Transcript THYROID EYE DISEASE - Diabetic Retinopathy

THYROID EYE DISEASE
Autoimmune disorder
characterised by infiltrative
orbitopathy
Graves' disease

Graves' disease is the most common thyroid
abnormality associated with thyroid
orbitopathy, but other disorders of the thyroid
can have similar ocular manifestations. These
include Hashimoto's thyroiditis, thyroid
carcinoma, primary hyperthyroidism, and
neck irradiation.
 Approximately 40% of patients with Graves'
disease have or will develop thyroid
orbitopathy.
THYROID EYE DISEASE
 Associated
with normal to abnormal
thyroid function which may coexist,
precede or follow the orbitopathy.
 Related to but not the same as Graves
Ophthalmopathy (GO) The natural
history was described by Rundle and
Wilson in 1945
Thyroid status
Of those patients with thyroid orbitopathy,
approximately 80% are clinically hyperthyroid
and 20% are clinically euthyroid.4 Most
patients with euthyroid Graves' orbitopathy,
however, have some detectable laboratory
evidence of subclinical hyperthyroidism.
 Both hyperthyroid and euthyroid patients can
develop clinical signs and symptoms of
thyroid orbitopathy. In general, patients with
euthyroid Graves' disease tend to have less
severe orbitopathy
THYROID EYE DISEASE



The goal is to identify and treat patients who are at
particular risk of sight threatening complications. The
disease has a finite period of activity until it becomes
burnt out.The yellow region shows the early phase
where there is the best response to treatment.
Type 1 younger age group, whiter eyes with
proptosis. Inflammation is mostly in orbital fat not
muscles.
Type 11 older patient with red eyes, severe sight
threatening disease, tobacco addiction is frequent.
General Considerations

Severe exophthalmos and compressive optic
neuropathy are slightly more common in older
men.
 There appears to be an increased prevalence
of thyroid disease in smokers, for whom the
relative risk of developing Graves' orbitopathy
is twice as high as it is for nonsmokers.
 The reason for this difference is not known,
but one possibility is that the decreased
immunosuppression in smokers may allow
greater expression of autoimmune processes.
PATHOGENESIS



Type II reaction:- autoimmune antibodies target somatic tissues
such as extraocular muscles causing an antigen-antibody
reaction. A large number of lymphokines are implicated in the
inflammatory process.
Inflammation results in production of mucopolysaccharides by
fibroblasts leading to swelling followed by collagen production
resulting in restriction.
There is a high concentration of macrophages in the inferior
rectus muscle as well as CD4+ memory T cells and CD8 T cells.
This may account for the clinical observation of maximal disease
activity in this muscle.
ETIOLOGY

In 1956, Adams and Purves isolated a factor in the serum of
patients with Graves' hyperthyroidism that caused stimulation of
the animal thyroid gland. This factor was very similar to TSH but
had a longer half-life. It was therefore called long-acting thyroid
stimulator (LATS).

In 1964, Kriss and colleagues showed that LATS had the
structure of an IgG immunoglobulin and its action could be
neutralized by thyroid tissue, indicating that it was an antibody.

Further experiments showed that the antibody was directed
against the receptor for TSH on the follicular cell of the thyroid
gland.
Thyrotropin receptor
antibodies (TRAb).
 antibodies
were originally classified into
those with stimulatory properties called
thyroid-stimulating immunoglobulin or
antibody (TSI, TSAb) and those with
inhibitory properties called TSH-binding
inhibiting immunoglobulin or antibody
(TBII, TBIA). Both of these groups are
now referred to as thyrotropin receptor
antibodies (TRAb).
PHYSIOLOGY
 Hypothalamus
TRH pituitary TSH
thyroid T3 and T4
 85% of T4 converted to T3 in tissues.
 T3 has 5 times the activity of T4.
Pathology

The predominant orbital pathology is
inflammation of the orbital soft tissues and
extraocular muscles. This immune-mediated
inflammation consists mostly of lymphocytes
and plasma cells, with a scattering of mast
cells. These inflammatory changes differ from
the more exuberant lymphocytic infiltration of
the orbital fat and muscles, including their
tendinous insertions seen in orbital
pseudotumor
Pathology

The earliest change in extraocular muscles
appears to be inflammation of the endomysial
connective tissues, which stimulates
endomysial fibroblasts to produce first
hyaluronic acid and then collagen. In the
acute stage there is inflammation, edema,
and deposition of glycosaminoglycans.
Eventually there is tethering of orbital tissues
due to fibroblast proliferation.
CLINICAL

(orbitopathy in general is worst in the older age groups.)



