MODERN OPPORTUNITIES IN UVEITIS TREATMENT

Uveitis is a heterogeneous group  of inflammatory  diseases of the  choroid  and  adjacent structures. The pathophysiology of uveitis may be different. The treatment approach of infectious and non-infectious uveitis or masquerade syndrome is also different, but the correction of immune  disorders of any uveitis should play a leading role.  Infectious etiology requires the  pathogen eradication with adequate antimicrobial therapy. Therapy of noninfectious  uveitis based on the suppression of the local immune response. Depending on the activit y of the inflammatory process it may require  system or topical anti-inflammatory and/or immunosuppressive treatment with corticosteroids or immunomodulatory therapeutic agents. The main groups  of drugs are presented with the immunosuppressive alkylating agents,  corticosteroids, antimetabolites, T-cell inhibitors  and  biological modulators of the  immune  response. They can reduce the amount  and intensit y of recurrence, the number of complications, decrease  the dose  of corticosteroids or even replace them  in the  case of the  development of side effects and resistance. An alternative uveitis treatment is extracorporal efferent-quantum hemocorrection methods. The most  commonly used  is plasmapheresis based on the removal of plasma  with dissolved mediators of inflammation,  immune complexes, antibodies, exoand endotoxins.  Treatment should  be  pathogenetically oriented  and  localized to  the  affected tissue in order  to  maximize the  ratio  of efficacy / side effect. Often, however, this can’t be achieved.  So the  search continues to develop new therapies for use  in uveitis that  aim  to  suppress inflammatory  activit y,  prevent  accumulation of damage, and  preserve  visual function  for  patients with the minimum possible  side effects.

1. Rupesh V Agrawal, Somasheila Murthy, Virender Sangwan, and Jyotirmay Biswas. Current approach in diagnosis and management of anterior uveitis. Indian J Ophthalmol. 2010;58(1):11–19. doi: 10.4103/0301‑4738.58468.

2. Denniston A, Barry R, Nguyen Q, Lee R, Murray P. Pharmacotherapy for uveitis: current management and emerging therapy. Clin Ophthalmol. 2014;8:1891‑1911. doi:10.2147/opth.s47778.

3. Miserocchi E, Fogliato G, Modorati G, Bandello F. Review on the worldwide epidemiology of uveitis. Eur J Ophthalmol. 2013;23(5):705–717. DOI:10.5301/ejo.

4. Cimino L, Aldigeri R, Salvarani C, et al. The causes of uveitis in a referral centre of Northern Italy. Int Ophthalmol. 2010;30(5):521–529. doi: 10.1007/s10792‑010‑9359‑y.

5. Streilein J. Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol. 2003;3(11):879–889. doi:10.1038/nri1224.

6. Papotto, P.H.; Marengo, E.B.; Sardinha, L.R.; Goldberg, A.C.; Rizzo, L.V. Immunotherapeutic strategies in autoimmune uveitis. Autoimmun. Rev. 2014,13:909–916. doi: 10.1016/j.autrev.2014.05.003

7. Mérida S, Palacios E, Navea A, Bosch‑Morell F. Macrophages and Uveitis in Experimental Animal Models. Mediators of Inflammation. 2015;2015:1–10. doi:10.1155/2015/671417.

8. Lee, R.W.; Nicholson, L.B.; Sen, H.N.; Chan, C.C.; Wei. L.; Nussenblatt, R.B.; Dick, A.D. Autoimmune and autoinflammatory mechanisms in uveitis. Semin. Immunopathol. 2014;36:581–594. doi: 10.1007/s00281‑014‑0433‑9.

9. Takase, H., Futagami, Y., Yoshida, T., Kamoi, K., Sugita, S., Imai, Y., Mochizuki, M. Cytokine profile in aqueous humor and sera of patients with infectious or noninfectious uveitis. Investig. Ophthalmol. Vis. Sci. 2006;47:1557–1561.

10. Velichko V., Lebedev V.V., Katargina L.A., Slepova O.S [Clinical and immunological study the new pathogenetic remedy for children endogenous uveitis treatment]. Kliniko‑immunologicheskoe issledovanie novogo sredstva patogeneticheskoy terapii endogennykh uveitov u detey. [Allergologie and immunology in pediatrics]. Allergologiya i immunologiya v pediatrii. 2008;3(14):31–37. (in Russ.).

