Association of Ocular Surface Immune Cells With Dry Eye Signs and Symptoms in the Dry Eye Assessment and Management (DREAM) Study.

Purpose: Dry eye disease (DED) is a multifactorial, heterogeneous disease of the ocular surface with one etiology being ocular surface inflammation. Studies using animal models demonstrate the role of ocular surface immune cells in the inflammatory pathway leading to DED, but few have evaluated humans. This study described the white blood cell population from the ocular surface of patients with DED and assessed its association with DED signs and symptoms in participants of the Dry Eye Assessment and Management (DREAM) study. Methods: Participants were assessed for symptoms using the Ocular Surface Disease Index, signs via corneal staining, conjunctival staining, tear break-up time, and Schirmer test, and Sjögren's syndrome (SS) based on the 2012 American College of Rheumatology classification criteria. Impression cytology of conjunctival cells from each eye was evaluated using flow cytometry: T cells, helper T cells (Th), regulatory T cells (Tregs), cytotoxic T cells, and dendritic cells. Results: We assessed 1049 eyes from 527 participants. White blood cell subtype percentages varied widely across participants. Significant positive associations were found for Th and conjunctival staining (mean score of 2.8 for 0% Th and 3.1 for >4.0% Th; P = 0.007), and corneal staining (mean score of 3.5 for 0% Th and 4.3 for >4.0% Th; P = 0.01). SS was associated with higher percent of Tregs (median 0.1 vs. 0.0; P = 0.01). Conclusions: Th were associated with more severe conjunctival and corneal staining, possibly indicating their role in inflammation leading to damage of the ocular surface. There is no consistent conclusion about Tregs in SS, but these results support that Tregs are elevated in SS.

Correlation of Measures From the OCULUS Keratograph and Clinical Assessments of Dry Eye Disease in the Dry Eye Assessment and Management Study.

PURPOSE: The purpose of this study was to compare objective, noninvasive assessments of tear function using the OCULUS Keratograph with the corresponding clinical assessments [tear break-up time (TBUT), Schirmer test, and bulbar erythema] among patients with moderate-to-severe dry eye disease. METHODS: Participants in the Dry Eye Assessment and Management study at centers having an OCULUS Keratograph were assessed using standardized procedures. Associations between the assessments from the Keratograph [noninvasive keratograph break-up time (NIKBUT), tear meniscus height (TMH), and bulbar redness (BR)] and clinical examination (TBUT, Schirmer test, and bulbar erythema) and between these test results and Ocular Surface Disease Index (OSDI) scores were summarized with Spearman correlation coefficients (r s ); 95% confidence intervals (95% CI) accounted for intereye correlation. RESULTS: Among 288 patients (576 eyes), the mean (standard deviation) age was 56.6 (13.8) years, 78.1% were female, and the mean baseline OSDI score was 44.3 (14.0). The mean was 2.9 (1.5) seconds for TBUT and 8.2 (5.7) seconds for NIKBUT (their correlation r s = 0.18, 95% CI = 0.09-0.28). The mean was 10.6 (7.6) mm for the Schirmer test and 0.3 (0.2) mm for TMH (r s = 0.15, 95% CI = 0.04-0.25). The median clinical grade redness was mild, and the mean BR score was 1.1 (0.5) (r s = 0.25, 95% CI = 0.15-0.35). Correlation between results of each of the 6 tests and OSDI scores was low (r s from -0.07 to 0.05). CONCLUSIONS: In the Dry Eye Assessment and Management study, NIKBUT, TMH, and BR were weakly correlated with their clinical counterparts. No measurements were correlated with the OSDI score.

Associations Between Systemic Omega-3 Fatty Acid Levels With Moderate-to-Severe Dry Eye Disease Signs and Symptoms at Baseline in the Dry Eye Assessment and Management Study.

