n-3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease

Abstract

Background: Dry eye disease is a common chronic condition that is characterized by ocular discomfort and visual disturbances that decrease quality of life. Many clinicians recommend the use of supplements of n-3 fatty acids (often called omega-3 fatty acids) to relieve symptoms.

Methods: In a multicenter, double-blind clinical trial, we randomly assigned patients with moderate-to-severe dry eye disease to receive a daily oral dose of 3000 mg of fish-derived n-3 eicosapentaenoic and docosahexaenoic acids (active supplement group) or an olive oil placebo (placebo group). The primary outcome was the mean change from baseline in the score on the Ocular Surface Disease Index (OSDI; scores range from 0 to 100, with higher scores indicating greater symptom severity), which was based on the mean of scores obtained at 6 and 12 months. Secondary outcomes included mean changes per eye in the conjunctival staining score (ranging from 0 to 6) and the corneal staining score (ranging from 0 to 15), with higher scores indicating more severe damage to the ocular surface, as well as mean changes in the tear break-up time (seconds between a blink and gaps in the tear film) and the result on Schirmer's test (length of wetting of paper strips placed on the lower eyelid), with lower values indicating more severe signs.

Results: A total of 349 patients were assigned to the active supplement group and 186 to the placebo group; the primary analysis included 329 and 170 patients, respectively. The mean change in the OSDI score was not significantly different between the active supplement group and the placebo group (-13.9 points and -12.5 points, respectively; mean difference in change after imputation of missing data, -1.9 points; 95% confidence interval [CI], -5.0 to 1.1; P=0.21). This result was consistent across prespecified subgroups. There were no significant differences between the active supplement group and the placebo group in mean changes from baseline in the conjunctival staining score (mean difference in change, 0.0 points; 95% CI, -0.2 to 0.1), corneal staining score (0.1 point; 95% CI, -0.2 to 0.4), tear break-up time (0.2 seconds; 95% CI, -0.1 to 0.5), and result on Schirmer's test (0.0 mm; 95% CI, -0.8 to 0.9). At 12 months, the rate of adherence to treatment in the active supplement group was 85.2%, according to the level of n-3 fatty acids in red cells. Rates of adverse events were similar in the two trial groups.

Conclusions: Among patients with dry eye disease, those who were randomly assigned to receive supplements containing 3000 mg of n-3 fatty acids for 12 months did not have significantly better outcomes than those who were assigned to receive placebo. (Funded by the National Eye Institute, National Institutes of Health; DREAM ClinicalTrials.gov number, NCT02128763 .).

Figure 1. Distribution of Scores on the Ocular Surface Disease Index

Shown are box-and-whisker plots of the scores on the Ocular Surface Disease Index (OSDI) in the active supplement group (who received a daily capsule of 3000 mg of n–3 fatty acids) and the placebo group between baseline and 12 months. The upper and lower edges of the boxes correspond to the 75th and 25th percentiles, respectively. Within the boxes, the asterisks correspond to the mean and the lines correspond to the 50th percentile (median). The upper and lower ends of the whiskers correspond to the highest score within 1.5× the interquartile range of the 75th percentile and the lowest score within 1.5× the interquartile range of the 25th percentile, respectively. Each dot outside the whiskers corresponds to one score.

Figure 2. Change in Signs of Dry Eye Disease

The following results constitute signs of dry eye disease in an eye: a conjunctival lissamine-green staining score of 1 or more (on a scale ranging from 0 to 6, with higher scores indicating greater abnormality), a corneal fluorescein staining score of 4 or more (on a scale ranging from 0 to 15, with higher scores indicating greater abnormality), a tear break-up time (the time from a blink to the appearance of gaps in the tear film, with shorter times indicating greater abnormality) of 7 seconds or less, and a result on Schirmer’s test with anesthesia (the length of wetting of paper strips placed in the inferior cul de sac of the lower eyelid, with shorter lengths indicating greater abnormality) of 1 to 7 mm in 5 minutes. In each trial group, there was a significant change between baseline and 12 months (with time as a continuous variable) in the conjunctival staining score, the corneal staining score, and the tear break-up time (P<0.001 for change for each measure in each group) but not in the result on Schirmer’s test (P = 0.79 for change in the active supplement group; P = 0.46 for change in the placebo group).