Tocilizumab treatment for refractory uveitis-related cystoid macular edema

  • Alfredo AdánEmail author
  • Marina Mesquida
  • Victor Llorenç
  • Gerard Espinosa
  • Blanca Molins
  • Maria V. Hernández
  • Laura Pelegrín
Inflammatory Disorders



This retrospective study investigated the efficacy of tocilizumab (TCZ), a fully humanized antibody that binds both to soluble and membrane bound IL-6 receptors, for the treatment of uveitis-related cystoid macular edema (CME) refractory to immunomodulatory therapy.


Five refractory patients with uveitis-related CME who received TCZ between January and August 2012 were included. All patients received 8 mg/kg TCZ at 4-week intervals. Data regarding patient demographics, use of immunosuppressive drugs, biologic agents or intravitreal therapies prior to TCZ infusions were collected. Main outcome measure was central foveal thickness (CFT) measured by optical coherence tomography at 6 months. Secondary outcome measures were degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria) and visual acuity (logarithm of the minimum angle of resolution [log-MAR]) at month 6. Adverse events (AEs) related to TCZ therapy were also assessed.


Eight eyes from five patients (all females) were included. Mean age was 49.4 years (range, 30–68). Mean follow-up was 8.4 months (range, 6–12). Before TCZ, all patients received and failed conventional immunosuppressive therapy and had received at least another biologic agent. Uveitis diagnoses were Birdshot chorioretinopathy (n = 3), juvenile idiopathic arthritis (JIA)-associated uveitis (n = 1), and idiopathic panuveitis (n = 1). Mean evolution of CME was 13.4 years (range, 2–30). Mean baseline CFT (95 % confidence interval) was 602 ± 236 μm at baseline, 386 ± 113 μm at month 1 (p = 0.006), 323 ± 103 μm at month 3 (p = 0.026), and 294.5 ± 94.5 μm at month 6 (p = 0.014). Median best-corrected visual acuity (BCVA) improved from 0.66 ± 0.57 at baseline to 0.47 ± 0.62 at month 6 (p = 0.035). After 6 months, an improvement of ≥ 2 lines of BCVA was observed in 50 % of eyes (p = 0.028) remained stable in 25 % and worsened in none of the patients. Sustained uveitis remission was achieved in all patients. No AEs were reported.


These data suggest that TCZ is effective for treating CME in otherwise treatment-refractory cases of uveitis.


Tocilizumab Uveitis Macular edema 


Financial support


Conflict of interest

No conflicting relationship exists for any author.


