Graves orbitoptathy Flashcards
what is the incidence of graves orbitopathy
The estimated incidence of GO is 16 women or 3 men per 100,000 person per year
Prevalence: 400 000 people in the UK with GO
Compare with Type 2 diabetes:
One in ten people over 40 in theUKare now living with a diagnosis of Type 2diabetes
Prevalence: 3.4 million people in the UK with a diagnosis of Type 2diabetes
what is the incidence of graves orbitopathy
The estimated incidence of GO is 16 women or 3 men per 100,000 person per year
Prevalence: 400 000 people in the UK with GO
Compare with Type 2 diabetes:
One in ten people over 40 in theUKare now living with a diagnosis of Type 2diabetes
Prevalence: 3.4 million people in the UK with a diagnosis of Type 2diabetes
describe the thyroid gland
Highly vascular endocrine organ
Lower neck anterior to trachea between the sternocleidomastoid muscles
Consists of densely packed follicles
Function
concentrates iodide to form thyroid hormones
Thyroid hormones synthesised and stored in the follicles
what does the thyroid hormone release
TRH stimulates release of TSH
TSH is secreted by the anterior pituitary and stimulates secretion of
T3 – Tri-iodothyronine
T4 - Tetra-iodothyronine (Thyroxine)
T3 & T4 secreted into bloodstream:
bound to plasma proteins
free form - intracellular
what are the role of thyroid hormones
Growth and Development
rate of growth of many tissues
maturation of CNS and bones
regulation of synthesis of some respiratory enzymes
Metabolic Effects
regulation of basal metabolic rate
regulation of water and ion transport
regulation of calcium and phosphorus metabolism
regulation of cholesterol and fat metabolism
regulation of nitrogen metabolism
what is hyperthyroidism
Enlarged thyroid gland – goitre
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 is hypothyroid (under active)
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
Goitre
More frequent periods, increased menstrual flow
Difficulty concentrating – brain fog
Hoarse voice
Muscle cramps
how to diagnose thyroid abnormalities
TSH – (considered outside normal if lower than 0.3 or higher than 3.0)
- Calculated free T4 index (10-20 pmol/L)
- Thyroid-stimulating immunoglobulin (TSI)
- Anti-thyroid antibodies
- Serum T3 (2.5 – 5.3 pmol/L)
what is the management for hyperthyroidism
Drug therapy
Radioactive iodine treatment
Thyroidectomy
what drugs are used for hyperthyroidism
Drug therapy
Thinomines (Carbimazole, Methamizole, Propylthiouracil) Interfere with thyroid hormone synthesis by blocking the build up of iodine. Most effective if the onset of disease within 1 year
Steroids (oral Prednisone) Decreases secretion of thyroid hormones and peripheral conversion of T4 and T3. Used in severe cases
Immunosuppressants (Azathioprine or Rituximab)
how is radioactive iodine used for hyperthyroidism
Radioactive iodine
- Radioactive iodine introduced to the body and taken up by the thyroid gland. Normal cell division and function is disturbed.
- Generally used on patients over 45 years of age or in younger patients if other treatments are contraindicated.
- 20% of patients become hypothyroid within 1 year of the treatment
- Ocular symptoms have been found to worsen following this treatment (Acharya 2008)
what does radioactive iodine and corticosteroids do in hyperthyroidsim
Prevents progression of GO in patients with pre-existing eye disease
Eye signs worsened in 6 months in:
15% after RI
2.7% after antithyroid drugs (carbimazole)
None who had RI and prednisone
what is a thyroidetomy in hyperhyroidism
removal of thyroid gland
Removal of most of the thyroid gland
Reduces hormone production
Post-op recurrence in 10-15% of patients
Post-op hypothyroidism in 40% of patients
Usually performed in younger patients
what medication is given for 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
what percentage of people with graves disease have graves orbitopathy
Approx 40% of GD have GO
define graves orbitopathy
Auto-immune disease
Disease of the orbit affecting the orbital soft tissues
Closely correlated to auto-immune (systemic) thyroid disease (Graves’ Disease)
Prescence of circulating antibodies that bind and stimulate the thyroid hormone receptor (TSH) leading to hyperthyroidism and goitre.
