Omega-3 polyunsaturated fatty acids and corneal nerve health: Current evidence and future directions.

Corneal nerves play a key role in maintaining ocular surface integrity. Corneal nerve damage, from local or systemic conditions, can lead to ocular discomfort, pain, and, if poorly managed, neurotrophic keratopathy. Omega-3 polyunsaturated fatty acids (PUFAs) are essential dietary components that play a key role in neural development, maintenance, and function. Their potential application in modulating ocular and systemic inflammation has been widely reported. Omega-3 PUFAs and their metabolites also have neuroprotective properties and can confer benefit in neurodegenerative disease. Several preclinical studies have shown that topical administration of omega-3 PUFA-derived lipid mediators promote corneal nerve recovery following corneal surgery. Dietary omega-3 PUFA supplementation can also reduce corneal epithelial nerve loss and promote corneal nerve regeneration in diabetes. Omega-3 PUFAs and their lipid mediators thus show promise as therapeutic approaches to modulate corneal nerve health in ocular and systemic disease. This review discusses the role of dietary omega-3 PUFAs in maintaining ocular surface health and summarizes the possible applications of omega-3 PUFAs in the management of ocular and systemic conditions that cause corneal nerve damage. In examining the current evidence, this review also highlights relatively underexplored applications of omega-3 PUFAs in conferring neuroprotection and addresses their therapeutic potential in mediating corneal nerve regeneration.

Interventions for the Management of Computer Vision Syndrome: A Systematic Review and Meta-analysis.

TOPIC: To evaluate the efficacy and safety of interventions for treating eye strain related to computer use relative to placebo or no treatment. CLINICAL RELEVANCE: Computer use is pervasive and often associated with eye strain, referred to as computer vision syndrome (CVS). Currently, no clinical guidelines exist to help practitioners provide evidence-based advice about CVS treatments, many of which are marketed directly to patients. This systematic review and meta-analysis was designed to help inform best practice for eye care providers. METHODS: Eligible randomized controlled trials (RCTs) were identified in Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and trial registries, searched from inception through November 23, 2021. Eligible studies were appraised for risk of bias and were synthesized. The certainty of the body of evidence was judged using the Grading of Recommendations, Assessment, Development, and Evaluation system. Standardized mean differences (SMDs) were used when differently scaled measures were combined. RESULTS: Forty-five RCTs, involving 4497 participants, were included. Multifocal lenses did not improve visual fatigue scores compared with single-vision lenses (3 RCTs; SMD, 0.11; 95% confidence interval [CI], -0.14 to 0.37; P = 0.38). Visual fatigue symptoms were not reduced by blue-blocking spectacles (3 RCTs), with evidence judged of low certainty. Relative to placebo, oral berry extract supplementation did not improve visual fatigue (7 RCTs; SMD, -0.27; 95% CI, -0.70 to 0.16; P = 0.22) or dry eye symptoms (4 RCTs; SMD, -0.10; 95% CI, -0.54 to 0.33; P = 0.65). Likewise, berry extract supplementation had no significant effects on critical flicker-fusion frequency (CFF) or accommodative amplitude. Oral omega-3 supplementation for 45 days to 3 months improved dry eye symptoms (2 RCTs; mean difference [MD], -3.36; 95% CI, -3.63 to -3.10 on an 18 unit scale; P < 0.00001) relative to placebo. Oral carotenoid supplementation improved CFF (2 RCTs; MD, 1.55 Hz; 95% CI, 0.42 to 2.67 Hz; P = 0.007) relative to placebo, although the clinical significance of this finding is unclear. DISCUSSION: We did not identify high-certainty evidence supporting the use of any of the therapies analyzed. Low-certainty evidence suggested that oral omega-3 supplementation reduces dry eye symptoms in symptomatic computer users.

Investigating the Neuroprotective Effect of Oral Omega-3 Fatty Acid Supplementation in Type 1 Diabetes (nPROOFS1): A Randomized Placebo-Controlled Trial.

