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Review

Options for systemic therapy of uveitis including alternative therapies

&
Pages 211-226 | Received 19 Jul 2023, Accepted 27 Feb 2024, Published online: 05 Mar 2024

References

  • Gonzalez MM, Solano MM, Porco TC, et al. Epidemiology of uveitis in a US population-based study. J Ophthalmic Inflamm Infect. 2018 Apr 17;8(1):6. doi: 10.1186/s12348-018-0148-5
  • Zhang Y, Amin S, Lung KI, et al. Incidence, prevalence, and risk factors of infectious uveitis and scleritis in the United States: a claims-based analysis. PLoS One. 2020;15(8):e0237995. doi: 10.1371/journal.pone.0237995
  • Joltikov KA, Lobo-Chan AM. Epidemiology and risk factors in Non-infectious Uveitis: a systematic review. Front Med. 2021;8:695904. doi: 10.3389/fmed.2021.695904
  • Forrester JV. Uveitis: pathogenesis. Lancet. 1991 Dec 14;338(8781):1498–501.
  • Rothova A, Suttorp-van Schulten MS, Frits Treffers W, et al. Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol. 1996 Apr;80(4):332–6.
  • Suttorp-Schulten MS, Rothova A. The possible impact of uveitis in blindness: a literature survey. Br J Ophthalmol. 1996 Sep;80(9):844–8. doi: 10.1136/bjo.80.9.844
  • AlBloushi AF, Alfawaz AM, Al-Dahmash SA, et al. Incidence, risk factors and surgical outcomes of cataract among patients with uveitis in a University Referral Hospital in Riyadh, Saudi Arabia. Ocul Immunol Inflamm. 2019;27(7):1105–1113. doi: 10.1080/09273948.2018.1504970
  • Herbert HM, Viswanathan A, Jackson H, et al. Risk factors for elevated intraocular pressure in uveitis. J Glaucoma. 2004 Apr;13(2):96–9.
  • Moorthy RS, Mermoud A, Baerveldt G, et al. Glaucoma associated with uveitis. Surv Ophthalmol. 1997 Mar;41(5):361–394.
  • Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Report. 2008 Dec;10(12):1–23.
  • Eisenberg DM, Kessler RC, Foster C, et al. Unconventional medicine in the United States. Prevalence, costs, and patterns of use. N Engl J Med. 1993 Jan 28;328(4):246–252.
  • Shelley BM, Sussman AL, Williams RL, et al. ‘They don’t ask me so I don’t tell them’: patient-clinician communication about traditional, complementary, and alternative medicine. Ann Fam Med. 2009 Mar;7(2):139–47.
  • Couret C, Ducloyer JB, Touhami S, et al. Treatment of noninfectious intermediate uveitis, posterior uveitis, or panuveitis. J Fr Ophtalmol. 2020 Apr;43(4):341–361.
  • Babu K, Mahendradas P. Medical management of uveitis–current trends. Indian J Ophthalmol. 2013 Jun;61(6):277–83. doi: 10.4103/0301-4738.114099
  • McGhee CN. Pharmacokinetics of ophthalmic corticosteroids. Br J Ophthalmol. 1992 Nov;76(11):681–4. doi: 10.1136/bjo.76.11.681
  • Vegas-Revenga N, Martín-Varillas JL, Calvo-Río V, et al. Intravenous methylprednisolone induces rapid improvement in non-infectious uveitis: a multicentre study of 112 patients. Clin Exp Rheumatol. 2022 Jan;40(1):142–149.
  • Schnabel A, Unger E, Brück N, et al. High-dose intravenous methylprednisolone in juvenile non-infectious uveitis: A retrospective analysis. Clin Immunol. 2020 Feb;211:108327.
  • Pasadhika S, Kempen JH, Newcomb CW, et al. Azathioprine for ocular inflammatory diseases. Am J Ophthalmol. 2009 Oct;148(4):500–509.e2.
  • Saadoun D, Wechsler B, Terrada C, et al. Azathioprine in severe uveitis of Behçet’s disease. Arthritis Care Res (Hoboken). 2010 Dec;62(12):1733–8.
  • Pacheco PA, Taylor SR, Cuchacovich MT, et al. Azathioprine in the management of autoimmune uveitis. Ocul Immunol Inflamm. 2008 Jul;16(4):161–165.
  • Galor A, Jabs DA, Leder HA, et al. Comparison of antimetabolite drugs as corticosteroid-sparing therapy for noninfectious ocular inflammation. Ophthalmol. 2008 Oct;115(10):1826–32.
  • Samson CM, Waheed N, Baltatzis S, et al. Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients. Ophthalmol. 2001 Jun;108(6):1134–9.
  • Gangaputra S, Newcomb CW, Liesegang TL, et al. Methotrexate for ocular inflammatory diseases. Ophthalmol. 2009 Nov;116(11):2188–98e1.
  • Allison AC. Mechanisms of action of mycophenolate mofetil. Lupus. 2005;14 Suppl 1:s2–8.
