff.ac.uk/id/eprint/59401

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