Patient enrollment and determination of ocular surface dryness

This cross-sectional, case-control clinical trial was conducted at two sites: Gangnam Severance Hospital (Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea) and Sacred Heart Hospital (College of Medicine, Hanllym University, Chuncheon, Gangwon-Do, Korea). All procedures conformed to the tenets of the Declaration of Helsinki. The study was approved by the Institutional Review Board of each hospital, and informed consent was obtained from all patients. DED was diagnosed according to the diagnostic criteria of Asia Dry Eye Society⁴³. The inclusion criteria were as follows: one or more DED-related symptoms, including tightness, foreign body sensation, irritation, red-eye, itching sensation, blurring, or pain; a Schirmer’s test I result (without anesthesia) of <5 mm in 5 minutes, a tear break-up time of <5 seconds or a typical DED pattern of superficial punctuate erosion of the conjunctiva or cornea. Patients were excluded if they had (1) a history of using eye drops within the current month, (2) infection, trauma, an ocular procedure, or other surgery within the previous 6 months, (3) severe blepharitis with meibomian gland dysfunction, (4) a blinking abnormality (e.g., Parkinson’s disease or facial nerve palsy), or (5) severe pterygium or an uncontrolled systemic disease. Pregnant or lactating patients were also excluded. Clinical tests for DED and human fluid-sampling of TF and LF were performed by an ophthalmologist (H.S.H). The other author (Y.W.J) collected the fluids and prepared them for analysis. The data were then analyzed by another author (E.J.C). All evaluations were performed in a blinded fashion on the disease status of all subjects. Table 1 summarizes the clinical parameters for the classification of DED and control samples at each step of proteomic analysis including global profiling and MRM assay.