Publications
214 results found
Chrystal PW, Lambacher NJ, Doucette LP, et al., 2022, The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision, NATURE COMMUNICATIONS, Vol: 13
Yap TE, Davis BM, Bloom PA, et al., 2022, Glaucoma Rose Plot Analysis Detecting Early Structural Progression Using Angular Histograms, OPHTHALMOLOGY GLAUCOMA, Vol: 5, Pages: 562-571, ISSN: 2589-4234
Fu MX, Normando EM, Luk SMH, et al., 2022, MicroShunt versus trabeculectomy for surgical management of glaucoma: a retrospective analysis, Journal of Clinical Medicine, Vol: 11, ISSN: 2077-0383
This case-control study aims to compare the efficacy, safety, and postoperative burden of MicroShunt versus trabeculectomy. The first consecutive cohort of MicroShunt procedures (n = 101) was matched to recent historical trabeculectomy procedures (n = 101) at two London hospital trusts. Primary endpoints included changes in intraocular pressure (IOP) and glaucoma medications. Secondary outcome measures included changes in retinal nerve fibre layer (RNFL) thickness, rates of complications, further theatre interventions, and the number of postoperative visits. From the baseline to Month-18, the median [interquartile range] IOP decreased from 22 [17–29] mmHg (on 4 [3–4] medications) to 15 [10–17] mmHg (on 0 [0–2] medications) and from 20 [16–28] mmHg (on 4 [3–4] medications) to 11 [10–13] mmHg (on 0 [0–0] medications) in the MicroShunt and trabeculectomy groups, respectively. IOP from Month-3 was significantly higher in the MicroShunt group (p = 0.006), with an increased number of medications from Month-12 (p = 0.024). There were greater RNFL thicknesses from Month-6 in the MicroShunt group (p = 0.005). The rates of complications were similar (p = 0.060) but with fewer interventions (p = 0.031) and postoperative visits (p = 0.001) in the MicroShunt group. Therefore, MicroShunt has inferior efficacy to trabeculectomy in lowering IOP and medications but provides a better safety profile and postoperative burden and may delay RNFL loss.
Abdulhussein D, Yap T, Manzer H, et al., 2022, Factors impacting participation in research during the COVID-19 pandemic, Trials, ISSN: 1745-6215
Background: Understanding public and patient attitudes to clinical research is paramount to successful recruitment. The COVID-19 pandemic has led to additional hurdles in achieving this. Our aim is to understand the current factors and attitudes towards clinical trial participation in order to assist recruitment to clinical trials. Methods:We conducted face-to-face interviews with patients in the outpatient department at a tertiary eye hospital facilitated by a 34-item questionnaire developed by the research team. Patient characteristics were correlated with their responses, in addition to qualitative thematic text analysis. Results: A total of 53 patients were interviewed. 40% indicated that they would be willing to participate in clinical research in the current climate. General motivating factors for involvement in research included personal gain, altruism and contribution to innovation. Factors limiting participation included concerns regarding own safety, inconvenience, accessibility and lack of benefit. 22.6% of participants felt that the COVID-19 pandemic has changed their outlook on research. These were categorised into positive (increased awareness of the importance and need for research, altruism) and negative influences (increased anxiety, need to minimise exposure to the hospital environment). Conclusions:Factors influencing patient’s decisions to participate in trials are similar to those observed prior to COVID-19 but with an increased focus on the environment the research is conducted in. The COVID-19 pandemic has had positive and negative impacts on patient attitudes towards research. Trial design, with a particular focus on setting and safety measures, in reassuring patients are increasingly important.
