Publications by authors named "Carolyn Begley"

Purpose: To investigate the roles of neural adaptation and sensitization in contact lens discomfort (CLD).

Methods: Cooling stimuli (20 °C) were applied to the cornea in a group comprising 24 symptomatic and 25 asymptomatic contact lens (CL) wearers as well as 15 non-CL wearing controls, using a computerized Belmonte esthesiometer. The adaptation paradigm consisted of 20 repetitive stimuli at threshold, sub- and supra-threshold levels.

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Purpose: Understanding of the role of the tear film lipid layer (TFLL) in evaporative dry eye requires knowledge of its structure. X-ray studies show 11.1-nm thick lamellae in meibum at tear film temperature (approximately 35°C), whereas below 30°C, 4.

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Tear film instability, which can lead to rapid tear film breakup (TBU), is considered to be a major etiological factor in dry eye. However, experimental support for many of the proposed theories for TBU mechanisms is relatively scarce. The major aim of this perspective is to show that fluorescence studies of TBU can be used to provide experimental evidence for two proposed underlying mechanisms of TBU, evaporation and divergent flow.

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Purpose: To explore the effect of time on grading corneal fluorescein and conjunctival lissamine green staining in dry eye disease (DED).

Methods: Photographs of 68 subjects with non-Sjogren's DED (nSS DED) and 32 with Sjogren's DED (SS DED) were taken of corneal fluorescein staining, then conjunctival lissamine green staining every 30 s for at least 5 min. Photographs of one randomly selected eye were then randomly ordered and graded on a scale from 0 to 5 (severe staining) by two clinicians, masked to both site and subject.

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The human tear film is rapidly established after each blink, and is essential for clear vision and eye health. This paper reviews mathematical models and theories for the human tear film on the ocular surface, with an emphasis on localized flows where the tear film may fail. The models attempt to identify the important physical processes, and their parameters, governing the tear film in health and disease.

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Purpose: In this study, we apply psychophysical scaling principles based on physical (photometric) attributes of images to better understand the factors involved in clinician judgement of ocular surface staining and, using that knowledge, to develop photographic scales for the assessment of staining for dry eye (DE) and related conditions.

Methods: Subjects with noninfectious ocular surface staining were enrolled at five clinical sites. Following instillation of fluorescein, photographs of corneal staining were taken every 30 seconds for at least 5 minutes.

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Etiologies of tear breakup include evaporation-driven, divergent flow-driven, and a combination of these two. A mathematical model incorporating evaporation and lipid-driven tangential flow is fit to fluorescence imaging data. The lipid-driven motion is hypothesized to be caused by localized excess lipid, or "globs.

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Purpose: To examine the diurnal variation of corneal threshold and suprathreshold sensory processing, symptoms, and tear secretion in symptomatic and asymptomatic contact lens (CL) wearers and controls.

Methods: 26 symptomatic and 25 asymptomatic CL wearers and 15 asymptomatic non-CL wearing controls participated. Cooling thresholds, symptoms and tear meniscus height (TMH) were measured on each of 3 measurement days (random order) on the following schedules; Day-1 within 1 h of awakening (Baseline) and 3, 6 and 9 h later, Day-2 baseline and 9 h later (CLs worn in CL group) and Day-3 baseline and 9 h later.

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Many parameters affect tear film thickness and fluorescent intensity distributions over time; exact values or ranges for some are not well known. We conduct parameter estimation by fitting to fluorescent intensity data recorded from normal subjects' tear films. The fitting is done with thin film fluid dynamics models that are nonlinear partial differential equation models for the thickness, osmolarity and fluorescein concentration of the tear film for circular (spot) or linear (streak) tear film breakup.

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Purpose: Pterygia are much more common nasally than temporally. Ultraviolet (UV) radiation is a major risk factor. Coroneo proposed that the nasal preference is caused by the "peripheral light focusing effect," (PLF), in which UV at an oblique angle passes through temporal cornea and is concentrated on and damages nasal limbal stem cells.

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Purpose: To use a human-based model to study the effects of repeated tear film instability on corneal detection thresholds to cold, mechanical, and chemical stimuli.

Methods: Twenty-five subjects participated in three study visits. A computer-controlled Belmonte esthesiometer was used to estimate corneal detection thresholds to cold, mechanical, and chemical stimuli before, after, and 30 minutes following 10 consecutive sustained tear exposure (STARE) trials.

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Purpose: To investigate the effects of tear film instability (TFI) induced by sustained tear exposure (STARE) on sensory responses to corneal cold, mechanical, and chemical stimuli.

Methods: Fifteen normal subjects were enrolled. TFI was induced during 10 repeated trials of STARE.

