Advances in treatment of refractory uveitic macular edema_Chinese Journal of Ocular Fundus Diseases

Authors：

JiangYunbin ,  WangHong

Department of Ophthalmology, The First People’s Hospital Affiliated to Shanghai JiaoTong University, Shanghai 200080, China;

Corresponding author：

WangHong, Email: wanghong700520@126.com

Keywords：

Uveitis/complications; Macular edema/drug therapy; Macular edema/surgery; Vitreoretinal surgery; Review

DOI：

10.3760/cma.j.issn.1005-1015.2017.01.031

Video：

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Uveitic macular edema (UME) is a major reason of permanent visual loss. Early treatment is essential for achieving a good visual outcome, but some patients are resistant or nonresponsive to the treatment, which is called refractory UME (RUME). Intravitreous injection of glucocorticoids can improve the intraocular drug concentration and avoid systemic side effects. Immunosuppressive agents have a certain role in improving RUME by inhibiting immune cells through a variety of ways. Non-steroidal anti-inflammatory drugs, carbonic anhydrase inhibitors and new biological agents also can improve RUME outcome, but their effectiveness and safety need to be confirmed by large scale randomized clinical trials. Vitrectomy can improve RUME outcome but whether peeling of internal limiting membrane is necessary or not is still controversial. Peeling the inner limiting membrane can eliminate the potential incentive for macular edema and remove the barrier. But the process of stripping may injury the retinal neurepithelium. To eliminate edema and protect the visual function, we should analysis the causes of RUME and treat it individually.

Citation： JiangYunbin, WangHong. Advances in treatment of refractory uveitic macular edema. Chinese Journal of Ocular Fundus Diseases, 2017, 33(1): 96-99. doi: 10.3760/cma.j.issn.1005-1015.2017.01.031 Copy

