Clinical Profile of Anti-Myelin Oligodendrocyte Glycoprotein Antibody Seropositive Cases of Optic Neuritis.

We have studied the clinical picture of anti-aquaporin antibody (AQP4-Ab)- and anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-positive optic neuritis. However, optic neuritis associated with MOG-Abs has not been elucidated using new methods such as cell-based assay. Hence, we conducted a comprehensive investigation on its clinical profile. Serum samples from 70 patients (17 males and 53 females, mean age 43.1 years) with optic neuritis were tested for MOG-Abs by cell-based assay. In MOG-Ab seropositive patients, the disease type, recurrence status, and visual function outcome were analysed. Among 70 patients, 18 were MOG-Ab seropositive. The 18 patients comprised 2 with chronic relapsing inflammatory optic neuropathy, 2 with AQP4-Ab seropositive optic neuritis (neuromyelitis optica), 12 with idiopathic optic neuritis, and 2 with optic neuritis associated with multiple sclerosis. Excluding two cases that were also AQP4-Ab seropositive, MOG-Ab seropositive cases had relatively favourable visual acuity outcome (although not significantly different from seronegative cases) but had significant residual visual field deficit (p = 0.0015). Furthermore, the number of relapses of optic neuritis per year was significantly greater in MOG-Ab seropositive cases than in seronegative cases (0.82 vs. 0.40; p = 0.0005). MOG-Abs may contribute to the heterogeneous clinical picture of optic neuritis, and although visual acuity outcome is favourable, there is a tendency of residual visual field deficit and a possibility of repeated relapses.

Use of systemic corticosteroids in patients newly registered at a claims database with a diagnosis of non-infectious uveitis: results from a real-world claims database analysis.

PURPOSE: To investigate the real-world dose of systemic corticosteroids in the treatment of non-infectious uveitis (NIU) in Japan. STUDY DESIGN: A retrospective, observational study. METHODS: Patients newly registered at the Japan Medical Data Center health insurance claims database with a diagnosis of NIU who received systemic corticosteroids were identified, and their systemic corticosteroid dose (prednisolone equivalent) was assessed over 12 months of treatment (data extraction period: January 2008 to May 2017). RESULTS: The mean cumulative systemic corticosteroid dose in 12 months in 1641 new patients with NIU who received systemic corticosteroids was 593.7 mg. The mean systemic corticosteroid dose was highest at month 1 (10.7, 218.1, 16.7, and 23.0 mg/day in Behçet's disease [BD]-associated NIU [n = 19], Vogt-Koyanagi-Harada [VKH] disease-associated NIU [n = 49], sarcoidosis-associated NIU [n = 27], and "undifferentiated NIU" [NIU without specific primary disease information, n = 1545], respectively) and decreased over time. Systemic corticosteroids were prescribed at month 12 to 68.4%, 22.4%, 44.4%, and 5.6% of patients with BD-associated NIU, VKH disease-associated NIU, sarcoidosis-associated NIU, and undifferentiated NIU, respectively (mean dose, 6.0-14.3 mg/day). Multivariate regression analysis identified female sex, middle age (30 to < 40 years), VKH disease, and immunosuppressive agent use as background factors associated with higher systemic corticosteroid dose. CONCLUSIONS: The systemic corticosteroid dose was highest at month 1 and decreased over time in all disease categories. This database research revealed that some patients with NIU continued being prescribed systemic corticosteroids for at least 1 year.

Anti-TNF-α Therapy for Refractory Uveitis Associated with Behçet's Syndrome and Sarcoidosis: A Single Center Study of 131 Patients.

PURPOSE: The efficacy of infliximab (IFX) and adalimumab (ADA) for treating Behçet's syndrome (BS) and sarcoidosis has not been compared adequately. METHODS: We reviewed the medical records of patients with uveitis diagnosed at Tokyo Medical University Hospital and compared the efficacy of IFX and ADA for BS and the efficacy of ADA for sarcoidosis and BS. RESULTS: 68 patients in IFX group and 63 patients in ADA group were analyzed. In BS patients, IFX and ADA were both effective in improving uveitic macular edema (UME). ADA improved UME in BS but not in sarcoidosis patients. The efficacy of ADA in reducing doses of corticosteroids and glaucoma medications was better in sarcoidosis than in the BS group. CONCLUSION: Both IFX and ADA are efficacious in improving UME in BS patients. The reason that ADA improves UME better in BS than in sarcoidosis may be due to the difference in pathogenesis between these diseases.

