Human Tear Serotonin Levels Correlate with Symptoms and Signs of Dry Eye

Purpose Serotonin, a neurotransmitter known to be involved in nociceptor sensitization, is present in human tears. The purpose of this study was to correlate tear serotonin levels, as a marker of nociceptor sensitization, to facets of dry eye (DE), including symptoms and signs. Design Cross-sectional study. Participants A total of 62 patients with normal eyelid and corneal anatomy were prospectively recruited from a Veterans Administration Ophthalmology Clinic over 11 months. Methods Dry eye symptoms (Ocular Surface Disease Index [OSDI]), signs (tear break-up time [TBUT], corneal staining, and Schirmer's score), and clinical descriptors of neuropathic ocular pain (NOP) (sensitivity to light or sensitivity to wind) were assessed. For tear analysis, each patient's tears were collected after instilling 50 μl of sterile saline to the lower cul-de-sac of each eye and using capillary action microcaps to collect the ocular wash. Tear serotonin levels were measured using enzyme-linked immunosorbent assay. Main Outcome Measures Correlations between tear serotonin concentrations and DE symptoms and signs. Results The mean age of the population was 61±14 years, and 84% (n = 52) of the patients were male. Serotonin concentrations negatively correlated with Schirmer's scores (r = -0.28; P = 0.02) but did not correlate with other DE parameters, such as OSDI scores, sensitivity to light or wind, TBUT, and staining. According to our hypothesis, we divided patients into groups based on both DE symptoms and aqueous tear production; serotonin concentrations were significantly higher in DE group 1 (OSDI ≥6 and Schirmer's <8) compared with both DE group 2 (OSDI ≥6 and Schirmer's ≥8) and controls (OSDI <6 and Schirmer's ≥8). Patients in DE group 2 more frequently reported sensitivity to light (64%) and wind (67%) compared with DE group 1 (40% and 60%, respectively) and controls (8% and 17%, respectively). Conclusions Patients with DE symptoms and aqueous tear deficiency had higher tear serotonin levels compared with those with DE symptoms but normal tear production and those without DE symptoms.