Molecular biomarker profiling in noninfectious uveitis: a chronological review of discovery

Noninfectious uveitis (NIU) encompasses a heterogeneous group of immune-mediated intraocular inflammatory diseases whose complexity has driven systematic molecular biomarker discovery. This review presents NIU molecular biomarkers organized by biological category; autoantigens, human leukocyte antigens (HLA) and genetic markers, cellular immune subsets, cytokines, chemokines, and multiomics platforms including proteomics, microbiome metagenomics, metabolomics, and single-cell transcriptomics with each category presented in strict chronological order of landmark discovery.

We present a review organized along two nested timelines. Categories are presented in the order they historically emerged in the field, and within each category, landmark discoveries appear in chronological sequence. This allows the reader to trace how each biomarker category evolved: from foundational autoantigen identification in experimental uveitis models, through the genomic revolution of HLA association studies, into cellular immunophenotyping, cytokine profiling of aqueous humor, chemokine mapping of intraocular trafficking, and finally the emerging omics platforms that may potentially anchor precision medicine in NIU. Each biomarker is paired in line with its linked targeted therapeutic.

Biomarker research has transformed the understanding of NIU from a clinically defined syndrome into a group of molecularly distinct immune disorders. Advances spanning autoantigens, genetics, immune-cell profiling, cytokines, chemokines, and multiomics have revealed novel pathogenic mechanisms and therapeutic targets. Integration of these biomarkers with targeted therapies may accelerate the transition toward precision medicine in uveitis care.