graves ophthalmopathy


Summary: An autoimmune disorder of the EYE, occurring in patients with Graves disease. Subtypes include congestive (inflammation of the orbital connective tissue), myopathic (swelling and dysfunction of the extraocular muscles), and mixed congestive-myopathic ophthalmopathy.

Top Publications

  1. Park S, Khwarg S, Kim N, Lee M, Choung H. Acquired lower eyelid epiblepharon in thyroid-associated ophthalmopathy of Koreans. Ophthalmology. 2012;119:390-5 pubmed publisher
    ..The association between lower eyelid retraction and acquired epiblepharon may lead to a better understanding of the cause of acquired epiblepharon in patients with TAO. ..
  2. Meyer Zu Hörste M, Ströher E, Berchner Pfannschmidt U, Schmitz Spanke S, Pink M, Gothert J, et al. A novel mechanism involved in the pathogenesis of Graves ophthalmopathy (GO): clathrin is a possible targeting molecule for inhibiting local immune response in the orbit. J Clin Endocrinol Metab. 2011;96:E1727-36 pubmed publisher well as inflammation resulting in the expansion and remodeling of orbital tissue, are characteristic of Graves ophthalmopathy (GO). Our aim was to analyze and inhibit signaling pathways in resident OF that are involved in GO...
  3. Monteiro M, Moritz R, Angotti Neto H, Benabou J. Color Doppler imaging of the superior ophthalmic vein in patients with Graves' orbitopathy before and after treatment of congestive disease. Clinics (Sao Paulo). 2011;66:1329-34 pubmed
    ..To compare superior ophthalmic vein blood flow parameters measured with color Doppler imaging in patients with congestive Graves' orbitopathy before and after treatment and in normal controls...
  4. Smith T. Pathogenesis of Graves' orbitopathy: a 2010 update. J Endocrinol Invest. 2010;33:414-21 pubmed
    ..As emerging insights into human autoimmunity becomes applied to the study of Graves' disease, we anticipate that improved therapeutic strategies will find their way to our patients with GO. ..
  5. Tsai C, Wu S, Cheng C, Kao S, Kau H, Chiou S, et al. Increased oxidative DNA damage, lipid peroxidation, and reactive oxygen species in cultured orbital fibroblasts from patients with Graves' ophthalmopathy: evidence that oxidative stress has a role in this disorder. Eye (Lond). 2010;24:1520-5 pubmed publisher
    ..We investigated the oxidative stress in orbital fibroadipose tissues and cultured orbital fibroblasts from patients with Graves' ophthalmopathy (GO)...
  6. Tomlinson J, Durrani O, Bujalska I, Gathercole L, Tomlins P, Reuser T, et al. The role of 11beta-hydroxysteroid dehydrogenase 1 in adipogenesis in thyroid-associated ophthalmopathy. J Clin Endocrinol Metab. 2010;95:398-406 pubmed publisher
    ..11beta-Hydroxysteroid dehydrogenase 1 (11beta-HSD1) increases cortisol bioavailability and is pivotal in mediating glucocorticoid responses in adipose tissue and inflammation...
  7. Liu Y, Chen C, Liao L, Wan L, Tsai C, Tsai F. Association of IL12B polymorphisms with susceptibility to Graves ophthalmopathy in a Taiwan Chinese population. J Biomed Sci. 2012;19:97 pubmed publisher
    ..gene polymorphisms have been linked to several inflammatory diseases, but their role in the development of Graves ophthalmopathy (GO) in Graves disease (GD) patients is unclear...
  8. Tsai C, Wu S, Cheng C, Kao S, Kau H, Lee S, et al. Increased response to oxidative stress challenge in Graves' ophthalmopathy orbital fibroblasts. Mol Vis. 2011;17:2782-8 pubmed
    ..Hypersensitivity to oxidative stress of GO orbital fibroblasts may play a role in the pathogenesis of GO. ..
  9. Douglas R, Gupta S. The pathophysiology of thyroid eye disease: implications for immunotherapy. Curr Opin Ophthalmol. 2011;22:385-90 pubmed publisher
    ..Continued understanding of the molecular mechanisms of disease will expand potential treatments for TED patients and obviate the need for reconstructive surgical therapies. ..

