Những tiến bộ gần đây trong liệu pháp y tế cho bệnh nhãn cầu Graves: Một tổng quan tài liệu toàn diện

International Ophthalmology - Tập 43 - Trang 1437-1449 - 2022
Xueting Li1, Senmao Li1, Wanlin Fan1, Alexander C. Rokohl1,2, Sitong Ju1, Xiaojun Ju1, Yongwei Guo1,3, Ludwig M. Heindl1,2
1Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
2Center for Integrated Oncology (CIO), Aachen-Bonn-Cologne-Duesseldorf, Cologne, Germany
3Eye Center, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Tóm tắt

Bệnh nhãn cầu Graves (GO), xảy ra trong bệnh tuyến giáp tự miễn, có thể làm giảm chất lượng cuộc sống của bệnh nhân do ảnh hưởng đến chức năng thị giác, diện mạo thể chất và sức khỏe cảm xúc. Corticosteroid đã là phương pháp điều trị hàng đầu cho GO. Gần đây, quá trình sinh bệnh học của GO đã tiến bộ vượt bậc. Nhiều tác nhân sinh học nhắm mục tiêu và các tác nhân ức chế miễn dịch khiến việc quản lý GO trở nên hứa hẹn hơn. Hiểu rõ quá trình sinh bệnh học GO và quản lý lâm sàng chính xác sẽ có lợi cho tiên lượng của bệnh nhân. Do đó, chúng tôi đã tiến hành một tổng quan toàn diện về quản lý y tế của GO và tóm tắt những phát triển nghiên cứu nhằm nhấn mạnh các vấn đề nghiên cứu trong tương lai.

Từ khóa

#Bệnh nhãn cầu Graves #điều trị #corticosteroid #sinh bệnh học #quản lý lâm sàng

Tài liệu tham khảo

Ponto KA et al (2015) Prevalence, Phenotype, and Psychosocial WellBeing in Euthyroid/Hypothyroid Thyroid-Associated Orbitopathy. Thyroid 5(8):942–948. https://doi.org/10.1089/thy.2015.0031 Perros P et al (2017) Graves’ orbitopathy as a rare disease in Europe: a European Group on Graves’ Orbitopathy (EUGOGO) position statement. Orphanet J Rare Dis 12(1):72. https://doi.org/10.1186/s13023-017-0625-1 Piantanida E et al (2013) Prevalence and natural history of Graves’ orbitopathy in the XXI century. J Endocrinol Invest 36(6):444–449. https://doi.org/10.3275/8937 Smith TJ, Hegedüs L (2016) Graves’ Disease. N Engl J Med 375(16):1552–1565. https://doi.org/10.1056/NEJMra1510030 Ponto KA et al (2013) Public health relevance of Graves’ orbitopathy. J Clin Endocrinol Metab 98(1):145–152. https://doi.org/10.1210/jc.2012-3119 Dik WA, Virakul S, van Steensel L (2016) Current perspectives on the role of orbital fibroblasts in the pathogenesis of graves’ ophthalmopathy. Exp Eye Res 142:83–91. https://doi.org/10.1016/j.exer.2015.02.007 Krieger CC et al (2016) TSH/IGF-1 receptor cross talk in graves’ ophthalmopathy pathogenesis. J Clin Endocrinol Metab 101(6):2340–2347. https://doi.org/10.1210/jc.2016-1315 Wang Y, Smith TJ (2014) Current concepts in the molecular pathogenesis of thyroid-associated ophthalmopathy. Invest Ophthalmol Vis Sci 55(3):1735–1748. https://doi.org/10.1167/iovs.14-14002 Shadel GS, Horvath TL (2015) Mitochondrial ROS signaling in organismal homeostasis. Cell 163(3):560–569. https://doi.org/10.1016/j.cell.2015.10.001 Diana T et al (2018) Stimulatory TSH-receptor antibodies and oxidative stress in graves disease. J Clin Endocrinol Metab 103(10):3668–3677. https://doi.org/10.1210/jc.2018-00509 Van Regemorter E et al (2021) Downregulation of Caveolin-1 and upregulation of deiodinase 3, associated with hypoxia-inducible factor-1α increase, are involved in the oxidative stress of graves’ orbital adipocytes. Thyroid 31(4):627–637. https://doi.org/10.1089/thy.2020.0238 Hou TY et al (2021) The role of oxidative stress and therapeutic potential of antioxidants in graves’ ophthalmopathy. Biomedicines. https://doi.org/10.3390/biomedicines9121871 Lanzolla G, Marcocci C, Marinò M (2020) Oxidative Stress in Graves Disease and Graves