CME Complex Strabismus

Dissociated Vertical Deviation

4. Stevens GT: On double vertical strabismus. Am Oculist, Paris, 113:225-232,
1895.

5. Bielschowsky A: Lectures on Motor Anomalies. Dartmouth Publications, New
Hampshire, 1940 p. 18.

6. Brodsky MC. Dissociated Vertical Vergence: a righting reflex gone wrong. Arch
Ophthalmol 1999;117:1216-1222.

7. Guyton D. Dissociated Vertical Deviation. An exaggerated normal eye movement
used to damp cyclovertical nystagmus. Trans Am Ophthalmol Soc 1998;96:389.

8. Guyton D. Dissociated Vertical Deviation: Etiology, Mechanism, and Associated
Phenomena J AAPOS 2000;4:131-44.

9. Rosenbaum-Santiago. Clinical Strabismus Management. W.B Saunders
Company 1999 (p.238)

10. Bechtel RT, Kushner BJ, Morton GV. The relationship between dissociated
vertical divergence (DVD) and head tilts. J Pediatr Ophthalmol Strabismus.
1996;33(6):303-6.

11. Velez Restrepo G. Desviacion vertical disociada. Arroyo-Yllanes ME. Ed.
Anales XIII Congreso del Consejo Latino Americano de Estrabismo Acapulco,
1998 p2-3.

12. Good WV, Hoyt CS. Divergent vertical deviation. In Good WV, Hoyt CS, eds
Strabismus Management. Boston, MA: Butterworth-Heinemann;1996.

13. Fitzgerald BA, Billson FA. Dissociated Vertical Deviation: evidence of abnormal
visual pathway projection. B J Ophthalmol,1984;68:801-806.

14. Mattheus S, Deberitz I, Kommerell G. Differentialdiagnose zwischen
inkomitierendem und dissoziiertem Schielen. Arbeitskreis Schielbehandlung
Berufsverband Augenärtzte Deutschlands 1976;10:135-7.

15. Bielschowsky A. Lectures on motor anomalies: II. The theory of heterophoria.
Am J Ophthalmol. 1938;21:1129.

16. Posner A. Noncomitant hyperphorias: Considered as aberrations of the postural
tonus of the muscular apparatus. Am J Ophthalmol. 1944;27:1275.

17. Olivares-Medina MR, Arroyo Yllanes ME. Comportamiento clínico de la
desviación vertical disociada. Rev Mex Oftalmol;67:43, 1995.

18. Bielschowsky A: Die einseitigen und gegensinnigen („dissoziierten“)
Vertikalbewegungen der Augen. Graefes Arch Ophthalmol 1931;125:493.

19. Raab EL: Dissociated vertical deviation. Int Ophthalmol Clin 1985;25:119.

20. Magoon E, Cruciger M, Jampolsky A. Dissociated Vertical Deviation: An
Asymmetric Condition treated with Large Bilateral Superior Rectus Recession. J
Pediatr Ophthalmol Strabismus, 1982;19(3):152-6.

CME on COMPLEX STRABISMUS 95

Dissociated Vertical Deviation

21. Esswein MB, von Noorden GK, Coburn A. Comparison of Surgical
Methods in the Treatment of Dissociated Vertical Deviation. Am J
Ophthalmol.1992;113:287-290.

22. Julio Prieto Diaz, Carlos Souza Días. Estrabismo. Ediciones Científicas
Argentinas, 5ta Edicion, 2005.(p.233)

23. Repka MX, Fishman PJ, Guyton DL. The Site of Reattachement of the
Extraocular Muscle Following Hang-Back Recession. J Pediatr Ophthalmol
Strabismus, 1990;27(6):286-290.

24. Scott AB. Planning inferior oblique muscle surgery. In Reinecke RD, editor.
Strabismus. New York: Grune and Stratton; 1978. p. 347-54.

25. Elliott RL, Nankin SJ. Anterior transposition of the inferior oblique. J Pediatr
Ophthalmol Strabismus 1981;18:35-8.

26. Mims JL, Wood RC. Bilateral transpositions of the inferior obliques. Arch
Ophthalmol 1989;107:41-4.

27. Kratz RE, Rogers GL, Bremer DL, Leguire LE. Anterior tendon displacement of
the inferior oblique for DVD. J Pediatr Ophthalmol Strabismus 1989;26:212-7.

28. Burke JP, Scott WE, Kutschke PJ. Anterior transposition of the inferior oblique
muscle for dissociated vertical deviation. Ophthalmology 1993;100:245-50.

29. Bacal DA, Nelson LB. Anterior transposition of the inferior oblique muscle for
both dissociated vertical deviation and/or inferior oblique overaction: results of
94 procedures in 55 patients. Binoc Vis Eye Muscle Surgery Qtrly 1992;7:219-25.

30. Caputo AR, Santiago AP. Bilateral anterior transposition of the inferior oblique
for dissociated vertical deviation in congenital esotropia. Am Orthoptic J
1996;46:133-42.

31. Black BC. Results of anterior transposition of the inferior oblique muscle in
incomitant dissociated vertical deviation. J AAPOS 1997;1:83-7.

32. Stager DR. The neurofibrovascular bundle of the inferior oblique muscle as the
ancillary origin of that muscle. J AAPOS 1997;1:216-25.

33. Snir M, Axer-Siegel R, Cotlear D, Sherf I, Yassur Y. Combined Resection and
Anterior Transposition of the Inferior Oblique Muscle for Asymmetric Double
Dissociated Vertical Deviation. Ophthalmology 1999;106:2372-76.

34. Quinn AG, Kraft SP, Day C, Taylor RS, Levin AV. A Prospective Evaluation of
Anterior Transposition of Inferior Oblique Muscle, With and Without Resection,
in the Treatment of Dissociated Vertical Deviation. J AAPOS 2000;4:348-53.

35. Engman JH, Egbert JE, Summers CG, Young TL. Efficacy of Inferior Oblique
Anterior Transposition Placement Grading for Dissociated Vertical Deviation.
Ophthalmology 2001;108:2045-2050.

96 CME on COMPLEX STRABISMUS

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36. Fard MA. Anterior and nasal transposition of the inferior oblique muscle for
dissociated vertical deviation associated with inferior oblique muscle overaction.
J AAPOS 2010;14:35-38.

37. Can D, Ozkan SB, Kasim R, Duman S. Surgical results in highly asymmetric
dissociated vertical deviations. Strabismus 1997;5(1):21-26.

38. Lorenz B, Raab I, Boergen KP. Dissociated Vertical Deviation: What Is The Most
Effective Surgical Approach? J Pediatr Ophthalmol Strabismus. 1992;29(1):21-
29.

39. Haslwanter T, Hoerantner R, Priglinger S. Reduction of ocular muscle power by
splitting of the rectus muscle I: Biomechnics. Br J Ophthalmol 2004;88:1403-
1408.

40. Arroyo Yllanes et al. Plegamiento del recto inferior unilateral para el tratamiento
de la desviacion vertical disociada. Cir y Cir 77:7, 2007

41. Esswein Kapp MB, von Noorden GK: Treatment of residual dissociated vertical
deviation with inferior rectus resection. J Pediatr Ophthalmol Strabismus
1994;31:262.

42. Gamio S. A surgical alternative for Dissociated Vertical Deviation based on
new pathlolgic concepts: weakening the all four oblique muscles. Outcome and
results in 9 cases. Binoc Vis Eye Muscle Surgery Qtrly 2002;17(1):15-24.

43. Acosta Silva MA, Campomanes G. Cirugía de cuatro oblicuos para Desviación
Vertical Disociada y sindrome en “A” .CLADE anais 2000 del XIV Congreso del
CLADE, Sao Paulo. Pag 359-360

44. Texeira Krieger F, Caron Lambert A. Efeito do debilitamento do músculo Oblicuo
superior hiperfuncionante associado a anteriorizacao do músculo oblicuo inferior
na Divergencia Vertical Dissociada . CLADE anais 2000 del XIV Congreso del
CLADE, Sao Paulo. Pag 447-450

45. Romero-Apis D, Castellanos-Bracamontes A. Inervational and inhibitional
surgery for dissociated vertical deviation. Acta Estrabológica Vol XLIV, Julio-
Diciembre 2015; 2: 00-00.

46. Varn MM, Saunders RA, Wilson ME. Combined Bilateral Rectus Muscle
Recession and Inferior Oblique Muscle Weakening for Dissociated Vertical
Deviation. J AAPOS 1997;1:134-7.

47. Velez FG, Ela-Dalman N, Velez G. Surgical management of dissociated vertical
deviation associated with A-pattern strabismus. J AAPOS 2009;13(1):31-35.

48. McCall LC, Rosenbaum AL: Incomitant dissociated vertical deviation and
superior oblique overaction. Ophthalmology 1991;98:911

CME on COMPLEX STRABISMUS 97

Dissociated Vertical Deviation
49. Shin GS, Elliott RL, Rosenbaum AL: Posterior superior oblique tenectomy at

the scleral insertion for collapse of A-pattern strabismus. J Pediatr Ophthalmol
Strabismus 1996;33:211.
50. Freeman RS, Rosenbaum AL. Residual incomitant DVD following large bilateral
superior rectus recession. J Pediatr Ophthalmol Strabismus1989;26:76-80.
51. Gamio S. Hypotropia In Patients with Dissociated Vertical Deviation.
Transactions of the 31st European Strabismological Association meeting.
Mykonos, Greece. May 2007. p 337-340.
52. Bremer DL, Rogers GL, Quick LD: Primary-position hypotropia after anterior
transposition of the inferior oblique. Arch Ophthalmol 1986;104:229.
53. Kushner BJ. Restriction of elevation in abduction after inferior oblique
anteriorization. J AAPOS 1997;1:55-62.
54. Raab EL. Dissociated vertical deviation. Int Ophthalmol Clin 1985;25:119.
55. Sargent RA. Surgical corrections of dissociated hyperdeviations. Am J
Ophthalmol 1976;26:89.
56. Kushner BJ. The effect of anterior transposition of the inferior oblique muscle on
the palpebral fissure. Arch Ophthalmol. 2000;118:1542-6.

