Author(s): Piera Versura [*] 2 , Emilio C Campos 1
clinical application; diagnostic performance; dry eye; lab-on-a-chip technology; tear osmolarity
In current use, dry eye (DE) is regarded as synonymous with the term keratoconjunctivitis sicca. It usually refers to a dysfunction of the ocular surface and tears in which patients mostly report subjective symptoms such as foreign body sensation, itching, burning, redness and photophobia. Although still popular and used worldwide, the term 'dry eye' is quite inappropriate as it suggests a condition where a lack of tears is the predominant factor leading to symptoms of discomfort; however, this is not the case, which is discussed later in this article.
Osmometry is the measurement of the number or concentration of dissolved solutes in solution, irrespective of their size, density, molecular weight or electric charge. The terms 'osmolarity' (expressed as mOsm/l) and 'osmolality' (mOsm/kg) are often used interchangeably, although they are not the same measure. However, when the concentration of solutes in a solution is relatively low compared with water, as it is in human tears, osmolarity and osmolality can be considered to be equivalent. The term osmolarity will be used throughout this paper unless otherwise expressly specified.
Estimation of DE prevalence is difficult, primarily because a consensus on combination of diagnostic criteria and thresholds is still lacking. A review of several large studies  reported ranges between 5 and 30% in people aged over 50 years; the number of women affected by DE is approximately two-thirds higher than that of men  .
Major risk factors for DE include female sex, aging, menopause, postmenopausal hormone-replacement therapy, an imbalance in omega 3 and omega 6 essential fatty diet assumption  , refractive surgery  , vitamin A deficiency  , bone marrow transplantation, hepatitis C  , as well as androgen deficiency; for a complete reference list see  .
DE disease is a previously under-recognized condition. On the basis of increasing evidence, it now represents a burden in public health due to its prevalence  , visual function impairment  and impact on patients' quality of life  . It is therefore evident that DE should be considered as worthy of diagnosis and appropriate treatment to optimize healthcare resources  .
The surface of the eye facing the external environment is a complex system comprising the lachrymal glands, ocular surface (cornea, conjunctiva and meibomian glands), the lids, and the sensory and motor nerves that connect them  . The system is called the lachrymal function unit since it is anatomically and functionally integrated in such a way that any dysfunction may affect the entire homeostasis and impair function, leading to ocular discomfort symptoms.
In 1994, a workshop sponsored by the National Eye Institute and supported by industry defined DE disease as a "disorder of the tear film due to tear deficiency or excessive evaporation, which causes damage to the interpalpebral ocular surface and is associated with symptoms of ocular discomfort"  . This document provided the definition of DE for over 20 years, but advances in both basic and clinical research induced...