Download china associate thyroid eye disease (ted)

CHINA ASSOCIATE
THYROID EYE DISEASE (TED)
THYROID EYE DISEASE (TED)
Revised 17 June 2002 by Dr. Georg Henneman
TED has recently been extensively reviewed.1,2 Two types of manifestations may occur in
TED: (1) functional abnormalities due to hyperactivity of the sympathetic nervous system,
produced by the thyrotoxicosis, and (2) infiltrative lesions involving the contents of the orbit. Only
the infiltrative type has a much more serious prognosis. A classification of eye signs finding used
until today is given in Table 1.
Table 1. Classification of the Ocular Changes in Graves' Disease
Classes Grades Ocular Symptoms and Signs
1
0,a,b, No signs or symptoms.
c
2
0
Only (signs limited to upper lid retraction and stare, with or without lid lag and
proptosis).
Soft tissue involvement (symptoms of excessive lacrimation, sandy sensation,
retrobulbar discomfort, and photophobia, but not diplopia); objective signs as
follows:
Absent
b
c
Minimal (edema of conjunctivae and lids, conjunctival injection, and fullness of
lids, often with orbital fat extrusion, palpable lacrimal glands, or swollen
extraocular muscle palpable beneath lower lids)
Moderate (above plus chemosis, lagopthalmos, lid fullness)
Marked
0
Proptosis associated with classes 2 to 6 only (specify if inequality of 3 mm or
more between eyes, or if progression of 3 mm or more under observation).
Absent (20 mm or less)
a
Minimal (21-23 mm)
b
Moderate (24-27 mm)
c
Marked (28 mm or more)
0
Extraocular muscle involvement (usually with diplopia)
Absent
a
3
4
b
c
Minimal (limitation of motion, evident at extremes of gaze in one or more
directions)
Moderate (evident restriction of motion without fixation of position)
Marked (fixation of position of a globe or globes)
0
Corneal involvement (primarily due to lagopthalmos)
Absent
a
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a
Minimal (stippling of cornea)
b
Moderate (ulceration)
c
Marked (clouding, necrosis, perforation)
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Sight loss (due to optic nerve involvement)
0
Absent
a Minimal (disc pallor or choking, or visual field defect; vision 20/20 to 20/60)
b Moderate (disc pallor or choking, visual field defect, 20/70 to 20/200)
c Marked (blindness, i.e. failure to perceive light; vision less than 20/200)
Note that in addition to classification by type of involvement, there is also a grading according to
severity.
Criticism has been raised with regard to this NOSPECS mnemonic (composed of the first
character describing each grade. See the table ). The criticism basically states that although
NOSPECS is "an ingenious catchy memory aid for medical students who have forgotten how to
examine a Graves' eye" it is insufficient in that it is directed towards the mean status of the eye so
that it is impossible, using this index, to evaluate isolated components separately. In other words,
although the NOSPECS index does not reflect it, important and essential components of the eye
complex may have improved or deteriorated. For this reason it was proposed that data should be
provided separately and not put together in an overall index.3 Others on the basis of the same
criticism proposed a modification of NOSPECS.4 In order to be able to assess treatment of active
inflammatory ophthalmopathy and also to predict therapeutic outcome and to select patients for
surgical or non-surgical treatment, they introduced the clinical activity score (CAS).5 (Table 2)
Table 2. Proposed Classification System to Assess Disease Activity in Thyroid Eye Disease
Pain
Painful, oppressive feeling on or behind the globe
Pain on attempted up, side, or down gaze
Redness
Redness of the eyelids
Diffuse redness of the conjunctiva
Swelling
Chemosis
Edema of the eyelid(s)
Increase proptosis of 2 mm or more during a period between 1 and 3 months
Impaired function
Decrease in visual acuity of 1 or more lines on the Snellen chart (using a pinhole) during a period
between 1 and 3 months
Decrease of eye movements in any direction equal to or more than 5 degrees during a period of
time between 1 and 3 months
One point is given for each sign present. The sum of these points defines the activity score.
