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The Cochrane Database of Systematic... Feb 2023Diabetic retinopathy (DR) is characterised by neurovascular degeneration as a result of chronic hyperglycaemia. Proliferative diabetic retinopathy (PDR) is the most... (Review)
Review
BACKGROUND
Diabetic retinopathy (DR) is characterised by neurovascular degeneration as a result of chronic hyperglycaemia. Proliferative diabetic retinopathy (PDR) is the most serious complication of DR and can lead to total (central and peripheral) visual loss. PDR is characterised by the presence of abnormal new blood vessels, so-called "new vessels," at the optic disc (NVD) or elsewhere in the retina (NVE). PDR can progress to high-risk characteristics (HRC) PDR (HRC-PDR), which is defined by the presence of NVD more than one-fourth to one-third disc area in size plus vitreous haemorrhage or pre-retinal haemorrhage, or vitreous haemorrhage or pre-retinal haemorrhage obscuring more than one disc area. In severe cases, fibrovascular membranes grow over the retinal surface and tractional retinal detachment with sight loss can occur, despite treatment. Although most, if not all, individuals with diabetes will develop DR if they live long enough, only some progress to the sight-threatening PDR stage. OBJECTIVES: To determine risk factors for the development of PDR and HRC-PDR in people with diabetes and DR.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 5), Ovid MEDLINE, and Ovid Embase. The date of the search was 27 May 2022. Additionally, the search was supplemented by screening reference lists of eligible articles. There were no restrictions to language or year of publication. SELECTION CRITERIA: We included prospective or retrospective cohort studies and case-control longitudinal studies evaluating prognostic factors for the development and progression of PDR, in people who have not had previous treatment for DR. The target population consisted of adults (≥18 years of age) of any gender, sexual orientation, ethnicity, socioeconomic status, and geographical location, with non-proliferative diabetic retinopathy (NPDR) or PDR with less than HRC-PDR, diagnosed as per standard clinical practice. Two review authors independently screened titles and abstracts, and full-text articles, to determine eligibility; discrepancies were resolved through discussion. We considered prognostic factors measured at baseline and any other time points during the study and in any clinical setting. Outcomes were evaluated at three and eight years (± two years) or lifelong. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from included studies using a data extraction form that we developed and piloted prior to the data collection stage. We resolved any discrepancies through discussion. We used the Quality in Prognosis Studies (QUIPS) tool to assess risk of bias. We conducted meta-analyses in clinically relevant groups using a random-effects approach. We reported hazard ratios (HR), odds ratios (OR), and risk ratios (RR) separately for each available prognostic factor and outcome, stratified by different time points. Where possible, we meta-analysed adjusted prognostic factors. We evaluated the certainty of the evidence with an adapted version of the GRADE framework. MAIN RESULTS: We screened 6391 records. From these, we identified 59 studies (87 articles) as eligible for inclusion. Thirty-five were prospective cohort studies, 22 were retrospective studies, 18 of which were cohort and six were based on data from electronic registers, and two were retrospective case-control studies. Twenty-three studies evaluated participants with type 1 diabetes (T1D), 19 with type 2 diabetes (T2D), and 17 included mixed populations (T1D and T2D). Studies on T1D included between 39 and 3250 participants at baseline, followed up for one to 45 years. Studies on T2D included between 100 and 71,817 participants at baseline, followed up for one to 20 years. The studies on mixed populations of T1D and T2D ranged from 76 to 32,553 participants at baseline, followed up for four to 25 years. We found evidence indicating that higher glycated haemoglobin (haemoglobin A1c (HbA1c)) levels (adjusted OR ranged from 1.11 (95% confidence interval (CI) 0.93 to 1.32) to 2.10 (95% CI 1.64 to 2.69) and more advanced stages of retinopathy (adjusted OR ranged from 1.38 (95% CI 1.29 to 1.48) to 12.40 (95% CI 5.31 to 28.98) are independent risk factors for the development of PDR in people with T1D and T2D. We rated the evidence for these factors as of moderate certainty because of moderate to high risk of bias in the studies. There was also some evidence suggesting several markers for renal disease (for example, nephropathy (adjusted OR ranged from 1.58 (95% CI not reported) to 2.68 (2.09 to 3.42), and creatinine (adjusted meta-analysis HR 1.61 (95% CI 0.77 to 3.36)), and, in people with T1D, age at diagnosis of diabetes (< 12 years of age) (standardised regression estimate 1.62, 95% CI 1.06 to 2.48), increased triglyceride levels (adjusted RR 1.55, 95% CI 1.06 to 1.95), and larger retinal venular diameters (RR 4.28, 95% CI 1.50 to 12.19) may increase the risk of progression to PDR. The certainty of evidence for these factors, however, was low to very low, due to risk of bias in the included studies, inconsistency (lack of studies preventing the grading of consistency or variable outcomes), and imprecision (wide CIs). There was no substantial and consistent evidence to support duration of diabetes, systolic or diastolic blood pressure, total cholesterol, low- (LDL) and high- (HDL) density lipoproteins, gender, ethnicity, body mass index (BMI), socioeconomic status, or tobacco and alcohol consumption as being associated with incidence of PDR. There was insufficient evidence to evaluate prognostic factors associated with progression of PDR to HRC-PDR. AUTHORS' CONCLUSIONS: Increased HbA1c is likely to be associated with progression to PDR; therefore, maintaining adequate glucose control throughout life, irrespective of stage of DR severity, may help to prevent progression to PDR and risk of its sight-threatening complications. Renal impairment in people with T1D or T2D, as well as younger age at diagnosis of diabetes mellitus (DM), increased triglyceride levels, and increased retinal venular diameters in people with T1D may also be associated with increased risk of progression to PDR. Given that more advanced DR severity is associated with higher risk of progression to PDR, the earlier the disease is identified, and the above systemic risk factors are controlled, the greater the chance of reducing the risk of PDR and saving sight.
