Open Journal of Ophthalmology, 2012, 2, 1-4
http://dx.doi.org/10.4236/ojoph.2012.21001 Published Online February 2012 (http://www.SciRP.org/journal/ojoph)
1
Usefulness of Botulinum Toxin Type-A in the Treatment
of Chronic Sixth Nerve Palsy
Lelio Sabetti*, Immacolata Greco, Domenico Di Lodovico, Antonio Berarducci
Eye Clinic, San Salvatore Hospital, University of L’Aquila, L’Aquila, Italy.
Received November 7th, 2011; revised December 16th, 2011; accepted January 28th, 2012
ABSTRACT
Purpose: The purpose of the study was to evaluate the efficacy of botulinum toxin type A (BTX-A) injection in patients
with acquired VI nerve palsy. Methods: Twenty-eight patients (16 F and 12 M), mean age 36.4 +/− 17.8 DS; range 10 -
69 years with acquired VI nerve palsy, have been treated with BTX-A injection into the ipsilateral medial rectus, at least
6 months after onset. At 6 months follow up, a paresis and a paralysis, were respectively diagnosed if the affected eye
could be actively abducted or not, across the mid-line; a simple horizontal rectus muscle procedure was performed for
the paresis whilst for the paralysis, both a horizontal and vertical muscle transportation procedure were required. Re-
sults: A gradual physiological recovery of the lateral rectus muscle was observed in 9 (32%) patients (GROUP I) and
surgical treatment was therefore unnecessary; the remaining 19 cases (68%), of which 5 paresis (GROUP II) and 14
paralysis (GROUP III) underwent surgery and within 1 year were all restored to orthotropia. Conclusion: Botulinum
toxin type-A (BTX-A) injection is an invaluable tool in the differential diagnosis between paresis versus paralysis of the
VIth nerve, allowing the correct choice of surgical procedure.
Keywords: Chronic Acquired VI Nerve Palsy; Botulinum Toxin Type-A
1. Introduction
Acquired sixth nerve palsy is usually a consequence of
vascular or neurological diseases, diabetes, head trauma
[1,2] or cerebral tumors [3]. Diagnosis and management
of this neurogenic ocular palsy are often difficult largely
due to the fact that the ophthalmologist has insufficient
and/or inaccurate clinical history of the patients. It is
generally necessary, prior to surgical treatment, to wait at
least for 6-8 months, in order for the paralysis to be con-
sidered stable. A spontaneous recovery of this paralysis
is rare [4]. It is important to note, however, that there is a
frequent occurrence of the contraction of the joint an-
tagonist muscle which may mask the functional recovery
of the latter. Patients thus affected manifest large angle
isotropia. Adults experience double vision and are forced
to tilt the head to neutralize diplopia or to use prismatic
lenses. If diplopia is not adequately controlled it may
require surgical treatment, the functional result of which
is often however unpredictable. Botulinum toxin type-A
(BTX-A) injected in the hyperfunctional muscles causes
a flaccid paralysis by preventing the release of acetylcho-
line at the neuromuscular junction and thus results in a
gradual physiological recovery of the hypofunctional
muscles [5]. BTX-A injection can be used either during
the waiting period for the spontaneous recovery or for
surgery; in cases where VI nerve palsy is resolved,
BTX-A help to prevent diplopia, whereas in the case of
unresolved palsy, the toxin is an invaluable tool in the
differential diagnosis between paresis versus palsy,
which in turn allows the correct choice of surgical pro-
cedure.
2. Materials and Methods
Between April 2001 and February 2007, twenty-eight
consecutive patients were referred to our clinic with ac-
quired sixth nerve palsy. The 16 women and the 12 men
were 10 to 69 years of age (mean 36.4 +/− 17.8 SD). All
patients underwent a complete preoperative ophthal-
mological and orthoptic clinical protocol, including ocu-
lar refraction with and withuot cycloplegia, Goldmann’s
tonometry, biomicroscopy of the anterior segment and
funduscopic examination. The orthoptic examination
evaluated the ocular motility in the nine diagnostic gaze
positions; strabismus was measured with the prism and
cover test for near and distance fixation and presence of
anomalous head positions was identified, Worth and mi-
cro-Worth 4-dot test, Lang test (I-II), Titmus, red filter
ladder test, Hess-Lancaster screen test and passive and
*Corresponding author.

