Severe corneal infections: Prevention, diagnosis and treatment

Context: Blinding corneal infections (Microbial keratitis, MK), caused by bacteria or fungi, are a major ophthalmic public health problem in low and middle-income countries. There are multiple critical issues: delayed presentation, traditional eye medicine use, limited health-worker training, limited availability and efficacy of anti-fungals, diagnostic uncertainty. Eyes are lost through progressive corneal ulceration and perforation, mediated by human and pathogen-derived proteases. Proposed Research: 1. Randomised controlled trial (RCT) of topical chlorhexidine 0.2% vs. topical natamycin 5% for fungal keratitis. Pilot trials of chlorhexidine, a cheap and readily available antiseptic, suggest it might be at least as effective as natamycin (current standard). 2. RCT of topical ilomastat 0.08% vs. placebo, to reduce corneal perforation from MK. Ilomastat, a potent matrix metalloproteinase inhibitor, reduced severe ulceration in animal models and earlier human clinical trials. Full-scale treatment trials are needed for translation into practice. 3. Cluster RCT of early intervention package (topical chlorhexidine, smartphone-assisted diagnosis, treatment, referral support) vs. standard practices, to reduce blindness from MK through reducing delay between infection onset and initiating intensive treatment, with an agent covering fungi and bacteria. 4. Evaluation of diagnostic approaches for identifying causative organism in MK (clinical, automated image-analysis, confocal microsopy, PCR) and testing potential isothermal point-of-care tests.