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      Human Meibum and Tear Film Derived (O-Acyl)-Omega-Hydroxy Fatty Acids as Biomarkers of Tear Film Dynamics in Meibomian Gland Dysfunction and Dry Eye Disease

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          Abstract

          Purpose

          To investigate the association between precorneal tear film (PCTF)– and meibum-derived (O-Acyl)-omega-hydroxy fatty acids (OAHFAs) and PCTF thinning in meibomian gland health and dysfunction.

          Methods

          Of 195 eligible subjects (18–84 years, 62.6% female), 178 and 170 subjects provided both PCTF optical coherence tomography (OCT) imaging and mass spectrometry data for tears (n = 178) and meibum (n = 170). The PCTF thinning rate was measured in the right eye using an ultra-high-resolution, custom-built OCT. Tear and meibum samples from the right eye were infused into the SCIEX 5600 TripleTOF mass spectrometer in the negative ion mode. Intensities ( m/z) of preidentified OAHFAs were measured with Analyst 1.7TF and LipidView 1.3 (SCIEX). Principal component (PC) analyses and Spearman's correlations ( ρ) were performed to evaluate the association between OAHFAs and PCTF thinning rates.

          Results

          In meibum and tear samples, 76 and 78 unique OAHFAs were detected, respectively. The first PC scores of the meibum-derived OAHFAs had statistically significant correlations with PCTF thinning rates ( ρ = 0.18, P = 0.016). Among 10 OAHFAs with the highest first PC loadings, six OAHFAs had negative correlations with PCTF thinning rate (18:2/16:2, ρ = −0.19, P = 0.01; 18:2/30:1, ρ = −0.21, P = 0.008; 18:1/28:1, ρ = −0.22, P = 0.004; 18:1/30:1, ρ = −0.22, P = 0.005; 18:1/25:0, ρ = 0.22, P = 0 .006; and 18:1/26:1, ρ = −0.22, P = 0.006), while one OAHFA had a positive correlation with PCTF thinning rate (18:2/18:1, ρ = 0.48, P = 0.006). Tear film-derived OAHFAs had no association with the PCTF thinning rate.

          Conclusions

          Several human meibum-derived OAHFAs showed significant associations with PCTF thinning, suggesting that these OAHFAs could be implicated in the mechanism underlying the stabilization and thinning of the PCTF. The tear-film derived OAHFAs were, however, independent of the rate of PCTF thinning.

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          Most cited references76

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          Reliability and validity of the Ocular Surface Disease Index.

          R M Schiffman, M Christianson, G Jacobsen … (2000)
          To evaluate the validity and reliability of the Ocular Surface Disease Index (OSDI) questionnaire. Participants (109 patients with dry eye and 30 normal controls) completed the OSDI, the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25), the McMonnies Dry Eye Questionnaire, the Short Form-12 (SF-12) Health Status Questionnaire, and an ophthalmic examination including Schirmer tests, tear breakup time, and fluorescein and lissamine green staining. Factor analysis identified 3 subscales of the OSDI: vision-related function, ocular symptoms, and environmental triggers. Reliability (measured by Cronbach alpha) ranged from good to excellent for the overall instrument and each subscale, and test-retest reliability was good to excellent. The OSDI was valid, effectively discriminating between normal, mild to moderate, and severe dry eye disease as defined by both physician's assessment and a composite disease severity score. The OSDI also correlated significantly with the McMonnies questionnaire, the National Eye Institute Visual Functioning Questionnaire, the physical component summary score of the Short Form-12, patient perception of symptoms, and artificial tear usage. The OSDI is a valid and reliable instrument for measuring the severity of dry eye disease, and it possesses the necessary psychometric properties to be used as an end point in clinical trials.
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            TFOS DEWS II pathophysiology report

            Yuichi Uchino, Víctor Pérez, Norihiko Yokoi … (2017)
            The TFOS DEWS II Pathophysiology Subcommittee reviewed the mechanisms involved in the initiation and perpetuation of dry eye disease. Its central mechanism is evaporative water loss leading to hyperosmolar tissue damage. Research in human disease and in animal models has shown that this, either directly or by inducing inflammation, causes a loss of both epithelial and goblet cells. The consequent decrease in surface wettability leads to early tear film breakup and amplifies hyperosmolarity via a Vicious Circle. Pain in dry eye is caused by tear hyperosmolarity, loss of lubrication, inflammatory mediators and neurosensory factors, while visual symptoms arise from tear and ocular surface irregularity. Increased friction targets damage to the lids and ocular surface, resulting in characteristic punctate epithelial keratitis, superior limbic keratoconjunctivitis, filamentary keratitis, lid parallel conjunctival folds, and lid wiper epitheliopathy. Hybrid dry eye disease, with features of both aqueous deficiency and increased evaporation, is common and efforts should be made to determine the relative contribution of each form to the total picture. To this end, practical methods are needed to measure tear evaporation in the clinic, and similarly, methods are needed to measure osmolarity at the tissue level across the ocular surface, to better determine the severity of dry eye. Areas for future research include the role of genetic mechanisms in non-Sjögren syndrome dry eye, the targeting of the terminal duct in meibomian gland disease and the influence of gaze dynamics and the closed eye state on tear stability and ocular surface inflammation.
            Article 0 comments Cited 377 times – based on 0 reviews     Review now
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              The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland.

              Erich Knop, Nadja Knop, Thomas Millar … (2011)
              Article 0 comments Cited 299 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Invest Ophthalmol Vis Sci
                Journal ID (iso-abbrev): Invest Ophthalmol Vis Sci
                Journal ID (pmc): iovs
                Journal ID (publisher-id): IOVS
                Title: Investigative Ophthalmology & Visual Science
                Publisher: The Association for Research in Vision and Ophthalmology
                ISSN (Print): 0146-0404
                ISSN (Electronic): 1552-5783
                Publication date (Electronic): 08 July 2021
                Publication date Collection: July 2021
                Volume: 62
                Issue: 9
                Electronic Location Identifier: 13
                Affiliations
                [1 ]Department of Optometry and Vision Science, School of Optometry, University of Alabama at Birmingham, Birmingham, Alabama, United States
                [2 ]Centre for Ocular Research & Education, School of Optometry & Vision Science, University of Waterloo, Waterloo, Ontario, Canada
                [3 ]Centre for Eye and Vision Research, 17W Hong Kong Science Park, Hong Kong
                [4 ]Department of Pharmacology and Toxicology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States
                [5 ]Targeted Metabolomics and Proteomics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama, United States
                Author notes
                Correspondence: Jason J. Nichols, The University of Alabama at Birmingham 1716 University Blvd, Birmingham, AL 35233, USA; jjn@ 123456uab.edu .
                Article
                Publisher ID: IOVS-21-32817
                DOI: 10.1167/iovs.62.9.13
                PMC ID: 8267210
                PubMed ID: 34236383
                SO-VID: a3040eb4-c6ab-4192-9142-98125b40b9b6
                Copyright © Copyright 2021 The Authors
                License:

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                Date accepted : 07 June 2021
                Date received : 22 April 2021
                Page count
                Pages: 9
                Categories
                Subject: Cornea
                Subject: Cornea

                Keywords: tear film,(o-acyl)-omega-hydroxy fatty acids,lipids,meibum,precorneal tear film,tear film lipid layer,meibomian gland,dry eye disease
                Data availability:
                Keywords: tear film, (o-acyl)-omega-hydroxy fatty acids, lipids, meibum, precorneal tear film, tear film lipid layer, meibomian gland, dry eye disease

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