Graves' ophthalmopathy
Graves ophthalmopathy | |
---|---|
Other names | Thyroid eye disease (TED), dysthyroid/thyroid-associated orbitopathy (TAO), Graves' orbitopathy (GO) |
Bulging eyes and lid retraction from Graves' disease | |
Specialty | Ophthalmology |
Graves' ophthalmopathy, also known as thyroid eye disease (TED), is an
It is part of a systemic process with variable expression in the eyes, thyroid, and skin, caused by
Annual incidence is 16/100,000 in women, 3/100,000 in men. About 3–5% have severe disease with intense pain, and sight-threatening corneal ulceration or compression of the optic nerve. Cigarette smoking, which is associated with many autoimmune diseases, raises the incidence 7.7-fold.[1]
Mild disease will often resolve and merely requires measures to reduce discomfort and dryness, such as artificial tears and smoking cessation if possible. Severe cases are a medical emergency, and are treated with glucocorticoids (steroids), and sometimes ciclosporin.[5] Many anti-inflammatory biological mediators, such as infliximab, etanercept, and anakinra are being tried.[1] In January 2020, the US Food and Drug Administration approved teprotumumab-trbw for the treatment of Graves' ophthalmopathy.[6]
Signs and symptoms
In mild disease, patients
- Eye signs[7]
Sign | Description | Named for |
---|---|---|
Abadie's sign | Elevator muscle of upper eyelid is spastic. | Jean Marie Charles Abadie (1842–1932) |
Ballet's sign | Paralysis of one or more EOM | Louis Gilbert Simeon Ballet (1853–1916) |
Becker's sign | Abnormal intense pulsation of retina's arteries | Otto Heinrich Enoch Becker (1828–1890) |
Boston's sign | Jerky movements of upper lid on lower gaze | Leonard Napoleon Boston (1871–1931) |
Cowen's sign | Extensive hippus of consensual pupillary reflex | Jack Posner Cowen, American ophthalmologist (1906–1989) |
Dalrymple's sign | Upper eyelid retraction | John Dalrymple (1803–1852) |
Enroth's sign | Edema esp. of the upper eyelid | Emil Emanuel Enroth, Finnish ophthalmologist (1879–1953) |
Gifford's sign | Difficulty in eversion of upper lid. | Harold Gifford (1858–1929) |
Goldzieher's sign | Deep injection of conjunctiva, especially temporal | Wilhelm Goldzieher, Hungarian ophthalmologist (1849–1916) |
Griffith's sign | Lower lid lag on upward gaze | Alexander James Hill Griffith, English ophthalmologist (1858–1937) |
Hertoghe's sign | Loss of eyebrows laterally | Eugene Louis Chretien Hertoghe, Dutch thyroid pathologist (1860–1928) |
Jellinek's sign | Superior eyelid folds is hyperpigmented | Edward Jellinek, English ophthalmologist and pathologist (1890–1963) |
Joffroy's sign | Absent creases in the fore head on upward gaze. | Alexis Joffroy (1844–1908) |
Jendrassik's sign | Abduction and rotation of eyeball is limited also | Ernő Jendrassik (1858–1921) |
Knies's sign | Uneven pupillary dilatation in dim light | Max Knies, German ophthalmologist (1851–1917) |
Kocher's sign | Spasmatic retraction of upper lid on fixation | Emil Theodor Kocher (1841–1917) |
Loewi's sign | Quick Mydriasis after instillation of 1:1000 adrenaline | Otto Loewi (1873–1961) |
Mann's sign | Eyes seem to be situated at different levels because of tanned skin. | John Dixon Mann, English pathologist and forensic scientist (1840–1912) |
Mean sign | Increased scleral show on upgaze (globe lag) | Named after the expression of being "mean" when viewed from afar, due to the scleral show |
Möbius's sign | Lack of convergence | Paul Julius Möbius (1853–1907) |
Payne–Trousseau's sign | Dislocation of globe | John Howard Payne, American surgeon (1916–1983), Armand Trousseau (1801–1867) |
Pochin's sign | Reduced amplitude of blinking | Sir Edward Eric Pochin (1909–1990) |
Riesman's sign | Bruit over the eyelid | David Riesman, American physician (1867–1940) |
Movement's cap phenomenon | Eyeball movements are performed difficultly, abruptly and incompletely | |
Rosenbach's sign | Eyelids are animated by thin tremors when closed | Ottomar Ernst Felix Rosenbach (1851–1907)
|
Snellen–Riesman's sign | When placing the stethoscope's capsule over closed eyelids a systolic murmur could be heard | Herman Snellen (1834–1908), David Riesman, American physician (1867–1940) |
Stellwag's sign | Incomplete and infrequent blinking | Karl Stellwag (1823–1904) |
Suker's sign | Inability to maintain fixation on extreme lateral gaze | George Francis "Franklin" Suker, American ophthalmologist (1869–1933) |
