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Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology 4/2014

01.04.2014 | Inflammatory Disorders

Anti-TNF-α agents for refractory cystoid macular edema associated with noninfectious uveitis

verfasst von: Michal Schaap-Fogler, Radgonde Amer, Ronit Friling, Ethan Priel, Michal Kramer

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 4/2014

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Abstract

Background

The use of anti-tumor necrosis factor (TNF)-α agents for uveitis has been increasing since the first efficacy studies in 2004. However, information on their specific role in cystic macular edema remains sparse. The aim of this study was to evaluate the efficacy of anti-TNF-α agents for the treatment of uveitis-related refractory cystoid macular edema.

Methods

The files of 23 consecutive patients treated for cystoid macular edema at the uveitis services of two tertiary medical centers in 2006-2011 were reviewed for demographic data, visual acuity, and optical coherence tomography measurements at baseline and 3, 6, and 12 months after treatment. Changes in mean visual acuity and macular thickness were analyzed. Findings were compared between patients treated with a conventional immunosuppressive regimen only (n = 18, 27 eyes) and patients treated with an anti-TNF-α agent after proving refractory to conventional treatment (n = 9, 15 eyes).

Results

Mean duration of cystoid macular edema before initiation of anti-TNF-α therapy was 12 ± 8 months. The two groups had similar baseline values of mean central macular thickness and visual acuity. Significant improvement in macular thickness was noted at 3 months in both groups, with a maximal effect at 6 months for the anti-TNF-α group (p = 0.002). Maximal improvement in visual acuity was achieved at 3 months in both groups, with a reduced effect towards 12 months. Mean visual acuity at 12 months was similar in both groups.

