Thyroid eye disease.
Thyroid eye disease (TED), also known as Graves opthalmopathy is the most common orbital disease and affects 25-50% of patients with Graves' disease (Kuryan et al 2008).
Most patients are only mildly affected, suffering ocular irritation with redness and watering, 'staring eyes' due to retraction of the eyelids, exophthalmos (protrusion of the eyeballs) and periorbital swelling (Figure 1). A minority of patients (around 28%) will develop ocular motility problems, leading to diplopia (double vision), exposure/damage to the cornea and optic neuropathy (Kumar & Clarke 2002, Forbes & Jackson 2003, Meyer 2006).
Pathology and diagnosis
The aetiology of TED is not known although an autoimmune basis is probable. There are a number of different hypotheses. It is likely to involve genetic and environmental factors, which may in turn potentiate inflammatory pathways in the orbit. Graves' disease and TED are both more common in women. Cigarette smoking is an important environmental factor (Kuryan et al 2008). No gene has as yet been identified and it is likely that multiple genes are involved and that these will interact with environmental factors (Kuryan et al 2008).
One theory is that the body produces antibodies that act on the thyroid gland, resulting in Graves' disease. The same antibodies may act against receptors on fibroblasts and fat cells in the orbit. The receptor or target involved in this process has not been established with certainty. The result of this process is that the fat cells and fibroblasts, which are immature cells, multiply and release a number of chemokines (Mizen 2003, Boulos & Hardy 2004, Meyer 2006). The chemokines attract cells of the immune system which further increase fibroblast proliferation and production of glycosaminoglycans. These large molecules soak up water and increase the mass of the tissue in which they are deposited (Heufelder & Joba 2000, Boulos & Hardy 2004, Cawood et al 2004, Meyer 2006). Inflammation of the muscle and fat behind the eye affects eye movements. The eyeball rotates because of the action of the muscles that are attached to it, much like a pulley. Some of the glycosaminoglycans are deposited in the extra-ocular muscles, where they attract and hold water causing swelling of the muscle bellies. This in turn affects the action of these muscles and the movement of the eye.
[FIGURE 1 OMITTED]
The eye sits within a cup shaped bony space called the orbit. The combination of inflammation, and soaking up of water, causes an increase in volume of the contents of the orbit and a subsequent increase in orbital pressure (Heufelder & Joba 2000, Boulos & Hardy 2004, Meyer 2006). If the eye lids and muscles allow, the eye can protrude forward through the eye lids (called proptosis), giving an appearance that the eyes are 'sticking out' (Figure 1). This allows some decompression (release of pressure) in the orbit. If the eyes protrude too much, there reaches a point where the optic nerve which takes visual information from the eye to the brain becomes affected, either by stretching or by compression from the swollen muscles. Damage to the optic nerve can lead to blindness. The cornea can also become exposed if the eyes protrude too much, as the eyelids may not cover it completely, eventually resulting in sight-threatening damage.
TED can present with a number of symptoms and signs. The main features are: pain, either as a constant ache behind the eye or on eye movement, redness of the conjunctiva and/or the eyelid, eyelid swelling and proptosis. In more severe disease there is limitation of eye movements or a decrease in visual acuity, but this only affects the minority of cases. In addition to the eye features, swelling can occur elsewhere for example in the skin of the shin (pretibial myxoedema) or in the finger nails (thyroid acropachy).
Blood tests including thyroid function tests, antibodies and an orbital magnetic resonance imaging (MRI) scan can be important diagnostic aids. Occasionally orbital biopsy can be important to exclude other pathologies, for example infective causes, tumours and other systemic inflammatory conditions such as sarcoidosis and Wegener's granulomatosis.
Muscles of eye movement
There are six extra-ocular muscles which control the movements of the eyes, four rectus muscles and two oblique muscles. The rectus muscles originate at the back of the bony orbit and insert onto the anterior aspect of the globe. The superior and inferior recti rotate the eye up and down respectively and the lateral and medial rotate the eye towards the temporal and nasal side respectively (Modi & Jones 2008). The inflammation and swelling of the muscles means that they are less able to allow movement and they then restrict the eyes motility. Subsequent fibrosis (stiffening) then causes them to permanently tighten. The muscles most commonly affected by thyroid eye disease are the inferior and medial rectus muscles. The patient may develop a squint (strabismus), usually a downwardly deviated eye (hypotropia) or a medially deviated eye (esotropia) (Heufelder & Joba 2000, Boulos & Hardy 2004, Meyer 2006, Schotthoefer & Wallace 2007).
