Temporal Progression and Spatial Repeatability of Tear Breakup

Invest. Ophthalmol. Vis. Sci.

Simpson

Liu

et al. 2013

Self Cite

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 (Spearman's, 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.Keywords: tear film instability, tear film break-up, tear film thinning, evaporation, fluorescein concentration quenching, corneal sensory nerves, nociception D ry eye is a common condition, affecting millions in the United States and elsewhere, 1-5 affecting quality of life, [6][7][8] and potentially engendering high health care costs now and in the future. 9 However, despite its prevalence and impact, the underlying etiology of the condition and the basis of dry eye symptoms remain subject to speculation. 10,11The recent international Dry Eye Workshop report identified the core mechanisms of dry eye as tear film hyperosmolarity and instability, which are thought to generate dry eye symptoms through repeated stress to the ocular surface, inflammation, and activation of corneal sensory nociceptors. 10In support of this hypothesis, tear hyperosmolarity has been shown to stress the surface and trigger ocular surface inflammation, 12,13 and recent reports have associated tear film hyperosmolarity with dry eye symptoms. 14 However, while tear film osmolarity is likely to fluctuate markedly or spike 15 in the interblink interval due to evaporation or other factors, [16][17][18] it cannot be measured directly over the cornea with current techniques of sampling the tears from the inferior meniscus. 19 Thus, changing conditions within the tear film during ins...

Section: Methodsmentioning

confidence: 99%

Section: Image Analysismentioning

confidence: 99%

mentioning

confidence: 99%

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

Invest. Ophthalmol. Vis. Sci.

Simpson

Liu

et al. 2013

Self Cite

“…The tear film is usually studied in the inter-blink period, where an unstable tear film quickly becomes evident as TBU progresses rapidly (Liu et al, 2006). This is measured clinically by fluorescein tear break-up time (TBUT), or the first appearance of a dark or “dry spot” after a blink (Norn, 1969).…”

Section: Introductionmentioning

confidence: 99%

Dynamics and function of the tear film in relation to the blink cycle

Braun

King‐Smith

Progress in Retinal and Eye Research

et al. 2015

110

163

Great strides have recently been made in quantitative measurements of tear film thickness and thinning, mathematical modeling thereof and linking these to sensory perception. This paper summarizes recent progress in these areas and reports on new results. The complete blink cycle is used as a framework that attempts to unify the results that are currently available. Understanding of tear film dynamics is aided by combining information from different imaging methods, including fluorescence, retroillumination and a new high-speed stroboscopic imaging system developed for studying the tear film during the blink cycle. During the downstroke of the blink, lipid is compressed as a thick layer just under the upper lid which is often released as a narrow thick band of lipid at the beginning of the upstroke. “Rippling” of the tear film/air interface due to motion of the tear film over the corneal surface, somewhat like the flow of water in a shallow stream over a rocky streambed, was observed during lid motion and treated theoretically here. New mathematical predictions of tear film osmolarity over the exposed ocular surface and in tear breakup are presented; the latter is closely linked to new in vivo observations. Models include the effects of evaporation, osmotic flow through the cornea and conjunctiva, quenching of fluorescence, tangential flow of aqueous tears and diffusion of tear solutes and fluorescein. These and other combinations of experiment and theory increase our understanding of the fluid dynamics of the tear film and its potential impact on the ocular surface.

“…(6, 40, 41) Briefly, color fluorescent images were converted to grayscale, and the region of total exposed cornea (region of interest) outlined. A custom MATLAB® program was used to calculate the percentage of TBU using a threshold pixel intensity set by the investigator for each trial.…”

Section: Methodsmentioning

confidence: 99%

The Effects of Mild Ocular Surface Stimulation and Concentration on Spontaneous Blink Parameters

Situ

et al. 2013

Current Eye Research

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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 2 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 0.6m/sec at the eye). At each visit, subjects performed a high (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 significant 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.