Biofilm Theory for Lid Margin and Dry Eye Disease

Abstract

Blepharitis and dry eye disease have long been viewed as two distinct diseases with overlapping presentations and separate etiologies. Evaporative dry eye, although frequently associated with aqueous deficiency, is also considered a separate entity. We propose viewing dry eye, both evaporative and insufficiency, as the natural sequelae of chronic blepharitis induced by biofilm. We suggest describing this one chronic disease as dry eye blepharitis syndrome (DEBS). The disease process begins when normal flora bacteria colonize the lid margin beginning shortly after birth. This colonization accompanies the development of a biofilm on the lid margin. As years pass, the biofilm matures, and the increased bacterial population initiates the production of inflammatory virulence factors, such as exotoxins, cytolytic toxins, and super-antigens, which persist on the lid margin for the rest of the patient’s life. These virulence factors cause early follicular inflammation and later, meibomian gland dysfunction followed by aqueous insufficiency, and finally, after many decades, loss of the dense collagen in the tarsal plate. We proposed four stages of DEBS, which correlate with the clinical manifestations of folliculitis (anterior blepharitis), meibomitis (meibomian gland dysfunction), lacrimalitis (aqueous deficiency), and lid structure damage evidenced by increased lid laxity resulting in entropion, ectropion, and floppy eyelid syndrome.