[FIGURE 2 OMITTED]
Normal vision relies on the image from both eyes being almost the same, this allows the brain to fuse the two together creating single vision with depth perception (stereopsis). If the eyes can't lock onto the same target then, in adults, double vision (diplopia) results. In thyroid eye disease the squint can be progressive and result in problematic double vision (Schotthoefer & Wallace 2007, Modi & Jones 2008).
TED should be managed with the supervision of a specialist. The principle is that active disease is usually managed medically with surgery reserved for when medical management fails, or to correct residual problems such as proptosis and strabismus, once the disease is stable (Chavis 2002, Modjtahedi et al 2006) . For mild disease, symptomatic treatment is all that is required for example lubricating eye drops and ointment. At night, if the lids don't close properly, the delicate surface of the eye, the cornea, may become damaged. Eyelids can be taped shut by the patients at night if required (Meyer 2006, Schotthoefer & Wallace 2007) and raising the head of the bed will help to reduce the periorbital oedema. Advice to stop smoking is important. Moderate disease, with pain or orbital ache but without diplopia is managed with non-steroidal anti-inflammatory drugs (NSAIDs) or lower dose oral steroids.
A significant proportion of patients (10-35%) need medical treatment for moderate to severe disease. Systemic treatment is aimed at first interrupting the autoimmune cycle acutely causing the damage, then retaining remission. Current research favours intravenous steroids, to decrease inflammation and induce remission. Other therapies can dampen the immune system, such as systemic immunosuppression, most commonly with oral steroids and/or azathioprine which may reduce the long-term severity of the disease. It has been shown that these therapies can decrease proptosis and significantly improve eye movements, strabismus and diplopia (Chavis 2002, Kauppinen-Makelin et al 2002, Meyer 2006, Modjtahedi et al 2006, Schotthoefer & Wallace 2007, Kuryan et al 2008). Orbital radiotherapy may be used in the acute setting to decrease inflammation behind the eye. Although it takes two to three weeks to work, some studies suggest that radiotherapy can be effective at treating optic neuropathy (compression of the optic nerve), improving eye movement and decreasing proptosis (Chavis 2002, Behbehani et al 2004, Modjtahedi et al 2006) . The evidence behind the use of azathioprine and radiotherapy is not consistent and there is a large trial between London and Bristol (Combined Immunosuppression and Radiotherapy in Thyroid Eye Disease--CIRTED) which is recruiting patients to investigate this further. For further information see www.cirted.org.
Controlling the underlying disease is important in the long-term management of TED. This is why it is important to treat the underlying Graves' disease, and this is usually done in conjunction with an endocrinologist. Patients can present with either an over or under active thyroid, or even a normal (euthyroid) state. The usual management of hyperthyroidism is to completely block the thyroid gland's own production of thyroxine hormone, using medication, and to replace it with an appropriate dose of thyroxine every day. Fluctuations in the blood-levels of thyroxine can cause a worsening of the thyroid eye disease and this 'block and replace' regime is thought to be the best way to maintain stable levels (Meyer 2006, Schotthoefer & Wallace 2007).
The vast majority of patients are managed successfully with medical therapy alone although some patients go on to have surgery. Most commonly, when the acute inflammation has settled and the eye disease is 'burnt-out', surgery can be used to correct residual deficits including eyelid abnormalities or problematic double vision due to strabismus. Less commonly, patients may have cosmetically disabling proptosis which may need orbital decompression surgery (Chavis 2002, Schotthoefer & Wallace 2007). In active disease, surgery is used when medical management fails i.e. optic nerve compression which has not improved with medical therapy, when release of pressure in the orbit (surgical orbital decompression) is needed to save sight (Chavis 2002).
