Corneal Cross-linking in the Management of Fungal Keratitis

Abstract

Fungal keratitis is a devastating corneal infection with a high level of ocular morbidity. Combined riboflavin/UV-A light-induced corneal cross-linking (PACK-CXL) has emerged as a potential primary or adjuvant therapy for treating corneal infections, in particular for the antibiotic resistant forms. The aims of this project were to develop a novel ex vivo human corneal Fusarium infection model, and to investigate the effect of PACK-CXL procedure as a primary or adjuvant with antifungal (natamycin) therapy in the management of different severities of Fusarium infection, following various regimes of the PACK-CXL procedure. In this project, an ex vivo human corneal Fusarium infection model was successfully established using donor post-mortem human corneas and a recombinant strain of Fusarium oxysporum expressing green fluorescent protein (GFP). The results obtained from using the PACK-CXL procedure as a primary therapy in treating the Fusarium infections showed a beneficial antifungal effect against Fusarium by suppressing the growth of hyphae and sporulation, and reducing the depth of hyphal penetration into the corneal tissues at the central (UV irradiated) region of the treated corneas. However, PACK-CXL procedure alone had a limited ability in controlling the progression of the Fusarium infections, along with a time-dependent decrease in its efficiency in reducing the load of the infection. Nevertheless, the PACK-CXL procedure as an adjuvant to antifungal natamycin therapy greatly controlled progression of the infection. The in vitro results suggest that the PACK-CXL procedure as a monotherapy is insufficient in controlling the Fusarium keratitis. The dual therapy of PACK-CXL and natamycin can be considered as a highly effective treatment in the management of Fusarium keratitis. However, PACK-CXL treatment could be used as an initial intervention in cases of infectious keratitis with unknown causative pathogen(s) to reduce pathogen load within the corneal tissues until the causative organism(s) is identified and appropriate antimicrobial therapy can be administered.

Date of Award	1 Aug 2018
Original language	English
Awarding Institution	The University of Manchester
Supervisor	M Chantal Hillarby (Supervisor), Susan Shawcross (Supervisor) & Hema Radhakrishnan (Supervisor)