In this study, we aimed to compare the tear fluid concentrations of IL-1ß and MMP-9 and ocular surface parameters for DED between healthcare professionals wearing masks for long periods and healthy participants wearing facial masks for a limited time in their daily routine. Our major findings were as:1-healthcare professionals had higher levels of IL-1ß and MMP-9 than healthy subjects. 2- Healthcare professionals had lower NIBUT, higher OSDI score, and higher rate of MGD findings than healthy participants.
Since MADE was first described in June 2020 by an American ophthalmologist, D.E. White, this condition has become a well-known entity with the results of several studies. 18,19,20 The prevalence of dry eye-like symptoms in MADE is highly variable depending on the current status of the ocular surface and the habits of regular mask users. People who had DED symptoms previously or had a long screen time would experience worsening of their symptoms when wearing a face mask. 21
MADE can affect approximately 18 % of the general population. 20 However, Chalmers et al. 22 observed that clinicians often underestimated the severity of participants’ self-assessment of dry eye. Previous studies have reported tear film and ocular surface abnormalities in regular mask wearers. 5,18,19,20,21 To our best knowledge this is the first study evaluating the severity of the ocular surface disease accompanying by basal tear film cytokines profiles of MMP-9 and IL-1ß by comparing normal subjects. The results of the present study showed marked increases in tear film instability and inflammation biomarkers among healthcare professionals who had to wear prolonged facemasks.
Some theories have been proposed regarding how facial masks affect the ocular surface. Devices that mechanically blow air around the face have been found to affect the eye. Powell et al. reported an increase in DED symptoms with a similar mechanism using powered air-purifying respirators in patients in intensive care units. 23 However, hypercapnic stress is another possible mechanism of ocular surface damage based on the outward movement of exhaled air through the mask. 6 In fact, there can be up to a 10-fold increase in carbon dioxide levels within the reservoir formed between the face and mask. 24
There is increasing evidence of the role of subclinical ocular surface inflammation in DED. 25 Inflammation can lead to ocular surface epithelial disease and altered corneal epithelial barrier function in DED patients. 25 Increased expression of immune activation markers, such as HLA-DR, intercellular adhesion molecule (ICAM)-1, and CD-40, by the conjunctival epithelium and infiltration of the conjunctiva by inflammatory cells has been reported in previous studies. 26,27 The anti-inflammatory therapies such as glucocorticoids and cyclosporin improve significantly signs and symptoms of DED. 28 However, in the past, the TFOS Dry Eye Workshop in 2007 concluded that levels of inflammatory factors in tears were increased only in Sjögren’s syndrome and rosacea dry eye, but not necessarily in evaporative and undifferentiated dry eye. 29 In contrast, in 2017, the TFOS Dry Eye Workshop demonstrated elevated levels of cytokines such as IL-1ß and MMP-9 in the tears of both the aqueous tear deficient form of dry eye and the evaporative form of dry eye. 9
The accurate detection of elevated MMP-9 levels in the tear film with a point-of-care immunoassay (InflammaDry), which is a noninvasive, relatively inexpensive test, was found to be effective in early diagnosis and improved treatment of ocular surface disease by Sambursky et al. 30 The results of a quantitative immunobead assay showed that the concentration of MMP-9 in tears had a direct relationship with tear osmolarity, and results of measuring tear production by Schirmer’s test showed an inverse correlation between tear amount and MMP-9 concentration. 31 Therefore, the design of novel MMP-9 inhibitors for the ocular surface, leading to improvement of tear production and recovery of corneal epithelial barriers, will yield great benefits for the treatment of DED. 32 In our study, the clinical findings of dry eye and subjective discomfort scores were increased in healthcare professionals wearing facial masks compared to normal subjects. Similarly, MMP-9 levels were significantly higher in the mask-user group, as expected. Regular mask use has been proven to negatively affect the ocular surface, leading to an increase in evaporation rate. Thus, facial masks could be a promoter factor for increasing dryness and inflammation biomarkers in tear fluid for regular mask-users.
