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Deborah Antwi, Carolyn G. Begley, Richard J Braun, Rayanne A Luke, Ping Situ; The Pain Response during Tear Breakup (TBU). Invest. Ophthalmol. Vis. Sci. 2019;60(9):6781.
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© ARVO (1962-2015); The Authors (2016-present)
Despite the importance of tear film instability and tear breakup (TBU) to dry eye disease (TFOS DEWS 2017), events within areas of TBU remain poorly understood. In this study, we examine the pain response during TBU to determine whether the onset of the “rapidly rising phase” (Varikooty and Simpson, 2009) is more closely associated with the onset of full-thickness TBU or the classic clinical measure, tear breakup time (TBUT).
Sustained tear exposure (STARE) trials from 12 normal subjects were included in the study. During STARE trials, fluorescein was instilled, subjects kept their tested eye open as long as possible while turning a pain knob to indicate their discomfort. A custom Matlab program (nonlinear least squares fits using the Levenberg-Marquardt algorithm) was used to determine the onset of the rapidly rising phase in the pain response, labeled as breakpoint (BP) in Figure 1. The pixel intensity of full-thickness TBU (set as 0.1% of the corneal area) in each fluorescent image was estimated by a custom Matlab program employing a masked observer (Begley et al., 2013). TBUT for each trial was determined by the average of 3 experienced clinicians.
The example in Figure 1 shows that the calculated BP in the pain response (15.2 sec) and the onset of 0.1% or full thickness TBU (15.0 sec) were very close for one subject, while the average clinically determined TBUT for that subject was much earlier, 8.4sec. Figure 2 shows pain knob BP versus the time to full thickness TBU and TBUT for all subjects. There was a high and statistically significant correlation (Pearson’s) between the pain knob BP time and the onset of full-thickness TBU (r=0.83, p=0.0009), compared to the poor correlation with TBUT (r=0.27, p=0.4001)
The BP in the pain response during TBU shows a higher association with the onset of estimated full thickness TBU than with the classic clinical measure of TBUT. These results suggest that conditions within the tear film when TBU becomes full thickness may accelerate or alter the response of underlying corneal neurons, thus accounting for the “rapidly rising phase’ in the pain response.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
Data from one subject showing the calculated breakpoint in pain response (15.2 sec) and the onset of estimated full thickness TBU (0.1% of corneal area).
Data from all subjects showing the relationship between the calculated pain breakpoint time and the estimated time to full thickness TBU versus TBUT.
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