ABSTRACT
Thyroid-associated orbitopathy (TAO) is usually diagnosed clinically. Early presentation of TAO such as ocular irritation, lid puffiness, and mild retraction may be overlooked and misdiagnosed. Careful clinical evaluation, laboratory investigations, and orbital imaging studies are needed for diagnosing early TAO. Knowing the pathogenesis will open the door for obtaining directed and effective treatment for the inflammatory process in TAO. Most patients with mild to moderate active TAO are treated with observation alone as the available treatment modalities effective in controlling the disease have many potential side effects. Severe active TAO, compressive optic neuropathy, and severe exposure keratopathy are the main indications for treatment with immunosuppressant agents, orbital radiotherapy, or orbital decompression. Surgery remains the final rehabilitation in TAO, which should be done during cicatricial (inactive) TAO when reliable and stable results can be obtained.
KEYWORDS
Thyroid-associated orbitopathy - Graves' ophthalmopathy - proptosis - lid retraction
REFERENCES
-
1
Wiersinga W M, Smit T, van der Gaag R et al..
Clinical presentation of Graves' ophthalmopathy.
Ophthalmic Res.
1989;
21
73-82
-
2
Durairaj V D, Bartley G B, Garrity J A.
Clinical features and treatment of graves ophthalmopathy in pediatric patients.
Ophthal Plast Reconstr Surg.
2006;
22
7-12
-
3
Bartley G B, Fatourechi V, Kadrmas E F et al..
The incidence of Graves' ophthalmopathy in Olmsted County, Minnesota.
Am J Ophthalmol.
1995;
120
511-517
-
4
Szucs-Farkas Z, Toth J, Kollar J et al..
Volume changes in intra- and extraorbital compartments in patients with Graves' ophthalmopathy: effect of smoking.
Thyroid.
2005;
15
146-151
-
5
Eckstein A, Quadbeck B, Mueller G et al..
Impact of smoking on the response to treatment of thyroid associated ophthalmopathy.
Br J Ophthalmol.
2003;
87
773-776
-
6
Graves R J.
Clinical lectures (part II).
London Med Surg J.
1835;
7
516-517
-
7
Ozgen A, Alp M N, Ariyurek M et al..
Quantitative CT of the orbit in Graves' disease.
Br J Radiol.
1999;
72
757-762
-
8
Bartley G B, Fatourechi V, Kadrmas E F et al..
Clinical features of Graves' ophthalmopathy in an incidence cohort.
Am J Ophthalmol.
1996;
121
284-290
-
9
Wiersinga W M, Smit T, van der Gaag R et al..
Temporal relationship between onset of Graves' ophthalmopathy and onset of thyroidal Graves' disease.
J Endocrinol Invest.
1988;
11
615-619
-
10
Mourits M P, Koornneef L, Wiersinga W M et al..
Clinical criteria for the assessment of disease activity in Graves' ophthalmopathy: a novel approach.
Br J Ophthalmol.
1989;
73
639-644
-
11
Grove Jr A S.
Evaluation of exophthalmos.
N Engl J Med.
1975;
292
1005-1013
-
12
Rothfus W E, Curtin H D.
Extraocular muscle enlargement: a CT review.
Radiology.
1984;
151
677-681
-
13
Streeten D H, Anderson Jr G H, Reed G F et al..
Prevalence, natural history and surgical treatment of exophthalmos.
Clin Endocrinol (Oxf).
1987;
27
125-133
-
14
Kadrmas E F, Bartley G B.
Superior limbic keratoconjunctivitis. A prognostic sign for severe Graves' ophthalmopathy.
Ophthalmology.
1995;
102
1472-1475
-
15
Henderson J W.
Optic neuropathy of exophthalmic goiter (Graves' disease).
AMA Arch Ophthalmol..
1958;
59
471-480
-
16
Bahn R S, Heufelder A E.
Pathogenesis of Graves' ophthalmopathy.
N Engl J Med.
1993;
329
1468-1475
-
17
Tallstedt L, Norberg R.
Immunohistochemical staining of normal and Graves' extraocular muscle.
Invest Ophthalmol Vis Sci.
1988;
29
175-184
-
18
Khurana A K, Sunder S, Ahluwalia B K et al..
Tear film profile in Graves' ophthalmopathy.
