Osmokinetics: A new dynamic concept in dry eye disease

Abstract

Tear fluid osmolarity has been increasingly accepted as an accessible parameter in the diagnosis of ocular surface and dry eye disease. After having been proposed as the gold standard, recent results have put this into question. However, the most recent guidelines for dry eye disease identify specific values of osmolarity as thresholds to help to differentiate between various stages of severity of ocular surface disease. The limits of this approach were investigated to propose a new concept, that of osmokinetics. Available data on tear fluid osmolarity in normal and diseased eyes were compared. The possibility of normo-osmolar dry eye was investigated and repeated measurements of osmolarity performed. The currently applied static model of a threshold value of osmolarity for diagnosing dry eye disease is apparently insufficient. Not only does it not take into account normo-osmolar dry eye, but it also applies too much significance to a single parameter. Instead, it was found that there is a daily variation in osmolarity (DVO), which appears to be higher in eyes with tear film deficiencies than in healthy eyes. Tear film osmolarity does vary considerably throughout the day. Its value should be considered in a kinetic model taking into account the dynamics of osmolarity changes moreso than the current static model. The terms of osmotic stress and diurnal variation of osmolarity were found to offer a more physiological understanding of osmolarity. A more dynamic model for osmolarity is presented in which not the value itself but the daily variation of osmolarity is identified. It is suggested that the amplitude of change in osmolarity over the course of a day or even shorter time periods could play a decisive role as a stress factor for the surface cells. The varying osmolar stress could be one of the key mechanisms leading to the cell death, inflammation, apoptosis, and goblet cell disappearance as observed in dry eye disease. Perhaps it is the mean osmolarity level at which these changes occur together with the magnitude of DVO which could identify the level of severity of dry eye disease.