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Frontiers in Neurology 2020The use of optical coherence tomography (OCT) of the retina to detect inner retinal degeneration is being investigated as a potential biomarker for mild cognitive...
The use of optical coherence tomography (OCT) of the retina to detect inner retinal degeneration is being investigated as a potential biomarker for mild cognitive impairment (MCI) and Alzheimer's disease (AD), and an overwhelming body of evidence indicates that discovery of disease-modifying treatments for AD should be aimed at the pre-dementia clinical stage of AD, i.e., MCI. We aimed to perform a systematic review and meta-analysis on retinal OCT in MCI. We performed a systematic review of the English literature in three databases (PubMed, Embase, and Latindex) for studies that measured retinal thickness using OCT in people with MCI and healthy controls, age 50 or older, between 1 January 2000 and 31 July 2019. Only cohort and case-control studies were reviewed, and independent extraction of quality data and established objective data was performed. We calculated the effect size for studies in the review that met the following criteria: (1) a statistically significant difference between MCI subjects and normal controls for several OCT variables, (2) use of spectral domain OCT, and (3) use of APOSTEL recommendations for OCT reporting. Weighted Hedges' g statistic was used to calculate the pooled effect size for four variables: ( in micrometers (μm), in μm, in μm, and in μm. For variables with high heterogeneity, a multivariate meta-regression was performed. We followed the PRISMA guidelines for systematic reviews. Fifteen articles met the inclusion criteria. A total of 58.9% of MCI patients had statistically significant thinning of the pRNFL compared with normal subjects, while 61.6% of all MCI patients who had macular volume measured had a statistically significant reduction in volume compared with controls, and 50.0% of the macular GCL-IPL complexes measured demonstrated significant thinning in MCI compared with normal controls. Meta-analysis demonstrated a large effect size for decreased macular thickness in MCI subjects compared with normal controls, but there was a substantial heterogeneity for macular thickness results. The other variables did not demonstrate a significant difference and also had substantial heterogeneity. Meta-regression analysis did not reveal an explanation for the heterogeneity. A better understanding of the cause of retina degeneration and longitudinal, standardized studies are needed to determine if optical coherence tomography can be used as a biomarker for mild cognitive impairment due to Alzheimer's disease.
PubMed: 33178120
DOI: 10.3389/fneur.2020.578698 -
Frontiers in Neuroscience 2018Glaucoma is a leading cause of irreversible blindness worldwide. The increasing interest in the involvement of the cortical visual pathway in glaucomatous patients is...
Glaucoma is a leading cause of irreversible blindness worldwide. The increasing interest in the involvement of the cortical visual pathway in glaucomatous patients is due to the implications in recent therapies, such as neuroprotection and neuroregeneration. In this review, we outline the current understanding of brain structural, functional, and metabolic changes detected with the modern techniques of neuroimaging in glaucomatous subjects. We screened MEDLINE, EMBASE, CINAHL, CENTRAL, LILACS, Trip Database, and NICE for original contributions published until 31 October 2017. Studies with at least six patients affected by any type of glaucoma were considered. We included studies using the following neuroimaging techniques: functional Magnetic Resonance Imaging (fMRI), resting-state fMRI (rs-fMRI), magnetic resonance spectroscopy (MRS), voxel- based Morphometry (VBM), surface-based Morphometry (SBM), diffusion tensor MRI (DTI). Over a total of 1,901 studies, 56 case series with a total of 2,381 patients were included. Evidence of neurodegenerative process in glaucomatous patients was found both within and beyond the visual system. Structural alterations in visual cortex (mainly reduced cortex thickness and volume) have been demonstrated with SBM and VBM; these changes were not limited to primary visual cortex but also involved association visual areas. Other brain regions, associated with visual function, demonstrated a certain grade of increased or decreased gray matter volume. Functional and metabolic abnormalities resulted within primary visual cortex in all studies with fMRI and MRS. Studies with rs-fMRI found disrupted connectivity between the primary and higher visual cortex and between visual cortex and associative visual areas in the task-free state of glaucomatous patients. This review contributes to the better understanding of brain abnormalities in glaucoma. It may stimulate further speculation about brain plasticity at a later age and therapeutic strategies, such as the prevention of cortical degeneration in patients with glaucoma. Structural, functional, and metabolic neuroimaging methods provided evidence of changes throughout the visual pathway in glaucomatous patients. Other brain areas, not directly involved in the processing of visual information, also showed alterations.
