after neck irradiation therapy for Hodgkin’s disease. Cancer Treat Rep 1979;63:1393–1395.
20 Khong JJ, Finch S, De Silva C, Rylander S, Craig JE, Selva D, Ebeling PR: Risk factors for Graves’ orbitopathy: the Australian Thyroid-Associated Orbitopathy Research (ATOR) Study. J Clin Endocrinol Metab 2016;7: 2711–2720.
21 Mimura LY, Villares SM, Monteiro ML, Guazzelli IC, Bloise W: Peroxisome proliferator-activated receptor-gamma gene expression in orbital adipose/connective tissues is increased during the active stage of Graves’ ophthalmopathy. Thyroid 2003;13:845–850.
22 Starkey K, Heufelder A, Baker G, Joba W, Evans M, Davies S, Ludgate M: Peroxisome proliferator-activated receptor-gamma in thyroid eye disease: contraindication for thiazolidinedione use? J Clin Endocrinol Metab 2003;88:55–59.
23 Guo N, Woeller CF, Feldon SE, Phipps RP: Peroxisome proliferator-activated receptor gamma ligands inhibit transforming growth factor-beta-induced, hyaluronan-dependent, T cell adhesion to orbital fibroblasts. J Biol Chem 2011;286:18856–18867.
24 Trinh T, Haridas AS, Sullivan TJ: Ocular Findings in Alemtuzumab (Campath-1H)-induced Thyroid Eye Disease. Ophthal Plast Reconstr Surg 2016;32:e128–e129.
25 Chakrabarti S: Thyroid functions and bipolar affective disorder. J Thyroid Res 2011;2011:306367.
26 Byrne AP, Delaney WJ: Regression of thyrotoxic ophthalmopathy following lithium withdrawal. Can J Psychiatry 1993;38:635–637.
27 Villanueva RB, Brau N: Graves’ ophthalmopathy associated with interferon-alpha treatment for hepatitis C. Thyroid 2002;12:737–738.
28 Hägg E, Asplund K: Is endocrine ophthalmopathy related to smoking? Br Med J 1987;295:634–635.
29 Shine B, Fells P, Edwards OM, Weetman AP: Association between Graves’ ophthalmopathy and smoking. Lancet 1990;335:1261–1264.
30 Thornton J, Kelly SP, Harrison RA, Edwards R: Cigarette smoking and thyroid eye disease: a systematic review. Eye 2006;15:1–11.
31 Szurks-Farkas Z, Toth J, Kollar J, Galuska L, Burman KD, Boda J, Leovey A, Varga J, Ujhelyi B, Szabo J, Berta A, Nagy EV: Volume changes in intra- and extraorbital compartments in patients with Graves’ ophthalmopathy: effect of smoking. Thyroid 2005;15:146–152.
32 Bartalena L, Pinchera A, Marcocci C: Management of Graves’ ophthalmopathy: reality and perspectives. Endocr Rev 2000;21:168–199.
33 Wiersinga WM, Bartalena L: Epidemiology and prevention of Graves’ ophthalmopathy. Thyroid 2002;12:855–860.
34 Lim NC, Sunda G, Amrith S, Lee KO: Thyroid eye disease: a Southeast Asian experience. Br J Ophthalmol 2015;99:512–518.
35 Wu Q, Rayman MP, Lv H, et al: Low selenium population status is associated with increased prevalence of thyroid disease. J Clin Endocrinol Metab 2015;100:4037–4047.
36 Jang SY, Lee KH, Oh JR, Kim BY, Yoon JS: Development of thyroid-associated ophthalmopathy in patients who underwent total thyroidectomy. Yonsei Med J 2015;56:1389–1394.
37 Giovansili L, Cayrolle G, Belange G, Clavel G, Herdan ML: Graves’ ophthalmopathy after total thyroidectomy for papillary carcinoma. Ann Endocrinol (Paris) 2011;72:42–44.
Prof. Chantal Daumerie
Service d’Endocrinologie et de Nutrition, Université Catholique de Louvain
Cliniques Universitaires Saint-Luc
Avenue Hippocrate 54, UCL 54.74
BE–1200 Brussels (Belgium)
E-Mail [email protected]
Wiersinga WM, Kahaly GJ (eds): Graves’ Orbitopathy: A Multidisciplinary Approach – Questions and Answers.
Basel, Karger, 2017, pp 41–60 (DOI: 10.1159/000475948)
___________________
Mario Salvia · Utta Berchner-Pfannschmidtb · Marian Ludgatec
aGraves’ Orbitopathy Center, Department of Endocrinology, Fondazione Cà Granda IRCCS, University of Milan, Milan, Italy; bMolecular Ophthalmology, Department of Ophthalmology, University of Duisburg-Essen, Essen, Germany; cDivision of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK
What Are the Pathological Changes in Orbital Tissue in Graves’ Orbitopathy?
The pathological processes within the orbit include:
•inflammatory infiltration of retro-ocular tissues within the orbit;
•expansion of the adipose tissue within the connective tissue located in (endomysium) and around (perimysium) the eye muscles and the fatty connective tissue which fills the intermuscular space;
•excess production by orbital fibroblasts of glycosaminoglycans (GAGs) resulting in an increase in the volume of the extraocular muscles and orbital fat/connective tissue (Fig. 1).
Orbit imaging shows a variable balance among patients between muscle enlargement (the most frequent abnormality observed) and expansion of orbital fat/connective tissue (Fig. 2). Preferential expansion of adipose tissue has been described in patients below 40 years of age, as has a predominant enlargement of extraocular muscles in older individuals with Graves’ orbitopathy (GO) [1].
Muscles may reach 2–3 times the normal volume, sometimes at the expense of the orbital fat tissue volume [2]. The inferior rectus muscle is predominantly affected, followed by the medial rectus, with the other muscles often being spared. Only the belly part of the muscles is affected, and the tendons remain unchanged, which differentiates