(From Mourits et al., (5) with permission)
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This scoring system was shown to have a high predictive value for therapeutic outcome of
immunosuppressive treatment of infiltrative ophthalmopathy.6
SIGNS AND SYMPTOMS
Noninfiltrative Ophthalmopathy
Almost all patients with active thyrotoxicosis have some abnormality that is detectable on
careful examination of their eyes. This abnormality may be only widening of the palpebral fissure,
lag of the globe on upward gaze, or lag of the upper lid on downward gaze, producing an increase
in the visible segment of the sclerae and a bright-eyed or pop-eyed appearance. These
abnormalities cause the eyes to appear exophthalmic, but measurement may show that there is no
proptosis. Similar changes may be produced by administration of thyroid hormone or by local
action of sympathetic stimuli on Muller's superior palpebral muscle, causing spasm and retraction
of the upper lid.7 This variety of ophthalmopathy is valuable diagnostically, and although it may
have some undesirable cosmetic effect, it carries no hazard to ocular function. These findings are
corrected by control of the thyrotoxicosis, no matter which therapeutic route is followed. It should
be noted in passing that lid lag is fairly common in normal subjects.
Infiltrative Ophthalmopathy
Infiltrative ophthalmopathy is considered a characteristic and unique feature of Graves'
disease. It may coexist with the noninfiltrative ophthalmopathy described above, but it is a
separate disorder.
The signs and symptoms are produced by the following related abnormalities .
1. Edema of the orbital contents. The lids and periorbital tissues are irritated, injected, and
characteristically swollen and puffy. The lids may be erythematous. The swollen lids usually feel
firm and do not pit. There is chemosis, and edema of the scleral conjunctiva. Edematous
conjunctiva may even protrude beyond the palpebral fissure. Associated with this condition may
be excessive lacrimation and photophobia. The lacrimal gland may be almost totally destroyed by
the infiltrative lesion. Nevertheless epiphora is typical. Eye pain, irritation, and "grittiness" of the
eyes are common complaints.
2. Protrusion of the globe. It is unusual for the anterior border of the cornea to protrude normally
more than 18 mm beyond the lateral margin of the orbit. If measurements with the Leudde or
Hertel exophthalmometer show that the globe is 2 or 3 mm beyond this limit, then true proptosis is
present (normal limits may be race-dependent). Often the globes cannot be easily displaced
backward by digital pressure. When this displacement is attempted, the examiner senses that the
retrobulbar tissue is firm and unyielding. Associated with this condition, and responsible for
exophthalmos, is an increase in the volume of orbital contents including fatty tissue and muscles.
The lacrimal gland may be enlarged and palpable, and even visible. Prolapse of the globe beyond
the orbital fissure in extreme proptosis may permit a startling closure of the lids behind the globe.
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The patient or friends usually note these abnormalities as an increased prominence of the
eyes or a "staring" or "wild" expression. Occasionally there is a severe pain behind the eyes.
Exophthalmos causes the exposed conjunctivae to be more readily irritated by all noxious agents.
If the lids fail to close completely over the cornea while the patient sleeps, development of
ulceration is a hazard.
3. Infiltration of the extraocular muscles. The muscles become infiltrated, inflamed, and enlarged.
Inflammation of the muscles gives rise to an important and characteristic sign that we find helpful
in differentiating the ophthalmopathy of Graves' disease from other causes of exophthalmos. The
insertion of the swollen lateral rectus is often visible as a beefy red area at the inner and outer
canthus when the patient turns the eye laterally or medially. Normally the muscle insertion is
barely visible and is pale pink. In tumors or other retrobulbar lesions, this change in muscle
insertion is not seen. The muscle enlargement can be recognized by ultrasound or, more certainly,
by computed tomography (CT) or MRI scanning. The enlargement is almost pathognomonic of
Graves' disease.
Paralysis, or paresis, of the extraocular muscles occurs. Upward gaze is affected first and
most seriously, and loss of convergence is common. Oculomotor paralysis may be severe when
exopthalmos is minimal or absent, but the changes are usually more or less parallel. These changes
in ocular muscle function often initially produce diplopia. As the lesion progresses, a permanent
strabismus may develop, with coincident suppression of the visual image in one eye and loss of
the diplopia. Oculomotor function is occasionally lost completely.
