Annabelle A. Okada

Frequency of Distinguishing Clinical Features in Vogt-Koyanagi-Harada Disease

PURPOSEnTo determine the frequency of occurrence of limited clinical features which distinguish patients with Vogt-Koyanagi-Harada (VKH) disease from those with non-VKH uveitis.nnnDESIGNnComparative case series.nnnPARTICIPANTSnWe included 1147 patients.nnnMETHODSnAll patients with bilateral ocular inflammatory disease presenting to any of 10 uveitis centers in the 3-month period between January 1 and March 31, 2006 (inclusive), were asked to participate. The clinical and historical features of disease were obtained from the participants via direct interview and chart review. Patients were stratified based on whether they were diagnosed with VKH disease or non-VKH uveitis for statistical analysis.nnnMAIN OUTCOME MEASURESnPresence or absence of various clinical features in the 2 populations.nnnRESULTSnOf 1147 patients, 180 were diagnosed with VKH disease and 967 with non-VKH uveitis. Hispanics and Asians were more likely to be diagnosed with VKH than non-VKH disease compared with other ethnicities. In acute disease, the finding of exudative retinal detachment was most likely to be found in VKH disease with a positive predictive value (PPV) of 100 and negative predictive value (NPV) of 88.4, whereas in chronic disease, sunset glow fundus was most likely to be found, with a PPV of 94.5 and NPV of 89.2.nnnCONCLUSIONSnNumerous clinical findings have been described in the past as important in the diagnosis of VKH. The current study reveals that of these, 2 are highly specific to this entity in an ethnically and geographically diverse group of patients with nontraumatic bilateral uveitis. These clinical findings are exudative retinal detachment during acute disease and sunset glow fundus during the chronic phase of the disease.

Decreased ocular inflammatory attacks and background retinal and disc vascular leakage in patients with Behçet's disease on infliximab therapy

Aim To evaluate the efficacy of infliximab treatment in patients with refractory uveoretinitis associated with Behçets disease. Methods Clinical records of 14 patients were retrospectively reviewed. Patients received infliximab infusions (5u2005mg/kg) at weeks 0, 2 and 6, and every 8u2005weeks thereafter. The main outcome measures were frequency of clinically observable ocular inflammatory attacks, background retinal and disc vascular leakage as assessed by fluorescein angiography during periods of clinical quiescence, visual acuity and adverse effects. Results The median follow-up after initiating infliximab therapy was 19u2005months (range 12–29u2005months). At 12u2005months, eight of 14 patients (57%) had experienced no inflammatory attacks, and the frequency of attacks was significantly reduced when compared with the 6-month period just prior to infliximab use. Background retinal and disc vascular leakage assessed at 12u2005months improved in 11 of 14 patients (79%). Visual acuity improved or remained unchanged at 12u2005months in 26 of 28 eyes (93%). Infliximab therapy was terminated in two patients owing to infusion reactions. However, no serious adverse effects were observed. Conclusion Infliximab over the first year of treatment appeared effective in reducing ocular inflammatory attacks, as well as background retinal and disc vascular leakage, in patients with refractory uveoretinitis associated with Behçets disease.

Frequency and clinical features of intraocular inflammation in Tokyo

Background:u2002 To investigate frequencies and clinical features of intraocular inflammation (uveitis) in Tokyo, Japan.

Anti-inflammatory effect of retinoic acid on experimental autoimmune uveoretinitis

Aims To determine whether an active metabolite of vitamin A, all-trans retinoic acid (ATRA), reduces inflammation in experimental autoimmune uveoretinitis (EAU). Methods Naive CD4+ T cells were activated with anti-CD3, anti-CD28 and transforming growth factor (TGF)-β, in the presence or absence of ATRA. Intracellular expression of transcription factor forkhead box P3 (Foxp3) and interleukin (IL)-17 in the activated CD4+ T cells was assessed by flow cytometry. C57BL/6 mice were immunised with human interphotoreceptor retinoid binding protein peptide 1–20 (IRBP1–20). ATRA was administered intraperitoneally every other day (0.2u2005mg/mouse per day) from day 0 to day 21. In vivo-primed draining lymph node cells from vehicle-treated or ATRA-treated mice were stimulated with IRBP1–20 and the culture supernatant fraction was harvested for assay of interferon (IFN)-γ and IL-17 by ELISA. Results ATRA synergised with TGF-β to induce Foxp3+ T regulatory cells (Treg) and reciprocally inhibited development of IL-17-producing T helper cells (Th17) induced by TGF-β and IL-6. ATRA treatment reduced the severity of EAU clinically, and IFN-γ and IL-17 production were significantly reduced in ATRA-treated mice. Conclusion These findings demonstrate that ATRA treatment ameliorates severity of EAU and reduces the Th1/Th17 responses. ATRA may represent a new therapeutic modality for human refractory uveitis.

Effect of infliximab on gene expression profiling in Behcet's disease.

