Beyond dry eye: how co-morbidities influence disease phenotype in dry eye disease

Dry Eye Disease (DED) is a complex and multifactorial disorder of tear homoeostasis that results in pain, visual disturbance, and ocular surface damage. It is highly prevalent around the world and is associated with many co-morbidities that may contribute to or exacerbate symptoms and signs of disease and affect disease phenotype. However, DED is not one disease and can manifest with a variety of symptoms and/or signs. In this review, we discuss relationships between various co-morbidities and DED phenotypes. For example, individuals with immune mediated diseases, like Sjögren's Syndrome and Graft versus Host Disease, often present with aqueous tear deficiency (ADDE) in the setting of lacrimal gland dysfunction. Individuals with disorders that affect the periocular skin, like rosacea and seborrhoeic dermatitis, often present with evaporative dry eye (EDE) in the setting of eyelid and/or meibomian gland abnormalities. Individuals with pain related disorders, such as chronic pain syndrome and migraine, often present with ocular pain out of proportion to tear film abnormalities, often with accompanying corneal nerve hypersensitivity. Individuals with diabetes mellitus often present with an epitheliopathy in the setting of decreased sensation (neurotrophic keratitis). While not absolute, understanding relationships between co-morbidities and DED phenotypes can help tailor a therapeutic plan to the individual patient.