Optometry and Vision Sciences - Research Publications

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    Optical coherence tomography in children with inherited retinal disease
    Jolly, JK ; Rodda, BM ; Edwards, TL ; Ayton, LN ; Ruddle, JB (TAYLOR & FRANCIS LTD, 2024-01-22)
    Recent advances have led to therapeutic options becoming available for people with inherited retinal disease. In particular, gene therapy has been shown to hold great promise for slowing vision loss from inherited retinal disease. Recent studies suggest that gene therapy is likely to be most effective when implemented early in the disease process, making consideration of paediatric populations important. It is therefore necessary to have a comprehensive understanding of retinal imaging in children with inherited retinal diseases, in order to monitor disease progression and to determine which early retinal biomarkers may be used as outcome measures in future clinical trials. In addition, as many optometrists will review children with an inherited retinal disease, an understanding of the expected imaging outcomes can improve clinical care. This review focuses on the most common imaging modality used in research assessment of paediatric inherited retinal diseases: optical coherence tomography. Optical coherence tomography findings can be used in both the clinical and research setting. In particular, the review discusses current knowledge of optical coherence tomography findings in eight paediatric inherited retinal diseases - Stargardt disease, Bests disease, Leber's congenital amaurosis, choroideremia, RPGR related retinitis pigmentosa, Usher syndrome, X-linked retinoschisis and, Batten disease.
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    Writing an Introduction to a scientific paper
    Anderson, AJ (WILEY, 2023-01)
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    Systematic review and appraisal of quality, definitions and treatment recommendations of clinical guidelines for glaucoma suspects
    Wu, Z ; Karunaratne, S ; Ang, GS ; Martin, KR ; Downie, LE (WILEY, 2023-12-13)
    BACKGROUND: To appraise the quality of clinical practice guidelines for glaucoma suspects, and to assess their consistency for how a 'glaucoma suspect' is defined and their recommendations for treatment initiation for such individuals. METHODS: This study included all documents that self-identified as a 'guideline' and provided recommendation(s) for the clinical care of glaucoma suspects. The quality of eligible guidelines was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. RESULTS: From 1196 records retrieved from comprehensive searches and two records manually included, 20 clinical practice guidelines were deemed eligible. Based on an appraisal using the AGREE II instrument, 16 (80%) guidelines had ≤2 domains with scores >66%. Overall, the lowest scoring domains were for applicability, editorial independence and stakeholder involvement. There was relatively poor agreement across the guidelines for what defines a 'glaucoma suspect' or 'primary open angle glaucoma [POAG] suspect', as well as the recommendations and criteria for treatment initiation in these populations. There was better agreement for the definition and recommendations for treatment initiation for 'primary angle closure suspects'. CONCLUSIONS: There is substantial room to improve the methodological quality of most current international clinical guidelines for glaucoma suspects. Clinicians should consider this finding when using such guidelines to inform their care of glaucoma suspects. Substantial variation in the definition of a POAG suspect and recommendations for treatment initiation underscores important gaps in the current evidence for the accurate prediction of glaucoma development and treatment effectiveness in these individuals.
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    Ocular development after highly effective modulator treatment early in life.
    Zhu, Y ; Li, D ; Reyes-Ortega, F ; Chinnery, HR ; Schneider-Futschik, EK (Frontiers Media SA, 2023)
    Highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapies (HEMT), including elexacaftor-tezacaftor-ivacaftor, correct the underlying molecular defect causing CF. HEMT decreases general symptom burden by improving clinical metrics and quality of life for most people with CF (PwCF) with eligible CFTR variants. This has resulted in more pregnancies in women living with CF. All HEMT are known to be able pass through the placenta and into breast milk in mothers who continue on this therapy while pregnant and breast feeding. Toxicity studies of HEMT in young rats demonstrated infant cataracts, and case reports have reported the presence of congenital cataracts in early life exposure to HEMT. This article reviews the evidence for how HEMT influences the dynamic and interdependent processes of healthy and abnormal lens development in the context of HEMT exposure during pregnancy and breastfeeding, and raises questions that remain unanswered.
