miRNAs: una nueva mirada de la enfermedad de Vogt-Koyanagi-Harada / miRNAs: a new look at Vogt-Koyanagi-Harada disease

Vogt-Koyanagi-Harada disease (VKH) is an autoimmune multisystemic syndrome that includes bilateral intraocular inflammation, associated with exudative retinal detachments, and systemic manifestations in the auditory, integumentary, and central nervous systems. The frequency of VKH disease in the world is variable, but in Santiago, Chile, it causes approximately 17% of non-infectious uveitis, an incidence 2 to 3-fold greater than in the USA or European countries. The evidence shows that the pathogenesis of VKH would be caused by cell-mediated autoimmunity directed against melanocytes present in the uveal tissue. CD4+ T lymphocytes (especially hyperactivity of Th17 and Th1 cells), B lymphocytes, cytokines (e.g., TGF-ß, IL-2, IL-6, IL-23 and INF-γ) and chemokines appear to play an important role in the development of VKH. Several lines of evidence support that the pathogenesis of uveitis observed in VKH involves an altered pattern of micro-ribonucleic acids (miRNA) expression, driving the loss of immunological tolerance. In this review, we discuss the evidence related to regulation and altered expression of miRNA associated with Vogt-Koyanagi-Harada and other autoimmune diseases. (AU)

Characteristics, Upon Presentation, of a Cohort of Patients with Vogt-Koyanagi-Harada Disease in Puerto Rico.

OBJECTIVE: To describe the clinical features, upon initial presentation, of a cohort of patients with Vogt-Koyanagi-Harada (VKH) disease who live in Puerto Rico. METHODS: A retrospective medical record review of patients with VKH was performed. The demographic and clinical characteristics were analyzed. RESULTS: Twenty-two patients who met the diagnostic criteria for VKH were identified and included in the analysis. The median age at presentation was 41 years; 68.2% were female, and all patients were Hispanics. Bilateral disease was present in 90.9% of patients, and 59.1% of patients were categorized as having probable VKH. A headache was reported in 54.5% of patients and was the most common complaint at the time of presentation; the second most common complaint was tinnitus, which was present in 22.7% of patients. Vitiligo, alopecia, and meningismus were each preset in 9.1% of patients while hearing loss and aseptic meningitis were each reported in 4.5% of patients. Seventy-seven percent of patients had either topical or systemic corticosteroid use prior to the initial encounter. CONCLUSION: Our study suggests that in Puerto Rico, patients with Vogt-Koyanagi-Harada disease may have a distinctive prevalence of characteristics at the presentation when compared to other ethnic groups, including other Hispanic cohorts.

Impact of Inflammation and Treatment on Self-reported Quality of Life in Patients with Non-acute Vogt-Koyanagi-Harada Disease (VKHD).

Aims: To evaluate associations between vision-related (VR-) and health-related (HR-) QoL metrics and inflammation and treatment in non-acute VKHD patients.Methods: Cross-sectional study in a tertiary center in Sao Paulo, Brazil with 22 patients with non-acute VKHD followed prospectively for ≥12 months since acute disease onset, with systematic evaluation and predefined treatment protocols. VR- and HR-QoL aspects were assessed by VFQ-25 and SF-36 questionnaires, respectively. Associations between the questionnaire's subscale item scores with inflammation and systemic medical therapies were assessed.Results: After generalized linear model analysis, worse VA, severe fundus changes, fluctuation of VA and fluctuation of anterior chamber cells impacted negatively on VR-QoL items. Higher cumulative total dose of corticosteroids and use of immunosuppressive therapy impacted negatively on both questionnaires.Conclusion: Worse VA, clinical inflammation and systemic treatment have a significant impact on VR- and HR-QoL questionnaires. Subclinical choroidal inflammation did not seem to impact QoL.

Vogt-Koyanagi-Harada Syndrome in Brazilian Children.

Purpose To evaluate the characteristics of Vogt-Koyanagi-Harada (VKH) syndrome in Brazilian children.Methods Clinical data were obtained from the medical records of six children with VKH disease from March 2014 to June 2018 at the Federal University of São Paulo, Brazil.Results Six patients met the diagnostic criteria for VKH. The patients, who ranged in age from 5 to 8 years, all presented with chronic disease. The most common ocular finding was abnormal fundus pigmentation in five patients followed by band keratopathy in four. Two patients had glaucoma, cataract, and subretinal neovascularization. The final visual acuity was less than 20/40 in 50% of the eyes.Conclusion Visual outcomes were favorable in half of patients depending on the long-term sequelae. VKH is rarely reported in children and it may be sight-threatening, and requires careful attention, being an important differential diagnosis.