More Information


  1. Matthiesen C, Thompson J, Thompson D, Farris B, Wilkes B, Ahmad S, et al. The efficacy of radiation therapy in the treatment of Graves' orbitopathy. Int J Radiat Oncol Biol Phys. 2012;82:117-23 pubmed publisher
    ..Orbital reirradiation is beneficial for patients who do not respond to initial RT or experience symptom recurrence without an apparent risk of increased morbidity. ..
  2. Pedro A, Romaldini J, Takei K. Changes of serum cytokines in hyperthyroid Graves' disease patients at diagnosis and during methimazole treatment. Neuroimmunomodulation. 2011;18:45-51 pubmed publisher
    ..These results support the notion that serum cytokines could be used as a marker of GD activity, and the decrease in cytokine levels might be related to the achievement of euthyroidism and the immunomodulatory effects of MMI treatment. ..
  3. Naik V, Naik M, Goldberg R, Smith T, Douglas R. Immunopathogenesis of thyroid eye disease: emerging paradigms. Surv Ophthalmol. 2010;55:215-26 pubmed publisher
    ..Based upon these new insights, several therapeutic strategies can now be proposed that, for the first time, might specifically interrupt its pathogenesis...
  4. Marcocci C, Kahaly G, Krassas G, Bartalena L, Prummel M, Stahl M, et al. Selenium and the course of mild Graves' orbitopathy. N Engl J Med. 2011;364:1920-31 pubmed publisher
    ..Funded by the University of Pisa and the Italian Ministry for Education, University and Research; EUGOGO Netherlands Trial Register number, NTR524.). ..
  5. Douglas R, Afifiyan N, Hwang C, Chong K, Haider U, Richards P, et al. Increased generation of fibrocytes in thyroid-associated ophthalmopathy. J Clin Endocrinol Metab. 2010;95:430-8 pubmed publisher
    ..Specifically why activating antibodies are generated against self-antigens remains uncertain as does the identity of the antigen(s) that provokes orbital involvement in GD, a process known as thyroid-associated ophthalmopathy (TAO)...
  6. Arslan E, Yavasoglu I, Cildağ B, Kocaturk T. Unilateral optic neuropathy as the initial manifestation of euthyroid Graves' disease. Intern Med. 2009;48:1993-4 pubmed
    ..Graves' disease should be considered in the differential diagnosis of optic neuropathy of unknown origin. ..
  7. Sung M, Lee M, Choung H, Kim N, Khwarg S. Lower eyelid epiblepharon associated with lower eyelid retraction. Korean J Ophthalmol. 2010;24:4-9 pubmed publisher
    ..To describe a series of patients with lower eyelid epiblepharon associated with lower eyelid retraction...
  8. Bahn R. Graves' ophthalmopathy. N Engl J Med. 2010;362:726-38 pubmed publisher
  9. Lytton S, Ponto K, Kanitz M, Matheis N, Kohn L, Kahaly G. A novel thyroid stimulating immunoglobulin bioassay is a functional indicator of activity and severity of Graves' orbitopathy. J Clin Endocrinol Metab. 2010;95:2123-31 pubmed publisher
    ..Immunoglobulins stimulating the TSH receptor (TSI) influence thyroid function and likely mediate extrathyroidal manifestations of Graves' disease (GD)...
  10. Gillespie E, Papageorgiou K, Fernando R, Raychaudhuri N, Cockerham K, Charara L, et al. Increased expression of TSH receptor by fibrocytes in thyroid-associated ophthalmopathy leads to chemokine production. J Clin Endocrinol Metab. 2012;97:E740-6 pubmed publisher
    ..Because they infiltrate both orbit and thyroid in GD, they may represent the link between systemic immunoreactivity and organ-specific autoimmunity. ..
  11. Regensburg N, Wiersinga W, Berendschot T, Potgieser P, Mourits M. Do subtypes of graves' orbitopathy exist?. Ophthalmology. 2011;118:191-6 pubmed publisher
    ..An increase of the FV is seen in only 14% of GO patients and characterized by proptosis. Muscle enlargement occurs in 70% of patients and is associated with older age, higher TBII values, more proptosis, and impaired motility. ..
