甲状腺相关眼病的治疗进展
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摘要
甲状腺相关眼病是最常见的眼眶疾病,公认是一种自身免疫性疾病,因眶内免疫及增殖反应而致突眼、压迫性视神经病变等各种临床表现。近年眼科、内分泌科、核医学科、放疗科针对该疾病开展了一系列的临床研究,制定了相应的临床处理指南。研究显示,被转诊到三级中心的甲状腺相关眼病患者的严重度和活动性有下降的趋势,这可能与对该疾病认识的增强、甲亢和甲状腺相关眼病的早期诊断和治疗以及更有效地使用预防措施有关。但国内临床工作中碰到严重的甲状腺相关眼病患者反有增加的趋势,这可能与临床对该疾病的重视和规范化诊治程度不够有关。
Thyroid-associated ophthalmopathy is the most common orbital disease. It is recognized as an autoimmune disease, which causes exophthalmos, oppressive optic neuropathy and other clinical manifestations due to infraorbital immunity and proliferation reaction. In recent years, ophthalmologists, endocrinologists, nuclear medicine doctors and radiotherapists have carried out a series of clinical studies on the disease and formulated corresponding clinical treatment guidelines. Overseas reports indicate that the severity and activity of thyroidassociated ophthalmopathy patients referred to tertiary centers are declining, which may be related to increased awareness of the disease, early diagnosis and treatment of hyperthyroidism and thyroid-associated ophthalmopathy, and more effective use of preventive measures. However, the number of patients with severe thyroid-associated ophthalmopathy is increasing in our clinical work, which may be related to our lack of attention to the disease and standardized diagnosis and treatment.
Thyroid-associated ophthalmopathy is the most common orbital disease. It is recognized as an autoimmune disease, which causes exophthalmos, oppressive optic neuropathy and other clinical manifestations due to infraorbital immunity and proliferation reaction. In recent years, ophthalmologists, endocrinologists, nuclear medicine doctors and radiotherapists have carried out a series of clinical studies on the disease and formulated corresponding clinical treatment guidelines. Overseas reports indicate that the severity and activity of thyroidassociated ophthalmopathy patients referred to tertiary centers are declining, which may be related to increased awareness of the disease, early diagnosis and treatment of hyperthyroidism and thyroid-associated ophthalmopathy, and more effective use of preventive measures. However, the number of patients with severe thyroid-associated ophthalmopathy is increasing in our clinical work, which may be related to our lack of attention to the disease and standardized diagnosis and treatment.
引文
1.Smith TJ,Janssen JAMJL.Insulin-like growth factor-I receptor and thyroid-associated ophthalmopathy[J].Endocr Rev,2019,40(1):236-267.
2.Estcourt S,Quinn AG,Vaidya B.Quality of life in thyroid eye disease:impact of quality of care[J].Eur J Endocrinol,2011,164(5):649-655.
3.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[J].Eur Thyroid J,2016,5(1):9-26.
4.Mourits MP,Prummel MF,Wiersinga WM,et al.Clinical activity score as a guide in the management of patients w ith Graves’ophthalmopathy[J].Clin Endocrinol(Oxf),1997,47(1):9-14.
5.Nita M,Grzybowski A.Smoking and eye pathologies.a systemic Review.Part II.Retina diseases,uveitis,optic neuropathies,thyroidassociated orbitopathy[J].Curr Pharm Des,2017,23(4):639-654.
6.Pfeilschifter J,Ziegler R.Smoking and endocrine ophthalmopathy:impact of smoking severity and current vs lifetime cigarette consumption[J].Clin Endocrinol(Oxf),1996,45(4):477-481.
7.Tallstedt L,Lundell G,Torring O,et al.Occurrence of ophthalmopathy after treatment for Graves’hyperthyroidism.The Thyroid Study Group[J].N Engl J Med,1992,326(26):1733-1738.
8.Prummel MF,Wiersinga WM,Mourits MP,et al.Amelioration of eye changes of Graves’ophthalmopathy by achieving euthyroidism[J].Acta Endocrinol(Copenh),1989,121(Suppl 2):185-189.