1.	Tomkins-Netzer O, Talat L, Bar A, et al. Long-term clinical outcome and causes of vision loss in patients with uveitis[J]. Ophthalmology, 2014, 121(12):2387-2392. DOI:10.1016/ j.ophtha.2014.07.007.
2.	Liu T, Bi H, Wang X, et al. Macular abnormalities in chinese patients with uveitis[J]. Optom Vis Sci, 2015, 92(8):858-862. DOI: 10.1097/OPX.0000000000000645.
3.	Xu HZ, Song Z, Fu S, et al. RPE barrier breakdown in diabetic retinopathy: seeing is believing[J]. J Ocul Biol Dis Infor, 2011, 4(1-2):83-92. DOI: 10.1007/s12177-011-9068-4.
4.	van Kooij B, Rothova A, Rijkers GT, et al. Distinct cytokine and chemokine profiles in the aqueous of patients with uveitis and cystoid macular edema[J]. Am J Ophthalmol, 2006, 142(1):192-194.
5.	Khera TK, Dick AD, Nicholson LB. Mechanisms of TNFalpha regulation in uveitis: focus on RNA-binding proteins[J]. Prog Retin Eye Res, 2010, 29(6):610-621. DOI: 10.1016/j.preteyeres. 2010.08.003.
6.	Gulati N, Forooghian F, Lieberman R, et al. Vascular endothelial growth factor inhibition in uveitis: a systematic review[J]. Br J Ophthalmol, 2011, 95(2):162-165. DOI: 10.1136/bjo.2009.177279.
7.	梁亮, 王红, 彭晓燕, 等. IL-17在实验性自身免疫性葡萄膜炎大鼠模型眼部的表达[J]. 眼科研究, 2010, 28(4):315-318. DOI: 10.3969/j.issn.1003-0808.2010.04.007.Liang L, Wang H, Peng XY, et al. Study on the expression of IL-17 in experimental autoimmune uveoretinitis[J]. Chin Ophthal Res, 2010, 28(4):315-318. DOI: 10.3969/j.issn.1003-0808.2010.04.007.
8.	Funatsu H, Yamashita H, Ikeda T, et al. Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema[J]. Ophthalmology, 2003, 110(9):1690-1696.
9.	Rothova A. Inflammatory cystoid macular edema[J]. Curr Opin Ophthalmol, 2007, 18(6):487-492.
10.	Acharya NR, Hong KC, Lee SM. Ranibizumab for refractory uveitis-related macular edema[J]. Am J Ophthalmol, 2009, 148(2):303-309. DOI: 10.1016/j.ajo.2009.03.028.
11.	Soheilian M, Eskandari A, Ramezani A, et al. A pilot study of intravitreal diclofenac versus intravitreal triamcinolone for uveitic cystoid macular edema[J]. Ocul Immunol Inflamm, 2013, 21(2):124-129. DOI: 10.3109/09273948.2012.745883.
12.	Leder HA, Jabs DA, Galor A, et al. Periocular triamcinolone acetonide injections for cystoid macular edemacomplicating noninfectious uveitis[J]. Am J Ophthalmol, 2011, 152(3):441-448. DOI: 10.1016/j.ajo.2011.02.009.
13.	Byun YS, Park YH. Complications and safety profile of posterior subtenon injection of triamcinolone acetonide[J].J Ocul Pharmacol Ther, 2009, 25(2):159-162. DOI: 10.1089/jop.2008.0087.
14.	Choudhry S, Ghosh S. Intravitreal and posterior subtenon triamcinolone acetonide in idiopathic bilateral uveitic macular oedema[J]. Clin Exp Ophthalmol, 2007, 35(8):713-718.