LID RETRACTION1. sympathetic overactivity2. infiltration of levator / SR complex3.
hypotropia (retraction disappears on downgaze)
SIGNS:- Dalrymples (lid retraction), von Graefe (lid lag), Kocher´s (staring appearance)




INFILTRATION
1. soft tissue involvement :- chemosis, conjunctival injection over the recti insertions, puffy
lids



Superior limbic keratoconjunctivitis (SLK) due to redundant conjunctiva





2. muscle involvement :- diplopia due to restriction.
Order of involvement IR, MR, SR (LR)
Braley´s sign = increased IOP on upgaze (>4mmHg)



3. proptosis :- TED is the commonest cause of unilateral or bilateral proptosis
Sight Threatening
Complications




optic nerve compression :- <5% affected, due to
compression of orbital apex by enlarged EOM. Look
for decreased VA, colour vision defects, arcuate or
central scotomata, swollen optic disc. Confirmation
by orbital CT.
Treatment by medical or surgical decompression.
corneal exposure:- potentially serious:- treat with
lubricants, lid taping, tarsorrhaphy, decompression
less common causes of visual loss:- glaucoma,
vascular compression
Corneal involvement

Corneal involvement due to exposure keratitis
may result from proptosis, upper eyelid
retraction, lower eyelid retraction,
lagophthalmos, or a combination of these. A
primary lacrimal gland dysfunction may also
be present in Graves' orbitopathy. Although
still speculative, there is some evidence of a
change in the protein composition of tears in
patients with thyroid orbitopathy. This change
might be caused by an altered rate of tear
production or by a general change in tear
composition
CLINICAL ASSESSMENT

MOURITS CLASSIFICATION Indicates position on Rundles curve (the
score reduces as inflammation decreases).Parameters of disease
activity: Integrated severity score of Graves ophthalmopathy
(GO).Oppressive feelingPain on deviation from primary positn, redness
of lids (ie. recent inflammation), diffuse redness of conjunctiva,
chemosis, swollen caruncle, oedema of eyelids, Proptosis (increase of
2mm or more)....

WERNER´S CLASSIFICATION Indicates the damage level (so the
score may not reverse as activity diminishes).0 Nil (no symptoms or
signs).1 Only signs of: a) stare b) lid lag,2. Soft tissue involvement: 0)
absent a) minimal b) moderate c) marked.3 Proptosis of 3mm or more:
0) absent a) 3-4 mm b) 5-7 mm c) 8 or more mm.4 Diplopia: 0) absent
a) limitation at extremes of gaze b) evident restriction of motion c)
fixation of globe.5 Corneal involvement: 0) absent a) SPE b) corneal
ulceration, c) necrosis or perforation.6 Sight loss (due to optic nerve):
0) absent a) 20/20-20/60 b)20/70-20/200 c)Worse than 20/200.
THYROID EYE DISEASE


LID RETRACTION1.
sympathetic overactivity
infiltration of levator /
SR complex. hypotropia
(retraction disappears
on downgaze)
SIGNS:- Dalrymples
(lid retraction), von
Graefe (lid lag),
Kocher´s (staring
appearance)
THYROID EYE DISEASE

INFILTRATION
 1. soft tissue
involvement :chemosis,
conjunctival injection
over the recti
insertions, puffy lids
THYROID EYE DISEASE

Superior limbic
keratoconjunctivitis
(SLK)
Optic neuropathy with visual
loss



The prevalence of optic neuropathy with visual loss in
patients with thyroid orbitopathy is less than 5%.
Optic neuropathy is, however, the most common
cause of blindness secondary to thyroid orbitopathy.
Its onset is often insidious and may be masked by
other symptoms. These patients are usually older
(age 50 to 70) are more frequently male, have a later
onset of thyroid disease, and more often have
diabetes.
Optic neuropathy is usually bilateral, but up to one
third of cases may be unilateral.
Optic neuropathy

