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Eye (London, England) Jul 2023
Meta-Analysis
Topics: Humans; Cytokines; Diabetic Retinopathy; Vitreous Body; Vitrectomy; Diabetes Mellitus
PubMed: 36310184
DOI: 10.1038/s41433-022-02294-x -
Forensic Science, Medicine, and... Jun 2023The K and hypoxanthine (Hx) concentrations of the vitreous humour (VH) rise gradually after death, providing a means of estimating the post-mortem interval (PMI). The... (Review)
Review
The K and hypoxanthine (Hx) concentrations of the vitreous humour (VH) rise gradually after death, providing a means of estimating the post-mortem interval (PMI). The correlation between these analytes and the PMI is good since the vitreous chamber is partially isolated from autolytic events occurring elsewhere; the [K +] and [Hx] recorded is thus the result of changes within the eye. The present work provides a systematic review, following PRISMA recommendations, of 36 articles (3 reviews and 33 retrospective cohort studies) discussing the many procedures and regression models that have been developed for improving PMI estimates involving VH analytes. The results of a descriptive study are also provided, highlighting the causes and distribution of mortality as registered in medico-legal autopsies performed in 2019 in Galicia (northwestern Spain), and revealing the use of these PMI estimation methods in real forensic practice. Great heterogeneity was detected in the collection of VH samples, the treatments to which they were subjected before examination, and in their conservation and analysis. A lack of reproducibility in the analytical methods employed to estimate [K +] and [Hx] was noted, as well as an absence of external validation for most of the regression formulae used to determine the PMI from analyte values. The use of methods based on high-performance liquid chromatography, focal electrophoresis, or thermogravimetric/chemometric procedures might solve the problems encountered with traditional analytical techniques, offering reliable results more quickly and effectively (even when samples are contaminated). This study recommends using flexible multiple regression models that combine physical and chemical variables, and that population databases be constructed so that models can be properly validated.
Topics: Humans; Autopsy; Postmortem Changes; Vitreous Body; Spain; Reproducibility of Results; Retrospective Studies; Hypoxanthine
PubMed: 36271219
DOI: 10.1007/s12024-022-00539-5 -
Forensic Science, Medicine, and... Mar 2023The persistence and infectivity of SARS-CoV-2 in different postmortem COVID-19 specimens remain unclear despite numerous published studies. This information is essential... (Review)
Review
The persistence and infectivity of SARS-CoV-2 in different postmortem COVID-19 specimens remain unclear despite numerous published studies. This information is essential to improve corpses management related to clinical biosafety and viral transmission in medical staff and the public community. We aim to understand SARS-CoV-2 persistence and infectivity in COVID-19 corpses. We conducted a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocols. A systematic literature search was performed in PubMed, Science Direct Scopus, and Google Scholar databases using specific keywords. We critically reviewed the collected studies and selected the articles that met the criteria. We included 33 scientific papers that involved 491 COVID-19 corpses. The persistence rate and maximum postmortem interval (PMI) range of the SARS-CoV-2 findings were reported in the lungs (138/155, 89.0%; 4 months), followed by the vitreous humor (7/37, 18.9%; 3 months), nasopharynx/oropharynx (156/248, 62.9%; 41 days), abdominal organs (67/110, 60.9%; 17 days), skin (14/24, 58.3%; 17 days), brain (14/31, 45.2%; 17 days), bone marrow (2/2, 100%; 12 days), heart (31/69, 44.9%; 6 days), muscle tissues (9/83, 10.8%; 6 days), trachea (9/20, 45.0%; 5 days), and perioral tissues (21/24, 87.5%; 3.5 days). SARS-CoV-2 infectivity rates in viral culture studies were detected in the lungs (9/15, 60%), trachea (2/4, 50%), oropharynx (1/4, 25%), and perioral (1/4, 25%) at a maximum PMI range of 17 days. The SARS-CoV-2 persists in the human body months after death and should be infectious for weeks. This data should be helpful for postmortem COVID-19 management and viral transmission preventive strategy.
Topics: Humans; COVID-19; SARS-CoV-2; Oropharynx; Nasopharynx; Cadaver
PubMed: 36001241
DOI: 10.1007/s12024-022-00518-w -
Graefe's Archive For Clinical and... Feb 2023To review the literature on the application of bioinformatics and artificial intelligence (AI) for analysis of biofluid biomarkers in retinal vein occlusion (RVO) and... (Review)
Review
PURPOSE
To review the literature on the application of bioinformatics and artificial intelligence (AI) for analysis of biofluid biomarkers in retinal vein occlusion (RVO) and their potential utility in clinical decision-making.
