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Meta-Analysis
. 2019 Dec 18;12(12):CD011016.
doi: 10.1002/14651858.CD011016.pub2.

Omega-3 and omega-6 polyunsaturated fatty acids for dry eye disease

Laura E Downie  1 , Sueko M Ng  2 , Kristina B Lindsley  3 , Esen K Akpek  4
Affiliations
Meta-Analysis

Omega-3 and omega-6 polyunsaturated fatty acids for dry eye disease

Laura E Downie et al. Cochrane Database Syst Rev. .

Abstract

Background: Polyunsaturated fatty acid (PUFA) supplements, involving omega-3 and/or omega-6 components, have been proposed as a therapy for dry eye. Omega-3 PUFAs exist in both short- (alpha-linolenic acid [ALA]) and long-chain (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) forms, which largely derive from certain plant- and marine-based foods respectively. Omega-6 PUFAs are present in some vegetable oils, meats, and other animal products.

Objectives: To assess the effects of omega-3 and omega-6 polyunsaturated fatty acid (PUFA) supplements on dry eye signs and symptoms.

Search methods: CENTRAL, Medline, Embase, two other databases and three trial registries were searched in February 2018, together with reference checking. A top-up search was conducted in October 2019, but the results have not yet been incorporated.

Selection criteria: We included randomized controlled trials (RCTs) involving dry eye participants, in which omega-3 and/or omega-6 supplements were compared with a placebo/control supplement, artificial tears, or no treatment. We included head-to-head trials comparing different forms or doses of PUFAs.

Data collection and analysis: We followed standard Cochrane methods and assessed the certainty of the evidence using GRADE.

Main results: We included 34 RCTs, involving 4314 adult participants from 13 countries with dry eye of variable severity and etiology. Follow-up ranged from one to 12 months. Nine (26.5%) studies had published protocols and/or were registered. Over half of studies had high risk of bias in one or more domains. Long-chain omega-3 (EPA and DHA) versus placebo or no treatment (10 RCTs) We found low certainty evidence that there may be little to no reduction in dry eye symptoms with long-chain omega-3 versus placebo (four studies, 677 participants; mean difference [MD] -2.47, 95% confidence interval [CI] -5.14 to 0.19 units). We found moderate certainty evidence for a probable benefit of long-chain omega-3 supplements in increasing aqueous tear production relative to placebo (six studies, 1704 participants; MD 0.68, 95% CI 0.26 to 1.09 mm/5 min using the Schirmer test), although we did not judge this difference to be clinically meaningful. We found low certainty evidence for a possible reduction in tear osmolarity (one study, 54 participants; MD -17.71, 95% CI -28.07 to -7.35 mOsmol/L). Heterogeneity was too substantial to pool data on tear break-up time (TBUT) and adverse effects. Combined omega-3 and omega-6 versus placebo (four RCTs) For symptoms (low certainty) and ocular surface staining (moderate certainty), data from the four included trials could not be meta-analyzed, and thus effects on these outcomes were unclear. For the Schirmer test, we found moderate certainty evidence that there was no intergroup difference (four studies, 455 participants; MD: 0.66, 95% CI -0.45 to 1.77 mm/5 min). There was moderate certainty for a probable improvement in TBUT with the PUFA intervention relative to placebo (four studies, 455 participants; MD 0.55, 95% CI 0.04 to 1.07 seconds). Effects on tear osmolarity and adverse events were unclear, with data only available from a single small study for each outcome. Omega-3 plus conventional therapy versus conventional therapy alone (two RCTs) For omega-3 plus conventional therapy versus conventional therapy alone, we found low certainty evidence suggesting an intergroup difference in symptoms favoring the omega-3 group (two studies, 70 participants; MD -7.16, 95% CI -13.97 to -0.34 OSDI units). Data could not be combined for all other outcomes. Long-chain omega-3 (EPA and DHA) versus omega-6 (five RCTs) For long-chain omega-3 versus omega-6 supplementation, we found moderate certainty evidence for a probable improvement in dry eye symptoms (two studies, 130 participants; MD -11.88, 95% CI -18.85 to -4.92 OSDI units). Meta-analysis was not possible for outcomes relating to ocular surface staining, Schirmer test or TBUT. We found low certainty evidence for a potential improvement in tear osmolarity (one study, 105 participants; MD -11.10, 95% CI -12.15 to -10.05 mOsmol/L). There was low level certainty regarding any potential effect on gastrointestinal side effects (two studies, 91 participants; RR 2.34, 95% CI 0.35 to 15.54).