  • Teoh SC, Hogan AC, Dick AD, et al. Mycophenolate mofetil for the treatment of uveitis. Am J Ophthalmol. 2008 Nov;146(5):752–60, 760.e1–3.
  • Ali S, Kharel Sitaula R, Biswas J. Efficacy and safety of Mycophenolate Mofetil in the treatment of recalcitrant intermediate uveitis. Ocul Immunol Inflamm. 2019;27(5):851–857. doi: 10.1080/09273948.2018.1453524
  • Bhat P, Cervantes-Castañeda RA, Doctor PP, et al. Mycophenolate mofetil therapy for sarcoidosis-associated uveitis. Ocul Immunol Inflamm. 2009 May;17(3):185–90.
  • El-Asrar AM A, Hemachandran S, HS A-M, et al. The outcomes of mycophenolate mofetil therapy combined with systemic corticosteroids in acute uveitis associated with Vogt-Koyanagi-Harada disease. Acta Ophthalmol. 2012 Dec;90(8):e603–8.
  • El-Asrar AM A, Dosari M, Hemachandran S, et al. 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.
  • Sobrin L, Christen W, Foster CS. Mycophenolate mofetil after methotrexate failure or intolerance in the treatment of scleritis and uveitis. Ophthalmol. 2008 Aug;115(8):1416–21, 1421 e1.
  • Rathinam SR, Gonzales JA, Thundikandy R, et al. Effect of corticosteroid-sparing treatment with mycophenolate mofetil vs methotrexate on inflammation in patients with uveitis: a randomized clinical trial. JAMA. 2019 Sep 10;322(10):936–945. doi: 10.1001/jama.2019.12618
  • Tsui E, Rathinam SR, Gonzales JA, et al. Outcomes of Uveitic Macular Edema in the First-line Antimetabolites as steroid-sparing treatment uveitis trial. Ophthalmol. 2022 Jun;129(6):661–667.
  • Bui AD, Kong CL, Kelly NK, et al. Time to Uveitis Control with methotrexate and Mycophenolate Mofetil. Ophthalmol. 2022 Jun;129(6):721–723.
  • Pasadhika S, Rosenbaum JT. Update on the use of systemic biologic agents in the treatment of noninfectious uveitis. Biologics. 2014;8:67–81.
  • Lindstedt EW, Baarsma GS, Kuijpers RW, et al. Anti-TNF-alpha therapy for sight threatening uveitis. Br J Ophthalmol. 2005 May;89(5):533–536.
  • Alizadegan F, Yalcinbayir O, Ucan Gunduz G, et al. Infliximab therapy in Behçet’s uveitis. J Fr Ophtalmol. 2022 Nov;45(9):1036–1041.
  • Fabiani C, Sota J, Vitale A, et al. Ten-year Retention Rate of Infliximab in patients with Behcet’s disease-related uveitis. Ocul Immunol Inflamm. 2019;27(1):34–39.
  • Handa T, Tsunekawa H, Yoneda M, et al. Long-term remission of ocular and extraocular manifestations in Behcet’s disease using infliximab. Clin Exp Rheumatol. 2011 Jul;29(4 Suppl 67):S58–63.
  • Kruh JN, Yang P, Suelves AM, et al. Infliximab for the treatment of refractory noninfectious uveitis: a study of 88 patients with long-term follow-up. Ophthalmol. 2014 Jan;121(1):358–364.
  • Suhler EB, Smith JR, Giles TR, et al. Infliximab therapy for refractory uveitis: 2-year results of a prospective trial. Arch Ophthalmol. 2009 Jun;127(6):819–822.
  • Ardoin SP, Kredich D, Rabinovich E, et al. Infliximab to treat chronic noninfectious uveitis in children: retrospective case series with long-term follow-up. Am J Ophthalmol. 2007 Dec;144(6):844–849.
  • Richards JC, Tay-Kearney ML, Murray K, et al. Infliximab for juvenile idiopathic arthritis-associated uveitis. Clin Exp Ophthalmol. 2005 Oct;33(5):461–8.
  • Miraldi Utz V, Bulas S, Lopper S, et al. Effectiveness of long-term infliximab use and impact of treatment adherence on disease control in refractory, non-infectious pediatric uveitis. Pediatr Rheumatol Online J. 2019 Nov 29;17(1):79. doi: 10.1186/s12969-019-0383-9
  • Kahn P, Weiss M, Imundo LF, et al. Favorable response to high-dose infliximab for refractory childhood uveitis. Ophthalmol. 2006 May;113(5):860–4.e2.
  • Suhler EB, Jaffe GJ, Fortin E, et al. Long-term safety and efficacy of adalimumab in patients with noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Ophthalmol. 2021 Jun;128(6):899–909.
  • Jaffe GJ, Dick AD, Brézin AP, et al. Adalimumab in patients with active noninfectious uveitis. N Engl J Med. 2016;375(10):932–943. doi: 10.1056/NEJMoa1509852
  • Suhler EB, Adán A, Brézin AP, et al. Safety and efficacy of adalimumab in patients with Noninfectious Uveitis in an ongoing open-label study: VISUAL III. Ophthalmol. 2018 Jul;125(7):1075–1087.