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    Awareness of Usher Syndrome and the Need for Multidisciplinary Care: A Cross-Occupational Survey of Allied Health Clinicians
    Ayton, LN ; Galvin, KL ; Johansen, L ; O'Hare, F ; Shepard, ER (DOVE MEDICAL PRESS LTD, 2023)
    BACKGROUND: Usher syndrome is the most common cause of deaf-blindness, affecting up to 1 in 6000 people. Multidisciplinary care is required to maximize outcomes for individuals and families. This study assessed awareness of Usher Syndrome amongst allied health clinicians who provide care related to the primarily affected senses of hearing and vision, ie, optometry, orthoptics and audiology. METHODS: A prospective cross-sectional online survey of clinicians working in Australian university-affiliated clinics (7 optometry, 1 orthoptics and 4 audiology) was completed between September 2021 and January 2022. Questions were asked about the cause, common symptoms, and awareness of health professions who manage Usher syndrome. RESULTS: The 27 audiologists, 40 optometrists, and 7 orthoptists who completed the survey included 53 females (71.6%), had an average age of 37 years (range 24-70), and had an average duration of clinical experience of 13 years (range 1-45 years). The majority of respondents correctly identified Usher syndrome as a genetic condition (86%), identified at least two of the affected senses (97%), and identified the progressive nature of the vision and hearing losses (>90%). Awareness of vestibular dysfunction and its characteristics was low, as was knowledge of the key treatment roles that speech pathologists, genetic counsellors and geneticists play in the management of Usher Syndrome. The majority of respondents also did not identify important aspects of care within their own discipline. CONCLUSION: This study has shown that there is a need for targeted education to be delivered to hearing and vision care allied health clinicians to raise awareness of the vestibular impacts and aspects of vision loss experienced by people with Usher syndrome. This education needs to target the broad range of clinicians who have a key role in providing multidisciplinary care (including speech pathologists, geneticists, and genetic counsellors) and to identify the key aspects of good-quality multidisciplinary care.
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    Mapping the human parafoveal vascular network to understand flow variability in capillaries.
    Neriyanuri, S ; Bedggood, P ; Symons, RCA ; Metha, A ; Grulkowski, I (Public Library of Science (PLoS), 2023)
    Capillary flow is known to be non-homogenous between vessels and variable over time, for reasons that are poorly understood. The local properties of individual vessels have been shown to have limited explanatory power in this regard. This exploratory study investigates the association of network-level properties such as vessel depth, branch order, and distance from the feeding arteriole with capillary flow. Detailed network connectivity analysis was undertaken in 3 healthy young subjects using flood-illuminated adaptive optics retinal imaging, with axial depth of vessels determined via optical coherence tomography angiography. Forty-one out of 70 vessels studied were of terminal capillary type, i.e. fed from an arterial junction and drained by a venous junction. Approximately half of vessel junctions were amenable to fitting with a model of relative branch diameters, with only a few adhering to Murray's Law. A key parameter of the model (the junction exponent) was found to be inversely related to the average velocity (r = -0.59, p = 0.015) and trough velocity (r = -0.67, p = 0.004) in downstream vessels. Aspects of cellular flow, such as the minimum velocity, were also moderately correlated (r = 0.46, p = 0.009) with distance to the upstream feeding arteriole. Overall, this study shows that capillary network topology contributes significantly to the flow variability in retinal capillaries in human eyes. Understanding the heterogeneity in capillary flow is an important first step before pathological flow states can be properly understood. These results show that flow within capillary vessels is not affected by vessel depths but significantly influenced by the upstream feeder distance as well as the downstream vessel junction exponents, but there remains much to be uncovered regarding healthy capillary flow.
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    Preexisting immunity restricts mucosal antibody recognition of SARS-CoV-2 and Fc profiles during breakthrough infections
    Selva, KJ ; Ramanathan, P ; Haycroft, ER ; Reynaldi, A ; Cromer, D ; Tan, CW ; Wang, L-F ; Wines, BD ; Hogarth, PM ; Downie, LE ; Davis, SK ; Purcell, RA ; Kent, HE ; Juno, JA ; Wheatley, AK ; Davenport, MP ; Kent, SJ ; Chung, AW (AMER SOC CLINICAL INVESTIGATION INC, 2023-09-22)
    Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against emerging viral variants. We profiled serial paired mucosal and plasma antibodies from COVID-19 vaccinated only vaccinees (vaccinated, uninfected), COVID-19-recovered vaccinees (recovered, vaccinated), and individuals with breakthrough Delta or Omicron BA.2 infections (vaccinated, infected). Saliva from COVID-19-recovered vaccinees displayed improved antibody-neutralizing activity, Fcγ receptor (FcγR) engagement, and IgA levels compared with COVID-19-uninfected vaccinees. Furthermore, repeated mRNA vaccination boosted SARS-CoV-2-specific IgG2 and IgG4 responses in both mucosa biofluids (saliva and tears) and plasma; however, these rises only negatively correlated with FcγR engagement in plasma. IgG and FcγR engagement, but not IgA, responses to breakthrough COVID-19 variants were dampened and narrowed by increased preexisting vaccine-induced immunity against the ancestral strain. Salivary antibodies delayed initiation following breakthrough COVID-19 infection, especially Omicron BA.2, but rose rapidly thereafter. Importantly, salivary antibody FcγR engagements were enhanced following breakthrough infections. Our data highlight how preexisting immunity shapes mucosal SARS-CoV-2-specific antibody responses and has implications for long-term protection from COVID-19.
