198 results found
Cordeiro MF, Hill D, Patel R, et al., 2021, Detecting retinal cell stress and apoptosis with DARC: Progression from lab to clinic., Prog Retin Eye Res
DARC (Detection of Apoptosing Retinal Cells) is a retinal imaging technology that has been developed within the last 2 decades from basic laboratory science to Phase 2 clinical trials. It uses ANX776 (fluorescently labelled Annexin A5) to identify stressed and apoptotic cells in the living eye. During its development, DARC has undergone biochemistry optimisation, scale-up and GMP manufacture and extensive preclinical evaluation. Initially tested in preclinical glaucoma and optic neuropathy models, it has also been investigated in Alzheimer, Parkinson's and Diabetic models, and used to assess efficacy of therapies. Progression to clinical trials has not been speedy. Intravenous ANX776 has to date been found to be safe and well-tolerated in 129 patients, including 16 from Phase 1 and 113 from Phase 2. Results on glaucoma and AMD patients have been recently published, and suggest DARC with an AI-aided algorithm can be used to predict disease activity. New analyses of DARC in GA prediction are reported here. Although further studies are needed to validate these findings, it appears there is potential of the technology to be used as a biomarker. Much larger clinical studies will be needed before it can be considered as a diagnostic, although the relatively non-invasive nature of the nasal as opposed to intravenous administration would widen its acceptability in the future as a screening tool. This review describes DARC development and its progression into Phase 2 clinical trials from lab-based research. It discusses hypotheses, potential challenges, and regulatory hurdles in translating technology.
Choi S, Guo L, Cordeiro MF, 2021, Retinal and Brain Microglia in Multiple Sclerosis and Neurodegeneration, CELLS, Vol: 10
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, ISSN: 1120-6721
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
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
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
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, 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, Vol: 21, Pages: 109-118, ISSN: 1473-7159
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, Vol: 20, Pages: 3970-3979, ISSN: 1473-0197
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.
Yap TE, Cordeiro MF, 2020, Treating the whole glaucoma spectrum: A new treatment approach is required, BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Vol: 87, Pages: 717-718, ISSN: 0306-5251
Balendra SI, Shamsher E, Cordeiro MF, 2020, Trehalose is neuroprotective in in vitro models of glaucoma, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Yap TE, Kelada M, de Imperial-Ollero JAM, et al., 2020, Phosphodiesterase inhibitors in glaucoma (PhIGS): a prospective OCTA study, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Balendra SI, Zollet P, Casasca GCADGE, et al., 2020, Personalized approaches for the management of glaucoma, EXPERT REVIEW OF PRECISION MEDICINE AND DRUG DEVELOPMENT, Vol: 5, Pages: 145-164, ISSN: 2380-8993
Normando EM, Yap TE, Maddison J, et al., 2020, A CNN-aided method to predict glaucoma progression using DARC (Detection of Apoptosing Retinal Cells), EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, Vol: 20, Pages: 737-748, ISSN: 1473-7159
Diagnosis and monitoring of psychiatric disorders rely heavily on subjective self-reports of clinical symptoms, which are complicated by the varying consistency of accounts reported by patients with an impaired mental state. Hence, more objective and quantifiable measures have been sought to provide clinicians with more robust methods to evaluate symptomology and track progression of disease in response to treatments. Owing to the shared origins of the retina and the brain, it has been suggested that changes in the retina may correlate with structural and functional changes in the brain. Vast improvements in retinal imaging, namely optical coherence tomography (OCT) and electrodiagnostic technology, have made it possible to investigate the eye at a microscopic level, allowing for the investigation of potential biomarkers in vivo. This review provides a summary of retinal biomarkers associated with schizophrenia, bipolar disorder and major depression, demonstrating how retinal biomarkers may be used to complement existing methods and provide structural markers of pathophysiological mechanisms that underpin brain dysfunction in psychiatric disorders.
Traber GL, Della Volpe-Waizel M, Maloca P, et al., 2020, New technologies for outcome measures in glaucoma: review by the European vision institute special interest focus group., Ophthalmic Research: journal for research in experimental and clinical ophthalmology, Vol: 63, Pages: 88-96, ISSN: 0030-3747
Glaucoma is the leading cause of irreversible blindness worldwide, with an increasing prevalence. The complexity of the disease has been a major challenge in moving the field forward with regard to both pathophysiological insight and treatment. In this context, discussing possible outcome measures in glaucoma trials is of utmost importance and clinical relevance. A recent meeting of the European Vision Institute (EVI) special interest focus group was held on "New Technologies for Outcome Measures in Retina and Glaucoma," addressing both functional and structural outcomes, as well as translational hot topics in glaucoma and retina research. In conjunction with the published literature, this review summarizes the meeting focusing on glaucoma.