Wu Y, Hu Y, Jiang N, et al., 2022, Quantitative brain-derived neurotrophic factor lateral flow assay for point-of-care detection of glaucoma., Lab Chip
Glaucoma, a ruinous group of eye diseases with progressive degeneration of the optic nerve and vision loss, is the leading cause of irreversible blindness. Accurate and timely diagnosis of glaucoma is critical to promote secondary prevention and early disease-modifying therapies. Reliable, cheap, and rapid tests for measuring disease activities are highly required. Brain-derived neurotrophic factor (BDNF) plays an important role in maintaining the function and survival of the central nervous system. Decreased BDNF levels in tear fluid can be seen in glaucoma patients, which indicates that BDNF can be regarded as a novel biomarker for glaucoma. Conventional ELISA is the standard method to measure the BDNF level, but the multi-step operation and strict storage conditions limit its usage in point-of-care settings. Herein, a one-step and a portable glaucoma detection method was developed based on the lateral flow assay (LFA) to quantify the BDNF concentration in artificial tear fluids. The results of the LFA were analyzed by using a portable and low-cost system consisting of a smartphone camera and a dark readout box fabricated by 3D printing. The concentration of BDNF was quantified by analyzing the colorimetric intensity of the test line and the control line. This assay yields reliable quantitative results from 25 to 300 pg mL-1 with an experimental detection limit of 14.12 pg mL-1. The LFA shows a high selectivity for BDNF and high stability in different pH environments. It can be readily adapted for sensitive and quantitative testing of BDNF in a point-of-care setting. The BDNF LFA strip shows it has great potential to be used in early glaucoma detection.
MacCormick IJC, Zhang B, Hill D, et al., 2022, A proposed theoretical framework for retinal biomarkers, Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Vol: 14, ISSN: 2352-8729
ObjectivePropose a theoretical framework for retinal biomarkers of Alzheimer's disease (AD).BackgroundThe retina and brain share important biological features that are relevant to AD. Developing retinal biomarkers of AD is a strategic priority but as yet none have been validated for clinical use. Part of the reason may be that fundamental inferential assumptions have been overlooked. Failing to recognize these assumptions will disadvantage biomarker discovery and validation, but incorporating them into analyses could facilitate translation.New theoryThe biological assumption that a disease causes analogous effects in the brain and retina can be expressed within a Bayesian network. This allows inferences about abstract theory and individual events, and provides an opportunity to falsify the foundational hypothesis of retina–brain analogy. Graphical representation of the relationships between variables simplifies comparison between studies and facilitates judgements about whether key assumptions are valid given the current state of knowledge.Major challengesThe framework provides a visual approach to retinal biomarkers and may help to rationalize analysis of future studies. It suggests possible reasons for inconsistent results in existing literature on AD biomarkers.Linkage to other theoriesThe framework can be modified to describe alternative theories of retinal biomarker biology, such as retrograde degeneration resulting from brain disease, and can incorporate confounding factors such as co-existent glaucoma or macular degeneration. Parallels with analogue confirmation theory and surrogate marker validation suggest strengths and weaknesses of the framework that can be anticipated when developing analysis plans.
Guo L, Choi S, Bikkannavar P, et al., 2022, Microglia: Key Players in Retinal Ageing and Neurodegeneration, FRONTIERS IN CELLULAR NEUROSCIENCE, Vol: 16
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- Citations: 3
Choi S, Hill D, Guo L, et al., 2022, Automated characterisation of microglia in ageing mice using image processing and supervised machine learning algorithms, Scientific Reports, Vol: 12, ISSN: 2045-2322
The resident macrophages of the central nervous system, microglia, are becoming increasingly implicated as active participants in neuropathology and ageing. Their diverse and changeable morphology is tightly linked with functions they perform, enabling assessment of their activity through image analysis. To better understand the contributions of microglia in health, senescence, and disease, it is necessary to measure morphology with both speed and reliability. A machine learning approach was developed to facilitate automatic classification of images of retinal microglial cells as one of five morphotypes, using a support vector machine (SVM). The area under the receiver operating characteristic curve for this SVM was between 0.99 and 1, indicating strong performance. The densities of the different microglial morphologies were automatically assessed (using the SVM) within wholemount retinal images. Retinas used in the study were sourced from 28 healthy C57/BL6 mice split over three age points (2, 6, and 28-months). The prevalence of ‘activated’ microglial morphology was significantly higher at 6- and 28-months compared to 2-months (p < .05 and p < .01 respectively), and ‘rod’ significantly higher at 6-months than 28-months (p < 0.01). The results of the present study propose a robust cell classification SVM, and further evidence of the dynamic role microglia play in ageing.