Orbitopathy. Eur Thyroid J 9(Suppl 1):40–50. https://doi.org/10.1159/000509615 Du P, Ma X, Wang C (2014) Associations of CTLA4 gene polymorphisms with graves’ ophthalmopathy: a meta-analysis. Int J Genomics 2014:537969. https://doi.org/10.1155/2014/537969 Lahooti H et al (2015) Novel single-nucleotide polymorphisms in the calsequestrin-1 gene are associated with Graves’ ophthalmopathy and Hashimoto’s thyroiditis. Clin Ophthalmol 9:1731–1740. https://doi.org/10.2147/opth.S87972 RotondoDottore G et al (2021) Genetic profiling of orbital fibroblasts from patients with graves’ orbitopathy. J Clin Endocrinol Metab 106(5):e2176–e2190. https://doi.org/10.1210/clinem/dgab035 Prummel MF et al (1990) Effect of abnormal thyroid function on the severity of Graves’ ophthalmopathy. Arch Intern Med 150(5):1098–1101 Karlsson F et al (1989) Ophthalmopathy and thyroid stimulation. Lancet 2(8664):691. https://doi.org/10.1016/s0140-6736(89)90945-8 Bartalena L et al (2021) The 2021 European group on graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of graves’ orbitopathy. Eur J Endocrinol 185(4):G43–G67. https://doi.org/10.1530/eje-21-0479 George A et al (2020) Stimulatory thyrotropin receptor antibodies are a biomarker for graves’ orbitopathy. Front Endocrinol (Lausanne) 11:629925. https://doi.org/10.3389/fendo.2020.629925 Kampmann E et al (2015) Thyroid stimulating but not blocking autoantibodies are highly prevalent in severe and active thyroid-associated orbitopathy: a prospective study. Int J Endocrinol 2015:678194. https://doi.org/10.1155/2015/678194 Kahaly GJ et al (2019) High titers of thyrotropin receptor antibodies are associated with orbitopathy in patients with graves disease. J Clin Endocrinol Metab 104(7):2561–2568. https://doi.org/10.1210/jc.2018-02705 Fatourechi V (2012) Thyroid dermopathy and acropachy. Best Pract Res Clin Endocrinol Metab 26(4):553–565. https://doi.org/10.1016/j.beem.2011.10.001 Eckstein AK et al (2006) Thyrotropin receptor autoantibodies are independent risk factors for Graves’ ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab 91(9):3464–3470. https://doi.org/10.1210/jc.2005-2813 Hägg E, Asplund K (1987) Is endocrine ophthalmopathy related to smoking? Br Med J (Clin Res Ed) 295(6599):634–635. https://doi.org/10.1136/bmj.295.6599.634 Xing L et al (2015) Smoking was associated with poor response to intravenous steroids therapy in Graves’ ophthalmopathy. Br J Ophthalmol 99(12):1686–1691. https://doi.org/10.1136/bjophthalmol-2014-306463 Tanda ML et al (2013) Prevalence and natural history of Graves’ orbitopathy in a large series of patients with newly diagnosed graves’ hyperthyroidism seen at a single center. J Clin Endocrinol Metab 98(4):1443–1449. https://doi.org/10.1210/jc.2012-3873 Pfeilschifter J, Ziegler R (1996) Smoking and endocrine ophthalmopathy: impact of smoking severity and current vs lifetime cigarette consumption. Clin Endocrinol (Oxf) 45(4):477–481. https://doi.org/10.1046/j.1365-2265.1996.8220832.x Görtz GE et al (2016) Hypoxia-dependent HIF-1 activation impacts on tissue remodeling in graves’ ophthalmopathy-implications for smoking. J Clin Endocrinol Metab 101(12):4834–4842. https://doi.org/10.1210/jc.2016-1279 Reiners C, Drozd V, Yamashita S (2020) Hypothyroidism after radiation exposure: brief narrative review. J Neural Transm (Vienna) 127(11):1455–1466. https://doi.org/10.1007/s00702-020-02260-5 Träisk F et al (2009) Thyroid-associated ophthalmopathy after treatment for Graves’ hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab 94(10):3700–3707. https://doi.org/10.1210/jc.2009-0747 