Topolanski's sign | Around insertion areas of the four rectus muscles of the eyeball a vascular band network is noticed and this network joints the four insertion points. | Alfred Topolanski, Austrian ophthalmologist (1861–1960) |
von Graefe's sign | Upper lid lag on down gaze | Friedrich Wilhelm Ernst Albrecht von Gräfe (1828–1870) |
Wilder's sign | Jerking of the eye on movement from abduction to adduction | Helenor Campbell Wilder (née Foerster), American ophthalmologist (1895–1998) |
In moderate active disease, the signs and symptoms are persistent and increasing and include myopathy. The inflammation and edema of the extraocular muscles lead to gaze abnormalities. The inferior rectus muscle is the most commonly affected muscle and patient may experience vertical diplopia on upgaze and limitation of elevation of the eyes due to fibrosis of the muscle. This may also increase the intraocular pressure of the eyes. The double vision is initially intermittent but can gradually become chronic. The medial rectus is the second-most-commonly-affected muscle, but multiple muscles may be affected, in an asymmetric fashion.[citation needed]
In more severe and active disease, mass effects and cicatricial changes occur within the orbit. This is manifested by a progressive
Pathophysiology
Graves' is an orbital autoimmune disease. The thyroid-stimulating hormone receptor (TSH-R) is an antigen found in orbital fat and connective tissue, and is a target for autoimmune assault.[citation needed]
On histological examination, there is an infiltration of the orbital connective tissue by
Diagnostic
Graves' ophthalmopathy is diagnosed clinically by the presenting ocular signs and symptoms, but positive tests for
Orbital imaging is an integral tool for the diagnosis of Graves' ophthalmopathy and is useful in monitoring patients for progression of the disease. It is, however, not warranted when the diagnosis can be established clinically.
Classification
Mnemonic: "NO SPECS":[11]
Class | Description |
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Class 0 | No signs or symptoms |
Class 1 | Only signs (limited to upper lid retraction and stare, with or without lid lag) |
Class 2 | Soft tissue involvement (oedema of conjunctivae and lids, conjunctival injection, etc.) |
Class 3 | Proptosis |
Class 4 | Extraocular muscle involvement (usually with diplopia) |
Class 5 | Corneal involvement (primarily due to lagophthalmos) |
Class 6 | Sight loss (due to optic nerve involvement) |
Prevention
Not smoking is a common suggestion in the literature. Apart from smoking cessation, there is little definitive research in this area. In addition to the selenium studies above, some recent research also is suggestive that statin use may assist.[12][13]
Treatment
Even though some people undergo spontaneous remission of symptoms within a year, many need treatment. The first step is the regulation of thyroid hormone levels. Topical lubrication of the eye is used to avoid corneal damage caused by exposure.
In January 2020, the US Food and Drug Administration approved teprotumumab-trbw for the treatment of Graves' ophthalmopathy.[6]
Surgery
There is some evidence that a total or sub-total thyroidectomy may assist in reducing levels of
Surgery may be done to decompress the orbit, to improve the proptosis, and to address the strabismus causing diplopia. Surgery is performed once the person's disease has been stable for at least six months. In severe cases, however, the surgery becomes urgent to prevent blindness from optic nerve compression. Because the eye socket is bone, there is nowhere for eye muscle swelling to be accommodated, and, as a result, the eye is pushed forward into a protruded position. Orbital decompression involves removing some bone from the eye socket to open up one or more sinuses and so make space for the swollen tissue and allowing the eye to move back into normal position and also relieving compression of the optic nerve that can threaten sight.[citation needed]
Eyelid surgery is the most common surgery performed on Graves ophthalmopathy patients. Lid-lengthening surgeries can be done on upper and lower eyelid to correct the patient's appearance and the ocular surface exposure symptoms. Marginal
A summary of treatment recommendations was published in 2015 by an Italian taskforce,[25] which largely supports the other studies.