Cordeiro MF, Hill D, Patel R, et al., 2022, Detecting retinal cell stress and apoptosis with DARC: Progression from lab to clinic, PROGRESS IN RETINAL AND EYE RESEARCH, Vol: 86, ISSN: 1350-9462
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- Citations: 4
Zollet P, Yap TE, Cordeiro MF, 2021, Detecting Apoptosis as a Clinical Endpoint for Proof of a Clinical Principle, OPHTHALMOLOGICA, Vol: 244, Pages: 408-417, ISSN: 0030-3755
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- Citations: 6
Wu Y, Szymanska M, Hu Y, et al., 2021, Measures of disease activity in glaucoma, Biosensors and Bioelectronics, Vol: 196, ISSN: 0956-5663
Glaucoma is the leading cause of irreversible blindness globally which significantly affects the quality of life and has a substantial economic impact. Effective detective methods are necessary to identify glaucoma as early as possible. Regular eye examinations are important for detecting the disease early and preventing deterioration of vision and quality of life. Current methods of measuring disease activity are powerful in describing the functional and structural changes in glaucomatous eyes. However, there is still a need for a novel tool to detect glaucoma earlier and more accurately. Tear fluid biomarker analysis and new imaging technology provide novel surrogate endpoints of glaucoma. Artificial intelligence is a post-diagnostic tool that can analyse ophthalmic test results. A detail review of currently used clinical tests in glaucoma include intraocular pressure test, visual field test and optical coherence tomography are presented. The advanced technologies for glaucoma measurement which can identify specific disease characteristics, as well as the mechanism, performance and future perspectives of these devices are highlighted. Applications of AI in diagnosis and prediction in glaucoma are mentioned. With the development in imaging tools, sensor technologies and artificial intelligence, diagnostic evaluation of glaucoma must assess more variables to facilitate earlier diagnosis and management in the future.
Shi Y, Jiang N, Bikkannavar P, et al., 2021, Ophthalmic sensing technologies for ocular disease diagnostics, Analyst, Vol: 146, Pages: 6416-6444, ISSN: 0003-2654
Point-of-care diagnosis and personalized treatments are critical in ocular physiology and disease. Continuous sampling of tear fluid for ocular diagnosis is a need for further exploration. Several techniques have been developed for possible ophthalmological applications, from traditional spectroscopies to wearable sensors. Contact lenses are commonly used devices for vision correction, as well as for other therapeutic and cosmetic purposes. They are increasingly being developed into ocular sensors, being used to sense and monitor biochemical analytes in tear fluid, ocular surface temperature, intraocular pressure, and pH value. These sensors have had success in detecting ocular conditions, optimizing pharmaceutical treatments, and tracking treatment efficacy in point-of-care settings. However, there is a paucity of new and effective instrumentation reported in ophthalmology. Hence, this review will summarize the applied ophthalmic technologies for ocular diagnostics and tear monitoring, including both conventional and biosensing technologies. Besides applications of smart readout devices for continuous monitoring, targeted biomarkers are also discussed for the convenience of diagnosis of various ocular diseases. A further discussion is also provided for future aspects and market requirements related to the commercialization of novel types of contact lens sensors.
Szymanska M, Mahmood D, Yap TE, et al., 2021, Recent advancements in the medical treatment of diabetic retinal disease, International Journal of Molecular Sciences, Vol: 22, Pages: 1-25, ISSN: 1422-0067
Diabetic retinal disease remains one of the most common complications of diabetes mellitus (DM) and a leading cause of preventable blindness. The mainstay of management involves glycemic control, intravitreal, and laser therapy. However, intravitreal therapy commonly requires frequent hospital visits and some patients fail to achieve a significant improvement in vision. Novel and long-acting therapies targeting a range of pathways are warranted, while evidence to support optimal combinations of treatments is currently insufficient. Improved understanding of the molecular pathways involved in pathogenesis is driving the development of therapeutic agents not only targeting visible microvascular disease and metabolic derangements, but also inflammation and accelerated retinal neurodegeneration. This review summarizes the current and emerging treatments of diabetic retinal diseases and provides an insight into the future of managing this important condition.