This randomized, double-masked, placebo-controlled trial evaluated the effects of oral omega-3 (n-3) fatty acid supplementation on peripheral nerves in type 1 diabetes. Participants with type 1 diabetes were assigned (1:1) to n-3 (1,800 mg/day fish oil) or placebo (600 mg/day olive oil) supplements for 180 days. The primary outcome was change from baseline in central corneal nerve fiber length (CNFL) at day 180. Secondary outcomes included change in other corneal nerve parameters, corneal sensitivity, peripheral small and large nerve fiber function, and ocular surface measures. Efficacy was analyzed according to the intention-to-treat principle. Safety assessments included diabetic retinopathy grade and adverse events. Between July 2017 and September 2019, 43 participants received n-3 (n = 21) or placebo (n = 22) supplements. All participants, except for two assigned to placebo, completed the trial. At day 180, the estimated increase in CNFL in the n-3 group, compared with placebo, was 2.70 mm/mm2 (95% CI 1.64, 3.75). The Omega-3 Index increased relative to placebo (3.3% [95% CI 2.4, 4.2]). There were no differences in most small or large nerve fiber functional parameters. Adverse events were similar between groups. In conclusion, we found in this randomized controlled trial that long-chain n-3 supplements impart corneal neuroregenerative effects in type 1 diabetes, indicating a role in modulating peripheral nerve health.

Omega-3 Fatty Acids and Eye Health: Opinions and Self-Reported Practice Behaviors of Optometrists in Australia and New Zealand.

This study investigated optometrists' attitudes and self-reported practice behaviors towards omega-3 fatty acids for eye health, and knowledge and understanding of their potential risks and benefits. An anonymous online survey was distributed to optometrists in Australia and New Zealand. Questions included practitioner demographics and practice modality; self-reported practices and recommendations relating to diet, nutritional supplements, and omega-3 fatty acids for age-related macular degeneration (AMD) and dry eye disease (DED); and practitioner knowledge about omega-3 fatty acids. Of 206 included surveys, most respondents (79%) indicated recommending for their patients to consume omega-3 fatty acids to improve their eye health. Sixty-eight percent of respondents indicated recommending omega-3-rich foods for AMD management, while 62% indicated recommending omega-3 supplements. Most respondents (78%) indicated recommending omega-3-rich foods or supplements for DED. For DED, recommended omega-3 supplement dosages were (median [inter-quartile range, IQR]) 2000 mg [1000-2750 mg] per day. The main sources of information reported by respondents to guide their clinical decision making were continuing education articles and conferences. In conclusion, optometrists routinely make clinical recommendations about diet and omega-3 fatty acids. Future education could target improving optometrists' knowledge of differences in the evidence for whole-food versus supplement sources of omega-3 fatty acids in AMD. Further research is needed to address uncertainties in the evidence regarding optimal omega-3 dosage and formulation composition in DED.

Intense pulsed light (IPL) therapy for the treatment of meibomian gland dysfunction.

