Ocular Manifestations in Hashimoto's Thyroiditis and Graves' Disease Review article

Article Sidebar

PDF


Published: Feb 19, 2026
DOI: https://doi.org/10.24292/01.OT.090226
Keywords:
Hashimoto’s thyroiditis, thyroid autoimmunity, Graves’ disease, Graves’ ophthalmopathy, ophthalmic symptoms

Main Article Content

Paulina Malon
Nicolaus Copernicus University in Toruń, Collegium Medicum, Bydgoszcz
https://orcid.org/0009-0008-9311-001X
Szymon Konczyński
Nicolaus Copernicus University in Toruń, Collegium Medicum, Bydgoszcz
Anna Bych
Nicolaus Copernicus University in Toruń, Collegium Medicum, Bydgoszcz
https://orcid.org/0009-0009-2686-8434
Karolina Kaźmierczak
Department of Ophthalmology, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Collegium Medicum, Bydgoszcz
https://orcid.org/0000-0001-6434-0037

Abstract

Introduction: Autoimmune thyroid diseases such as Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) can present with ocular manifestations. While these are well documented in GD, less is known about their prevalence and characteristics in HT.
Methods: This narrative review summarizes current knowledge on the epidemiology, pathophysiology, clinical features, diagnostics, and treatment of ophthalmic symptoms in HT and GD. Special focus is placed on dry eye syndrome, thyroid-associated ophthalmopathy (TAO), and diagnostic approaches including imaging and tear biomarker analysis.
Results: HT most frequently presents with dry eye syndrome, eyelid edema, and rare manifestations like diplopia or vision loss. TAO, typically associated with GD, is also observed in a small percentage of HT cases. GD-related orbitopathy affects up to 50% of patients and may lead to severe complications, including optic neuropathy. Several immunological markers, including TSHR and IGF-1R, play a key role in the pathogenesis of Graves’ orbitopathy (GO).
Conclusion: Ocular symptoms in HT and GD are diverse and can significantly impact patients’ quality of life. Although GO is more characteristic of GD, its presence in HT should not be underestimated. Comprehensive ophthalmologic evaluation is essential for timely diagnosis and treatment.

Downloads

Download data is not yet available.

Article Details

How to Cite
1.
Malon P, Konczyński S, Bych A, Kaźmierczak K. Ocular Manifestations in Hashimoto’s Thyroiditis and Graves’ Disease. Ophthatherapy [Internet]. 2026Feb.19 [cited 2026May30];12(4). Available from: https://www.journalsmededu.pl/index.php/ophthatherapy/article/view/3267
Issue
Vol 12 No 4 (2025)
Section
Diagnostics
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Copyright: Medical Education sp. z o.o. License allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

Address reprint requests to: Medical Education, Marcin Kuźma (marcin.kuzma@mededu.pl)