Bartalena L et al (1998) Relation between therapy for hyperthyroidism and the course of graves’ ophthalmopathy. N Engl J Med 338(2):73–78. https://doi.org/10.1056/nejm199801083380201 Perros P et al (2005) A prospective study of the effects of radioiodine therapy for hyperthyroidism in patients with minimally active graves’ ophthalmopathy. J Clin Endocrinol Metab 90(9):5321–5323. https://doi.org/10.1210/jc.2005-0507 Sabini E et al (2018) High serum cholesterol is a novel risk factor for graves’ orbitopathy: results of a cross-sectional study. Thyroid 28(3):386–394. https://doi.org/10.1089/thy.2017.0430 Lanzolla G et al (2019) Cholesterol serum levels and use of statins in graves’ orbitopathy: a new starting point for the therapy. Front Endocrinol (Lausanne) 10:933. https://doi.org/10.3389/fendo.2019.00933 Lanzolla G et al (2018) Relationship between serum cholesterol and Graves’ orbitopathy (GO): a confirmatory study. J Endocrinol Invest 41(12):1417–1423. https://doi.org/10.1007/s40618-018-0915-z Tall AR, Yvan-Charvet L (2015) Cholesterol, inflammation and innate immunity. Nat Rev Immunol 15(2):104–116. https://doi.org/10.1038/nri3793 Menconi F, Marcocci C, Marinò M (2014) Diagnosis and classification of Graves’ disease. Autoimmun Rev 13(4–5):398–402. https://doi.org/10.1016/j.autrev.2014.01.013 Blandford AD et al (2017) Dysthyroid optic neuropathy: update on pathogenesis, diagnosis, and management. Expert Rev Ophthalmol 12(2):111–121. https://doi.org/10.1080/17469899.2017.1276444 Khazaei H et al (2021) The potential of tear proteomics for diagnosis and management of orbital inflammatory disorders including Graves’ ophthalmopathy. Exp Eye Res 213:108813. https://doi.org/10.1016/j.exer.2021.108813 Aass C et al (2016) Comparative proteomic analysis of tear fluid in Graves’ disease with and without orbitopathy. Clin Endocrinol (Oxf) 85(5):805–812. https://doi.org/10.1111/cen.13122 Aass C et al (2017) Establishment of a tear protein biomarker panel differentiating between Graves’ disease with or without orbitopathy. PLoS ONE 12(4):e0175274. https://doi.org/10.1371/journal.pone.0175274 Kishazi E et al (2018) Thyroid-associated orbitopathy and tears: a proteomics study. J Proteomics 170:110–116. https://doi.org/10.1016/j.jprot.2017.09.001 Chng CL et al (2018) Tear proteins calcium binding protein A4 (S100A4) and prolactin induced protein (PIP) are potential biomarkers for thyroid eye disease. Sci Rep 8(1):16936. https://doi.org/10.1038/s41598-018-35096-x Oeverhaus M et al (2021) Graves’ orbitopathy: current concepts for medical treatment. Klin Monbl Augenheilkd 238(1):24–32. https://doi.org/10.1055/a-1328-2884 Werner SC (1969) Classification of the eye changes of Graves’ disease. Am J Ophthalmol 68(4):646–648. https://doi.org/10.1016/0002-9394(69)91246-x Werner SC (1977) Modification of the classification of the eye changes of graves’ disease: recommendations of the Ad Hoc committee of the American thyroid association. J Clin Endocrinol Metab 44(1):203–204. https://doi.org/10.1210/jcem-44-1-203 Dolman PJ, Rootman J (2006) VISA classification for graves orbitopathy. Ophthalmic Plast Reconstr Surg 22(5):319–324. https://doi.org/10.1097/01.iop.0000235499.34867.85 Bartalena L et al (2008) Consensus statement of the European group on graves’ orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol 158(3):273–285. https://doi.org/10.1530/eje-07-0666 Fayers T, Dolman PJ (2011) Validity and reliability of the TED-QOL: a new three-item questionnaire to assess quality of life in thyroid eye disease. Br J Ophthalmol 