Geoffrey E. Rose
Geoffrey Rose graduated BSc Pharmacology, MBBS, and MRCP. His postgraduate ophthalmic training culminated in award of FRCS in 1985 and FRCOphth at its foundation in 1988. In 1990, the University of London granted an MS doctorate for corneal research and, in 2004, a Doctor of Science in Ophthalmology and Ophthalmic Surgery.
Professor Rose was appointed consultant to Moorfields Eye Hospital, London, in 1990 and is also a Senior Research Fellow of the NIHR Biomedical Research Centre of the Institute of Ophthalmology. He served as the British Council member of the European Society of Ophthalmic Plastic and Reconstructive, is a Past-President of the British Oculoplastic Surgical Society, and is President of the European Society of Oculoplastic and Reconstructive Surgeons.
David H. Verity
Dr. Verity is a Consultant Ophthalmic Surgeon, and Adnexal Service Director, Moorfields Eye Hospital, London.He is a Honorary Senior Clinical Lecturer, University College London.Trained in ophthalmology in the UK, Dr. Verity undertook two Fellowships in ophthalmic adnexal disease before joining the Consultant staff at Moorfields Eye Hospital in 2004.He is a Full Member of the British Oculoplastic Surgery Society (current Treasurer), Treasurer Elect for the European Society of Ophthalmic Plastic and Reconstructive Surgery, and Full Member of the International Society of Ocular Oncology.In 2009, he was elected to the Orbital Society, in 2010 became Editor-in Chief of the journal ORBIT, and in 2016 became Oculoplastic Section Editor for the Journal of Ophthalmic and Vision Research.His medical publications in peer-reviewed journals and books include 90(+) publications, and with a wide range of research interests, he is an active national and international teacher and surgical trainer.Dr. Verity also has a life-long interest in the charitable work of the St John Eye Hospital Group. In 2014, he was invested in the Order of St John, and in 2016 he joined the Board as Trustee of the Hospital Group.
Thyroid eye disease (TED) is an idiopathic lymphocytic orbital inflammation that usually occurs in patients with autoimmune thyrotoxicosis (Graves’ disease), but can occur in hypothyroid patients or those without any measured abnormality of thyroid gland function. The underlying autoimmune mechanisms remain uncertain, but activation of orbital fibroblasts is thought to be central – with these cells displaying TSH receptors and producing inflammatory molecules, orbital adipocytes and extracellular matrix [1, 2].
The acute inflammatory phase of TED mainly affects the extraocular muscles and orbital adipose tissue, with increasing accruement of tissue oedema, pro-inflammatory cytokines and lymphocytes. Expansion of the extraocular muscles and fat within the rigid confines of the bony orbit – together with deposition of glycosaminoglycans and other extracellular matrix – leads to rising intraorbital pressures, particularly in the orbital apex. The effect of this escalation in hydrostatic pressure is a projection of the soft tissues from within the socket (exophthalmos) and, where eyelid and septum laxity permit gross exophthalmos, ocular surface exposure which can rapidly progress to severe keratopathy and even corneal perforation. The risk of corneal perforation is exacerbated by the upper eyelid retraction and lagophthalmos that typically accompany TED (Fig. 23.1). Where the anterior orbital tissues no longer permit progression of exophthalmos – this being most problematic in patients with healthy septal collagen – there will be an acute rise in intraorbital pressure, with embarrassment of arteriolar perfusion and tissue ischaemia, this being manifest as loss of optic nerve function and visual failure.
Fig. 23.1
Patient with fulminant thyroid eye disease, having marked bilateral orbital inflammation causing gross proptosis, and spontaneous left corneal perforation due to untreated exposure keratopathy
Although severe disease is rare (fewer than 5 % of patients), in a small minority, the condition accelerates rapidly due to marked venous congestion, this causing corneal exposure, orbital congestion and optic neuropathy (Fig. 23.2a). Such patients with fulminant TED should be treated urgently to avoid irreversible visual impairment due to corneal scarring or optic neuropathy.