98 CME on COMPLEX STRABISMUS

06Monocular Elevation Deficit

Monocular Elevation
Deficit

Dr Subhash Dadeya, Dr Shipra Sarda

Guru Nanak Eye Centre, Maulana Azad Medical College, New Delhi

Introduction

Monocular elevation deficiency (MED) syndrome complex (or the
Double elevator palsy) a common cause of hypotropia, is defined as the
inability to elevate the paretic eye from any position of gaze provided
the ductions are normal in all other positions of gaze. Initially, it was
described by Dunlap and known as Double Elevator Palsy. This term
was misnomer, because paralytic, restrictive as well as supranuclear
lesions can lead to impaired unilateral upgaze palsy, therefore it was
replaced by MED, which is a more accurate term. Currently MED is
considered part of a group of conditions caused by loss of innervation
to an eye muscle called congenital innervation dysgenesis syndrome
(CID).2

Pathophysiology

The supranuclear centres for upgaze are situated in midbrain
pretectum. The crucial centre for mediating vertical gaze is rostral
intermediary nucleus of median longitudinal fasciculus (riMLF) and
posterior commissure. From riMLF, fibres leave and decussate in
posterior commissures, then through pretectum enter the nucleus of
superior rectus (SR) muscle. After leaving the subnucleus the fibres
decussate again. So, SR is innervated from ipsilateral riMLF as well
as contralateral pretectum and SR subnucleus. In cases of MED, it
is presumed that there is an interruption of supranuclear input from
riMLF into the third cranial nerve nucleus. As supranuclear elevation
deficiency affects fibres controlling upgaze, so Kircham & Kline
mentioned a compartmentalization of supranuclear gaze up and below
primary position. This theory explains that in some patients with MED
have a normal vertical saccadic test below midline but an abnormal
test above midline.4

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Etiology

MED can be congenital or acquired.

yy Congenital MED can occur sporadically and caused by
supranuclear defects, primary IR restriction or secondary IR
restriction secondary to SR paresis. Some congenital cases are
associated with neonatal hypoxia also.5

yy Acquired MED is caused by variety of disorders including – cerebro
vascular disease (hypertension, arteritis, thromboembolism)
midbrain tumours, granulomatous (sarcoidosis) and infectious
diseases (syphilis)6 and cysticercosis which is common in this part
of country.

ZIFFER et al3 classified MED on the basis of saccadic velocities
evaluated by scleral research coil into three types :-

a. TYPE 1 MED – due to primary IR restriction or fibrosis. Patient
often does not have hypotropia in primary gaze. FDT shows
restriction of upward rotation because of tight IR. Upward
saccades are normal and intact until stopped by tight IR. Bell’s is
usually poor. An exaggerated infraorbital lid crease can be seen on
attempted up gaze in patients with IR restriction

b. TYPE 2 MED- due to primary SR palsy which is characterised
by FDT showing no restriction to full upward rotation. Upward
saccades are slow or floating both below and above the midline.
Bell’s is generally absent in these cases.

c. TYPE 3 MED- includes supranuclear MED characterised by
intact or mildly reduced vertical saccadic velocity below midline
but reduced velocity above midline. FDT shows negative results.
Bell’s phenomenon is present as a result of an intact oculomotor
nerve, fasciculus and nucleus.

Clinical Characteristics

1. Limitation of upgaze
Most common presentation of MED is unilateral limitation of
upgaze which is same in all three horizontal positions – abduction,
adduction and primary position above the midline with accompanying

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ptosis (Figure 1-4). Hypotropia is usually seen on the affected side.
Horizontal deviations have been reportedly seen in some cases of
MED.7,8 Patient may also present with diplopia,15,16 abnormal head
posture or amblyopia6 depending upon fixation preference and degree
of binocularity.

2. Abnormal Head Posture

In a patient with some degree of fusion has a head tilt backwards with
a chin-up position in order to maintain binocularity if hypotropia is
present in the affected eye. In a patient with normal head posture either
hypotropia is not present in affected eye or the patient has developed
amblyopia in the hypotropic affected eye. On rare occasions patient
may take fixation from affected eye which leads to large secondary
hypertropia in the non-affected eye. In patients where secondary
hypertropia is present, the unaffected eye may be amblyopic.9

Figure 1: Showing Clinical photo of a patient with MED depicting deficit in
elevation on adduction, abduction and primary elevation.

3. Ptosis

Due to presence of fascial attachments between the levator palpabrae
superiosis and the superior rectus muscle, ptosis is usually associated
with hypotropic eye. True levator weakness can be seen in 25% cases.10
Ptosis is more profound when normal eye takes fixation. MED can
have a component of both pseudoptosis and true levator weakness.11,12
Pseudoptosis can be differentiated from true ptosis in such a way that

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Monocular Elevation Deficit

is disappears when hypotropic eye takes fixation in primary position
(Figure 1-4). In such cases, ptosis is partly recovered when patient
takes fixation with affected eye. Marcus gunn jaw winking ptosis has
also been reported in patients with MED.13

Figure 2: Showing a male patient with hypotropia on primary gaze with
pseudoptosis.

Figure 3: Showing nine gaze photos of a patient with MED

Figure 4: Showing abnormal head posture i.e. chin elevation in a patient with MED
102 CME on COMPLEX STRABISMUS

Monocular Elevation Deficit

4. Bell’s Phenomenon
It is usually absent in all cases except MED caused by supranuclear
defects.14

5. Upward Saccades
In all cases of SR palsy, the upward saccades are slow or floating.
In cases of IR restriction saccades are usually intact. In cases of
supranuclear defects, saccades are absent above the midline.

6. Diplopia
MED with congenital onset usually has no complaints of diplopia as the
affected eye is usually amblyopic. In acquired MED however,usually
presents with diplopia in upgaze.15-16

7. Amblyopia
Amblyopia is present in congenital cases depending upon fixation
preference and degree of binocularity

Acquired MED has following characteristics clinically6 (Figure 5).
1. Acute onset of diplopia in primary position and upgaze
2. Ptosis is usually mild or not present
3. Associated with pupillary abnormalities, convergence weakness

or downgaze paresis.

Figure 5: Case of Acquired MED

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Monocular Elevation Deficit

4. Bell’s phenomenon usually present
5. Chin-up head position in order to maintain binocularity or reduce

diplopia.

Diagnosis

History and clinical examination
A relevant history is to be obtained from the patient or the parent.
Presence of amblyopia suggests a congenital etiology if sequence of
events is unclear. In cases of acquired MED, history of any neurological
symptoms, past medical and general systemic history is to be noted.

Clinical examination plays the most important role in finding
the etiology behind MED. The amount of IR restriction, bell’s
phenomenon, upward saccades, head posture, amount of ptosis are
some of the relevant clinical findings to be examined in a patient with
MED. Cover and uncover tests are done to measure the amount of
vertical deviation as well as horizontal deviation if present. Certain
tests like Worth-4 dot and Stereopsis tests also holds importance and
should be done in forced primary gaze and downgaze. Many patients
develop suppression or diplopia in primary gaze and will fuse in
downgaze. Hess carting is also useful in these cases.

Park’s Three Step Test. Park 3-step test and Bielschowsky’s head tilt
test are used to rule out a superior oblique palsy.

PBCT: The amount of vertical strabismus and any horizontal deviation
may be recorded with the prism cover test. It helps in deciding the
management.

Stereopsis: Binocularity is tested by worth four dot testing, and
stereopsis tests should be done in both primary gaze and down gaze.
Many patients would fuse in down gaze, but suppress or develop
diplopia in primary gaze

Investigations
In cases of acquired MED

Laboratory tests should include complete blood count with differential
leucocyte count, rapid plasma antigen or venereal disease research

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Monocular Elevation Deficit

laboratory test, fluorescent antibody absorption test, erythrocyte
sedimentation rate and angiotensin converting enzyme levels. Imaging
modalities include CXR, CT, MRI, MRA as per requirement.

Forced Duction Test- It is done to rule out IR restriction. If IR
restriction is present the affected eye would not rotate passively
relative to the other eye.

Forced Generation Test- This test quantifies the degree of paresis. If
paresis of SR muscle is there, examiner will feel a less powerful tug as
compared to the unaffected eye. If palsy is present, no or minimal tug
is felt in the affected eye.6

Vertical Saccadic Velocity- it can be measured clinically as well as
objectively i.e. by EOG and sclera search coil testing. The latter is
more accurate.3

Table 1 showing differences between congenital and acquired
MED

Congenital Acquired MED
MED

Age Usually a child Any age, usually adult

Onset At birth Can start at any age depending

upon the cause but more often in

older age group with diabetes,

hypertension, atherosclerosis,

arteritis, other CV disorders

Clinical Strabismus, Acute onset diplopia in primary
features ptosis and upgaze. Ptosis is usually not
present. Pupillary abnormalities
may be present. Ataxia, tinnitus,
loss of consciousness

Systemic No relevant Cardiovascular, neurological
disease may be present
status systemic disease

Sensoy Amblyopia, Diplopia common
adaptations suppression

common

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Differential Diagnosis

Congenital MED has the following disease entities as differential
diagnosis-

1. Brown’s Syndrome- This clinical entity has a patient with
hypotropia which is worse on adduction along with V-pattern
strabismus (exotropia on downgaze), exaggerated FDT shows
tight SO muscle.

2. Vertical Duane - in this disorder patient has globe retraction on
downgaze and hypotropia worse in upgaze along with signs of co-
contraction.

3. CFEOM - it is often familial and is bilateral in presentation.
Hypotropia is worse on upgaze, positive FDT of other extraocular
muscles along with IR restriction.

4. Congenital absence of SR+/- absence of IO muscle- patient
generally present with craniofacial dysostosis and often mimics
MED.

5. Third nerve palsy- exotropia and pupillary abnormalities may be
present.

6. Anomalous insertion of IR and SR- It has variable findings.

Differential diagnosis of acquired MED-6

1. Thyroid orbitopathy – the patient has diplopia, proptosis, lid
signs. It can be diagnosed clinically by exophthalmometry,
abnormal FDT, normal FGT. Abnormal TFT’s and USG for
muscle thickness are done to reach to a final diagnosis.

2. Myasthenia gravis – presents with ptosis, diplopia, Cogan’s lid
twitch, the symptoms worsen with fatigue and can have diurnal
variation. FDT and FGT will be normal. Edrophonium test and ice
pack test can be done in these cases. Investigations include Ach-
Rab and electromyography.

3. Orbital floor fracture- it leads to either IR entrapment or paresis
which can mimic MED. There is a history of trauma and patient
has diplopia with/without enophthalmos. There can be associated
anesthesia or hypoaesthesia around region supplied by V2.

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Abnormal FDT and normal FGT can be seen. Orbital imaging is
the main modality to reach to a final diagnosis.

4. Progressive external ophthalmoplegia - Bilateral signs,
decreased saccades in all EOM, orbicularis weakness, ptosis
and retinal changes are present, no restriction on forced duction.
Weakened to normal force generation. Ragged red fibres are seen
on muscle biopsy.ECG changes may be present.

5. Orbital inflammatory disease/ Orbital cellulitis – patient
presents with painful extraocular muscles, chemosis, lid swelling,
exophthalmos. Blood investigations include ESR, CRP, CBC,
DLC, CT+/- MRI of brain, orbit and paranasal sinuses.

Other disorders mimicking acquired MED include labrynthine and
cerebellar disorders. These disorders are differentiated by the spectrum
of signs and symptoms with which the patient usually presents i.e.
vertigo, tinnitus, nystagmus in cases of labyrinthine disorders and
ataxia, ocular flutter, dysmetria or papilledema in cases of cerebellar
disorders.

