Graves' orbitopathy is an autoimmune condition affecting the eye muscles and surrounding tissues that can cause proptosis, diplopia, and sight loss. It occurs in 30-50% of patients with Graves' disease. The condition is caused by antibodies targeting the thyroid stimulating hormone receptor, which is highly expressed in the retro-orbital tissues. Graves' orbitopathy can become sight threatening in 1-2% of cases due to corneal breakdown or dysthyroid optic neuropathy, requiring urgent treatment with high dose steroids to reduce inflammation and pressure on the optic nerve. Long term management involves monitoring for disease activity and use of steroids or surgery depending on activity level.

1. Sight threatening
Graves’ orbitopathy
Ahmed Elmoughazy (Elsheaita)
Assistant lecturer, Hepatology and Gastroenterology, Medical Research
Institute, Alexandria University

2. Introduction
 It is an autoimmune process affecting retro-
ocular tissues. In its severe form, it can be sight-
threatening; thus, prompt evaluation and timely
referral and management become of utmost
importance.

3. Introduction
Generally occurring in patients with hyperthyroidism or a
history of hyperthyroidism due to Graves’ disease, Graves’
ophthalmopathy is also known as thyroid-associated
ophthalmopathy or thyroid eye disease, because it sometimes
occurs in patients with euthyroid or hypothyroid chronic
autoimmune thyroiditis.
Bahn RS. Graves' ophthalmopathy. N Engl J Med. 2010;362(8):726–738. doi:10.1056/NEJMra0905750

4. Epidemiology
Graves’ orbitopathy has been
said to occur in as many as
to 50% of patients diagnosed
with Graves' disease.
Incidence rate of 16 women
and 3 men per 100,000
population.
Fox TJ, Anastasopoulou C. Graves Orbitopathy. [Updated 2019 Nov 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK549889/

5. Etiology
 The culprit antibody in Graves’
disease is the thyroid-stimulating
hormone (TSH) receptor antibody. Its
main site of action is on TSH
receptors in the thyroid. However,
evidence has suggested that the
expression of the TSH receptor is in
higher concentration in retro-ocular
tissue in patients with Graves disease.
Fox TJ, Anastasopoulou C. Graves Orbitopathy. [Updated 2019 Nov 16]. In: StatPearls [Internet]. Treasure Island
(FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK549889/

6. Risk factors
 Several risk factors are implicated:
 Higher titers of TSH receptor
 Female gender
 Exposure to radioiodine as a treatment
modality for Graves disease.
 Smoking is the most significant modifiable
risk factor.
Fox TJ, Anastasopoulou C. Graves Orbitopathy. [Updated 2019 Nov 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK549889/

7. Clinical assessment
 Eye inspection for proptosis and commenting on whether it is symmetrical
or asymmetrical.
 Inspection for conjunctival injection, chemosis, and periorbital edema.
 Assessment if the patient can fully close their eyes.
 Testing the extraocular muscles by asking the patient to look in all directions
(? Pain in particular direction).
 Testing both visual acuity and color vision should be included as part of the
comprehensive examination.

8. Clinical assessment
 Eponymous signs :
 Jellinek's sign: hyperpigmentation of the superior fold of the eyelid
 Tella's sign: hyperpigmentation of the inferior eyelid.
 Rosenbach's sign: fine tremors of the eyelids when closed.
 Moebius' sign : lack of convergence.
 Beck's sign : Pulsating retinal arteries.
 Snellen-Rieseman's sign : a systolic murmur When placing a stethoscope over the
closed eyelid.

9. o Panel A shows a 59-year-old woman
with excess proptosis, moderate
eyelid edema, and erythema with
moderate eyelid retraction affecting
all four eyelids. Conjunctival
chemosis (edema) and erythema
with bilateral edema of the
caruncles, with prolapse of the right
caruncle, are evident.
o Panel B shows a 40-yearold woman
with excess proptosis, minimal
bilateral injection, and chemosis with
slight erythema of the eyelids. She
also had evidence, on slit-lamp
examination, of moderate superior
limbic keratoconjunctivitis.

10. Assessment of activity

11. Assessment of activity

12.  GO may be sight
threatening in 1-2% of
cases which
represents an
emergency requiring
immediate treatment.

17. GO-related sight loss may be due to
1. Corneal breakdown .
2. Dysthyroid optic neuropathy (DON).

18. Corneal
breakdown
 Minor corneal abnormalities can be detected by
slit lamp examination of the cornea which
reveals punctate fluorescein staining.
 Severe corneal damage is evident simply using
a strong light.
 Marked redness of the lower conjunctiva,
 A grey corneal opacity,
 A corneal abscess.
 The eyelids do not close over the cornea and the
cornea is visible on attempted eye closure.

19. Management: Corneal breakdown

20. Management: Corneal breakdown

21. Dysthyroid optic neuropathy (DON).
 DON is due to optic nerve
compression, most
frequently occurring at the
orbital apex (apical
crowding), by the enlarged
extraocular muscles, or to
optic nerve stretching in the
event of extreme
exophthalmos.

23. Management

24. Management: DON

26. Management: DON

27. Management: DON

29. Follow up
If the disease is still active, glucocorticoid treatment can be
continued using either oral or intravenous glucocorticoids.
It is recommended not to exceed a cumulative dose of 8 grams
of intravenous methylprednisolone per cycle because of
potential severe hepatotoxicity.
If the ophthalmopathy is inactive, rehabilitative surgery is
recommended.
All patients should be urged to refrain from smoking.