The initial inflammatory lesion is followed gradually by recovery and fibrosis, and often the
scarred and fibrotic muscle causes a fixed strabismus that persists indefinitely unless corrected
surgically.
The oculomotor paresis is occasionally seen without significant exophthalmos or edema, and
may be difficult to distinguish from myasthenia gravis or from paresis that is part of the
neuropathy of diabetes. In such cases, it is wise to test for the presence of myasthenia by injection
of 2-10 mg edrophonium intravenously. The function of muscles damaged by the ophthalmopathy
of Graves' disease is not significantly improved during the test. Myasthenic weakness will be
corrected within 1 minute and the benefit will last for several minutes, depending on the dose.
4. Damage to the optic nerve and the retina. The retina may be injured by venous congestion or
hemorrhages. Field defects are occasionally found. Papilledema may be present, especially in
severe involvement of the eye. If the optic nerve is involved, there may be pallor of the optic disc
and a decrease in central visual acuity or field cuts, valuable and ominous signs. Blindness may
occur without protrusion of the globe. Thus, TED may have the clinical features of optic neuritis.
5. Increased intraocular pressure occurs in about 25% of patients with TED, especially in those
with infiltrative disease8. It was shown in two clinical studies that upon upgaze an increase in
intraocular pressure correlated with severity of infiltrative disease. No increase in intraocular
pressure is seen in patients with non-infiltrative ophthalmopathy and in normals.9,10
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The clinical picture is altered by subsequent complications. The edematous conjunctivae are
easily irritated by wind, smoke, or dust, and frequently become infected. Panophthalmitis is a most
feared complication. Corneal ulcers are a serious hazard and may not heal while exophthalmos
persists.
Pathology
TED involves histologic abnormalities in orbital tissues including extraocular muscles,
orbital fat, lacrimal glands and interstitial connective tissue.
On gross inspection extraocular muscles are enlarged, firm and have a rubbery consistency.
Microscopically intense infiltration is seen by mononuclear inflammatory cells like lymphocytes,
plasma cells, macrophages and mast cells. Interstitial edema is almost invariably present. The
muscle fibers may be normal using light and electron microscopy as well. In end stage
ophthalmopathy fibrosis and infiltration of extraocular muscles is present. Affection of extraocular
muscles is in most instances asymmetrical. The medial and inferior recti are more frequently
involved than the superior or lateral recti or the oblique muscles. There is controversy with regard
to changes in fat volume in TED. In contrast to earlier findings, later publications report no
significant abnormalities in volume or density of retrobulbar fat in patients with active eye disease
(for review ref. 11). Lacrimal glands often show mild mononuclear infiltration and interstitial
edema. Fibrosis however does not occur. Characteristically orbital tissues show varying degrees of
intercellular edema that has been attributed to increased concentrations of mucopolysaccharides
generated by orbital fibroblasts that are stimulated by activated lymphocytes (Fig. 1). (for general
review ref. 1,2).
Figure 1.
(a) Extraocular muscle
from a patient with
Graves' disease and
infiltrative
ophthalmopathy. The
lymphocytic infiltration
and fibrosis are
characteristic findings.
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Edematous
orbital fat and
cellular
infiltrate.
(b)
Lacrimal gland
with
mononucelar
infiltrate, fibrosis, and
an increase in ground
substance. (Figures
provided through the
courtesy of Dr. David
Cogan).
(c)
Diagnosis
The ophthalmopathy of Graves' disease must be differentiated from other conditions that
cause oculomotor weakness, proptosis, and congestive phenomena of the orbit and periorbital
tissues (Table 3). If bilateral exophthalmos occurs in patients with thyrotoxicosis, there is little
difficulty in diagnosis and one does not undertake a rigorous exclusion of other diseases. The
same holds true when the exophthalmos follows clinical thyrotoxicosis. Patients who have not
been thyrotoxic but who develop exophthalmos, especially if it is unilateral, pose a more difficult
problem.12 A search must be made for orbital or intracranial tumors. Evidence of bone erosion
suggests a tumor, although erosion of the orbital roof has been seen due to Graves'
ophthalmopathy. Evidence of encroachment upon the optic nerve should be sought. Quadrantic
defects are seen in infiltrative ophthalmopathy, but are rare. Occasionally, allergic reactions may
produce puffiness of the lids and injection and edema of the conjunctivae and sclerae, but not
exophthalmos.
