Optometry and Vision Sciences - Research Publications

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    Changes to the shape, orientation and packing of red cells as a function of retinal capillary size.
    Bedggood, P ; Ding, Y ; Metha, A (Optica Publishing Group, 2024-02-01)
    The free diameter of a red blood cell exceeds the lumen diameter of capillaries in the central nervous system, requiring significant deformation of cells. However the deformations undertaken in vivo are not well established due to the difficulty in observing cellular capillary flow in living human tissue. Here, we used high resolution adaptive optics imaging to non-invasively track 17,842 red blood cells in transit through 121 unique capillary segments of diameter 8 µm or less in the retina of 3 healthy human subjects. Within each vessel, a 2D en face profile was generated for the "average cell", whose shape was then inferred in 3D based on the key assumption of a circular capillary cross-section. From this we estimated the average volume, surface area, orientation, and separation between red cells within each capillary tube. Our results showed a network filtration effect, whereby narrower vessels were more likely to contain smaller cells (defined by surface area, which is thought not to vary during a cell's passage through the vascular system). A bivariate linear model showed that for larger cells in narrower vessels: cells re-orient themselves to align with the flow axis, their shape becomes more elongated, there are longer gaps between successive cells, and remarkably, that cell volume is less which implies the ejection of water from cells to facilitate capillary transit. Taken together, these findings suggest that red cells pass through retinal capillaries with some reluctance. A biphasic distribution for cell orientation and separation was evident, indicating a "tipping point" for vessels narrower than approx. 5 µm. This corresponds closely to the typical capillary lumen diameter, and may maximize sensitivity of cellular flow to small changes in diameter. We suggest that the minimization of unnecessary oxygen exchange, and hence of damage via reactive oxygen pathways, may have provided evolutionary pressure to ensure that capillary lumens are generally narrower than red blood cells.
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    Validation of an automated method for studying retinal capillary blood flow.
    Neriyanuri, S ; Bedggood, P ; Symons, RCA ; Metha, AB (Optica Publishing Group, 2024-02-01)
    Two major approaches for tracking cellular motion across a range of biological tissues are the manual labelling of cells, and automated analysis of spatiotemporal information represented in a kymograph. Here we compare these two approaches for the measurement of retinal capillary flow, a particularly noisy application due to the low intrinsic contrast of single red blood cells (erythrocytes). Image data were obtained using a flood-illuminated adaptive optics ophthalmoscope at 750 nm, allowing the acquisition of flow information over several cardiac cycles which provided key information in evaluating tracking accuracy. Our results show that in addition to being much faster, the automated method is more accurate in the face of rapid flow and reduced image contrast. This study represents the first validation of commonly used kymograph approaches to capillary flow analysis.
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    Establishing the Calibration Curve of a Compressive Ophthalmodynamometry Device.
    Kaplan, MA ; Bui, BV ; Ayton, LN ; Nguyen, B ; Grayden, DB ; John, S (IEEE, 2023-07)
    The relationship between externally applied force and intraocular pressure was determined using an ex-vivo porcine eye model (N=9). Eyes were indented through the sclera with a convex ophthalmodynamometry head (ODM). Intraocular pressure and ophthalmodynamometric force were simultaneously recorded to establish a calibration curve of this indenter head. A calibration coefficient of 0.140 ± 0.009 mmHg/mN was established and was shown to be highly linear (r = 0.998 ± 0.002). Repeat application of ODM resulted in a 0.010 ± 0.002 mmHg/mN increase to the calibration coefficient.Clinical Relevance- ODM has been highlighted as a potential method of non-invasively estimating intracranial pressure. This study provides relevant data for the practical performance of ODM with similar compressive devices.
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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.