The Potential of Tear Proteomics for Diagnosis and Management of Orbital Inflammatory Disorders

Orbital compartments harbor a variety of tissues that can be independently targeted in a plethora of disorders resulting in sight-threatening risks. Orbital inflammatory disorders (OIDs) including Graves’ ophthalmopathy, sarcoidosis, IgG4 disease, granulomatosis with polyangiitis, and nonspecific orbital inflammation constitute an important cause of pain, diplopia, and vision loss. Physical examination, laboratory tests, imaging, and even biopsy are not always adequate to classify orbital inflammation which is frequently deemed “nonspecific.” Tear sampling and testing provide a potential “window” to the orbital disease process through a noninvasive technique that allows longitudinal sampling as the disease evolves. Using PubMed/Medline, we identified potentially relevant articles on tear proteomics published in the English language between 1988 and 2020. Of 293 citations obtained, 215 contained empirical data on tear proteins, including 33 publications on inflammatory conditions, 14 in glaucoma, 11 in thyroid eye disease, and one in uveitis. Review articles were used to identify an additional 56 relevant articles through the examination. We summarize previous work studying tear proteome alterations in Graves’ ophthalmopathy (GO) and discuss the major proteomic technologies currently driving tear protein research that have the potential to discover tear protein biomarkers to diagnose, select therapy, predict prognosis, and understand pathogenesis for patients with orbital inflammatory disease. The review concludes by pointing out current limitations of mass spectrometric analysis of tear proteins and summarizes future needs for the field.