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Clinical Neurology and Neurosurgery Sep 2020Thinning of retinal layers, measured using optical coherence tomography (OCT), is associated with some neurodegenerative disorders such as established Alzheimer's... (Meta-Analysis)
Meta-Analysis
Thinning of retinal layers, measured using optical coherence tomography (OCT), is associated with some neurodegenerative disorders such as established Alzheimer's disease and multiple sclerosis. The evidence for retinal layer thinning in both mild cognitive impairment (MCI), a precursor of dementia, and delirium, a potential pre-clinical stage of neurodegenerative disorder, is unclear. We performed a systematic review of the associations, in older people, between retinal layer thickness changes (measured using OCT) and delirium or MCI compared to controls (Protocol registration ID (Prospero) CRD42019122165). We did not identify any relevant studies on delirium. This report is therefore a review of retinal nerve layer changes in mild cognitive impairment. Databases were searched using predetermined keywords such as mild cognitive impairment, retinal nerve fibre layer and delirium. Where there were sufficient data, meta-analyses were performed. Twenty-six relevant studies were identified on retinal layer thickness in people with MCI compared to controls. There was significant heterogeneity in the studies for all retinal layers investigated (retinal nerve fibre layer (RNFL), ganglion cell inner plexiform layer (GCIP), foveal thickness and macular volume). Analysis of 17 studies of mean RNFL thickness in MCI (n = 622) compared to controls (n = 1154), irrespective of the type of OCT device, demonstrated a significant thinning in MCI (SMD: - 0·42 and 95 % confidence interval: - 0·68 to - 0·16). This difference was non-significant when studies using only spectral-domain devices were analysed. Subgroup analysis of studies using spectral-domain devices in amnestic MCI diagnosed using comparable criteria, showed statistically significant thinning of RNFL in amnestic MCI (p = 0·02). Meta-analysis of foveal thickness did not show a significant difference between MCI and controls. In conclusion, there is some evidence of an association between retinal nerve fibre layer thinning and MCI. We found no data on the association between RNFL and delirium.
Topics: Cognitive Dysfunction; Humans; Retina; Tomography, Optical Coherence
PubMed: 32623211
DOI: 10.1016/j.clineuro.2020.106036 -
Frontiers in Neuroscience 2022Glaucoma is a leading cause of blindness worldwide. It is suggested that primary open angle glaucoma (POAG), the most common form of glaucoma, may be associated with...
Glaucoma is a leading cause of blindness worldwide. It is suggested that primary open angle glaucoma (POAG), the most common form of glaucoma, may be associated with significant metabolic alternations, but the systemic literature review and meta-analysis in the area have been missing. Altered metabolomic profiles in the aqueous humor and plasma may serve as possible biomarkers for early detection or treatment targets. In this article, we performed a systematic meta-analysis of the current literature surrounding the metabolomics of patients with POAG and metabolites associated with the disease. Results suggest several metabolites found to be specifically altered in patients with POAG, suggesting broad generalizability and pathways for future research.
PubMed: 35645711
DOI: 10.3389/fnins.2022.835736 -
Ophthalmology Apr 2019OCT is a noninvasive tool to measure specific retinal layers in the eye. The relationship of retinal spectral-domain (SD) OCT measurements with Alzheimer's disease (AD)... (Meta-Analysis)
Meta-Analysis
TOPIC
OCT is a noninvasive tool to measure specific retinal layers in the eye. The relationship of retinal spectral-domain (SD) OCT measurements with Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains unclear. Hence, we conducted a systematic review and meta-analysis to examine the SD OCT measurements in AD and MCI.
CLINICAL RELEVANCE
Current methods of diagnosing early AD are expensive and invasive. Retinal measurements of SD OCT, which are noninvasive, technically simple, and inexpensive, are potential biomarkers of AD.
METHODS
We conducted a literature search in PubMed and Excerpta Medica Database to identify studies published before December 31, 2017, that assessed the associations between AD, MCI, and measurements of SD OCT: ganglion cell-inner plexiform layer (GC-IPL), ganglion cell complex (GCC), macular volume, and choroidal thickness, in addition to retinal nerve fiber layer (RNFL) and macular thickness. We used a random-effects model to examine these relationships. We also conducted meta-regression and assessed heterogeneity, publication bias, and study quality.
