Skip to main content

Advertisement

Log in

Outcomes of toll-like receptors’ antagonism in steroid-resistant optic neuritis; a pilot study

  • Neurophthalmology
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Background

To investigate the safety and outcomes of off-label immunomodulator Mycobacterium w. (Mw), a TLR 9 antagonist in steroid-resistant idiopathic unilateral optic neuritis.

Methods

Case series. Eight patients with documented idiopathic unilateral optic neuritis who did not improve with methyl prednisolone followed by oral steroids as per the Optic Neuritis Treatment Trial (ONTT) were administered Mw 5 ml in 500 ml normal saline, 30 days after the last of dose of steroids had been administered. The dose was repeated at 3 months. Outcome measures monitoring the change in the best-corrected visual acuity (BCVA), pupillary reaction, colour vision, visual field (VF) examination (when possible), fundus examination and photography, visually evoked potential (VEP) testing. BCVA, pupillary reaction, and color vision were monitored immediately prior to steroid therapy, on days 1 and 7 post steroid therapy, pre Mw administration (i.e., 30 days after the last dose of steroids had been completed) and post Mw administration on days 1, 7, 30, 90, 120 and 180. VF, VEP and fundus photography was performed immediately prior to steroid administration, 30 days after the last dose of steroids (i.e., immediately prior to Mw), and days 30, 90,120 and 180 post Mw administration.

Results

There were five females and three males in an age range of 30–54 years. Six patients were available for follow-up at 6 months. All patients showed improvement in visual acuity, colour vision & pupillary reaction. Visual field monitoring was possible in four patients; all four had a centrocecal scotoma that persisted post steroid therapy but resolved 1 month post Mw therapy. Three out of five patients who had disc edema were available for all follow-ups, and showed resolution of disc edema post Mw therapy. The disc edema had persisted post steroid therapy. No adverse events were seen. The 2nd dose did not improve any of the said parameters. There was no recurrence of the disease up to the end of the follow-up period.

Conclusions

Mw appears to improve steroid resistant optic neuritis; future randomized clinical trials would help affirm this observation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Beck RW, Cleary PA, Anderson MM Jr, Keltner JL, Shults WT, Kaufman DI, Buckley EG, Corbett JJ, Kupersmith MJ, Miller NR, Savino P, Guy J, Trobe J, McCrary-III J, Smith C, Chrousos G, Thompson SH, Katz B, Brodsky MC, Goodwin JA, Atwell CW; The Optic Neuritis Study Group (1992) A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med 326(9):581–588

    Article  PubMed  CAS  Google Scholar 

  2. Rothstein AM (2006) Toll-like receptors in systemic autoimmune disease. Nat Rev Immunol 6(11):823–835

    Article  Google Scholar 

  3. Guo X, Harada C, Namekata K, Matsuzawa A, Camps M, Ji H, Swinnen D, Jorand-Lebrun C, Muzerelle M, Vitte PA, Rückle T, Kimura A, Kohyama K, Matsumoto Y, Ichijo H, Harada T (2010) Regulation of the severity of neuroinflammation and demyelination by TLR-ASK1-p38 pathway. EMBO Mol Med 2(12):504–515

    Article  PubMed  CAS  Google Scholar 

  4. O’Brien K, Gran B (2008) Toll like receptors and autoimmune demylenating disorders; Special relevance to multiple sclerosis. FASEB J 22: 668.6

    Google Scholar 

  5. Deng YN, Zhou WB (2007) Expression of TLR4 and TLR9 mRNA in Lewis rats with experimental allergic neuritis. Neuroimmunomodulation 14(6):337–343

    Article  PubMed  CAS  Google Scholar 

  6. Balashov KE, Aung LL, Vaknin-Dembinsky A, Dhib-Jalbut S, Weiner HL (2010) Interferon-β inhibits toll-like receptor 9 processing in multiple sclerosis. Ann Neurol 68(6):899–906

    Article  PubMed  CAS  Google Scholar 

  7. Zahednasab H, Bahreini SA (2011) Interferon-beta and toll-like receptor-9 processing. Ann Neurol 69(4):740–741. doi:10.1002/ana.22350, author reply 741

    Article  PubMed  Google Scholar 

  8. Tselis A, Perumal J, Caon C, Hreha S, Ching W, Din M, Van Stavern G, Khan O (2008) Treatment of corticosteroid refractory optic neuritis in multiple sclerosis patients with intravenous immunoglobulin. Eur J Neurol 15(11):1163–1167

    Article  PubMed  CAS  Google Scholar 

  9. Achiron A (2008) Winning combination: the additive/synergistic benefits of IVIg in corticosteroid refractory optic neuritis. Eur J Neurol 15(11):1145

