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Review

Thyroid Eye Disease: How A Novel Therapy May Change The Treatment Paradigm

, ORCID Icon &
Pages 1305-1318 | Published online: 11 Nov 2019

References

  • Bartalena L, Baldeschi L, Boboridis K, et al. The 2016 European Thyroid Association/European group on Graves’ orbitopathy guidelines for the management of graves’ orbitopathy. Eur Thyroid J. 2016;5(1):9–26. doi:10.1159/00044382827099835
  • Douglas RS. Teprotumumab, an insulin-like growth factor-1 receptor antagonist antibody, in the treatment of active thyroid eye disease: a focus on proptosis. Eye (Lond). 2019;33(2):183–198. doi:10.1038/s41433-018-0321-y30575804
  • Smith TJ. New advances in understanding thyroid-associated ophthalmopathy and the potential role for insulin-like growth factor-I receptor. F1000Res. 2018;7:134. doi:10.12688/f1000research29744034
  • Smith TJ, Hegedus L. Graves’ disease. N Engl J Med. 2016;375(16):1552–1565. doi:10.1056/NEJMra151003027797318
  • Verity DH, Rose GE. Acute thyroid eye disease (TED): principles of medical and surgical management. Eye (Lond). 2013;27(3):308–319. doi:10.1038/eye.2012.28423412559
  • Kahaly GJ, Petrak F, Hardt J, Pitz S, Egle UT. Psychosocial morbidity of Graves’ orbitopathy. Clin Endocrinol (Oxf). 2005;63(4):395–402. doi:10.1111/j.1365-2265.2005.02352.x16181231
  • Park JJ, Sullivan TJ, Mortimer RH, Wagenaar M, Perry-Keene DA. Assessing quality of life in Australian patients with Graves’ ophthalmopathy. Br J Ophthalmol. 2004;88(1):75–78. doi:10.1136/bjo.88.1.7514693779
  • Minakaran N, Ezra DG. Rituximab for thyroid-associated ophthalmopathy. Cochrane Database Syst Rev. 2013;5:CD009226.
  • Hamed Azzam S, Kang S, Salvi M, Ezra DG. Tocilizumab for thyroid eye disease. Cochrane Database Syst Rev. 2018;11:CD012984.30480323
  • Douglas RS, Gupta S. The pathophysiology of thyroid eye disease: implications for immunotherapy. Curr Opin Ophthalmol. 2011;22(5):385–390. doi:10.1097/ICU.0b013e328349944621730841
  • Bothun ED, Scheurer RA, Harrison AR, Lee MS. Update on thyroid eye disease and management. Clin Ophthalmol. 2009;3:543–551. doi:10.2147/opth.s522819898626
  • Cyranska-Chyrek E, Olejarz M, Szczepanek-Parulska E, Stajgis P, Pioch A, Ruchala M. Severe unilateral orbitopathy in a patient with Hashimoto’s thyroiditis - a case report. BMC Ophthalmol. 2019;19(1):9. doi:10.1186/s12886-018-1018-530621642
  • Perros P, Neoh C, Dickinson J. Thyroid eye disease. Br Med J. 2009;338:b560. doi:10.1136/bmj.b90219270020
  • Mohyi M, Smith TJ. IGF1 receptor and thyroid-associated ophthalmopathy. J Mol Endocrinol. 2018;61(1):T29–T43. doi:10.1530/JME-17-027629273685
  • Sahli E, Gunduz K. Thyroid-associated ophthalmopathy. Turk J Ophthalmol. 2017;47(2):94–105. doi:10.4274/tjo.8068828405484
  • Gillespie EF, Smith TJ, Douglas RS. Thyroid eye disease: towards an evidence base for treatment in the 21st century. Curr Neurol Neurosci Rep. 2012;12(3):318–324. doi:10.1007/s11910-012-0256-922354545
  • Khoo DH, Eng PH, Ho SC, et al. Graves’ ophthalmopathy in the absence of elevated free thyroxine and triiodothyronine levels: prevalence, natural history, and thyrotropin receptor antibody levels. Thyroid. 2000;10(12):1093–1100. doi:10.1089/thy.2000.10.109311201855
  • Perros P, Hegedus L, Bartalena L, et al. Graves’ orbitopathy as a rare disease in Europe: a European Group on Graves’ Orbitopathy (EUGOGO) position statement. Orphanet J Rare Dis. 2017;12(1):72. doi:10.1186/s13023-017-0625-128427469
