Optometry and Vision Sciences - Theses
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ItemIncreased spatial sampling in automated static visual field testing( 2022)The overarching aim of this thesis was to explore various approaches to increase spatial sampling in clinical static automated perimetry (SAP) testing. The motivation for this aim arose from observations that clinically implemented SAP methods use a “one-test-fits-all” fixed test pattern, despite the fact that patterns of visual field loss vary markedly between individuals. This thesis explored whether it is possible to increase spatial sampling without increasing test duration, and the pros and cons of such as approach. To approach this problem, this thesis engaged a range of methods, including direct experimental work with patients, survey research with healthcare consumers, and explored the opinions of expert clinicians. The Australian Reduced Range Extended Spatial Test (ARREST) is a new perimetric approach that has been shown to increase spatial sampling individually without increasing the test time. ARREST has previously been developed and evaluated using computer simulations. The first experiment in this thesis (Chapter 3) evaluated the feasibility and performance of the ARREST approach in testing people with established visual field loss. Chapter 4 in this thesis investigated patients’ subjective experience with current SAP testing using a mixed-method survey and asked their preferences and priorities for future perimetric developments. The final experiment in this thesis (Chapter 5) explored potential alternative methods for a glaucoma-specific ARREST approach by utilising clinically available information such as clinicians’ views and data from OCT imaging. Taken together, the results of these experiments demonstrate that increasing spatial sampling without increasing test duration is feasible with the ARREST approach. Furthermore, patients report that they would prefer tests that produce more information about their vision. In order to gain more information about their vision, patients also report being willing to perform more visual field tests and increase the frequency of visits for testing. The ARREST approach is currently agnostic to disease-specific needs hence this thesis also explored other clinically available information that might potentially be useful for stimulus placement for a glaucoma-specific ARREST approach. The results from the final experiment demonstrate that clinical experts vary significantly in their choice of stimulus locations to prioritise for further testing, but tend to favour placement in areas important for quality of life. Overall, this thesis provides possible methods for increasing spatial sampling without increasing test duration and demonstrates the importance of considering user and consumer input in the design of perimetric procedures.
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ItemMapping the Parafoveal Capillary Network and Its Flow Characteristics in Healthy Eyes( 2022)Capillary blood flow plays an essential role in the nourishment and maintenance of healthy neural tissue while, in disease, altered capillary flow patterns form the earliest signs of diabetic vasculopathy and are implicated in other major conditions including stroke and dementia. Despite its obvious importance, the difficult-to-meet demands of high spatial and temporal imaging resolution have hitherto limited detailed characterisation of how blood flows through normal capillary networks to maintain healthy retinal structure and function. In this thesis, capillary flow characteristics were studied in the central retina of three healthy young individuals using an adaptive optics ophthalmoscope to provide the required cellular-level spatial resolution, combined with fast frame rates (200-300 frames/second) adequate to capture the single-file flow of red blood cells in capillaries over the course of about 3 seconds. In the first part of the thesis, an automated kymograph method was validated against manual tracking of single red blood cells over successive movie frames for the measurement of instantaneous flow velocities. The automated method proved much faster, and arguments are presented to demonstrate its superior accuracy and robustness, particularly for vessels in which manual tracking is challenging due to high flow speeds. In the second part of the thesis, using the validated kymography approach, velocities were estimated contemporaneously from many neighbouring vessels of the parafoveal capillary network for each subject. Our findings show that capillaries universally exhibit a pulsatile flow pattern with alternating peaks and troughs in velocity with every heartbeat. A high degree of inter-vessel variability over a range of flow parameters (such as the peak, trough velocities, pulsatility, abruptness and peaktime), within a single subject and even within each retinal field, was `noted. This variability could not be explained by “local” vessel factors such as the vessel diameter, tortuosity, vessel length, linear cell density and hematocrit of the vessel. However, within a vessel, a moderate relation between velocities and hematocrit was noted, suggesting a redistribution of plasma between cells with changes in flow. Given the failure of local vessel factors to explain flow variability, the final part of the thesis explored associations between flow and capillary network variables including vessel depth, branch order, and distance from the feeding arteriole of a network. A detailed network analysis to establish the vessel connections and classifications are also presented. Most of the vessels studied were of terminal capillary type with collecting and supplying junctions on either side. Nearly 47 % of the upstream and downstream vessel junctions were amenable to fitting with a model of relative branch diameters based on Murray’s Law, with only a few adhering to modelled expectations. However, a key parameter of the model (the junction exponent) was found to be inversely related to the average velocity and trough velocity in downstream vessels. Cellular flow velocities were also moderately correlated with the length of vessel segments, and with distance to the upstream “feeding” arteriole. In summary, this thesis presents a validated method for studying retinal capillary flow characteristics in normal subjects and provides insights on flow variability within individual vascular networks.
