Tatsushi Kawaguchi

Comparison of infliximab versus ciclosporin during the initial 6-month treatment period in Behçet disease

Aim To compare the efficacy and safety of infliximab versus ciclosporin A (CsA) in refractory uveoretinitis in Behçet disease. Methods In this retrospective clinical chart review of patients with Behçet disease who were treated with CsA or infliximab, we collected information on the number of uveitis attacks, visual acuity and adverse side effects that occurred during the 6 months prior to and after the initiation of CsA (n=20) or infliximab (n=17). Results The number of acute episodes of uveitis during the 6 months before and after initiation of CsA were 3.3±2.4 and 1.2±1.2, and those of infliximab were 3.1±2.7 and 0.4±1.0, respectively (p<0.005). The number of episodes after infliximab administration was significantly lower than that seen for CsA (p<0.05). During the 6-month treatment period, there were no significant differences noted in the improvement of the visual acuity between the two therapies. After CsA administration, neurological symptoms and renal toxicity were seen in one patient each, while after the infliximab administration, an infusion reaction and leucopenia were seen in one patient each. Conclusion During the initial 6 months of treatment, infliximab proved to be more effective in reducing acute episodes of uveitis in Behçet disease.

Evaluation of Characteristic Ocular Signs and Systemic Investigations in Ocular Sarcoidosis Patients

PurposeTo evaluate the diagnostic values of ocular signs and systemic investigations in ocular sarcoidosis, in a retrospective case–control study.MethodsSubjects were 67 consecutive uveitis patients with biopsy-proven sarcoidosis and 111 control patients with other clinical uveitis entities. The predictive values analyzed were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The five ocular signs for ocular sarcoidosis are (1) mutton fat keratic precipitates and iris nodules; (2) nodules at the trabecular meshwork and tent-shaped peripheral anterior synechia; (3) snowball vitreous opacities; (4) nodular periphlebitis, and (5) multiple chorioretinal lesions (active or atrophic) in the peripheral fundus. In addition, the results of the following five systemic investigations were considered: (1) negative tuberculin skin test; (2) elevated serum angiotensin-converting enzyme; (3) elevated serum lysozyme; (4) elevated serum γ-globulin; and (5) bilateral hilar lymphadenopathy on chest X-ray.ResultsThe incidence of all ocular signs and positive results for the systemic investigations were significantly higher in sarcoidosis patients than in controls (P < 0.001). The presence of two or three of the five ocular signs were indicative of a positive finding in the diagnostic parameters. The presence of two positive results among the five systemic investigations showed values higher than 0.800 for all diagnostic parameters.ConclusionsCombinations of the specified ocular signs and the results of systemic investigations can be used for the diagnosis of ocular sarcoidosis. Jpn J Ophthalmol 2007;51:121–126

Role of IL-22- and TNF-α-producing Th22 cells in uveitis patients with Behcet's disease.

Behçet’s disease is a systemic inflammatory disorder with recurrent episodes of oral ulceration, skin lesions, genital ulceration, and intraocular inflammation (uveitis). The intraocular inflammation is strictly associated with Th effector cells. IL-22 is a member of the IL-10 cytokine family that is involved in inflammatory processes. Recently, Th22 cells were identified as a Th cell population that produces IL-22 and TNF-α and are distinct from Th1, Th2, and Th17 cells. In this study, we established Th22-type T cell clones from ocular samples taken from Behçet’s disease patients with active uveitis. These clones produced large amounts of IL-22 and TNF-α but not the Th1 cytokine IFN-γ and the Th17 cytokine IL-17. CD4+ T cells from the peripheral blood of Behçet’s disease patients differentiated into Th22 cells in the presence of IL-6 and TNF-α in vitro. The polarized Th22 cell lines produced large amounts of IL-22, and the polarized Th1 and Th17 cells also produced IL-22. In the presence of anti–TNF-α– and anti–IL-6–blocking Abs, Behçet’s disease Th22-type T cells failed to produce IL-22. In addition, infliximab-pretreated Th22 cells and Th22-type ocular T cells produced less IL-22 and TNF-α. Moreover, IL-22–producing T cells were isolated from mice with experimental autoimmune uveitis, an animal model of Behçet’s disease, and the intraocular T cells from uveitis models produced large amounts of IL-22 in the presence of retinal Ags. Our results suggest that inflammatory cytokines IL-22 and TNF-α may play a key role in the ocular immune response in Behçet’s disease.