15.	Maca SM, Abela-Formanek C, Kiss CG, et al. Intravitreal triamcinolone for persistent cystoid macular oedema in eyes with quiescent uveitis[J]. Clin Exp Ophthalmol, 2009, 37(4):389-396. DOI: 10.1111/j.1442-9071.2009.02033.x.
16.	Sonmez K, Ozturk F. Complications of intravitreal triamcinolone acetonide for macular edema and predictive factors for intraocular pressure elevation[J]. Int J Ophthalmol, 2012, 5(6):719-725. DOI: 10.3980/j.issn.2222-3959.2012.06.13.
17.	Sallam A, Taylor SR, Habor-Wilner Z, et al. Repeat intravitreal triamcinolone acetonide injections in uveitic macular oedema[J]. Acta Ophthalmol, 2012, 90(4):323-325. DOI: 10.1111/j.1755-3768.2011.02247.
18.	Tomkins-Netzer O, Lightman S, Drye L, et al. Outcome of treatment of uveitic macular edema: the multicenter uveitis steroid treatment trial 2-year results[J]. Ophthalmology, 2015, 122(11):2351-2359. DOI: 10.1016/j.ophtha.2015.07.036.
19.	Khurana RN, Porco TC. Efficacy and safety of dexamethasone intravitreal implant for persistent uveitic cystoid macular edema[J]. Retina, 2015, 35(8):1640-1646. DOI: 10.1097/IAE.0000 000000000515.
20.	Lowder C, Belfort R Jr, Lightman S, et al. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis[J]. Arch Ophthalmol, 2011, 129(5):545-553. DOI: 10.1001/archophthalmol.2010.339.
21.	Arcinue CA, Ceron OM, Foster CS. A comparison between the fluocinolone acetonide (Retisert) and dexamethasone (Ozurdex) intravitreal implants in uveitis[J]. J Ocul Pharmacol Ther, 2013, 29(5):501-507. DOI: 10.1089/jop.2012.0180.
22.	Taylor SR, Habot-Wilner Z, Pacheco P, et al. Intraocular methotrexate in the treatment of uveitis and uveitic cystoid macular edema[J]. Ophthalmology, 2009, 116(4):797-801. DOI: 10.1016/j.ophtha.2008.10.033.
23.	Allegri P, Murialdo U, Peri S, et al. Randomized, double-blind, placebo-controlled clinical trial on the efficacy of 0.5% indomethacin eye drops in uveitic macular edema[J]. Invest Ophthalmol Vis Sci, 2014, 55(3):1463-1470. DOI: 10.1167/iovs.13-13202.
24.	Schilling H, Heiligenhaus A, Laube T, et al. Long-term effect of acetazolamide treatment of patients with uveitic chronic cystoid macular edema is limited by persisting inflammation[J]. Retina, 2005, 25(2):182-188.
25.	Cervantes-Castaneda RA, Giuliari GP, Gallagher MJ, et al. Intravitreal bevacizumab in refractory uveitic macular edema: one-year follow-up[J]. Eur J Ophthalmol, 2009, 19(4):622-629.
26.	Soheilian M, Rabbanikhah Z, Ramezani A, et al. Intravitreal bevacizumab versus triamcinolone acetonide for refractory uveitic cystoid macular edema: a randomized pilot study[J]. J Ocul Pharmacol Ther, 2010, 26(2):199-206. DOI: 10.1089/jop.2009.0093.
27.	Gillies MC, Su T. Interferon-alpha 2b enhances barrier function of bovine retinal microvascular endothelium in vitro[J]. Microvasc Res, 1995, 49(3):277-288.
