"Hyperosmolarity is at the heart of the problem in dry eye. It has tremendous negative implications, and is common across all the different forms of dry eye disease," said Dr. McDonald, clinical professor of ophthalmology, NYU Langone Medical Center, New York, and adjunct clinical professor of ophthalmology, Tulane University Health Sciences Center. She presented the results from an interim analysis of a study done at 16 sites across the United States and Europe.
Hyperosmolarity causes epithelial cell death, inflammation, and up-regulation of the known inflammatory markers, including the pro-inflammatory cytokines and HLA-DR. It also reduces the ability of mucins to lubricate the ocular surface, she explained.
"This causes friction, which leads to wear, which gives us a rough ocular surface, which causes shortened tear break-up time, and keeps the cycle of inflammation going," Dr. McDonald said.
Hyperosmolarity in the population
According to Dr. McDonald, the prevalence of hyperosmolarity in the general patient population has been studied.
Currently, 582 subjects are enrolled in the study, 405 of whom are female. Overall, 60% of patients had dry eye, with osmolarities ≥308 mOsm/l. In all, 62% of these 582 subjects reported symptoms of dry eye disease, 225 had dry eye disease, and 133 had some other form of ocular irritation. A total of 38% (n = 224) were asymptomatic. Of these patients, 124 had mild to moderate dry eye disease with no symptoms. The remaining 100 patients in this group were normal, Dr. McDonald explained.
Most importantly, she added, normal subjects had an average inter-eye variability of 6.9 (±5.5) mOsm/l, but the dry eye subjects had an average inter-eye variability of 17.3 (±15.9) mOsm/l.
"So far, this study indicates that normal subjects exhibit low and stable osmolarity around 209 mOsm/l, which happens to be equivalent to blood osmolarity. It's indicative that the tears are being held in proper homeostasis," noted Dr. McDonald.
"[Patients with dry eye] have very elevated and unstable osmolarity. The osmolarity changes between eyes and over time in each eye. Therefore, variability rather than the absolute score is the true hallmark of dry eye disease," Dr. McDonald said.
"If there is greater than an 8 mOsm/l difference between the eyes, that's indicative of dry eye disease," she added.