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The Lancet. Neurology Oct 2017Structural retinal imaging biomarkers are important for early recognition and monitoring of inflammation and neurodegeneration in multiple sclerosis. With the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Structural retinal imaging biomarkers are important for early recognition and monitoring of inflammation and neurodegeneration in multiple sclerosis. With the introduction of spectral domain optical coherence tomography (SD-OCT), supervised automated segmentation of individual retinal layers is possible. We aimed to investigate which retinal layers show atrophy associated with neurodegeneration in multiple sclerosis when measured with SD-OCT.
METHODS
In this systematic review and meta-analysis, we searched for studies in which SD-OCT was used to look at the retina in people with multiple sclerosis with or without optic neuritis in PubMed, Web of Science, and Google Scholar between Nov 22, 1991, and April 19, 2016. Data were taken from cross-sectional cohorts and from one timepoint from longitudinal studies (at least 3 months after onset in studies of optic neuritis). We classified data on eyes into healthy controls, multiple-sclerosis-associated optic neuritis (MSON), and multiple sclerosis without optic neuritis (MSNON). We assessed thickness of the retinal layers and we rated individual layer segmentation performance by random effects meta-analysis for MSON eyes versus control eyes, MSNON eyes versus control eyes, and MSNON eyes versus MSON eyes. We excluded relevant sources of bias by funnel plots.
FINDINGS
Of 25 497 records identified, 110 articles were eligible and 40 reported data (in total 5776 eyes from patients with multiple sclerosis [1667 MSON eyes and 4109 MSNON eyes] and 1697 eyes from healthy controls) that met published OCT quality control criteria and were suitable for meta-analysis. Compared with control eyes, the peripapillary retinal nerve fibre layer (RNFL) showed thinning in MSON eyes (mean difference -20·10 μm, 95% CI -22·76 to -17·44; p<0·0001) and in MSNON eyes (-7·41 μm, -8·98 to -5·83; p<0·0001). The macula showed RNFL thinning of -6·18 μm (-8·07 to -4·28; p<0·0001) in MSON eyes and -2·15 μm (-3·15 to -1·15; p<0·0001) in MSNON eyes compared with control eyes. Atrophy of the macular ganglion cell layer and inner plexiform layer (GCIPL) was -16·42 μm (-19·23 to -13·60; p<0·0001) for MSON eyes and -6·31 μm (-7·75 to -4·87; p<0·0001) for MSNON eyes compared with control eyes. A small degree of inner nuclear layer (INL) thickening occurred in MSON eyes compared with control eyes (0·77 μm, 0·25 to 1·28; p=0·003). We found no statistical difference in the thickness of the combined outer nuclear layer and outer plexiform layer when we compared MSNON or MSON eyes with control eyes, but we found a small degree of thickening of the combined layer when we compared MSON eyes with MSNON eyes (1·21 μm, 0·24 to 2·19; p=0·01).
INTERPRETATION
The largest and most robust differences between the eyes of people with multiple sclerosis and control eyes were found in the peripapillary RNFL and macular GCIPL. Inflammatory disease activity might be captured by the INL. Because of the consistency, robustness, and large effect size, we recommend inclusion of the peripapillary RNFL and macular GCIPL for diagnosis, monitoring, and research.
FUNDING
None.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Optic Neuritis; Retina; Tomography, Optical Coherence; Young Adult
PubMed: 28920886
DOI: 10.1016/S1474-4422(17)30278-8 -
BMC Neurology Nov 2016Neurosarcoidosis is a rare variant of sarcoidosis and is only described in small cohort studies. We define clinical features, treatment and outcome of patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neurosarcoidosis is a rare variant of sarcoidosis and is only described in small cohort studies. We define clinical features, treatment and outcome of patients with neurosarcoidosis over the last 35 years.
METHODS
We performed a systematic review and meta-analysis of studies on neurosarcoidosis published between 1980 and 2016. Studies were included if they reported at least 5 cases. Studies describing one specific neurological presentation were excluded.