9.Huang DP,Luo Q,Yang HS,et al.Changes of lacrimal gland and tear inflammatory cytokines in thyroid-associated ophthalmopathy[J].Invest Ophthalmol Vis Sci,2014,55(8):4935-4943.
10.Marcocci C,Kahaly GJ,Krassas GE,et al.Selenium and the course of mild Graves’orbitopathy[J].N Engl J Med,2011,364(20):1920-1931.
11.杨光圻.我国硒缺乏和硒过多及地方病预防[J].中国地方病防治杂志,1990(5):266-268.YANG Guangqi.A proposal for the prevention of Se-related diseases on a comprehensive consideration[J].Chinese Journal of Control of Endemic Diseases,1990(5):266-268.
12.Zang S,Ponto KA,K ahaly G J.Clinical rev iew:intravenous glucocorticoids for Graves’orbitopathy:efficacy and morbidity[J].JClin Endocrinol Metab,2011,96(2):320-332.
13.Kahaly GJ,Pitz S,Hommel G,et al.Randomized,single blind trial of intravenous versus oral steroid monotherapy in Graves’orbitopathy[J].J Clin Endocrinol Metab,2005,90(9):5234-5240.
14.Zhu W,Ye L,Shen L,et al.A prospective,randomized trial of intravenous glucocorticoids therapy with different protocols for patients with Graves’ophthalmopathy[J].J Clin Endocrinol Metab,2014,99(6):1999-2007.
15.Riedl M,Kolbe E,Kampmann E,et al.Prospectively recorded and Med DRA-coded safety data of intravenous methylprednisolone therapy in Graves’orbitopathy[J].J Endocrinol Invest,2015,38(2):177-182.
16.Zang S,Ponto KA,Pitz S,et al.Dose of intravenous steroids and therapy outcome in Graves’orbitopathy[J].J Endocrinol Invest,2011,34(11):876-880.
17.Rucha?a M,Hernik A,Zybek A.Orbital radiotherapy in the management of Graves’orbitopathy-current state of knowledge[J].Endokrynol Pol,2014,65(5):388-396.
18.Kahaly G,Yuan JP,Krause U,et al.Ciclosporin and thyroid-stimulating immunoglobulins in endocrine orbitopathy[J].Res Exp Med(Berl),1989,189(5):355-362.
19.Gayno JP,Strauch G.Ciclosporine and Graves’ophthalmopathy[J].Horm Res,1987,26(1/4):190-197.
20.Smith TJ,Kahaly GJ,Ezra DG,et al.Teprotumumab for thyroid-associated ophthalmopathy[J].N Engl J Med,2017,376(18):1748-1761.
21.Stan MN,Salvi M.Management of endocrine disease rituximab therapy for Graves’orbitopathy-lessons from randomized control trials[J].Eur J Endocrinol,2017,176(2):R101-R109.
22.Ruiz-Medrano J,Diaz-Valle D,Cuina R,et al.The role of tocilizumab in the treatment of inflammatory diseases of the eye and orbit:a useful alternative[J].J Fr Ophtalmol,2018,41(8):759-766.
23.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[J].Am J Ophthalmol,2018,195:181-190.
24.Durrani OM,Reuser TQ,Murray PI.Infliximab:A novel treatment for sight-threatening thyroid associated ophthalmopathy[J].Orbit,2005,24(2):117-119.
25.van Steensel L,van Hagen PM,Paridaens D,et al.Whole orbital tissue culture identifies imatinib mesylate and adalimumab as potential therapeutics for Graves'ophthalmopathy[J].Br J Ophthalmol,2011,95(5):735-738.
26.Soeters MR,van Zeijl CJJ,Boelen A,et al.Optimal management of Graves orbitopathy:a multidisciplinary approach[J].Neth J Med,2011,69(7):302-308.
