In the present study, we investigated the prevalence of DED and systemic and psychiatric risk factors for the disease in Korean adults aged ≥40 years using representative national data. The prevalence of DED in the representative study population was 7.9% ± 0.6%. The age of ≥ 70 years and residence in rural areas were associated with a reduced risk, whereas female sex was associated with an increased risk of DED.
It is remarkable that patients aged ≥70 years, particularly women showed a lower prevalence of DED, although previous studies have indicated that aging is related to a higher prevalence of DED 17-19. A previous study that used data from KNHANES V, 2010–2012, also reported that participants aged ≥80 years tended to show a decreased prevalence of DED 20. Although the basis for this phenomenon is unclear, we speculate that limited access to healthcare and reduced sensitivity to ocular discomfort may have contributed to the underdiagnosis of DED in participants aged ≥70 years.
The finding that residence in rural areas was associated with a reduced risk of DED is consistent with the results of previous studies 20, 29, 30. Air pollution is shown to increase the risk of DED 23, 31, 32, which may explain the higher risk of DED in an urban population 20, 29, 30. A relatively relaxed lifestyle in rural areas can also be associated with a reduced risk of DED 20.
As previous studies have consistently demonstrated, the present study also revealed the increased risk of DED in female sex 8, 22, 23, 25, 29, 33-41. A higher prevalence of the disease in women than in men was revealed in young students and workers 8, 35, 39, 40, as well as in older individuals 20, 28, 29, which indicates the possible role of sex hormones in the pathogenesis of DED 39, 40. Schaumberg et al 42. observed that women had more frequent and severe dry eye symptoms than men, and reported more marked interference in daily activities caused by DED. Vehof et al 43. also found that women had higher DED symptom scores compared to men and a more pronounced discrepancy between symptoms and signs of the disease. Song et al 44. reported that menstrual irregularity was significantly associated with an increased risk of DED. A recent study by García-Marqués et al 22. also showed an association between menopause and an increased risk of DED. These findings suggest the possible effects of sex hormones on the maintenance of the ocular surface environment and perception of ocular discomfort, dryness, and pain 29, 36, 38.
The results of the present study indicate that psychiatric conditions, including perceived stress and depression, are significantly associated with an increased risk of DED. A literature review suggested that psychiatric disorders, such as depression, psychological stress, anxiety, hypochondriasis, and sleep disorders may cause severe unexplained dry eye symptoms disproportionate to ocular surface signs 45. A study that included 6655 Korean women also reported an association between DED and psychological stress, anxiety, and depression 46.
These results are consistent with the findings of our prior studies that psychological stress is associated with the risk of DED among medical students and hospital workers 39, 40. Recent studies have also confirmed that high psychological stress was associated with an increased risk of DED 25, 47. Although contributors to the association between DED and psychological stress remain unclear, we speculate that the following mechanisms may play an important role: (1) Psychological stress may promote production of inflammatory cytokines 48, which conceivably increase the risk of ocular surface inflammation 49, 50. (2) Perceived stress may trigger cortisol secretion and inhibit pain modulation and thereby predispose to ocular pain 51, 52. (3) Psychological stress may trigger somatization 53, which can aggravate dry eye symptoms.
Our previous study demonstrated that depression was associated with symptomatic DED in patients with normal or mildly decreased tear secretion, which is in agreement with the findings of the present study 21. A recent large-scale study showed that depressive symptoms occurred more frequently in patients with more severe dry eye symptoms 54. A meta-analysis and systematic review of 22 studies concluded that depression and anxiety were associated with an increased prevalence of DED 55. Although the pathophysiology underlying the association between these two diseases has not been fully elucidated, several mechanisms may play a role. First, overlaps in the pathogenesis of the two diseases may exist. Inflammation is a proven contributor to both DED and depression 56, 57. Both diseases share risk factors, such as female sex and menopause, which indicates the possible effects of sex hormones on both diseases 58, 59. Second, dry eye symptoms and depressive mood may have a bidirectional association. Depressive mood can enhance systemic inflammation, which leads to the aggravation of dry eye symptoms 60, 61. Depressive mood may also lower the threshold for perception of pain and discomfort, which predisposes patients to dry eye symptoms 21, 62. Likewise, visual impairment and chronic discomfort caused by symptomatic DED may also aggravate depressive mood 7, 63.
In this study, systemic comorbidities such as rheumatoid arthritis, degenerative arthritis, osteoporosis, ischemic heart disease, and chronic renal failure were significantly associated with an increased risk of DED. Recent studies have demonstrated a significant correlation between poor self-perceived health status and an increased risk of DED, suggesting an association between an individual’s systemic health status and DED 25, 47.
Previous studies have also reported an association between DED and systemic rheumatologic diseases 22, 64, 65 and rheumatoid arthritis 20, 65. Exacerbation of systemic inflammation in patients with rheumatic diseases may result in the upregulation of inflammatory cytokine production on the ocular surface, aggravation of ocular surface injury, and dry eye signs 20, 66.
A few studies have reported an association between degenerative diseases, including degenerative arthritis and osteoporosis, and DED 20, 23. A large population-based cohort study showed that osteoporosis increased the risk of DED, which was attributable to sex hormone deficiency, purinergic signaling, and vitamin D deficiency 67. We believe further studies are warranted to confirm the association between degenerative diseases and DED.
An association between ischemic heart disease and DED was also reported in a previous study 65. A recent study observed that patients with DED showed abnormal retinal microvascular function and an elevated risk of cardiovascular disease 68, which is possibly attributable to an autonomic nervous system imbalance 69. A meta-analysis showed an increased risk of cardiovascular disease in patients with Sjögren syndrome, indicating increased arterial stiffness in these patients 70.
Previous studies have reported that chronic renal failure was also associated with an increased risk of DED 20, 65, 71-73. Chronic renal failure was associated with higher grades of corneoconjunctival calcification and squamous metaplasia 71, reduced tear breakup time, and more severe dry eye symptoms 72, 73.
Although several studies have suggested an association between DED and diabetes mellitus 74-76, hypertension 2, thyroid disease 2, 77, 78, and dyslipidemia 20, the results of our study did not show a significant association between these systemic diseases and DED. Further studies are needed to determine the association between DED and various systemic diseases.
The present study has the following limitations: (1) As only participants who answered the question for the diagnosis of DED were included, there is a possibility of selection bias. (2) The diagnosis of DED was based on a history of DED diagnosed by ophthalmologists; therefore, the risk of recall bias cannot be completely excluded. Further studies with more objective diagnostic criteria for DED that include questionnaires for dry eye symptoms and clinical examination for dry eye signs are therefore warranted to evaluate the association between DED and the psychiatric and systemic diseases. (3) Because of the cross-sectional nature of this study, causal relationships could not be identified. Further prospective studies are necessary to determine the causality. However, we believe that the results of the present study still have clinical significance, as we analyzed both psychiatric and systemic risk factors for DED using data from a large population study.
In conclusion, this study showed that psychiatric conditions, including depression and psychological stress, and systemic diseases, such as rheumatoid arthritis, ischemic heart disease, degenerative arthritis, osteoporosis, and chronic renal failure, were associated with an increased risk of DED in Korean adults. These findings indicate that a comprehensive approach for the possibility of these psychiatric and systemic diseases can be useful for the treatment of DED.