Graves' Orbitopathy Flashcards
What is the incidence of Graves’ Orbitopathy (GO)?
Estimated incidence of GO is 16 women or 3 men per 100,00
= Women affected 5x more than men
Approx. 400,000ppl in the UK with GO
Why may have Graves’ Orbitopathy prevalence reduced?
Risk factors such as smoking and employment may have been the cause for the reduction in GO over the years
What is the thyroid gland?
Butterfly shaped gland in the lower neck anterior to the trachea between the SCM muscles that’s a highly vascular endocrine organ consisting of densely packed follicles
What is the function of the Thyroid Gland?
- Concentrates iodide to form thyroid hormones
- Thyroid hormones synthesised and stored in the follicles
What stimulates the release of TSH?
TRH in the hypothalamus to the pituitary gland to the thyroid gland
Where is TSH secreted?
Anterior pituitary
What does TSH stimulate secretion of?
T3 - Tri-iodothyronine
T4 - Tetra-iodothyronine (Thyroxine)
T3 & T4 secreted into bloodstream (bound to plasma proteins and free form intracellular)
What growth and development role do thyroid hormones have?
- Help regulate rate of growth of many tissues
- Maturation of CNS and bones
- Regulation and synthesis of some respiratory enzymes
What Metabolic effects do thyroid hormones have?
Regulate:
- Basal metabolic rate
- Water & ion transport
- Calcium & phosphorus metabolism
- Cholesterol & fat metabolism
- Nitrogen metabolism
What is the main sign and symptom of Hyperthyroidism?
As the thyroid is overactive in hyperthyroidism this leads to an enlarged thyroid gland (‘Goitre’)
What is ‘Goitre’?
Enlarged thyroid gland
What are the signs and symptoms of hyperthyroidism following goitre?
As goitre can lead to overproduction of hormones it can lead to:
- Abnormal heart rhythms – tachycardia
- Increased appetite but may have weight loss
- Hand tremors
- Fine brittle hair
- Hyperactivity
- Heat intolerance and increased perspiration – warm, moist skin
- Lighter or less frequent periods
- Irritability
- Anxiety
- Muscle weakness – upper arms and thighs
What are the signs and symptoms of Hypothyroidism?
An under-active thyroid can lead to:
- Fatigue, exhaustion
- Feeling run down and sluggish
- Unexplained / excessive weight gain
- Dry, coarse, itchy skin and hair
- Slow heart rate
- Feeling cold – especially in the extremities
- More frequent periods, increased menstrual flow
- Difficulty concentrating – brain fog
- Hoarse voice
- Muscle cramps
How do we diagnose thyroid abnormalities?
- Blood test for TSH – (considered outside normal if lower than 0.3 or higher than 3.0)
- Blood test for Thyroid-stimulating immunoglobulin (TSI)
- Blood test for Anti-thyroid antibodies
- Calculated free T4 index (10-20 pmol/L)
- Serum T3 (2.5 – 5.3 pmol/L)
- Normative values often vary based on location so always best to speak to a medic about this if further information required!
What drugs can we used for treating hyperthyroidism?
- Thinomines
- Steroids
- Immunosuppressants
- Radioactive Iodine
What are the types of thinomines and what are they for?
They’re for treating hyperthyroidism
Carbimazole, Methamizole, Propylthiouracil
What do Thinomines do and how do they work??
For reducing hyperthyroidism
- Interfere with thyroid hormone synthesis by blocking the build up of iodine. Most effective if the onset of disease within 1 year
What steroids can we use in hyperthyroidism?
Oral Prednisolone
How do steroids (oral prednisolone) help with hyperthyroidism?
By decreasing secretion of thyroid hormones and peripheral conversion of T4 and T3. Used in severe cases
What are the types of immunosuppressants used in hyperthyroidism?
Azathioprine or Rituximab
How often are immunosuppressants used in hyperthyroidism?
Very rarely - mainly used for comorbidities
How is Radioactive Iodine used in hyperthyroidism?
- Radioactive iodine introduced to the body and taken up by the thyroid gland. Normal cell division and function is disturbed.
Who is radioactive iodine used in most commonly?
Hyperthyroid patients over 45 years of age or in younger patients if other treatments are contraindicated
What are some drawbacks to radioactive iodine?
- 20% of patients become hypothyroid within 1 year of the treatment (after hyperthyroid treatment using radioactive iodine)
- Ocular symptoms have been found to worsen following this treatment (Acharya 2008)
What is a thyroidectomy?
