CME Complex Strabismus

Brown’s Syndrome

yy Divergence in upgaze with Y pattern – due to slippage of the globe
against the tight SO tendon.

yy Compensatory head posture – The patient might adopt chin
elevation and contralateral face turn (to keep the affected eye
abducted, avoid hypotropia, and promote binocular fusion).

yy Binocular function is usually preserved, even in severe cases,
via a compensatory head position. The presence of amblyopia is
uncommon, varying between 4% and 25% of the cases.7

yy Brown Syndrome secondary to an inflammatory condition is often
intermittent in nature and frequently associated with orbital pain
on movement or tenderness on palpation of the trochlear area. A
tendon cyst or a mass may be palpable in the superonasal orbit. A
‘click’ may be heard or felt by the patient with movement of the
eye when attempting to elevate the eye in adduction.

yy Forced duction test shows restriction to passive elevation of globe
in adduction – differentiating feature from inferior oblique palsy.

yy Guyton’s exaggerated forced duction test - the globe is held at 4
and 10 O’ clock position, followed by retro placement of globe
so as to create stretch on the tendon; the globe is then forcibly
extorted and moved supero nasally (Figure 3A). From this
position the globe is turned temporally (Figure 3B). In case of
tight superior oblique tendon the globe seems to suddenly jump as
the SO tendon slips nasally over the surface of the globe to a less
stressed position. The magnitude of the jump provides a tactile
measure of the superior oblique tightness.

Figure 2: Limited elevation of left eye in adduction (A), normal elevation in
abduction (C)

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Figure 3: Exaggerated traction test. A: The eye ball held at 3 o’clock limbus,
retropulsed and moved superonasally to produce stretch on the SO tendon. B: The

eye ball is then turned temporally to feel tightness of the SO tendon.

Table 1: Clinical features of Brown’s syndrome

Consistent Features Variable Features

1. Deficient or absent elevation 1. Down shoot in adduction
in adduction
2. Divergence in up gaze
2. Normal or minimal deficient causing a V-pattern (Y
elevation in abduction subtype)

3. Mild elevation deficit in 3. Widening of palpebral fissure
primary position in abduction

4. Positive forced duction test 4. Anomalous head posture (chin
up and contralateral face turn)
5. Minimal or no superior
oblique overaction 5. Hvpotropia in primary
position

Table 2: Stager et al classification of Brown’s syndrome

Mild No hypotropia

Moderate Hypotropia in adducted position

Severe Hypotropia in primary position

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Differential Diagnosis

yy Inferior oblique palsy: It is characterized by overaction of the
superior oblique muscle, A pattern and positive head tilt test.
Forced duction test is negative.

yy Monocular elevation deficit: Limitation of elevation is present in
both adduction and abduction. True or pseudoptosis is associated.

yy Congenital fibrosis syndrome: Limitation of all extraocular
movements, convergence on up gaze.

yy Orbital floor fracture: The elevation deficiency is more marked
in abduction. Imaging reveals a fracture and entrapped inferior
rectus. There may be associated enophthalmos.

yy Thyroid ophthalmopathy: Elevation deficiency is due to tight
inferior rectus and is worse in abduction compared to adduction.

yy Adherence syndrome: History of previous surgery or trauma -
during inferior oblique surgery, adhesions may form due to fat
prolapse.

Management

Treatment depends on the etiology, symptoms and course of the
disease. Spontaneous resolution is likely to occur in intermittent and
acquired cases, but is rare among long standing congenital cases.
Patients with acquired Brown’s syndrome should be evaluated for
coexisting systemic disease such as rheumatoid arthritis, Sjogren’s
syndrome, systemic lupus erythematosus. Imaging can be helpful
to exclude the presence of cyst or secondary metastasis. Patients
with signs of inflammation (i.e., pain or tenderness) can be treated
with systemic anti-inflammatory medication – oral NSAIDs such as
ibuprofen or oral steroids (Prednisolone 1 mg/kg body weight).8 If
this does not sufficiently relieve symptoms, then local corticosteroid
injections can be administered. Depot steroid injection (intra-trochlear
injection of 1ml of triamcinolone acetonide 40 mg/ml) is effective in
patients with acquired Brown syndrome secondary to trochleitis, with
complete recovery of signs and symptoms in the majority of treated
patients.9,10 Congenital Brown's syndrome is unlikely to improve
spontaneously, so surgery is an important option to consider.

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Indications for surgery include:
yy Diplopia in primary position
yy Hypotropia in primary
yy Anomalous head posture
yy Loss of binocularity

Surgical Treatment

1. Superior oblique tenotomy and tenectomy (Figure 4): Popular
procedures used to elongate the superior oblique tendon thereby
improving elevation in adduction11but there occurs an uncontrolled
separation of the cut ends of the tendon. In some cases, the
tendon ends will separate widely, causing consecutive superior
oblique paresis; in other cases, the cut ends may reunite and
scar back together, producing an undercorrection. Also, patients
with bifoveal fusion do not tolerate small induced postoperative
cyclovertical deviations. The incidence of postoperative superior
oblique palsy is reported to be between 50% and 85%. Parks and
Eustis added a simultaneous ipsilateral inferior oblique recession
along with a superior oblique tenotomy to reduce the incidence of
secondary superior oblique palsy.1

Figure 4: Superior oblique tenectomy

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2. Silicon tendon expander procedure: Wright13 introduced the
use of silicone band expander to lengthen the superior oblique
tendon. This procedure allows a quantitative slackening of the
tendon. Also, it maintains the fan shaped insertion of SO thus the
functional integrity of the tendon.

Figure 5: Schematic diagram showing silicon expander elongation of SO tendon

Procedure: The superior rectus is hooked through the supero
temporal conjunctival incision. The conjunctiva is reflected
nasally to expose the nasal border of the superior rectus. The SO
tendon is identified approximately 12 mm posterior to the SR
insertion along the nasal border of the superior rectus muscle.
Four non absorbable sutures (5-0 Ethibond) are applied superiorly
and inferiorly about 2-3 mm apart on the SO tendon (Figure
6A). The tendon is cut between the sutures. A segment of 240
silicone retinal band is sutured between the cut ends and tied in a
horizontal mattress configuration (Figure 6B). Care must be taken
to minimally disturb the adjoining tissues to prevent adhesion
formation. A supero-temporal fornix conjunctival incision and
performing a nasal SO tenotomy preserves the nasal intermuscular
septum and the floor of the SO tendon capsule. This acts as a barrier
between the silicone expander and the sclera preventing adhesion
formation. It is important to perform the Guyton’s exaggerated
forced duction test of oblique before and after the surgery. This
sensitive test will be positive even if a few residual posterior fibres
have been missed.

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Figure 6: Wright’s silicon tendon expander procedure

Advantages: The expander provides measured elongation of
the SO tendon. There is no consecutive SO palsy.14 In children
with good fusion, it avoids the risk of post-operative torsional
diplopia.15 The procedure is completely reversible as the expander
can be removed and the tendon ends can be sutured.

Disadvantages:  Persistent inflammation, formation of adhesions,
extrusion of band, technical difficulty.16

Chicken suture lengthening: Knapp17 described this procedure
initially, where lengthening of the SO tendon is achieved by
securing a loose nonabsorbable suture to the cut ends of the superior
oblique tendon. A modification of this procedure is described
by Suh et al,18 where the superior oblique tendon is exposed, 2
nonabsorbable sutures (5-0 Ethibond polyester) are placed 4 mm
apart, and the tendon is cut. With the use of a slip knot, the cut ends
of the tendon are separated by 2 to 8 mm. Tendon separation can
be adjusted intraoperatively according to the exaggerated traction
test and, in some cases, fundus torsion. The superior oblique
tendon suture spacer is effective, intraoperatively adjustable, and
technically easier to perform than a silicone expander procedure.19
Other materials like autologous fascia lata,20 achilles tendon
allograft21 are also used for graded elongation of SO tendon

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Figure 7: Chicken suture lengthening A) Isolation of SO tendon; B) Non absorbable
sutures placed; C) SO tendon cut in between the sutures to produce graded elongation

3. Split tendon lengthening: In this procedure, the SO tendon is
isolated and split into 2 halves for 3-4 mm and the cut ends are
tied together. It has a significant effect on reducing primary gaze
hypotropia and improving elevation in adduction.22 This procedure
has the advantage of producing graded elongation without placing
a foreign body.

Figure 8: Schematic illustration of split tendon elongation.

Limited elevation in adduction

FDT positive FDT negative Inferior oblique palsy

Orbital Endocrine Brown’s
fracture myopathy syndrome

Congenital Acquired latrogenic
(after SO tuck)
Normal head posture Traumatic-
and ortho in primary surgical Lessen the
tuck or recess
- Observe exploration contralateral SR

Abnormal head posture, Inflammatory -
hypotropia in primary gaze, local steroids
asthenopic symptoms - SO
surgery-silicon tendon expander
or chicken suture lengthening

Flowchart summarising management of Brown’s syndrome

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Key Points

yy Brown’s syndrome is a rare type of restrictive strabismus
characterised by limited elevation in adduction caused due to
mechanical restriction of SO muscle, tendon-trochlear complex.

yy Inferior oblique paresis, monocular elevation deficit, orbital floor
fracture are important conditions in the differential diagnosis.

yy Patients with acquired onset should be evaluated for systemic
associations and require orbital imaging.

yy Acquired and inflammatory cases of Brown’s syndrome may
resolve spontaneously and can be managed conservatively.

yy Congenital and long standing cases require surgical correction.
Chicken suture lengthening or Wright’s silicon tendon expander
procedure are preferred to achieve graded elongation of SO
tendon avoiding iatrogenic SO paresis and preserve the functional
anatomy of SO insertion.

