of the ocular surface. Tears hydrate and lubricate the mucous membranes constituting the ocular surface, supply nourishment to the avascular corneal epithelium, and provide a smooth optical surface essential for visual acuity. The drainage of tears via the lacrimal puncta fl ushes contaminants and irritants out of the eye, thereby functioning as a fi rst line of defense for the anterior eye against invading pathogens ( 1, 2 ). The typical volume of tears in normal eyes ranges from 3.4 to 10.7 l per eye ( 3 ). Despite its small volume, tears represent a biological fl uid of immense complexities with a wide array of proteins/peptides, electrolytes, lipids, and small molecule metabolites contributed by distinct sources ( 1 ). The precise balance of these various metabolites is crucial in ensuring proper physiological function and maintaining biophysical integrity of the precorneal tear fi lm. Perturbations in this delicate equilibrium may be manifested in various ocular conditions such as dry eye syndrome (DES) and blepharitis ( 1,4,5 ).Recent decades have witnessed tremendous progress in the systematic profi ling of proteins as well as small molecule metabolites present in tears ( 1, 6-9 ). Furthermore, with technological advancements in MS and nuclear magnetic Abstract The tear fi lm covers the anterior eye and the precise balance of its various constituting components is critical for maintaining ocular health. The composition of the tear fi lm amphiphilic lipid sublayer, in particular, has largely remained a matter of contention due to the limiting concentrations of these lipid amphiphiles in tears that render their detection and accurate quantitation tedious. Using systematic and sensitive lipidomic approaches, we validated dif ferent tear collection techniques and report the most comprehensive human tear lipidome to date; comprising more than 600 lipid species from 17 major lipid classes. The tear fl uid covers the anterior surface of the cornea and serves critical functions in maintaining the homeostasis

Aim The main treatment for meibomian gland dysfunction (MGD), a major cause of dry eye, is eyelid warming. Lack of compliance is the main reason for treatment failure. This has led to the development of eyelid-warming devices that are safe, effective and convenient. To obtain robust evidence demonstrating their efficacy, the authors conducted a 3-arm randomized clinical study.MethodsThe authors conducted a 3-month assessor-blinded, randomized, controlled trial of patients from the Singapore National Eye Centre experiencing at least one of eight dry eye symptoms ‘often’ or ‘all the time’. Patients who wore contact lenses, had an active infection or known diagnosis of thyroid dysfunction and rheumatoid arthritis were excluded from the study. MGD participants were randomly assigned to warm towel (n = 25), EyeGiene® (Eyedetec Medical Inc., Danville, CA, USA) (n = 25) and Blephasteam® (Spectrum Thea Pharmaceuticals LTD, Macclesfield, UK) (n = 25) treatments. The primary efficacy and safety outcomes included the proportions of participants with improved symptoms and changes in best corrected visual acuity (BCVA), respectively. Other outcomes included tear break up time (TBUT), Schirmer test, corneal fluorescein dye staining and number of visibly occluded meibomian gland (MG) orifices.ResultsThe study population was 53.5 ± 11.1 years old and predominantly Chinese. For severity of symptom after 3 months of treatment, 78.3% Blephasteam® participants reported improvement compared to 45.5% warm towel participants (p = 0.023). The corresponding proportions for improvement in the frequency of symptoms were 82.6% and 50.0%, respectively (p = 0.020). The proportions of improvement of symptoms in EyeGiene® patients were not significantly different from warm towel intervention. At 1 month of treatment, the crude odds ratio of improvement of severity of irritation for Blephasteam® compared to control was 3.0 (95% CI 0.88–10.18). However, the odds ratio adjusted by age was 5.67 (1.30–24.66). The lid-warming treatments did not significantly change the TBUT, Schirmer test results or number of visibly occluded MGs in the study period. All treatment modalities did not worsen BCVA after 3 months.ConclusionBlephasteam® is more effective than warm towel for MGD treatment, with warm towel and EyeGiene® being comparable effective. Older age might predict for treatment efficacy. All studied therapies were safe for visual acuity (VA) for 3 months of treatment.Electronic supplementary materialThe online version of this article (doi:10.1007/s40123-014-0025-8) contains supplementary material, which is available to authorized users.

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Dry eye syndrome (DES) represents one of the most frequently encountered ocular morbidities, which can affect up to approximately one-third of the population worldwide depending on the criteria and defi nition used in the various studies conducted across the continents ( 1 ). Recent studies in China and Japan have, however, revealed a much higher prevalence than the average value reported globally ( 2, 3 ), indicating that Asian populations might have a greater predisposition to the disease. Despite its prevalence, there is presently no universal consensus on the diagnostic guidelines for the disease ( 4 ). Current clinical tests lack reproducibility and are not suffi ciently predictive of symptomatology to facilitate effective disease diagnosis and prognosis ( 5 ).The importance of tear lipids in maintaining ocular surface homeostasis and visual acuity due to their critical roles in constituting the outermost layer of the tear fi lm has been extensively reported and discussed ( 5-8 ). In particular, with the recent development in mass spectrometric technology, lipidomics has been transformed into a principal tool in biomedical research to decipher fi ne changes in lipid metabolism in various diseases including the DES ( 9, 10 ). Elucidating single tear components that are specifi cally altered with disease therefore marks the future of dry eye research by revealing novel molecular targets for improving current diagnostic and therapeutic platforms. Compared with tears, meibum-derived lipid markers indicative of DES Abstract As current diagnostic markers for dry eye syndrome (DES) are lacking in both sensitivity and specifi city, a pressing concern exists to develop activity markers that closely align with the principal axes of disease progression. In this study, a comprehensive lipidomic platform designated for analysis of the human tear lipidome was employed to characterize changes in tear lipid compositions from a cohort of 93 subjects of different clinical subgroups classifi ed based on the presence of dry eye symptoms and signs. Positive correlations were observed between the tear levels of cholesteryl sulfates and glycosphingolipids with physiological secretion of tears, which indicated the possible lacrimal (instead of meibomian) origin of these lipids. Notably, we found wax esters of low molecular masses and those containing saturated fatty acyl moieties were specifi cally reduced with disease and signifi cantly correlated with various DES clinical parameters such as ocular surface disease index, tear breakup time, and Schirmer's I test (i.e., both symptoms and signs). These structure-specifi c changes in tear components with DES could potentially serve as unifying indicators of disease symptoms and signs. In addition, the structurally-specifi c aberrations in tear lipids reported here were found in patients with or without aqueous deficiency, suggesting a common pathology for both DES subtypes.