The ocular surface tear film as a biomarker for systemic health

The tear film is a complex structure with rich interactions with the human body. A growing body of evidence suggests that measuring changes in protein, lipid, or other metabolite concentration in the tear film can be used to help detect disease. Particularly in the era of precision medicine, the tear film serves as a promising source of non-invasive insights into systemic health for early diagnosis and treatment. This paper analyzes the latest research in tear film biomarkers for systemic diseases. The review was conducted through PubMed and Embase databases using the PRISMA protocol and includes 54 articles. This paper first reviews the anatomy and physiology of tear film, as well as the latest proteomic analysis techniques on the tear film. We then provide a disease-by-disease review on the tear film as a biomarker including 5 articles related to Alzheimer's Disease, 10 articles related to Cancers, 1 article related to Cystic Fibrosis, 1 article related to Migraines, 4 articles related to Multiple Sclerosis, 15 articles related to Parkinson's Disease, 7 articles related to Rheumatoid Arthritis, and 11 articles related to Thyroid Disease. This paper highlights the promising results of these studies yet also reviews the challenges with limited sample sizes, reproducibility, and biological understanding of biomarkers. We conclude this paper with insights for future work to ensure clinical validity and generalizability. Ultimately, the tear film is a clinically accessible, complex structure that provides a wealth of information that may contribute to a more comprehensive understanding of systemic health.