Hyperthyroid Surgery where they remove most of thyroid gland to reduce hormone production
What is the post-op recurrence rate for thyroidectomies? What is the post-op hypothyroidism rate?
- Post-op recurrence in 10-15% of patients
- Post-op hypothyroidism in 40% of patients
Who are more likely to undergo thyroidectomies?
Younger patients as it’s a one-stop surgery for most so no need for lifelong medication. There’s also fewer side effects and lower costs for the NHS.
What drugs are used in hypothyroidism?
Oral Thyroxine
What is Graves’ Disease?
Graves’ disease is an autoimmune disorderthat causes hyperthyroidism. The immune systemattacks the thyroid and causes it to make more thyroid hormone than the body needs.
Are the majority of Graves’ Disease congenital or acquired? Why?
Congenital cases are usually toxicity related so majority of cases of GD (Graves Disease) are acquired cases
What else can Graves’ Orbitopathy (GO) be called?
- Thyroid eye disease (TED)
- Dysthyroid eye disease (DED)
- Dysthyroid ophthalmopathy / orbitopathy
- Endocrine ophthalmopathy
- Thyroid associated ophthalmopathy (TAO)
- Endocrine exophthalmos
What is Graves’ Orbitopathy?
An auto-immune disease (systemic) of the orbit that affects the orbital soft tissues
How does Graves’ Orbitopathy happen?
Presence of circulating antibodies that bind and stimulate the thyroid hormone receptor (TSH) leading to hyperthyroidism and goitre.
Who does Graves’ Orbitopathy affect more?
Incidence - Male / female
16/100 000 women
3/100 000 men
Age
Women 45-50 years
Men 50-55 years (> severity)
Greater severity with age
How does smoking impact Graves’ Orbitopathy?
- Main known risk factor 7 - 8 fold increase
- Severity of eye signs and symptoms increased with increased tobacco consumption (Shine et al, 1990 Lancet)
In patients with Graves’ Orbitopathy what % have hyperthyroidism, hypothyroidism & euthyroidism?
Hyperthyroidism 90%
Hypothyroid 3-5%
Euthyroid 5%
What % of patients have hyperthyroidism without eye signs on initial assessment vs. after CT imaging?
Patients hyperthyroid without eye signs = 50-60%
80-90% have EOM changes on CT imaging
What are the stages of Graves’ Orbitopathy?
Wet (AKA Congestive / Inflammatory / Active phase)
- Eyes are painful and red
- Can last around 3 years
Dry (AKA Fibrotic / Inactive phase)
- Eyes are white
- Painless, restrictive myopathy may be present
How long does the active phase of GO last?
Active phase (1 - 3 years)
What are the signs related to Graves’ Orbitopathy?
- Lid retraction (90-98%)
- Lid lag – von Graefe’s sign
- Exophthalmos (proptosis)
- Lid oedema
- Periorbital oedema
- Epiphora (watery eyes)
- Visual loss – Dysthyroid optic neuropathy DON ~5%
- Chemosis (swelling of eye lids)
- Strabismus
- AHP
- Thyroid disease
Some similarities to myasthenia gravis but a big tell-tale sign of MG is variability in the ptosis
When is the inflammation and fibrosis stage in GO?
Muscles become fibrosed (weaker) over time so left with some symptoms that don’t change like they did the first 3 years so inflammation is at 1-3yrs
What symptoms are related to Graves’ Orbitopathy?
- Most common is change in appearance and/or ocular irritation
- Dry eyes
- Epiphora
- Grittiness
- Diplopia
- Photophobia /Flashing lights
- Reduced vision / colour vision (if optic neuropathy present)
- Pain/ ache on extreme of gaze
- Psychological distress at changing appearance
How do we measure lid retraction?
- Position patient’s head correctly
- Ask patient to fixate on target positioned at their eye level and in the distance.
- Ask patient to relax as much as possible to record the minimum amount of retraction for that patient (i.e. Müller’s muscle as relaxed as possible).
- Observer holds vertical clear plastic ruler near to visual axis without touching eyelashes
- Observer should consistently use only one of their eyes, and on same horizontal level as patient’s eye.
- For patients with manifest strabismus, the contralateral visual axis is occluded prior to measurement.
Record in mm
If you measure lid retraction and it gets worse over appointments what does this mean?
