Statin Efficacy in the Management of Graves' Ophthalmopathy

Analysis

Authors

  • Maria Vania Tri Ekaputri Faculty of Medicine and Health Sciences, Catholic University of Indonesia Atma Jaya, Jakarta, Indonesia
  • Megawati Tanu Faculty of Medicine and Health Sciences, Catholic University of Indonesia Atma Jaya, Jakarta, Indonesia

DOI:

https://doi.org/10.55175/cdk.v52i7.1546

Keywords:

Cholesterol, Graves ophthalmopathy, management, autoimmune thyroid disease, statin

Abstract

Graves’ ophthalmopathy (OG) is an ocular manifestation of autoimmune thyroid disease. The inflammation and tissue remodeling of OG can cause mild to severe symptoms that can damage the nerves in the eye and lead to blindness. Early identification of diagnosis, classification of activity and severity of the disease, and risk factors for the disease are crucial. Those steps can support comprehensive further management to prevent severe and permanent damage. The complex interactions between endogenous (unmodifiable), exogenous (modifiable), and environmental factors play as risk factors for OG development. Hypercholesterolemia which is also caused by long-term systemic inflammation is one of the risk factors associated with OG. Hypercholesterolemia can be treated by administering statin. Beside it’s role in lowering cholesterol level, statins have preventive and therapeutic effects especially in patient with active moderate to severe OG. Statin also have pleiotropic effects, act as immunoregulator, inhibiting adipogenesis and synergize with methylprednisolone in management of OG.

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References

Men CJ, Kossler AL, Wester ST. Updates on the understanding and management of thyroid eye disease. Ther Adv Opthalmol. 2021;13:25158414211027760. DOI: 10.1177/25158414211027760.

Moledina M, Damato EM, Lee V. The changing landscape of thyroid eye disease: Current clinical advances and future outlook. Eye (Lond). 2024;38(8):1425–37. DOI: 10.1038/s41433-024-02967-9.

Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C, et al. The 2021 European group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy. Eur J Endocrinol. 2021;185(4):G43–67. DOI: 10.1530/EJE-21-0479.

Chin YH, Ng CH, Lee MH, Koh JWH, Kiew J, Yang SP, et al. Prevalence of thyroid eye disease in Graves’ disease: A meta-analysis and systematic review. Clin Endocrinol. 2020;93(4):363–74. DOI: 10.1111/cen.14296.

Lanzolla G, Comi S, Cosentino G, Pakdel F, Marino M. Statins in Graves orbitopathy: A new therapeutic tool. Ophthalmic Plast Reconstr Surg. 2023;39(6S):S29–39. DOI: 10.1097/IOP.0000000000002525.

Nilsson A, Tsoumani K, Planck T. Statins decrease the risk of orbitopathy in newly diagnosed patients with Graves disease. J Clin Endocrinol Metab. 2021;106(5):1325–32. DOI: 10.1210/clinem/dgab070.

Malboosbaf R, Maghsoomi Z, Emami Z, Khamseh ME, Azizi F. Statins and thyroid eye disease (TED): A systematic review. Endocrine 2024;85(1):11–7. DOI: 10.1007/s12020-023-03680-5.

Marino M, Lanzolla G, Marcocci C. Statins: A new hope on the horizon of Graves orbitopathy? J Clin Endocrinol Metab. 2021;106(7):e2819–21. DOI: 10.1210/clinem/dgab184.

Muralidhar A, Das S, Tiple S. Clinical profile of thyroid eye disease and factors predictive of disease severity. Indian J Ophthalmol. 2020;68(8):1629-34. DOI: 10.4103/ijo.IJO_104_20.

Gandhi R, Durairaj VD, Shah K, Nguyen Burkat C, Epley KD, Phelps PO, et al. Thyroid eye disease. American Academy of Ophthalmology (AAO) [Internet]. 2024. Available from: https://eyewiki.org/Thyroid_Eye_Disease.

Bartalena L, Gallo D, Tanda ML, Kahaly GJ. Thyroid eye disease: Epidemiology, natural history, and risk factors. Ophthalmic Plast Reconstr Surg. 2023;39(6S):S2-8. DOI: 10.1097/IOP.0000000000002467.

Korn BS. 2021-2022 Basic and clinical science course, section 7: Oculofacial plastic and orbital surgery. In: Rapuano CJ, Stout J, McCannel C, editors. American Academy of Ophthalmology; 2021.

Weiler DL. Thyroid eye disease: A review. Clin Exp Optom. 2017;100(1):20–5. DOI: 10.1111/cxo.12472.

Lim NCS, Sundar G, Amrith S, Lee KO. Thyroid eye disease: A Southeast Asian experience. Br J Ophthalmol. 2015;99(4):512–8. DOI: 10.1136/bjophthalmol-2014-305649.

Campi I, Fugazzola L. How can we prevent disease relapse in Graves’ orbitopathy after immunosuppressive treatment? Expert Rev Endocrinol Metab. 2022;17(4):269–74. DOI: 10.1080/17446651.2022.2100344.