References

1. Coussens T, Ellis FJ. Considerations on the etiology of congenital Brown
syndrome. Curr Opin Ophthalmol. 2015 Jul;26(5):357-61. doi:10.1097/
ICU.0000000000000191. PMID: 26163776.

2. Ellis FJ, Jeffery AR, Seidman DJ, Sprague JB, Coussens T, Schuller J. Possible
association of congenital Brown syndrome with congenital cranial dysinnervation
disorders. J AAPOS. 2012 Dec;16(6):558-64. doi: 10.1016/j.jaapos.2012.09.005.
PMID: 23237754.

3. Wilson ME, Eustis HS, Parks MM. Brown’s syndrome. Surv Ophthalmol. 1989
Nov-Dec;34(3):153-72

4. Crosswell HH, Haldi B A, The superior oblique tendon sheath syndrome. A
report of two bilateral cases. J Pediatric Ophthalmol. 1967; 4:8.

5. Kenawy N, Pilz DT, Watts P. Familial unilateral Brown syndrome. Indian J
Ophthalmol. 2008;56(5):430-434. doi:10.4103/0301-4738.42427

6. Magli A, Fusco R, Chiosi E, Del Bono G. Inheritance of Brown′s syndrome.
Ophthalmologica. 1986;192:82–7.

7. Sekeroglu, H.T., Muz, E., Sanac, A.S., Sener, E.C. and Arslan, U. (2013)
Amblyopia and Sensory Features at Initial Presentation of Brown Syndrome: An
Issue to Recognize. Eye (Lond), 27, 515-518.

8. Chhablani PP, Chandrasekharan A. Resolution of acquired Brown syndrome
with oral steroid therapy. Oman J Ophthalmol 2017;10:128-30.

152 CME on COMPLEX STRABISMUS

Brown’s Syndrome

9. Lee J. Management of Brown syndrome. Semin Ophthalmol. 2008 Sep-
Oct;23(5):291-3. doi: 10.1080/08820530802505971. PMID: 19085429.

10. Giannaccare, Giuseppe & Primavera, Laura & Maiolo, Chiara & Fresina, Michela
& Campos, Emilio. (2017). Steroid intra-trochlear injection for the treatment of
acquired Brown syndrome secondary to trochleitis. Graefe’s Archive for Clinical
and Experimental Ophthalmology. 255. 10.1007/s00417-017-3757-z.

11. von Noorden GK, Olivier P. Superior oblique tenectomy in Brown’s syndrome.
Ophthalmology 1982;89:303-308.

12. Parks MM, Eustis HS. Simultaneous superior oblique tenotomy and inferior
oblique recession in Brown’s syndrome. Ophthalmology 1987;94:1043-1048

13. Wright KW. Superior oblique silicone expander for Brown’s syndrome and
superior oblique overaction. J Pediatr Ophthalmol Strabismus 1991;28(2): 101-
107.

14. Wright KW, Min BM, Park C. Comparison of superior oblique tendon expander
to superior oblique tenotomy for the management of superior oblique overaction
and Brown’s syndrome. J Pediatr Ophthalmol Strabismus 1992;29(2):92-97.

15. Jayakumar, Manjula. (2012). Superior Oblique silicon tendon expander. Delhi
Journal Of Ophthalmology. 22. 199-201.

16. Keskinbora KH. Long-term outcome of a silicone expander for Brown’s
syndrome. J Pediatr Ophthalmol Strabismus. 2007 May-Jun;44(3):163-9. doi:
10.3928/0191-3913-20070301-09. PMID: 17542438.

17. Scott AB, Knapp P. Surgical treatment of the superior oblique tendon sheath
syndrome. Arch Ophthalmol, 1972; 88:282-6.

18. Suh DW, Guyton DL, Hunter DG. An adjustable superior oblique tendon spacer
with the use of nonabsorbable suture. J AAPOS. 2001 Jun;5(3):164-71. doi:
10.1067/mpa.2001.114190. PMID: 11404743.

19. Yazdian Z, Kamali-Alamdari M, Ali Yazdian M, Rajabi MT. Superior oblique
tendon spacer with application of nonabsorbable adjustable suture for treatment
of Brown syndrome. J AAPOS. 2008 Aug;12(4):405-8. doi: 10.1016/j.
jaapos.2007.11.020. Epub 2008 Apr 18. PMID: 18396080.

20. Talebnejad MR, Eghtedari M, Owji N, Alavi A. Super oblique tendon
elongation with fascia lata. J AAPOS. 2008 Oct;12(5):507-9. doi: 10.1016/j.
jaapos.2008.02.014. PMID: 18929307.

21. Talebnejad MR, Mosallaei M, Azarpira N, Nowroozzadeh MH, Zareifar
A. Superior oblique tendon expansion with Achilles tendon allograft for
treating Brown syndrome. J AAPOS. 2011 Jun;15(3):234-7. doi: 10.1016/j.
jaapos.2011.02.009. Epub 2011 Jun 12. PMID: 21665503.

22. Moghadam AA, Sharifi M, Heydari S. The results of Brown syndrome surgery
with superior oblique split tendon lengthening. Strabismus. 2014 Mar;22(1):7-
12. doi: 10.3109/09273972.2013.877943. PMID: 24564724.

CME on COMPLEX STRABISMUS 153

10Lost Muscle in Strabismus Surgery-‘Useful tips not to get lost in problems’

Lost Muscle in Strabismus
Surgery­- ‘Useful Tips not
to get Lost in Problems’

Dr. Seyhan B. Özkan

Professor of Ophthalmology, Private Clinic, AYDIN, Turkey

Lost muscle is accepted as one of the most serious complications
in strabismus surgery. Prevention is far more important than the
treatment and the majority of this complication develops due to the
problems with the surgical technique. If an extraocular muscle is lost
it must be searched with respect to the tissues and if it cannot be found
transposition surgery may be considered. Botulinum toxin A may
be helpful to reduce the contracture of the antagonist muscle where
necessary or to rescue residual or consecutive deviations.

Introduction

An extraocular muscle (EOM) may be lost related to strabismus
surgery, pterygium surgery and retinal detachment surgery. Orbital
surgery, endoscopic sinus surgery and trauma are the other main causes
of this problem. Lost muscle is most commonly seen during strabismus
surgery and it is a nightmare complication for the surgeon. The term
“lost muscle” is something to be questioned as most of the time the
EOM is there in its anatomical location with only a disinsertion.
Most of the time the problem is the “lost surgeon” rather than the
“lost muscle”. The former is much more harmful for the patient that
indicates an inexperienced surgeon without a good knowledge of the
anatomy of the surgical field. In this article etiology and types of lost
muscle, preventive measures, clinical presentation and methods of
management will be discussed.

Clinical Types

The types of lost EOM are evaluated in four categories.

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yy Slipped EOM within its capsule
yy Cut and lost EOM
yy Broken (snapped) EOM
yy Inadvertently transected EOM

Slipped EOM within its capsule: The extraocular muscle slips within
its capsule1. The sutures do not include the muscle – tendon fibers
but only the capsule. The recognition of the slipped muscle is at the
postoperative stage (Figure.1).

Empty muscle capsule

Figure 1. In slipped extraocular muscle the sutures do not include the muscle tendon
fibers but only the capsule (Adapted from Özkan SB. Lost muscle in strabismus
surgery - How to handle the problem? DOS Times. 2017; 23:5255).

It is demonstrated that stretched scar tissue formation may cause
consecutive deviations and the stretched scar tissue and slipped
EOM may be confused in diagnosis2,3. In stretched scars there is
minimal or no limitation of versions, less separation of the tendons
from sclera with thicker and amorphous shaped appearance of the
scar segments. The empty capsule of a slipped muscle is translucent

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and the strabismus hook underneath is visible in contrast to stretched
scar. Magnetic resonance imaging (MRI) demonstrates the EOM in
distant location to limbus in slipped EOM, in contrast to stretched scar
formation4. Coexistence of slipped EOM and stretched scars is also
possible (Figure. 2).

Figure 2: Coexistence of stretched scar and slipped muscle. Note the translucent
empty capsule of slipped muscle in comparison with the thick, amorphous shaped

stretched scar tissue.

Cut and lost EOM: The muscle is lost during the surgery. If the
problem occurs during recession there is a long muscle with its tendon,
however if it occurs after resection there is a short muscle without
tendon. If the latter is the case, it is much more difficult to re-localize
the muscle (Figure. 3).

During recession Following resection
“Long muscle with tendon” “Short muscle, no tendon”

Figure 3: The EOM muscle may be lost during recession where there is a long
tendon and the muscle. If the EOM muscle is lost after resection, there is a short
muscle with almost no tendon. (Adapted from Özkan SB. Lost muscle in strabismus

surgery - How to handle the problem? DOS Times. 2017; 23:5255).

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Broken (snapped) EOM: The break usually occurs at the tendon –
muscle junction and the major etiological factor is excessive pulling
of the EOM; which is called as “pulled - in - two syndrome” (Figure.
4). It occurs most commonly in medial rectus muscle, followed by
inferior rectus muscle5.