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Conditions that may be confused with Graves' ophthalmopathy include pseudotumor of the
orbit, infiltrative leukemia of the orbit, trichinosis, fibrous dysplasia of bone, retrobulbar
hemangiomas, ophthalmic vein thrombosis, cavernous sinus thrombosis, sphenoid ridge
meningiomas, retrobulbar hemorrhage, and any other involvement of the orbit by malignancy.
(Table 3).
Table 3.Conditions that may be confused with TED
Pseudo-orbital tumor or cyst of the orbit
Primary orbital tumor including glioma
Metastatic tumors
Lymphomas
Developmental abnormalities of the orbit
Paget's disease
Fibrous dysplasia of bones
Meningioma
Lacrimal tumors
Nasopharynageal carcinoma
Orbital hematomas secondary to trauma
Subarachnoid hemorrhage
Subdural hematoma
Carotid-cavernous sinus fistula
Carotid aneurysm
Cavernous sinus thrombosis
Nasal sinus emphysema
Granulomatous disease
Cellulitis
Histiocytosis
Pituitary adenoma
Cushing's disease
Acromegaly
Cirrhosis
Arteritis
Trichinosis
If the clinical diagnosis is not obvious, circumstantial evidence may be obtained by
laboratory examinations. It is useful to determine thyroid-stimulating or thyrotropin-displacing
antibodies and anti thyroglobulin and peroxidase antibodies. A positive result does not certify the
cause of exophthalmos but does prove that autoimmune thyroid disease is present. TSH, FT4 and
T3 levels should be measured. Results will vary from the values typical of hyperthyroidism to the
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levels suggestive of hypothyroidism. Measurement of basal TSH in a sensitive assay may show
it suppressed. Currently, we place greatest reliance on the presence of an abnormal CT or MRI
scan showing muscle enlargement. (Fig. 2) NMR scanning of the orbit may equal or surpass
orbital CT scanning.13-16Pseudotumor causing a density about the optic nerve is the most frequent
problem in the differential diagnosis. Orbital sonography can be helpful if skillfully done,17,18and
occasionally angiograms or venograms are required. When iodine containing x-ray contrast is
administered, thyrotoxicosis or thyroid autonomy should be considered or ruled out first. The
major problem is differentiation of unilateral exophthalmos from a tumor requiring surgery. Time
often provides the answer, with the development of other signs of Graves' disease, growth of a
lesion on CT scan, or shrinkage on steroids.
Fig. 2.
End stage in severe
involvement
of
extraocular muscles in
ophthalmopathy (courtesy
of
Prof.
Wiersinga,
Amsterdam).
The clinical diagnosis of unilateral exophthalmos of Graves' disease may be impossible. Very
rarely there may be recourse to exploration of the orbit. Biopsy may then show the microscopic
changes in the tissues described above.
It is most important that the degree of exophthalmos, limitations of ocular mobility, visual
acuity, visual fields be determined during the initial evaluation, and repeatedly during the course if
the exophthalmos requires active therapy.
Pseudotumor
In a significant number of patients, unilateral exophthalmos and sometimes loss of visual
acuity occur without any evidence of Graves' disease and with the only laboratory finding a
posterior orbital density on CT scans. These patients may have pseudo tumor, a designation of
dubious value. Pseudotumor is said to be a chronic inflammatory process that can be related to
some systemic disease or granulomatous process or may be idiopathic. It has been treated with
iodide and x-rays, and currently is treated with glucocorticoids. The process may be unilateral or
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bilateral. It can cause muscle thickening17,18 and visual loss. The authors believe, without certain
proof, that many cases of pseudotumor are examples of Graves' ophthalmopathy.