RESULTS
We identified 30 eligible studies, involving 1257 AD patients, 305 MCI patients, and 1460 controls, all of which were cross-sectional studies. In terms of the macular structure, AD patients showed significant differences in GC-IPL thickness (standardized mean difference [SMD], -0.46; 95% confidence interval [CI], -0.80 to -0.11; I = 71%), GCC thickness (SMD, -0.84; 95% CI, -1.10 to -0.57; I = 0%), macular volume (SMD, -0.58; 95% CI, -1.03 to -0.14; I = 80%), and macular thickness of all inner and outer sectors (SMD range, -0.52 to -0.74; all P < 0.001) when compared with controls. Peripapillary RNFL thickness (SMD, -0.67; 95% CI, -0.95 to -0.38; I = 89%) and choroidal thickness (SMD range, -0.88 to -1.03; all P < 0.001) also were thinner in AD patients.
CONCLUSIONS
Our results confirmed the associations between retinal measurements of SD OCT and AD, highlighting the potential usefulness of SD OCT measurements as biomarkers of AD.
Topics: Alzheimer Disease; Biomarkers; Cognitive Dysfunction; Cross-Sectional Studies; Humans; Nerve Fibers; Organ Size; Retina; Retinal Diseases; Retinal Ganglion Cells; Tomography, Optical Coherence
PubMed: 30114417
DOI: 10.1016/j.ophtha.2018.08.009 -
Frontiers in Neuroscience 2024Internal carotid artery stenosis (ICAS) is a prevalent vascular condition associated with ischemic cerebrovascular disease. The ophthalmic artery is the first branch of...
BACKGROUND
Internal carotid artery stenosis (ICAS) is a prevalent vascular condition associated with ischemic cerebrovascular disease. The ophthalmic artery is the first branch of the internal carotid artery stenosis (ICA). Given the crucial role of the ICA in ocular perfusion, we aimed to assess the thickness and vessel density of the retina and choroid in individuals with ICAS.
METHODS
The PubMed and Embase databases were searched from inception to 10 January 2023 for studies evaluating retinal and choroidal changes between ICAS patients and healthy controls using optical coherence tomography (OCT) or optical coherence tomography angiography (OCTA). Data of interest were extracted and analyzed using Stata software version 16.
RESULTS
Thirteen studies involving 419 ICAS eyes and 398 healthy eyes were included. The pooled results demonstrated that the average thickness of peripapillary retinal nerve fiber layer (pRNFL) (WMD = -0.26, 95% CI: -0.45 to -0.08, = 0.005), ganglion cell complex (GCC) (WMD = -0.36, 95% CI: -0.65 to -0.06, = 0.017), and choroid (WMD = -1.06, 95% CI: -1.59 to -0.52, = 0.000), were significantly thinner in patients with ICAS than in healthy controls. The overall vessel density of the radial peripapillary capillaries (RPC) in whole-image scans was lower in ICAS patients than in healthy control subjects (WMD = -0.94, 95% CI: -1.49 to -0.39, = 0.001). No differences were detected in the vessel density of the superficial capillary plexus (SCP) (WMD = -0.84, 95% CI: -1.15 to -0.53, = 0.092), the deep capillary plexus (DCP) (WMD = -0.27, 95% CI: -0.56 to 0.03, = 0.074), or the choriocapillaris (CC) (WMD = -0.39, 95% CI: -1.12 to 0.35, = 0.300).
CONCLUSION
This systematic review and meta-analysis demonstrated that ICAS can reduce the vessel density of the RPC and the thickness of the retina and choroid. The retinal and choroidal microvasculature is a potential biomarker of the initial signal of ICAS.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/, identifier NPLASY202410038.