PubMed: 29896087
DOI: 10.3389/fnins.2018.00363 -
Penetration Enhancers for Topical Drug Delivery to the Ocular Posterior Segment-A Systematic Review.Pharmaceutics Feb 2021There is an unmet clinical need for eye drop formulations to efficiently treat the diseases of the posterior ocular segment by non-invasive topical administration. Here,... (Review)
Review
There is an unmet clinical need for eye drop formulations to efficiently treat the diseases of the posterior ocular segment by non-invasive topical administration. Here, we systematically reviewed the literature on ocular penetration enhancers and their ability to transfer drugs to the posterior segment of the eye in experimental studies. Our aim was to assess which penetration enhancer is the most efficient at delivering drugs to the posterior segment of the eye, when topically applied. We conducted a comprehensive search in three electronic databases (Ovid Embase, Ovid MEDLINE, and PubMed) to identify all the relevant manuscripts reported on ocular penetration enhancers based on the PRISMA guidelines. We identified 6540 records from our primary database search and filtered them per our inclusion/exclusion criteria to select a final list of 14 articles for qualitative synthesis. Of these, 11 studies used cell penetrating peptides (CPPs), 2 used chitosan, and 1 used benzalkonium chloride (BAC) as the penetration enhancer. Cationic and amphipathic CPPs, transactivator of transcription (TAT), and penetratin can be inferred to be the best among all the identified penetration enhancers for drug delivery to the fundus oculi via topical eye drop instillation. Further high-quality experimental studies are required to ascertain their quantitative efficacy.
PubMed: 33670762
DOI: 10.3390/pharmaceutics13020276 -
Plastic and Reconstructive Surgery.... Apr 2023There are over 43 million individuals in the world who are blind. As retinal ganglion cells are incapable of regeneration, treatment modalities for this condition are...
UNLABELLED
There are over 43 million individuals in the world who are blind. As retinal ganglion cells are incapable of regeneration, treatment modalities for this condition are limited. Since first incepted in 1885, whole-eye transplantation (WET) has been proposed as the ultimate cure for blindness. As the field evolves, different aspects of the surgery have been individually explored, including allograft viability, retinal survival, and optic nerve regeneration. Due to the paucity in the WET literature, we aimed to systematically review proposed WET surgical techniques to assess surgical feasibility. Additionally, we hope to identify barriers to future clinical application and potential ethical concerns that could be raised with surgery.
METHODS
We conducted a systematic review of PubMed, Embase, Cochrane Library, and Scopus from inception to June 10, 2022, to identify articles pertaining to WET. Data collection included model organisms studied, surgical techniques utilized, and postoperative functional outcomes.
RESULTS
Our results yielded 33 articles, including 14 mammalian and 19 cold-blooded models. In studies performing microvascular anastomosis in mammals, 96% of allografts survived after surgery. With nervous coaptation, 82.9% of retinas had positive electroretinogram signals after surgery, indicating functional retinal cells after transplantation. Results on optic nerve function were inconclusive. Ocular-motor functionality was rarely addressed.
CONCLUSIONS
Regarding allograft survival, WET appears feasible with no complications to the recipient recorded in previous literature. Functional restoration is potentially achievable with a demonstrated positive retinal survival in live models. Nevertheless, the potential of optic nerve regeneration remains undetermined.
PubMed: 37113307
DOI: 10.1097/GOX.0000000000004946 -
Bioengineering (Basel, Switzerland) Jan 2024Hereditary optic neuropathies (HONs) such as dominant optic atrophy (DOA) and Leber Hereditary Optic Neuropathy (LHON) are mitochondrial diseases characterized by a... (Review)
Review
Hereditary optic neuropathies (HONs) such as dominant optic atrophy (DOA) and Leber Hereditary Optic Neuropathy (LHON) are mitochondrial diseases characterized by a degenerative loss of retinal ganglion cells (RGCs) and are a cause of blindness worldwide. To date, there are only limited disease-modifying treatments for these disorders. The discovery of induced pluripotent stem cell (iPSC) technology has opened several promising opportunities in the field of HON research and the search for therapeutic approaches. This systematic review is focused on the two most frequent HONs (LHON and DOA) and on the recent studies related to the application of human iPSC technology in combination with biomaterials technology for their potential use in the development of RGC replacement therapies with the final aim of the improvement or even the restoration of the vision of HON patients. To this purpose, the combination of natural and synthetic biomaterials modified with peptides, neurotrophic factors, and other low- to medium-molecular weight compounds, mimicking the ocular extracellular matrices, with human iPSC or iPSC-derived cell retinal progenitors holds enormous potential to be exploited in the near future for the generation of transplantable RGC populations.