RESULTS
We identified 29 articles describing 1088 patients diagnosed between 1965 and 2015. Neurosarcoidosis occurred in 5% of patients with systemic sarcoidosis. Mean age at presentation was 43 years and neurological symptoms were the first clinical manifestation of sarcoidosis in 52%. The most commonly reported feature of neurosarcoidosis was cranial neuropathy in 55%, with the facial and optic nerve most commonly affected, followed by headache in 32%. Pleiocytosis and elevated CSF protein were found in 58 and 63%. MRI of the brain showed abnormalities in 70%. Chest X-ray, chest CT, or gallium-67-scintigraphy showed findings consistent with sarcoidosis in 60%, 70% and 69%, respectively. First line therapy with corticosteroids was initiated in 434 of 539 patients (81%). Second and third line therapy was started in 27 and 9%. Outcome consisted of complete remission in 27%, incomplete remission in 32%, stable disease in 24%, deterioration in 6% and death in 5%.
CONCLUSION
Neurosarcoidosis has a heterogeneous clinical presentation and the diagnosis can be difficult because of low sensitivity of ancillary investigations. New treatments have emerged, but nevertheless one third of patients do not respond to treatment. Prospective cohort studies and RCTs on treatment are urgently needed.
Topics: Adult; Central Nervous System Diseases; Humans; Sarcoidosis
PubMed: 27846819
DOI: 10.1186/s12883-016-0741-x -
Cureus Jan 2021The anatomy of the nasal cavities and paranasal sinuses is one of the most varied in the human body. The aim of this study is to review the prevalence of anatomical... (Review)
Review
The anatomy of the nasal cavities and paranasal sinuses is one of the most varied in the human body. The aim of this study is to review the prevalence of anatomical variations in the sinonasal area. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We performed on PubMed a literature search from October 2004 until May 2020. The search strategy included the following keywords: ('paranasal sinus' OR 'frontal sinus' OR 'maxillary sinus' AND ('anatomical variants' OR 'anomalies')). Fifty studies were eligible and included in the analysis. Overall, the studies encompassed a total of 18,118 patients included in this review. Most common anatomical variations include agger nasi cells, nasal septum deviation and concha bullosa. Other variations seen in this region are uncinate process variations, paradoxical middle turbinate, Haller, Onodi and supraorbital ethmoid cells, accessory ostia of maxillary sinus. Less common variations include any sinus aplasia, crista galli pneumatization and dehiscence of the optic or maxillary nerve, internal carotid artery and lamina papyracea. Anatomical variations of this region also differ among ethnic groups. This study highlights the amount, variability and significance of most anatomical variants reported in the literature in the last years. It is essential for the sinus surgeon to have a broad spectrum of knowledge not only of "the typical" anatomy but also all the possible anatomical variations. With modern imaging modalities, anatomical variations can be detected, and uneventful pitfalls might be prevented.
PubMed: 33614330
DOI: 10.7759/cureus.12727 -
BMJ (Clinical Research Ed.) Jul 2019To summarise and compare the accuracy of physical examination, computed tomography (CT), sonography of the optic nerve sheath diameter (ONSD), and transcranial Doppler... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To summarise and compare the accuracy of physical examination, computed tomography (CT), sonography of the optic nerve sheath diameter (ONSD), and transcranial Doppler pulsatility index (TCD-PI) for the diagnosis of elevated intracranial pressure (ICP) in critically ill patients.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Six databases, including Medline, EMBASE, and PubMed, from inception to 1 September 2018.
STUDY SELECTION CRITERIA
English language studies investigating accuracy of physical examination, imaging, or non-invasive tests among critically ill patients. The reference standard was ICP of 20 mm Hg or more using invasive ICP monitoring, or intraoperative diagnosis of raised ICP.
DATA EXTRACTION
Two reviewers independently extracted data and assessed study quality using the quality assessment of diagnostic accuracy studies tool. Summary estimates were generated using a hierarchical summary receiver operating characteristic (ROC) model.