References

1. Baretić M. 100 years of Hashimoto thyroiditis, still an intriguing disease. Acta Med Croatica. 2011; 65: 453-7.
2. Jacobson EM, Tomer Y. The CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22 gene quintet and its contribution to thyroid autoimmunity: back to the future. J Autoimmun. 2007; 28: 85-98.
3. Tunbridge WM, Vanderpump MP. Population screening for autoimmune thyroid disease. Endocrinol Metab Clin North Am. 2000; 29: 239-53.
4. Vanderpump MP. The epidemiology of thyroid disease. Br Med Bull. 2011; 99: 39-51.
5. Taylor PN, Albrecht D, Scholz A et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol. 2018; 14: 301-16.
6. Weetman AP. Autoimmune thyroid disease. Autoimmunity. 2004; 37: 337-40.
7. Lee SY, Pearce EN. Hyperthyroidism: A Review. JAMA. 2023; 330(15): 1472-83. http://doi.org/10.1001/jama.2023.19052.
8. George A, Diana T, Langericht J et al. Stimulatory Thyrotropin Receptor Antibodies Are a Biomarker for Graves’ Orbitopathy. Front Endocrinol (Lausanne). 2021; 11: 629925. http://doi.org/10.3389/fendo.2020.629925.
9. 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.
10. Abraham-Nordling M, Bystrom K, Torring O et al. Incidence of hyperthyroidism in Sweden. Eur J Endocrinol. 2011; 165(6): 899-905. http://doi.org/10.1530/EJE-11-0548.
11. Laurberg P, Berman DC, Bulow Pedersen I et al. Incidence and clinical presentation of moderate to severe Graves’ orbitopathy in a Danish population before and after iodine fortification of salt. J Clin Endocrinol Metab. 2012; 97(7): 2325-32. http://doi.org/10.1210/jc.2012-1275.
12. Bartalena L, Piantanida E, Gallo D et al. Epidemiology, Natural History, Risk Factors, and Prevention of Graves’ Orbitopathy. Front Endocrinol (Lausanne). 2020; 11: 615993. http://doi.org/10.3389/fendo.2020.615993.
13. Dai X, Gakidou E, Lopez AD. Evolution of the global smoking epidemic over the past half century: strengthening the evidence base for policy action. Tob Control. 2022; 31(2): 129-37. http://doi.org/10.1136/tobaccocontrol-2021-056535.
14. Taylor PN, Zhang L, Lee RWJ et al. New insights into the pathogenesis and nonsurgical management of Graves orbitopathy. Nat Rev Endocrinol. 2020; 16: 104-16. https://doi.org/10.1038/s41574-019-0305-4.
15. Bartalena L, Tanda ML. Current concepts regarding Graves’ orbitopathy. J Intern Med. 2022; 292(5): 692-716. http://doi.org/10.1111/joim.13524.
16. Zhang L, Grennan-Jones F, Lane C et al. Adipose tissue depot-specific differences in the regulation of hyaluronan production of relevance to Graves’ orbitopathy. J Clin Endocrinol Metab. 2012; 97(2): 653-62. http://doi.org/10.1210/jc.2011-1299.
17. Antonelli A, Fallahi P, Elia G et al. Graves’ disease: Clinical manifestations, immune pathogenesis (cytokines and chemokines) and therapy. Best Pract Res Clin Endocrinol Metab. 2020; 34(1): 101388. http://doi.org/10.1016/j.beem.2020.101388.
18. Jarząb B, Płaczkiewicz-Jankowska E. Orbitopatia tarczycowa. In: Choroby wewnętrzne. Tom I. Szczeklik A (ed.). Medycyna Praktyczna, Krakow 2005: 1057-9.
19. Altin Ekin M, Karadeniz Ugurlu S, Egrilmez ED et al. Ocular Surface Changes in Hashimoto’s Thyroiditis Without Thyroid Ophthalmopathy. Eye Contact Lens. 2021; 47(1): 32-7. http://doi.org/10.1097/icl.0000000000000686.
20. Ju C, Zhang L. Diplopia in a patient with Hashimoto’s thyroiditis. A case report and literature review. Medicine (Baltimore). 2017; 96(26): e7330. http://doi.org/10.1097/MD.0000000000007330.
21. Kan E, Kilickan E, Ecemiş G et al. Presence of Dry Eye in Patients with Hashimoto’s Thyroiditis. 2014; 2014: 754923. http://doi.org/10.1155/2014/754923.
22. Glover K, Mishra D, Singh TRR. Epidemiology of Ocular Manifestations in Autoimmune Disease. Front Immunol. 2021; 12: 744396. http://doi.org/10.3389/fimmu.2021.744396.
23. Antonelli A, Ferrari SM, Ragusa F et al. Graves’ disease: Epidemiology, genetic and environmental risk factors and viruses. Best Pract Res Clin Endocrinol Metab. 2020; 34(1): 101387. http://doi.org/10.1016/j.beem.2020.101387.
24. Rashad R, Pinto R, Li E et al. Thyroid Eye Disease. Life (Basel). 2022; 12(12): 2084. http://doi.org/10.3390/life12122084.
25. Scarabosio A, Surico PL, Singh RB et al. Thyroid Eye Disease: Advancements in Orbital and Ocular Pathology Management. J Pers Med. 2024; 14(7): 776. http://doi.org/10.3390/jpm14070776.
