Naoki Furudate

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.

Increased Osteopontin Levels in the Vitreous of Patients with Diabetic Retinopathy

Purpose: Osteopontin (OPN) has diverse functions such as cell adhesion, chemoattraction, immunomodulation, and angiogenesis. The aim of this study is to analyze the OPN levels in vitreous fluid obtained from diabetic retinopathy (DR) and non-DR patients. Methods: Nineteen patients out of 11 with DR and 8 without DR underwent pars plana vitrectomy and vitreous fluid was obtained simultaneously. Two distinct sandwich enzyme-linked immunosorbent assay systems (systems 1 and 2) were applied, which have been developed in our laboratories to quantify the OPN concentrations in vitreous fluid. Results: The non-thrombin-cleaved full-length OPN levels in the vitreous fluid were 921.63 ± 45.38 ng/ml in DR and 632.80 ± 83.43 ng/ml in non-DR using system 1. Also, vitreous thrombin-cleaved and noncleaved OPN levels were increased to 2,109.22 ± 151.651 and 1,651.13 ± 229.82 ng/ml in patients with DR and non-DR using system 2. The vitreous OPN levels were significantly higher in DR than those in non-DR (p < 0.01 by system 1 and p < 0.05 by system 2). Conclusion: Thrombin-cleaved and noncleaved vitreous OPN levels in patients with DR were increased compared with control subjects, suggesting that OPN plays a potential role in the pathogenesis of diabetic retinal ischemia.

Expression of erythropoietin receptor in human epiretinal membrane of proliferative diabetic retinopathy

Purpose: It is widely accepted that intravitreous levels of erythropoietin (Epo) are elevated in patients with ischaemic retinal diseases such as proliferative diabetic retinopathy (PDR). The aim of this study was to examine the expression of Epo and the Epo receptor (EpoR) in epiretinal membranes with and without diabetes. Methods: Eighteen epiretinal membranes (PDR (n = 10), idiopathic epiretinal membranes (IERMs) without diabetes (n = 4) and inner limiting membranes (ILMs) (n = 4)) were obtained during pars plana vitrectomy. Formalin-fixed and paraffin-embedded tissues were examined by immunohistochemistry with anti-Epo and EpoR antibodies. Results: The histopathological findings demonstrated that PDR membranes consisted of a variety of endothelial cells forming a microvascular cavity with red blood cells and non-vascular stromal mononuclear cells. Membranous and cytoplasmic immunoreactivity for EpoR was strongly detected in endothelial cells and stromal cells in all PDR patients. Although microvessels were not observed in IERMs and ILMs, immunoreactivity for EpoR was noted in the cellular component of IERMs, and was weakly detected in ILMs. Epo was not expressed in any membrane. Conclusion: EpoR was strongly expressed in microvessels of all PDR membranes. The in vivo evidence in this study suggests that Epo in the vitreous binds to EpoR in PDR membranes, which subsequently leads to the proliferation of new retinal vessels. EpoR immunoreactivity in non-vascular stromal cells in PDR membranes, and IERMs and ILMs might be indirectly correlated with ischaemia.

Expression of glutamine synthetase and cell proliferation in human idiopathic epiretinal membrane

Background/aim: The mechanisms of the cellular origin and cell proliferation in the idiopathic epiretinal membrane (ERM) are unsolved. The aim of this study was to examine the expression of cell cycle related molecules and glutamine synthetase (GS), which is expressed in Müller cells and their processes, in ERM tissues. Methods: The ERMs were surgically removed using pars plana vitrectomy. Formalin fixed, paraffin embedded ERM tissues were analysed by immunohistochemistry with anti-cyclin D1, p27 (KIP1), proliferating cell nuclear antigen (PCNA), and GS antibodies. Results: The histopathological findings showed that all the ERMs consisted of oval or spindle mononuclear cells with thin collagen-like tissues. Immunoreactivity for GS was detected in collagen-like tissues of ERM, presenting a continuous, isodense pattern. GS immunopositive cells in all cases expressed PCNA in their nuclei. Nuclear immunoreactivity for cyclin D1 was noted in the ERM constituent cells, whereas p27 (KIP1) positive nuclei were not detected. Conclusion: Cyclin D1 and PCNA were expressed in the idiopathic ERM, which was mainly derived from Müller cells and extensions of their processes.

