The study comprised 19 volunteer patients (52.1 ± 16.4 years old), all of whom had established dry eye diagnosed by experienced clinicians who used standard techniques during regular eye examination. Dry eye was diagnosed by the physician by the patient's report of ocular discomfort, TFBUT, corneal staining with fluorescein, and conjunctival staining with lissamine green. These tests were used to qualify patients for inclusion in the study and for grading dry eye disease severity. Meibomian gland dysfunction was not used to include or exclude patients. The dry eye patients were a mixed group with aqueous-deficient or evaporative dry eye disease. Research in this study adhered to the tenets of the Declaration of Helsinki.
After providing informed consent according to Mount Sinai School of Medicine's Program for the Protection of Human Subjects (PPHS), the patients completed an evaluation of the signs and symptoms of dry eye disease that included the Ocular Surface Disease Index (OSDI) questionnaire, corneal staining with fluorescein, conjunctival staining with lissamine green, TFBUT, and Schirmer's test with anesthesia. Corneal staining with fluorescein was evaluated using the National Eye Institute (NEI) method, a standardized scale (0–3) for each of the five regions of the cornea: central, inferior, nasal, superior, and temporal. Conjunctival staining with lissamine green was evaluated by using the Oxford Schema (0–4) for three regions of the conjunctiva: central, nasal, and temporal. TFBUT was measured as the time from a patient's blink to the appearance of the first dry spot on the cornea. Schirmer's test was performed for 5 minutes with anesthesia and eyes closed. All tests were performed on both eyes by the same researcher.
In addition, 5 to 10 μL of tears were collected from both eyes. Tear samples were collected from the lower meniscus/marginal tear strip of the lower lid near the lateral canthus of both eyes of each subject by using 5-μL microcapillaries (Microcaps 5 μL; Drummond Scientific, Broomall, PA). Samples from the right eye were chosen. Sample microcapillary tubes were inserted into a nano-dispensing sampler, precalibrated to 0.5 μL. The 0.5-μL sample was then transferred into the small end of the sample cell (TearTip; Advanced Instruments) and inserted into the thermal chamber of the tear osmometer (model 3100; Advanced Instruments), to measure the tear osmolarity on the basis of the freezing point. The osmolarity of the samples was calculated in milliosmolar/kilogram H2O.
Patients' signs and symptoms were analyzed for classification into the dry eye severity grade outlined by the DEWS report
3 and the 2006 International Task Force Delphi Expert Consensus,
2 by using the five selected criteria (OSDI, corneal staining, conjunctival staining, TFBUT, and Schirmer's test with anesthesia). The DEWS classification table was modified with numeric ranges for classification of the disease state, rather than the descriptions by Asbell et al.
1 (
Table 1), and each patient was classified as having a dry eye severity on a scale of 1 to 4.
The modified DEWS table (
Table 1) shows the descriptive definitions for dry eye disease severity with the ranges established for its classification. Mild dry eye disease, categorized as DEWS severity 1 and 2, and moderate-severe dry eye disease, which is DEWS severity 3 and 4, were distinguished by ranges of OSDI score, TFBUT, Schirmer's test with anesthesia, corneal staining, and conjunctival staining.
Patient test results were rated on the numeric dry eye severity scale (
Table 1) for each diagnostic test, and the patient was assigned an overall dry eye severity grade of 1, 2, 3, or 4, based on the mode and arithmetic mean of the individual severity grades for the selected criteria. (See
Table 3 for de-identified patient data for the study.)