Figure 4: The ‘pulled-in-two’ syndrome occurs at the tendon-muscle junction
with excessive pulling of the EOM. (Adapted from Özkan SB. Lost muscle
in strabismus surgery - How to handle the problem? DOS Times. 2017;

23:5255).

Inadvertently transected EOM: The most frequently transected
EOM are the inferior rectus and lateral rectus muscles that develop
during inferior oblique surgery. Superior rectus transection may occur
during superior oblique surgery. The main etiological factor for this
problem is blind hooking.

Etiology

The etiological factors may be evaluated in 5 groups:
yy Poor surgical technique
yy Inexperienced assistance
yy Poor instrumentation
yy Problems with the suture quality
yy Patient with high risk

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Poor surgical technique: Improper suture placement, inadvertent
cutting of the sutures, damage to the sutures with cautery, cutting
the muscle before placement of the sutures are the major faults in
surgical techniques that may result with lost muscle. In a tight EOM,
disinsertion of the muscle must be done in a stepwise manner; after
cutting one half it must be checked whether the suture end is holding
the EOM securely or not. If the suture end disengages from the
EOM, the other uncut half will hold the EOM, preventing it to retract
posteriorly.

Inexperienced assistance: Excessive pulling may cause a break of the
EOM. The assistant should not turn towards the surgical table while
holding an EOM with the strabismus hook. Inadvertent suture cutting
may also occur because of inexperienced assistance.

Poor instrumentation: Instruments with rough surface may tear off
the sutures. Slippage of the EOM from the muscle clamp may occur,
so the insertion should not be cut before locking the preplaced sutures.

Problems with the suture quality: The 6/0 coated polyglactin 910
is the gold standard suture material for strabismus surgery but it is
not perfect. The suture may easily tear with repeated touch with the
instruments. Theoretically that risk increases with adjustable suture
surgery and with hang loose recessions.

Patient with high risk: Sometimes the individual structural changes
may make a patient prone to a loss of an EOM. It is known that in
patients with old age the EOM are fragile. Patients with previous
surgery or trauma, chronic progressive external ophthalmoplegia,
Ehler Danlos syndrome and restrictive strabismus have a higher risk
for lost muscle5,6.

Preventive Measures

Placement of the full thickness locking bite at the edges of the muscle
leaving a safe distance from the insertion, careful removal of the
anterior Tenon’s capsule, avoiding dissection over the EOM area
without hooking the muscle, avoiding the use of serrated instruments
for sutures and avoiding unnecessary posterior dissection of fascial

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structures are the major preventive measures to reduce the risk of
a lost muscle in strabismus surgery. It was demonstrated that after
disinsertion most EOM retain their function via orbital connective
tissue attachments and keeping them intact may prevent the EOM
to retract through the posterior orbit7. In reoperations the risk of lost
muscle is higher because of the adhesions and scar tissue. Especially
in previously recessed muscles there are some adhesions at the
original insertion area and dissection of those adhesions carry the risk
of inadvertent cutting of the muscle tissue. Severing the tissues from
the sclera must be done after hooking the muscle and locating the
EOM insertion.

Clinical Findings

A large over or under correction with marked limitation of ductions
or marked incomitance in the field of action of the operated EOM are
the signs that suggest a lost muscle problem. A mild exophthalmos or
widening of the palpebral fissure may develop in some of the cases.

Medial rectus (MR) muscle is the most commonly lost EOM. Unlike
other rectus muscles MR has no fascial attachments with the oblique
muscles. When the MR muscle is lost, it recoils easily posterior to the
penetrance of the Tenon’s capsule.

If a lost muscle is suggested, imaging methods may be helpful for
location of the muscle. Ultrasonic biomicroscopy and anterior segment
OCT are helpful to see the insertion site but the EOM location may be
beyond the limits of those examination methods. Magnetic resonance
imaging (MRI) is not precise to demonstrate the insertion site but it
demonstrates the location of the EOM with reference to the globe and
the orbit, and seems to have more advantages in lost muscle problem.
In case of any doubt about the innervation of the posterior fibers,
kinematic MRI is required to demonstrate the functional capacity of
the posterior fibers. In case of any nerve damage, attempts to find the
posterior EOM fibers will be effortless and transposition surgery needs
to be considered. Forced generation test can easily be performed in an
office setting and saccadic velocity measurements give reliable results
if it is available.

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Management

When lost muscle is recognized during surgery the first rule is not to
fall into panic and to be calm. The anesthesiologist must be warned
about the problem and the anesthesia must be deepened in order to
prevent any contraction of the muscle that may cause the muscle to
retract backwards further. The anesthesiologist must be informed not
to use atropine as the oculocardiac reflex may be helpful to differentiate
the EOM tissue8.

Using magnification preferably by operating microscope is very
useful to differentiate the tissues. The major rule is not to make more
harm to the patient. The most devastating problem that may occur in
lost muscle is penetration of the posterior Tenon’s capsule by blind
fishing and addition of the fat adherence syndrome which converts the
problem into a much more complicated one. If it cannot be possible to
find the EOM, transposition might be considered. However it is not an
easy decision to consider transposition during primary surgery if the
two rectus muscles have already been operated keeping in mind the
risk of anterior segment ischemia.

When a lost muscle is suspected in post operative period, early
intervention is essential in order to increase the chance for finding
the lost muscle. However in some cases the patient may present at a
later stage with an excessive inflammatory reaction. In such cases it
is preferable to wait for six weeks till the inflammation resolves. It
is stated that the contracture of the unopposed antagonist can occur
as early as 2 weeks time9,10. We found botulinum toxin A (BTXA)
very effective to prevent the contracture of the antagonist during the
waiting period for surgical intervention. It also enables the eye to stay
at primary position during wound healing that enables the surrounding
soft tissues attach to a more anterior point to the globe which represents
another additional advantage of BTXA injection.

While attempting to find a lost muscle, the globe should not be pulled
towards the opposite direction. Retropulsion of the globe increases
the chance for locating the EOM (Figure. 5). During the search for a
lost muscle, all of the clues of fascial structures that may be attached
with the muscle must be used. It is a useful strategy to find the oblique

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muscles first if the lost muscle is superior, inferior or lateral rectus
muscles. Their intermuscular septa may hold the rectus muscles.
Trypan blue dye 0.1% may be helpful to differentiate some tissues
and it stains fibrotic tissue, muscle sheath and tendon but not muscle
fibers11.

Lost EOM retracts posterior to the Retropulsion of the globe in PP allows
Tenon’s capsule penetraction site grasping of the EOM

Figure 5: The globe should not be pulled towards the other side and retropulsion
of the globe helps to reach the lost EOM (Adapted from Özkan SB. Lost muscle in

strabismus surgery - How to handle the problem? DOS Times. 2017; 23:5255).

One of the most common mistakes is
to search for the muscle at the scleral
site. However scleral plane may take
the surgeon even to the optic nerve.
When an EOM is lost it moves
posteriorly within the Tenon’s capsule
at the orbital site, so the surgeon must
be aware of the correct plane to look
for the muscle (Figure. 6).

Figure 6: The search for finding the lost EOM
must be done in the correct plane. The search
on the scleral site takes the surgeon towards
the optic nerve (Adapted from Özkan SB.
Lost muscle in strabismus surgery - How to
handle the problem? DOS Times. 2017; 23:5255).

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If the problem is a slipped muscle
within the capsule the search must
be done through the empty muscle
capsule (Figure. 7). The relocation of
MR muscle is reported between 10%
and 86% in lost muscle and 92% and
100% in slipped muscles .9,10,12,13

Figure 7 : In slipped muscle the search must
be done through the empty capsule (Adapted
from Özkan SB. Lost muscle in strabismus
surgery - How to handle the problem? DOS
Times. 2017; 23:5255).

If standard conjunctival approach fails some alternative methods are;
transcutaneous medial orbitotomy, transnasal endoscopic approach,
trans caruncular incision and anterior orbitotomy14-16 (Figure. 8).
Before considering those methods, the innervational status of the
lost muscle should be evaluated and tranposition surgery must be
considered with their potential risk of complications.

The muscle is identified in The sutures are passed
the extraconal space to the sub Tenon space

Figure 8: The schematic representation of the orbital approaches to reach the lost
EOM. (Adapted from Özkan SB. Lost muscle in strabismus surgery - How to handle

the problem? DOS Times. 2017; 23:5255).

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It is known that a lost and found muscle may function even years after
surgery however these muscles may have contracture and it may not
be possible to suture at their original insertion. Consecutive deviations
may develop following reattachment of a secondarily contractured lost
muscle and botulinum toxin may be helpful to release that contracture
(Figure. 9).

Figure 9: Right consecutive exotropia related to slipped medial rectus muscle in
combination with stretched scar with limitation of adduction. Medial rectus muscle

was found and advanced to the insertion site with excision of stretched scar. B.
Patient was orthophoric on post operative first day but the secondarily contracted
slipped medial rectus pulled the eye resulting with consecutive esotropia on post
operative second week. C. Botulinum toxin A (BTXA) was injected into the right
medial rectus and one week later she had a small exodeviation with limitation of
adduction. D. Nine months after BTXA injection the patient was orthophoric and

adduction was free.

