A corneal infection called microbial keratitis blinds 1.5–2 million people each year, mostly in rural communities across Asia and Africa, where over 60% of patients are left with moderate or worse visual impairment. The problem is that diagnosis requires specialist ophthalmologists and microbiology labs that can be hundreds of kilometres away, so patients arrive late and with advanced disease. Even at tertiary centres, the pathogen is never identified in about 50% of cases. Existing treatments target the microbe but not the immune response that actually destroys the cornea. This project aims to change that by validating a point-of-care diagnostic prototype that could be used in primary care settings, and by testing immunomodulatory treatments that calm the damaging immune reaction. If successful, it could shift the definition of treatment success from simply clearing the infection to preserving or restoring the patient's vision. For the UK’s 35,000 annual cases—where over 80% of fungal keratitis patients require more than two weeks of inpatient care—this could mean shorter hospital stays and fewer corneal transplants, which currently succeed only 10–30% of the time.
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Context: Microbial keratitis (MK) is a painful and sight-threatening infection of the cornea. While the true incidence and burden of disease is not accurately known, estimates indicate that 1.5-2 million people are unilaterally blinded by MK each year. MK predominantly affects rural communities of low- and middle-income countries (LMICs), where ~50% of cases are caused by bacteria and 50% by fungi. Across Asia, over 60% of MK patients are left with moderate (or worse) visual impairment, and >10% of patients require surgical intervention (e.g., therapeutic keratoplasty (TPK) – a corneal transplant), the success rate of which is only 10-30%. Furthermore, MK leads to significant social and economic difficulties for LMIC patients, with quality of life negatively impacted beyond the time of active disease. While there is no doubt that the greatest burden of MK persists across LMICs, MK also exhibits significant morbidity and economic impact within high income countries. In the UK, the annual incidence is >35,000 people, with up to 9% of cases caused by fungi. >80% of UK fungal keratitis patients require in-patient care for over two weeks because the treatment regimen is so demanding, and over 50% of these patients require additional surgical interventions. Challenge: Poor outcomes for MK patients are related to the infecting pathogen (which can’t be controlled), and inadequacies of the care-pathway – which can be addressed. Currently, MK can only be diagnosed at tertiary care, with specialised ophthalmologists and microbiology infrastructure. These may be hundreds of kilometres from the patient’s home in LMICs, causing patients to access care late, and with significant financial implications. Even when patients can access gold-standard diagnostics, the pathogen may fail to be identified in ~50% of cases, and treatments only target the pathogen, not the immune response, which causes much of the corneal damage and resultant vision-loss. Aims and objectives: My aim is to develop and implement tools and technologies to address these care pathway inadequacies – bringing point-of-care diagnostics and alternative treatment strategies to the entire microbial keratitis care pathway, including primary care. My objectives are: 1. Validate our lead MK diagnostic prototypes in a clinical setting with patient samples with Aravind Eye Care System (AECS, India). 2. Determine efficacy of treatments to influence the immune response in our model MK systems. 3. Determine clinical feasibility of immunomodulatory treatments for MK with AECS. 4. Establish a nuanced understanding of similarities and differences in the MK care pathway and patient needs across different settings, with a community of global MK stakeholders. Applications and benefits Developing and deploying improved diagnostics and treatments for MK will enable correct and better treatments to be initiated earlier – when there is a greater chance of success. This could redefine the definition of MK “treatment success” to maintenance/restoration of the patient’s vision, rather than simply the absence of infection. Improved diagnostics and treatments for fungal and bacterial infections are well recognised priorities of the WHO. The need is specifically highlighted in the context of MK by GAFFI (Global Action For Fungal Infections), who recommend development of a point-of-care test for rapid diagnosis of MK as a key opportunity for improving patient outcomes, and the UK Clinical Eye Research Strategy report, which highlighted improved MK treatments as the top priority for cornea research.
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