  12. Liu Y, Chen R, Chen W, Tsai Y, Wan L, Tsai F. Disease association of the CD103 polymorphisms in Taiwan Chinese Graves' ophthalmopathy patients. Ophthalmology. 2010;117:1645-51 pubmed publisher
    ..These data suggest that patients with Graves' disease in the presence of the G allele of SNP rs11652878, especially Ht5-GCGCG, in CD103 are less susceptible toward the development of GO. ..
  13. Kumar S, Nadeem S, Stan M, Coenen M, Bahn R. A stimulatory TSH receptor antibody enhances adipogenesis via phosphoinositide 3-kinase activation in orbital preadipocytes from patients with Graves' ophthalmopathy. J Mol Endocrinol. 2011;46:155-63 pubmed publisher
    ..This antibody appears to act via the PI3K signaling cascade, suggesting that inhibition of PI3K signaling may represent a potential novel therapeutic approach in GO. ..
  14. Raychaudhuri N, Douglas R, Smith T. PGE2 induces IL-6 in orbital fibroblasts through EP2 receptors and increased gene promoter activity: implications to thyroid-associated ophthalmopathy. PLoS ONE. 2010;5:e15296 pubmed publisher
    ..Moreover, they might therefore define an attractive therapeutic target for the treatment of TAO. ..
  15. Regensburg N, Wiersinga W, Berendschot T, Saeed P, Mourits M. Effect of smoking on orbital fat and muscle volume in Graves' orbitopathy. Thyroid. 2011;21:177-81 pubmed publisher
    ..Cigarette smoke enhances adipogenesis in cultured human orbital fibroblasts. The present study tested our hypothesis that smoking is associated with increased orbital fat in GO patients...
  16. Liu N, Li X, Liu C, Zhao Y, Cui B, Ning G. The association of interleukin-1alpha and interleukin-1beta polymorphisms with the risk of Graves' disease in a case-control study and meta-analysis. Hum Immunol. 2010;71:397-401 pubmed publisher
    ..70, p = 0.002) and GO (OR = 0.65, p = 0.02). The results confirmed that the rs1800587 (IL-alpha, T-889 C) and rs16944 (IL-1beta, A-511 G) polymorphisms may confer susceptibility to GD and GO in Asian population. ..
  17. Liu Y, Chen R, Wu H, Liao W, Chen W, Tsai Y, et al. Association of interleukin-1beta (IL1B) polymorphisms with Graves' ophthalmopathy in Taiwan Chinese patients. Invest Ophthalmol Vis Sci. 2010;51:6238-46 pubmed publisher
    ..The data for IL1B polymorphisms and the association of GD and GO with plasma IL1? levels show that IL1B polymorphisms may be associated with the development of GD and GO. ..
  18. Liao S, Huang S. Correlation of retrobulbar volume change with resected orbital fat volume and proptosis reduction after fatty decompression for Graves ophthalmopathy. Am J Ophthalmol. 2011;151:465-9.e1 pubmed publisher
    ..To evaluate the correlation of retrobulbar volume change, resected orbital fat volume, and proptosis reduction after fatty decompression...
  19. van Steensel L, Dik W. The orbital fibroblast: a key player and target for therapy in graves' ophthalmopathy. Orbit. 2010;29:202-6 pubmed publisher
    ..Finally, we propose the orbital fibroblast, and especially the PDGF system acting on orbital fibroblasts, as an important therapeutic target in GO. ..
  20. Yin X, Latif R, Bahn R, Davies T. Genetic profiling in Graves' disease: further evidence for lack of a distinct genetic contribution to Graves' ophthalmopathy. Thyroid. 2012;22:730-6 pubmed publisher
  21. Ponto K, Kanitz M, Olivo P, Pitz S, Pfeiffer N, Kahaly G. Clinical relevance of thyroid-stimulating immunoglobulins in graves' ophthalmopathy. Ophthalmology. 2011;118:2279-85 pubmed publisher
    ..Thyroid-stimulating immunoglobulins show more significant association with clinical features of GO than TBII and may be regarded as functional biomarkers for GO. Proprietary or commercial disclosure may be found after the references. ..
