Effectiveness of Mediterranean Diet Implementation in Dry Eye Parameters: A Study of PREDIMED-PLUS Trial.

The purpose of this study is to evaluate the effect of a Mediterranean diet supplemented with extra virgin olive oil and nuts on dry eye parameters. The participants in this study were randomized into one of the two interventional arms: (1) a standard intervention group, a Mediterranean diet supplemented with extra virgin olive oil and nuts; and (2) an intensive intervention group, based on a hypocaloric Mediterranean diet and an intensive lifestyle program with physical activity and weight-loss goals. In both groups, common dry eye tests were conducted at baseline and after six months: the Ocular Surface Disease Index (OSDI), the Dry Eye Scoring System (DESS), tear break-up time (TBUT), the Schirmer's test, and the Oxford staining grade. Sixty-seven eyes were examined. After six months, dry eye parameters improved in both groups; differences between groups were favorable for the intensive intervention group. The implementation of a Mediterranean diet pattern was beneficial for the selected patients with dry eye, and could be beneficial for patients with dry eye in general. Behavioral support for diet adherence and the promotion of healthy lifestyles (exercise) and weight loss (calorie restriction) have an added positive effect.

The Role of Nutrition and Nutritional Supplements in Ocular Surface Diseases.

Dry eye disease (DED) is a multifactorial disease of the ocular surface system whose chore mechanisms are tear film instability, inflammation, tear hyperosmolarity and epithelial damage. In recent years, novel therapies specifically targeting inflammation and oxidative stress are being investigated and used in this field. Therefore, an increasing body of evidence supporting the possible role of different micronutrients and nutraceutical products for the treatment of ocular surface diseases is now available. In the present review, we analyzed in detail the effects on ocular surface of omega-3 fatty acids, vitamins A, B12, C, D, selenium, curcumin and flavonoids. Among these, the efficacy of omega-3 fatty acid supplementation in ameliorating DED signs and symptoms is supported by robust scientific evidence. Further long-term clinical trials are warranted to confirm the safety and efficacy of the supplementation of the other micronutrients and nutraceuticals.

Effects of Polyunsaturated Fatty Acids on Nonspecific Typical Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

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's 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 < 0.001), osmolarity (MD = -15.95; p < 0.001), and OSDI scores (MD = -10.19; p < 0.001) than those who received placebo treatment. However, the effects of PUFAs on TBUT (p < 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.

Efficacy of nutritional supplementation with omega-3 and omega-6 fatty acids in dry eye syndrome: a systematic review of randomized clinical trials.

PURPOSE: To critically appraise scientific evidence regarding the efficacy of nutritional supplementation with omega-3 and omega-6 fatty acids for the treatment of dry eye syndrome (DES). METHODS: A systematic review of randomized clinical trials was performed. Two independent reviewers selected and analysed the scientific papers that met inclusion and exclusion criteria. Objective and subjective efficacy outcomes were assessed. RESULTS: The trials involved a total of 2591 patients in fifteen independent studies. All studies were published between 2005 and 2015. The supplements used were mostly omega-3 and omega-6 in different proportions. Subjective improvement was measured using mainly Ocular Surface Disease Index (OSDI) test and Dry Eye Severity Score (DESS) test: significant differences in favour of the experimental group were found in seven of the studies. The objective amelioration was assessed by lacrimal function parameters: Tear break-up time (TBUT) significantly increased in nine studies and Schirmer's test in four studies. CONCLUSION: We observed a discrete improvement in the parameters of tear function. Scientific evidence is not strong enough to systematically recommend the use of omega-3 and omega-6 fatty acids as a standalone treatment of DES independently from its aetiology. However, they could be considered as an effective alternative to topical treatment in patients with DES secondary to certain pathologies.

Autologous and allogeneic serum eye drops. The Dutch perspective.

If regular artificial tears are ineffective for treatment of ocular surface disorders (including extreme dry eye syndrome), serum eye drops (SEDs) may provide a way to relieve the symptoms. However, not all patients are eligible to donate blood to produce autologous SEDs. Therefore, the use of allogeneic SEDs (obtained from voluntary blood donors) should be explored as an alternative for autologous SEDs. The Dutch blood bank organization is currently looking into the possibilities to provide allogeneic SEDs, as (GMP) regulations become stricter, making it for hospitals more difficult to provide autologous SEDs. To demonstrate effectiveness of both autologous and allogeneic SEDs, a clinical trial is planned. The current status of SEDs in The Netherlands is described. This paper is based on summary of the presentation given at the DGTI meeting in Dresden.

