Association between lid margin collarettes and dry eye disease severity in the Dry Eye Assessment and Management (DREAM) study.

BACKGROUND/OBJECTIVES: Lid margin collarettes are a distinct clinical finding and their association with meibomian gland dysfunction (MGD) and dry eye symptoms and signs remains uncertain. We leverage the large cohort of subjects in the Dry Eye Assessment and Management (DREAM) study data to elucidate collarettes' impact on dry eye disease (DED). SUBJECTS/METHODS: We performed secondary analysis of DREAM study data, a multicentre, double-blinded clinical trial evaluating omega-3 supplementation in patients with moderate-to-severe DED. DED symptoms (Ocular Surface Disease Index [OSDI] and Ocular Discomfort) and signs (conjunctival staining, corneal staining, tear break-up time (TBUT), Schirmer test, MGD grade) were compared by collarette presence and severity. Data from all visits (baseline, months 3, 6, 12) were assessed and adjusted for demographics and baseline comorbidities. RESULTS: Of 1070 eyes at baseline, 65.3% had no collarettes, 28.0% had 1-5, and 6.6% had 6-20. Over the 1 year period of the study, 67% of eyes had no change in collarette severity, while 19% had increased severity and 14% had decreased severity. Collarettes were more common in Whites (82.1% vs 69.9%, p = 0.001), non-Hispanics (92.3% vs 83.2%, p = 0.006), and those with facial rosacea (25.0% vs 17.7%, p = 0.05). Multivariate analysis showed collarettes were associated with increased corneal staining (5.06 vs 4.59, p = 0.01), decreased TBUT (3.24 vs 3.54 s, p = 0.01), decreased Schirmer test (7.92 vs 8.63, p = 0.04), more severe eyelid erythema (18.6% vs 12.2%, p < 0.001), and higher composite DED sign severity (0.51 vs 0.49, p = 0.03). However, they were not associated with conjunctival staining, MGD grade, or DED symptoms (p ≥ 0.30). Similar findings were observed in comparisons of collarette severity. Subjects with collarettes had lower tear levels of IL-1β (p = 0.04), IL-10 (p = 0.02), and INF-γ (p = 0.001). CONCLUSIONS: Collarettes were common in patients with moderate-to-severe DED, and most do not progress over time. Although they were associated with worse ocular surface signs, notably eyelid erythema, no association was found with dry eye symptoms. Our results will help physicians counsel and guide the approach to treating dry eye patients with collarettes, and generate pilot data for tear film biomarker identification.