Therapy
Therapeutic possibilities include local measures to combat inflammation, glucocorticoids,
plasmapheresis and immune suppressants, orbital radiation, decompressive surgery, and thyroid
ablation. There is no perfect basis for selecting one form of therapy for coincident thyrotoxicosis
over another, insofar as effects on the exophthalmos are concerned. Many thyroidologists believe
that as long as eye signs are active, conservative treatment of the concomitant hyperthyroidism, i.e.
medical treatment, is best to avoid worsening of TED even promote improvement. In this situation
serum TSH is kept suppressed and FT4 in the high normal range in the assumption to keep antigen
(TSH-R) release from the thyroid at a minimum.
Radioactive iodine as a treatment for the concomitant hyperthyroidism is considered by some
authors as having a worsening effect on TED.19,20 In a recent study eye signs worsened more often
in patients treated with 131I as compared to treatment with antithyroid drugs and worsening could
be prevented by temporary administration of prednisone.21Several studies have been published
concerning possible effects on development of eyesigns after partial thyroidectomy. In a total of
five studies22comprising 245 patients no significant worsening or improvement after
thyroidectomy was found. The possible effect of the three forms of treatment (medical, RAI,
thyroidectomy), on infiltrative ophthalmopathy was studied prospectively.23 No influence of type
of treatment on the clinical course of eye signs was found. The authors found that in patients who
had no ophthalmopathy before treatment, the occurrence of post-treatment exophthalmos was
about similar in the surgical, medical and 131I-treated group (7.1%, 6.7%, and 4.9%, resp.). The
incidence and the degree of progression of ophthalmopathy in patients who already had
exophthalmos before treatment, was also not different in the three groups (19.8%, 19.2%, and
22.7%, resp.) as was the improvement of ophthalmopathy (12.7%, 14.1%, and 12.3%, resp.). The
most recently published data indicate that 131I therapy is more apt to be followed by worsening of
exophthalmos than is surgical treatment. This may occur because of the well-recognized flair of
autoimmunity produced by 131I.24
A prospective study evaluated the protective effect of prednisone on treatment of radioactive
iodine with regard to development of eyesigns in patients with only slight or no signs
ophthalmopathy. In the group of patients not treated with prednisone, ocular disease worsened in 9
out of 16 patients who had some ophthalmopathy before therapy and did not change in 6 out of 16.
In the group of patients treated with prednisone (0.4 - 0.5 mg prednisone/ kg bodyweight for 1
month with subsequent tapering and withdrawal after 3 months) ophthalmopathy improved in 11
out of 21 patients and did not change in 10 out of 21 patients. Eyesigns did not develop after
radioiodine treatment in ophthalmopathy negative patients in either groups. 19,22The authors
conclude that in patients with Graves' hyperthyroidism and ophthalmopathy, treatment with
radioactive iodine or should be performed under protection with systemic glucocorticoids if
ophthalmopathy is mild to moderate.
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In general the hyperthyroidism in patients with mild TED is treated by whatever means
seems most appropriate. If after treatment eyesigns deteriorate despite carefully maintained
euthyroidism administration of a short course of glucocorticoids should be considered.
Although not proven by prospective study, some physicians advise ablation of thyroid tissue at
this point, in order to remove potential antigenic stimulation to the eye disease.
Mild infiltrative ophthalmopathy is best treated by reassuring the patient and controlling the
thyrotoxicosis medically, thereby keeping serum TSH suppressed. It may be helpful to elevate the
head of the bed at night, to decrease salt intake, to use shielded glasses whenever the eyes may be
exposed to irritation, and to use protective drops, such as 0.5% methylcellulose, or a protective
ointment at night. Deeply tinted glasses may help combat photophobia on bright days. A 0.5%
solution of hydrocortisone may prove beneficial when used for a brief period as eyedrops three
times daily in combating some of the local irritative phenomena. This therapy is not without
danger, however, since steroid hormones may diminish normal resistance to the herpes simplex
virus and may increase intraocular pressure. If there is difficulty in closing the eyelids during sleep,
it is necessary to protect them from dehydration. Diplopia can sometimes be corrected by prism
lenses or be handled temporarily by using an eyepatch or by occluding one lens of the patient's
glasses. The majority of patients respond to this program with a gradual improvement as the
thyrotoxicosis becomes controlled.