A metabolomic approach to dry eye disorders. The role of oral supplements with antioxidants and omega 3 fatty acids.

PURPOSE: We used nuclear magnetic resonance spectroscopy of hydrogen-1 nuclei ((1)H NMR S) to analyze the metabolic profile of reflex tears from patients with dry eye disorders. METHODS: We performed a prospective case-control study involving 90 participants: 55 patients diagnosed with dry eye syndrome (DESG) and 35 healthy subjects (control group, CG). From the DESG, two subgroups were formed: mild DES (n=22) and moderate DES (n=33). Participants were prescribed an oral nutraceutic supplementation containing antioxidants and essential polyunsaturated fatty acids to be taken as three capsules per day for 3 months. Reflex tears (20-30 µl) were collected from the tear meniscus of both eyes of each subject with a microglass pipette. Nuclear magnetic resonance (NMR) spectra were acquired with a standard one-dimensional pulse sequence with water suppression; 256 free induction decays were collected into 64,000 data points with 14 ppm spectral width. RESULTS: Basal tears showed a differential metabolomic profile between groups. Almost 50 metabolites were identified by H cholesterol, N-acetylglucosamine, glutamate, amino-n-butyrate, choline, glucose, and formate were detected before supplementation and choline/acetylcholine after supplementation. The metabolic profile of the tears was statistically different between groups, as well as before and after supplementation. CONCLUSIONS: Our data indicate that DES induces changes in the tear metabolic profile that can be modified with appropriate oral supplementation with antioxidants and essential polyunsaturated fatty acids.

Efficacy of polyunsaturated fatty acids for dry eye syndrome: a meta-analysis of randomized controlled trials.

Dry eye syndrome (DES) is a common ocular disease that significantly affects the quality of life. Polyunsaturated fatty acids (PUFAs) have been used to treat DES; however, randomized controlled trials (RCTs) of PUFA therapy yield discordant results. The objective of this study was to clarify the effects of PUFAs on DES through meta-analysis of all relevant RCTs. To do so, a comprehensive search of PubMed, Embase, the Cochrane Library, ISI Web of Science, and unpublished data was conducted. The changes in clinical and laboratory examinations, symptomatic scores, and rates of relevant symptoms were analyzed. Nine RCTs were included in the current meta-analysis. Compared with placebo, PUFA supplementation was not related to changes in tear film break-up time (weighted mean difference [WMD], 0.33; 95% confidence interval [CI], -0.05 to 0.72), Schirmer's test score (WMD, 0.32; 95%CI, -0.23 to 0.86), or lissamine green staining score (WMD, -0.77; 95%CI, -1.66 to 0.12). However, significant reductions were detected in the symptom score on the ocular surface disease index (WMD, -2.26; 95%CI, -4.44 to -0.08) and in the rate of cells positive for human leukocyte antigen DR (WMD, -5.80; 95%CI, -8.62 to -2.97). This comprehensive meta-analysis supports the use of PUFA supplementation as a potential effective therapy for DES.

Effect of a Mediterranean dietary pattern and vitamin D levels on Dry Eye syndrome.

PURPOSE: The aim of this study was to evaluate the association between a Mediterranean dietary pattern (MeDi) and Vitamin D levels on dry eye syndrome (DES). METHODS: This was a cross-sectional study. Male patients seen in the Miami Veterans Affairs eye clinic with normal eyelid, corneal, and conjunctival anatomy were recruited to participate in the study. The patients filled out the 2005 Block Food Frequency Questionnaire and the Dry Eye Questionnaire 5 and underwent measurement of tear film parameters. The serum level of 25-hydroxy vitamin D was also measured. The main outcome measures included the association among MeDi, Vitamin D levels, and DES. RESULTS: Two hundred forty-seven men underwent DES testing. The mean patient age was 69 years (range, 55-95). Using latent class analysis to categorize the presence or absence of disease and quantify its severity, we found that adherence to the MeDi was positively associated with the risk of having DES (odd ratio 1.25, 95% confidence interval, 1.06-1.47, P = 0.007) and with increasing disease severity. Vitamin D levels were not significantly associated with the presence or severity of disease. However, higher levels of vitamin D were associated with decreased DES symptoms, with a -1.24 decrease in median Dry Eye Questionnaire 5 score for every 10-U increase in Vitamin D levels (P = 0.01). CONCLUSIONS: Adherence to the MeDi was not associated with a beneficial effect on DES. Higher vitamin D levels had a small but favorable effect on DES symptoms.

