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American Journal of Ophthalmology Aug 2021The purpose of this study was to determine classification criteria for spondyloarthritis/HLA-B27-associated anterior uveitis DESIGN: Machine learning of cases with... (Comparative Study)
Comparative Study
PURPOSE
The purpose of this study was to determine classification criteria for spondyloarthritis/HLA-B27-associated anterior uveitis DESIGN: Machine learning of cases with spondyloarthritis/HLA-B27-associated anterior uveitis and 8 other anterior uveitides.
METHODS
Cases of anterior 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 in the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated in the validation set.
RESULTS
A total of 1,083 cases of anterior uveitides, including 184 cases of spondyloarthritis/HLA-B27-associated anterior uveitis, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% CI: 92.4-98.6). Key criteria for spondyloarthritis/HLA-B27-associated anterior uveitis included 1) acute or recurrent acute unilateral or unilateral alternating anterior uveitis with either spondyloarthritis or a positive test result for HLA-B27; or 2) chronic anterior uveitis with a history of the classic course and either spondyloarthritis or HLA-B27; or 3) anterior uveitis with both spondyloarthritis and HLA-B27. The misclassification rates for spondyloarthritis/HLA-B27-associated anterior uveitis were 0% in the training set and 3.6% in the validation set.
CONCLUSIONS
The criteria for spondyloarthritis/HLA-B27-associated anterior uveitis had a low misclassification rate and appeared to perform well enough for use in clinical and translational research.
Topics: Adolescent; Adult; Female; HLA-B27 Antigen; Humans; Machine Learning; Male; Middle Aged; Spondylarthritis; Translational Research, Biomedical; Uveitis, Anterior; Young Adult
PubMed: 33845004
DOI: 10.1016/j.ajo.2021.03.049 -
Ophthalmology Dec 2018In recent decades, the treatment paradigm for noninfectious intermediate uveitis, posterior uveitis, and panuveitis, a group of intraocular inflammatory diseases, has... (Review)
Review
In recent decades, the treatment paradigm for noninfectious intermediate uveitis, posterior uveitis, and panuveitis, a group of intraocular inflammatory diseases, has included systemic and local (periocular or intraocular) corticosteroids, biologics, and other steroid-sparing immunomodulatory therapy agents. Recently, an intravitreal formulation of sirolimus, an immunosuppressant that inhibits the mammalian target of rapamycin, a key regulator of cell growth in the immune system, was developed. On the basis of this mechanism and the local method of delivery, it was hypothesized that intravitreal sirolimus can improve ocular inflammation in patients with noninfectious intermediate uveitis, posterior uveitis, and panuveitis, with minimal systemic exposure and systemic adverse events (AEs). This review summarizes the pharmacokinetics, efficacy, and safety results of intravitreal sirolimus from 3 preclinical studies and 4 phase 1-3 clinical studies. Preclinical studies in rabbits showed that 22 to 220 μg intravitreal sirolimus results in sustained release of sirolimus in the vitreous for 2 months or more, with systemic concentrations below the threshold for systemic immunosuppression (approximately 8 ng/ml). Subsequently, 2 phase 1 studies (n = 50 and n = 30) established that intravitreal sirolimus improves ocular inflammation in humans. Further investigation in phase 2 and 3 studies (n = 24 and n = 347, respectively) suggested that 440 μg has the best benefit-to-risk profile. In the phase 3 study, the proportion of patients who showed complete resolution of ocular inflammation at month 5 was significantly higher in the 440-μg group than in the 44-μg group (22.8% vs. 10.3%; P = 0.025, Fisher exact test). In addition, 47 of 69 patients (68.1%) who were treated with systemic corticosteroids at baseline discontinued corticosteroid use at month 5. No sirolimus-related systemic AEs were reported in phase 1-3 studies. Collectively, these preclinical and clinical study data of intravitreal sirolimus support the therapeutic rationale of treating noninfectious uveitis with a local mammalian target of rapamycin inhibitor and suggest that 440 μg intravitreal sirolimus has the potential to be an effective and well-tolerated anti-inflammatory and corticosteroid-sparing treatment for noninfectious intermediate uveitis, posterior uveitis, and panuveitis.
Topics: Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Immunosuppressive Agents; Intravitreal Injections; Panuveitis; Sirolimus; Uveitis, Intermediate; Uveitis, Posterior
PubMed: 30060978
DOI: 10.1016/j.ophtha.2018.06.015 -
Mediators of Inflammation 2017Behçet's disease (BD) is a multisystemic disorder of unknown etiology mainly defined by recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral... (Review)
Review
Behçet's disease (BD) is a multisystemic disorder of unknown etiology mainly defined by recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis, all of which represent the "stigmata" of disease. However, many other organs including the vascular, neurological, musculoskeletal, and gastrointestinal systems can be affected. The gastrointestinal involvement in Behçet's disease (GIBD), along with the neurological and vascular ones, represents the most feared clinical manifestation of BD and shares many symptoms with inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis. Consequently, the differential diagnosis is often a daunting task, albeit the presence of typical endoscopic and pathologic findings may be a valuable aid to the exact diagnosis. To date, there are no standardized medical treatments for GIBD; therefore therapy should be tailored to the single patient and based on the severity of the clinical features and their complications. This work provides a digest of all current experience and evidence about pharmacological agents suggested by the medical literature as having a potential role for managing the dreadful features of GIBD.