Phacoemulsification cataract extraction and intraocular lens implantation in patients with uveitis

PURPOSE: To analyze the outcomes of phacoemulsification cataract extraction and intraocular lens (IOL) implantation in patients with uveitis. SETTING: Miyata Eye Hospital, Miyakonojo, Miyazaki, Japan. METHODS: The records of 95 patients (131 eyes) with uveitis who had phacoemulsification cataract extraction and IOL implantation between 1990 and 2001 were retrospectively examined. The postoperative visual outcomes and complications were analyzed. RESULTS: The mean age of the 36 men and 59 women was 61.7 years (range 30 to 87 years) At the final follow‐up examination, 111 eyes (84.7%) had improved visual acuity and 97 eyes (74.0%) had a final visual acuity of 0.5 or better. Patients with Behçets disease had significantly worse visual outcomes than patients with other clinical etiologies of uveitis such as human T‐lymphotropic virus type 1 uveitis and Vogt–Koyanagi–Harada disease. In 17 eyes (13.0%), relapse of intraocular inflammation occurred within 6 months after surgery; the rate of relapse was highest in patients with Behçets disease (35.2%). Posterior synechias occurred in 8 eyes (6.1%), pupillary capture in 1 eye (0.8%), intraocular pressure elevation in 11 eyes (8.4%), and cystoid macula edema in 8 eyes (6.1%). In 31 eyes (23.7%), posterior capsule opacification required neodymium:YAG capsulotomy. CONCLUSIONS: The outcomes of phacoemulsification cataract extraction and IOL implantation in patients with uveitis were satisfactory. Patients with Behçets disease related to intraocular inflammation, however, appeared to have a higher risk for complications and therefore worse outcomes than patients with other clinical etiologies of uveitis.

Choroidal thickness in convalescent vogt-koyanagi-harada disease.

Purpose: To evaluate the subfoveal choroidal thickness (SCT) at the convalescent stage of Vogt–Koyanagi–Harada disease and to investigate the correlations among SCT, the presence of the sunset glow fundus, and size of the peripapillary atrophy (PPA). Methods: The medical records of consecutive patients with Vogt–Koyanagi–Harada disease without active intraocular inflammation were reviewed, and one eye was randomly chosen for analyses. The disease duration was more than 3 years. Enhanced depth imaging optical coherence tomography was performed to measure SCT. The area of PPA was measured using the PDT/MPS software. Sunset glow fundi were classified into two groups according to the degree of depigmentation. Results: Nineteen eyes with Vogt–Koyanagi–Harada disease were studied. The mean SCT of 12 eyes with severe sunset glow fundus was 144 ± 72 &mgr;m which was thinner than that of the 7 eyes with no or mild depigmentation (P = 0.0057). The SCT was inversely correlated with the disease duration (P = 0.048) and the PPA area (P = 0.0002). The PPA area was positively correlated with the disease duration (P = 0.007). Conclusion: The thinner choroid and larger PPA areas were correlated with the degree of depigmentation or disease duration and might be caused by latent choroidal inflammation in the convalescent stage of Vogt–Koyanagi–Harada disease.

Therapy for Acute Retinal Necrosis

Acute retinal necrosis is a progressive necrotizing retinopathy caused by herpes simplex virus (HSV) or varicella zoster virus (VZV). The mainstay of its treatment is antiviral therapy against these pathogenic organisms, such as intravenous acyclovir or oral valacyclovir. Systemic and topical corticosteroids together with antiviral therapy are used as an anti-inflammatory treatment to minimize damages to the optic nerve and retinal blood vessels. Because the majority of severe cases of the disease show occlusive retinal vasculitis, a low dosage of aspirin is used as anti-thrombotic treatment. Vitreo-retinal surgery is useful to repair rhegmatogenous retinal detachment, one of the main late-stage complications. Moreover, recent articles have reported some encouraging results of prophylactic vitrectomy before rhegmatogenous retinal detachment occurs. The efficacy of laser photocoagulation to prevent the development or extension of rhegmatogenous retinal detachment is controversial. Despite these treatments, the visual prognosis of acute retinal necrosis is still poor, in particular VZV-induced acute retinal necrosis.