When the ophthalmopathy is severe or progressive, an active approach is
required. The modalities most used are administration of glucocorticoids, mostly prednisone in
moderate to high doses as a single regimen, x-ray irradiation of the orbit preferably in combination
with glucocorticoids, and surgical decompression of the orbit. As noted below, thyroid ablation
can also be considered.
Although in the acute situation administration of prednisone relieves symptoms in most cases,
relapse occurs in many patients after glucocorticoids have been withdrawn.24,25 When prednisone
is used in the acute situation, large doses may be required. A usual regimen is to begin with 40 mg
prednisone daily in divided doses and continue until a response is obtained. If vision worsens or
no response is obtained, doses of 60-200 mg/day may be justified for a short period, and may be
helpful when lower doses are ineffective. As soon as the threat to vison is reversed, the dose of
prednisone is gradually reduced over 4-12 weeks, is switched to an every-other-day program, and
is finally reduced to a 5-10 mg maintenance dose or discontinued. Antacids, to reduce gastric acid
secretion, salt restriction, and diuretics may be needed, and one must be prepared to contend with
all the usual problems, including weight gain, hypertension, infection, ulcers, diabetes, and
osteoporosis.
High dose intermittent IV steroid therapy has been extensively studied, and recently reported
to be slightly more effective and to cause fewer side effects than oral steroid therapy for
ophthalmopathy. ( Comparison of the effectiveness and tolerability of intravenous or oral
glucocorticoids associated with orbital radiotherapy in the management of severe
Graves?ophthalmopathy: results of a prospective, single-blind, randomized study. J Clin
Endocrinol Metab 86:3562-3567, 2001.) These authors gave iv methylprednisone, 15 mg/kg for 4
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cycles and then 7.5mg/kg for four cycles, each cycle consisting of two infusions on alternate days
at two week intervals.
If steroid therapy does not control the problem in the sense that visual acuity is still lower
than normal and further deterioration is suspected, then surgical orbital decompression must be
considered (see below). An alternative is to institute x-ray irradiation. However, a positive short
term effect is not readily obtained in these circumstances.
The consensus is emerging that in case of active eyesigns, X ray irradiation is preferred over
surgical intervention as a first choice of treatment. When active signs have subsided no spectacular
effect may be expected from irradiation and decompressive surgery promises better results. The
different aspects of both treatment modalities are discussed in separate sections (see below).
If keratitis represents the main problem, eyelid surgery26should be performed if necessary in
combination with radiation therapy or surgical decompression.
Thyroid Ablation
Ablation of thyroid tissue by surgery or 131I therapy to destroy the source of antigens has
been recommended by Bauer and Catz, but studies by others indicated that it had no predictable
success. However a role for thyroid ablation remains at least theoretically a possibility as total
removal of the thyroid may also remove the antigenic stimulus that causes the ophthalmopathy
and reduce both humoral and T cell mediated responses to TSH-R. A recent retrospective study
supports the use of thyroid ablation in managing patients with active severe TED.27 The still
controversial aspects of this therapy have recently been discussed.28 As noted above, some
physicians believe that early ablation of the thyroid inhibits progress and promotes resolution of
TED. Later in the course of ophthalmopathy this treatment may be less or ineffective because
orbital antigens may then drive the immunologic reaction.
Other Medical Therapies
Some patients have been treated with azothioprine or cyclophosphamide with varied
results.29,30 Plasmapheresis, combined with either steroids or immunosuppressants,31 has also been
used for acute exophthalmos, but published experience is limited32 (Fig. 3). Cyclophosphamide,
50-100 mg/day for 2.5 months, was reported to give complete or partial clearing of exophthalmos
in 28 patients in two studies30, but its ineffectiveness was subsequently shown in a controlled
trial.33 Furthermore most physicians are afraid of the long-term carcinogenic properties of
immunosuppressant drugs other than steroids. Results of a controlled trial on the effects of
cyclosporin and prednisone in ophthalmic Graves' disease revealed that cyclosporin is inferior to
prednisone as a single drug, but the combined administration of both drugs may be of benefit in
patients who do not react favorably to either drug alone.25 Somatostatin analogues have shown to
be effective in patients with TED, especially when soft tissue is involved.34-36Large series of
patients however have so far not been published.