  • van der Heijde D, Kivitz A, Schiff MH, et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2006 Jul;54(7):2136–2146.
  • Rudwaleit M, Rodevand E, Holck P, et al. Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: results of a prospective open-label study. Ann Rheum Dis. 2009 May;68(5):696–701.
  • Bober E, Frain K, Fotuhi M, et al. Adalimumab in the treatment of refractory non-infectious scleritis: 6-month outcomes. Eye (Lond). 2024 Feb;38:628–630.
  • Evereklioglu C, Sonmez HK, Sevim DG, et al. Adalimumab rapidly controls both anterior and posterior inflammation in patients with ocular behçet syndrome and non-infectious uveitis refractory to conventional therapy: a prospective, 6-month follow-up investigation. Int Ophthalmol. 2023 Aug 9;43(12):4461–4472. doi: 10.1007/s10792-023-02846-4
  • Ramanan AV, Dick AD, Jones AP, et al. Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis. N Engl J Med. 2017 Apr 27;376(17):1637–1646. doi: 10.1056/NEJMoa1614160
  • Atienza-Mateo B, Martin-Varillas JL, Calvo-Rio V, et al. Comparative study of infliximab versus adalimumab in refractory uveitis due to Behcet’s disease: national multicenter study of 177 cases. Arthritis & Rheumat. 2019 Dec;71(12):2081–2089.
  • Simonini G, Taddio A, Cattalini M, et al. Prevention of flare recurrences in childhood-refractory chronic uveitis: an open-label comparative study of adalimumab versus infliximab. Arthritis Care Res (Hoboken). 2011 Apr;63(4):612–8.
  • Ashkenazy N, Saboo US, Abraham A, et al. Successful treatment with infliximab after adalimumab failure in pediatric noninfectious uveitis. J AAPOS. 2019 Jun;23(3):e151 1–e151 5.
  • Fabiani C, Vitale A, Rigante D, et al. Comparative efficacy between adalimumab and infliximab in the treatment of non-infectious intermediate uveitis, posterior uveitis, and panuveitis: a retrospective observational study of 107 patients. Clin Rheumatol. 2019 Feb;38(2):407–415.
  • Lejoyeux R, Diwo E, Vallet H, et al. INFLIXIMAB and ADALIMUMAB in Uveitic Macular Edema. Ocul Immunol Inflamm. 2018;26(7):991–996. doi: 10.1080/09273948.2018.1498110
  • Liu W, Bai D, Kou L. Comparison of infliximab with adalimumab for the treatment of non-infectious uveitis: a systematic review and meta-analysis. BMC Ophthalmol. 2023 May 29;23(1):240.
  • Kramer M, Monselise Y, Bahar I, et al. Serum cytokine levels in active uveitis and remission. Curr Eye Res. 2007 Jul;32(7–8):669–75.
  • Uludag G, Karaca I, Akhavanrezayat A, et al. Efficacy and safety of Tocilizumab in the management of non-infectious uveitis failed with conventional immunomodulatory and anti-TNFα therapies. Ocul Immunol Inflamm. 2022 Dec;21:1–7.
  • Papo M, Bielefeld P, Vallet H, et al. Tocilizumab in severe and refractory non-infectious uveitis. Clin Exp Rheumatol. 2014 Jul;32(4 Suppl 84):S75–9.
  • Sepah YJ, Sadiq MA, Chu DS, et al. Primary (month-6) outcomes of the STOP-Uveitis study: evaluating the safety, tolerability, and efficacy of Tocilizumab in patients with noninfectious uveitis. Am J Ophthalmol. 2017 Nov;183:71–80.
  • Sadiq MA, Hassan M, Afridi R, et al. Posterior segment inflammatory outcomes assessed using fluorescein angiography in the STOP-UVEITIS study. Int J Retina Vitreous. 2020;6(1):47. doi: 10.1186/s40942-020-00245-w
  • Mesquida M, Molins B, Llorenc V, et al. Long-term effects of tocilizumab therapy for refractory uveitis-related macular edema. Ophthalmol. 2014 Dec;121(12):2380–6.
  • Leclercq M, Andrillon A, Maalouf G, et al. Anti-tumor necrosis factor α versus Tocilizumab in the Treatment of Refractory Uveitic Macular Edema: a multicenter study from the French Uveitis Network. Ophthalmol. 2022 May;129(5):520–529.
  • Khitri MY, Bartoli A, Maalouf G, et al. Tocilizumab in Behçet disease: a multicenter study of 30 patients. J Rheumatol. 2023 Mar 1;50(7):916–923. doi: 10.3899/jrheum.221106
  • Marino A, Marelli L, Nucci P, et al. Subcutaneous Tocilizumab in Juvenile Idiopathic Arthritis Associated Uveitis. Ocul Immunol Inflamm. 2023Jan;19:1–4.