Indocyanine green angiography findings in initial acute pretreatment Vogt-Koyanagi-Harada disease in Japanese patients

PurposeIndocyanine green angiography (IA) is a highly sensitive method to evaluate choroidal inflammatory lesions. We present standardized IA findings of initial acute Vogt-Koyanagi-Harada (VKH) disease in Japanese patients before therapeutical intervention.MethodsMedical records of patients with VKH disease at Tokyo Medical and Dental University Hospital and Miyata Eye Hospital were retrospectively analyzed. We analyzed six IA signs: choroidal perfusion inhomogeneity, early hyperfluorescent stromal vessels, hypofluorescent dark dots (HDDs), fuzzy or lost pattern of large stromal vessels, disc hyperfluorescence, and diffuse late choroidal hyperfluorescence.ResultsTen patients from the two hospitals were studied. The most constant findings present in all eyes were early hyperfluorescent stromal vessels, HDDs, and either fuzzy or lost pattern of large stromal vessels. Disc hyperfluorescence was present in 18 eyes. Choroidal perfusion inhomogeneity was seen in six patients, and diffuse late choroidal hyperfluorescence was seen to a certain degree in all eyes.ConclusionsFour of the analyzed signs, including early hyperfluorescent stromal vessels, HDDs, fuzzy or lost pattern of large stromal vessels, and disc hyperfluorescence were consistent findings in Japanese VKH patients. Because the primary lesion is situated in the choroid, IA is the method of choice to monitor disease activity in VKH disease.

A Clinical Survey of Uveitis in HTLV-1 Endemic Region

Purpose: To investigate a clinical survey of uveitis in southern Kyushu of Japan, where human T-lymphotropic virus type 1 (HTLV-1) and toxoplasmosis is highly endemic. Methods: The clinical records of patients with uveitis between 1975 and 2007 at Miyata Eye Hospital were reviewed. Results: A total number of 1338 patients (2012 eyes), consisting of 526 men and 812 women with mean age of 50.5 years old, were analyzed. The most common clinical entity was HTLV-1 uveitis (17.1%), followed by Vogt–Koyanagi–Harada disease (9.9%), sarcoidosis (7.2%), toxoplasmosis (7.1%), Behçet’s disease (4.3%) and others. Unclassified uveitis comprised 41.1% in the series. Anterior uveitis was seen in 30.8%, intermediate uveitis in 17.3%, posterior uveitis in 9.3%, and pan-uveitis in 42.6%. Conclusions: HTLV-1 uveitis and toxoplasmosis were the major clinical entities in southern Kyushu of Japan. This relates to the high seroprevalence of the infectious agents in this region of Japan.

Regression of Optic Disc Neovascularization in Patients with Behçet's Uveoretinitis After Infliximab Therapy

PURPOSE Optic disc neovascularization (NVD) in patients with Behçets uveoretinitis is a relatively uncommon but severe complication that lacks standardized treatments. We report 2 cases of Behçets uveoretinitis that achieved partial regression of NVD after infliximab therapy. METHODS Intravenous infliximab infusions were administrated to 2 immunosuppressive therapy-resistant Behçets uveoretinitis patients with severe NVD accompanied by vitreous hemorrhage (both eyes in case 1 and the left eye in case 2 ). Best-corrected visual acuity, funduscopic findings, and fluorescein angiography were evaluated before and after the treatments. RESULTS After being switched to infliximab therapy, NVD in both cases stopped developing and regressed partially, as confirmed by fluorescein angiography and resolution of vitreous hemorrhage, which led to an improvement of the best-corrected visual acuity. CONCLUSIONS Results suggest that infliximab administration might be an effective treatment in NVD patients with Behçets uveoretinitis.

Seroprevalence of Bartonella henselae in patients with uveitis and healthy individuals in Tokyo

PurposeTo compare the seroprevalence of Bartonella henselae, a pathogen of cat scratch disease, in patients with uveitis and in healthy individuals.MethodsSerum samples were collected from 197 consecutive patients with various entities of uveitis at Tokyo Medical and Dental University Hospital, and from 83 healthy age- and sex-matched volunteers. Anti-Bartonella IgG and IgM antibodies were examined by indirect immunofluorescent antibody.ResultsSerum antibodies to B. henselae were positive in 39 of 197 (19.8%) patients with uveitis, and in 21 of 83 (25.3%) of the healthy volunteers. There was no statistical difference in the seroprevalence between the two groups. The overall seroprevalence of B. henselae was 60 of 280 (21.4%).ConclusionsThe seroprevalence of B. henselae was similar in both patients with uveitis and in healthy volunteers in Tokyo, Japan. These data indicate that a significant number of healthy individuals are asymptomatic carriers of B. henselae, which should be kept in mind when a diagnosis of cat scratch disease is made.