Thyroid Associated Ophthalmopathy – A Review
AbstractThyroid associated ophthalmopathy is an autoimmune disorder affecting the orbital and periorbital tissues. Hyperthyroidismis commonly associated with thyroid associated ophthalmopathy, however in 5% to 10% of cases it is euthyroid. Genetic,environmental and endogenous factors play a role in the initiation of the thyroid ophthalmopathy. Smoking has been identifiedas the strongest risk factor for the development of the disorder. The pathogenesis involves activation of both humoral and cellmediated immunity with subsequent production of gycoaminoglycans, hyaluronic acid resulting in oedema formation, increaseextraocular mass and adipogenesis in the orbit. The natural history of the disease progresses from active to inactive fibroticstage over a period of years. Diagnosis is mainly clinical and almost all patients with ophthalmopathy exhibit some form ofthyroid abnormality on further testing. Treatment is based on the clinical severity of the disease. Non-severe cases aremanaged by supportive measures to reduce the symptomatology and severe cases are treated by either medical or surgicaldecompression. Rehabilitative surgery is done for quiescent disease to reduce diplopia and improve cosmesis.
Gleeson H, Kelly W, Toft A, et al. Severe thyroid eye disease associated with primary hypothyroidism and thyroid-associated dermopathy. Thyroid. 1999; 9(11):1115-8.
Salvi M, Zhang Z-G, Haegert D, et al. Patients with endocrine ophthalmopathy not associated with overt thyroid disease have multiple thyroid immunologic abnormalities. J Clin Endocrinol Metab. 1990; 70(1):89-94.
Kemp EH, Ridgway JN, Smith KA, et al. Autoantibodies to the flavoprotein subunit of succinate dehydrogenase: Analysis of specificity in autoimmune thyroid disease. Clin Endocrinol (Oxf). 2000;53(3):291-9.
Burch HB, Wartofsky L. Graves’ ophthalmopathy: Current concepts regarding pathogenesis and management. Endocr Rev. 1993;14(6):747-93.
Larsen PR, Davies TF, Hay ID. The thyroid gland. In: Wilson JD, Foster DW, Kronenberg HM, Larsen PR, editors. Williams textbook of Endocrinology. Philadelphia: WB Saunders Company; 1998. page 389-515.
Bahn RS, Heufelder AE. Mechanisms of disease: Pathogenesis of Graves’ ophthalmopathy. N Eng J Med. 1993;329(20):1468-75.
Bartley GB. The epidemiological characteristics and clinical course of ophthalmology associated with autoimmune thyroid disease in Olmsted Country, Minnesota. Trans Am Ophthalmol Soc. 1994;92:477–588.
Lim SL, Lim AK, Mumtaz M, Hussein E, Wan Bebakar WM, Khir AS. Prevalence, risk factors, and clinical features of thyroidassociated ophthalmopathy in multiethnic Malaysian patients with Graves’ disease. Thyroid. 2008;18(12):1297-301.
Forbes G, Gorman CA, Brennan MD, et al. Ophthalmopathy of Graves’ disease: Computerized volume measurements of the orbital fat and muscle. AJNR Am Neuroradiol. 1986;7(4):651-6.
Perros P, Crombie AL, Matthews JNS, et al. Age and gender influence the severity of the the thyroid-associated ophthalmopathy: A study of 101 patients attending a combined thyroid-eye clinic. Clin Endocrinol (Oxf). 1993;38(4):367-72.
Krassas GE, Segni M, Wiersinga WM. Childhood Graves’ ophthalmopathy: Results of a European questionnaire study. Eur J Endocrinol. 2005;153(4):515-21.
Kendall –Taylor P, Perros P. Clinical presentation of thyroid associated orbitopathy. Thyroid 1998; 8(5):427-8.
Marcocci C, Bartalena L, Bogazzi F, et al. Studies on the occurrence of ophthalmopathy in Graves’ disease. Acta Endocrinol (Copenh). 1989;120(4):473-8.
Day RM. Hyperthyroidism: clinical manifestations of eye changes. In: Werner SC, Ingbar SH, editors. The thyroid: a fundamental and clinical text. 4th ed. New York: Har-Row; 1978. page 663-70.
Inoue D, Sato K, Maeda M, et al. Genetic differences shown by HLA typing among Japanese patients with euthyroid Graves’ ophthalmopathy, Graves’ disease and Hashimoto’s thyroiditis: Genetic characteristics of euthyroid Graves’ ophthalmopathy. Clin Endocrinol (Oxf). 1991;34(1):57–62.
