Satoshi Kotake

Epidemiological Survey of Intraocular Inflammation in Japan

PurposeTo report the frequency and trend of intraocular inflammation based on a survey of new ophthalmology patient visits to university hospitals throughout Japan during 2002.MethodsA questionnaire was sent to the departments of ophthalmology in 110 university hospitals nationwide to survey the total number of new patients who visited the outpatient clinics for the first time between 1 January and 31 December 2002, and also the number of patients diagnosed with intraocular inflammation during this period.ResultsThe surveys completed by 41 university hospitals were analyzed in this study. During 2002, a total of 151 299 new ophthalmological patients presented at the 41 institutions, and 3060 (2.2%) of the new patients were diagnosed as having intraocular inflammation. The most frequent intraocular inflammatory disease identified was sarcoidosis (13.3%), followed by Vogt-Koyanagi-Harada (VKH) disease (6.7%), Behçet disease (6.2%), bacterial endophthalmitis (3.8%), herpetic iridocyclitis (3.6%), diabetic iritis (1.6%), human leukocyte antigen-B27-associated uveitis (1.5%), acute retinal necrosis (1.3%), ocular toxoplasmosis (1.1%), ocular toxocariasis (1.1%), uveitis associated with human T lymphotropic virus-1 (also known as HAU) (1.1%), and others. Infectious intraocular inflammation accounted for 16% of all uveitis cases.ConclusionsThrough the collaboration of a large number of institutions, some aspects of the epidemiology of intraocular inflammation in Japan were elucidated. However, the disease concept and diagnostic criteria remain ambiguous for a considerable number of diseases within the spectrum of intraocular inflammation, and the possibility that such factors may bias the present findings cannot be denied. In the future, a prospective survey based on well-defined, common diagnostic criteria is required to obtain more precise epidemiological data. Jpn J Ophthalmol 2007;51:41–44

Central nervous system symptoms in patients with Behçet disease receiving cyclosporine therapy

OBJECTIVE To investigate the association between the development of central nervous system (CNS) symptoms in patients with Behçet disease and medical therapy. DESIGN Retrospective cohort study. PARTICIPANTS A total of 317 patients with Behçet disease with ocular complications who visited Hokkaido University Hospital, Sapporo, Japan, between 1978 and 1994. MAIN OUTCOME MEASURES The incidence of CNS symptoms in different medical therapies. RESULTS Twenty-one (6.6%) of the 317 patients developed CNS symptoms, namely neuro-Behçet disease. Of the 21 patients, 12 were undergoing cyclosporine therapy. Of the 47 patients who underwent cyclosporine therapy, 12 (25.5%) developed CNS symptoms, whereas only 9 (3.3%) of 270 patients who did not undergo cyclosporine therapy developed CNS symptoms. CONCLUSIONS Cyclosporine in the treatment of Behçet disease appears to cause neurotoxicity or to accelerate the development of CNS symptoms. Thus, neurologic complications appear to represent a major side effect of cyclosporine in the treatment of patients with Behçet disease.

Chemiluminescence of neutrophils from patients with Behçet's disease and its correlation with an increased proportion of uncommon serotypes of Streptococcus sanguis in the oral flora.

Zymosan-induced chemiluminescence was investigated in whole blood and in neutrophils: in both, the peak count was frequently elevated in Behçets disease, and was significantly higher than in healthy controls; similarly the peak time was shorter. There were more uncommon serotypes of Streptococcus sanguis in the oral flora of patients with Behçets disease. Common serotypes were present in the flora of healthy controls, but not in patients with the disease. The percentage of Strep. sanguis in the oral flora was significantly correlated with the level of chemiluminescence response. Thus infection with uncommon serotypes of Strep. sanguis may play a role in the aetiology of Behçets disease.

Characteristics of endogenous uveitis in Hokkaido, Japan

Abstract• Background: Etiological characteristics of endogenous uveitis vary around the world. There are few epidemiological reports on the etiology of uveitis from areas within Asia. We set out to examine the statistical data on uveitis in Japan. • Methods: We reviewed all the records of patients with endogenous uveitis who visited the Uveitis Survey Clinic of Hokkaido University Hospital in 1981 and 1994 and extended the survey to include new patients with uveitis seen over the past 3 years. • Results: Behçets disease, sarcoidosis and Vogt-Koyanagi-Harada disease were the three most frequently diagnosed diseases in patients with endogenous uveitis in both 1981 and 1994. The proportion of patients with unclassified disease entities decreased (from 38% to 30%) during the 13-year period from 1981 to 1994 as a result of the new disease categories established during this interval. Notable additions included human T-lymphotropic virus type I-associated uveitis and tubulointerstitial nephritis and uveitis syndrome. Sarcoidosis is now the most frequent cause of endogenous uveitis in our clinic. • Conclusion: Not only does the etiological basis of uveitis vary with ethnicity, but advances in clinical and basic research have changed the approach to the diagnosis of uveitis, altering the etiological profile over time.

Clinical features of intraocular inflammation in Hokkaido, Japan

Purpose:  We aimed to investigate the clinical features of intraocular inflammation/uveitis in Hokkaido, Japan.