  • Bartley GB. The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota. Trans Am Ophthalmol Soc. 1994;92:477–588.7886878
  • Perros P, Zarkovic M, Azzolini C, et al. PREGO (presentation of Graves’ orbitopathy) study: changes in referral patterns to European Group On Graves’ Orbitopathy (EUGOGO) centres over the period from 2000 to 2012. Br J Ophthalmol. 2015;99(11):1531–1535. doi:10.1136/bjophthalmol-2015-30673325953846
  • Stan MN, Bahn RS. Risk factors for development or deterioration of Graves’ ophthalmopathy. Thyroid. 2010;20(7):777–783. doi:10.1089/thy.2010.163420578901
  • Eckstein A, Quadbeck B, Mueller G, et al. Impact of smoking on the response to treatment of thyroid associated ophthalmopathy. Br J Ophthalmol. 2003;87(6):773–776. doi:10.1136/bjo.87.6.77312770979
  • Roos JCP, Paulpandian V, Murthy R. Serial TSH-receptor antibody levels to guide the management of thyroid eye disease: the impact of smoking, immunosuppression, radio-iodine, and thyroidectomy. Eye (Lond). 2019;33(2):212–217. doi:10.1038/s41433-018-0242-930401900
  • Bartalena L, Marcocci C, Bogazzi F, et al. Relation between therapy for hyperthyroidism and the course of Graves’ ophthalmopathy. N Engl J Med. 1998;338(2):73–78. doi:10.1056/NEJM1998010833802019420337
  • Smith TJ. TSHR as a therapeutic target in Graves’ disease. Expert Opin Ther Targets. 2017;21(4):427–432. doi:10.1080/14728222.2017.128821528127991
  • Smith TJ, Janssen JA. Building the case for insulin-like growth factor receptor-I involvement in thyroid-associated ophthalmopathy. Front Endocrinol (Lausanne). 2017;7:167. doi:10.3389/fendo.2016.0016728096798
  • Tsui S, Naik V, Hoa N, et al. Evidence for an association between thyroid-stimulating hormone and insulin-like growth factor 1 receptors: a tale of two antigens implicated in Graves’ disease. J Immunol. 2008;181(6):4397–4405. doi:10.4049/jimmunol.181.6.439718768899
  • Bahn RS, Dutton CM, Natt N, Joba W, Spitzweg C, Heufelder AE. Thyrotropin receptor expression in graves’ orbital adipose/connective tissues: potential autoantigen in Graves’ ophthalmopathy. J Clin Endocrinol Metab. 1998;83(3):998–1002. doi:10.1210/jcem.83.3.46769506762
  • Weightman DR, Perros P, Sherif IH, Kendall-Taylor P. Autoantibodies to IGF-1 binding sites in thyroid associated ophthalmopathy. Autoimmunity. 1993;16(4):251–257.7517705
  • Alsuhaibani AH, Nerad JA. Thyroid-associated orbitopathy. Semin Plast Surg. 2007;21(1):65–73. doi:10.1055/s-2007-96775120567660
  • Smith TJ, Hegedus L, Douglas RS. Role of insulin-like growth factor-1 (IGF-1) pathway in the pathogenesis of Graves’ orbitopathy. Best Pract Res Clin Endocrinol Metab. 2012;26(3):291–302. doi:10.1016/j.beem.2011.10.00222632366
  • Krieger CC, Neumann S, Place RF, Marcus-Samuels B, Gershengorn MC. Bidirectional TSH and IGF-1 receptor cross talk mediates stimulation of hyaluronan secretion by Graves’ disease immunoglobins. J Clin Endocrinol Metab. 2015;100(3):1071–1077. doi:10.1210/jc.2014-356625485727
  • Douglas RS, Gianoukakis AG, Kamat S, Smith TJ. Aberrant expression of the insulin-like growth factor-1 receptor by T cells from patients with Graves’ disease may carry functional consequences for disease pathogenesis. J Immunol. 2007;178(5):3281–3287. doi:10.4049/jimmunol.178.5.328117312178