METHODS
We systematically searched MEDLINE, Embase, Cochrane, and Web of Science databases for articles reporting on AI or bioinformatics in RVO involving biofluids from inception to August 2021. Simple AI was categorized as logistics regressions of any type. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Tools.
RESULTS
Among 10,264 studies screened, 14 eligible articles, encompassing 578 RVO patients, met the inclusion criteria. The use and reporting of AI and bioinformatics was heterogenous. Four articles performed proteomic analyses, two of which integrated AI tools such as discriminant analysis, probabilistic clustering, and string pathway analysis. A metabolomic study used AI tools for clustering, classification, and predictive modeling such as orthogonal partial least squares discriminant analysis. However, most studies used simple AI (n = 9). Vitreous humor sample levels of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and aqueous humor levels of intercellular adhesion molecule-1 and IL-8 were implicated in the pathogenesis of branch RVO with macular edema. IL-6 and VEGF may predict visual acuity after intravitreal injections or vitrectomy, respectively. Metabolomics and Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified the metabolic signature of central RVO to be related to lower aqueous humor concentration of carbohydrates and amino acids. Risk of bias was low or moderate for included studies.
CONCLUSION
Bioinformatics has applications for analysis of proteomics and metabolomics present in biofluids in RVO with AI for clinical decision-making and advancing the future of RVO precision medicine. However, multiple limitations such as simple AI use, small sample volume, inconsistent feasibility of office-based sampling, lack of longitudinal follow-up, lack of sampling before and after RVO, and lack of healthy controls must be addressed in future studies.
Topics: Humans; Angiogenesis Inhibitors; Artificial Intelligence; Computational Biology; Interleukin-6; Intravitreal Injections; Proteomics; Retinal Diseases; Retinal Vein Occlusion; Vascular Endothelial Growth Factor A
PubMed: 35925451
DOI: 10.1007/s00417-022-05769-5 -
Ocular Immunology and Inflammation Apr 2022The current gold standard to grade vitreous inflammation is the Nussenblatt scale based in clinical examination, published in 1985. Nowadays a big effort is undergoing...
PURPOSE
The current gold standard to grade vitreous inflammation is the Nussenblatt scale based in clinical examination, published in 1985. Nowadays a big effort is undergoing to come out with more objective and reliable methods based in optical coherence (OCT) imaging analysis.
METHODS
A systematic review was done to identify the articles that quantify or assess qualitatively vitreous inflammation with OCT.
RESULTS
Twelve papers were included. Only one paper analyzed qualitatively the anatomy of the vitreous body and its potential influence in cystoid macular edema, while the rest assessed vitreous inflammation quantitatively using the relative reflectivity of the vitreous body with different retinal structures or quantifying the hyperreflective dots in the vitreous.
CONCLUSION
The new development of OCT-based scales for measuring vitreous inflammation could replace the current clinical grading scales as an end point for future clinical trials.
Topics: Humans; Inflammation; Macular Edema; Tomography, Optical Coherence; Uveitis; Vitreous Body
PubMed: 35901539
DOI: 10.1080/09273948.2022.2075399 -
Eye (London, England) Jun 2022Diabetic retinopathy is a major complication of diabetes mellitus, where in its most advanced form ischemic changes lead to the development of retinal... (Review)
Review
BACKGROUND
Diabetic retinopathy is a major complication of diabetes mellitus, where in its most advanced form ischemic changes lead to the development of retinal neovascularization, termed proliferative diabetic retinopathy (PDR). While the development of PDR is often associated with angiogenic and inflammatory cytokines, studies differ on which cytokines are implicated in disease pathogenesis and on the strength of these associations. We therefore conducted a systematic review and meta-analysis to quantitatively assess the existing body of data on intraocular cytokines as biomarkers in PDR.
METHODS
A comprehensive search of the literature without year limitation was conducted to January 18, 2021, which identified 341 studies assessing vitreous or aqueous cytokine levels in PDR, accounting for 10379 eyes with PDR and 6269 eyes from healthy controls. Effect sizes were calculated as standardized mean differences (SMD) of cytokine concentrations between PDR and control patients.
