Masahiko Usui

Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report of an international committee on nomenclature.

PURPOSE To present revised criteria for the diagnosis of Vogt-Koyanagi-Harada disease, a chronic, bilateral, granulomatous ocular and multisystem inflammatory condition of unknown cause. METHODS Diagnostic criteria and nomenclature were subjects of discussion at the First International Workshop on Vogt-Koyanagi-Harada Disease on October 19-21, 1999, at the University of California, Los Angeles, Conference Center, Lake Arrowhead, California. A committee appointed by the workshop participants was charged with drafting revised criteria for Vogt-Koyanagi-Harada disease, based on discussions held during the conference. This article is the consensus committee report. RESULTS New criteria, taking into account the multisystem nature of Vogt-Koyanagi-Harada disease, with allowance for the different ocular findings present in the early and late stages of the disease, were formulated and agreed upon by the committee. These criteria are based on additional knowledge and experience of experts in the field and are believed to reflect disease features more fully than previously published criteria. CONCLUSIONS The revised definition of Vogt-Koyanagi-Harada disease, with expanded diagnostic criteria, will facilitate performance of studies involving homogeneous populations of patients, at various stages of disease, that address unanswered questions regarding treatment and disease mechanisms.

Epidemiological Survey of Intraocular Inflammation in Japan

PurposeTo report the frequency and trend of intraocular inflammation based on a survey of new ophthalmology patient visits to university hospitals throughout Japan during 2002.MethodsA 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.ResultsThe 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.ConclusionsThrough 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. Jpn J Ophthalmol 2007;51:41–44

A Clinical Trial of FK506 in Refractory Uveitis

We performed a clinical open trial to evaluate the efficacy and the adverse side effects of a single therapy with FK506 in refractory uveitis as a multicenter study in Japan. Fifty-three patients (41 patients with Bechçets disease, five with Vogt-Koyanagi-Harada disease, four with idiopathic retinal vasculitis, and three with other forms of uveitis) were enrolled in the study. FK506 was given orally for 12 weeks. Treatment with FK506 exhibited therapeutic effects in a dosage-dependent manner: the effectiveness was 38% in patients treated with an initial dosage of 0.05 mg/kg of body weight per day, 60% with 0.10 mg/kg of body weight per day, 83% with 0.15 mg/kg of body weight per day, and 79% with 0.20 mg/kg of body weight per day. Overall efficacy with dosage adjustment when needed was 76.5% at the conclusion of the study at the end of the 12th week. The FK506 therapy induced a variety of adverse side effects, the incidence of which depended on the dosage. The major side effects were renal impairment (28.3%, 15 of 53 patients), neurologic symptoms (20.8%, 11 of 53 patients), gastrointestinal symptoms (18.9%, ten of 53 patients), and hyperglycemia (13.2%, seven of 53 patients). The trough level of FK506 in the whole blood correlated with both the efficacy of the therapy and with the incidence of adverse effects. It is recommended to maintain the trough level between 15 and 25 ng/ml. On the basis of these results, a daily dosage of 0.10 to 0.15 mg/kg of body weight per day was suggested as an appropriate therapeutic dosage for refractory uveitis.

Verteporfin photodynamic therapy for choroidal neovascularization associated with toxoplasmic retinochoroiditis.

PURPOSE To evaluate the efficacy and safety of verteporfin photodynamic therapy (V-PDT) for young adults and children with subfoveal choroidal neovascularization (CNV) associated with toxoplasmic retinochoroiditis. METHODS Patients with subfoveal CNV associated with toxoplasmic retinochoroiditis were treated with V-PDT and prospectively followed up. Before V-PDT and during follow-up, patients underwent visual acuity testing, complete ophthalmic examination including color photography, angiography with fluorescein and/or indocyanine green, and optical coherence tomography. The decision to retreat CNV was based on the criteria used in the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy investigation. RESULTS Eight patients (5 males and 3 females) were treated at a mean age of 15.3 years (range, 5-31 years). CNV was 100% classic or predominantly classic in all study patients. Mean visual acuity increased from 20/225 (range, 20/400 to 20/50) to 20/123 (range, 20/200 to 20/25) during a mean follow-up period of 25 months (range, 5-49 months). Persistent closure of CNV was achieved in all eight patients (mean number of treatments, 1.75). Vascular anastomosis developed in the treated area in two patients, but there was no additional visual loss. No significant adverse effects of V-PDT were observed. CONCLUSION V-PDT for subfoveal CNV associated with toxoplasmic retinochoroiditis appears to be effective and safe even in young adults and children. However, a longer follow-up is recommended to confirm our observations.