  • Douglas RS, Naik V, Hwang CJ, et al. B cells from patients with Graves’ disease aberrantly express the IGF-1 receptor: implications for disease pathogenesis. J Immunol. 2008;181(8):5768–5774. doi:10.4049/jimmunol.181.8.576818832736
  • Chen H, Mester T, Raychaudhuri N, et al. Teprotumumab, an IGF-1R blocking monoclonal antibody inhibits TSH and IGF-1 action in fibrocytes. J Clin Endocrinol Metab. 2014;99(9):E1635–E1640. doi:10.1210/jc.2014-158024878056
  • Pritchard J, Horst N, Cruikshank W, Smith TJ. Igs from patients with Graves’ disease induce the expression of T cell chemoattractants in their fibroblasts. J Immunol. 2002;168(2):942–950. doi:10.4049/jimmunol.168.2.94211777993
  • Smith TJ, Hoa N. Immunoglobulins from patients with Graves’ disease induce hyaluronan synthesis in their orbital fibroblasts through the self-antigen, insulin-like growth factor-I receptor. J Clin Endocrinol Metab. 2004;89(10):5076–5080. doi:10.1210/jc.2004-071615472208
  • Li Q, Ye H, Ding Y, et al. Clinical characteristics of moderate-to-severe thyroid associated ophthalmopathy in 354 Chinese cases. PLoS One. 2017;12(5):e0176064. doi:10.1371/journal.pone.017606428472149
  • Bartley GB, Fatourechi V, Kadrmas EF, et al. Clinical features of Graves’ ophthalmopathy in an incidence cohort. Am J Ophthalmol. 1996;121(3):284–290. doi:10.1016/s0002-9394(14)70276-48597271
  • Albert D, Miller J, Azar D, Blodi B. Albert & Jakobiec’s Principles & Practice of Ophthalmology. 3rd ed. Philadelphia, PA: Saunders; 2008.
  • Savar LM, Menghani RM, Chong KK, Chokron Garneau H, Goldberg RA. Eyebrow tissue expansion: an underappreciated entity in thyroid-associated orbitopathy. Arch Ophthalmol. 2012;130(12):1566–1569. doi:10.1001/archophthalmol.2012.254323229698
  • Kim BJ, Kazim M. Prominent premalar and cheek swelling: a sign of thyroid-associated orbitopathy. Ophthalmic Plast Reconstr Surg. 2006;22(6):457–460. doi:10.1097/01.iop.0000244972.03781.c617117102
  • Trobe JD, Glaser JS, Laflamme P. Dysthyroid optic neuropathy. clinical profile and rationale for management. Arch Ophthalmol. 1978;96(7):1199–1209. doi:10.1001/archopht.1978.03910060033007666628
  • Hedges TR Jr, Scheie HG. Visual field defects in exophthalmos associated with thyroid disease. AMA Arch Ophthalmol. 1955;54(6):885–892.13268144
  • Neigel JM, Rootman J, Belkin RI, et al. Dysthyroid optic neuropathy. The crowded orbital apex syndrome. Ophthalmology. 1988;95(11):1515–1521. doi:10.1016/s0161-6420(88)32978-73211460
  • McKeag D, Lane C, Lazarus JH, et al. Clinical features of dysthyroid optic neuropathy: a European Group on Graves’ Orbitopathy (EUGOGO) survey. Br J Ophthalmol. 2007;91(4):455–458. doi:10.1136/bjo.2006.09460717035276
  • Rundle FF, Wilson CW. Development and course of exophthalmos and ophthalmoplegia in Graves’ disease with special reference to the effect of thyroidectomy. Clin Sci. 1945;5(3–4):177–194.21011937
  • Selva D, Chen C, King G. Late reactivation of thyroid orbitopathy. Clin Experiment Ophthalmol. 2004;32(1):46–50. doi:10.1046/j.1442-9071.2004.00756.x14746591
  • Patel P, Khandji J, Kazim M. Recurrent thyroid eye disease. Ophthalmic Plast Reconstr Surg. 2015;31(6):445–448. doi:10.1097/IOP.000000000000037125621464
  • Baldeschi L, Lupetti A, Vu P, Wakelkamp IM, Prummel MF, Wiersinga WM. Reactivation of Graves’ orbitopathy after rehabilitative orbital decompression. Ophthalmology. 2007;114(7):1395–1402. doi:10.1016/j.ophtha.2006.10.03617320178