RESULTS
Concentrations (SMD, 95% confidence interval, and p-value) of aqueous IL-1β, IL-6, IL-8, MCP-1, TNF-α, and VEGF, and vitreous IL-2, IL-4, IL-6, IL-8, angiopoietin-2, eotaxin, erythropoietin, GM-CSF, GRO, HMGB-1, IFN-γ, IGF, IP-10, MCP-1, MIP-1, MMP-9, PDGF-AA, PlGF, sCD40L, SDF-1, sICAM-1, sVEGFR, TIMP, TNF-α, and VEGF were significantly higher in patients with PDR when compared to healthy nondiabetic controls. For all other cytokines no differences, failed sensitivity analyses or insufficient data were found.
CONCLUSIONS
This extensive list of cytokines speaks to the complexity of PDR pathogenesis, and informs future investigations into disease pathogenesis, prognosis, and management.
PubMed: 35672457
DOI: 10.1038/s41433-022-02127-x -
The Cochrane Database of Systematic... Jun 2022Endophthalmitis refers to severe infection within the eye that involves the aqueous humor or vitreous humor, or both, and that threatens vision. Most cases of... (Review)
Review
BACKGROUND
Endophthalmitis refers to severe infection within the eye that involves the aqueous humor or vitreous humor, or both, and that threatens vision. Most cases of endophthalmitis are exogenous (i.e. due to inoculation of organisms from an outside source), and most exogenous endophthalmitis is acute and occurs after an intraocular procedure. The mainstay of treatment is emergent administration of broad-spectrum intravitreous antibiotics. Due to their anti-inflammatory effects, steroids in conjunction with antibiotics have been proposed as being beneficial in endophthalmitis management.
OBJECTIVES
To assess the effects of antibiotics combined with steroids versus antibiotics alone for the treatment of acute endophthalmitis following intraocular surgery or intravitreous injection.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2021, Issue 8), MEDLINE Ovid (1946 to August 2021), Embase Ovid (1980 to August 2021), LILACS (Latin American and Caribbean Health Sciences Literature database) (1982 to August 2021), the ISRCTN registry; searched August 2021, ClinicalTrials.gov; searched August 2021, and the WHO International Clinical Trials Registry Platform; searched August 2021. We did not use any date or language restrictions in the electronic searches for trials.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing the effectiveness of adjunctive steroids with antibiotics alone in the management of acute, clinically diagnosed endophthalmitis following intraocular surgery or intravitreous injection. We excluded trials with participants with endogenous endophthalmitis unless outcomes were reported by source of infection. We imposed no restrictions on the method or order of administration, dose, frequency, or duration of antibiotics and steroids.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology, and graded the certainty of the body of evidence for six outcomes using the GRADE classification.
MAIN RESULTS
We included four RCTs with a total of 264 eyes of 264 participants in this review update. The studies were conducted in South Africa, India, and the Netherlands. All studies used intravitreous dexamethasone for adjunctive steroid therapy and a combination of two intravitreous antibiotics that provided gram-positive and gram-negative coverage for the antibiotic therapy. We judged two trials to be at overall low risk of bias, and the other two studies to be at overall unclear risk of bias due to lack of reporting of study methods. Only one study was registered in a clinical trial register. While none of the included studies reported the primary outcome of complete resolution of endophthalmitis as defined in our protocol, one study reported combined anatomical and functional success (i.e. proportion of participants with intraocular pressure of at least 5 mmHg and visual acuity of at least 6/120). Very low certainty evidence suggested no difference in combined success when comparing adjunctive steroid to antibiotics alone (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.80 to 1.45; 32 participants). Low certainty evidence from two studies suggested that adjunctive dexamethasone may result in having a good visual outcome (Snellen visual acuity 6/6 to 6/18) at 3 months compared with antibiotics alone (RR 1.95, 95% CI 1.05 to 3.60; 60 participants); however, the evidence was less conclusive at 12 months (RR 1.12, 95% CI 0.92 to 1.37; 2 studies; 195 participants; low certainty evidence). Investigators of one study reported improvement in visual acuity, but we could not estimate the effect of adjunctive steroid therapy because the study investigators did not provide any estimates of precision. Only one study examined intraocular pressure (IOP). The evidence suggests that adjunctive dexamethasone may reduce IOP slightly after 12 months of interventions (mean difference -1.90, 95% CI -3.78 to 0.07; 1 study; 167 participants; low certainty evidence). Three studies reported adverse events (retinal detachment, hypotony, proliferative vitreoretinopathy, seclusion of pupil, floaters, and pucker). The total numbers of adverse events were 14 out of 111 (12.6%) for those who received dexamethasone versus 12 out of 116 (10.3%) for those who did not. We could only perform a pooled analysis for the occurrence of retinal detachment: any difference between the two treatment groups was uncertain (RR 1.41, 95% CI 0.53 to 3.74; 227 participants; low certainty evidence). No study reported cost-related outcomes.