Acta Ophthalmol (Copenh).
1992;
70
346-349
-
19
Smith T J, Bahn R S, Gorman C A.
Connective tissue, glycosaminoglycans, and diseases of the thyroid.
Endocr Rev.
1989;
10
366-391
-
20
Bahn R S.
Thyrotropin receptor expression in orbital adipose/connective tissues from patients with thyroid-associated ophthalmopathy.
Thyroid.
2002;
12
193-195
-
21
Saravanan P, Dayan C M.
Thyroid autoantibodies.
Endocrinol Metab Clin North Am.
2001;
30
315-337
-
22
Kubota S, Gunji K, Stolarski C, Kennerdell J S, Wall J.
Reevaluation of the prevalences of serum autoantibodies reactive with “64-kd eye muscle proteins” in patients with thyroid-associated ophthalmopathy.
Thyroid.
1998;
8
175-179
-
23
Dragan L R, Seiff S R, Lee D C.
Longitudinal correlation of thyroid-stimulating immunoglobulin with clinical activity of disease in thyroid-associated orbitopathy.
Ophthal Plast Reconstr Surg.
2006;
22
13-19
-
24
Gasser P, Flammer J.
Optic neuropathy of Graves' disease. A report of a perimetric follow-up.
Ophthalmologica.
1986;
192
22-27
-
25
Kahaly G J.
Recent developments in Graves' ophthalmopathy imaging.
J Endocrinol Invest.
2004;
27
254-258
-
26
Bartley G B.
The differential diagnosis and classification of eyelid retraction.
Ophthalmology.
1996;
103
168-176
-
27
Mombaerts I, Goldschmeding R, Schlingemann R O et al..
What is orbital pseudotumor?.
Surv Ophthalmol.
1996;
41
66-78
-
28
Nugent R A, Rootman J, Robertson W D et al..
Acute orbital pseudotumors: classification and CT features.
AJR Am J Roentgenol.
1981;
137
957-962
-
29
Harris G J.
Idiopathic orbital inflammation: a pathogenetic construct and treatment strategy: The 2005 ASOPRS Foundation Lecture.
Ophthal Plast Reconstr Surg.
2006;
22
79-86
-
30
Moster M L, Bosley T M, Slavin M L et al..
Thyroid ophthalmopathy presenting as superior oblique paresis.
J Clin Neuroophthalmol.
1992;
12
94-97
-
31
Chen C C, Chang P C, Shy C G et al..
CT angiography and MR angiography in the evaluation of carotid cavernous sinus fistula prior to embolization: a comparison of techniques.
AJNR Am J Neuroradiol.
2005;
26
2349-2356
-
32
Prummel M F, Wiersinga W M, Mourits M P et al..
Effect of abnormal thyroid function on the severity of Graves' ophthalmopathy.
Arch Intern Med.
1990;
150
1098-1101
-
33
Tallstedt L, Lundell G, Torring O et al..
Occurrence of ophthalmopathy after treatment for Graves' hyperthyroidism. The Thyroid Study Group.
N Engl J Med.
1992;
326
1733-1738
-
34
Bartalena L, Marcocci C, Bogazzi F et al..
Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy.
N Engl J Med.
1998;
338
73-78
-
35
Wiersinga W M.
Preventing Graves' ophthalmopathy.
N Engl J Med.
1998;
338
121-122
-
36
Bartalena L, Pinchera A, Marcocci C.
Management of Graves' ophthalmopathy: reality and perspectives.
Endocr Rev.
2000;
21
168-199
-
37
Day R M, Carroll F D.
Corticosteroids in the treatment of optic nerve involvement associated with thyroid dysfunction.
Arch Ophthalmol.
1968;
79
279-282
-
38
Hiromatsu Y, Tanaka K, Sato M et al..
Intravenous methylprednisolone pulse therapy for Graves' ophthalmopathy.
Endocr J.
1993;
40
63-72
-
39
Matejka G, Verges B, Vaillant G et al..
Intravenous methylprednisolone pulse therapy in the treatment of Graves' ophthalmopathy.
Horm Metab Res.
1998;
30
93-98
-
40
Ebner R, Devoto M H, Weil D et al..
Treatment of thyroid associated ophthalmopathy with periocular injections of triamcinolone.
