Optic disc morphology in diabetes mellitus

Background: Diabetes mellitus is a systemic disease affecting multiple tissues throughout the body. This study was performed to evaluate intravitally the diabetic changes of the optic disc Methods: Color photographs of 115 eyes with varying severity of diabetic retinopathy and of 29 normal eyes were morphometrically examined Results: We found that the size and shape of the optic disc, the neuroretinal rim and the parapapillary atrophy did not differ significantly between the diabetic eyes and the normal eyes. These variables were independent of the degree of diabetic retinopathy. There was a tendency toward decreased visibility of the retinal nerve fiber layer and increased optic disc pallor in the diabetic eyes Conclusion: The results indicate that the area and form of the optic disc, the neuroretinal rim and parapapillary atrophy are not altered by diabetes mellitus. This is important for the diagnosis of glaucoma in diabetic patients, since glaucoma leads to a decrease of rim area and an enlargement of parapapillary atrophy. The reduced visibility of the retinal nerve fiber layer, the increased optic disc pallor and the unchanged size of the neuroretinal rim and parapapillary atrophy suggest that diabetes mellitus may be associated with nonglaucomatous optic nerve atrophy.     

Optic disc morphology in myopic primary open-angle glaucoma

Objective: To evaluate the morphology of the optic disc in highly myopic eyes with primary open-angle glaucoma. Methods: Color stereo optic disc photographs of 44 patients with primary open-angle glaucoma and a myopic refractive error exceeding –8 diopters were morphometrically examined and compared with disc photographs of 571 patients with primary open-angle glaucoma and a myopic refractive error of less than –8 diopters. Results: In the highly myopic group, compared to the control group, the optic disc was significantly (P<0.0001) larger, the disc shape was significantly (P<0.0005) more elongated, and the optic cup depth was significantly (P<0.0001) more shallow. The loss of neuroretinal rim was more concentric, and localized retinal nerve fiber layer defects were found significantly less frequently in the highly myopic group than in the control group. In the highly myopic group, zone beta of parapapillary atrophy was significantly (P<0.0001) larger. Conclusion: The optic disc morphology in primary open-angle glaucoma differs significantly between highly myopic eyes and eyes with hyperopia or low to moderate myopia. The highly myopic eyes are characterized by secondary macrodiscs with elongated shape, shallow and concentric disc cupping, large parapapillary atrophy, and low frequency of localized retinal nerve fiber layer defects. Glaucomatous optic nerve damage in highly myopic eyes, compared to eyes with a normal refractive error, is more diffuse than localized.     

The use of tissue plasminogen activator in post-traumatic total hyphaema

Background: We wanted to evaluate whether intracameral injection of tissue plasminogen activator (tPA) is useful in managing traumatic hyphaema. Methods: Two eyes with total hyphaema after a severe penetrating injury were treated with a single intracameral injection of 25 g of tPA 5 and 14 days after the injury, respectively. Results: Most of the blood coagulum dissolved within 24 h, and in one of the two eyes the intraocular pressure decreased from 45 to 8 mmHg. The other eye was hypotonic. No re-bleeding or complications related to the use of tPA were noticed. Conclusion: The results in these two cases suggest that tPA is a useful adjunct in managing total hyphaema.     

The cumulative normalised rim/disc area ratio curve

Background: The assessment of the cup of the optic disc depends, among other criteria, on the disc area. A small cup in a small optic disc can indicate an advanced glaucomatous lesion, while on the other hand a large cup in a large optic disc can be normal. Therefore, a cumulative normalised rim/disc area ratio curve could help to distinguish between glaucomatous and normal optic cups. The aim of our study was to calculate and to evaluate such a cumulative normalised rim/disc area ratio curve. Methods: Heidelberg Retina Tomograph examinations of the optic nerve head of 100 randomly selected eyes of 100 normal subjects were evaluated. We calculated the disc area-adjusted normalised rim/disc area ratio in sectors of 10°. The 95th, 90th and 50th percentiles of each of the 36 sectors were displayed in descending order. Results: In relation to the normal percentile curves, it is possible to display an individual normalised rim/disc area ratio curve. We obtained such curves for a normal optic disc, optic nerve heads with moderate and advanced lesions and a small optic disc with glaucomatous damage. Conclusion: We present a new display mode for the results of Heidelberg Retina Tomograph optic nerve head examination, which may be helpful for easy and reliable assessment of the local, diffuse and combined components of glaucomatous optic nerve head damage depending on optic disc size.     