Preoperative Disinfection of the Conjunctival Sac with Antibiotics and Iodine Compounds: A Prospective Randomized Multicenter Study

PurposeTo compare disinfection by povidone-iodine (PI) solution with that by polyvinyl alcohol-iodine (PAI) solution in preoperative eyewash and to assess the optimal duration of the preoperative application of 0.5% levofloxacin (LVFX) ophthalmic solution.MethodsTwo-hundred-seventy-two elderly cataract patients who had undergone phacoemulsification aspiration with intraocular lens insertion at 12 clinical facilities in Japan were randomized into three groups: 3-day, 1-day, and 1-h preoperative application of 0.5% LVFX ophthalmic solution. Each LVFX group was further divided into two subgroups; the patients in one subgroup were treated with diluted PI eyewash, and those in the second subgroup with diluted PAI eyewash, immediately before the surgery. Thus, a total of six groups were studied. Conjunctival scrapings were collected four times: before LVFX application, after LVFX application, after the eyewash with iodine compounds, and after the surgery. Samples of the aqueous humor were collected immediately after the surgery. All samples were cultured aerobically and anaerobically.ResultsThe 3-day application of LVFX had a significantly higher disinfection rate than the 1-day or 1-h applications (P < 0.05). The disinfection rate of PI was 78.0%, and that of PAI was 79.4%; PAI was not inferior to PI as a preoperative disinfectant. However, new isolates, mainly Propionibacterium acnes and Staphylococcus epidermidis, were detected after LVFX application and even after use of the eyewash with iodine compounds.ConclusionThree-day administration of LVFX ophthalmic solution and use of an eyewash with diluted iodine compounds is effective for preoperative disinfection. However, complete elimination of bacteria from the conjunctival sac is difficult.

Risk and prognostic factors of poor visual outcome in Behcet's disease with ocular involvement

PurposeThe purpose of the study was to determine factors correlated with the progression of irreversible visual disturbance in Behcets disease (BD) with ocular involvement.MethodsForty-seven BD patients with ocular inflammation, who presented with the first ocular episode, and who had been followed continuously for 5–10 years in our hospital, were studied. Charts were reviewed for gender, onset age of uveitis, complete or incomplete type BD, HLA-B51 status, final visual acuity at the last remission period, mean number of ocular attacks per year, and clinical findings of iridocyclitis with profuse hypopyon, strong vitreous opacity blocking the observation of retinal vessels, diffuse retinal vasculitis, and exudates with hemorrhage within the retinal vascular arcade.ResultsPatients with a visual acuity of ≤20/200 and those with >20/200 differed significantly in the mean number of ocular attacks per year and clinical findings of strong vitreous opacity and exudates within the retinal vascular arcade, but not with regard to the other factors. In addition, the frequency of ocular attacks showed a significant negative correlation with the outcome of visual acuity. Logistic regression analysis indicated a significant association of an average of more than three ocular attacks per year, strong vitreous opacity, and exudates within the retinal vascular arcade with poor visual outcome.ConclusionsThis study indicates that more than three ocular attacks per year, strong vitreous opacity, and exudates within the retinal vascular arcade are the risk and prognostic factors for a poor outcome of visual acuity in BD patients.

Sunset glow fundus in Vogt-Koyanagi-Harada disease with or without chronic ocular inflammation.

Abstract Background. Sunset glow fundus is considered an important ocular finding for diagnosing and understanding the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. In this study, we investigated the association between the incidence of chronic ocular inflammation in VKH disease and the appearance of sunset glow fundus. Methods. The study was a retrospective noncomparative interventional case series. Eighty patients with VKH disease treated with high-dose corticosteroid therapy from initial onset were included in the study. We compared the incidence of sunset glow fundus between patients with VKH disease with chronic ocular inflammation lasting more than 6 months and those without chronic ocular inflammation. Results. Chronic ocular inflammation was seen in 14 of 80 patients (17.5%). The presence of severe anterior uveitis were significantly more frequent in the chronic group. Forty-one patients (62%) without chronic ocular inflammation showed sunset glow fundus, while 13 patients (93%) with chronic ocular inflammation developed sunset glow fundus. Duration from disease onset to appearance of sunset glow fundus was significantly shorter in patients with than in patients without chronic inflammation. Conclusions. There is a significant association between the incidence of chronic ocular inflammation lasting more than 6 months and the appearance of sunset glow fundus. In addition, more severe disease at onset might be associated with chronic ocular inflammation in VKH disease.

