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The Cochrane Database of Systematic... Jan 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. 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] 0.22 logMAR, 95% CI 0.13 to 0.31; 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 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; Glaucoma; Panuveitis; Quality of Life; Steroids; Uveitis; Uveitis, Intermediate; Randomized Controlled Trials as Topic
PubMed: 36645716
DOI: 10.1002/14651858.CD010469.pub3 -
Journal of the Formosan Medical... Aug 2023Cytomegalovirus (CMV) uveitis, a type of herpetic uveitis, is a major cause of infectious uveitis. Anterior and posterior CMV uveitis have diverse clinical presentations...
Cytomegalovirus (CMV) uveitis, a type of herpetic uveitis, is a major cause of infectious uveitis. Anterior and posterior CMV uveitis have diverse clinical presentations and treatment modalities. Based on expert consensus in Taiwan, this article provides suggestions regarding clinical manifestations, diagnosis, and treatment strategies for CMV uveitis based on clinical practice experience in Taiwan. CMV uveitis may have a distinct clinical presentation. Polymerase chain reaction (PCR) is an essential diagnostic tool to confirm a diagnosis. Antiviral therapy is the mainstay of treatment. Different agents, routes, and other supplemental treatments have been summarized and discussed in this article. Early diagnosis and appropriate treatment of CMV uveitis are crucial to avoid irreversible complications and vision loss. This consensus provides practical guidelines for ophthalmologists in Taiwan.
Topics: Humans; Cytomegalovirus; Cytomegalovirus Infections; Taiwan; Consensus; Uveitis, Anterior; Eye Infections, Viral; DNA, Viral; Uveitis
PubMed: 37003913
DOI: 10.1016/j.jfma.2023.03.014 -
Arthritis Research & Therapy Jun 2023This study aimed to investigate the expression profile of immune response-related proteins of Behcet's disease (BD) patients and identify potential biomarkers for this...
BACKGROUND
This study aimed to investigate the expression profile of immune response-related proteins of Behcet's disease (BD) patients and identify potential biomarkers for this disease.
METHODS
Plasma was collected from BD patients and healthy controls (HC). Immune response-related proteins were measured using the Olink Immune Response Panel. Differentially expressed proteins (DEPs) were used to construct prediction models via five machine learning algorithms: naive Bayes, support vector machine, extreme gradient boosting, random forest, and neural network. The prediction performance of the five models was assessed using the area under the curve (AUC) value, recall (sensitivity), specificity, precision, accuracy, F1 score, and residual distribution. Subtype analysis of BD was performed using the consensus clustering method.
RESULTS
Proteomics results showed 43 DEPs between BD patients and HC (P < 0.05). These DEPs were mainly involved in the Toll-like receptor 9 and NF-κB signaling pathways. Five models were constructed using DEPs [interleukin 10 (IL10), Fc receptor like 3 (FCRL3), Mannan-binding lectin serine peptidase 1 (MASP1), NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor (NF2), FAM3 metabolism regulating signaling molecule B (FAM3B), and O-6-methylguanine-DNA methyltransferase (MGMT)]. Among these models, the neural network model showed the best performance (AUC = 0.856, recall: 0.692, specificity: 0.857, precision: 0.900, accuracy: 0.750, F1 score: 0.783). BD patients were divided into two subtypes according to the consensus clustering method: one with high disease activity in association with higher expression of tripartite motif-containing 5 (TRIM5), SH2 domain-containing 1A (SH2D1A), phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1), hematopoietic cell-specific Lyn substrate 1 (HCLS1), and DNA fragmentation factor subunit alpha (DFFA) and the other with low disease activity in association with higher expression of C-C motif chemokine ligand 11 (CCL11).
CONCLUSIONS
Our study not only revealed a distinctive immune response-related protein profile for BD but also showed that IL10, FCRL3, MASP1, NF2, FAM3B, and MGMT could serve as potential immune biomarkers for this disease. Additionally, a novel molecular disease classification model was constructed to identify subsets of BD.