The expression of IL-1ß, another frequently studied proinflammatory cytokine in tear fluid, was found to be increased in Sjögren’s syndrome and non-Sjögren’s syndrome DED. 9 In our study, IL-1ß was found to be significantly increased in the prolonged mask-user group, accompanied by clinical findings of DED. In a study by Landsend et al., correlations were demonstrated between cytokines, including IL-1ß, and clinical parameters for DED and MGD. 33 Similarly, Enriquez-de-Salamanca et al. were reported that the IL-1ß levels were increased in 30% of patients with moderate forms of evaporative DED due to MGD and correlated with pain and with clinical parameters measuring tear stability, tear production, or ocular surface integrity. 34 However, in another study in which IL-1β, IL-6, and pro-MMP-9 tear levels were measured in patients with different types of ocular diseases, including moderate dry eye patients, only pro-MMP-9 was found to be significantly increased in DED patients. 35
Few studies have assessed the relationship between mask use and tear film cytokine profile. In a recent study that evaluated a large number of tear film cytokines, the authors found that the level of IL-1ß in pre-mask usage significantly increased after mask use in a daily period. In addition, the study indicated that IL-1ß showed a positive correlation with OSDI scores in the study group of practicing ophthalmologists. 6 Similarly, we found positive correlations between OSDI scores and both cytokines, IL-1ß and MMP-9, in our study. The same study found that hypo-osmolar lubrication and mucin secretagogues would be necessary to avoid MADE in view of pre-existing hypo-osmolar tear secretion and increased mucin secretion. 6
In a recent study, the use of face masks throughout the day was found to lead to a significant reduction in NIBUT regardless of age, sex, and OSDI score. 36 likely that the NIBUT scores were shorter in the healthcare worker group associated with the increased tear evaporation rates in the mask-using population. Ocular damage due to mask use. In contrast, high activity of MMP-9 in tears was associated with decreased fluorescein tear break-up time and a substantial direct relationship with conjunctival corneal fluorescein staining, sign severity values, topographic surface regularity index, and visual acuity scores. 37 In the current cohort, the percentage of subjects with symptomatic OSDI scores in healthcare professionals’ group was 73.7% and was 22.5% in control group. Similarly, Bilici S. et al. reported that 82.4% of the participants who were health care professionals showed symptomatic OSDI scores. 36
In addition to the traditional Schirmer strip test, the examination of the quantity of tear secretion with TMH score is an important indicator for the diagnosis of aqueous deficiency-type dry eye. 38 To the best of our knowledge, this is the first study to assess the effect of facial mask use on the basal TMH scores. In a recent study, diurnal changes in the TMH scores were evaluated before and after mask use. The results showed that TMH scores decreased after wearing the facial mask. 39 However, depending on the evaporative nature of MADE, the TMH scores were similar in both study groups, as expected. In contrast, in a recent study, the Schirmer strip test scores and TBUT measurements were reported to increase after facial mask wearing by healthcare professionals. 6
Ocular surface staining is an important endpoint for the treatment of dry eye disease that reflects ocular surface integrity. 40 In the current study the mean Oxford corneal staining score was slightly higher in the mask-user group, but the difference was not statistically significant. However, Aksoy et al. noted a significantly higher score after eight hours of wearing facial masks. 41
MGD and lipid layer deficiency are the main causes of evaporative dry eye, which leads to uncontrolled evaporation and excess water loss from the ocular surface. 42 In a study by Enriquez-de-Salamanca et al., increased levels of inflammatory cytokines were found in patients with moderate forms of evaporative DED due to MGD. 34 In a recent study, the mean score of MG loss was reported as 22.8% in healthcare workers wearing surgical masks. 43 Likely, In the current study, the rate of the clinical findings of MGD and meibomiography scores of the prolonged mask-user group were found to be higher than those of normal individuals correlated with proinflammatory cytokine scores. The presence of MGD seems to support the increase in tear film evaporation, in addition to factors related to mask use.
Our study has some limitations. First, the small sample size may have hampered the detection of statistical significance for some parameters. Second, it would be better if the number of evaluated tear film cytokines were higher. Third, we did not evaluate the effect of taping of the upper mask edge, which is highly blocking the breathing air reaching the ocular surface.