Course of the optic nerve fibers through the lamina cibrosa in human eyes

Background: This study investigated whether regional variations in the course of the optic nerve fibers through the lamina cribrosa may be one of the reasons why the local susceptibility for glaucomatous optic nerve fiber loss differs among the various regions of the optic disc. Methods: The study included 34 human eyes enucleated because of a malignant melanoma of the peripheral choroid without involvement of the anterior chamber angle or the optic nerve. Anterior-posterior sections through the pupil and the optic disc were histomorphometrically evaluated. In the central region and the peripheral part of the optic disc, we measured the thickness of the lamina cribrosa and the length of the lamina cribrosa channels through which the nerve fibers pass. Results: In the peripheral parts of the disc, compared with its central region, the lamina cribrosa was significantly thicker (P<0.0001, Wilcoxon test), the lamina cribrosa channels with the nerve fibers passing through were significantly longer (P<0.0001), and the ratio of length of the fiber channels to the thickness of the lamina cibrosa was significantly higher (P=0.0001). Conclusion: The lamina cribrosa is thicker and the course of the optic nerve fibers through the lamina cribrosa is more curvilinear in the disc pheriphery than in the disc center. These variations in the anatomy of the lamina cribrosa may be one of several factors influencing the regional susceptibility for glaucomatous optic nerve fiber loss within the optic nerve head.     

Management of fibrous histiocytoma of the corneoscleral limbus: Report of a case and review of the literature

Background: Fibrous histiocytomas of the corneoscleral limbus are rare tumors. We present an additional case and review the treatment approaches in the literature. So far, only light and electron microscopic studies have been performed. We used immunohistochemical stains to further characterize the cellular composition. Methods: The excised lesion was routinely fixed and processed for light microscopy and immunohistochemical studies. For comparison, three dermal fibrous histiocytomas were also examined and processed similarly. Results: The corneolimbal tumor was mainly composed of fibroblasts and histiocytes with a large amount of interstitial collagen, arranged in a storiform pattern. Immunohistochemical stains were positive for histiocytes, fibroblasts, and a marker for mesenchymal cells. The staining pattern of the dermal lesions was similar. Conclusion: Fibrous histiocytomas of the corneolimbal region are morphologically benign, slowly growing and infiltrative tumors. Complete resection, especially of the deep margin, is suggested. The immunohistochemical staining pattern is similar to that of dermal fibrous histiocytomas, which behave in a benign manner.     

Galactose-containing glycoconjugates of the iris,the aqueous outflow passages and the cornea in capsular glaucoma

Background: The aim of the study was to compare galactose-containing glycoconjugates of the iris, the aqueous outflow pas sages and the cornea with exfoliation material in capsular glaucoma. Methods: Six formalinfixed, paraffin-embedded human eyes with capsular glaucoma and six control eyes were studied by using a panel of 11 biotinylated lectins to galactose- and N-acetylgalactosamine-containing glycoconjugates. Results: The Gal ( 3) GaINAc-reactive lectins peanut agglutinin (PNA) and Bauhinia purpurea alba agglutinin (BPA) and the Gal (14)GlcNAc-reactive lectins Ricinus communis agglutinin (RCA-I) and Phaseolus vulgaris erythroagglutinin (PHA-E) gave the strongest label with exfoliation material. Lectin binding to the iris was variable. The binding of PNA, BPA, RCA-I, Erythrina cristagalli agglutinin (ECA), PHA-E and Glycine max agglutinin (SBA) to the subendothelial region of iris blood vessels closely resembled their binding to exfoliation material. RCA-I and PHA-E bound moderately to the aqueous outflow passages. The surface of the corneal epithelium showed positive reaction with most lectins studied, but the keratocytes reacted with RCA-I and PHA-E only. Neuraminidase pretreatment generally increased the reaction intensity. Conclusions: The findings suggest that the glycoconjugate composition of exfoliation material in the classical locations along the anterior and posterior chamber closely resembles that in the subendothelial region of iris blood vessels.The authors have no financial interest in any product or process mentioned herein     

