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Purpose : Smartphone use is now ubiquitous and is associated with a range of ocular and visual symptoms. However, little is known about the etiology of the symptoms which accompany smartphone use and the relative contribution of accommodation/vergence versus that of the ocular surface and of blinking. This study examined the effects of 60 min reading on a smartphone on ocular symptoms, binocular vision, tear function, blinking and working distance. Methods : Twelve young adults (18-23 years; 9F:3M) with normal vision and without dry eye, or major accommodative/binocular vision disorders, completed this pilot study. Participants read a novel on a smartphone for 60 min and the following were measured before and after the reading task: eye strain and ocular surface symptoms, non-invasive tear break-up time (NIBUT), lipid layer appearance, tear meniscus height, horizontal fixation disparity, binocular accommodative facility. Spontaneous blink rate and amplitude were counted every 10 min, and viewing distance was measured at the same timepoints. Pre- and post-task comparisons were made using Wilcoxon signed-rank test and changes during the task were assessed using Friedman test. Associations were examined using Spearman's correlation. Results : Eyestrain symptoms and ocular surface symptoms increased after smartphone use, specifically comfort, tiredness and sleepiness items ( p ≤ .02). Binocular accommodative facility decreased from a median of 11.3 (IQR 6.6) cycles/min pre-task to 7.8 (2.5) cycles/min post-task ( p = .01), but there was no significant change in fixation disparity or working distance. There were no changes in NIBUT, lipid layer or tear meniscus height. Number of incomplete blinks per minute increased from a median of 6 blinks at 1 min to 15 at 60 min ( p = .0049). Total blink rate (complete plus incomplete blinks) gradually increased over time, but this trend was not significant ( p = .08). A greater increase in incomplete blinks over 60 min of reading was associated with worsening of the overall ocular surface symptoms score (ρ = -0.65, p = .02) and of the tiredness item (ρ = 0.70, p = .01). Conclusions : Extended use of smartphones appears to have important implications for ocular surface health and binocular function.

Sex steroids impact regulation of the ocular surface tissues and thus influence dry eye. Most tissues in the human body synthesise and metabolise active sex steroids at levels required by the tissue. This is likely to also be the case for humans in ocular surface tissues. This study investigated the presence and quantities of selected sex steroids, in addition to sex steroid precursors and metabolites, in human tears. Detection of sex steroids in tears is challenging due to trace level analyte concentrations and low volumes of available tears. Immunoassays have previously been employed to assess sex steroids in tears, however, this approach only allows a single analyte to be measured and can overestimate concentrations. This study evaluated ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) and tandem mass spectrometry (MS/MS) methods for the concurrent detection and estimation of fourteen sex steroid and metabolite compounds in human tears. Basal tears were collected and pooled from 5 healthy pre-menopausal women (total 100 μL). Following protein precipitation and centrifuging, extract volumes equivalent to 14 μL of pooled tears were analysed. A Thermo Scientific Q Exactive™ Plus MS was used to compare novel high-resolution MS atmospheric pressure chemical ionization (APCI) and electrospray ionisation (ESI) methods for detection of fourteen target sex steroids, including dehydroepiandrosterone-sulphate (DHEAS), testosterone, oestradiol and their metabolites, using standards and pooled tears. The MS was programmed to switch between positive and negative polarity ionization modes at designated times through the UPLC run, in order to detect each analyte at optimal sensitivity. Analytes were analysed using APCI in standard mixtures at concentrations of 0.1, 0.3, 1, 3, 10, 30, 100 and 1000 pg/mL, per component, to determine the limits of detection (LOD) and quantification. Both parallel reaction monitoring (PRM) MS/MS and selected ion monitoring (SIM) MS, were evaluated by plotting narrow range mass-to-charge ratio (m/z) chromatograms for each analyte. An APCI UPLC-MS method to simultaneously measure 14 sex steroids using standards was successfully developed following comparative evaluation of all available LC-MS techniques. Preliminary experiments found APCI to be more sensitive than ESI using standards. Narrow m/z range SIM MS resulted in better sensitivity, in tear samples, than PRM. One sex steroid and two androgen metabolites were detected, with the developed APCI UPLC-MS method, and their concentrations estimated in human tears that had been extracted with a protein crash. Progesterone, androsterone-glucuronide (ADT-G) and 3αDiol-G were successfully detected in the tear extract and their concentrations in the pooled tear sample were estimated (with 95% confidence intervals) to be 0.10 ± 0.03 pg/μL, 30.9 ± 18.3 pg/μL and 9.8 ± 4.3 pg/μL respectively. The concentrations of the remaining 11 sex steroids in the tear sample were below the LODs of the method. This work shows that high mass resolution UPLC-MS can detect certain sex steroids and metabolites in tears, but that sensitivity