Review: Emerging Eye-Based Diagnostic Technologies for Traumatic Brain Injury

Harris, Georgia; Rickard, Jonathan James Stanley; Butt, Gibran; Kelleher, Liam; Cooper, Jonathan M.; Oppenheimer, Pola Goldberg

doi:10.1109/rbme.2022.3161352

Cited by 9 publications

(7 citation statements)

References 443 publications

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“…The most frequent victims of TBI are infants (< 4 years), young adults (15–25 years), and the elderly (65+ years). There are a variety of emerging diagnostic techniques for TBI, one of the most relevant being OCT [ 61 ]. TBI is associated with retinal ganglion cell loss [ 127 ], as well as reduced retinal vasculature [ 128 ].…”

Section: Resultsmentioning

confidence: 99%

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Oculomics: A Crusade Against the Four Horsemen of Chronic Disease

Patterson,

Bounds,

Wagner

et al. 2024

Ophthalmol Ther

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Chronic, non-communicable diseases present a major barrier to living a long and healthy life. In many cases, early diagnosis can facilitate prevention, monitoring, and treatment efforts, improving patient outcomes. There is therefore a critical need to make screening techniques as accessible, unintimidating, and cost-effective as possible. The association between ocular biomarkers and systemic health and disease (oculomics) presents an attractive opportunity for detection of systemic diseases, as ophthalmic techniques are often relatively low-cost, fast, and non-invasive. In this review, we highlight the key associations between structural biomarkers in the eye and the four globally leading causes of morbidity and mortality: cardiovascular disease, cancer, neurodegenerative disease, and metabolic disease. We observe that neurodegenerative disease is a particularly promising target for oculomics, with biomarkers detected in multiple ocular structures. Cardiovascular disease biomarkers are present in the choroid, retinal vasculature, and retinal nerve fiber layer, and metabolic disease biomarkers are present in the eyelid, tear fluid, lens, and retinal vasculature. In contrast, only the tear fluid emerged as a promising ocular target for the detection of cancer. The retina is a rich source of oculomics data, the analysis of which has been enhanced by artificial intelligence-based tools. Although not all biomarkers are disease-specific, limiting their current diagnostic utility, future oculomics research will likely benefit from combining data from various structures to improve specificity, as well as active design, development, and optimization of instruments that target specific disease signatures, thus facilitating differential diagnoses.

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Section: Resultsmentioning

confidence: 99%

“…Review articles identify numerous ocular features related to neurodegenerative disease [16,21,49,[59][60][61][62][63][64][65]].…”

Section: Horseman Three: Neurodegenerative Diseasementioning

confidence: 99%

Oculomics: A Crusade Against the Four Horsemen of Chronic Disease

Patterson,

Bounds,

Wagner

et al. 2024

Ophthalmol Ther

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“…These were divided into three main groups of acute, sub-acute, and chronic phases (Figure 1). The TBI cohort selection was based on an extensive literature overview of recent research on TBI biomarkers (animal and human) and temporal courses studied in a range of biofluids including blood, plasma, CSF, urine, and the key biomarkers of neuroinflammation [3,[38][39][40][41][42][43][44][45]. Biomarkers included in the panel were obtained in the purest form without any active additives, to avoid impacting spectral signatures.…”

