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Louis Tong, Lei Zhou, Roger W Beuerman, Susan Simonyi, David A Hollander, Michael E Stern; Effects of punctal occlusion on tear protein levels in dry eye patients. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Proteins play an important role in the ocular surface microenvironment and tear protein dysregulation has been observed in dry eye disease. We previously demonstrated that punctal occlusion commonly used to improve dry eye symptoms does not significantly alter cytokine levels, and baseline Schirmer’s score was the most important factor associated with tear cytokine levels. Here, we explored global tear protein levels in dry eye patients at baseline and after occlusion.
In this prospective, longitudinal, single-center study, 30 patients with moderate dry eye had non-absorbable punctal plugs inserted bilaterally in lower puncta. In the more severe eye, global dry eye symptoms scores, fluorescein corneal staining, Schirmer’s I test, tear film break-up time (TBUT) and safety were assessed at baseline, week 1 and week 3. Proteins in tear samples collected using Schirmer’s test strips were quantified and compared relative to preocclusion baseline levels using isobaric tagging for relative and absolute quantification (iTRAQ) and nano-liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS).
Twenty nine patients (mean age 49.7 years) completed the study; mean (SD) baseline global irritation symptoms score 53.8 (26.5), Schirmer’s score 5.1 (2.8) mm, and TBUT 2.2 (0.6) seconds. Levels of more than 400 tear proteins were analyzed from 23 patients with sufficient tear samples. Hierarchical clustering analysis based on 94 proteins with <20% missing values revealed two distinct tear protein clusters: cluster 1 characterized by inflammatory-related proteins (eg, S100A8, S100A9); cluster 2 characterized by lacrimal supportive proteins (eg, lysozyme, lacritin, prolactin-inducible protein). After 1 week occlusion, 5 patients showed improvement with decreased levels of inflammatory-related proteins and increased levels of lacrimal supportive proteins, whereas after 3 weeks occlusion, 10 patients had a positive response while 13 patients were unresponsive. Logistic regression analysis revealed that these 10 patients had significantly lower baseline Schirmer’s scores compared to the 13 non-responding patients (mean [SD]: 4.3 [1.3] vs 6.8 [2.6]; P=0.006).
Low Schirmer’s score at baseline is associated with a higher inflammatory tear protein profile. Patients with dry eye who do not response to punctal occlusion may require other treatments, such as anti-inflammatory agents, for management of their disease.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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