  • Shadpour JM, Menghani RM, Douglas RS, Goldberg RA, Tsirbas A. Reactivation of thyroid-associated orbitopathy after cataract surgery. Jpn J Ophthalmol. 2009;53(1):44–46. doi:10.1007/s10384-008-0607-x19184309
  • Barrio-Barrio J, Sabater AL, Bonet-Farriol E, Velazquez-Villoria A, Galofre JC. Graves’ ophthalmopathy: VISA versus EUGOGO classification, assessment, and management. J Ophthalmol. 2015;2015:249125.26351570
  • Nicosia L, Reverberi C, Agolli L, et al. Orbital radiotherapy plus concomitant steroids in moderate-to-severe Graves’ ophthalmopathy: good results after long-term follow-up. Int J Endocrinol Metab. 2019;17(1):e84427.30881470
  • Bartalena L, Pinchera A, Marcocci C. Management of Graves’ ophthalmopathy: reality and perspectives. Endocr Rev. 2000;21(2):168–199. doi:10.1210/edrv.21.2.039310782363
  • Tanda ML, Bartalena L. Efficacy and safety of orbital radiotherapy for Graves’ orbitopathy. J Clin Endocrinol Metab. 2012;97(11):3857–3865. doi:10.1210/jc.2012-275822962421
  • Kahaly G, Beyer J. Immunosuppressant therapy of thyroid eye disease. Klin Wochenschr. 1988;66(21):1049–1059. doi:10.1007/bf017119173070148
  • Gorman CA, Garrity JA, Fatourechi V, et al. A prospective, randomized, double-blind, placebo-controlled study of orbital radiotherapy for Graves’ ophthalmopathy. Ophthalmology. 2001;108(9):1523–1534. doi:10.1016/s0161-6420(01)00632-711535445
  • Mourits MP, van Kempen-Harteveld ML, Garcia MB, Koppeschaar HP, Tick L, Terwee CB. Radiotherapy for Graves’ orbitopathy: randomised placebo-controlled study. Lancet (London, England). 2000;355(9214):1505–1509. doi:10.1016/S0140-6736(00)02165-6
  • Prummel MF, Terwee CB, Gerding MN, et al. A randomized controlled trial of orbital radiotherapy versus sham irradiation in patients with mild Graves’ ophthalmopathy. J Clin Endocrinol Metab. 2004;89(1):15–20. doi:10.1210/jc.2003-03080914715820
  • Bartalena L, Marcocci C, Chiovato L, et al. Orbital cobalt irradiation combined with systemic corticosteroids for Graves’ ophthalmopathy: comparison with systemic corticosteroids alone. J Clin Endocrinol Metab. 1983;56(6):1139–1144. doi:10.1210/jcem-56-6-11396341388
  • Ng CM, Yuen HK, Choi KL, et al. Combined orbital irradiation and systemic steroids compared with systemic steroids alone in the management of moderate-to-severe Graves’ ophthalmopathy: a preliminary study. Hong Kong Med J. 2005;11(5):322–330.16219950
  • Marcocci C, Bartalena L, Bogazzi F, Bruno-Bossio G, Lepri A, Pinchera A. Orbital radiotherapy combined with high dose systemic glucocorticoids for Graves’ ophthalmopathy is more effective than radiotherapy alone: results of a prospective randomized study. J Endocrinol Invest. 1991;14(10):853–860. doi:10.1007/BF033479431802923
  • Prummel MF, Mourits MP, Blank L, Berghout A, Koornneef L, Wiersinga WM. Randomized double-blind trial of prednisone versus radiotherapy in Graves’ ophthalmopathy. Lancet (London, England). 1993;342(8877):949–954. doi:10.1016/0140-6736(93)92001-a
  • Bradley EA, Gower EW, Bradley DJ, et al. Orbital radiation for Graves ophthalmopathy: a report by the American Academy of ophthalmology. Ophthalmology. 2008;115(2):398–409. doi:10.1016/j.ophtha.2007.10.02818082885
  • Bartalena L, Krassas GE, Wiersinga W, et al. Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves’ orbitopathy. J Clin Endocrinol Metab. 2012;97(12):4454–4463. doi:10.1210/jc.2012-238923038682
