Microbial Keratitis Sampling for Biomarker Discovery

Overview

The goal of this observational study is to identify prognostic and/or diagnostic signatures (biomarkers) related to microbial keratitis outcomes. We will compare tear and ocular swab samples from participants currently suffering from microbial keratitis to healthy control participants. The primary study objective is to undertake analysis (proteomics and metabolomics) of microbial keratitis patient (and healthy control) ocular samples collected throughout the patient treatment course to better understand the ocular microenvironment and to identify candidate biomarkers for future targeted screening and validation studies. The secondary study objective is to define the microorganisms in patients with microbial keratitis through a better understanding of the ocular surface micro/mycobiome (the resident bacteria and fungi) in health and disease Participants will have their tears collected via capillary tube during their treatment course, and swabs of their conjunctiva collected at their first and final appointments.

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.