  22. Kook K, Choi Y, Kim Y, Park S, Jou I, Kim S, et al. Altered ganglioside expression modulates the pathogenic mechanism of thyroid-associated ophthalmopathy by increase in hyaluronic acid. Invest Ophthalmol Vis Sci. 2011;52:264-73 pubmed publisher
    ..The aim of this study was to determine the role of gangliosides in pathogenic mechanisms of thyroid-associated ophthalmopathy (TAO)...
  23. Bednarczuk T, Gopinath B, Ploski R, Wall J. Susceptibility genes in Graves' ophthalmopathy: searching for a needle in a haystack?. Clin Endocrinol (Oxf). 2007;67:3-19 pubmed
    ..However, the possibility that GO may be a genetically heterogeneous disorder, or that the development of GO may be predominantly influenced by environmental factors such as cigarette smoking, can not be disregarded. ..
  24. Huber A, Jacobson E, Jazdzewski K, Concepcion E, Tomer Y. Interleukin (IL)-23 receptor is a major susceptibility gene for Graves' ophthalmopathy: the IL-23/T-helper 17 axis extends to thyroid autoimmunity. J Clin Endocrinol Metab. 2008;93:1077-81 pubmed
    ..Variants in the IL-23R gene are strongly associated with GO. These variants may predispose to GO by changing the expression and/or function of IL-23R, thereby promoting a proinflammatory signaling cascade. ..
  25. Hassan I, Danila R, Maurer E, Osei Agymang T, Zielke A. Severe Graves' ophthalmopathy may be a risk factor for the development of postthyroidectomy hypocalcaemia. Exp Clin Endocrinol Diabetes. 2008;116:614-8 pubmed publisher
    ..Therefore, patients with GO should be considered for surgery at high volume centres specialised in thyroid and parathyroid surgery. ..
  26. Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall Taylor P, Marcocci C, et al. Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol. 2008;158:273-85 pubmed publisher
  27. Lin M, Hsu F, Bee Y, Ger L. Age influences the severity of Graves' ophthalmopathy. Kaohsiung J Med Sci. 2008;24:283-8 pubmed publisher
    ..In conclusion, the severity of Graves' ophthalmopathy is correlated with age (r = 0.286). Thus, older patients should be more closely followed up and more aggressively treated. ..
  28. Eckstein A, Plicht M, Lax H, Neuhauser M, Mann K, Lederbogen S, et al. Thyrotropin receptor autoantibodies are independent risk factors for Graves' ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab. 2006;91:3464-70 pubmed
    ..Follow-up measurements of TBII allow, in half of the patients, assessment of the prognosis of GO and, therefore, could be of additional help for the disease management. ..
  29. Kuriyan A, Phipps R, Feldon S. The eye and thyroid disease. Curr Opin Ophthalmol. 2008;19:499-506 pubmed publisher
  30. Labonia A, Carnovale Scalzo G, Paola A, De Morelli G, Scorcia V, Bruzzichessi D, et al. Subclinical visual field alterations are commonly present in patients with Graves' Orbitopathy and are mainly related to the clinical activity of the disease. Exp Clin Endocrinol Diabetes. 2008;116:347-51 pubmed
    ..0005), while no relationship occurred with proptosis degree (p = 0.115). In conclusion, a great proportion of GO patients without clinically evident DON presents visual field defects, mainly related to GO activity. ..
  31. Dayan C, Dayan M. Dysthyroid optic neuropathy: a clinical diagnosis or a definable entity?. Br J Ophthalmol. 2007;91:409-10 pubmed
  32. Cawood T, Moriarty P, O Farrelly C, O Shea D. Smoking and thyroid-associated ophthalmopathy: A novel explanation of the biological link. J Clin Endocrinol Metab. 2007;92:59-64 pubmed
    ..1 ng/ml IL-1 reduced the degree of adipogenesis by 82% (P < 0.001). These findings may help explain how cigarette smoking has a detrimental effect in TAO and suggests that IL-1 may be an attractive therapeutic target in TAO. ..
  33. Kvetny J, Puhakka K, Røhl L. Magnetic resonance imaging determination of extraocular eye muscle volume in patients with thyroid-associated ophthalmopathy and proptosis. Acta Ophthalmol Scand. 2006;84:419-23 pubmed
    ..Our results support the hypothesis of a role of thyrotropin receptor antibodies in the pathogenesis of TAO and suggest that only EOM enlargement is responsible for proptosis in TAO. ..
