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The Cochrane Database of Systematic... Aug 2023Uveitis is a term used to describe a group of intraocular inflammatory diseases. Uveitis is the fifth most common cause of vision loss in high-income countries, with the... (Review)
Review
BACKGROUND
Uveitis is a term used to describe a group of intraocular inflammatory diseases. Uveitis is the fifth most common cause of vision loss in high-income countries, with the highest incidence of disease in the working-age population. Corticosteroids are the mainstay of treatment for all subtypes of non-infectious uveitis. They can be administered orally, topically with drops, by periocular (around the eye) or intravitreal (inside the eye) injection, or by surgical implantation.
OBJECTIVES
To determine the efficacy and safety of steroid implants in people with chronic non-infectious posterior uveitis, intermediate uveitis, and panuveitis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE Ovid, Embase, PubMed, LILACS, and three trials registries to November 2021.
SELECTION CRITERIA
We included randomized controlled trials comparing either fluocinolone acetonide (FA) or dexamethasone (DEX) intravitreal implants with standard-of-care therapy or sham procedures, with at least six months of follow-up after treatment. We included studies that enrolled participants of all ages, who had chronic non-infectious posterior uveitis, intermediate uveitis, or panuveitis with vision that was better than hand-motion.
DATA COLLECTION AND ANALYSIS
We applied standard Cochrane methodology.
MAIN RESULTS
We included data from four trials (683 participants, 907 eyes) that compared corticosteroid implants with either sham or standard-of-care therapy. Study characteristics and risk of bias Of the two trials that compared corticosteroid implants with sham procedure, one examined a 0.18 mg FA implant, and the other, a 0.7 mg DEX implant. The other two trials compared a 0.59 mg FA implant with standard-of-care therapy, which included systemic corticosteroids and immunosuppressive medications, if needed. Considering improvement in visual acuity, we assessed the four trials to be at either low risk, or with some concerns of risk of bias across all domains. Findings Using sham procedure as control, combined results at the six-month primary time point suggested that corticosteroid implants may decrease the risk of uveitis recurrence by 60% (relative risk [RR] 0.40, 95% confidence interval [CI] 0.30 to 0.54; 2 trials, 282 participants; low-certainty evidence); and lead to a greater improvement in best-corrected visual acuity (BCVA; mean difference [MD] 0.15 logMAR, 95% CI 0.06 to 0.24; 1 trial, 153 participants; low-certainty evidence). Evidence based on a single-study report (146 participants) suggested that steroid implants may have no effects on visual functioning quality of life, measured on the National Eye Institute 25-Item Visual Function Questionnaire (MD 2.85, 95%CI -3.64 to 9.34; 1 trial, 146 participants; moderate-certainty evidence). Using standard-of care therapy as control, combined estimates at the 24-month primary time point suggested that corticosteroid implants were likely to decrease the risk of recurrence of uveitis by 54% (RR 0.46, 95% CI 0.35 to 0.60; 2 trials, 619 eyes). Combined estimates at 24 months also suggested that steroid implants may have little to no effects on improving BCVA (MD 0.05 logMAR, 95% CI -0.02 to 0.12; 2 trials, 619 eyes; low-certainty evidence). Evidence based on a single-study report (232 participants) suggested that steroid implants may have minimal clinical effects on visual functioning (MD 4.64, 95% CI 0.13 to 9.15; 1 trial, 232 participants; moderate-certainty evidence); physical functioning (SF-36 physical subscale MD 2.95, 95% CI 0.55 to 5.35; 1 trial, 232 participants; moderate-certainty evidence); or mental health (SF-36 mental subscale MD 3.65, 95% CI 0.52 to 6.78; 1 trial, 232 participants; moderate-certainty evidence); but not on EuroQoL (MD 6.17, 95% CI 1.87 to 10.47; 1 trial, 232 participants; moderate-certainty evidence); or EuroQoL-5D scale (MD 0.02, 95% CI -0.04 to 0.08; 1 trial, 232 participants; moderate-certainty evidence). Adverse effects Compared with sham