Conclusions

In conclusion, for a correct management and not to be the “lost
surgeon” a good knowledge of the anatomy is essential. The majority
of lost muscle complications develop because of the mistakes about

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Lost Muscle in Strabismus Surgery-‘Useful tips not to get lost in problems’

the basic rules of surgery. Blind fishing during attempts to find an
EOM may result with penetration of posterior Tenon’s capsule and
development of adherence syndrome which is much worse than a
pure lost muscle. BTXA has a significant role in management of lost
muscle by preventing the contracture of the antagonist and to control
residual or consecutive deviations after surgical repair. An acceptable
outcome is possible in most of the cases either with retrieval of the lost
muscle or muscle transposition procedures.

References

1. Parks MM, Bloom JN. The “slipped” muscle. Ophthalmology. 1979;86:1389–
1396.

2. Ludwig IH, Chow AY. Scar remodeling after strabismus surgery. J AAPOS.
2000;4:326–333.

3. Jung JH, Leske DA, Holmes JM. Classifying medial rectus muscle attachment in
consecutive exotropia. J AAPOS. 2016 Jun; 20(3): 197–200.

4. Negishi T, Hikoya A, Isoda H, et al. Magnetic resonance imaging of the medial
rectus muscle of patients with consecutive exotropia after medial rectus muscle
recession. Ophthalmology. 2010;117:1876–1882.

5. Ellis EM, Kinori M, Robbins SL, Granet DB. Pulled-in-two syndrome: A multi-
center survey of risk factors, management and outcomes. JAAPOS 2016; 20:
387-391.

6. Alexander MJ, Starte J, Dunn H, Ahmad K, Tan K. Surgical technique for pulled
in two syndrome: Three cases with chronic progressive external ophthalmople-
gia. J Pediatr Ophthalmol Strabismus 2017; 54: 83-7.

7. Hakim OM, El-Hag YG, Maher H. Persistence of eye movement following
disinsertion of extraocular muscle. JAAPOS 2008; 12: 62-5.

8. Apt L, Isenberg SJ. The oculocardiac reflex as a surgical aid in identifying a
slipped or ‘lost’ extraocular muscle. Br J Ophthalmol 1980; 64:362-365.

9. Murray ADN. Slipped and lost muscles and other tales of the unexpected. Journal
of AAPOS 1998; 2:133-143.

10. MacEwen CJ, Lee JP, Fells P. Aetiology and management of the ‘detached’
rectus Muscle. Br J Ophthalmol 1992; 76: 131-136.

11. Shokida F, Aguirre R, Croxatto O. The Use of Trypan Blue Dye for Strabismus
Re operations, Surgery Complications, and Especially for the Identification
and Recovery of a “Slipped” or “Lost” Extraocular Muscle. Binocular Vision &
Strabismus Quarterly 2011;26:1-8.

164 CME on COMPLEX STRABISMUS

Lost Muscle in Strabismus Surgery-‘Useful tips not to get lost in problems’

12. Plager DA, Parks MM. Recognition and repair of the “lost” rectus muscle.
Ophthalmology 1990; 97:131-137.

13. Duranoglu Y, Ilhan HD, Alis MG. Surgical results of the slipped medial rectus
muscle after hang back recession surgery. Int J Ophthalmol. 2014; 7(6): 1035–
1038.

14. Underdahl JP, Demer JL, Goldberg RL, Rosenbaum AL. Orbital wall approach
with preoperative orbital imaging for identification and retrieval of lost or
transected extraocular muscles. Journal of AAPOS 2001;5:230-237.

15. Lenart TD, Reichman OS, Mcmahon SJ, Lambert S. Retrieval of lost medial
rectus muscles with a combined ophthalmologic and otolaryngologic surgical
approach. Am J Ophthalmol 2000; 130:645-652.

16. Jordan DR, Stoica B, Dutton JJ. Localising the lost rectus muscle using the
connective tissue framework: Revisiting the tunnel technique. Ophthal Plast
Reconstr Surg 2017; 33; 477-81.

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A Complex Strabismus Entity: Strabismus Fixus 11

A Complex Strabismus
Entity: Strabismus Fixus

Dr. Soveeta Rath, Dr. Priya Goyal, Dr. Shailja Tibrewal,
Dr. Suma Ganesh

Department of Paediatric Ophthalmology, Strabismus and Neuro Ophthalmology
Dr Shroff’s Charity Eye Hospital, Delhi

Introduction

Strabismus fixus can be convergent or divergent. Convergent
strabismus fixus is more commonly noted than divergent fixus and
is a condition in which one or both eyes are anchored in extreme
adduction. Convergent strabismus fixus is of two types (Figure 1)

TYPES

Congenital Acquired

Myopic Nonmyopic

Figure 1: Types of convergent strabismus fixus

History

This entity was initially considered as a type of retraction syndrome
due to fibrosis of medial rectus muscle. Villaseca first described this
condition as different from retraction syndromes and documented this
condition as an acquired condition rather than a congenital anomaly.1

Etiology

Classically it is known to occur in very high myopes -otherwise called
as ‘Heavy eye syndrome’.2 The non-myopic strabismus fixus which
occurs in elderly is known as ‘Sagging eye syndrome’. Convergent
strabismus fixus can also be associated with amyloidosis.2

Myopic strabismus fixus is a rare entity characterized by progressive

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esotropia and hypotropia with limitation of abduction and elevation. It
is also known as ‘Heavy Eye syndrome’ due to the fact that abnormally
grown myopic eyeball becomes heavy and rests on the orbit.1 Several
hypotheses have been described for strabismus in degenerative myopia.
Such restrictive pattern could be due to compression of lateral rectus
against lateral orbital wall or from contact between posterior globe
with orbital apex. Further exploration with MRI studies by Krizok
et al showed that superotemporal prolapse lead to inferior shift of
lateral rectus.4 Nishida et al also reported inferior shift of lateral rectus
and nasal shift of superior rectus in eyes with esotropia associated
with high myopia.5 The most accepted theory today is, progressive
prolapse of the posterior portion of the eyeball to the superotemporal
quadrant of the orbit, due to axial distension of the globe which was
first described by Yokoyama and associates.6

Sagging eye syndrome (SES), was first described by Rutar and
Demer.7 It most often occurs in elderly patients (70 years or more).
It also presents with esotropia and hypotropia but in the absence of
high myopia. It usually occurs secondary to involutional changes
in the extraocular muscles and orbital connective tissues resulting
in inferomedial displacement of the LR. SES is a mechanical and
not a neurological, etiology for an acquired strabismus in the older
population.

Pathogenesis

The main pathogenesis is alteration of the muscle paths causing
change in action of the muscle.6,7

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Figure 2: Anatomical pathogenesis of strabismus fixus

The inferior displacement of lateral rectus causes it to act as a depressor
more than as an abductor, whereas nasalization of the superior rectus
causes it to act as an adductor rather than an elevator. This explains the
cause of esotropia and hypotropia being the commonest presentation.

Clinical Features

Patients typically complain of their eyes being fixed and the inability
to move the eyes outward. Esotropia and hypotropia are the most
common presenting features.6,7,8 In view of its acquired and progressive
nature some of them also complain of diplopia. Typical age-related
changes due to the levator aponeurosis, aponeurotic blepharoptosis or
superior sulcus deformities, baggy eyelids are external manifestations
of sagging eye syndrome.7 Limitation of abduction and elevation are
noted in different degrees in almost all patients. Change in extraocular
muscle position causes shift in the direction of action leading to
esotropia and hypotropia. Pseudo proptosis may be noted in high
myopes.
However, there are some clinically differentiating features between
myopic and non-myopic strabismus fixus (Table 1).

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Table 1: Differences between myopic and nonmyopic strabismus
fixus

NON MYOPES MYOPES

Axil length Normal range >27 mm

EOM path LR inferiorization SR nasalization
>> SR nasalization more
Esotropia
Hypotropia Less profound Significant
Limitation of
abduction Less Significant limitation

Diagnosis

Diagnosis of strabismus fixus is based upon the presence of extreme
esotropia and/or hypotropia associated with limitation of abduction
and/or elevation. Retinoscopy values of high myopia of greater than
-9 dioptres and axial length more than 28 millimetres confirms the
diagnosis of myopic strabismus fixus.8,9 Force duction test will also
show tightness of the medial rectus suggesting a restrictive pathology.
Additional imaging in the form of CT scan or MRI orbit localises the
change in path of extraocular muscles such as nasalisation of superior
rectus and inferior displacement of the lateral rectus along with globe
prolapse into superotemporal quadrant. (Figure 3) This displacement
can be quantified in terms of the angle of dislocation of the globe.10
This angle is defined between the line GS and the line GL to the
superotemporal quadrant of the orbit, that is, angle LGS (L-Lateral
rectus, G- centroid of the globe, S- superior rectus) as shown in Figure
3. When this angle exceeds 180 degrees, more than half of the cross-
section of the globe is located outside the muscle cone through an
opening between the SR and LR muscles.(Figure 4)10

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Figure 3: Coronal scan through the orbit showing inferior displacement of lateral
rectus muscle path and nasal displacement of superior rectus and inferior rectus

muscle paths.

