Clinical features of intraocular inflammation in Hokkaido, Japan.

PURPOSE: We aimed to investigate the clinical features of intraocular inflammation/uveitis in Hokkaido, Japan. METHODS: We retrospectively reviewed the medical records of 1240 uveitis patients (511 men, 729 women) who visited Hokkaido University Hospital, Sapporo, Japan between 1994 and 2003. RESULTS: Mean age at disease onset was 41.7 +/- 17.8 years in men and 45.7 +/- 18.3 years in women. Anterior, posterior and combined anterior and posterior segment intraocular inflammation accounted for 45.1%, 4.7% and 50.2% of cases, respectively. Sarcoidosis was the most frequent aetiology (14.9%), followed by Vogt-Koyanagi-Harada (VKH) disease (9.7%) and Behçet's disease (6.7%). Aetiologies in 49.8% patients were unknown. In sarcoidosis, women represented 72.4% of patients, and disease onset occurred at 35.1 +/- 19.0 years of age in men and 50.3 +/- 16.5 years in women. In VKH disease, 54.2% of patients were women, and disease onset took place at 45.9 +/- 15.8 years in men and 46.4 +/- 14.1 years in women. In Behçet's disease, men accounted for 56.6% of patients, and disease onset occurred at 35.5 +/- 8.5 years in men and 44.5 +/- 11.5 years in women. CONCLUSIONS: Women were more prone to developing sarcoidosis compared with men. By contrast, men were more prone to developing Behçet's disease. The mean age at disease onset in both sarcoidosis and Behçet's disease was significantly lower in men than in women.

[Clinical features of acute retinal necrosis at Hokkaido University Hospital].

PURPOSE: To study clinical features of acute retinal necrosis (ARN) at Hokkaido University Hospital. METHODS: Twenty-one eyes of 19 patients with ARN (10 male and 9 female patients) who were treated at Hokkaido University Hospital between 1992 and 2006 were retrospectively examined from clinical records. RESULTS: The average age of the patients was 53.4 years (range, 13 to 91 years). 17 cases were unilateral and 2 were bilateral. The pathogenic virus was herpes simplex virus-1 (HSV-1) in 2 patients, and varicella-zoster virus (VZV) in 17 patients. Clinical severity was assessed from spreading speed and area of the retinal exudation, and 5 eyes were judged as fulminant cases (4 VZV eyes, 1 HSV eye), 6 eyes as severe cases (6 VZV eyes), and 10 eyes as mild cases (9 VZV eyes, 1 HSV eye). The range of retinal exudation was 1 to 2 quadrants in 7 eyes, 3 to 4 quadrants in 3 eyes, and increased to all quadrants in 11 eyes. Retinal detachment (RD) was observed in 8 eyes (38%), and the final visual acuity was less than 0.1 in 9 eyes (43%). CONCLUSIONS: The leading cause of ARN at Hokkaido University Hospital was VZV, and no HSV-2 ARN was seen. Compared with other areas in Japan, ARN at Hokkaido University Hospital seems to show less frequent RD, but the same prognosis for final visual acuity.

Repeated exacerbations of ocular inflammation with vitreous hemorrhage in a patient with HLA-B27 associated uveitis.

HLA-B27 associated uveitis is characterized by recurrent alternating acute unilateral attacks of intraocular inflammation in the anterior chamber. The aim of this study was to report an unusual case of repeated exacerbations with vitreous hemorrhage in HLA-B27 associated uveitis. Thirty four-year-old man was diagnosed as HLA-B27 associated uveitis in his right eye. He showed repeated exacerbation of ocular inflammation with retinal vein dilation and small retinal hemorrhage following vitreous hemorrhage. Fluorescein fundus angiography a week before the appearance of vitreous hemorrhage showed no neovascularization. Oral prednisolone administration was started from 40mg/day with gradual tapering. About 3 weeks after the onset, most of the vitreous hemorrhage disappeared and visual acuity was improved to 20/20. Through the decreased vitreous hemorrhage, Weiss ring was detected later. The vitreous hemorrhage found in this patient is a severe exacerbation, and might be a consequence of the vitritis that leads to posterior vitreous detachment.

Epidemiological survey of intraocular inflammation in Japan.

PURPOSE: To report the frequency and trend of intraocular inflammation based on a survey of new ophthalmology patient visits to university hospitals throughout Japan during 2002. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: Through 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.

Clinical features in tubulointerstitial nephritis and uveitis (TINU) syndrome.