Management

1) Observation- it is to be followed in patients with limited changes
in head position and orthotropia in primary position

2) Refraction and amblyopia management

3) Surgery- Main indications for surgery are6
a) Significant vertical deviation in primary gaze
b) Deviation causing suppression and amblyopia
c) Diplopia in primary position
d) Contracted binocular fields.
e) Significant AHP

4) Ptosis management- Pseudoptosis will resolve after successful
strabismus surgery. If ptosis persists after squint surgery, it has to
be addressed.

Goals of surgery is to improve position in primary gaze, hence
increasing the binocular field of vision.

There are various scenarios in management of MED described in
Figure 5;

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Monocular Elevation Deficit

Primary IR IR recession SR
restriction (5-6 mm) resection

+

Secondary IR IR Knapp
restriction recession procedure

FDT

Knapp
procedure

– SR paresis or
Supranuclear
MED
SR

resection

Figure 5 : Algorithm of management of monocular elevation deficit

Surgery For Type 1 MED

Forced duction testing should be repeated in the operating room. If
restriction to up gaze is demonstrated, IR restriction is present (Type
1 MED). An IR recession with/without conjunctival recession should
be done in these cases. Usually IR recession of 5 to 6 mm can correct
hypotropia of around 15 to 18 PD.

Surgery For Type 2 MED

If FDT is negative, in these cases, a Knapps procedure (vertical
transposition of horizontal rectus muscles) should be performed.
Knapp’s procedure is commonly practiced and now a well-
established treatment for double elevator palsy. Knapp’s procedure
corrects between 20-35 PD of hypotropia in primary position but
may cause only a small improvement in up gaze. A partial tendon
Knapp procedure is recommended in patients who have undergone
IR recession and have less than 25 PD hypotropia in primary position
or those with no previous surgery who have less than 10 PD of
hypotropia in primary position

Surgery For Type 3 MED

Knapp’s procedure and IR recession both the procedures are required

108 CME on COMPLEX STRABISMUS

Monocular Elevation Deficit

in such cases. It is important to wait at least 6 months between the
two procedures in adults to reduce the chance of anterior segment
ischemia. For MED with more than 35PD of hypotropia but no IR
restriction, reports good result with posterior fixation sutures to
augment superior transposition of horizontal rectus muscles following
the spiral of Tillaux. Patient with less than 25 PD hypotropia and
upgaze ability above midline may benefit from SR resection as an
alternative to horizontal rectus transposition. Nishida procedure has
been described recently to treat hypotropia after IR recession. It can be
done concurrently as it doesn’t involve cutting and prevents anterior
segment ischemia.

Surgery For MED with Horizontal Deviation

A modification of Knapp’s procedure, using partial rather than
full tendon transposition of medial and lateral rectus is procedure
recommended by us. Upper part is used for correction of vertical
deviation & lower part is used for horizontal deviation. For MED with
more than 35 PD of hypotropia but no IR restriction, posterior fixation
suture to augment superior transposition of the horizontal rectus
muscles following spiral of Tillaux is recommended.

Ptosis Surgery

Pseudoptosis will resolve after successful strabismus surgery in MED.
Ptosis repair should be considered only if significant ptosis persists
after strabismus surgery. True ptosis will not improve after strabismus
surgery and in fact will appear worse after the eye has moved from its
hypotropic position to an improved midline position. If there is enough
upgaze to avoid exposure keratitis, external levator resection can be
done after strabismus surgery to lessen the residual ptosis. The surgery
should be performed at least one year after squint surgery. True ptosis
if present can be managed by levator resection or a tarsofrontal sling
depending on the levator action. If the Bells is poor, it is advisable
to use crutch glasses to lift the ptotic eyelid and in such cases ptosis
surgery is contraindicated.

The various surgical procedures are described in detail:

IR Recession- FDT to be performed before/in operating room.

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Monocular Elevation Deficit

yy An IR recession with conjunctival recession should be done if
restriction in upgaze is demonstrated.6,17

yy In a study it has been shown that 73% patients of MED and
restricted forced duction on upward rotation developed full upgaze
after IR recession.

yy To avoid postoperative lid retraction, as many attachments
between IR and lower lid retractors are excised.

yy After IR is disinserted, FDT is repeated .
yy IR recession usually corrects 15-25 PD of hypotropia. If the patient

has a very large primary position hypotropia before surgery, SR
resection may be required.
yy The conjunctiva is recessed 4mm from the limbus or up to the
level of the original IR insertion.
yy Depending upon severity of hypotropia, 5-8 mm recession is to
be done.
yy After reattaching IR, globe can rotate 20-25 degrees superiorly.

Knapp’s Procedure- In knapp’s procedure, the tendons of MR and
LR are transposed to the insertion of SR. In a study done by Knapp’s18
21-55 PD of hypotropia was corrected. Among 15 cases, 8 of them
were fully corrected and 7 of them had mild restriction in upgaze.

In another study, Burke et al19 concluded that magnitude of vertical
correction does not correlate with preoperative amount of deviation
with or without prior IR recession. Average vertical correction was
around 21.1PD.

Bandoupadhyay et al20 did a study on 28 patients. They found 86% of
patients were aligned to within 10PD. 36% patients had improvement
in elevation. They also reported average correction following IR
recession being 16PD from an average preoperative deviation of
25.8PD.

Cooper et al21 performed Knapp’s in 6 patients with simultaneous
horizontal R&R in one patient for horizontal deviation. Postoperatively
horizontal correction was not good. Hence, they concluded that
horizontal deviation correction should be done on horizontal restriction
of normal eye when doing Knapp’s in the affected eye.

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Calderia et al22 found the effect of transposition increases with time
leading to overcorrection. Mean correction was 36.4PD for distance
and 29.5PD for near.

Kamlesh and Dadeya et al23 described modified Knapp’s where in half
the belly of horizontal muscle was transposed while the other half
used for correcting horizontal deviation. They noted mean correction
of 25PD.

Snir et al24 did augmented Knapp’s i.e. Knapp’s with posterior fixation
sutures on horizontal recti and compared with conventional Knapp’s.
They concluded that augmented Knapp’s gave superior results.

Disadvantages of Knapp’s procedure-23
1. It is not a graded procedure
2. Large variability in amount of correction obtained
3. Drift towards overcorrection with time
4. Correction of horizontal deviation becomes difficult.
5. The patient loses some adduction and abduction in extreme gazes.
6. Another drawback of the procedure is that resection and recession

cannot be performed. Recession would negate the benefit of
surgery and resection is impossible because the transposed muscle
is already stretched maximally.

Vertical R&R

Kamlesh et al25 demonstrated vertical R&R for management of
hypotropia in MED type 2. 92.3% patients were aligned with in 5PD
and 46.15% patients had gain in elevation.

Bagheri et al26 studied vertical R&R in 5 patients. 4 among 5 cases
were orthophoric in postoperative period.

Other less commonly performed surgeries are-
1. Contralateral SR recession with faden’s procedure.27
2. Resection of IO of affected eye.28
3. Resection or tuck of contralateral IR.29

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Monocular Elevation Deficit

Murthy et al30 performed Modified Nishida technique in three cases
of monocular elevation deficit. It is a No split-No tenotomy technique
which involves using non-absorbable suture to transpose superior
1/3rd of MR and LR 10 mm behind the insertion to a point on sclera
at a distance of 12mm behind the limbus around midway between SR
and MR, SR and LR respectively. This procedure allows IR recession
to be done simultaneously without risk of anterior segment ischemia
and is also reversible.

Complications (Figure 6)

1. Residual hypotropia: residual hypotropia following a Knapp
procedure may improve with time. For a mild to large hypotropia
after a Knapp procedure, IR recession or contralateral SR recession
may be done. For hypotropia following IR recession, modified
partial Knapp is recommended.

2. Hypertropia: Patients with hypertropia following Knapp
procedure tend to worsen with time. In such cases, medial and
lateral rectus should be moved to a lower position. If hypertropia
occurs after IR recession, IR advancement is to be done. It is
accepted that 1mm change in IR position causes 3PD shift in
vertical position.

Residual Overcorrection
hypotropia with hypertropia

May improve
with time

Previously Previously Worsens with Previously done
done knapp done IR time IR recession with
procedure recession or without Knapp
Modified Previously
IR recession partial Kanpp done Knapp
procedure procedure

Contralateral Move MR and Advance IR
SR recession LR to lower
position

Figure 6 Algorithm showing management of complications post surgery.

112 CME on COMPLEX STRABISMUS

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3. Diplopia: increased diplopia in reading position may occur after
large unilateral recession of IR. In such cases, the unoperated IR
depresses the normal eye more than the eye with weakened IR.
A fadenoperation or small IR recession of uninvolved eye may
be done. Prism glasses may be needed for reading if diplopia on
downgaze persists.

3. Lower lid retraction: it occurs if fascial attachments between IR
and lower lid are not completely excised

4. Anterior segment ischemia: it occurs if more than two rectus
muscles are operated on at a time. It is more common in adults than
in children. Ischemia results from disruption of the ciliary vessels
that are carried in the rectus muscle. A vessel-sparing procedure
can be done on rectus muscle to avoid this complication.

References

1. Dunlap EA. Vertical displacement of horizontal recti; Symposium on strabismus
transactions of the new Orleans Academy of Ophthalmology; St Louis: Mosby;
1971. pp. 307–29.

2. Metz HS. Double elevator palsy. Arch Ophthalmol 1979; 97: 901–03.

3. Ziffer AJ, Rosenbaum AL, Demer JL, Yee RD. Congenital double elevator palsy:
vertical saccadic velocity utilizing the scleral search coil technique. J Pediatr
Ophthalmol Strabismus 1992; 29:142–49.

4. Kline LB, Bajandas FJ. Neuro-Ophthalmology: Review Manual. Fifth edition.
Thorofare, NJ 08086: Slack Inc; 2003;pp 73.

5. Barsoum M. Congenital double elevator palsy. J Pediatr Ophthalmol Strabismus
1983; 20:185–91.

6. Rosenbaum AL, Santiago AP. Clinical strabismus management. Philadelphia:
WB Saunders

7. Shenoy S, Maiya A. Sudden onset of double elevator palsy: a rare clinical entity.
JEMDS 2014; 3:1291-97

8. Wright KW. Complex Strabismus: Restriction, Paresis, Dissociated Strabismus
and Torticollis. In: Wright KW, Spiegel PH eds. Pediatric Ophthalmology and
Strabismus. Springer 2003; pp 258.

9. Zafar SN, Azad N, Khan A. Outcome of surgical treatment of monocular
elevation deficiency. J Pak Med Assoc 2012; 62:355-7.

CME on COMPLEX STRABISMUS 113

Monocular Elevation Deficit

10. Bell JA, Fielder AR, Viney S. Congenital double elevator palsy in identical
twins. J Clin Neuro-ophthalmol 1990; 10:32-34.