Topics: Adrenal Cortex Hormones; Animals; Behcet Syndrome; Gastrointestinal Tract; Humans; Immunologic Factors; Mesalamine; Sulfasalazine; Thalidomide
PubMed: 28210071
DOI: 10.1155/2017/1460491 -
American Journal of Ophthalmology Aug 2021To determine classification criteria for cytomegalovirus (CMV) anterior uveitis.
PURPOSE
To determine classification criteria for cytomegalovirus (CMV) anterior uveitis.
DESIGN
Machine learning of cases with CMV anterior uveitis and 8 other anterior uveitides.
METHODS
Cases of anterior 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 anterior uveitides. The resulting criteria were evaluated on the validation set.
RESULTS
One thousand eighty-three cases of anterior uveitides, including 89 cases of CMV anterior uveitis, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for CMV anterior uveitis included unilateral anterior uveitis with a positive aqueous humor polymerase chain reaction assay for CMV. No clinical features reliably diagnosed CMV anterior uveitis. The misclassification rates for CMV anterior uveitis were 1.3% in the training set and 0% in the validation set.
CONCLUSIONS
The criteria for CMV anterior uveitis had a low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research.
Topics: Adolescent; Adult; Aged; Aqueous Humor; Consensus; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Eye Infections, Viral; Female; Humans; Machine Learning; Male; Middle Aged; Uveitis, Anterior; Young Adult
PubMed: 33845019
DOI: 10.1016/j.ajo.2021.03.060 -
Clinics in Dermatology 2023Adamantiades-Behçet disease is an inflammatory, vascular disease of unknown etiology. The disease is named after two physicians, Benediktos Adamantiades and Hulȗsi...
Adamantiades-Behçet disease is an inflammatory, vascular disease of unknown etiology. The disease is named after two physicians, Benediktos Adamantiades and Hulȗsi Behçet, who both made significant contributions to the study of the disease. It was probably first described by Hippocrates in 500 BCE. Adamantiades-Behçet disease is most common in the region encompassing the ancient trade route known as the Silk Road. In Turkey, the disease is estimated to affect 80 to 370 people per 100,000 inhabitants, and it is also the country with the highest incidence rate. The frequency of the disease associated with the clinical picture differs from the origin of the onset. The disease is characterized by recurrent aphthous ulcers of the mouth, genitals, skin lesions, and eye lesions. The disease process can also involve other organs, including the joints, nervous system, large vessels, heart, and gastrointestinal tract. Aphthous oral ulcers appear as the first harbinger of the disease and affect almost all patients (97%-99%). The scientific interest in Adamantiades-Behçet disease has increased exponentially in the past decade.
Topics: Humans; Behcet Syndrome; Ophthalmology; Dermatology; Stomatitis, Aphthous
PubMed: 37572969
DOI: 10.1016/j.clindermatol.2023.08.001 -
Pediatric Rheumatology Online Journal Oct 2023Pediatric uveitis is a severe inflammatory ocular condition that can lead to sight-threatening complications and can negatively impact quality of life. The retinal...
BACKGROUND
Pediatric uveitis is a severe inflammatory ocular condition that can lead to sight-threatening complications and can negatively impact quality of life. The retinal microcirculation is often affected in intermediate uveitis and panuveitis. Here, we examined the extraocular (i.e., systemic) microcirculation in pediatric uveitis cases and healthy controls using nailfold capillaroscopy (NFC).
METHODS
We performed NFC in 119 children with noninfectious uveitis and 25 healthy pediatric controls, and assessed the following parameters: capillary density (number of capillaries/mm), dilated capillaries (apex > 20 µm), avascular area, the presence of microhemorrhages, and capillary morphology. Differences in NFC parameters between cases and controls were calculated using regression analysis after adjusting for age and sex.
RESULTS
The mean (± SD) age of the patient group was 13.7 (± 3) years, with 56% females; 46%, 18%, and 36% of cases presented as anterior uveitis, intermediate uveitis, and panuveitis, respectively, with an overall mean disease duration of 4.7 (± 4.0) years. Compared to the control group, the pediatric uveitis cases had a significantly higher number of dilated capillaries/mm and a higher prevalence of ramified capillaries. Moreover, compared to the control group the intermediate uveitis cases had a significantly higher number of dilated capillaries, whereas the anterior uveitis cases had a lower capillary density and a higher prevalence of ramified capillaries.
CONCLUSIONS
Children with uveitis without systemic disease can present with changes in systemic microcirculation. These changes vary amongst the subtypes of uveitis.