Although a history of decreased vision should be carefully
sought, it is important to realize that optic neuropathy can occur
in a significant number (18%) of patients with visual acuities in
the range of 20/20 to 20/25 (6/6 to 6/7.5).*An afferent pupillary
defect is present in 35%. An abnormal disc (either swollen or
pale) is seen in only 52%. Visual field defects are present in
66%.Other tests that can be useful include color vision testing
and visual evoked potentials (VEPs). The Farnsworth-Munsell
100-hue test is a sensitive indicator of optic nerve dysfunction,
but pseudoisochromatic screening procedures (e.g.,Ishihara
plates) rarely identify an acquired color defect unless optic
neuropathy is severe.The pattern reversal VEP is very sensitive
at detecting early optic neuropathy and may be a useful means
of following patients after treatment.
Intraocular pressure


The increased intraocular pressure measured during
upgaze in patients with thyroid orbitopathy has been
a controversial finding. When restriction of the inferior
rectus muscle occurs, the intraocular pressure may
increase by 6 mm Hg or more in upgaze as
compared with primary gaze. The increased
intraocular pressure in upgaze is a normal
phenomenon exaggerated by thyroid orbitopathy
In patients with severe infiltrative disease there is an
increased pressure on upgaze as compared with
normal controls and patients with mild disease. It is
often not an indicator of early disease because it
occurs infrequently in patients with minimal eye
findings
INVESTIGATION



SEROLOGICALT3 (hyperthyroid)T4 TSH
(hypothyroid)TSI (thyroid stimulating
immunoglobulin).
RADIOLOGICAL TESTSOrbital CT (enlarged muscle
belly, tendon normal). Coca-Cola bottle sign = muscle
swelling deforming ethmoidal bones.MRI T2 showing
oedema of muscles; repeating the scan in different
positions of gaze can create a pseudo-video of eye
movements (for assessment of muscle restriction).
RADIOISOTOPE TESTS Octreoscan: quantitative
uptake of radio-labelled octreotide (which is a
somatostatin analogue).
VISUAL FIELD

A visual field should be performed in all
patients suspected to have optic neuropathy
and is useful when following patients after
initiation of treatment. Characteristically, a
central scotoma or an inferior altitudinal
defect is seen in cases of compressive optic
neuropathy. Other visual field defects include
an enlarged blind spot, paracentral scotoma,
nerve fiber bundle defect, or generalized
constriction.
ULTRASONOGRAPHY


Ultrasonography can be useful to detect early thyroid disease in
patients with equivocal laboratory tests. Most patients with
Graves' disease, even those without overt eye findings, have
ultrasonographic evidence of extraocular muscle involvement.46
Ultrasonography is believed by some to be more accurate than
CT in detecting enlargement of the extraocular muscles. Also,
visualization of the tendinous insertions onto the globe may be
more accurately assessed using ultrasonography when
differentiating enlarged extraocular muscles secondary to
myositis from hyperthyroid orbitopathy. Ultrasonography is,
however, less suited than CT to assessing muscle thickness at
the orbital apex.
This test may also be helpful in distinguishing between active
and inactive disease. Examination of the extraocular muscles
shows that there is a lower internal reflectivity in active as
compared with inactive disease.
CT findings in thyroid orbitopathy

The most characteristic CT finding in thyroid
orbitopathy is enlargement of the extraocular muscles
with normal tendinous insertions onto the globe.
Other findings include proptosis and anterior prolapse
of the orbital septum due to excessive orbital fat and
muscle swelling (see Fig. 4).Patients at risk for
developing optic neuropathy may also have severe
apical crowding, a dilated superior ophthalmic vein,
and anterior displacement of the lacrimal gland. Of
these, apical crowding is the most sensitive indicator
for the presence of optic neuropathy The CT scan
should be done in the coronal plane to assess the
enlargement of the extraocular muscles at the apex
because axial sections can sometimes be
misleading.
THYROID EYE DISEASE