11. Siatkowski RM, Glaser JS. Pediatric Neuroophthalmology. Philadelphia:
Lippincott Williams & Wilkins;1999; pp 473.

12. Manley DR. Strabismus. In: Harley RD, ed. Paediatric ophthalmology.
Philadelphia: Saunders;1983:247-48.

13. Wright, K.W. et al: Double Elevator Palsy, ptosis and Jaw Winking. Am. Orthopt.
J 1989; 39:143.

14. Ceiser EJ, Richards R. Vertical Strabismus Pediatric Ophthalmology. New York:
Thieme Medical publishers Inc; 2000;pp 152-3.

15. Jampel RS, Fell P: Monocular elevation paresis caused by a central nervous
system lesion. Arch Ophthalmol 1968: 80:4.

16. Kirkham TH, Kline LB: Monocular elevator paresis, Argyll Robertson pupils
and sarcoidosis. Can J Ophthalmol 1976; 11:330

17. Scott WE, Jackson OB. Double elevator palsy: the significance of inferior rectus
restriction. Am Orthop J 1977; 27:5-10.

18. Knapp P. The surgical treatment of double elevator paralysis. Trans Am
Ophthalmol Soc 1969; 67:304–23

19. Burke JP, Ruben JB, Scott WE. Vertical transposition of the horizontal recti for
the treatment of double elevator palsy: Effectiveness and long-term stability. Br
J Ophthalmol 1992; 76:734–7.

20. Bandyopadhyay R, Shetty S, Vijayalakshmi P. Surgical outcome in monocular
elevation deficit: A retrospective interventional study. Ind J Ophthalmol 2008;
56:127-33.

21. Cooper EL, Greenspan J. Operation for double elevator palsy. J Pedtr Ophthalmol
1971; 8:8-14

22. Calderia JA. Vertical transposition of the horizontal rectus muscles for congenital/
early onset “acquired” double elevator palsy: a retrospective long term study of
ten consecutive patients. Binocul Vision Strabismus Q 2000; 15:29–38.

23. Kamlesh, Dadeya S. Surgical management of unilateral elevator deficiency
associated with horizontal deviation using a modified Knapp’s procedure.
Ophthalmic Surg Lasers Imaging 2003; 34:230–5.

24. Snir M, Frilling R, Steibel HK, Bourla D, Weinberger D. Combined rectus
muscle transposition for posterior fixation sutures for the treatment of double
elevator palsy. Am J Ophthalmol 2005;112:933-8.

25. Kamlesh, Dhiman S, Thacker P, Karothiya B, Goel Y, Rastogi A, Chaudhary R.
To assess the efficacy of vertical muscle surgery for management of hypotropia in

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Monocular Elevation Deficit

monocular elevation deficiency type II. Int Ophthalmol. 2017 Aug;37(4):1009-
1016

26. Bagheri A, Sahebghalam R, Abrishami M (2008) Double elevator palsy, subtypes
and outcomes of surgery. J Ophthalmic Vis Res 3(2):108

27. Ficker LA, Collin JR, Lee JP. Management of ipsilateral ptosis with hypotropia.
Br J Ophthalmol 1986; 70:732-6.

28. Wagman OH. Resection of inferior oblique muscle in hypotropia. Am J
Ophthalmol 1945; 28:1226-36.

29. Samir A, Hakim O. A New Approach for Management of Monocular Elevation
Deficiency. J Clinic Experiment Ophthalmol 2011; 2:136.

30. Murthy SR, Pappuru M, Modified Nishida’s procedure for monocular elevation
deficiency, Journal of AAPOS (2018), doi: 10.1016/j.jaapos.2018.01.018.

CME on COMPLEX STRABISMUS 115

07Congenital Cranial dysinnervation Disorders; Expanding Horizons, Shrinking Borders

Congenital Cranial
Dysinnervation Disorders;
Expanding Horizons,
Shrinking Borders

Dr. Pramod Kumar Pandey, MD

Ex- Director Professor, Guru Nanak Eye Center, MAMC, New Delhi

The term, congenital cranial dysinnervation disorders (CCDD) was
coined at the 110th ENMC international workshop held at Naarden,
the Netherlands in 20021 to a clutch of non -progressive congenital
disorders, primarily involving ocular motility that share the common
feature of dysinnervation. Lack of innervation is termed as primary
dysinnervation and aberrant innervation from other cranial nerves
is termed secondary dysinnervation. Earlier these entities were
collectively known for almost a century as congenital fibrosis
syndromes or similar synonyms. It slowly dawned that the muscle
fibrosis was a secondary event, the primary event being abnormal
development of the hind brain structures or its cranial nerve nuclei
and / or nerves. Neuro imaging and advances in the molecular genetics
have added a wealth of material to our understanding of these abstruse
motility disorders and many novel phenotypes and genotypes have
been identified and pigeonholed.

The purpose of this write up is to highlight some of the emerging
precepts of these complex ocular motility disorders, frequently posing
diagnostic and therapeutic dilemmas in clinical practice. It’s not
intended to be a comprehensive review on such enigmatic entities.
Some of the prototype entities are elaborated upon to drive home the
point.

Congenital fibrosis of the extraocular muscles
(CFEOMs)

A relatively rare presentation with incidence of about 1 in 1.25 lac

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births. The phenotypes can be quite variable and diverse but quite
often well characterized. There are at least 8 well defined genotypes,
CFEOM 1A, CFEOM1B, CFEOM2, CFEOM3A, CFEOM3B,
CFEOM3C, CFEOM3 with poly microgyria and Tukel syndrome.
The inheritance could be autosomal dominant, autosomal recessive
or cases could be sporadic arising from de novo mutations. The
characteristic features are congenital non progressive ophthalmoplegia
with (out) ptosis, affecting all or part of the 3rd nerve nucleus and or
nerve and it’s innervated muscles or 4rth nerve nucleus and or the
nerve and its innervated muscle (superior oblique). Characteristically
the phenotypes have severe limitation of vertical gaze, invariably
upgaze and variable limitation of horizontal gaze. Such individuals
compensate for the motility limitation by chin up head posture.
Frequently they have high cylindrical errors, poor or absent binocularity
and the incidence of amblyopia is much higher. Due to poor Bell’s
and attendant facial nerve weakness, the chances of exposure keratitis
are a real concern. Phenotypes harboring from TUBB 3, TUBB2 B
pathogenic variants may also betray intellectual disability, Kallmann
syndrome, facial weakness, vocal cord paralysis and progressive
sensory motor axonal polyneuropathy. Tukel syndrome patients also
betray postaxial oligodactyly or oligosyndactyly2. KIF21A pathogenic
variants give rise to CFEOM1A and CFEOM3B, PHOX2A are
associated with CFEOM 2, TUBB3 pathogenic variants are associated
with CFEOM3A, CFEOM1B, TUBB 2B variants are associated
with CFEOM3A and CFEOM3 with polymicrogyria. Phenotypes
express lot of heterogeneity even within the same family. Involvement
is typically bilateral symmetrical/ asymmetrical, may be strictly
unilateral, ptosis may be bilateral, may be absent or rarely even lid
retraction may be present. Eyes may be fixed in down gaze or with
no hypotropia. Horizontal deviation may be absent, exotropias are far
more frequent than esotropias. Horizontal movements between two
eyes are variably limited. There can be esotropia in attempted upgaze
and exotropia in down gaze, other features of aberrant innervation
like synergistic convergence / divergence, Marcus Gunn Jaw winking
phenomena may be encountered. Associations with Duane syndrome,
Mobius syndrome, Kallmann syndrome and infantile esotropias are
also well known. A fine pendular nystagmus may be present. On

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brain MRI, especially in TUBB3 / TUBB2B variants malformations
of cortical development, corpus callosal dysgenesis, hypoplasia of
anterior commissure, corticospinal tracts and basal ganglia may
be seen. Hypoplasia of oculomotor nerves especially levator and
superior rectus muscles may be seen on MRI. Forced duction test is
invariably positive for elevation, binocular vision is usually absent.
High refractive errors with large cylinders are a common place and
cylindrical powers may change following surgery, an important point
to keep in mind while contemplating surgical interventions.

Bosley -Salih- Alorainy Syndrome and
Athabascan brainstem dysgenesis syndrome

These are HOXA 1 related syndromes, the first one initially described
from consanguineous families from Saudi Arabia and named after the
collaborators. The affected children classically have bilateral Duane
Syndrome (DS), congenital sensory neural deafness emanating from
bilateral absence of the cochlea, semicircular canals and vestibules
(common cavity disorders), variable malformation of internal carotid
arteries ( unilateral hypoplasia to bilateral agenesis), delayed motor
milestones and autism spectral disorders3.

The Athabscan brainstem dysgenesis syndrome is an overlapping
autosomal recessive syndrome described in native American children.
Additionally, ABDS children have central hypoventilation, mental
retardation and frequent facial weakness, vocal cord paralysis,
cono-truncal heart defects including tetralogy of Fallot and double
aortic arch.3. The conditions map to chromosome 7 encompassing
HOXA gene cluster. HOXA1 defects result in errors in hind brain
differentiation. The autism and mental retardation seen in such
patients point to a link between cortical dysfunction and brain stem
dysgenesis3.

Horizontal gaze palsy with progressive scoliosis

Presents with bilateral conjugate horizontal gaze palsy for saccadic,
smooth pursuit and vestibulo-ocular reflex movements. Convergence is
spared, there is invariably marked hypotony, a fine pendular nystagmus

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is often encountered. Scoliosis may take time to appear but is typically
severe by 1st decade, scoliosis with convexity to right side is seen
more frequently. Patient may primarily present with scoliosis, ocular
movement disorder may not be a complaint at all and even missed
on cursory examination. Imaging may reveal pontine hypoplasia,
split pons, butterfly pattern to medulla due to midline cleft, absent
facial colliculi and tenting of the 4rth ventricle. Some patients may
use convergence as a substitute for horizontal gaze limitation. ROBO
3, residing on chromosome 11 is crucial for neural migration, axonal
growth and motor neuron development. It’s an autosomal recessive
disorder, 24 mutations have been described. Long tract fibers, the
major cortico spinal and dorsal somatosensory tracts whose axons
normally cross the midline in the medulla and lower pons are not able
to cross to the opposite side, giving rise to typical presentation. A rarer
disorder, HGPPS 2 has been described due to mutation on CDC gene
on chromosome 18. Sporadic HGPPS can also result from compound
heterozygous mutation in ROBO34.

Homozygous nonsense, frame shift, splice site and missense
mutations have been reported on ROBO3 in HGPPS.ROBO3 is
a large gene that encodes a cell adhesion molecule containing
extracellular immunoglobulin like motifs, 3 fibronectin like motifs, a
transmembrane domain and an intracellular tail containing signaling
motifs5. Abducens axons exiting the brainstem are present bilaterally
with normal extra ocular muscle configuration and size suggesting
that HGPPS results from inability of fibers from medial longitudinal
fasciculus and paramedian pontine reticular formation to cross the
midline and innervate neurons in the abducens nucleus3. Attendant
hypermetropia may give rise to a superadded accommodative
component and an esotropia. However, correction of hypermetropia
does not bring about the desired change in the deviation and most such
patients may need surgery for accommodative esotropia.