BACKGROUND: Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease, which is the more prevalent form of dry eye disease. Intense pulsed light (IPL) therapy, involving treatment of the skin near the eyelids, has emerged as a potential treatment for MGD. OBJECTIVES: To evaluate the effectiveness and safety of intense pulsed light (IPL) for the management dry eye disease resulting from meibomian gland dysfunction (MGD). SEARCH METHODS: We searched CENTRAL, MEDLINE (Ovid), Embase Ovid and three trial registers for eligible clinical trials on 1 August 2019. There were no restrictions on publication status, date or language. SELECTION CRITERIA: We included randomised controlled trials (RCTs) studying the effectiveness or safety of IPL for treating MGD. DATA COLLECTION AND ANALYSIS: Our outcomes of interest were the change from baseline in subjective dry eye symptoms, adverse events, changes to lipid layer thickness, tear break-up time (TBUT), tear osmolarity, eyelid irregularity, eyelid telangiectasia, meibomian gland orifice plugging, meibomian gland dropout, corneal sodium fluorescein staining and conjunctival lissamine green staining. Two review authors independently screened abstracts and full-text articles, extracted data from eligible RCTs and judged the risk of bias using the Cochrane tool. We reached consensus on any disagreements by discussion. We summarised the overall certainty of the evidence using the GRADE Working Group approach. MAIN RESULTS: We included three RCTs, one from New Zealand, one from Japan and one from China, published between 2015 and 2019. Together, these trials enrolled 114 adults (228 eyes). Two studies used a paired-eye (inter-eye comparison) design to evaluate the effects of a sham (control) IPL treatment relative to an actual IPL treatment. One study randomised individuals to either an IPL intervention combined with meibomian gland expression (MGX), or MGX alone (standard therapy). The study follow-up periods ranged from 45 days to nine months. None of the trials were at low risk of bias in all seven domains. The first authors of two included studies were in receipt of funding from patents or the manufacturers of IPL devices. The funding sources and declaration of interests were not given in the report of the third included trial. All three trials evaluated the effect of IPL on dry eye symptoms, quantified using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Pooling data from two trials that used a paired-eye design, the summary estimate for these studies indicated little to no reduction in dry eye symptoms with IPL relative to a sham intervention (mean difference (MD) -0.33 units, 95% confidence interval (CI) -2.56 to 1.89; I² = 0%; 2 studies, 144 eyes). The other study was not pooled as it had a unit-of-analysis error, but reported a reduction in symptoms in favour of IPL (MD -4.60, 95% CI -6.72 to -2.48; 84 eyes). The body of evidence for this outcome was of very low certainty, so we are uncertain about the effect of IPL on dry eye symptoms. There were no relevant combinable data for any of the other secondary outcomes, thus the effect of IPL on clinical parameters relevant to dry eye disease are currently unclear. For sodium fluorescein TBUT, two studies indicated that there may be an improvement in favour of IPL (MD 2.02 seconds, 95% CI 0.87 to 3.17; MD 2.40 seconds, 95% CI 2.27 to 2.53; 172 eyes total; low-certainty evidence). We are uncertain of the effect of IPL on non-invasive tear break-up time (MD 5.51 seconds, 95% CI 0.79 to 10.23; MD 3.20, 95% CI 3.09 to 3.31 seconds; two studies; 140 eyes total; very low-certainty evidence). For tear osmolarity, one study indicated that there may be an improvement in favour of IPL (MD -7.00 mOsmol/L, 95% -12.97 to -1.03; 56 eyes; low-certainty evidence). We are uncertain of the effect of IPL on meibomian gland orifice plugging (MD -1.20 clinical units, 95% CI -1.24 to -1.16; 84 eyes; very low-certainty evidence). We are uncertain of the effect of IPL on corneal sodium fluorescein staining. One study reported no evidence of a difference between the IPL and sham intervention arms at three months of follow-up (P = 0.409), and a second study reported data favouring IPL (MD -1.00 units, 95% CI -1.07 to -0.93 units; 172 eyes in total; very low-certainty evidence). We considered the incidence of adverse events at the study endpoint, as a measure of safety. As most trials did not specifically report adverse events, the safety of IPL as a treatment for MGD could also not be determined with any certainty. Very low-certainty results from individual studies suggest some adverse effects that may be experienced by participants, include mild pain and burning, and the potential for partially losing eyelashes (due to clinician error). AUTHORS' CONCLUSIONS: This systematic review finds a scarcity of RCT evidence relating to the effectiveness and safety of IPL as a treatment for MGD. Whether IPL is of value for modifying the symptoms or signs of evaporative dry eye disease is currently uncertain. Due to a lack of comprehensive reporting of adverse events, the safety profile of IPL in this patient population is also unclear. The current limitations in the evidence base should be considered by clinicians using this intervention to treat MGD, and outlined to individuals potentially undergoing this procedure with the intent of treating dry eye disease. The results of the 14 RCTs currently in progress will be of major importance for establishing a more definitive answer regarding the effectiveness and safety of IPL for treating MGD. We intend to update this review when results from these trials become available.

Omega-3 polyunsaturated fatty acid oral supplements for improving peripheral nerve health: a systematic review and meta-analysis.

CONTEXT: Peripheral nerve damage can occur in a variety of systemic conditions and can have a profound impact on functional and psychological health. Currently, therapeutic interventions for peripheral nerve damage are limited. OBJECTIVE: The aim of this systematic review, conducted in accordance with the Cochrane Collaboration's handbook and reported according to the PRISMA checklist, was to evaluate the efficacy and safety of omega-3 oral supplements for improving peripheral nerve structure and function. DATA SOURCES: PubMed, Embase, and Cochrane databases, along with clinical trial registries, were searched from inception to February 2019. Evidence was identified, critically appraised, and synthesized, and the certainty of evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation approach. STUDY SELECTION: Randomized controlled trials assessing the effects of omega-3 oral supplementation on outcomes of peripheral nerve structure, peripheral nerve function, or both were eligible for inclusion. Titles and abstracts of identified articles were independently assessed for potential eligibility by 2 review authors. For studies judged as eligible or potentially eligible, full text articles were retrieved and independently assessed by 2 review authors to determine eligibility; disagreements were resolved by consensus. DATA EXTRACTION: Fifteen trials were included. Two clinically similar studies that investigated the effect of omega-3 supplementation in individuals receiving chemotherapy were meta-analyzed. Pooled data showed a reduced incidence of peripheral neuropathy (RR = 0.58; 95%CI, 0.43-0.77) and a preservation of sensory nerve action potential amplitudes with omega-3 supplementation compared with placebo (MD = 4.19 µV; 95%CI; 2.19-6.19). CONCLUSION: This review finds, with low certainty, that omega-3 supplementation attenuates sensory loss and reduces the incidence of neuropathy secondary to oxaliplatin and paclitaxel treatment relative to placebo. There is currently limited evidence to ascertain whether omega-3 supplementation is beneficial in other systemic conditions characterized by peripheral nerve damage. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD 42018086297.