what are the risk factors for graves disease
Genetic
Environmental
Smoking
Stress
Immune factors
what populations are most affected by graves orbitopathy
Male / female
female - 86%
16/10 000 women
3/10 000 men
Age
women 45-50 years
men 50-55 years (> severity)
Greater severity with age
(Lin et al 2008)
what are the risk factors for smoking
Smoking
Main known risk factor 7-8 fold increase
Severity of eye signs and symptoms increased with increased tobacco consumption (Shine et al, 1990 Lancet)
what type of thyroid problem do most people with graves orbitopathy have
Hyperthyroidism 90%
Hypothyroid 3-5%
Euthyroid 5% ? Sensitivity of detection
Patients hyperthyroid without eye signs = 50-60%
80-90% have EOM changes on CT imaging
what is the natural history of graves orbitopaty
natural history is called bundles curve
active phase where their is inflammation for 1-3 years and then fibrosis = inactive phase 3 years and later where fibrosis occurs
what are the stages of graves orbitopathy
Wet / Congestive / Inflammatory / Active phase
Eyes are painful and red
Can last around 3 years
Dry / Fibrotic / Inactive phase
Eyes are white
Painless, restrictive myopathy may be present
what is the history of graves orbitiopathy
Signs
Lid retraction
– 90-98%
Lid lag – von Graefe’s sign
Exophthalmos (proptosis)
Lid oedema
Periorbital oedema
Epiphora
Visual loss – Dysthyroid optic neuropathy DON ~5%
Chemosis
Strabismus – Eso/ Hypo
AHP
Thyroid disease
what lid symptoms do people with graves have
upper lid , lower lid and palpebral appeture lid retraction
how to 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
what is used to measure exopthalomos/ propotosis
hertel mirrpor exopthalmoeter
what are the normal ranges for exopthalmost
12-21
12-33
12-20
12-24
what do you need to note when measuring exopthalmos
Bilateral
Asymmetric
Unilateral ?
Normal
exophthalmometry >22mm or
asymmetry greater than 3mm
Amount depends on severity of disease/ inflammation and structure of anterior orbital septum
Axial / non-axial
what happens during the wet/actve phase of ted
Wet phase – Active phase
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 restriced motility and diplopia
This phase tends to settle within 3 years
what happens to the eom during the dry/fibrotic phase
Fibrotic Phase / Dry Phase
Muscle fibres become distorted, contracted and damaged due to fibrosis
Eyes are white and quiet
Painless, restrictive myopathy may be present
what can be seen on a MRI of eom
enlarged by 10 times muscle but not tendon
what would you see on ocular movements
Limitation
Reversal
Saccades
Cog wheel pursuit
Fatigue
Pain
Retraction
Bilateral involvement
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 pt unable to elevate as eye becomes tethered down
what can help diagnosis
mri scans can aid diagnosis
what is graves orbitopathy
GO is an autoimmune condition diagnosed by blood tests along with clinical history and assessment
how many phases of ted are there
3 phases
what type of thyroid defect to people usually have with ted
Patients are usually hyperthyroid, but can be hypothyroid or euthyroid
what position of gaze is usually affected
Upgaze typically affected first
Multiple distinctive eye signs
Can result in painful eye movements, diplopia or visual loss
why is up gaze typically affected first
because of inferior rectus enlargement
when can ted be diagnosed
TED can be diagnosed when two of the following three signs are present:
clinical orbital signs (lid retraction / proptosis / optic neuropathy)
laboratory tests (positive bloods for autoantibodies)
typical orbital imaging finding (swollen EOMs)
what are the signs and symptoms of ted in the mild/early stage
symptons
Foreign body sensation;
dry eye; excessive tearing; conjunctival or eyelid redness
and swelling;
blurred vision;
retro-orbital pain
signs
Mild, soft tissue inflammation;
Dilated conjunctival vasculature;
keratoconjunctivitis;
corneal staining
in moderate ted what are the signs and symptons
pulling sensation around the eye
eyelid redness and welling , eyelid retraction and bulging in the eyes
swelling of eom
chemises
eyelid oedema
proptosis
what are the advanced symptoms of ted
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)
Progressive proptosis with eyelid retraction;
corneal ulceration;
inflammation of extraocular muscles and scarring leading to strabismus and
ophthalmoplegia;
increased intraocular pressure;
what is the role of an orthoptist in ted
Diagnosis
Assessment of visual function
Document effects on ocular muscles
Record disease progress
Establish when ocular signs stabilise
Explanation and information and signposting
Eliminate symptoms / diplopia
Plan long term management
§
what is needed in orthoptic investigation
Assess visual function
CT
Note any AHP
OM + measure PA
BSV tests (inc VPFR)
PCT + torsion (synoptophore or torsionometer)
Uniocular field of fixation
Field of BSV
?Lees screen / Hess (not useful in bilateral cases)
what tests are done to assess visual function
contrast sensitivity
visual fields
pupils
what are clinical signs of optic nerve compression
on compression = ocular emergency
reduced va
reduced cs
reduced colour vision
visual field defect
rapid - relative afferent pupillary defect
optic disc exam - normal/ serving / pallor
optic neuropathy - approx 5%
what is a modified unioocualr field of fixation
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, particularly where several observers are involved, and this has important implications for the monitoring of GO, especially when using the CAS.