Moebius Syndrome

Congenital facial and abducens palsy was first described in 1880 by
Von Graefe. Paul Julius Moebius, a Leipzig neurologist, well known
for an ocular sign in hyperthyroidism (Moebius sign) and description

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of ophthalmoplegic migraine ( Moebius disease), described congenital
facial weakness (Moebius syndrome) in 1888. Moebius is also known
for his monographs on ‘Physiologic weakmindedness of women’ and
‘Pathology of men of genius’. Moebius in 1888 classified congenital
cranial nerve palsies and clubbed 7th and 6th nerve palsies together,
the condition came to be known eponymously by his name thereafter.
Moebius syndrome may have associated anomalies of the face, limbs,
chest wall and spine. It may have overlapping presentations with Poland
anomaly, autistic behavior, Kallmann syndrome and hypopituitarism.
Thus eponymously, Mobius is a sequence rather a syndrome, overtly
heterogeneous in etiology and presentation. A variety of criteria have
been applied for it’s diagnosis, including congenital facial palsy with
abducens palsy, congenital facial palsy without abducens palsy and
with or without craniofacial dysmorphism and congenital anomalies
of the extremities. The most accepted criteria is unilateral or
bilateral facial palsy with bilateral (rarely unilateral) 6th nerve palsy,
infrequently 5th, 8rth, 9th, 10th, 11th and 12th cranial nerve may be
affected. Facial diplegia could be complete or incomplete, there could
be palsy of upper face with relative sparing of lower face including the
perioral muscles and platysma.

Esotropia at birth is the commonest presentation but orthotropia
and rarely exotropia can also occur. Convergence is intact. The
presentation could mimic horizontal gaze palsy, about 1/3 of
cases may present with bilateral Duane retraction syndrome and
rare presentations may sport features of congenital fibrosis of the
extraocular muscles6.Hypoplastic tongue that can not be protruded
beyond the lips is frequently encountered. Asymmetry with a central
groove with elevations on both sides are common features. Some may
demonstrate unilateral paresis of the tongue.

Palate and pharynx abnormalities may add up in feeding problems
along-with insufficient sucking and swallowing difficulties. Nasal
dysarthria may be present. Trigeminal paralysis alongwith hearing
loss, smell and taste disorders may be encountered. Craniofacial
malformations include flattened nasal bridge, micrognathia, high arch
palate, external ear defects, teeth defects and hypertelorism6.Upper limb

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anomalies may include brachydactyly, campylodactyly, clinodactyly,
syndactyly and ectrodactyly, low set thumbs, hypoplasia of the
phalanxes, aplasia and hypoplasia of metacarpals and nail deformities.
Lower limb deformities may include pes planus, hypoplasia of lower
legs, talipes equinovarus and arthrogryposis multiplex. Patients may
show poor motor development. Autism is a frequent presentation,
overlapping presentations with Poland anomaly, Kallmann syndrome,
Johnson- Macmillin Syndrome may be encountered. Hypotonia at
birth is frequently present. Lack of fine motor skills, poor coordination
/ balance and primary respiratory dysfunction could result from
maldevelopment of corticospinal and corticobulbar- cerebellar long
tracts. Moebius syndrome could be viewed as a syndrome of rhombo-
mesencephalic maldevelopment involving both nuclei and traversing
long tracts. In extreme cases the caudal part of the brainstem is so
poorly developed that it’s incompatible with life. Various hypothesis
have been proposed regarding etiopathogenesis including hormonal,
pharmacologic, toxic and vascular theory that supposes ischemic
events in the median avascular and paramedian watershed zones of
the lower brainstem as a result of hypoperfusion or occlusion of the
developing primitive subclavian artery. The vascular hypothesis does
not explain frequent occurrence of lower limb anomalies nor other
congenital abnormalities outside the subclavian artery bed6.

Synergistic Divergence

A rare CCDD, likely at the level of pons manifests as paradoxical
abduction of the adducting eye on attempted side gazes. Condition
could be uni / bilateral, most are unilateral7. It is always associated
with limited adduction on the affected side and medial rectus could
be found to be hypoplastic on MRI. The pathophysiology of the
aberrant movement is unsettled but could result from mechanical
factors, anomalous innervation of the ipsilateral medial and lateral
rectus muscles or even the cross innervation between the 2 lateral
recti. SD could be an isolated ocular motility disorder but has been
described with CFEOM 1, CFEOM3, Duane retraction syndrome
and with congenital 3rd nerve palsies8,9. A large exotropia is usually
present, associated vertical vectors can also be present in the form

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of elevation or depression of the globe9. No mutation in any gene
associated with CCDDs has been found as yet, most cases appear
sporadic. Hypoplasia / fibrosis of the medial rectus has been noted
almost universally pointing towards primary dysinnervation from
the 3rd nerve and consequent secondary dysinnervation from the 6th
nerve. It’s likely that fibers destined for medial rectus innervate lateral
rectus causing anomalous abduction on attempted contralateral gaze.

SD shares some similarities with DRS, both affect primarily horizontal
recti, both are predominantly unilateral with about 10 % being bilateral
and sometimes both may coexist9. SD may be associated with Marcus
Gunn jaw winking phenomena and anomalous innervation of the
medial rectus by the motor branch of the trigeminal nerve10,11,12. These
findings illustrate that miswiring extends beyond pons and abducens
nuclei to higher midbrain structures. The negative genetic studies
corroborate that SD is not associated with currently identified CCDD
genes, local environmental, teratogenic or epigenetic, developmental
factors could also play a role. Future studies will help clearly delineate
the etiological factors that lead to dysinnervation.

Marcus Gunn jaw winking phenomena

First described by Scottish ophthalmologist, Robert Marcus Gunn
in 1883 in a 15 year old girl. Other synonyms are Marcus Gunn
ptosis, Marcus Gunn jaw winking, trigemino oculomotor synkinesis,
maxillo- palpebral synkinesis and pterygoid -levator synkinesis. Most
have a variable amount of ptosis in resting primary position, vast
majority are unilateral but bilateral cases have also been described.
There is a coordinated synkinetic movement of the upper eye lid and
the jaw due to the abnormal connections between the motor branches
of the mandibular branch of the trigeminal and the superior division
of the oculomotor nerve13,14. Familial cases with autosomal dominant
inheritance have been described but are exceedingly rare. Rare cases
with MGP without ptosis and acquired cases following trauma have
also been documented.

The incidence of MGP in individuals with congenital ptosis varies
from 2 to 13 %, on an average about 5% ptosis may betray the
phenomenon. Like DRS, it’s more common on left side and there is no

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gender predilection. Electromyographic studies have shown that the
impulse for synkinesis originate from proprioceptive receptors of the
external pterygoid muscles. The Muller’s is known to act like a muscle
spindle for the levator palpebrae superioris muscle with proprioceptive
afferents travelling in the transverse nerve to join the lacrimal
nerve15. It is open to speculation that this happens through Muller’s
or without it. The synkinesis can be triggered by chewing, suction,
lateral mandibular movement, Valsalva maneuver, sterno-cleido-
mastoid muscle contraction, tongue protrusion, sucking, smiling
and breathing. In a few patients the synkinesis is between internal
pterygoids and the LPS, in such cases the lid elevates on closing the
mouth or clenching the teeth. The location of miswiring is speculative
and could be at cortical / sub cortical level, internuclear connections in
the posterior longitudinal bundle, infra-nuclear between the trigeminal
and oculomotor or peripherally through auriculo- temporal nerve.

The ocular associations include strabismus in 50 to 60% of cases which
may include monocular elevation deficit, superior rectus paresis,
esotropia and exotropia. A quarter of cases may sport anisometropia
and almost half have amblyopia. The rare associations include morning
glory syndrome, Duane retraction syndrome, CHARGE syndrome,
cleft lip/ cleft palate and olfactory nerve disturbances. Correction
of refractive errors and treatment of amblyopia form the mainstay
of nonsurgical treatment. In the inverse MGP the ptosis in primary
position is worsened with mouth opening, the abnormal synkinesis is
between the superior division of the 3rd nerve and the motor division
of the mandibular supplying the internal pterygoids. Martin Amat
syndrome also has to be kept in mind while evaluating these entities.
The jaw winking phenomena is considered cosmetically significant
only if it is 2 mm or more. If the ptosis is mild (<2mm) and jaw
winking not significant, such cases are not considered as candidates
for surgery. An atypical oculo-cardiac reflex could be precipitated in
these patients during ptosis surgery, precautions need to be taken to
forestall it.

Congenital 3rd and 4th cranial nerve palsies

Magnetic Resonance imaging using thin section T2- weighted

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imaging based on gradient-echo or turbo- spin echo sequence shows
CNS as dark linear structures in contrast to high signal intensity of
surrounding cerebrospinal fluid16. Image resolution of (voxel size) of
approximately0.5x 0.5 mm in the x plane and 0.7 mm section thickness
is sufficient to identify the cranial nerves 3 and 6 with an average
diameter of 1.8 and 1mm. CN4 with an average diameter of 0.54
mm needs voxel size of approximately 0.3 x 0.3 mm and 0.3 mm of
section thickness which can be achieved with only 3 Tesla systems17.

There has been overriding evidence regarding CN3 hypoplasia /
aplasia on MRI imaging in about 1/3rd of cases with CN3 palsy18.
The degree of atrophy of superior, inferior and medial recti increased
with age in some patients studied19. Developmental brain anomalies
including anomalies in the basal ganglia, optic nerve hypoplasia,
pituitary gland malformations, hypoplasia of the midbrain, corpus
callosum, septo-optic dysplasia, ventricular dilatation and absence of
septum pellucidum have been reported, providing further evidence
that at least some of the CN3 palsies need to be classified as CCDDs20.

Kim and Hwang first reported absent CN4 in 10 patients with hypoplasia
of the superior oblique muscle with congenital 4th nerve palsy and
suggested that congenital 4NP with superior oblique hypoplasia can be
classified as a CCDDs21. Upto 70% of patients with Superior oblique
palsy showed CN4 aplasia and variable degrees of superior oblique
hypoplasia. Patients without CN4 showed more frequent head tilts and
an earlier onset before 1 year of age and a larger degree of hypertropia
on ipsilateral tilt. Yang et al showed significantly smaller superior
oblique muscle volume on the paretic side in patients without CN422.

It was believed till recently that congenital CN4 palsies were a direct
consequence of primary structural abnormality of the SO muscle or
tendon and tendon abnormalities were reported in over 89% of cases
in some studies. MR imaging has shown that volume reduction in
SO palsies is more prominent in congenital than acquired palsies23.
Infra-placement of contralateral lateral recti could produce diagnostic
difficulties with 4th nerve palsies24.