Figure 4: MRI image showing angle of displacement of globe prior to surgery (on
left )and post-surgery (on right)- defined between the line GS and the line GL to the

superotemporal quadrant of the orbit, that is, angle LGS (L-Lateral rectus,
G- centroid of the globe, S- superior rectus)10

Management

Management of myopic strabismus fixus is essentially surgical.11 The
procedures available for surgical correction for strabismus fixus can
be divided into two groups:
a) Procedures altering the muscle forces: - recess-resect10,11
b) Procedures aiming at restoration of muscle paths: - muscle belly

union, myopexy of lateral rectus at equator, transposition11-15

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The choice of the procedure depends upon the amount of limitation
of abduction and elevation, angle of esodeviation and the amount of
deviation of LR and SR paths on MRI. With the traditional techniques
of recess-resect, there has been success but with suboptimal outcomes.
Esotropia often reappears after a few months.

Transposition of the superior and inferior rectus was effective in very
severe cases, but risk of anterior segment ischemia was a matter of
concern. Authors have proposed bimedial rectus disinsertion with
lateral fixation of the sclera to the periosteum in a severe case, but
significant motility deficiencies were noted post operatively.12

In general, belly union or transposition procedures are preferred when
the limitation of movement is severe, and the eye fails to cross the
midline. After Krizok explained the change in lateral rectus path, these
approaches saw multiple modifications.4 Yokoyama et al were the
first to perform a full loop myopexy of LR and SR 15 mm behind the
insertions using a polyester (non-absorbable) suture.13 Loop myopexy
using a suture has the potential complications of muscle cheese wiring
and/or strangulation of the anterior ciliary vessels. Therefore, other
materials have been used to avoid the above complications. Wong et
al performed loop myopexy using a silicone 240 band and tightened
it with a sleeve.14 Shih et al used Gore-Tex sling for muscle belly
union.15 Shenoy et al performed loop myopexy by passing the 240
silicone band through a scleral tunnel.16 This additional modification
by Shenoy et al to the loop myopexy by Wong secures the silicone
band to the sclera, thereby prevents its anterior migration. We prefer
using a silicone band to unite the muscles and restoring the muscle
path.

A limbal based superior and temporal conjunctival incision is made.
The lateral rectus and superior rectus are hooked and isolated using
muscle hooks and tenon capsule reflected. The paths of both muscles
are checked intraoperative for any shift and noted. Adequate precaution
is taken not to involve superior oblique while operating on the SR.
A scleral tunnel of 3–4 mm length is constructed 14 mm from the
limbus in between the bellies of SR and LR and a 240 silicone band
is passed under the lateral rectus and through the scleral tunnel and

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under superior rectus. The two ends were then tightened by pulling
across through a Watzke sleeve. The ends of the band is cut close to
the sleeve (Figure 5)

Hooking of lateral rectus (LR, image on
right), and superior rectus (SR, image on left)
through limbal incision
Shift of muscle path noted intraoperative

Scleral tunnel made 14 mm posterior to
limbus

240 silicone band passed under LR,
through tunnel and SR and tightened
using Watzke sleeve

Figure 5: Intraoperative Steps of Loop Myopexy using Silicone band

Recession of medial rectus has to be performed in all cases where
force duction testing reveals tightness, mostly in long standing cases.
Reports of post-operative exotropia have been noted in cases where
MR tightness is not noted. Moreover, if large recessions are needed in
cases with grade 4+ tightness, hang back or hemi-hang back techniques
can be employed.17

Another relevant point is regarding unilateral or bilateral surgery in
cases of heavy eye syndrome with significant difference in visual
acuity. It has been proposed that bilateral loop myopexy is preferable
to correct deviant muscle paths, however medial rectus surgery can be
staged based on tightness.18

Though loop myopexy is the most accepted surgical approach at present
yet chances of anterior segment ischemia, necrosis of band, extrusion
and infection of band, cheese wiring of suture, suture granuloma are
few of the rare post operative complications about which one must be
vigilant.

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Restoration of muscle path to correct the underlying pathophysiology
in the patients with esotropia with or without high myopia is the major
surgical principle. This holds true if orbital imaging suggests alteration
of paths of superior and lateral rectus muscles. Loop myopexy is a
well- tolerated and effective surgical procedure in these patients.
This can be performed with concurrent medial rectus recession in the
setting of muscle contracture to treat strabismus fixus.

References

1. Villasecca A: Strabismus fixus. Am J Ophthalmol 48:51, 1959.

2. Bagshaw J. The heavy eye phenomenon: a preliminary report. Br J Ophthalmol.
1966;23:73–78.

3. Bagolini B, Tamburrelli C, Dickmann A, Colosimo C. Convergent strabismus
fixus in high myopic patients. Doc Ophthalmol 1990; 74: 309–320.

4. Krzizok TH, Schroeder BU. Measurement of recti eye muscle paths by magnetic
resonance imaging in highly myopic and normal subjects. Invest Ophthalmol Vis
Sci 1999;40:2554–60.

5. Aoki Y, Nishida Y, Hayashi O, Nakamura J, Oda S, Yamade S, et al. Magnetic
resonance imaging measurements of extraocular muscle path shift and posterior
eyeball prolapse from the muscle cone in acquired esotropia with high myopia.
Am J Ophthalmol. 2003;136:482–

6. Yokoyama T, Tabuchi H, Ataka S, et al. The mechanism of development in
progressive esotropia with high myopia. In: de Faber J-T, ed. Transactions: 26th
Meeting, European Strabismological Association, Barcelona, Spain, 2000. Lisse
(Netherlands): Swets & Zeitlinger, 2001:218–22.

7. Demer JL et al.. Sagging eye syndrome: connective tissue involution as a cause
of horizontal and vertical strabismus in older patients. JAMA Ophthalmol
2013;131:619-25

8. Hayashi T, Iwashige H, Maruo T. Clinical features and surgery for acquired
progressive esotropia associated with severe myopia. Acta Ophthalmol Scand
1999;77:66–71 Sep; 22(3): 298–306.

9. Webb H, Lee J. Acquired distance esotropia associated with myopia. Strabismus.
2004;12:149–155

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A Complex Strabismus Entity: Strabismus Fixus
10. Yamaguchi M et al. Surgical Procedure for Correcting Globe Dislocation in

Highly Myopic Strabismus.Am J Ophthalmol 2010;149:341–346
11. Krzizok TH et al. New approach in strabismus surgery in high myopia. Br J

Ophthalmol 1997; 81:625– 630
12. Murthy R. Lateral fixation of sclera to the periosteum with medial rectus

disinsertion for severe myopic strabismus fixus. Indian J Ophthalmol 2008;
56:419 – 421
13. Yokoyama T, Ataka S, Tabuchi H, Shiraki K, Miki T. Treatment of progressive
esotropia caused by high myopia-a new surgical procedure based on its
pathogenesis. In de Faber JT, (ed)Transactions of the 27th ESA Meeting Swets
& Zeitlinger: Lisse (Netherlands)2002145–148
14. Wong I, Leo SW, Khoo BK. Loop myopexy for treatment of myopic strabismus
fixus. J AAPOS. 2005;9:589–591
15. Shih MH, Li ML, Huang FC. A preequatorial Gore-Tex sling to restore rectus
muscle pathways in myopic strabismus fixus. J AAPOS 2012;16:80–2
16. Shenoy BH, Sachdeva V, Kekunnaya R. Silicone band loop myopexy in the
treatment of myopic strabismus fixus: surgical outcome of a novel modification.
Br J Ophthalmol. 2015;99:36-40
17. Ranka MP, Steele MA. Esotropia associated with high myopia. Curr Opin
Ophthalmol. 2015 Jul;26(5):362-5
18. Morad Y, Pras E, Goldich Y, et al. Surgical treatment of esotropia associated with
high myopia: unilateral versus bilateral surgery. Eur J Ophthalmol 2010; 20:653
– 658

174 CME on COMPLEX STRABISMUS

12Ocular Myasthenia Gravis

Ocular Myasthenia Gravis

Dr. Savleen Kaur, Dr. Jaspreet Sukhija, Dr. Shagun Korla

Advanced Eye Centre, PGIMER, Chandigarh

Myasthenia gravis (MG) is a disease that affects the
neuromuscular junction resulting in classical symptoms of
variable muscle weakness and fatigability. History in patients
of myasthenia gravis may be vague and the patients might
complain of intermittent diplopia. In assessing these patients,
we need to establish diurnal variation and/or ptosis. They can
present with multiple muscle involvement. Pharmacological
testing with anticholinesterases can be diagnostic test of choice
besides serological and electrophysiological testing. Surgery of
strabismus is contraindicated in active stages of disease. Once
the disease is quiescent, a few patients may be candidates for
surgery. Considerations include careful general anaesthesia
and counselling for multiple procedures to achieve result.
Long-term surgical outcomes in these patients are still unclear.

