IgG4-related disease (IgG4-RD) is a fascinating clinical entity first reported in this century in Japan, and includes a wide variety of diseases, such as formerly named Mikulicz's disease (MD), ...autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis and retroperitoneal fibrosis. The Japanese IgG4 team organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan has published the first criteria, comprehensive diagnostic (CD) criteria for IgG-RD 2011. Thereafter, IgG4-RD has been accepted widely and many cases have been reported from all over the world. Several problems have arisen in clinical practice, however, including the difficulty obtaining biopsy samples, and the sensitivity and specificity in cut off level of serum IgG4 and impaired immunostaining of IgG4. Given these situations, the Japanese IgG4 team has updated the 2011 comprehensive diagnostic criteria for IgG4-RD and propose the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD, which consists of 3 domains; 1) Clinical and radiological features, 2) Serological diagnosis and 3) Pathological diagnosis. In addition, the new pathological diagnosis is composed by three sub-items including storiform fibrosis and obliterative phlebitis.
Immunoglobulin G4 (IgG4)-related disease is a novel clinical entity characterized by infiltration of IgG4-immunopositive plasmacytes and elevated serum IgG4 concentration accompanied by enlargement ...of and masses in various organs, including the lacrimal gland, salivary gland, and pancreas. Recent studies have clarified that conditions previously diagnosed as Mikulicz disease as well as various types of lymphoplasmacytic infiltrative disorders of the ocular adnexa are consistent with a diagnosis of IgG4-related disease. Against this background, the diagnostic criteria for IgG4-related ophthalmic disease have recently been established, based on both the clinical and the histopathologic features of the ocular lesions. This article reviews these new criteria with reference to the comprehensive diagnostic criteria for IgG4-related disease for all systemic conditions reported in 2012.
Purpose
To investigate the epidemiology of uveitis in Japan and assess its changes over time.
Study design
Retrospective multicenter study
Methods
Sixty-six hospitals in Japan with uveitis specialty ...clinics participated in this retrospective nationwide survey. A questionnaire was sent to each hospital to survey the total number of patients who made a first visit to the outpatient uveitis clinic of each hospital between 1 April 2016 and 31 March 2017. The diagnosis of uveitis was based on guidelines when available or on commonly used diagnostic criteria.
Results
In 2016, new patients with uveitis accounted for 3.2% of the total number of new patients with ophthalmic diseases. A total of 5378 patients were enrolled in the survey; 3408 cases could be classified with a specific uveitis entity, and 1970 cases were described as unclassified intraocular inflammation. Among the classified cases, the most frequent disease was sarcoidosis (10.6%), followed by Vogt–Koyanagi–Harada disease (8.1%), herpetic iritis (6.5%), acute anterior uveitis (5.5%), sclerouveitis (4.4%), Behçet’s disease (4.2%), malignant disease (2.6%), acute retinal necrosis (1.7%), Posner–Schlossman syndrome (1.7%), and diabetic iritis (1.4%). The rates of sarcoidosis, Vogt–Koyanagi–Harada disease, and Behçet’s disease were similar; however, the rate of herpes iritis increased (4.2–6.5%) when compared with the 2009 survey.
Conclusions
Some changes were observed between the previous nationwide surveys (2002 and 2009) and the present survey. It must be valuable to continue such nationwide epidemiologic surveys at regular intervals.
To investigate the 2-year healing rate of macular edema (ME) secondary to branch retinal vein occlusion (BRVO) treated initially with intravitreal ranibizumab (IVR) and later combined with other ...treatment as needed, and the characteristics of refractory cases.
130 patients (130 eyes) with BRVO-ME who received IVR initially were studied. Anti-vascular endothelial growth factor drug was additionally administered when ME relapsed or persisted. Photocoagulation was performed when the non-perfusion area (NPA) was ≥5 disc diameter (DD), and/or when ME relapsed due to microaneurysm. Patients were classified into a healed group ME resolved in <2 years or mild ME remained without best-corrected visual acuity (BCVA) loss for ≥6 months or refractory group (ME persisted for ≥2 years).