Intraocular silicone lenses in silicone oil: an experimental study

Background: To evaluate a potential effect of silicone oil on flexible silicone intraocular lenses, four lenses (STAAR AA-4203) were stored in silicone oil under sterile conditions for periods between 1 month and 3 years. Method: The edge and surface of the lenses were examined by scanning electron micrography and the findings compared with a lens of the same model which had been stored in Ringer's solution for 2 years. Results: After 1 year of silicone oil exposure, droplets of different sizes adherent to the surface of the lens were found. These changes proceeded to a wave-like appearance of the surface after 2 and 3 years of storage, so that a continuous layer of silicone oil polymers is probably covering the intraocular lens. Conclusion: Optical interference has to be considered a possibility if it turns out that the droplets cannot be removed during silicone oil evacuation. Consequently silicone intraocular lenses without hydrophilic preparation of the surface should not be implanted in eyes undergoing combined anterior and posterior segment surgery with silicone oil tamponade or in eyes with high risk for vitreoretinal complications.The authors state that they have no proprietary interest in the marketing of the products mentioned herein or competing products     

Experimental microendoscopic photoablative laser goniotomy as a surgical model for the treatment of dysgenetic glaucoma

Purpose: The aim of this study was to investigate the feasibility of photoablative Er:YAG laser goniotomy under microendoscopic control in a surgical cloudy corneal model of primary infantile glaucoma. Methods: Pectinate ligaments of 12 freshly enucleated cadaver porcine eyes were treated by ab interno single-pulse (5 mJ, 200 s) Er:YAG laser (2.94 m) photoablation. Through a clear corneal incision near the limbus an ophthalmic microendoscope (18 and 20 gauge) was inserted into the anterior chamber. Internal structures were observed and photoablative laser goniotomy was conducted under video guidance. Following treatment all eyes were prepared for light and scanning electron microscopy. Results: Anterior chamber angle structures and tissue photoablation were clearly visualized on the videoscreen using ophthalmic microendoscopy. Energy settings of 5 mJ per pulse proved to be sufficient for reproducible photoablation of pectinate ligaments, accompanied by the root of the iris falling back and exposing trabecular meshwork. This was confirmed histopathologically. Scatter thermal damage was less than 30 m. Conclusion: This new therapeutic modality, which combines endoscopic visualization of the internal structures with photoablative laser goniotomy, can be effective in the management of dysgenetic glaucoma in the presence of a cloudy cornea. High reproducibility of contact laser photoablation enabled sufficient control of incision depth and was not accompanied by inadvertent tissue damage to adjacent intraocular structures.     

Increase in choroidal blood flow in rabbits with endothelin-1 induced transient complete obstruction of retinal vessels

Background: In a previous paper, we reported that retinal blood flow (RBF) ceased immediately after injection of 1 nmol endothelin-1 (ET-1) and no recovery of RBF was detected for at least 50 min. In this study, we confirmed the same duration of RBF cessation and measured choroidal blood flow (CBF) for 180 min. Methods: We measured CBF in a rabbit model of transient complete obstruction of retinal vessels induced by intravitreal injection of a high dose of ET-1, using the hydrogen clearance method. We also investigated the effects of intravitreal injection of ET-1 on intraocular pressure (IOP), blood pressure, pulse rate and blood gases. Results: CBF was significantly greater in the ET-1-injected eyes than in the control eyes 40–130 min after injection of ET-1 (P < 0.05). The maximal CBF ratio in the ET-1-injected eyes was 128 ± 7.4% at 40 min. CBF decreased to the pre-injection level at 140 min after the injection of ET-1. There was no significant change in blood pressure, pulse rate and blood gases throughout this experiment, and there was no significant difference in IOP between ET-1-injected eyes and control eyes. Conclusion: It seems likely that the increase in CBF resulted from some local mechanisms of control that compensated for the decrease in RBF induced by intravitreal injection of ET-1. This model may be useful for investigation of the regulatory system of intraocular circulation, including endothelin receptors.     