28.	Deuter CM, Koetter I, Guenaydin I, et al. Interferon alfa-2a: a new treatment option for long lasting refractory cystoid macular edema in uveitis? A pilot study[J]. Retina, 2006, 26(7):786-791. DOI:10.1097/01.iae.0000244265.75771.71.
29.	Mackensen F, Jakob E, Springer C, et al. Interferon versus methotrexate in intermediate uveitis with macular edema: results of a randomized controlled clinical trial[J]. Am J Ophthalmol, 2013, 156(3):478-486. DOI: 10.1016/j.ajo.2013.05.002.
30.	Schaap-Fogler M, Amer R, Friling R, et al. Anti-TNF-α agents for refractory cystoids macular edema associated with noninfectious uveitis[J]. Graefe's Arch Clin Exp Ophthalmol, 2014, 252(4):633-640. DOI: 10.1007/s00417-013-2552-8.
31.	Farvardin M, Afarid M, Mehryar M, et al. Intravitreal infliximab for the treatment of sight-threatening chronic noninfectious uveitis[J]. Retina, 2010, 30(9):1530-1535. DOI: 10.1097/IAE.0b013e 3181d3758a.
32.	Markomichelakis NN, Theodossiadis PG, Pantelia E, et al. Infliximab for chronic cystoid macular edema associated with uveitis[J]. Am J Ophthalmol, 2004, 138(4):648-650. DOI:10.1016/j.ajo.2004.04.066.
33.	Diaz-Llopis M, Salom D, Garcia-de-Vicuna C, et al. Treatment of refractory uveitis with adalimumab: a prospective multicenter study of 131 patients[J]. Ophthalmology, 2012, 119(8):1575-1581. DOI: 10.1016/j.ophtha.2012.02.018.
34.	Mesquida M, Molins B, Llorenc V, et al. Long-term effects of tocilizumab therapy for refractory uveitis-related macular edema[J]. Ophthalmology, 2014, 121(12):2380-2386. DOI: 10.1016/ j.ophtha.2014.06.050.
35.	Kishi S, Kamei Y, Shimizu K. Tractional elevation of Henle's fiber layer in idiopathic macular holes[J]. Am J Ophthalmol, 1995, 120(4):486-496.
36.	Tranos P, Scott R, Zambarakji H, et al. The effect of pars plana vitrectomy on cystoid macular oedema associated with chronic uveitis: a randomised, controlled pilot study[J]. Br J Ophthalmol, 2006, 90(9):1107-1110.
37.	Matsunaga N, Ozeki H, Hirabayashi Y, et al. Histopathologic evaluation of the internal limiting membrane surgically excised from eyes with diabetic maculopathy[J]. Retina, 2005, 25(3):311-316.
38.	Radetzky S, Walter P, Fauser S, et al. Visual outcome of patients with macular edema after pars plana vitrectomy and indocyanine green-assisted peeling of the internal limiting membrane[J]. Graefe’s Arch Clin Exp Ophthalmol, 2004, 242(4):273-278.
39.	Gutfleisch M, Spital G, Mingels A, et al. Pars plana vitrectomy with intravitreal triamcinolone: effect on uveitic cystoid macular oedema and treatment limitations[J]. Br J Ophthalmol, 2007, 91(3):345-348. DOI: 10.1136/bjo.2006.101675.
40.	Lardenoye CW, van Schooneveld MJ, Frits Treffers W, et al. Grid laser photocoagulation for macular oedema in uveitis or the Irvine-Gass syndrome[J]. Br J Ophthalmol, 1998, 82(9):1013-1016.