Choi S, Guo L, Cordeiro MF, 2021, Retinal and brain microglia in multiple sclerosis and neurodegeneration, Cells, Vol: 10, Pages: 1-21, ISSN: 2073-4409
Microglia are the resident immune cells of the central nervous system (CNS), including the retina. Similar to brain microglia, retinal microglia are responsible for retinal surveillance, rapidly responding to changes in the environment by altering morphotype and function. Microglia become activated in inflammatory responses in neurodegenerative diseases, including multiple sclerosis (MS). When activated by stress stimuli, retinal microglia change their morphology and activity, with either beneficial or harmful consequences. In this review, we describe characteristics of CNS microglia, including those in the retina, with a focus on their morphology, activation states and function in health, ageing, MS and other neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, glaucoma and retinitis pigmentosa, to highlight their activity in disease. We also discuss contradictory findings in the literature and the potential ways of reducing inconsistencies in future by using standardised methodology, e.g., automated algorithms, to enable a more comprehensive understanding of this exciting area of research.
Guo L, Luong V, Gregson A, et al., 2021, VSN16S, an agonist of the cannabinoid receptor, reduces IOP profiles and exhibits neuroprotective properties in a rat model of glaucoma, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Choi S, Hill D, Guo L, et al., 2021, Automated Characterisation of Retinal Microglia in a Multiple Sclerosis Mouse Model and Age-Matched Controls, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Shamsher E, Guo L, Davis BM, et al., 2021, Resveratrol nanoparticles are neuroprotective in a rat model of glaucoma, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
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- Citations: 1
Lemmens S, Rossetti L, Oddone F, et al., 2021, Comparison of preserved bimatoprost 0.01% with preservative-free tafluprost: A randomised, investigator-masked, 3-month crossover, multicentre trial, SPORT II, EUROPEAN JOURNAL OF OPHTHALMOLOGY, Vol: 32, Pages: 968-975, ISSN: 1120-6721
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- Citations: 1
Hill D, Compagnoni C, Cordeiro MF, 2021, Investigational neuroprotective compounds in clinical trials for retinal disease, EXPERT OPINION ON INVESTIGATIONAL DRUGS, Vol: 30, Pages: 571-577, ISSN: 1354-3784
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- Citations: 4
Abdulhussein D, Kanda M, Aamir A, et al., 2021, Apoptosis in health and diseases of the eye and brain, APOPTOSIS IN HEALTH AND DISEASE, PT B, Vol: 126, Pages: 279-306, ISSN: 1876-1623
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- Citations: 1
Guo L, Ravindran N, Shamsher E, et al., 2021, Retinal Changes in Transgenic Mouse Models of Alzheimer's Disease, CURRENT ALZHEIMER RESEARCH, Vol: 18, Pages: 89-102, ISSN: 1567-2050
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- Citations: 1
Snyder PJ, Alber J, Alt C, et al., 2021, Retinal imaging in Alzheimer's and neurodegenerative diseases, Alzheimers & Dementia, Vol: 17, Pages: 103-111, ISSN: 1552-5260
In the last 20 years, research focused on developing retinal imaging as a source of potential biomarkers for Alzheimer's disease and other neurodegenerative diseases, has increased significantly. The Alzheimer's Association and the Alzheimer's & Dementia: Diagnosis, Assessment, Disease Monitoring editorial team (companion journal to Alzheimer's & Dementia) convened an interdisciplinary discussion in 2019 to identify a path to expedite the development of retinal biomarkers capable of identifying biological changes associated with AD, and for tracking progression of disease severity over time. As different retinal imaging modalities provide different types of structural and/or functional information, the discussion reflected on these modalities and their respective strengths and weaknesses. Discussion further focused on the importance of defining the context of use to help guide the development of retinal biomarkers. Moving from research to context of use, and ultimately to clinical evaluation, this article outlines ongoing retinal imaging research today in Alzheimer's and other brain diseases, including a discussion of future directions for this area of study.
