Precision Medicine for Diagnosis of Microbial Keratitis.

Abstract

Microbial keratitis (MK) is the leading cause of corneal blindness and can be caused by several species of bacteria, fungi, or parasites. Accurate and timely identification of the causative microbe is critical for initiating targeted antimicrobial and anti-inflammatory treatment and preventing vision loss. MK diagnosis currently relies on corneal culture or microscopy, which have suboptimal yield and can produce inconclusive results. MK requires immediate treatment with empiric antimicrobials, followed by targeted treatment after the microbe is identified. The clinical utility of anti-inflammatory therapy in MK remains controversial and likely differs due to host- and microbe-specific factors. Newer diagnostic techniques such as whole genome sequencing, metagenomic deep sequencing, transcriptomics, and proteomics have the potential to greatly improve timeliness, accuracy, and precision when diagnosing and treating MK. Metagenomic deep sequencing can identify pathogenic microbes with comparable or superior accuracy to traditional microbiology techniques, enabling faster and more accurate diagnosis and initiation of appropriate treatment. Whole genome sequencing of corneal culture isolates has the potential to provide patient-specific insights about microbial phylogenetics, antimicrobial resistance genes, and virulence factors to enable more targeted antimicrobial therapy. Characterization of the host immune response using RNA sequencing or tear proteomics could help inform the use of tailored anti-inflammatory therapies to prevent corneal damage. Although most of these precision medicine approaches are in the research phase, they show the potential to customize MK treatment based on host and microbial factors and improve clinical outcomes.