We report a new diagnostic test, called the BTT test, for evaluating tear film instability. This test evaluates the stability of the tear film indirectly by measuring the time interval between eye blinks when the participant has been asked to refrain from blinking for as long as possible before feeling a foreign body sensation or irritation. Tear film instability is a key mechanism of dry eye disease[10], and new, effective diagnostic approaches that are inexpensive and noninvasive would be beneficial.
The present study revealed no statistically significant difference between the tBUTBE and BTT among all participants, and a significant positive correlation between the 2 measurements. Further, there was no significant difference in the AUC between the tBUTBE and BTT values. The BTT values for the dry eye group were significantly shorter than those for the normal control group. Thus, the BTT test can be used for self-diagnosis of dry eye disease.
Sophisticated scientific diagnostic instruments, such as the TearLab system (TearLab, San Diego, CA, USA) and LipiView (TearScience, Morrisville, NC, USA) interferometry systems, which incorporate remarkable technologic innovations, have been developed for clinical use. Dry eye disease is a prevalent disorder that represents a major public health burden due to its negative impact on patient vision and quality of life. The BTT test is a simple method for self-diagnosis of this disease with high reliability. This inexpensive new diagnostic tool can also be used widely 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.[11] performed a computerized analysis of video recordings of spontaneous blinking in normal and dry eye patients, and reported that the inter-blinking time (IBT) differed significantly between the 2 groups (4.0 ± 2.0 s for the normal group and 1.5 ± 0.9 s for the dry eye group). The IBT in their study corresponds to the BTT used in our study. The BTT differs from the IBT, however, in that the participant is asked not to blink after the reset blink until he or she feels ocular pain. 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, in contrast to the study by Pult et al.[11]. We first confirmed that there was no significant difference between the BTT and tBUTBE values; second, we found a significant positive correlation between the 2 tests; third, the ICC of the BTT test was superior to that of the tBUTBE test; and finally, there was no significant difference between the AUCs of the 2 tests. These findings confirmed that the BTT test is appropriate for dry eye diagnosis, having comparable utility to the tBUT test. The diversity of the blink rate is related to the severity of dry eye disease. Previous studies reported that the blink rate 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]. Several reports have described the mechanism underlying blinking in patients with dry eye disease.
Ocular surface temperature decreases over time after blinking [14]. The tear film begins to destabilize after blinking due to evaporation, which cools the ocular surface[15]. The rate of evaporation is increased in patients with dry eye due to the instability of the lipid layer[16]. The ocular surface temperature may therefore be decreased in patients with dry eye due to tear film instability immediately after blinking compared with 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]. Reduced sensitivity of these thermoreceptors in patients with dry eye, who already have a cooler-than-normal corneal temperature of 34℃, can decrease the physiologic 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 patients with dry eye. Therefore, we analyzed the correlation between the BTT and OSDI results, but detected no significant association.
In the present study, we aimed to demonstrate the efficacy of the BTT test, a new method for diagnosing dry eye, compared with the conventional tBUT test. The BTT test can serve as a useful dry eye diagnostic tool as an adjunct to the tBUT test: first, the mean values of the BTT and tBUT in the normal control group did not differ significantly from each other; second, there was no statistically significant difference in the AUC between the BTT and tBUT; and third, both the tBUT and the BTT were significantly shorter in patients with dry eye than in the normal controls. The BTT and tBUT measurements, however, 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, an 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 with 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 perform, such that anyone can use it to evaluate dry eye disease without assistance from a clinician. In this study, we found no significant difference between the BTT and tBUT results among all participants, and the BTT was shorter in patients with dry eye than in 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 reflects the physiologic status of the tear film, because no fluorescein dye is needed for the testing procedure.
The BTT test has some weaknesses. First, the BTT is affected not only by tear film stability, but also by each individual pain threshold; a person with a high pain threshold will have a longer BTT and vice versa. As such, we expected that the OSDI, which reflects the subjective symptoms of patients with dry eye, would be significantly correlated with the BTT, but instead, the results of BTT test showed a significant positive correlation with the results 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 1 eye at a time). Of course, we can measure the BTT in 1 eye at a time, with the other eye closed, but this method would not reflect the physiologic status of the tear film.