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ItemMeasuring central visual field loss using visual stimuli with natural scene statistics( 2021)Routine visual field assessments are performed using static automated perimetry that measures contrast detection performance for white luminance increment targets presented on a uniform luminance background. While offering a standardised measure of the visual field, such clinical visual field tests are not representative of natural viewing conditions. Previous studies show that some visual field defects are detectable via visual search behaviour analysis; for example, when watching a video or performing daily living tasks. Such measurements of performance using visual stimuli representing everyday tasks can provide information regarding how people with visual field loss perform day to day activities, but due to widely varying visual content, it is difficult to predict a generalised explanation of performance with these tasks to create a widely applicable screening tool. This thesis aimed to develop a method for detecting central visual field loss by measuring the number of fixations to find targets on a background with spatial frequency content similar to natural scenes (referred to as 1/f noise). An advantage of this proposed approach is the existence of an established theoretical framework [Najemnik, J., & Geisler, W.S. (2005), Nature, 434(7031), 387-391] that links the detectability of targets within an image to the number of fixations required by a Bayesian ideal observer to find the targets. The stimulus and behavioural methods used in this thesis were chosen to be consistent with those used to validate the Bayesian ideal observer model. Four experiments were explored in this thesis that stepped through creating the screening protocol for detecting central visual loss. In the first step, Experiment One computationally assessed the suitability of using similar stimuli and behavioural methods as Najemnik and Geisler (2005) to detect field loss. Experiment Two evaluated the need for an age-matched normative limit for setting the contrast of the target for the screening protocol using such a method. Experiment Three determined the requirement of age-matched normative data for the number of the fixations to find the targets on the 1/f noise background, the outcome measure for the screening protocol. The outcomes from Experiment One to Three were then applied to Experiment Four that developed a prototype test for detecting central visual field loss by measuring the number of fixations required to search for a target on a 1/f noise background. This experiment also tested if the developed prototype was able to detect central visual field loss in a group of glaucoma participants. The prototype test demonstrated 85% sensitivity for a fixed specificity of 95.2% in screening abnormal areas in central vision in the glaucoma group. The task requirements of the screening protocol were designed to be representative of natural visual environments and to be intuitive for participants to perform the test. While the prototype test was tested in participants with glaucoma, the developed methods in this experiment are designed to generalise to any form of central visual field loss.
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ItemNo Preview AvailableFunctional and structural adaptations to ageing and acute intraocular pressure elevation in mouse retina( 2021)In response to stress, neurons undergo a series of adaptations, which include changes to their synapses, dendrites and eventually axons and cell bodies. One might presume that such stress responses help to prevent cell death, providing a window of time where recovery remains possible. As glaucoma is a disease of the ageing, it may be reasonable to suggest that older eyes somehow show poorer adaptations to stress or have reduced intrinsic abilities to detect pressure changes in their environment (e.g., via mechanosensitive channels such as transient receptor potential (TRP) channels), and thus less capacity to recover. Whilst support for these ideas can be gleaned from a range of studies in other systems including the central nervous system, there has been less work in this area in the context of glaucoma. The overarching aim of the thesis is to understand the functional and structural adaptations that occur in normal ageing, and to consider if such age-related changes modify the way that retinal ganglion cells (RGCs) cope with intraocular pressure (IOP) elevation. Using the mouse as a platform, it was possible to show that in normal ageing, there was a relative preservation of ganglion cell function despite an age-related decline in outer retinal responses. Age-related inner retinal functional adaptations were associated with increases in bipolar cell sensitivity to light and changes to RGC dendritic complexity. Ageing was also associated with slower recovery from a short period of controlled IOP elevation. IOP elevation resulted in smaller ON RGCs in both young and older mice. Importantly, analysis of RGC morphology showed that better functional recovery in younger eyes was associated with adaptations in OFF RGC dendrites, which was not observed in older eyes. The absence of RGC morphological adaptations following IOP elevation may account for the delayed recovery in older eyes. Furthermore, better ganglion cell functional recovery in younger eyes was also associated with TRPV4 upregulation in the ganglion cell layer. In contrast, there was TRPV4 downregulation in older eyes. Consistent with the importance of TRPV4 upregulation for recovery, inhibiting TRPV4 further worsened recovery in older eyes. This work advances our understanding of age-related functional and structural adaptations, providing insights into how normal function is maintained in ageing, with potential negative impacts on the capacity for RGCs to recover from IOP elevation.
