This study introduced a new diagnostic test, called the BTT test, for evaluating tear film instability. This test evaluated the stability of the tear film indirectly via measurement of the time interval between blinking of the eyes, by preventing the participant from blinking as far as possible before feeling a foreign body sensation or irritation. Tear film instability is a key mechanism of dry eye disease[10], so new diagnostic approaches should be considered carefully.
The present study showed that there was no statistically significant difference between the tBUTOU and BTT among all participants, and a significant positive correlation was observed between the two measurements. There was no significant difference in the AUC of the ROC curve between the tBUTOU and BTT values. However, BTT values for the dry eye group were significantly shorter than those for the normal control group. Thus, the BTT test can be used as a self-diagnosis.
More sophisticated scientific diagnostic instruments, such as the TearLab system (TearLab, San Diego, CA, USA) and LipiView (TearScience, Morrisville, NC, USA) interferometry systems, which display remarkable technological innovations, have been developed for clinical use. However, dry eye disease is a prevalent disorder, usually with relatively mild clinical features. The BTT test, as a simple and inexpensive method to perform self-diagnosis with high reliability, is necessary because dry eye disease represents a major public health burden due to its negative impact on patient vision and quality of life. In addition to self-diagnosis, this new diagnostic tool can be used by clinicians to diagnose dry eye disease.
Several studies have been conducted to determine the association between eye blinking and dry eye disease. Pult et al. performed computerized analysis of video recordings of spontaneous blinking in normal and dry eye patients[11]. The study reported that the inter-blinking time (IBT) was 4.0 ± 2.0 s for the normal group and 1.5 ± 0.9 s for the dry eye group, where there was a statistically significant difference between the two groups. In their study, the IBT corresponded to the BTT used in our study. However, a characteristic of the BTT that differs from the IBT is that the participant must wait until he or she feels ocular pain, followed by measurement of the time until eye blink. In addition, our study focused on analyzing the correlation between the BTT and tBUT tests without using complex equipment, such as video capture and analysis equipment, unlike the study of Pult et al.[1]. We determined the following regarding the BTT and tBUT tests: first, there was no significant difference between the BTT and tBUTOU values; second, there was a positive correlation between the two tests third, the ICC of the BTT test was superior to that of the tBUTOU test; and finally, there was no significant difference between the AUCs of the two tests. In conclusion, we confirmed that the BTT test is appropriate for dry eye diagnosis, showing comparable utility to the tBUT test. The diversity of the blink rate is known to be related to the severity of dry eye disease. Previous studies reported that the blink rate was increased in the aqueous-deficient type of dry eye disease; furthermore, the increased blink rate was positively correlated with corneal staining and subjective dry eye symptoms, and negatively correlated with the tBUT[12, 13]. In addition, there are several reports that explain the mechanism underlying the blinking seen in dry eye disease.
Ocular surface temperature is known to decrease across time after blinking [14]. The tear film starts to destabilize after blinking due to evaporation, leading to cooling of the ocular surface[15]. The rate of evaporation is known to be increased in dry eye patients due to the instability of the lipid layer[16]. The ocular surface temperature could therefore be increased in dry eye patients with tear film instability immediately after blinking compared to normal controls[17]. Stimulation of cold thermoreceptors in the cornea between blinks can result in basal tear secretion, and such stimulation in normal controls is related to ocular comfort and wetness[18]. However, reduced sensitivity of thermoreceptors in dry eye patients, who have a cooler-than-normal corneal temperature of 34℃, can decrease the physiological tearing stimulation, thus leading to increased subjective dry eye symptoms such as pain and a stinging sensation[13].
The concept of the BTT is different from the blinking interval in a relaxed state. The BTT test measures the time until the participant blinks after sensing a foreign body sensation or irritation. The BTT measurement is therefore consistent with the concept of tear film stability, which is not related to the pain threshold or nociceptor activation. It is possible that the BTT is related to the pain threshold and nociceptor activation, and that this test is thus less objective than the tBUT test, being relatively strongly associated with the symptoms afflicting dry eye patients. Therefore, we analyzed the correlation between the BTT and OSDI results, but no significant association was seen.
In the present study, we aimed to demonstrate the efficacy of the BTT test, a new method for diagnosing dry eye, compared to the conventional tBUT test. The BTT test can serve as a useful dry eye diagnostic tool, as an adjunct to tBUT test: first, the mean values of the BTT and tBUT in the normal control group were not statistically different from each other; second, there was no statistically significant difference in the AUC of the ROC curves between the BTT and tBUT; and third, both the tBUT and the BTT were significantly shorter in the dry eye patients than in the normal controls. However, the BTT and tBUT measurements showed a weakly positive correlation, for the following reasons: first, both the BTT and tBUT tests may not be highly reproducible; second, the pain threshold may differ among participants; and third, understanding of, and willingness to undergo, the BTT test (which involves blinking naturally after feeling a foreign body sensation or irritation) may also differ among individuals.
The BTT test has several advantages compared to the tBUT test. First, it can be used as a self-test of dry eye disease. The BTT test is very easy and simple to apply, such that anyone can use it to evaluate dry eye disease without assistance from a clinician. In this study, there was no significant difference between the BTT and tBUT results among all participants, and the BTT was shorter in dry eye patients versus normal subjects. Because the AUC of the BTT was 0.628, it was insufficient to diagnose dry eye disease alone, but could be used as a self-test for screening purposes. Second, the BTT test was superior to the tBUT test with respect to the reproducibility of the results. In our study, the ICC of the BTT test was 0.904 and that of the tBUT test was 0.679; the BTT test was therefore more reproducible than the tBUT test. Third, the BTT test better reflected the physiological status of the tear film, because no fluorescein dye is needed in the testing procedure.
However, the BTT test showed some weaknesses. First, the BTT was affected not only by tear film stability, but also by each individual pain threshold; a person with a high threshold for pain will have a longer BTT and vice versa. Considering this, we expected the OSDI, which reflects the subjective symptoms of dry eye patients, to show a significant correlation with the BTT, but the BTT test instead showed a significant positive correlation with the tBUT test. Second, the BTT test examines both eyes simultaneously, so that the condition of each eye cannot be measured separately, unlike in the tBUT or Schirmer tests (both of which test one eye at a time). Of course, we can measure the BTT in one eye at a time, with the other eye closed, but this method would not reflect the physiological status of the tear film.