SSDE patients usually have more severe discomfort symptoms and ocular surface damage than NSSDE patients according to previous studies.(9-14) The current study obtained similar results: SSDE patients had higher OSDI values, less tear production, more unstable tear film, more severe corneal staining, and even a higher rate of meibomian gland dropout.
As far as FTBUP was concerned, we found that FTBUP predominantly occurred in the inferior quadrant, which was seen in 90% eyes of SSDE and 70% of NSSDE. This result was similar to previous studies focused on aqueous-deficient dry eye and meibomian gland dysfunction.(19, 20) Three possible reasons might contribute to the predominance of FTBUP in the inferior area. First, the inferior region had a thinner tear film than the superior region,(28-30) which was more likely to break up earlier. Second, subbasal nerve abnormalities caused by long-term ocular surface inflammation, especially in dry eye patients, are characterized with reduced density, abnormal morphology, impaired corneal sensation and abnormal blinking.(31, 32) Reduced blinking rate and incomplete blinking contributed to overexposure of the ocular surface, especially the interpalpebral area, and increased tear evaporation.(33) Third, a higher rate of meibomian gland dropout of the lower eyelid caused reduced lipid production in the inferior region, which also contributed to the instability of the inferior tear film. Therefore, FTBUP was more likely to occur in this area in both SSDE and NSSDE groups.
The current study showed a higher proportion of eyes with positive fluorescein staining and higher fluorescein staining scores in SSDE, which was in agreement with previous studies.(13, 34) Moreover, the location of FTBUP was strongly correlated with positive corneal fluorescein staining in SSDE. Amplified inflammatory response and desiccation stress of the ocular surface in SSDE could lead to the destruction of intracellular tight junctions of the corneal epithelium and consequent damage barrier function,(35, 36) which caused the infiltration of fluorescein in this area, as well as an unsmooth corneal surface and an unstable tear film. This might explain the observed strong correlation between the location of FTBUP and corneal fluorescein staining in SSDE.
The tear film serves as the most anterior refractive surface, playing an important role in maintaining optical quality.(37-39) Many studies have shown that irregular astigmatism and wavefront aberrations caused by an unstable tear film are increased in dry eye patients.(40, 41) A short tear film break-up time increased the post-blink higher order aberrations (HOAs) and ocular forward light scattering, leading to "fluctuated vision" or "glare".(42) Liu et al (43) reported that irregularity of the ocular surface was positively correlated with corneal fluorescein staining. Our previous study showed that SSDE patients had worse visual quality.(44) The current study confirmed that tear film instability and ocular surface damage might be possible reasons. Nevertheless, the impact of different locations of FTBUP on visual quality needs further investigation.
Qi et al (20) showed that meibomian gland dropout was positively correlated with OSDI values in patients with dry eye, while Zang et al (10) suggested that meibomian gland dropout was inconsistent with symptoms in SSDE. In our study, although SSDE patients had a higher rate of meibomian gland dropout than NSSDE patients, no significant correlation was found between meibomian gland dropout and OSDI values in either SSDE or NSSDE. Heterogeneity of the signs and symptoms of dry eye, which have a close relationship to the course and condition of the disease and corneal sensation, existed in different studies. Hence, mild or well-controlled SSDE patients may have fewer symptoms than severe or uncontrolled NSSDE patients.
Several limitations of the current study should be addressed. First, the OSDI questionnaire only evaluated ocular symptoms within the most recent week. However, most SSDE patients in our study had a long course of disease and might have decreased corneal sensation. The symptoms evaluated by the OSDI questionnaire may not be consistent with the ocular surface signs. Second, 90.9% of SSDE in the present study were not newly diagnosed, and 86.3% had already had immunosuppressant treatment such as cyclosporin A. Different treatment regimens might affect the results. The sample size was also limited. Further study with a larger number of newly diagnosed SSDE is needed to verify the findings of the current study and to investigate the impact of different locations of FTBUP on visual quality.
In conclusion, FTBUP was more likely to occur in the inferior quadrant in both SSDE and NSSDE. The location of FTBUP in SSDE had a close relationship with corneal fluorescein staining. Hence, the maintenance of an intact and healthy corneal epithelium is crucial to a stable tear film and good visual quality.