A revolutionary hypothesis to explain Marx's line and progressive disease at the lid margin

Purpose The conjunctiva of the lid margin is protected from direct exposure to the atmosphere, by the tear meniscus. We examine the pathophysiological consequences of evaporation from this compartment. Methods A consideration of empirical data. Results The concave meniscus thins progressively to the point where it is pinned at the mucocutaneous junction (MCJ). We predict that, as a result, over the interblink period, evaporation generates a solute gradient which peaks behind the MCJ and is amplified over multiple cycles of the blink. We hypothesise that this creates a hyperosmolar state here which: i. stresses epithelial cells behind the MCJ, ii. stimulates a high cell turnover and iii. leads to immaturity of the surface cells and their glycocalyx. This is considered to explain an increased permeability to dyes at this site (rose bengal, lissamine green and fluorescein) and the stainability with dyes which is termed Marx’s line.This gradient mechanism could also concentrate proteins, such as inflammatory mediators, at this location. Conclusion Since Marx’s line lies directly behind the terminal Meibomian ducts and acini, chronic stress in this region is further invoked to explain forward migration of Marx's line and the MCJ which occurs with age and the induction of primary Meibomian gland dysfunction. Arguments are put forward to explain how this mechanism might be accentuated in dry eye and how the globe might be protected from this gradient effect in the region of the ‘black line’, where the tear film is segregated from the meniscus after the blink. Factors pro and con the hypothesis are discussed.