Weetman AP, Zhang L, Webb S, et al. Analysis of HLA-DQB and HLA-DPB alleles in Graves’ disease by oligonucleotide probing of enzymatically amplified DNA. Clin Endocrinol (Oxf). 1990;33(1):65–71.
Payami H, Joe S, Farid NR, et al. Relative predispositional effects (RPEs) of marker allele with disease: HLA-DR alleles and Graves’ disease. Am J Hum Genet. 1989;45(4):541–6.
Weetman AP, So AK, Warner CA, et al. Immunogenetics of Graves’ ophthalmopathy. Clin Endocrinol(Oxf). 1988;28(6):619–28.
Hagg E, Asplund K. Is endocrine ophthalmopathy related to smoking? Br Med J. 1987;295:634-5.
Prummel MF, Wiersinga WM. Smoking and risk of Graves’disease. JAMA. 1993; 269(4):479-82.
Bartalena L, Bogazzi F, Tanda ML, et al. Cigarette smoking and thyroid. Eur J Endocrinol. 1995; 133(5):507-12.
Pfeilschifter J, Ziegler R. Smoking and endocrine ophthalmopathy: Impact of smoking severity and current vs lifetime cigarette consumption. Clin Endocrinol (Oxf). 1996; 45(4):477-81.
Bartalena L, Martina E, Marcocci C, et al. More on smoking habits and Graves’ ophthalmopathy. J Endocrinol Invest. 1989; 12(10):733-7.
Metcalfe RA, Weetman AP. Stimulation of extraocular muscle fibroblasts by cytokines and hypoxia: Possible role in thyroid associated ophthalmopathy. Clin Endocrinol (Oxf). 1994;40(1):67-72.
Cawood TJ, Moriarty P, O’Farrelly C, et al. Smoking and thyroidassociated ophthalmopathy: A novel explanation of the biological link. J Clin Endocrinol Metab. 2007;92(1):59-64.
Thornton J, Kelly SP, Harrison RA, et al. Cigarette smoking and thyroid eye disease: a systematic review. Eye. 2007;21(9):1135-45.
Hegediüs L, Brix TH, Vestergaard P. Relationship between cigarette smoking and Graves’ ophthalmopathy. J Endocrinol Invest. 2004;27(3):265-71.
McKenzie JM. Pathogenesis of Graves’ disease: Role of the long –acting thyroid stimulator. J Clin Endocrinol Metab. 1965; 25:424-61.
Hoffman MJ, Hetzel BS. The clinical significance of plasma thyroid-stimulating activity in hyperthyroidism. Australas Ann Med. 1966;15(3):204-9.
Heufelder AE, Joba W. Thyroid-associated eye disease. Strabismus. 2000;8(2):101-11.
Van Dyk HJ. Orbital Graves’ disease: A modification of the “NO SPECS” classification. Ophthalmology. 1981;88(6):479-83.
Sharanjeet-Kaur, Dickinson CM, O’Donoghue E, et al. Spectral sensitivity in patients with dysthyroid eye disease. Ophthalmic Physiol Opt. 1997;17(3):232-8.
Bartley GB. Evolution and classification systems for Graves’ ophthalmopathy. Ophthal Plast Reconstr Surg. 1995;11(4):229-37.
Bartley GB. The differential diagnosis and classification of eyelid retraction. Ophthalmology. 1996;103(1):168-76.
Danesh-Meyer HV, Savino PJ, Deramo V, et al. Intraocular pressure changes after treatment for Graves’ orbitopathy. Ophthalmology. 2001;108(1):145-50.
Jordan DR, Anderson RL. Orbital decompression. Ophthalmic Plast Reconstr Surg. 2000;16(2):167–8.
Fatourechi V. Pretibial myxedema: pathophysiology and treatment options. Am J Clin Dermatol. 2005;6(5):295-309.
Garrity JA, Fatourechti V, Bergstralh EJ, et al. Results of transantral orbital decompression in 428 patients with severe Graves’ophthalmopathy. Am J Ophthalmol. 1993;116(5):533-47.
Gilbard JP, Farris RL. Ocular surface drying and tear film osmolarity in thyroid eye disease. Acta Ophthalmol (Copenh). 1983;61(1):108-16.