Myasthenia gravis (MG) is a disease that affects the neuromuscular
junction resulting in classical symptoms of variable muscle weakness
and fatigability. It is the most common disease of the neuromuscular
junction. The pathophysiology involves an autoimmune process
which produces antibodies against the motor end plate reducing the
number of acetylcholine receptors. This in turn leads to inefficient
muscle contraction and premature muscle fatigue. Table 1 below
outlines the broad types of myasthenia. Ocular myasthenia gravis
(OMG) is a form of myasthenia gravis whereby the patients’
weakness is limited to the muscles of the eye and eyelids (levator
palpebrae superioris). The acetylcholine receptors (AChRs) are
most involved in this entity. Other antibodies include anti-muscle-
specific kinase (anti-MuSK) and anti-lipoprotein receptor-related
protein 4 (anti-LRP4). The hallmark of the disease is muscle fatigue.
The incidence is estimated at 0.3–2.8/100,000 and the prevalence

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Ocular Myasthenia Gravis

at 700,000 worldwide.1 Out of the total myasthenics, 15% is purely
“ocular” where no signs and symptoms of generalized disease
develop in a patient with ocular signs.2

Table 1: Enumerating the types of myasthenia gravis

Congenital

Juvenile

Adult onset
yy Pure ocular form
yy Mild generalized myasthenia
yy Moderate generalized myasthenia
yy Acute fulminant myasthenia
yy Late severe myasthenia gravis

Ocular myasthenia has male preponderance, good response to
steroids, relatively poor response to anticholinesterase drugs and
lower incidence of thymoma. Symptoms include intermittent diplopia,
diurnal variation such as the symptoms increase as the day progresses,
spontaneous closure of lid, and family history of autoimmune disease
like-graves; rheumatoid arthritis. Systemic signs of fatigue, dyspnoea
can also be present. Between 50 to 80% of all myasthenics present
with ocular signs and symptoms and half to two thirds with ocular
signs will develop generalized disease.

Why is there a preferential involvement of EOM: Twitch fibers in
EOMs develop tension faster and have a higher frequency of synaptic
firing than limb muscles therefore are more susceptible to fatigue/
blockade. Specific antigens make them susceptible to immune attack.
In addition, EOMs have a lower density of AChR, thus making them
more susceptible to symptoms. It is also theorized that differing epitope
expression in EOMs plays a role in their preferential involvement.5,6

Clinical features

1. Ptosis and diplopia constitute about 50% of the symptoms. The
patients usually present with intermittent diplopia. The symptoms

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also have a diurnal variation and increase as the day progresses
(Figure 1). Patients may also complain of spontaneous closure
of the lid. Family history of autoimmune disease like graves,
rheumatoid arthritis and systemic signs of fatigue, dyspnoea can
be elicited in some.

Figure 1: Forty-year female presenting with variable ptosis (Left).
On Lid Fatigability test, the lid droop increased after prolonged gaze at a

distance target (right)

2. After ptosis, under action of the extraocular muscles is the
second most common presenting complaint. The decreasing order
of muscle involvement include inferior rectus → superior oblique
→ medial rectus . These patients can have prominent vertical
strabismus also. They can mimic any type of neurogenic palsy.
Gaze palsies, generalized external ophthalmoplegia, as well as
features resembling internuclear ophthalmoplegia/ one and a half
syndrome can be seen.4 Muscle weakness usually fluctuates and
increases with muscle activity. Weakness of the extraocular
muscles occurs in nearly 90% at disease onset . In children. this
disease presents with strabismus in 88%. It may present as a
decompensating exo or esophoria even without ptosis. It has been
referred to as “The great masquerader”: because it may present
with any extraocular movement limitation so a combination of
findings that cannot be localized at one place should raise concern
for ocular myasthenia gravis (Figure 2 and 3). In children the most
commonly affected movements are supra and infraduction.

3. Abnormal head posture maybe seen due to the incomitant nature
of strabismus.

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Ocular Myasthenia Gravis

Figure 2: Forty-nine-year male presenting with left inferior rectus palsy.
Diurnal variation of symptoms led to the diagnosis of myasthenia gravis proven

on serology.

Figure 3: Ocular myasthenia may present with a multiple muscle involvement
as well.

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4. Pupillographic studies have confirmed reduced velocities of
pupillary constriction and there are also reports of fatigue of
accommodation with improvement after drug treatment in some.
Clinically, no involvement of pupils is seen and, muscarinic
receptors are spared.2,3

Assessment

The diagnosis of GMG/OMG is clinical, supported by a combination of
laboratory, imaging, and electrophysiology tests. In highly suspected
cases, clinical tests (sleep test, ice-pack test, edrophonium test) can
confirm the diagnosis.3,7

Bedside Tests

yy Sleep test: This test measures the improvement in manifestations
of OMG after a period of rest. The patient is asked to sleep or
rest with his or her eyes closed for a period of about 30 min.
Prior to the test, the patient is examined, and the ocular motility
deficits and/or ptosis present are measured. The diagnosis of
myasthenia can be confirmed by observing resolution of ptosis
or ophthalmoparesis immediately after a 30 min period of sleep.
Reappearance of the myasthenic signs over the next 30 s to 5 min
adds further confirmation.44

yy Deliberately fatigue extraocular muscles by asking to maintain
fixation on a target well above the eye level or on prolonged
upgaze. The ptosis and the symptoms worsen making a provisional
diagnosis of ocular myasthenia. COGAN LID TWITCH sign is as
sensitive as ice pack test for the diagnosis of myasthenia.

yy Ice pack test: An ice pack is placed over the patient’s closed eyelids
for a period of 2 min (for ptosis) to 5 min (for ophthalmoparesis).
The ocular motility deficits and ptosis are measured before and
after the test. Cooling reduces anticholinesterase (AChE) activity,
which increases the amount of available ACh at the neuromuscular
junction. It is positive when the upper eyelid elevates by at least 2
mm following ice application (Figure 4). Negative ice test result in
the presence of complete ptosis and does not rule out MG. The ice
test result may be positive in patients with negative edrophonium

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or anti-AChR-ab testing. The ice pack test sensitivity is about
76.9% in patients with diplopia8 and 92–96% in those with ptosis
with specificity ranging 79–98% 8-10

Figure 4: Middle aged female presented with left sided ptosis with diurnal variation
(A). On application of an ice pack for two minutes (B), the ptosis decreased
substantially (C).

yy Tensilon test: In this test, edrophonium (anticholinesterase) is
given intravenously, and muscle function compared before and
after the injection. In OMG patients, clinical improvement is seen
within 1 minute and can be readily quantified when obvious ptosis
and/or severe restriction of ocular motility are present. In different
studies, it is reported to have a 95% sensitivity, response rates
ranging between 88 and 95% 11,12

yy Neostigmine test: Neostigmine is a longer acting anticholinesterase
inhibitor, given 1.5 mg IM or 0.5 mg IV. Its action begins in 15-30
mins and lasts for up to 3 hours.

yy A trial of oral pyridostigmine for 1 week can also help in diagnosis.
These slow-acting ChE-Is may have a lower diagnostic sensitivity
than edrophonium given the more gradual clinical effect.

Electrophysiological Studies

yy Single fibre-electromyography (SF-EMG), when performed in the
orbicularis oculi muscle, is 79–100% sensitive for the detection
of OMG12-15, but it is time consuming and not largely available.
Repetitive nerve stimulation ( RNS) has limited sensitivity in
patients with OMG. In different studies, positivity rates ranged
from 16.7 to 44%16-18, Repetitive ocular vestibular evoked
myogenic potentials (RoVEMPs) can detect muscle fatigability
through direct recording from EOMs. RoVEMPs, at stimulation
rates of 20–30 Hz and recording from inferior oblique muscles
have sensitivity 71–89% and specificity 64–86%)19-21

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Serological Testing

Acetylcholine receptors (AChR) and muscle-specific tyrosine kinase 
( MuSK) Ab detection by radioimmunoassay (RIA) is highly specific
for the diagnosis. The sensitivity of AChR Abs in OMG is generally
thought to be around 50%. However, recent studies reported positivity
rates higher than 70%, particularly in male patients.22-23 Conversely,
there have been very few reports of MuSK-positive OMG 24.

An overview of all tests and their sensitivity and specificity are given
in table 2.

Test Ocular Myasthenia
Ice test myasthenia gravis

80% 88-95%

Repeated nerve stimulation 18-35% 60-85%

Acetylcholine receptor antibodies 45-65% 90%
Single fibre-SFEMG (gold standard) 95% 99%

Therapeutic Options

yy Oral pyridostigmine (90-300 mg/ day) or neostigmine: It is
the first-line treatment in nearly all OMG patients.  Side effects
include  diarrhea, hyperhidrosis and muscle cramps.25-26

yy Patients with unsatisfactory response to oral pyridostigmine are
candidates for immunosuppressive treatment. In retrospective
studies, prednisone and prednisolone were reported to be effective
in relieving symptoms, with response rates ranging from 66–
86%.27-29 High-dose intravenous methyl prednisolone (IVMP)
was also associated with faster improvement as compared to oral
route.3 Azathioprine31, Mycophenolate mofetil32 and Tacrolimus33
are beneficial both in relieving symptoms and in preventing
disease progression. Rituximab is very effective in the few OMG
subjects treated so far.34

yy Surgery: In current practice, thymectomy is considered on an
individual basis35, as initial treatment in early-onset AChR-
positive OMG36 or for patients with unsatisfactory response to
immunosuppression.26

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yy Other treatments like plasmapheresis is limited to management of
myasthenic exacerbations or crises. It can be used preoperatively
to prepare patients for thymectomy or other surgical procedures.38
Intravenous immunoglobulin (IVIg) accelerates the catabolism of
IgG in addition to suppressing antibody production and inhibiting
complement activation and Fc receptor function. Its role is limited
to the perioperative management of patients and treatment of
myasthenic crisis.39

