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Ocul Surf. 2018 Jan;16(1):84-92. doi: 10.1016/j.jtos.2017.09.003. Epub 2017 Sep 14.

Topical fluorometholone treatment and desiccating stress change inflammatory protein expression in tears.

Author information

1
SILK, Department of Ophthalmology, University of Tampere, Finland; BioMediTech Institute, Tampere, Finland. Electronic address: janika.nattinen@uta.fi.
2
SILK, Department of Ophthalmology, University of Tampere, Finland.
3
IOBA (Institute of Applied OphthalmoBiology), University of Valladolid, Valladolid, Spain; CIBER-BBN (Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine), Spain.
4
IOBA (Institute of Applied OphthalmoBiology), University of Valladolid, Valladolid, Spain; VISIÓN I+D, SL, Valladolid, Spain.
5
Allergan, Inc., Irvine, CA, USA.
6
Singapore Eye Research Institute, Singapore; Duke-NUS Medical School Ophthalmology and Visual Sciences Academic Clinical Program, Singapore; Ophthalmology, Yong Loo Lin Medical School, National University of Singapore, Singapore.
7
BioMediTech Institute, Tampere, Finland.
8
SILK, Department of Ophthalmology, University of Tampere, Finland; Tays Eye Center, Finland.
9
SILK, Department of Ophthalmology, University of Tampere, Finland; Singapore Eye Research Institute, Singapore; Duke-NUS Neuroscience, Singapore; Duke-NUS Medical School Ophthalmology and Visual Sciences Academic Clinical Program, Singapore; Ophthalmology, Yong Loo Lin Medical School, National University of Singapore, Singapore.

Abstract

PURPOSE:

It was hypothesized that tear protein biomarkers could predict the effects of topical steroid treatment and desiccating stress in patients with dry eye disease (DED). To test this concept, a randomized, double-masked, controlled clinical trial with 41 patients was conducted.

METHODS:

The patients were treated topically with either 0.1% fluorometholone (FML) or polyvinyl alcohol (PA). Tear samples were collected using 1 μl glass capillaries at recruitment into the study and after a 3-week treatment period, both before and after 2 h exposure to desiccating stress, in a controlled environment chamber. Relative quantification of tear proteins was conducted by NanoLC-MSTOF using sequential window acquisition of all theoretical mass spectra (SWATH). Ocular surface integrity (corneal and conjunctival staining and conjunctival hyperemia) was selected as the key DED-related sign and analyzed with proteomic data. Analysis of covariance (ANCOVA) and linear models were used to analyze the data with R.

RESULTS:

758 proteins were identified and relatively quantified from each tear sample. Analysis revealed 9 differentially expressed proteins between FML and PA treatments after 3 weeks and 7 after desiccating stress (P < 0.05). We also identified several differentially expressed proteins at the initial collection, which could be used to predict changes of conjunctival and corneal staining and conjunctival hyperemia after FML treatment and after desiccating stress. These proteins include complement C3 (C3) and calmodulin like 5 (CALML5), which could also differentiate the severity of DED at baseline.

CONCLUSIONS:

The identified proteins could be further used as biomarkers to identify patients most benefiting from FML treatment.

KEYWORDS:

Clinical proteomics; Corticosteroid; Desiccating stress; Dry eye disease; Tear fluid

PMID:
28918083
DOI:
10.1016/j.jtos.2017.09.003
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