Síndrome de Vogt-Koyanagi-Harada en niños / Vogt-Koyanagi-Harada syndrome in children

Vogt-Koyanagi-Harada (VKH) syndrome is a systemic inflammatory disease that causes chronic and bilateral granulomatous panuveitis, usually described in adults. Objectives: To describe manifestations and complications of VKH in pediatric patients. Methods: Retrospectivedescriptive study upon patients <14 years-old with VKH, attended from January 1985 to July 2010 in three different centers. Results: A total of 17 patients (34 eyes) were studied; 9 (53%) female. The mean age was 10.8 years-old. Among extraocular manifestations; neurological (71%), dermatological (29%) and auditive (24%) signs were observed. Ocular findings included optic-disc involvement (94%), anterior uveitis (79%), choroiditis (77%), serous retinal detachment (71%) and vitritis (71%). Initial visual acuity (VA) was ≤0.05 in 47% of cases and ≥0.6 in 12% of patients. 71% presented complications: glaucoma (20 eyes), sinechiae (10 eyes), maculopathy (6 eyes) cataract (5 eyes) and ptisis bulbi (1 eyes). 35% received only corticosteroids and 65% inmunosupressive drugs. After treatment, 6% had VA ≤0.05 and 59% ≥0.6. Ten patients (59%) recurred: 30% compromising posterior pole, and 50% recurred >3 times. Conclusions: VKH in children is infrequent. It presents with optic-disc involvement and complications of posterior pole. It requires a high degree of suspicion, quick evaluation and early treatment, which include inmunosupressive and extended corticosteroid therapy. Nevertheless, a high rate of recurrence is seen among this group of patients. (AU)

High rate of clinical recurrence in patients with Vogt-Koyanagi-Harada disease treated with early high-dose corticosteroids.

PURPOSE: To analyse the rate of clinical recurrences in Brazilian patients with Vogt-Koyanagi-Harada (VKH) disease after early high-dose corticosteroid treatment. METHODS: Retrospective study including patients treated with early high-dose corticosteroids (prednisone, 1-1.5 mg/kg/day, or 3-day 1 g methylprednisolone pulsetherapy) within 1 month from disease onset followed by slow taper (at least 6 months). Patients with a minimum 12-month follow-up were subdivided based on the presence of disease recurrence or persistence after 6 months from initial presentation into: acute-resolved (AR, no recurrences), chronic-recurrent (CR), and chronic-recurrent with subretinal fibrosis (SRF). Recurrences were defined as the presence of clinical and/or fluorescein angiography findings. RESULTS: Twenty-nine patients (58 eyes) with a median follow-up of 65 months were included. Six (21 %), 11 (38 %) and 12 (41 %) patients were allocated to AR, CR, and SRF groups respectively. Though having received treatment within 1 month of onset, median time to initial treatment differed among groups (11, 15, and 25 days, in AR, CR, and SRF groups respectively). Intensity of immunosuppression, cataract development, and longer time to achieve logMAR visual acuity ≤0.8 differed significantly among the groups, being more severe in SRF group. HLA-DRB1*0405 allele followed the same trend, though not reaching significance (0.5 in AR group, 0.6 in CR, and 0.8 in SRF). CONCLUSION: VKH disease in Brazilian patients evolved to chronic-recurrent disease in 79 % of cases; 38 % developed subretinal fibrosis, in spite of similar initial treatment regimens. Time to initiate treatment influenced outcomes.

Vogt-Koyangi-Harada en fase crónica y terapia biológica: reporte de cuatro casos / Vogt-Koyanagi-Harada in chronic phase of recurrence and biological therapy: report of four cases

Objetivo: describir cuatro casos de Vogt Koyanagi Harada (VKH), con uveítis en fase crónica de recurrencia y la respuesta a fármacos anti TNF alfa. Diseño: reporte de casos. Métodos: se realizó estudio descriptivo tipo reporte de caso, mediante recolección y análisis de historias clínicas de pacientes adultos de un centro de referencia de enfermedades autoinmunes, que cumplieran criterios diagnósticos de VKH y que estuvieran en tratamiento con terapia biológica para dicha patología. Resultados: en el presente artículo informamos una serie de cuatro casos de VKH, de los cuales todas fueron mujeres entre los 19 y 57 años, en fase crónica y de recurrencia de la enfermedad. En todos los casos existió refractariedad al uso de esteroides a dosis altas y no respuesta a inmunosupresores como ciclosporina y metotrexate, requiriéndose instauración de terapia biológica anti TNF alfa con control de su patología. Conclusiones: En el VKH en fases tardías la respuesta a altas dosis de esteroides y a inmunosupresores convencionales puede ser fallida, ante lo cual el uso de terapia biológica con fármacos anti TNF alfa y anti CD20 es una alternativa factible, requiriéndose aún mayores estudios en este campo que permitan una prescripción eficaz y segura.

Objective: to describe four cases of Vogt Koyanagi Harada (VKH) disease, in chronic and recurrence phase that were treated with anti-TNF biological therapy and their response to this therapy. Design: cases reports. Methods: We performed a descriptive, case report with clinical chart review of adult patients in a center of autoimmune diseases who met diagnostic criteria for VKH and treated with biological therapy. Results: We report four cases of VKH treated in our center of autoimmune diseases, which were all women between 19 and 57 years, in chronic and recurrence phase of disease. In all cases there was refractory to steroid use at high doses and no response to immunosuppressive treatment as cyclosporine and methotrexate, requiring introduction of anti-TNF biological therapy to control their disease. Conclusions: In chronic phases of VKH the response to high doses of steroids and conventional immunosuppressive therapy may be failed, therefore the use of biological therapy with anti-CD20 and anti-TNF alpha is a viable alternative, still requiring further study in this fi eld to enable an eff ective and safe prescription.

