Innovations for the prevention of ocular surface scarring

Butt, Gibran (2025). Innovations for the prevention of ocular surface scarring. University of Birmingham. Ph.D.

Butt2025PhD.pdf
Text - Accepted Version
Available under License Creative Commons Attribution.
Download (6MB)

Abstract

Background Corneal scarring from various diseases is a leading cause of blindness globally and considered a priority by the World Health Organisation. Microbial keratitis (MK) is the commonest cause, often associated with regionally distinctive risk factors such as trauma in agricultural workplaces in lower- and middle-income countries versus ocular surface disease in upper- and middle-income countries. MK’s impact on working-age people means the burden of disease is vast considering it impacts the productivity. There are no approved medical therapies to prevent or reverse corneal scarring, and the only sight restoring options involve corneal transplantation or implantation, which necessitate access to specialised eye-care infrastructure and long-term healthcare service engagement. As such, there is an unmet need for non-invasive and easily accessible treatments for MK.
Aims
To investigate a novel mechanism through which decorin inhibits fibrosis in corneal fibroblasts in vitro; horizon scanning for other approved or developmental therapies for corneal scarring; to conduct a human clinical trial of decorin to prevent corneal scarring in patients with MK. The COVID-19 pandemic considerably delayed the development of this intervention, therefore additional aims were added to determine the impact of the pandemic on the project. These oriented understanding the UK public’s perception and health seeking behaviours with regards to eye symptoms in the pandemic, and finally understanding the impact of the pandemic on MK patients attending a tertiary eye care centre.
Methods A mixed methods study including a systematic scoping review, an in vitro investigation of decorin’s mechanism, a survey of public perceptions, a clinical cohort study and an early phase clinical trial. Results Eye health was a primary concern for the UK population who demonstrated proportionality of health seeking behaviour in response to eye symptoms of varying severity. The severity of MK during the pandemic was found to be no different compared to pre-pandemic times. No approved treatment for
ii
corneal fibrosis exists. Decorin is one such candidate which is imminently due to enter human clinical trials, with the potential to change the corneal fibrosis landscape. Decorin did not induce or inhibit autophagy in primary human corneal fibroblasts however the results helped to generate novel hypotheses for further investigations. Conclusions Although some of decorin’s mechanisms of action are yet to be elucidated, understanding the significant mechanistic checkpoints in corneal fibrosis are key, thus mechanistic studies have been incorporated into the clinical trial. Well-designed clinical trial outcome measures are required to generate robust evidence for the adoption of novel therapeutics that have the potential to change lives around the world. The public were reportedly apprehensive about volunteering for eye research, therefore researchers must be proactive in reassuring patients.
Impact of COVID on proposed thesis
The COVID-19 pandemic considerably impacted the implementation of the trial, which remains indefinitely delayed. Moreover, the university laboratories were closed for several months shutting down any in vitro work. Finally, I was seconded onto the wards to deal with patients of the pandemic. Therefore, additional project aims were required to determine the impact of the pandemic on the trial, ophthalmic conditions and research. The first new objective was therefore to understand the UK public’s perception of eye symptoms and health seeking behaviours with regards to eye symptoms in the pandemic, as well as their willingness to volunteer for research. The second was to determine the impact of the pandemic on MK patients’ clinical outcomes at a tertiary eye care centre.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):