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JAMA Ophthalmology Aug 2023Idiopathic multifocal choroiditis (MFC) is poorly understood, thereby hindering optimal treatment and monitoring of patients.
IMPORTANCE
Idiopathic multifocal choroiditis (MFC) is poorly understood, thereby hindering optimal treatment and monitoring of patients.
OBJECTIVE
To identify the genes and pathways associated with idiopathic MFC.
DESIGN, SETTING, AND PARTICIPANTS
This was a case-control genome-wide association study (GWAS) and protein study of blood plasma samples conducted from March 2006 to February 2022. This was a multicenter study involving 6 Dutch universities. Participants were grouped into 2 cohorts: cohort 1 consisted of Dutch patients with idiopathic MFC and controls, and cohort 2 consisted of patients with MFC and controls. Plasma samples from patients with idiopathic MFC who had not received treatment were subjected to targeted proteomics. Idiopathic MFC was diagnosed according to the Standardization of Uveitis Nomenclature (SUN) Working Group guidelines for punctate inner choroidopathy and multifocal choroiditis with panuveitis. Data were analyzed from July 2021 to October 2022.
MAIN OUTCOMES AND MEASURES
Genetic variants associated with idiopathic MFC and risk variants associated with plasma protein concentrations in patients.
RESULTS
This study included a total of 4437 participants in cohort 1 (170 [3.8%] Dutch patients with idiopathic MFC and 4267 [96.2%] controls; mean [SD] age, 55 [18] years; 2443 female [55%]) and 1344 participants in cohort 2 (52 [3.9%] patients with MFC and 1292 [96.1%] controls; 737 male [55%]). The primary GWAS association mapped to the CFH gene with genome-wide significance (lead variant the A allele of rs7535263; odds ratio [OR], 0.52; 95% CI, 0.41-0.64; P = 9.3 × 10-9). There was no genome-wide significant association with classical human leukocyte antigen (HLA) alleles (lead classical allele, HLA-A*31:01; P = .002). The association with rs7535263 showed consistent direction of effect in an independent cohort of 52 cases and 1292 control samples (combined meta-analysis OR, 0.58; 95% CI, 0.38-0.77; P = 3.0 × 10-8). In proteomic analysis of 87 patients, the risk allele G of rs7535263 in the CFH gene was strongly associated with increased plasma concentrations of factor H-related (FHR) proteins (eg, FHR-2, likelihood ratio test, adjusted P = 1.1 × 10-3) and proteins involved in platelet activation and the complement cascade.
CONCLUSIONS AND RELEVANCE
Results suggest that CFH gene variants increase systemic concentrations of key factors of the complement and coagulation cascades, thereby conferring susceptibility to idiopathic MFC. These findings suggest that the complement and coagulation pathways may be key targets for the treatment of idiopathic MFC.
Topics: Humans; Male; Female; Middle Aged; Complement Factor H; Multifocal Choroiditis; Genome-Wide Association Study; Proteomics; Polymorphism, Single Nucleotide; Choroiditis; Proteins
PubMed: 37410486
DOI: 10.1001/jamaophthalmol.2023.2557 -
Indian Journal of Ophthalmology 2010Posterior uveitic entities are varied entities that are infective or non-infective in etiology. They can affect the adjacent structures such as the retina, vitreous,... (Review)
Review
Posterior uveitic entities are varied entities that are infective or non-infective in etiology. They can affect the adjacent structures such as the retina, vitreous, optic nerve head and retinal blood vessels. Thorough clinical evaluation gives a clue to the diagnosis while ancillary investigations and laboratory tests assist in confirming the diagnosis. Newer evolving techniques in the investigations and management have increased the diagnostic yield. In case of diagnostic dilemma, intraocular fluid evaluation for polymerase chain testing for the genome and antibody testing against the causative agent provide greater diagnostic ability.
Topics: Anti-Inflammatory Agents; Choroiditis; Diagnosis, Differential; Fluorescein Angiography; Fundus Oculi; Humans; Infections; Prognosis; Retinitis; Tomography, Optical Coherence; Uveitis, Posterior
PubMed: 20029144
DOI: 10.4103/0301-4738.58470 -
Internal and Emergency Medicine Oct 2022Purpose of the present paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to...