Indocyanine Green Angiography in a Case of Punctate Inner Choroidopathy Associated with Acute Zonal Occult Outer Retinopathy

BackgroundThe etiology of punctate inner choroidopathy (PIC) and acute zonal occult outer retinopathy (AZOOR) are currently unknown, although both diseases are hypothesized to be part of the spectrum of a single disorder.CaseWe report indocyanine green (ICG) angiographic findings in a 24-year-old woman in whom PIC was associated with AZOOR.ObservationsThe patient had been diagnosed with bilateral PIC. She noticed a visual field defect in her right eye 8 months later, and a defect in her left eye 25 months later. Perimetry showed an arcuate scotoma (right eye) and a central scotoma (left eye), which could not be explained by funduscopy or late-phase fluorescein angiography. Multifocal electroretinography led to a diagnosis of bilateral AZOOR. ICG angiography demonstrated late multiple patchy hypofluorescent spots throughout the posterior pole in the right eye and geographic hypofluorescence in the macular region from initial to late phase in the left eye. However, these findings were not evident at the onset of PIC.ConclusionThese angiographic results suggest that at the onset of AZOOR, choriocapillaris injuries had occurred in the areas corresponding to the scotomas. Jpn J Ophthalmol 2007;51:295–300 @ Japanese Ophthalmological Society 2007

Increased expression of mucinous glycoprotein KL-6 in human pterygium.

Pterygia represent growth onto the cornea of fibrovascular tissue continuous with the conjunctiva.1 KL-6 (Krebs von den Lunge-6) is a high molecular weight mucinous glycoprotein, and the monoclonal antibody reacts with the sugar moiety of MUC-1.2,3 We have reported that measurement of serum KL-6 levels is useful for the diagnosis and management of uveitis patients with sarcoidosis.4,5 The aim of this study was to examine the expression of KL-6, and Ki-67, a proliferation marker, in normal human conjunctiva, pterygium, and pseudopterygium tissues. Five samples consisting of one normal conjunctiva, three pterygia, and one pseudopterygium were surgically collected. Formalin fixed and paraffin embedded tissue sections were incubated with anti-KL-6 and anti-Ki-67 monoclonal antibodies, and then examined immunohistochemically. Immunoreactivity for KL-6 was detected on the apical membrane of the wing and basal …

Clinical study on patients with Behçet's disease in Hokkaido

Behçets disease is the most frequently encountered form of endogenous uveitis in Japan. The authors examined the clinical manifestations in cases with Behçets disease over six years (1987-1992), and compared the results with those of a previous study (1978-1983). In the more recent study the number of new patients who visited our clinic was 54, compared to 180 in the previous study. As for the frequencies of the four major symptoms in the recent study, oral aphtha were seen in 100%, skin lesions in 88.9%, ocular lesions in 74.0%, and genital ulcers in 61.1% of the patients. The frequencies of these major symptoms were not significantly different between the two time periods investigated. Analysis of the type of ocular involvement showed that 94.4% of the patients in the more recent study belonged to the uveoretinitis type and 5.6% of the patients belonged to the iridocyclitis type, whereas in the previous study the figures were 71.5% and 28.5%, respectively. The ratio of the patients with severe eye involvement has increased recently. However the visual prognosis of patients was better in the more recent study than in the previous study. In the previous study a marked decrease in visual acuity was observed during a two-year follow-up, whereas in the 1987-1992 period it was observed that visual acuity hardly changed over two years. The observed improvement in the visual prognosis may be due to the fact that the treatment of Behçets disease has become more effective in recent years.

Pseudomonas scleral abscess following pars plana vitrectomy.

test was not performed in our case, it is highly likely that the frosted branch angiitis-like fundus was related to infl uenza virus type A infection. Our patient had had fever with a very high titer for that virus, and her daughter, who also had a similar systemic illness, had tested positive for infl uenza virus type A before the mother came to our clinic. Rabon et al. reported a case of acute bilateral posterior angiopathy following infl uenza virus type A infection. In their case, the condition resolved spontaneously within several days. In some ways, our case was similar to that of Rabon et al., but the ocular changes appeared to be more severe and the area of retinal change was larger in our case. In addition, we selected systemic use of corticosteroid. However, it is unclear how the corticosteroid treatment in our case affected the clinical outcome. In conclusion, clinicians should be aware that the infl uenza virus can cause frosted branch angiitis-like retinal vascular changes.