Changes in Etiology of Uveitis in a Single Center in Japan.

Purpose: We investigated the changes in etiology of uveitis at the Uveitis Clinic of Tokyo Medical University Hospital in recent years.Methods: Medical records of patients with uveitis diagnosed between 2011 and 2017 (Group A) and between 2001 and 2007 (Group B) were reviewed.Results: 1,587 patients in group A and 1,507 patients in group B were analyzed. For noninfectious uveitis, frequencies of Vogt-Koyanagi-Harada disease, intraocular lymphoma (IOL) and iridocyclitis in young girls increased, while those of sarcoidosis and Behçet's disease decreased in the recent era. For infectious uveitis, herpetic iridocyclitis, ocular toxoplasmosis, ocular syphilis, and bacterial endophthalmitis increased, while acute retinal necrosis and ocular toxocariasis decreased. Unclassified uveitis decreased, whereas infectious uveitis and IOL increased due to the availability of new diagnostic tests.Conclusion: Etiologies of uveitis have changed over the years. Further development of novel tests and diagnostic criteria would increase definitive diagnosis for unclassified uveitis. (147/150 words).

Prevalence and incidence rates and treatment patterns of non-infectious uveitis in Japan: real-world data using a claims database.

PURPOSE: To estimate the nationwide, longitudinal prevalence and incidence rates and assess treatment patterns of non-infectious uveitis (NIU) in Japan. STUDY DESIGN: A retrospective study. METHODS: Health insurance claims' data of patients with NIU were extracted from the Japan Medical Data Center (JMDC) database and analyzed descriptively (data extraction period, January 2011 to May 2017). Behçet's disease (BD), Vogt-Koyanagi-Harada (VKH) disease, and sarcoidosis were selected as the primary diseases of NIU. RESULTS: From 2011 to 2016, the mean and median age of patients increased. Most (> 90%) patients were categorized as "undifferentiated NIU" (NIU without specific primary disease information after excluding BD-, VKH disease-, and sarcoidosis-associated NIU). Over 60% of patients with NIU were treated at non-hospital clinics, while the rest were treated at university, public, or other hospitals. The estimated prevalence rate of NIU was 386.5 per 100,000 persons (95% confidence interval [CI], 374.5-398.6) in 2011 and 439.3 per 100,000 persons (95% CI, 432.3-446.3) in 2016; the estimated incidence rate was 189.7 per 100,000 persons (95% CI, 181.2-198.5) in 2012 and 207.8 per 100,000 persons (95% CI, 202.2-213.5) in 2016. Most patients' prescribed uveitis drugs were ophthalmic drops over the first 6 months after patient presentation and entry into the JMDC database, followed by systemic corticosteroids. CONCLUSION: The estimated prevalence of NIU in Japan in recent years was approximately 400 with incidence of 200 per 100,000 persons.

Evaluation of efficacy of infliximab for retinal vasculitis and extraocular symptoms in Behçet disease.

PURPOSE: We evaluated ocular symptoms and activity of retinal vasculitis of Behçet disease before and after infliximab therapy, using Behçet disease ocular attack score 24 (BOS24) and fluorescein angiography (FA) score. We also analyzed the efficacy of infliximab for ocular and extraocular symptoms. STUDY DESIGN: Retrospective study. SUBJECT AND METHODS: Using medical records, we analyzed FA and BOS24 to evaluate the association between the efficacy of infliximab therapy and FA as well as BOS24 scores. Further, we evaluated the association between FA scores and extraocular symptoms. RESULTS: After 2 years of infliximab therapy, 6-month BOS24 was significantly reduced compared to that before treatment (PreBOS24-6M). After 4 years of infliximab therapy, 6-month BOS24 was also significantly reduced compared to preBOS24-6M. After 2 years of infliximab therapy, FA score median (interquartile range) decreased significantly compared to that before treatment [FA-2Y vs. preFA: 0 (0-0) vs.15.5 (12-24); P < 0.0001; n = 38]. The FA-4Y score in subjects followed for at least 4 years was also significantly lower than the preFA score [0 (0-0) vs.16.5 (12-24.5); P < 0.0001; n = 28]. Among 38 patients, extraocular symptoms were resolved following treatment in 29 cases (76.3%). No significant correlation was observed between the improvement in FA-2Y and FA-4Y scores and the occurrence and persistence of extraocular symptoms (P = 0.33; n = 38 or P = 0.4; n = 28). CONCLUSION: Infliximab therapy is effective for the treatment of ocular and extraocular involvement of Behçet disease. BOS24 and FA scores are useful for evaluating the efficacy of infliximab therapy.