Purpose of the present paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to pediatric and adult patients with Behçet's disease (BD). The Registry is a clinical physician-driven non-population- and electronic-based instrument implemented for the retrospective and prospective collection of real-life data about demographics, clinical, therapeutic, laboratory, instrumental and socioeconomic information from BD patients; the Registry is based on the Research Electronic Data Capture (REDCap) tool, which is thought to collect standardised information for clinical real-life research, and has been realised to change over time according to future scientific acquisitions and potentially communicate with other existing and future Registries dedicated to BD. Starting from January 31st, 2021, to February 7th, 2022, 110 centres from 23 countries in 4 continents have been involved. Fifty-four of these have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 175 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry collects baseline and follow-up data using 5993 fields organised into 16 instruments, including patient's demographics, history, clinical manifestations and symptoms, trigger/risk factors, therapies and healthcare access. The development of the AIDA International Registry for BD patients will facilitate the collection of standardised data leading to real-world evidence, enabling international multicentre collaborative research through data sharing, international consultation, dissemination of knowledge, inclusion of patients and families, and ultimately optimisation of scientific efforts and implementation of standardised care.Trial registration NCT05200715 in 21/01/2022.
Topics: Adult; Behcet Syndrome; Child; Humans; Prospective Studies; Registries; Retrospective Studies
PubMed: 35831701
DOI: 10.1007/s11739-022-03038-1 -
Revista de Neurologia Jul 2023Limbic encephalitis (LE) can have a wide range of etiologies, most frequently infectious (especially viral) or autoimmune. Behcet's disease (BD) can present with... (Review)
Review
INTRODUCTION
Limbic encephalitis (LE) can have a wide range of etiologies, most frequently infectious (especially viral) or autoimmune. Behcet's disease (BD) can present with heterogeneous neurological manifestations. However, LE is not considered a typical presentation of neuro-Behcet's disease (NBD).
CASE REPORT
A 40-years-old male presented with new-onset subacute headaches, memory problems and apathy. A review of systems revealed an unrecorded past history of recurrent oral sores for years, recent malaise and fever, as well as an episode of bilateral panuveitis four months before presentation. His general and neurologic examination revealed slight fever, an isolated oral aphtha, anterograde amnesia and signs of bilateral retinal vasculitis. Brain magnetic resonance imaging displayed a pattern of limbic meningoencephalitis, and his cerebrospinal fluid showed mononuclear inflammation. The patient met BD diagnostic criteria. Considering LE is a very rare presentation of NBD, alternative etiologies were thoroughly assessed and excluded, including infectious, autoimmune and paraneoplastic encephalitis. Therefore, he was diagnosed with NBD, and he recovered well after immunosuppression.
DISCUSSION
Only two cases of NBD presenting with LE have been previously reported. We report a third case of this rare presentation and compare it with the previous two. We aim to highlight this association and contribute to enlarge the rich clinical spectrum of NBD.
Topics: Humans; Male; Adult; Behcet Syndrome; Limbic Encephalitis; Brain; Magnetic Resonance Imaging; Headache
PubMed: 37403244
DOI: 10.33588/rn.7702.2022049 -
The Cochrane Database of Systematic... Oct 2022Non-infectious intermediate, posterior, and panuveitis (NIIPPU) represent a heterogenous collection of autoimmune and inflammatory disorders isolated to or concentrated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-infectious intermediate, posterior, and panuveitis (NIIPPU) represent a heterogenous collection of autoimmune and inflammatory disorders isolated to or concentrated in the posterior structures of the eye. Because NIIPPU is typically a chronic condition, people with NIIPPU frequently require treatment with steroid-sparing immunosuppressive therapy. Methotrexate, mycophenolate, cyclosporine, azathioprine, and tacrolimus are non-biologic, disease-modifying antirheumatic drugs (DMARDs) which have been used to treat people with NIIPPU.