Jiang et al25 found ARIX gene polymorphism in patients with
congenital SOP. ARIX gene is expressed in the midbrain nuclei of 3

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and 4 CN and mutations are known to result in some forms of CFEOM.
This association was one of the initial hints that SOP could be part of
the CCDDs. It now appears that absence of 4th cranial nerve leads
to hypoplasia / atrophy of the superior oblique muscle with laxity or
aplasia of the tendon.

Congenital Brown’s Syndrome

Congenital Brown’s is characterized by limited active and passive
elevation of the eye which is maximum in adduction, a large V
pattern with exotropia in upgaze, widening of the palpebral fissure
and downshoot of the eye in adduction in a minority of cases. An
innervational origin is suspected in view of the latter findings which
are not in consonance with a strictly mechanical etiology. Some
evidence was first collated when electromyographic studies revealed
paradoxical innervation of the superior oblique muscle. Kolling and
colleagues proposed that congenital Brown’s could fall within the
realm of CCDDs26.

Kaeser and colleagues found the ipsilateral fourth nerve to be absent
on MRI imaging in 2 patients with congenital Brown’s syndrome27.
The size of the superior oblique remained constant during vertical
movement suggesting no physiological relaxation of the muscle in
upgaze suggesting synkinetic innervation of the muscle by the branches
of the oculomotor nerve supplying medial rectus and/ or inferior
oblique. A co-innervation could produce the clinical picture seen in
congenital Brown’s including widening of the palpebral aperture in
adduction and downshoot of the eye due to co- contraction of both
the obliques and superior oblique and the medial rectus respectively.
The associated exotropia in upgaze and restriction to passive elevation
could result from contracture of the superior oblique muscle. A
combined neurogenic and mechanical theory has been invoked for both
congenital superior oblique palsy and congenital Brown’s syndrome
but without paradoxical innervation28. The absence of innervation can
lead to abnormal development of the superior oblique muscle, trochlea
and the tendon. This can take 2 forms, either hypoplastic SO muscle
with lax tendon causing SO palsy or a significant fibrosis and abnormal
insertion of the tendon with (out) dysinnervation from the third cranial

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nerve giving rise to Congenital Brown’s syndrome28. Cases have been
described with Brown’s syndrome in one eye and Superior oblique
palsy in the fellow eye attesting to a common etiopathogenesis.

Many aspects regarding intriguing CCDDs remain unresolved.
Some known genetic pathogenetic variants, the underlying etiology,
especially for the sporadic ones remains largely unknown, some
may also result from thromboembolic episodes as has been recently
proposed by Roberts and colleagues29. Covert dysinnervation from
superior rectus to SO muscle explain large fusional amplitudes and
gradual development of superior rectus contracture in the setting of
congenital SOP drawing a limited kinship with Duane syndrome.

In CFEOMs due to TUBB3 / TUBB2B pathogenic variants, it’s known
that neural agenesis / dysgenesis involving CNS structures can be
part and parcel of such disorders. Whether the same applies to many
other disorders involving both afferent and efferent pathways as well
as to varied systemic involvement, begs the quintessential question.
With advances in genetics and imaging, the emerging genotypes
and phenotypes may offer better insights and many clinically
heterogeneous conditions may inevitably run conterminous and many
may part company. The future holds great promise for these esoteric
entities.

References

1. Gutowsky NJ, Bosley TM, Engle EC, 110thENMC International workshop; the
congenital cranial dysinnervation disorders (CCDDs). Naarden, The Netherlands,
25-27 October, 2002, Neuromuscul Disord. 2003, 13, 573-578.

2. Whitman M, Hunter DG, Engle EC, Congenital Fibrosis of the Extraocular
muscles, 2004 April 27 (updated 2016 Jan. 14 ) in AdamsMP, Ardinger HH,
PaganRA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors Gene reviews,
Seattle (WA), University of Washington, Seattle, 1993-2021PMID 20301522.

3. Engle EC, The genetic basis of complex strabismus, Pediatric Research, 59, 343-
48, 2006.

4. Chan WM, Traboulsi EI, Arthur B, Friedman M, Engle EC, Horizontal gaze palsy
with progressive scoliosis can result from compound heterozygous mutation in
ROBO3, J. Med. Genetics 2006, 43, 11.

5. Jen JC, Chan WM, Bosley TM, Wan J, Carr JR, Rub U et al, Mutations in human

126 CME on COMPLEX STRABISMUS

Congenital Cranial dysinnervation Disorders; Expanding Horizons, Shrinking Borders

ROBO gene disrupt hindbrain axonal pathway crossing and morphogenesis,
Science, 2004, 304, 1509-1513.

6. Verazijil TFM, Zwang BV, Cruysberg RM, Padberg GW, Moebius syndrome
redefined, Neurology, 2003, 63, 327-333.

7. Friedmann HL, Burian BJ, , Congenital Ocular aberrant innervation; New
Concepts, J. Pediatr.. Ophthalmol. Strabismus, 1997, 34, 10-16.

8. Pandey PK, Kishore D, Joon Annu, saraf Priya, Congenital third cranial nerve
palsy with prenuclear dysinnervation involving otolithic pathways, Indian J.
Ophthalmol, 2020, 68, 1478-1480.

9. Oystrek DT, Khan AO, Vilacoro AQ, Owaru O, Al -Tassan N, Chan WM, Engle
EC, Bosley TM, Invest. Ophthamol.Vis. Sci. 2009, 50, 11, 5213-5216.

10. Brodsky MC, Hereditary external ophthalmoplegia, synergistic divergence, jaw
winking and oculocutaneous hypopigmentation; a congental fibrosis syndrome
caused by deficient innervation to extraocular muscles, Ophthalmology, 1998,
105, 717-725.

11. Kaban TJ, Smith K, Orton RB, Synergistic divergence associated with aberrant
trigeminal innervation. Can. J. Ophthalmol.1994, 29, 146, 150.

12. Kim JH, Hwang JM, Adduction on attempted abduction, the opposite of
synergistic divergence, Arch. Ophthalmol. 2016, 124, 918-920.

13. Traboulsi EL, Congenital cranial dysinnervation disorders and more, JAAPOS
2007, 11 (3), 215-17.

14. Demirci H, Frueh BR, Nelson CC, Marcus Gunn jaw winking synkinesis;
clinical features and management; Ophthalmology, 2010, 117,1447-52.

15. Yuzuriha S, Matsuo K, Ishgaki Y, Kikuchi N, Kawagishi K, Morlizumi T, Efferent
and afferent innervations of Mueller’s muscle related to involuntary contraction
of the levator muscle: important for avoiding injury during eyelid surgery, The
British association of Plastic Surgeons, 2005, 58, 42-52.

16. Kim JH, Hwang JM, Presence of the abducens nerve according to the type of
Duane retraction syndrome, Ophthalmology, 2005, 112, 109-113.

17. Kim JH, Hwang JM, Imaging of Cranial nerves III, IV, VI in congenital cranial
dysinnervation disorders, Korean J, Ophthalmol., 2017, 31, 183-193.

18. Lim KH, Engle EC, Demer JL, Abnormalities of the oculomotor nerve in
congenital fibrosis of the extraocular muscles and congenital oculomotor palsy,
Invest. Ophthalmol. Vis. Sci. , 2007, 48, 16011606

19. Kim JH, Hwang JM, Magnetic resonance imaging in three patients with
congenital oculomotor nerve palsy, Br, J. Ophthalmol., 2009, 93, ,1266-1267.

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Congenital Cranial dysinnervation Disorders; Expanding Horizons, Shrinking Borders

20. Hamed LM, Associated neurologic and ophthalmologic findings in congenital
oculomotor nerve palsy, Ophthalmology, ,1991, 98, 708, -714.

21. Kim JH, Hwang JM, Absence of the trochlear nerve in patients with euperior
oblique hypoplasia, Ophthalmology, 2010, 17, 2208-2213.

22. Yang HK, Lee DS, Kim JH, Hwang JH, Association of superior oblique muscle
volume with the presence or absence of the trochlear nerve on high resolution
MR imaging in congenital superior oblique palsy, AJNR Am. J. Neuroradiol.
2015, 36, 774-778.

23. Sato M, magnetic resonance imaging and tendon anomaly associated with
congenital superior oblique palsy, Am. J. Ophthalmol., 1999, 127, 379.

24. Clark RA, Miller JM, Rosenbaum AL, Demer JL, Heterotopic rectus muscle
pulleys or oblique muscle dysfunction, JAAPOS, 1998, 2, 17-25.

25. Jiang Y, Matsuo T, Fujiwara H, et al, ARIX gene polymorphism in patients with
congenital superior oblique muscle palsy, Br. J. Ophthalmol., 2004, 88, 263-7.

26. Kolling G, Rohde S, Kress B, Congenital Brown’s syndrome is caused by
missing fourth cranial nerve in some cases, Presented at the 32nd meeting of
the European Strabismological Association, Munich, Germany, September 7-10,
2008.

27. Kaeser PF, Kress b, Rohde S, Kolling G, Absence of the fourth cranial nerve in
congenital Brown’s syndrome, Acta Ophthalmol.2012, 90:e310-3.

28. Ellis FJ, Jeffery JR, Seidman DJ, Sprague JB, Coussens T, Schuller J,
Possible association of congenital Brown;s syndrome with congenital cranial
dysinnervation disorders, J AAPOS, 2012, 16, 558-64.

29. Roberts MP, Parsa CF, Thromboembolism and congenital malformations; from
Duane syndrome to Thalidomide embryopathy, Arch. Ophthalmol., 2012, 10,
1-9.

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08Strabismus in Craniosynostosis

Strabismus in
Craniosynostosis

Dr. Meenakshi Swaminathan MS, Dr. Debahuti Midya MS

Department of Pediatric Ophthalmology, Sankara Nethralaya

Overview

Craniosynostosis, a disorder first described in 1851 by Virchow1,
is characterized by premature closure of one or more of the cranial
sutures2, resulting in characteristic skull deformities. It affects one in
2500 live births2. (Figure 1) It is mainly divided into syndromic and
non-syndromic craniosynostosis2. Non-syndromic craniosynostosis
involves a single-suture and most commonly presents with premature
fusion of the sagittal or coronal sutures2. Syndromic craniosynostosis
involves multiple sutures with several syndromes, like Muenke,
Crouzon, Pfeiffer, Apert and Saethre-Chotzen syndromes.3 Sagittal
synostosis is the most common cause of isolated craniosynostosis
followed by metopic suture involvement.2 Muenke is the most
common syndrome followed by Crouzon and Pfeiffer syndrome.2

Figure 1: Crouzon syndrome

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Clinical characteristics:

In 1906, Apert described patients with oxycephaly (a flattened occiput
and steep forehead), horizontal groove above the supraorbital ridge,
hypoplastic midfacial region, parrot-beak nose, hypertelorism,
proptosis, and strabismus.4 (Figure 2)

Figure 2: "Thuan - Apert's Syndrome (DSCN5472)" by ReSurge International
is licensed with CC BY-NC-ND 2.0. To view a copy of this license, visit https://

creativecommons.org/licenses/by-nc-nd/2.0/

Crouzon in 1912, described a group of patients with hypertelorism and
exophthalmos, an increased angle of orbital divergence (greater than
90 degrees), and an increased medial and lateral interorbital distance
and partial subluxation of the globe.4 In 1964, Pfeiffer reported
another clinical variant of craniosynostosis that was associated with
broadened thumbs and great toes. These patients tend to have more
airway problems and exorbitism than other groups and can have
complete subluxation of the globe.4 (Figure 3)

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Figure 3: "File:Baby with Crouzon Syndrome.jpg" by KateVUk is licensed with
CC BY-SA 4.0. To view a copy of this license, visit https://creativecommons.org/

licenses/by-sa/4.0

In all the syndromes other ocular features that have been described
include amblyopia, corneal ulcer secondary to exposure keratopathy,
sixth nerve paresis , papilledema, optic atrophy secondary to raised
intracranial pressure3 (Figure 4)

Figure 4: "File:Pfeiffer's syndrome type II with cloverleaf shaped skull and
bilateral proptosis.png" by Singh RK, Verma JS, Srivastava AK, Jaiswal AK,
Behari S - is licensed with CC BY 2.0. To view a copy of this license, visit https://

creativecommons.org/licen

Among all the ocular features proptosis and strabismus are seen in a
majority of individuals.