11. Rodriguez A, Calonge M, Pedroza‑Seres M, et al. Referral patterns of uveitis in a tertiary eye care center. Arch Ophthalmol. 1996;114(5):593–599.

12. Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005 Sep;140(3):509–16.

13. McClellan K. A., Coster D. J. Uveitis: a strategy for diagnosis. Australian and New Zealand Journal of Ophthalmologv 1987;15:227–24.

14. Intraocular Inflammation, Uveitis. Clinical & Experimental Ophthalmology. 2008;36:A282‑A304. doi:10.1111/j.1442‑9071.2008.01751.x.

15. L.K. Moshetova, A.P. Nesterov, E.A. Egorov. [Ophthalmology. Clinical recommendations. Scientific‑practical publication]. M:GEOTAR‑Media; 2007.(in Russ.).

16. Happe W. [Ophthalmology.Practitioners Handbook]. M.:MedPress; 2005. (in Russ.).

17. Senchenko N.Ya., Shchuko A.G, Malyshev V.V. [Uveitis: manual]. M:GEOTAR‑Media;2010 (in Russ.).

18. Zaytseva N.S., Katsnel'son L.A. [Uveitis]. M.Medicina; 1984 (in Russ.).

19. Deschenes J, Murray P, Rao N, Nussenblatt R. International Uveitis Study Group (IUSG) Clinical Classification of Uveitis. Ocular Immunology and Inflammation. 2008;16(1‑2):1‑2. doi:10.1080/09273940801899822.

20. Tempest‑Roe S, Joshi L, Dick A, Taylor S. Local therapies for inflammatory eye disease in translation: past, present and future. BMC Ophthalmology. 2013;13(1). doi:10.1186/1471‑2415‑13‑39.

21. Durrani K, Zakka FR, Ahmed M, Memon M, Siddique SS, Foster CS. Systemic therapy with conventional and novel immunomodulatory agents for ocular inflammatory disease. Surv Ophthalmol. 2011;56(6): 474–510. doi: 10.1016/j.survophthal.2011.05.003.

22. S S. Pujari, , J H. Kempen, , CW. Newcomb, S Gangaputra, E Daniel, E B. Suhler, J E. Thorne, DA. Jabs, GA. Levy‑Clarke, R B. Nussenblatt, J T.Rosenbaum, C. S Foster. Cyclophosphamide for ocular inflammatory diseases. Ophthalmology. 2010;117(2):356. doi: 10.1016/j.ophtha.2009.06.060.

23. Rebecca S Hunter, Ann‑Marie Lobo. Dexamethasone intravitreal implant for the treatment of noninfectious uveitis. Clinical Ophthalmology. 2011;5:1613–1621.

24. The Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group, John H. Kempen, Michael M. Altaweel, Janet T. Holbrook, Douglas A. Jabs, Thomas A. Louis, Elizabeth A. Sugar, Jennifer E.Thorne. Randomized Comparison of Systemic Anti‑inflammatory Therapy Versus Fluocinolone Acetonide Implant for Intermediate, Posterior and Panuveitis: The Multicenter Uveitis Steroid Treatment Trial. Ophthalmology. 2011 October ; 118(10):1916–1926. doi:10.1016/j.ophtha.2011.07.027

25. Kiernan DMieler W. The use of intraocular corticosteroids. Expert Opinion on Pharmacotherapy. 2009;10(15):2511‑2525. doi:10.1517/14656560903160671.

26. Jaffe GJ, McCallum RM, Branchaud B, Skalak C, Butuner Z, Ashton P. Long‑term follow‑up results of a pilot trial of a fluocinolone acetonide implant to treat posterior uveitis. Ophthalmology. 2005 Jul;112(7):1192‑8.