26. Johnson BT, Jameyfield E, Aakalu VK. Optic neuropathy and diplopia from thyroid eye disease: update on pathophysiology and treatment. Curr Opin Neurol. 2021; 34(1): 116-21. http://doi.org/10.1097/WCO.0000000000000894.
27. Bartalena L, Kahaly GJ, Baldeschi L et al.; EUGOGO. The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy. Eur J Endocrinol. 2021; 185(4): G43-G67. https://doi.org/10.1530/EJE-21-0479.
28. Shi TT, Zhao RX, Xin Z et al. Tear-derived exosomal biomarkers of Graves’ ophthalmopathy. Front Immunol. 2022; 13: 1088606. http://doi.org/10.3389/fimmu.2022.1088606.
29. Kishazi E, Dor M, Eperon S et al. Differential profiling of lacrimal cytokines in patients suffering from thyroid-associated orbitopathy. Sci Rep. 2018; 8(1): 10792. http://doi.org/10.1038/s41598-018-29113-2.
30. Cai K, Wei R. Interleukin-7 expression in tears and orbital tissues of patients with Graves’ ophthalmopathy. Endocrine. 2013; 44: 140-4. https://doi.org/10.1007/s12020-012-9840-7.
31. Ujhelyi B, Gogolak P, Erdei A et al. Graves’ orbitopathy results in profound changes in tear composition: a study of plasminogen activator inhibitor-1 and seven cytokines. Thyroid. 2012; 22(4): 407-14. http://doi.org/10.1089/thy.2011.0248.
32. Cai Y, Su H, Si Y et al. Machine learning-based prediction of diagnostic markers for Graves’ orbitopathy. Endocrine. 2023; 81(2): 277-89. http://doi.org/10.1007/s12020-023-03349-z .
33. Olejarz M, Szczepanek-Parulska E, Dadej D et al. IgG4 as a Biomarker in Graves’ Orbitopathy. Mediators Inflamm. 2021; 2021: 5590471. http://doi.org/10.1155/2021/5590471.
34. Ugradar S, Goldberg RA, Douglas RS. Changing the face of thyroid eye disease. Eye (Lond). 2023; 37(2): 197-9. http://doi.org/10.1038/s41433-022-02186-0.
35. Park JJ, Sullivan TJ, Mortimer RH et al. Assessing quality of life in Australian patients with Graves’ ophthalmopathy. Br J Ophthalmol. 2004; 88(1): 75-8. http://doi.org/10.1136/bjo.88.1.75.
36. Rajput R, Dhingra A, Kumar K et al. Infiltrative ophthalmopathy and primary hypothyroidism: a rare clinical manifestation of a common disease. Postgrad Med J. 2009; 85: 40-2. http://doi.org/10.1136/pgmj.2008.071704.
37. Alajmi S, Alshehri S, Ekhzaimy A. Graves’ Ophthalmopathy in the Setting of Primary Hypothyroidism. Cureus. 2022; 14(5): e24954. http://doi.org/10.7759/cureus.24954.
38. Marino M, Menconi F, Rotondo Dottore G et al. Selenium in Graves hyperthyroidism and orbitopathy. Ophthalmic Plast Reconstr Surg. 2018; 34(4S Suppl 1): S105-10.
39. Ventura M, Melo M, Carrilho F. Selenium and thyroid disease: from pathophysiology to treatment. Int J Endocrinol. 2017; 2017: 1297658.
40. Rotondo Dottore G, Leo M, Casini G et al. Antioxidant actions of selenium in orbital fibroblasts: a basis for the effects of selenium in Graves’ orbitopathy. Thyroid. 2017; 27(2): 271-8.
41. Marcocci C, Kahaly GJ, Krassas GE. Selenium and the course of mild Graves’ orbitopathy. N Engl J Med. 2011; 364(20): 1920-31.
42. Hodgson NM, Rajaii F. Current Understanding of the Progression and Management of Thyroid Associated Orbitopathy: A Systematic Review. Ophthalmol Ther. 2020; 9(1): 21-33. http://doi.org/10.1007/s40123-019-00226-9.
43. Burnstine MA, Elner SG, Strieter RM et al. Orbital fibroblast interleukin-6 gene expression and immunomodulation. Ophthalmic Plast Reconstr Surg. 1999; 15(5): 306-11.
44. Burnstine MA, Elner SG, Elner V. Orbital fibroblast chemokine modulation: effects of dexamethasone and cyclosporin A. Br J Ophthalmol. 1998; 82(3): 318-22.
45. Bartalena L, Tanda ML. Current concepts regarding Graves’ orbitopathy. J Intern Med. 2022; 292(5): 692-716. http://doi.org/10.1111/joim.13524.
46. Kahaly GJ, Pitz S, Hommel G et al. Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves’ orbitopathy. J Clin Endocrinol Metab. 2005; 90(9): 5234-40.
47. Aktaran S, Akarsu E, Erbagci I et al. Comparison of intravenous methylprednisolone therapy vs. oral methylprednisolone therapy in patients with Graves’ ophthalmopathy. Int J Clin Pract. 2007; 61(1): 45-51.
48. Bartalena L, Fatourechi V. Extrathyroidal manifestations of Graves’ disease: a 2014 update. J Endocrinol Invest. 2014; 37: 691-700.