Relaxing incisions with compression sutures for control of astigmatism after penetrating keratoplasty

Background: Ten percent of patients with persisting postoperative astigmatism following penetrating keratoplasty (PK) require surgical re-intervention, despite an otherwise successful transplant. Relaxing incisions (RIs) in combination with compression sutures seem to be the preferable procedure. However, poor predictability and lack of long-term experience complicate the issue. Here we report the 2-year follow-up results of 25 patients with high PK astigmatism treated by means of RIs and compression sutures Methods: Commonly, free-handed RIs were placed at the graft-host interface and 10–0 nylon compression sutures were placed perpendicular to the incisions. PK sutures had been removed no less than 4 months prior to refractive surgery Results: Nineteen eyes regained a functional vision of >- 0.4. The net decrease in astigmatism was 6.1 ± 4.3 D (47 ± 21 %). The mean vector-corrected change in astigmatism was 13.1 ± 5.7 D. Cylinder axis variation was reasonably low, with a correlation of attempted versus achieved axis of r=0.85. Within the first 3 months after operation the induced astigmatism regressed by, on average, 5.5 ± 4.3 D, making intraoperative overcorrection necessary. As an inevitable side effect, refractive procedures resulted in a myopic shift (4.7 ± 6.9 D) in spherical equivalence Conclusion: RIs and compression sutures are very useful in reducing postkeratoplasty astigmatism if correction of extremely high cylinder (> 10 D) is not intended. However, predictability still remains unsatisfactory and more than one operation may be required.     

Expression of vascular endothelial growth factor in experimental choroidal neovascularization

Background: Although the choroidal neovascularization (CNV) is a common pathologic feature of a number of different eye diseases, its pathological mechanisms have not been fully elucidated. We investigated the expression of vascular endothelial growth factor (VEGF) in CNV using an experimental primate model. Method: CNV was induced by intense laser photocoagulation in four monkey eyes. Single eyes were enucleated at 1, 3, 7 or 14 days after photocoagulation and examined immunohistochemically for VEGF, macrophage antigen, von Willebrand factor and glial fibrillary acidic protein (GFAP). Expression of VEGF mRNA was examined byin situ hybridization. Results: One day after photocoagulation, the normal structure of the outer portion of the retina and the inner portion of the choroid was destroyed. Three days after photocoagulation, choroidal vascular endothelial cells migrated into the subretinal space through the defect in Bruch's membrane. Increased expression of VEGF was detected in the accumulating macrophages, migrating retinal pigment epithelial (RPE) cells and Muller cells. Maximal expression of VEGF was observed between 3 and 7 days after wounding, and many newly formed vessels extended into the subretinal space 7–14 days after photocoagulation. Conclusion: VEGF derived from RPE cells, macrophages and Müller cells may play a role in the formation of CNV.     

Poly (triethylenglycol monomethacrylate) and poly(glycerol monomethacrylate) cross-linked gel as potential viscoelastics for intraoperative use

Background: The highly swelling poly(glycerol monomethacrylate) gel (polyGLYMA) and hydrophilic polymer poly(triethylenglycol monomethacrylate (polyTEGMA) were tested as potential viscoelastics for intraopertive use in anterior segment surgery. Methods: PolyGLYMA was implanted into the anterior chamber in 5 rabbits, and 40% polyTEGMA in 16 rabbits. The eyes were enucleated 1 week to 3 months after the operation. The corneal endothelium was examined with specular microscopy, and then the whole eye histopathologically. Results: In all eyes of the polyGLYMA group, the clinical findings were characterized by a marked ciliary injection and severe secondary glaucoma, and the histologic ones by a marked inflammatory infiltration and thickening of Descemet's membrane in the anterior chamber angle. Specular microscopy revealed a decrease in the endothelial cell density and polymorphism of the endothelial cells. In the polyTEGMA group, the anterior segment and the fundus were physiologic all the time, and specular microscopy and histologic findings showed no degenerative and/or inflammatory changes. Conclusions: PolyGLYMA proved unsuitable for intracameral application in rabbits. The new polymer polyTEGMA is characterized by high biologic tolerance after its implantation into the anterior chamber of rabbits. PolyTEGMA 40% might be considered as a potential viscoelastic material in humans.     