Topics: Adult; Female; Humans; Male; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Glycated Hemoglobin; Prognosis; Prospective Studies; Retinal Hemorrhage; Retrospective Studies; Triglycerides; Vitreous Hemorrhage
PubMed: 36815723
DOI: 10.1002/14651858.CD013775.pub2 -
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 -
Graefe's Archive For Clinical and... Aug 2023Foldable capsular vitreous body (FCVB) is an emerging vitreous substitute that has been recently introduced to treat various advanced vitreoretinal conditions including... (Review)
Review
PURPOSE
Foldable capsular vitreous body (FCVB) is an emerging vitreous substitute that has been recently introduced to treat various advanced vitreoretinal conditions including severe ocular trauma, complicated retinal detachment (RD), and proliferative vitreoretinopathy.
METHODS
Review protocol was prospectively registered at PROSPERO (CRD42022342310). A systematic literature search using PubMed, Ovid MEDLINE, and Google Scholar for articles published until May 2022 was performed. The search included the following keywords: foldable capsular vitreous body, FCVB, artificial vitreous substitutes, and artificial vitreous implants. Outcomes included indications of FCVB, anatomical success rates, postoperative intraocular pressure (IOP), best-corrected visual acuity (BCVA), and complications.
RESULTS
A total of 17 studies that utilized FCVB up to May 2022 were included. FCVB was used intraocularly as a tamponade or extraocularly as a macular/scleral buckle for various retinal conditions including severe ocular trauma, simple and complex RD, silicone oil-dependent eyes, and highly myopic eyes with foveoschisis. FCVB was reported to be successfully implanted in the vitreous cavity of all patients. Final retinal reattachment rate ranged from 30 to 100%. Postoperative IOP improved or was maintained in most eyes, with low postoperative complication rates. Improvement in BCVA ranged from 0 to 100% of subjects.
CONCLUSION
Indications of FCVB implantation have recently widened to include multiple advanced ocular conditions such as complex RD, but also include simpler conditions as uncomplicated RD. FCVB implantation showed good visual and anatomical outcomes, few IOP fluctuations, and a good safety profile. Larger comparative studies are required to further evaluate FCVB implantation.
Topics: Vitreous Body; Retinal Detachment; Vitrectomy; Eye Injuries; Vitreoretinopathy, Proliferative; Humans; Orbital Implants; Intraocular Pressure
PubMed: 36795160
DOI: 10.1007/s00417-023-05995-5 -
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 -
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 -
Acta Ophthalmologica Feb 2022Diabetic macular oedema (DME) is considered a chronic inflammatory disease associated with aberrations in many intraocular cytokines. Studies assessing the role of these... (Meta-Analysis)
Meta-Analysis
Diabetic macular oedema (DME) is considered a chronic inflammatory disease associated with aberrations in many intraocular cytokines. Studies assessing the role of these cytokines as biomarkers in the diagnosis and management of DME have demonstrated inconsistent findings. We quantitatively summarized data related to 116 candidate aqueous and vitreous inflammatory cytokines as biomarkers in DME. A systematic search without year limitation was performed up to 19 October 2020. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with DME. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with DME and controls. Data were extracted from 128 studies that included 4163 study eyes with DME and 1281 control eyes. Concentrations (standard mean difference, 95% confidence interval and p-value) of aqueous IL-6 (1.28, 0.57-2.00, p = 0.004), IL-8 (1.06, 0.74-1.39, p < 0.00001), MCP-1 (1.36, 0.57-2.16, p = 0.0008) and VEGF (1.31, 1.01-1.62, p < 0.00001) and vitreous VEGF (2.27, 1.55-2.99, p < 0.00001) were significantly higher in patients with DME (n = 4163) compared to healthy controls (n = 1281). No differences, failed sensitivity analyses or insufficient data were found between patients with DME and healthy controls for the concentrations of the remaining cytokines. This analysis implicates multiple cytokine biomarker candidates other than VEGF in DME and clarifies previously reported inconsistent associations. As the therapeutic options for DME expand to include multiple agents with multiple targets, it will be critical to manage the treatment burden with tailored therapy that optimizes outcomes and minimizes treatment burden. Intraocular cytokines have the promise of providing a robust individualized assessment of disease status and response to therapy. We have identified key candidate cytokines that may serve as biomarkers in individualized treatment algorithms.
