Maximal tear secretion evoked by controlled stimulation of corneal sensory nerves in healthy individuals and dry eye subjects

Abstract

Purpose: To measure, the tear flow changes evoked in healthy subjects and dry eye disease (DED) patients by controlled sensory stimulation of the eye surface with i-Onion™, a new stimulation device. Methods: Sensory corneal nerves were stimulated with an instrument (i-Onion™) that ejects puffs of CO2 gas (99.9%) at 200 ml·min-1 for 3s, delivered 5 mm from the cornea. Using Schirmer test strips, tear volumes were measured over 3 min in the cornea of one eye before (basal tear volume -BTV) and in the other eye after stimulation of the sensory nerves with CO2 (stimulated tear volume -STV). These measurements were obtained from a control group of adults of either sex (17 students aged 20-30 and 29 subjects without signs of dry eye aged 25-61), a cohort of DED patients (aged 34-75) that included 12 asymptomatic, suspected DED subjects (Schirmer <7 mm and/or TBUT <10s), and 30 Sjögren's syndrome (SS) patients. Results: CO2 stimulation significantly increased the tear volume (BTV = 14.6 ± 1.0 mm, STV = 19.0 ± 1.1 mm: n = 46) in 78% of control subjects, reflecting a mean tear reserve volume (TRV = STV-BTV) of 4.4 ± 0.8 mm. Individual differences were wide, and while no increase in reflex tearing was evoked in 30% of subjects with a BTV >10 mm, the remaining 70% responded vigorously to stimulation, even those with a BTV >18 mm. Asymptomatic DED subjects displayed weaker responses to CO2 stimulation, with lower STVs. Both the BTV and STV of SS patients were low, significantly below those of the healthy controls. Conclusions: Measuring the rise in reflex tearing volume evoked by controlled corneal stimulation provides objective information about the tear glands' secretory capacity in health and disease.