27.王毅,杨娜,李月月,等.微创多壁眼眶减压术治疗轻和中度甲状腺相关眼病的眼球突出[J].中华眼科杂志,2017,53(2):128-135.WA N G Yi,YA N G Na,L I Yu e y u e,et a l.Mu l t i-wa l l o r b i ta l decompression for disfiguring proptosis in patients with mild or moderate thyroid eye disease[J].Chinese Journal of Ophthalmology,2017;53(2):128-135.
28.颜建华,吴中耀.甲状腺相关眼病上睑退缩的治疗[J].眼视光学杂志,2005,7(1):50-52.YAN Jianhua,WU Zhongyao.Treatment of upper eyelid retraction in patients with thyroid-associated ophthalmopathy[J].Chinese Journal of Optometry Ophthalmology and Visual Science,2005;7(1):50-52.
29.Kazim M,Gold KG.A review of surgical techniques to correct upper eyelid retraction associated with thyroid eye disease[J].Curr Opin Ophthalmol,2011,22(5):391-393.
30.CurròN,Covelli D,Vannucchi G,et al.Therapeutic outcomes of high-dose intravenous steroids in the treatment of dysthyroid optic neuropathy[J].Thyroid,2014,24(5):897-905.
31.Wakelkamp IM,Baldeschi L,Saeed P,et al.Surgical or medical decompression as a first-line treatment of optic neuropathy in Graves’ophthalmopathy?A randomized controlled trial[J].Clin Endocrinol(Oxf),2005,63(3):323-328.
32.王毅,李月月,杨娜,等.最大化眼眶减压术治疗重度甲状腺相关眼病视神经病变的疗效及影响因素[J].中华眼科杂志,2017,53(6):416-423.WANG Yi,LI Yueyue,YANG Na,et al.Therapeutic outcomes and influence factors of maximal orbital decompression in the treatment of severe dysthyroid optic neuropathy[J].Chinese Journal of Ophthalmology,2017,53(6):416-423.
33.王毅,肖利华,杨忠昆,等.改良眼眶减压术治疗重度甲状腺相关眼病的疗效观察[J].中华眼科杂志,2013,49(3):242-249.WANG Yi,XIAO Lihua,YANG Zhongkun,et al.Modified orbital decompression for severe thyroid associated ophthalmopathy[J].Chinese Journal of Ophthalmology,2013,49(3):242-249.
34.Perros P,?arkovi?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[J].Br J Ophthalmol,2015,99(11):1531.
35.Kotwal A,Stan M.Current and future treatments for Graves’disease and Graves’ophthalmopathy[J].Horm Metab Res,2018,50(12):871-886.
36.Smith TJ.Challenges in orphan drug development:identification of effective therapy for thyroid-associated ophthalmopathy[J].Annu Rev Pharmacol Toxicol,2019,59:129-148.
37.Smith TJ.Potential roles of CD34+fibrocytes masquerading as orbital fibroblasts in thyroid-associated ophthalmopathy[J].J Clin Endocrinol Metab,2019,104(2):581-594.
38.Hikage F,Atkins S,Kahana A,et al.HIF2A-LOX pathway promotes fibrotic tissue remodeling in thyroid-associated orbitopathy[J].Endocrinology,2019,160(1):20-35.
39.Fernando R,Grisolia ABD,Lu Y,et al.Slit2 modulates the inflammatory phenotype of orbit-infiltrating fibrocytes in Graves’disease[J].J Immunol,2018,200(12):3942-3949.
2.Estcourt S,Quinn AG,Vaidya B.Quality of life in thyroid eye disease:impact of quality of care[J].Eur J Endocrinol,2011,164(5):649-655.
3.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[J].Eur Thyroid J,2016,5(1):9-26.
4.Mourits MP,Prummel MF,Wiersinga WM,et al.Clinical activity score as a guide in the management of patients w ith Graves’ophthalmopathy[J].Clin Endocrinol(Oxf),1997,47(1):9-14.
5.Nita M,Grzybowski A.Smoking and eye pathologies.a systemic Review.Part II.Retina diseases,uveitis,optic neuropathies,thyroidassociated orbitopathy[J].Curr Pharm Des,2017,23(4):639-654.