If you measure and it is getting worse you’d think they’re in their active/wet phase of Graves Orbitopathy
In patients with manifest strabismus what must you do when measuring lid retraction?
For patients with manifest strabismus, the contralateral visual axis is occluded prior to measurement.
How do we measure exophthalmos/proptosis?
Hertel Mirror Exophthalmometer
What are the normal ranges of exophthalmos in caucasian males, caucasian females, African males and African females?
12-21mm Caucasian males
12-20mm Caucasian females
12-24mm African males
12-23mm African females
Why is it important to do a CT scan for exophthalmos?
Patients thought to have unilateral orbitopathy then had a CT/MRI showed bilateral asymmetrical cases in a lot of these patients
exophthalmometry >22mm or
asymmetry greater than 3mm
What is Von Graefe’s Sign?
Lid Lag
What areas does Graves’ Orbitopathy affect?
- EOMs
- Orbit
- Lids
- Sight
What happens in wet phase/active phase Graves’ orbitopathy to the EOMs?
- Cellular infiltration with glycosaminoglycans (GAGs) and osmotic inhibition of water
- This leads to EOMs becoming up to 8-10x enlarged
- May compress ON leading to visual loss
- Subsequent degeneration of muscle fibres leads to fibrosis resulting in restricted motility and diplopia
This phase tends to settle within 3 years
What OMs are apparently in Graves’ Orbitopathy?
- Limitation
- Reversal
- Saccadic issues
- Cog wheel pursuit
- Fatigue
- Pain
- Retraction
- Bilateral involvement (can present as unilateral but often asymmetric so masked)
What happens in fibrotic phase / dry phase Graves’ orbitopathy to the EOMs?
- Muscle fibres become distorted, contracted and damaged due to fibrosis
- Eyes are white and quiet
- Painless, restrictive myopathy may be present
What is the order of EOM involvement?
- IR
- MR
- SR, LR
- SO, IO (Thacker et al 2005)
- Vertical, horizontal and torsional diplopia
- Swelling of EOM results in restriction: if IR affected then patient is unable to elevate as eye becomes tethered down
Questions to ask in clinic someone with Graves’ Orbitopathy?
- Do you have any thyroid issues or being investigated for thyroid issues? Any treatments for this? Medications?
- What symptoms do you have (and prompt questions around the answers)?
- Are you a smoker?
- Age?
- Length of time symptoms have been going on? Specifically orbital?
- Any investigations?
- Medications
- Family History of thyroid issues or Graves orbitopathy?
How do we do a differential diagnosis of Graves’ Orbitopathy?
- Lid retraction and lid-lag, which are typical of Graves’ orbitopathy but are absent in orbital myositis
- Pain is often severe and may be the mode of presentation in orbital myositis
- Thyroid function, which should be normal in myositis, with absence of thyroid autoantibodies
- The onset is usually gradual in Graves’ orbitopathy and more acute in myositis
- Graves’ orbitopathy is usually bilateral, with evidence of multiple muscle involvement on CT imaging
- In myositis there is CT scan evidence of involvement of the extraocular muscle tendon, which is usually spared in Graves’ orbitopathy.
How are palpebral fissure measurements helpful in GO?
An increase or decrease in the height of the palpebral fissure can be characteristic of some incomitant conditions, for example:
- Narrowing of the fissure on adduction and widening on abduction are diagnostic features of Duane’s retractions syndrome
- The fissure commonly widens on attempted elevation in Graves’ orbitopathy and orbital blow-out fracture
- Widening of the fissure occurs on abduction in some cases of acquired CNVI and on adduction in CNIII palsy associated with aberrant regeneration
What can result in increased drive to the SR in effort to elevate the eye in GO?
Mechanical restriction of elevation due to tethering of the inferior rectus in GO results in increased drive to the superior rectus in an effort to elevate the eye. As the superior rectus and LPS are synergists, equal innervation goes to the LPS resulting in overaction and lid retraction.
Why should we test visual fields in GO?
Visual fields should be tested in all patients with orbital pathology such as ischaemic optic nerve defects caused by elevated intraorbital pressure are a sight-threatening complication of Graves’ orbitopathy, calling for very urgent treatment.
Who should we use a Hess Chart in GO?
Hess Chart to be plotted for all incomitant strabismus and in Graves’ orbitopathy it is to provide a baseline in conditions likely to develop defective ocular movements in the course of the disease.