of the technique and the low available tear volumes limit its application to a broader range of sex steroids. The investigation of sex steroids in tears and ocular surface tissue will aid understanding of the influence of sex steroids on ocular surface tissues facilitating better targeted treatment for dry eye., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: A review of ocular surface and meta-analysis of tear stability (tear break up time, TBUT) and tear secretion (Schirmer test) values in healthy children was conducted., Methods: Articles published between 1996 and 2017 indexed on MEDLINE, PubMed, Embase, Scopus and Google Scholar were retrieved using defined search terms. Statistical analysis (including sensitivity analysis and meta-regression) was performed., Results: 23 studies were summarised (5,291 participants; neonates (0-29 days), infants (1 month - 1 year) or children (1-18 years) and a meta-analysis conducted using 15 eligible studies (1,077 participants). The combined mean TBUT in children was 14.64 seconds (s) (95% CI, 11.64, 17.64) and 21.76 s (95% CI, 20.43, 23.09) for sodium fluorescein TBUT and non-invasive TBUT respectively (NIBUT). The combined mean NIBUT was 32.5 s (95% CI, 31.78-33.22) in neonates. The combined mean Schirmer I with and without anesthesia were 16.26 mm/5 min (95% CI, 13.17, 19.36) and 29.30 mm/5 min (95% CI, 27.65, 30.96) in children and 9.36 mm/5 min (95% CI, 6.54, 12.18) and 17.63 mm/5 min (95% CI, 12.03, 23.23) in neonates. Meta-regression showed a significantly lower TBUT in children from studies conducted in Asia (p = 0.004)., Conclusion: There is paucity of data on ocular surface variables in healthy children, making it difficult to draw valid comparisons with adult values., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Sex hormones are associated with the physiology and pathophysiology of almost all organs in the body, as well as most diseases. Interest in the associations between sex hormones and ocular tissues has increased in recent years. Androgens may have a positive effect on dry eye, whereas the effects of oestrogen on ocular conditions remain unclear. Intracrinology, the local synthesis and metabolism of hormones that is unique to humans, is of relevance to the eye and may help to explain why studies of the relationship between oestrogens and dry eye signs and symptoms are inconclusive. Knowledge of the pathways of hormone formation and metabolism is crucial to understanding the pathogenesis of ocular disease including dry eye. This review examines the mechanisms of steroidal sex hormone biosynthesis and reviews the significance of locally produced sex hormones, with a focus on ocular surface tissues. Much of the current literature is based on animal studies, which may not be transferable to humans due to the absence of intracrine production in animals. A large proportion of the human studies investigate systemic hormone levels rather than local levels. There is subsequently a need for additional studies to provide a better understanding of the local production of sex hormones within the human eye and ocular surface and to clarify the relationships between ocular levels of sex hormones and conditions including dry eye., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aims: Sex hormones could provide a future treatment avenue for dry eye post menopause. However, there are few well-controlled studies. This study investigates the impact of testosterone and oestrogen on dry eye symptoms and signs in postmenopausal women., Methods: A randomised double-blind placebo-controlled pilot study was conducted involving 40 women with dry eye (age 63.9±5.1 years, 13.2±6.3 years post menopause). Ten women were assigned to each of four treatment groups: transdermal testosterone, oestradiol, testosterone/oestradiol combination and placebo. Assessment at baseline and after 8 weeks: ocular symptoms, tear osmolarity, tear stability, tear secretion, meibomian gland assessment, corneal and conjunctival sensitivity, serum concentrations of 17β-oestradiol, 3-α-androstanediol-glucuronide and dehydroepiandrosterone sulfate. Differences from placebo were examined using one-way analysis of variance and Dunnett's t-test. Within-group analyses included paired t-tests and Spearman correlation., Results: Dryness intensity after 8 weeks was significantly worse in the oestrogen group compared with placebo (p=0.04). No significant changes in other symptoms, tear function, meibomian gland function, lid morphology, corneal or conjunctival sensitivity were observed in any of the groups when compared with the change in placebo after 8 weeks. Within-group analyses showed increased tear secretion in the testosterone/oestradiol combination group (p=0.03) and a strong association between increased serum androgen and improved tear stability in the testosterone group (ρ=0.83,p=0.01)., Conclusions: Oestrogen supplementation may worsen ocular symptoms in postmenopausal women with dry eye, whereas no impact of testosterone therapy on symptoms was apparent. The positive effects of oestrogen and testosterone on tear function require confirmation in a larger study, with sample size calculated from the data generated herein. Placebo control is essential in studies of dry eye therapies., Trial Registration Number: ACTRN12612000281897., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To determine tear neuropeptide levels in contact lens wearers