RESULTS
40 studies (n=5123) were included. Of physical examination signs, pooled sensitivity and specificity for increased ICP were 28.2% (95% confidence interval 16.0% to 44.8%) and 85.9% (74.9% to 92.5%) for pupillary dilation, respectively; 54.3% (36.6% to 71.0%) and 63.6% (46.5% to 77.8%) for posturing; and 75.8% (62.4% to 85.5%) and 39.9% (26.9% to 54.5%) for Glasgow coma scale of 8 or less. Among CT findings, sensitivity and specificity were 85.9% (58.0% to 96.4%) and 61.0% (29.1% to 85.6%) for compression of basal cisterns, respectively; 80.9% (64.3% to 90.9%) and 42.7% (24.0% to 63.7%) for any midline shift; and 20.7% (13.0% to 31.3%) and 89.2% (77.5% to 95.2%) for midline shift of at least 10 mm. The pooled area under the ROC (AUROC) curve for ONSD sonography was 0.94 (0.91 to 0.96). Patient level data from studies using TCD-PI showed poor performance for detecting raised ICP (AUROC for individual studies ranging from 0.55 to 0.72).
CONCLUSIONS
Absence of any one physical examination feature is not sufficient to rule out elevated ICP. Substantial midline shift could suggest elevated ICP, but the absence of shift cannot rule it out. ONSD sonography might have use, but further studies are needed. Suspicion of elevated ICP could necessitate treatment and transfer, regardless of individual non-invasive tests.
REGISTRATION
PROSPERO CRD42018105642.
Topics: Critical Illness; Humans; Intracranial Hypertension; Physical Examination; Reproducibility of Results; Tomography, X-Ray Computed; Ultrasonography, Doppler, Transcranial
PubMed: 31340932
DOI: 10.1136/bmj.l4225 -
BMJ Clinical Evidence Jun 2011Glaucoma is characterised by progressive optic neuropathy and peripheral visual field loss. It affects 1% to 2% of white people aged over 40 years and accounts for 8% of... (Review)
Review
INTRODUCTION
Glaucoma is characterised by progressive optic neuropathy and peripheral visual field loss. It affects 1% to 2% of white people aged over 40 years and accounts for 8% of new blind registrations in the UK. The main risk factor for glaucoma is raised intraocular pressure, but 40% of people with glaucoma have normal intraocular pressure and only 10% of people with raised intraocular pressure are at risk of optic-nerve damage. Glaucoma is more prevalent, presents earlier, and is more difficult to control in black people than in white populations.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for established primary open-angle glaucoma, ocular hypertension, or both? What are the effects of lowering intraocular pressure in people with normal-tension glaucoma? What are the effects of treatment for acute angle-closure glaucoma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 12 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: laser trabeculoplasty (alone or plus topical medical treatment), topical medical treatments, and surgical trabeculectomy.
Topics: Glaucoma; Glaucoma, Angle-Closure; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension
PubMed: 21658300
DOI: No ID Found -
Journal of the Neurological Sciences Nov 2023To review the optimal diagnostic cut-off of ultrasonographic optic nerve sheath diameter (ONSD) in the diagnosis of increased intracranial pressure (IICP). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To review the optimal diagnostic cut-off of ultrasonographic optic nerve sheath diameter (ONSD) in the diagnosis of increased intracranial pressure (IICP).
METHODS
A systematic search was conducted of available studies assessing the use of ONSD ultrasonography in patients with suspected IICP. Meta-analysis of diagnostic accuracy of ultrasonographic ONSD was performed using a bivariate model of random effects to summarize pooled sensitivity and specificity. A summary receiver operating characteristics (SROC) curve was plotted. Accuracy measures associated with ONSD cut-off and predefined covariates were investigated with meta-regression.