procedures, corticosteroid implants may slightly increase the risk of cataract formation (RR 2.69, 95% CI 1.17 to 6.18; 1 trial, 90 eyes; low-certainty evidence), but not the risk of cataract progression (RR 2.00, 95% CI 0.65 to 6.12; 1 trial, 117 eyes; low-certainty evidence); or the need for surgery (RR 2.98, 95% CI 0.82 to 10.81; 1 trial, 180 eyes; low-certainty evidence), during up to 12 months of follow-up. These implants may increase the risk of elevated intraocular pressure ([IOP] RR 2.81, 95% CI 1.42 to 5.56; 2 trials, 282 participants; moderate-certainty evidence); and the need for IOP-lowering eyedrops (RR 1.85, 95% CI 1.05 to 3.25; 2 trials, 282 participants; moderate-certainty evidence); but not the need for IOP-lowering surgery (RR 0.72, 95% CI 0.13 to 4.17; 2 trials, 282 participants; moderate-certainty evidence). Evidence comparing the 0.59 mg FA implant with standard-of-care suggested that the implant may increase the risk of cataract progression (RR 2.71, 95% CI 2.06 to 3.56; 2 trials, 210 eyes; low-certainty evidence); and the need for surgery (RR 2.98, 95% CI 2.33 to 3.79; 2 trials, 371 eyes; low-certainty evidence); along with the risk of elevated IOP (RR 3.64, 95% CI 2.71 to 4.87; 2 trials, 605 eyes; moderate-certainty evidence); and the need for medical (RR 3.04, 95% CI 2.36 to 3.91; 2 trials, 544 eyes; moderate-certainty evidence); or surgical interventions (RR 5.43, 95% CI 3.12 to 9.45; 2 trials, 599 eyes; moderate-certainty evidence). In either comparison, these implants did not increase the risk for endophthalmitis, retinal tear, or retinal detachment (moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Our confidence is limited that local corticosteroid implants are superior to sham therapy or standard-of-care therapy in reducing the risk of uveitis recurrence. We demonstrated different effectiveness on BCVA relative to comparators in people with non-infectious uveitis. Nevertheless, the evidence suggests that these implants may increase the risk of cataract progression and IOP elevation, which will require interventions over time. To better understand the efficacy and safety profiles of corticosteroid implants, we need future trials that examine implants of different doses, used for different durations. The trials should measure core standard outcomes that are universally defined, and measured at comparable follow-up time points.
Topics: Humans; Adrenal Cortex Hormones; Cataract; Panuveitis; Quality of Life; Uveitis, Intermediate
PubMed: 37642198
DOI: 10.1002/14651858.CD010469.pub4 -
BMJ Open Ophthalmology Jun 2023This study aimed to review effectiveness studies comparing two biological anti-tumour necrosis factor agents, adalimumab (ADA) and infliximab (IFX), in the management of...
OBJECTIVE
This study aimed to review effectiveness studies comparing two biological anti-tumour necrosis factor agents, adalimumab (ADA) and infliximab (IFX), in the management of autoimmune uveitis.
METHODS
A systematic search was conducted across PubMed, Scopus, Web of Science and Google Scholar from 2014 until February 2022. The search included the following keywords "Adalimumab", "Infliximab", "Autoimmune", "Anterior", "Intermediate", "Posterior", "Panuveitis", "Refractory" and "Uveitis". Primary studies comparing both ADA and IFX in a population of autoimmune uveitis patients were considered. Outcomes of interest were measures of response to treatment and incidence of adverse events.
RESULTS
The preliminary literature search generated 7156 references. Six studies fulfilled the eligibility criteria and were included in the final analysis; all were non-randomised, retrospective or observational. The included studies found similar effectiveness and side effect profiles for both ADA and IFX in the management of autoimmune uveitis, however, one did not report effectiveness for each separately, and three were limited to Behcet's disease.
CONCLUSION
ADA and IFX seem to display comparable effectiveness and safety profiles. However, the available evidence remains scarce, of low quality and at high risk of bias. A direct comparison between ADA and IFX through large randomised controlled trials is needed to provide more substantial evidence of equivalence or superiority in uveitis.
