Biomarkers of Dry Eye Disease

Abstract

The multifactorial nature of Dry Eye Disease (DED) and the poor correlation between signs and symptoms make diagnosis and management challenging, particularly in the early stages. An increasing prevalence, particularly in younger generations, has led to an increased workload for optometrists. Therefore, the search for validated biomarkers to accurately and objectively measure a disease whose pathogenesis is not yet fully understood, is vital. The key focus of this thesis was to explore clinical signs, and potential biomarkers of evaporative DED from tears and meibum, in a young population. Initially, UK primary care optometrists were surveyed to discover whether research, in particular use of an existing commercially available biomarker, is being translated into practice. The results unveiled current clinical practice patterns in the UK, and limited use of available biomarker tests, although an increase in evidence-based practice and steroid prescribing was identified.A prospective, longitudinal study in young adults found significant overlap in clinical signs between subjects with and without DED. Conjunctival staining was the best single predictor, with female sex and contact lens wear the most significant risk factors; screen use and stress were key modifiable factors. Findings implicating inflammation in the pathogenesis of early DED were found from tear protein and cytokine analysis, including the upregulation of albumin. Furthermore, zinc-α2-glycoprotein was downregulated and correlated with increasing signs of meibomian gland dysfunction (MGD). Along with the upregulation of certain pro-inflammatory cytokines (IL-1β and fractalkine), a corresponding upregulation of the anti-inflammatory cytokines IL-1Ra occurred, indicating a coordinated suppression of the immune response. Higher meibomian gland loss was significantly associated with up-regulation of polar phospholipids and down-regulation of (O-acyl)-ω-hydroxy fatty acids, which correlated with clinical signs of MGD. Overall, this thesis has identified several key clinical findings and molecular biomarkers for the early detection of evaporative DED in a young cohort.