Topics: Humans; Behcet Syndrome; Interleukin-10; Proteomics; Bayes Theorem; Biomarkers; Neoplasm Proteins; Cytokines
PubMed: 37264476
DOI: 10.1186/s13075-023-03074-y -
Acta Medica Portuguesa Sep 2023Behçet's disease is a relapsing multisystemic inflammatory syndrome characterized by recurrent oral and/or genital ulcers, uveitis, arthritis, skin lesions, and... (Review)
Review
Behçet's disease is a relapsing multisystemic inflammatory syndrome characterized by recurrent oral and/or genital ulcers, uveitis, arthritis, skin lesions, and gastrointestinal and neurological involvement. Neuro-Behçet corresponds to nervous system involvement and is one of the most severe complications of Behçet disease. It occurs in 3% to 30% of cases and is categorized into parenchymal (most common) or non-parenchymal disease. The most common manifestation of parenchymal neuro-Behçet is meningoencephalitis with involvement of the brainstem, where patients present with cranial neuropathies, encephalopathy, sensory-motor syndromes, epilepsy, or myelitis. The main non-parenchymal manifestation is cerebral venous thrombosis. Neuro-Behçet has a predominantly subacute course, with remission within weeks, or clinical progression in one third of the cases. The diagnosis is essentially clinical and diagnostic tests help to corroborate the suspicion, distinguish from differential diagnoses, and exclude complications. Brain magnetic resonance imaging allows the identification of acute lesions (hypointense or isointense on T2-weighted and hypointense on T1-weighted sequences) contrast-enhanced, and chronic lesions characterized by non-contrast enhanced small lesions and brainstem atrophy. If non-parenchymal involvement is suspected, cerebral veno-magnetic resonance imaging /computed tomography should be performed. Cerebrospinal fluid shows elevated proteinorachia and pleocytosis in parenchymal and no changes in non-parenchymal neuro-Behçet (except increased opening pressure). Outbursts of parenchymal disease should be treated with high dose intravenous corticosteroid therapy, with subsequent switch to oral corticoids, followed by biologic therapy, usually an anti-TNF. The treatment of cerebral venous thrombosis is controversial and may consist of a combination of corticosteroids and anticoagulation.
Topics: Humans; Behcet Syndrome; Tumor Necrosis Factor Inhibitors; Brain; Magnetic Resonance Imaging; Diagnosis, Differential; Adrenal Cortex Hormones; Venous Thrombosis
PubMed: 37345389
DOI: 10.20344/amp.19734 -
Medicina (Kaunas, Lithuania) Mar 2024Inflammation plays a key role in the induction of choroidal neovascularization (CNV). Inflammatory choroidal neovascularization (iCNV) is a severe but uncommon... (Review)
Review
Inflammation plays a key role in the induction of choroidal neovascularization (CNV). Inflammatory choroidal neovascularization (iCNV) is a severe but uncommon complication of both infectious and non-infectious uveitides. It is hypothesized that its pathogenesis is similar to that of wet age-related macular degeneration (AMD), and involves hypoxia as well as the release of vascular endothelial growth factor, stromal cell-derived factor 1-alpha, and other mediators. Inflammatory CNV develops when inflammation or infection directly involves the retinal pigment epithelium (RPE)-Bruch's membrane complex. Inflammation itself can compromise perfusion, generating a gradient of retinal-choroidal hypoxia that additionally promotes the formation of choroidal neovascularization in the course of uveitis. The development of choroidal neovascularization may be a complication, especially in conditions such as punctate inner choroidopathy, multifocal choroiditis, serpiginous choroiditis, and presumed ocular histoplasmosis syndrome. Although the majority of iCNV cases are well defined and appear as the "classic" type (type 2 lesion) on fluorescein angiography, the diagnosis of iCNV is challenging due to difficulties in differentiating between inflammatory choroiditis lesions and choroidal neovascularization. Modern multimodal imaging, particularly the recently introduced technology of optical coherence tomography (OCT) and OCT angiography (noninvasive and rapid imaging modalities), can reveal additional features that aid the diagnosis of iCNV. However, more studies are needed to establish their role in the diagnosis and evaluation of iCNV activity.