Topics: Humans; Adalimumab; Infliximab; Retrospective Studies; Treatment Outcome; Uveitis; Tumor Necrosis Factor-alpha; Behcet Syndrome
PubMed: 37493653
DOI: 10.1136/bmjophth-2023-001303 -
Clinical and Experimental Rheumatology Oct 2023The aim of this review was to describe the changes in the microbiota of patients with Behçet's disease (BD) and the mechanisms involved in the relationship between the... (Review)
Review
The aim of this review was to describe the changes in the microbiota of patients with Behçet's disease (BD) and the mechanisms involved in the relationship between the microbiome and immunity in BD. A systematic search for relevant articles was made on PubMed and the Cochrane Library database using the following terms: "microbiota AND Behçet's disease" or "microbiome AND Behçet's disease". Sixteen articles were included in a qualitative synthesis. This systematic review on the microbiome and Behçet's disease underlines the presence of gut dysbiosis in BD patients. This dysbiosis is marked by (i) a decrease in butyrate-producing bacteria, which could affect T cell differentiation and epigenetic regulation of immune-related genes, (ii) a modification of tryptophan-metabolising bacteria, which could be linked to dysregulated IL-22 secretion, and (iii) a decrease in bacteria known to have anti-inflammatory properties. Regarding oral microbiota, this review underlines the possible role of Streptococcus sanguinis through molecular mimicry and NETosis. Clinical studies of BD have shown that (i) need for dentistry is associated with a more severe course in BD, and (ii) antibiotic-supplemented mouthwash reduces pain and ulcers. Fecal transplantation of BD patients' microbiota into mouse models led to decreased SCFA production, neutrophil activation, and Th1/Th17 responses.Recipient mice showed exacerbated experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE). In Herpes Virus Simplex-1 (HSV-1) infected mice mimicking BD, administration of butyrateproducing bacteria improved symptoms and immune variables. The microbiome may thus be involved in BD through immunity regulation and epigenetic modifications.
Topics: Humans; Animals; Mice; Behcet Syndrome; Dysbiosis; Epigenesis, Genetic; Uveitis; Microbiota; Bacteria
PubMed: 37382445
DOI: 10.55563/clinexprheumatol/zbt4gx -
The Journal of International Medical... May 2023To study the effectiveness of infliximab for the treatment of refractory central neuro-Behçet's disease. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To study the effectiveness of infliximab for the treatment of refractory central neuro-Behçet's disease.
METHODS
In this systematic review and meta-analysis, the research question was designed using the 'Population, Intervention, Comparator, and Outcomes' (PICO) model and the search methodology was developed according to the PRISMA statement. The study was registered on PROSPERO. Web of Science, PubMed, and Cochrane Library databases were searched for articles published in English between January 2000 and January 2020. Data were analysed using Meta-Essentials software, version 10.12. Treatment effect size was determined by a random effects model. Interstudy heterogeneity was explored using I statistics. Cumulative meta-analysis was conducted to assess the temporal trend for accumulating evidence.
RESULTS
Twenty-one studies, comprising 64 patients (mean age, 38 .21 years and mean disease duration, 84.76 months) were included. Effect-size analysis showed that 93.7% of the treated patients in the analysis were responders to infliximab therapy (95% confidence interval 0.88, 0.993). There was no significant inter-study heterogeneity (I = 0%). Cumulative analysis showed accumulating evidence favoring increasing effectiveness over the last 20 years.
CONCLUSION
Infliximab showed considerable therapeutic effectiveness in the treatment of refractory neuro-Behçet's disease.
Topics: Humans; Adult; Infliximab; Behcet Syndrome; Antibodies, Monoclonal; Tumor Necrosis Factor-alpha; Necrosis
PubMed: 37203384
DOI: 10.1177/03000605231169895 -
Ocular Immunology and Inflammation Apr 2023The present study aimed to estimate the global prevalence of ocular toxoplasmosis in the general population and patients with uveitis.
PURPOSE
The present study aimed to estimate the global prevalence of ocular toxoplasmosis in the general population and patients with uveitis.
METHODS
Four electronic databases were searched and 130 studies for evaluating the prevalence of OT among the general population and uveitis patients were included.
RESULTS
The pooled prevalence of OT among the general population was estimated at 2% (95% CI, 2-3%; 762/486 051). The highest prevalence rate was observed in America 6% (95% CI, 1-11%). In uveitis patients, a prevalence rate of 9% (95% CI, 8-10%; 5668/88 006) was reported. The countries with a lower middle income had higher prevalence rates. The prevalence of OT in posterior uveitis 33% (95%CI, 24-42%) was substantially higher than in panuveitis 7% (95% CI, 5-8%).
CONCLUSION
Our results provide a new perspective on the prevalence of OT. Knowledge of international and regional patterns of disease is essential for the establishment of precise diagnostic protocols and control programs.
