Intravitreal Bevacizumab for the Treatment of CNV in VKH Disease - A Prospective Study

Study Overview
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Brief Summary
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Efficacy of monthly intravitreal anti-vascular endothelial growth factor (VEGF) associated to systemic immunosuppression in patients with Vogt-Koyanagi-Harada Disease and choroidal neovascularization. Minimum follow-up 12 months. Endpoints: 6 and 12 months of follow-up. Outcome measures: improvement of VA, decrease in central foveal thickness as measured by Optical Coherence Tomography (OCT) and absence of intra/subretinal fluid.

Detailed Description
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Choroidal neovascularization (CNV) in Vogt-Koyanagi-Harada (VKH) disease is associated with poor visual prognosis. Several treatments have been suggested, though there is still no standard therapy. CNV diagnosis will be based on fundus biomicroscopy (presence of serous retinal detachment with or without retinal hemorrhages), fluorescein angiography (FA) (presence of early phase hyperfluorescence with late phase leakage) and OCT findings (hyperreflective lesion related to a CNV complex with serous foveal detachment or intraretinal fluid with increased foveal thickness). Inflammation will be considered active if anterior chamber cells or optic disc leakage in FA is observed. Each patient will undergo a complete clinical exam, including best corrected visual acuity (VA) (Snellen charts). Once active CNV is identified, a loading dose of 3 injections of IV bevacizumab will be proceeded monthly and systemic immunosuppression will be introduced or intensified. After the first 3 injections, the patient will be clinically examined and OCT will be proceeded monthly. The persistence of intra/subretinal fluid in the OCT will indicate one more IV bevacizumab injection. Immunosuppression status evaluation will be done at 3, 6, 9 and 12 months of follow up and intensification will be done if inflammatory signs or persistence of intraretinal fluid is observed. Presence of intra/subretinal fluid and manual measurement of retina central foveal thickness (CFT) will be proceeded in horizontal scan by the same examiner.

Official Title
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Intravitreal Bevacizumab for the Treatment of Choroidal Neovascularization in Vogt-Koyanagi-Harada Disease - A Prospective Study

Conditions
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Choroidal Neovascularization

Intervention / Treatment
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* Drug: bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with Vogt-Koyanagi-Harada disease based on Revised Diagnostic Criteria presented by the International Committee on VKH disease in 2001; Presence of choroidal neovascularization identified by fundus biomicroscopy, fluorescein angiography and OCT. Exclusion Criteria: Media opacities precluding posterior segment exam, ametropia over 5 dioptries, glaucoma (defined as a disease with characteristic damage at the optic nerve or characteristic visual field defect with compatible nerve fiber layer lesion), Age related Macular degeneration, impossibility to increase immunosuppression.

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anti-VEGF and Immunosuppression<br>Bevacizumab: Dosage 1.25mg/0.05ml; Frequency monthly injections; Duration at least 3 months. Immunosuppression: cyclosporine and/or azathioprine | Drug: bevacizumab<br>* Injection technique: After lid speculum insertion and irrigation of the conjunctiva with 5% povidone-iodine, 0,05ml of bevacizumab will be inserted through the pars plana 3.5mm to 4.0mm posterior to the surgical limbus using a 30 gauge needle. After injection, topical antibiotics will be immediately applied in the injected eye. Immunosuppression: Corticosteroids will be prescribed (1mg/Kg/d) with tapering along 5 months. Immunosuppressive drug of choice is cyclosporine (3-5mg/Kg/d). In case of contraindication to cyclosporine use, azathioprine or mycophenolate mofetil will be prescribed.<br>* Other names: Bevacizumab (Avastin;Genentech Inc,USA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Acuity change | Visual Acuity will be measured using Snellen charts with best refraction by the same examiner. | 6 months | 
| Change in central foveal thickness | Central foveal thickness will be measured manually using the caliper by the same examiner. Measurements will be proceeded from the Bruch's membrane till the internal limiting membrane and comparison with previous measurement will be done. | 6 months | 
| Presence or absence of intra/subretinal fluid in OCT | OCT will be analyzed at 6 and 12 months for the presence of intra or subretinal fluid. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Acuity change | Visual Acuity will be measured using Snellen charts with best refraction by the same examiner. | 12 months | 
| Change in Central Foveal Thickness | Central foveal thickness will be measured manually using the caliper by the same examiner. Measurements will be proceeded from the Bruch's membrane till the internal limiting membrane and comparison with previous measurement will be done. | 12 months | 
| Presence or Absence of Intra/Subretinal fluid in OCT | OCT will be analyzed at 6 and 12 months for the presence of intra or subretinal fluid. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Choroidal neovascularization, Vogt Koyanagi Harada Disease, Inflammatory choroidal neovascularization, Anti-VEGF