MGD had a high prevalence worldwide, and it is higher in Asians than in Caucasians10–12. As a leading cause of DED, MGD often presents chronic ocular health problems, especially eye pain, foreign body, and alterations of optical quality, etc. It not only can adversely affect anyone’s life quality but also the mental health of patients. Moreover, depression symptoms also strengthen the subjective feeling about ocular surface discomfort and always coexist with other health conditions. Till now the risk factors and the correlation between MGD and depression remains unclear. Based on our study, the prevalence of depression in the MGD group was higher than normal controls. Risk factors such as OSAHS, allergy, skin disease, contact lens wearing, and inactive time were correlated with the depression symptoms of MGD patients. The results enabled early detection of the signs of mental changes in the MGD group and offer the appropriate support promptly.
In this study, the prevalence of depression in the MGD group was 9.3%, which is significantly higher than that in normal controls (3.5%). As a major cause of DED, MGD can increase the evaporation of tear and decrease the tear volume, which induce short tear breakup times and tear hyperosmolarity. Some studies declared that hyperosmolarity could cause ocular surface inflammation and/or nerve damage, which may increase symptoms by peripheral sensitization. With functional magnetic resonance imaging (fMRI), Yu et al13 found regional homogeneity (ReHo) values of the middle frontal gyrus, inferior frontal gyrus, and superior frontal gyrus were significantly lower in dry eye patients compared to healthy controls. Symptoms of ocular surface injury in DED, especially MGD patients are associated with dysfunction in specific brain regions. And rianopoulou et al14 investigated brain function and microstructural changes in primary Sjögren syndrome (pSS) and found the functional connectivity abnormalities of the somatosensory cortex and microstructural abnormalities appeared in pSS, which were more pronounced in depression. In addition, depression could also increase the symptom of MGD. Mahmut et al15 invited 40 newly diagnosed depression patients and found that patients without a history of psychiatric drug use showed dry eye symptoms. Some studies revealed that negative emotional states would induce or enhance the perception of pain and irritation16. And the symptoms of pain, dryness, itchiness, stinging, foreign body sensation and sensitivity to light and wind from MGD can also negatively impact the mood of patients and have potential consequences of depression. So, patients with dry eye symptoms but no signs would have the lowest happiness scores. Subjective happiness scores in DED cases were found to be inversely correlated with dry eye symptoms17. At last, several studies have confirmed antidepressants may play an important role in provoking DED. Emel et al18 found that selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors increased the risk for eye dryness. Furthermore, Zhang et al19 proved that SSRIs could aggravate DED by activating the NF-κB pathway, which shows the interaction between dry eye and depression. Therefore, the depressive symptom could be alleviated by applying the managing MGD, which open the options of cooperative therapy between Ophthalmologists and psychiatrists to MGD cases.
Many risk factors make MGD patients more prone to develop depression, for instance, living in rural areas could be associated with depression in our study. However, results from a Korean elder cross-sectional study showed that living in the urban area is also strongly correlated with depression (P < 0.001)3. The economical differences between developed countries and developing countries may provide a reasonable explanation. Wang et al20 conducted a study about socio-demographic characteristics of depressive symptoms and found that educational attainment, the economic level had a significant association between depressive symptoms, which may explain the different results between Chinese and Korean studies.
Moreover, our study found that some systemic diseases (OSAHS, allergy, skin disease) were also related to depression. The results of the current study are consistent with previous results21,22. A meta-analysis by Jennifer et al concluded that the risk of developing depressive disorders was two to three times more likely among individuals with two or more chronic conditions23. Just as MGD, OSAHS, allergy and skin disease are always chronic and incurable diseases. Chronic pain and irritation are associated with sleep deficiency, activity and mobility limitations, social withdrawal, and loneliness. All these negative effects will induce cognitive impairment, loss of self-confidence and self-esteem, even anxiety and depression24.
Wearing a contact lens could also be argued to have potential adverse towards the development of depression. Patients with MGD who also wears contact lenses revealed an increase in dry eye symptom and ocular surface staining25,26. Consequently, the shorter TBUT result suggests that MGD and contact lens both contributes to the negative outcome of tear film integrity. Therefore, contact lens maybe induces depressive symptoms in MGD cases due to the aggravation of dry eye symptoms.
We have applied the M-SDS questionnaire to compared and analyzed some characteristics of depression between the MGD group and controls. For depressive patients in the MGD group, they presented with frequent crying, sleep disturbance and depressed appetite. It is still unclear about the reason causing the repeated crying but trying to get more tear secretion maybe a way to relieve mental tension in patients with MGD. Regarding decreased appetite previous study reported five patients with severe anorexia nervosa, all 5 patients complained of dry and irritated eye symptoms27, which indicate a possible cause-effect relationship between dry eye and appetite. Sherwin et al28 revealed that deficiency of vitamin A is a significant risk factor of DED. Change of appetite can potentially decrease the level of intake of vitamin A which then adversely affect depressive symptom. However, no clear evidence articulates the MGD or DED patients' eating habit changes.
Additionally, dry eye and insomnia influence each other in many ways. Masahiko et al29 reviewed 7 articles and concluded that dry eye patients suffer more from bad quality sleep. Wu et al30 also found that poor sleep quality may aggravate DED by affecting tear secretion and tear film stability, even indirectly aggravate depression at the same time. The result from the M-SDS questionnaire showed the difference in frequent crying, sleep disturbance and depressed appetite between MGD patients and control. Another interesting point is that depressive patients in the MGD group may more easily lose hope for their aspirations (2.60 ± 1.00 vs. 1.75 ± 0.50, P = 0.095). In Van’s study of patients with Sjögren's syndrome, these patients with a lower “cryability” had a higher score on frustration31. Gomes reported that the effect of the quality of life by dry eye may be underestimated32.
Our study offered insight into the importance of early detection and intervention of depressive disorder among MGD patients. Questionnaire results regarding sleep, eat changing and cry intention could help ophthalmologists screening depression patients. Such early conversation with the patient can not only prevent further prognosis but also facilitate a speedy recovery.
Even though this study is a focused multi-center cross-sectional study, the sample size could have improved to have more generalizability. Second, alongside the M-SDS questionnaire, other means of measure for the participants mental status could be employed. Third, this study is a cross-sectional study, more robust follow-up evidence is favorable for a deeper understanding of the relationship between MGD and depression.
In conclusion, this study served a pioneering role in connecting MGD and depression. Ophthalmologists should be aware of the association between MGD and depression, better understand patients' mental changes and better treat MGD patients with depression. Furthermore, the correlation between MGD patients with depression and the changing of their cytokines, chemokine, and inflammatory factors could be fascinating to investigate further.