Ong, Hon Shing; (2025) Clinical and Genetic Phenotyping Studies in Major Causes of Ocular Surface Inflammation and Scarring (Cicatrisation) – Mucous Membrane Pemphigoid and Stevens-Johnson Syndrome. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis focuses on advancing clinical and genetic phenotyping of ocular surface inflammation and scarring disorders, particularly cicatrising conjunctivitis (CC). CC can lead to complications such as trichiasis, lid malposition, dry eyes, limbal stem cell deficiency, and corneal ulceration, ultimately resulting in blindness. Diagnosing CC is challenging due to overlapping clinical features of its various aetiologies, often delaying appropriate treatment. Ocular mucous membrane pemphigoid (MMP), a major cause of progressive CC, exemplifies these diagnostic complexities. My research emphasises the importance of diagnosing ocular-only MMP, even in patients with negative immunopathology, a finding that has influenced recent updates to international guidelines. Despite the significant morbidity associated with CC, the mechanisms driving inflammation and scarring are poorly understood, hampering the development of targeted therapies. Current treatments rely on empirical, non-targeted immunosuppressive therapies aimed at controlling inflammation. However, these therapies often result in suboptimal outcomes and significant adverse effects. Recent research highlights the critical need for effective anti-fibrotic therapies that can specifically target CC. To evaluate potential anti-fibrotic treatments in clinical trials, a validated clinical assessment tool is important. This thesis details the development of an innovative assessment tool for CC, improving reproducibility and eliminating redundancies compared to previous methodologies. Additionally, the thesis explored advanced imaging techniques like second harmonic generation microscopy to quantify biomorphological characteristics of collagen changes for assessment of conjunctival scar development. Gene expression studies conducted on MMP patients also identified differentially expressed molecular biomarkers. Understanding these biomarkers can improve disease detection and monitoring, while offering insights into the molecular pathways driving CC. This knowledge can guide targeted therapy development and improve the evaluation of new treatments for ocular surface diseases. Overall, this thesis highlights the importance of timely diagnosis, robust assessment tools, and more effective phenotyping strategies to mitigate the severe impacts of conjunctival scarring and improve patient outcomes.

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