1. Tomkins-Netzer O, Talat L, Bar A, et al. Long-term clinical outcome and causes of vision loss in patients with uveitis[J]. Ophthalmology, 2014, 121(12):2387-2392. DOI:10.1016/ j.ophtha.2014.07.007.
2. Liu T, Bi H, Wang X, et al. Macular abnormalities in chinese patients with uveitis[J]. Optom Vis Sci, 2015, 92(8):858-862. DOI: 10.1097/OPX.0000000000000645.
3. Xu HZ, Song Z, Fu S, et al. RPE barrier breakdown in diabetic retinopathy: seeing is believing[J]. J Ocul Biol Dis Infor, 2011, 4(1-2):83-92. DOI: 10.1007/s12177-011-9068-4.
4. van Kooij B, Rothova A, Rijkers GT, et al. Distinct cytokine and chemokine profiles in the aqueous of patients with uveitis and cystoid macular edema[J]. Am J Ophthalmol, 2006, 142(1):192-194.
5. Khera TK, Dick AD, Nicholson LB. Mechanisms of TNFalpha regulation in uveitis: focus on RNA-binding proteins[J]. Prog Retin Eye Res, 2010, 29(6):610-621. DOI: 10.1016/j.preteyeres. 2010.08.003.
6. Gulati N, Forooghian F, Lieberman R, et al. Vascular endothelial growth factor inhibition in uveitis: a systematic review[J]. Br J Ophthalmol, 2011, 95(2):162-165. DOI: 10.1136/bjo.2009.177279.
7. 梁亮, 王红, 彭晓燕, 等. IL-17在实验性自身免疫性葡萄膜炎大鼠模型眼部的表达[J]. 眼科研究, 2010, 28(4):315-318. DOI: 10.3969/j.issn.1003-0808.2010.04.007.Liang L, Wang H, Peng XY, et al. Study on the expression of IL-17 in experimental autoimmune uveoretinitis[J]. Chin Ophthal Res, 2010, 28(4):315-318. DOI: 10.3969/j.issn.1003-0808.2010.04.007.
8. Funatsu H, Yamashita H, Ikeda T, et al. Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema[J]. Ophthalmology, 2003, 110(9):1690-1696.
9. Rothova A. Inflammatory cystoid macular edema[J]. Curr Opin Ophthalmol, 2007, 18(6):487-492.
10. Acharya NR, Hong KC, Lee SM. Ranibizumab for refractory uveitis-related macular edema[J]. Am J Ophthalmol, 2009, 148(2):303-309. DOI: 10.1016/j.ajo.2009.03.028.
11. Soheilian M, Eskandari A, Ramezani A, et al. A pilot study of intravitreal diclofenac versus intravitreal triamcinolone for uveitic cystoid macular edema[J]. Ocul Immunol Inflamm, 2013, 21(2):124-129. DOI: 10.3109/09273948.2012.745883.
12. Leder HA, Jabs DA, Galor A, et al. Periocular triamcinolone acetonide injections for cystoid macular edemacomplicating noninfectious uveitis[J]. Am J Ophthalmol, 2011, 152(3):441-448. DOI: 10.1016/j.ajo.2011.02.009.
13. Byun YS, Park YH. Complications and safety profile of posterior subtenon injection of triamcinolone acetonide[J].J Ocul Pharmacol Ther, 2009, 25(2):159-162. DOI: 10.1089/jop.2008.0087.
14. Choudhry S, Ghosh S. Intravitreal and posterior subtenon triamcinolone acetonide in idiopathic bilateral uveitic macular oedema[J]. Clin Exp Ophthalmol, 2007, 35(8):713-718.
15. Maca SM, Abela-Formanek C, Kiss CG, et al. Intravitreal triamcinolone for persistent cystoid macular oedema in eyes with quiescent uveitis[J]. Clin Exp Ophthalmol, 2009, 37(4):389-396. DOI: 10.1111/j.1442-9071.2009.02033.x.
16. Sonmez K, Ozturk F. Complications of intravitreal triamcinolone acetonide for macular edema and predictive factors for intraocular pressure elevation[J]. Int J Ophthalmol, 2012, 5(6):719-725. DOI: 10.3980/j.issn.2222-3959.2012.06.13.
17. Sallam A, Taylor SR, Habor-Wilner Z, et al. Repeat intravitreal triamcinolone acetonide injections in uveitic macular oedema[J]. Acta Ophthalmol, 2012, 90(4):323-325. DOI: 10.1111/j.1755-3768.2011.02247.
18. Tomkins-Netzer O, Lightman S, Drye L, et al. Outcome of treatment of uveitic macular edema: the multicenter uveitis steroid treatment trial 2-year results[J]. Ophthalmology, 2015, 122(11):2351-2359. DOI: 10.1016/j.ophtha.2015.07.036.
19. Khurana RN, Porco TC. Efficacy and safety of dexamethasone intravitreal implant for persistent uveitic cystoid macular edema[J]. Retina, 2015, 35(8):1640-1646. DOI: 10.1097/IAE.0000 000000000515.
20. Lowder C, Belfort R Jr, Lightman S, et al. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis[J]. Arch Ophthalmol, 2011, 129(5):545-553. DOI: 10.1001/archophthalmol.2010.339.
21. Arcinue CA, Ceron OM, Foster CS. A comparison between the fluocinolone acetonide (Retisert) and dexamethasone (Ozurdex) intravitreal implants in uveitis[J]. J Ocul Pharmacol Ther, 2013, 29(5):501-507. DOI: 10.1089/jop.2012.0180.
