Case 1 - Thyroid Eye Disease

Case History:

A 69-year-old woman presents to her optometrist for a refractive assessment. She mentions that she

also has some mild blurring of vision in her right eye. Upon questioning, she informs you she has a

ten-year history of Grave’s disease with thyrotoxicosis. She had radioiodine treatment eight years

prior and is currently taking levothyroxine for her hypothyroid status post treatment. She reports

her mother having a history of thyroid eye disease. The patient is an ex-smoker.

Examination:

Right eye Left eye

BCVA 6/9.5 6/7.5

Ishihara colour plates 14/14 14/14

Pupils Right RAPD Goldmann IOP – primary gaze 18mmHg 15mmHg

Goldmann IOP - upgaze 25mmHg 18mmHg

Slit lamp examination

Lids Lid retraction and lid lag. Approximately 1 mm scleral show both superiorly and inferiorly.

Mild lid retraction and lid lag. No obvious scleral show.

Anterior segment

Grade 2 fluorescein staining of the inferior cornea

Grade 1 fluorescein staining of the inferior cornea

Optic Nerve

See disc photos See disc photos

Retina Clear and flat Clear and flat

Gonioscopy Open angles: scleral spur seen all quadrants

Open angles: scleral spur seen all quadrants

Corneal pachymetry 494 µm 469µm Exophthalmometry 20mm 18mm

Eye movements Full, no restriction Full, no restriction

Refractive error -6.25 DS -5.00/-0.50 x 090

Question 1: Please comment further on the disc appearance based on the disc photos below.

Figure 1a: Disc photo right eye

Figure 1b: Disc photo left eye

Question 1 answer:

The right optic disc is average in size. There is circumferential peripapillary atrophy. The disc is tilted,

which is in keeping with the patient’s myopic refractive error. The CDR is approximately 0.8, and

there is thinning of the neuroretinal rim, with associated bayonetting of the blood vessels inferiorly.

There is a faint disc haemorrhage in the 7 o’clock position.

The left optic disc is also average in size, with a temporal crescent of peripapillary atrophy. The disc

is less tilted compared with the right. The CDR is approximately 0.7. There appears to be mild

thinning of the inferior neuroretinal rim. There is no RNFL haemorrhage.

Question 2: Describe the following visual fields and OCT scan findings.

Figure 2a: Right eye visual field

Figure 2b. Left eye visual field

Figure 3a. OCT retinal nerve fibre layer analysis

Figure 3b. OCT macular ganglion cell Analysis

Answer 2:

Humphrey SITA Standard 24-2 tests are reliable for each eye, with low fixation losses, false positives

and false negative errors. The right visual field shows superior-nasal and superior-temporal

paracentral visual field defects and early superior-nasal arcuate field loss. Both the mean deviation

and pattern standard deviation have probability values of <0.5% and the glaucoma hemifield test is

outside normal limits. The left visual field is within normal limits on the glaucoma hemifield test. The

mean deviation and pattern standard deviation have probability values of <2% and <5% respectively.

There are a few scattered points with probability values of <0.5%, but no significant pattern visual

field loss.

The RNFL OCT scans have adequate signal strength in both eyes (7/10 and 6/10 respectively). The

vertical cup to disc ratios as measured by OCT correspond with the cup to disc ratios and disc

appearance noted clinically. In the right eye there is marked RNFL and neuroretinal rim thinning

inferiorly, particularly at the 6 o’clock position. RNFL thickness in the left eye is still ‘within normal

limits’ on inspection of quadrant values. However, at the 11 o’clock position the RNFL thickness is in

the lowest 5% of ‘normal’ values. This does not appear to be accompanied by corresponding

neuroretinal rim thinning. Due to the absence of signs of disc damage, this is unlikely to be of

significance. There is significant inter-eye asymmetry.

The macula OCT scans have adequate signal strength in both eyes measuring at 8/10 and 7/10 and

retinal layer segmentation appears accurate on cross-sectional inspection. The thickness values in

two sectors (inferior central and inferior-temporal) of the right macula are in the lowest 1% of

measurements in the age-normal database. This is consistent with the clinically observed optic disc

appearance, and the RNFL scan which shows thinning of the inferior neuroretinal rim and RNFL. The

left macular GCC thickness values are within normal limits compared with the age-normal database,

although the deviation map is showing some possible early GCC thinning in the inferior-temporal

region.