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Strabismus in craniosynostosis

It is more common in syndromic craniosynostosis than non-syndromic,
predominantly manifested in coronal suture involvement. The
prevalence of strabismus in syndromic variety is 39 % to 90.9 %.2,3

‘V’ pattern strabismus with true or pseudo superior oblique palsy
is more common in both exodeviations and esodeviations. Among
horizontal deviations, exodeviations are common followed by
esodeviations.2,3

Presentation

‘V’ pattern strabismus in patients with craniosynostosis usually
presents with overelevation and under depression of the adducting eye,
and in more severe cases is accompanied by limitation of elevation
in abduction.2,3,4 Unilateral Coronal Synostosis is the most common
single-suture synostosis associated with V pattern1,5

Pathophysiology

Anatomic and sensorimotor factors contribute to the development of
strabismus associated with craniosynostosis.

The anatomic features include:4
1. Abnormally shallow and exorotated orbits, provide poor support

for the globe.
2. Short orbital walls that alter the arc of contact of the globe with

the extraocular muscles.
3. Magnetic resonance imaging demonstrates excyclorotation of

the entire extraocular muscle cone, resulting in altered vectors
of muscular action and leading to clinical pseudo-overaction and
pseudo-under action of the extraocular muscles.
• Specific extraocular muscle abnormalities may include
complete absence, anomalous insertion, and anomalous
microanatomy. Superior Rectus (SR) is most common
hypoplastic or absent muscle and can lead to contralateral
IOOA due to fixation duress.

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Other possible theories that may contribute to pattern strabismus:

1. Inadequate support of the globe and orbital contents by the short
orbital floor forces the globe to rest on the inferior oblique (IO)
and inferior rectus muscles. This increases their arc of contact
with the globe and results in increased activity, particularly of the
IO.4

2. Gobin has given the theory of sagittalisation further to explain in
another way. He suggested that Sagittalization of the origin of the
inferior oblique causes a V pattern and the Sagittalization of the
trochlea of the superior oblique causes an A pattern.1

Sagittalization is defined as reduction of the angle between
the muscle and the visual axis. Sagittalization of the muscle
increases the vertical and reduces the torsional action, leading to
excyclotorsion.

Superior Oblique (SO) sagittalisation:1

This sagittalization occurs when the bulbar insertion of the superior
oblique lies further posterior, or when the trochlea is anterior to
the corresponding attachments of the inferior oblique.

This excyclotorsion ultimately is compensated by incyclotorsion
and contraction of the superior rectus and superior oblique and
inhibition of the inferior rectus and inferior oblique. This produces
a depression in adduction and more abduction in downgaze leading
to an "A" pattern strabismus.

IO sagittalisation:1

The angle between this muscle and the visual axis is reduced, and
this results in a decreased extorsional and an increased vertical
action, leading to incyclotorsion,which ultimately compensated
by excyclotorsion and inhibition of superior rectus and superior
oblique. This leads to elevation in adduction and more abduction
in upgaze and causes V pattern.

3. Cheng et al hypothesized that strabismus and V pattern are caused
by the applying of Hering’s law to extraocular muscles that
are anatomically excyclorotated in patients with many types of
craniosynostotic disorders.1

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4. Relative IO overaction that results from under action or absence
of the SO may lead to a V pattern.2,3,4

5. Another theory is also the absence of rectus and/or oblique
muscles in craniosynostosis syndromes establish this as a possible
reason for strabismus and incomitant patterns.2,3,5

Management

It includes diagnosis and treatment strategy4.

yy Ophthalmologist has to perform baseline ophthalmologic evalua-
tion before any planned craniofacial reconstruction.

yy The ophthalmologist should be consulted for problems such as
exorbitism, subluxation of the whole globe and strabismus, both
before and after cranial surgery.

yy The diagnostically helpful craniofacial features include head
shape, orbital divergence, parrot-beak nose with a flat midfacial
region, antimongoloid slanting of the lid fissures.

yy Peripheral features include short stature, broad thumbs and toes,
and syndactyly of the hands or feet.

yy Anomalous head positions are common- but it is better to confirm
whether torticollis is ocular or not?3,7

yy Nischal has indicated that some patients can present with
torticollis after strabismus surgery also if non-ocular cause is
not ruled out.7

Strabismus evaluation

1. Measurement of Stereopsis: Despite aggravating conditions,
fusion has been demonstrated in 33% of patients with Crouzon,
25% with Apert, and 28% with Pfeiffer syndrome.

2. Binocular status may be tested in younger children using the Lang
test or the 4-PD base-out prism test. In older children, TNO stereo
test, Titmus stereo test, Lee screen and synoptophore evaluation
can be done. If the child spontaneously holds the head in an
eccentric gaze position, it is probable that fusion is present in that

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position. The absence or presence of fusion will clarify the reason
for the anomalous head posture.

3. Measuring the deviation: Pattern strabismus is the predominant
feature in craniosynostotic strabismus.The prism cover test must
be recorded in all standard gaze positions at distance (6 m or 20 ft)
and at near (40 cm) to get the accurate deviation. Most individuals
will demonstrate at least some apparent oblique dysfunction. Most
commonly seen is IO overaction, then SO underaction and LR
underaction. Ductions should be examined when version testing
will give abnormal extraocular movement.3 Hence versions are
highly informative in strabismus with craniosynostosis

4. Measurement of torsion: Ocular torsion is difficult to measure
objectively in young patients, but fundus torsion is easily observed
by indirect ophthalmoscopic examination of the dilated fundus. It
has been suggested that failure of fusion induces torsion, which in
turn causes an alphabet-pattern strabismus.3

Investigation

Imaging of extraocular muscles can be very helpful prior to strabismus
surgery. The extraocular muscles are most easily identified on a coronal
computed tomography (CT) scan or on magnetic resonance imaging.2

Current computed tomography (CT) and magnetic resonance imaging
(MRI) techniques allow coronal views that can be used to assess for
EOM excyclorotation around the orbit’s anterior–posterior axis.2,3,4

Anatomical cyclorotation of the horizontal rectus muscles can be
measured in both coronal and quasicoronal views. Quasicoronal
views provide the most accurate analysis of the centroid of each rectus
muscle, as the standard coronal view often presents the lateral rectus
obliquely.

In unilateral coronal synostosis Harlequin – shaped orbit is seen in
MRI imaging2.

The role of 3D ultrasound in identifying the extraocular muscles in
craniosynostosis has been shown to yield an acceptably accurate
anatomic imaging of the extraocular muscles.

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Preoperative awareness of structural variations and extraocular
muscle anomalies in craniosynostosis patients provides the surgeon
with valuable information for preoperative planning. A muscle that
the surgeon is going to operate may be absent, malformed, or located
in an aberrant position.5,6,8

It is important to note that Orbital imaging can be most helpful in
planning surgery in patients with craniosynostosis to know the
anatomy in advance and to plan surgery accordingly.2,5,6,

Treatment

Nonsurgical management:4
Amblyopia therapy: For the best chance of regaining normal vision
and developing binocular (bifoveal) fusion, strabismic children with
craniosynostosis should receive appropriate amblyopia therapy before
and after craniofacial and orbital surgery. It responds well to traditional
therapy with glasses, occlusion, and atropine penalization.

Orbital repositioning for hypertelorism frequently causes esotropia,
with subsequent suppression and amblyopia. For this regular follow
up is needed after cranial and facial repair to manage amblyopia and
other ocular problems.

Botulinum toxin injection of the ipsilateral antagonist MR could also
be indicated for both diagnosing LR recovery (if masked by MR
contracture) and to avoid secondary contracture. It may be useful
for creating ptosis to enable protection of the globe also apart from
tarsorraphy.

Surgical management2,3,4,5,6,8
yy Several factors should be considered before planning the surgical

correction of strabismus.
1. V-pattern strabismus is common in craniosynostosis and has

proven to be difficult to treat
2. Whether the shape and angulation of the bony orbit appear to be

factors causing significant excyclorotation of the rectus muscles
and secondary V pattern or not.

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3. Severity of the V pattern, the position at which the pattern is worse
and the presence or absence of binocular fusion.

4. In patients presenting with significant head tilt, the monocular
patch test is a helpful tool to predict whether strabismus surgery
has a chance to reduce torticollis.

5. The timing of craniofacial reconstruction is best left to the
surgeons involved. In general, early surgery is preferred because
full-thickness bone graft, which has can regenerate bone, may
be used rather than partial-thickness grafts. The current trend
is towards earlier craniofacial intervention by 4 months of age
for endoscopic procedures and waiting for child to turn one for
cranial vault expansion.

6. But urgent surgery is indicated when there is a threat to the globe
or vision, as in severe corneal exposure due to exorbitism or severe
lid retraction or the onset of optic atrophy.

Timing of strabismus surgery:

Early surgery can help to restore binocular fusion. If surgery to advance
the midface or adjust the orbit is anticipated, strabismus surgery should
be delayed six months to a year, as such craniofacial surgery will alter
the orbital volume and ability to achieve perfect alignment.

After initial craniofacial repair, usually at 3 to 4 months of age,
strabismus surgery may be contemplated when it is clinically
indicated like : reversal of amblyopia after patching or penalization,
appropriate optical correction, and reliable cover tests or light reflex
measurements.

Surgical approach:2,3,4,5,6,8

1) V pattern strabismus: V-pattern strabismus in patients with
craniosynostosis does not result from simple IO overaction.

It is primarily due to the excyclorotation of the globe; anomalous
vectors of muscle action; a shorter orbital floor, causing increased
arc of contact; and loss of fusion.

For torsional anomalies of horizontal muscles the most effective
outcome is with vertical transposition in the appropriate direction
by one-half tendon width to collapse the V.