PURPOSE: Omega-3 (n-3) fatty acid supplementation is used to treat systemic inflammatory diseases, but the role of n-3 in the pathophysiology and therapy of dry eye disease (DED) is not definitive. We evaluated the relationship of systemic n-3 levels with signs and symptoms at baseline in the Dry Eye Assessment and Management (DREAM) Study. METHODS: Blood samples from participants at baseline were analyzed for n-3 and n-6, measured as relative percentage by weight among all fatty acids in erythrocytes. Symptoms were evaluated using the Ocular Surface Disease Index. Signs including conjunctival staining, corneal staining, tear breakup time (TBUT), and Schirmer's test with anesthesia were also evaluated. RESULTS: There was no correlation between the systemic n-3 levels and DED symptoms. When the associations with signs of DED were assessed, lower DHA levels were associated with higher conjunctival staining, with mean scores of 3.31, 2.96, and 2.82 for low, medium, and high levels of DHA, respectively (linear trend P=0.007). None of the other signs were associated with DHA or the other measures of n-3. CONCLUSION: Previous studies have found varying results on the role of n-3 supplementation with the signs and symptoms of DED. Among patients with DED enrolled in the DREAM Study, lower systemic n-3 levels were not associated with worse symptoms and most signs of DED.

Ocular Discomfort and Quality of Life Among Patients in the Dry Eye Assessment and Management Study.

PURPOSE: To assess the association of severity of ocular discomfort with measures of quality of life among patients with moderate to severe dry eye disease (DED). METHODS: This is a prospective, observational, cohort study within a randomized clinical trial. Patients (N = 535) in the Dry Eye Assessment and Management study with moderate to severe DED completed the Ocular Surface Disease Index on DED symptoms, the SF-36 on quality of life, and the Brief Ocular Discomfort Inventory questionnaire and had a comprehensive ophthalmic assessment by a study-certified clinician. The ocular discomfort on average over the past week was scored on an 11-point scale (0 for no discomfort and 10 for discomfort as bad as you can imagine). RESULTS: The average ocular discomfort scores for patients ranged from 0 to 10, with a mean of 4.28. Discomfort scores did not vary with demographic characteristics, signs of DED, self-reported depression, or self-reported nonocular pain conditions. Ocular discomfort scores did correlate moderately to strongly with total Ocular Surface Disease Index scores (Spearman correlation coefficient, rs, 0.47-0.67) and with measures of interference with activities of daily living [general activity level, mood, walking ability, ability for normal work, relations with other people, sleep, and enjoyment of life (rs = 0.39-0.65)]. CONCLUSIONS: Among patients in the Dry Eye Assessment and Management study, worse ocular discomfort was associated with worse overall DED symptoms and interfered to a greater degree with activities of daily living. Ocular discomfort is an important part of the assessment of patients with DED.

Dry Eye Assessment and Management (DREAM©) Study: Study design and baseline characteristics.

PURPOSE: Describe trial design and baseline characteristics of participants in the DRy Eye Assessment and Management (DREAM©) Study. DESIGN: Prospective, multi-center, randomized, double-masked "real-world" clinical trial assessing efficacy and safety of oral omega-3 (ω3) supplementation for the treatment of dry eye disease (DED). METHODS: RESULTS: Mean age of participants was 58.0 ±â€¯13.2 years. Mean OSDI score at baseline was 44.4 ±â€¯14.2. Mean conjunctival staining score (scale 0-6) was 3.0 ±â€¯1.4, corneal staining score (scale 0-15) was 3.9 ±â€¯2.7, tear break-up time was 3.1 ±â€¯1.5 s, and Schirmer test was 9.6 ±â€¯6.5 mm/5 min. CONCLUSIONS: DREAM© participants mirror real world patients who seek intervention for their DED-related symptoms despite their current treatments. Results regarding the efficacy of omega-3 supplementation will be helpful to clinicians and patients with moderate to severe DED who are considering omega-3 as a treatment. This trial design may be a model for future RCT's on nutritional supplements and DED treatments seeking to provide useful information for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02128763.