  • Karkhur S, Hasanreisoglu M, Vigil E, et al. Interleukin-6 inhibition in the management of non-infectious uveitis and beyond. J Ophthalmic Inflamm Infect. 2019 Sep 16;9(1):17. doi: 10.1186/s12348-019-0182-y
  • Heissigerová J, Callanan D, de Smet MD, et al. Efficacy and safety of Sarilumab for the treatment of posterior segment noninfectious uveitis (SARIL-NIU): the phase 2 SATURN study. Ophthalmol. 2019 Mar;126(3):428–437.
  • Ng CC, Sy A, Cunningham ET Jr. Rituximab for non-infectious uveitis and scleritis. J Ophthalmic Inflamm Infect. 2021 Aug 16;11(1):23.
  • El-Asrar AM A, Dheyab A, Khatib D, et al. Efficacy of B cell depletion therapy with Rituximab in refractory chronic recurrent uveitis associated with Vogt-Koyanagi-Harada Disease. Ocul Immunol Inflamm. 2022 Apr 3;30(3):750–757.
  • Miserocchi E, Modorati G, Berchicci L, et al. Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis. Br J Ophthalmol. 2016 Jun;100(6):782–6.
  • Bayry J, Misra N, Latry V, et al. Mechanisms of action of intravenous immunoglobulin in autoimmune and inflammatory diseases. Transfus Clin Biol. 2003 Jun;10(3):165–9.
  • Garcia-Geremias M, Carreño E, Epps SJ, et al. Clinical outcomes of intravenous immunoglobulin therapy in refractory uveitis. Int Ophthalmol. 2015 Apr;35(2):281–5.
  • Onal S, Foster CS, Ahmed AR. Efficacy of intravenous immunoglobulin treatment in refractory uveitis. Ocul Immunol Inflamm. 2006 Dec;14(6):367–74. doi: 10.1080/09273940601025966
  • Ediriwickrema LS, Chhadva P, Rodger DC, et al. Intravenous immunoglobulin in the treatment of juvenile retinitis pigmentosa-associated cystoid macular edema and uveitis. Retin Cases Brief Rep. 2018 Summer;12(3):242–246.
  • Guy J, Aptsiauri N. Treatment of paraneoplastic visual loss with intravenous immunoglobulin: report of 3 cases. Arch Ophthalmol. 1999 Apr;117(4):471–477.
  • LeHoang P, Cassoux N, George F, et al. Intravenous immunoglobulin (IVIg) for the treatment of birdshot retinochoroidopathy. Ocul Immunol Inflamm. 2000 Mar;8(1):49–57.
  • Seider N, Beiran I, Scharf J, et al. Intravenous immunoglobulin therapy for resistant ocular Behcet’s disease. Br J Ophthalmol. 2001 Nov;85(11):1287–8.
  • Stiehm ER. Adverse effects of human immunoglobulin therapy. Transfus Med Rev. 2013 Jul;27(3):171–8. doi: 10.1016/j.tmrv.2013.05.004
  • Guo Y, Tian X, Wang X, et al. Adverse effects of immunoglobulin therapy. Front Immunol. 2018;9:1299. doi: 10.3389/fimmu.2018.01299
  • Nussenblatt RB, Palestine AG, Chan CC. Cyclosporine therapy for uveitis: long-term followup. J Ocul Pharmacol. 1985 Winter;1(4):369–82. doi: 10.1089/jop.1985.1.369
  • Mathews D, Mathews J, Jones NP. Low-dose cyclosporine treatment for sight-threatening uveitis: efficacy, toxicity, and tolerance. Indian J Ophthalmol. 2010 Jan;58(1):55–8. doi: 10.4103/0301-4738.58472
  • Isnard Bagnis C, du Montcel S T, Beaufils H, et al. Long-term renal effects of low-dose cyclosporine in uveitis-treated patients: follow-up study. J Am Soc Nephrol. 2002 Dec;13(12):2962–2968.
  • Figueroa MS, Ciancas E, Orte L. Long-term follow-up of tacrolimus treatment in immune posterior uveitis. Eur J Ophthalmol. 2007 Jan;17(1):69–74. doi: 10.1177/112067210701700110
  • Luis J, Alsaedi A, Phatak S, et al. Efficacy of tacrolimus in uveitis, and the usefulness of serum tacrolimus levels in predicting disease control. Results from a single large center. Ocul Immunol Inflamm. 2022 Oct;30(7–8):1654–1658.
  • Wakefield D. Does cyclophosphamide still have a role in the treatment of severe inflammatory eye disease? Ocul Immunol Inflamm. 2014 Aug;22(4):306–10. doi: 10.3109/09273948.2013.854395
  • Ahmed A, Foster CS. Cyclophosphamide or Rituximab Treatment of Scleritis and uveitis for patients with granulomatosis with polyangiitis. Ophthalmic Res. 2019;61(1):44–50. doi: 10.1159/000486791
  • Rosenbaum JT. Treatment of severe refractory uveitis with intravenous cyclophosphamide. J Rheumatol. 1994 Jan;21(1):123–5.
  • Pujari SS, Kempen JH, Newcomb CW, et al. Cyclophosphamide for ocular inflammatory diseases. Ophthalmol. 2010 Feb;117(2):356–65.
