Choroid Disease, Inflammation, Uveomeningoencephalitic Syndrome, Visual Impairment
Conditions
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.
Interventions
DRUGCorticosteroid monotherapy
Patients will receive corticosteroid monotherapy as a pulsetherapy (1000mg/ day for 3 days) followed by oral corticosteroid.
Sponsors
University of Sao Paulo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
All patients were treated with a standard high-dose corticosteroid
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* clinical diagnosis of Vogt-Koyanagi-Harada disease * acute onset with no previous treatment
Exclusion criteria
* non-acute VKHD * media opacities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| Ocular Hypertension | 6 to 24 months after disease onset | Ocular hypertension was defined as an intraocular pressure (IOP) above 21mmHg |
| 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 |
| 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 |
Countries
Brazil
Participant flow
Recruitment details
Date of recruitment: June, 2011 through January, 2017 Location: Ophthalmology service -Hospital das Clínicas da Universidade São Paulo
Participants by arm
| Arm | Count |
|---|---|
| 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.
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.
prednisolone and prednisone | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Corticosteroid Monotherapy |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 31 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Brazil | 12 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 6 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Median Values of ERG Scotopic Parameters 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).
Time frame: assessed at 12-month
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Corticosteroid Monotherapy | Median Values of ERG Scotopic Parameters at 12-month | Scotopic b amplitude | 201 microvolts |
| Corticosteroid Monotherapy | Median Values of ERG Scotopic Parameters at 12-month | Maximum scotopic a amplitude | 210 microvolts |
| Corticosteroid Monotherapy | Median Values of ERG Scotopic Parameters at 12-month | Maximum scotopic b amplitude | 508 microvolts |
| Corticosteroid Monotherapy | Median Values of ERG Scotopic Parameters at 12-month | Oscillatory potential | 92 microvolts |
| Corticosteroid Monotherapy | Median Values of ERG Scotopic Parameters at 12-month | Photopic a amplitude | 42 microvolts |
| Corticosteroid Monotherapy | Median Values of ERG Scotopic Parameters at 12-month | Photopic B amplitude | 202 microvolts |
| Corticosteroid Monotherapy | Median Values of ERG Scotopic Parameters at 12-month | Flicker | 52 microvolts |
p-value: <0.001generalized estimated equation
Primary
Median Values of ERG Scotopic Parameters 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).
Time frame: assessed at 24-month
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Corticosteroid Monotherapy | Median Values of ERG Scotopic Parameters at 24-month | Flicker | 54 microvolts |
| Corticosteroid Monotherapy | Median Values of ERG Scotopic Parameters at 24-month | Scotopic b amplitude | 189 microvolts |
| Corticosteroid Monotherapy | Median Values of ERG Scotopic Parameters at 24-month | Maximum scotopic a amplitude | 189 microvolts |
| Corticosteroid Monotherapy | Median Values of ERG Scotopic Parameters at 24-month | Maximum scotopic b amplitude | 484 microvolts |
| Corticosteroid Monotherapy | Median Values of ERG Scotopic Parameters at 24-month | Oscillatory potential | 114 microvolts |
| Corticosteroid Monotherapy | Median Values of ERG Scotopic Parameters at 24-month | Photopic a amplitude | 43 microvolts |
| Corticosteroid Monotherapy | Median Values of ERG Scotopic Parameters at 24-month | Photopic B amplitude | 186 microvolts |
Primary
Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-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.
