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EW CORNEA 46 February 2017 by Vanessa Caceres EyeWorld Contributing Writer levels of the cytokine interleukin 17A compared with placebo. The study also showed that improvements in objective clinical signs took place before significant changes to dry eye symptoms. The focus on krill oil was an angle not used before in ophthalmic dry eye research, Dr. Downie said. Krill oil, derived from Antarctic krill, is thought to increase tissue distri- bution and bioavailability compared to the triglyceride form, Dr. Downie said. "Krill oil, being in predomi- nantly the phospholipid form of omega-3, is relatively unique, which is why we were interested in investi- gating its application to treat dry eye diseases in our study." A larger, multicenter clinical trial would help confirm the long- term efficacy and safety of krill oil, Dr. Downie said. Assessing oral re-esterified supplements Research published in September 2016 found a statistically significant improvement in various dry eye endpoints after use of oral re-esteri- fied omega-3 fatty acids, provided in the form of Dry Eye Omega Benefits (Physician Recommended Nutriceuticals, PRN, Plymouth Meet- ing, Pennsylvania). 2 The prospective, interventional, double-masked, placebo-controlled study gave 105 subjects 1,680 mg of EPA/560 mg of DHA or 3,136 mg of linoleic acid (control group) every day for 12 weeks. Participants improved their tear osmolarity, tear break-up time (TBUT), and omega-3 index levels, according to co-investigator Cynthia Matossian, MD, Matossian Eye Associates, Doylestown, Penn- sylvania. They also had a decrease in their OSDI scores and in their MMP- 9 positivity. "Having achieved this data further demonstrates the correlation between omega-3 levels and dry eye," Dr. Matossian said. "This is the only study to date that has hit these clinical endpoints collectively." Based on her research and clinical experience, Dr. Matossian recommends oral consumption of omega-3s to help treat lipid- depleted tear film. "I recommend clean sourced, PCB-, heavy metal- and mercury-free omega-3s for data is unmasked, will be shared with all," Dr. Asbell said. Here is a summary from three other researchers involved with re- cent dry eye/omega-3 studies. Considering krill oil An Australian randomized, double- masked, placebo-controlled trial that was recently published aimed to assess the efficacy of two long-chain omega-3 supplements in a 3-month period. 1 The first was the predom- inantly phospholipid form in krill oil, and the second was the triglycer- ide form in fish oil, said Dr. Downie, the lead investigator of the study. Sixty participants with moder- ate dry eye disease received placebo (1,500 mg/day of olive oil), krill oil (945 mg/day EPA + 510 mg/day DHA), or fish oil (1,000 mg/day EPA + 500 mg/day DHA). Investigators measured the mean change in tear osmolarity and dry eye symptoms (using the OSDI) as primary out- comes over the 3-month period. "We found that both forms of long-chain omega-3 supplements significantly reduced tear osmo- larity, improved tear stability, and reduced ocular bulbar redness in our dry eye participants," Dr. Downie said. Krill oil consumption led to slightly better improvement in dry eye symptoms and lower basal tear pating in DREAM; each will be fol- lowed for a year to 2 years, Dr. Asbell said. One advantage the trial has is that it takes place in real-world conditions, so patients can continue other treatments. "This is unlike Food and Drug Administration trials that typically require stopping all medications other than the study medication," Dr. Asbell said. Subjects in the study receive 2,000 mg eicosapentaenoic acid (EPA) and 1,000 mg docosahexaeno- ic acid (DHA) per day taken in five gel caps or a placebo of olive oil gel caps. The primary endpoint is the mean change from baseline in Ocular Surface Disease Index (OSDI) score at 6 and 12 months, but an ex- tension study will analyze the mean change in OSDI from 12 months to 18 and 24 months, according to ClinicalTrials.gov. Trial investigators also will ana- lyze inflammation biomarkers, tear osmolarity, anterior surface imaging, systemic inflammation, and the eco- nomic impact of dry eye disease. Many anticipate that the DREAM trial will shed light on the effect of omega-3 consumption on dry eye improvement. "Studies to date have shown mixed results, so the jury is still out on omega-3s and dry eye disease. Results, once the Findings show connections, but many await large trial results O mega-3 fatty acids gener- ate a great deal of interest in their potential to im- prove dry eye disease. Still, there are many questions to be answered, including the ideal dose, composition, and treatment duration, said Laura Downie, PhD, Department of Optometry and Vision Sciences, University of Mel- bourne, Parkville, Australia. A few researchers are attempting to pinpoint just how omega-3s help patients with dry eye. One much-anticipated study is a dream—literally. Dry Eye Assessment and Measurement—DREAM for short—is a randomized, controlled trial sponsored by the U.S. National Eye Institute. Its focus is to deter- mine the safety and effectiveness of oral omega-3 supplementation in dry eye patients, said Penny Asbell, MD, professor of ophthalmology, director of cornea and refractive services, and director of the cornea fellowship program, Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York. Dr. Asbell is the study chair. There are 500 subjects partici- Researchers continue to link omega-3 consumption and dry eye treatment

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