Surgery is only indicated for more severe disease, and, where it is required, patients may need several procedures. Patients most commonly need surgery for their eyelids, followed by squint surgery and orbital surgery is least commonly required. If more than one type of surgery is required, orbital surgery is usually performed first, as surgical manipulation of the orbit may induce squint. Squint surgery is therefore performed second, and because the position of the eyelids cannot be determined until both eyes are correctly aligned, the eyelid surgery is performed last of all.
It may take up to two years to reach the 'burnt-out' stage of the eye disease. After this, rehabilitative surgery can be considered for cosmetic issues. Eyelid retraction can be treated with lid-lengthening or canthoplasty, and eyelid puffiness can be treated with blepharoplasty (Kuryan et al 2008). Strabismus surgery is aimed at correcting the misalignment of the eyes, when the eye disease and squint have been stable for at least three to six months and if double vision is not successfully managed by glasses with prisms. The goal is to restore single, stereoptic (depth perception) vision both when looking straight forward and when reading. Careful measurement of each eye's deviation from straight must be made pre-operatively, as must the range of pre-operative eye movements. This will assist in determining how much correction is needed intra-operatively (Chavis 2002, Mills et al 2004, Meyer 2006, Schotthoefer & Wallace 2007, Thomas & Cruz 2007). There are two indications for orbital decompression. The first--a 'hot decompression' is to relieve optic nerve compression unresponsive to medical treatment. The second--a 'cold decompression' is to treat residual proptosis or corneal exposure after the disease is 'burnt-out'. The technique used in orbital decompression surgery depends on the individual case and the significant side effects should be considered in preoperative planning. After orbital decompression, because of the change in position of the eye in the orbit, there may be worsening of, or new onset of, strabismus and diplopia and this may require squint surgery, often followed by eyelid surgery. There is also a risk of complications associating with operating around the eye including meningitis, sinusitis and fluid leaking from around the brain. For all of these indications, patients need to be well informed through the consent process about the possible complications and the need for further surgery afterwards.
Planning for this type of surgery must be assiduous and based on appropriate imaging. There are a range of surgical techniques that can be used, and the procedure to be performed must be chosen based on clinical examination, CT and magnetic resonance imaging (MRI) of the orbit and examination of old photos (Chavis 2002, Siracuse-Lee & Kazim 2002, Goh & McNab 2005, Schotthoefer & Wallace 2007).
Orbital decompression has been carried out since 1911, techniques have continued to evolve but most involve removing some of the walls of the orbit. The number of walls which need to be removed correlates to the severity of the disease. In most techniques the innermost (medial) wall is removed as this relieves most pressure on the optic nerve. The most common side effect is new onset or the worsening of pre-existent squint and diplopia.
Up until the 1980s the most popular operation was removal of the medial wall and the floor of the orbit. Fat-removal orbital decompressions may be performed whereby the walls of the orbit are left intact. This seems to have a lower rate of postoperative diplopia but limited benefit in treating optic nerve compression (Siracuse-Lee & Kazim 2002, Goh & McNab 2005, Goldberg 2008, Kuryan et al 2008).
The operation can be done from a number of different incisions but the prime consideration for the surgeon is access as the material to be removed is situated posteriorly in the orbit. One method is a transconjunctival (through the conjunctiva) incision, which gives access to all three walls of the orbit but can be difficult. A relatively new technique which leaves no scarring is to approach via the nose using an endoscope. This approach has comparable efficacy in bringing the eye ball back into the orbit but seems to be no better at avoiding postoperative squints than any other technique. Another technique is the removal of just the lateral wall. This technique is less risky as it avoids going into the sinuses, scars can be hidden, and there is a lower incidence of postoperative squint (Siracuse-Lee & Kazim 2002, Goh & McNab 2005, Simon et al 2005, Prabhakaran & Selva 2008, www.cirted.org).