Orbital CT (enlarged muscle
belly, tendon
normal)
MAGNETIC RESONANCE
IMAGING


MRI using 1.5 tesla units and orbital surface coils
provides optimal spatial resolution of the orbit.34 MRI
may also be useful in distinguishing between active
and inactive disease. The changing intensities
between T1- and T2-weighted images may
differentiate the active edematous from the inactive
fibrotic muscle changes.
Extraocular muscles that have acute inflammation
have longer T2 times owing to the higher water
content. Because acute inflammatory disease
responds better to radiation therapy than chronic
fibrosis, the information gained from MRI may
theoretically be helpful in choosing patients for
radiation therapy.
SYSTEMIC THYROID DISEASE

There are no good recent studies of the
natural history of untreated hyperthyroidism,
but based on older reports, Wilson56
determined that about one third of patients
spontaneously improve, one third remain
chronically hyperthyroid, and one third
progress to thyroid storm and occasionally
death. Because it is not possible to predict
which patients will spontaneously improve,
treatment of thyroid dysfunction is
recommended.
Treatment
 acute
congestive ophthalmopathy,
 compressive optic neuropathy,
 motility disorders,
 eyelid abnormalities.
TREATMENT
Acute Congestive Orbitopathy

1. SYMPTOMATIC:- elevate bedhead, lubricants, lid taping,
diuretics


2. SYSTEMIC:a) Normalise thyroid function with or without thyroxine.

Patients rendered euthyroid do improve their GO score
Tallstedt trial N Eng J Med 1992
antithyroid drugs cause a 10% chance of new or worsening GO
but radio-iodine causes a 30% chance of new or worsening GO.

Corticosteroids have been used successfully in
the treatment of acute congestive orbitopathy

Corticosteroids have been used successfully in the treatment of
acute congestive orbitopathy. They are believed to work by
altering cell-mediated immune response and diminishing the
production of mucopolysaccharides by the orbital
fibroblasts.Corticosteroids result in improvement of soft tissue
involvement and compressive optic neuropathy (but do not have
as much of an effect on diplopia Traditionally, a "short burst" of
high-dose corticosteroids has been given, usually in the range of
60 to 120 mg/day of oral prednisone. Improvement in subjective
symptoms such as pain and tearing usually occurs first, often as
early as 24 to 48 hours, followed by improvement in soft tissue
congestion and muscle function over a period of days to weeks.
Steroid Therapy
 Prednisone or prednisolone

This is standard treatment but there are frequent side effects.
No response in 35% of patients and anyway the response is
only partial. High dose steroids given early in the disease when
muscle swelling occurs does not necessarily limit the long term
course of the disease. If there is no response to high dose
steroids in the first three weeks they should be rapidly reduced.
Prednisolone + orbital radiotherapy has slightly more effect than
either alone.Use high dose pulsed methylprednisolone if urgent
optic nerve decompression is required, This is more effective
than oral treatment but it is expensive and not justified in most
cases of TED.
Radiation therapy

During the past few years, radiation therapy has reemerged as a
useful form of treatment of severe orbitopathy. The rationale for
the use of radiation therapy is reduction or elimination of the
pathogenic orbital lymphocytes, which are markedly
radiosensitive. It is also thought that the glycosaminoglycan
production by fibroblasts is reduced, thereby reducing orbital
edema, orbital tension, and conjunctival injection. Although
congestive findings improve most consistently, significant
improvement in proptosis and extraocular muscle function has
been reported.Like corticosteroids, radiation therapy is most
effective within the first year, when significant fibrotic changes
have not yet occurred. Mourits and associates,135 however,
suggest that periods of active orbital inflammation within the
long natural history of thyroid orbitopathy would benefit from
corticosteroids or radiation therapy.
Radiotherapy

RETROBULBAR RADIOTHERAPY:- Trial of
prednisone versus radiotherapy showed no
difference in clinical improvement (about
50%).The patients all tolerated retrobulbar
radiotherapy better than steroids Consider if
steroid maintenance > 25mg/ day. Best effect
in acute disease.Do not irradiate patients with
diabetes mellitus as they are more
susceptible to radiation retinopathy.2000rads/
10days, effect starts at 4 weeks, maximal 4
months.
Compressive Optic Neuropathy