Conclusions

Anti-TNF-α agents may serve as an effective lasting treatment for long-standing refractory uveitis-related cystoid macular edema. Their role as first-line therapy in this setting warrants further investigation.
Literatur
1.
Zurück zum Zitat Curnow SJ, Murray PI (2006) Inflammatory mediators of uveitis: cytokines and chemokines. Curr Opin Ophthalmol 17:532–537PubMedCrossRef Curnow SJ, Murray PI (2006) Inflammatory mediators of uveitis: cytokines and chemokines. Curr Opin Ophthalmol 17:532–537PubMedCrossRef
2.
Zurück zum Zitat Ouchi M, West K, Crabb JW, Kinoshita S, Kamei M (2005) Proteomic analysis of vitreous from diabetic macular edema. Exp Eye Res 81:176–182PubMedCrossRef Ouchi M, West K, Crabb JW, Kinoshita S, Kamei M (2005) Proteomic analysis of vitreous from diabetic macular edema. Exp Eye Res 81:176–182PubMedCrossRef
3.
Zurück zum Zitat 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 46:4251–4259PubMedCrossRef 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 46:4251–4259PubMedCrossRef
4.
Zurück zum Zitat 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 142:192–194PubMedCrossRef 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 142:192–194PubMedCrossRef
6.
Zurück zum Zitat De Vos AF, Hoekzema R, Kijlstra A (1992) Cytokines and uveitis, a review. Curr Eye Res 11(6):581–597PubMedCrossRef De Vos AF, Hoekzema R, Kijlstra A (1992) Cytokines and uveitis, a review. Curr Eye Res 11(6):581–597PubMedCrossRef
7.
Zurück zum Zitat Ossewaarde-van Norel A, Rothova A (2011) Clinical review: update on treatment of inflammatory macular edema. Ocul Immunol Inflamm 19(1):75–83PubMedCrossRef Ossewaarde-van Norel A, Rothova A (2011) Clinical review: update on treatment of inflammatory macular edema. Ocul Immunol Inflamm 19(1):75–83PubMedCrossRef
8.
Zurück zum Zitat Roesel M, Ruttig A, Schumacher C, Heinz C, Heiligenhaus A (2011) Risk factors for the development of macular edema in noninfectious uveitis. Eur J Ophthalmol 21(5):625–630PubMedCrossRef Roesel M, Ruttig A, Schumacher C, Heinz C, Heiligenhaus A (2011) Risk factors for the development of macular edema in noninfectious uveitis. Eur J Ophthalmol 21(5):625–630PubMedCrossRef
9.
Zurück zum Zitat Sreekantam S, Denniston AK, Murray PI (2011) Survey of expert practice and perceptions of the supporting clinical evidence for the management of uveitis-related cataract and cystoid macular oedema. Ocul Immunol Inflamm 19(5):353–357PubMedCrossRef Sreekantam S, Denniston AK, Murray PI (2011) Survey of expert practice and perceptions of the supporting clinical evidence for the management of uveitis-related cataract and cystoid macular oedema. Ocul Immunol Inflamm 19(5):353–357PubMedCrossRef
10.
Zurück zum Zitat Lardenoye CW, van Kooij B, Rothova A (2006) Impact of macular edema on visual acuity in uveitis. Ophthalmology 113(8):1446–1449PubMedCrossRef Lardenoye CW, van Kooij B, Rothova A (2006) Impact of macular edema on visual acuity in uveitis. Ophthalmology 113(8):1446–1449PubMedCrossRef
11.
Zurück zum Zitat Rothova A, Suttorp-van Schulten MS, Frits Treffers W, Kijlstra A (1996) Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol 80(4):332–336PubMedCentralPubMedCrossRef Rothova A, Suttorp-van Schulten MS, Frits Treffers W, Kijlstra A (1996) Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol 80(4):332–336PubMedCentralPubMedCrossRef
12.
Zurück zum Zitat Rothova A (2002) Medical treatment of cystoid macular edema. Ocul Immunol Inflamm 10(4):239–246PubMedCrossRef Rothova A (2002) Medical treatment of cystoid macular edema. Ocul Immunol Inflamm 10(4):239–246PubMedCrossRef
13.
Zurück zum Zitat Papadaki T, Zacharopoulos I, Iaccheri B, Fiore T, Foster CS (2005) Somatostatin for uveitic cystoid macular edema (CME). Ocul Immunol Inflamm 13(6):469–470PubMedCrossRef Papadaki T, Zacharopoulos I, Iaccheri B, Fiore T, Foster CS (2005) Somatostatin for uveitic cystoid macular edema (CME). Ocul Immunol Inflamm 13(6):469–470PubMedCrossRef
14.
