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Background: Uveitis is not often reported in patients with multiple sclerosis(MS) in Japan, but retinal vasculitis and pars planitis are common findings in uveitis patients with MS in the U.S. and European countries., Case: A 50-year-old man developed bilateral granulomatous panuveitis 10 years after initial onset of MS., Findings: Examination showed bilateral anterior uveitis with mutton fat keratic precipitate and retinal vasculitis for 360 degrees. The anterior uveitis responded well to topical corticosteroid but the retinal vasculitis did not. The possibility of sarcoidosis, tuberculosis, and other diseases associated with granulomatous uveitis were excluded by systemic examinations., Conclusion: We encountered a rare case of granulomatous panuveitis associated with MS.

Purpose: To evaluate changes in the ciliary body during accommodation using an ultrasound biomicroscope (UBM)., Subjects and Methods: Eleven healthy persons, aged from 24 to 33 years, served as subjects. They were asked to lie in the supine position and to fixate a target placed on the ceiling 2 m above with the left eye. A concave lens with the power of -6 to -8 diopters was then placed before the fixating left eye. The thickness of the ciliary body in the right eye was measured by UBM in the nonaccommodative and accommodative states., Findings: The anterior chamber in the right eye became significantly shallow during accommodation. The thickness of the ciliary body significantly increased during accommodation at 0.5 mm and 1.0 mm posterior to the scleral spur. It significantly decreased at 2.0 mm, 2.5 mm and 3.0 mm posterior to the scleral spur., Conclusion: During induced accommodation in the left eye, the anterior portion of the ciliary body in the right eye increased and the posterior portion decreased in thickness. The findings imply that the circular ciliary muscles are mainly involved in accommodation and not the longitudinal muscles.

We reviewed the records of new patients with uveitis who visited the Hokkaido University Hospital between 1991 and 1994. For the diagnosis of sarcoidosis, we used the criteria revised by the Diffuse Pulmonary Disease Research Committee of Japan in 1989. The total number of patients was 374, and 61 cases were diagnosed as sarcoidosis. Of 61 patients with sarcoidosis, 58 cases were diagnosed histologically. Transbronchial lung biopsy was the basis for 70% of the histological diagnosis. After the revision of the criteria of sarcoidosis, the percentage of histological diagnosis increased. The Diffuse Pulmonary Disease Research Committee of Japan also proposed guidelines for the diagnosis of ocular sarcoidosis in 1990. We applied these guidelines to our uveitis patients. Most of the patients (77.1%) with sarcoidosis were included in the group of probable sarcoidosis, but 20% of patients with uveitis who were not diagnosed as having sarcoidosis were also included in this group. These guidelines are not yet adequate.

Experimental autoimmune uveoretinitis (EAU) can be induced in rats by interphotoreceptor retinoid-binding protein (IRBP), and served as a model for human uveitis. Using IRBP-derived peptide R16, we investigated the MHC and non-MHC genes' effect on the regulation and susceptibility to EAU. EAU-high susceptible LEW (RT1l), EAU-low susceptible WKAH (RT1k), and WKAH.1L rats which carry RT1l and WKAH background were immunized with 2 nmol of R16. One hundred percent of LEW rats developed EAU and 92.9% of WKAH. 1L rats. Only, 18.8% of WKAH rats developed EAU. Among these strains tested, the severity of EAU was 2.06 in LEW, 1.23 in WKAH.1L, and 0.38 in WKAH. R16 evoked substantial proliferative responses in all these strains. The present data suggest that both MHC and non-MHC genes play distinct roles in development of EAU.

A case of multiple sclerosis (MS) associated with granulomatous panuveitis was reported. A 45-year-old woman developed diplopia in 1972, at age 24, optic neuritis in 1974 and acute transverse myelopathy in 1981. Subsequently, while being under our care with the clinical diagnosis of MS, right abducens palsy in 1989, deterioration of paraparesis with remission in 1991, and weakness of left arm in 1992 occurred. CSF study revealed high IgG index and brain MRI showed multiple abnormal intensity areas in the deep white matter and periventricular areas bilaterally. On the beginning in March, 1993, she noticed left hazy vision and the ophthalmological examinations revealed marked mutton-fat like keratic precipitates, posterior synechiae, cells and flare in anterior chamber, retinal phlebitis and snow ball vitreous opacity. Granulomatous panuveitis was diagnosed and treated by topical steroid with improvement within two months. During this episode, no neurological deterioration was seen. Granulomatous uveitis in MS was rarely documented in the literatures, but this seems to be more common in women, mildly symptomatic or asymptomatic and responds well to topical steroid treatment.

Interphotoreceptor retinoid-binding protein (IRBP) can induce experimental autoimmune uveoretinitis (EAU) in different rat strains. This is because IRBP has many epitopes, each of which binds to a specific class II molecule. However, there is the possibility that one epitope can bind to different class II molecules. In this study we attempted to examine this postulate, by checking uveitogenicity and immunogenicity of IRBP-derived peptide R16. We used rat strains LEW, WKAH, SDJ, LEJ, and BUF, which have RT1 haplotype l, k, u, i, and b, respectively. Immunization with R16 caused EAU in LEW (100%), WKAH (75%), SDJ (0%), LEJ (75%), and BUF (19%). We also examined the immunogenicity of R16 by lymphocyte proliferative assay in which lymph node cells from rats of each strain immunized with R16 were stimulated with the immunogen peptide. R16 evoked substantial proliferative responses in LEW, WKAH, LEJ, and BUF, but not in SDJ. An inhibition test with anticlass II monoclonal antibodies showed that OX6 (anti-RT1-B) could inhibit the proliferation against R16, but OX17 (anti-RT1-D) could not. These experiments demonstrated that the same peptide induces the disease and immunity in different strains of rats.