PURPOSE: To analyze clinical features of the tubulointerstitial nephritis and uveitis (TINU) syndrome in Japan, especially exacerbations or recurrences of uveitis. DESIGN: Retrospective observational study. METHODS: We reviewed the clinical features in 12 patients with TINU syndrome diagnosed by renal biopsy, who were evaluated and treated at the Department of Ophthalmology, Hokkaido University Hospital. Visual acuity was measured using decimal visual acuity. RESULTS: Patient age ranged from 10 to 33 years (mean 21 years), and females accounted for 83% of the cases. Both eyes were affected in 11 patients (92%). All 12 patients initially experienced ocular symptoms, with hyperemia being the chief complaint. We diagnosed patients as having uveitis and conducted blood tests and urinalysis. Urinalysis did show characteristic findings, most notably glucosuria, increased beta2 microglobulin that were > or = 10 times that of normal levels, and increased N-acetylglucosaminidose levels in a high percentage of patients. Recurrent or exacerbating uveitis was seen in six patients (50%). In exacerbated or recurrent uveitis, inflammation was more severe (> or = 3+ cells of the anterior eye segment). The ocular inflammation generally responded well to treatment with oral corticosteroids, and the number of recurrences was lower at corticosteroid doses of > or = prednisolone 40 mg. CONCLUSIONS: Ophthalmologists play an important role in the initial discovery of patients with TINU syndrome. Because inflammation was more severe in exacerbated or recurrent uveitis, in instances where uveitis is refractory to local therapy, oral corticosteroids should be considered as early as possible.

Comparative study of two sets of criteria for the diagnosis of Vogt-Koyanagi-Harada's disease.

PURPOSE: The Vogt-Koyanagi-Harada's (VKH) Disease Committee established the "Revised diagnostic criteria for VKH disease" in 2001. The purpose of the present study was to assess the concordance between these criteria and the traditional Sugiura's diagnosis system. DESIGN: Observational case series. METHODS: The medical records of patients previously diagnosed with VKH disease based upon Sugiura's criteria at the Uveitis Survey Clinic of the Hokkaido University Hospital between 1991 and 2003 were retrospectively reevaluated using the VKH Committee's revised diagnostic criteria for VKH disease. RESULTS: Sugiura's criteria were used to identify 169 patients with VKH disease. All patients were Japanese, and 95 cases (56%) were women. Mean age at the time of their first visit to our clinic was 44.7 +/- 13.9 years (range, 9 to 74 years). Using the VKH Committee's new criteria, 91.7% of the previously diagnosed VKH patients were classified as having the disease. Of this group, 11.8% were classified as complete, 71% incomplete, and 8.9% as probable VKH disease. CONCLUSIONS: The VKH Committee's revised diagnostic criteria proved useful for VKH disease diagnosis, as the concordance rate for the two criteria was more than 90%. However, patients who had prior cataract surgery or who lacked signs of serous retinal detachment were not classified as having VKH disease because of exclusion by the VKH Committee's new criteria.

A patient with sarcoidosis diagnosed by a biopsy of scleral nodules.

PURPOSE: To report the case of a patient with nodular scleritis who was diagnosed as having sarcoidosis by a biopsy of scleral nodules. METHODS: Case report. RESULTS: A 26-year-old man with nodular scleritis underwent a biopsy of scleral nodules. The year before, he had been diagnosed with granulomatous iridocyclitis of the right eye. Although sarcoidosis had been suspected, extensive systemic examinations resulted in no positive findings of sarcoidosis. Histopathological specimens revealed non-caseating epithelioid granuloma with giant cells. The nodular scleritis was resolved by topical corticosteroids. CONCLUSIONS: A scleral biopsy is useful for the diagnosis of sarcoidosis when the patient has nodular scleritis with no systemic signs.

Diverse NF-kappaB expression in epiretinal membranes after human diabetic retinopathy and proliferative vitreoretinopathy.

PURPOSE: Formation of epiretinal membranes (ERMs) after proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR) results in progressive deterioration of vision, but its pathogenic mechanisms are still unknown. This study was conducted to examine the role of nuclear factor kappa B (NF-kappaB) in the formation of ERMs after PDR and PVR. METHODS: ERM samples were obtained by vitrectomy from 10 patients with PDR (aged 53+/-12 years with 14+/-5 years of diabetes), 20 patients with PVR, and 17 patients with idiopathic ERMs. Ten PVR and 17 idiopathic ERM samples were processed for reverse transcription-polymerase chain reaction (RT-PCR) analysis. In addition, 10 PDR and 10 PVR membranes were processed for immunohistochemical analysis. RESULTS: NF-kappaB mRNA expression levels were significantly higher (10 of 10 versus 9 of 17 subjects in idiopathic ERM, p=0.0119) in PVR subjects. Immunohistochemical analysis showed NF-kappaB protein expression in 8 of the 10 PDR samples as well as all 10 PVR samples, and NF-kappaB positive cells were partially double labeled with glial cell markers. Interestingly, NF-kappaB protein was also overlapped with angiogenic factor interleukin-8 (IL-8) in glial cells as well as vascular endothelial cells. CONCLUSIONS: These results suggest that NF-kappaB is involved in the formation of both glial and vascular endothelial cell components, and that these two cell types might have functional interactions that lead to the enlargement of intraocular proliferative membranes.

Increase of KL-6 in sera of uveitis patients with sarcoidosis.