An artificial tear containing flaxseed oil for treating dry eye disease: A randomized controlled trial.

PURPOSE: To evaluate the efficacy and safety of a nano-emulsion artificial tear (OM3) containing carboxymethylcellulose (CMC) and glycerin, flaxseed oil and castor oil, and three osmoprotectants (levocarnitine, erythritol, and trehalose) compared with an artificial tear (Refresh Optive Advanced [ROA]) containing the same ingredients with the exception of trehalose and flaxseed oil. METHODS: In this multicenter, double-masked, randomized, two-arm, parallel-group, 6-visit study (screening, baseline, and days 7, 30, 60, and 90), subjects with dry eye disease underwent an open-label, 7-day run-in with CMC 0.5% (Refresh Plus), before 1:1 randomization to OM3 or ROA for 90 days (both instilled ≥2 daily). Ocular Surface Disease Index (OSDI; primary endpoint change from baseline at day 90), tear film breakup time (TBUT), and ocular staining (combined/corneal/conjunctival) were assessed; change from baseline in these parameters was calculated at each timepoint. Treatment-related adverse events (AEs) were assessed at each visit. RESULTS: Overall, 242 subjects were randomized (OM3, n = 120; ROA, n = 122). At day 90, significant improvements in OSDI, ocular staining and TBUT were evident in both treatment groups. Significant (P < 0.05) between-group differences in favor of OM3 were observed for combined ocular staining (all timepoints), corneal staining (day 90), and conjunctival staining (day 30). Treatment-related AEs were higher in the ROA (9.8%) versus OM3 (6.7%) group; blurred vision was among the most commonly reported AE (OM3 0% vs ROA 4.1%). CONCLUSION: These findings support the application of OM3, a novel preservative-free, nano-emulsion tear formulation with trehalose and flaxseed oil, for the treatment of dry eye disease.

Omega-3 and omega-6 polyunsaturated fatty acids for dry eye disease.

BACKGROUND: Polyunsaturated fatty acid (PUFA) supplements, involving omega-3 and/or omega-6 components, have been proposed as a therapy for dry eye. Omega-3 PUFAs exist in both short- (alpha-linolenic acid [ALA]) and long-chain (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) forms, which largely derive from certain plant- and marine-based foods respectively. Omega-6 PUFAs are present in some vegetable oils, meats, and other animal products. OBJECTIVES: To assess the effects of omega-3 and omega-6 polyunsaturated fatty acid (PUFA) supplements on dry eye signs and symptoms. SEARCH METHODS: CENTRAL, Medline, Embase, two other databases and three trial registries were searched in February 2018, together with reference checking. A top-up search was conducted in October 2019, but the results have not yet been incorporated. SELECTION CRITERIA: We included randomized controlled trials (RCTs) involving dry eye participants, in which omega-3 and/or omega-6 supplements were compared with a placebo/control supplement, artificial tears, or no treatment. We included head-to-head trials comparing different forms or doses of PUFAs. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 34 RCTs, involving 4314 adult participants from 13 countries with dry eye of variable severity and etiology. Follow-up ranged from one to 12 months. Nine (26.5%) studies had published protocols and/or were registered. Over half of studies had high risk of bias in one or more domains. Long-chain omega-3 (EPA and DHA) versus placebo or no treatment (10 RCTs) We found low certainty evidence that there may be little to no reduction in dry eye symptoms with long-chain omega-3 versus placebo (four studies, 677 participants; mean difference [MD] -2.47, 95% confidence interval [CI] -5.14 to 0.19 units). We found moderate certainty evidence for a probable benefit of long-chain omega-3 supplements in increasing aqueous tear production relative to placebo (six studies, 1704 participants; MD 0.68, 95% CI 0.26 to 1.09 mm/5 min using the Schirmer test), although we did not judge this difference to be clinically meaningful. We found low certainty evidence for a possible reduction in tear osmolarity (one study, 54 participants; MD -17.71, 95% CI -28.07 to -7.35 mOsmol/L). Heterogeneity was too substantial to pool data on tear break-up time (TBUT) and adverse effects. Combined omega-3 and omega-6 versus placebo (four RCTs) For symptoms (low certainty) and ocular surface staining (moderate certainty), data from the four included trials could not be meta-analyzed, and thus effects on these outcomes were unclear. For the Schirmer test, we found moderate certainty evidence that there was no intergroup difference (four studies, 455 participants; MD: 0.66, 95% CI -0.45 to 1.77 mm/5 min). There was moderate certainty for a probable improvement in TBUT with the PUFA intervention relative to placebo (four studies, 455 participants; MD 0.55, 95% CI 0.04 to 1.07 seconds). Effects on tear osmolarity and adverse events were unclear, with data only available from a single small study for each outcome. Omega-3 plus conventional therapy versus conventional therapy alone (two RCTs) For omega-3 plus conventional therapy versus conventional therapy alone, we found low certainty evidence suggesting an intergroup difference in symptoms favoring the omega-3 group (two studies, 70 participants; MD -7.16, 95% CI -13.97 to -0.34 OSDI units). Data could not be combined for all other outcomes. Long-chain omega-3 (EPA and DHA) versus omega-6 (five RCTs) For long-chain omega-3 versus omega-6 supplementation, we found moderate certainty evidence for a probable improvement in dry eye symptoms (two studies, 130 participants; MD -11.88, 95% CI -18.85 to -4.92 OSDI units). Meta-analysis was not possible for outcomes relating to ocular surface staining, Schirmer test or TBUT. We found low certainty evidence for a potential improvement in tear osmolarity (one study, 105 participants; MD -11.10, 95% CI -12.15 to -10.05 mOsmol/L). There was low level certainty regarding any potential effect on gastrointestinal side effects (two studies, 91 participants; RR 2.34, 95% CI 0.35 to 15.54). AUTHORS' CONCLUSIONS: Overall, the findings in this review suggest a possible role for long-chain omega-3 supplementation in managing dry eye disease, although the evidence is uncertain and inconsistent. A core outcome set would work toward improving the consistency of reporting and the capacity to synthesize evidence.

