This study followed the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of Korea University Hospital. All patients provided written informed consent prior to beginning the study.
Subjects and study design.
This was a prospective and randomized study conducted from June 2017 to February 2018 that included participants who met the Korean guidelines for dry eye syndrome[12] and whose tear osmolarity as assessed using TearLab®[11] was 300 mOsm/L or greater. Patients with external ocular disease, glaucoma or other concomitant ocular pathology, a history of ocular surgery, viral or bacterial infection of the cornea and conjunctiva, who regularly wore contact lenses within the past three months, or who reported any current systemic disease that might affect tear film stability were excluded. Only one eye per patient with higher osmolarity was included in this study.
A total of 80 patients was recruited, and they were randomly divided into four groups of 20 patients: Group 1 (isotonic 0.1% SH; Hyalein ophthalmic solution 0.1%®, Taejoon, Seoul, Korea), Group 2 (isotonic 0.15% SH; New Hyaluni ophthalmic solution 0.15%®, Taejoon, Seoul, Korea), Group 3 (isotonic 0.3% SH; Hyaluni ophthalmic solution 0.3%®; Taejoon, Seoul, Korea), and Group 4 (hypotonic 0.18% SH; Kynex2 ophthalmic solution 0.18%®, Alcon, Seoul, Korea).
Clinical evaluation included slit-lamp examination, tear film break up time (TBUT), corneal staining score, and tear osmolarity. Ocular surface examinations were performed on both eyes by the same physician (IHW). The TBUT was evaluated as follows; after instillation of fluorescein, the participants were asked to blink several times. The time between the last complete blink and the appearance of the first corneal black spot in seconds was measured three times, and the mean value was recorded[13]. The corneal staining score was evaluated using the National Eye Institute scoring method (NEI score) between 0 and 15[14]. The tear osmolarity was assessed using the TearLab® system immediately after blinking; the osmometer required a tiny tear sample obtained directly from the inferior tear meniscus using lab-on-chip technology[15]. All tests were performed in the same space using the same devices. The subjective discomfort when the drops were instilled was assessed using the visual analogue scale (VAS) from 0–10 where 0 means no pain and 10 indicates severe pain or discomfort.
Tear osmolarity was evaluated four times for each participant: at baseline and at 1, 5, and 10 minutes after instillation of the eye drop.
Statistical analysis.
All statistical analyses were performed using IBM SPSS Statistics for Windows, Version 21.0 (IBM Corp., Armonk, NY, USA). The Kruskal-Wallis test, Mann-Whitney U test, T-test, and one-way analysis of variance (ANOVA) were used to compare the measurements between groups. Repeated measures ANOVA was used to compare points within a group. P-values < 0.05 were considered statistically significant.