Question 3: Based on the case history and initial examination and test findings, discuss the

differential diagnoses and appropriate investigations.

Answer 3:

The patient has a combination of raised IOP, right RAPD and corresponding optic disc pathology and

visual field loss, strongly suggestive of glaucoma. However, our patient has known thyroid disease

with family history and multiple examination findings consistent with thyroid eye disease (TED): lid

retraction, lid lag on downgaze (Von Graefe’s sign) and proptosis with exposure of the inferior

cornea and staining with fluorescein. There is also an increase of intraocular pressure on upgaze

which is related to an enlarged inferior rectus muscle. The optic neuropathy observed here is a

mixed picture, with both glaucomatous and compressive (thyroid eye disease) features. The pattern

of RNFL loss and the optic disc cupping is glaucomatous. Despite the thyroid eye disease, the

patient’s colour vision is preserved, and there is no pallor of the neuroretinal rim.

Differential diagnoses include non-specific orbital inflammation/orbital pseudotumour, orbital

neoplasm (those that invade the extraocular muscles or compressing venous drainage causing

secondary muscle enlargement), sarcoidosis, vasculitis and arterio-venous malformations or carotid-

cavernous fistula.

Appropriate investigations could involve the following:

• Blood tests including thyroid function tests (TSH, T4 and thyroid stimulating

immunoglobulin)

• Ultrasound scan to demonstrate asymmetric enlargement of extraocular muscles. The

muscle bellies are enlarged, and the tendon insertions are spared in thyroid eye disease.

• CT scan or MRI: We expect to see proptosis of the globe, enlargement of the extraocular

muscles and fatty attenuation and possible enlarged superior ophthalmic vein.

Other differentials, as listed above, can be excluded with neuroimaging based on the density of the

abnormal tissue that is involved. E.g orbital pseudotumour will involve the tendinous insertion which

is spared in thyroid eye disease.

Overall, CT is the imaging modality of choice as it is widely available and can provide a detailed

assessment of orbital bony and soft-tissue anatomy.

Question 4: What is thyroid eye disease and its natural history?

Answer 4: Thyroid eye disease (TED) is an autoimmune inflammatory disorder of the orbit, which

also goes by many other names: thyroid-associated ophthalmopathy, Graves’ ophthalmopathy or

thyroid orbitopathy. Graves’ disease (an autoimmune disease that affects the thyroid resulting in

hyperthyroidism) and Hashimoto’s thyroiditis (or chronic lymphocytic thyroiditis, an autoimmune

disease in which the thyroid gland is gradually destroyed) are the most common causes of TED.

Approximately 90% of TED patients are expected to be hyperthyroid and only 5% each are

hypothyroid or euthyroid (Bartley et al., 1996). The pathology arises from inflammation of the

periorbital connective tissues, extraocular muscles and orbital fat. The prognosis can range from self-

limiting mild ocular irritation to compressive optic neuropathy or corneal exposure ulcerations

leading to significant disfiguration and vision loss in 3-5% (Wiersinga and Bartalena, 2002).

TED is usually bilateral and asymmetric. Common symptoms and signs are conjunctival hyperaemia,

ocular surface discomfort and double vision. The most common initial symptom is a change in facial

appearance from eyelid retraction or periorbital swelling.

The most frequently reported clinical findings are: (Bartley et al., 1996)

• Eyelid retraction (90%). This is responsible for the patient-experienced ocular surface

dryness and clinically observed corneal exposure.

• Proptosis (60%). This is the result of enlargement of orbital contents. Proptosis can also lead

to signs and symptoms of corneal exposure.

• Ocular misalignment (40%). This is due to inflammation and fibrosis of extraocular muscles.

Interestingly, patients with minimal proptosis are at higher risk of the more severe complication of

compressive optic neuropathy due to a ‘compartment syndrome effect’ with enlargement of the

muscles within the fixed confines of the walls of the orbital bones.

The ‘Rundle Curve’ (see Figure 4) describes the natural history of the TED as follows:

• Active (progressive) phase: The initial phase in the first 6-24 months where we see proptosis,

conjunctival injection, chemosis and diplopia. Severe complications, including compressive

optic neuropathy and corneal ulceration due to exposure, are rare.

• Stable/static phase: The phase after active inflammation settles and some improvement is

observed. This lasts for approximately one year and progressive fibrosis develops which

leads to stable proptosis, eyelid retraction and persistent restrictive strabismus.