Detection of Antibodies Against Borrelia burgdorferi in Patients With Uveitis

We determined the antibody response against Borrelia burgdorferi strains isolated from Japanese Ixodes ovatus and Ixodes persulcatus ticks by enzyme-linked immunosorbent assay and indirect immunofluorescence assay of serum specimens from 127 patients with uveitis. We examined samples of serum from Japanese patients with unclassified uveitis, iridocyclitis caused by herpes zoster virus, Behçets disease, Vogt-Koyanagi-Harada syndrome, sarcoidosis, or other conditions (sympathetic ophthalmia, Posner-Schlossman syndrome and acute anterior uveitis with ankylosing spondylitis). Serum from healthy individuals and patients with Lyme disease served as negative and positive control samples, respectively. Significantly higher antibody titers were demonstrated in patients with uveitis than in control subjects. Of 29 patients with unclassified uveitis, nine (31) had significantly increased antibody titers against B. burgdorferi strain H014 by ELISA testing. Five patients also showed higher IgG and IgM responses than in three control subjects with Lyme disease. All positive controls showed joint problems characteristic of rheumatoid arthritis. One of three patients had uveitis. The patients were diagnosed as having Lyme disease on the basis of their history and serologic tests. A positive antibody response was recognized in several patients with Behçets disease, Vogt-Koyanagi-Harada syndrome, sarcoidosis, and other conditions (acute anterior uveitis with ankylosing spondylitis), but not in control subjects.

Diminution of experimental autoimmune uveoretinitis (EAU) in mice depleted of NK cells

To evaluate the potential role of NK1.1 (CD161c) cells in autoimmune uveoretinitis, we treated experimental autoimmune uveoretinitis (EAU)‐susceptible mice with anti‐CD161c antibodies (PK136) to deplete natural killer (NK) cells. Injection of anti‐CD161c antibodies deleted NK cells from the peripheral blood of EAU‐susceptible mice. The T cell proliferative response against the ocular autoantigen K2 was not suppressed in mice treated with anti‐CD161c antibody when compared with T cells from control mice. Although mice treated with anti‐CD161c developed EAU, the clinical severity on days 17 and 19 after induction of EAU was significantly mild in anti‐CD161c‐treated mice compared with control mice. In addition, the histopathological severity of EAU was significantly milder in mice treated with anti‐CD161c antibodies than controls 21 days after induction of EAU. Our results indicate that the severity of EAU is augmented by NK1.1+ NK cells.

Identification of a peptide inducing experimental autoimmune uveoretinitis (EAU) in H-2Ak-carrying mice

When certain strains of mice bearing H‐2Ak are immunized with the interphotoreceptor retinoid‐binding protein (IRBP), EAU is induced. Thus far uveitogenic determinant(s) has not been determined in the H‐2Ak mouse system. In addition it is hard to prepare purified IRBP. In the present study, to circumvent these problems we attempted to identify uveitogenic peptides derived from bovine IRBP in H‐2Ak haplotype mice. Six peptides which had been selected according to the H‐2Ak binding motif (Dxxxxxxxx[A, R, T]) were synthesized. We report here that all the peptides are immunogenic but only one peptide, K2, which consisted of IRBP201–216 residues, induces EAU in various mice carrying H‐2Ak. Amino acid substitution of K2 revealed that the core region interacted with both H‐2Ak and T cell antigen receptor (TCR). The amino acid sequence of the core region derived from bovine IRBP was identical to the corresponding region of mouse IRBP. In addition, K2 appeared to be a natural peptide antigen processed from bovine IRBP. Altogether, we concluded that K2 is one of the natural autoantigens involved in induction of EAU in H‐2Ak mice.

Antibody Response to Oral Streptococci in Behçet's Disease

The serum antibody titers against oral streptococci were studied by enzyme‐linked immunosorbent assay (ELISA) both in patients with Behçets disease (BD) and control groups. The patients with BD showed significantly higher antibody titers to S. sanguis strains 113‐20, 114‐23, and 118‐1 which were isolated from patients with BD, in comparison with control groups. Also, the reactions of hightitered sera to the crude cell wall and soluble (or membrane) fractions of the 113‐20 strain were observed by western blot test. The sera of the patients with BD demonstrated strong bands of approximately 36 kDa, 82 kDa, and 87 kDa in the crude cell wall fractions, and many bands of 80 kDa to 150 kDa in the membrane fractions, indicating that these proteins are the ones leading the high antibody titers to this bacterium in the sera of patients with BD.

Characterization of Streptococcus sanguis isolated from patients with Behçet's disease.

The DNA homology and cell wall sugar constituents of eight Streptococcus sanguis(‐like) strains, three isolated from the patients with Behçets disease (BD114‐23, BD113‐20, BD118‐1), two from patients with Kawasaki disease (MCLS‐1, MCLS‐2), and three type and reference strains of ATCC (ATCC10556T: S. sanguis, ATCC10557: S. oralis, and ATCC10558T: S. gordonii) were analyzed. Strains BD114‐23 and BD118‐1 showed high DNA homology to ATCC10556T, and their cell wall constituents were identical. Conversely, BD113‐20, MCLS‐1, MCLS‐2, and ATCC10557 showed little DNA homology to ATCC10556T and ATCC10558T, but showed approximately 50 to 60% homology to each other. The cell wall constituents of BD113‐20, MCLS‐1, MCLS‐2, and ATCC10557, however, were somewhat different, indicating that some of the clinical isolates have different characters from those of the three ATCC strains.