22. Taylor SR, Habot-Wilner Z, Pacheco P, et al. Intraocular methotrexate in the treatment of uveitis and uveitic cystoid macular edema[J]. Ophthalmology, 2009, 116(4):797-801. DOI: 10.1016/j.ophtha.2008.10.033.
23. Allegri P, Murialdo U, Peri S, et al. Randomized, double-blind, placebo-controlled clinical trial on the efficacy of 0.5% indomethacin eye drops in uveitic macular edema[J]. Invest Ophthalmol Vis Sci, 2014, 55(3):1463-1470. DOI: 10.1167/iovs.13-13202.
24. Schilling H, Heiligenhaus A, Laube T, et al. Long-term effect of acetazolamide treatment of patients with uveitic chronic cystoid macular edema is limited by persisting inflammation[J]. Retina, 2005, 25(2):182-188.
25. Cervantes-Castaneda RA, Giuliari GP, Gallagher MJ, et al. Intravitreal bevacizumab in refractory uveitic macular edema: one-year follow-up[J]. Eur J Ophthalmol, 2009, 19(4):622-629.
26. Soheilian M, Rabbanikhah Z, Ramezani A, et al. Intravitreal bevacizumab versus triamcinolone acetonide for refractory uveitic cystoid macular edema: a randomized pilot study[J]. J Ocul Pharmacol Ther, 2010, 26(2):199-206. DOI: 10.1089/jop.2009.0093.
27. Gillies MC, Su T. Interferon-alpha 2b enhances barrier function of bovine retinal microvascular endothelium in vitro[J]. Microvasc Res, 1995, 49(3):277-288.
28. Deuter CM, Koetter I, Guenaydin I, et al. Interferon alfa-2a: a new treatment option for long lasting refractory cystoid macular edema in uveitis? A pilot study[J]. Retina, 2006, 26(7):786-791. DOI:10.1097/01.iae.0000244265.75771.71.
29. Mackensen F, Jakob E, Springer C, et al. Interferon versus methotrexate in intermediate uveitis with macular edema: results of a randomized controlled clinical trial[J]. Am J Ophthalmol, 2013, 156(3):478-486. DOI: 10.1016/j.ajo.2013.05.002.
30. Schaap-Fogler M, Amer R, Friling R, et al. Anti-TNF-α agents for refractory cystoids macular edema associated with noninfectious uveitis[J]. Graefe's Arch Clin Exp Ophthalmol, 2014, 252(4):633-640. DOI: 10.1007/s00417-013-2552-8.
31. Farvardin M, Afarid M, Mehryar M, et al. Intravitreal infliximab for the treatment of sight-threatening chronic noninfectious uveitis[J]. Retina, 2010, 30(9):1530-1535. DOI: 10.1097/IAE.0b013e 3181d3758a.
32. Markomichelakis NN, Theodossiadis PG, Pantelia E, et al. Infliximab for chronic cystoid macular edema associated with uveitis[J]. Am J Ophthalmol, 2004, 138(4):648-650. DOI:10.1016/j.ajo.2004.04.066.
33. Diaz-Llopis M, Salom D, Garcia-de-Vicuna C, et al. Treatment of refractory uveitis with adalimumab: a prospective multicenter study of 131 patients[J]. Ophthalmology, 2012, 119(8):1575-1581. DOI: 10.1016/j.ophtha.2012.02.018.
34. Mesquida M, Molins B, Llorenc V, et al. Long-term effects of tocilizumab therapy for refractory uveitis-related macular edema[J]. Ophthalmology, 2014, 121(12):2380-2386. DOI: 10.1016/ j.ophtha.2014.06.050.
35. Kishi S, Kamei Y, Shimizu K. Tractional elevation of Henle's fiber layer in idiopathic macular holes[J]. Am J Ophthalmol, 1995, 120(4):486-496.
36. Tranos P, Scott R, Zambarakji H, et al. The effect of pars plana vitrectomy on cystoid macular oedema associated with chronic uveitis: a randomised, controlled pilot study[J]. Br J Ophthalmol, 2006, 90(9):1107-1110.
37. Matsunaga N, Ozeki H, Hirabayashi Y, et al. Histopathologic evaluation of the internal limiting membrane surgically excised from eyes with diabetic maculopathy[J]. Retina, 2005, 25(3):311-316.
38. Radetzky S, Walter P, Fauser S, et al. Visual outcome of patients with macular edema after pars plana vitrectomy and indocyanine green-assisted peeling of the internal limiting membrane[J]. Graefe’s Arch Clin Exp Ophthalmol, 2004, 242(4):273-278.
39. Gutfleisch M, Spital G, Mingels A, et al. Pars plana vitrectomy with intravitreal triamcinolone: effect on uveitic cystoid macular oedema and treatment limitations[J]. Br J Ophthalmol, 2007, 91(3):345-348. DOI: 10.1136/bjo.2006.101675.
40. Lardenoye CW, van Schooneveld MJ, Frits Treffers W, et al. Grid laser photocoagulation for macular oedema in uveitis or the Irvine-Gass syndrome[J]. Br J Ophthalmol, 1998, 82(9):1013-1016.

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