Figure 4: Rundle’s curve (Bartley, 2011)

Question 5: What is the epidemiology of thyroid eye disease (TED) and what are its risk factors?

Answer 5:

Epidemiological studies have estimated an incidence of 2.9 cases per 100,000 per year for males and

16.0 cases per 100,000 per year for females. Incidence rates are of a bimodal distribution for both

genders: Males have peak rates in the 45-49 years and 65-69 years age groups and females in the

40-44 years and 60-64 years groups (Bartley et al., 1996).

Significant thyroid dysfunction and radioactive iodine treatment for Grave’s disease has been shown

to have an association with worsening or development of TED in several studies (Stan and Bahn,

2010).

One of the most significant risk factors is cigarette smoking, which increases the incidence and

severity of the disease and affects responsiveness to treatment. The connection is unclear, but it is

certainly in the patient’s best interests to cease smoking. Smoking increases the risk of developing

thyroid eye disease by 7.7 times (Wiersinga and Bartalena, 2002).

Other potential risk factors, outlined more recently, include:

• Selenium deficiency. Selenium has a role in the protection of the body against oxidative

damage and metabolism of thyroid hormones. Selenium levels have been found to be low in

patients with TED, with the degree of deficiency being proportional to severity of the disease

(Khong et al., 2014)

• High serum cholesterol. A large study has found that the risk of developing TED in patients

with Graves’ disease was decreased by 40% with the use of statins for more than 60 days

(Stan and Bahn, 2010). Initially it was thought that this was due to the anti-inflammatory

effects of the statins but a study demonstrated that Graves’ patients with TED had higher

levels of total cholesterol and low-density lipoprotein (LDL) cholesterol (Sabini et al., 2018).

Question 6: What is the conservative/preventative treatment of TED?

Answer 6:

As the majority of patients have mild TED, they are largely asymptomatic, or they may complain of

ocular discomfort or diplopia. The ocular discomfort is secondary to the lid retraction and/or

proptosis and, if mild, can be treated with ocular lubricants. For those with mild ocular misalignment

in the primary position, this can be treated with prism correction. It is also recommended that

patients wear sunglasses when outdoors due to increased corneal exposure to light, wind or other

irritants.

As outlined above, the most significant modifiable risk factor for TED is cigarette smoking. Advising a

patient to stop smoking and suggesting they see their GP, or a smoking cessation service is vital as

smoking will not only increase the severity of their disease but also hamper the effectiveness of

current and future treatment.

Assessing and addressing those with high cholesterol/hyperlipidaemia is also important and patients

should be encouraged to engage with their primary care physician and have regular blood tests and

be compliant with any therapy to address cholesterol levels.

Selenium supplementation has also been shown to be beneficial for TED. A large randomised

controlled trial (RCT) demonstrated slowed TED progression and less ocular involvement with

selenium supplementation (Marcocci et al., 2011). Patients need to have normal iodine levels prior

to selenium supplementation as hypothyroidism can worsen with selenium supplementation if a

patient is deficient in both selenium and iodine.

Thyroid dysfunction (both hyperthyroidism and hypothyroidism) has also been shown to increase

the severity of TED (Prummel et al., 1990). It is therefore vital that the patient engages with their GP

or endocrinologist to have regular thyroid function tests and appropriate management to maintain a

euthyroid status. Patients with hyperthyroidism who have been treated with radioactive iodine are

at risk of hypothyroidism and need to be monitored and treated accordingly.

Question 7: What is the role of orbital irradiation therapy?

Answer 7:

The aim of orbital radiotherapy is to reduce inflammation and the associated changes to the eye

caused by TED. It is considered in severe cases of autoimmune inflammation such as compressive

optic neuropathy. It is administered across multiple visits in an outpatient setting. It has been shown

to be more effective than sham radiation for patients with diplopia and shown to be better in

conjunction with glucocorticoid therapy vs glucocorticoid therapy alone (Rajendram et al., 2012)

though it has not been shown to improve quality of life compared with other treatment groups.

Short-term adverse events are mainly mild, such as redness of skin and temporal hair loss. Hair loss

is usually temporary at lower doses but can be permanent with higher doses. There is a risk of

secondary malignancy and worsening of pre-existing diabetic retinopathy which therefore limits its

use in younger patients and those with diabetic retinopathy.