Preliminary Validation of a Food Frequency Questionnaire to Assess Long-Chain Omega-3 Fatty Acid Intake in Eye Care Practice.

Clinical recommendations relating to dietary omega-3 essential fatty acids (EFAs) should consider an individual's baseline intake. The time, cost, and practicality constraints of current techniques for quantifying omega-3 levels limit the feasibility of applying these methods in some settings, such as eye care practice. This preliminary validation study, involving 40 adults, sought to assess the validity of a novel questionnaire, the Clinical Omega-3 Dietary Survey (CODS), for rapidly assessing long-chain omega-3 intake. Estimated dietary intakes of long-chain omega-3s from CODS correlated with the validated Dietary Questionnaire for Epidemiology Studies (DQES), Version 3.2, (Cancer Council Victoria, Melbourne, Australia) and quantitative assays from dried blood spot (DBS) testing. The 'method of triads' model was used to estimate a validity coefficient (ρ) for the relationship between the CODS and an estimated "true" intake of long-chain omega-3 EFAs. The CODS had high validity for estimating the ρ (95% Confidence Interval [CI]) for total long-chain omega-3 EFAs 0.77 (0.31-0.98), docosahexaenoic acid 0.86 (0.54-0.99) and docosapentaenoic acid 0.72 (0.14-0.97), and it had moderate validity for estimating eicosapentaenoic acid 0.57 (0.21-0.93). The total long-chain omega-3 EFAs estimated using the CODS correlated with the Omega-3 index (r = 0.37, p = 0.018) quantified using the DBS biomarker. The CODS is a novel tool that can be administered rapidly and easily, to estimate long-chain omega-3 sufficiency in clinical settings.

A Critical Appraisal of National and International Clinical Practice Guidelines Reporting Nutritional Recommendations for Age-Related Macular Degeneration: Are Recommendations Evidence-Based?

: Eye care professionals should have access to high quality clinical practice guidelines that ideally are underpinned by evidence from robust systematic reviews of relevant research. The aim of this study was to identify clinical guidelines with recommendations pertaining to dietary modification and/or nutritional supplementation for age-related macular degeneration (AMD), and to evaluate the overall quality of the guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. We also mapped recommendations to existing systematic review evidence. A comprehensive search was undertaken using bibliographic databases and other electronic resources for eligible guidelines. Quality appraisal was undertaken to generate scores for each of the six AGREE II domains, and mapping of extracted nutritional recommendations was performed for systematic reviews published up to March 2017. We identified 13 national and international guidelines, developed or updated between 2004 and 2019. These varied substantially in quality. The lowest scoring AGREE II domains were for 'Rigour of Development', 'Applicability' (which measures implementation strategies to improve uptake of recommendations), and 'Editorial Independence'. Only four guidelines used evidence from systematic reviews to support their nutritional recommendations. In conclusion, there is significant scope for improving current Clinical Practice Guidelines for AMD, and guideline developers should use evidence from existing high quality systematic reviews to inform clinical recommendations.

