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

Choroidal Neovascularization Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02015351
• Other study ID #: Brazilian VKH Study Group
• Status: Completed
• Phase: N/A
• Start date: September 2012
• Est. completion date: October 2018

Study information

• Verified date: January 2022
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: October 2018
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients diagnosed with Vogt-Koyanagi-Harada disease based on Revised Diagnostic Criteria presented by the International Committee on VKH disease in 2001;

2. 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.

Related Conditions & MeSH terms

• Choroidal Neovascularization
• Neovascularization, Pathologic

Intervention

Drug:
• bevacizumab
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.

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas- University of Sao Paulo	Sao Paulo

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	Fundação de Amparo à Pesquisa do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (8)

Adán A, Mateo C, Navarro R, Bitrian E, Casaroli-Marano RP. Intravitreal bevacizumab (avastin) injection as primary treatment of inflammatory choroidal neovascularization. Retina. 2007 Nov-Dec;27(9):1180-6. — View Citation

Kolomeyer AM, Roy MS, Chu DS. The use of intravitreal ranibizumab for choroidal neovascularization associated with vogt-koyanagi-harada syndrome. Case Rep Med. 2011;2011:747648. doi: 10.1155/2011/747648. Epub 2011 Aug 3. — View Citation

Mansour AM, Arevalo JF, Ziemssen F, Mehio-Sibai A, Mackensen F, Adan A, Chan WM, Ness T, Banker AS, Dodwell D, Chau Tran TH, Fardeau C, Lehoang P, Mahendradas P, Berrocal M, Tabbarah Z, Hrisomalos N, Hrisomalos F, Al-Salem K, Guthoff R. Long-term visual o — View Citation

Nowilaty SR, Bouhaimed M; Photodynamic Therapy Study Group. Photodynamic therapy for subfoveal choroidal neovascularisation in Vogt-Koyanagi-Harada disease. Br J Ophthalmol. 2006 Aug;90(8):982-6. Epub 2006 May 10. — View Citation

Perentes Y, Van Tran T, Sickenberg M, Herbort CP. Subretinal neovascular membranes complicating uveitis: frequency, treatments, and visual outcome. Ocul Immunol Inflamm. 2005 Apr-Jun;13(2-3):219-24. — View Citation

Rouvas A, Petrou P, Douvali M, Ntouraki A, Vergados I, Georgalas I, Markomichelakis N. Intravitreal ranibizumab for the treatment of inflammatory choroidal neovascularization. Retina. 2011 May;31(5):871-9. doi: 10.1097/IAE.0b013e3182003ca8. — View Citation

Tran TH, Fardeau C, Terrada C, Ducos De Lahitte G, Bodaghi B, Lehoang P. Intravitreal bevacizumab for refractory choroidal neovascularization (CNV) secondary to uveitis. Graefes Arch Clin Exp Ophthalmol. 2008 Dec;246(12):1685-92. doi: 10.1007/s00417-008-0 — View Citation

Wu L, Evans T, Saravia M, Schlaen A, Couto C. Intravitreal bevacizumab for choroidal neovascularization secondary to Vogt-Koyanagi-Harada syndrome. Jpn J Ophthalmol. 2009 Jan;53(1):57-60. doi: 10.1007/s10384-008-0600-4. Epub 2009 Jan 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visual Acuity change	Visual Acuity will be measured using Snellen charts with best refraction by the same examiner.	6 months
Primary	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
Primary	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	Visual Acuity change	Visual Acuity will be measured using Snellen charts with best refraction by the same examiner.	12 months
Secondary	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
Secondary	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