Guo L, Davis BM, Ravindran N, et al., 2020, Topical recombinant human Nerve growth factor (rh-NGF) is neuroprotective to retinal ganglion cells by targeting secondary degeneration, Scientific Reports, Vol: 10, ISSN: 2045-2322
Optic neuropathy is a major cause of irreversible blindness worldwide, and no effective treatment is currently available. Secondary degeneration is believed to be the major contributor to retinal ganglion cell (RGC) death, the endpoint of optic neuropathy. Partial optic nerve transection (pONT) is an established model of optic neuropathy. Although the mechanisms of primary and secondary degeneration have been delineated in this model, until now how this is influenced by therapy is not well-understood. In this article, we describe a clinically translatable topical, neuroprotective treatment (recombinant human nerve growth factor, rh-NGF) predominantly targeting secondary degeneration in a pONT rat model. Topical application of rh-NGF twice daily for 3 weeks significantly improves RGC survival as shown by reduced RGC apoptosis in vivo and increased RGC population in the inferior retina, which is predominantly affected in this model by secondary degeneration. Topical rh-NGF also promotes greater axonal survival and inhibits astrocyte activity in the optic nerve. Collectively, these results suggest that topical rh-NGF exhibits neuroprotective effects on retinal neurons via influencing secondary degeneration process. As topical rh-NGF is already involved in early clinical trials, this highlights its potential in multiple indications in patients, including those affected by glaucomatous optic neuropathy.
Mohamed NG, Yap TE, Almonte M, et al., 2020, Focusing on surgical and laser advances in glaucoma management, EXPERT REVIEW OF OPHTHALMOLOGY, Vol: 15, Pages: 27-41, ISSN: 1746-9899
Yetisen AK, Jiang N, Castaneda Gonzalez CM, et al., 2020, Scleral lens sensor for ocular electrolyte analysis, Advanced Materials, Vol: 32, ISSN: 0935-9648
The quantitative analysis of tear analytes in point-of-care settings can enable early diagnosis of ocular diseases. Here, a fluorescent scleral lens sensor is developed to quantitatively measure physiological levels of pH, Na+ , K+ , Ca2+ , Mg2+ , and Zn2+ ions. Benzenedicarboxylic acid, a pH probe, displays a sensitivity of 0.12 pH units within pH 7.0-8.0. Crown ether derivatives exhibit selectivity to Na+ and K+ ions within detection ranges of 0-100 and 0-50 mmol L-1 , and selectivities of 15.6 and 8.1 mmol L-1 , respectively. A 1,2 bis(o-aminophenoxy)ethane-N,N,-N',N'-tetraacetic-acid-based probe allows Ca2+ ion sensing with 0.02-0.05 mmol L-1 sensitivity within 0.50-1.25 mmol L-1 detection range. 5-Oxazolecarboxylic acid senses Mg2+ ions, exhibiting a sensitivity of 0.10-0.44 mmol L-1 within the range of 0.5-0.8 mmol L-1 . The N-(2-methoxyphenyl)iminodiacetate Zn2+ ion sensor has a sensitivity of 1 µmol L-1 within the range of 10-20 µmol L-1 . The fluorescent sensors are subsequently multiplexed in the concavities of an engraved scleral lens. A handheld ophthalmic readout device comprising light-emitting diodes (LEDs) and bandpass filters is fabricated to excite as well as read the scleral sensor. A smartphone camera application and an user interface are developed to deliver quantitative measurements with data deconvolution. The ophthalmic system enables the assessment of dry eye severity stages and the differentiation of its subtypes.
Normando EM, Cordeiro MF, 2020, Animal models in neuro ophthalmology, OCT and Imaging in Central Nervous System Diseases: The Eye as a Window to the Brain: Second Edition, Pages: 401-426, ISBN: 9783030262686
Yap TE, Shamsher E, Guo L, et al., 2020, Ophthalmic Research Lecture 2018: DARC as a Potential Surrogate Marker, OPHTHALMIC RESEARCH, Vol: 63, Pages: 1-7, ISSN: 0030-3747
Patel RP, Shamsher E, Hill D, et al., 2020, Naturally occurring neuroprotectants in glaucoma, GLAUCOMA: A NEURODEGENERATIVE DISEASE OF THE RETINA AND BEYOND - PT B, Vol: 257, Pages: 119-140, ISSN: 0079-6123
Considering the retina as an extension of the brain provides a platform from which to study diseases of the nervous system. Taking advantage of the clear optical media of the eye and ever-increasing resolution of modern imaging techniques, retinal morphology can now be visualized at a cellular level in vivo. This has provided a multitude of possible biomarkers and investigative surrogates that may be used to identify, monitor and study diseases until now limited to the brain. In many neurodegenerative conditions, early diagnosis is often very challenging due to the lack of tests with high sensitivity and specificity, but, once made, opens the door to patients accessing the correct treatment that can potentially improve functional outcomes. Using retinal biomarkers in vivo as an additional diagnostic tool may help overcome the need for invasive tests and histological specimens, and offers the opportunity to longitudinally monitor individuals over time. This review aims to summarise retinal biomarkers associated with a range of neurological conditions including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and prion diseases from a clinical perspective. By comparing their similarities and differences according to primary pathological processes, we hope to show how retinal correlates can aid clinical decisions, and accelerate the study of this rapidly developing area of research.
Mercuri S, Davis B, Yap T, et al., 2019, Longitudinal morphological assessment of macular changes in glaucoma, Publisher: WILEY, ISSN: 1755-375X
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