Effects of dietary supplementation with fish oil on dry eye syndrome subjects: randomized controlled trial.

The purpose of this study was to evaluate the efficacy of fish oil supplementation added to usual dry eye treatment in dry eye subjects in a randomized controlled trial. Twenty-seven typical dry eye subjects were selected from 43 candidates by the diagnostic criterion for dry eye in this study. They were assigned to the randomized fish oil group (n = 15) or the placebo group (n = 12). Fish oil group ingested fish oil capsules containing eicosapentaenoic acid (EPA, 1245 mg/day) and docosahexaenoic acid (DHA, 540 mg/day) for 12 weeks. Placebo group ingested placebo capsules without EPA or DHA. A visual analog scale test estimating subjective symptoms, the Schirmer I test, tear film break-up time (BUT) measurement, fluorescein staining, and rose bengal staining were performed every 4 weeks during the 12-week supplementation period and 4-week washout period. The subjective symptom of "eye pain", BUT, and changes in rose bengal staining score of the fish oil group were significantly improved after 8-12 weeks of supplementation and/or 4 weeks of washout, compared to those of the placebo group. These results suggest that fish oil supplementation added to usual care may be effective in the treatment of dry eye.

Effect of calorie restriction on change in lacrimal gland with age.

Rapid growth in the number of dry eye syndrome patients has been observed worldwide. Increased life span is considered to be at least part of the reason for this because there is a close association between aging and decreased secretory function in the lacrimal gland. Recent advances have led to a new way of thinking about intervention in the aging process. Calorie restriction (CR) is believed to retard functional decline in various organs with age. We hypothesized that CR could prevent age-related lacrimal dysfunction. In this paper, we begin by reviewing the epidemiology of dry eye syndrome and explaining how aging affects lacrimal gland function. We then introduce a possible therapeutic approach to this problem, intervention by means of CR. Finally, suggestions are made for further prospective research that would elucidate the molecular mechanisms by which CR maintains lacrimal gland function.

[Efficacy assessment of Nutrilarm®, 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]. / Évaluation de l'efficacité du Nutrilarm®, complément nutritionnel à base d'acides gras essentiels polyinsaturés oméga 3 et oméga 6, versus placebo chez des patients atteints de sécheresse oculaire bilatérale modérée et traitée.

INTRODUCTION: Inflammation is one of the main mechanisms common to all forms of dry eye. Since polyunsaturated acids are known to show biological anti-inflammatory properties, the aim of this study was to evaluate the efficacy of dietary n-6 and n-3 fatty acids in patients suffering from ocular dryness. PATIENTS AND METHODS: One hundred and eighty-one patients diagnosed with bilateral moderate dry eye who were already treated with lachrymal substitutes were randomized in a double-blind international study to receive placebo or Nutrilarm(®) capsules (combination of omega-3 and omega-6), twice a day for 6 months. In all subjects, dryness feeling, overall subjective comfort, and ocular symptoms (burning, stinging, sandy and/or gritty sensation, light sensitivity, reflex tearing, and ocular fatigue) were evaluated at each visit. Furthermore, fluorescein tests (break-uptime and Oxford scheme) and lissamine green test were performed at each visit. The Schirmer test was performed at inclusion and after 6 months of treatment. RESULTS: After 6 months of supplementation with Nutrilarm(®), both the BUT scores and ocular fatigue were significantly improved when compared with placebo (P=0.036 and P=0.044, respectively). There was a trend in favor of Nutrilarm(®) in terms of the efficacy evaluated by the investigator (P=0.061). Fewer patients experienced a feeling of severe dryness with Nutrilarm(®) compared with placebo after 6 months of treatment (2.5 and 9.3%, respectively), but the difference was not statistically significant. CONCLUSION: Oral administration of a double supplementation dietary n-6 and n-3 fatty acids present an additional therapeutic advantage in patients suffering from ocular dryness who were already treated with lachrymal substitutes.

