Optometry and Vision Sciences - Research Publications

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    Survey of perspectives of people with inherited retinal diseases on ocular gene therapy in Australia
    Mack, HG ; Britten-Jones, AC ; McGuinness, MB ; Chen, FK ; Grigg, JR ; Jamieson, RV ; Edwards, TL ; De Roach, J ; O'Hare, F ; Martin, KR ; Ayton, LN (SPRINGERNATURE, 2022-10-02)
    Many gene therapies are in development for treating people with inherited retinal diseases (IRD). We hypothesized that potential recipients of gene therapy would have knowledge gaps regarding treatment. We aimed to assess knowledge, attitudes, and perceptions of genetic therapies among potential recipients with IRD, using a novel instrument we designed (Attitudes to Gene Therapy-Eye (AGT-Eye)) and their associations with demographic data, self-reported visual status, and tools assessing quality of life and attitudes toward clinical trials using a community-based cross-sectional survey of Australian adults with IRD. AGT-Eye, overall quality of life EQ-5D-5L, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and Patient Attitudes to Clinical Trials (PACT-22) instruments were administered. Six hundred and eighty-one people completed the study, 51.7% women of mean age 53.5 years (SD ± 15.8). Most participants (91.6%) indicated they would likely accept gene therapy if it was available to them or family members. However, only 28.3% agreed that they had good knowledge of gene therapy. Most obtained information about gene therapy from the internet (49.3%). Respondents with post-graduate degrees scored highest compared to other educational levels on methods (p < 0.001) and outcomes (p = 0.003) and were more likely to see economic value of treatment (p = 0.043). Knowledge gaps were present regarding methods and outcomes of gene therapy. This survey has shown high level of interest in the IRD community for gene therapies, and highlights areas for improved clinician and patient education.
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    Association between systemic omega-3 polyunsaturated fatty acid levels, and corneal nerve structure and function
    Britten-Jones, AC ; Craig, JP ; Anderson, AJ ; Downie, LE (SPRINGERNATURE, 2022-09-26)
    BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have anti-inflammatory and neuroprotective properties. This study sought to determine the relationship between corneal parameters and systemic omega-3 fatty acid levels. METHODS: Forty-seven participants with no/mild peripheral neuropathy (26 with diabetes and 21 without) underwent comprehensive ocular surface and systemic PUFA assessments. Corneal anatomical parameters were assessed using in vivo confocal microscopy. Corneal sensitivity was measured using non-contact esthesiometry. Relationships between systemic PUFA levels and corneal parameters were evaluated with multiple linear regression, adjusted for age, sex, neuropathy symptom score, and presence of diabetes and dry eye disease. The relationship between corneal nerve fibre length (CNFL) and corneal sensitivity threshold was evaluated. RESULTS: The median Omega-3 Index, a measure of erythrocyte EPA and DHA, was 5.21% (interquartile range: 4.44-5.94%) in the study population. Mean ( ± SD) CNFL was 13.53 ± 3.37 mm/mm2. Multiple linear regression showed that Omega-3 Index (β = 0.33; p = 0.02), age (β = -0.46; p = 0.001) and diabetes (β = -0.30; p = 0.03) were independently associated with CNFL (R2 = 0.39, p = 0.002). In a separate model, DHA (β = 0.32; p = 0.027) and age (β = -0.41; p = 0.003) were associated with CNFL (R2 = 0.37, p = 0.003). Neither systemic EPA nor omega-6 fatty acid levels correlated with CNFL. There was no association between PUFA levels and corneal sensitivity or corneal immune cell density. A negative correlation was found between CNFL and corneal sensation thresholds to a cooled stimulus in diabetes participants, in the central (ρ = -0.50; p = 0.009) and peripheral (ρ = -0.50; p = 0.01) cornea. CONCLUSIONS: A positive relationship between the systemic Omega-3 Index and corneal nerve parameters suggests omega-3 PUFA intake may influence corneal nerve architecture.
