This talk is on thyroid eye disease and will cover a brief overview on what thyroid eye disease entails, as well as classification of its activity, severity, and how it ought to be managed. Thyroid eye disease is also known as Graves ophthalmopathy or thyroid associated orbitopathy. It is an autoimmune inflammatory disorder associated with thyroid disease and affects ocular and orbital tissues. It’s characterized by inflammation and swelling of extraocular muscles, which can lead to problems such as compressive optic neuropathy resulting in fibrosis and producing a restrictive myopathy and diplopia. Accumulation of inflammatory cells may cause even more swelling of the extraocular muscles and hence an increase in intraocular pressure and glaucoma as an end result. Graves disease is the most common abnormality associated with thyroid orbitopathy. Approximately 30% of patients with Graves’ disease have or will develop thyroid orbitopathy. However normal to abnormal thyroid function may co-exist, precede, or follow the orbitopathy. And there is a temporal relationship between hyperthyroidism and thyroid eye disease. Rundle’s Curve demonstrates how severity of thryoid orbitopathy fellows a temporal relationship. Rundle found that untreated eye disease runs a course of increasing severity which reaches a plateau and thereafter follows a mostly incomplete recession of symptoms or a static phase. It is thus to a certain extent a self-limiting condition. The best response to treatment of the activity is in the early phase to prevent worsening of the severity. However Rundle warned that correcting any stigmata of the disease before two years of the peak of activity has passed may have complications. This busy slide shows what some poor prognostic factors are. Notably cigarette smoking, advanced age, as well the Asian race in our local population. Some baseline investigations which should be performed in patients with thyroid eye disease consists of a thyroid function test, as well as an autoimmune serology which includes TSH receptor antibody and imaging such as CT orbits with contrast. It’s important to note that on CT we’d be looking for an enlarged muscle belly which spares the tendons and to characterize any proptosis and anterior prolapse of the orbital septum due to excessive orbital fat and muscle swelling. Patients who have apical crowding are at higher risk of compressive optic neuropathy. This slide shows some CT cuts of patients with severe thyroid eye disease. On the left, we see that the patient has very large muscle bellies. And on the top right picture, we see that there is apical crowding accompanied by proptosis. This patient is at a higher risk of compressive optic neuropathy. There are many different systems for classifying thyroid eye disease, the basis of which is classifying activity and severity. The Clinical Activitie Score, VISA, and EUGOGO systems help to classify activity and severity. But severity is usually classified according to mild, moderate, and severe. On this slide, we see patients with obvious signs of thyroid eye disease such as lid retraction, lid edema and swelling, as well as [INAUDIBLE] edema and chemosis. The EUGOGO classification of severity is divided as such. However, at Singapore National Eye Center, we do use more of the VISA classification, which can be divided into optic neuropathy, inflammation or congestion, signs divided into diplopia or restriction of extraocular motility, and the overall appearance of the patient. This is an example of the thyroid eye disease forms which we use at Singapore National Eye Center. We can see on the left here that we have a broad classification of the VISA used to characterize the patient’s eye condition. The patient is thus diagnosed with either active or inactive thyroid eye disease and either mild, moderate, or severe thyroid eye disease based on their clinical appearance. The principles of management of thyroid eye disease are to establish an euthyroid state, which includes cessation of smoking, the use of anti-thyroid drugs which would be co-managed with an endocrinologist. Some patients might even require radioactive iodine. However, these patients need to be warned that some hyperthyroidism following the use of radioactive iodine may actually precipitate or worsen thyroid eye disease and these patients may need to have adjuvant steroid cover. Patients may also require surgical thyroidectomy in order to control their thyroid function. It’s also important to identify and treat these patients who are at risk of sight-threatening complications which, as mentioned previously, were glaucoma, optic nerve compression, and exposure keratopathy from proptosis. In managing patients who are in the active phase, Rundle described various severities and how these patients ought to be managed. Mild ophthalmopathy with mostly lid signs or injection and erythema should be managed with topical lubricants as well as non-steroidal anti-inflammatory drugs. Patients however with moderate ophthalmopathy who experience ocular discomfort and eyelid dysfunction ought to be covered with all nonsteroidals or all steroids. If patients do have diplopia, then a steroid cover systemically may be considered. Other steroid sparing agents such as cyclosporin methotrexate and rituximab have also been described in the literature. Importantly, persons with severe ophthalmopathy, those with optic nerve dysfunction or exposure keratopathy or glaucoma ought to be controlled first with intravenous Methylprednisolone. Some patients who are poor responders may even require radiotherapy. And if indicated, these patients may even require surgical orbital decompression if there is optic neuropathy. Patients who are in the static phase, i.e. those who are stable over the course of five to six months, can be observed and supportive treatment in the form of topical lubricants can be offered. If they have diplopia and are not keen for surgery, then prisms may be offered and the anti-inflammatory treatment ought to be tapered. Patients who are in the burnt out phase may be offered cosmetic orbital decompression, squint surgery, and eyelid surgery in that order. This is a slide showing the stepwise surgical management of inactive thyroid eye disease. For patients who have proptosis which are deemed cosmetically unacceptable, an orbital decompression can be offered to these patients. Patients who have diplopia can be offered strabismus surgery. And those who have lid problems such as upper lid retraction can be offered surgery but only to be done at the last instance. It is important that the ocular surface be managed first. Patients must have stable myopathy and be in a euthyroid state for at least six months before surgery is offered. And the aims of surgery are to restore function of the useful binocular single vision. This can be done under topical or general anesthesia depending on the patient. And the surgery can be performed with either adjustable sutures or fixed sutures. In terms of lid surgery, there are various options available depending on what the lid signs are. It is important in operating with patients with ptosis that it should be approached with caution. The patient’s Bell’s reflex should be checked pre-operatively to ascertain if he or she is in danger of having exposure keratopathy. A quick word on radiotherapy and thyroid eye disease. Studies have shown that radiotherapy does help with reducing or eliminating the pathogenic orbital lymphocytes, which are markedly radio sensitive. Radiotherapy can also be used as an adjunct to high dose or pulsed steroid treatment, for moderately active disease, and for patients with compressive optic neuropathy. Radio therapy is most effective within the first year when significant fibrotic changes have not yet occurred. And a course of 20 gray given over 10 courses should be given to the patient. It is however contraindicated in patients with diabetes mellitus, hypertension, or vascular diseases who may have preexisting retinopathy. In summary, thyroid eye disease is a chronic eye condition. And these patients ought to be co-managed with an endocrinologist. The aim is to achieve a euthryoid status. It’s also important that we know how to classify activity and severity as this will guide our management of the treatment, be it conservatively or surgically.