what can graves orbitopathy be differenitally diagnosed
Acute presentation
Carotid-cavernous Fistula
Myositic pseudotumour
Ocular myositis
Leukemia see Pai et al 2011 for case study
Chronic presentation
Metastatic tumours
Lymphoma
Chronic progressive external ophthalmoplegia
Myasthenia
Fatigue
Variable ptosis
Limitation not persisting on FDT
what is wrens classification of myasthenia
1 None
2 Only signs, no symptoms
3 Soft tissue involvement
4 Proptosis
5 Extraocular muscle involvement
6 Corneal involvement
7 Sight loss
what is mouritis clinical activity score
First visit score only 1-7, review visits score 1-10
1. Painful oppressive feeling on or behind the globe in last 4 weeks
2. Pain on eye movement in last 4 weeks
3. Redness of eye lid
4. Diffuse redness on conjunctiva covering at least 1 quad
5. Swelling of lid (erythema)
6. Chemosis
7. Swollen caruncle
8. Increase in proptosis >2mm in 1-3 months
9. Reduced motility 5 degrees
10. Reduction in VA of 1 line with PH over 3 months
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
how is graves classified by eugogo
sight threatening graves - patients with dysthyroid optic neuropathy and corneal breakdown
moderate to sever go - patients without sight threatening go whose eye disease has sufficient impact on daily life to justify the risks of immunosuppression or surgical intervention - patients with moderate or sever soft tissue involvement usually have one of the following lid retraction exothalmos
mild go - patients with mild have a minor impact - insuffiecnt for surgery , minor lid retraction/exopthalmos or soft tissue involevemt, corneal exposure responsive to lubricants
what are the management options for people
Orthoptic / conservative
Surgical:
Sight saving
Strabismus
Lid
what are the aims of orthoptic management
Preserve visual function
Keep patient comfortable and symptom free
Allow comfortable BSV in pp and reading position where possible
what are the orthoptic management options for ahp
Encourage use of AHP
Prisms - temporary / incorporated
Occlusion – blenderm / patch / frosted lens
Surgery
BT
what needs further imput from an opthalmologist (non urgently)
Non urgently
“Gritty” sensation and/or eyes sensitive to light
Progressive change in eye appearance
Pain in or behind the eyes
Diplopia
Eyelid retraction
Swelling/redness of eyelids and/or conjunctiva
Restriction of eye movement
Tilting of head to avoid double vision
what needs further imput from an ophthalmologist (urgently)
Urgently
Sudden deterioration in vision
Problems with colour vision
Sudden onset proptosis
Failure of full eye closure
Corneal opacity
Abnormal disc possible described on referral optometrist/eye casualty
what surgical intervention options are there for people with graves
ON compression – orbital surgery
2. Strabismus / ocular realignment surgery
3. Lid surgery
Multidisciplinary approach:
May involve maxillary facial surgeons, strabismologist and orbital surgeons
what orbital changes occur to people with graves
Orbital changes
Retrobulbar adipose tissue is increased in volume and may have lymphocytic infiltrate.
Increased volume of orbital contents typically leads to exophthalmos
May lead to ON compression / neuropathy
what can be done to treat optic neuropathy
steroids
radiation
orbital decompression
what steroids are used and what are its indications for use
Mechanisms
anti-inflammatory
immune response - immunosuppressive
decrease mucopolysaccharide production by orbital fibroblasts
Indications
acute inflammatory disease
optic neuropathy - mild VA loss
recent onset <6m, predominantly severe soft tissue signs
following other treatments
pre / post decompression
why is steroids and azathioprine prescribed
Another immunosuppressant
Allows reduction of steroid if prolonged large doses – reduces side effects of steroids
Effects modest
what are the pros and cons of radiation therapy
Well tolerated
no short term side affects
usually no long term side affects
Reduces symptoms but not the course of the disease
Referral to oncologist
face mask to immobilise patient and allow accurate delivery of radiation
planning with CT
2 weeks of treatment delivered daily
50 centres, ? priority
what is radiotherapy
reduce the cells which cause the inflammation and so reduce the swelling behind the eye.
