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

Inflammation Clinical Trial

Official title:

Multimodal Analysis and Electroretinogram in VKH From Acute Onset - a Prospective Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03811366
• Other study ID #: Brazilian VKH Study Group I
• Status: Completed
• Phase: N/A
• Start date: June 1, 2011
• Est. completion date: January 31, 2017

Study information

• Verified date: January 2019
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with acute onset Vogt-Koyanagi-Harada disease (VKHD) was 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.

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 information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 31, 2017
• Est. primary completion date: January 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• clinical diagnosis of Vogt-Koyanagi-Harada disease

• acute onset with no previous treatment

Exclusion Criteria:

• non-acute VKHD

• media opacities

Related Conditions & MeSH terms

• Choroid Disease
• Inflammation
• Uveomeningoencephalitic Syndrome
• Vision Disorders
• Vision, Low
• Visual Impairment

Intervention

Drug:
• Meticorten
All patients were treated with 3-day methylprednisolone pulse therapy followed by 1mg/day oral prednisone with slow tapper over a median 13 months

Locations

Country	Name	City	State
Brazil	Hospital das Clinicas HCFMUSP, Faculdade de Medicina Universidade de Sao Paulo	São Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (15)

Abu El-Asrar AM, Dosari M, Hemachandran S, Gikandi PW, Al-Muammar A. Mycophenolate mofetil combined with systemic corticosteroids prevents progression to chronic recurrent inflammation and development of 'sunset glow fundus' in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease. Acta Ophthalmol. 2017 Feb;95(1):85-90. doi: 10.1111/aos.13189. Epub 2016 Aug 18. — View Citation

Chee SP, Jap A, Bacsal K. Spectrum of Vogt-Koyanagi-Harada disease in Singapore. Int Ophthalmol. 2007 Apr-Jun;27(2-3):137-42. Epub 2006 Nov 11. — View Citation

Chee SP, Luu CD, Cheng CL, Lim WK, Jap A. Visual function in Vogt-Koyanagi-Harada patients. Graefes Arch Clin Exp Ophthalmol. 2005 Aug;243(8):785-90. Epub 2005 Mar 11. — View Citation

da Silva FT, Hirata CE, Olivalves E, Oyamada MK, Yamamoto JH. Fundus-based and electroretinographic strategies for stratification of late-stage Vogt-Koyanagi-Harada disease patients. Am J Ophthalmol. 2009 Dec;148(6):939-45.e3. doi: 10.1016/j.ajo.2009.06.029. Epub 2009 Sep 24. — View Citation

Du L, Kijlstra A, Yang P. Vogt-Koyanagi-Harada disease: Novel insights into pathophysiology, diagnosis and treatment. Prog Retin Eye Res. 2016 May;52:84-111. doi: 10.1016/j.preteyeres.2016.02.002. Epub 2016 Feb 11. Review. — View Citation

Herbort CP Jr, Abu El Asrar AM, Takeuchi M, Pavésio CE, Couto C, Hedayatfar A, Maruyama K, Rao X, Silpa-Archa S, Somkijrungroj T. Catching the therapeutic window of opportunity in early initial-onset Vogt-Koyanagi-Harada uveitis can cure the disease. Int Ophthalmol. 2018 Jun 11. doi: 10.1007/s10792-018-0949-4. [Epub ahead of print] — View Citation

Herbort CP Jr, Abu El Asrar AM, Yamamoto JH, Pavésio CE, Gupta V, Khairallah M, Tugal-Tutkun I, Soheilian M, Takeuchi M, Papadia M. Reappraisal of the management of Vogt-Koyanagi-Harada disease: sunset glow fundus is no more a fatality. Int Ophthalmol. 2017 Dec;37(6):1383-1395. doi: 10.1007/s10792-016-0395-0. Epub 2016 Nov 14. Review. — View Citation

