• Credits
  • Section Writer: Dr. Om J Lakhani
  • Section Editor: Dr. Om J Lakhani

• Abbreviations
  • GO = Graves' orbitopathy
  • TAO= Thyroid associated orbitopathy

• Q. Describe the pathogenesis of GO  ?
  • 
  • 

• **Epidemiology **
  • Sex
    • It is more common in females
    • It is more severe in males
  • Age
    • More common in 40-60 years of age
    • More severe in elderly

• **RISK FACTORS **

• Q. What are the risk factors for GO ?
  • Age- older the age- worse the disease
  • Sex- more severe in males
  • TSH Receptor antibody- higher the titer- more severe the disease
  • Radioactive iodine therapy – may worsen the disease
  • Smoking – worsening of the disease

• **ASSOCIATION WITH THYROID DISORDER **

• Association with Grave's disease

  • 20-25% with Grave's disease have overt TAO
  • 30-40% of patients with Grave's disease may have changes on CT Scan or ultrasound but no overt disease

• Timing with Grave's
  • 20% - Precedes  hyperthyroidism
  • 40%- diagnosed concurrently
  • 20%- Follows the diagnosis of hyperthyroidism
  • 20%- Occurs after Radioactive iodine therapy

• With patients having TAO
  • 80%- Hyperthyroid
  • 10-20%- Euthyroid
  • 1-10%- Hypothyroid

• Q. What are the symptoms of GO ?
  • Proptosis
  • Watering and redness of eyes
  • Photophobia
  • Diplopia
  • Retro-orbital pain
  • Pain on movement of eyeballs
  • Loss of color vision
  • Vision loss

• **SIGNS **

• Q. Enlist the signs to look for in a patient with GO ?

  • Here is a sample clinical examination sheet enlisting the signs of GO
    • 

• Q. What are the clinical features of optic neuropathy in patients with Grave's ophthalmopathy?
  • Loss of color vision
  • Disc swelling or optic atrophy
  • RAPD
  • Loss of visual acuity

• Q. How to test for RAPD? (Marcus Gunn Pupil)
  • Step 1
    • Ask the patient to fixate in the distance
    • Ask him to hold the light source for 3 seconds in that position
    • Assess the degree of contraction and how long it sustains.
  • Step 2
    • Now Move the light source to position 2 shown below. and hold for 3 seconds.
    • Assess the degree of contraction and how long it sustains.
    • Compare with what you remember from the other eye.
  • Step 3
    • Move light source back to position 1 and hold for 3 seconds. Assess the degree of contraction and how long it sustains.
    • Compare with what you remember from the other eye.
  • Step 4
    • Repeat the swing from side to side until you are sure whether one side contracts less or sustains for less time (+ RAPD), or whether the pupil reflexes are equal in these respects (-RAPD).
  • 

• Q. What is RAPD suggest?
  • The presence of RAPD suggests compression of the optic nerve (proximal to the chiasma)

• Q. How is the retraction of eyelid measured?
  • Normally the upper eyelid covers the sclero-corneal junction by 1-2 mm.
  • If the sclera is visible above the sclero-corneal junction – then there is at least 1.5 mm retraction and suggests upper eyelid retraction.
  • Eyelid retraction >1-2 mm is significant.

• Q. What is the importance of upper eyelid retraction?
  • It is mainly due to sympathetic overactivity. It can be present in other causes of thyrotoxicosis other than Graves. It is one of the early signs of eye involvement.

• Q. Which other autoimmune diseases must be looked for while dealing with GOc?
  • Look for Ptosis, which may be associated with Myasthenia gravis.

• Q. What distance is measured by Hertel's exompthalmometer?
  • Between the lateral canthus of the eye and the orbital apex.

• Q.  What is the normal distance here?
  • Normal is 20 mm in whites and 22 mm in blacks.

• Q. How is the Bells phenomenon assessed?
  • Bells phenomenon is the rotation of the eyeball on the closure of the eyelid
  • Examiner holds the patient's eyelid tightly and asks her to attempt to close the eyes
  • The eyelid doesn't close, but the eyeball rotates upward
  • This is a normal bells phenomenon
  • Absent bells phenomenon is seen in 10 % of patients
  • They have a higher risk of corneal ulceration of eyelid doesn't close properly.

• Q. What is Lagophthalmos ?
  • Lagophthalmos is defined as the inability to close the eyelids completely.
  • Ask the patient to look down and gently close both eyes.
  • Lagophthalmos is present when space remains between the upper and lower eyelid margins in extreme downgaze.
  • Document the degree of lagophthalmos by measuring this space, in millimeters, with a ruler.
  • Also, record the blink rate as well as the completeness of the blink.

