Dry Eye Disease and Depression: Epidemiological and Biological Links

This thesis focused on understanding the potential epidemiological and biological links between dry eye disease (DED) and depression using tools that measure and correlate the symptoms, and through examining biological links using hypothesized single nucleotide polymorphisms (SNPs). Four studies were performed. The first study was a cross-sectional study to measure DED symptoms. A symptom burden tool was developed with two dimensions and four domains. This tool was administered to DED patients and showed that persistence of DED symptoms correlates with affective interference more than activity interference, and that intensity of symptoms may be important for treatment decisions. The second study was a case-control study designed to measure depressive symptoms and DED symptoms to determine the symptom correlation between the two diseases. The Beck Depression Index questionnaire, Ocular Surface Disease Index Questionnaire, and the symptom burden tool were administered to DED patients and controls. This study showed that patients with DED exhibit more depressive symptoms than controls. The adjusted regression coefficient was 1.71 (95% CI 1.02, 2.40) between DED symptoms and depressive symptoms. Logistic regression revealed an adjusted OR of 2.86 (95% CI 1.04, 7.87) for the association between DED and diagnosis of depression. To complement the clinical epidemiological association between DED and depression, this thesis also included a study on the biological links between DED and depression. Twelve SNPs in three main genes were investigated: Brain-Derived Neurotrophic Factor, Vitamin-D Receptor, and Deoxyribonuclease 1 in DED patients and controls. Val66Met, an SNP in the BDNF gene and two SNPs Fokl and Apal in the VDR gene were found to be potentially associated with DED. Results, while not significant, seem to show that the association between DED and Val66Met varies by depression status. Additionally, the role of Val66Met in treatment response was investigated through DED symptom measurement over time. A fourth study was performed where patients were followed up for a minimum of six months. The study revealed that symptoms like dryness and pain persist in patients with the minor allele a (Met carriers) of Val66Met despite treatment; whereas symptoms are significantly reduced in patients without the minor allele.