NIHR DC Discover

NIHR Signal Fish oil supplements are ineffective for treating dry eyes

Published on 3 July 2018

doi: 10.3310/signal-000612

Omega-3 fatty acids or ‘fish oil’ supplements are no more effective than inactive olive oil capsules for relieving dry eye disease. Some patients take fish oil supplements for this common problem, but this new evidence suggests that they consider alternatives.

Dry eye disease is a common long-term inflammatory condition causing discomfort, and disturbances including blurred vision. Treatment of symptoms includes using artificial tears. Although guidelines recognise the lack of existing evidence for fish oil supplements, people continue to use them on the advice of health professionals.

This US-based trial did not find a difference on several measures compared with placebo over one year of follow up.

The trial was based on community patients, so is likely to apply to people visiting their GP for help with dry eye disease, or who buy supplements over the counter. Practitioners can now confidently tell their patients that new evidence suggests this widely available supplement is no better than taking olive oil for relieving dry eye symptoms.

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Why was this study needed?

Dry eye disease is a long-term, inflammatory, age-related condition leading to discomfort, eye-tiredness, and visual disturbances. These symptoms can impair quality of life and everyday activities, such as reading and driving.

Symptoms may affect as many as 7 to 33% of adults, though figures vary depending on how the condition is defined and the presence of common risk factors such as age, female sex, and smoking. Treatment focusses on relieving symptoms by using artificial tear drops or reducing inflammation with medication such as cyclosporin A.

While there is no definitive evidence for the use of omega-3 fatty acids for a cure or symptom relief, this supplement is frequently recommended by healthcare professionals since omega-3 fatty acids are thought to have anti-inflammatory properties and few side effects. Current UK speciality guidelines suggest that they are worth a try despite acknowledging “insufficient evidence” to prove this. The American Academy of Ophthalmology notes that food industry failure to standardise supplement strength makes it difficult to compare findings between studies.

This well-designed placebo-controlled trial was carried out to address this uncertainty.

What did this study do?

The Dry Eye Assessment and Management (DREAM) trial recruited 349 patients with moderate-to-severe dry eye disease in the US. Participants had experienced dry eyes for at least six months before the start of the study.

Participants were randomised to receive 3,000mg omega-3 fatty acid supplements per day for 12 months, or olive oil placebo capsules, an omega-9 fatty acid. The main outcome was the mean change of the Ocular Surface Disease Index (OSDI) score, a scale of 0-100 where higher scores indicate more severe symptoms. Also, mean change in conjunctival staining score, corneal staining score, tear break-up time, and the result of Schirmer’s test were compared. 

To reduce the risk of bias, all participants and staff were unaware of treatment assignments. The supplement dose was the highest used in previous trials. Most participants adhered well to treatment (85.2%). The study also considered a broad range of patients from various settings, which improves its relevance to real-life practice.

What did it find?

  • There was no significant difference in the primary outcome at one year (mean change in OSDI score) between those treated with omega-3 fatty acid supplements and those prescribed an inactive placebo (-13.9 points and -12.5 points, 95% confidence interval -5.0 to 1.1, where higher score denotes more severe disease). This suggests a small “placebo effect” with both oils.
  • There was also no significant difference between the treatment groups for the trial’s secondary outcomes (conjunctival staining score, corneal staining score, tear break-up time, and Schirmer’s test).
  • Rates of serious and non-serious adverse events were similar between groups (6.0% serious and 61.9% non-serious in the omega-3 fatty acid group compared with 8.1% serious and 60.8% non-serious in the placebo group).

What does current guidance say on this issue?

The American Academy of Ophthalmology guidelines (published 2013) advises that omega-3 fatty acid products may be beneficial in the treatment of dry eye. Although they say evidence is insufficient to support the effectiveness of any particular formulation.

Similarly, UK guidelines from the College of Optometrists (2018) recommend a diet rich in omega-3 essential fatty acids for patients with dry eyes. A weak recommendation for oral essential fatty acid ‘fish oil’ supplements is also given, though the absence of high-quality trials to inform practice is noted.

What are the implications?

Using a representative group of patients, multiple outcome measures, and one-year follow up, this randomised controlled trial provides strong evidence that fish oil supplements are no more effective than placebo for the treatment of dry eyes.

This is high-quality evidence that resolves the uncertainty surrounding the use of this treatment and is likely to influence future advice on the topic and probably applies to diets rich in omega-3 fatty acids too.

Citation and Funding

Dry Eye Assessment and Management Study Research Group, Asbell PA, Maguire MG, Pistilli M, et al. n-3 fatty acid supplementation for the treatment of dry eye disease. N Engl J Med. 2018;378(18):1681-90.

Bibliography

American Academy of Ophthalmology. Dry eye syndrome preferred practice patterns. San Francisco: American Academy of Ophthalmology; 2013.

Gayton JL. Etiology, prevalence, and treatment of dry eye disease. Clinical Ophthalmology. 2009;3:405.

NHS Choices. Dry eye syndrome. London: Department of Health; updated 2016.

The College of Optometrists. Dry eye (keratoconjunctivitis sicca, KCS) clinical management guidelines. London: The College of Optometrists; 2018.

Vehof J, Kozareva D, Hysi PG, Hammond CJ. Prevalence and risk factors of dry eye disease in a British female cohort. British J Ophthalmol. 2014;98(12):1712-17.

Why was this study needed?

