Effects of punctal occlusion on global tear proteins in patients with dry eye

Abstract Purpose To investigate effects of punctal occlusion on global tear protein levels in patients with dry eye. Methods In this prospective, longitudinal, single-center study, nonabsorbable punctal plugs were inserted bilaterally into the lower punctum of 30 patients with moderate dry eye. Dry eye symptoms, fluorescein corneal staining, Schirmer I test, tear film break-up time, and safety were assessed in the more severely affected eye. Tear proteins at weeks 1 and 3 were quantified by iTRAQ relative to baseline preocclusion levels. Results Of 29 patients who completed the study, 23 (mean age 49.8 years) had sufficient tear samples for analysis. After 3 weeks, punctal occlusion significantly upregulated tear proteins, including glutathione synthase (mean of 1.6-fold, P = 0.01) and interleukin-1 receptor antagonist (1.7-fold, P = 0.032) and downregulated cholinergic receptor (neuronal) alpha-7 (0.79-fold, P = 0.039) and lymphocyte cytosolic protein-1 (0.66-fold, P = 0.012). Clustering analysis of global tear proteins revealed two clear profile changes; the first group of patients (cluster 1, n = 10) had a reduction in the inflammatory proteins (e.g., S100A8) and rise in lacrimal proteins supporting the ocular surface (e.g., lysozyme), whereas the second group (cluster 2, n = 13) had an increase in inflammatory proteins and a decrease in lacrimal proteins. Logistic regression analysis revealed that cluster 1 patients had significantly ( P = 0.006) lower Schirmer scores at baseline (mean [standard deviation]: 4.3 [4.3] mm) than cluster 2 (6.8 [2.6] mm). Conclusions Punctal plugs produced a beneficial pattern of tear protein change in patients with relatively low Schirmer scores within 3 weeks of punctal occlusion.