  • van Geest RJ, Sasim IV, Koppeschaar HP, et al. Methylprednisolone pulse therapy for patients with moderately severe Graves’ orbitopathy: a prospective, randomized, placebo-controlled study. Eur J Endocrinol. 2008;158(2):229–237. doi:10.1530/EJE-07-055818230831
  • Ebner R, Devoto MH, Weil D, et al. Treatment of thyroid associated ophthalmopathy with periocular injections of triamcinolone. Br J Ophthalmol. 2004;88(11):1380–1386. doi:10.1136/bjo.2004.04619315489477
  • Riedl M, Kuhn A, Kramer I, Kolbe E, Kahaly GJ. Prospective, systematically recorded mycophenolate safety data in Graves’ orbitopathy. J Endocrinol Invest. 2016;39(6):687–694. doi:10.1007/s40618-016-0441-926886940
  • Ye X, Bo X, Hu X, et al. Efficacy and safety of mycophenolate mofetil in patients with active moderate-to-severe Graves’ orbitopathy. Clin Endocrinol (Oxf). 2017;86(2):247–255. doi:10.1111/cen.1317027484048
  • Kahaly GJ, Riedl M, Konig J, et al. Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves’ orbitopathy (MINGO): a randomised, observer-masked, multicentre trial. Lancet Diabetes Endocrinol. 2018;6(4):287–298. doi:10.1016/S2213-8587(18)30020-229396246
  • Prummel MF, Mourits MP, Berghout A, et al. Prednisone and cyclosporine in the treatment of severe Graves’ ophthalmopathy. N Engl J Med. 1989;321(20):1353–1359. doi:10.1056/NEJM1989111632120022519530
  • Kahaly G, Schrezenmeir J, Krause U, et al. Ciclosporin and prednisone v. prednisone in treatment of Graves’ ophthalmopathy: a controlled, randomized and prospective study. Eur J Clin Invest. 1986;16(5):415–422. doi:10.1111/j.1365-2362.1986.tb01016.x3100309
  • Antonelli A, Saracino A, Alberti B, et al. High-dose intravenous immunoglobulin treatment in Graves’ ophthalmopathy. Acta Endocrinol (Copenh). 1992;126(1):13–23. doi:10.1530/acta.0.12600131736548
  • Kahaly G, Pitz S, Muller-Forell W, Hommel G. Randomized trial of intravenous immunoglobulins versus prednisolone in Graves’ ophthalmopathy. Clin Exp Immunol. 1996;106(2):197–202. doi:10.1046/j.1365-2249.1996.d01-854.x8918563
  • Perros P, Weightman DR, Crombie AL, Kendall-Taylor P. Azathioprine in the treatment of thyroid-associated ophthalmopathy. Acta Endocrinol (Copenh). 1990;122(1):8–12. doi:10.1530/acta.0.12200082305608
  • Kahaly G, Lieb W, Muller-Forell W, et al. Ciamexone in endocrine orbitopathy. A randomized double-blind, placebo-controlled study. Acta Endocrinol (Copenh). 1990;122(1):13–21. doi:10.1530/acta.0.12200132305603
  • Dickinson AJ, Vaidya B, Miller M, et al. Double-blind, placebo-controlled trial of octreotide long-acting repeatable (LAR) in thyroid-associated ophthalmopathy. J Clin Endocrinol Metab. 2004;89(12):5910–5915. doi:10.1210/jc.2004-069715579735
  • Wemeau JL, Caron P, Beckers A, et al. Octreotide (long-acting release formulation) treatment in patients with Graves’ orbitopathy: clinical results of a four-month, randomized, placebo-controlled, double-blind study. J Clin Endocrinol Metab. 2005;90(2):841–848. doi:10.1210/jc.2004-133415562016
  • Chang TC, Liao SL. Slow-release lanreotide in Graves’ ophthalmopathy: a double-blind randomized, placebo-controlled clinical trial. J Endocrinol Invest. 2006;29(5):413–422. doi:10.1007/BF0334412416794364
  • Stan MN, Garrity JA, Carranza Leon BG, Prabin T, Bradley EA, Bahn RS. Randomized controlled trial of rituximab in patients with Graves’ orbitopathy. J Clin Endocrinol Metab. 2015;100(2):432–441. doi:10.1210/jc.2014-257225343233
  • Fichter N, Guthoff RF, Schittkowski MP. Orbital decompression in thyroid eye disease. ISRN Ophthalmol. 2012;2012:739236. doi:10.5402/2012/73923624558591