Role of PU.1 Expression as an Inflammatory Marker in Experimental Autoimmune Uveoretinitis.

PURPOSE: PU.1 is an Ets family transcription factor, which is essential for the development of immune system through generation of myeloid and lymphoid lineages. In this study, we investigated PU.1 expression in the retina of mice with experimental autoimmune uveoretinitis (EAU) and the association between PU.1 expression level and inflammation in EAU. METHODS: IRBP 1-20 peptide-immunized mice were used. Quantitative PCR, ELISA analysis, cytometric bead array (CBA), assay and immunostaining were conducted using ocular tissues and lymph nodes. RESULTS: Quantitative PCR showed significant increases in mRNA levels of PU.1 in the retina at the peak of inflammation. Immunostaining of retina flat mounts revealed that most PU.1-positive cells were co-stained with anti-CD11c and anti-F4/80 antibodies. PU.1 knockdown in lymph node cells significantly suppressed IRBP-stimulated IFN-γ production measured by ELISA and IL-2 production measured by CBA. CONCLUSION: PU.1 may play crucial roles in the development and progression of inflammation in EAU.

Propionibacterium acnes as a possible pathogen of granuloma in patients with ocular sarcoidosis.

BACKGROUND/AIMS: To detect Propionibacterium acnes from intraocular granuloma in patients with ocular sarcoidosis. METHODS: Ten patients (10 eyes) with uveitis associated with sarcoidosis, who underwent vitrectomy to remove the epiretinal membrane were analysed. The patients were 70.4±7.6 (mean±SD) years of age, and the observation period from diagnosis of sarcoidosis until vitrectomy was 27.6±15.1 months. Histopathological examination of paraffin-embedded sections of the excised epiretinal membranes was conducted by H&E staining and immunohistochemical staining using PAB antibody, which is a monoclonal antibody against P. acnes. Four patients with idiopathic epiretinal membrane and four patients with epiretinal membrane caused by chronic uveitis other than sarcoidosis were included as control. RESULTS: Granuloma in the epiretinal membrane was observed in 4 of 10 patients with sarcoidosis, and all the granulomas were positive for PAB. In one patient without granuloma in the epiretinal membrane, PAB immunoreactivity was found in inflammatory cells, presumably macrophages. No granuloma and no PAB immunoreactivity were detected in all control patients, except one with chronic uveitis in whom faint PAB immunoreactivity was detected in inflammatory cells. CONCLUSIONS: P. acnes was detected from granulomas formed in the epiretinal membrane of patients with sarcoidosis. The significance of P. acnes in the pathogenesis of uveitis associated with sarcoidosis remains to be determined.

Prediction of severe cardiac involvement by fundus lesion in sarcoidosis.

PURPOSE: We examined the relation between ocular sarcoidosis and severe cardiac sarcoidosis necessitating pacemaker implantation. METHODS: In this retrospective, observational, cross-sectional study, we reviewed the clinical records of 108 patients diagnosed with ocular sarcoidosis based on new diagnostic criteria established in Japan. We examined and compared the relationship between fundus findings of ocular sarcoidosis and severe cardiac sarcoidosis necessitating pacemaker implantation. RESULTS: Of 108 patients with ocular sarcoidosis, seven patients (6.5 %) with median age of 61 years (interquartile range 59-63 years) also had severe heart disease leading to implantation of a pacemaker. Median duration of ocular symptoms was 4.5 years (interquartile range 3.6-7.8 years). Of seven patients with severe cardiac involvement, six had multiple peripheral chorioretinal atrophic lesions (MPCAL), two had nodules in the angle and tent-like peripheral anterior synechia, and two had snowball vitreous opacity. The prevalence of atrophic MPCAL lesions was significantly higher than that of other ocular findings (P < 0.05). CONCLUSIONS: In patients with concurrent ocular sarcoidosis and severe cardiac sarcoidosis, MPCAL atrophic lesions were observed significantly more frequently, suggesting that severe cardiac involvement may be predicted by specific fundus lesions.