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N Engl J Med. 2018 May 3;378(18):1681-1690. doi: 10.1056/NEJMoa1709691. Epub 2018 Apr 13.

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

Collaborators (218)

Hom MM, Quintana M, Zermeno A, Pendleton R, McCluskey D, Amador D, Corona I, Wechter V, Childs C, Do U, Lerma M, Li W, Young Z, Yuen T, Dubiner H, Ambrosia H, Bowser M, Chen P, Dubiner H, Fuller C, New K, Nguyen TV, Seville E, Strait D, Wang C, Williams S, Weber R, Sutphin J, Bishara M, Bryan A, Ertel A, Green K, Pantoja G, Small A, Williamson C, Greiner J, DiPronio E, Lindsay M, McPherson A, Oliver P, Wu R, Dana R, Abud T, Adams L, Arnofsky M, Candlish J, Chilakamarri P, Ciolino J, Crandall N, Di Zazzo A, Fernandes M, Jafri M, Johnson B, Kheirkhah A, Kiebdaj S, Mullins A, Nova M, Satitpitakul V, Shao C, Suri K, Tadla V, Ujwala S, Yin J, Yu M, Hood C, Hussain M, Manno E, Rozek L, Baker K, Belsaas A, Berg E, Blakstad A, DauSchmidt K, Fallenstein L, Fahmy AM, Fahmy MM, Georges G, Harter DE, Hauswirth SG, Johnson M, Meshalkin E, Pelzer R, Tisdale J, Wick JC, Tauber J, Hefter M, Silverstein S, Bentley C, Dominguez E, Kleinsasser K, Barry B, Kuklinski E, Amir A, Chen N, Oydanich M, Spahiu V, Vo A, Weinstein M, Vaz T, Hindman H, Aleese R, Czubinski A, Gagarinas G, McDowell P, O’Gara G, Steinmetz K, Bunya V, Bezzerides M, Caggiano D, Drossner S, Dupont J, Keiser M, Massaro M, Orlin S, O’Sullivan R, Christensen M, Adkins H, Brafford R, Ervin C, Grant R, Newman C, Shettle L, Shettle D, Cohen S, Rodman D, Caster T, Gupta P, Raghupathy S, Sayegh R, Shen J, Drutz N, Joyner L, Mathis M, Menghini M, Robinson C, Goldberg D, Jenkins L, Rodriguez B, Jones JP, Thompson N, Wolstan B, Jones M, Lemaster A, Ransom-Chaney J, Rudy W, Hamrah P, Commodore M, Iyore C, Lazarev L, Mullen L, Pondelis N, Satsuma C, Jain S, Cowen P, Hallak J, Mun C, Toh R, Singh I, Lightfield P, Lowery E, Ornelas S, Sanka RK, Saunders B, Mulqueeny SP, Pohlmeier M, Aune C, Gabriel H, Walker KM, Newsome J, Centers R, Farkouh M, Kim-Schulze S, Chapkin R, Greco G, Simopoulos A, Lashley I, Dentone P, Gadaria-Rathod N, Massingale M, Antonova N, Brightwell-Arnold M, Farrar J, Harkins S, Huang J, McWilliams K, Peskin E, Ryan S, Smolen H, Whearry C, Yu Y, Wei Y, Roy N, Epstein S, Rockwell K Jr, Moser A, Jones RO, Daniel E, Martin ER, Ostroff CP, Smith E, Kadakia PA, Redford M, McWilliams K, Wisniewski S, Brenna T, Christen WG Jr, Huang JF, McCarthy CS, Mayne ST, Palta M, Schein OD, Chuang J, Marchan M, Hao T, Heisler C, Hu C, Throop C, Moolchandani V.

Author information

Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York
Department of Ophthalmology, University of Pennsylvania, Philadelphia
Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland
Minnesota Eye Consultants, Bloomington
School of Optometry, University of California, Berkeley, Berkeley
Department of Ophthalmology, University of Michigan, Ann Arbor



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.


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.


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.


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 number, NCT02128763 .).

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