Section: Tbi Biomarkersmentioning

confidence: 99%

Raman Spectroscopy Spectral Fingerprints of Biomarkers of Traumatic Brain Injury

Harris,

Stickland,

Lim

et al. 2023

Cells

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Traumatic brain injury (TBI) affects millions of people of all ages around the globe. TBI is notoriously hard to diagnose at the point of care, resulting in incorrect patient management, avoidable death and disability, long-term neurodegenerative complications, and increased costs. It is vital to develop timely, alternative diagnostics for TBI to assist triage and clinical decision-making, complementary to current techniques such as neuroimaging and cognitive assessment. These could deliver rapid, quantitative TBI detection, by obtaining information on biochemical changes from patient’s biofluids. If available, this would reduce mis-triage, save healthcare providers costs (both over- and under-triage are expensive) and improve outcomes by guiding early management. Herein, we utilize Raman spectroscopy-based detection to profile a panel of 18 raw (human, animal, and synthetically derived) TBI-indicative biomarkers (N-acetyl-aspartic acid (NAA), Ganglioside, Glutathione (GSH), Neuron Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), Ubiquitin C-terminal Hydrolase L1 (UCHL1), Cholesterol, D-Serine, Sphingomyelin, Sulfatides, Cardiolipin, Interleukin-6 (IL-6), S100B, Galactocerebroside, Beta-D-(+)-Glucose, Myo-Inositol, Interleukin-18 (IL-18), Neurofilament Light Chain (NFL)) and their aqueous solution. The subsequently derived unique spectral reference library, exploiting four excitation lasers of 514, 633, 785, and 830 nm, will aid the development of rapid, non-destructive, and label-free spectroscopy-based neuro-diagnostic technologies. These biomolecules, released during cellular damage, provide additional means of diagnosing TBI and assessing the severity of injury. The spectroscopic temporal profiles of the studied biofluid neuro-markers are classed according to their acute, sub-acute, and chronic temporal injury phases and we have further generated detailed peak assignment tables for each brain-specific biomolecule within each injury phase. The intensity ratios of significant peaks, yielding the combined unique spectroscopic barcode for each brain-injury marker, are compared to assess variance between lasers, with the smallest variance found for UCHL1 (σ2 = 0.000164) and the highest for sulfatide (σ2 = 0.158). Overall, this work paves the way for defining and setting the most appropriate diagnostic time window for detection following brain injury. Further rapid and specific detection of these biomarkers, from easily accessible biofluids, would not only enable the triage of TBI, predict outcomes, indicate the progress of recovery, and save healthcare providers costs, but also cement the potential of Raman-based spectroscopy as a powerful tool for neurodiagnostics.

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“…90 Other biological analyses such as oculomics, which measures nonophthalmological anatomical and physiological biomarkers in the eye, have also shown promise as biomarkers of brain health. 97 In schizophrenia, shrinkage of the retinal neural layers occurs in parallel with illness progression, brain volume loss, and cognitive impairment, and represents a means of assessing pathophysiology and treatment efficacy in patients. 98 The integration of large-scale analysis of datasets from highthroughput sequencing and genotyping technologies, broadspectrum omics studies in combination with the wealth of data from neuroimaging, consortia, repositories, and smartphone apps, can be achieved using artificial intelligence (AI) and machinelearning technologies (eg, support vector machines, modern neural-network algorithms, cross-validation procedures), thus affording new insights into complex patterns in brain, behavior, and genes.…”

Section: How Omics Analyses Can Progress Precision Psychiatrymentioning

confidence: 99%

“…Other biological analyses such as oculomics, which measures nonophthalmological anatomical and physiological biomarkers in the eye, have also shown promise as biomarkers of brain health 97 . In schizophrenia, shrinkage of the retinal neural layers occurs in parallel with illness progression, brain volume loss, and cognitive impairment, and represents a means of assessing pathophysiology and treatment efficacy in patients 98 …”

Section: Precision Psychiatry and Why The Incorporation Of Biological...mentioning

confidence: 99%

Precision psychiatry and Research Domain Criteria: Implications for clinical trials and future practice

Williams,

Carpenter,

Carretta

et al. 2023

CNS Spectr.

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Psychiatric disorders are associated with significant social and economic burdens, many of which are related to issues with current diagnosis and treatments. The coronavirus (COVID-19) pandemic is estimated to have increased the prevalence and burden of major depressive and anxiety disorders, indicating an urgent need to strengthen mental health systems globally. To date, current approaches adopted in drug discovery and development for psychiatric disorders have been relatively unsuccessful. Precision psychiatry aims to tailor healthcare more closely to the needs of individual patients and, when informed by neuroscience, can offer the opportunity to improve the accuracy of disease classification, treatment decisions, and prevention efforts. In this review, we highlight the growing global interest in precision psychiatry and the potential for the National Institute of Health-devised Research Domain Criteria (RDoC) to facilitate the implementation of transdiagnostic and improved treatment approaches. The need for current psychiatric nosology to evolve with recent scientific advancements and increase awareness in emerging investigators/clinicians of the value of this approach is essential. Finally, we examine current challenges and future opportunities of adopting the RDoC-associated translational and transdiagnostic approaches in clinical studies, acknowledging that the strength of RDoC is that they form a dynamic framework of guiding principles that is intended to evolve continuously with scientific developments into the future. A collaborative approach that recruits expertise from multiple disciplines, while also considering the patient perspective, is needed to pave the way for precision psychiatry that can improve the prognosis and quality of life of psychiatric patients.

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Review: Emerging Eye-Based Diagnostic Technologies for Traumatic Brain Injury

Cited by 9 publications

References 443 publications

Oculomics: A Crusade Against the Four Horsemen of Chronic Disease

Oculomics: A Crusade Against the Four Horsemen of Chronic Disease

Raman Spectroscopy Spectral Fingerprints of Biomarkers of Traumatic Brain Injury

Precision psychiatry and Research Domain Criteria: Implications for clinical trials and future practice

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