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ItemComputer vision syndrome and blue light blocking lenses: closing the evidence gap( 2021)Computer use is ubiquitous in this digital era and the majority of computer users report eye strain, often referred to as “computer vision syndrome” (CVS) or “digital eye strain”. The most common ocular symptoms associated with CVS are visual fatigue, followed by blurred vision, and dry eyes; these symptoms can occur immediately, or after several hours of computer use. Recently, blue light has been hypothesised to be a cause of CVS and blue light-blocking lenses were introduced with an aim to alleviate symptoms of CVS. However, there is a dearth of evidence from high quality clinical trials to support the efficacy of these lenses, and the potential mechanism of action of blue light-blocking lenses for modifying CVS remains unknown. The major aim of this thesis was to close the evidence gap in relation to the use and applicability of blue light-blocking spectacle lenses for alleviating eye strain associated with CVS. First, a systematic review was conducted to investigate the efficacy and safety of different interventions for treating CVS (Chapter 2). Randomised controlled trials investigating any intervention for managing signs or symptoms of CVS were identified, appraised for risk of bias, and synthesised. A range of interventions - including optical aids, oral supplements, complementary medicines, artificial tears, environmental modifications, yoga, and rest breaks - were identified. For the risk of bias assessment, the three domains that were judged to have the highest risks of bias in the included studies were performance bias, detection bias, and industry sponsorship bias. This systematic review found, with moderate certainty, that oral omega-3 fatty acid supplementation for 45 days improved symptoms of dry eyes in computer users compared to placebo. This review also found with low certainty, that oral berry extract supplementation for 8-12 weeks improved symptoms of visual fatigue and dry eyes, compared to placebo. The studies presented in Chapter 3 and 4 investigated the knowledge and self-reported practice patterns of Australian optometrists and ophthalmologists towards prescribing blue light-blocking ophthalmic lenses. In the optometrist’s survey, three in four respondents indicated prescribing blue light blocking lenses in their clinical practice. Forty-four percent of respondents considered daily environmental exposure to blue light as a potential cause of retinal damage, and approximately one in two respondents thought blue light emitted from computer screens was an important factor in causing CVS. The two main sources of information used by the respondents to guide their practice were conference presentations and manufacturer product information. In the ophthalmologist’s survey, 88% of respondents were cataract surgeons, of whom approximately half indicated recommending blue light blocking intraocular lenses to their patients. About one in four ophthalmologists considered daily environmental exposure to blue light to cause retinal damage. Similarly, 19% of respondents considered blue light emitted from computer screens to be a cause of CVS. The two main sources of information used by ophthalmologists to guide their clinical decision-making were published research papers and conference presentations. Finally, a double-masked, randomised controlled trial (RCT) was conducted to evaluate the efficacy and safety of blue light-blocking spectacles for reducing symptoms and clinical signs of CVS (Chapter 5). A novel aspect of the study design involved a randomisation step to modulate clinical advocacy of the intervention, whereby the investigator did/did not present the assigned intervention in a positive light. We found that blue light-blocking spectacle lenses did not modulate key signs or symptoms of eye strain associated with computer use, relative to standard (clear) lenses, and the relative advocacy of the clinician had no bearing on the clinical outcome. The work presented in this thesis advances our scientific understanding, and broadens the evidence base, relating to the management of CVS, and the current clinical practice behaviours of Australian optometrist and ophthalmologists towards prescribing blue light-blocking ophthalmic products. It provides evidence that blue light-blocking spectacle lenses do not reduce computer-induced eye strain relative to clear lenses, irrespective of whether or not they are advocated for by a clinician. Overall, findings from this thesis will contribute towards informing clinical guidelines that will assist practitioners with making evidence-based clinical decisions when treating CVS.
