Correlation Between the Inflammatory Marker HLA-DR and Signs and Symptoms in Moderate to Severe Dry Eye Disease

Invest Ophthalmol Vis Sci. 2017 Apr 1;58(4):2438-2448. doi: 10.1167/iovs.15-16555.


Purpose: To investigate correlations of the inflammatory HLA-DR marker with clinical signs and symptoms commonly used to assess dry eye disease (DED) severity.

Methods: Baseline data were collected from three clinical studies conducted on moderate to severe DED patients. Characteristics of DED were analyzed and correlations were performed in 311 patients. Data were analyzed after treatment with 1 mg/mL cyclosporine (CsA) and vehicle. We quantified HLA-DR by flow cytometry in impression cytology specimens.

Results: We found HLA-DR significantly increased with diagnosis of Sjögren syndrome (P < 0.0001) and meibomian gland disease (P = 0.0223). The strongest significant correlation was seen with the corneal fluorescein staining (CFS, r = 0.30, P < 0.0001). Significant negative relationships were also found with Schirmer's test (r = -0.20, P = 0.0003) and tear break-up time (TBUT, r = -0.13, P = 0.0226). Correlations were statistically significant with total Ocular Surface Disease Index and visual analog scale scores (r = 0.12, P = 0.0426, and r = 0.14, P= 0.0176, respectively). We found HLA-DR arbitrary units of fluorescence were statistically reduced after CsA treatment compared to vehicle (P = 0.022 and P = 0.021 in two studies).

Conclusions: In clinical research on DED, discrepancy is often observed between symptoms and signs. We found HLA-DR correlated significantly with CFS clinical signs and to a lower extent Schirmer's test and weakly with TBUT and symptom reporting questionnaires. HLA-DR was reported to be useful for monitoring anti-inflammatory efficacy treatments in DED, which was confirmed with the reduction of HLA-DR while on CsA treatment. Its expression by conjunctival cells has the potential to serve as a biomarker, bridging signs and symptoms in clinical research in DED, but there is still a need for additional validation studies.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / metabolism
  • Clinical Studies as Topic
  • Cornea / metabolism
  • Dry Eye Syndromes / metabolism*
  • Female
  • Flow Cytometry
  • Fluorescein Angiography
  • HLA-DR Antigens / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Severity of Illness Index
  • Tears / metabolism


  • Biomarkers
  • HLA-DR Antigens