6.Pfeilschifter J,Ziegler R.Smoking and endocrine ophthalmopathy:impact of smoking severity and current vs lifetime cigarette consumption[J].Clin Endocrinol(Oxf),1996,45(4):477-481.
7.Tallstedt L,Lundell G,Torring O,et al.Occurrence of ophthalmopathy after treatment for Graves’hyperthyroidism.The Thyroid Study Group[J].N Engl J Med,1992,326(26):1733-1738.
8.Prummel MF,Wiersinga WM,Mourits MP,et al.Amelioration of eye changes of Graves’ophthalmopathy by achieving euthyroidism[J].Acta Endocrinol(Copenh),1989,121(Suppl 2):185-189.
9.Huang DP,Luo Q,Yang HS,et al.Changes of lacrimal gland and tear inflammatory cytokines in thyroid-associated ophthalmopathy[J].Invest Ophthalmol Vis Sci,2014,55(8):4935-4943.
10.Marcocci C,Kahaly GJ,Krassas GE,et al.Selenium and the course of mild Graves’orbitopathy[J].N Engl J Med,2011,364(20):1920-1931.
11.杨光圻.我国硒缺乏和硒过多及地方病预防[J].中国地方病防治杂志,1990(5):266-268.YANG Guangqi.A proposal for the prevention of Se-related diseases on a comprehensive consideration[J].Chinese Journal of Control of Endemic Diseases,1990(5):266-268.
12.Zang S,Ponto KA,K ahaly G J.Clinical rev iew:intravenous glucocorticoids for Graves’orbitopathy:efficacy and morbidity[J].JClin Endocrinol Metab,2011,96(2):320-332.
13.Kahaly GJ,Pitz S,Hommel G,et al.Randomized,single blind trial of intravenous versus oral steroid monotherapy in Graves’orbitopathy[J].J Clin Endocrinol Metab,2005,90(9):5234-5240.
14.Zhu W,Ye L,Shen L,et al.A prospective,randomized trial of intravenous glucocorticoids therapy with different protocols for patients with Graves’ophthalmopathy[J].J Clin Endocrinol Metab,2014,99(6):1999-2007.
15.Riedl M,Kolbe E,Kampmann E,et al.Prospectively recorded and Med DRA-coded safety data of intravenous methylprednisolone therapy in Graves’orbitopathy[J].J Endocrinol Invest,2015,38(2):177-182.
16.Zang S,Ponto KA,Pitz S,et al.Dose of intravenous steroids and therapy outcome in Graves’orbitopathy[J].J Endocrinol Invest,2011,34(11):876-880.
17.Rucha?a M,Hernik A,Zybek A.Orbital radiotherapy in the management of Graves’orbitopathy-current state of knowledge[J].Endokrynol Pol,2014,65(5):388-396.
18.Kahaly G,Yuan JP,Krause U,et al.Ciclosporin and thyroid-stimulating immunoglobulins in endocrine orbitopathy[J].Res Exp Med(Berl),1989,189(5):355-362.
19.Gayno JP,Strauch G.Ciclosporine and Graves’ophthalmopathy[J].Horm Res,1987,26(1/4):190-197.
20.Smith TJ,Kahaly GJ,Ezra DG,et al.Teprotumumab for thyroid-associated ophthalmopathy[J].N Engl J Med,2017,376(18):1748-1761.
21.Stan MN,Salvi M.Management of endocrine disease rituximab therapy for Graves’orbitopathy-lessons from randomized control trials[J].Eur J Endocrinol,2017,176(2):R101-R109.
22.Ruiz-Medrano J,Diaz-Valle D,Cuina R,et al.The role of tocilizumab in the treatment of inflammatory diseases of the eye and orbit:a useful alternative[J].J Fr Ophtalmol,2018,41(8):759-766.
23.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[J].Am J Ophthalmol,2018,195:181-190.
24.Durrani OM,Reuser TQ,Murray PI.Infliximab:A novel treatment for sight-threatening thyroid associated ophthalmopathy[J].Orbit,2005,24(2):117-119.
