Provocation of the ocular surface to investigate the evaporative pathophysiology of dry eye disease

Abstract

Purpose

To investigate whether standard clinical measures of tear film stability, meniscus height and symptomology reflect changes in evaporation rate induced by ocular surface provocations.

Methods

Forty participants (23.8 ± 4.5 years, 53 % female) with healthy to mild dry eyes underwent two tear film provocations in random sequence on separate occasions: playing a tablet computer high concentration game (http://slither.io/) for 30 min; and receiving treatment with humidity goggles for 10 min followed by liposomal spray application. Measures at baseline and 30 min later were: Symptom Assessment iN Dry Eye (SANDE) questionnaire, tear film lipid layer thickness (LLT), non-invasive tear film break-up time (NIBUT), tear meniscus height (TMH), dynamic tear film lipid layer pattern (DLP) and tear film evaporation (TFE).

Results

There were no differences in the baseline measurements before each provocation (p > 0.05). Dry eye symptoms significantly worsened with concentration task (p < 0.001) and improved with treatment (p < 0.001). DLP and LLT significantly increased with treatment (p < 0.05), but was unaffected with the concentration task (p > 0.05). NIBUT declined with the concentration task (p = 0.015), but was not enhanced with treatment (p = 0.142). TMH increased after treatment (p = 0.001) and decreased with the concentration task (p = 0.006). While evaporation decreased with the concentration task (p < 0.001), treatment had no effect (p = 0.333). LLT was associated with evaporation (p = 0.036) and additionally with symptom severity (p = 0.002) and tear volume (p = 0.017).

Conclusions

Sub-classifying dry eye based on an ‘evaporative’ component to inform treatment seems over-simplistic. However objective TMH, NIBUT and LLT seem to be the key clinical metrics that drive ocular comfort.

Introduction

It has recently been clarified that dry eye disease subtypes of aqueous deficient and evaporative pathophysiological components are believed to exist on a continuum rather than separate entities [1]. This subclassification is a key element of the consensus of dry eye treatment [2]. However, this is somewhat confounded by the often reported weak or lack of correlation between signs investigated by commonly used diagnostic tests and symptoms of dry eye and between the tests themselves [[3], [4], [5], [6]].

Measures of evaporation have been associated with dry eye symptoms, where increased rates are associated with ocular dryness and discomfort [7,8]; and with measures of tear film stability such as non-invasive tear film break-up time (NIBUT) [9]. Indeed, evaporation of the tear film is considered the major contributor to tear film thinning and break-up, which results in an increased and variable tear film osmolarity as observed in dry eye patients [[10], [11], [12]]. Kimball and colleagues (2010) found significantly increased tear film thinning rate in patients in free air conditions compared to the same patient wearing air-tight goggles, suggesting evaporation as the main cause of tear film thinning [11].

The principal function of the lipid layer is purported to stabilise and prevent evaporation of the tear film [9,13,14]. The complete loss of the tear film lipid layer is strongly linked to increased evaporation rate – indeed, a four-fold increase in evaporation rate has been shown in patients with absent or non-confluent lipid layers [9]. Using automated image analysis of slit lamp interference pattern videos to estimate lipid layer thickness (LLT), Hwang and colleagues (2017) observed thinner LLT in patients with hypo-secretory meibomian gland dysfunction (MGD) compared to patients with dry eye without MGD and normal patients; and thicker LLT was observed in patients with hyper-secretory MGD compared to patients with dry eye without MGD [15] – these studies suggests abnormal composition and/or absence of the lipid layer is a more important factor in evaporation rate than LLT. More recently, Finis et al. (2013) reported significant positive correlation between LLT and the number of expressible meibomian glands, suggesting those with reduced LLT have fewer expressing meibomian glands and are more likely to have MGD, a major cause of evaporative dry eye [16]. In turn, measures of LLT has been shown by Blackie et al. (2009) to better correlate with symptoms of dry eye compared to traditional dry eye tests, with approximately 75 % of participants with LLT less than 60 nm reporting severe symptoms; and 75 % of participants with LLT greater than 75 nm being asymptomatic [17].

Previous cross-sectional studies show an association between evaporation, lipid thickness and dry eye symptoms. However, measurement conditions need to be carefully controlled as evaporation rates are influenced by time of day, ambient temperature and humidity [18,19]. Based on these findings, evaporation rates are predicted to increase in conditions where LLT and/or NIBUT is reduced, and vice-versa. This study therefore aimed to use ocular surface provocations to investigate whether standard clinical measures of tear film stability, meniscus height and symptomology reflect changes in evaporation rate induced by ocular surface provocations.