Why do we do field of BSV in GO?
The field of BSV can be measured in degrees from the perimeter chart and these measurements compared with those of the normal field. The greater the limitation of ocular movement, the smaller the field of BSV. However, the size is influenced by the patient’s fusion amplitude; if this is good the field will be enlarged, at least in congenital vertical muscle palsies and in patients with Graves’ orbitopathy involving vertically acting muscles. A narrow field of BSV, is characteristic of mechanically caused limitation of movement in opposing directions; a blow-out fracture of the orbital floor with entrapment of tissue is an example of this.
Who would we measure uniocular fixation in GO?
Field of uniocular fixation is a measurement of ductions. The field is plotted on a kinetic perimeter and recorded on a perimeter chart. It is useful in plotting any change from visit-to-visit. A modification of the technique is used in monitoring Graves’ orbitopathy. It is useful if there is no binocular vision or if gross restriction of ocular movement is present, preventing the use of the Lees screen. It is also useful in patients with bilateral limitation where only the asymmetry would be plotted using the Hess chart and is of limited value in these cases. Field of uniocular fixation is a useful measurement of the degree of movement present on ductions in mechanical limitations of movement.
Why would we record Prism Fusion Range in GO?
The vertical fusion amplitude is mainly measured in patients with Graves’ orbitopathy and those with long-standing vertical muscle palsies, who often have an increased fusion amplitude. The measurement is useful in determining prism strength and can influence the amount of surgery performed.
How are we doing surgery in GO?
The most commonly affected muscles are the inferior and medial recti muscles. Undercorrection of the angle of deviation, indicated when operating on esotropia for aesthetic reasons, in adults with decompensating exophoria, in many congenital cranial nerve palsies and in Graves’ orbitopathy.
The inferior rectus has a strong indirect attachment to the lower eyelid that can result in lower eyelid retraction after a recession of 6mm or mote, especially in patients with Graves’ orbitopathy who may have pre-existing lid retractionGraves can benefit from post-op or intraoperative adjustments to enable patients to fuse their diplopia
How long should we wait before doing surgery in GO?
A period of observation to allow time for spontaneous recovery and treatment for the underlying condition. A period of 9-12 months is necessary in neurogenic palsies. The patient has to be medically stable before undergoing surgery and the ocular movements must have been static for at least 3 months but this observation period is longer in those with Graves’ orbitopathy.
What % of Myasthenia Gravis patients have Graves’ Orbitopathy?
If patients have myasthenia gravis, 10% of them will also have Graves’ orbitopathy.
What should we pay attention to in OMs in GO?
If patients have myasthenia gravis, 10% of them will also have Graves’ orbitopathy.
How can we investigate optic nerve function?
- Best corrected VA which should be recorded on each visit and contrast sensitivity
- Colour vision measured each visit
- Pupil response for an RAPD defect in unilateral or asymmetrical bilateral compressive optic neuropathy.
- Automated visual fields
- Serial visual evoked potentials to provide an objective assessment of the optic nerve function.
Look at the Hess charts on the powerpoint for Graves’ Orbitopathy!
What does Somatostatin do?
Inhibits release of other hormones like growth, thyroid, insulin and glucagon
What hormones do the anterior pituitary secrete?
ACTH - Adrenal cortex drives cortical hormones
TSH - Thyroid gland for thyroid hormones
Where is the thyroid gland located?
In the neck, just below the thyroid cartilage and is butterfly shaped.
What two hormones do the thyroid secrete?
T4 (thyroxine) and T3 (tri-idothyronine)
What’s the difference between T3 and T4?
T3 is the biologically active hormone whereas T4 is the circulating store that’s converted to T3 outside of the thyroid at the target tissues
What is the role of thyroid hormones?
To regulate basal metabolic rate (i.e. metabolism)
What happens if there isn’t enough T3 or T4?
If there isn’t enough T3 or T4 this is fedback to the pituitary and the hypothalamus that release hormones. Hypothalamus releases Thyrotropin Releasing Hormone (TRH) the pituitary releases Thyroid Stimulating Hormone (TSH) and act on the thyroid to increase hormone T3 or T4 secretion)
What are the symptoms of an overactive thyroid?
Weight loss, heat intolerance, tachycardia, diarrhoea, tremor and hyperactivity
What are the symptoms of an underactive thyroid?