110 eyes were classified into the healed group, and 20 eyes into the refractory group. The healed group and refractory group had, respectively, mean follow-up periods of 21.2 and 37.4 months, and frequencies of NPA ≥5 DD of 55.5 and 25.0% (p = 0.015). In the healed group, mean BCVA (logMAR) improved significantly compared to baseline in all the periods until 24 months after treatment initiation and at the last visit (p<0.001). In the refractory group, mean BCVA improved significantly compared to baseline until 12 months after treatment initiation (p<0.05 for all periods), but was not significantly different at 18 or 24 months or at the last visit.
In patients with BRVO-ME treated initially with IVR and later given additional treatments as needed, the healing rate was 84.6%. In eyes that healed within 2 years, BCVA improved relative to baseline throughout 24 months and at the last visit. In refractory eyes, BCVA improved only until 12 months, and thereafter deteriorated to baseline level at the last examination.
To determine distinguishing features of the clinical characteristics of anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), and cytomegalovirus (CMV).
...Retrospective, multicenter case series.
Consecutive patients with herpetic AU examined at 11 tertiary centers in Japan between January 2012 and December 2017 and who were followed for ≥3 months were evaluated. Diagnosis was made by polymerase chain reaction (PCR) for HSV, VZV, or CMV in the aqueous humor, or classical signs of herpes zoster ophthalmicus.
This study enrolled 259 herpetic AU patients, including PCR-proven HSV-AU (30 patients), VZV-AU (50), and CMV-AU (147), and herpes zoster ophthalmicus (32). All HSV-AU and VZV-AU patients were unilateral, while 3% of CMV-AU patients were bilateral. Most HSV-AU and VZV-AU patients were sudden onset with an acute clinical course, while CMV-AU had a more insidious onset and chronic course. There were no significant differences for all surveyed symptoms, signs, and complications between HSV-AU and VZV-AU. However, significant differences were detected for many items between CMV-AU and the other two herpetic AU types. Ocular hyperemia and pain, blurring of vision, ciliary injection, medium-to-large keratic precipitates (KPs), cells and flare in the anterior chamber, and posterior synechia significantly more often occurred in HSV-AU and VZV-AU vs CMV-AU. In contrast, small KPs, coin-shaped KPs, diffuse iris atrophy, elevated intraocular pressure, and glaucoma surgery were significantly more frequent in CMV-AU vs HSV-AU and VZV-AU.
This multicenter, retrospective study identified distinguishing features of HSV-AU, VZV-AU, and CMV-AU.
Purpose
There is no consensus concerning restarting anti-tumour necrosis factor (TNF)-α therapy for uveitis after treatment for active tuberculosis (TB). We report a case of Behcet disease (BD) in ...which treatment with TNF inhibitor was successfully resumed after treatment for miliary TB.
Case report
A 48-year-old Japanese male was treated for uveitis of unknown aetiology in the left eye at a general ophthalmology clinic. He was referred to Department of Ophthalmology, Tokyo Medical University Hospital because of macula oedema (ME) not responding to prednisolone (PSL) 20 mg. BD was diagnosed based on fluorescein angiographic findings of diffuse retinal vasculitis characteristic of BD, recurrent oral aphthous ulcer, erythema nodosum-like rash in his legs, and HLA-A26 positivity. After a screening test, adalimumab (ADA) was started as steroid-sparing therapy. Eight months after starting ADA, the patient was diagnosed with miliary TB. ADA and PSL were discontinued immediately due to TB. Anti-TB treatment was completed after 6 months based on clinical improvement, although T-SPOT.TB was still positive. Infliximab with isoniazid was started due to relapse of ME, worsened vitreous haze, and worsened visual acuity in his left eye. Subsequently, his ocular symptoms subsided and there was no relapse of TB.
Conclusion
This case suggests that in patients with BD who have discontinued anti-TNF therapy due to miliary TB, restarting anti-TNF therapy may be a therapeutic option after TB has been treated appropriately with careful monitoring for relapse.