PubMed: 37043543
DOI: 10.1080/09273948.2023.2190801 -
Journal of Clinical Medicine Mar 2023To evaluate the morbidity frequency measures in terms of the cumulative incidence of sympathetic ophthalmia (SO) triggered by single or multiple vitreoretinal (VR)... (Review)
Review
BACKGROUND
To evaluate the morbidity frequency measures in terms of the cumulative incidence of sympathetic ophthalmia (SO) triggered by single or multiple vitreoretinal (VR) surgery procedures in eyes without an antecedent history of trauma and previous ocular surgery, except for previous or concomitant uneventful lens extraction, and to further investigate the relationship between VR surgery and SO.
METHODS
A literature search was conducted using PubMed, Embase, and Scopus from inception until 11 November 2022. The Joanna Briggs Institute (JBI) critical appraisal checklist for the case series and the Newcastle-Ottawa Scale were used to assess the risk of bias. The research was registered with the PROSPERO database (identifier, CRD42023397792). Meta-analyses were conducted using the measurement of risk and a 95% confidence interval (CI) for each study.
RESULTS
A random-effect meta-analysis demonstrated that the pooled cumulative incidence of SO triggered by single or multiple VR surgery procedures in eyes without an antecedent history of trauma and previous ocular surgery, except for previous or concomitant uneventful lens extraction among patients who developed SO regardless of the main trigger, was equal to 0.14 with a CI between 0.08 and 0.21 (I = 78.25, z: 7.24, < 0.01). The pooled cumulative incidence of SO triggered by single or multiple VR surgery procedures in eyes without an antecedent history of trauma and previous ocular surgery, except for previous or concomitant uneventful lens extraction among patients who underwent VR surgery, was equal to 0.03 for every 100 people, with a confidence interval (CI) between 0.02% and 0.004% (I = 27.77, z: 9.11, = 0.25).
CONCLUSIONS
Despite postsurgical SO being a rare entity, it is a sight-threatening disease. VR surgery should be viewed as a possible inciting event for SO and considered when counseling patients undergoing VR surgery.
PubMed: 36983316
DOI: 10.3390/jcm12062316 -
Eye (London, England) Oct 2023Ocular syphilis is a vision-threatening disease that can lead to permanent blindness if left untreated. The global re-emergence of syphilis warrants greater...
BACKGROUND/OBJECTIVES
Ocular syphilis is a vision-threatening disease that can lead to permanent blindness if left untreated. The global re-emergence of syphilis warrants greater investigations into the visual prognosis of eyes affected by this potentially devastating disease. This systematic review investigates the impact of HIV on visual acuity (VA) outcomes in ocular syphilis.
METHODS
A literature search of Medline, PubMed, Embase, Clinicaltrials.gov and Cochrane Reviews was conducted for studies published between 01 January 2011 and 19 March 2022, reporting non-aggregate initial and post-treatment VA data of eyes with ocular syphilis and corresponding HIV status in patients ≥ 18 years.
RESULTS
A total of 95 studies, including 364 patients and 568 eyes, were evaluated. Among people living with HIV with a diagnosis of ocular syphilis, affected eyes were more likely to have optic nerve involvement and panuveitis. However, HIV status, CD4 cell count, and HIV viral load were not predictive of VA outcomes of treated ocular syphilis. Prognostic factors of final VA worse than 1.00 logMAR were female sex, the presence of macular edema, and VA ≥ 1.00 at presentation. The strongest predictor of a worse final VA was VA ≥ 1.00 at presentation.
CONCLUSIONS
This systematic review demonstrates that HIV status, CD4 cell count, and HIV viral load are not significant factors impacting VA outcomes of eyes with ocular syphilis. While visual prognosis is generally good, poor visual outcome is most strongly predicted by poor VA at presentation. This underscores the importance of early recognition and treatment prior to permanent vision loss.
PubMed: 36944709
DOI: 10.1038/s41433-023-02504-0 -
Clinical and Experimental Medicine Oct 2023The present meta-analysis aimed to elucidate the association of Behçet's disease (BD) with the risk of metabolic syndrome (MetS) and its components. Observational... (Meta-Analysis)
Meta-Analysis
The present meta-analysis aimed to elucidate the association of Behçet's disease (BD) with the risk of metabolic syndrome (MetS) and its components. Observational cohort studies were searched from the Embase, Web of Science, Medline, and Cochrane Library databases. The primary outcome was the association of BD with the risk of MetS and its relevant components. Effect estimates with odds ratios (ORs) were pooled using either the random-effects or fixed-effects models, according to heterogeneity. Leave-one-out sensitivity analyses were used to determine the stability of the results. Twenty-three studies, comprising 42,834 patients with BD, were included. Overall, a significant association between BD and the risk of MetS was found (pooled OR 2.26; 95% confidence interval [CI] 1.61-3.17; P < 0.0001). Among the components of MetS, significant associations were found between BD and diabetes mellitus (OR 1.21; 95% CI 1.10-1.33; P < 0.0001), BD and hypertension (OR 1.39; 95% CI 1.13-1.70; P = 0.002), and BD and dyslipidemia (OR 1.21; 95% CI 1.01-1.45; P = 0.04). Our study indicated an association between BD and the risk of MetS and some of its components (diabetes mellitus, hypertension, and dyslipidemia). Physician should consider these associations so that specific treatments are available for patients with comorbidities. Moreover, patients with BD should regularly monitor their blood pressure, fasting plasma glucose, and blood lipid levels.
