Ziwei Wu

Quantitative Analysis of Tear Film Fluorescence and Discomfort During Tear Film Instability and Thinning

PURPOSE The purpose of this study was to test the association between tear film fluorescence changes during tear break-up (TBU) or thinning and the concurrent ocular sensory response. METHODS Sixteen subjects kept one eye open as long as possible (MBI), indicated their discomfort level continuously, and rated ocular sensations of irritation, stinging, burning, pricking, and cooling using visual analog scales (VAS). Fluorescence of the tear film was quantified by a pixel-based analysis of the median pixel intensity (PI), TBU, and percentage of dark pixels (DarkPix) over time. A cutoff of 5% TBU was used to divide subjects into either break-up (BU) or minimal break-up (BUmin) groups. RESULTS Tear film fluorescence decreased (median PI) and the percentage of TBU and DarkPix increased in all trials, with the rate significantly greater in the BU than the BUmin group (Mann-Whitney U test, P < 0.05). The rate of increasing discomfort during trials was highly correlated with the rate of decrease in median PI and developing TBU (Spearmans, r ≥ 0.70). Significant correlations were found between corneal fluorescence, MBI, and sensory measures. CONCLUSIONS Concentration quenching of fluorescein dye with tear film thinning best explains decreasing tear film fluorescence during trials. This was highly correlated with increasing ocular discomfort, suggesting that both tear film thinning and TBU stimulate underlying corneal nerves, although TBU produced more rapid stimulation. Slow increases in tear film hyperosmolarity may cause the gradual increase in discomfort during slow tear film thinning, whereas the sharp increases in discomfort during TBU suggest a more complex stimulus.

The Effects of Increasing Ocular Surface Stimulation on Blinking and Sensation

PURPOSE The purpose of this study was to determine how increasing ocular surface stimulation affected blinking and sensation, while controlling task concentration. METHODS Ten healthy subjects concentrated on a task while a custom pneumatic device generated air flow toward the central cornea. Six flow rates (FRs) were randomly presented three times each and subjects used visual analog scales to record their sensory responses. The interblink interval (IBI) and the FR were recorded simultaneously and the IBI, sensory response, and corresponding FR were determined for each trial. The FR associated with a statistically significant decrease in IBI, the blink increase threshold (BIT), was calculated for each subject. RESULTS Both the mean and SD of IBI were decreased with increasing stimulation, from 5.69 ± 3.96 seconds at baseline to 1.02 ± 0.37 seconds at maximum stimulation. The average BIT was 129 ± 20 mL/min flow rate with an IBI of 2.33 ± 1.10 seconds (permutation test, P < 0.001). After log transformation, there was a significant linear function between increasing FR and decreasing IBI within each subject (Pearsons r ≤ -0.859, P < 0.05). The IBI was highly correlated with wateriness, discomfort, and cooling ratings (Pearsons r ≤ -0.606, P < 0.001). CONCLUSIONS There was a dose-response-like relationship between increased surface stimulation and blinking in healthy subjects, presumably for protection of the ocular surface. The blink response was highly correlated with ocular surface sensation, which is not surprising given their common origins. The BIT, a novel metric, may provide an additional end point for studies on dry eye or other conditions.

The effects of mild ocular surface stimulation and concentration on spontaneous blink parameters.

Abstract Purpose: This exploratory, pilot study compared the effects of concentrating on a visual task and a very mild ocular surface air stimulus on multiple blink parameters. Methods: Ten subjects participated in this study. There were two visits, one with an ocular surface air stimulus (AS) and one without (NS). The AS was set at a level barely perceptible by subjects (approximately 0.6 m/s at the eye). At each visit, subjects performed a high-concentration (HC) and low-concentration (LC) task. Blinking was tracked and tear-film breakup (TBU) was monitored simultaneously to measure blink parameters, including the interblink interval (IBI), blink amplitude, duration, maximum velocity and TBU before and after each blink. Results: During the HC tasks, IBI was significantly higher and blink duration was lower (repeated measures ANOVA, p < 0.05) than the LC tasks. The IBI in the AS-LC condition was significantly lower and less variable than in the NS-HC condition, whereas blink duration showed the opposite effect (Hotelling T2 test, p < 0.005). There was high individual variation in correlations between blink amplitude and maximum velocity. The area of TBU was not significantly correlated with any blink parameter. Conclusions: The lack of correlation between TBU and blinking suggests that many blinks are stimulated by internal controls, rather than direct stimulation of the ocular surface by TBU. This pilot study suggests that even very mild ocular surface stimulation produces opposite effects on the timing and duration of the blink, when compared to concentrating on a visual task. The HC task tends to decrease blink frequency and duration, presumably to minimize interruption by the eyelids, whereas mild ocular surface AS increased blink frequency and duration, most likely to increase protection of the ocular surface.

The Effects of Increasing Ocular Surface Stimulation on Blinking and Tear Secretion

PURPOSE To investigate the effect of varying levels of ocular surface stimulation on the timing and amplitude of the blink and tear secretion. METHODS Following instillation of fluorescein dye, increasing levels of air flow were directed toward the central corneas of 10 healthy subjects. Interblink interval (IBI), tear meniscus height (TMH), and fluorescence intensity were measured simultaneously. Because blinking can obscure changes in TMH, we developed novel measures of tear secretion by calculating tear meniscus fluorescein concentration (TMFC) from intensity using a mathematical model. The change of TMH and TMFC over trials and the slope of the TMFC within each IBI (IBI-TTR) were further calculated. RESULTS The mean IBI was decreased by 8.08 ± 8.54 seconds from baseline to maximum air stimulation. The TMH increase was highly variable (0.41 ± 0.39 mm) among subjects, compared to the fluorescence tear turnover metrics: decrease in TMFC of 2.84 ± 0.98 natural logarithm or ln(%) and IBI-TTR of 0.065 ± 0.032 ln(%)/sec. Ocular surface stimulation was highly correlated with the TMFC and IBI-TTR, but less so with TMH (Pearsons r = 0.71, 0.69, and 0.40, P < 0.01, respectively). Blinking and tearing were significantly correlated with each other (Pearsons r = 0.56, P < 0.01), but tearing lagged behind by an average of 6.54 ± 4.07 seconds. CONCLUSIONS Blinking and tearing share a common origin with sensory stimulation at the ocular surface. Both showed a dose-response increase with surface stimulation and were correlated with each other. These methods can potentially be used to understand alterations in ocular surface sensory function and associated protective responses in dry eye and other disorders of the ocular surface.