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    Test Reliability and Compliance to a Twelve-Month Visual Field Telemedicine Study in Glaucoma Patients
    Prea, SM ; Vingrys, AJ ; Kong, GYX (MDPI, 2022-08-01)
    BACKGROUND: Our primary aim is to quantify test reliability and compliance of glaucoma patients to a weekly visual field telemedicine (VFTM) schedule. A secondary aim is to determine concordance of the VFTM results to in-clinic outcomes. METHODS: Participants with stable glaucoma in one eye were recruited for a 12 month VFTM trial using the Melbourne Rapid Fields (MRF-home, MRFh) iPad application. Participants attended routine 6 month clinical reviews and were tasked with weekly home monitoring with the MRFh over this period. We determined compliance to weekly VFTM (7 + 1 days) and test reliability (false positives (FPs) and fixation loss (FL) <33%). A secondary aim considered concordance to in-clinic measures of visual field (MRF-clinic (MRFc) and the Humphrey Field Analyzer (HFA)) in active participants (≥10 home examinations and 5 reliable HFA examinations). The linear trend in the MRFh mean deviation (MD) was compared to the HFA guided progression analysis (GPA) using Bland-Altman methods. Data are shown as the mean ± standard deviation. RESULTS: Forty-seven participants with a mean age of 64 ± 14.6 years were recruited for the trial. The VFTM uptake was 85% and compliance to weekly home monitoring was 75% in the presence of weekly text reminders in the analysed group (n = 20). The analysed group was composed of test subjects with five reliable in-clinic HFA examinations (GPA analysis available) and who submitted a minimum of 10 MRFh examinations from home. Of the 757 home examinations returned, approximately two-thirds were reliable, which was significantly lower than the test reliability of the HFA in-clinic (MRFh: 65% vs. HFA: 85%, p < 0.001). The HFA-GPA analysis gave little bias from the MRFh slope (bias: 0.05 dB/yr, p > 0.05). Two eyes were found to have clinical progression during the 12 month period, and both were detected by VFTM. CONCLUSIONS: VFTM over 12 months returned good compliance (75%) to weekly testing with good concordance to in-clinic assays. VFTM is a viable option for monitoring patients with glaucoma for visual field progression in between clinical visits.
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    A Second-Generation (44-Channel) Suprachoroidal Retinal Prosthesis: Long-Term Observation of the Electrode-Tissue Interface
    Titchener, SA ; Nayagam, DAX ; Kvansakul, J ; Kolic, M ; Baglin, EK ; Abbott, CJ ; McGuinness, MB ; Ayton, LN ; Luu, CD ; Greenstein, S ; Kentler, WG ; Shivdasani, MN ; Allen, PJ ; Petoe, MA (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2022-06-01)
    Purpose: To report the long-term observations of the electrode-tissue interface and perceptual stability in humans after chronic stimulation with a 44-channel suprachoroidal retinal implant. Methods: Four subjects (S1-4) with end-stage retinitis pigmentosa received the implant unilaterally (NCT03406416). Electrode impedances, electrode-retina distance (measured using optical coherence tomography imaging), and perceptual thresholds were monitored up to 181 weeks after implantation as the subjects used the prosthesis in the laboratory and in daily life. Stimulation charge density was limited to 32 µC/cm2 per phase. Results: Electrode impedances were stable longitudinally. The electrode-retina distances increased after surgery and then stabilized, and were well-described by an asymptotic exponential model. The stabilization of electrode-retina distances was variable between subjects, stabilizing after 45 weeks for S1, 63 weeks for S2, and 24 weeks for S3 (linear regression; Pgradient > 0.05). For S4, a statistically significant increase in electrode-retina distance persisted (P < 0.05), but by the study end point the rate of increase was clinically insignificant (exponential model: 0.33 µm/wk). Perceptual electrical thresholds were stable in one subject, decreased over time in two subjects (linear model; P < 0.05), and increased slightly in one subject but remained within the predefined charge limits (P = 0.02). Conclusions: Chronic stimulation with the suprachoroidal retinal prosthesis over 3 years resulted in stable impedances, small individual changes in perceptual electrical thresholds, and no clinically significant increase in electrode-retina distances after a period of settling after surgery. Translational Relevance: Chronic stimulation with the 44-channel suprachoroidal retinal implant with a charge density of up to 32 µC/cm2 per phase is suitable for long-term use in humans.