Prognosis
Risk factors of progressive and severe thyroid-associated orbitopathy are:[citation needed]
- Age greater than 50 years
- Rapid onset of symptoms under 3 months
- Cigarette smoking
- Diabetes
- Severe or uncontrolled hyperthyroidism
- Presence of pretibial myxedema
- High cholesterol levels (hyperlipidemia)
- Peripheral vascular disease
Epidemiology
The pathology mostly affects persons of 30 to 50 years of age. Females are four times more likely to develop Graves' than males. When males are affected, they tend to have a later onset and a poor prognosis. A study demonstrated that at the time of diagnosis, 90% of the patients with clinical orbitopathy were
History
In medical literature, Robert James Graves, in 1835, was the first to describe the association of a thyroid goitre with exophthalmos (proptosis) of the eye.[29] Graves' ophthalmopathy may occur before, with, or after the onset of overt thyroid disease and usually has a slow onset over many months.[citation needed]
See also
References
- ^ PMID 20181974.
- PMID 12487767.
- PMID 25161935.
- PMID 576175.
- ^ Harrison's Principles of Internal Medicine, 16th Ed., Ch. 320, Disorders of the Thyroid Gland
- ^ a b Office of the Commissioner (2020-03-24). "FDA approves first treatment for thyroid eye disease". FDA. Retrieved 2021-02-06.
- ^ Rao R (2013). "Thyroid Eye diseases". Online Resources of Ophthalmology. Archived from the original on 2014-04-17. Retrieved 2013-09-04.
- PMID 6548373.
- PMID 9323958.
- PMID 28492870.
- PMID 15310608.
- ^ S2CID 8197441.
- ^ Kuehn BM (15 December 2014). "Surgery, Statins Linked to Lower Graves' Complication Risk". Medscape Medical News.
- PMID 35959086.
- ^ "FDA approves first treatment for thyroid eye disease". FDA. 21 January 2020. Retrieved 27 January 2020.
- S2CID 9780703.
- PMID 30480323.
- PMID 14614216.
- PMID 29217903.
- PMID 18658008.
- PMID 19848063.
- PMID 26606533.
- PMID 18166819.
- ^ Muratet JM. "Eyelid retraction". Ophthalmic Plastic Surgery. Le Syndicat National des Ophtalmologistes de France. Archived from the original on June 9, 2007. Retrieved 2007-07-12.
- PMID 25722226.
- PMID 8597271.
- ^ Davies TF, Burch HB (September 2009). Ross DS, Martin KA (eds.). "Pathogenesis and clinical features of Graves' ophthalmopathy (orbitopathy)". UpToDate.
- PMID 11916611.
- Who Named It?
Further reading
- Behbehani R, Sergott RC, Savino PJ (December 2004). "Orbital radiotherapy for thyroid-related orbitopathy". Current Opinion in Ophthalmology. 15 (6): 479–482. S2CID 31340321.
- Boncoeur MP (September 2004). "[Dysthyroid orbitopathy: imaging]" [Imaging techniques in Graves disease : Dysthyroid orbitopathy]. Journal Français d'Ophtalmologie (in French). 27 (7): 815–818. .
- Boulos PR, Hardy I (October 2004). "Thyroid-associated orbitopathy: a clinicopathologic and therapeutic review". Current Opinion in Ophthalmology. 15 (5): 389–400. S2CID 23194226.
- Camezind P, Robert PY, Adenis JP (September 2004). "[Clinical signs of dysthyroid orbitopathy]" [Clinical signs of dysthyroid orbitopathy : Dysthyroid orbitopathy]. Journal Français d'Ophtalmologie (in French). 27 (7): 810–814. .
- Duker JS, Yanoff M (2004). "chapt 95". Ophthalmology (2nd ed.). Saint Louis: C.V. Mosby. ISBN 978-0-323-02907-0.
- Morax S, Ben Ayed H (September 2004). "[Orbital decompression for dysthyroid orbitopathy: a review of techniques and indications]" [Orbital decompression for dysthyroid orbitopathy: a review of techniques and indications]. Journal Français d'Ophtalmologie (in French). 27 (7): 828–844. PMID 15499287.
- Rose JG, Burkat CN, Boxrud CA (October 2005). "Diagnosis and management of thyroid orbitopathy". Otolaryngologic Clinics of North America. 38 (5): 1043–1074. PMID 16214573.