BACKGROUND: KL-6 is a human glycoprotein secreted by type II alveolar cells in lung, and its serum levels increase in pneumonia of various causes. KL-6 is a member of the MUC-1 family, which is expressed in lung, cornea, and conjunctiva. The purpose of the present study was to investigate the clinical usefulness of quantifying serum KL-6 levels for diagnosing sarcoidosis in patients with uveitis. METHODS: Sera were obtained from 24 uveitis patients diagnosed with sarcoidosis, 37 uveitis patients with other etiologies, and 138 healthy control subjects. Serum concentration of KL-6 was determined by a human KL-6 electrochemiluminescence immunoassay. RESULTS: The average level of KL-6 in the sera of uveitis patients with sarcoidosis was 387 U/ml. This was significantly higher than in healthy subjects and uveitis patients with other etiologies. The KL-6 measurements identified 45.8% of sarcoidosis-positive patients. When the KL-6 results were combined with serum angiotensin-converting enzyme (ACE) concentrations, 87.5% of sarcoidosis patients were identified, compared to 66.7% using ACE results alone. The combined measurement identified 10.8% of the non-sarcoid patients and 0.72% of healthy subjects as positive (false positive). CONCLUSION: Combined measurements of serum KL-6 and ACE may be useful as a screening for sarcoidosis in uveitis patients.

Effect of human cationic antimicrobial protein 18 Peptide on endotoxin-induced uveitis in rats.

PURPOSE: Human cationic antimicrobial protein 18 (hCAP18, 18 kDa) was originally identified in leukocytes on the basis of its antimicrobial activity. The peptide composed of the 27 C-terminal amino acids of hCAP18 (hCAP18(109-135)) binds lipopolysaccharide (LPS). The purpose of the present study was to investigate the effects of hCAP18 peptide on endotoxin-induced uveitis (EIU) in rats. METHODS: EIU was induced by footpad injection of LPS. Each rat was injected intravenously with 1, 10, or 100 micro g hCAP18 peptide in 0.1 mL of PBS immediately after LPS injection in male Lewis rats. At 24 hours after LPS injection, enzyme-linked immunosorbent assay was performed to evaluate concentrations of protein, nitric oxide (NO), tumor necrosis factor (TNF)-alpha, prostaglandin (PG)-E2, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-2 in aqueous humor. Also, EIU was evaluated by counting inflammatory cells in aqueous humor. RESULTS: hCAP18 peptide at 10 and 100 micro g significantly suppressed an LPS-induced increase in the number of inflammatory cells and the levels of protein, NO, TNF-alpha, PGE2, MCP-1, and MIP-2. The anti-inflammatory effect of 10 micro g hCAP18 peptide was as strong as that of 100 micro g hCAP18 peptide. Treatment with 1 micro g hCAP18 peptide did not suppress EIU, compared with the LPS group. CONCLUSIONS: The present results indicate that hCAP18 peptide suppresses development of EIU. A possible mechanism for the ocular anti-inflammatory effect of hCAP18 peptide is that it suppresses onset of LPS-triggered inflammatory reactions by binding directly to LPS.

Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo.

PURPOSE: Astaxanthin (AST) is a carotenoid that is found in marine animals and vegetables. Several previous studies have demonstrated that AST exhibits a wide variety of biological activities including antioxidant, antitumor, and anti-Helicobacter pylori effects. In this study, attention was focused on the antioxidant effect of AST. The object of the present study was to investigate the efficacy of AST in endotoxin-induced uveitis (EIU) in rats. In addition, the effect of AST on endotoxin-induced nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor (TNF)-alpha production in a mouse macrophage cell line (RAW 264.7) was studied in vitro. METHODS: EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). AST or prednisolone was administered intravenously at 30 minutes before, at the same time as, or at 30 minutes after LPS treatment. The number of infiltrating cells and protein concentration in the aqueous humor collected at 24 hours after LPS treatment was determined. RAW 264.7 cells were pretreated with various concentrations of AST for 24 hours and subsequently stimulated with 10 microg/mL of LPS for 24 hours. The levels of PGE2, TNF-alpha, and NO production were determined in vivo and in vitro. RESULTS: AST suppressed the development of EIU in a dose-dependent fashion. The anti-inflammatory effect of 100 mg/kg AST was as strong as that of 10 mg/kg prednisolone. AST also decreased production of NO, activity of inducible nitric oxide synthase (NOS), and production of PGE2 and TNF-alpha in RAW264.7 cells in vitro in a dose-dependent manner. CONCLUSIONS: This study suggests that AST has a dose-dependent ocular anti-inflammatory effect, by the suppression of NO, PGE2, and TNF-alpha production, through directly blocking NOS enzyme activity.

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.

Macrophage migration inhibitory factor in uveitis.

To summarize, we found that high levels of MIF were detected in the serum of uveitis patients with Behçet's disease, VKH disease, and sarcoidosis, as well as idiopathic iridocyclitis. In Behçet's disease and sarcoidosis, the MIF levels were higher in the active uveitis stage than in the inactive stage. Serum MIF increased after corticosteroid therapy in VKH disease. A high aqueous humor MIF concentration was detected at the onset of EAU. Finally, anti-MIF antibody suppressed EAU when administered in the early phase. MIF is thought to be an important cytokine in the pathogenesis of uveitis.

[A case of granulomatous panuveitis associated with multiple sclerosis].

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.