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ItemVisual search and visual performance in infantile nystagmus syndrome( 2020)Abstract Infantile nystagmus syndrome (INS) is an involuntary ocular motor oscillation, which presents at or near birth and persists throughout life. The nystagmus intensity and visual acuity in INS may vary with gaze angle. The gaze with minimal nystagmus intensity and better visual performance is known as the null position. Nearly all the research on INS focused on visual acuity and the time needed to get the eyes onto the desired target (i.e., target acquisition time). In daily routines, we are constantly presented with search tasks that require us to find a target among distracters or tracking tasks where we need to identify moving objects and to estimate their speed of motion. These real-life visual activities entail complex visual functions, such as visual search and motion perception. However, research on INS and these visual functions is limited. Thus, this study aims to investigate how individuals with INS perform, compared with controls, when carrying out visual search tasks and motion perception tasks. Particularly, the study also aims to assess how the null position affects their visual performance. For visual search, two search conditions were presented: conjunction search and feature search. Search time and accuracy were used to assess visual search performance. For motion perception, three tasks were performed: coherent motion, velocity discrimination, and biological motion. Motion coherence thresholds, discrimination thresholds, and accuracy were measured for the three tasks, respectively. In visual search tasks, INS subjects showed poorer search performance, with longer search times compared to controls in both conjunction and feature search. No difference in accuracy between INS and control subjects was found. The null position did not affect the visual search performance in INS. In coherent motion and velocity discrimination tasks, INS subjects showed poorer performance, with elevated motion coherence and discrimination thresholds compared with controls. A positive null position effect was found only in velocity discrimination. In the biological motion task, no difference in accuracy between INS subjects and controls was found. In summary, visual search, coherent motion, and velocity discrimination were impaired in INS subjects, with the null position having a positive effect in velocity discrimination. However, biological motion perception was not affected by INS. Findings from this study could assist us in understanding of how INS actually affects the daily activities of patients, and aid us in developing new clinical visual function assessment for INS.
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ItemCentral and peripheral motion perception in healthy older adults and its potential relevance to driving( 2021)Aging of the population is a common phenomenon in many countries. This increase in the number of older individuals consequently implies an increase in the number of older drivers. Older adults have changes to vision that could potentially influence driving behavior, as visual information is the predominant sensory input for operating a motor vehicle. One visual function that is potentially relevant for driving performance is motion perception, as both the motor vehicle and the surroundings are in motion. This project explored differences to motion perception between older and younger adults and considered in the applied context of driving. Experiment One explored the differences in performance of healthy older and younger adults on different aspects of motion perception under daylight viewing conditions. A battery of seven psychophysical motion perception tasks was applied to a cohort of participants belonging to two age groups (older and younger adults). Motion perception was also studied comparing central and peripheral vision. This experiment demonstrated that older adults had different results to their younger counterparts for some aspects of motion perception. In addition, for most of the tasks, the effects of aging were similar in central and peripheral vision. In Experiments Two and Three, four motion perception tasks were selected from the battery of tasks used in Experiment One to further test under viewing conditions that are commonly described as problematic by older drivers. These conditions included vision at mesopic light levels, such as those found during nighttime driving (Experiment Two) and driving under headlight glare similar to that of oncoming cars (Experiment Three). These two viewing conditions were simulated in a laboratory-based testing procedure. The results showed that thresholds were in general poorer under low light levels in both age groups. Experiment Three demonstrated that the presence of a continuous glare source simulating car headlights did not impact performance on the selected motion perception tasks. Experiment Four explored the relationship between motion perception and the measurement of the ability to predict potential traffic hazards in a computerized video test (the hazard perception test). The results of this experiment showed that two motion perception tasks (Dmin and motion contrast) were statistically related to the scores in the hazard perception test, and better predicted performance than measurements of visual acuity. This thesis, therefore, contributed to the knowledge of how aging impacts different components of motion perception, not only under photopic viewing conditions, but also under mesopic light levels and under simulated glare. This thesis demonstrated that some motion perception tasks clearly distinguished between age groups (Dmin, motion contrast and biological motion), but these group differences were absent for other tasks (global motion coherence). In addition, some motion perception tasks presented a wide range of interindividual differences in performance, suggesting that aging is a very individual process that cannot be assumed from chronological age.