Question 8: Describe the medical treatments for more severe thyroid eye disease

Answer 8:

As described above, the Rundle Curve shows an ‘active phase’ in the natural course of TED. This is

the best time to initiate therapy with medications that address inflammation. The first line

treatment for those with moderate or severe disease is high-dose systemic intravenous

glucocorticoids such as intravenous methylprednisolone. It has been shown that intravenous

steroids are more effective than oral variants and high doses have a short-term advantage over

lower doses. Great care needs to be taken with high-dose intravenous steroids as accumulation can

result in toxicity-related adverse events such as cardiovascular collapse. Patients should be screened

for contraindications, including severe hepatic dysfunction, recent viral hepatitis, cardiovascular or

psychiatric morbidity and diabetes. Treatment is usually a weekly intravenous infusion of 0.5 g over

6 weeks with a decrease in dose to 0.25 g for another 6 weeks - a cumulative dose of 4.5g

methylprednisolone (Kahaly et al., 2005). Cyclosporine has also been shown to have effective results

in combination with glucocorticoids.

Patients who do not respond satisfactorily to steroids, or in whom steroids are contraindicated, can

be offered immunomodulatory drugs. However, further studies are required to confirm their

efficacy. Rituximab has been investigated in two recent small RCTs. These have produced

contradictory results (Salvi et al., 2015, Stan et al., 2015). Meta-analyses show some reduction in

clinical activity of the disease, but more evidence is required. Teprotumumab is another monoclonal

antibody inhibitor which has demonstrated reduced proptosis and clinical activity scores versus

placebo in a multicentre, double-masked RCT (Smith et al., 2017).

Question 9: What are the surgical treatment options for patients with TED?

Answer 9:

Surgical treatment is generally reserved for when the patient is in the stable phase of the Rundle

Curve, where symptoms have remained stable for at least six months. Surgical treatment serves

more of a rehabilitative purpose. The exception to this urgent surgical decompression in patients

with evidence of compressive optic neuropathy or those responding very poorly to medical

treatment.

The procedures performed (and usually in this order as each one affects the following procedures)

are:

1) Orbital decompression to address the proptosis and discomfort associated with it.

2) Strabismus surgery for diplopia and/or cosmesis

3) Lid surgery for lid retraction. Tarsorrhaphy can be considered to help with eyelid closure if there is

risk of vision loss due to severe corneal exposure and breakdown.

Question 10: How do we assess disease severity and disease response in order to decide the

appropriate course of action?

Answer 10:

Assessment of disease severity and activity for patients with thyroid eye disease is done using the

Clinical Activity Score developed by Mouritis et al in 1989 and later amended by the European Group

of Graves’ Orbitopathy (EUGOGO) Classification.

For the initial Clinical Activity Score (CAS), 1 point is given for each of the following (maximum score

of 7) and if the score is 3/7 or greater, the patient is considered to have active ophthalmopathy

1) Spontaneous orbital pain

2) Gaze evoked orbital pain

3) Eyelid swelling that is considered to be due to active Graves’ Ophthalmopathy (GO)

4) Eyelid erythema

5) Conjunctival redness that is considered to be due to active GO

6) Chemosis

7) Inflammation of caruncle or plica

When a patient is assessed after follow-up (1-3 months), they can be scored out of 10, by including

items 8-10. If the score is 4/10 or greater then they considered to have active ophthalmopathy.

8) Increase of >2mm in proptosis

9) Decrease in uniocular excursion in any one direction of >8 degrees

10) Decrease of acuity equivalent to 1 Snellen line

Question 11: How would you manage our patient’s optic neuropathy?

Answer 11:

Our patient was initially started on topical anti-hypertensive therapy. She was initially started on latanoprost and, when brimonidine 0.2% was added, she developed an allergy to the alpha agonist. She was subsequently managed with dortim (dorzolamide 2% and timolol 0.5%) eye drops twice a day in the right eye. She went on to receive SLT treatment in the right eye and although there was some reduction in IOP, bimatoprost 0.03% was added at night to improve control. Her IOP in primary gaze reduced to 13mmHg. However, she continued to show visual field progression in the right eye. Her IOP on upgaze remained high, at 24 mmHg. A CT scan was performed on our patient to assess the degree of proptosis. It showed bilateral moderate prominence of the inferior recti muscles. The proptosis was more apparent on the right. An oculoplastics opinion was sought at this stage for the consideration of orbital decompression. She has been waitlisted for the procedure which is expected to address her proptosis and also reduce her intraocular pressure. Elevated intraocular pressure has been noted in around 5-24% of patients with TED, although it is not something frequently reported (Danesh-Meyer et al., 2001). There have been several theories on why IOP is increased in patients with TED including:

• Orbital congestion and venous outflow obstruction causing increased episcleral venous pressure

• increased resistance to trabecular outflow, possibly from increased mucopolysaccharide deposition in the trabecular meshwork

• Enlarged and fibrotic extraocular muscles causing restriction and compression of the globe

• A genetically linked predisposition to glaucoma. (Danesh-Meyer et al., 2001)

A retrospective case review of 172 patients with TED evaluated IOP changes after orbital decompression, strabismus surgery and orbital radiation in Philadelphia (Danesh-Meyer et al., 2001). For those who underwent orbital decompression, a reduction of 18.9% in IOP was noted in primary position and 27.9% in upgaze. Those who were taking a glaucoma medication already or had a preoperative IOP >21mmHg had a greater reduction in IOP. For those who had strabismus surgery, the reduction in IOP was 13.3% in primary position and 31.2% in upgaze. Orbital radiation did not produce any statistically significant reduction in IOP. This is further supported by a study in Korea on 113 orbits (60 patients) undergoing orbital decompression with 14.5% reduction in IOP after 2 months (Jeong et al., 2016). They did, however, report a transient increase in IOP of around 10% during the first week. References: BARTLEY, G. B. 2011. Rundle and his curve. Arch Ophthalmol, 129, 356-8. BARTLEY, G. B., FATOURECHI, V., KADRMAS, E. F., JACOBSEN, S. J., ILSTRUP, D. M., GARRITY, J. A. &

GORMAN, C. A. 1996. Clinical features of Graves' ophthalmopathy in an incidence cohort. Am J Ophthalmol, 121, 284-90.

DANESH-MEYER, H. V., SAVINO, P. J., DERAMO, V., SERGOTT, R. C. & SMITH, A. F. 2001. Intraocular pressure changes after treatment for Graves' orbitopathy. Ophthalmology, 108, 145-50.

JEONG, J. H., LEE, J. K., LEE, D. I., CHUN, Y. S. & CHO, B. Y. 2016. Clinical factors affecting intraocular pressure change after orbital decompression surgery in thyroid-associated ophthalmopathy. Clin Ophthalmol, 10, 145-50.

KAHALY, G. J., PITZ, S., HOMMEL, G. & DITTMAR, M. 2005. Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves' orbitopathy. J Clin Endocrinol Metab, 90, 5234-40.

KHONG, J. J., GOLDSTEIN, R. F., SANDERS, K. M., SCHNEIDER, H., POPE, J., BURDON, K. P., CRAIG, J. E. & EBELING, P. R. 2014. Serum selenium status in Graves' disease with and without orbitopathy: a case-control study. Clin Endocrinol (Oxf), 80, 905-10.

MARCOCCI, C., KAHALY, G. J., KRASSAS, G. E., BARTALENA, L., PRUMMEL, M., STAHL, M., ALTEA, M. A., NARDI, M., PITZ, S., BOBORIDIS, K., SIVELLI, P., VON ARX, G., MOURITS, M. P., BALDESCHI, L., BENCIVELLI, W. & WIERSINGA, W. 2011. Selenium and the course of mild Graves' orbitopathy. N Engl J Med, 364, 1920-31.

PRUMMEL, M. F., WIERSINGA, W. M., MOURITS, M. P., KOORNNEEF, L., BERGHOUT, A. & VAN DER GAAG, R. 1990. Effect of abnormal thyroid function on the severity of Graves' ophthalmopathy. Arch Intern Med, 150, 1098-101.

RAJENDRAM, R., BUNCE, C., LEE, R. W. & MORLEY, A. M. 2012. Orbital radiotherapy for adult thyroid eye disease. Cochrane Database Syst Rev, Cd007114.

SABINI, E., MAZZI, B., PROFILO, M. A., MAUTONE, T., CASINI, G., ROCCHI, R., IONNI, I., MENCONI, F., LEO, M., NARDI, M., VITTI, P., MARCOCCI, C. & MARINO, M. 2018. High Serum Cholesterol Is a Novel Risk Factor for Graves' Orbitopathy: Results of a Cross-Sectional Study. Thyroid, 28, 386-394.

