Progressively Increased Variation in Tear Osmolarity Mirrors Dry Eye Severity

To the Editor Progressively increased variation in tear osmolarity that mirrors dry eye severity, a result recapitulated by Bunya et al,¹ is a well-established hallmark of dry eye disease² that does not invalidate the utility of tear osmolarity as a biomarker. Tear instability and hyperosmolarity are strongly linked as core mechanisms of this disease. As dry eye disease gets worse, so too does the blink-to-blink instability of the tear film, moving from a stable equilibrium in healthy individuals to a chaotic system with dynamically blurred vision in more severe disease.² Therefore, the precepts that there is a true value of osmolarity and that variation from the mean can be attributed to measurement error disregard several physiological processes of the dry eye. A fixed-effects model applied in the manner of Bunya and colleagues discounts information that is otherwise very valuable to the understanding of tear film homeostasis. Rather, one can quantify the difference in osmolarity between 2 eyes to establish a linear estimate of tear film stability.² Despite this progressive variation, tear osmolarity has been shown to have the highest resolution of common clinical signs when tracking therapy,³ as other signs can vary far more than tear osmolarity when the ocular surface is compromised.³ However, the authors do not appear to take this relative performance into account when making conclusions about the utility of the marker.