Trobe JD, Glaser JS, Laflamme P. Dysthyroid optic neuropathy. Clinical profile and rationale for management. Arch Ophthalmol. 1978;96(7):1199-209.
Trobe JD. Optic nerve involvement in dysthyroidism. Ophthalmology. 1981;88(6):488-92.
Warren JD, Spector JG, Burde R. Long-term follow up and recent observations on 305 cases of orbital decompression for dysthyroid orbitopathy. Laryngoscope. 1989;99(1):35-40.
Behrouzi Z, Rabei HM, Azizi F, et al. Prevalence of open-angle glaucoma, glaucoma suspect, and ocular hypertension in thyroidrelated immune orbitopathy. J Glaucoma. 2007;16(4):358-62.
Werner SC. Modification of the classification of the eye changes of Graves’ disease. Am J Ophthalmol. 1977;83(5):725-7.
Wiersinga WM, Prummel MF, Mourits MP, et al. Classification of the eye changes of Graves’ disease. Thyroid. 1991;1(4):357-60.
Wall JR, Henderson J, Strakosch CR, et al. Graves’ ophthalmopathy. Can Med Assoc J. 1981;124(7):855-62, 866.
Teng CS, Smith BR, Clayton B, et al. Thyroid-stimulating immunoglobulins in ophthalmic Graves’ disease. Clin Endocrinol (Oxf). 1977;6(3):207-11.
Wall JR, Odgers RJ, Hetzel BS. Immunological studies of the eye changes of thyrotoxicosis. Aust NZ J Med. 1973;3(2):162-8.
Bahn RS, Garrity JA, Gorman CA. Diagnosis and management of Graves’ ophthalmopathy. J Clin Endocrinol Metab. 1990;71(3):559-63.
Bahn RS, Gorman CA. Choice of therapy and criteria for assessing treatment outcome in thyroid-associated ophthalmopathy. Endocrinol Metab Clin North Am. 1987;16(2):391-407.
Bartalena L, Marcocci, Bogazzi F, et al. Glucocorticoid therapy of Graves’ ophthalmopathy. Exp Clin Endocrinol. 1991;97(2-3):320-7.
Wiersinga WM. Graves’ ophthalmopathy. Thyroid Int. 1997;3:1-15.
Marcocci C, Bartalena L, Tanda ML, et al. Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves’ ophthalmopathy: Results of a prospective, single-blind, randomized study. J Clin Endocrinol Metab. 2001;86(8):3562-7.
Hiromatsu Y. Steroid therapy for Graves’ ophthalmopathy.Nippon Rinsho. 2006;64(12):2279-85.
Bartalena L, Marcocci C, Manetti L, et al. Orbital radiotherapy for Graves’ ophthalmopathy. Thyroid. 1998;8(5):439-41.
Pinchera A, Bartalena L, Chiovato L, et al. Radiotherapy of Graves’ ophthalmopathy. In: Gorman CA, Waller RR, Dyer JA, editors. The eye and the orbit in thyroid disease. New York: Raven Press; 1984:301-16.
Kahaly G, Roesler HP, Pitz S, et al. Low-versus high dose radiotherapy for Graves’ ophthalmopathy: A randomized single blind trial. J Clin Endocrinol Metab. 2000;85(1):102-8.
Wei RL, Cheng JW, Cai JP. The use of orbital radiotherapy for Graves’ ophthalmopathy: Quantitative review of the evidence. Ophthalmologica. 2008;222(1):27-31.
Kulwin DR, Cotton RT, Kersten RC. Combined approach to orbital decompression. Otolaryngol Clin North Am. 1990;23(3):381-90.
Krassas GE, Doumas A, Kaltsas T, et al. Somatostatin receptor scintigraphy before and after treatment with somatostatin analogues in patients with thyroid eye disease. Thyroid. 1999;9(1):47-52.
Prummel MF, Mouritis MP, Berghout A, et al. Prednisolone and cyclosporine in the treatment of severe Graves’ ophthalmopathy. N Engl J Med. 1989; 321(20):1353-9.
Leibe A, Levy Y, Shoenfeld Y. Intravenous immunoglobulins treatment of patients with Graves’ ophthalmopathy. Harefuah. 2001;140(5):392-4,455,454.
Wiersinga WM, Bartalena L. Epidemiology and prevention of Graves’ ophthalmopathy. Thyroid. 2002;12(10):855-60.