Abstract
Dry eye disease (DED) is a multifactorial disorder of the ocular surface unit resulting in eye discomfort, visual disturbance, and ocular surface damage; the risk of DED increases with age in both sexes, while its incidence is higher among females caused by an overall hormonal imbalance. The role of androgens has recently investigated and these hormones were considered to have a protective function on the ocular surface. In order to correlate DED to tear steroid levels, a robust, specific, and selective method for the simultaneous quantification of cortisol (CORT), corticosterone (CCONE), 11-deoxycortisol (11-DECOL), 4-androstene-3,17-dione (ADIONE), testosterone (TESTO), 17α-hydroxyprogesterone (17-OHP), and progesterone (PROG) was developed and applied for the analysis of tear samples. The method involves a simple extraction procedure of steroids from tears collected on Schirmer strips, followed by a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis. In total, tear samples from 14 DED female patients and 13 healthy female controls were analysed and, CORT, ADIONE, and 17-OHP response levels resulted significantly decreased in dry eye patients respect to controls. The receiver operating characteristic (ROC) curve obtained by the combination of these three steroids (AUC = 0.964) demonstrated the good diagnostic power of the differential tear steroids in identifying DED. In conclusion, the present method made it possible, for the first time, to study steroid profiling directly in tear fluid.
Highlights
The ocular surface is an integrated unit comprising corneal and conjunctival epithelia, meibomian glands (MGs), main and accessory lachrymal glands, and trigeminal neurons; their dysfunction results in a scarce or unstable tear film that causes dry eye, with a higher incidence among postmenopausal women [1].Dry eye disease (DED), as a multifactorial disease, presents a complex aetiology and pathophysiology [2]
Following the criteria described above limit of detection (LOD) and lower limit of quantification (LLOQ) were established to be: 0.30 and 0.50 ng/mL for CORT; 0.1 and 0.29 ng/mL for CCONE; 0.05 and 0.10 ng/mL for 11-DECOL; 0.05 and 0.08 ng/mL for ADIONE; 0.02 and 0.08 ng/mL for TESTO; 0.05 and 0.08 ng/mL for 17-OHP
The only exception was PROG, for which LOD and LLOQ coincided with the lowest concentration Schirmer strip calibrator (0.05 ng/mL)
Summary
The ocular surface is an integrated unit comprising corneal and conjunctival epithelia, meibomian glands (MGs), main and accessory lachrymal glands, and trigeminal neurons; their dysfunction results in a scarce or unstable tear film that causes dry eye, with a higher incidence among postmenopausal women [1].Dry eye disease (DED), as a multifactorial disease, presents a complex aetiology and pathophysiology [2]. Sex hormone imbalance plays a crucial role in the pathophysiology of different ocular surface diseases including dry eye, with a different impact of oestrogens and steroids In detail, their imbalance may significantly increase the risk and modify the course of DED, since serum oestrogen levels are strongly associated with the development and progression of dry eye [4]. Their imbalance may significantly increase the risk and modify the course of DED, since serum oestrogen levels are strongly associated with the development and progression of dry eye [4] This is supported by the fact that women are more likely to experience DED during periods of substantial hormonal alteration, such as pregnancy, lactation, oral contraceptive use and after the menopause [5,6]
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