Differential Effects of Dry Eye Disorders on Metabolomic Profile by 1H Nuclear Magnetic Resonance Spectroscopy

We used (1)H NMR spectroscopy to analyze the metabolomic profile of reflex tears from patients with dry eye disorders (DEDs). 90 subjects were divided into 2 groups: (1) patients with DEDs (DEDG; n = 55) and (2) healthy subjects (CG; n = 35). Additionally, the DEDG was subdivided into 2 subgroups based on DED severity: mild-to-moderate and moderate (n = 22 and n = 33, resp.). Personal interviews and systematized ophthalmologic examinations were carried out. Reflex tears (20-30  μL) were collected by gently rubbing in the inferior meniscus of both eyelids with a microglass pipette and stored at -80°C until analysis. NMR spectra were acquired using a standard one-dimensional pulse sequence with water suppression. Data were processed and transferred to MATLAB for further chemometric analysis. Main differences in tear composition between DEDG and CG were found in cholesterol, N-acetylglucosamine, glutamate, creatine, amino-n-butyrate, choline, acetylcholine, arginine, phosphoethanolamine, glucose, and phenylalanine levels. This metabolic fingerprint helped also to discriminate between the three additional subgroups of DEDG. Our results suggest that tear metabolic differences between DEDG and CG identified by NMR could be useful in understanding ocular surface pathogenesis and improving biotherapy.