Corneal permeability changes in dry eye disease: an observational study.

BACKGROUND: Diagnostic tests for dry eye disease (DED), including ocular surface disease index (OSDI), tear breakup time (TBUT), corneal fluorescein staining, and lissamine staining, have great deal of variability. We investigated whether fluorophotometry correlated with previously established DED diagnostic tests and whether it could serve as a novel objective metric to evaluate DED. METHODS: Dry eye patients who have had established signs or symptoms for at least 6 months were included in this observational study. Normal subjects with no symptoms of dry eyes served as controls. Each eye had a baseline fluorescein scan prior to any fluorescein dye. Fluorescein dye was then placed into both eyes, rinsed with saline solution, and scanned at 5, 10, 15, and 30 min. Patients were administered the following diagnostic tests to correlate with fluorophotometry: OSDI, TBUT, fluorescein, and lissamine. Standard protocols were used. P < 0.05 was considered significant. RESULTS: Fifty eyes from 25 patients (DED = 22 eyes, 11 patients; Normal = 28 eyes, 14 patients) were included. Baseline scans of the dry eye and control groups did not show any statistical difference (p = 0.84). Fluorescein concentration of DED and normal patients showed statistical significance at all time intervals (p < 10(-5), 0.001, 0.002, 0.049 for 5, 10, 15, & 30 min respectively). Fluorophotometry values converged towards baseline as time elapsed, but both groups were still statistically different at 30 min (p < 0.01). We used four fluorophotometry scoring methods and correlated them with OSDI, TBUT, fluorescein, and lissamine along with adjusted and aggregate scores. The four scoring schemes did not show any significant correlations with the other tests, except for correlations seen with lissamine and 10 (p = 0.045, 0.034) and 15 min (p = 0.013, 0.012), and with aggregate scores and 15 min (p = 0.042, 0.017). CONCLUSIONS: Fluorophotometry generally did not correlate with any other DED tests, even though it showed capability of differentiating between DED and normal eyes up to 30 min after fluorescein dye instillation. There may be an aspect of DED that is missed in the current regimen of DED tests and only captured with fluorophotometry. Adding fluorophotometry may be useful in screening, diagnosing, and monitoring patients with DED.

Omegas and Dry Eye: More Knowledge, More Questions.

The omega-3 (ω3) and omega-6 (ω6) essential fatty acid knowledge base has been exploding. In the last 5 years, at least 12 clinical trials on ω3 and ω6 supplementation and dry eye disease (DED) were published in the peer-reviewed literature (2010 to 2015), about double the amount published in the 5 years prior. Although there is increasing scientific evidence that supports the potential use of ω3 and ω6 supplementation for DED, there are limited randomized controlled trials to properly inform evidence-based medicine. Dry eye disease is one of the most common eye conditions that patients seek care for and cannot be disregarded as a trivial condition. The roles of ω3 and ω6 polyunsaturated fatty acids (PUFAs) in the treatment of DED are still not completely understood. There are distinct and sometimes opposite effects of ω3 and ω6 PUFAs, both of which are essential and cannot be synthesized de novo in the body. These fatty acids must be obtained from the diet, which varies widely by region, even within the United States. Omega-3 PUFAs have anti-inflammatory effects; a proper ratio of ω6:ω3 in the diet must be established. Objectively correlating changes in dry eye syndrome with blood levels of ω3 PUFAs has not been done in a large-scale multisite study. Just as Wilder's law of initial value states that "the direction of response of a body function to any agent depends to a large degree on the initial level of that function," the baseline status needs to be taken into account. There is also no consensus on the dose, composition, length of treatment, and so on with ω3 or ω6 PUFAs. Increased quality evidence on the usefulness of over-the-counter supplements is needed to enable eye care providers to confidently outline specific treatment recommendations for using ω3 PUFAs in DED.

Conjunctival HLA-DR Expression and Its Association With Symptoms and Signs in the DREAM Study.

PURPOSE: Evaluation of dry eye disease (DED) relies on subjective symptoms and signs. We examined HLA-DR expression (HLA-DR%) in conjunctival cells, a minimally invasive biomarker with objective metrics, as an alternative method. METHODS: Dry Eye Assessment and Management (DREAM) study participants completed the Ocular Surface Disease Index questionnaire. Clinicians evaluated tear volume, tear breakup time, and corneal and conjunctival staining. Conjunctival impression cytology samples (n = 1049) were assessed for HLA-DR% in total cells (TCs), epithelial cells (ECs), and white blood cells (WBCs). Associations (categorized into <5%, 5%-15%, >15%-25%, and >25%) with symptoms and signs were evaluated. RESULTS: The HLA-DR% varied markedly across samples. Over 40% had <5 HLA-DR% positive cells in TCs and ECs and under 23% in WBCs. Higher HLA-DR% was associated with higher conjunctival staining for ECs (mean score 2.77 for <5% and 3.28 for >25%, linear trend P = 0.009) and TCs (mean score 2.82 for <5% and 3.29 for >25%, linear trend P = 0.04) and in TCs was associated with higher corneal staining (mean score 3.59 for <5% and 4.46 for >25%, linear trend P = 0.03). HLA-DR% in WBCs did not correlated with signs (all P ≥ 0.58), and in TCs, ECs or WBCs were not associated with symptoms (P > 0.06). CONCLUSIONS: The distribution of HLA-DR% in conjunctival cells reflects the heterogeneity of disease in DREAM participants. High percentages of samples with <5% positive cells indicate that HLA-DR% may not be a sensitive marker for DED in all patients. TRANSLATIONAL RELEVANCE: High HLA-DR% in ECs in association with high conjunctival staining may identify a subgroup of DED patients prone to epithelial disease and possibly need a different approach from current standards of treatment.