OBJECTIVES
To compare the effectiveness and safety of selected DMARDs (methotrexate, mycophenolate mofetil, tacrolimus, cyclosporine, and azathioprine) in the treatment of NIIPPU in adults.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase, the Latin American and Caribbean Health Sciences database, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform, most recently on 16 April 2021.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing selected DMARDs (methotrexate, mycophenolate, tacrolimus, cyclosporine, and azathioprine) with placebo, standard of care (topical steroids, with or without oral steroids), or with each other.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 11 RCTs with a total of 601 participants in this review. DMARDs versus control Two studies compared an experimental DMARD (cyclosporine A or enteric-coated mycophenolate [EC-MPS]) plus oral steroid with steroid monotherapy. We did not pool these results into a meta-analysis because the dose of cyclosporine used was much higher than that used in current clinical practice. The evidence is very uncertain about whether EC-MPS plus low-dose oral steroid results in a higher proportion of participants achieving control of inflammation over steroid monotherapy (risk ratio [RR] 2.81, 95% confidence interval [CI] 1.10 to 7.17; 1 study, 41 participants; very low-certainty evidence). The change in best-corrected visual acuity (BCVA) was reported separately for right and left eyes. The evidence for improvement (lower logarithm of the minimum angle of resolution (logMAR) indicates better vision) between the groups is very uncertain (mean difference [MD] -0.03 and -0.10, 95% CI -0.96 to 0.90 and -0.27 to 0.07 for right and left, respectively; 1 study, 82 eyes; very low-certainty evidence). No data were available for the following outcomes: proportion of participants achieving a 2-line improvement in visual acuity, with confirmed macular edema, or achieving steroid-sparing control. The evidence for the proportion of participants requiring cessation of medication in the DMARD versus control group is very uncertain (RR 2.61, 95% CI 0.11 to 60.51; 1 study, 41 participants; very low-certainty evidence). Methotrexate versus mycophenolate We were able to combine two studies into a meta-analysis comparing methotrexate versus mycophenolate mofetil. Methotrexate probably results in a slight increase in the proportion of participants achieving control of inflammation, including steroid-sparing control, compared to mycophenolate at six months (RR 1.23, 95% CI 1.01 to 1.50; 2 studies, 261 participants; moderate-certainty evidence). Change in BCVA was reported per eye and the treatments likely result in little to no difference in change in vision (MD 0.01 logMAR higher [worse] for methotrexate versus mycophenolate; 2 studies, 490 eyes; moderate-certainty evidence). No data were available for the proportion of participants achieving a 2-line improvement in visual acuity. The evidence is very uncertain regarding the proportion of participants with confirmed macular edema between methotrexate versus mycophenolate (RR 0.49, 95% CI 0.19 to 1.30; 2 studies, 35 eyes; very low-certainty). Methotrexate versus mycophenolate may result in little to no difference in the proportion of participants requiring cessation of medication (RR 0.99, 95% CI 0.43 to 2.27; 2 studies, 296 participants; low-certainty evidence). Steroids with or without azathioprine versus cyclosporine A Four studies compared steroids with or without azathioprine (oral steroids, intravenous [IV] steroids, or azathioprine) to cyclosporine A. We excluded two studies from the meta-analysis because the participants were treated with 8 mg to 15 mg/kg/day of cyclosporine A, a significantly higher dose than is utilized today because of concerns for nephrotoxicity. The remaining two studies were conducted in all Vogt-Koyanagi-Harada disease (VKH) populations and compared cyclosporine A to azathioprine or IV pulse-dose steroids. The evidence is very uncertain for whether the steroids with or without azathioprine or cyclosporine A influenced the proportion of participants achieving control of inflammation (RR 0.84, 95% CI 0.70 to 1.02; 2 studies, 112 participants; very low-certainty evidence), achieving steroid-sparing control (RR 0.64, 95% CI 0.33 to 1.25; 1 study, 21 participants; very low-certainty evidence), or requiring cessation of medication (RR 0.85, 95% 0.21 to 3.45; 2 studies, 91 participants; very low-certainty evidence). The evidence is uncertain for improvement in BCVA (MD 0.04 logMAR lower [better] with the steroids with or without azathioprine versus cyclosporine A; 2 studies, 91 eyes; very low-certainty evidence). There were no data available (with current cyclosporine A dosing) for the proportion of participants achieving a 2-line improvement in visual acuity or with confirmed macular edema. Studies not included in synthesis We were unable to include three studies in any of the comparisons (in addition to the aforementioned studies excluded based on historic doses of cyclosporine A). One was a dose-response study comparing cyclosporine A to cyclosporine G, a formulation which was never licensed and is not clinically available. We excluded another study from meta-analysis because it compared cyclosporine A and tacrolimus, considered to be of the same class (calcineurin inhibitors). We were unable to combine the third study, which examined tacrolimus monotherapy versus tacrolimus plus oral steroid, with any group.
AUTHORS' CONCLUSIONS
There is a paucity of data regarding which DMARD is most effective or safe in NIIPPU. Studies in general were small, heterogenous in terms of their design and outcome measures, and often did not compare different classes of DMARD with each other. Methotrexate is probably slightly more efficacious than mycophenolate in achieving control of inflammation, including steroid-sparing control (moderate-certainty evidence), although there was insufficient evidence to prefer one medication over the other in the VKH subgroup (very low-certainty evidence). Methotrexate may result in little to no difference in safety outcomes compared to mycophenolate.