PubMed: 38686328
DOI: 10.3389/fnins.2024.1368957 -
Eye (London, England) Apr 2024Mild traumatic brain injury (mTBI) is common with many patients suffering disabling long-term sequelae, with visual symptoms frequently reported. There are no objective... (Review)
Review
Mild traumatic brain injury (mTBI) is common with many patients suffering disabling long-term sequelae, with visual symptoms frequently reported. There are no objective biomarkers of mTBI that are routinely used in clinical practice. Optical coherence tomography (OCT) has been used in mTBI research, as it enables visualisation of the neuroretina, allowing measurement of the retinal nerve fibre layer and ganglion cell layer. This systematic review aims to appraise the available literature and assess whether there are significant changes within the retinal nerve fibre layer and ganglion cell layer in subjects after mTBI. A systematic review was carried out in accordance with PRISMA guidelines and registered with PROSPERO (Number: CRD42022360498). Four databases were searched for relevant literature published from inception until 1 September 2022. Abstracts and full texts were screened by three independent reviewers. Initial screening of databases yielded 341 publications, of these, three fulfilled all the criteria for inclusion. All three studies showed thinning of the retinal nerve fibre layer, whereas there were no significant changes in the ganglion cell layer. This systematic review demonstrated that thinning of the retinal nerve fibre layer (but not of the ganglion cell layer) is associated with mTBI. It provides preliminary evidence for the use of the retinal nerve fibre layer as a potential biomarker of damage to the visual system in mTBI. Further prospective longitudinal studies ensuring uniform diagnosis and accurate phenotyping of mTBI are needed to understand the effects on the visual system and potential of OCT as a prognostic biomarker.
Topics: Adult; Humans; Retinal Ganglion Cells; Tomography, Optical Coherence; Brain Concussion; Nerve Fibers; Biomarkers
PubMed: 38238577
DOI: 10.1038/s41433-023-02845-w -
Ophthalmic Research 2024Anterior ischemic optic neuropathy (AION) can mimic glaucoma and consequently cause difficulties in differential diagnosis. The purpose of this paper was to summarize... (Review)
Review
INTRODUCTION
Anterior ischemic optic neuropathy (AION) can mimic glaucoma and consequently cause difficulties in differential diagnosis. The purpose of this paper was to summarize differences in diagnostic tests that can help perform a correct diagnosis.
METHODS
The search strategy was performed according to the PRISMA 2009 guidelines, and four databases were used: MEDLINE, Embase, Web of Science, and Cochrane. Totally, 772 references were eligible; 39 were included after screening with respect to inclusion criteria that included English language and published in the 20 years before search date.
RESULTS
Ninety percent (n = 35) of included studies used optical coherence tomography (OCT). Glaucomatous eyes had a significantly greater cup area, volume and depth, cup-to-disk ratio, a lower rim volume and area, and a thinner Bruch's membrane opening-minimum rim width. Retinal nerve fiber layer (RNFL) thinning in glaucomatous eyes occurred primarily at the superotemporal, inferotemporal, and inferonasal sectors, while AION eyes demonstrated mostly superonasal thinning. Glaucoma eyes showed greater macular ganglion cell layer thickness, except at the inferotemporal sector. OCT angiography measurements demonstrated a significant decrease in superficial and deep macular vessel density (VD) in glaucoma compared to AION with similar degree of visual field damage; the parapapillary choroidal VD was spared in AION eyes compared to glaucomatous eyes.
CONCLUSION
By use of OCT imaging, optic nerve head parameters seem most informative to distinguish between glaucoma and AION. Although both diseases affect the RNFL thickness, it seems to do so in different sectors. Differences in structure and vascularity of the macula can also help in making the differential diagnosis.
Topics: Humans; Optic Neuropathy, Ischemic; Diagnosis, Differential; Tomography, Optical Coherence; Nerve Fibers; Retinal Ganglion Cells; Optic Disk; Glaucoma; Visual Fields; Intraocular Pressure
PubMed: 38262372
DOI: 10.1159/000535568 -
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 -
Current Eye Research May 2017Many studies have assessed the changes of retinal nerve fiber layer (RNFL) thickness in patients with obstructive sleep apnea syndrome (OSAS), but the results were... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Many studies have assessed the changes of retinal nerve fiber layer (RNFL) thickness in patients with obstructive sleep apnea syndrome (OSAS), but the results were inconsistent. Therefore, a meta-analysis was performed to evaluate the RNFL changes in OSAS measured in vivo.
METHODS
Pertinent studies were identified by a comprehensive search of PubMed, Embase, Web of science, Cochrane library, Scopus, and Chinese biomedical disc databases from inception to August 2016. A fixed effects model was used to pool the weighted mean difference (WMD) and 95% confidence interval (CI) between OSAS group and control group.
