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Original Investigation
March 10, 2022

Association Between Depression and Severity of Dry Eye Symptoms, Signs, and Inflammatory Markers in the DREAM Study

Author Affiliations
  • 1Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
  • 2Depression and Anxiety Center for Discovery and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York
  • 3Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania
  • 4Department of Ophthalmology, Hamilton Eye Institute, The University of Tennessee Health Science Center, Memphis, Tennessee
  • 5Cole Eye Institute, Lerner College of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio
JAMA Ophthalmol. 2022;140(4):392-399. doi:10.1001/jamaophthalmol.2022.0140
Key Points

Question  Is severity of dry eye symptoms and signs associated with presence of depression?

Findings  In this multicenter study of 535 participants with dry eye disease, those who screened positive for depression had worse dry eye symptoms and overall dry eye signs but similar inflammatory markers compared with those of participants with dry eye who screened negative for depression.

Meaning  In this study, patients with dry eye disease and depression may have more severe dry eye symptoms and signs than those without depression.


Importance  Depression is more prevalent in patients with dry eye disease (DED) than in the general population; however, the association between severity of DED and depression needs further evaluation.

Objective  To investigate the association between depression and severity of DED symptoms and signs, including inflammatory markers.

Design, Setting, and Participants  Secondary cross-sectional and longitudinal analysis performed in April to December 2020 of data from Dry Eye Assessment and Management (DREAM) study, a randomized clinical trial from October 2014 to July 2016 including patients with moderate to severe symptoms and signs of DED. Enrolled from 27 ophthalmology and optometry centers, both academic and private, in 17 US states, 535 patients were followed up for 1 year.

Exposure  Participants screened positive for depression if they scored 42 or less on the Mental Component Summary (MCS) of the 36-Item Short Form Health Survey.

Main Outcomes and Measures  Symptoms of DED were assessed by Ocular Surface Disease Index (OSDI) and Brief Ocular Discomfort Index (BODI) and signs assessed by tear film breakup time, Schirmer test, corneal and conjunctival staining, tear osmolarity, and meibomian gland dysfunction at baseline, 6 months, and 12 months. A composite severity sign score was calculated from all 6 signs. Inflammatory markers (cytokines in tears and HLA-DR expression by conjunctival surface cells) were measured for some trial participants. Features of DED were compared between participants with and without depression and adjusted for age, sex, race, visits, and baseline comorbidities.

Results  Among the 535 participants, mean (SD) age was 58 (13.2) years, 434 participants (81%) were women, and 398 (74.4%) were White. Participants who screened positive for depression had worse DED symptoms by OSDI (effect size = 0.45, P < .001) and BODI (effect size = 0.46, P < .001) and composite DED sign score (effect size = 0.21, P = .006). Lower MCS score (ie, worse depression) was correlated with higher OSDI score (ie, worse DED symptoms) at baseline (Spearman ρ = −0.09, P = .03), 6 months (ρ = −0.20, P < .001), and 12 months (ρ = −0.21, P < .001). Inflammatory markers did not differ by depression status.

Conclusions and Relevance  Depression was associated with more severe dry eye symptoms and overall signs, suggesting that among patients with moderate to severe DED, those with depression may be likely to have more severe DED. These findings support consideration of depression as a comorbidity when managing patients with DED. Further study is needed to elucidate the relationship.

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    1 Comment for this article
    Suggested pursuit of link between DED and depression
    Ian Schorr, M.D. | Retired ophthalmologist
    Many popular medications for depression (e.g. SSRIs, tricyclics, etc.) have anticholinergic effects which can effect the lacrimal glands production of tears.

    There may not be a comorbidity and there may be just a medication side effect; that probably should be considered as part of any further study.