Inhibition of corneal allograft reaction by CTLA4-Ig

Background: Activation of T cells requires both the interaction of T-cell receptor with major histocompatibility complex on the antigen-presenting cell and costimulatory signals, for instance the B7 antigens expressed on antigen-presenting cells and the CD28 molecule expressed on T cells. A recombinant fusion protein, CTLA4-Ig, has been produced that contains the extracellular domain of human CTLA4 fused to IgGl constant region and that binds the B7 molecule with high affinity. Blocking the CD28/B7 interaction with CTLA4-Ig inhibits T cell activation in vitro and in vivo. Methods: We used CTLA4-Ig in a fully MHC-mismatched mouse keratoplasty model. The animals were divided into four groups: (1) no treatment, (2) intraperitoneal treatment with 130 g CTLA4-Ig, (3) intraperitoneal treatment with 300 g CTLA4-Ig, (4) subconjunctival treatment with 290 g CTLA4-Ig. Results: The allograft reaction occurred in untreated animals between days 12 and 16 (mean 13.5). While topical application of CTLA4-Ig seemed to shorten the graft survival (mean 11.6 days) and systemic application of 130 g had no influence (mean 14.0), only intraperitoneal injection of 300 g of CTLA4-Ig prolonged the survival of allografts (mean >20 days) (P<0.01). Conclusion: CTLA4-Ig prolonged significantly the survival of corneal allografts in a fully MHC-mismatched mouse keratoplasty model, but the small antigen load of the corneal transplant and the anterior chamber-associated immune deviation (ACAID) may have a disadvantage to induce tolerance in this model of CTLA4-Ig therapy.Presented at JERMOV 1996 in Montpellier     

Therapeutic use of the 193-nm excimer laser in corneal pathologies

Purpose: To analyze the results of phototherapeutic keratectomy. Patients and methods: We performed 193-nm excimer laser phototherapeutic keratectomy (PTK) in 252 eyes of 216 patients suffering from pain and/or decrease in visual acuity. One hundred and three eyes had recurrent erosions of the cornea, 86 eyes underwent excimer laser smoothing of the cornea after pterygium surgery, 29 eyes had a bandlike keratopathy (25 rough, 4 smooth) and 34 eyes had other pathologic conditions such as amyloidosis of the cornea, anterior corneal dystrophies, scars after injuries, alkali burns, superficial stromal dystrophies and infections. Recurrent erosions and epithelial dystrophies were treated with 15–20 pulses (160–200 mJ/cm², 8 mm ablation zone) after mechanical abrasion of the epithelium. Removal of corneal opacities and scars required the use of a masking fluid (methylcellulose) in different concentrations and slit-lamp control (integrated in the delivery system of the excimer laser). Results: Some 91% of the eyes with recurrent erosions were recurrence-free. Fifty-two per cent of the eyes with pterygium had recurrences if the baresclera technique was used and 33% of the eyes if a free conjunctival graft was used. The difference was not significant. All of the patients with bandlike keratopathy were pain-free. In 88% of the eyes with special indications the treatment goal was achieved. No positive effect was seen after alkali burn, in a patient with anterior membrane dystrophy (Grayson-Wilbrandt corneal dystrophy) or in a patient with a corneal protuberance. In one patient with scleroperikeratitis a late recurrence of the opacity was observed 3 years after surgery. A loss of best corrected visual acuity was found only in one patient with bullous keratopathy in whom the treatment goal was the reduction of pain. All patients with smooth bandlike keratopathy had an improvement in best corrected visual acuity of at least one line. About 70% of patients with special indications improved by at least one line, up to nine lines. A possible hyperopic shift in all groups could be minimized using a large ablation zone. Conclusion: PTK with the 193-nm excimer laser is a safe and effective treatment for many superficial diseases of the cornea.Werner Förster is the Primary Investigator for Schwind Keratom     

Role of protein tyrosine phosphorylation in rat corneal neovascularization

Background: Recent studies have suggested that tyrosine kinase pathways that are activated by angiogenic growth factors may play a role in corneal neovascularization. Methods: Corneal neovascularization was induced in rat corneas by chemical cauterization. At 6, 24, 48, 96, and 168 h after chemical cauterization the rat corneas without the corneal epithelium were prepared for gel electrophoresis. Total protein profiles of the corneal samples were examined by staining gels with Coomassie brilliant blue. Tyrosine-phosphorylated proteins, three angiogenic growth factors (basic fibroblast growth factor, vascular endothelial growth factor, and platelet-derived growth factor-B chain), and three intracellular signal proteins in the tyrosine kinase pathways (phospholipase C, SHC, and mitogen-activated protein kinase) in the corneal samples were examined by western blot analysis. A topical treatment of genistein eye drop (5 mg/ml) was used for inhibition of corneal neovascularization after chemical cauterization in rats. Results: In total protein profiles, three bands in the corneal samples were increased after cauterization. Overall tyrosine-phosphorylated proteins and all three angiogenic growth factors increased with progression of corneal neovascularization. The tyrosine-phosphorylated forms of three intracellular signal proteins were also increased after cauterization. Treatment with topical genistein was effective in inhibiting corneal neovascularization in rats. Conclusion: Protein tyrosine phosphorylation was involved in inflammation-induced corneal neovascularization. Tyrosine kinase inhibitors may have utility as inhibitors of corneal neovascularization.     