Topics: Humans; Vascular Endothelial Growth Factor A; Choroiditis; Choroidal Neovascularization; Inflammation; Tomography, Optical Coherence; Hypoxia
PubMed: 38541191
DOI: 10.3390/medicina60030465 -
American Journal of Ophthalmology Aug 2021To determine classification criteria for serpiginous choroiditis.
PURPOSE
To determine classification criteria for serpiginous choroiditis.
DESIGN
Machine learning of cases with serpiginous choroiditis and 8 other posterior uveitides.
METHODS
Cases of posterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior uveitides / panuveitides. The resulting criteria were evaluated on the validation set.
RESULTS
One thousand sixty-eight cases of posterior uveitides, including 122 cases of serpiginous choroiditis, were evaluated by machine learning. Key criteria for serpiginous choroiditis included (1) choroiditis with an ameboid or serpentine shape; (2) characteristic imaging on fluorescein angiography or fundus autofluorescence; (3) absent to mild anterior chamber and vitreous inflammation; and (4) the exclusion of tuberculosis. Overall accuracy for posterior uveitides was 93.9% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for serpiginous choroiditis were 0% in both the training set and the validation set.
CONCLUSIONS
The criteria for serpiginous choroiditis had a low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research.
Topics: Adult; Choroid; Female; Fluorescein Angiography; Fundus Oculi; Humans; Machine Learning; Male; Middle Aged; White Dot Syndromes
PubMed: 33845013
DOI: 10.1016/j.ajo.2021.03.038 -
American Journal of Ophthalmology Aug 2021The purpose of this study was to determine classification criteria for sympathetic ophthalmia.
PURPOSE
The purpose of this study was to determine classification criteria for sympathetic ophthalmia.
DESIGN
Machine learning of cases with sympathetic ophthalmia and 5 other panuveitides.
METHODS
Cases of panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used in the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the panuveitides. The resulting criteria were evaluated in the validation set.
RESULTS
A total of 1,012 cases of panuveitides, including 110 cases of sympathetic ophthalmia, were evaluated by machine learning. The overall accuracy for panuveitides was 96.3% in the training set and 94.0% in the validation set (95% confidence interval: 89.0-96.8). Key criteria for sympathetic ophthalmia included bilateral uveitis with 1) a history of unilateral ocular trauma or surgery and 2) an anterior chamber and vitreous inflammation or a panuveitis with choroidal involvement. The misclassification rates for sympathetic ophthalmia were 4.2% in the training set and 6.7% in the validation set.
CONCLUSIONS
The criteria for sympathetic ophthalmia had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.
Topics: Adult; Anterior Chamber; Female; Humans; Male; Middle Aged; Ophthalmia, Sympathetic; Tomography, Optical Coherence
PubMed: 33845005
DOI: 10.1016/j.ajo.2021.03.048 -
American Journal of Ophthalmology Aug 2021To determine classification criteria for pars planitis.
PURPOSE
To determine classification criteria for pars planitis.
DESIGN
Machine learning of cases with pars planitis and 4 other intermediate uveitides.
METHODS
Cases of intermediate uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation set.
RESULTS
Five hundred eighty-nine cases of intermediate uveitides, including 226 cases of pars planitis, were evaluated by machine learning. The overall accuracy for intermediate uveitides was 99.8% in the training set and 99.3% in the validation set (95% confidence interval 96.1, 99.9). Key criteria for pars planitis included unilateral or bilateral intermediate uveitis with either 1) snowballs in the vitreous or 2) snowbanks on the pars plana. Key exclusions included: 1) multiple sclerosis, 2) sarcoidosis, and 3) syphilis. The misclassification rates for pars planitis were 0% in the training set and 1.7% in the validation set, respectively.