Zurück zum Zitat van Kooij B, Rothova A, de Vries P (2006) The pros and cons of intravitreal triamcinolone injections for uveitis and inflammatory cystoid macular edema. Ocul Immunol Inflamm 14(2):73–85PubMedCrossRef van Kooij B, Rothova A, de Vries P (2006) The pros and cons of intravitreal triamcinolone injections for uveitis and inflammatory cystoid macular edema. Ocul Immunol Inflamm 14(2):73–85PubMedCrossRef
15.
Zurück zum Zitat Gutfleisch M, Spital G, Mingels A, Pauleikhoff D, Lommatzsch A, Heiligenhaus A (2007) Pars plana vitrectomy with intravitreal triamcinolone: effect on uveitic cystoid macular oedema and treatment limitations. Br J Ophthalmol 91(3):345–348PubMedCentralPubMedCrossRef Gutfleisch M, Spital G, Mingels A, Pauleikhoff D, Lommatzsch A, Heiligenhaus A (2007) Pars plana vitrectomy with intravitreal triamcinolone: effect on uveitic cystoid macular oedema and treatment limitations. Br J Ophthalmol 91(3):345–348PubMedCentralPubMedCrossRef
16.
Zurück zum Zitat Jabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, Louie JS, Nussenblatt RB, Stiehm ER, Tessler H, Van Gelder RN, Whitcup SMS, Yocum D (2000) Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol 130(4):492–513PubMedCrossRef Jabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, Louie JS, Nussenblatt RB, Stiehm ER, Tessler H, Van Gelder RN, Whitcup SMS, Yocum D (2000) Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol 130(4):492–513PubMedCrossRef
17.
Zurück zum Zitat Gulati N, Forooghian F, Lieberman R, Jabs DA (2011) Vascular endothelial growth factor inhibition in uveitis: a systematic review. Br J Ophthalmol 95(2):162–165, Epub 2010 May 21PubMedCrossRef Gulati N, Forooghian F, Lieberman R, Jabs DA (2011) Vascular endothelial growth factor inhibition in uveitis: a systematic review. Br J Ophthalmol 95(2):162–165, Epub 2010 May 21PubMedCrossRef
18.
Zurück zum Zitat Bae JH, Lee CS, Lee SC (2011) Efficacy and safety of intravitreal bevacizumab compared with intravitreal and posterior sub-tenon triamcinolone acetonide for treatment of uveitic cystoid macular edema. Retina 31(1):111–118PubMedCrossRef Bae JH, Lee CS, Lee SC (2011) Efficacy and safety of intravitreal bevacizumab compared with intravitreal and posterior sub-tenon triamcinolone acetonide for treatment of uveitic cystoid macular edema. Retina 31(1):111–118PubMedCrossRef
19.
Zurück zum Zitat Habot-Wilner Z, Sallam A, Pacheco PA, Do HH, McCluskey P, Lightman S (2010) Intravitreal triamcinolone acetonide as adjunctive treatment with systemic therapy for uveitic macular edema. Eur J Ophthalmol 21(S6):56–61 Habot-Wilner Z, Sallam A, Pacheco PA, Do HH, McCluskey P, Lightman S (2010) Intravitreal triamcinolone acetonide as adjunctive treatment with systemic therapy for uveitic macular edema. Eur J Ophthalmol 21(S6):56–61
20.
Zurück zum Zitat Santos Lacomba M, Marcos Martín C, Gallardo Galaera JM, Gómez Vidal MA, Collantes Estévez E, Ramírez Chamond R, Omar M (2001) Aqueous humor and serum tumor necrosis factor-alpha in clinical uveitis. Ophthalmic Res 33:251–255PubMedCrossRef Santos Lacomba M, Marcos Martín C, Gallardo Galaera JM, Gómez Vidal MA, Collantes Estévez E, Ramírez Chamond R, Omar M (2001) Aqueous humor and serum tumor necrosis factor-alpha in clinical uveitis. Ophthalmic Res 33:251–255PubMedCrossRef
21.
Zurück zum Zitat Pérez-Guijo V, Santos-Lacomba M, Sánchez-Hernández M, Castro-Villegas Mdel C, Gallardo-Galera JM, Collantes-Estévez E (2004) Tumour necrosis factor-alpha levels in aqueous humour and serum from patients with uveitis: the involvement of HLA-B27. Curr Med Res Opin 20(2):155–157PubMedCrossRef Pérez-Guijo V, Santos-Lacomba M, Sánchez-Hernández M, Castro-Villegas Mdel C, Gallardo-Galera JM, Collantes-Estévez E (2004) Tumour necrosis factor-alpha levels in aqueous humour and serum from patients with uveitis: the involvement of HLA-B27. Curr Med Res Opin 20(2):155–157PubMedCrossRef
22.