Nutritional supplements for dry eye syndrome.

PURPOSE OF REVIEW: Essential fatty acids have been of interest in the treatment of systemic and ocular diseases, and is most recently of interest in the area of dry eye disease. RECENT FINDINGS: Systemic and topical omega-3 fatty acids and omega-6 fatty acids have been used recently as an adjunctive treatment for patients with dry eye disease. They appear to have efficacy against the symptoms of dry eye that many patients experience. This symptom is postulated to be secondary to the anti-inflammatory effects that have been previously described. Although this effect is promising, more investigation is warranted in order to standardize indication for use, and composition and dosing for treatment. SUMMARY: The use of essential fatty acids as a nutritional supplement is a novel treatment for patients with dry eye syndrome.

Essential fatty acids for dry eye: A review.

PURPOSE: Dry eye is a common complaint often encountered in optometric practice. However, it is a difficult condition to treat as clinical signs do not always correlate with patient symptoms. Essential fatty acids (EFA), particularly omega-3 EFA, may be effective in dealing with the underlying causes. METHODS: A literature review was carried out on the PubMed, ScienceDirect and Ovid databases. Searches included keywords such as 'dry eye', 'essential fatty acids' and 'nutrition' to find articles relating to the treatment of dry eye syndrome (DES) with omega-3 EFAs. RESULTS: Omega-3 and -6 EFAs need to be consumed together within a reasonable ratio to be effective. Currently, typical diets in developed countries lack omega-3 EFA and this results in an overexposure to omega-6. Omega-3 supplementation has an anti-inflammatory effect, inhibiting creation of omega-6 prostaglandin precursors. Omega-3 EFAs also demonstrate anti-inflammatory action in the lacrimal gland preventing apoptosis of the secretory epithelial cells. Supplementation clears meibomitis, allowing a thinner, more elastic lipid layer to protect the tear film and cornea. CONCLUSION: Dietary supplementation of omega-3 EFA has already proven to be effective in coronary heart disease and arthritis. Safety is not a concern as it works synergistically with omega-6 in the body. Evidence suggests that supplementation with omega-3 EFA may be beneficial in the treatment and prevention of DES.

Efficacy of a 2-month dietary supplementation with polyunsaturated fatty acids in dry eye induced by scopolamine in a rat model.

BACKGROUND: This study was conducted to evaluate the efficacy of dietary n-6 and n-3 polyunsaturated fatty acids (PUFAs) in dry eye in a rat model. METHODS: Female Lewis rats were fed with diets containing (1) gamma-linolenic acid (GLA), (2) eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), or (3) GLA + EPA + DHA, for 2 months before the induction of dry eye using a continuous delivery of scopolamine and during scopolamine treatment. Two, 10 and 28 days after dry-eye induction, clinical signs of corneal dryness were evaluated in vivo using fluorescein staining. MHC II expression and mucin rMuc5AC production in the conjunctival epithelium were evaluated by immunostaining. Lipids and prostaglandins (PGs) E(1) and E(2) were analysed from the exorbital lacrimal gland (LG). RESULTS: Dietary PUFAs minimised the occurrence of corneal keratitis 28 days after induction of dry eye. The decrease in mucin production observed on the conjunctival epithelium was partially prevented by EPA + DHA supplementation after 2 days of scopolamine treatment, as well as by GLA and GLA + EPA + DHA diets after 10 days of treatment. The overexpression of MHC II in the conjunctival epithelium caused by dry eye induction was significantly reduced only with the GLA + EPA + DHA diet after 28 days of treatment. Dietary PUFAs were incorporated into phospholipids of the exorbital LG. Induction of dry eye was associated with a significant increase in PGE(1) and PGE(2) levels in the exorbital LG, which was inhibited by dietary EPA + DHA at 10 days (for PGE(2)) and 28 days (for PGE(1)). CONCLUSIONS: Dietary GLA, EPA and DHA significantly interfered with lipid homeostasis in the exorbital LG and partially prevented the course of dry eye. In particular, our results demonstrate the efficacy of the combination of n-6 and n-3 PUFAs.