Topics: Aqueous Humor; Biomarkers; Cytokines; Diabetic Retinopathy; Humans; Inflammation; Macular Edema; Vitreous Body
PubMed: 33945678
DOI: 10.1111/aos.14891 -
Survey of Ophthalmology 2022Ocriplasmin is used to treat vitreomacular traction (VMT), with or without full-thickness macular hole (MH). We systematically reviewed the evidence on ocriplasmin's... (Meta-Analysis)
Meta-Analysis Review
Ocriplasmin for treatment of vitreomacular traction and macular hole: A systematic literature review and individual participant data meta-analysis of randomized, controlled, double-masked trials.
Ocriplasmin is used to treat vitreomacular traction (VMT), with or without full-thickness macular hole (MH). We systematically reviewed the evidence on ocriplasmin's effect on vitreomacular adhesion resolution (VMAR), MH closure, vitrectomy, and best-corrected visual acuity (BCVA) and investigated the effect of baseline covariates on outcome. We applied individual participant data meta-analyses to the entire population and to subgroups defined by MH or epiretinal membrane (ERM) presence. Safety data were pooled and tabulated. Five randomized controlled trials (1,067 participants) were included. Six months after treatment, ocriplasmin achieved higher rates of VMAR and MH closure versus control, lowered vitrectomy odds, and increased the likelihood of a ≥10-letter BCVA increase. VMAR rates were lower when ERM, broad VMA (> 1500 µm), diabetic retinopathy, or pseudophakia were present and higher in younger participants, women, and eyes with MHs. Ocriplasmin-treated participants experienced more short-term visual impairment that was not predictive of final BCVA, as well as vitreous floaters, photopsia, photophobia, eye pain, blurred vision, and dyschromatopsia. The most common serious adverse events for ocriplasmin and control, respectively, were MH progression (22.5%, 17.3%), new MH (1.5%, 3.4%) and retinal detachment (0.8%, 1.2%). Ocriplasmin promotes VMAR and MH closure. Transient visual phenomena are not uncommon.
Topics: Female; Fibrinolysin; Humans; Intravitreal Injections; Peptide Fragments; Retinal Diseases; Retinal Perforations; Tomography, Optical Coherence; Traction; Treatment Outcome; Vision Disorders; Visual Acuity; Vitreous Body; Vitreous Detachment
PubMed: 34480895
DOI: 10.1016/j.survophthal.2021.08.003 -
BMC Ophthalmology Nov 2023Vitreoretinal lymphoma (VRL) is usually treated with a combination of intraocular methotrexate (ioMTX), high-dose intravenous methotrexate (HD-MTX), or local... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitreoretinal lymphoma (VRL) is usually treated with a combination of intraocular methotrexate (ioMTX), high-dose intravenous methotrexate (HD-MTX), or local radiotherapy (RT) as the first options. The effectiveness and safety of monotherapy like bruton's tyrosine kinase inhibitors (BTKi) for PVRL remain uncertain.
METHODS
A systematic review and meta-analysis of clinical trial data and conference abstracts in VRL patients treated with first-line combination therapy or monotherapy were conducted through a search of PubMed, Embase, and Scopus databases until December 2022. A total of 24 studies comprising 517 patients were included, and survival data were extracted from 279 patients due to inconsistent units across studies.