Weight gain, cold intolerance, bradycardia, constipation and lethargy
How does Grave’s Disease occur?
The result of an overactive thyroid
What happens in Grave’s Disease?
Where Thyroid Stimulating Hormone (TSH) receptor auto-antibodies attack the thyroid causing it to produce too much T3 and T4. It also attacks the periorbital muscles to cause swelling which damages the cornea.
When can TED (Thyroid Eye Disease) be diagnosed?
When 2 of the following 3 are present:
- Clinical orbital signs (lid retraction / proptosis / optic neuropathy)
- Laboratory tests (positive bloods for autoantibodies)
- Typical orbital imaging finding (swollen EOMs)
What are some symptoms of Mild Stage GO?
Foreign body sensation;
Dry eye; excessive tearing; conjunctival or eyelid redness
and swelling;
Blurred vision;
Retro-orbital pain
What are some clinical signs of Mild Stage GO?
Mild, soft tissue inflammation;
Dilated conjunctival vasculature;
Keratoconjunctivitis
What are some signs & symptoms of Moderate Stage GO?
Pulling sensation around the eye;
Eyelid redness and swelling;
Eyelid retraction and bulging eyes
Swelling of extraocular muscles;
Chemosis;
Eyelid oedema;
Proptosis
What are some symptoms of Marked Stage GO?
Horizontal, vertical, and torsional
Strabismus with double vision;
Deteriorating blurred vision;
fading colour vision in one or both eyes;
Decrease in visual acuity, visual field, and colour vision
(signs of optic neuropathy)
What are some clinical signs of Marked Stage GO?
Progressive proptosis with eyelid retraction;
Corneal ulceration;
Inflammation of extraocular muscles and scarring leading to strabismus and
Ophthalmoplegia;
Increased intraocular pressure;
When assessing colour vision in GO, what tests should we use?
100 hue
D15
Ishihara – more commonly used in congenital cases as it may not be sensitive enough to indicate lesser issues in CV
Should we assess contrast sensitivity in GO?
Yes
What should we look at with pupils in GO patients?
Check for optic nerve damage which may occur in ON compression through RAPD
What are some clinical signs of ON compression?
Constitute an ocular emergency
- Reduced VA
- Reduced CS
- Reduced colour vision
- Visual field defect
- RAPD (Relative Afferent Pupillary Defect)
- Optic disc exam – normal / swelling / pallor
Optic neuropathy – approx 5%
What is the modified UFOF?
This modified technique for measuring UFOF gives additional quantified information on the vertical extraocular muscles. Its reliability is equivalent to that of other measurement methods in healthy subjects and in those with restricted motility. It can be performed rapidly, minimizing patient discomfort, and may be particularly helpful in the sequential assessment of GO. The data on patients with GO suggest that a difference of 8° is required to detect significant change.
What differential diagnosis do we prescribe to GO in acute presentations?
- Carotid-cavernous Fistula
- Myositic pseudotumour
- Ocular myositis
What differential diagnosis do we prescribe to GO in Chronic presentations?
- Metastatic tumours
- Lymphoma
- Chronic progressive external ophthalmoplegia (CPEO)
? + Myasthenia
- Fatigue
- Variable ptosis
- Limitation not persisting on FDT
What classification systems are there for GO?
- Werner’s classification
- Mourit’s Clinical Activity Score (CAS)
- EUGOGO
What are the management options in GO?
- Encourage use of AHP
- Prisms - temporary / incorporated
- Occlusion – blenderm / patch / frosted lens
- BT
- Surgery
What are the main reasons for surgical intervention in GO?
- ON compression requires orbital surgery
- Strabismus/Ocular Issues requires realignment surgery
- Lid problems requires lid surgery
How can ON compression occur in GO?
Retrobulbar adipose tissue is increased in volume and may have lymphocytic infiltrate.
Increased volume of orbital contents typically leads to exophthalmos/proptosis
May lead to ON compression /neuropathy
What 3 options are there for treating optic neuropathy?
- Steroids
- Radiation
- Orbital Decompression
What steroids do we use in GO?
IV Methylprednisolone
What are the indications for steroid use in GO?
- Acute inflammatory disease
- Optic neuropathy - mild VA loss
- Recent onset <6m, predominantly severe soft tissue signs
- Following other treatments
pre / post decompression
Why would we combine steroids and Azathioprine?
