<p>Changes in Tear Lipid Layer Thickness and Symptoms Following the Use of Artificial Tears with and Without Omega-3 Fatty Acids: ARandomized, Double-Masked, Crossover Study</p>

Abstract

Purpose: To determine if an eye drop containing omega-3 fatty acids (Refresh Optive MEGA-3 ® , Allergan plc, Dublin, Ireland) increases the lipid layer thickness (LLT) of the tear film versus a non-emollient eye drop (Refresh Optive, Allergan plc). Methods: Patients (≥30 years) with baseline LLT ≤75 nm completed the Current Symptoms Survey (CSSa visual analog survey of dry eye symptoms), and LLT was measured pre-and post-instillation (15 and 60 mins) of their randomly assigned treatment. After washout, patients were tested with the other treatment. Primary endpoint: change in LLT from baseline. Secondary endpoint: CSS results. Results: Of 21 patients enrolled, 19 completed the study. With the omega-3-containing eye drop, the mean (standard deviation) LLT increase from baseline at 15 mins was statistically significant in the overall field (8.8 [11.5] nm; P<0.001), and in each individual zone (superior, central, and inferior). At 1 hr, the LLT change from baseline was statistically significant overall (4.4 [9.7] nm; P<0.02) and in the inferior and central zones. With the aqueous eye drop, LLT change from baseline was only significant at 15 mins in the inferior field. The CSS analysis revealed a ≥8.68-unit decrease in mean average dryness score from baseline at 15 and 60 mins post-instillation of the lipid-based treatment (P≤0.03). Conclusion: The eye drop containing omega-3 fatty acids increased LLT at 15 mins, maintaining it at 1 hr post-instillation. Dryness symptoms also improved and maintained improved levels 1 hr after instillation, indicating that the product may benefit symptomatic patients with evaporative dry eye.

Topical Omega-3 Polyunsaturated Fatty Acids for the Treatment of Dry Eye – Results from a Pilot Randomized Controlled Masked-Observer Study

“… 39 In a crossover study, an omega-3 PUFA containing eye drop formulation showed the increase in the lipid layer thickness of the tear film and dryness symptom relief to be superior to non-emollient aqueous formulation. 40 …”

“…39 In a crossover study, an omega-3 PUFA containing eye drop formulation showed the increase in the lipid layer thickness of the tear film and dryness symptom relief to be superior to non-emollient aqueous formulation. 40 Moreover, topical omega 3-PUFA proved to be beneficial in related ophthalmic indications, eg a faster regeneration of corneal nerve fibers was shown in patients with keratoconus after epi-off cross-linking 41 and reduced tear concentrations of pro-inflammatory cytokines in patients suffering from contact lens discomfort. 20 However, in this study, there was no effect on tear osmolarity and a greater symptomatic relief compared with placebo turned out not to be significant.…”

Docosanoid signaling modulates corneal nerve regeneration: effect on tear secretion, wound healing, and neuropathic pain

“… No control of placebo No/No No Improved A total of 68.1% of patients reported better tolerance to contact lenses after treatment Georgakopoulos et al, 2017 ( 91 ) Diabetic patients with DE, time = 3 months Group 1, n = 36 170 mg EPA and 115 mg DHA, three times daily No/No No Improved — Bhargava et al., 2015 ( 92 ) Computer-related DE, n = 456, time = 3 months Group 1, n = 220 180 mg EPA and 120 mg DHA, two times daily Group 2, n = 236 Placebo containing olive oil, two times daily Baseline (T0), 1 month of treatment (T1), 2 months of treatment (T2), 3 months of treatment (T3) Yes/Yes Double Improved — Deinema et al., 2017 ( 56 ) DE, n = 54, time = 3 months Group 1, n = 18 Krill oil (945 mg/day EPA + 510 mg/day DHA) Group 2, n = 19 Fish oil (1,000 mg/day EPA + 500 mg/day DHA) Group 3, n = 17 Placebo (olive oil, 1,500 mg/day) Yes/Yes Double Slightly improved Both krill and fish oil moderately reduced the DE symptoms. The pro-inflammatory cytokine, interleukin 17A, was significantly reduced in the krill oil group only at day 90 Goyal et al., 2017 ( 93 ) LASIK patients, n = 60, time = 12 weeks Group 1, n = 30 180 mg EPA and 120 mg DHA, four times daily Group 2, n = 3 Placebo Yes/Yes Double Slightly improved Fewer eyes had conjunctival staining with Lissamine DREAM, 2019 ( 52 ) DE, n = 499, time = 12 months Group 1, n = 329 400 mg EPA and 200 mg DHA, five times daily Group 2, n = 170 Placebo, 1,000 mg refined olive oil, five times daily Yes/Yes Double No significant effect Significantly increased EPA and DHA in red blood cells Fogt et al., 2019 ( 58 ) DE, n = 19, time = 1 h Drug 1, n = 19 Refresh Optive plus Omega-3, flaxseed oil Drug 2, n = 19 Refresh Optive The drug is randomly picked for two different visits (>2 days between) Yes/Yes Double Improved (short time) The lipid layer thickn...…”

“…To our knowledge, there is only one clinical trial using topical DHA ( 58 ) ( Table 2 ). This trial was based on previous studies showing that AA, DHA, and EPA were found in the tears of patients with DED and that the ratio of ω-6 (AA):ω-3 (DHA+EPA) correlates with the severity of the tear film dysfunction ( 59 ).…”

“…This trial was based on previous studies showing that AA, DHA, and EPA were found in the tears of patients with DED and that the ratio of ω-6 (AA):ω-3 (DHA+EPA) correlates with the severity of the tear film dysfunction ( 59 ). The small trial (19 patients treated topically with DHA) demonstrated that treatment with eye drops containing omega-3 fatty acids increases lipid layer thickness of the tear film up to 1 h after instillation ( 58 ).…”