Early Immunosuppressive Therapy on the Course of Vogt-Koyanagi-Harada Disease

Study Overview
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Brief Summary
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This prospective study will include patients with Vogt-Koyanagi-Harada disease from disease onset, treated with early systemic high-dose corticosteroid and immunosuppressive therapy. Clinical and subclinical signs of disease activity added with electroretinogram exams, through predefined intervals, will be evaluated through a minimum 12-month follow-up.

Detailed Description
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Vogt-Koyanagi-Harada disease (DVKH) is an autoimmune disorder, which is mainly a T CD4+ Th1 lymphocyte mediated aggression to melanocytes, in individuals with a genetic predisposition, in particular, the presence of HLA-DRB1*0405 allele. It is an important cause of non-infectious uveitis at tertiary services in Brazil and a major cause of uveitis in general, in some regions of the world, such as in Japan and Asia. Its clinical course is classically defined in four phases: prodromal, with general symptoms possibly related to a viral trigger; uveitic, with sudden decrease in visual acuity in both eyes with a diffuse choroiditis associated or not to iridocyclitis; convalescent, wherein the depigmentation of the integument and choroid is more evident, with an apparently quiescent disease from a clinical point of view; and chronic or recurrent, in which the predominant inflammatory signs of anterior segment are clinically detected and complications are more evident, such as choroidal neovascularization, cataract and glaucoma. Recent studies have shown subclinical inflammation of the choroid, detected by indocyanine green angiography (ICGA) and also by enhanced-depth imaging spectral-domain optical coherence tomography (EDI-OCT). Several authors have been taking these findings into account for inflammation monitoring and treatment follow-up. However, the wider knowledge of these subclinical signs of inflammation and the understanding of the disease's course from a global perspective are still scarce. The study developed by Sakata et al. (2012-2015) established an early and aggressive treatment with pulsetherapy of methylprednisolone, followed by high doses of oral prednisone (1 mg / kg / day) with slow and gradual tapering over a 15-month period. Such study has showed that, despite an adequate treatment: a) 94% of patients had worsening of visual acuity or disease relapse during a 12-month follow-up; b) subclinical signs fluctuated without changing the initial treatment ; c) particular cases, in which there was an increase of treatment, showed better retinal function at final follow-up. Thus, this study aims to continue the evaluation of subclinical signs and their clinical and functional relevance, as well as, with an early immunomodulatory treatment, to observe the clinical course of DVKH and its behavior in functional terms and development of complications. Study design: prospective and longitudinal, with a minimum 12-month follow-up, with integrated clinical, angiographic, tomographic and functional assessments. On clinical examination, anterior segment inflammatory signs will be evaluated (cells in anterior chamber), as well as posterior findings (observed in the acute phase: optic disc hyperemia, exudative retinal detachment, macular edema, vasculitis, vitreous haze); on angiographic evaluation, fluorescein angiogram (FA) and ICGA will be included; on tomographic evaluation, evaluation of retina and choroid will be included (EDI-OCT); and, on the functional tests, it will be included: the full-field electroretinography (ERGct) and multifocal electroretinography (ERGmf); as well as autofluorescence (AF) with blue light (Bl-AF) and near-infrared light (NIR-AF); automated perimetry (30-2) and contrast sensitivity test. Quality of life questionnaires and visual function evaluation will be included in pre-defined intervals. Expected results: 1. To reaffirm the importance of an integrated analysis of the clinical and ancillary tests for better patient monitoring and to improve disease prognosis; 2. To increase the understanding of the disease natural course; 3. To increase the understanding of the disease pathogenesis; and, 4. To set parameters (outcomes) that can guide therapy.

Official Title
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Influência de imunomodulação Precoce Influence of Early Immunosuppressive Therapy on the Course of Vogt-Koyanagi-Harada Disease: a Prospective Study

Conditions
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Vogt Koyanagi Harada Disease

Intervention / Treatment
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* Drug: Early high-dose corticosteroid and immunosuppressive therapy


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: - acute Vogt-Koyanagi-Harada disease Exclusion criteria: non collaborative patient minimum one-year follow-up

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Early systemic high-dose corticosteroid and immunosuppressive therapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment group<br>Early high-dose corticosteroid and immunosuppressive therapy | Drug: Early high-dose corticosteroid and immunosuppressive therapy<br>* Early high-dose corticosteroid and immunosuppressive therapy<br>* Other names: Treatment group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| scotopic electroretinogram results | scotopic results variation between 12 months and 6 months | 6 month; 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| presence of optic disc hyperfluorescence detected on fluorescein angiography | presence of optic disc hyperfluorescence and variation in intensity in consecutive examinations | between 6 and 12 months from disease onset. | 
| presence of perivascular leakage on fluorescein angiography | presence of perivascular leakage and variation in extension and intensity in consecutive examinations | between 6 and 12 months from disease onset. | 
| presence of dark dots on indocyanine green angiography | dark dots score and its fluctuation | between 6 and 12 months from disease onset. | 
| subfoveal choroidal thickness on enhanced depth imaging optical coherence tomography | subfoveal choroidal thickness and its variation | between 6 and 12 months from disease onset. | 
| presence of cells in anterior chamber graduated according to SUN criteria | presence of cells in anterior chamber and its variation | between 6 and 12 months from disease onset. | 
| presence of choroidal neovascular membrane on OCT and/or FA | choroidal neovascular membrane | between 6 and 12 months from disease onset. | 
| presence of macular edema on OCT and/or FA | macular edema detected clinically, angiographically and/or by optical coherence tomography | between 6 and 12 months from disease onset. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vogt-Koyanagi-Harada disease, Immunosuppressive therapy, Indocyanine green angiography, Enhanced depth imaging optical coherence tomography, Electroretinogram