{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:32:57Z","timestamp":1791844377467,"version":"4.3.4"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T00:00:00Z","timestamp":1556236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>To investigate the effects of polyunsaturated fatty acids (PUFAs) in patients with dry eye disease (DED), a multifactorial inflammatory disorder, we searched Cochrane Library, EMBASE, PubMed, and Web of Science for randomized clinical trials (RCTs) investigating the effect of PUFAs in patients with DED before March 2019. Two reviewers independently abstracted data of tear breakup time (TBUT), Schirmer\u2019s test, osmolarity, and ocular surface disease index (OSDI). We conducted pairwise meta-analysis using means and standard deviations (SDs) in a random-effects model for continuous outcomes. Thirteen eligible RCTs with 1782 patients with nonspecific typical DED were included. Patients who received PUFA treatment without other eye medications exhibited greater improvements in TBUT (MD = 1.80; p = 0.001), Schirmer test scores (MD = 0.50; p &lt; 0.001), osmolarity (MD = \u221215.95; p &lt; 0.001), and OSDI scores (MD = \u221210.19; p &lt; 0.001) than those who received placebo treatment. However, the effects of PUFAs on TBUT (p &lt; 0.001) and OSDI scores (p = 0.03) weakened with treatment duration. PUFAs are effective in treating nonspecific typical DED, particularly as a short-term treatment, with relatively few adverse events. Therefore, in real-world clinical practice, PUFA supplements are worth being suggested to patients with nonspecific typical DED who are not concurrently using other topical or systematic eye medications.<\/jats:p>","DOI":"10.3390\/nu11050942","type":"journal-article","created":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T07:52:59Z","timestamp":1556265179000},"page":"942","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Effects of Polyunsaturated Fatty Acids on Nonspecific Typical Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2544-2353","authenticated-orcid":false,"given":"Sheng-Chu","family":"Chi","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 110, Taiwan"},{"name":"Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan City 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6327-6889","authenticated-orcid":false,"given":"Hsin-I","family":"Tuan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan"},{"name":"School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8244-2846","authenticated-orcid":false,"given":"Yi-No","family":"Kang","sequence":"additional","affiliation":[{"name":"Center for Evidence-Based Medicine, Department of Education, Taipei Medical University Hospital, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/j.ophtha.2017.07.010","article-title":"The pathophysiology of dry eye disease: What we know and future directions for research","volume":"124","author":"Pflugfelder","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_2","first-page":"733","article-title":"International dry eye workshop (dews). Update of the disease","volume":"82","author":"Peral","year":"2007","journal-title":"Arch. Soc. Esp. Oftalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.jtos.2017.08.003","article-title":"Tfos dews ii report executive summary","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"Tfos dews ii definition and classification report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jtos.2017.05.006","article-title":"Tfos dews ii management and therapy report","volume":"15","author":"Jones","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_6","first-page":"71","article-title":"The pathophysiology, diagnosis, and treatment of dry eye disease","volume":"112","author":"Messmer","year":"2015","journal-title":"Dtsch. Arztebl Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1056\/NEJM198902023200501","article-title":"The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells","volume":"320","author":"Endres","year":"1989","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S0952-3278(99)80015-5","article-title":"Human peripheral blood t lymphocyte proliferation after activation of the t cell receptor: Effects of unsaturated fatty acids","volume":"60","author":"Zurier","year":"1999","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s00417-009-1080-z","article-title":"Efficacy of a 2-month dietary supplementation with polyunsaturated fatty acids in dry eye induced by scopolamine in a rat model","volume":"247","author":"Viau","year":"2009","journal-title":"Graefes. Arch. Clin. Exp. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exer.2013.12.014","article-title":"Alpha-lipoic acid restores tear production in an animal model of dry eye","volume":"120","author":"Andrade","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1093\/ajcn\/82.4.887","article-title":"Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women","volume":"82","author":"Miljanovic","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_12","first-page":"169","article-title":"Effectiveness and tolerability of dietary supplementation with a combination of omega-3 polyunsaturated fatty acids and antioxidants in the treatment of dry eye symptoms: Results of a prospective study","volume":"8","year":"2014","journal-title":"Clin. Ophthalmol. (Auckland, N.Z.)"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1097\/00003226-200303000-00002","article-title":"Systemic linoleic and gamma-linolenic acid therapy in dry eye syndrome with an inflammatory component","volume":"22","author":"Barabino","year":"2003","journal-title":"Cornea"},{"key":"ref_14","first-page":"811","article-title":"A randomized controlled trial of omega-3 fatty acids in dry eye syndrome","volume":"6","author":"Bhargava","year":"2013","journal-title":"Int. J Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/opo.12365","article-title":"Omega-3 supplementation is neuroprotective to corneal nerves in dry eye disease: A pilot study","volume":"37","author":"Chinnery","year":"2017","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_16","first-page":"448","article-title":"Efficacy assessment of nutrilarm(r), a per os omega-3 and omega-6 polyunsaturated essential fatty acid dietary formulation versus placebo in patients with bilateral treated moderate dry eye syndrome","volume":"34","author":"Baudouin","year":"2011","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ophtha.2016.09.023","article-title":"A randomized, double-masked, placebo-controlled clinical trial of two forms of omega-3 supplements for treating dry eye disease","volume":"124","author":"Deinema","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1016\/j.ophtha.2013.04.006","article-title":"Short-term consumption of oral omega-3 and dry eye syndrome","volume":"120","author":"Kangari","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"215","DOI":"10.2220\/biomedres.34.215","article-title":"Effects of dietary supplementation with fish oil on dry eye syndrome subjects: Randomized controlled trial","volume":"34","author":"Kawakita","year":"2013","journal-title":"Biomed. Res."