- Another immunosuppressant
- Allows reduction of steroid if prolonged large doses – reduces side effects of steroids
- Effects modest
What are the benefits for using Radiation in GO?
- Well tolerated
- No short term side affects
- Usually no long term side affects*
- Reduces symptoms but not the course of the disease
How do we do Radiation Therapy in GO?
Referral to oncologist
Planning with CT scans
Face mask to immobilise patient and allow accurate delivery of radiation
Daily doses of radiation beams directed at the orbital area
Low dose of 2Gy x ten days
Destroys lymphocytes and fibroblasts reducing auto-immune response
First weeks often in conjunction with steroids
Increased chemosis in first week of treatment
Improvement after 2 weeks of treatment
If no improvement in 1 month of treatment unlikely to improve
What are the drawbacks of Radiotherapy in GO?
2 weeks of treatment delivered daily (10 days)
Can feel intensive for patient
It may take up to a year to notice the full effect.
Risk of cataract and dry eyes
How does Radiotherapy in GO work?
Reduce the cells which cause the inflammation and so reduce the swelling behind the eye.
When is Radiation Therapy indicated in GO?
- Severe acute soft tissue signs - (steroids initially as radiotherapy not immediate)
- Recent onset progressive proptosis
- Acute ophthalmoplegia
- Acute vision loss
- Where steroid treatment has failed
When is Radiotherapy contraindicated in GO?
- Chronic TED
- Minimal or no inflammation
- Proptosis without inflammatory changes
- Longstanding restrictive myopathy or rapid progression of disease
- Male patients / smokers
- Age >50 years
According to Mourits (1997) how successful is radiotherapy?
Patients with CAS > 4 = 80% chance of improvement
Patients with CAS < 4 = 36% chance of improvement
What is Orbital Decompression Surgery?
Operation to remove bone from the walls of the orbit (the eye socket) in order to reduce the amount of protrusion of the eye and reduce pressure!
When is orbital decompression surgery used in GO?
In sight threatening situations mainly
What Orbital Decompression types are there?
- Lateral
- Transantral
- Transfrontal
- Ethmoidal
- Maxillary
When do we do lateral orbital decompression surgery?
Moderate Proptosis
When do we do two-&-a-half wall decompression (medial wall, medial half of floor and lateral wall) decompression surgery?
Severe Proptosis
When do we do a medial one-and-a-half wall approach (medial wall and medial half of floor removed) decompression surgery?
Used after a trial of 3 daily/alternate day injections of high-dose IV methylprednisolone in patients with sight-threatening orbitopathy
When do we do orbital fat decompression alone?
Mild Proptosis
What are the complications of orbital decompression?
- Temporary lip numbness
- Sinusitis
- Orbital cellulitis
- Meningitis
- Lower lid entropian
- Blindness (very rare)
- Asymmetric correction of proptosis
- Apparent upper lid retraction
- Late enophthalmos
- Epiphora
- Diplopia
How often does strabismus occur in TED?
Occurs in 15 - 51% of patients with TED
What are some indications for strabismus surgery?
- Medical condition stable
- Eye condition stable
- Problematic diplopia
- Uncomfortable head posture
- Centralise and / or enlarge field of BSV
What’s the timing for surgery?
“Six months stability” seems a general rule that’s accepted!
In practice tend to wait longer until sure disease has stabilised
How does lid retraction occur in upper and lower lids?
- Levator palpebral superioris - muscle fibre enlargement and oedema
- Overaction of Muller’s muscle (sympathetic overaction)
- Innervation to SR and levator palpebral superioris
What drugs can we use to help in lid retraction?
Guanethidine – eye drops
Triamcinolone – oral (tablet)
What is the aim of lid retraction surgery?
Aim to leave ptotic - gradually elevates
Levator muscle procedures
Müller’s muscle procedures
Combination of above
What is lateral tarsorrphaphy?
When the outer lids are pinned together.
It’s rarely used now as not as effective but can prevent exophthalmos
What is Henderson’s operation?
A weakening of Muller’s muscle
What other options are there for lid retraction surgery?
- Levator muscle procedures; recession, tenotomy or BT
What is Blepharoplasty?
Blepharoplasty (surgical correction of a lid deformity such as peri-orbital oedema)
- Mark out excess skin
- Excise skin and orbicularis
- Remove fat
What surgery do we do for treating peri-orbital oedema?
Blepharoplasty
What are the complications of peri-orbital oedema surgery (Blepharoplasty)?
