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

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

Clinical applications of omega-3 fatty acids for corneal and peripheral nerve health

© 2020 Alexis Ceecee ZhangPeripheral neuropathy, a common complication of diabetes, can lead to debilitating functional impairment and adversely impact daily living. In diabetes, damage to small sensory nerves in the cornea, visible using in vivo confocal microscopy (IVCM), precedes large nerve fibre involvement. Quantitative corneal nerve parameters, derived from IVCM images, provide reliable markers for evaluating small fibre damage and repair in diabetic peripheral neuropathy. A current challenge in the management of diabetic peripheral neuropathy is a lack of effective treatments. Omega-3 polyunsaturated fatty acids (PUFAs) modulate systemic inflammation and impart neurotrophic effects and, thus, show promise as neuroprotective agents. Although omega-3 PUFAs have established utility in the management of a number of ocular conditions, including dry eye disease, their potential role for modulating corneal and peripheral nerve health in diabetes has not been thoroughly investigated. This thesis focuses on evaluating the role of omega-3 PUFAs in improving peripheral nerve health using corneal nerve parameters as surrogate markers. First, a clinician survey was developed and administered to explore current practices relating to omega-3 fatty acids in eye care settings. The survey outcomes provide an overview of Australian and New Zealand optometrists’ knowledge and practice patterns relating to omega-3 PUFAs and identify potential avenues for improving clinical implementation. To assist in providing a tailored clinical approach, a dietary questionnaire for quantifying an individual’s omega-3 PUFAs intake was designed and validated. In a cross-sectional study, the association between systemic omega-3 fatty acid levels and corneal nerve parameters was evaluated in healthy controls and individuals with diabetes. This study identified a relationship between corneal nerve structural parameters and the systemic Omega-3 Index, a metric combining erythrocyte docosahexaenoic acid (DHA) and eicosapentanoic acid (EPA) levels. Furthermore, an association between corneal nerve structure and DHA levels, but not EPA levels, was identified. Using a systematic review methodology, randomised controlled trials (RCTs) evaluating the effects of oral omega-3 PUFA supplementation on peripheral nerve structure and function were identified, appraised, and synthesised. This review found, with low certainty, that omega-3 PUFAs attenuate sensory function deficits in chemotherapy-induced peripheral neuropathy. It also identified a paucity of RCTs evaluating the role of omega-3 PUFAs in treating diabetic peripheral neuropathy. These finding supported the rationale for conducting an RCT evaluating the effects of six-months of omega-3 PUFA supplementation in individuals with type 1 diabetes. This study found that, relative to placebo, oral omega-3 PUFA supplementation for six months significantly improved corneal nerve parameters, consistent with a corneal neuroregenerative effect. However, no significant differences were found for small or large nerve fibre function relative to placebo. Overall, this body of work advances scientific understanding of the clinical practices relating to omega-3 PUFAs in eye care settings and provides a dietary assessment tool for improving clinical implementation. Using corneal nerve health as a marker, findings from the prospective clinical studies provide evidence for the role of omega-3 PUFAs in modulating peripheral nerve health

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

Identification of presumed corneal neuromas and microneuromas using laser-scanning in vivo confocal microscopy: a systematic review

BACKGROUND/AIMS: This systematic review critically evaluated peer-reviewed publications describing morphological features consistent with, or using terms related to, a \u27neuroma\u27 or \u27microneuroma\u27 in the human cornea using laser-scanning in vivo confocal microscopy (IVCM). METHODS: The review was prospectively registered on PROSPERO (CRD42020160038). Comprehensive literature searches were performed in Ovid MEDLINE, Ovid Embase and the Cochrane Library in November 2019. The review included primary research studies and reviews that described laser-scanning IVCM for examining human corneal nerves. Papers had to include at least one of a pre-specified set of keyword stems, broadly related to neuromas and microneuromas, to describe a corneal nerve feature. RESULTS: Twenty-five papers (20 original studies; 5 reviews) were eligible. Three original studies evaluated corneal nerve features in healthy eyes. Most papers assessed corneal nerves in ocular and systemic conditions; seven studies did not include a control/comparator group. There was overlap in terminology used to describe nerve features in healthy and diseased corneas (eg, bulb-like/bulbous, penetration, end/s/ing). Inspection of IVCM images within the papers revealed that features termed \u27neuromas\u27 and \u27microneuromas\u27 could potentially be physiological corneal stromal-epithelial nerve penetration sites. We identified inconsistent definitions for terms, and limitations in IVCM image acquisition, sampling and/or reporting that may introduce bias and lead to inaccurate representation of physiological nerve characteristics as pathological. CONCLUSION: These findings identify a need for consistent nomenclature and definitions, and rigorous IVCM scanning and analysis protocols to clarify the prevalence of physiological, as opposed to pathological, corneal nerve features