  • Baker GL, Kahl LE, Zee BC, et al. Malignancy following treatment of rheumatoid arthritis with cyclophosphamide. Long-term case-control follow-up study. Am J Med. 1987 Jul;83(1):1–9.
  • Baltus JA, Boersma JW, Hartman AP, et al. The occurrence of malignancies in patients with rheumatoid arthritis treated with cyclophosphamide: a controlled retrospective follow-up. Ann Rheum Dis. 1983 Aug;42(4):368–73.
  • Kempen JH, Gangaputra S, Daniel E, et al. Long-term risk of malignancy among patients treated with immunosuppressive agents for ocular inflammation: a critical assessment of the evidence. Am J Ophthalmol. 2008 Dec;146(6):802–12.e1.
  • Godfrey WA, Epstein WV, O’Connor GR, et al. The use of chlorambucil in intractable idiopathic uveitis. Am J Ophthalmol. 1974 Sep;78(3):415–28.
  • Mamo JG, Azzam SA. Treatment of Behçet’s disease with chlorambucil. Arch Ophthalmol. 1970 Oct;84(4):446–450.
  • Mudun BA, Ergen A, Ipcioglu SU, et al. Short-term chlorambucil for refractory uveitis in Behcet’s disease. Ocul Immunol Inflamm. 2001 Dec;9(4):219–29.
  • Dinning WJ, Perkins ES. Immunosuppressives in uveitis. A preliminary report of experience with chlorambucil. Br J Ophthalmol. 1975 Aug;59(8):397–403. doi: 10.1136/bjo.59.8.397
  • Miserocchi E, Baltatzis S, Ekong A, et al. Efficacy and safety of chlorambucil in intractable noninfectious uveitis: the Massachusetts eye and ear infirmary experience. Ophthalmol. 2002 Jan;109(1):137–42.
  • Ruperto N, Brunner HI, Synoverska O, et al. Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial. Lancet. 2021 Nov 27;398(10315):1984–1996. doi: 10.1016/S0140-6736(21)01255-1
  • Bauermann P, Heiligenhaus A, Heinz C. Effect of Janus Kinase Inhibitor Treatment on Anterior Uveitis and Associated Macular Edema in an adult patient with juvenile idiopathic arthritis. Ocul Immunol Inflamm. 2019;27(8):1232–1234. doi: 10.1080/09273948.2019.1605453
  • Dutta Majumder P, Shah A, Kaushik V. Tofacitinib in Vogt-Koyanagi-Harada disease. Indian J Ophthalmol. 2020 Sep;68(9):1938–1939. doi: 10.4103/ijo.IJO_998_20
  • Paley MA, Karacal H, Rao PK, et al. Tofacitinib for refractory uveitis and scleritis. Am J Ophthalmol Case Rep. 2019Mar; 13:53–55.
  • Zhang S, Cai Z, Mo X, et al. Tofacitinib effectiveness in Blau syndrome: a case series of Chinese paediatric patients. Pediatr Rheumatol Online J. 2021 Nov 15;19(1):160. doi: 10.1186/s12969-021-00634-x
  • Manoharan A, Atmakur H, Dutta Majumder P, et al. Branch retinal vein occlusion in a case of recalcitrant diffuse anterior scleritis treated with tofacitinib. J Ophthalmic Inflamm Infect. 2023 Sep 27;13(1):45. doi: 10.1186/s12348-023-00359-w
  • Kaneko Y, Murakami T, Nishitsuka K, et al. Effectiveness of Baricitinib in Refractory Seronegative Rheumatoid Arthritis and uveitis: a case report. Front Med. 2021;8:764067.
  • Ramanan AV, Guly CM, Keller SY, et al. Clinical effectiveness and safety of baricitinib for the treatment of juvenile idiopathic arthritis-associated uveitis or chronic anterior antinuclear antibody-positive uveitis: study protocol for an open-label, adalimumab active-controlled phase 3 clinical trial (JUVE-BRIGHT). Trials. 2021 Oct 9;22(1):689. doi: 10.1186/s13063-021-05651-5
  • Baquet-Walscheid K, Heinz C, Rath T, et al. Beneficial effect of Upadacitinib in an adult patient with Juvenile Idiopathic Arthritis-associated Uveitis after unsatisfactory response to Tofacitinib: A case report. Ocul Immunol Inflamm. 2023 Jul;31(5):1079–1080.
  • Tao T, He D, Peng X, et al. Successful remission with upadacitinib in two patients with anti-TNF-Refractory Macular Edema Associated with Behcet’s uveitis. Ocul Immunol Inflamm. 2023Oct; 6:1–4.
  • Kötter I, Eckstein AK, Stübiger N, et al. Treatment of ocular symptoms of Behçet’s disease with interferon alpha 2a: a pilot study. Br J Ophthalmol. 1998 May;82(5):488–494.
  • Pivetti-Pezzi P, Accorinti M, Pirraglia MP, et al. Interferon alpha for ocular Behçet’s disease. Acta Ophthalmol Scand. 1997 Dec;75(6):720–722.