CONCLUSIONS
The criteria for pars planitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.
Topics: Adolescent; Adult; Child; Female; Humans; Machine Learning; Male; Pars Planitis; Visual Acuity; Young Adult
PubMed: 33845006
DOI: 10.1016/j.ajo.2021.03.045 -
American Journal of Ophthalmology Aug 2021To determine classification criteria for birdshot chorioretinitis.
PURPOSE
To determine classification criteria for birdshot chorioretinitis.
DESIGN
Machine learning of cases with birdshot chorioretinitis and 8 other posterior uveitides.
METHODS
Cases of posterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior uveitides / panuveitides. The resulting criteria were evaluated on the validation set.
RESULTS
One thousand sixty-eight cases of posterior uveitides, including 207 cases of birdshot chorioretinitis, were evaluated by machine learning. Key criteria for birdshot chorioretinitis included a multifocal choroiditis with (1) the characteristic appearance of a bilateral multifocal choroiditis with cream-colored or yellow-orange, oval or round choroidal spots ("birdshot" spots); (2) absent to mild anterior chamber inflammation; and (3) absent to moderate vitreous inflammation; or multifocal choroiditis with positive HLA-A29 testing and either classic "birdshot spots" or characteristic imaging on indocyanine green angiography. Overall accuracy for posterior uveitides was 93.9% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for birdshot chorioretinitis were 10% in the training set and 0% in the validation set.
CONCLUSIONS
The criteria for birdshot chorioretinitis had a low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research.
Topics: Birdshot Chorioretinopathy; Choroid; Consensus; Female; Fluorescein Angiography; Fundus Oculi; Humans; Machine Learning; Male; Middle Aged; Retina
PubMed: 33845003
DOI: 10.1016/j.ajo.2021.03.059 -
Clinical and Experimental Rheumatology 2019Several epidemiologic studies report on the prevalence of Behçet's syndrome (BS) and demographic and clinical findings in patients from different countries and... (Review)
Review
Several epidemiologic studies report on the prevalence of Behçet's syndrome (BS) and demographic and clinical findings in patients from different countries and ethnicities. Although these studies point out geographic differences in disease course, methodologic differences make it difficult to compare the results of these studies. Recent data suggest that neutrophil extracellular trap levels are elevated in patients with BS, and that it may be a potential therapeutic target for the reduction or prevention of BS-associated thrombotic risk. Details on the mode of functioning of ERAP have been delineated and further epigenetic data reported. Wall thickness of lower extremity veins is increased among BS patients without any apparent clinical involvement. Magnetic resonance (MR) venography and Doppler ultrasonography (USG) were comparable in the diagnosis of chronic deep vein thrombosis, while MR venography is more effective in detecting collateral formations. Results were also collected on some dietary and non-dietary factors in triggering oral ulcers, while smoking seems to have a protective role. With regards to the therapy, it has been demonstrated that endovascular interventions carry the risk of inducing pathergy phenomenon. Apremilast has been convincingly shown to be useful for oral ulcers of BS and classical immunosuppressives are effective as first line therapy in more than half of patients with uveitis. While infliximab and adalimumab seem to be equally effective in the treatment of refractory uveitis of BS, the combination of adalimumab and immunosuppressives appears to be superior to immunosuppressives alone for venous thrombosis of the extremities. In addition, tocilizumab might be an alternative to anti-TNF agents for patients with arterial involvement refractory to immunosuppressives. On the other hand, the place of IL-17 inhibition in the treatment of BS still remains questionable.
Topics: Adalimumab; Behcet Syndrome; Genetic Predisposition to Disease; Humans; Immunosuppressive Agents; Oral Ulcer; Prevalence; Tumor Necrosis Factor-alpha; Uveitis; Venous Thrombosis
PubMed: 31856939
DOI: No ID Found