SALVI, M., VANNUCCHI, G., CURRO, N., CAMPI, I., COVELLI, D., DAZZI, D., SIMONETTA, S., GUASTELLA, C., PIGNATARO, L., AVIGNONE, S. & BECK-PECCOZ, P. 2015. Efficacy of B-cell

targeted therapy with rituximab in patients with active moderate to severe Graves' orbitopathy: a randomized controlled study. J Clin Endocrinol Metab, 100, 422-31.

SMITH, T. J., KAHALY, G. J., EZRA, D. G., FLEMING, J. C., DAILEY, R. A., TANG, R. A., HARRIS, G. J., ANTONELLI, A., SALVI, M., GOLDBERG, R. A., GIGANTELLI, J. W., COUCH, S. M., SHRIVER, E. M., HAYEK, B. R., HINK, E. M., WOODWARD, R. M., GABRIEL, K., MAGNI, G. & DOUGLAS, R. S. 2017. Teprotumumab for Thyroid-Associated Ophthalmopathy. N Engl J Med, 376, 1748-1761.

STAN, M. N. & BAHN, R. S. 2010. Risk factors for development or deterioration of Graves' ophthalmopathy. Thyroid, 20, 777-83.

STAN, M. N., GARRITY, J. A., CARRANZA LEON, B. G., PRABIN, T., BRADLEY, E. A. & BAHN, R. S. 2015. Randomized controlled trial of rituximab in patients with Graves' orbitopathy. J Clin Endocrinol Metab, 100, 432-41.

WIERSINGA, W. M. & BARTALENA, L. 2002. Epidemiology and prevention of Graves' ophthalmopathy. Thyroid, 12, 855-60.

Recommended reading: LI, Z., CESTARI, D. M. & FORTIN, E. 2018. Thyroid eye disease: what is new to know? Curr Opin

Ophthalmol, 29, 528-534. DANESH-MEYER, H. V., SAVINO, P. J., DERAMO, V., SERGOTT, R. C. & SMITH, A. F. 2001. Intraocular

pressure changes after treatment for Graves' orbitopathy. Ophthalmology, 108, 145-50.

Case 1 Exam

Question 1: Which of the following is a cause of enlarged extraocular muscles?

Answer A: Thyroid eye disease

Answer B: Non-specific orbital inflammation

Answer C: Orbital neoplasm

Answer D: Arterio-venous malformations

Answer E: All of the above

Question 2: Which of the following tests is not considered a relevant investigation for thyroid eye

disease?

Answer A: T4 levels

Answer B: Iodine levels

Answer C: Selenium levels

Answer D: Iron levels

Answer E: TSH levels

Question 3: What is the approximate incidence of thyroid eye disease in females?

Answer A: 1 per 100,000 per year

Answer B: 7 per 100,000 per year

Answer C: 16 per 100,000 per year

Answer D: 24 per 100,000 per year

Answer E: 50 per 100,000 per year

Question 4: For how long should a patient remain stable during the stable/static phase before

undergoing surgical treatment?

Answer A: Immediately once they enter the stable/static phase

Answer B: Minimum 3 months after entering the stable/static phase

Answer C: Minimum 6 months after entering the stable/static phase

Answer D: Minimum 9 months after entering the stable/static phase

Answer E: Minimum 12 months after entering the stable/static phase

Question 5: The Jeong study (2016) showed the IOP was reduced by 10.1% in the first week

following orbital decompression. True or false?

Question 6: Which of the following signs is least likely to be seen in the active phase of TED?

Answer A: Proptosis

Answer B: RNFL thinning

Answer C: Chemosis

Answer D: Lid retraction

Answer E: Raised IOP on up-gaze

Question 7: What is the correct order of clinical findings for TED, in decreasing frequency? (Li 2018)

Answer A: Eyelid retraction, Proptosis, Ocular misalignment

Answer B: Eyelid retraction, Ocular misalignment, RNFL thinning

Answer C: Proptosis, Colour vision defect, Ocular misalignment

Answer D: Proptosis, Ocular Misalignment, Corneal ulceration

Answer E: Ocular misalignment, Eyelid retraction, Proptosis

Question 8: Which problem does not match its cause in TED?

Answer A: Optic neuropathy: Compartment syndrome with enlarged extraocular muscles within

confines of orbital walls

Answer B: Corneal ulceration: Eyelid retraction

Answer C: Increased intraocular pressure: Enlargement of inferior oblique muscle

Answer D: Diplopia: Inflammation and fibrosis of extraocular muscles

Answer E: Proptosis: Enlargement of orbital contents (fat, muscles)

Question 9: After which of the following would you least expect to measure a significant reduction in

IOP for a patient with TED?