RESULTS
We included 38 studies, comprising a total of 2824 patients. A total of 21 studies used invasive techniques as a reference standard estimation of IICP and meta-analysis revealed a pooled sensitivity of 0.90 (95% CI 0.85-0.93) and specificity of 0.87 (95% CI 0.80-0.91). Optimal ONSD cut-off values ranged between 4.1 mm and 7.2 mm. Meta-regression analysis showed that ONSD cut-off values of 5.6 to 6.3 mm were associated with higher pooled specificity compared to cut-off values of 4.9 to 5.5 mm (0.93, 95% CI 0.85-0.97 vs. 0.78, 95% CI 0.65-0.87; p = 0.036).
CONCLUSIONS
Ultrasonography of ONSD shows a high diagnostic accuracy for IICP, with high pooled sensitivity and specificity. Additionally, larger cut-off values seem to significantly increase specificity without compromising sensitivity, which support their use as optimal ONSD cut-off. The overall high sensitivity of ultrasonographic ONSD suggests its usefulness as a screening tool for IIC, which may provide an estimate of when invasive methods are warranted.
CLINICAL RELEVANCE
ONSD ultrasonography is a fast and cost-effective method with a high diagnostic accuracy to detect IICP. The optimum ONSD cut-off hasn't been established before, but we suggest the 5.6 to 6.3 mm range as the best for the diagnosis of IICP.
Topics: Humans; Intracranial Pressure; Optic Nerve; Intracranial Hypertension; Sensitivity and Specificity; Ultrasonography
PubMed: 37925899
DOI: 10.1016/j.jns.2023.120853 -
Journal of Personalized Medicine Mar 2022We aimed to identify the efficacy of optic nerve sheath diameter (ONSD) in predicting mortality and poor neurological outcomes (PNO) in post-cardiac arrest syndrome... (Review)
Review
We aimed to identify the efficacy of optic nerve sheath diameter (ONSD) in predicting mortality and poor neurological outcomes (PNO) in post-cardiac arrest syndrome (PCAS) by the measurement time of outcomes. We conducted an extensive literature search in EMBASE, MEDLINE, and Cochrane Library, which included studies on the prognostic accuracy of ONSD in predicting PNO and mortality in PCAS by the measured time of outcomes. A total of 791 patients from nine studies were included. Increased ONSD was weakly associated with PNO by a high heterogeneity (standardized mean difference with 95% confidence interval = 0.74 (0.22, 1.27); I = 87%). The analysis by the measurement time of PNO and mortality for ONSD had no significant difference due to insufficient articles or high heterogeneities. The prognostic accuracy of ONSD was 23.97 (pooled diagnostic odds ratio, I = 0%) and 0.94 (area under the curve) for short-term PNO. The pooled results showed low or very low quality and very low quality of evidence for PNO and mortality, respectively. ONSD measurement might be an effective predictor for short-term PNO in PCAS. An analysis by measurement time of outcomes showed no significant evidence for ONSD measurement effectiveness in predicting mortality and PNO.
PubMed: 35330499
DOI: 10.3390/jpm12030500 -
Genetics in Medicine : Official Journal... Mar 2022This study aimed to systematically review and summarize gene therapy treatment for monogenic retinal and optic nerve diseases. (Review)
Review
PURPOSE
This study aimed to systematically review and summarize gene therapy treatment for monogenic retinal and optic nerve diseases.
METHODS
This review was prospectively registered (CRD42021229812). A comprehensive literature search was performed in Ovid MEDLINE, Ovid Embase, Cochrane Central, and clinical trial registries (February 2021). Clinical studies describing DNA-based gene therapy treatments for monogenic posterior ocular diseases were eligible for inclusion. Risk of bias evaluation was performed. Data synthesis was undertaken applying Synthesis Without Meta-analysis guidelines.
RESULTS
This study identified 47 full-text publications, 50 conference abstracts, and 54 clinical trial registry entries describing DNA-based ocular gene therapy treatments for 16 different genetic variants. Study summaries and visual representations of safety and efficacy outcomes are presented for 20 unique full-text publications in RPE65-mediated retinal dystrophies, choroideremia, Leber hereditary optic neuropathy, rod-cone dystrophy, achromatopsia, and X-linked retinoschisis. The most common adverse events were related to lid/ocular surface/cornea abnormalities in subretinal gene therapy trials and anterior uveitis in intravitreal gene therapy trials.