25.van Steensel L,van Hagen PM,Paridaens D,et al.Whole orbital tissue culture identifies imatinib mesylate and adalimumab as potential therapeutics for Graves'ophthalmopathy[J].Br J Ophthalmol,2011,95(5):735-738.
26.Soeters MR,van Zeijl CJJ,Boelen A,et al.Optimal management of Graves orbitopathy:a multidisciplinary approach[J].Neth J Med,2011,69(7):302-308.
27.王毅,杨娜,李月月,等.微创多壁眼眶减压术治疗轻和中度甲状腺相关眼病的眼球突出[J].中华眼科杂志,2017,53(2):128-135.WA N G Yi,YA N G Na,L I Yu e y u e,et a l.Mu l t i-wa l l o r b i ta l decompression for disfiguring proptosis in patients with mild or moderate thyroid eye disease[J].Chinese Journal of Ophthalmology,2017;53(2):128-135.
28.颜建华,吴中耀.甲状腺相关眼病上睑退缩的治疗[J].眼视光学杂志,2005,7(1):50-52.YAN Jianhua,WU Zhongyao.Treatment of upper eyelid retraction in patients with thyroid-associated ophthalmopathy[J].Chinese Journal of Optometry Ophthalmology and Visual Science,2005;7(1):50-52.
29.Kazim M,Gold KG.A review of surgical techniques to correct upper eyelid retraction associated with thyroid eye disease[J].Curr Opin Ophthalmol,2011,22(5):391-393.
30.CurròN,Covelli D,Vannucchi G,et al.Therapeutic outcomes of high-dose intravenous steroids in the treatment of dysthyroid optic neuropathy[J].Thyroid,2014,24(5):897-905.
31.Wakelkamp IM,Baldeschi L,Saeed P,et al.Surgical or medical decompression as a first-line treatment of optic neuropathy in Graves’ophthalmopathy?A randomized controlled trial[J].Clin Endocrinol(Oxf),2005,63(3):323-328.
32.王毅,李月月,杨娜,等.最大化眼眶减压术治疗重度甲状腺相关眼病视神经病变的疗效及影响因素[J].中华眼科杂志,2017,53(6):416-423.WANG Yi,LI Yueyue,YANG Na,et al.Therapeutic outcomes and influence factors of maximal orbital decompression in the treatment of severe dysthyroid optic neuropathy[J].Chinese Journal of Ophthalmology,2017,53(6):416-423.
33.王毅,肖利华,杨忠昆,等.改良眼眶减压术治疗重度甲状腺相关眼病的疗效观察[J].中华眼科杂志,2013,49(3):242-249.WANG Yi,XIAO Lihua,YANG Zhongkun,et al.Modified orbital decompression for severe thyroid associated ophthalmopathy[J].Chinese Journal of Ophthalmology,2013,49(3):242-249.
34.Perros P,?arkovi?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[J].Br J Ophthalmol,2015,99(11):1531.
35.Kotwal A,Stan M.Current and future treatments for Graves’disease and Graves’ophthalmopathy[J].Horm Metab Res,2018,50(12):871-886.
36.Smith TJ.Challenges in orphan drug development:identification of effective therapy for thyroid-associated ophthalmopathy[J].Annu Rev Pharmacol Toxicol,2019,59:129-148.
37.Smith TJ.Potential roles of CD34+fibrocytes masquerading as orbital fibroblasts in thyroid-associated ophthalmopathy[J].J Clin Endocrinol Metab,2019,104(2):581-594.
38.Hikage F,Atkins S,Kahana A,et al.HIF2A-LOX pathway promotes fibrotic tissue remodeling in thyroid-associated orbitopathy[J].Endocrinology,2019,160(1):20-35.
39.Fernando R,Grisolia ABD,Lu Y,et al.Slit2 modulates the inflammatory phenotype of orbit-infiltrating fibrocytes in Graves’disease[J].J Immunol,2018,200(12):3942-3949.