  • Feron EJ, Rothova A, van Hagen PM, et al. Interferon-alpha 2b for refractory ocular Behçet’s disease. Lancet. 1994 Jun 4;343(8910):1428.
  • Guillaume-Czitrom S, Berger C, Pajot C, et al. Efficacy and safety of interferon-alpha in the treatment of corticodependent uveitis of paediatric Behcet’s disease. Rheumatology (Oxford). 2007 Oct;46(10):1570–1573.
  • Lee JH, Lee CS, Lee SC. Interferon alpha-2a treatment for refractory behcet uveitis in Korean patients. BMC Ophthalmol. 2018 Feb 20;18(1):52.
  • Yang P, Huang G, Du L, et al. Long-term efficacy and Safety of Interferon Alpha-2a in the treatment of Chinese patients with Behcet’s uveitis not responding to conventional therapy. Ocul Immunol Inflamm. 2019;27(1):7–14.
  • Celiker H, Kazokoglu H, Direskeneli H. Long-term efficacy of pegylated interferon alpha-2b in Behcet’s Uveitis: a Small Case Series. Ocul Immunol Inflamm. 2019;27(1):15–22.
  • De Simone L, Invernizzi A, Aldigeri R, et al. Effectiveness of infliximab and interferon alpha-2a for the Treatment of Behcet’s uveitis: customizing therapy according to the clinical features. Ocul Immunol Inflamm. 2022 Feb 17;30(2):506–514.
  • Fardeau C, Simon A, Rodde B, et al. Interferon-alpha2a and systemic corticosteroid in monotherapy in chronic uveitis: results of the randomized controlled BIRDFERON study. Am J Ophthalmol. 2017 May;177:182–194.
  • Butler NJ, Suhler EB, Rosenbaum JT. Interferon alpha 2b in the treatment of uveitic cystoid macular edema. Ocul Immunol Inflamm. 2012 Apr;20(2):86–90. doi: 10.3109/09273948.2011.645989
  • Sobaci G, Bayraktar Z, Bayer A. ORIGINAL ARTICLE, interferon alpha-2A treatment for Serpiginous Choroiditis. Ocul Immunol Inflamm. 2005 Feb;13(1):59–66. doi: 10.1080/09273940490518865
  • Velazquez-Villoria D, Macia-Badia C, Segura-Garcia A, et al. Efficacy of immunomodulatory therapy with interferon-beta or glatiramer acetate on multiple sclerosis-associated uveitis. Arch Soc Esp Oftalmol. 2017 Jun;92(6):273–279.
  • Becker MD, Heiligenhaus A, Hudde T, et al. Interferon as a treatment for uveitis associated with multiple sclerosis. Br J Ophthalmol. 2005 Oct;89(10):1254–1257.
  • Mackensen F, Jakob E, Springer C, et al. Interferon versus methotrexate in intermediate uveitis with macular edema: results of a randomized controlled clinical trial. Am J Ophthalmol. 2013 Sep;156(3):478–486 e1.
  • Panitch H, Goodin DS, Francis G, et al. Randomized, comparative study of interferon beta-1a treatment regimens in MS: the EVIDENCE trial. Neurology. 2002 Nov 26;59(10):1496–1506.
  • Ebers GC. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (prevention of relapses and disability by interferon beta-1a subcutaneously in multiple sclerosis) study group. Lancet. 1998 Nov 7;352(9139):1498–1504.
  • Radomska-Lesniewska DM, Osiecka-Iwan A, Hyc A, et al. Therapeutic potential of curcumin in eye diseases. Cent Eur J Immunol. 2019;44(2):181–189. doi: 10.5114/ceji.2019.87070
  • Miserocchi E, Giuffre C, Cicinelli MV, et al. Oral phospholipidic curcumin in juvenile idiopathic arthritis-associated uveitis. Eur J Ophthalmol. 2020 Nov;30(6):1390–1396.
  • Lal B, Kapoor AK, Asthana OP, et al. Efficacy of curcumin in the management of chronic anterior uveitis. Phytother Res. 1999 Jun;13(4):318–22.
  • Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001 Jul;21(4b):2895–900.
  • Anand P, Kunnumakkara AB, Newman RA, et al. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007 Nov;4(6):807–18.
  • Shoba G, Joy D, Joseph T, et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998 May;64(4):353–6.
  • Allegri P, Mastromarino A, Neri P. Management of chronic anterior uveitis relapses: efficacy of oral phospholipidic curcumin treatment. Long-term follow-up. Clin Ophthalmol. 2010 Oct 21;4:1201–1206.
  • Allegri P, Rosa R, Masala A, et al. Clinical effectiveness of a new oral curcumin formulation in acute non-infectious uveitic macular edema: a 12-month observational study. Eur Rev Med Pharmacol Sci. 2022 Jan;26(1):46–53.
  • Allegri P, Cimino L, Davis JL, et al. Assessment of the anti-inflammatory effects of NORFLO® ORO in acute relapses of HLA-B27-associated autoimmune uveitis: a multicenter, randomized, placebo-controlled, double-blind clinical study. Ocul Immunol Inflamm. 2023 Apr;31(3):526–535.