Authors' conclusions: Overall, the findings in this review suggest a possible role for long-chain omega-3 supplementation in managing dry eye disease, although the evidence is uncertain and inconsistent. A core outcome set would work toward improving the consistency of reporting and the capacity to synthesize evidence.

PubMed Disclaimer

Conflict of interest statement

SMN and KL received salary support from Cochrane Eyes and Vision @ US Project, funded by the National Eye Institute, at the National Institutes of Health. LED is the senior author on two studies considered in this review (Chinnery 2017; Deinema 2017); in view of this, a third (independent) person verified data extraction and risk of bias assessment for these studies.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Forest plot of comparison: 1 Oral long‐chain omega‐3 PUFAs (ie, EPA and DHA) versus placebo, outcome: 1.1 Dry eye symptoms, measured using the OSDI score [OSDI] units.
5
5
Forest plot of comparison: 1 Oral long‐chain omega‐3 PUFAs (ie, EPA and DHA) versus placebo, outcome: 1.3 Schirmer test (tear production) (mm/5 min).
6
6
Forest plot of comparison: 1 Oral long‐chain omega‐3 PUFAs (ie, EPA and DHA) versus placebo, outcome: 1.4 Tear break‐up time (TBUT) measured using fluorescein (seconds).
7
7
Forest plot of comparison: 1 Oral long‐chain omega‐3 PUFAs (ie, EPA and DHA) versus placebo, outcome: 1.6 Adverse event: gastrointestinal disorders.
8
8
Forest plot of comparison: 2 Combined omega‐3 and omega‐6 PUFAs versus placebo, outcome: 2.1 Schirmer test (tear production) (mm/5 min).
9
9
Forest plot of comparison: 2 Combined omega‐3 and omega‐6 PUFAs versus placebo, outcome: 2.2 TBUT: Mean change from baseline (seconds).
10
10
Forest plot of comparison: 3 Oral omega‐3 PUFAs plus conventional therapy versus conventional therapy alone (two RCTs), outcome: 3.1 OSDI score: mean score at study endpoint [OSDI units].
11
11
Forest plot of comparison: 4 Oral long‐chain omega‐3 PUFAs versus oral omega‐6 PUFAs, outcome: 4.1 Dry eye symptoms, measured using the OSDI score [OSDI] units.
12
12
Forest plot of comparison: 4 Oral long‐chain omega‐3 PUFAs versus oral omega‐6 PUFAs, outcome: 4.5 Adverse event: gastrointestinal disorders.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD011016

References

References to studies included in this review

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References to studies awaiting assessment

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References to ongoing studies

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NCT00344721 {published data only}
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NCT00357201 {published data only}
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NCT01102257 {published data only}
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NCT01733745 {published data only}
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NCT01880463 {published data only}
    1. NCT01880463. Dry eye disease in the vitamin D and omega‐3 Trial (VITAL). clinicaltrials.gov/ct2/show/NCT01880463 (first received June 19, 2013).
NCT02014922 {published data only}
    1. NCT02014922. A study to determine the relief of dry eye symptoms with the use of TheraTears® products (DUNLIN). https://clinicaltrials.gov/ct2/show/NCT02014922 (first received December 18, 2013).
NCT02802150 {published data only}
    1. NCT02802150. The effect of oral Zanthoxylum Schinifolium seed oil in individuals with dry eye disease. https://clinicaltrials.gov/ct2/show/NCT02802150 (first received June 16, 2016).
NCT02871440 {published data only}
    1. NCT02871440. A two comparator, controlled phase 3 study in patients with and without evaporative dry eye. clinicaltrials.gov/ct2/show/NCT02871440 (first received August 18, 2016).
NCT02908282 {published data only}
    1. NCT02908282. Topical omega‐3 fatty acids (REMOGEN OMEGA) in the treatment of dry eye (REMOTOP). clinicaltrials.gov/ct2/show/NCT02908282 (first received September 20, 2016).
NCT03141931 {published data only}
    1. NCT03141931. The effects of dietary supplementation with a combination of flaxseed oil, borage oil and fish oil omega‐3 fatty acids on ocular comfort including symptoms of dry eye. clinicaltrials.gov/ct2/show/NCT03141931 (first received May 5, 2017).
NCT03265327 {published data only}
    1. NCT03265327. Effect of an oral supplement containing omega‐3 and omega‐6 on dry eye symptoms (TURMERIC). clinicaltrials.gov/ct2/show/NCT03265327 (first received August 29, 2017).
NCT03460548 {published data only}
    1. NCT03460548. REMOGEN® omega versus Cationorm® in the treatment of patients suffering from dry eye. https://clinicaltrials.gov/ct2/show/NCT03460548 (first received March 9, 2018).

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References to other published versions of this review

Ng 2014
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