27. Foster S. Uveitis—Current Standard of Care. US Ophthalmic Review. 2007;02:16. doi:10.17925/usor.2007.02.00.16.

28. Theresa Larson, MD, Robert B. Nussenblatt, MD, MPH, and H. Nida Sen. Emerging Drugs for Uveitis. Expert Opin Emerg Drugs. 2011 June ; 16(2):309–322. doi:10.1517/14728214.2011.537824

29. Jabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, Louie JS, Nussenblatt RB, Stiehm ER, Tessler H, Van Gelder RN, Whitcup SM, Yocum D. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol. 2000 Oct;130(4):492‑513.

30. W. Benton Boone, MD, and Lewis Slater, MD Immunosuppressive Therapy of Ocular Disease Journal of the national medical association. 1979;71(9):564‑573

31. Ermakova N. A. [Clinic, diagnostics, etiopathogenesis and treatment of ocular manifestations of Behcet's disease]. Klinika, diagnostika, etiopatogenez i lechenie glaznykh proyavleniy bolezni Bekhcheta. [Clinical ophthalmology]. Klinicheskaya oftal'mologiya. 2002;3(1):12‑15. (in Russ.).

32. Tamesis RR, Rodriguez A, Christen WG, Akova YA, Messmer E, Foster CS. Systemic drug toxicity trends in immunosuppressive therapy of immune and inflammatory ocular disease. Ophthalmology. 1996 May;103(5):768‑775.

33. Mirshahi A, Hoehn R., Lorenz K, Kramann Ch., Holger Baatz. Anti‑Tumor Necrosis Factor Alpha for Retinal Diseases: Current Knowledge and Future Concepts. J Ophthalmic Vis Res 2012;7 (1):39‑44.

34. Newell R. Washburn et al Polymer conjugated inhibitors of tumor necrosis factor‑α for local control of inflammation. Biomatter. 2013;3:3.

35. Yu He. New options for uveitis treatment. Int J Ophtalmol 2013;6(5):702‑707. doi:10.3980/j.issn.2222‑3959.2013.

36. Santos Lacomba M, Marcos Martín C, Gallardo Galera JM, Gómez Vidal MA, Collantes Estévez E, Ramírez Chamond R, Omar M. Aqueous humor and serum tumor necrosis factor‑alpha in clinical uveitis. Ophthalmic Res. 2001 Sep‑Oct;33(5):251‑255.

37. Sánchez‑Cano D, Callejas‑Rubio J, Ruiz‑Villaverde R, Ríos‑Fernández R, Ortego‑Centeno N. Off‑Label Uses of Anti‑TNF Therapy in Three Frequent Disorders: Behçet’s Disease, Sarcoidosis, and Noninfectious Uveitis. Mediators of Inflammation. 2013;2013:1‑10. doi:10.1155/2013/286857.

38. E W Lindstedt, G S Baarsma, R W A M Kuijpers, P M van Hagen Anti‑TNF‑a therapy for sight threatening uveitis Br J Ophthalmol 2005;89:533–536. doi: 10.1136/bjo.2003.037192

39. Weiss K, Steinbrugger I, Weger M, et al. Intravitreal VEGF levels in uveitis patients and treatment of uveitic macular oedema with intravitreal bevacizumab. Eye (Lond) 2009;23(9):1812–1818. doi: 10.1038/eye.2008.388.

40. Mackensen F, Heinz C, Becker MD, Heiligenhaus A. Intravitreal bevacizumab (avastin) as a treatment for refractory macular edema in patients with uveitis: a pilot study. Retina. 2008;28(1):41–45. doi: 10.1097/IAE.0b013e318156db75.

41. Acharya NR, Hong KC, Lee SM. Ranibizumab for refractory uveitis‑related macular edema. Am J Ophthalmol. 2009;148(2):303–309. doi: 10.1016/j.ajo.2009.03.028.

42. Voinov V.A. [Efferent therapy. Membrane plasmapheresis]. M., OAO «Novosti»; 2010. (in Russ.).

43. Yu X, Ma J, Tian J, Jiang S, Xu P, Han H, Wang L. A controlled study of double filtration plasmapheresis in the treatment of active rheumatoid arthritis. J Clin Rheumatol. 2007Aug;13(4):193‑198. doi: 10.1097/RHU.0b013e318124a483.