49. Salvi M, Vannucchi G, Campi I et al. Efficacy of rituximab treatment for thyroid-associated ophthalmopathy as a result of intraorbital B-cell depletion in one patient unresponsive to steroid immunosuppression. Eur J Endocrinol. 2006; 154(4): 511-7.
50. 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: 422-31.
51. Stan MN, Garrity JA, Carranza Leon BG et al. Randomized controlled trial of rituximab in patients with Graves’ orbitopathy. J Clin Endocrinol Metab. 2015; 100(2): 432-41.
52. Chen B, Tsui S, Smith TJ. IL-1 beta induced IL-6 expression in human orbital fibroblasts: identification of an anatomicsite specific phenotypic attribute relevant to thyroid associated ophthalmopathy. J Immunol. 2005; 175: 1310-9.
53. Kumar S, Schiefer R, Coenen MJ et al. A stimulatory thyrotropin receptor antibody (M22) and thyrotropin increase interleukin-6 expression and secretion in Graves’ orbital preadipocyte fibroblasts. Thyroid. 2010; 20: 59-65.
54. Hallengren B, Planck T, Asman P et al. Presence of thyroid-stimulating hormone receptor antibodies in a patient with subacute thyroiditis followed by hypothyroidism and later Graves’ disease with ophthalmopathy: a case report. Eur Thyroid J. 2015; 4: 197-200.
55. Chiovato L, Santini F, Vitti P et al. Appearnce of thyroid stimulating antibody and Graves’ disease after radioiodine therapy for toxic nodular goitre. Clin Endocrinol. 1994; 40: 803-6.
56. Tahrani AA, Rangan S, Moulik P. Grave’s eye disease developing after radioiodine treatment for toxic nodular goitre. Exp Clin Endocrinol Diabetes. 2007; 115: 471-3.
57. Monzani F, Del Guerra P, Caraccio N et al. Appearance of Graves’ disease after percutaneous ethanol injection for the treatment of hyperfunctioning thyroid adenoma. J Endocrinol Invest. 1997; 20: 294-8.
58. Neag EJ, Smith TJ. 2021 update on thyroid-associated ophthalmopathy. J Endocrinol Invest. 2022; 45: 235-59.
59. Smith TJ, Kahaly GJ, Ezra DG et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017; 376: 1748-61.
60. Douglas RS, Kahaly GJ, Patel A et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020; 382: 341-52.
61. Hoang TD, Nguyen NT, Chou E et al. Rapidly progressive cognitive decline associated with teprotumumab in thyroid eye disease. BMJ Case Rep. 2021; 14: e242153. https://doi.org/10.1136/bcr-2021-242153.
62. Safo MB, Silkiss RZ. A case of ulcerative colitis associated with teprotumumab treatment for thyroid eye disease. Am J Ophthalmol Case Rep. 2021; 22: 101069. https://doi.org/10.1016/j.ajoc.2021.101069.
63. Ashraf DC, Jankovic I, El-Nachef N et al. New-onset of inflammatory bowel disease in a patient treated with teprotumumab for thyroid associated ophthalmopathy. Ophthalmic Plast Reconstr Surg. 2021; 37: e160-4. https://doi.org/10.1097/IOP. 0000000000001943.
64. Bartalena L, Marino M, Marcocci C et al. Teprotumumab for Graves’ orbitopathy and ototoxicity: moving problems for eyes to ears? J Endocrinol Invest. 2022; 45(7): 1455-7. https://doi.org/10.1007/s40618-022-01791-w.
65. Prummel MF, Mourits MP, Blank L et al. Randomized doubleblind trial of prednisone versus radiotherapy in Graves’ ophthalmopathy. Lancet. 1993; 342(8877): 949-54.
66. Marcocci C, Bartalena L, Bogazzi F et al. 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 Investig. 1991; 14(10): 853-60.
67. Bartalena L. What to do for moderate-to-severe and active Graves’ orbitopathy if glucocorticoids fail? Clin Endocrinol (Oxf). 2010; 73(2): 149-52.
68. 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.
69. Eckstein A, Schittkowski M, Esser J. Surgical treatment of Graves’ ophthalmopathy. Best Pract Res Clin Endocrinol Metab. 2012; 26(3): 339-58. https://doi.org/10.1016/j.beem.2011.11.002.
70. 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. 2017; 86: 247-55.
71. 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: 287-98.
72. Kahaly GJ, Schrezenmeir J, Krause U et al. Ciclosporin and prednisone in treatment of Graves’ ophthalmopathy: a controlled, randomized and prospective study. Eur J Clin Invest. 1986; 16: 415-22.
73. Prummel MF, Mourits MP, Berghout A et al. Prednisone and cyclosporine in the treatment of severe Graves’ ophthalmopathy. N Engl J Med. 1989; 321: 1353-9.
74. Kashkouli MB, Jam S, Sabzvari D et al. Thyroid-associated ophthalmopathy in Iranian patients. Acta Med Iran. 2011; 49(9): 612-8.