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    Defining an Optimal Sample Size for Corneal Epithelial Immune Cell Analysis Using in vivo Confocal Microscopy Images
    Zhang, XY ; Wu, M ; Chinnery, HR ; Downie, LE (FRONTIERS MEDIA SA, 2022-06-01)
    Purpose: In vivo confocal microscopy (IVCM) images are frequently used to quantify corneal epithelial immune cell (IC) density in clinical studies. There is currently limited evidence to inform the selection of a representative image sample size to yield a reliable IC density estimate, and arbitrary numbers of images are often used. The primary aim of this study was to determine the number of randomly selected, unique IVCM images required to achieve an acceptable level of accuracy when quantifying epithelial IC density, in both the central and peripheral cornea. The secondary aim was to evaluate the consistency and precision of an image selection approach where corneal epithelial IC density was quantified from "three representative images" selected independently by three experienced observers. Methods: All combinations of two to 15 non-overlapping IVCM images were used for deriving IC density estimates, for both the central and peripheral cornea, in 20 healthy participants; the density value from averaging quantifications in the 16 images was defined as the "true mean". IC density estimates were compared with the true mean in each corneal region using a mean ratio. Intraclass correlation coefficients (ICCs) were used to evaluate the consistency of the mean ratios of IC density estimates derived from the method involving the manual selection of "three representative images" by the observers. The precision of the IC density estimates was compared to a scenario involving three randomly selected images. Results: A total of 12 randomly selected, non-overlapping IVCM images were found to be required to produce a corneal epithelial IC density estimate that was within 30% of the true mean, 95% of the time, for the central cornea; seven such images produced an equivalent level of precision in the peripheral cornea. Mean ratios of corneal IC density estimates derived from "three representative images" methods had poor consistency between observers (ICC estimates <0.5) and similar levels of precision when compared with using three randomly selected images (p > 0.05 for all comparisons), in both the central and peripheral cornea. Conclusions: Data presented in this study can inform image selection methods, and the sample size required for a preferred level of accuracy, when quantifying IC densities in the central and peripheral corneal epithelium using IVCM images.
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    Exercise alone impacts short-term adult visual neuroplasticity in a monocular deprivation paradigm
    Virathone, L ; Nguyen, BN ; Dobson, F ; Carter, OL ; McKendrick, AM (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2021-10-01)
    Adult homeostatic visual plasticity can be induced by short-term patching, heralded by a shift in ocular dominance in favor of the deprived eye after monocular occlusion. The potential to boost visual neuroplasticity with environmental enrichment such as exercise has also been explored; however, the results are inconsistent, with some studies finding no additive effect of exercise. Studies to date have only considered the effect of patching alone or in combination with exercise. Whether exercise alone affects typical outcome measures of experimental estimates of short-term visual neuroplasticity is unknown. We therefore measured binocular rivalry in 20 healthy young adults (20-34 years old) at baseline and after three 2-hour interventions: patching (of the dominant eye) only, patching with exercise, and exercise only. Consistent with previous work, the patching interventions produced a shift in ocular dominance toward the deprived (dominant) eye. Mild- to moderate-intensity exercise in the absence of patching had several effects on binocular rivalry metrics, including a reduction in the dominant eye percept. The proportion of mixed percept and the time to first switch (onset rivalry) did not change from baseline across all interventions. Thus, we demonstrate that exercise alone can impact binocular rivalry outcomes measures. We did not observe a synergistic effect between patching and exercise in our data.
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    Visual contrast perception in visual snow syndrome reveals abnormal neural gain but not neural noise.
    Brooks, CJ ; Chan, YM ; Fielding, J ; White, OB ; Badcock, DR ; McKendrick, AM (Oxford University Press (OUP), 2022-05-24)
    Visual snow syndrome is a neurological condition characterized by a persistent visual disturbance, visual snow, in conjunction with additional visual symptoms. Cortical hyperexcitability is a potential pathophysiological mechanism, which could be explained by increased gain in neural responses to visual input. Alternatively, neural noise in the visual pathway could be abnormally elevated. We assessed these two potential competing neural mechanisms in our studies of visual contrast perception. Cortical hyperexcitation also occurs in migraine, which commonly co-occurs with visual snow syndrome. Therefore, to determine whether the effect of visual snow syndrome can be distinguished from interictal migraine, we recruited four participant groups: controls, migraine alone, visual snow syndrome alone and visual snow syndrome with migraine. In the first experiment, we estimated internal noise in 20 controls, 21 migraine participants and 32 visual snow syndrome participants (16 with migraine) using a luminance increment detection task. In the second experiment, we estimated neural contrast gain in 21 controls, 22 migraine participants and 35 visual snow syndrome participants (16 with migraine) using tasks assessing sensitivity to changes in contrast from a reference. Contrast gain and sensitivity were measured for the putative parvocellular and 'on' and 'off' magnocellular pathways, respectively. We found that luminance increment thresholds and internal noise estimates were normal in both visual snow syndrome and migraine. Contrast gain measures for putative parvocellular processing and contrast sensitivity for putative off magnocellular processing were abnormally increased in visual snow syndrome, regardless of migraine status. Therefore, our results indicate that visual snow syndrome is characterized by increased neural contrast gain but not abnormal neural noise within the targeted pathways.
