Microbial Keratitis Sampling for Biomarker Discovery

Microbial keratitis (MK) (infection of the cornea) is a leading cause of blindness globally with an incidence of >2m cases per year (particularly across Low and Middle Income Countries - LMICs), and a common acute eye disease in Edinburgh (~ 100 cases treated at the Princes Alexandra Eye Pavilion (PAEP) per year). MK is an "ophthalmic emergency" and even where gold-standard diagnostics and treatment are available, over 60% of MK patients are still left with visual impairment across LMICs, and >10% of patients require expensive and often unsuccessful surgical interventions such as corneal transplant. These permanent, debilitating outcomes are often attributed to an excessive and uncontrolled immune response, leading to scarring and corneal perforation.

Despite this, current diagnostic and treatment strategy targets only the invading pathogen and does not address the host response. Even where microbiological evaluation is conducted, the average culture-positive rate is just 50% and Gram-stain positivity is reported between 27.3%-61.6%2. Where microbiological evaluation is not possible, antimicrobials are prescribed empirically and often inappropriately, potentially contributing to the emergence of antimicrobial resistance (AMR) and worsening outcomes.

We are seeking to better understand the inflammatory response and the host-pathogen interactions to develop improved diagnostics and alternative treatment strategies. We propose to achieve this by studying the tears and the conjunctiva of those currently with, and without MK to identify biomarkers which can be utilised to achieve these goals.

Research Question: Can prognostic and diagnostic signatures (biomarkers) for MK be identified from patient ocular samples (tears and swabs)?

Hypothesis: Biomarkers will be identified through proteomic/metabolomic and micro/mycobiome analysis of patient ocular samples and these can provide us with more information about the disease and could inform the development of novel diagnostic platforms and possible alternative treatment strategies.

Inclusion criteria

• 16 years old or older.
• Able to provide informed consent for themselves.
• Patient group: Appearances typical of a new infective keratitis of the cornea, in one eye only.
• Control group: healthy volunteers with no recent history (within 1 year) of MK or inflammatory eye condition.

Exclusion criteria

• <16 years old.
• Not able to provide consent for themselves.
• Patients with suspected viral rather than bacterial/fungal corneal infection, such as herpetic keratitis.
• Patients who present with MK in both eyes.
• Control group: Individuals receiving topical steroid or antimicrobial therapy to the eye, or any other form of systemic immunosuppression/antimicrobial drug.