Repository corticosteroid was injected into the posterior sub-Tenon's space in 29 cases (39 eyes) of cystoid macular edema (CME) secondary to uveitis. They included 12 cases of Behçet's disease, 7 cases of Sarcoidosis, one case of tuberculous uveitis and 9 cases of etiology unknown uveitis. In some of the patients injections were repeated twice to seven times at intervals of more than 2 weeks. Twenty two of the 39 treated eyes (56.4%) showed visual improvement in at least two lines of visual acuity. Eleven eyes showed no improvement in vision. Most of them had already had bad visual acuity (0.2 or less) before the injections. Complications of the treatment included cataract in 6 eyes, glaucoma in one, and blepharoptosis in one. Injection of repository corticosteroids into the posterior sub-Tenon's space was effective in the treatment of CME secondary to uveitis. However, we have to beware of the complications of this treatment.

It is known that the susceptibility of experimental autoimmune uveitis (EAU) is controlled by both major histocompatibility antigen complex (MHC) and non-MHC genes. In this report, we studied the role of non-MHC gene in the induction of EAU. LEW, WKAH, (LEW x WKAH) F1 and (LEW x WKAH) F2 rats were examined for their incidence and severity to develop EAU by immunization with bovine S-antigen (S-Ag). We found that all LEW rats developed severe EAU within 2 weeks after immunization, but no WKAH rat did. Most F1 rats developed mild inflammation in 3-4 weeks after immunization. A quarter of F2 rats developed EAU within 2 weeks, half of them developed it in 3-6 weeks after immunization, and the others did not. These findings suggest that only one non-MHC gene controls the susceptibility to S-Ag induced EAU in rats.

A total of 131 patients with typical ocular manifestations of sarcoidosis were studied. From systemic examinations, 56 cases were confirmed histologically as sarcoidosis, 59 cases were clinically diagnosed as sarcoidosis and 16 cases were not diagnosed as sarcoidosis. There were no differences among the three groups in terms of laterality of eye involvement, sex distribution, ocular findings and prognosis. The only difference was that the age of patients not diagnosed as sarcoidosis was lower than the other two groups. In systemic examinations, patients diagnosed as sarcoidosis histologically or clinically had higher ratios of positive findings of bilateral hilar lymphadenopathy, 67Ga scanning, bronchoalveolar lavage fluid and serum angiotensin converting enzyme than patients who were not diagnosed as sarcoidosis. Some cases of the third group may be diagnosed as sarcoidosis in the future by repeated systemic examinations. The difficulty of diagnosis of sarcoidosis from ocular findings alone was discussed.

The oral flora of patients with Behçet's disease was investigated and compared to that of controls. The proportion of Streptococcus (S.) sanguis in the flora of patients with this disease was always higher than that of healthy controls. It is noteworthy that serotypes of S. sanguis in the oral flora of patients were different from controls. Immune responses against S. sanguis were also examined in the patients. Antibody titers against S. sanguis were higher in patients than in controls. Furthermore, the patients showed significantly increased skin reactivity to S. sanguis. These results suggest that uncommon serotypes of S. sanguis play an important role in the pathogenesis of Behçet's disease.

The exact cause of Behçet's disease is still unknown. Recently, advanced bacterial studies revealed that Behçet's disease was related to Streptococcus (S.) sanguis. However, the antigenicity of S. sanguis has not been fully studied. In this study, we clarified the antigenicity of S. sanguis. We made S. sanguis antigens: Mechanical Braun Extract (MBE) and Crude Cell Wall (CCW) from the whole cells, Membrane Fraction (MF) and Cytoplasmic Fraction (CF) from MBE, Cell Wall Fragment (CWF) and Lipoteichoic acid (LTA) from MBE. We found that the major antigenicity of S. sanguis was present in CF by use of the Ouchterlony method and the ELISA method. However, apart from S. pyogenes, we could not recognize a common antigenicity among S. sanguis and several other antigens, such as S-Ag, IRBP, retinal soluble fraction, retinal insoluble fraction and Enterococcus faecalis, by the Ouchterlony method. Since we have clarified the antigenicity of S. sanguis in this study, we can now perform detailed examinations with samples from patients with Behçet's disease for S. sanguis antigens.

Delayed type hypersensitivity of patients with Behçet's disease was investigated by intradermal skin test and prick test, using various inactivated microorganisms as antigens. In the intradermal skin test, 13 patients showed significantly increased skin reactivity to E. faecalis, compared with 5 normal controls. No significant differences were observed between these two groups in terms of reaction to S. pyogenes. Prick test was performed in 11 patients and 6 controls, using S. pyogenes, S. sanguis, S. salivarius and E. faecalis as antigens. It was shown that patients with this disease had significantly greater skin reactions to crude cell wall antigens, as well as to whole cell antigens of these streptococci than the controls. The antigenicity of streptococci seemed to be present mainly in the cell wall fragment, and these streptococci seemed to have cross reactivity with each other. These results suggest that streptococci may have some significant role in the immunopathogenesis of this disease.