Indocyanine green angiography findings in patients with long-standing Vogt-Koyanagi-Harada disease: a cross-sectional study.

BACKGROUND: To investigate indocyanine green angiography (ICGA) findings in patients with long-standing Vogt-Koyanagi-Harada (VKH) disease and their correlation with disease activity on clinical examination as well as with systemic corticosteroid therapy. METHODS: Twenty-eight patients (51 eyes) with long-standing (≥6 months from disease onset) VKH disease whose treatment was tapered based only in clinical features were prospectively included at a single center in Brazil. All patients underwent standardized clinical evaluation, which included fundus photography, fluorescein angiography and ICGA. Clinical disease activity was determined based in the Standardization in Uveitis Nomenclature Working Group. Fisher exact test and logistic regression models were used for statistical analysis. RESULTS: Disease-related choroidal inflammation on ICGA was observed in 72.5% (31 of 51 eyes). Angiographic findings suggestive of (choroidal and/or retinal) disease activity were not observed on FA. Clinically active disease based on clinical evaluation was observed in 41.2% (21 of 51 eyes). In these 21 eyes, disease-related choroidal inflammation on ICGA was observed in 76.2% (16 of 21 eyes); in the remaining eyes (without clinical active disease) disease-related choroidal inflammation on ICGA was observed in 70.0% (21 of 30 eyes). In respect to systemic corticosteroid therapy, 10 patients (18 of 51 eyes) were under treatment with prednisone. In these 10 (18 of 51 eyes) patients, disease-related choroidal inflammation on ICGA was observed in 83.3% (15 of 18 eyes); in the remaining patients (33 of 51 eyes) disease-related choroidal inflammation on ICGA was observed in 66.7% (22 of 33 eyes). CONCLUSION: ICGA findings suggestive of disease-related choroidal inflammation were observed in a considerable proportion of patients with long-standing VKH disease, independent of the inflammatory status of the disease on clinical examination or current use of systemic corticosteroid. Therefore, the current study reinforces the crucial role of ICGA to assist the management and treatment of patients with long-standing VKH disease.

Síndrome de Vogt Koyanagi Harada / Vogt-Koyanagi-Hada syndrome

El síndrome de Vogt Koyanagi Harada es una uveitis difusa, bilateral, aguda, granulomatosa, asociada a manifestaciones dermatológicas, auditivas y del sistema nervioso central. Es la panuveitis bilateral más frecuentemente encontrada en la población mestiza e indígena mexicana. Una respuesta autoinmune, regulada por factores genéticos y aparentemente dirigada contra los melanocitos parece ser la causa del proceso inflamatorio. El diagnóstico básicamente es clínico, aunque la florangiografía de retina y el estudio ecográfico pueden ayudar a sustentar el diagnóstico básicamente es clínico, aunque la florangiografía de retina y el estudio ecográfico pueden ayudar a sustentar el diagnóstico en algunos casos. En el presente artículo revisamos los conocimientos que en relación a fisiopatogenia, diagnóstico, pronóstico, tratamiento médico y quirúrgico se tienen actualmente

Sindrome de Vogt-Koyanagi-Harada / Vogt-Koyanagi-Harada syndrome

Se informan tres pacientes con el sindrome de Vogt-Koyanagi-Harada, conocido tambien como uveomeningoencefalitis, entidad poco conocida, de causa no claramente determinada, caracterizada por un proceso inflamatorio que compremete uvea, retina, meninges y piel.

Vogt-Koyanagi-Harada's disease in Brazil.

A retrospective analysis of 33 patients with Vogt-Koyanagi-Harada disease (VKH disease) seen in São Paulo, Brazil, from 1976 to 1985 at a uveitis referral clinic revealed that VKH disease represents 2.5% of the total uveitis cases seen. All cases were bilateral, 30% being men and 70% women. The ethnic distribution was the following: 60% white (with variable Indian or black extraction), 24% darkly pigmented, 9% Orientals (Sansei, third-generation Japanese) and 6% black. The frequency among Orientals was 7 times higher than what would be expected according to the relative frequency of Japanese in the Brazilian population. The age distribution at the onset of the disease was as follows: 12% less than 20 years of age, 60% between 20 and 40 years of age and 27% over 40 years of age. The disease was classified into 3 types with variable extraocular signs. Type I disease was present in 24% of the patients, type II in 51% and type III disease in 24% of the patients. Cataract was present in 40% of the cases and glaucoma was present in 9%. No correlation was found between sex, age at onset, race, type of extraocular involvement and number of extraocular manifestations in considering either visual status or visual prognosis. All patients were treated with systemic steroids. Most of them also received cytotoxic immunosuppressive agents. In this uncontrolled clinical study cytotoxic drug-treated patients seemed to have a better clinical course.