Modulating Contact Lens Discomfort With Anti-Inflammatory Approaches: A Randomized Controlled Trial.

Purpose: To assess the efficacy of anti-inflammatory approaches, comprising a topical corticosteroid and omega-3 supplements, for modulating the inflammatory overlay associated with contact lens discomfort (CLD). Methods: This randomized controlled trial involved 72 adults with CLD, randomized (1:1:1:1) to one of the following: placebo (oral olive oil), oral fish oil (900 mg/d eicosapentaenoic acid [EPA] + 600 mg/d docosohexaenoic acid [DHA]), oral combined fish+flaxseed oils (900 mg/d EPA + 600 mg/d DHA + 900 mg/d alpha-linolenic acid), or omega-3 eye-drops (0.025% EPA + 0.0025% DHA four times per day [qid]) for 12 weeks, with visits at baseline, weeks 4 and 12. At week 12, participants who received placebo were assigned a low-potency corticosteroid (fluorometholone [FML] 0.1%, drops, three times per day [tid]) for 2 weeks (week 14). Results: Sixty-five participants completed the primary endpoint. At week 12, contact lens dry-eye questionnaire (CLDEQ-8) score was reduced from baseline with oral fish oil (-7.3 ± 0.8 units, n = 17, P < 0.05), compared with placebo (-3.5 ± 0.9 units, n = 16). FML produced significant reductions in tear IL-17A (-71.1 ± 14.3%, n = 12) and IL-6 (-47.6 ± 17.5%, n = 12, P < 0.05) relative to its baseline (week 12). At week 12, tear IL-17A levels were reduced from baseline in the oral fish oil (-63.2 ± 12.8%, n = 12, P < 0.05) and topical omega-3 (-76.2 ± 10.8%, n = 10, P < 0.05) groups, compared with placebo (-3.8 ± 12.7%, n = 12). Tear IL-6 was reduced with all omega-3 interventions, relative to placebo (P < 0.05) at week 12. Conclusions: CLD was attenuated by oral long-chain omega-3 supplementation for 12 weeks. Acute (2 week) topical corticosteroids and longer-term (12 week) omega-3 supplementation reduced tear levels of the proinflammatory cytokines IL-17A and IL-6, demonstrating parallels in modulating ocular inflammation with these approaches.

Omega-3 polyunsaturated fatty acid supplementation for improving peripheral nerve health: protocol for a systematic review.

INTRODUCTION: Damage to peripheral nerves occurs in a variety of health conditions. Preserving nerve integrity, to prevent progressive nerve damage, remains a clinical challenge. Omega-3 polyunsaturated fatty acids (PUFAs) are implicated in the development and maintenance of healthy nerves and may be beneficial for promoting peripheral nerve health. The aim of this systematic review is to assess the effects of oral omega-3 PUFA supplementation on peripheral nerve integrity, including both subjective and objective measures of peripheral nerve structure and/or function. METHODS AND ANALYSIS: A systematic review of randomised controlled trials that have evaluated the effects of omega-3 PUFA supplementation on peripheral nerve assessments will be conducted. Comprehensive electronic database searches will be performed in Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), US National Institutes of Health Clinical Trials Registry and the WHO International Clinical Trials Registry Platform. The title, abstract and keywords of identified articles will be assessed for eligibility by two reviewers. Full-text articles will be obtained for all studies judged as eligible or potentially eligible; these studies will be independently assessed by two reviewers to determine eligibility. Disagreements will be resolved by consensus. Risk of bias assessment will be performed using the Cochrane Collaboration risk of bias tool to appraise the quality of included studies. If clinically meaningful, and there are a sufficient number of eligible studies, a meta-analysis will be conducted and a summary of findings table will be provided. ETHICS AND DISSEMINATION: This is a systematic review that will involve the analysis of previously published data, and therefore ethics approval is not required. A manuscript reporting the results of this systematic review will be published in a peer-reviewed journal and may also be presented at relevant scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42018086297.

TFOS DEWS II Management and Therapy Report.