  1. 1.
    Lardenoye CW, van Kooij B, Rothova A (2006) Impact of macular edema on visual acuity in uveitis. Opthalmology 113:1146–1149CrossRefGoogle Scholar
  2. 2.
    Rothova A (2002) Medical treatment of cystoid macular edema. Ocul Immunol Inflamm 10:239–246PubMedCrossRefGoogle Scholar
  3. 3.
    Díaz Llopis M, Salom D, Garcia de Vicuña C, Cordero Coma M, Ortega G, Ortego N, Suarez de Figueroa M, Rio Pardo MJ, Fernandez-Cid C, Fonollosa A, Blanco R, Garcia-Aparicio AM, Benitez del Castillo JM, Olea JL, Arevalo JF (2012) Treatment of refractory uveitis with adalimumab: a prospective multicenter study of 131 patients. Ophthalmology 119:1575–1581PubMedCrossRefGoogle Scholar
  4. 4.
    Markomichelakis NN, Theodossiadis PG, Pantelia E, Papaefthimiou S, Theodossiadis GP, Sfikakis PP (2004) Infliximab for chronic cystoid macular edema associated with uveitis. Am J Ophthalmol 138:648–650PubMedCrossRefGoogle Scholar
  5. 5.
    Adán A, Pelegrín L, Rey A, Llorenç V, Mesquida M, Molins B, Ríos J, Keller J (2013) Dexamethasone intravitreal implant for treatment of uveitic persistent cystoid macular edema in vitrectomized patients. Retina. 2013 Mar 19. PMID:23514796Google Scholar
  6. 6.
    Taylor SR, Lightman SL, Sugar EA, Jaffe GJ, Freeman WR, Altaweel MM, Kozak I, Holbrook JT, Jabs DA, Kempen JH (2012) The impact of macular edema on visual function in intermediate, posterior, and panuveitis. Ocul Immunol Inflamm 20:171–181PubMedCrossRefGoogle Scholar
  7. 7.
    Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J (2008) IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 67:1516–1523PubMedCrossRefGoogle Scholar
  8. 8.
    Jabs DA, Nussenblatt RB, Rosenbaum JT (2005) Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 140:509–516PubMedCrossRefGoogle Scholar
  9. 9.
    Nussenblatt RB, Palestine AG, Chan CC, Roberge F (1985) Standardization of vitreal inflammatory activity in intermediate and posterior uveitis. Ophthalmology 92:467–471PubMedGoogle Scholar
  10. 10.
    Tanaka T, Kishimoto T (2012) Targeting interleukin-6: all the way to treat autoimmune and inflammatory diseases. Int J Biol Sci 8:1227–1236PubMedCrossRefGoogle Scholar
  11. 11.
    Kramer M, Monselise Y, Bahar I, Cohen Y, Weinberger D, Goldenberg-Cohen N (2007) Serum cytokine levels in active uveitis and remission. Curr Eye Res 32:669–675PubMedCrossRefGoogle Scholar
  12. 12.
    van Kooij B, Rothova A, Rijkers GT, de Groot-Mijnes JD (2006) Distinct cytokine and chemokine profiles in the aqueous of patients with uveitis and cystoid macular edema. Am J Ophthalmol 142:192–194PubMedCrossRefGoogle Scholar
  13. 13.
    Valentincic NV, de Groot-Mijnes JD, Kraut A, Korosec P, Hawlina M, Rothova A (2001) Intraocular and serum cytokine profiles in patients with intermediate uveitis. Mol Vis 17:2003–2010Google Scholar
  14. 14.
    Kuiper JJ, Mutis T, de Jager W, de Groot-Mijnes JD, Rothova A (2011) Intraocular interleukin-17 and proinflammatory cytokines in HLA-A29-associated birdshot chorioretinopathy. Am J Ophthalmol 152:177–182PubMedCrossRefGoogle Scholar
  15. 15.
    Curnow SJ, Falciani F, Durrani OM, Cheung CM, Ross EJ, Wloka K, Rauz S, Wallace GR, Salmon M, Murray PI (2005) Multiplex bead immunoassay analysis of aqueous humor reveals distinct cytokine profiles in uveitis. Invest Ophthalmol Vis Sci 46:4251–4259PubMedCrossRefGoogle Scholar
  16. 16.
    Ongkosuwito JV, Feron EJ, van Doornik CE, Van der Lelij A, Hoyng CB, La Heij EC, Kijlstra A (1998) Analysis of immunoregulatory cytokines in ocular fluid samples from patients with uveitis. Invest Ophthalmol Vis Sci 39:2659–2665PubMedGoogle Scholar
  17. 17.
    Yoshimura T, Sonoda KH, Ohguro N, Ohsugi Y, Ishibashi T, Cua DJ, Kobayashi T, Yoshida A, Yoshimura A (2009) Involvement of Th17 cells and the effect of anti-IL-6. Therapy in autoimmune uveitis. Rheumatology 48:347–354PubMedCrossRefGoogle Scholar
  18. 18.
    Hohki S, Ohguro N, Haruta H, Nakai K, Terabe F, Serada S, Fujimoto M, Nomura S, Kawahata H, Kishimoto T, Naka T (2010) Blockade of interleukin-6 signaling suppresses experimental autoimmune uveoretinitis by the inhibition of inflammatory Th17 responses. Exp Eye Res 91:162–170PubMedCrossRefGoogle Scholar
  19. 19.
    Muselier A, Bielefeld P, Bidot S, Vinit J, Besancenot JF, Bron A (2011) Efficacy of tocilizumab in two patients with anti-TNF-alpha refractory uveitis. Ocul Immunol Inflamm 19:382–383PubMedCrossRefGoogle Scholar
  20. 20.
    Tappeiner C, Heinz C, Ganser G, Heiligenhaus A (2012) Is tocilizumab and effective option for treatment of refractory uveitis associated with juvenile idiopathic arthritis? J Rheumatolol 39:1294–1295CrossRefGoogle Scholar
  21. 21.
    Oshitari T, Kajita F, Tobe A, Itami M, Yotsukura J, Baba T, Yamamoto S (2012) Refractory uveitis in patient with castleman disease successfully treated with tocilizumab. Case Rep Ophthalmol Med. Epub 2012 Nov 6. PMID:23198204Google Scholar
  22. 22.
    Urbaniak P, Hasler P, Kretzschmar S (2012) Refractory neuro-Behçet treated by tocilizumab: a case report. Clin Exp Rheumatol 30(3 Suppl 72):S73–S75PubMedGoogle Scholar
  23. 23.
    Hirano T, Ohguro N, Hohki S, Hagihara K, Shima Y, Narazaki M, Ogata A, Yoshizaki K, Kumanogoh A, Kishimoto T, Tanaka T (2012) A case of Behçet’s disease treated with a humanized anti-interleukin-6 receptor antibody, tocilizumab. Mod Rheumatol 22:298–302PubMedCrossRefGoogle Scholar
  24. 24.
    Adán A, Llorenç V, Mesquida M, Pelegrín L (2012) Tocilizumab treatment for recalcitrant uveitic macular edema. Graefes Arch Clin Exp Ophthalmol. Dec 28 PMID:23271335Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Alfredo Adán
    • 1
    Email author
  • Marina Mesquida
    • 1
  • Victor Llorenç
    • 1
  • Gerard Espinosa
    • 3
  • Blanca Molins
    • 4
  • Maria V. Hernández
    • 2
  • Laura Pelegrín
    • 1
  1. 1.Department of Ophthalmology, Hospital Clínic of BarcelonaUniversitat of BarcelonaBarcelonaSpain
  2. 2.Department Rheumatology, Hospital Clinic of BarcelonaUniversitat of BarcelonaBarcelonaSpain
  3. 3.Department of Autoimmune Diseases, Hospital Clinic of BarcelonaUniversitat of BarcelonaBarcelonaSpain
  4. 4.Fundació Clínic per la Recerca Biomèdica, IDIBAPSBarcelonaSpain

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