Topics: Female; Humans; Child; Adolescent; Male; Microcirculation; Quality of Life; Nails; Uveitis; Uveitis, Anterior; Uveitis, Intermediate; Panuveitis; Microscopic Angioscopy
PubMed: 37784087
DOI: 10.1186/s12969-023-00896-7 -
Internal Medicine (Tokyo, Japan) Feb 2022Behçet disease and its related disorder, Sweet disease, are multifactorial disorders whose susceptibility loci have been identified in the genes of various...
Behçet disease and its related disorder, Sweet disease, are multifactorial disorders whose susceptibility loci have been identified in the genes of various immunological factors aside from human leukocyte antigens. The neurological involvement of these diseases, including encephalitis, myelitis, and meningitis, referred to as neuro-Behçet disease (NBD) and neuro-Sweet disease (NSD) respectively, is sometimes difficult to diagnose, especially when the characteristic mucocutaneous symptoms do not precede neurological symptoms or when characteristics of both diseases are present in a single patient. NBD and NSD constitute a spectrum of diseases that are differentiated according to the combination of risk factors, including the genetic background. Encephalitis, myelitis, and meningitis similar to NBD or NSD can be diagnosed as spectrum disorders, even if the characteristic mucocutaneous symptoms fail to be detected. Understanding these conditions as a disease spectrum may help elucidate the disease pathogenesis and assist in the development of therapeutic agents.
Topics: Behcet Syndrome; Diagnosis, Differential; Encephalitis; Humans; Meningitis; Sweet Syndrome
PubMed: 34615825
DOI: 10.2169/internalmedicine.8227-21 -
Indian Journal of Ophthalmology Jun 2023Vogt-Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis associated with multisystem involvement, is a T-cell-mediated autoimmune disorder in which...
Vogt-Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis associated with multisystem involvement, is a T-cell-mediated autoimmune disorder in which cytotoxic T-cell target melanocytes in genetically susceptible individuals. Recently, there has been an increase in literature on the new onset of uveitis and reactivation of previously diagnosed cases of uveitis following Covid-19 vaccinations. It has been postulated that Covid-19 vaccines can lead to an immunomodulatory change resulting in an autoimmune phenomenon in the recipients. VKH following COVID-19 infection was reported in four patients and a total of 46 patients developing VKH or VKH-like disease following COVID-19 vaccinations. There are reports of four patients who had been recovering or recovered from VKH after receiving the first dosage of the vaccine and developed worsening of ocular inflammation after receiving the second dose of the vaccine.
Topics: Humans; Uveomeningoencephalitic Syndrome; COVID-19 Vaccines; COVID-19; Panuveitis; Uveitis
PubMed: 37322685
DOI: 10.4103/IJO.IJO_172_23 -
The Canadian Veterinary Journal = La... Sep 2016
Topics: Animals; Chorioretinitis; Dog Diseases; Dogs; Endophthalmitis; Male; Retinal Detachment
PubMed: 27587897
DOI: No ID Found -
Medicina (Kaunas, Lithuania) Jan 2022Primary inflammatory choriocapillaropathies (PICCPs) belong to a group of intraocular inflammatory diseases with the common characteristic of inflammatory... (Review)
Review
PURPOSE
Primary inflammatory choriocapillaropathies (PICCPs) belong to a group of intraocular inflammatory diseases with the common characteristic of inflammatory choriocapillaris hypo- or non-perfusion as the main clinicopathological mechanism. The purpose of our article is to describe clinical characteristics and multimodal imaging, that can help the diagnosis and treatment of PICCPs.
METHODS
Narrative review with multimodal imaging analysis.
RESULTS
Choriocapillaris non-perfusion can affect the end-choriocappilaries, at the benign end of the PICCP spectrum (MEWDS), to larger choriocapillaris vessels or precapillary vessels at the origin of more severe forms such as acute posterior multifocal placoid pigment epitheliopathy (APMPPE), idiopathic multifocal choroiditis (MFC) and Serpiginous Choroiditis (SC). Diagnosis is mostly based on multimodal imaging and especially on indocyanine green angiography (ICGA), fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT)/OCT-angiography (OCT-A). ICGA shows the typical pattern of patchy lobular hypofluorescence reflecting hypo- or non-perfusion of the choriocapillaris that can also take the aspect of geographic areas in the more severe forms. Treatment depends on the severity of the disease and goes from observation in MEWDS and some mild cases of APMPPE, to oral corticosteroid and/or immunomodulator agents in the more severe conditions of APMPPE and MFC and SC cases. Close multimodal monitoring is crucial in order to introduce or adjust treatment.
CONCLUSION
PICCPs are resulting from one common clinicopathological mechanism, inflammatory choriocapillaris hypo- or non-perfusion. ICGA findings are essential for the diagnosis and follow-up of PICCPs, but non-invasive methods such as FAF and SD-OCT/OCT-A also have their role especially in follow-up of the diseases. Treatment should be individualized according to the pathology and the evolution of lesions.
Topics: Choroid; Choroiditis; Fluorescein Angiography; Humans; Multifocal Choroiditis; Tomography, Optical Coherence
PubMed: 35208488
DOI: 10.3390/medicina58020165