RESULTS
The combined treatment group used ioMTX + chemotherapy (in 4 studies), RT + chemotherapy (in 2 studies), ioMTX/HD-MTX based regimen (in 2 studies), ioMTX + RT + chemotherapy (in 2 studies), ioMTX + lenalidomide/BTKi (in 2 studies) and combination of multiple therapies (in 7 studies). The monotherapy group was mainly treated with oral monotherapies such as BTKi. The combination therapy had a higher overall response rate (ORR) and complete response rate (CRR) than monotherapy (ORR: 96% vs. 72%, CRR: 92% vs. 63%). Combination therapy also resulted in a longer median progression-free survival (28.8 months vs. 13 months, p = 0.012). However, the combination therapy group had more severe side effects (grade 3/4 toxicity) than the monotherapy group (45% vs. 8%).
CONCLUSION
The study showed combination therapy had better OR and CR rates, longer survival, and more toxicity than monotherapy. While BTK inhibitors were well-tolerated, long-term effectiveness needs confirmation from prospective studies. In addition, given the small number of studies of monotherapy for VRL, more studies are needed to validate its effects.
TRIAL REGISTRATION
CRD42023400305.
Topics: Humans; Methotrexate; Retinal Neoplasms; Prospective Studies; Vitreous Body; Central Nervous System Neoplasms; Lymphoma
PubMed: 37993841
DOI: 10.1186/s12886-023-03226-3 -
Acta Ophthalmologica Mar 2021Inflammatory cytokines are involved in the pathogenesis of neovascular age-related macular degeneration (nAMD) and have been shown to be useful as diagnostic and... (Meta-Analysis)
Meta-Analysis
Inflammatory cytokines are involved in the pathogenesis of neovascular age-related macular degeneration (nAMD) and have been shown to be useful as diagnostic and predictive biomarkers. Given the heterogeneity of data within the literature, we aimed to quantitatively summarize data related to inflammatory cytokines in nAMD. A systematic search without year limitation was performed up to 13 April 2020. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with nAMD. Data were extracted from 95 studies that encompassed 3105 study eyes with nAMD and 1209 control eyes. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with nAMD and controls. Among the 4314 eyes in 95 studies, aqueous concentrations (standard mean difference, 95% confidence interval and p-value) of MCP-1 (0.43, 0.09 to 0.77 and p = 0.01), MIG (0.63, 0.31 to 0.94 and p = 0.0001), TGF-β (0.45, 0.07 to 0.82 and p = 0.02) and VEGF (0.64, 0.31 to 0.98 and p = 0.0001) were significantly higher in patients with nAMD compared to healthy controls. No differences, failed sensitivity analyses or insufficient data were found between patients with nAMD and healthy controls for the concentrations of the remaining cytokines and with all vitreous samples. Previous studies had shown conflicting associations with nAMD for all 27 cytokines assessed. Our analysis indicates multiple candidate cytokines other than VEGF that are implicated in nAMD and adds clarity to the previous literature. This will help focus translational research in nAMD investigating biomarkers and therapeutic targets.
Topics: Aqueous Humor; Biomarkers; Cytokines; Humans; Inflammation; Vitreous Body; Wet Macular Degeneration
PubMed: 32602185
DOI: 10.1111/aos.14537 -
Regulatory Toxicology and Pharmacology... Mar 2023This study aimed to systematically review and synthesize epidemiological evidence evaluating the association between occupational man-made vitreous fiber (MMVF) exposure... (Review)
Review
This study aimed to systematically review and synthesize epidemiological evidence evaluating the association between occupational man-made vitreous fiber (MMVF) exposure and non-malignant respiratory disease (NMRD). We searched PubMed and Scopus databases to identify epidemiological studies evaluating the association between occupational MMVF exposure (limited to insulation wools) and at least 1 NMRD outcome published prior to January 2023. A total of 23 studies met our inclusion criteria. Studies of NMRD mortality among workers with MMVF exposure (n = 9) predominately reported null findings. Qualitative and quantitative synthesis of evidence from these studies suggests that MMVF exposure is not associated with elevated risk of NMRD mortality. The remaining 14 studies evaluated NMRD morbidity, specifically self-reported respiratory symptoms and/or subclinical measures of respiratory disease. Our review did not identify any consistent or compelling evidence of an association between MMVF exposure and any NMRD morbidity outcome; however, this body of evidence was largely limited by cross-sectional design, self-reported exposure and/or outcome ascertainment, incomplete statistical analysis and reporting, and questionable generalizability given that 13/14 studies were published over 20 years ago. We recommend that future studies aim to overcome the limitations of this literature to more accurately characterize the association between occupational MMVF exposure and NMRD morbidity.
Topics: Animals; Humans; Cross-Sectional Studies; Respiratory Tract Diseases; Occupational Exposure; Epidemiologic Studies; Occupational Diseases; Mineral Fibers
PubMed: 36806369
DOI: 10.1016/j.yrtph.2023.105361