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Figure 3.
CT scan of the orbital
contents in a patient with
severe active exophthalmos.
The
characteristic
enlargement
of
the
extraocular
muscles
is
clearly evident, as is the
proptosis. Normally the
muscles are thin, although
visible, and appear to be 2
or 3 mm in diameter.
The development of corneal ulceration warrants the most prompt and careful attention in
conjunction with an ophthalmologist. Local therapy with antibiotics may be helpful. Local
application of cortisone is contraindicated. Emergency suturing of the lids together may be
required to protect the cornea. Often it fails to be helpful, and frequently the sutures become
infected, leaving scarred lids. Scleral implants in the lower lids may protect the cornea.
Decompression of the orbits by one of the techniques described below is frequently the only
successful method for healing the ulcer.
Surgical Procedures
Orbital decompression is in fact not a treatment intended to influence the basic process; It
primarily aims at enlarging the intra-orbital space to relieve retrobulbar pressure. Decompression
is considered, or indicated, in specific conditions; compressive optic neuropathy not responding to
steroids, exposure keratitis, chronic eye pain, subluxation of the globe, and severe eyelid retraction.
This technique is often of value in inactive TED in patients who have a major cosmetic deformity,
or who have severe proptosis and need eye muscle corrective surgery for diplopia. There are
several approaches: the lateral, the superior and the inferior (Fig. 4), the coronal, the combined
transpalpebral and endonasal approach and most recently the transcaruncular approach to the
medial wall and orbital apex. In the lateral approach the lateral orbital wall is removed leaving the
lateral orbital rim intact. In the superior approach the superior and lateral wall are removed via
frontal craniotomy. In the inferior approach the inferior and medial walls are removed. The
approach is usually transantrally, but sometimes the transorbital route is used. The lateral and
superior approach are less frequently used than the inferior approach by the transantral route.
When serious proptosis is present, three walls (lateral, inferior and medial) may be removed. In
such cases a reduction of proptosis between 6 and 10 mm may be achieved. In the combined
approach palpebral adipose tissue of upper and lower lids and the medial orbital wall are
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removed.37 In rare cases a four-wall decompression may be indicated resulting in a reduction of
proptosis between 10 - 17 mm.38
Figure 4.
Different
approaches
decompression.
in
orbital
（a) Inferior approach,
（b) lateral approach,
（ c) Superior approach (taken with
permission from ref. 44)
The three-wall removal may be performed by a combination of the transantral/transorbital
technique, or by the recently described coronal approach.39 This technique, where the incision is
made behind the hairline from ear to ear, results in only ~3% of patients having new diplopia. 40
Transantral orbital decompression in 428 patients with severe ophthalmopathy after a mean
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follow-up of 8.7 years (probably in most instances two walls were removed), gave the following
results. Optic neuropathy was present in 11% of patients and improved or remained unaltered in
89%. Scotomas improved or resolved in 91%, papilledema in 94% and keratitis in 92% of eyes.
Mean reduction in proptosis was 4.7 mm. However, postoperative diplopia developed in 64% of
patients and 300 patients needed strabismus surgery. Worsening of any eyesigns due to the
operation occurred in 10% or less of patients.41The risk of diplopia may be reduced by
preservation of the anterior orbita42. in the transcaruncular approach the medial wall may be safely
exposed and this procedure avoids scarring43. Other surgical procedures that may be of benefit, are
those related to eyelid malpositions. Sometimes eyelid surgery is necessary to prevent keratitis
that may result from ocular exposure, particularly when lagophthalmos is present. It may also be
necessary to correct disturbing cosmetic upper or lower eyelid retraction. ( Some newer techniques
are reviewed elsewhere44).