    Article  PubMed  CAS  Google Scholar 

  10. Huchzermeyer C, Mardin C, Holbach L, Zwerina J, Schett G, Rech J (2010) Successful remission induction with a combination therapy of rituximab, cyclophosphamide, and steroids in a patient with refractory optic neuritis in Wegener’s granulomatosis. Clin Rheumatol Sep 23 [Epub ahead of print]

  11. Mok CC, To CH, Mak A, Poon WL (2008) Immunoablative cyclophosphamide for refractory lupus-related neuromyelitis optica. J Rheumatol 35(1):172–174

    PubMed  Google Scholar 

  12. Galindo-Rodríguez G, Aviña-Zubieta JA, Pizarro S, Díaz de León V, Saucedo N, Fuentes M, Lavalle C (1999) Cyclophosphamide pulse therapy in optic neuritis due to systemic lupus erythematosus: an open trial. Am J Med 106(1):65–69

    Article  PubMed  Google Scholar 

  13. Jacob A, Matiello M, Weinshenker BG, Wingerchuk DM, Lucchinetti C, Shuster E, Carter J, Keegan BM, Kantarci OH, Pittock SJ (2009) Treatment of neuromyelitis optica with mycophenolate mofetil: retrospective analysis of 24 patients. Arch Neurol 66(9):1128–1133

    Article  PubMed  Google Scholar 

  14. Perry MC (2007) The chemotherapy source book, 4th edn. Lippincott, Williams and Wilkins, Philadelphia

    Google Scholar 

  15. Chaudhari P, Mukhopadhyaya S (2003) Bladder preserving approach for muscle invasive bladder cancer--role of mycobacterium w. J Indian Med Assoc 101(9):559–560

    Google Scholar 

  16. Kaur I, Dogra S, Kumar B, Radotra V (2002) Combined 12-month WHO/MDT MB regimen and Mycobacterium w. vaccine in multibacillary leprosy: a follow-up of 136 patients. Int J Lepr Other Mycobact Dis 70(3):174–181

    PubMed  Google Scholar 

  17. Kumar B, Sandhu K, Kaur I (2005) Role of Mycobacterium w vaccine in the management of psoriasis. Br J Dermatol 152:368–403

    Article  Google Scholar 

  18. Sarkar S, Dasgupta C (2005) Role of Mycobacterium W as an adjuvant treatment of head & neck cancer: a randomised trial. J Clinical Oncology 23(16S Part 1):521 s

    Google Scholar 

  19. Holladay JT (2004) Visual acuity measurements. J Cataract Refract Surg 30:287–290

    Article  PubMed  Google Scholar 

  20. Ishihara Instructions:The Series of PlatesDesigned as aTest for Color DeficiencySHINOBU ISHIHARA M.D., Dr.Med. Sc.Professor Emeritus of the University of TokyoMember of the Japan Academy24 Plates EditionKANEHARA TRADING INC.TOKYO · JAPAN. www.dfisica.ubi.pt/∼hgil/P.V.2/Ishihara/Ishihara.24.Plate.Instructions.I.pdf; Accessed 30th July 2011

  21. Schneck ME, Haegerstrom-Portnoy G (1997) Colour vision defect type and spatial vision in optic neuritis. Invest Ophthalmol Vis Sci Oct 38(11):2278–2289

    CAS  Google Scholar 

  22. Farnsworth D (1957) The Farnsworth-Munsell 100 Hue test for for the examination ofcolor discrimination. Munsell Color, New Windsor, NY, USA.http://qcqa.com/docs/doc2_2552.pdf. Accessed 30th July 2011

  23. Fleishman JA, Beck RW, Linares OA, Klein JW (1987) Defects in visual function after resolution of optic neuritis. Ophthalmology 94:102–105

    Google Scholar 

  24. Mathew A, Mathai K, Abraham J, Taori GM (1971) Incidence and pattern of demyelinating disease in India. J Neurol Sci 13(1):27–38

    Article  PubMed  CAS  Google Scholar 

  25. Albert D, Azar D, Blodi B, Miller J (2008) Albert and Jackobiec’s principles and practice of ophthalmology, 3rd edn. Saunders–Elsevier, Philadelphia

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Aditya Sudhalkar.

Additional information

None of the authors have any financial or proprietary interest in the presentation

No conflicting relationship exists for any author

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sudhalkar, A., Khamar, M. & Khamar, B. Outcomes of toll-like receptors’ antagonism in steroid-resistant optic neuritis; a pilot study. Graefes Arch Clin Exp Ophthalmol 250, 871–877 (2012). https://doi.org/10.1007/s00417-011-1896-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-011-1896-1

Keywords

Navigation