PubMed: 38247929
DOI: 10.3390/bioengineering11010052 -
Biological Psychiatry Global Open... Jan 2024Inner retinal atrophy has been demonstrated in schizophrenia spectrum disorder (SSD) using optical coherence tomography (OCT). This systematic review and meta-analysis...
BACKGROUND
Inner retinal atrophy has been demonstrated in schizophrenia spectrum disorder (SSD) using optical coherence tomography (OCT). This systematic review and meta-analysis investigated the role of contemporary Fourier domain OCT devices in SSD.
METHODS
MEDLINE, PubMed, Scopus, Embase, PsycInfo, PYSNDEX, World Health Organization, and Cochrane databases were searched from inception until May 2022. All peer-reviewed adult SSD case-control studies using Fourier domain OCT were included. Ocular pathologies known to affect retinal OCT scans were excluded. Search, data appraisal, and summary data extraction were independently performed by 2 authors.
RESULTS
The review criteria was met by k = 36 studies, with k = 24 studies (1074 cases, 854 controls) suitable for meta-analysis. The SSD group exhibited a thinner global peripapillary retinal nerve fiber layer (-3.26 μm, 95% CI, -5.07 to -1.45, = 64%, k = 21), thinner average macular layer (-7.88 μm, 95% CI, -12.73 to -3.04, = 65%, k = 11), and thinner macular ganglion cell-inner plexiform sublayer (-2.44 μm, 95% CI, -4.13 to -0.76, = 30%, k = 8) compared with the control group. Retinal nerve fiber layer findings remained significant after exclusion of metabolic disease, low quality, outlier, and influential studies. Studies involving eye examinations to exclude eye disease were associated with greater atrophy in SSD. Except for cardiometabolic disease, most studies did not report clinically significant covariate data known to influence retinal thickness.
CONCLUSIONS
Individuals with SSD generally exhibited retinal atrophy, possibly paralleling reduced brain volumes documented in clinical imaging. Prospective longitudinal studies that collect clinical data, including various illness phases, and control for confounders will be necessary to evaluate retinal atrophy as a biomarker in SSD.
PubMed: 38021252
DOI: 10.1016/j.bpsgos.2023.08.013 -
PloS One 2021To systematically review the evidence on the diagnostic accuracy and prognostic value of retinal optical coherence tomography (OCT) to detect visual acuity (VA) or... (Meta-Analysis)
Meta-Analysis
PURPOSE
To systematically review the evidence on the diagnostic accuracy and prognostic value of retinal optical coherence tomography (OCT) to detect visual acuity (VA) or visual field (VF) loss in children with a brain tumour.
METHODS
PubMed, Embase and Cochrane Library databases were searched from inception to February 2021. We included studies evaluating retinal OCT and standard visual function parameters (VA and or VF) in children with a brain tumour. Two authors independently extracted data from each included study. They also assessed the methodological quality of the studies using the QUADAS-2 or QUIPS tool. The diagnostic accuracy of OCT was evaluated with receiver operating characteristic analysis, sensitivity, specificity, positive predictive value and negative predictive value. The prognostic value of OCT was evaluated with predictive measures (odds ratio).
RESULTS
We included five diagnostic studies, with a total of 186 patients, all diagnosed with optic pathway glioma. No prognostic studies were eligible for inclusion. Included studies evaluated either retinal nerve fiber layer (RNFL) thickness or ganglion cell layer-inner plexiform layer (GCL-IPL) thickness. There was considerable heterogeneity between OCT devices, OCT protocols, visual function parameters and threshold values. Sensitivity and specificity for RNFL thickness measurement ranged from 60.0% to 100.0% and 76.6% to 100%, respectively. For GCL-IPL thickness measurement, area under the curve ranged from 0.91 to 0.98 for different diameters.