CONCLUSION
There is a high degree of variability in ocular monogenic gene therapy trials with respect to study design, statistical methodology, and reporting of safety and efficacy outcomes. This review improves the accessibility and transparency in interpreting gene therapy trials to date.
Topics: Color Vision Defects; Genetic Therapy; Humans; Optic Nerve Diseases; Retina; Retinal Dystrophies
PubMed: 34906485
DOI: 10.1016/j.gim.2021.10.013 -
BMJ Open Ophthalmology Nov 2023To explore the current research about the role of optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in dysthyroid optic neuropathy... (Meta-Analysis)
Meta-Analysis
PURPOSE
To explore the current research about the role of optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in dysthyroid optic neuropathy (DON).
METHODS
Studies in the literature that focused on OCT, OCTA and DON were retrieved by searching PubMed, EMBASE, Cochrane databases and Clinical Trial before 20 June 2023. The methodological quality was assessed using the Newcastle-Ottawa scale. The quantitative calculation was performed using Review Manager V.5.3.
RESULTS
Twelve studies met the eligibility criteria and were included. DON group presented lower macular ganglion cell complex in the overall, superior and inferior hemifields compared with the non-DON group. Furthermore, the ganglion cell layer and inner plexiform layer in DON group was thinner in contrast to the non-DON group. The optic nerve head vessel density was lower in the DON group than that in the non-DON group. A reduction of radial peripapillary capillary vessel density could be seen in the DON group than the non-DON group in overall, inside disc, peripapillary, superior-hemifield, temporal and nasal. Besides, the macular superficial retinal capillary layer of non-DON and DON is lower than the healthy control group.
CONCLUSIONS
This study supported the potential value of OCT and OCTA metrics as novel biomarkers of DON. Ophthalmologists should comprehensively consider the retinal structure and microvasculature in dealing with DON.
ETHICS AND DISSEMINATION
This systematic review included data from published literature and was exempt from ethics approval. Results would be disseminated through peer-reviewed publication and presented at academic conferences engaging clinicians.
PROSPERO REGISTRATION NUMBER
CRD42023414907.
Topics: Humans; Tomography, Optical Coherence; Optic Disk; Angiography; Retinal Ganglion Cells; Optic Nerve Diseases
PubMed: 37996119
DOI: 10.1136/bmjophth-2023-001379 -
The Cochrane Database of Systematic... Nov 2015The diagnosis of glaucoma is traditionally based on the finding of optic nerve head (ONH) damage assessed subjectively by ophthalmoscopy or photography or by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The diagnosis of glaucoma is traditionally based on the finding of optic nerve head (ONH) damage assessed subjectively by ophthalmoscopy or photography or by corresponding damage to the visual field assessed by automated perimetry, or both. Diagnostic assessments are usually required when ophthalmologists or primary eye care professionals find elevated intraocular pressure (IOP) or a suspect appearance of the ONH. Imaging tests such as confocal scanning laser ophthalmoscopy (HRT), optical coherence tomography (OCT) and scanning laser polarimetry (SLP, as used by the GDx instrument), provide an objective measure of the structural changes of retinal nerve fibre layer (RNFL) thickness and ONH parameters occurring in glaucoma.
OBJECTIVES
To determine the diagnostic accuracy of HRT, OCT and GDx for diagnosing manifest glaucoma by detecting ONH and RNFL damage.
SEARCH METHODS
We searched several databases for this review. The most recent searches were on 19 February 2015.
SELECTION CRITERIA
We included prospective and retrospective cohort studies and case-control studies that evaluated the accuracy of OCT, HRT or the GDx for diagnosing glaucoma. We excluded population-based screening studies, since we planned to consider studies on self-referred people or participants in whom a risk factor for glaucoma had already been identified in primary care, such as elevated IOP or a family history of glaucoma. We only considered recent commercial versions of the tests: spectral domain OCT, HRT III and GDx VCC or ECC.