It may take up to a year to notice the full effect.
ten radiotherapy treatments given over two weeks
face mask to immobilise patient and allow accurate delivery of radiation
Risk of cataract
Risk of dry eyes
how is radiation therapy implemented
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
in what type of patients is radiation therapy indicated
Indicated in patients with
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
what effect does radiotherapy treatment have - clincical activity score
Mourits 1997
Success of radiotherapy treatment
Patients with CAS > 4 = 80% chance of improvement
Patients with CAS < 4 = 36% chance of improvement
what effect does radiotherapy treatment have - clincical activity score
Mourits 1997
Success of radiotherapy treatment
Patients with CAS > 4 = 80% chance of improvement
Patients with CAS < 4 = 36% chance of improvement
what is orbital decompression and its indications for use
an operation to remove bone from the walls of the orbit (the eye socket) in order to reduce the amount of protrusion of the eye
Indications
sight threatening situations
Improve cosmesis (40%, Lyons & Rootman 1994)
what are the types of orbital decompression
Lateral
2. Transantral
3. Transfrontal
4. Ethmoidal
5. Maxillary
what type of orbital decompression is indicated for what disease
lateral orbital (single) for moderated
orbital fat decompression alone for mild proptosis
what are the complications of orbital decompression
Temporary lip numbness Asymmetric correction of proptosis
Sinusitis* Apparent upper lid retraction
Orbital cellulitis* Late endophthalmos
Meningitis* Epiphora
Lower lid entropian Diplopia
Blindness 1/10000
- 10/7 antibiotics
is there an advantage for early rehabilitative decompression
No advantage in having early rehabilitative decompression for aesthetics
Associated with higher risk of diplopia
what are ted’s associations with strabismus
Occurs in 15-51% of patients with TED
Diplopia which impacts on work / driving / ability to function independently
Vertical
what are indications for strabismus surgery
Medical condition stable
Eye condition stable
Problematic diplopia
Uncomfortable head posture
Centralise and / or enlarge field of BSV
what eom surgery is done
Extraocular Muscle Surgery
Forced duction testing - pre, intra and post op
Recession of muscles, avoid resections
Free adhesions
Undercorrection
Adjustable sutures – allow fine tuning and adjustment of AHP
Inferior rectus dissected from attachments to lower lid
Inferior rectus recession
Medial rectus recessions
when is surgery usually done
Six months stability”
In practice tend to wait longer until sure disease has stabilised
what happens to the lids during surgery
Lid retraction (upper and lower lid)
Levator palpebral superioris - muscle fibre enlargement and oedema - rarely affects function
Overaction of Muller’s muscle (sympathetic overaction)
Innervation to SR and levator palpebral superioris
how does drug effect lid retraction
Guanethidine
Topical (drops) alpha-adrenergic
blocking agent
Triamcinolone - oral
anti-inflammatory / anti-
fibrotic effect
what procedures are done on people with lid retraction
Levator muscle procedures
Müller’s muscle procedures
Combination of above
Aim to leave ptotic - gradually elevates
Lateral tarsorrhaphy
rarely used now
not very effective
may prevent exophthalmos
what levator muscle procedures would be done
Levator muscle procedures
recession
tenotomy
BT - Ozkan et al, 1997 4 patients (8 eyes)
effective for 3-4 months
Noah & Eckstein (2007) 5-15 IU BT to levator or Mullers muscle
Transient diplopia or ptosis in up to 20% cases
what surgery is done for lid retraction
Lid retraction – Henderson’s operationWeakening of Müller’s muscle
what is done for peri- orbital odema
Blepharoplasty (surgical correction of a lid deformity)
mark out excess skin
excise skin and orbicularis
remove fat
Complications
Infection
Bleeding
Dry / irritated eyes
Difficulty closing eyelids
what can be done for the cornea
Tape lids
Glasses with side protection
hypromellose
Steroids
Orbital decompression
Tarsorraphy
what is rituximab
Rituximab is a drug which depletes B cells promoting antibody-dependent cellular toxicity
It was used initially to treat non-Hodgkin B-cell lymphoma and more recently has benefited individuals with rheumatoid arthritis.
Sustained resolution of Optic neuropathy & inflamation
But
proptosis and strabismus were unimproved
by RTX
no sufficient evidence to support its effectiveness
what is 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)
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
Possible side effects: hearing loss, hyperglycemia, and muscle spasm
