April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
A metabolome-wide study of dry eye disease
Author Affiliations & Notes
  • Jelle Vehof
    Twin Research & Genetic Epidemiology, St. Thomas' Hospital, King's College London, London, United Kingdom
    Ophthalmology, University Medical Center Groningen, Groningen, Netherlands
  • Pirro G Hysi
    Twin Research & Genetic Epidemiology, St. Thomas' Hospital, King's College London, London, United Kingdom
  • Christopher J Hammond
    Twin Research & Genetic Epidemiology, St. Thomas' Hospital, King's College London, London, United Kingdom
    Ophthalmology, St. St. Thomas' Hospital, King's College London, London, United Kingdom
  • Footnotes
    Commercial Relationships Jelle Vehof, None; Pirro Hysi, None; Christopher Hammond, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3054. doi:
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      Jelle Vehof, Pirro G Hysi, Christopher J Hammond; A metabolome-wide study of dry eye disease. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3054.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: The study of metabolomics, profiling of small molecules of biological samples, is an emerging approach for biological research. Metabolic traits as functional intermediates may act as biomarkers and help identify functional pathways in some cases better than other existing methodologies because they are a measurable direct product of genes and environmental factors. The aim of the study was to explore the relationship between dry eye disease and serum metabolites, given the known associations of dry eye with several metabolic dysfunctions.

Methods: 1622 population-representative female volunteers, mean age 63 years (range 23-87), from the TwinsUK Adult Twin Registry underwent non-targeted metabolomic analysis of plasma samples, using gas- and liquid-chromatography in combination with mass spectrometry (Metabolon Inc, Durham, NC), to quantitatively measure 390 metabolites in plasma samples. Dry eye was assigned by questionnaires in 2011 and 2013. A dry eye diagnosis using the SQ-DES, and the incidence of a dry eye diagnosis were used as outcome variables. Analysis was assessed in regression models that included age and BMI of the subjects, corrected to take into account the paired nature of the data.

Results: Prevalence of dry eye measured by SQ-DES was 16.7%. The incidence of dry eye between 2011 and 2013 was 6.8%. A strong and metabolome-wide significant association with dry eye diagnosis was found with the metabolite epiandrosterone (p=0.00021). Epiandrosterone (p=0.00001) and two other steroids that are also involved in androgen metabolism (4-androsten-3beta,17beta-diol disulfate 2 (p=0.0004), androsterone sulfate (p=0.00005)) were particularly strongly associated with dryness symptoms on the SQ-DES. Epiandrosterone was also associated with incidence of dry eye diagnosis (p=0.0026). Dehydroepiandosterone sulfate (DHEAS) seemed also associated with a dry eye diagnosis (p=0.005) but this did not reach metabolome-wide significance. Animal studies have shown androgens have a role in lacrimal and meibomian gland function.

Conclusions: A hypothesis-free metabolomic approach has suggested androgen metabolism may be an important pathway in development of dry eye disease in females. In particular, epiandrosterone sulfate may be a biomarker of dry eye, as it was associated with prevalence and incidence of disease. Further research using genome-metabolome-wide Mendelian randomization will be performed to examine genetic associations with these metabolites.

Keywords: 486 cornea: tears/tear film/dry eye • 592 metabolism • 464 clinical (human) or epidemiologic studies: risk factor assessment  

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