Following any orbital decompression surgery a second operation to correct the strabismus is often needed (Siracuse-Lee & Kazim 2002). Strabismus surgery in patients with thyroid eye disease has a number of special challenges compared to normal paediatric or adult squint surgery. It is performed through incision of the conjunctiva; in these patients the tissue can be fragile, especially if there has been prior radiotherapy (Schotthoefer & Wallace 2007, Goldberg 2008). Surgery usually involves recession (loosening) of the tightened muscles. Medial rectus is loosened if the eye is deviated inwards and inferior rectus if it is deviated downwards. The first stage of surgery is to separate the muscle from the eye ball at its attachment point and to reattach it further back on the eyeball so it pulls less on the eye. This step can be difficult as the muscles are very tight against the sclera (Schotthoefer & Wallace 2007, Modi & Jones 2008). After the muscle is separated from the eyeball, there is a risk that it can slip off the suture that is holding it. If this happens, then that muscle may be irretrievable and this can be difficult to correct (Schotthoefer & Wallace 2007, Modi & Jones 2008). Deciding where to re-attach the muscle is another challenge, there are published tables which allow calculation of the correction needed based on the preoperative deviation between the two eyes. However in thyroid related strabismus the tables don't apply very well. A high proportion of thyroid associated strabismus patients need to undergo re-operation before correction is achieved (Mills et al 2004, Schotthoefer & Wallace 2007, Thomas & Cruz 2007). A second method of deciding where to attach the muscle is done intra-operatively; once the muscle is released it is sutured to the eye where it naturally lies. This has been shown to be quite effective in some studies (Schotthoefer & Wallace 2007, Thomas & Cruz 2007). Once the position is decided, the muscle is sutured to the eyeball. Some surgeons use an adjustable suture to allow some later correction postoperatively, but others don't try to reduce the risk of slippage of the muscle postoperatively (Boulos & Hardy 2004, Mills et al 2004, Schotthoefer & Wallace 2007, Thomas & Cruz 2007.
Finally, after any necessary decompression and strabismus surgery has been performed, the eyelid position can be adjusted to provide a good cosmetic and functional result. Upper and lower lid retraction can be improved by lengthening the tendons of the eyelid retractor muscles and this is usually performed under local anaesthetic, allowing greater accuracy in positioning the lids. This lengthening is usually performed by recession of the upper-lid retractor muscle and repositioning these to weaken their action on the upper eyelid. An adjustable suture technique is possible to increase accuracy in final eyelid position (Collin 2006). Botox has also been used to relax upper lid retraction with some success. Lower eyelid retraction may be treated by means of grafts taken from the hard palate (roof of the mouth) or artificial spacer, usually under general anaesthesia. Although the graft will provide enough tissue, the lower eyelid may need support medially and laterally as the attachments may have weakened. This can be provided by a canthoplasty to tighten the medial support. To achieve a better cosmetic result and treat the "lateral flare" or rounding of the lateral canthus, a tarsorraphy or lateral canthoplasty can be performed (Collin 2006). Often eyelid retraction surgery is not required in patients who have undergone an orbital decompression as the eyelid retraction may resolve following such surgery. Also swelling from TED, once settled, may leave very baggy skin around the eyelids, which can be corrected by performing a skin and fat blepharoplasty.
TED is a disease with an unknown aetiology which can present the ophthalmologist with many challenges. It needs to be assessed and managed carefully by a multidisciplinary team. Surgery is necessary for the minority of patients in the management of this condition. It can be effective in both the management of the active disease and in the resolution of residual dysfunction or disfigurement. Surgical techniques continue to improve, decreasing the incidence of some of the worst complications especially new onset diplopia after orbital decompression. Incisions are becoming smaller and surgery less invasive, leading to a quicker postoperative recovery. Although challenging, when carried out successfully, surgery for TED has a huge impact on quality of life, helping not only with debilitating physical symptoms, but also with self esteem and psychological well being.
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Correspondence address: Neil C Modi, Torbay Hospital, Lawes Bridge, Torquay, TQ2 7AA. Email: firstname.lastname@example.org
Neil C Modi
MBBS, BSc, DHMSA
ST2 Ophthalmology, Torbay Hospital, Devon
Trauma and Orthopaedics, Chesterfield Royal Hospital, Derbyshire
MA, BM BCh, FRCOphth
Consultant Ophthalmologist, Torbay General Hospital, Devon
With thanks to Sister Terry Artus and Wendy Phillips.
Provenance and Peer review: Commissioned by the Editor; Peer reviewed.
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|Title Annotation:||CLINICAL FEATURE|
|Author:||Modi, Neil C.; James, Jennifer; Sleep, Tamsin|
|Publication:||Journal of Perioperative Practice|
|Date:||Sep 1, 2009|
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