Lanzolla G, Sabini E, Marenza L, Francesca M, Rocchi R, Sframeli A, et al. Statins for Graves’ orbitopathy (STAGO): A phase 2, open-label, adaptive, single centre, randomised clinical trial. Lancet Diabetes Endocrinol. 2021;9(11):733–42. DOI: 10.1016/S2213-8587(21)00238-2.

Nancy AM. Adding statins to steroids in thyroid eye disease improves outcomes. Medscape [Internet]. 2021. Available from: https://www.medscape.com/viewarticle/960172.

Lanzolla G, Vannucchi G, Ionni I, Campi I, Sileo F, Lazzaroni E, et al. Cholesterol serum levels and use of statins in Graves’ orbitopathy: A new starting point for the therapy. Front Endocrinol (Lausanne). 2019;10:933. DOI: 10.3389/fendo.2019.00933.

Busnelli M, Manzini S, Froio A, Vargiolu A, Cerrito MG, Smolenski RT, et al. Diet induced mild hypercholesterolemia in pigs: Local and systemic inflammation, effects on vascular injury – rescue by high-dose statin treatment. PLos One. 2013;8(11):e80588. DOI: 10.1371/journal.pone.0080588.

Naselli A, Moretti D, Regalbuto C, Arpi ML, Lo Giudice F, Frasca F, et al. Evidence that baseline levels of low-density lipoproteins cholesterol affect the clinical response of Graves’ ophthalmopathy to parenteral corticosteroids. Front Endocrinol. 2020;11:609895.

Rotondo Dottore G, Bucci I, Lanzolla G, Dallan I, Sframeli A, Torregrossa L, et al. Genetic profiling of orbital fibroblasts from patients with Graves’ orbitopathy. J Clin Endocrinol Metab. 2021;106(5):e2176–90. DOI: 10.1210/clinem/dgab035.

Sabini E, Mazzi B, Profilo MA, Mautone T, Casini G, Rocchi R, et al. High serum cholesterol is a novel risk factor for Graves’ orbitopathy: Results of a cross-sectional study. Thyroid 2018;28(3):386–94. DOI: 10.1089/thy.2017.0430.

Lanzolla G, Sabini E, Profilo MA, Mazzi B, Sframeli A, Rocchi R, et al. Relationship between serum cholesterol and Graves’ orbitopathy (GO): A confirmatory study. J Endocrinol Invest. 2018;41(12):1417–23. DOI: 10.1007/s40618-018-0915-z.

Hsu GCY, Shih SR, Chang FY, Liao SL, Wei YH. An appraisal of the preventive effect of statins on the development of Graves’ ophthalmopathy: A hospital-based cohort study. Ophthalmol Ther. 2024;13(6):1499–511. DOI: 10.1007/s40123-024-00930-1.

Fonseca FAH, Izar MCO. Primary prevention of vascular events in patients with high levels of C-reactive protein: The JUPITER study. Expert Rev Cardiovasc Ther. 2009;7(9):1041-56. DOI: 10.1586/erc.09.93.

Bełtowski J, Wojcicka G, Jamroz-Wisniewska A. Adverse effects of statins - mechanisms and consequences. Curr Drug Saf. 2009;4(3):209–28. DOI: 10.2174/157488609789006949.

Bifulco M, Ciaglia E. Statin reduces orbitopathy risk in patients with Graves’ disease by modulating apoptosis and autophagy activities. Endocrine 2016;53(3):649–50. DOI: 10.1007/s12020-015-0762-z.

Kawashima A, Tanigawa K, Akama T, Yoshihara A, Ishii N, Suzuki K. Innate immune activation and thyroid autoimmunity. J Clin Endocrinol Metab. 2011;96(12):3661–71. DOI: 10.1210/jc.2011-1568.

Fulcher J, O’Connell R, Voysey M, Emberson J, Blackwell L, Mihaylova B, et al. Efficacy and safety of LDL-lowering therapy among men and women: Meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet. 2015;385(9976):1397–405. DOI: 10.1016/S0140-6736(14)61368-4.

Koch CA, Krabbe S, Hehmke B. Statins, metformin, proprotein-convertase-subtilisin-kexin type-9 (PCSK9) inhibitors and sex hormones: Immunomodulatory properties? Rev Endocr Metab Disord. 2018;19(4):363–95. DOI: 10.1007/s11154-018-9478-8.

Clark JE, Stan MN. Statin use associated with lower incidence of developing thyroid eye disease in newly-diagnosed Graves’ disease. Clin Thyroidology. 2021;33(6):266–8. DOI: 10.1089/ct.2021;33.266-268.

Published

07-07-2025

How to Cite

Ekaputri, M. V. T., & Tanu, M. (2025). Statin Efficacy in the Management of Graves’ Ophthalmopathy: Analysis. Cermin Dunia Kedokteran, 52(7), 490–496. https://doi.org/10.55175/cdk.v52i7.1546