A link between tear breakup and symptoms of ocular irritation☆
Introduction
Dry eye (DE) disease is a common ocular condition that affects millions in the United States and elsewhere [1], [2], [3], [4]. Twenty percent of adults over 45 years of age report symptoms of DE or ocular irritation [2]. DE disease is classified into various syndromes, yet many types share similar symptoms: eye irritation, dryness, burning, stinging, and blurry vision [5]. The 2007 International Dry Eye Workshop (DEWS) report identified tear film instability as a core mechanism of DE, but its connection to symptoms has not been fully characterized [6].
Tear film instability, which includes tear film breakup (TBU) and rapid tear thinning, can be an initiating event in some forms of DE and is assumed to lead to local surface drying and increased hyperosmolarity [6]. Indeed, experimental data and mathematical modeling suggest that levels of hyperosmolarity may reach greater than 800–1000 mOsm/Kg within areas of TBU [7], [8], [9], [10]. Furthermore, optical studies of developing TBU areas demonstrated an increase in micro-aberrations and scatter within TBU, suggestive of drying and exposure of the rough epithelial surface as TBU becomes a full-thickness break in the tear film [11], [12]. In support of these findings, we [13] and others [14] have shown a temporal association between increasing growth of TBU areas and sensations of burning, stinging, pricking and/or cooling, presumably due to stimulation of ocular surface neurons by hyperosmolarity, drying, or other factors associated with areas of TBU or extensive tear thinning [15]. Furthermore, we have shown that three consecutive episodes of TBU can result in slightly increased DE-like symptoms of ocular irritation in some subjects [16]. These studies suggest that tear film instability, in this case manifested by TBU, can directly stimulate ocular surface neurons.
In this investigation, we further test this hypothesis by using soft contact lenses (CLs), which cover the cornea, limbus, and a very small portion of the bulbar conjunctiva, as a tool to interfere with the direct effects of TBU on the corneal surface. We hypothesize that wearing a CL will dampen the sensory response to TBU because the CL presents a physical barrier between the tear film and the corneal surface. We employ extended eye opening trials as a method for inducing TBU or tear thinning [13], [14], [16], [17] to compare the ocular discomfort during TBU with and without CLs. We also study the effect of repeated eye opening trials on the development of persistent discomfort and other symptoms of ocular irritation.
Section snippets
Subjects
The study was approved by the Indiana University Institutional Review Board and was conducted at the Borish Center for Ophthalmic Research at Indiana University School of Optometry, Bloomington, Indiana. Informed consent was obtained from all subjects prior to beginning the study. Ten habitual CL wearers were recruited from the Borish Center for Ophthalmic Research database of subjects interested in participating in research projects. We included subjects with and without DE, attempting to
Results
Ten subjects participated in this study, including two males and eight females. The average age was 32.5 ± 12.4 years (range: 23–59 years). The total symptom score on the DEQ-5 [18] averaged 9.9 ± 4.8 (range: 1 to 15). Fluorescein tear breakup time (TBUT) among subjects ranged from 2.5 to 45 s, with an average of 8.9 ± 12.3 s. Tear secretion, as measured by the Schirmer tear test (without anesthetic), averaged 8.8 ± 4.7 mm, with a range of 3–15 mm. Six of the subjects in the study thought they
Discussion
In this study, we show that developing TBU is associated with increasing discomfort, and that this discomfort can be at least partially blocked by wearing a soft CL. Furthermore, repeated TBU without CLs in STARE trials led to increasing discomfort and other symptoms of ocular irritation that persisted even after normal blinking was restored. These results support the hypothesis that TBU stimulates ocular surface sensory neurons and that repeated episodes of TBU can produce an alteration in
Conclusions
In summary, an unstable tear film has long been associated with the DE condition [61], [62], but its connection to symptoms [63], as with other DE clinical signs [64], [65], [66], [67], has been difficult to establish. Our STARE model demonstrated that TBU was associated with increased discomfort, which was at least partially blocked by wearing a CL, suggesting ocular surface neural stimulation by adverse conditions within TBU. Furthermore, repeated TBU led to increased, persistent dry-eye like
Funding
This work was supported by Grant Number R01EY021794 (Dr. Begley) from the National Eye Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Eye Institute or the National Institutes of Health.
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This study involved no commercial relationships.