},{"key":"ref_20","first-page":"139","article-title":"Effects of a nutraceutical formulation based on the combination of antioxidants and omega-3 essential fatty acids in the expression of inflammation and immune response mediators in tears from patients with dry eye disorders","volume":"8","year":"2013","journal-title":"Clin. Interv. Aging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1097\/ICO.0b013e318299549c","article-title":"Long-term supplementation with n-6 and n-3 pufas improves moderate-to-severe keratoconjunctivitis sicca: A randomized double-blind clinical trial","volume":"32","author":"Sheppard","year":"2013","journal-title":"Cornea"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1056\/NEJMoa1709691","article-title":"N\u22123 fatty acid supplementation for the treatment of dry eye disease","volume":"378","author":"Asbell","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e591","DOI":"10.1111\/j.1755-3768.2011.02196.x","article-title":"A multicentre, double-masked, randomized, controlled trial assessing the effect of oral supplementation of omega-3 and omega-6 fatty acids on a conjunctival inflammatory marker in dry eye patients","volume":"89","author":"Baudouin","year":"2011","journal-title":"Acta. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.3945\/jn.109.118901","article-title":"Oral sea buckthorn oil attenuates tear film osmolarity and symptoms in individuals with dry eye","volume":"140","author":"Larmo","year":"2010","journal-title":"J. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1097\/ICO.0b013e3181f22e03","article-title":"Pilot, prospective, randomized, double-masked, placebo-controlled clinical trial of an omega-3 supplement for dry eye","volume":"30","author":"Wojtowicz","year":"2011","journal-title":"Cornea"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.cct.2018.06.002","article-title":"Dry eye assessment and management (dream(c)) study: Study design and baseline characteristics","volume":"71","author":"Asbell","year":"2018","journal-title":"Contemp. Clin. Trials"},{"key":"ref_27","first-page":"e677","article-title":"Efficacy of nutritional supplementation with omega-3 and omega-6 fatty acids in dry eye syndrome: A systematic review of randomized clinical trials","volume":"95","year":"2017","journal-title":"Acta. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/S0181-5512(06)70106-1","article-title":"Improvement of dry eye symptoms with polyunsaturated fatty acids","volume":"29","author":"Creuzot","year":"2006","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jtos.2017.09.007","article-title":"Mechanisms, imaging and structure of tear film breakup","volume":"16","author":"Begley","year":"2018","journal-title":"Ocul. Surf."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.exer.2015.05.002","article-title":"The real reason for having a meibomian lipid layer covering the outer surface of the tear film - a review","volume":"137","author":"Millar","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1006\/jcis.1996.0595","article-title":"Deposition and thinning of the human tear film","volume":"184","author":"Wong","year":"1996","journal-title":"J. Colloid. Interface Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"511","DOI":"10.2147\/VHRM.S85165","article-title":"Comparison of bioavailability of krill oil versus fish oil and health effect","volume":"11","author":"Ulven","year":"2015","journal-title":"Vas. Health Risk Manag."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0260-8774(02)00272-8","article-title":"Oxidative stability of carotenoid pigments and polyunsaturated fatty acids in microparticulate diets containing krill oil for nutrition of marine fish larvae","volume":"56","author":"Bustos","year":"2003","journal-title":"J. Food Eng."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.ophtha.2014.11.006","article-title":"Effects of corneal nerve density on the response to treatment in dry eye disease","volume":"122","author":"Kheirkhah","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.ophtha.2015.09.029","article-title":"Topical fluorometholone protects the ocular surface of dry eye patients from desiccating stress: A randomized controlled clinical trial","volume":"123","author":"Fernandez","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/ICL.0000000000000049","article-title":"Effect of loteprednol etabonate 0.5% on initiation of dry eye treatment with topical cyclosporine 0.05%","volume":"40","author":"Sheppard","year":"2014","journal-title":"Eye Contact Lens"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.jtos.2014.12.006","article-title":"Efficacy and safety of topical 0.05% cyclosporine eye drops in the treatment of dry eye syndrome: A systematic review and meta-analysis","volume":"13","author":"Wan","year":"2015","journal-title":"Ocul. Surf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1111\/nure.12145","article-title":"Efficacy of polyunsaturated fatty acids for dry eye syndrome: A meta-analysis of randomized controlled trials","volume":"72","author":"Zhu","year":"2014","journal-title":"Nutr. Rev."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/5\/942\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:47:18Z","timestamp":1760186838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/5\/942"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,26]]},"references-count":38,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["nu11050942"],"URL":"https:\/\/doi.org\/10.3390\/nu11050942","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,26]]}}}