Optic disc histomorphometry in normal eyes and eyes with secondary angle-closure glaucoma

Parapapillary atrophy has been reported to occur in glaucoma eyes. Seeking the microscopical equivalent, we evaluated histomorphometrically serial sections of 21 human eyes enucleated due to secondary angle-closure glaucoma and 28 nonglaucomatous eyes with malignant choroidal melanoma. In the parapapillary region two zones were differentiated: in zone B adjacent to the optic disc, Bruch's membrane was denuded of retinal pigment epithelium cells; zone A peripheral to zone B showed pigment irregularities in the retinal pigment epithelium. Both zones B and A were significantly larger and zone B occurred more frequently in glaucomatous eyes than in the control group. Additionally, the outer and inner retinal layers and the parapapillary retina as a whole were significantly thinner in the glaucoma eyes than in the control eyes. Photoreceptors were completely lost or markedly decreased in number in zone B The findings may indicate that zones B and A represent the histological correlate of the glaucomatous parapapillary chorioretinal atrophy. Offprint requests to: J. JonasSupported by Deutsche Forschungsgemeinschaft DFG Nan 55/61/Jo, and Förderverein Augenheilkunde Erlangen     

Employment of bioluminescence for the quantification of adenosine phosphates in the human cornea

Background: Quantification of adenosine phosphates in human corneal extracts has been performed using spectrophotometry. We employed the bioluminescence technique to obtain a more sensitive assay for adenosine phosphates and to reduce the volume of the test sample. Methods: The bioluminescence assay for ATP, already known from sterility control, was modified and expanded. Standard curves were established using a standard solution with equimolar concentrations of ATP, ADP and AMP. To monitor the method, adenosine phosphates were measured in 35 human corneal extracts using both spectrophometry and bioluminescence. Results: Linear standard curves ranging from 1 to 45 pmol were established. The two methods yielded comparable results despite the use of a basic dilution of 1: 100 for the new technique. Conclusion: Bioluminescence provides a highly sensitive quantification of adenosine phosphates in the human cornea and facilitates an extremely detailed evaluation of the metabolic status of the cornea.Dedicated to Prof. Martin Reim on the occasion of his 65th birthday     

Retinopathy in diabetic hypertensive monkeys: a pathologic study

Background: No satisfactory primate model of diabetic retinopathy has been produced. The clinical picture of microangiopathic retinopathy in diabetic hypertensive monkeys has been previously reported. The present study describes the pathologic findings of these animals. Methods: Eleven eyes of six monkeys (five rhesus, one cynomolgus) were studied. Diabetes mellitus was either spontaneous or induced by streptozocin; mild arterial hypertension was either spontaneous or induced by fludrocortisone acetate. In two monkeys, the horseradish peroxidase tracer technique was employed. Trypsin flat preparations of the nasal retinal vasculature were prepared. The material was studied by light and electron microscopy. Results: We divided the development of the microangiopathic retinopathy into three stages. In the early stage, background retinopathy was characterized by microvascular abnormalities and capillary dropout. Massive vascular leakage, intraretinal exudates and hemorrhage, cystoid degeneration, and cotton-wool spots were features of an exudative retinopathy in the second stage. In the final stage, chronic ischemic retinopathy was characterized by vascular occlusions and areas of retinal atrophy. Conclusion: Microangiopathic retinopathy in diabetic monkeys with mild hypertension presented many features of human diabetic and hypertensive retinopathy, except vitreous neovascularization.     

HLA antigens in a Japanese family with Behçet's disease

Background: Familial Behçet's disease is rare. Methods: HLA antigens in a Japanese family with Behçet's disease were examined. Results: The affected patients had HLA B51, and unaffected family members also had the same antigen. Conclusion: It is likely that not only HLA B51 but also other factors may be involved in the pathogenesis of Behçet's disease in Japanese patients.