PURPOSEnRecent studies have demonstrated that a new anti-tumor necrosis factor (TNF)-α antibody, infliximab, is effective in controlling ocular inflammatory attacks in Behçets disease. In this study, the effect of infliximab on gene expression patterns in peripheral blood mononuclear cells of Behçets disease patients was investigated before and after initiation of infliximab treatment.nnnMETHODSnA human whole-genome microarray of 54,359 genes was used to analyze mRNA expression profiles of peripheral blood mononuclear cells obtained from four patients (three women, one man, 21-64 years at age) at baseline and at 22 weeks after initiation of infliximab. Quantitative polymerase chain reaction (PCR) analysis was performed for selected up- or downregulated genes, to confirm the microarray results.nnnRESULTSnAnti-TNF-α therapy reduced the frequency of ocular episodes in three of four patients. Among inflammatory cytokine-related genes, TNF blockade reduced expression of interleukin (IL)-1 receptor type 2, interferon-γ receptors, IL6, IL6 receptor, gp130, and IL17 receptors. Furthermore, gene expression of Toll-like receptor 2 (TLR2), receptor for mycobacterial glycolipid (C-type lectin domain family 4, member E: CLEC4E), and complexin 2 (CPLX2) was downregulated in all patients.nnnCONCLUSIONSnSeveral up- or downregulated genes identified in this study may be candidates for further investigation in identifying the molecular mechanism of infliximab in the treatment of Behçets disease with refractory uveoretinitis.

Cost-effectiveness of cataract surgery in Japan.

PurposeTo evaluate the cost-effectiveness of cataract surgery through measurement of the cost per quality-adjusted life-year (QALY) in Japan.MethodsA total of 549 patients scheduled for cataract surgery at 12 clinical sites from November 2008 through February 2010 were included in the study. Prospective assessment of patient preference-based quality of life (utility) was performed before and after the surgery using the time tradeoff method, EuroQol, and Health Utilities Index Mark 3. Multiple regression analysis was used to determine the correlation between utility and visual acuity. The QALYs gained through cataract surgery were estimated, and cost-utility analysis was performed.ResultsThe utilities significantly correlated with the visual acuity in the better seeing eye. In all the subgroups (first eye surgery, second eye surgery, and bilateral surgery), mean utility improvement was statistically significant. Average QALYs for unilateral cataract surgery and bilateral cataract surgery were 2.40 and 3.40, respectively. The cost per QALY gained from surgery was estimated at ¥122,472 (US

Clinical features and visual outcomes of Japanese patients with scleritis

1,307) for unilateral surgery and ¥145,562 (US

Cystoid Macular Edema in Uveitis

1,553) for bilateral surgery.ConclusionsRoutine cataract surgery in Japan is highly cost-effective. Factors that contribute to this are the high clinical effectiveness of the surgery, the substantial improvement in patient-perceived quality of life, and the reasonable cost of the surgery.

Clinical Features of Polypoidal Choroidal Vasculopathy and Visual Outcomes in the Absence of Classic Choroidal Neovascularization

Purpose To analyse clinical features, systemic associations, treatment and visual outcomes in Japanese patients with scleritis. Methods Clinical records of 83 patients with scleritis who presented between 1998 and 2008 to the Ocular Inflammation Service of the Kyorin Eye Center, Tokyo, were reviewed. Results Of the 83 patients, 57 (69%) had diffuse anterior scleritis, 9 (11%) had nodular anterior scleritis, 8 (10%) had necrotising anterior scleritis and 9 (11%) had posterior scleritis. There was a slight predominance of women (55%) and unilateral disease (53%). Mean age at presentation was 51u2005years (range 12–82u2005years). Secondary ocular complications were observed in 78% of patients, including anterior uveitis in 25% and increased intraocular pressure in 40%. Investigation revealed a systemic disease association in 24 patients (29%), including six patients (7.2%) with tuberculosis and 18 patients (22%) with rheumatologic disease. Thirty-five patients (42%) received systemic corticosteroid treatment and 19 patients (23%) received immunosuppressive agents. All 17 patients with necrotising anterior scleritis or posterior scleritis were treated with oral corticosteroids and/or immunosuppressive drugs. Visual outcomes were generally good; however, poorer outcomes were observed in eyes with necrotising scleritis, mostly due to corneal ulceration or corneal opacification. Conclusions A systemic disease association was identified in 29% of Japanese patients with scleritis. Roughly one-half of patients received oral corticosteroids and/or immunosuppressive drugs to control inflammation, with generally good visual outcomes.

Intravitreal bevacizumab for iris metastasis of small-cell lung carcinoma with neovascular glaucoma

Macular edema is a major cause of morbidity in uveitis patients. Inflammatory mediators act on the integrity of the blood ocular barrier and on the function of the RPE pump. Chronicity leads to irreversible changes and is reported to cause up to 30% of permanent visual loss in uveitis patients. Assessing the presence and severity of edema with appropriate investigational techniques (Spectral domain OCT, and angiography) help to determine its reversibility and define a therapeutic strategy wherein intraocular steroids play a key role while RPE pump stimulators and surgery are restricted to more severe disease or the presence of tractional syndromes.