Various immune mediators have crucial roles in the pathogenesis of intraocular diseases. Machine learning can be used to automatically select and weigh various predictors to develop models maximizing ...predictive power. However, these techniques have not yet been applied extensively in studies focused on intraocular diseases. We evaluated whether 5 machine learning algorithms applied to the data of immune-mediator levels in aqueous humor can predict the actual diagnoses of 17 selected intraocular diseases and identified which immune mediators drive the predictive power of a machine learning model.
Cross-sectional study.
Five hundred twelve eyes with diagnoses from among 17 intraocular diseases.
Aqueous humor samples were collected, and the concentrations of 28 immune mediators were determined using a cytometric bead array. Each immune mediator was ranked according to its importance using 5 machine learning algorithms. Stratified k-fold cross-validation was used in evaluation of algorithms with the dataset divided into training and test datasets.
The algorithms were evaluated in terms of precision, recall, accuracy, F-score, area under the receiver operating characteristic curve, area under the precision-recall curve, and mean decrease in Gini index.
Among the 5 machine learning models, random forest (RF) yielded the highest classification accuracy in multiclass differentiation of 17 intraocular diseases. The RF prediction models for vitreoretinal lymphoma, acute retinal necrosis, endophthalmitis, rhegmatogenous retinal detachment, and primary open-angle glaucoma achieved the highest classification accuracy, precision, and recall. Random forest recognized vitreoretinal lymphoma, acute retinal necrosis, endophthalmitis, rhegmatogenous retinal detachment, and primary open-angle glaucoma with the top 5 F-scores. The 3 highest-ranking relevant immune mediators were interleukin (IL)-10, interferon-γ-inducible protein (IP)-10, and angiogenin for prediction of vitreoretinal lymphoma; monokine induced by interferon γ, interferon γ, and IP-10 for acute retinal necrosis; and IL-6, granulocyte colony-stimulating factor, and IL-8 for endophthalmitis.
Random forest algorithms based on 28 immune mediators in aqueous humor successfully predicted the diagnosis of vitreoretinal lymphoma, acute retinal necrosis, and endophthalmitis. Overall, the findings of the present study contribute to increased knowledge on new biomarkers that potentially can facilitate diagnosis of intraocular diseases in the future.
Purpose
To clarify the proportion of ocular sarcoidosis with severe, refractory, and prolonged inflammation and their association with ocular complications and visual prognosis.
Study Design
...Multicenter, retrospective, longitudinal cohort study.
Methods
Three hundred and twenty-three eyes of 164 patients (45 men; 119 women) with ocular sarcoidosis who visited Hokkaido University Hospital and Yokohama City University Hospital from 2010 to 2015. We newly defined severe, refractory, and prolonged inflammation in ocular sarcoidosis, and investigated their proportions, ocular complications and final visual acuity from medical records of our sarcoidosis patients.
Results
The eyes with severe inflammation numbered 72/323 (22.3%), with refractory inflammation, 80/323 (24.8%), and with prolonged inflammation, 91/323 (28.2%). The number of eyes having neither severe, refractory, nor prolonged inflammation (defined as none) was 114/323 (35.3%). The numbers of eyes that reached irreversible visual dysfunction were 6/72 (8.3%) of those with severe inflammation, 10/80 (12.5%) with refractory inflammation, 12/91 (13.2%) with prolonged inflammation, and 4/114 (6.2%) with none. As complications, cataract (62.2%), glaucoma (28.5%), epiretinal membrane (24.1%), cystoid macular edema (22.6%), vitreous hemorrhage (2.8%), choroidal atrophy (2.5%), macular degeneration (1.2%), macular hole (0.9%) and retinal detachment (0.3%) were identified. Among them, secondary glaucoma (16 eyes) and macular degeneration (4 eyes) were major complications related to irreversible visual dysfunction.
Conclusions
Although most of the patients with ocular sarcoidosis had a relatively good visual prognosis, some developed severe, refractory, and/or prolonged inflammation related to the development of ocular complications, that resulted in poor visual prognosis.
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