Answer A: Strabismus surgery

Answer B: Orbital decompression surgery

Answer C: Selective laser trabeculoplasty

Answer D: Orbital radiation

Answer E: Topical antihypertensive medications

Question 10: Selenium deficiency should always be addressed prior to correcting iodine deficiency in

patients with Graves’ disease. True or false?

Question 11: A patient (pack-a-day smoker) presents to your clinic and is found to have mild thyroid

eye disease. What is the most impactful thing you can do for them?

Answer A: Advise them to take over-the-counter selenium supplementation

Answer B: Suggest scheduling an examination with their GP to get a blood test to check cholesterol

levels

Answer C: Prescribe artificial tears to use twice a day

Answer D: Immediately schedule an appointment with an endocrinologist to assess their thyroid and

thyroid function

Answer E: Arrange a smoking cessation referral

Question 12: What percentage of patients with TED could be expected to lose vision due to the

disease?

Answer A: <1%

Answer B: 3-5%

Answer C: 8-10%

Answer D: 13-15%

Answer E: 24-26%

Question 13: Which of the following findings suggests the presence of a compressive optic

neuropathy?

Answer A: RAPD

Answer B: Paracentral visual field loss

Answer C: Decrease in colour vision

Answer D: Pallor of the optic nerve

Answer E: All of the above

Question 14: Which of the following is true for treatment of TED?

Answer A: Oral glucocorticoids are more effective than intravenous glucocorticoids

Answer B: First line treatment for TED is topical steroids

Answer C: Orbital radiotherapy is not recommended in those with pre-existing diabetic retinopathy

Answer D: Strabismus surgery should be performed as soon as the patient reports diplopia

Answer E: Lid surgery should be performed prior to orbital decompression

Question 15: All patients with thyroid eye disease are hyperthyroid. True or false?

Question 16: Which of the following is the least likely to be risk factor/group at risk for developing

TED?

Answer A: Age >80 years

Answer B: Smokers

Answer C: Patients post radioactive-iodine treatment

Answer D: Female gender

Answer E: Selenium deficiency

Question 17: Which of the following would not add points on the TED Clinical Activity Score?

Answer A: Spontaneous orbital pain

Answer B: Increase of 1mm in proptosis across successive visits

Answer C: Inflammation of caruncle or plica

Answer D: Gaze evoked orbital pain

Answer E: Eyelid erythema

Question 18: Which of the following is not a drug used in the treatment of TED?

Answer A: Cyclosporine

Answer B: Intravenous methylprednisolone

Answer C: Rituximab

Answer D: Teprotumumab

Answer E: Aspirin

Question 19: By what factor does smoking increase the risk of developing TED? (Wiersinga 2002)

Answer A: 2.3 x

Answer B: 1.8 x

Answer C: 4.1 x

Answer D: 7.7x

Answer E: 10.6 x

Question 20: Von Graefe’s sign is the lagging of the upper eyelid on downward rotation of the eye.

True or false?

Question 21: Which of the following statements is true?

Answer A: TED is always bilateral and symmetrical

Answer B: Most patients with TED are at risk of developing compressive optic neuropathy

Answer C: A patient can be hypothyroid and have thyroid eye disease

Answer D: Low iron stores contribute towards risk of worsening TED

Answer E: Surgical decompression should be performed as soon as there is evidence of proptosis.

Question 22: Which of the following statements is true?

Answer A: Orbital decompression is to address proptosis

Answer B: Strabismus surgery is to address diplopia and/or cosmesis

Answer C: Eyelid surgery is to address cosmesis and/or corneal exposure

Answer D: Tarsorrhaphy is to address corneal exposure

Answer E: All of the above

Question 23: Which of the following clinical signs would be the greatest indication for performing

orbital decompression?

Answer A: Fluorescein uptake on corneal surface

Answer B: Proptosis of 2mm

Answer C: Diplopia in primary gaze

Answer D: Progressive acquired colour vision defect

Answer E: Chemosis

Question 24: Which of the following is most likely to be the initial symptom of TED?

Answer A: Change in facial appearance

Answer B: Photophobia

Answer C: Ocular discomfort

Answer D: Tearing

Answer E: Diplopia

Question 25: The extraocular muscle most likely to be affected by TED is inferior rectus. True or

false?