Kawaguchi T, Horie S, Bouchenaki N, Ohno-Matsui K, Mochizuki M, Herbort CP. Suboptimal therapy controls clinically apparent disease but not subclinical progression of Vogt-Koyanagi-Harada disease. Int Ophthalmol. 2010 Feb;30(1):41-50. doi: 10.1007/s10792-008-9288-1. Epub 2009 Jan 17. — View Citation

Lavezzo MM, Sakata VM, Morita C, Rodriguez EE, Abdallah SF, da Silva FT, Hirata CE, Yamamoto JH. Vogt-Koyanagi-Harada disease: review of a rare autoimmune disease targeting antigens of melanocytes. Orphanet J Rare Dis. 2016 Mar 24;11:29. doi: 10.1186/s13023-016-0412-4. Review. — View Citation

Nakayama M, Keino H, Watanabe T, Okada AA. Clinical features and visual outcomes of 111 patients with new-onset acute Vogt-Koyanagi-Harada disease treated with pulse intravenous corticosteroids. Br J Ophthalmol. 2018 Apr 17. pii: bjophthalmol-2017-311691. doi: 10.1136/bjophthalmol-2017-311691. [Epub ahead of print] — View Citation

Rao NA. Pathology of Vogt-Koyanagi-Harada disease. Int Ophthalmol. 2007 Apr-Jun;27(2-3):81-5. Epub 2007 Apr 14. Review. — View Citation

Rubsamen PE, Gass JD. Vogt-Koyanagi-Harada syndrome. Clinical course, therapy, and long-term visual outcome. Arch Ophthalmol. 1991 May;109(5):682-7. — View Citation

Tugal-Tutkun I, Herbort CP, Khairallah M; Angiography Scoring for Uveitis Working Group (ASUWOG). Scoring of dual fluorescein and ICG inflammatory angiographic signs for the grading of posterior segment inflammation (dual fluorescein and ICG angiographic scoring system for uveitis). Int Ophthalmol. 2010 Oct;30(5):539-52. doi: 10.1007/s10792-008-9263-x. Epub 2008 Sep 16. — View Citation

Yang P, Fang W, Wang L, Wen F, Wu W, Kijlstra A. Study of macular function by multifocal electroretinography in patients with Vogt-Koyanagi-Harada syndrome. Am J Ophthalmol. 2008 Nov;146(5):767-71. doi: 10.1016/j.ajo.2008.05.044. Epub 2008 Jul 30. — View Citation

Yuan W, Zhou C, Cao Q, Du Z, Hu R, Wang Y, Kijlstra A, Yang P. Longitudinal Study of Visual Function in Vogt-Koyanagi-Harada Disease Using Full-Field Electroretinography. Am J Ophthalmol. 2018 Jul;191:92-99. doi: 10.1016/j.ajo.2018.04.013. Epub 2018 Apr 25. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	number of eyes with changes in full-field scotopic electroretinogram results	variation >= 30% in the results between 12 and 24 months will define stable or worsening group	at inclusion, 1 month, 6 month, 12 month, 18 month and 24 month
Secondary	recurrence or worsening of cells in anterior chamber	Standardization Uveitis Nomenclature´s classification of anterior chamber cells, any step increase will be considered (Am J Ophthalmo, 2005)	0, 30 days, 3 months, 6 months, 12 months, 18 months and 24 months from disease onset.
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)	0, 30 days, 3 months, 6 months, 12 months, 18 months and 24 months from disease onset.
Secondary	change in subfoveal choroidal thickness on enhanced depth optical coherence tomography	increase of 30% or more in consecutive exams on horizontal scan after 6months from disease onset	0, 30 days, 3 months, 6 months, 12 months from disease onset.
Secondary	change in optic disk hyperfluorescence on fluorescein angiography	appearance or worsening of optic disk hyperfluorescence in consecutive exams after 6months from disease onset	0, 30 days, 3 months, 6 months, 12 months from disease onset.
Secondary	change in perivascular leakage on fluorescein angiography	perivascular leakage appearance or worsening after 6months from disease onset	0, 30 days, 3 months, 6 months, 12 months from disease onset.