  • Victores AJ, Takashima M. Thyroid eye disease: optic neuropathy and orbital decompression. Int Ophthalmol Clin. 2016;56(1):69–79. doi:10.1097/IIO.000000000000010126626933
  • Rootman DB, Golan S, Pavlovich P, Rootman J. Postoperative changes in strabismus, ductions, exophthalmometry, and eyelid retraction after orbital decompression for thyroid orbitopathy. Ophthalmic Plast Reconstr Surg. 2017;33(4):289–293. doi:10.1097/IOP.000000000000075827487726
  • Yeatts RP. Quality of life in patients with Graves ophthalmopathy. Trans Am Ophthalmol Soc. 2005;103:368–411.17057811
  • Jackson JL. Nonsurgical management of diplopia after orbital decompression surgery. Am Orthopt J. 2012;62:29–33.23002472
  • Frueh BR, Musch DC, Garber FW. Lid retraction and levator aponeurosis defects in Graves’ eye disease. Ophthalmic Surg. 1986;17(4):216–220.3754942
  • Ivekovic R, Novak-Laus K, Tedeschi-Reiner E, Masnec-Paskvalin S, Saric D, Mandic Z. Full-thickeness anterior blepharotomy and transpalpebral fat decompression in Graves’ orbitopathy. Coll Antropol. 2005;29(Suppl 1):33–36.
  • Dixon R. The surgical management of thyroid-related upper eyelid retraction. Ophthalmology. 1982;89(1):52–57. doi:10.1016/s0161-6420(82)34861-77070774
  • Ribeiro SF, Shekhovtsova M, Duarte AF, Velasco Cruz AA. Graves lower eyelid retraction. Ophthalmic Plast Reconstr Surg. 2016;32(3):161–169. doi:10.1097/IOP.000000000000061326784547
  • Gardner TA, Kennerdell JS, Buerger GF. Treatment of dysthyroid lower lid retraction with autogenous tarsus transplants. Ophthalmic Plast Reconstr Surg. 1992;8(1):26–31.1554649
  • Oestreicher JH, Pang NK, Liao W. Treatment of lower eyelid retraction by retractor release and posterior lamellar grafting: an analysis of 659 eyelids in 400 patients. Ophthalmic Plast Reconstr Surg. 2008;24(3):207–212. doi:10.1097/IOP.0b013e318170684018520836
  • Genere N, Stan MN. Current and emerging treatment strategies for Graves’ orbitopathy. Drugs. 2019;79(2):109–124. doi:10.1007/s40265-018-1045-930659423
  • Planck T, Shahida B, Parikh H, et al. Smoking induces overexpression of immediate early genes in active Graves’ ophthalmopathy. Thyroid. 2014;24(10):1524–1532. doi:10.1089/thy.2014.015325135760
  • Nita M, Grzybowski A. Smoking and eye pathologies. a systemic review. part ii. retina diseases, uveitis, optic neuropathies, thyroid-associated orbitopathy. Curr Pharm Des. 2017;23(4):639–654. doi:10.2174/138161282366617011109572328078992
  • Marcocci C, Kahaly GJ, Krassas GE, et al. Selenium and the course of mild Graves’ orbitopathy. N Engl J Med. 2011;364(20):1920–1931. doi:10.1056/NEJMoa101298521591944
  • Burch HB, Lahiri S, Bahn RS, Barnes S. Superoxide radical production stimulates retroocular fibroblast proliferation in Graves’ ophthalmopathy. Exp Eye Res. 1997;65(2):311–316. doi:10.1006/exer.1997.03539268599
  • Bouzas EA, Karadimas P, Mastorakos G, Koutras DA. Antioxidant agents in the treatment of Graves’ ophthalmopathy. Am J Ophthalmol. 2000;129(5):618–622. doi:10.1016/s0002-9394(00)00359-710844053
  • Smolen JS, Beaulieu A, Rubbert-Roth A, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet (London, England). 2008;371(9617):987–997. doi:10.1016/S0140-6736(08)60453-5
  • ACTEMRA® (tocilizumab) [package insert] Injection, for Intravenous or Subcutaneous Use. Full Prescribing Information. South San Francisco, CA: Genentech, Inc.; 2019.