AUTHORS' CONCLUSIONS
The currently available evidence on the effectiveness of adjunctive steroid therapy versus antibiotics alone in the management of acute endophthalmitis after intraocular surgery is inadequate. We found no studies that had enrolled cases of acute endophthalmitis following intravitreous injection. A combined analysis of two studies suggests that use of adjunctive steroids may provide a higher chance of having a good visual outcome at three months than not using adjunctive steroids. However, considering that most of the confidence intervals crossed the null, and that this review was limited in scope and applicability to clinical practice, it is not possible to conclude whether the use of adjunctive steroids is effective at this time. Any future trials should examine whether adjunctive steroids may be useful in certain clinical settings such as type of causative organism or etiology. These studies should include outcomes that take patients' symptoms and clinical examination into account; report outcomes in a uniform and consistent manner; and follow up at short- and long-term intervals.
Topics: Anti-Bacterial Agents; Dexamethasone; Endophthalmitis; Eye Diseases; Humans; Retinal Detachment; Steroids
PubMed: 35665485
DOI: 10.1002/14651858.CD012131.pub3 -
Acta Ophthalmologica Aug 2022The pathophysiology of diabetic macular oedema (DME) remains poorly understood. Proteomic analysis of the vitreous using mass spectrometry (MS) can potentially identify... (Review)
Review
The pathophysiology of diabetic macular oedema (DME) remains poorly understood. Proteomic analysis of the vitreous using mass spectrometry (MS) can potentially identify proteins of pathophysiological importance. In this systematic review, we summarize the available evidence on protein changes in DME detected by MS. We systematically searched 13 literature databases on 19 September 2021. Eligible studies were defined as those using samples from human eyes with DME analysed with MS. Two authors assessed the studies for eligibility, extracted data and evaluated risk of bias independently. Six eligible studies were identified. All were designed in a cross-sectional fashion comparing results to either a non-diabetic control group or a control group without DME. A total of 62 eyes from 60 patients contributed as study group and 48 eyes from 48 patients served as control group. Proteomic analyses revealed significant differences in the vitreous protein levels in patients with DME when compared with controls. Three studies or more identified increased contents of apolipoprotein A-I, apolipoprotein A-II, apolipoprotein A-IV, apolipoprotein C-III, gelsolin, pigment epithelium-derived factor, serum albumin, transthyretin, vitamin D-binding protein in DME. Two studies found increased levels of complement factors B and C3. Protein changes reproduced across the studies suggested that DME was associated with retinal lipid accumulation, angiogenesis, retinal protective mechanisms, inflammation and complement activation. Proteome studies support the multifactorial pathogenesis of DME as proteins with highly different biological functions are regulated in DME. An important number of proteins differ, provide pathophysiological insight and suggest the direction for future research.
Topics: Cross-Sectional Studies; Diabetes Mellitus; Diabetic Retinopathy; Humans; Macular Edema; Proteomics; Vitreous Body
PubMed: 35507578
DOI: 10.1111/aos.15168 -
Annals of Palliative Medicine Dec 2021Diabetic macular edema (DME) is a type of retinopathy caused by diabetes, and the 2 main clinical treatment modalities are drug therapy intravitreal triamcinolone... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of triamcinolone acetonide injection combined with laser photocoagulation in the treatment of diabetic macular edema: a systematic review and meta-analysis.
BACKGROUND
Diabetic macular edema (DME) is a type of retinopathy caused by diabetes, and the 2 main clinical treatment modalities are drug therapy intravitreal triamcinolone acetonide injection (IVTA) and laser photocoagulation. This meta-analysis investigated the efficacy of combining both the 2 treatment modalities.