44. Yu X, Wang L, Xu P, Lu W, Lan G, Ping L, Wang X, Tian J, Liu J.Effects of double filtration plasmapheresis, leflunomide, and methotrexate on inflammatory changes found through magnetic resonance imaging in early rheumatoid arthritis. J Rheumatol.2012 Jun;39(6):1171‑1178. doi: 10.3899/jrheum.110978.

45. Pepper RJ, Chanouzas D, Tarzi R, et al. Intravenous Cyclophosphamide and Plasmapheresis in Dialysis‑Dependent ANCA‑Associated Vasculitis. Clinical Journal of the American Society of Nephrology : CJASN. 2013;8(2):219‑224. doi:10.2215/CJN.03680412.

46. Muangchan C, van Vollenhoven RF, Bernatsky SR, Smith CD, Hudson M, Inanç M, Rothfield NF, Nash PT, Furie RA, Senécal JL, Chandran V, Burgos‑Vargas R, Ramsey‑Goldman R, Pope JE. Treatment Algorithms in Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). 2015 Sep;67(9):1237‑45. doi: 10.1002/acr.22589.

47. Cardenas‑Garcia J., D Farmakiotis, B Baldovino , P Kim. Wegener’s granulomatosis in a middle‑aged woman presenting with dyspnea, rash, hemoptysis and recurrent eye complaints: a case report. Journal of Medical Case Reports 2012;6:335. DOI: 10.1186/1752‑1947‑6‑335

48. Frolov A.B. [The use of extracorporeal hemocorrection based on plasmapheresis in the treatment of endogenous uveitis and autoimmune eye diseases]. Primenenie ekstrakorporal'noy gemokorrektsii na osnove plazmafereza pri lechenii endogennykh uveitov i autoimmunnykh zabolevaniy glaz. [Annals of Ophthalmology]. Vestnik oftal'mologii. 2009; 125(5):57‑60. (in Russ.).

49. Chernyshjova A.D. [The use of ozone and plasmapheresis in treatment of uveitis]. Primenenie ozona i plazmafereza v kompleksnom lechenii uveitov. Primenenie ozona i plazmafereza v kompleksnom lechenii uveitov. [Bulletin of the Siberian medicine]. Byulleten' sibirskoy meditsiny. 2009;3:117121. (in Russ.).

50. Rjabceva A.A. [Effect of exchange plasmapheresis hydroand hemodynamics and functional eye indices during uveitis]. Vlijanie obmennogo plazmafereza na gidro‑i gemodinamiku i funkcional'nye pokazateli glaza pri uveitah. [Ophthalmology Journal]. Oftal'mologicheskij Zhurnal. 1999;6:361‑365. (in Russ.).

51. Grechanyi M.P., Chentsova O.B., Kildushevskii A.V, Tret’yak E.B. [Prospects for the use of extracorporeal blood correction in the treatment of autoimmune diseases of the eye]. Perspektivy ispol'zovaniya ekstrakorporal'noy gemokorrektsii v lechenii autoimmunnykh zabolevaniy glaz. [Russian Medical Journal. Clinical Ophthalmology]. Rossiyskiy meditsinskiy zhurnal. Klinicheskaya oftal'mologiya. 2006;3:115‑119 (in Russ.).

52. Razumova I.Ju., Safonova T.N., Komov V.V., Fedorov A.A. [Extracorporeal treatment of certain autoimmune diseases of the eye]. Jekstrakorporal'nye metody lechenija nekotoryh autoimmunnyh zabolevanij glaz. [Annals of ophthalmology]. Vestnik oftal'mologii. 2010;3:21‑25. (in Russ.).

53. Onishhenko A.L. [Exchange plasmapheresis with ozonation cell mass in the treatment of endogenous uveitis]. Obmennyj plazmaferez s ozonirovaniem kletochnoj massy pri lechenii jendogennyh uveitov. [Annals of ophthalmology]. Vestnik oftal'mologii. 2011;127(6):33‑35. (in Russ.).

54. Kopaeva V.G. [Eye diseases. Fundamentals of Ophthalmology]. M.:Meditsina; 2012. (In Russ)