Dry eye disease is a long-term, inflammatory, age-related condition leading to discomfort, eye-tiredness, and visual disturbances. These symptoms can impair quality of life and everyday activities, such as reading and driving.

Symptoms may affect as many as 7 to 33% of adults, though figures vary depending on how the condition is defined and the presence of common risk factors such as age, female sex, and smoking. Treatment focusses on relieving symptoms by using artificial tear drops or reducing inflammation with medication such as cyclosporin A.

While there is no definitive evidence for the use of omega-3 fatty acids for a cure or symptom relief, this supplement is frequently recommended by healthcare professionals since omega-3 fatty acids are thought to have anti-inflammatory properties and few side effects. Current UK speciality guidelines suggest that they are worth a try despite acknowledging “insufficient evidence” to prove this. The American Academy of Ophthalmology notes that food industry failure to standardise supplement strength makes it difficult to compare findings between studies.

This well-designed placebo-controlled trial was carried out to address this uncertainty.

What did this study do?

The Dry Eye Assessment and Management (DREAM) trial recruited 349 patients with moderate-to-severe dry eye disease in the US. Participants had experienced dry eyes for at least six months before the start of the study.

Participants were randomised to receive 3,000mg omega-3 fatty acid supplements per day for 12 months, or olive oil placebo capsules, an omega-9 fatty acid. The main outcome was the mean change of the Ocular Surface Disease Index (OSDI) score, a scale of 0-100 where higher scores indicate more severe symptoms. Also, mean change in conjunctival staining score, corneal staining score, tear break-up time, and the result of Schirmer’s test were compared. 

To reduce the risk of bias, all participants and staff were unaware of treatment assignments. The supplement dose was the highest used in previous trials. Most participants adhered well to treatment (85.2%). The study also considered a broad range of patients from various settings, which improves its relevance to real-life practice.

What did it find?

  • There was no significant difference in the primary outcome at one year (mean change in OSDI score) between those treated with omega-3 fatty acid supplements and those prescribed an inactive placebo (-13.9 points and -12.5 points, 95% confidence interval -5.0 to 1.1, where higher score denotes more severe disease). This suggests a small “placebo effect” with both oils.
  • There was also no significant difference between the treatment groups for the trial’s secondary outcomes (conjunctival staining score, corneal staining score, tear break-up time, and Schirmer’s test).
  • Rates of serious and non-serious adverse events were similar between groups (6.0% serious and 61.9% non-serious in the omega-3 fatty acid group compared with 8.1% serious and 60.8% non-serious in the placebo group).

What does current guidance say on this issue?

The American Academy of Ophthalmology guidelines (published 2013) advises that omega-3 fatty acid products may be beneficial in the treatment of dry eye. Although they say evidence is insufficient to support the effectiveness of any particular formulation.

Similarly, UK guidelines from the College of Optometrists (2018) recommend a diet rich in omega-3 essential fatty acids for patients with dry eyes. A weak recommendation for oral essential fatty acid ‘fish oil’ supplements is also given, though the absence of high-quality trials to inform practice is noted.

What are the implications?

Using a representative group of patients, multiple outcome measures, and one-year follow up, this randomised controlled trial provides strong evidence that fish oil supplements are no more effective than placebo for the treatment of dry eyes.

This is high-quality evidence that resolves the uncertainty surrounding the use of this treatment and is likely to influence future advice on the topic and probably applies to diets rich in omega-3 fatty acids too.

Citation and Funding

Dry Eye Assessment and Management Study Research Group, Asbell PA, Maguire MG, Pistilli M, et al. n-3 fatty acid supplementation for the treatment of dry eye disease. N Engl J Med. 2018;378(18):1681-90.

Bibliography

American Academy of Ophthalmology. Dry eye syndrome preferred practice patterns. San Francisco: American Academy of Ophthalmology; 2013.

Gayton JL. Etiology, prevalence, and treatment of dry eye disease. Clinical Ophthalmology. 2009;3:405.

NHS Choices. Dry eye syndrome. London: Department of Health; updated 2016.

The College of Optometrists. Dry eye (keratoconjunctivitis sicca, KCS) clinical management guidelines. London: The College of Optometrists; 2018.

Vehof J, Kozareva D, Hysi PG, Hammond CJ. Prevalence and risk factors of dry eye disease in a British female cohort. British J Ophthalmol. 2014;98(12):1712-17.

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

Published on 14 April 2018

The Dry Eye Assessment and Management Study Research Group

N Engl J Med , 2018

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 .).

Schirmer's test determines whether the eye produces enough tears to keep it moist. The test uses paper strips inserted into the eye for several minutes to measure the production of tears. A negative (more than 10mm of moisture on the filter paper in 5 minutes) test result is normal. Both eyes normally secrete the same amount of tears.

Expert commentary

Nutritional supplements for eye conditions like dry eye disease are aggressively marketed. Symptomatic patients with dry eyes whose quality of life is considerably affected will try anything and everything that is available, despite lack of evidence. This has been the case with omega-3 supplements.

This study’s welcome evidence helps to establish that omega-3 does not play a role in alleviating symptoms and signs of dry eye disease, and stopping them could save the patients and health providers a lot of money. Dry eye disease is most likely a conundrum of conditions that are currently grouped under one diagnosis. Other more specific studies will follow, and evidence will build to establish the true potential of omega-3 in each disease.

Harminder S Dua, Chair & Professor of Ophthalmology, University of Nottingham