Topics: Adult; Humans; Macular Edema; Cyclosporine; Mycophenolic Acid; Tacrolimus; Azathioprine; Methotrexate; Steroids; Immunosuppressive Agents; Panuveitis; Inflammation; Antirheumatic Agents
PubMed: 36315029
DOI: 10.1002/14651858.CD014831.pub2 -
Ocular Immunology and Inflammation Jul 2022To present a patient with Rosai-Dorfman Disease (RDD), a histiocytic proliferative disorder typified by lymphadenopathy with rare ocular manifestations, who developed...
PURPOSE
To present a patient with Rosai-Dorfman Disease (RDD), a histiocytic proliferative disorder typified by lymphadenopathy with rare ocular manifestations, who developed panuveitis that responded to pegylated interferon.
METHODS
Descriptive case report of a patient with RDD with multi-organ involvement including ocular manifestations including bilateral panuveitis with choroidal masses.
RESULTS
A 54-year-old African American woman with known systemic RDD of the breast, lung, and gastrointestinal tract presented with panuveitis with choroidal masses in both eyes. Her systemic and ocular disease initially responded well to oral and topical steroid therapy. Later, however, her systemic disease progressed with multiple muscular and bony lesions. Systemic therapy was switched to pegylated interferon, a cytokine with antiviral, antitumor and immunomodulatory activity. After 14 months of therapy with pegylated interferon, the patient's systemic and ocular disease stabilized.
CONCLUSION
Rosai-Dorfman disease may be complicated by panuveitis and choroidal masses that may respond to pegylated interferon with stabilization of systemic and ocular manifestations. A multi-disciplinary approach is essential given the unique diagnostic and management challenges of RDD.
Topics: Antiviral Agents; Female; Histiocytosis, Sinus; Humans; Interferons; Middle Aged; Panuveitis; Polyethylene Glycols; Steroids
PubMed: 33683183
DOI: 10.1080/09273948.2020.1867190 -
BMC Ophthalmology May 2021Sympathetic ophthalmia (SO) is a bilateral diffuse uveitis that can arise after ocular trauma or ocular surgery in the inciting eye. Pars plana vitrectomy (PPV) is one...
BACKGROUND
Sympathetic ophthalmia (SO) is a bilateral diffuse uveitis that can arise after ocular trauma or ocular surgery in the inciting eye. Pars plana vitrectomy (PPV) is one of the risk factors for SO. Several reports have described SO developing after 23- and 25-G PPV, but none have described SO occurring after 27-G PPV. We describe herein a case of SO after 27-G PPV for rhegmatogenous retinal detachment.
CASE PRESENTATION
A 42-year-old woman presented with visual disturbance in the right eye. Best-corrected visual acuity (BCVA) was 6/200 in the right eye. Fundus examination revealed off-macula retinal detachment with retinal tears at both ends of retinal lattice degeneration at the temporal-oven peripheral retina of the right eye. We therefore performed 27-G sutureless PPV on the right eye. After 12 days, the retina was reattached, and BCVA improved to 6/30 in the right eye. Fifteen days postoperatively, she experienced headache and reduced vision in both eyes. Symptoms gradually worsened, and she visited our hospital 21 days postoperatively. BCVA was 6/30 in the right eye and 6/15 in the left eye. Slit-lamp examination revealed uveitis in the anterior chambers of both eyes, and fundus examination showed papillitis and subretinal detachment at the posterior poles of both eyes. Optical coherence tomography revealed subretinal fluid in the maculae of both eyes and fluorescein angiography showed multiple hyperfluorescent leakage sites in the retinal pigment epithelium. Cerebrospinal fluid examination showed pleocytosis and human leukocyte antigen testing showed expression of the DR04 phenotype; therefore, the patient was diagnosed with SO. She was treated with steroid therapy, and her visual disturbance subsided and the subretinal fluid improved as well. Her BCVA was 6/15 for the right eye and 6/5 for the left eye 93 days after the initial surgery.
CONCLUSION
The present case shows that even if the sclerotomy site of 27-G PPV is small, there is still a risk of SO occurring in the eyes of patients who underwent transconjunctival vitrectomy. Ophthalmologists should recognize SO as complication of 27-G PPV and carry out proper management as early as possible.
