A study of UV-A Corneal Cross-Linking in Juvenile Corneas

Abstract

The aim of this project was to explore whether juvenile corneas respond to cross-linking (CXL) treatment better than adult corneas. The project evaluated the effect of CXL on corneal biomechanics in eye-banked human corneas from different age groups, and it explored the effects of CXL on corneal curvature and thickness in juvenile and adult keratoconic patients in two different populations. Pilot studies were conducted to assess the feasibility of using atomic force microscopy (AFM) and nanoindentation to evaluate the effects of CXL on corneal biomechanical properties of eye-banked human corneas, and to examine the possibility of measuring depth-dependent biomechanical effects of CXL. Both techniques enabled the evaluation of localised CXL effects on the biomechanical properties of the stroma. Nanoindentation was effective in identifying biomechanical changes between control and cross-linked corneas and across stromal depths. The results of the experiment comparing the biomechanical response to CXL between corneas from different age groups indicated that younger corneas (26–41 years old) are more likely to benefit from CXL treatment than older corneas (> 42 years old). By extrapolating these findings to even younger corneas, it is reasonable to assume that CXL might be more successful in treating juvenile keratoconus than in treating adult keratoconus. The increase in corneal elastic modulus was found to be concentrated in the anterior and mid stroma. In the clinical study conducted in a UK-based population (Manchester), CXL was effective in halting the progression of keratoconus in 82.45% of patients. By three years after treatment, keratometry (Kmax) had improved significantly, while a reduction was observed in pachymetry measurements. Kmax had improved in all age groups; however, the improvement was marginally higher in the juvenile group than in the adult groups. This could be due to the high severity of keratoconus in the study sample. In the clinical study conducted in a Middle Eastern-based population (Saudi Arabia), CXL was effective in halting the progression of keratoconus in 84.30% of patients. By three years, Kmax had improved significantly, while a reduction in pachymetry measurements was observed. Kmax improved significantly in all age groups. The results of these two cohorts showed that keratoconus presented at a more severe stage in the Manchester cohort than in the Saudi cohort. However, CXL was successful in stabilising the progression of keratoconus in the vast majority of patients in both cohorts, despite this difference in keratoconus severity at the time of treatment between the two populations. In conclusion, eye-banked human corneas of different donor ages were successfully used to explore the effect of age on CXL outcomes. Nanoindentation was ideal for investigating localised biomechanical changes in the cornea following CXL treatment in ex vivo settings. Potentially, it could be used to further improve our understanding of CXL treatment and contribute to the development of customised CXL protocols. CXL was effective in stabilising the progression of keratoconus in the vast majority of patients from all age groups and in both populations.

Date of Award	1 Aug 2023
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Susmito Biswas (Supervisor) & Hema Radhakrishnan (Supervisor)