DATA COLLECTION AND ANALYSIS
We adopted standard Cochrane methods. We fitted a hierarchical summary ROC (HSROC) model using the METADAS macro in SAS software. After studies were selected, we decided to use 2 x 2 data at 0.95 specificity or closer in meta-analyses, since this was the most commonly-reported level.
MAIN RESULTS
We included 106 studies in this review, which analysed 16,260 eyes (8353 cases, 7907 controls) in total. Forty studies (5574 participants) assessed GDx, 18 studies (3550 participants) HRT, and 63 (9390 participants) OCT, with 12 of these studies comparing two or three tests. Regarding study quality, a case-control design in 103 studies raised concerns as it can overestimate accuracy and reduce the applicability of the results to daily practice. Twenty-four studies were sponsored by the manufacturer, and in 15 the potential conflict of interest was unclear.Comparisons made within each test were more reliable than those between tests, as they were mostly based on direct comparisons within each study.The Nerve Fibre Indicator yielded the highest accuracy (estimate, 95% confidence interval (CI)) among GDx parameters (sensitivity: 0.67, 0.55 to 0.77; specificity: 0.94, 0.92 to 0.95). For HRT measures, the Vertical Cup/Disc (C/D) ratio (sensitivity: 0.72, 0.60 to 0.68; specificity: 0.94, 0.92 to 0.95) was no different from other parameters. With OCT, the accuracy of average RNFL retinal thickness was similar to the inferior sector (0.72, 0.65 to 0.77; specificity: 0.93, 0.92 to 0.95) and, in different studies, to the vertical C/D ratio.Comparing the parameters with the highest diagnostic odds ratio (DOR) for each device in a single HSROC model, the performance of GDx, HRT and OCT was remarkably similar. At a sensitivity of 0.70 and a high specificity close to 0.95 as in most of these studies, in 1000 people referred by primary eye care, of whom 200 have manifest glaucoma, such as in those who have already undergone some functional or anatomic testing by optometrists, the best measures of GDx, HRT and OCT would miss about 60 cases out of the 200 patients with glaucoma, and would incorrectly refer 50 out of 800 patients without glaucoma. If prevalence were 5%, e.g. such as in people referred only because of family history of glaucoma, the corresponding figures would be 15 patients missed out of 50 with manifest glaucoma, avoiding referral of about 890 out of 950 non-glaucomatous people.Heterogeneity investigations found that sensitivity estimate was higher for studies with more severe glaucoma, expressed as worse average mean deviation (MD): 0.79 (0.74 to 0.83) for MD < -6 db versus 0.64 (0.60 to 0.69) for MD ≥ -6 db, at a similar summary specificity (0.93, 95% CI 0.92 to 0.94 and, respectively, 0.94; 95% CI 0.93 to 0.95; P < 0.0001 for the difference in relative DOR).
AUTHORS' CONCLUSIONS
The accuracy of imaging tests for detecting manifest glaucoma was variable across studies, but overall similar for different devices. Accuracy may have been overestimated due to the case-control design, which is a serious limitation of the current evidence base.We recommend that further diagnostic accuracy studies are carried out on patients selected consecutively at a defined step of the clinical pathway, providing a description of risk factors leading to referral and bearing in mind the consequences of false positives and false negatives in the setting in which the diagnostic question is made. Future research should report accuracy for each threshold of these continuous measures, or publish raw data.
Topics: Diagnostic Errors; Glaucoma; Humans; Nerve Fibers; Odds Ratio; Ophthalmoscopy; Optic Disk; Prospective Studies; Retrospective Studies; Scanning Laser Polarimetry; Sensitivity and Specificity; Tomography, Optical Coherence; Visual Field Tests
PubMed: 26618332
DOI: 10.1002/14651858.CD008803.pub2