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.
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ItemThe effects of ageing on ocular surface integrity( 2019)Purpose: Ageing is recognised as a major risk factor for several ocular pathologies, including dry eye disease. The aim of this thesis was to characterise the specific effect of ageing on key ocular surface parameters, in humans and mice. We hypothesised that there would be common ageing effects in both species that paralleled the pathophysiological features observed in dry eye disease. Method: The animal study involved healthy C57BL/6 female mice, aged 2 months (young, n=10) and 22 months (aged, n=10). Clinical assessments included measurements of corneal sensitivity (Cochet-Bonnet aesthesiometry, which is a contact corneal aesthesiometer), tear secretion (Phenol red thread test), tear film osmolarity (TearLab osmometer) and corneal thickness (optical coherence tomography). The anatomical integrity of the corneal nerves was examined ex vivo (using immunohistochemistry) by quantifying nerve density in the superficial epithelium (superficial terminals) and sub-basal plexus. The density and tree area of resident epithelial dendritic cells (DCs) were assessed using immunofluorescence and confocal microscopy. For the clinical study, 37 healthy male and female participants (15 male participants and 22 female participants) were recruited, and divided into four age categories: 20-35 years, 36-50 years, 51-65 years, and >65 years. Participants underwent a comprehensive characterisation of ocular surface health, including quantification of tear osmolarity, blink rate, slit lamp biomicroscopy and corneal sensitivity (using non-contact corneal aesthesiometry). In vivo confocal microscopy (IVCM) was performed to quantify a range of corneal nerve parameters, microneuroma density and DC density, in the central and peripheral cornea. Results: In the animal study, aged mice had significantly higher tear secretion, lower corneal sensitivity and a thicker corneal stroma but thinner epithelium compared with young mice. There was no significant inter-group difference for tear osmolarity. Aged mice showed a significantly lower cornea nerve density, in both the superficial terminals and sub-basal plexus, relative to young mice. DC density and morphology were similar in both age groups. In the human study, older age was associated with a reduction in central corneal sensitivity to a room temperature air stimulus, but not to a cold temperature stimulus. Tear osmolarity remained within normative ranges (<308mOsmol/L) in all age groups, although it was relatively higher in this parameter amongst individuals aged 36 to 50 years, compared to the 20 to 35 year olds (p = 0.0047). A range of ocular surface parameters, including corneal sub-basal nerve plexus density, DC density and microneuroma density were not subject to ageing effects but showed eccentricity-dependent differences. Blink rate and most standard clinical biomicroscopic findings were not significantly different between age groups. Conclusion: Ageing has differential effects on ocular surface parameters. A reduction in corneal sensitivity, and a relative maintenance of corneal DC density, was evident in older eyes in both species. The apparently disparate findings in relation to corneal nerve density between mice and humans may relate to the established limitations of in vivo imaging techniques, particularly with respect to image resolution. These findings, relating to ocular surface changes with physiological ageing, are of value for understanding the potential contribution of the ageing process to ocular surface diseases.