Yap TE, Husein S, Miralles de Imperial-Ollero JA, et al., 2020, The efficacy of dexamethasone implants following anti-VEGF failure for macular oedema in retinal vein occlusion, EUROPEAN JOURNAL OF OPHTHALMOLOGY, Vol: 31, Pages: 3214-3222, ISSN: 1120-6721
Corazza P, Maddison J, Bonetti P, et al., 2020, Predicting wet age-related macular degeneration (AMD) using DARC (detecting apoptosing retinal cells) AI (artificial intelligence) technology, Expert Review of Molecular Diagnostics: new diagnostic technologies are set to revolutionise healthcare, Vol: 21, Pages: 109-118, ISSN: 1473-7159
ObjectivesTo assess a recently described CNN (convolutional neural network) DARC (Detection of Apoptosing Retinal Cells) algorithm in predicting new Subretinal Fluid (SRF) formation in Age-related-Macular-Degeneration (AMD).MethodsAnonymized DARC, baseline and serial OCT images (n = 427) from 29 AMD eyes of Phase 2 clinical trial (ISRCTN10751859) were assessed with CNN algorithms, enabling the location of each DARC spot on corresponding OCT slices (n = 20,629). Assessment of DARC in a rabbit model of angiogenesis was performed in parallel.ResultsA CNN DARC count >5 at baseline was significantly (p = 0.0156) related to development of new SRF throughout 36 months. Prediction rate of eyes using unique DARC spots overlying new SRF had positive predictive values, sensitivities and specificities >70%, with DARC count significantly (p < 0.005) related to the magnitude of SRF accumulation at all time points. DARC identified earliest stages of angiogenesis in-vivo.ConclusionsDARC was able to predict new wet-AMD activity. Using only an OCT-CNN definition of new SRF, we demonstrate that DARC can identify early endothelial neovascular activity, as confirmed by rabbit studies. Although larger validation studies are required, this shows the potential of DARC as a biomarker of wet AMD, and potentially saving vision-loss.
Davis BM, Guo L, Ravindran N, et al., 2020, Dynamic changes in cell size and corresponding cell fate after optic nerve injury, Scientific Reports, Vol: 10, ISSN: 2045-2322
Identifying disease-specific patterns of retinal cell loss in pathological conditions has been highlighted by the emergence of techniques such as Detection of Apoptotic Retinal Cells and Adaptive Optics confocal Scanning Laser Ophthalmoscopy which have enabled single-cell visualisation in vivo. Cell size has previously been used to stratify Retinal Ganglion Cell (RGC) populations in histological samples of optic neuropathies, and early work in this field suggested that larger RGCs are more susceptible to early loss than smaller RGCs. More recently, however, it has been proposed that RGC soma and axon size may be dynamic and change in response to injury. To address this unresolved controversy, we applied recent advances in maximising information extraction from RGC populations in retinal whole mounts to evaluate the changes in RGC size distribution over time, using three well-established rodent models of optic nerve injury. In contrast to previous studies based on sampling approaches, we examined the whole Brn3a-positive RGC population at multiple time points over the natural history of these models. The morphology of over 4 million RGCs was thus assessed to glean novel insights from this dataset. RGC subpopulations were found to both increase and decrease in size over time, supporting the notion that RGC cell size is dynamic in response to injury. However, this study presents compelling evidence that smaller RGCs are lost more rapidly than larger RGCs despite the dynamism. Finally, using a bootstrap approach, the data strongly suggests that disease-associated changes in RGC spatial distribution and morphology could have potential as novel diagnostic indicators.