- Infection
- Bleeding
- Dry/Irritated eyes
- Difficulty closing eyelids
How might we manage issues with the cornea?
- Tape lids
- Glasses with side protection
- Hypromellose
- Steroids
- Orbital decompression
- Tarsorraphy
What is the management for Mild (CAS 1-3) GO?
- Correct thyroid function
- Eye comfort; lubricants
- Smoking cessation
- Selenium supplement
What is the management for moderate to severe GO (CAS >3)?
- IV methylprednisolone used where GO having a sufficient impact on QOL for risks to be justified
- Azathioprine as adjuvant
- Orbital radiotherapy
- Management of thyroid gland dysfunction
What is the treatment for sight threatening GO?
Orbital decompression surgery if there’s no response to medical treatment
What is Rituximab (RTX)?
A monoclonal antibody
Rituximab is a drug which depletes B cells, thus promoting antibody-dependent cellular toxicity
Used in non-Hodgkin B-cell lymphoma and rheumatoid arthritis with some very promising results
What is Teprotumumab (Tepezza)?
New medicine to treat GO
Human monoclonal antibody
Approved for use in USA in Jan 2020
Expensive - $343000 per patient for 6 months of treatment (approx. £250k)
How is Tepezza being used in GO?
Ugradar et al (2022) found:
Reverse proptosis by reducing inflammation and preventing tissue expansion
Imaging studies show reduction in EOM size
Possibly better strabismus outcomes
Teprotumumab significantly reduces proptosis, inflammation, diplopia, strabismus and orbital soft tissue volume in patients with chronic TED
Only medication that reduces the fat and muscle expansion within the orbit
Only medicine to possibly reduce ON compression
Some patients remain non-responders to treatment
What are some possible side effects of Tepezza?
Possible side effects: hearing loss, hyperglycemia, and muscle spasm
What is Grave’s Orbitopathy (GO)? What is it characterised by?
Grave’s orbitopathy is part of Graves’ disease, a systemic autoimmune disorder characterised by hyperthyroidism, orbitopathy and, in a minority of patients, pretibial myxoedema (lumpy reddish skin of the lower leg) and acropachy (finger clubbing).
What does normal control of circulating thyroid hormone rely on?
An intact hypothalamic-pituitary thyroid axis
How does the hypothalamic-pituitary-thyroid axis work?
Thyrotropin-releasing hormone is produced by the hypothalamus that acts on the anterior pituitary gland which releases thyroid stimulating hormone (TSH) which binds to TSH receptors resulting in thyroid hormone release. There’s a negative feedback loop of T4, T3 and the pituitary to regulate the amount of circulating hormone.
How does smoking increase risk of GO?
Smoking alters the function of the T-cell, known to affect the immune system or the cigarette smoke has a direct immunological effect and thus increases risk of GO and results in a more severe disease course.
What are the two phases in GO?
There are two identifiable phases; an early acute or subacute active inflammatory phase and a late inactive or cicatricial phase. Sometimes they don’t have an active phase.
What happens in the active phase of GO?
Early phase = connective tissue inflammation and activation of EOM fibroblast. The activate fibroblasts increase orbital volume by differentiating into orbital fat and increase amounts of glycoasminoglycans that attract water.
Early phase – connective tissue inflammation, corneal exposure, EOM enlargement, Muller’s muscle overaction and increased orbital volume.
In the active phase what does connective issue inflammation lead to?
Ocular redness, puffiness and mild discomfort
What happens in corneal exposure in the active phase of GO?
– Inflam agents in tears and drying of corneal epithelium from proptosis, upper eyelid retraction, poor blink pattern or reduced Bell’s phenomenon (eyes roll upwards and outwards when closed) from contracture of IR. Leads to gritty feeling, photophobia, epiphora and vision loss.
What does Increased Orbital Volume lead to in active phase GO?
Proptosis and lower eyelid retraction, corneal exposure, diplopia, compressive optic neuropathy
What does EOM Enlargement lead to in active phase GO?
Enlarged during inflammatory phase, restricting ocular movement and raising IOP. Mechanical restrictions also common and pain when looking in the direction of the limited movement.
Hypotropia is most common in the more affected eye, sometimes associated with esotropia
AHP, commonly head up, is often adopted with or without a head turn either to get BSV or avoid uncomfortable gaze position or to facilitate fixation when there’s marked bilateral restriction of movement.