Differentials: Condition such as Chronic Progressive External
ophthalmoplegia, Thyroid related ophthalmopathy can be confused
with ocular myasthenia. Pseudo myasthenia is a term used to describe
ocular involvement in parasellar meningiomas, aneurysms, or space
occupying lesions (Table 2)

Myasthenia Chronic Thyroid related
Gravis progressive ophthalmopa-
external thy
Etiology Autoimmune ophthalmoplegia
Autoimmune
Genetic,
mitochondrial DNA

Age Bimodal , peak in Progressive from Middle age

young adults adolescent to adult Proptosis,
diplopia,
Clinical Ptosis Ptosis decreased vision
features Diplopia progressive in severe cases.
Variability ophthalmoplegia
Diplopia less IR most common
FDT positive
Movements IR/SO/MR Horizontal
movements Local
inflammation,
Associated Fatiguability Pharyngeal muscle
features Generalized weakness, enlargement
weakness ataxia, deafness,
neuropathy Thyroid profile,
increased bulk
Diagnostic Neostigmine test, Muscle biopsy of EOM (tendon
tests Cogan lid sign, (GMS stain), sparing)
Anticholinester- thin, symmetrical
ase antibody extraocular
muscles

182 CME on COMPLEX STRABISMUS

Ocular Myasthenia Gravis

Extraocular muscle Surgery for strabismus in MG : Complete
remission of symptoms occur in only about 37% without surgery
so there may be selected patients who are candidates for surgery.
Prisms can be tried as a temporary measure. Conventional recessions
resections/ Faden operations are the most commonly needed surgeries.
Weakening of obliques may be needed in few cases. Usually more
than one procedure is needed. Success rates of strabismus surgery
are reported between 67-89% postoperatively in various studies37
Patients with positive forced ductions are reported to have poor
outcome37 However there is no correlation between length of stability
of preoperative ocular alignment and long-term success in patients
undergoing surgery. Greatest risk or limitation of surgery is lack of
symptomatic improvement because the disease is such that it is not
fully curable because of an inherent weakness of muscles. There is a
risk of ending up worse than beginning and persistence of diplopia.

The overall conversion rate to generalized disease is 20.9%. If MG
remains limited to ocular features for 1 year, the likelihood of
progression is 16%, whereas if disease remains localized for 3 years,
the likelihood of progression to generalized MG is only 6%.29

Pediatric myasthenia: MG in children can be classified based on the
age at onset and disease pathogenesis – transient neonatal myasthenia,
congenital myasthenia, and juvenile autoimmune myasthenia.40,41
Congenital myasthenia42 syndromes refer to a subset of children with
myasthenia where the disease is caused by structural or functional,
presynaptic or postsynaptic abnormalities. The treatment in these
cases is mainly supportive.43,44

References

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3. Smith SV, Lee AG. Update on Ocular Myasthenia Gravis. Neurol Clin. 2017
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4. Cleary M, Williams G, Metcalfe RA. The pattern of extra-ocular muscle
involvement in ocular myasthenia. Strabismus. (2008) 16:11–8. doi:
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5. Kaminski, H.J.; Maas, E.; Spiegel, P.; Ruff, R.L. Why Are Eye Muscles
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8. Chatzistefanou KI, Kouris T, Iliakis E, Piaditis G, Tagaris G, Katsikeris N,
et al. The ice pack test in the differential diagnosis of myasthenic diplopia.
Ophthalmology. (2009) 116:2236–43. doi: 10.1016/j.ophtha.2009.04.039

9. Natarajan B, Saifudheen K, Gafoor VA, Jose J. Accuracy of the ice test in
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10. Fakiri MO, Tavy DL, Hama-Amin AD, Wirtz PW. Accuracy of the ice test in
the diagnosis of myasthenia gravis in patients with ptosis. Muscle Nerve. (2013)
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11. Benatar M. A systematic review of diagnostic studies in myasthenia gravis.
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12. Kusner LL, Puwanant A, Kaminski HJ. Ocular myasthenia: diagnosis,
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13. Giannoccaro MP, Di Stasi V, Zanesini C, Donadio V, Avoni P, Liguori R.
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15. Giannoccaro MP, Paolucci M, Zanesini C, Di Stasi V, Donadio V, Avoni P, et
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18. Lo YL, Najjar RP, Teo KY, Tow SL, Loo JL, Milea D. A reappraisal of diagnostic
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21. de Meel RHP, Keene KR, Wirth MA, Weber KP, Badrising UA, Verschuuren JJ, et
al. Repetitive ocular vestibular evoked myogenic potentials in myasthenia gravis.
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013-0421-9

23. Hendricks TM, Bhatti MT, Hodge DO, Chen JJ. Incidence, epidemiology, and
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24. Bennett DLH, Mills KR, Riordan-Eva P, Barnes PRJ, Rose MR. Anti-MuSK
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25. Kupersmith MJ, Ying G. Ocular motor dysfunction and ptosis in ocular
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10.1136/bjo.2004.063404

26. Kerty E, Elsais A, Argov Z, Evoli A, Gilhus NE. EFNS/ENS Guidelines for the
treatment of ocular myasthenia. Eur J Neurol. (2014) 21:687–93. doi: 10.1111/
ene.12359

27. Evoli A, Tonali P, Bartoccioni E, Lo Monaco M. Ocular myasthenia: diagnostic
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j.1600-0404.1988.tb06970

28. Sommer N, Sigg B, Melms A, Weller M, Schepelmann K, Herzau V, et al.
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29. Kupersmith MJ. Ocular myasthenia gravis: treatment successes and failures in
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30. Ozawa Y, Uzawa A, Kanai T, Oda F, Yasuda M, Kawaguchi N, et al. Efficacy of
high-dose intravenous methylprednisolone therapy for ocular myasthenia gravis.
J Neurol Sci. (2019) 402:12–15. doi: 10.1016/j.jns.2019.05.003

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31. Sommer N, Sigg B, Melms A, Weller M, Schepelmann K, Herzau V, et al.
Ocular myasthenia gravis: response to long-term immunosuppressive treatment.
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32. Yagi Y, Sanjo N, Yokota T, Mizusawa H. Tacrolimus monotherapy: a promising
option for ocular myasthenia gravis. Eur Neurol. (2013) 69:344–5. doi:
10.1159/000347068

33. Mantegazza R, Antozzi C. When myasthenia gravis is deemed refractory:
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09191-6

35. Melzer N, Ruck T, Fuhr P, Gold R, Hohlfeld R, Marx A, et al. Clinical features,
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36. Sussman J, Farrugia ME, Maddison P, Hill M, Leite MI, Hilton-Jones D.
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Mar;33(1):40-4

38. López-Cano M, Ponseti-Bosch JM, Espin-Basany E, Sánchez-García JL,
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gravis: A review. Indian J Ophthalmol 2014;62:985-91.

186 CME on COMPLEX STRABISMUS

13Treatment of Thyroid Related Strabismus

Treatment of Thyroid
Related Strabismus

Prof Dr Rosario Gomez de Liaño, Dr E.Hernandez,
Dr B Domingo, Dr L Morales

Hospital Clínico San Carlos, Madrid, Spain

Introduction

Thyroid eye disease (TED) is an inflammatory, autoimmune, self-
limiting disease that affects orbital and periorbital tissues. It is
associated with Graves’ Disease (GD) with hyperthyroidism, although
it may be present in hypothyroid patients, euthyroid patients and in
3% of cases in patients with Hashimoto’s thyroiditis.1

In 60-85% of the patients, the orbitopathy appears together with
hyperthyroidism within a period of 18 months, but there are cases in
which the orbitopathy may precede the hyperthyroidism and in others
appear months to years after. TED is more common in women but may
be more severe in males.

The activity and evolution of the disease can be very long until
stability is obtained being often between a 1.5-3 years from the
beginning. Some patients have unpredictable reactivations. The level
of thyroid-stimulating hormone-receptor (TSH-R) antibody, thyroid-
binding inhibitory immunoglobulin (TBII), and anti-microsomal
antibody is related to greater severity of orbitopathy. However today
there is no laboratory test that confirms the inactivity2,3,4. When the
TED is associated with Myasthenia Gravis (MG) they seem to have a
more unpredictable evolution and treatment becomes longer and more
complex.5

There are different clinical forms of TED. There are patients who
develop more exophthalmic and lipogenic forms, in others we
find more restrictive myogenic forms, other patients have greater
involvement of the apex and others mixed characteristics.6 Muscle

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fibrosis occurs in a long progressive deterioration. Of all the clinical
aspects that affect thyroid patients, strabismus is what most affects the
quality of life (QoL) and is the one that improves the most when it is
resolved.7

Types of strabismus

About 20-30% of patients with TED and hyperthyroidism have
clinically visible orbitopathy, but up to 80% of them have radiological
signs. It is common that the disease affects several muscles in both
eyes in an asymmetric way. In a study conducted at our institution of
the orbital MRI of a series of 137 patients, the muscle most frequently
affected was the IR followed by the MR, and therefore the strabismus
most frequently found was an esotropia with limitation of abduction
and hypotropia with limitation of elevation (Table 1). However, all
muscles can be affected to different degrees, and if the antagonist
muscles or the yoke muscles are also tight it can be a cause of surgical
overcorrection after a muscle recession. Therefore, it is important
to evaluate all muscles during examination, on the passive duction
and imaging tests. In recent years the importance of the involvement
of oblique muscles especially the superior oblique muscle and its
influence on the postoperative A pattern and incyclotorsion has been
increasingly highlighted.8,9

The types of strabismus that we will find most often associated in
patients with TED are:
1. Esotropia with limitation of abduction
2. Vertical strabismus with limitation of one or both eyes and greater

in elevation and less frequent in depression.
3. The mixed horizontal and vertical deviations.
4. A Pattern type and incyclotorsion deviation.