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    Mucosal antibody responses following Vaxzevria vaccination
    Selva, KJ ; Ramanathan, P ; Haycroft, ER ; Tan, CW ; Wang, L-F ; Downie, LE ; Davis, SK ; Purcell, RA ; Kent, HE ; Juno, JA ; Wheatley, AK ; Davenport, MP ; Kent, SJ ; Chung, AW (WILEY, 2023)
    Mucosal antibodies play a key role in protection against breakthrough COVID-19 infections and emerging viral variants. Intramuscular adenovirus-based vaccination (Vaxzevria) only weakly induces nasal IgG and IgA responses, unless vaccinees have been previously infected. However, little is known about how Vaxzevria vaccination impacts the ability of mucosal antibodies to induce Fc responses, particularly against SARS-CoV-2 variants of concern (VoCs). Here, we profiled paired mucosal (saliva, tears) and plasma antibodies from COVID-19 vaccinated only vaccinees (uninfected, vaccinated) and COVID-19 recovered vaccinees (COVID-19 recovered, vaccinated) who both received Vaxzevria vaccines. SARS-CoV-2 ancestral-specific IgG antibodies capable of engaging FcγR3a were significantly higher in the mucosal samples of COVID-19 recovered Vaxzevria vaccinees in comparison with vaccinated only vaccinees. However, when IgG and FcγR3a engaging antibodies were tested against a panel of SARS-CoV-2 VoCs, the responses were ancestral-centric with weaker recognition of Omicron strains observed. In contrast, salivary IgA, but not plasma IgA, from Vaxzevria vaccinees displayed broad cross-reactivity across all SARS-CoV-2 VoCs tested. Our data highlight that while intramuscular Vaxzevria vaccination can enhance mucosal antibodies responses in COVID-19 recovered vaccinees, restrictions by ancestral-centric bias may have implications for COVID-19 protection. However, highly cross-reactive mucosal IgA could be key in addressing these gaps in mucosal immunity and may be an important focus of future SARS-CoV-2 vaccine development.
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    Genetic testing and gene therapy in retinal diseases: Knowledge and perceptions of optometrists in Australia and New Zealand
    Britten-Jones, AC ; Mack, HGG ; Vincent, ALL ; Hill, LJJ ; Edwards, TLL ; Ayton, LNN (WILEY, 2024-01)
    With advances in gene-based therapies for heritable retinal diseases, primary eye care clinicians should be informed on ocular genetics topics. This cross-sectional survey evaluated knowledge, attitudes, and concerns regarding genetic testing and gene therapy for retinal diseases among optometrists in Australia and New Zealand. Survey data included practitioner background, attitudes and practices towards genetic testing for monogenic inherited retinal disease (IRDs) and age-related macular degeneration, and knowledge of ocular genetics and gene therapy. Responses were received from 516 optometrists between 1 April and 31 December 2022. Key perceived barriers to accessing genetic testing were lack of clarity on referral pathways (81%), cost (65%), and lack of treatment options if a genetic cause is identified (50%). Almost all respondents (98%) believed that ophthalmologists should initiate genetic testing for IRDs and fewer understood the role of genetic counsellors and clinical geneticists. This study found that optometrists in Australia and New Zealand have a high level of interest in ocular genetics topics. However, knowledge gaps include referral pathways and awareness of genetic testing and gene therapy outcomes. Addressing perceived barriers to access and promoting sharing of knowledge between interdisciplinary networks can set the foundation for genetic education agendas in primary eye care.