Optometry and Vision Sciences - Theses
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ItemClinical applications of omega-3 fatty acids for corneal and peripheral nerve health( 2020)Peripheral 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.