The members of the Management and Therapy Subcommittee undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size. Reflecting on all available evidence, a staged management algorithm was derived that presents a step-wise approach to implementing the various management and therapeutic options according to disease severity. While this exercise indicated that differentiating between aqueous-deficient and evaporative dry eye disease was critical in selecting the most appropriate management strategy, it also highlighted challenges, based on the limited evidence currently available, in predicting relative benefits of specific management options, in managing the two dry eye disease subtypes. Further evidence is required to support the introduction, and continued use, of many of the treatment options currently available to manage dry eye disease, as well as to inform appropriate treatment starting points and understand treatment specificity in relation to dry eye disease subtype.

Omega-3 supplementation is neuroprotective to corneal nerves in dry eye disease: a pilot study.

PURPOSE: To investigate whether oral, long-chain omega-3 (ω-3) essential fatty acid (EFA) supplementation, for 3 months, induces changes to the central corneal sub-basal nerve plexus in dry eye disease and whether nerve alterations correlate with clinical findings. METHODS: This prospective, comparative study involved the final 12 participants enrolled in a randomised, double-masked, placebo-controlled clinical trial of 60 participants with moderate dry eye disease. Participants received either placebo (olive oil 1500 mg/day; n = 4) or ω-3 EFA supplements (~1000 mg/day eicosapentaenoic acid + ~500 mg/day docosahexaenoic acid; n = 8) for 90 days. The main outcome measure was the mean change in central corneal sub-basal plexus nerve parameters between days one and 90, quantified using in vivo confocal microscopy. Secondary outcomes included mean change in tear osmolarity, corneal dendritic cell density and basal epithelial cell density. RESULTS: Compared with baseline, the reduction in OSDI score and tear osmolarity at day 90 were greater in the ω-3 EFA group than the placebo group (OSDI: ω-3 EFA, mean ± SEM: -15.6 ± 2.8 vs placebo: -2.8 ± 4.1 units, t5 = 2.6, p = 0.04; tearosmolarity: ω-3 EFA: -22.63 ± 5.7 vs placebo: -8 ± 2.7 mOsmol/L, t9 = 2.3, p = 0.04). At day 90, corneal total nerve branch density (CTBD: 91.1 ± 8.6 vs 45.1 ± 13.4 branches/mm2 , F1,10 = 14, p = 0.004) and corneal nerve branch density on the main fibre (CNBD: 63.4 ± 6.5 vs 27.9 ± 11.5 branches/mm2 , F1,10 = 6, p = 0.03) were higher in the ω-3 EFA group compared with placebo. Relative to day 1, CNBD (branches/mm2 ) increased at day 90 in the ω-3 EFA group (+20.0 ± 9.2, t8 = 3.2 p = 0.01) compared with placebo (-10.8 ± 3.2). Similar changes were evident for corneal nerve fibre length (CNFL, mm/mm2 ), which increased from baseline at day 90 in the omega-3 EFA group (+2.9 ± 1.6, t8 = 3.4 p = 0.01) compared with placebo (-2.7 ± 0.5). There was a negative correlation between CTBD and tear osmolarity (r10 = -0.70, p = 0.01). No significant changes were observed for basal epithelial cell or corneal dendritic cell density. CONCLUSION: These pilot study findings suggest that ω-3 EFA supplementation imparts neuroprotective effects in the corneal sub-basal plexus that correlate with the extent of tear osmolarity normalisation.

A Randomized, Double-Masked, Placebo-Controlled Clinical Trial of Two Forms of Omega-3 Supplements for Treating Dry Eye Disease.