Ocular myasthenia must be ruled out in a patient with exotropia and
ptosis.

In cases of vertical deviations, it is necessary to consider the situation
of the four vertical rectus of both eyes. The cyclotorsion deviation
must be understood as the balance of the different muscles affected.

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When we have a patient with an IR fibrosis, we expect to have an
hypotropia with limitation of elevation and excyclotorsion. If bilateral
IR are affected, the hypotropia in primary gaze will depend on the
asymmetry of involvement of the two eyes, but the excyclotorsion
will be greater. If the patient does not have a marked exyclotorsion
(10-15º), it must be suspected that it is counteracted by the SR or SO
contracture. When the upper complex is affected, the diplopia will be
greater in the downgaze. It is rare to have a patient with involvement
of the oblique muscles alone. The cross-sectional area of SO increased
in 96% of patients with TED in a mean of 2 standard deviations
compared to the control group in a study.10

In more severe cases we may have a horizontal and vertical
involvement of both eyes with large ET and hypotropia. (Figure 1).
In addition, there are many situations that we may have patients with
atypical pictures due to their form of ocular onset such as those that
begin without inflammation, with exotropia, or are associated with an
Ocular Myasthenia. In cases which are euthyroid, the evolution is less
predictable and may present more reactivations. (Figure 2).

Figure 1: Large ET and Hypotropia in a TED patient before (A) and after (B)
Bilateral MR recessions and RE IR recession.

A B C D

Figure 2: A. Atypical presentation of TED who debuted in 2007 with right XT and HT
with thyroid MRI characteristics but seronegative. B. He had a bilateral reactivation
two years later. The laboratory test became positive for Hyperthyroidism (7 years after)
and MG (5 years). C. Fibrotic changes made that then patient developed an ET with
important restrictions of all eye movements. D. After bilateral OD and muscle surgery.

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Not all patients with TED have diplopia. Diplopia in TED can be
intermittent or permanent or appear only in some position of gaze.
Many patients relieve it by adopting a head compensating position,
often with a chin up position, and generating a fusion amplitude
that compensate the deviation. Quality of life is more affected when
diplopia is present in the primary position and downgaze than upgaze,
and in vertical movements than in Lateral gazes. After surgery, quality
of life improves due to elimination of diplopia but patients feel great
symptomatic benefit due to reduction in pain on ocular rotations.11
Strabismus and ocular restrictions may appear or increase after orbital
decompression (OD) (between 0 and 45 %) (Figure 3)12. However,
lower eyelid retraction may improve by reducing exophthalmos.
In a series of 30 patients reviewed at our center, undergoing OD,
strabismus increased in 17 patients; 14% were new strabismus cases.
The horizontal and vertical deviation increased from an ET of 15.1
PD and vertical of 16 PD pre-decompression to an ET of 24.6 PD
and vertical of 17.9 PD after decompression. The modification of
strabismus depends on the intensity of fibrosis and the technique of
decompression that was practiced. Deterioration is more frequent in

Figure 3 : TED Patient with restrictive ET. First line deviation before OD, second
line, ET increased after OD, third line after MR recession, 4 line after LRL plication

of 5 mm, good alignment in PP is obtained but limitation of LE abduction is
observed

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Treatment of Thyroid Related Strabismus

patients who already had previous diplopia, when the medial wall
is decompressed versus the lateral one, the decompression is of the
infero-medial wall or patient had 3-wall decompression (9% the
lateral wall, 39% other walls and mixed surgeries)13. Other factors of
poor prognosis after OD are advanced age, sex (male) and history of
smoking.14,15

Ocular torsion in TED as mentioned previously is the result of the
balance of all muscles affected in both orbits by the disease, as well
as by the displacement of the muscles and their pulleys after orbital
decompression. Table 1 shows ocular torsion in a series of patients
measured at our institution. Ocular torsion is an important measure
for the analysis of the involvement of the different muscles, as well
as a predictive factor to evaluate the risk of over-correction after
muscle recessions. Some patients with significant cyclotorsion do not
manifest it while being hidden by the large vertical and/or horizontal
deviation. In non-operated patients the most frequent ocular torsion to
find is an excyclotorsion due to the greater involvement of the IRs and
to some extent due to a secondary overaction of the ipsilateral IO.16 If
excyclotorsion is greater than 15º, both IR are usually very fibrotic.
But if we have an intense fibrosis of the IR and the excyclotorsion
is less than 3-4º we must reevaluate the involvement of the superior
complex (SR – SO) that are balancing this torsion. Incyclotorsion
occurs more frequent postoperatively after IR recessions, when there
is involvement of the superior complex or after OD. The decrease

Table 1 Ocular torsion in a series of patients measured at our institution.

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Treatment of Thyroid Related Strabismus

in the depression after recession of the IR favors the overaction of
the SO and SR muscles creating an A-pattern with incyclotorsion in
downgaze. OD modifies the position of the eyeball depending on the
decompressed walls. In the most intense OD surgeries, a displacement
of the eyeball towards the medial and inferior decompressed spaces
induces greater ET and hypotropia and this modification also has an
impact on the actions of the oblique muscles.17

Oculomotor examination in the patient with TED

In our institution patients are examined in a multidisciplinary
Graves’ Disease unit in which the simultaneous evaluation by an
endocrinologist, an oculoplastic and an expert in ocular motility
are combined on the same day. The VISA (vision, inflammation,
strabismus, and appearance), NOSPECS and the European Group
of Graves’ Orbitopathy (EUGOGO) classifications are widely used
grading systems used to assess the activity and severity of TED.
Ocular motility and binocular vision examination include anamnesis
on diplopia evolution, evaluation of the compensating head position,
Prism cover test at distance and near, ocular versions and ductions.
We note the arching of eyebrows characteristic of the effort of the
eyes to fix on PP against the restriction of the IR. We evaluate ocular
torsion by means of double Maddox rod. We perform passive duction
if needed to evaluate restriction of a certain muscle.

Figure 4 : BSV field in a patient in whose restrictions increased, evaluated
six months apart

192 CME on COMPLEX STRABISMUS

Treatment of Thyroid Related Strabismus

On the same sheet we record the examination with the Weiss or Hess
screen and the single visual field (BSV).18,19 BSV testing is very useful
for the follow-up of patients specially when both eyes have marked
restrictions. In our sheet protocol we also add imaging details of the
patient. (Figure 4)

Imaging tests provide important information in TED patients. There
are patients without apparent orbitopathy who present muscular
radiological manifestations that are not so evident in the versions.
CT and MRI are reserved for the differential diagnosis, management

D

E
F

Figure 5: Medial rectus muscle thickness measurements and response to
tocilizumab. Medial rectus thickness measured at 7.2 and 9.2 mm from the limbus
by optical coherence tomography in a healthy control (A), in an inactive (B) and in
an active (C) Graves’ ophthalmopathy patient. (D) Chemosis before and following

tocilizumab treatment (D, E) (22,23)

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Treatment of Thyroid Related Strabismus

of complex cases or prior to surgery. In some centers ultrasound is
used for inflammatory follow-up.20 Muscle reflectibility changes
with edema and muscle thickening is seen, but an experienced staff
is needed.21 OCT allows us to analyze with high quality the anterior
part of the extraocular muscles and being a technique available to the
ophthalmologist allows us to follow the inflammatory evolution, as
well as the response to various types of steroid or immunomodulatory
treatments22,23. (Figure 5) The CT is the imaging test of choice prior to
the OD to analyze the walls, as well as their remodeling. MRI is most
useful technique for the evaluation of muscle involvement.24 In T1
with fat suppression we can see muscle activity bright while orbital
fat is seen dark. It is most visible in T2 where bright fat and dark
muscle are seen intensified in activity; MRI informs us if there is still
inflammation, helps to complement the diagnosis we make with the
motility examination. Short-tau inversion recovery (STIR) sequences
are also useful to detect an active inflammatory process in muscles.
We can analyze the involvement of each muscle in both orbits, their
antagonist and yoke muscles to avoid surgical overcorrection. It also
provides us with information on the muscular position after OD, as
well as the situation of the optic nerve and possible apical compression.

There are several techniques to evaluate the cyclotorsion, the most
standardized measurement being the double Maddox rod. Harms
screen and the Synoptophore can quantify it with great precision.
However, the torsion can be very variable from one examination to
another and from the primary position up and downgaze so it must
be repeated and consider that when exploring the patient, he has the
head well positioned and does not have the head with the chin raised
to compensate for the tension of the IR.

It is important to evaluate the compensating torticollis presented in
TED, often patients raise the chin either because the deviation is lower
or disappears in downgaze or because the tension of the IR is reduced
in that position. It is advisable to evaluate this torticollis monocularly.
If the patient elevates the chin with both eyes fixing it is a sign of
severe fibrosis in both eyes and suggests the need for symmetrical or
asymmetric bilateral recession of the IR depending on the magnitude
of deviation in PP.

194 CME on COMPLEX STRABISMUS