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Vital dye staining has been used for over a century to assess the severity of ocular surface disease. However, despite common usage, a universally accepted "gold standard" grading scale does not exist for corneal and conjunctival staining, which can impact the ability to diagnose and monitor ocular surface conditions such as dry eye. The Food and Drug Administration (FDA) and other international regulatory agencies rely on ocular surface staining as a primary endpoint for new drug approvals, so that absence of a "gold standard" scale may affect approval of new drug treatments.

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Purpose: The purpose of this study was to develop a clinically feasible method for obtaining dye concentrations of 2% fluorescein (FL) and 1% lissamine green (LG) by soaking commercially available dye impregnated strips in saline.

Methods: Calibration curves were established to related known concentrations of dye to prepared FL fluorescence and LG absorbance. To determine the optimum number of dye strips and soaking times (preliminary testing), 1, 2, 3 FL or LG strips were soaked in 200 μl commercially available saline for 0.

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Tear film breakup (BU) is an important aspect of dry eye disease, as a cause of ocular aberrations, irritation and ocular surface inflammation and disorder. Additionally, measurement of breakup time (BUT) is a common clinical test for dry eye. The current definition of BUT is subjective; here, a more objective concept of "touchdown" - the moment when the lipid layer touches down on the corneal surface - is proposed as an aid to understanding processes in early and late stages of BU development.

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Pain associated with mechanical, chemical, and thermal heat stimulation of the ocular surface is mediated by trigeminal ganglion neurons, while cold thermoreceptors detect wetness and reflexly maintain basal tear production and blinking rate. These neurons project into two regions of the trigeminal brain stem nuclear complex: ViVc, activated by changes in the moisture of the ocular surface and VcC1, mediating sensory-discriminative aspects of ocular pain and reflex blinking. ViVc ocular neurons project to brain regions that control lacrimation and spontaneous blinking and to the sensory thalamus.

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We report the results of some recent experiments to visualize tear film dynamics. We then study a mathematical model for tear film thinning and tear film breakup (TBU), a term from the ocular surface literature. The thinning is driven by an imposed tear film thinning rate which is input from in vivo measurements.

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Purpose: We used the presence or absence of a soft contact lens (CL) as a barrier to test the hypothesis that tear breakup (TBU) presents a direct noxious stimulus to the ocular surface.

Methods: Ten subjects kept one eye open as long as possible, termed sustained tear exposure (STARE), for 10 consecutive trials while discomfort was monitored with and without a CL in place. The area of TBU was quantified in each frame.

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Purpose: To document the time course and resolution of contact lens-related corneal infiltrative events (CIEs) comparing slit-lamp images with anterior segment ocular coherence tomography (AS-OCT) images.

Methods: Six silicone hydrogel (SiHy) soft contact lens (SCL) wearers presenting with newly diagnosed symptomatic CIEs were monitored with slit-lamp images, detailed drawings, and AS-OCT until the resolution of the CIE. A final follow-up visit was completed 4 weeks after CIE resolution to determine whether scar formation was present.

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Purpose: To examine the cooling thresholds and the estimated sensation magnitude at stimulus detection in controls and symptomatic and asymptomatic contact lens (CL) wearers, to determine whether detection thresholds depend on the presence of symptoms of dryness and discomfort.

Methods: Forty-nine adapted CL wearers and 15 non-lens wearing controls had room temperature pneumatic thresholds measured using a custom Belmonte esthesiometer, during Visits 1 and 2 (Baseline CL), Visit 3 (2 weeks no CL wear), and Visit 4 (2 weeks after resuming CL wear). CL wearers were subdivided into symptomatic and asymptomatic groups based on comfortable wearing time (CWT) and CLDEQ-8 score (<8 hours CWT and ≥14 CLDEQ-8 stratified the symptom groups).

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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.

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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.

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Purpose: We developed a mathematical model predicting dynamic changes in fluorescent intensity during tear film thinning in either dilute or quenching regimes and we model concomitant changes in tear film osmolarity.

Methods: We solved a mathematical model for the thickness, osmolarity, fluorescein concentration, and fluorescent intensity as a function of time, assuming a flat and spatially uniform tear film.

Results: The tear film thins to a steady-state value that depends on the relative importance of the rates of evaporation and osmotic supply, and the resulting increase of osmolarity and fluorescein concentrations are calculated.

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This report characterizes the neurobiology of the ocular surface and highlights relevant mechanisms that may underpin contact lens-related discomfort. While there is limited evidence for the mechanisms involved in contact lens-related discomfort, neurobiological mechanisms in dry eye disease, the inflammatory pathway, the effect of hyperosmolarity on ocular surface nociceptors, and subsequent sensory processing of ocular pain and discomfort have been at least partly elucidated and are presented herein to provide insight in this new arena. The stimulus to the ocular surface from a contact lens is likely to be complex and multifactorial, including components of osmolarity, solution effects, desiccation, thermal effects, inflammation, friction, and mechanical stimulation.

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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 two visits, one with an ocular surface air stimulus (AS) and one without (NS).

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