• CLASSICAL THYROID EYE SIGNS

• Q. Enlist the classical thyroid eye signs?
  • Dalrymple's sign – lid retraction- gives the patient a staring look
  • Von Gaffes' sign – lid lag in downgaze- ask the patient to look downwards- the upper lid lags behind the globe, exposing the sclera between the limbus and the eyelid
  • Stellway's sign- infrequent blinking and incomplete blinking + proptosis
  • Rosenbach's sign- the fine tremor of the eyelid on closure- esp the upper eyelid
  • Mobius sign- failure of convergence of eyes on accommodation
  • Kocher's sign- the reverse of von-grafe- on upward gaze the upper eyelid retract quickly
  • Joffroy's sign- absent wrinkling of the forehead when the eyes are looked up
  • Other lesser common
  • Saiton's sign- on looking upwards, the frontalis muscle contracts after the upper eyelid is fully retracted
  • Jellinek's sign- brownish pigmentation of upper-eyelid
  • Topolansky's sign- pericorneal congestion in patients with Graves disease

• Q. Which is the earliest sign to appear?
  • Lid retraction Dalrymple's sign
  • Normally upper eyelid covers the iris by >1 mm – it <1 mm or sclera see above the limbus – this sign is present
  • The upper sclera is seen- due to eyelid retraction
  • The lower sclera is seen- due to exophthalmos

-Q. What is Gifford's sign?
- Unilateral exophthalmos has to be differentiated from thyroid involvement vs. orbital tumor
- Retract the eyelid of the patient
- In Orbital tumor- you would be able to do so
- In exophthalmos due to thyroid- it is not possible

• **Assessment of severity **

• Q. What is NO SPECS classification of severity of GO ? – also called the ATA classification
  • NO SPECS CLASSIFICATION OF WERNER
    • Class 0- No signs of Symptoms
    • 1-  Only Signs present but no symptoms
    • 2- Soft tissue involvement
    • 3- Proptosis
    • 4- Extraocular muscle involvement
    • 5- Corneal involvement
    • 6- Sight loss

• Q. Describe the EUGOGO clinical activity score?
  • EUGOGO Clinical activity score
  • Here is a sample clinical assesment sheet for EUGOGO clinical activity
    • 
  • Score > 3 /7 is suggestive of active ophthalmopathy

• Q. Which are additional points in EUGOGO on follow-up?
  • 3 more points for follow up
    • Reduce in visual acuity by 1 on Snellen chart
    • More than 2mm increase of proptosis
    • More than 8-degree reduction in eyeball movement in one direction
    • Plus the usual 7 points taking total to 10 points
  • Score >4/10 on follow up is suggestive of active GO

• Q. What is the EUGOGO classification for the severity of GO ?
  • Mild
  • Moderate to severe
  • Sight threatening

• Q. Describe the Mild vs Moderate to severe in EUGOGO severity classification
  • 

• Q. When is it considered sight threatening ?
  • Sight threatening
    • Also called DON- Dysthyroid optic neuropathy
    • Optic neuropathy present
    • Sight threatening corneal exposure
    • Globe subluxation

• Q. What is the VISA classification?
  • It is developed by the International Thyroid Eye Disease Society (ITEDS)
  • It has 4 parameters
    • V- vision
    • I- inflammation and congestion
    • S- strabismus and eyeball movement
    • A- Appearance/ exposure

• **Diagnosis **

• Q. Which are the tests that you will order for a patient with GO ?
  • Blood tests
  • Thyroid function test
  • TSH Receptor antibody
  • Imaging – CT Scan Preferred

• Q. What is the classical CT scan picture of the patient with Grave's ophthalmopathy?
  • 1. Proptosis
  • 2. Thickening of extraocular muscles with sparing of the tendinous insertion
  • 3. Muscle diameter > 4 mm

• **DIFFERENTIAL DIAGNOSIS **

• Q. What is the differential diagnosis of bilateral exophthalmos?
  • Cushing's syndrome
  • Obesity
  • Super vena cava syndrome

• Q. What is the Differentials of unilateral exophthalmos?
  • Carotid- cavernous fistula
  • Orbital neoplasm
  • Infiltrative eye disease
  • Cavernous sinus thrombosis
  • Pseudotumor of orbit

• **COMPLICATIONS **

• Q. What are the causes of vision loss in GO ?
  • 1. Extreme proptosis leading subluxation of the globe
  • 2. Severe corneal ulceration
  • 3. Optic nerve involvement

• **NATURAL HISTORY **

• Q. What is the Natural history of GO ?
  • 66%- Remains same
  • 8-10%- Worsens
  • 20 % - Improves spontaneously

• IMPACT OF TREATMENT OF HYPERTHYROIDISM

• Q. What is the impact of treatment of Hyperthyroidism on GO ?
  • Impact of surgery and anti-thyroid drugs
    • Little impact on TAO severity
    • Hypothyroidism must be avoided- hypothyroidism will worsen the TAO
  • Radioactive iodine
    • Can potentially worsen the Ophthalmopathy
    • It can also lead to new onset of clinical GO, which was not present or noticed earlier