  • Slowik M, Urbaniak-Kujda D, Bohdanowicz-Pawlak A, et al. CD8+CD28-lymphocytes in peripheral blood and serum concentrations of soluble interleukin 6 receptor are increased in patients with Graves’ orbitopathy and correlate with disease activity. Endocr Res. 2012;37(2):89–95. doi:10.3109/07435800.2011.63562222489922
  • Russell DJ, Wagner LH, Seiff SR. Tocilizumab as a steroid sparing agent for the treatment of Graves’ orbitopathy. Am J Ophthalmol Case Rep. 2017;7:146–148. doi:10.1016/j.ajoc.2017.07.00129260102
  • Perez-Moreiras JV, Gomez-Reino JJ, Maneiro JR, et al. Efficacy of tocilizumab in patients with moderate-to-severe corticosteroid-resistant Graves orbitopathy: a randomized clinical trial. Am J Ophthalmol. 2018;195:181–190. doi:10.1016/j.ajo.2018.07.03830081019
  • Ayabe R, Rootman DB, Hwang CJ, Ben-Artzi A, Goldberg R. Adalimumab as steroid-sparing treatment of inflammatory-stage thyroid eye disease. Ophthalmic Plast Reconstr Surg. 2014;30(5):415–419. doi:10.1097/IOP.000000000000021124978425
  • Durrani OM, Reuser TQ, Murray PI. Infliximab: a novel treatment for sight-threatening thyroid associated ophthalmopathy. Orbit. 2005;24(2):117–119. doi:10.1080/0167683059091256216191800
  • Rajaii F, McCoy AN, Smith TJ. Cytokines are both villains and potential therapeutic targets in thyroid-associated ophthalmopathy: from bench to bedside. Expert Rev Ophthalmol. 2014;9(3):227–234. doi:10.1586/17469899.2014.91796025544859
  • RITUXAN® (rituximab) [package insert] Injection, for Intravenous Use. Full Prescribing Information. South San Francisco, CA: Genentech, Inc.; 2019.
  • Salvi M, Vannucchi G, Curro N, et al. Efficacy of B-cell targeted therapy with rituximab in patients with active moderate to severe Graves’ orbitopathy: a randomized controlled study. J Clin Endocrinol Metab. 2015;100(2):422–431. doi:10.1210/jc.2014-301425494967
  • Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for Thyroid-Associated ophthalmopathy. N Engl J Med. 2017;376(18):1748–1761. doi:10.1056/NEJMoa161494928467880
  • Douglas RS, Sile S, Thompson EHZ, et al. Teprotumumab treatment effect on proptosis in patients with active thyroid eye disease: results from a phase 3, randomized, double-masked, placebo-controlled, parallel-group, multicenter study. Proceedings of the American Association of clinical endocrinologists. Endocr Pract. 2019;25(Supplement 1). doi:10.4158/EP-2018-0405
  • Bartley GB. Rundle and his curve. Arch Ophthalmol. 2011;129(3):356–358. doi:10.1001/archophthalmol.2011.2921402995
  • Zang S, Ponto KA,Kahaly GJ. Clinical review:Intravenous glucocorticoids for Graves' orbitopathy: efficacy and morbidity. J Clin Endocrinol Metab. 2011;96:320–332.21239515
  • Marcocci C, Bartalena L, Tanda ML, Manetti L, Dell'Unto E, Rocchi R, Barbesino G, Mazzi B, Bartolomei MP, Lepri P, Cartei F, Nardi M, Pinchera A. Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves' ophthalmopathy: results of a prospective, single-blind, randomized study. J Clin Endocrinol Metab. 2001;(86):3562–3567.11502779