Clinical metagenomics for infectious corneal ulcers: Rags to riches?

The emergence of clinical metagenomics as an unbiased, hypothesis-free approach to diagnostic testing is set to fundamentally alter the way infectious diseases are detected. Long envisioned as the solution to the limitations of culture-based conventional microbiology, next generation sequencing methods will soon mature, and our attention will inevitably turn to how they can be applied to areas of medicine which need it most urgently. In ophthalmology, the demand for this technology is particularly pressing for the care of infectious corneal ulcers, where current diagnostic tests may fail to identify a causative organism in over half of cases. However, the optimism found in the budding discourse surrounding clinical metagenomics belies the reality that clinicians and scientists will soon be inundated by oppressive volumes of sequencing data, much of which will be foreign and unfamiliar. Therefore, our success in translating clinical metagenomics is likely to hinge on how we make sense of these data, and understanding its implications for the interpretation and implementation of sequencing into routine clinical care. In this consortium-led review, we provide an outline of these data-related issues and how they may be used to inform technical workflows, with the hope that we may edge closer to realizing the potential of clinical metagenomics for this important unmet need. •By conservative measures, infectious corneal ulcers are estimated to account for up to 3.5% of global blindness.•To reduce the burden of disease, improvements in current culture and stain-based methods of diagnosis are necessary.•These current methods are notoriously insensitive and do not provide timely identification of implicated pathogens.•Clinical metagenomics, achieved with next generation sequencing, is an unbiased and rapid method for genotypic diagnosis.•Prior to implementation, these molecular assays require validation and must meet performance benchmarks for clinical care.