  34. Bradley E, Gower E, Bradley D, Meyer D, Cahill K, Custer P, et al. Orbital radiation for graves ophthalmopathy: a report by the American Academy of Ophthalmology. Ophthalmology. 2008;115:398-409 pubmed
    To investigate whether orbital radiation offers effective and safe treatment for Graves ophthalmopathy. Medical literature databases were searched to identify all published reports relating to orbital radiation treatment for Graves ..
  35. Perry J. Transcaruncular orbital decompression: an alternate procedure for graves ophthalmopathy with compressive optic neuropathy. Am J Ophthalmol. 2006;142:889; author reply 889-90 pubmed
  36. Tsai C, Kao S, Cheng C, Kau H, Hsu W, Lee C, et al. Oxidative stress change by systemic corticosteroid treatment among patients having active graves ophthalmopathy. Arch Ophthalmol. 2007;125:1652-6 pubmed
    To measure the 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in patients having active Graves ophthalmopathy (GO) and to compare this oxidative stress biomarker and the clinical evolution of patients after systemic corticosteroid treatment...
  37. Paridaens D, Lie A, Grootendorst R, van den Bosch W. Efficacy and side effects of 'swinging eyelid' orbital decompression in Graves' orbitopathy: a proposal for standardized evaluation of diplopia. Eye (Lond). 2006;20:154-62 pubmed
    ..To calculate the incidence of postoperative new-onset diplopia (NOD) using a newly proposed scoring system for diplopia...
  38. Vondrichova T, de Capretz A, Parikh H, Frenander C, Asman P, Aberg M, et al. COX-2 and SCD, markers of inflammation and adipogenesis, are related to disease activity in Graves' ophthalmopathy. Thyroid. 2007;17:511-7 pubmed
    ..This may represent a putative future treatment of endocrine ophthalmopathy. ..
  39. Jazdzewski K, Bednarczuk T, Stepnowska M, Liyanarachchi S, Suchecka Rachon K, Limon J, et al. beta-2-adrenergic receptor gene polymorphism confers susceptibility to Graves disease. Int J Mol Med. 2007;19:181-6 pubmed
    ..frequency of the 79GG protective genotype was significantly smaller in the GD patients without symptoms of Graves ophthalmopathy compared to controls (10% vs 22%, OR=0.41, 95% CI: 0.234-0.706, p=0.0017, pcorr=0.015)...
  40. Lim S, Lim A, Mumtaz M, Hussein E, Wan Bebakar W, Khir A. Prevalence, risk factors, and clinical features of thyroid-associated ophthalmopathy in multiethnic Malaysian patients with Graves' disease. Thyroid. 2008;18:1297-301 pubmed publisher
    ..However, lower lid retraction was also common and present in 60% of cases with other signs of TAO. In Chinese, Malay, and Indian Asians with GD, lower lid retraction should be a diagnostic criterion for TAO. ..
  41. Tsai C, Cheng C, Liu C, Kao S, Kau H, Hsu W, et al. Oxidative stress in patients with Graves' ophthalmopathy: relationship between oxidative DNA damage and clinical evolution. Eye (Lond). 2009;23:1725-30 pubmed publisher
    ..3+/-4.9 vs 8.6+/-3.0 ng/mg creatinine). Our findings suggest that urinary 8-OHdG is increased in GO patients and is correlated with the disease activity. Smoking had a higher impact on the increased 8-OHdG among GO patients. ..
  42. Naik V, Khadavi N, Naik M, Hwang C, Goldberg R, Tsirbas A, et al. Biologic therapeutics in thyroid-associated ophthalmopathy: translating disease mechanism into therapy. Thyroid. 2008;18:967-71 pubmed publisher
    ..It is imperative that agents targeting B-and T-cell functions be further evaluated in the treatment of aggressive forms of TAO utilizing multicenter clinical trials that allow adequate statistical power and sample size. ..
  43. Goldstein S, Katowitz W, Moshang T, Katowitz J. Pediatric thyroid-associated orbitopathy: the Children's Hospital of Philadelphia experience and literature review. Thyroid. 2008;18:997-9 pubmed publisher
    ..Surgery is indicated in a small number of patients for cornea exposure or appearance issues. Graves' disease-associated optic neuropathy has never been reported in the pediatric population. ..