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    THE LIMITED LEVEL OF DIGITAL SKILLS AND COMPETENCIES OF OPTOMETRY STUDENTS
    Nguyen, KP ; Luke, AK ; Cheng, Y ; John, A ; Cham, KM (INFORMING SCIENCE INST, 2022-01-01)
    Aim/Purpose: Digital health is increasingly being utilized in clinical practice given its ease of accessibility, but it lacks emphasis from universities and accreditation bodies. This study attempted to better understand the digital capabilities of optometry students. Background: With technological advancements transforming the Australian workforce and healthcare, there is a growing demand for digitally competent graduates. This study investigated digital perceptions and preferences of optometry students relating to their studies and readiness for work in healthcare. Methodology: Current optometry students participated in an anonymous online survey. Questions were designed to evaluate their understanding and awareness of digital skills and competencies for learning whilst at university, and for use in the health sector workforce. Results were analyzed to underscore key trends and answers to open-ended questions underwent inductive thematic analysis to generate themes for discussion. Contribution: Optometry educators can bridge the gap in digital practices between students and the workplace by obtaining a baseline of their capabilities and incorporating specific activities within the curriculum to increase student awareness and support their understanding and development in this aspect. Findings: Most students were confident in using daily technologies for learning. Reference management software was perceived to be most important and useful skill to attain. While students were less confident in creating applications, they were keen to learn even though it seemed peripheral to their career and professional development. 70% of the students knew how to manage their online privacy and security. Of the students, 92% highlighted that attaining competency in digital skills would enhance their career and professional development, but only 54% believed they possessed the relevant skills for entering the workforce. Only 19% of the students reported having sufficient university support. Recommendations for Practitioners: Digital capabilities of learners do need to be taught explicitly and should not be assumed. To improve student learning outcomes, digital skills and competencies need to be embedded throughout the curriculum and addressed through learning objectives. Recommendation for Researchers: More work needs to be done in implementing digital training and services at a subject, course, and institutional level. Some international benchmarking of optometry curricula and optometry research would clarify the need for digital education, to educators and students alike. Impact on Society: Currently, there is a lack of recognition of digital health by accrediting bodies, thus preventing digital competency from being a priority in the curriculum of schools. There is a further need to establish dialogue between universities, employers, and accrediting bodies to set consistent and realistic expectations of digital skills and competencies. Future Research: Future studies should consider having larger sample sizes to observe similarities and differences in digital capabilities between year levels. Student focus groups and interviews can be performed to better understand the rationale behind the desire and interest to learn digital technologies that seemed irrelevant to optometry.
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    Developing a Screening Tool for Areas of Abnormal Central Vision Using Visual Stimuli With Natural Scene Statistics
    Srinivasan, R ; Turpin, A ; McKendrick, AM (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2022-02-01)
    PURPOSE: Previous studies show that some visual field (VF) defects are detectable from visual search behavior; for example, when watching video. Here, we developed and tested a VF testing approach that measures the number of fixations to find targets on a background with spatial frequency content similar to natural scenes. METHODS: Twenty-one older controls and 20 people with glaucoma participated. Participants searched for a Gabor (6 c/°) that appeared in one of 25 possible locations within a 15° (visual angle) 1/f noise background (RMS contrast: 0.20). Procedure performance was assessed by calculating sensitivity and specificity for different combinations of control performance limits (p = 95%, 98%, 99%), number of target locations with fixations outside control performance limits (k = 0 to 25) and number of repeated target presentations (n = 1 to 20). RESULTS: Controls made a median of two to three fixations (twenty-fifth to seventy-fifth percentile: two to four) to locate the target depending on location. A VF was flagged "abnormal" when the number of fixations was greater than the p = 99% for k = 3 or more locations with n = 2 repeated presentations, giving 85% sensitivity and 95.2% specificity. The median test time for controls was 85.71 (twenty-fifth to seventy-fifth percentile: 66.49-113.53) seconds. CONCLUSION: Our prototype test demonstrated effective and efficient screening of abnormal areas in central vision. TRANSLATIONAL RELEVANCE: Visual search behavior can be used to detect central vision loss and may produce results that relate well to performance in natural visual environments.
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    Stem cell therapies for eye conditions: A survey of Australian ophthalmologists
    Cabrera-Aguas, M ; Downie, L ; Munsie, MM ; Watson, SL (WILEY, 2022-02-01)