Time frame: 12 and 24-months
Population: One patient had an eye classified as ERG stable group and the other eye as ERG worsening group thus the sum of both groups exceed the total 12 participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Corticosteroid Monotherapy | Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months | Maximum scotopic b amplitude | 2.8 percentage of change on ERG parameters |
| Corticosteroid Monotherapy | Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months | Photopic a amplitude | 0 percentage of change on ERG parameters |
| Corticosteroid Monotherapy | Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months | Maximum scotopic a amplitude | 7 percentage of change on ERG parameters |
| Corticosteroid Monotherapy | Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months | Photopic b amplitude | 2.4 percentage of change on ERG parameters |
| Corticosteroid Monotherapy | Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months | Oscillatory potential | 5.9 percentage of change on ERG parameters |
| Corticosteroid Monotherapy | Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months | Flicker | 6.2 percentage of change on ERG parameters |
| Corticosteroid Monotherapy | Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months | Scotopic b amplitude | 9.5 percentage of change on ERG parameters |
| ERG Worsening Group | Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months | Flicker | -6.9 percentage of change on ERG parameters |
| ERG Worsening Group | Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months | Scotopic b amplitude | -32.9 percentage of change on ERG parameters |
| ERG Worsening Group | Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months | Maximum scotopic a amplitude | -21.4 percentage of change on ERG parameters |
| ERG Worsening Group | Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months | Maximum scotopic b amplitude | -10.8 percentage of change on ERG parameters |
| ERG Worsening Group | Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months | Oscillatory potential | -47.1 percentage of change on ERG parameters |
| ERG Worsening Group | Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months | Photopic a amplitude | -5 percentage of change on ERG parameters |
| ERG Worsening Group | Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months | Photopic b amplitude | -13.6 percentage of change on ERG parameters |
Secondary
Cataract
Cataract was defined as any lens opacification greater than nuclear or cortical 2+/4 or subcapsular 1+/4
Time frame: 6 to 24 months after disease onset
Population: One patient had an eye classified as ERG stable group and the other eye as ERG worsening group thus the sum of both groups exceed the total 12 participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corticosteroid Monotherapy | Cataract | 5 eyes |
| ERG Worsening Group | Cataract | 0 eyes |
p-value: 0.272Fisher Exact
Secondary
Change in Perivascular Leakage on Fluorescein Angiography
Perivascular leakage was observed as an increase in hyperfluorescence around retinal vasculature over time on FA exam at midperiphery.
Time frame: 6 to 24 months after disease onset
Population: One patient had an eye classified as ERG stable group and the other eye as ERG worsening group thus the sum of both groups exceed the total 12 participants
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Corticosteroid Monotherapy | Change in Perivascular Leakage on Fluorescein Angiography | 9 eyes |
| ERG Worsening Group | Change in Perivascular Leakage on Fluorescein Angiography | 4 eyes |
Comparison: Change in perivascular leakage in ERG-stable and ERG- worsening groups.p-value: 0.936Generalized estimated equation
Secondary
Change in Subfoveal Choroidal Thickness on Enhanced Depth Optical Coherence Tomography
Increase of 30% or more in choroidal thickness EDI in consecutive exams on horizontal scan
Time frame: 6 to 24 months from disease onset
Population: One patient had an eye classified as ERG stable group and the other eye as ERG worsening group thus the sum of both groups exceed the total 12 participants
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Corticosteroid Monotherapy | Change in Subfoveal Choroidal Thickness on Enhanced Depth Optical Coherence Tomography | 8 eyes |
| ERG Worsening Group | Change in Subfoveal Choroidal Thickness on Enhanced Depth Optical Coherence Tomography | 4 eyes |
Secondary
Choroidal Neovascularization
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.
Time frame: 6 to 24 months after disease onset
Population: One patient had an eye classified as ERG stable group and the other eye as ERG worsening group thus the sum of both groups exceed the total 12 participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corticosteroid Monotherapy | Choroidal Neovascularization | 2 eyes |
| ERG Worsening Group | Choroidal Neovascularization | 1 eyes |
p-value: 0.853Generalized estimated equation
Secondary
Increase in the Score of Dark Dots on Indocyanine Green Angiography
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)
Time frame: 6 to 24 months from disease onset
Population: One patient had an eye classified as ERG stable group and the other eye as ERG worsening group thus the sum of both groups exceed the total 12 participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corticosteroid Monotherapy | Increase in the Score of Dark Dots on Indocyanine Green Angiography | 17 eyes |
| ERG Worsening Group | Increase in the Score of Dark Dots on Indocyanine Green Angiography | 5 eyes |
p-value: 0.478generalized estimated equation
Secondary
Ocular Hypertension
Ocular hypertension was defined as an intraocular pressure (IOP) above 21mmHg
Time frame: 6 to 24 months after disease onset
Population: One patient had an eye classified as ERG stable group and the other eye as ERG worsening group thus the sum of both groups exceed the total 12 participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corticosteroid Monotherapy | Ocular Hypertension | 7 eyes |
| ERG Worsening Group | Ocular Hypertension | 5 eyes |
p-value: 0.983Generalized estimated equation with bino
Secondary
Recurrence or Worsening of Cells in Anterior Chamber
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
Time frame: 6 to 24 months from disease onset.
Population: One patient had an eye classified as ERG stable group and the other eye as ERG worsening group thus the sum of both groups exceed the total 12 participants
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Corticosteroid Monotherapy | Recurrence or Worsening of Cells in Anterior Chamber | 8 eyes |
| ERG Worsening Group | Recurrence or Worsening of Cells in Anterior Chamber | 0 eyes |
Comparison: Recurrence or worsening of cells in anterior chamber in ERG-stable and ERG worsening group.p-value: 0.054Fisher Exact