Orbital X ray treatment
This form of treatment has been used for several decades in many patients. When TED is
active and moderate or severe, it should be used as a first choice preferably in combination with
administration of corticoids as this combination is more effective than irradiation alone45. Both
modalities are known to be effective in suppressing lymphocyte activity that plays such a
dominant role in the activation of TED. Although treatment with prednisone alone is equally
effective as irradiation, side effects of prednisone are more prominent.46 Irradiation is delivered by
megavoltage linear accelerators to the retrobulbar space. Ten daily doses of 2Gy each are given in
a period of two weeks. A total dose of 10 Gy has been reported to be less effective47 and equally
effective but that a total dose of 30 Gy does not add benefit.48Favourable results are obtained in
about 60% of patients with active TED.47 Orbital irradiation is usually well tolerated49 and there is
little if any risk for inducing lens cataract.50In a series of eleven patients, treated this way, a mean
decrease of proptosis of 5mm was noted, while visual acuity improved substantially as well.Kriss
et al.51 report on a large series of 80 patients treated by radiotherapy alone. An excellent or good
result was obtained in 67% of cases. On analysis it appeared that improvement was seen in 95%
for soft tissue involvement, 60% for both proptosis and extra-ocular muscle involvement, 50% for
cornea lesions, and 85% for loss of visual acuity. It is generally felt that patients with diabetes
mellitus should not be treated by X ray irradiation, especially when diabetic retinopathy is present.
Choice of Treatment
The choice among the several modalities of therapy available for the control of severe
progressive infiltrative exophthalmos (Table 4) cannot be made with certainty at this point. If local
measures, and rest are inadequate, our first line of attack is X-ray to the retrobulbar tissues. Many
prefer to combine this with a course of glucocorticoids, to achieve maximal effect, and some
physicians advise thyroid ablation. If this therapy does not halt exophthalmos, or if progression of
the disease forces further intervention, operative decompression of the orbit should probably be
instituted. In mild to moderate TED, irradiation to the orbit is only indicated if eye movement is
compromised52,53. Use of plasmapheresis or immunosuppressent drugs must be considered
experimental. Reports suggest that disease activity may be assessed using non-invasive techniques
(for review see ref 54). Using ultrasonography eye muscle reflectivity was lowered in patients with
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THYROID EYE DISEASE (TED)
active extra-ocular orbitopathy and who did respond to prednisone treatment, whereas reflectivity
was normal in non-responders.55 In patients with active ophthalmopathy retrobulbar uptake of
labeled octreotide was visualized by isotopic scanning.56-58 Uptake of octreotide predicted response
to immunosuppression and can also be used to monitor such therapy 58. Signal intensity ratio of
orbital connective tissue and extra-ocular muscle was significantly greater in responders to
prednisone than in non-responders.59
Table 4. Treatment of TED
Local nonspecific:
Head elevation at night
Dark glasses, side shields
Ointment-petrolatum,
methylcellulose, antibiotic
Lid Surgery
Therapeutic:
Established effect:
Glucocorticoids
X irradiation +/- glucocorticoids
Surgical decompression
Unproven or preliminary:
Plasmapheresis
Antimetabolite treatment
Thyroid ablation
Octreotide treatment
Gamma globulins(iv)
Late:
Muscle insertion correction
Lid surgery
Removal of redundant eyelid skin
Infiltrative ophthalmopathy often becomes stationary and symptoms either progress no
further, but an unacceptable cosmetic problem or diplopia may continue to harass the patient.
Orbital decompression in such (inactive) cases is then to be considered. The surgical risk is very
low when the operation is performed by an experienced surgeon, and the results may be most
gratifying. Knitting together of the lateral quarter of the eyelids may strikingly improve the
appearance of a patient with proptosis and a wide palpebral fissure, and scleral implants can help
cover the cornea. If established diplopia cannot be helped by prisms or a ground-glass, then
extraocular muscle balance may be restored, under propitious circumstances, by any of several
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operative procedures on the muscles. This procedure should be done when the inflammatory
changes of the eye disease have subsided. Many patients find that surgical procedures removing
redundant skin or orbital fat, and/or scleral implants, vastly improves the appearance of their eyes.
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