PURPOSE: To assess the efficacy of 2 forms of oral long-chain omega-3 (ω-3) essential fatty acid (EFA) supplements, phospholipid (krill oil) and triacylglyceride (fish oil), for treating dry eye disease (DED). DESIGN: Randomized, double-masked, placebo-controlled clinical trial. PARTICIPANTS: This study was conducted at a single site and involved 60 participants with mild to moderate DED who were randomized (1:1:1) to 1 of 3 groups: placebo (olive oil), krill oil, or fish oil supplements. METHODS: Participants received 1 of the 3 interventions: placebo (olive oil 1500 mg/day), krill oil (945 mg/day eicosapentaenoic acid [EPA], + 510 mg/day docosahexaenoic acid [DHA]), or fish oil (1000 mg/day EPA + 500 mg/day DHA) for 90 days, with monthly study visits. MAIN OUTCOME MEASURES: Primary outcome measures were mean change in (1) tear osmolarity and (2) DED symptoms (Ocular Surface Disease Index [OSDI] score) between days 1 and 90. Secondary outcomes included mean change in key clinical signs (tear stability, tear production, ocular surface staining, bulbar and limbal redness, tear volume, anterior blepharitis, meibomian gland capping) and tear inflammatory cytokine levels. RESULTS: In total, 54 participants completed the study. At day 90, tear osmolarity was reduced from baseline with both krill oil (mean ± standard error of the mean: -18.6±4.5 mOsmol/l; n = 18; P < 0.001) and fish oil (-19.8±3.9 mOsmol/l; n = 19; P < 0.001) supplements, compared with placebo (-1.5±4.4 mOsmol/l; n = 17). OSDI score was significantly reduced at day 90 relative to baseline in the krill oil group only, compared with placebo (-18.6±2.4 vs. -10.5±3.3; P = 0.02). At day 90, there were also relative improvements in tear breakup time and ocular bulbar redness, compared with placebo, for both forms of ω-3 EFAs. Basal tear levels of the proinflammatory cytokine interleukin 17A were significantly reduced in the krill oil group, compared with placebo, at day 90 (-27.1±10.9 vs. 46.5±30.4 pg/ml; P = 0.02). CONCLUSIONS: A moderate daily dose of both forms of long-chain ω-3 EFAs, for 3 months, resulted in reduced tear osmolarity and increased tear stability in people with DED. Omega-3 EFAs in a predominantly phospholipid form (krill oil) may confer additional therapeutic benefit, with improvements in DED symptoms and lower basal tear levels of interleukin 17A, relative to placebo.

The personal nutrition-related attitudes and behaviors of Australian optometrists: is there evidence for an evidence-based approach?

OBJECTIVE: The aim of this study was to investigate the personal nutrition-related attitudes and behaviors of Australian optometrists and, in particular, their understanding of the evidence relating to the merit of specific dietary supplements, as applicable to their own health. METHODS: An online survey was distributed to optometrists registered in Australia (N = 4242). Respondents anonymously provided information regarding their demographic characteristics (age, sex, practice location and modality), diet and lifestyle behaviors (assessment of self-perceived diet quality, smoking status), and nutritional supplement intake (including the rationale for consumption). RESULTS: Completed surveys were received from 283 practitioners. Although most respondents considered themselves to eat a healthy, balanced diet, approximately 75% indicated taking nutritional supplements in the preceding year. The four most common supplements were fish oil/ω-3 (62%), multivitamins (54%), vitamin C (30%), and vitamin D (29%). In addition to vitamin D, which was typically recommended by a general medical practitioner for an established deficiency, the other three supplement categories were consumed on the basis of the respondents' self-assessment and decision. Analyses of the motivations for taking these supplements highlighted a significant misunderstanding of the evidence; furthermore, these practitioners appeared to base their personal behaviors on this misinterpretation. CONCLUSIONS: These findings demonstrate scope for optometrists to enhance their critical thinking and/or understanding of the available evidence relating to the merit, or otherwise, of nutritional supplementation in managing their own health, and more broadly, improving their understanding of what a healthy diet is and its role in eye health.

An evidence-based analysis of Australian optometrists' dry eye practices.

PURPOSE: The aims of this study were to investigate the clinical practices of Australian optometrists as related to the diagnosis, quantification, and management of dry eye and to assess whether these are consistent with research evidence and current guidelines. METHODS: An online survey was distributed to registered optometrists (n = 654). Respondents provided information regarding their preferred diagnostic procedures and management strategies for dry eye, practice modality, year of commencing practice, and whether they possessed an interest in dry eye. RESULTS: Respondents (n = 144) used multiple procedures for diagnosis. Recording patient symptoms ranked as the most important, most valuable, and most commonly used technique. The main objective tests were fluorescein-assisted tear breakup time, corneal fluorescein staining, and meibomian gland evaluation. Optometrists with an interest in dry eye more frequently used lissamine green, phenol red test, interference fringes, and tear osmolarity than nonspecialist practitioners. Dry eye treatment varied with severity. The mainstay of therapy was nonpreserved lubricants and eyelid hygiene; more practitioners recommended topical corticosteroids, systemic omega-3 fatty acid supplementation and increased dietary intake of omega-3 fatty acids for moderate and severe disease, respectively. The primary sources of information used to guide practitioners' management were derived from continuing education conferences. CONCLUSIONS: This study indicates that although Australian optometrists use subjective and objective diagnostic tests and stratify treatment based on dry eye severity, there is a lack of uniformity regarding diagnostic testing, infrequent use of standardized grading scales, and significant variability in clinical care. These findings highlight the potential to improve the translation of dry eye research evidence and evidence-based guidelines into Australian optometric practice.