Manzar H, Abdulhussein D, Yap TE, et al., 2020, Cellular consequences of coenzyme Q10 deficiency in neurodegeneration of the retina and brain, International Journal of Molecular Sciences, Vol: 21, ISSN: 1422-0067
Coenzyme Q10 (CoQ10) is a ubiquitous cofactor in the body, operating in the inner mitochondrial membrane, where it plays a vital role in the generation of adenosine triphosphate (ATP) through the electron transport chain (ETC). In addition to this, CoQ10 serves as an antioxidant, protecting the cell from oxidative stress by reactive oxygen species (ROS) as well as maintaining a proton (H+) gradient across lysosome membranes to facilitate the breakdown of cellular waste products. Through the process of ageing, the body becomes deficient in CoQ10, resulting in several systemic manifestations. On a cellular level, one of the consequences of CoQ10 deficiency is apoptosis, which can be visualised in tissues of the central nervous system (CNS). Diseases affecting the retina and brain such as age-related macular degeneration (AMD), glaucoma, Alzheimer’s disease (AD) and Parkinson’s disease (PD) have shown defects in cellular biochemical reactions attributed to reduced levels of CoQ10. Through further research into the pathogenesis of such conditions, the effects of CoQ10 deficiency can be counteracted through supplementation, early detection and intervention.
Moreddu R, Elsherif M, Adams H, et al., 2020, Integration of paper microfluidic sensors into contact lenses for tear fluid analysis, Lab on a Chip: miniaturisation for chemistry, physics, biology, materials science and bioengineering, Vol: 20, Pages: 3970-3979, ISSN: 1473-0189
In this article, using the integration of paper microfluidics within laser-inscribed commercial contact lenses, we demonstrate the multiplexed detection of clinically relevant analytes including hydrogen ions, proteins, glucose, nitrites and L-ascorbic acid, all sampled directly from model tears. In vitro measurements involved the optimization of colorimetric assays, with readouts collected, stored and analyzed using a bespoke Tears Diagnostics smartphone application prototype. We demonstrate the potential of the device to perform discrete measurements either for medical diagnosis or disease screening in the clinic or at the point-of-care (PoC), with future applications including monitoring of ocular infections, uveitis, diabetes, keratopathies and assessing oxidative stress.
Kelada M, Hill D, Yap TE, et al., 2020, Innovations and revolutions in reducing retinal ganglion cell loss in glaucoma, EXPERT REVIEW OF OPHTHALMOLOGY, Vol: 16, Pages: 33-46, ISSN: 1746-9899
Maurice J, Lett A, Skinner C, et al., 2020, Transcutaneous fluorescence spectroscopy as a tool for non-invasive monitoring of gut function: first clinical experiences, Scientific Reports, Vol: 10, ISSN: 2045-2322
Gastro-intestinal function plays a vital role in conditions ranging from inflammatory bowel disease and HIV through to sepsis and malnutrition. However, the techniques that are currently used to assess gut function are either highly invasive or unreliable. Here we present an alternative, non-invasive sensing modality for assessment of gut function based on fluorescence spectroscopy. In this approach, patients receive an oral dose of a fluorescent contrast agent and a fibre-optic probe is used to make fluorescence measurements through the skin. This provides a readout of the degree to which fluorescent dyes have permeated from the gut into the blood stream. We present preliminary results from our first measurements in human volunteers demonstrating the potential of the technique for non-invasive monitoring of multiple aspects of gastro-intestinal health.
Soomro T, Shah N, Niestrata-Ortiz M, et al., 2020, Recent advances in imaging technologies for assessment of retinal diseases., Expert Review of Medical Devices, Vol: 17, Pages: 1095-1108, ISSN: 1743-4440
INTRODUCTION: Retinal imaging is a key investigation in ophthalmology. New devices continue to be created to keep up with the demand for better imaging modalities in this field. This review looks to highlight current trends and the future of retinal imaging. AREAS COVERED: This review looks at the advances in topographical imaging, photoacoustic microscopy, optical coherence tomography and molecular imaging. There is future scoping on further advances in retinal imaging. EXPERT OPINION: Retinal imaging continues to develop at a rapid pace to improve diagnosis and management of patients. We will see the development of big data to gain powerful insights and new technologies such as teleophthalmology mature in the future.
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