  • Bhat AK, Krishnakumar V. Ayurvedic management of recurrent anterior uveitis (Raktaja adhimantha) with bloodletting therapy: A case report. J Ayurveda Case Reports. 2021;4(2):54–57.
  • Shilpa S, SMP K. An Ayurvedic approach to non infectious choroiditis–prospective single case study. J Ayurveda Integr Med Sci. 2019 Oct 31;4(5):366–370.
  • CT N, Sujathamma K. Anterior Uveitis and management in Ayurveda–A Case Study. J Ayurveda Integr Med Sci. 2017 Oct 31;2(5):206–210.
  • Pushpa RP, Ashwini MJ. Ayurvedic management of acute anterior uveitis (Pittaja Adhimantha): a case study. Int J Res Ayurveda Pharm. 2018;9(2):113–117.
  • Telgote D, Dakhore J, Waghmare R. Management of the juvenile idiopathic arthritis (JIA) associated anterior uveitis with special references to Pittaja Adhimantha, by an Ayurvedic and modern aspect-a single case study. Int J Res Indian Med. 2022;6(4):1–7.
  • Yang Y, Wang Q, Xie M, et al. Berberine exerts an anti-inflammatory role in ocular Behcet’s disease. Mol Med Rep. 2017 Jan;15(1):97–102.
  • Yang Y, Qi J, Wang Q, et al. Berberine suppresses Th17 and dendritic cell responses. Invest Ophthalmol Vis Sci. 2013 Apr 5;54(4):2516–22. doi: 10.1167/iovs.12-11217
  • Li M, Chen X, Liu J, et al. Treatment of experimental autoimmune uveoretinitis with different natural compounds. Mol Med Rep. 2016 Jun;13(6):4654–8.
  • Du Z, Wang Q, Huang X, et al. Effect of berberine on spleen transcriptome and gut microbiota composition in experimental autoimmune uveitis. Int Immunopharmacol. 2020 Apr;81:106270.
  • Chan E. Displacement of bilirubin from albumin by berberine. Biol Neonate. 1993;63(4):201–8. doi: 10.1159/000243932
  • Deng Z, Wu YF, Jiang L, et al. Matrine eye fluid regulates TLR4/NF- B pathway and affects the expression of cytokines associated with experimental uveitis in rabbits. Chin J Gen Pract. 2020;18(4):568–572.
  • Li S, Liu F, Zhang K, et al. Research progress on the mechanism of natural product ingredients in the treatment of uveitis. J Immunol Res. 2021;2021:6683411.
  • Luo J, Jin DE, Yang GY, et al. Total glucosides of paeony for rheumatoid arthritis: a systematic review of randomized controlled trials. Complement Ther Med. 2017 Oct;34:46–56.
  • Xiong C, Qi J, Deng R, et al. Total glucosides of paeony inhibits proliferation and promotes activation- induced cell death of mouse T cells in vitro. Nan Fang Yi Ke Da Xue Xue Bao. 2020 Jan 30;40(1):118–124.
  • Wu W, He MF, Guo ZL, et al. Protective effect of total glucosides of paeony on uveitis model rats. Chin Pharm. 2014;25(11):994–996.
  • Xu QB, Zhong LY, Zhu LW, et al. Adjuvant treatment of systemic lupus erythematosus with uveitis by total glucosides of paeony. Chin J Mod Appl Pharm. 2015;32(2):202–205.
  • Jin L, Li C, Li Y, et al. Clinical efficacy and safety of total glucosides of paeony for primary Sjögren’s syndrome: a systematic review. Evid Based Complement Alternat Med. 2017;2017:3242301.
  • Ma G. Effect of Tripterygium wilfordii on recurrent uveitis. J Integr Ophthalmol. 1996;2:86–87.
  • Huang QS, Zhang ZL, Liu YM. Effect of tripterygium wilfordii polyglycoside on serum IL-2 and TNF-alpha in patients with acute anterior U-veitis. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2002 Jun;22(6):432–434.
  • Song Q, Lu JZ, Li J. Effect of tripterygium glycosides on serum interleukin-1β, interleukin-2, tumor necrosis factor α, and interferon-γ levels in patients with Behcet’s disease. Chin J Integr Med. 2010;30(6):598–600.
  • Yang HZ, Liu N, Dai C. Detection of endothelium function in patients with Behcet’disease and effect of tripterygium glycosides. Chin J Integr Dermatol Venereol. 2016;15(2):94–96.
  • Liu B, Meng X, Ma Y, et al. Clinical safety of total glucosides of paeony adjuvant therapy for rheumatoid arthritis treatment: a systematic review and meta-analysis. BMC Complement Med Ther. 2021 Mar 26;21(1):102. doi: 10.1186/s12906-021-03252-y
  • Song CY, Xu YG, Lu YQ. Use of Tripterygium wilfordii Hook F for immune-mediated inflammatory diseases: progress and future prospects. J Zhejiang Univ Sci B. 2020 Apr;21(4):280–290.