Usefulness of Botulinum Toxin Type-A in the Treatment of Chronic Sixth Nerve Palsy
2
active abduction test were also performed. Mean pre-
injection angle deviation was 22˚ ET (+/− 0.64 SD) near
and 24.9˚ ET (+/− 0.74 SD) distance. Inclusion criteria
were sixth nerve palsy more than 6 months after onset
and an anomalous position of the head. The patients were
divided into 3 class according the time of onset of the
palsy: 9 patients (CLASS I) with more than 24 months
after onset; 11 patients (CLASS II) between 12 and 24
months after onset; 8 patients (CLASS III) between 6 and
12 months after onset. Exclusion criteria were: previous
surgical treatments, congenital abnormalities of ex-
traocular muscles and cases where there had been ad-
ministration of aminoglycosides or other drug causing
interference with the neuromuscular system, in the last 6
months. Appropriate informed consent was obtained in
all cases. Each patient underwent a single injection of
BTX-A (20 IU, Botox, Dysport, Ipsen) under local an-
aesthesia directly in the ipsilateral medial rectus muscle.
3. Results
Follow ups were performed at 1 and 6 months intervals.
At 6 months the differential diagnosis between a paresis
and paralysis was respectively defined if the affected eye
could or could not be actively abducted or not across the
midline. Patients with paresis underwent a single hori-
zontal rectus muscle procedure, whilst patients with pa-
ralysis further underwent horizontal and vertical muscle
transposition procedure [6,7]. The patients were divided
into 3 groups. Nine of them (32%) (group I) manifested a
gradual physiological recovery of the lateral rectus mus-
cle at 1 month follow up (mean 4.57˚ ET +/− 0.90 SD
near and 3.42˚ ET +/− 0.51 SD distance). This group was
composed of 4 patients with head trauma, 3 patients with
vascular diseases, 1 patient with diabetes and 1 patient
with an idiopathic case; six of them belonged to CLASS
I, one of them belonged to CLASS II and two of them
belonged to CLASS III. These patients complained of
diplopia within only two months of the BTX-A injection
but this condition could be neutralized with prismatic
lenses. Consequently these patients did not require a sur-
gical procedure. In contrast, at 1 and 6 months follow up,
five patients (18%) (group II) manifested paresis with an
active abduction across the mid-line, at 1 month (mean
14.28˚ ET +/− 0.90 SD near and 18.28˚ ET +/− 0.90 SD
distance). This group was composed of two patients with
vascular diseases, 1 patient with head trauma, 1 patient
with diabetes and 1 patient with cerebral tumor; two of
them belonged to CLASS I, two of them belonged to
CLASS II and one of them belonged to CLASS III.
These patients underwent horizontal procedure of muscle
recession and/or resection. Finally, 14 cases (50%) (group
III) manifested paralysis without an active abduction
across the mid-line, at 1 month (mean 21.34˚ ET +/−
1.06 SD near and 22.28˚ ET +/− 0.74 SD distance) and at
6 months follow up (mean 23.05˚ ET +/− 0.91 SD near
and 24.48˚ ET +/− 0.86 SD distance) consequently all of
them underwent a horizontal as well as a vertical muscle
transposition procedure. This group was composed of 6
patients with head trauma, 3 patients with vascular dis-
eases, 3 patients with cerebral tumors, 1 patient with di-
abetes and 1 patient with an idiopathic case; one of them
belonged to CLASS III. Within a year of surgery all pa-
tients were either restored to orthotropia or remained
with a small-angle residual isotropy in primary position,
easily corrected with lenses.
4. Discussion
The aim of surgery in paralytic strabismus is to restore
the best equilibrium between muscle forces unbalanced
by ocular palsy. Moreover it is necessary to eliminate the
eventual presence of diplopia and/or of anomalous head
posture. In the VI nerve palsy the choice of the surgical
strategy could depend on the extent of recovery induced
by BTX-A injection, which thus becomes an invaluable
tool in surgical evaluation [8]. During the first 3 months
after the onset of palsy, it is possible to have a spontane-
ous recovery, but in the following period there is often
the occurrence of contraction of the joint antagonist
muscle. Elasticity of the deficient muscle is gradually
reduced due to a constant elongation resulting in a grad-
ual loss of tonus, hyper-extensibility and progressive
degeneration of muscolar fibres [9]. According to avail-
able literature, the degeneration becomes irreversible
after one or two years of the reduction of active muscle
tension, and the high-resolution MRI can directly dem-
onstrate the degeneration of muscolar fibres [10]. How-
ever, as demonstrated in this study, a full recovery (24%)
or a partial recovery of the lateral rectus function (20%)
are possible even in long term VI nerve palsy [11].
