Skip to main content

Advertisement

SpringerLink
Log in

Tocilizumab treatment for refractory uveitis-related cystoid macular edema

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

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Lardenoye CW, van Kooij B, Rothova A (2006) Impact of macular edema on visual acuity in uveitis. Opthalmology 113:1146–1149

    Article  Google Scholar 

  2. Rothova A (2002) Medical treatment of cystoid macular edema. Ocul Immunol Inflamm 10:239–246

    Article  PubMed  Google Scholar 

  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 119:1575–1581

    Article  PubMed  Google Scholar 

  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 138:648–650

    Article  PubMed  CAS  Google Scholar 

  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:23514796

  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 20:171–181

    Article  PubMed  Google Scholar 

  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 67:1516–1523

    Article  PubMed  CAS  Google Scholar 

  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 140:509–516

    Article  PubMed  Google Scholar 

  9. Nussenblatt RB, Palestine AG, Chan CC, Roberge F (1985) Standardization of vitreal inflammatory activity in intermediate and posterior uveitis. Ophthalmology 92:467–471

    PubMed  CAS  Google Scholar 

  10. Tanaka T, Kishimoto T (2012) Targeting interleukin-6: all the way to treat autoimmune and inflammatory diseases. Int J Biol Sci 8:1227–1236

    Article  PubMed  CAS  Google Scholar 

  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 32:669–675

    Article  PubMed  CAS  Google Scholar 

  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 142:192–194

    Article  PubMed  Google Scholar 

  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 17:2003–2010

    Google Scholar 

  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 152:177–182

    Article  PubMed  CAS  Google Scholar 

  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 46:4251–4259

    Article  PubMed  Google Scholar 

  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 39:2659–2665

    PubMed  CAS  Google Scholar 

  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 48:347–354

    Article  PubMed  CAS  Google Scholar 

  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 91:162–170

    Article  PubMed  CAS  Google Scholar 

  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 19:382–383

    Article  PubMed  CAS  Google Scholar 

  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 39:1294–1295

    Article  Google Scholar 

  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:23198204

  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–S75

    PubMed  CAS  Google Scholar 

  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 22:298–302

    Article  PubMed  Google Scholar 

  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:23271335

    Google Scholar 

Download references

Financial support

None.

Conflict of interest

No conflicting relationship exists for any author.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Hospital Clínic of Barcelona, Universitat of Barcelona, Sabino de Arana, 1 08028, Barcelona, Spain

    Alfredo Adán, Marina Mesquida, Victor Llorenç & Laura Pelegrín

  2. Department Rheumatology, Hospital Clinic of Barcelona, Universitat of Barcelona, Barcelona, Spain

    Maria V. Hernández

  3. Department of Autoimmune Diseases, Hospital Clinic of Barcelona, Universitat of Barcelona, Barcelona, Spain

    Gerard Espinosa

  4. Fundació Clínic per la Recerca Biomèdica, IDIBAPS, Barcelona, Spain

    Blanca Molins

Authors
  1. Alfredo Adán
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marina Mesquida
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Victor Llorenç
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gerard Espinosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Blanca Molins
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maria V. Hernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Laura Pelegrín
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alfredo Adán.

Additional information

The material of the manuscript is not under consideration for presentation.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adán, A., Mesquida, M., Llorenç, V. et al. Tocilizumab treatment for refractory uveitis-related cystoid macular edema. Graefes Arch Clin Exp Ophthalmol 251, 2627–2632 (2013). https://doi.org/10.1007/s00417-013-2436-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-013-2436-y

Keywords

Search

Navigation