Enlarged vertical fusion amplitude often develops to allow patients to control large vertical deviations
Diplopia
What is the most common deviation type in GO?
Hypotropia is most common in the more affected eye, sometimes associated with esotropia
What is the most common AHP in GO?
AHP, commonly head up, is often adopted with or without a head turn either to get BSV or avoid uncomfortable gaze position or to facilitate fixation when there’s marked bilateral restriction of movement.
Do people with GO have increased vertical fusion range?
Yes - Enlarged vertical fusion amplitude often develops to allow patients to control large vertical deviations
What can Muller’s Muscle overaction lead to in active phase GO?
Upper eyelid retraction and upper eyelid lag (lag occurs on down-gaze)
What does the CAS score say about when someone is in the active or inactive phase of GO?
The clinical activity score (CAS) quantities disease activity. A CAS of <= 3 indicates inactive disease and warrants a wait and watch approach whereas >=4 indicates active disease, warranting treatment with immunosuppression and/or radiotherapy
What does the NOSPECS score say about GO?
1) Sight-threatening GO: patients with thyroid optic neuropathy and/or corneal breakdown. Warrants immediate intervention.
2) Moderate-to-severe GO: without sight-threat but with sufficient impact on daily life to justify immunosuppression risks or surgical intervention. Lid retraction >2mm, mod-severe soft tissue involvement, exophthalmos, >3mm above normal for race and gender, diplopia
3) Mild GO: minor impact on daily life. Only usually have 1 of the above. Don’t usually have diplopia and corneal exposure is responsive to lubricants.
How do we investigate optic nerve function?
Investigating optic nerve function:
Best corrected VA
Colour Vision
RAPD
Automated visual fields
Serial visual evoked potentials (objective assessment of the optic nerve function)
What simple advice can we give for treatment during the active phase?
During the active phase, advice is to sleep with the head of the bed raised to reduce ocular swelling in the morning.
Reinforce no smoking.
What treatment should we give during active phase GO?
Surgery to EOMs and eyelids is not indicated during the active phase of GO but instead should provide symptomatic treatment for corneal exposure and diplopia and systemic therapy based on CAS and NOSPECS score.
What corneal exposure treatment do we do in mild cases?
Mild = artificial tear preparations with protective sidepieces to glasses which reduces tear evaporation.
What corneal exposure treatment do we do in marked proptosis and eyelid retraction?
If with marked proptosis and eyelid retraction BT can be used into LPS to reduce retraction or into IR muscle which indirectly effects upper eyelid retraction.
What systemic treatments can we use in active phase GO?
Immunosuppression
Orbital Radiotherapy
Orbital Decompression
Why do we use immunosuppressants in active phase GO?
Intravenous steroids are more effective than oral steroids and have more rapid onset. Aim to reduce soft tissue swelling, EOM restriction and relieve optic nerve compression.
Why do we use Orbital Radiotherapy in active phase GO?
To reduce the size of affected EOM to relieve orbital pressure. Not immediate so have to use steroids in the interim if vision is at risk. Contraindicated in young patients due to increased risk of cancer in later years and should be avoided in patients with diabetic and hypertensive retinopathy.
What treatments, and when, do we do during inactive phase GO?
Rehabilitative surgery can be considered provided the patient has had a minimum of 6 months of stable thyroid function and GO. Orbital decompression should be considered first because of influence on ocular motility and eyelid position, followed by strabismus surgery and then eyelid reconstruction.
What are the complications of Orbital Decompression?
- If they have preoperative strabismus they’re at greater risk of diplopia being made worse after.
- Lateral wall decompression has low risk of postop diplopia but least effective in reducing proptosis
- Sig. restriction of movement postop
Should be carried out before EOM surgery
What is the clinical activity score (CAS) based on?
The clinical signs of inflammation being pain, redness, swelling and impaired function
10 items with a point for each one
First visit score only 1-7, review visits score 1 -10
According to the clinical activity score (CAS) what is considered mild, moderate and severe?
Mild: Mourits Activity score 4
Moderate: Mourits Activity 4-6
Severe: Mourits Activity 7 – 10 or presence of vision threatening signs (Exposure, optic nerve oedema, or RAPD)
What does EUGOGO stand for?
European Group on Grave’s Orbitopathy
What is the EUGOGO classification of GO?
Combines CAS with measures of severity
> = 3 means active GO