95(12):1670–1674. https://doi.org/10.1136/bjophthalmol-2011-300487 Vestergaard P (2002) Smoking and thyroid disorders–a meta-analysis. Eur J Endocrinol 146(2):153–161. https://doi.org/10.1530/eje.0.1460153 Kahaly GJ (2020) Management of graves thyroidal and extrathyroidal disease: an update. J Clin Endocrinol Metab 105(12):3704–3720. https://doi.org/10.1210/clinem/dgaa646 RotondoDottore G et al (2017) Selenium rescues orbital fibroblasts from cell death induced by hydrogen peroxide: another molecular basis for the effects of selenium in graves’ orbitopathy. Endocrine 58(2):386–389. https://doi.org/10.1007/s12020-016-1226-9 Xu B et al (2019) A pilot study on the beneficial effects of additional selenium supplementation to methimazole for treating patients with Graves’ disease. Turk J Med Sci 49(3):715–722. https://doi.org/10.3906/sag-1808-67 Marcocci C et al (2011) Selenium and the course of mild Graves’ orbitopathy. N Engl J Med 364(20):1920–1931. https://doi.org/10.1056/NEJMoa1012985 Negro R et al (2019) A 2018 European thyroid association survey on the use of selenium supplementation in graves’ hyperthyroidism and graves’ orbitopathy. Eur Thyroid J 8(1):7–15. https://doi.org/10.1159/000494837 Lanzolla G, Marinò M, Marcocci C (2020) Selenium in the treatment of graves’ hyperthyroidism and eye disease. Front Endocrinol (Lausanne) 11:608428. https://doi.org/10.3389/fendo.2020.608428 Lisi S et al (2011) Quercetin decreases proliferation of orbital fibroblasts and their release of hyaluronic acid. J Endocrinol Invest 34(7):521–527. https://doi.org/10.3275/7321 RotondoDottore G et al (2018) Action of three bioavailable antioxidants in orbital fibroblasts from patients with Graves’ orbitopathy (GO): a new frontier for GO treatment? J Endocrinol Invest 41(2):193–201. https://doi.org/10.1007/s40618-017-0718-7 RotondoDottore G et al (2018) Antioxidant effects of β-carotene, but not of retinol and vitamin E, in orbital fibroblasts from patients with Graves’ orbitopathy (GO). J Endocrinol Invest 41(7):815–820. https://doi.org/10.1007/s40618-017-0809-5 CORTISONE in exophthalmos: report on a therapeutic trial of cortisone and corticotrophin (A.C.T.H.) in exophthalmos and exophthalmic ophthalmoplegia by a panel appointed by the Medical Research Council. Lancet, 1955. 268(6853):6–9 Marcocci C et al (2012) Fatal and non-fatal adverse events of glucocorticoid therapy for Graves’ orbitopathy: a questionnaire survey among members of the European Thyroid Association. Eur J Endocrinol 166(2):247–253. https://doi.org/10.1530/eje-11-0779 Goldberg RA (2004) Orbital steroid injections. Br J Ophthalmol 88(11):1359–1360 Zang S, Ponto KA, Kahaly GJ (2011) Clinical review: Intravenous glucocorticoids for Graves’ orbitopathy: efficacy and morbidity. J Clin Endocrinol Metab 96(2):320–332. https://doi.org/10.1210/jc.2010-1962 Stiebel-Kalish H et al (2009) Treatment modalities for Graves’ ophthalmopathy: systematic review and metaanalysis. J Clin Endocrinol Metab 94(8):2708–2716. https://doi.org/10.1210/jc.2009-0376 Gao G et al (2014) Meta-analysis of methylprednisolone pulse therapy for Graves’ ophthalmopathy. Clin Exp Ophthalmol 42(8):769–777. https://doi.org/10.1111/ceo.12317 Allison AC, Eugui EM (2000) Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 47(2–3):85–118. https://doi.org/10.1016/s0162-3109(00)00188-0 Ye X et al (2017) Efficacy and safety of mycophenolate mofetil in patients with active moderate-to-severe Graves’ orbitopathy. Clin Endocrinol (Oxf) 86(2):247–255. https://doi.org/10.1111/cen.13170 Kahaly GJ et al (2018) Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves’ orbitopathy (MINGO): a randomised, observer-masked, multicentre trial. Lancet Diabetes Endocrinol 6(4):287–298. https://doi.org/10.1016/s2213-8587(18)30020-2 Hassan AV, Sinha MD, Waller S (2013) A single-centre retrospective study of the safety and efficacy of mycophenolate mofetil in children and adolescents with nephrotic syndrome. Clin Kidney J 6(4):384–389. https://doi.org/10.1093/ckj/sft071 Arns W et al (2005) Enteric-coated mycophenolate sodium delivers bioequivalent MPA exposure compared with mycophenolate mofetil. Clin Transplant 19(2):199–206. https://doi.org/10.1111/j.1399-0012.2004.00318.x Jia Y et al (2018) Sites of gastrointestinal lesion induced by mycophenolate mofetil: a comparison with enteric-coated mycophenolate sodium in rats. BMC Pharmacol Toxicol 19(1):39. https://doi.org/10.1186/s40360-018-0234-1 Prummel MF et al (1989) Prednisone and cyclosporine in the treatment of severe Graves’ ophthalmopathy. N Engl J Med 321(20):1353–1359. https://doi.org/10.1056/nejm198911163212002 Kahaly G et al (1986) Ciclosporin and prednisone v. prednisone in treatment of Graves’ ophthalmopathy a controlled, randomized and prospective study. Eur J Clin Invest 16(5):415–422. https://doi.org/10.1111/j.1365-2362.1986.tb01016.x Rajendram R et al (2018) Combined immunosuppression and radiotherapy in thyroid eye disease (CIRTED): a multicentre, 2 × 2 factorial, double-blind, randomised controlled trial. Lancet Diabetes Endocrinol 6(4):299–309. https://doi.org/10.1016/s2213-8587(18)30021-4 Strianese D (2018) Efficacy and safety of immunosuppressive agents for thyroid eye disease. Ophthalmic Plast Reconstr Surg 34(4S Suppl 1):S56–S59. https://doi.org/10.1097/iop.0000000000001131 Chalvatzis NT et al (2014) Safety and efficacy of combined immunosuppression and orbital radiotherapy in thyroid-related restrictive myopathy: two-center experience. Eur J Ophthalmol 24(6):953–959. https://doi.org/10.5301/ejo.5000463 Shahida B et al (2019) Simvastatin downregulates adipogenesis in 3T3-L1 preadipocytes and orbital fibroblasts from Graves’ ophthalmopathy patients. Endocr Connect 8(9):1230–1239. https://doi.org/10.1530/ec-19-0319 Marinò M, Lanzolla G, Marcocci C (2021) Statins: a new hope on the horizon of graves orbitopathy? J Clin Endocrinol Metab 106(7):e2819–e2821. https://doi.org/10.1210/clinem/dgab184 Lanzolla G et al (2021) Statins for graves’ orbitopathy (STAGO): a phase 2, open-label, adaptive, single centre, randomised clinical trial. Lancet Diabetes Endocrinol 9(11):733–742. https://doi.org/10.1016/s2213-8587(21)00238-2 Nilsson A, Tsoumani K, Planck T (2021) Statins decrease the risk of orbitopathy in newly diagnosed patients with graves disease. J Clin Endocrinol Metab 106(5):1325–1332. https://doi.org/10.1210/clinem/dgab070 Durrani OM, Reuser TQ, Murray PI (2005) Infliximab: a novel treatment for sight-threatening thyroid associated ophthalmopathy. Orbit 24(2):117–119. https://doi.org/10.1080/01676830590912562 Paridaens D et al (2005) The effect of etanercept on Graves’ ophthalmopathy: a pilot study. Eye (Lond) 19(12):1286–1289. https://doi.org/10.1038/sj.eye.6701768 van Steensel L et al (2011) Whole orbital tissue culture identifies imatinib mesylate and adalimumab as potential therapeutics for Graves’ ophthalmopathy. Br J Ophthalmol 95(5):735–738. https://doi.org/10.1136/bjo.2010.192302 Ayabe R et al (2014) Adalimumab as steroid-sparing treatment of inflammatory-stage thyroid eye disease. Ophthalmic Plast Reconstr Surg 30(5):415–419. https://doi.org/10.1097/iop.0000000000000211 Salvi M et al (2007) Treatment