Fig. 23.2
(a) Untreated severe active thyroid eye disease leading to complete corneal dessication and keratitis; view with attempted eye closure. (b) Placement of multiple bolstered traction sutures in both the upper and lower eyelids allows complete closure of the eyelids whilst intravenous immunosuppression is started. (c) Marked improvement in the cornea after 24 h of occlusion, with complete corneal rehydration and reduced stromal keratitis
Treatment of Fulminant Thyroid Eye Disease
The vast majority of patients with TED experience only mild symptoms and signs, these being mainly upper eyelid retraction and altered blink pattern. Such symptoms are treated with ocular protection (from wind and bright lights), topical lubricants, oral selenium, cessation of smoking and late upper lid repositioning. Likewise, most patients with moderate disease – that is, those with proptosis, diplopia, orbital congestion and more marked inflammatory signs – will generally respond well to systemic immunosuppression and later rehabilitative surgery. Although low-dose orbital radiotherapy is an effective steroid-sparing agent in the treatment of moderate TED (where there is a recognised response to systemic steroids), treatment is given in fractions over 2–3 weeks, and this, together with the delay to maximum response, precludes its use as a primary therapy in patients with severe TED.
Most patients with mild or moderate disease do not progress to severe and fulminant TED. However, men, elderly patients, smokers and those with poorly controlled disease are at risk of more severe orbital inflammation, and among smokers the risk of disease progression is estimated to be 8- to 14-fold greater than for non-smokers [3–5]. Furthermore, in patients with TED who continue to smoke, immunosuppressive therapy – the mainstay of treatment for fulminant disease – is generally less effective at controlling disease, and such patients are also at significantly increased risk of requiring rehabilitative squint surgery [6]. Thus, cessation of smoking and urgent control of thyroid gland function are of paramount importance in the care of patients with fulminant TED.
Suppression of Severe Inflammation in Fulminant TED
For decades, systemic corticosteroids have formed the mainstay of treatment for TED (Table 23.1), with a trend towards parenteral treatment in recent years. Typically, patients with fulminant disease respond well to systemic immunosuppression: parenteral corticosteroids have a higher efficacy (83 % response, compared with 64 % on oral steroids) [7] and fewer side effects (56 % and 85 %, respectively) [8] than oral steroids. In practical terms, 500 mg intravenous methylprednisolone once-weekly for 6 weeks and then 250 mg once-weekly for 6 weeks provides a useful regime, with a good response in three-quarters of patients with severe active TED [9].
Table 23.1
Typical corticosteroid regimes for treating active thyroid eye disease
Oral prednisolone |
Start with 1 mg/kg body weight to a maximum of 80 mg daily |
Review at 1 week and taper dosage over 2–3 weeks towards 20 mg prednisolone daily (dependent on clinical response) |
Consider low-dose orbital radiotherapy if an objective clinical response to the steroids |
After radiotherapy completed, tail off the dosage from 20 mg daily over about 3 months |
If persistent optic neuropathy at 1 week after starting high-dose prednisolone, consider early orbital decompression |
Consider oral calcium and vitamin D supplements and/or biphosphonates where steroid courses are prolonged or in patients at risk of osteopaenia |
Intravenous methylprednisolone |
Many: a well-established and convenient regime with relatively few side effects is that of 500 mg weekly for 6 weeks and then 250 mg weekly for 6 weeks |
If severe optic neuropathy, consider 1 g methylprednisolone on alternate days to a total of 3 g in the first week; continue with 500 mg weekly for 6 weeks and then 250 mg weekly for 6 weeks |
Careful systemic monitoring required during the slow intravenous infusion of methylprednisolone |
Avoid doses of >500 mg daily for three or more consecutive days or >3 g in the first week |
Consider low-dose orbital radiotherapy if an objective clinical response to the steroids |
If persistent optic neuropathy at 1 week after starting high-dose prednisolone, consider early orbital decompression |
Major cardiac and hepatic morbidity, and even deaths, have been associated with total dosages of >8 g methylprednisolone; total doses above 8 g should therefore be avoided |
Consider oral calcium and vitamin D supplements and/or biphosphonates where steroid courses are prolonged or in patients at risk of osteopaenia |
Parenteral steroids are, however, recognised to cause major morbidity – or even death with total doses of >8 g methylprednisolone – and are best avoided in patients with a history of major hepatic, cardiovascular or renal disease, uncontrolled hypertension or severe diabetes [10–12].
Steroid-sparing medications and other ‘biologic’ immunosuppressants can be effective in treating steroid-resistant disease or reducing steroid side effects. However, because most steroid-sparing medications (in common with low-dose orbital radiotherapy, as discussed above) have a slow onset, they have no practical use in the acute phase of patients with fulminant disease.
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