Revisiting the vicious circle of dry eye disease: a focus on the pathophysiology of meibomian gland dysfunction

Meibomian gland dysfunction (MGD) is the most frequent cause of dry eye disease (DED). Eyelid inflammation, microbial growth, associated skin disorders as well as potentially severe corneal complications culminate to make MGD a complex multifactorial disorder. It is probable that MGD is a heterogeneous condition arising from any combination of the following five separate pathophysiological mechanisms: eyelid inflammation, conjunctival inflammation, corneal damage, microbiological changes and DED resulting from tear film instability. The pathogenesis of both MGD and DED can be described in terms of a 'vicious circle': the underlying pathophysiological mechanisms of DED and MGD interact, resulting in a double vicious circle. The MGD vicious circle is self-stimulated by microbiological changes, which results in increased melting temperature of meibum and subsequent meibomian gland blockage, reinforcing the vicious circle of MGD. Meibomian gland blockage, dropout and inflammation directly link the two vicious circles. MGD-associated tear film instability provides an entry point into the vicious circle of DED and leads to hyperosmolarity and inflammation, which are both a cause and consequence of DED. Here we propose a new pathophysiological scheme for MGD in order to better identify the pathological mechanisms involved and to allow more efficient targeting of therapeutics. Through better understanding of this scheme, MGD may gain true disease status rather than being viewed as a mere dysfunction.