Progressive outer retinal necrosis caused by herpes simplex virus type 1 in a patient with acquired immunodeficiency syndrome.

OBJECTIVE/BACKGROUND To identify the etiologic agent of rapidly progressive outer retinal necrosis (PORN) in a 32-year-old man with acquired immunodeficiency syndrome (AIDS), who had retinitis developed from cytomegalovirus (CMV). Multiple yellowish spots appeared in the deep retina without evidence of intraocular inflammation or retinal vasculitis, diagnosed clinically as PORN. Death occurred after failure of multiple organs. DESIGN Case report. METHODS Both globes were taken at autopsy, fixed in formalin, and examined histopathologically and immunohistochemically to identify causative agents in the retinal lesions. MAIN OUTCOME MEASURE Immunohistochemistry. RESULTS All layers of the retina were severely damaged and contained focal calcification. Cytomegalic inclusion bodies were found in cells in the damaged retina of the right eye. Immunohistochemical studies for herpesviruses revealed the presence of CMV antigens in the right retina at the posterior pole and herpes simplex virus type 1 (HSV-1)-specific antigen in the periphery of both retinas. No varicella-zoster virus (VZV) antigen was detected in either retina. CONCLUSIONS PORN has been described as a variant of necrotizing herpetic retinopathy, occurring particularly in patients with AIDS. Although the etiologic agent has been reported to be VZV, HSV-1 can be an etiologic agent.

Clinical features of ocular toxocariasis in Japan

Purpose: To characterize the clinical features of ocular toxocariasis and to describe the unique aspects of the disease in Japan. Methods: Thirty-six cases diagnosed as ocular toxocariasis at the uveitis clinic of Tokyo Medical University Hospital were analyzed retrospectively. Results: Thirty-six cases comprised 34 adults (average age: 39 ± 10 years) and two nine-year-old boys. All cases were classified into two clinical types: posterior pole type (13 cases) and peripheral type (23 cases). Visual acuity was maintained over 20/20 in 50% and less than 20/200 in 14% of the cases. The peripheral type had worse outcomes than the posterior pole type in all of the endpoints examined: final visual outcome, frequency of ocular complications, and effectiveness of vitreous surgery. Antibody titers in intraocular fluids led to a diagnosis of ocular toxocariasis in eight seronegative cases of 33 cases examined for antibodies in both serum and intraocular fluid samples. Conclusions: The peripheral type had a worse prognosis than the posterior pole type. However, in general, ocular toxocariasis resulted in fair visual outcomes. The antibody titer in intraocular fluid was helpful in the diagnosis.

Videofunduscopy and videoangiography using the scanning laser ophthalmoscope in Vogt–Koyanagi–Harada syndrome

AIM To observe pathophysiological changes in patients with Vogt–Koyanagi–Harada (VKH) syndrome using the scanning laser ophthalmoscope (SLO) to perform videofunduscopy, and indocyanine green (ICG) and fluorescein videoangiography. METHODS 18 patients diagnosed with VKH syndrome were studied. 15 patients were examined in both acute and convalescent phases, and three patients were examined in the convalescent phase only. Retrospective review of charts was performed to obtain data on visual acuities, clinical findings, and results of cerebrospinal fluid cytology and histocompatibility leucocyte antigen D locus testing. RESULTS Videofunduscopy revealed abnormalities in the central macula at the level of the retinal pigment epithelium or choroid in 40% of patients in the acute phase and 83% of patients in the convalescent phase. ICG videoangiography showed irregular hypofluorescence (80%), slow or patchy filling (67%), indistinct or fewer choroidal vessels (73%), filling defects (73%), and focal leakage (33%) in patients in the acute phase. These changes improved with systemic corticosteroid treatment, although at least one ICG videoangiographic abnormality persisted into the convalescent phase in 83% of patients in the absence of clinical inflammation. In contrast, fluorescein videoangiography revealed fewer and decreased severity of abnormalities, with greater resolution in the convalescent phase when compared with ICG videoangiography. CONCLUSIONS SLO videofunduscopy and videoangiography revealed numerous abnormalities in patients with VKH syndrome, many of which persisted well after clinical recovery, suggesting the development of permanent morphological changes in the fundus. ICG videoangiography was more sensitive than fluorescein videoangiography in delineating abnormalities in layers deep to the sensory retina.