  • Tang K, Guo D, Zhang L, et al. Immunomodulatory effects of Longdan Xiegan Tang on CD4+/CD8+ T cells and associated inflammatory cytokines in rats with experimental autoimmune uveitis. Mol Med Rep. 2016 Sep;14(3):2746–54.
  • Yan SK, Xin WF, Luo GA, et al. Simultaneous determination of major bioactive components in qingkailing injection by high-performance liquid chromatography with evaporative light scattering detection. Chem Pharm Bull (Tokyo). 2005 Nov;53(11):1392–5.
  • Tian Q, Bi H, Cui Y, et al. Qingkailing injection alleviates experimental autoimmune uveitis in rats via inhibiting Th1 and Th17 effector cells. Biol Pharm Bull. 2012;35(11):1991–6. doi: 10.1248/bpb.b12-00449
  • Song J, Tian Q, Lu D, et al. Clinical study on treatment of chronic uveitis with Qinghuo Rougan Mingmu formula. Chin J Chin Ophthal. 2017;27:158–162.
  • Jing C, Sun Z, Xie X, et al. Network pharmacology-based identification of the key mechanism of Qinghuo Rougan Formula acting on uveitis. Biomed Pharmacother. 2019 Dec;120:109381.
  • Xu H, Liu M, Cao J, et al. The Dynamic Interplay between the gut microbiota and autoimmune diseases. J Immunol Res. 2019;2019:7546047.
  • Kalyana Chakravarthy S, Jayasudha R, Sai Prashanthi G, et al. Dysbiosis in the gut bacterial microbiome of patients with Uveitis, an inflammatory disease of the eye. Indian J Microbiol. 2018 Dec;58(4):457–469.
  • Huang X, Ye Z, Cao Q, et al. Gut microbiota composition and fecal metabolic phenotype in patients with acute anterior uveitis. Invest Ophthalmol Vis Sci. 2018 Mar 1;59(3):1523–1531. doi: 10.1167/iovs.17-22677
  • Janetos TM, Zakaria N, Goldstein DA. The microbiome and uveitis: a narrative review. Am J Pathol. 2023 Apr 5;193(11):1638–1647.
  • Kim J, Choi SH, Kim YJ, et al. Clinical effect of IRT-5 probiotics on immune modulation of autoimmunity or alloimmunity in the eye. Nutrients. 2017 Oct 25;9(11):1166.
  • Llop SM, Davoudi S, Stanwyck LK, et al. Association of Low Vitamin D Levels with noninfectious uveitis and Scleritis. Ocul Immunol Inflamm. 2019;27(4):602–609. doi: 10.1080/09273948.2018.1434208
  • Susarla G, Chan W, Li A, et al. Mendelian randomization shows a causal effect of low vitamin D on Non-infectious Uveitis and scleritis risk. Am J Ophthalmol. 2022 Dec;244:11–18.
  • Chiu ZK, Lim LL, Rogers SL, et al. Patterns of vitamin D levels and exposures in active and inactive noninfectious uveitis patients. Ophthalmol. 2020 Feb;127(2):230–237.
  • Noyan T, Sahin I, Sekeroğlu MR, et al. The serum vitamin C levels in Behçet’s disease. Yonsei Med J. 2003 Oct 30;44(5):771–8. doi: 10.3349/ymj.2003.44.5.771
  • Kükner AS, Kükner A, Naziroğlu M, et al. Protective effects of intraperitoneal vitamin C, aprotinin and melatonin administration on retinal edema during experimental uveitis in the guinea pig. Cell Biochem Funct. 2004 Sep;22(5):299–305.
  • Pararajasegaram G, Sevanian A, NA R. Suppression of S antigen-induced uveitis by vitamin E supplementation. Ophthalmic Res. 2009;23(3):121–127.
  • Nussenblatt RB, Kim J, Thompson DJ, et al. Vitamin E in the treatment of uveitis-associated macular edema. Am J Ophthalmol. 2006 Jan;141(1):193–194.
  • van Rooij J, Schwartzenberg SG, Mulder PG, et al. Oral vitamins C and E as additional treatment in patients with acute anterior uveitis: a randomised double masked study in 145 patients. Br J Ophthalmol. 1999 Nov;83(11):1277–1282.
  • Hewlings SJ, DS K. Curcumin: a review of its effects on human health. Foods. 2017 Oct 22;6(10):92.
  • Wang M, Wang Z, Liu Y, et al. The effectiveness and safety of total glucosides of paeony in systemic lupus erythematosus: a systematic review and meta-analysis. Medicine (Baltimore). 2022 Dec 16;101(50):e32029. doi: 10.1097/MD.0000000000032029
  • Li Q, Huang Y, Liu P, et al. Effect of tripterygium wilfordii polyglycoside tablets on serum inflammatory factors and T cells in patients with chronic nephritis. Am J Transl Res. 2021;13(7):8385–8390.
  • Smeele HTW, Röder E, AGMGJ M, et al. Tumour necrosis factor inhibitor use during pregnancy is associated with increased birth weight of rheumatoid arthritis patients’ offspring. Ann Rheumatic Dis. 2022;81(10):1367–1373.

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