Topics: Adult; Female; Humans; Ophthalmia, Sympathetic; Retinal Detachment; Retrospective Studies; Visual Acuity; Vitrectomy
PubMed: 33934701
DOI: 10.1186/s12886-021-01961-z -
Internal and Emergency Medicine Apr 2023This study aims to describe musculoskeletal manifestations (MSM) in children with Behçet's syndrome (BS), their association with other disease manifestations, response... (Clinical Trial)
Clinical Trial
This study aims to describe musculoskeletal manifestations (MSM) in children with Behçet's syndrome (BS), their association with other disease manifestations, response to therapy, and long-term prognosis. Data were retrieved from the AIDA Network Behçet's Syndrome Registry. Out of a total of 141 patients with juvenile BS, 37 had MSM at disease onset (26.2%). The median age at onset was 10.0 years (IQR 7.7). The median follow-up duration was 21.8 years (IQR 23.3). Recurrent oral (100%) and genital ulcers (67.6%) and pseudofolliculitis (56.8%) were the most common symptoms associated with MSM. At disease onset, 31 subjects had arthritis (83.8%), 33 arthralgia (89.2%), and 14 myalgia (37.8%). Arthritis was monoarticular in 9/31 cases (29%), oligoarticular in 10 (32.3%), polyarticular in 5 (16.1%), axial in 7 (22.6%). Over time, arthritis became chronic-recurrent in 67.7% of cases and 7/31 patients had joint erosions (22.6%). The median Behçet's Syndrome Overall Damage Index was 0 (range 0-4). Colchicine was inefficacious for MSM in 4/14 cases (28.6%), independently from the type of MSM (p = 0.46) or the concomitant therapy (p = 0.30 for cDMARDs, p = 1.00 for glucocorticoids); cDMARDs and bDMARDs were inefficacious for MSM in 6/19 (31.4%) and 5/12 (41.7%) cases. The presence of myalgia was associated with bDMARDs inefficacy (p = 0.014). To conclude, MSM in children with BS are frequently associated with recurrent ulcers and pseudofolliculitis. Arthritis is mostly mono- or oligoarticular, but sacroiliitis is not unusual. Prognosis of this subset of BS is overall favorable, though the presence of myalgia negatively affects response to biologic therapies. ClinicalTrials.gov Identifier: NCT05200715 (registered on December 18, 2021).
Topics: Child; Humans; Arthritis; Behcet Syndrome; Myalgia; Registries; Ulcer
PubMed: 36881285
DOI: 10.1007/s11739-023-03215-w -
Journal of the Royal College of... 2000We report our clinical experience of 230 patients referred to the Hammersmith hospital with a working diagnosis of Behçet's syndrome. The pathogenesis, diagnosis and... (Review)
Review
We report our clinical experience of 230 patients referred to the Hammersmith hospital with a working diagnosis of Behçet's syndrome. The pathogenesis, diagnosis and management of the syndrome are discussed.
Topics: Adolescent; Adult; Aged; Algorithms; Behcet Syndrome; Eye Diseases; Female; Humans; Inflammation; Male; Middle Aged
PubMed: 10816874
DOI: No ID Found -
European Journal of Ophthalmology May 2023To report recurrence of tubercular choroiditis following anti-SARS-CoV-2 vaccination in two patients with quiescent disease activity for more than a year.
PURPOSE
To report recurrence of tubercular choroiditis following anti-SARS-CoV-2 vaccination in two patients with quiescent disease activity for more than a year.
METHODS
Retrospective observational case reports.
RESULTS
Two patients (one female and one male) under follow-up for posterior uveitis having stable course with absence of ocular inflammation for more than a year presented with recurrence of choroiditis lesions 2-6 weeks following anti-SARS-CoV-2 vaccination. Both the patients were managed with intravitreal dexamethasone implant (Ozurdex®, Allergan, Inc., Irvine, CA, USA) and showed resolution of choroiditis lesions upon follow-up.
CONCLUSIONS
Acute onset recurrence of inflammation, in absence of any change in health status or treatment suggests the potential role of vaccination being the trigger of this reactivation. Given large-scale vaccination against novel coronavirus- SARS-CoV-2, careful vigilance is warranted to pick up the disease recurrence in patients with posterior uveitis.
Topics: Humans; Male; Female; Retrospective Studies; COVID-19; SARS-CoV-2; Choroiditis; Dexamethasone; Uveitis, Posterior; Inflammation
PubMed: 35306917
DOI: 10.1177/11206721221088439