CONCLUSION
The literature regarding the diagnostic accuracy and prognostic value of OCT parameters in children with a brain tumour is scarce. Due to heterogeneity and a considerable risk of bias of included studies, we cannot draw solid conclusions regarding the accuracy of retinal OCT. Future research should investigate the potential of OCT as diagnostic and prognostic tool for the evaluation of the visual function and detection of visual impairment in children with any type of brain tumour.
Topics: Brain Neoplasms; Child; Humans; Optic Nerve Glioma; Prognosis; Tomography, Optical Coherence; Visual Acuity; Visual Field Tests
PubMed: 34941930
DOI: 10.1371/journal.pone.0261631 -
Journal of Traditional Chinese Medicine... Aug 2023To evaluate the effectiveness and safety of Xuebijing injection (XBJ) on coronavirus disease 2019 (COVID-19) in patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effectiveness and safety of Xuebijing injection (XBJ) on coronavirus disease 2019 (COVID-19) in patients.
METHODS
Related studies on multiple biological databases and websites were searched up to December 11, 2021 without language and publication time restrictions. Review Manager V.5.3 and Stata 14 software were used for data analysis.
RESULTS
Seven studies were finally included. The Metaanalysis showed that compared with the routine treatment alone, XBJ combined with the routine treatment can reduce the 28day mortality ( = 0.3, 95% : 0.12, 0.74), Creactive protein ( = -12.8, 95% : -23.13, 3.46), erythrocyte sedimentation rate ( = -9.32, 95% : -14.66, -3.98) and interleukin-6 (S = -0.6, 95% : -1.04, -0.17) levels and increase the leukocyte ( = 0.73, 95% : 0.42, 1.04) and lymphocyte count ( = 0.18, 95% : 0.07, 0.29) in peripheral blood; additionally, it has no obvious side effects ( = 1.11, 95% : 0.65, 1.9). There was no evidence that the XBJ combined therapy can improve the nucleic acid conversion rate and computed tomography improvement rate of COVID19 patients.
CONCLUSIONS
Preliminary evidence suggests that XBJ combined with routine treatment seems to be more effective than routine treatment for patients with COVID19. Limited by the number and quality of included papers, this finding still needs further validation by more studies.
Topics: Humans; COVID-19; Drugs, Chinese Herbal; Injections
PubMed: 37454247
DOI: 10.19852/j.cnki.jtcm.20230517.002 -
Frontiers in Neurology 2020To investigate the application of optical coherence tomography angiography (OCTA) in cerebral small vessel disease (SVD), ischemic stroke and dementia. We conducted a...
To investigate the application of optical coherence tomography angiography (OCTA) in cerebral small vessel disease (SVD), ischemic stroke and dementia. We conducted a systematic search in MEDLINE (from inception) and EMBASE (from 1980) to end 2019 for human studies that measured retinal parameters in cerebral SVD, ischemic stroke, and dementia using OCTA. Fourteen articles ( = 989) provided relevant data. Ten studies included patients with Alzheimer disease (AD) and mild cognitive impairment ( = 679), two investigated pre-symptomatic AD participants ( = 154), and two investigated monogenic SVD patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ( = 32) and Fabry disease ( = 124). Methods to reduce bias and risk factor adjustment were poorly reported. Substantial methodological variations between studies precluded a formal meta-analysis. Quantitative measurements revealed significant yet inconclusive changes in foveal avascular zone, perfusion density, and vessel density (VD) in AD, presymptomatic AD, and SVD patients. Two ( = 160) of three studies ( = 192) showed association between decreased VD and increased white matter hyperintensities. In three ( = 297) of seven studies ( = 563), better cognitive function was associated with increased VD. One study ( = 52) suggested increased VD was associated with increased ganglion cell-inner plexiform layer thickness in AD yet with no covariate adjustment. Changes in retinal microvasculature identified using OCTA are associated with monogenic SVD and different stages of AD, but data are limited and partly confounded by methodological differences. Larger studies with risk factors adjustment and more consistent OCTA methods are needed to fully exploit this technology. CRD42020166929.
PubMed: 33013667
DOI: 10.3389/fneur.2020.01009