RESULTS
Seventeen studies were included in the final analysis, with 12 for descriptive analysis and 5 for meta-analysis, involving a total of 1757 eyes (1106 in the OSAS group and 651 in the control group). The RNFL in OSAS was significantly lower than control group, with pooled WMD -3.53 (95%CI: -4.80 to -2.26, P < 0.001) for average RNFL, -3.69 (95%CI:-5.49 to -1.89 P < 0.001) for superior RNFL, -4.66 (95%CI: -6.92 to -2.39, P < 0.001) for inferior RNFL, -3.15 (95%CI:-5.19 to -1.10, P = 0.003) for nasal RNFL, and -2.45 (95%CI: -4.59 to -0.31, P = 0.025) for temporal RNFL. Along with severities of OSAS, a trend of more profound reduction of average RNFL was observed in advanced OSAS, with WMD of average RNFL thickness -1.75 (95%CI:-4.47 to -0.98, P = 0.209) for mild OSAS, -3.54 (95%CI:-6.33 to -0.73, P = 0.013) for moderate OSAS, and -7.17 (95%CI:-10.00 to -4.34, P < 0.001) for severe OSAS. The majority of studies in the descriptive review demonstrated similar findings.
CONCLUSION
The OSAS was associated with a reduced RNFL in all quadrants compared to controls. Evaluation of RNFL may serve as a tool for grading severities of OSAS. Considering the limited evidence, the conclusions should be interpreted cautiously.
Topics: Disease Progression; Humans; Nerve Fibers; Retinal Diseases; Retinal Ganglion Cells; Sleep Apnea, Obstructive; Tomography, Optical Coherence
PubMed: 27854132
DOI: 10.1080/02713683.2016.1238942 -
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 -
Ophthalmology May 2016Macular parameters have been proposed as an alternative to retinal nerve fiber layer (RNFL) parameters to diagnose glaucoma. Comparing the diagnostic accuracy of macular... (Review)
Review
TOPIC
Macular parameters have been proposed as an alternative to retinal nerve fiber layer (RNFL) parameters to diagnose glaucoma. Comparing the diagnostic accuracy of macular parameters, specifically the ganglion cell complex (GCC) and ganglion cell inner plexiform layer (GCIPL), with the accuracy of RNFL parameters for detecting manifest glaucoma is important to guide clinical practice and future research.
METHODS
Studies using spectral domain optical coherence tomography (SD OCT) and reporting macular parameters were included if they allowed the extraction of accuracy data for diagnosing manifest glaucoma, as confirmed with automated perimetry or a clinician's optic nerve head (ONH) assessment. Cross-sectional cohort studies and case-control studies were included. The QUADAS 2 tool was used to assess methodological quality. Only direct comparisons of macular versus RNFL parameters (i.e., in the same study) were conducted. Summary sensitivity and specificity of each macular or RNFL parameter were reported, and the relative diagnostic odds ratio (DOR) was calculated in hierarchical summary receiver operating characteristic (HSROC) models to compare them.
RESULTS
Thirty-four studies investigated macular parameters using RTVue OCT (Optovue Inc., Fremont, CA) (19 studies, 3094 subjects), Cirrus OCT (Carl Zeiss Meditec Inc., Dublin, CA) (14 studies, 2164 subjects), or 3D Topcon OCT (Topcon, Inc., Tokyo, Japan) (4 studies, 522 subjects). Thirty-two of these studies allowed comparisons between macular and RNFL parameters. Studies generally reported sensitivities at fixed specificities, more commonly 0.90 or 0.95, with sensitivities of most best-performing parameters between 0.65 and 0.75. For all OCT devices, compared with RNFL parameters, macular parameters were similarly or slightly less accurate for detecting glaucoma at the highest reported specificity, which was confirmed in analyses at the lowest specificity. Included studies suffered from limitations, especially the case-control study design, which is known to overestimate accuracy. However, this flaw is less relevant as a source of bias in direct comparisons conducted within studies.
CONCLUSIONS
With the use of OCT, RNFL parameters are still preferable to macular parameters for diagnosing manifest glaucoma, but the differences are small. Because of high heterogeneity, direct comparative or randomized studies of OCT devices or OCT parameters and diagnostic strategies are essential.
Topics: Glaucoma; Humans; Macula Lutea; Nerve Fibers; Optic Disk; Reproducibility of Results; Retinal Ganglion Cells; Sensitivity and Specificity; Tomography, Optical Coherence
PubMed: 26891880
DOI: 10.1016/j.ophtha.2015.12.041