Topics: Humans; Metabolic Syndrome; Behcet Syndrome; Odds Ratio; Hypertension
PubMed: 36939969
DOI: 10.1007/s10238-023-01044-x -
Expert Review of Clinical Immunology May 2023Noninfectious uveitis related to systemic inflammatory diseases represents a leading cause of blindness. Anti-TNFα agents are the first-line biologic therapy after...
INTRODUCTION
Noninfectious uveitis related to systemic inflammatory diseases represents a leading cause of blindness. Anti-TNFα agents are the first-line biologic therapy after traditional immunosuppressants, for ocular and systemic involvement. However, some patients fails anti-TNFα agents, due to primary inefficacy, loss of efficacy or adverse events.
AREAS COVERED
This systematic review summarizes evidence on the efficacy and safety of non-anti-TNFα biologics in adult patients with noninfectious uveitis associated with systemic inflammatory diseases. The systematic review of PubMed and Embase yielded 3663 records, from which 16 studies were included (13 non-controlled, 3 controlled trials). Most studies focused on Behçet's syndrome (BS) and juvenile idiopathic arthritis (JIA) and assessed the efficacy of tocilizumab ( = 11), rituximab ( = 3), secukinumab ( = 1), or anakinra/canakinumab ( = 1). A body of evidence supports the use of tocilizumab BS and JIA-associated uveitis, for improving visual acuity, reducing central macular thickness, inducing ocular remission, and sparing corticosteroids. Preliminary data suggest that rituximab may represent a valid alternative, particularly in JIA, while anakinra/canakinumab might play a role in BS-associated uveitis. The role of secukinumab appears limited.
EXPERT OPINION
Current evidence encourages investigations on the efficacy and safety of non-anti-TNFα agents in noninfectious non-idiopathic uveitis.
Topics: Adult; Humans; Arthritis, Juvenile; Behcet Syndrome; Biological Factors; Immunosuppressive Agents; Interleukin 1 Receptor Antagonist Protein; Rituximab; Uveitis; Tumor Necrosis Factor-alpha
PubMed: 36939549
DOI: 10.1080/1744666X.2023.2193687 -
International Journal of Molecular... Feb 2023Urinary and serological markers play an essential role in the diagnostic process of autoimmune diseases. However, to date, specific and reliable biomarkers for... (Review)
Review
Urinary and serological markers play an essential role in the diagnostic process of autoimmune diseases. However, to date, specific and reliable biomarkers for diagnosing Behçet's disease (BD) are still lacking, negatively affecting the management of these patients. To analyze the currently available literature on serological and urinary BD biomarkers investigated in the last 25 years, we performed a systematic literature review using the Population, Intervention, Comparison, and Outcomes (PICO) strategy. One hundred eleven studies met the eligibility criteria (6301 BD patients, 5163 controls). Most of them were retrospective, while five (5%) were prospective. One hundred ten studies (99%) investigated serological biomarkers and only two (2%) focused on urinary biomarkers. One hundred three studies (93%) explored the diagnostic potential of the biomolecules, whereas sixty-two (56%) tested their effect on disease activity monitoring. Most articles reported an increase in inflammatory markers and pro-oxidant molecules, with a decrease in antioxidants. Promising results have been shown by the omics sciences, offering a more holistic approach. Despite the vast number of investigated markers, existing evidence indicates a persistent gap in BD diagnostic/prognostic indices. While new steps have been taken in the direction of pathogenesis and disease monitoring, international efforts for the search of a diagnostic marker for BD are still needed.
Topics: Humans; Behcet Syndrome; Retrospective Studies; Prospective Studies; Case-Control Studies; Biomarkers
PubMed: 36769366
DOI: 10.3390/ijms24033041