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ItemThe utility of clinical audit and point-of-care tools to support optometric evidence-based practice in age-related macular degeneration( 2021)Age-related macular degeneration (AMD) is a leading cause of vision impairment worldwide. Currently, there are no approved therapies for earlier stages of AMD. Furthermore, treatments available for later stages of the disease may not reverse vision loss. Of key importance for reducing patients’ risk of progression to sight-threatening late-stage AMD, is the early identification and management of modifiable risk factors. Optometrists in Australia have a key role in providing primary eye care to people who are at risk of developing, or who have earlier stages of, AMD. They are therefore ideally placed to ask and counsel their patients about lifestyle modifications that can reduce the risk of disease progression. Our research team has recently developed the Macular Degeneration Clinical Care Audit Tool (MaD-CCAT), which is designed to audit the optometric care provided to people with AMD, relative to current best-practice standards. The first research project described in this thesis used self-audit data, collected by optometrists using the MaD-CCAT, to both characterise current optometric AMD practice patterns, and evaluate whether the process of clinical self-audit and receiving analytical feedback could improve AMD care. The second project involved a randomised, placebo-controlled trial to evaluate the efficacy of a novel AMD point-of-care clinical tool, delivered either in hardcopy (paper) or online format, for improving optometrists’ AMD knowledge and documented clinical care. In the first project it was found that there are several areas for improvement relating to optometrists’ documentation patterns for key areas relating to AMD care. In addition, self-audit with feedback significantly improved optometrists’ clinical record documentation, including: AMD risk factors, clinical examination techniques, AMD severity classification, and management, post-audit. The optometric practice patterns observed in this study were used to inform the development of two new AMD clinical tools designed to support evidence-based care. In the second study, use of the point-of-care AMD clinical tools, particularly in a paper-based format, was found to improve clinical record documentation, post-intervention (p<0.05), for documenting: patients’ current smoking status, nutritional supplementation intake, accurate AMD severity classification, discussing patient’s risk of progression to late-stage AMD, and providing advice regarding appropriate dietary and nutritional supplementation intake. Clinical self-audit with analytical feedback is a valuable method for improving clinical record documentation of key aspects of AMD care provision by optometrists. Furthermore, AMD point-of-care clinical tools, particularly in a paper-based format assist in documentation of patient risk factors, AMD severity classification, and facilitating communication with patients regarding modifiable risk factor advice. These studies provide insight into the efficacy of different clinical methods for enhancing optometric AMD care provision, to align with current, best available research evidence.
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ItemFunctional organisation of the tammar wallaby visual cortex( 2020)How are the complex maps for feature selectivity created in the mammalian visual cortex? In most Eutherian mammals (e.g. cats, ferrets, tree shrews, and primates), orientation selective cells are organised into columns, which are arranged in pinwheel-like patterns across the cortex. However, rodents and rabbits do not have the same cortical structure: although they have robust orientation selectivity (OS) in individual cells, these are randomly distributed across the cortex in salt-and-pepper maps. Many studies have tried to explain how the complex maps for orientation preference (OP) are created in the primary visual cortex (V1). However, it remains unknown why some mammals have random salt-and-pepper OP maps while others have pinwheel OP maps. In the first chapter, we used intrinsic optical imaging to determine the cortical map structures in the V1 of a marsupial, the tammar wallaby (Macropus Eugenii). Marsupials represent a phylogenetically distinct branch of early mammals and we are the first to examine cortical map structures in a mammal that is not a member of the following mammalian Clades: Glires (e.g. rats, mice, squirrels), Laurasitheria (e.g. cats, ferrets) or Euarchonta (e.g. primates).We found clear orientation columns, arranged in pinwheel-like patterns across the cortex. Based on the finding of pinwheel maps in a marsupial and their similarity to those found in cats and primates, we proposed that the columnar organisation of OPs may be a primitive feature of the mammalian visual cortex and that the species in the Clade Glires (i.e. rodents and rabbits) are the unusual case in terms of mammalian visual brain organisation. We also proposed that the type of cortical map can be predicted by the central-to-peripheral ratio (CP ratio) of retinal ganglion cell (RGC) densities. Second, we extracellularly recorded and estimated the spatial RFs of neurons from the wallaby V1 and LGN in response to white-Gaussian noise (WGN) using 32-channel array probes. Single units were characterised using the nonlinear input model (NIM). We found that OS in the V1 of marsupial wallabies emerges from less selective LGN cell inputs, similar to cats and primates. Again, rodents and rabbits were found to be the odd ones out, suggesting that they have a unique neural circuitry different to other mammals. The NIM framework provided a far more comprehensive analysis of RF properties of neurons in the marsupial cortex, with greater variation in RF structures of simple and complex cells than reported based on simplistic F1/F0 analysis. In the final chapter, we extracted the extracellular spikes of V1 neurons and examined their spatial RFs using the NIM. Consistent with findings from cat V1, we found five distinct classes of extracellular spike waveforms in wallaby V1: regular spiking, fast spiking, triphasic spiking, compound spiking, and positive spiking. The five different spike waveforms were correlated to their spatial RF types and spiking characteristics. We found that negative spiking units showed characteristics typical of cortical cells, and the positive spiking units have similar RF types and spiking characteristics to the thalamic afferents that originate outside the cortex. Moreover, the RF properties of cortical neurons with positive spiking units resembled the wallaby LGN neurons we recorded in the study.
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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.