Br J Ophthalmol.
2004;
88
1380-1386
-
41
Prummel M F, Mourits M P, Berghout A et al..
Prednisone and cyclosporine in the treatment of severe Graves' ophthalmopathy.
N Engl J Med.
1989;
321
1353-1359
-
42
Leovey A, Bako G, Szabo J, Kalman K, Forizs E.
Combined cyclosporin-A and methylprednisolone treatment of Graves' ophthalmopathy.
Acta Med Hung.
1992-93;
49
179-185
-
43
Bartalena L, Marcocci C, Manetti L et al..
Orbital radiotherapy for Graves' ophthalmopathy.
Thyroid.
1998;
8
439-441
-
44
Bartalena L, Marcocci C, Tanda M L et al..
Orbital radiotherapy for Graves' ophthalmopathy.
Thyroid.
2002;
12
245-250
-
45
Kahaly G J, Rosler H P, Pitz S et al..
Low- versus high-dose radiotherapy for Graves' ophthalmopathy: a randomized, single blind trial.
J Clin Endocrinol Metab.
2000;
85
102-108
-
46
Ohtsuka K, Sato A, Kawaguchi S, Hashimoto M, Suzuki Y.
Effect of steroid pulse therapy with and without orbital radiotherapy on Graves' ophthalmopathy.
Am J Ophthalmol.
2003;
135
285-290
-
47
Gorman C A, Garrity J A, Fatourechi V et al..
A prospective, randomized, double-blind, placebo-controlled study of orbital radiotherapy for Graves' ophthalmopathy.
Ophthalmology.
2001;
108
1523-1534
-
48
Meyer D R.
Orbital radiation therapy for Graves' ophthalmopathy.
Ophthalmology.
2003;
110
450-451
, author reply 451
-
49
Wakelkamp I M, Tan H, Saeed P et al..
Orbital irradiation for Graves' ophthalmopathy: Is it safe? A long-term follow-up study.
Ophthalmology.
2004;
111
1557-1562
-
50
Graham S M, Brown C L, Carter K D et al..
Medial and lateral orbital wall surgery for balanced decompression in thyroid eye disease.
Laryngoscope.
2003;
113
1206-1209
-
51
Shepard K G, Levin P S, Terris D J.
Balanced orbital decompression for Graves' ophthalmopathy.
Laryngoscope.
1998;
108(11 Pt 1)
1648-1653
-
52
Kalmann R, Mourits M P, van der Pol J P et al..
Coronal approach for rehabilitative orbital decompression in Graves' ophthalmopathy.
Br J Ophthalmol.
1997;
81
41-45
-
53
Goldberg R A, Shorr N, Cohen M S.
The medical orbital strut in the prevention of postdecompression dystopia in dysthyroid ophthalmopathy.
Ophthal Plast Reconstr Surg.
1992;
8
32-34
-
54
Olivari N.
Transpalpebral decompression of endocrine ophthalmopathy (Graves' disease) by removal of intraorbital fat: experience with 147 operations over 5 years.
Plast Reconstr Surg.
1991;
87
627-641
discussion 642-643
-
55
Liao S L, Shih M J, Lin L L.
A procedure to minimize lower lid retraction during large inferior rectus recession in graves ophthalmopathy.
Am J Ophthalmol.
2006;
141
340-345
-
56
Elner V M, Hassan A S, Frueh B R.
Graded full-thickness anterior blepharotomy for upper eyelid retraction.
Arch Ophthalmol.
2004;
122
55-60
-
57
Li T G, Shorr N, Goldberg R A.
Comparison of the efficacy of hard palate grafts with acellular human dermis grafts in lower eyelid surgery.
Plast Reconstr Surg.
2005;
116
873-878
-
58
Gay A J, Wolkstein M A.
Topical guanethidine therapy for endocrine lid retraction.
Arch Ophthalmol.
1966;
76
364-367
1 The authors have no conflicts of interest or proprietary interest in any of the instruments or topics presented in this manuscript.
Jeffrey A NeradM.D.
Professor Director; Oculoplastic, Orbital and Oncology Service Department of Ophthalmology and Visual Sciences, University of Iowa Hospital and Clinics
200 Hawkins Drive, Iowa City, IA 52242-1091