  44. Zhang L, Baker G, Janus D, Paddon C, Fuhrer D, Ludgate M. Biological effects of thyrotropin receptor activation on human orbital preadipocytes. Invest Ophthalmol Vis Sci. 2006;47:5197-203 pubmed
    Thyrotropin receptor (TSHR) expression is upregulated in the orbits of patients with Graves ophthalmopathy (GO), most of whom have TSHR-stimulating antibodies...
  45. Eckstein A, Johnson K, Thanos M, Esser J, Ludgate M. Current insights into the pathogenesis of Graves' orbitopathy. Horm Metab Res. 2009;41:456-64 pubmed
    ..To date most models have centered on provoking autoimmune responses to the TSHR, but other antigens, alone or in combination with this receptor, hopefully will succeed in inducing the full spectrum of GD. ..
  46. Khoo T, Coenen M, Schiefer A, Kumar S, Bahn R. Evidence for enhanced Thy-1 (CD90) expression in orbital fibroblasts of patients with Graves' ophthalmopathy. Thyroid. 2008;18:1291-6 pubmed publisher
  47. Gopinath B, Musselman R, Adams C, Tani J, Beard N, Wall J. Study of serum antibodies against three eye muscle antigens and the connective tissue antigen collagen XIII in patients with Graves' disease with and without ophthalmopathy: correlation with clinical features. Thyroid. 2006;16:967-74 pubmed
    ..These results are unique in that it is the first time the significance of a panel of three candidate eye muscle antibodies and a connective tissue antibody have been evaluated in the same patients with ophthalmopathy. ..
  48. Baldeschi L, MacAndie K, Koetsier E, Blank L, Wiersinga W. The influence of previous orbital irradiation on the outcome of rehabilitative decompression surgery in graves orbitopathy. Am J Ophthalmol. 2008;145:534-540 pubmed publisher
    ..The total radiation dose, fraction size, and irradiated volume commonly used to treat active Graves orbitopathy do not adversely interfere with the outcome of rehabilitative decompression surgery. ..
  49. Boyle B, Koranyi K, Patocs A, Liko I, Szappanos A, Bertalan R, et al. Polymorphisms of the glucocorticoid receptor gene in Graves ophthalmopathy. Br J Ophthalmol. 2008;92:131-4 pubmed
    ..whether these polymorphisms could be associated with the development or clinical manifestations of Graves ophthalmopathy (GO)...
  50. Kurylowicz A, Hiromatsu Y, Jurecka Lubieniecka B, Kula D, Kowalska M, Ichimura M, et al. Association of NFKB1 -94ins/del ATTG promoter polymorphism with susceptibility to and phenotype of Graves' disease. Genes Immun. 2007;8:532-8 pubmed
    ..009; OR=1.49 (1.10-2.01)), and the age of disease onset (P=0.009; OR=1.45 (1.09-1.91)). Our results suggest that NFKB1 -94ins/del ATTG polymorphism may be associated with susceptibility to and/or phenotype of GD. ..
  51. Liao S, Chang T, Lin L. Transcaruncular orbital decompression: an alternate procedure for Graves ophthalmopathy with compressive optic neuropathy. Am J Ophthalmol. 2006;141:810-818 pubmed
    To study the efficacy of transcaruncular orbital apex decompression for Graves ophthalmopathy with compressive optic neuropathy nonresponsive to pulse corticosteroids. Retrospective, interventional case series study...
  52. Bhatnagar A, Tsirbas A, Douglas R, Goldberg R, Hoyama E. Graves' orbitopathy. Ophthalmology. 2007;114:392.e1-2 pubmed
  53. Anvari M, Khalilzadeh O, Esteghamati A, Esfahani S, Rashidi A, Etemadi A, et al. Genetic susceptibility to Graves' ophthalmopathy: the role of polymorphisms in proinflammatory cytokine genes. Eye (Lond). 2010;24:1058-63 pubmed publisher
    ..We demonstrated that specific polymorphisms in IL-12, IFN- gamma, and TNF-alpha genes are associated with susceptibility to GO in the Iranian population. Our results open a new perspective to genetic correlates of GO. ..