Multimodal Analysis and Electroretinogram in VKH From Acute Onset - Part I

Not Applicable

Completed

Conditions: Uveomeningoencephalitic Syndrome
Choroid Disease
Visual Impairment
Inflammation

Interventions: Drug: Corticosteroid monotherapy

Registration Number: NCT03811366

Lead Sponsor: University of Sao Paulo

Brief Summary: Patients with acute onset Vogt-Koyanagi-Harada disease (VKHD) were prospectively included in this study. They were systematically followed with clinical, posterior segment imaging exams and full-field electroretinogram during a minimum 24-month of follow-up. All patients were treated with 3-day methylprednisolone pulse therapy followed by 1mg/day oral prednisone with a slow tapper during a median of 13 months. Non-steroidal immunosuppressive therapy (IMT) was introduced in cases of refractory disease or in cases of prednisone intolerance. Outcome measured by full-field electroretinogram was analyzed and patient was grouped as electroretinogram stable or electroretinogram worsening. Clinical data was analyzed in these two electroretinogram-based groups.

Detailed Description: Consecutive patients with acute onset VKHD were included and followed for a minimum 24-month as Part I of an ongoing prospective long-term study on VKHD. The main purpose was to understand the course of clinical and subclinical choroidal inflammation in patients receiving early and high-dose corticosteroid followed by high-dose oral prednisone and a very slow tapper. All patients were followed with clinical and posterior segment imaging (PSI) exams, i.e. fundus picture, fluorescein angiography, indocyanine green angiography and enhanced depth imaging optical coherence tomography, at inclusion, 1st month, and thereof every three months. Full-field electroretinogram was performed at inclusion, 1st month, and thereof every six months. Flare was defined as appearance or increase/worsening of inflammatory signs after the initial six-month from disease onset during the predefined treatment protocol. Inflammatory signs were cells in anterior chamber, macular edema; subclinical inflammatory signs were mainly those observed by PSI exams. Scotopic full-field electroretinogram results between 12 and 24 month were the main outcome. Clinical data was analyzed in the full-field electroretinogram-based groups.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 12

Inclusion Criteria

clinical diagnosis of Vogt-Koyanagi-Harada disease
acute onset with no previous treatment

Exclusion Criteria

non-acute VKHD
media opacities

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Corticosteroid monotherapy	Corticosteroid monotherapy	All patients in the acute phase will be treated with corticosteroid monotherapy, unless presents a contraindication or persistence/ recurrence of inflammation with regressive corticosteroid monotherapy.This is the unique arm of the present study. Treatment protocol includes a three-day course of intravenous methylprednisolone (1000 mg per day) followed by a high dose of oral prednisone (1.0 mg/kg/day) with a slow tapering with dose equal or less than 0.1mg/kg/day after 10 months. The prednisone dose is scheduled to be reduced in a 0.1 mg/kg-step ladder until it reaches 0.3 mg/kg (i.e. for an individual with 60 kg, dose would be 20 mg): from 1 to 0.8 mg/kg every two to three weeks; at 0.7 mg/kg for 4 weeks; at 0.6 mg/kg for two to three weeks; from 0.5 mg/kg every 4 weeks; from 0.3 to 0.15 mg/kg every 6 weeks; and 0.1 mg/kg, 0.075 mg/kg and 0.05 mg/kg for 8 weeks each.

Primary Outcome Measures

Name	Time	Method
Median Values of ERG Scotopic Parameters at 12-month	assessed at 12-month	Full-field electroretinogram (ERG) scotopic parameters were evaluated at 12 -month (scotopic parameters: amplitude of scotopic a and b wave, amplitude of maximum scotopic a and b wave, oscillatory potential).
Median Values of ERG Scotopic Parameters at 24-month	assessed at 24-month	Full-field electroretinogram (ERG) scotopic parameters were evaluated at 24 -month (scotopic parameters: amplitude of scotopic a and b wave, amplitude of maximum scotopic a and b wave, oscillatory potential).
Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months	12 and 24-months	Full-field electroretinogram (ERG) scotopic parameters at 12 and 24 months were compared (scotopic parameters: amplitude of scotopic a and b wave, amplitude of maximum scotopic a and b wave, oscillatory potential). The worsening of the ERG parameters was defined as a value reduction of ≥ 30 % in any these scotopic ERG parameters at month 12 and month 24. We report the change between the (value at month 24/ the value at month 12)\*100.

Secondary Outcome Measures

Name	Time	Method
Recurrence or Worsening of Cells in Anterior Chamber	6 to 24 months from disease onset.	Evaluation of anterior chamber (AC) cells was performed at visits 6 months, 12 months, 18 months and 24 months from disease onset, according to the Standardization of Uveitis Nomenclature´s classification of anterior chamber cells. (Am J Ophthalmol, 2005) Any step increase (fluctuation), when comparing sequential dates of follow up (e.g 6 and 12 months) were considered as one episode of clinical worsening in AC cells
Increase in the Score of Dark Dots on Indocyanine Green Angiography	6 to 24 months from disease onset	Dark dots scores had a maximum value of 8, any increase of 0.5 after 6 months from disease onset will be considered (Int Ophthalmo 2010) Dark dots Score based on pattern of distribution (Sparse/ Numerous) Minimum: 0 (better outcome) Maximum: 8 (worse outcome)
Change in Subfoveal Choroidal Thickness on Enhanced Depth Optical Coherence Tomography	6 to 24 months from disease onset	Increase of 30% or more in choroidal thickness EDI in consecutive exams on horizontal scan
Change in Perivascular Leakage on Fluorescein Angiography	6 to 24 months after disease onset	Perivascular leakage was observed as an increase in hyperfluorescence around retinal vasculature over time on FA exam at midperiphery.
Choroidal Neovascularization	6 to 24 months after disease onset	Choroidal neovascularization was diagnosed when increasingly localized hyperfluorescence at the posterior pole is detected on FA or a hyperreflective subretinal lesion associated with sub or intraretinal fluid on OCT.
Cataract	6 to 24 months after disease onset	Cataract was defined as any lens opacification greater than nuclear or cortical 2+/4 or subcapsular 1+/4
Ocular Hypertension	6 to 24 months after disease onset	Ocular hypertension was defined as an intraocular pressure (IOP) above 21mmHg