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V-pattern exotropia, a common finding, is often associated with
torsional anomalies in rectus muscle positions, especially the
LR.

The preferred surgical approach is supra placement of both LR
muscles, combined with recession if deviation is 15 PD exotropia
in primary gaze in patients without fusion.

2. With true IO overaction : These patients require some form
of IO weakening procedure. Bell's phenomenon should be
documented preoperatively to avoid inadvertent nocturnal
lagophthalmos.

• Strong Bell's phenomenon + severe IO overaction: Anterior
transposition of the IO

• Doubtful Bell’s phenomenon with moderate IO overaction : IO
recession, myectomy, or Z-tenotomy

• Also, in mild SO palsy or evidence of fusion, IO myectomy,
or recession can be anticipated to collapse the V pattern and
excyclotorsion of the globe.

Complication: Acquired Brown syndrome can happen after IO
weakening procedure.

3. V pattern with SO under action with no IO overaction, and no
displacement of the LR muscles (on imaging) - Intraoperative
forced ductions and exaggerated traction testing of the SO
should be performed as this provides critical information on
the contribution of SO palsy on V pattern and on the potential
advantage of considering SO surgery. IO tone should also be
checked.

Significant, SO laxity suggests treatment by bilateral SO tucks.
However, in some cases with very poor SO tone, palpation of the
notch may reveal a very posterior location of this reflection.

The result could also be less impressive because of the aberrant
trajectory of the SO.

4, Managing Absent or Fibrotic Muscles-

The presence of a poorly functioning extraocular muscle can be
easily seen on clinical examination. However, confirmation that

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the muscle is not more than a strand of fibrous tissue requires
operative observation.

Unlike the congenital fibrosis syndrome with tight muscles,
the fibrous strands in these cases usually have very little
tension and therefore, the muscle behaves as paretic rather
than restrictive.

5) Ocular torticollis: Patients are often treated with IO weakening,
or a SO tuck, or a combination if the IO weakening alone is
considered to be insufficient to improve ocular torticollis.9 SO
tuck is most effective, if the rest of the anatomy is unchanged
with significant SO laxity , reducing all aspects of V pattern and
effectively reducing torticollis if the patient has the potential for
binocular fusion.9

Unusual results1,2,3,5,6

Inadvertent surgery on muscles whose anatomical insertions
are close, such as the LR and IO, may result in unpredictable
postoperative results with worsening of the deviation vertically
and/or horizontally. Even with a huge V pattern, better to delay
surgery in patients whose eyes are straight in the primary position
and fusing. Only when the primary-position deviation changes
surgery can be considered.

Reoperation, for under correction, is often necessary in these patients.

Important considerations

Esotropia is more common in Apert’s whereas exotropia is more
common in Crouzon and Pfeiffer’s syndromes

Regular postoperative evaluations utmost needed in all patients with
(suspected) craniosynsotosis.

Patients who undergo repeated cranial surgery may temporarily defer
patching or penalization for amblyopia but not permanently.

Treatment needs to be intensified once amblyopia progresses or vision
deteriorates before any strabismus surgery.

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References

1. Ron Y, Dagi LR. The etiology of V pattern strabismus in patients with
craniosynostosis. Int Ophthalmol Clin. 2008 Spring;48(2):215-23

2. Ganesh A, Edmond J, Forbes B, Katowitz WR, Nischal KK, Miller M, Levin
AV. An update of ophthalmic management in craniosynostosis. J AAPOS. 2019
Apr;23(2):66-76

3. Abdelrahman M. Elhusseiny, Elisah M. Huynh & Linda R. Dagi (2020) Evaluation
and Management of V pattern Strabismus in Craniosynostosis, Journal of
Binocular Vision and Ocular Motility, 70:1, 40-45

4. Rosenbaum.Clinical strabismus management,393-403
5. Lehman S. Strabismus in craniosynostosis. Curr Opin Ophthalmol. 2006

Oct;17(5):432-4
6. Tan KP, Sargent MA, Poskitt KJ, Lyons CJ. Ocular overelevation in adduction in

craniosynostosis: is it the result of excyclorotation of the extraocular muscles? J
AAPOS. 2005 Dec;9(6):550-7
7. Nischal, Ken. (2002). Ocular Aspects of Craniofacial Disorders. The American
orthoptic journal. 52. 58-68.
8. Dagi LR, MacKinnon S, Zurakowski D, Prabhu SP. Rectus muscle excyclorotation
and V-pattern strabismus: a quantitative appraisal of clinical relevance in
syndromic craniosynostosis. Br J Ophthalmol. 2017 Nov;101(11):1560-1565. 
9. Holmes JM, Hatt SR, Leske DA. Superior oblique tucks for apparent inferior
oblique overaction and V-pattern strabismus associated with craniosynostosis.
Strabismus. 2010 Sep;18(3):111-5.

140 CME on COMPLEX STRABISMUS

09Brown’s Syndrome

Brown’s Syndrome

Dr. Cinnam Shailaja, Dr. Sandra C Ganesh1

Department of Paediatric Ophthalmology and Strabismus,
Aravind Eye Hospital, Coimbatore, India

Brown’s syndrome is a type of restrictive strabismus characterised
by limited elevation in adduction, normal elevation in abduction,
divergence on upgaze and positive forced duction test. It can occur
due to various congenital or acquired causes leading to mechanical
restriction of superior oblique tendon/trochlear complex. Inferior
oblique paralysis, monocular elevation deficit, orbital floor fracture
are important differential diagnosis of the condition. Spontaneous
resolution can occur in acquired, intermittent cases. Inflammatory
Brown’s syndrome responds to local corticosteroid therapy. Surgical
correction is required in long standing, congenital cases. Superior
oblique tendon lengthening procedures like chicken suture lengthening
or Wright’s silicon expander procedure are the preferred procedures
for surgical correction.

Introduction

Also known as Jaensch Brown syndrome, it is a type of restrictive
strabismus characterised by limitation of elevation in adduction. It is
caused by mechanical restriction of superior oblique tendon/trochlea
complex. It can be a congenital or an acquired condition. In 1928
Jaensch first described limitation of elevation of the adducted eye
following facial trauma. The clinical picture resembled a paralysis
of the inferior oblique muscle but forced duction test (FDT) showed
resistance to elevation of the adducted eye. A traumatic adhesion
between the trochlea and the globe anterior to or at the equator was
suspected. Such an adhesion would not interfere with depression of
the globe but would present an obstacle to elevation in adduction.
In 1950 Brown described an identical anomaly of ocular motility
which occurred on a congenital basis. Since then, many anomalies
involving the superior oblique muscle, its tendon and surrounding

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tissue, or the trochlea are described that may contribute to similar
picture.

Pathophysiology

Superior oblique anatomy: The muscle originates from the body of
sphenoid above the annulus of Zinn, runs forward parallel to the
superomedial orbital wall, passes through the trochlea, turns postero-
laterally and gets attached on to the superolateral aspect of the
globe posterior to the equator in a fan shaped insertion. Trochlea is
considered the functional origin of SO muscle as it acts as a pulley and
changes the direction of muscle pull. (Figure 1)

Trochlea

Superior
oblique
muscle

Figure 1: Picture showing superior oblique tendon and trochlear anatomy.
Source : Internet

Normal elevation of the eye into adduction increases the distance
between the trochlea and the superior oblique insertion as the back of
the eye moves down and out. A tight SO tendon complex or disorders
that limit normal movement of SO tendon would not allow the back of
the eye to move down and out and would restrict ocular elevation in
adduction. Other features of Brown's syndrome, such as divergence in
attempted up gaze (V-pattern Y subtype) and down shoot on adduction,
can also be attributed to a tight superior oblique tendon, since tension
on the posterior fibres results in depression and abduction.

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Causes of Brown’s syndrome

1. Congenital Brown’s syndrome

A) True congenital Brown’s syndrome – due to congenitally short
or inelastic SO muscle/tendon.

B) Pseudo Brown’s syndrome – due to non superior oblique
causes i.e., inferior orbital fibrous adhesions or fibrous bands
to the posterior globe, congenital inferior location of lateral
rectus muscle pulley.

2. Acquired Brown’s syndrome

A) Abnormal telescoping mechanism: due to vascular dilatation
of the tendon sheath vessels and local edema occurring within
the confined area of the trochlea.

B) Tight or inelastic superior oblique muscle: Thyroid disease, an
intramuscular injection of local anaesthetic, or Hurler-Scheie
syndrome.

C) Short or inelastic tendon: post superior oblique tendon tuck, a
mass that displaces the tendon, or a scleral buckling

D) Superior oblique click syndrome: Inflammatory causes -
superior oblique myositis, acute sinusitis, adult rheumatoid
arthritis, systemic lupus erythematosus. Inflammation
produces a nodule on the SO tendon, just posterior to the
trochlea restricting tendon movement.

E) Stenosing tenosynovitis (trigger-thumb analogy): Chronic
movement of the superior oblique tendon through the trochlea
can result in a traumatic tenosynovitis with tendon-swelling
and stenosis of the surrounding tendon sheath

F) Peri-trochlear scarring: Post trauma, chronic sinusitis,
periocular surgery, and upper lid blepharoplasty. It can result
in restriction of the tendon movement in both ways, resulting
in both a Brown syndrome and a superior oblique palsy
(canine tooth syndrome).

G) Acquired non superior oblique Brown syndrome:

- Inferior orbital fibrous adhesions to the posterior globe are
caused by orbital floor fracture and fat adherence.

CME on COMPLEX STRABISMUS 143

Brown’s Syndrome

- Superior nasal orbital mass: Glaucoma drainage implant or a
neoplasm

- Scarring in the inferior temporal anterior orbit after
transconjunctival blepharoplasty.

Recently, it has been suggested that some cases of congenital Brown
syndrome and congenital superior oblique paresis are related, and
these entities may be part of the congenital cranial disinnervation
disorders (CCDD) spectrum.1 Abnormal development of the trochlear
nerve results in physical changes in the superior oblique muscle-
tendon-trochlea complex causing restriction of the tendon movements
through the trochlea.2

Incidence: The incidence of this condition is 1 in 450 cases of
strabismus.3

Laterality: Unilateral occurrence is common. Bilateral occurrence is
seen in about 10% of cases.4

Gender predilection: It was initially considered to be more common
in females but further studies show that it equally affects males and
females.3

Inheritance: Although sporadic occurrence is most common, familial
cases and autosomal recessive or dominant inheritance with reduced
penetrance have been reported.5,6

Associated anomalies- Marcus gunn synkinetic movements, crocodile
tears, choroidal coloboma.3

Clinical Features

yy Limited elevation in adduction is the hallmark of Brown's
syndrome and is an invariable sign. Elevation in abduction is
normal. (Figure 2)

yy In cases with severe restriction, there can be a down shoot of the
affected eye in adduction.

yy A hypotropia may be present in primary position, and the amount
of the hypotropia is proportional to the severity of the restriction.

144 CME on COMPLEX STRABISMUS