of Graves’ disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study. Eur J Endocrinol 156(1):33–40. https://doi.org/10.1530/eje.1.02325 El Fassi D et al (2009) Treatment of Graves’ disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies. Clin Immunol 130(3):252–258. https://doi.org/10.1016/j.clim.2008.09.007 Stan MN et al (2015) Randomized controlled trial of rituximab in patients with Graves’ orbitopathy. J Clin Endocrinol Metab 100(2):432–441. https://doi.org/10.1210/jc.2014-2572 Salvi M et al (2015) 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 100(2):422–431. https://doi.org/10.1210/jc.2014-3014 Eid L et al (2020) The effects of rituximab on graves’orbitopathy: a retrospective study of 14 patients. Eur J Ophthalmol 30(5):1008–1013. https://doi.org/10.1177/1120672119845224 Ding C, Jones G (2003) Technology evaluation: MRA. Chugai Curr Opin Mol Ther 5(1):64–69 Pérez-Moreiras JV, Alvarez-López A, Gómez EC (2014) Treatment of active corticosteroid-resistant graves’ orbitopathy. Ophthalmic Plast Reconstr Surg 30(2):162–167. https://doi.org/10.1097/iop.0000000000000037 Perez-Moreiras JV et al (2018) Efficacy of tocilizumab in patients with moderate-to-severe corticosteroid-resistant graves orbitopathy: a randomized clinical trial. Am J Ophthalmol 195:181–190. https://doi.org/10.1016/j.ajo.2018.07.038 Copperman T et al (2019) Subcutaneous tocilizumab for thyroid eye disease: simplified dosing and delivery. Ophthalmic Plast Reconstr Surg 35(3):e64–e66. https://doi.org/10.1097/iop.0000000000001346 Chen H et al (2015) TSH-Mediated TNFα production in human fibrocytes is inhibited by teprotumumab, an IGF-1R antagonist. PLoS ONE 10(6):e0130322. https://doi.org/10.1371/journal.pone.0130322 Chen H et al (2014) Teprotumumab, an IGF-1R blocking monoclonal antibody inhibits TSH and IGF-1 action in fibrocytes. J Clin Endocrinol Metab 99(9):El635–El640. https://doi.org/10.1210/jc.2014-1580 Smith TJ et al (2017) Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med 376(18):1748–1761. https://doi.org/10.1056/NEJMoa1614949 Douglas RS et al (2020) Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med 382(4):341–352. https://doi.org/10.1056/NEJMoa1910434 Bartalena L et al (2022) Teprotumumab for Graves’ orbitopathy and ototoxicity: moving problems from eyes to ears? J Endocrinol Invest 45(7):1455–1457. https://doi.org/10.1007/s40618-022-01791-w Inserro A (2021) The American Journal of Managed Care. Dr Rona Silkiss Details the Use of Biologics to Treat Thyroid Eye Disease. News release of the American Journal of Managed Care. https://www.ajmc.com/view/dr-paul-hahn-highlights-emerging-technologies-in-ophthalmology. Accessed Oct 07 2022 Kahaly GJ et al (2021) Teprotumumab for patients with active thyroid eye disease: a pooled data analysis, subgroup analyses, and off-treatment follow-up results from two randomised, double-masked, placebo-controlled, multicentre trials. Lancet Diabetes Endocrinol 9(6):360–372. https://doi.org/10.1016/s2213-8587(21)00056-5 Belinsky I et al (2022) Teprotumumab and hearing loss: case series and proposal for audiologic monitoring. Ophthalmic Plast Reconstr Surg 38(1):73–78. https://doi.org/10.1097/iop.0000000000001995 Ding AS et al (2022) Sensorineural hearing loss after teprotumumab therapy for thyroid eye disease: a case report. Otol Neurotol 43(2):e148–e152. https://doi.org/10.1097/mao.0000000000003428 Allen RC et al (2021) A perspective on the current role of teprotumumab in treatment of thyroid eye disease. Ophthalmology 128(8):1125–1128. https://doi.org/10.1016/j.ophtha.2021.03.006