Zurück zum Zitat Murphy CC, Ayliffe WH, Booth A, Makanjuola D, Andrews PA, Jayne D (2004) Tumor necrosis factor alpha blockade with infliximab for refractory uveitis and scleritis. Ophthalmology 111(2):352–356PubMedCrossRef Murphy CC, Ayliffe WH, Booth A, Makanjuola D, Andrews PA, Jayne D (2004) Tumor necrosis factor alpha blockade with infliximab for refractory uveitis and scleritis. Ophthalmology 111(2):352–356PubMedCrossRef
23.
Zurück zum Zitat 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(8):1575–1581PubMedCrossRef 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(8):1575–1581PubMedCrossRef
24.
Zurück zum Zitat Murphy CC, Greiner K, Plskova J, Duncan L, Frost A, Isaacs JD, Rebello P, Waldmann H, Hale G, Forrester JV, Dick AD (2004) Neutralizing tumor necrosis factor activity leads to remission in patients with refractory noninfectious posterior uveitis. Arch Ophthalmol 122(6):845–851PubMedCrossRef Murphy CC, Greiner K, Plskova J, Duncan L, Frost A, Isaacs JD, Rebello P, Waldmann H, Hale G, Forrester JV, Dick AD (2004) Neutralizing tumor necrosis factor activity leads to remission in patients with refractory noninfectious posterior uveitis. Arch Ophthalmol 122(6):845–851PubMedCrossRef
25.
Zurück zum Zitat 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(4):648–650PubMedCrossRef 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(4):648–650PubMedCrossRef
26.
Zurück zum Zitat Diaz-Llopis M, García-Delpech S, Salom D, Udaondo P, Hernández-Garfella M, Bosch-Morell F, Quijada A, Romero FJ (2008) Adalimumab therapy for refractory uveitis: a pilot study. J Ocul Pharmacol Ther 24(3):351–361PubMedCrossRef Diaz-Llopis M, García-Delpech S, Salom D, Udaondo P, Hernández-Garfella M, Bosch-Morell F, Quijada A, Romero FJ (2008) Adalimumab therapy for refractory uveitis: a pilot study. J Ocul Pharmacol Ther 24(3):351–361PubMedCrossRef
27.
Zurück zum Zitat Farvardin M, Afarid M, Mehryar M, Hosseini H (2010) Intravitreal infliximab for the treatment of sight-threatening chronic noninfectious uveitis. Retina 30(9):1530–1535PubMedCrossRef Farvardin M, Afarid M, Mehryar M, Hosseini H (2010) Intravitreal infliximab for the treatment of sight-threatening chronic noninfectious uveitis. Retina 30(9):1530–1535PubMedCrossRef
28.
Zurück zum Zitat Androudi S, Tsironi E, Kalogeropoulos C, Theodoridou A, Brazitikos P (2010) Intravitreal adalimumab for refractory uveitis-related macular edema. Ophthalmology 117(8):1612–1616PubMedCrossRef Androudi S, Tsironi E, Kalogeropoulos C, Theodoridou A, Brazitikos P (2010) Intravitreal adalimumab for refractory uveitis-related macular edema. Ophthalmology 117(8):1612–1616PubMedCrossRef
29.
Zurück zum Zitat Olivieri I, Latanza L, Siringo S, Peruz G, Di Iorio V (2008) Successful treatment of severe Behçet’s disease with infliximab in an Italian Olympic athlete. J Rheumatol 35:930–932PubMedCrossRef Olivieri I, Latanza L, Siringo S, Peruz G, Di Iorio V (2008) Successful treatment of severe Behçet’s disease with infliximab in an Italian Olympic athlete. J Rheumatol 35:930–932PubMedCrossRef
30.
Zurück zum Zitat Erckens RJ, Mostard RL, Wijnen PA, Schouten JS, Drent M (2012) Adalimumab successful in sarcoidosis patients with refractory chronic non-infectious uveitis. Graefes Arch Clin Exp Ophthalmol 250(5):713–720PubMedCentralPubMedCrossRef Erckens RJ, Mostard RL, Wijnen PA, Schouten JS, Drent M (2012) Adalimumab successful in sarcoidosis patients with refractory chronic non-infectious uveitis. Graefes Arch Clin Exp Ophthalmol 250(5):713–720PubMedCentralPubMedCrossRef
31.
Zurück zum Zitat Calleja S, Cordero-Coma M, Rodriguez E, Llorente M, Franco M, Ruiz de Morales JG (2012) Adalimumab specifically induces CD3(+) CD4(+) CD25(high) Foxp3(+) CD127(-) T-regulatory cells and decreases vascular endothelial growth factor plasma levels in refractory immuno-mediated uveitis: a non-randomized pilot intervention study. Eye (Lond) 26(3):468–477CrossRef Calleja S, Cordero-Coma M, Rodriguez E, Llorente M, Franco M, Ruiz de Morales JG (2012) Adalimumab specifically induces CD3(+) CD4(+) CD25(high) Foxp3(+) CD127(-) T-regulatory cells and decreases vascular endothelial growth factor plasma levels in refractory immuno-mediated uveitis: a non-randomized pilot intervention study. Eye (Lond) 26(3):468–477CrossRef
