• Comprehensive Ophthalmology, Cornea/External Disease

    This large-scale multicenter trial evaluated data from patients with moderate to severe dry eye disease (DED) for associations between risk factors and severity of DED signs and symptoms.

    Study design

    A total of 535 adult patients with moderate to severe DED from 27 centers underwent ocular surface examinations and symptom evaluation. Systemic disease or smoking history as potential DED risk factors were analyzed for their association with the severity of dry eye signs and symptoms.


    Based on comprehensive evaluation of DED signs and symptoms, the study found that presence of Sjögren syndrome, facial rosacea, rheumatoid arthritis or peripheral artery disease, or a history of daily cigarette smoking are significantly associated with more severe dry eye signs.


    The study’s researchers may underestimate the association of certain systemic conditions with DED severity due to potential bias from coexisting systemic diseases that patients self-report to determine the presence of systemic disease without differentiating severity and duration.

    Clinical significance

    This study provides the largest dataset to date that establishes whether systemic diseases and cigarette smoking are associated with DED severity. The results of significant association of several disease conditions and daily cigarette smoking and severity of dry eye disease are significant because severe DED warrants more intense treatment strategies. Additionally, the profile of significant dry eye signs varied by systemic condition, reflecting a range of dry eye causes.