Reduced Levels of Tear Lacritin are Associated with Corneal Neuropathy in Sjögren’s Syndrome-associated Dry Eye Disease

Abstract

Purpose : Lacritin is an endogenous tear glycoprotein reported to be decreased in patients with various forms of dry eye disease. We hypothesized that reduced levels of lacritin are functionally linked to altered integrity and innervation of the ocular surface in Sjögren’s syndrome (SS) patients. The amount of total lacritin and its three major isoforms were quantified in tears of SS patients and age-matched controls. Changes in corneal innervation were assessed to examine the relationships between corneal nerve morphology and lacritin levels.

Methods : Clinical data and tear samples eluted from Schirmer strips were obtained from patients with SS (n=10) and age-matched controls (n=10). Lacritin was assessed by ELISA and Western blot with anti-lacritin antibodies. Quantification of active and inactive lacritin species was determined using densitometry. In vivo confocal microscopy was used to assess the density, length, branching, and tortuosity of sensory nerves innervating the cornea using CCMetrics. The relationships between corneal nerve morphology and total lacritin levels were assessed by Spearman correlation.

Results : Tear secretion assessed by Schirmer strips was significantly altered in SS patients compared to controls. Clinical signs of dry eye were accompanied by significant differences in total active lacritin measured by ELISA and each of its active and inactive species measured by Western blot. Corneal innervation was altered in SS patients with significant reductions noted in mean nerve fiber density and nerve fiber length. Association studies showed that reduced length and density of corneal nerves were highly correlated with reduced levels of total lacritin. Similarly, total lacritin levels were highly correlated with each of the clinical parameters used to assess dry eye. The diagnostic performance of tear lacritin was equivalent or better than standard clinical measures at differentiating SS-associated dry eye from control patients.

Conclusions : Our studies revealed profound reductions in corneal nerve fiber density and length that were highly correlated with reduced levels of active lacritin and increased levels of inactive lacritin in SS tears compared to age-matched controls. Tear lacritin levels were equivalent or better than standard clinical measures for diagnosing Sjogren’s syndrome-associated dry eye.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.