BTX-A injection in acquired sixth nerve palsy, avoids a
hyper-contraction of the ipsilateral medial rectus muscle
[12], promotes the recovery of the lateral rectus function
and eliminates the need of surgical intervention in pa-
tients who can benefit from restored orthotropia by a sole
injection. Patients who manifest a persistent large angle
isotropy with diplopia or anomalous head position, allow
for a differential diagnosis between a paresis vs paralysis;
as previously stated, this comparison becomes instru-
mental in establishing the need of surgery. If the affected
eye cannot be abducted beyond the mid-line, the transpo-
sition procedure will be required; if eye abduction is pos-
sible the recession and resection procedure should be
sufficient. Botulinum toxin treatment was originally de-
veloped 25 years ago by Ala B. Scott to produce reversi-
ble weakening of extraocular eye muscle (chemodener-
vation) [2,13] in the treatment of strabismus. Today it is

Usefulness of Botulinum Toxin Type-A in the Treatment of Chronic Sixth Nerve Palsy 3
an important aid in the preoperative evaluation of possi-
ble postoperative diplopia on patients in which this can-
not be done by means of prism or traction test; in acute
paretic loss of ocular muscle function; when surgical
treatment of the ocular muscles is not yet possible but the
patient is obviously affected by diplopia or a forced pos-
ture of the head [2], in situations where strabismus sur-
gery is not suitable (as in elderly patients unfit for gen-
eral anaesthesia; when the clinical condition is evolving
or unstable, or in case of unsuccessful surgery) [13], in
acute Graves’ disease, and especially into VI cranial
nerve paresis [2], or in association with the surgery [14].
Depending on the surgical approach in VI nerve palsies,
Botulinum toxin may be injected in the medial rectus
muscle before muscle transposition surgery to loosen
contracture [2] or, on the basis of our results, BTX-A
injection can be considered an invaluable tool in the
management and diagnosis of VI nerve palsy, and it al-
lows differential diagnosis between paresis vs paralysis,
which is the necessary condition to plan the correct sur-
gical treatment and to obtain a successful functional out-
come. In other strabismus, as congenital esotropia or
horizontal strabismus in adults, Botulinum toxin is defi-
nitely an inferior surgical treatment of the ocular muscles
[2]. Moreover the use of botulinum toxin type A is effi-
cient in the identification of adult patients with constant
strabismus who are at high risk o developing intractable
diplopia after surgery [15]. The majority of studies iden-
tify the Botulinum toxin A injection into extra-ocular
muscles the ideal therapy for the treatment of sixth cra-
nial nerve palsy [1], on 36.8% of the patients with a final
ocular alignment within 10 prism dioptres of orthotropia
and achieved fusion and primary gaze position. There
was no correlation among the number of injection for
patient (the mean number of injection is 1 to 5), the size
of strabismus, the grade of lateral rectus muscle function,
the age, the gender or the time paresis it occurred [1]. In
our study all patients had to undergo a single injection
and only in 32% of cases (9 patients) a gradual physio-
logical recovery of the lateral rectus muscle was obtained
at 6 months like if the surgical treatment could be
avoided and nobody of them was candidate for a second
injection; patients under-corrected at six months from the
onset were been treated with surgery. The most interest-
ing result was to identify in GROUP 1 six patients who
had been suffering with palsy for a period in excess of 24
months before the injection (CLASS I); although it is
known and documented that VI nerve deficit of traumatic
origin tends to normalize without any treatment or after
botulinum toxin injection [7,16,17] this has never been
recorded for cases where patients have been subject to
palsy for such a long time. Moreover it is also possible to
combine the injection with surgery [14] to preserve the
function of the medial rectus muscle, in order to avoid
surgery on more than two rectus muscles to prevent the
risk of anterior segment ischemia (which can occur when
there is surgery of multiple muscles) and to expand the
field of binocular single vision as much as possible. In
our trials, Botulinum toxin type-A (BTX-A) was directly
injected in the hyperfunctional muscle without electro-
myographic assistance, in order to reduce the incidence
of blepharoptosis [18]; a study of 2003 proposed that
subtenon injection of the medial rectus muscle for the
treatment of acute tramatic sixth nerve palsy [19]. The
results on the patients treated with subtenonian injection
of botulinum toxin without electromyography (EMG)
guidance was comparable to that obtained using EMG-
guided intramuscolar injection of botulinum toxin [19,
20], the reason is in fact that the substance injected in the
muscle has the tendency to diffuse into the surrounding
tissues. Finally BTX injection has been used for 11 years
by 292 ophthalmologists in 8854 patients, from the age
of three months to 90 years, in a variety of eye muscle
and eyelid disorders [21]. According to international lit-
erature, no systemic toxin reaction has occurred, local
complications are few and visual loss has not occurred in
any case [21]; ptosis and acquired vertical deviation caused
by diffusion of the substance into the surrounding tissues
are the commonest complications encountered. These are
minor and reversible damages induced by the traumatic
action of the needle and/or the substance into the tissues
(edema and minor subconjunctival hemorrhage), as fur-
ther proof that the repeated use of BTX-A could be con-
sidered safe [13].
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