32.
Zurück zum Zitat Taylor SR, Habot-Wilner Z, Pacheco P, Lightman SL (2009) Intraocular methotrexate in the treatment of uveitis and uveitic cystoid macular edema. Ophthalmology 116(4):797–801PubMedCrossRef Taylor SR, Habot-Wilner Z, Pacheco P, Lightman SL (2009) Intraocular methotrexate in the treatment of uveitis and uveitic cystoid macular edema. Ophthalmology 116(4):797–801PubMedCrossRef
33.
Zurück zum Zitat Campochiaro PA, Hafiz G, Channa R, Shah SM, Nguyen QD, Ying H, Do DV, Zimmer-Galler I, Solomon SD, Sung JU, Syed B (2010) Antagonism of vascular endothelial growth factor for macular edema caused by retinal vein occlusions: two-year outcomes. Ophthalmology 117(12):2387–2394, e1-5PubMedCrossRef Campochiaro PA, Hafiz G, Channa R, Shah SM, Nguyen QD, Ying H, Do DV, Zimmer-Galler I, Solomon SD, Sung JU, Syed B (2010) Antagonism of vascular endothelial growth factor for macular edema caused by retinal vein occlusions: two-year outcomes. Ophthalmology 117(12):2387–2394, e1-5PubMedCrossRef
34.
Zurück zum Zitat Stewart MW (2012) Anti-vascular endothelial growth factor drug treatment of diabetic macular edema: the evolution continues. Curr Diabetes Rev 8(4):237–246PubMedCrossRef Stewart MW (2012) Anti-vascular endothelial growth factor drug treatment of diabetic macular edema: the evolution continues. Curr Diabetes Rev 8(4):237–246PubMedCrossRef
35.
Zurück zum Zitat Deuter CM, Kötter I, Günaydin I, Stübiger N, Doycheva DG, Zierhut M (2009) Efficacy and tolerability of interferon alpha treatment in patients with chronic cystoid macular oedema due to non-infectious uveitis. Br J Ophthalmol 93(7):906–913PubMedCrossRef Deuter CM, Kötter I, Günaydin I, Stübiger N, Doycheva DG, Zierhut M (2009) Efficacy and tolerability of interferon alpha treatment in patients with chronic cystoid macular oedema due to non-infectious uveitis. Br J Ophthalmol 93(7):906–913PubMedCrossRef
36.
Zurück zum Zitat Adán A, Hernandez V, Ortiz S, Molina JJ, Pelegrin L, Espinosa G, Sanmartí R (2010) Effects of infliximab in the treatment of refractory posterior uveitis of Behçet’s disease after withdrawal of infusions. Int Ophthalmol 30(5):577–581PubMedCrossRef Adán A, Hernandez V, Ortiz S, Molina JJ, Pelegrin L, Espinosa G, Sanmartí R (2010) Effects of infliximab in the treatment of refractory posterior uveitis of Behçet’s disease after withdrawal of infusions. Int Ophthalmol 30(5):577–581PubMedCrossRef
37.
Zurück zum Zitat Yamada Y, Sugita S, Tanaka H, Kamoi K, Kawaguchi T, Mochizuki M (2010) Comparison of infliximab versus ciclosporin during the initial 6-month treatment period in Behçet disease. Br J Ophthalmol 94:284–288PubMedCrossRef Yamada Y, Sugita S, Tanaka H, Kamoi K, Kawaguchi T, Mochizuki M (2010) Comparison of infliximab versus ciclosporin during the initial 6-month treatment period in Behçet disease. Br J Ophthalmol 94:284–288PubMedCrossRef
38.
Zurück zum Zitat Lee RWJ, Dick AD (2010) Treat early and embrace the evidence in favour of anti-TNF-a therapy for Behcet’s uveitis. Br J Ophthalmol 94(3):269–270PubMedCrossRef Lee RWJ, Dick AD (2010) Treat early and embrace the evidence in favour of anti-TNF-a therapy for Behcet’s uveitis. Br J Ophthalmol 94(3):269–270PubMedCrossRef
39.
Zurück zum Zitat Olivieri I, Padula A, Leccese P, D’Angelo S, Giasi V (2009) Long-lasting remission of severe Behçet’s disease after the end of infliximab therapy. J Rheumatol 36(4):855PubMedCrossRef Olivieri I, Padula A, Leccese P, D’Angelo S, Giasi V (2009) Long-lasting remission of severe Behçet’s disease after the end of infliximab therapy. J Rheumatol 36(4):855PubMedCrossRef
Metadaten
Titel
Anti-TNF-α agents for refractory cystoid macular edema associated with noninfectious uveitis
verfasst von
Michal Schaap-Fogler
Radgonde Amer
Ronit Friling
Ethan Priel
Michal Kramer
Publikationsdatum
01.04.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 4/2014
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-013-2552-8

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