METHODS
The Embase, Cochrane library, PubMed, and Ovid databases were searched for English literatures. The literatures were screened and assessed for the risk of bias, after that the Revman 5.4 software was used to conduct the meta-analysis.
RESULTS
A total of 8 articles, including 549 patients, were included in this study. Meta-analysis showed that the effect of (IVTA + laser) on early central macular thickness (CMT) was not significantly different with IVTA alone [mean difference (MD) =-5.13, 95% confidence interval (CI): -17.06 to 6.80, P=0.40], however, significantly different with laser alone (MD =-94.31, 95% CI: -135.04 to -53.58, P<0.00001). Similarly, the effect of (IVTA + laser) on early best corrected visual acuity (BCVA) was not significantly different with IVTA alone (MD =0.02, 95% CI: -0.03 to 0.07, Z=0.79, P=0.43). but different with laser alone [MD =-0.20, 95% CI: -0.24 to -0.16, Z=10.16, P<0.00001). The effect of (IVTA + laser) on long-term CMT was not significantly different with IVTA alone (MD =-66.90, 95% CI: -132.66 to -1.15, Z=1.99, P=0.05) nor with laser alone (MD =-15.86, 95% CI: -31.37 to -0.35, Z=2.00, P=0.05). Similarly, the effect of combined intervention (IVTA + laser) on long-term BCVA was not significantly different with IVTA alone (MD =-0.18, 95% CI: -0.39 to 0.03, Z=1.71, P=0.09) nor with laser alone (MD =-0.11, 95% CI: -0.23 to 0.01, Z=1.74, P=0.08). Administration of IVTA before laser was superior to laser alone (MD =-0.19, 95% CI: -0.31 to -0.07, Z=3.09, P=0.002).
DISCUSSION
The effect of IVTA + laser therapy is similar to IVTA alone, but superior to laser alone for the early treatment of DME. However, the long-term effect is similar to IVTA alone or laser alone, a better therapeutic effect can be achieved if IVTA is administered before laser treatment.
Topics: Diabetes Mellitus; Diabetic Retinopathy; Glucocorticoids; Humans; Light Coagulation; Macular Edema; Treatment Outcome; Triamcinolone Acetonide; Visual Acuity; Vitreous Body
PubMed: 35016410
DOI: 10.21037/apm-21-3274 -
Journal of Forensic and Legal Medicine Oct 2021Vitreous humor has been extensively used in forensic practice to assess hyperglycemia after death. The results from different articles, for various hyperglycemia markers... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitreous humor has been extensively used in forensic practice to assess hyperglycemia after death. The results from different articles, for various hyperglycemia markers are highly variable, and a systematic analysis of the results from studies currently used in forensic practice as landmarks has not yet been performed. Therefore, we aimed to evaluate to usefulness and limits of using the values of vitreous glucose, lactic acid, beta-hydroxybutyrate, and 1,5 Anhydro-d-glucitol to detect postmortem hyperglycemia.
MATERIALS AND METHODS
For this purpose, we performed a systematic review and a meta-analysis using the random-effects model to identify the threshold values and average differences for the markers mentioned above in the vitreous humor of diabetic versus nondiabetic subjects.
RESULTS
We included eleven studies in the meta-analysis and found the following mean differences between the diabetic and nondiabetic groups: for glucose - 91.4 mg/dl, for lactate - 34.17 mg/dl, for the Traub formula - 111 mg/dl, for fructosamine - 0.71 mmol/L, for beta-hydroxybutyrate - 36.55 mg/dl and 1,5 Anhydro-d-glucitol - -15.2 mg/dl. We also gave practical recommendations, based on the range of values and 95% confidence intervals in normal subjects and controls to identify antemortem hyperglycemia and evaluated, whenever possible, threshold values for fatal diabetes.
CONCLUSIONS
Glucose, Traub formula, fructosamine, and beta-hydroxy-butyrate can be used to detect postmortem hyperglycemia with some limitations; 1,5 Anhydro-d-glucitol can only be used to suggest the absence of a hyperglycemic status before death.
Topics: 3-Hydroxybutyric Acid; Biomarkers; Deoxyglucose; Forensic Medicine; Fructosamine; Glucose; Humans; Hyperglycemia; Lactic Acid; Postmortem Changes; Vitreous Body
PubMed: 34488176
DOI: 10.1016/j.jflm.2021.102250