and non-wearers, and to examine relationships with indices of corneal innervation, tear function, and ocular discomfort., Methods: A cross-sectional, single-visit, investigator-masked pilot study. Assessments included Ocular Comfort Index (OCI), central and mid-peripheral corneal nerve density and morphology (HRT-Rostock), corneal sensitivity (Cochet-Bonnet aesthesiometer), tear Substance P and calcitonin gene-related peptide (CGRP) concentration (ELISA), in situ tear osmolarity (TearLab), tear secretion (Phenol Red Thread), and noninvasive tear break-up time (NITBUT; Keeler Tearscope). Groups were compared using independent t-test or Mann-Whitney U test, and regional differences assessed using paired t-tests. Associations were analyzed using Pearson or Spearman correlation. Significance was determined at P < .05., Results: Twenty contact lens wearers (7M:13F, 32 ± 5 years) and 20 non-wearers (7M:13F, 31 ± 5 years) completed the study. OCI score was numerically higher in lens wearers (32.27 ± 5.33) than non-wearers (27.66 ± 9.94). Tear osmolarity was higher [298.0 (IQR 291.0-309.8) vs. 288.5 (282.3-298.3) mOsmol/L; P = .01] whereas NITBUT was lower (9.8 ± 3.4 vs. 13.8 ± 5.6 s; P = .01) in lens wearers compared with non-wearers. Tear neuropeptide concentrations were not different between groups [Substance P 4.29 ng/ml (IQR 1.57-6.05), CGRP 14.89 ng/ml (5.08-59.26)], and there were no differences in nerve morphology or ocular surface sensitivity. Higher nerve density, interconnections, and tortuosity were observed in the central cornea than mid-peripherally (P < .05). OCI score was moderately associated with nerve tortuosity (r = 0.42, P = .01). CGRP was associated with central nerve density (ρ = 0.38, P = .02), as was tear secretion (r = -0.37, P = .02). Nerve interconnections were strongly associated with corneal sensitivity (ρ = 0.64, P < .001)., Conclusions: Relationships were demonstrated between nerve density, tear CGRP, and corneal sensitivity. Markers of corneal neurobiology and sensory function do not appear to be altered in contact lens wear despite worse tear function (osmolarity and stability) in lens wearers. This suggests that mechanisms other than overt changes in corneal innervation regulate tear function during lens wear. The relationship between nerve tortuosity and ocular discomfort requires elucidation.

Purpose: This study investigated changes in selected tear cytokine concentrations (IL-1β, IL-1Ra, IL-6, IL-10, IL-12 (p70), and TNF-α) after a 1-week washout from soft contact lens wear (CLW), and the repeatability of cytokine measurements using custom multiplex assays., Methods: A total of 10 subjects completed this 6-visit (immediately following contact lens removal, and after 1, 2, 3, 4, and 7 [±1] days without CLW) pilot study. Approximately 20 to 30 μL of pooled basal tears were collected from both eyes at each visit. Two custom multiplex assays were used by two operators to quantify the concentration of tear cytokines. Tear samples from subjects 1 to 6 were analyzed using the first kit by operator 1. Tear samples from subject 7 to 10 plus additional tear samples from subjects 1 to 5, which were used to determine the between-kit per operator repeatability, were analyzed using the second kit by operator 2. Linear mixed models were used to determine changes in tear cytokine concentrations over time. Between-kit per operator and within-kit per operator repeatabilities were assessed using the Bland and Altman analysis., Results: There were no significant changes in tear cytokine concentrations over a 1-week washout of CLW. More than 99% of the tear samples had detectable levels of cytokines using custom multiplex assays. Within-kit per operator repeatability was good, but between-kit per operator repeatability was poor; likely due to protein degradation, differences in operator experience, and operating procedures., Conclusion: A washout period may not be necessary when evaluating changes in tear cytokines with new contact lenses or lens care products. A well-trained operator using standardized operating procedures can produce repeatable measurements using custom multiplex assays.

The greater prevalence of dry eye in women compared to men suggests that sex hormones may have a role in this condition. This review aims to present evidence for how sex hormones may affect the ocular structures involved in the production, regulation and maintenance of the normal tear film. It is hypothesised that hormone changes alter the homeostasis of the ocular surface and contribute to dry eye. Androgens impact on the structure and function of the meibomian and lacrimal glands and therefore androgen deficiency is, at least in part, associated with the aetiology of dry eye. In contrast, reports of the effects of oestrogen and progesterone on these ocular structures and on the conjunctiva are contradictory and the mechanisms of action of these female-specific sex hormones in the eye are not well understood. The uncertainty of the effects of oestrogen and progesterone on dry eye symptoms is reflected in the controversial relationship between hormone replacement therapy and the signs and symptoms of dry eye. Current understanding of sex hormone influences on the immune system suggests that oestrogen may modulate a cascade of inflammatory events, which underlie dry eye., (© 2014 The Authors. Clinical and Experimental Optometry © 2014 Optometrists Association Australia.)