Compressive optic neuropathy can cause
permanent visual loss. The treatment
possibilities include high doses of
corticosteroids, irradiation, and orbital
decompression. Some patients require only
one of these modalities, while other patients
need combined therapies.
Compressive Optic Neuropathy


As in the treatment of acute congestive thyroid
orbitopathy, radiation therapy is becoming
increasingly popular. A retrospective series of 84
patients with compressive optic neuropathy treated
with either corticosteroids or radiation therapy
supports mounting evidence that radiation therapy
may be safer and more effective than corticosteroids.
Radiation therapy, however, must be administered in
fractionated doses, which delays its beneficial effect.
For this reason, if visual dysfunction progresses while
the patient is on corticosteroids, surgical
decompression is usually recommended if the patient
is a surgical candidate.
Orbital decompression

Orbital decompression is indicated for compressive
optic neuropathy when there has been failure of or
contraindication for corticosteroids or radiation
therapy or if corticosteroid dependence has
developed with intolerable side effects. Other
indications include excessive proptosis with exposure
keratitis and corneal ulceration, pain relief, and
cosmesis for disfiguring exophthalmos. Orbital
decompression may also be indicated as a
preliminary procedure to extraocular muscle surgery
on a patient with sufficient proptosis to suggest that
decompression might ultimately be required.
Orbital decompression

A variety of approaches may be used, each
with its own advantages and associated
complications.
 The transorbital (via fornix or eyelid)
approach to inferior and medial wall
decompression is the most common
approach used by ophthalmologists. The
addition of a lateral wall advancement has the
advantage of both further increasing the
orbital volume and simultaneously improving
upper eyelid retraction; this is the technique
we prefer.
ORBITAL DECOMPRESSION

Subciliary approach.Inferior & medial wall
(6mm proptosis).Remove bone to posterior
wall maxillary sinus (5mm more posterior on
medial wall), Avoid IO neurovascular bundle,
and the anterior and posterior ethmoidal
arteries.Incise periosteum in A-P direction
posteriorly and circumferentially anteriorly.
 Complications:
 visual loss,
 A pattern ET
Motility Disorders


A major source of morbidity in thyroid orbitopathy, and the most
frequent problem associated with orbital decompression
surgery, has been strabismus. In patients with relatively minimal
degrees of ocular misalignment, diplopia can be avoided with a
compensatory head posture, Fresnel plastic press-on prisms, or
temporary occlusion. Unfortunately there is significant image
degradation as larger prisms are used, limiting their efficacy. If
there is marked asymmetry in ocular deviation in different fields
of gaze, prisms are also less effective. In some cases during the
inflammatory period, use of intramuscular botulinum toxin has
shown some efficacy.
Extraocular muscle surgery should be postponed until the
muscles are no longer inflamed and the deviation has remained
stable for at least 6 months.
Surgery

STRABISMUS SURGERY:-Aim for maximal area of fusion without
abnormal head posture.IR recession on adjustable +/- contra SR
recession
iii) EYELID SURGERY:
Upper Lid retraction - Muller´s tenotomy (<2mm), levator Z myotomy or
recession on hangback sutures, levator tenotomy +/- horns.
 Lower Lid retraction - Usually needs a spacer from donor sclera (lid
retraction X 2 = amount of sclera required)

iv) BLEPHAROPLASTY for excess skin and fat
 Ideally treatment combines a multidisciplinary coherent approach such
as
 Combined radiotherapy and immunosuppression trial
Eyelid Abnormalities



As with other thyroid eye problems, eyelid retraction will often
improve with time, and only an estimated 50% of patients with
eyelid retraction have a significant eyelid abnormality 5 years
later.
Eyelid retraction can result from excessive autonomic discharge,
levator fibrosis, or contraction of the inferior rectus muscle.
Surgical correction of eyelid abnormalities should be performed
only after orbital or extraocular muscle surgery because these
operations may change eyelid position. For example, inferior
rectus muscle restriction may cause upper eyelid retraction
because of the superior rectus/levator palpebrae superioris
overaction against the restriction. Specific techniques for repair
of eyelid retraction are discussed in other chapters.