|Year : 1993 | Volume
| Issue : 3 | Page : 121-124
Botulinum toxin in the treatment of paralytic strabismus and essential blepharospasm
Ravi Thomas, Annie Mathai, B Rajeev, Subir Sen, Pushpa Jacob
Schell Eye Hospital, Christian Medical College, Vellore, India
Schell Eye Hospital, Vellore 632 001, Tamil Nadu
Source of Support: None, Conflict of Interest: None
As an alternative to conventional medical and surgical modalities that have met little success in the treatment of paralytic strabismus and essential blepharospasm, we explored the use of botulinum toxin as a treatment of choice in these two disorders. We used botulinum toxin in three patients with paralytic strabismus and in nine patients with essential blepharospasm. In three patients with paralytic strabismus, the botulinum toxin was injected into the ipsilateral antagonist of the paralysed muscle. The preinjection deviations ranged from 18 to 60 prism diopters. Two of these three patients achieved orthotropia around the thirtieth day and thereafter maintained it. The third patient became orthotropic on the eighteenth day, but deviation recurred and therefore required another injection of toxin. In nine patients with essential blepharospasm, botulinum toxin was injected into the orbicularis oculi muscles. Both objective and subjective improvement occurred in all nine patients within seven days and the effect lasted 12 to 15 weeks. Further injection of the toxin produced extremely beneficial results. However, the only significant complication that we encountered in both groups of strabismus and blepharospasm was ptosis, which was usually partial and temporary. From our experience, we advocate the use of botulinum toxin in the treatment of essential blepharospasm.
Keywords: Botulinum toxin - Paralytic strabismus - Essential blepharospasm - EMG.
|How to cite this article:|
Thomas R, Mathai A, Rajeev B, Sen S, Jacob P. Botulinum toxin in the treatment of paralytic strabismus and essential blepharospasm. Indian J Ophthalmol 1993;41:121-4
Botulinum toxin type A is a purified form of the exotoxin of Clostridium botulinum. The toxin blocks acetylcholine release at nerve terminals causing a temporary muscle paralysis.  The therapeutic use of botulinum toxin for paralytic strabismus and essential blepharospasm has been reported in the literature. ,, We present our experience with botulinum toxin in the treatment of these two disorders.
| Materials and methods|| |
Botulinum toxin was obtained from Public Health Laboratory Services, Porton Down, England. Vials containing 50-ng of the toxin were stored between 2° and 8°C. Vials were brought to room temperature before reconstitution with normal saline to obtain the required concentration.
| Paralytic strabismus|| |
Three patients with paralytic strabismus were injected with 6.25 X 10 -5 micrograms of botulinum toxin into the antagonist of the paralysed muscle. The toxin was diluted so as to provide the required dose in 0.1ml. The injection was administered with a 27-gauge monopolar needle under EMG control using an Oculinum Injection Amplifier  (Oculinum Incorporated, Berkeley, California, USA). The details of the patients are shown in [Table - 1]. An illustrative case is described below.
| Case report|| |
A 26-year-old-woman (Case #3) presented with a right lateral rectus palsy of one month duration [Figure l]a. The paralysis had followed accidental injury to the VI nerve during resection of a cerebellopontine angle tumour. The preinjection deviation was approximately 60 prism diopters and had remained static for one month. The forced duction test showed minimal limitation of adduction of the right eye. The patient was injected with botulinum toxin into the right medial rectus muscle. She became orthotropic on the eighteenth day [Figure - 1]b A right ptosis developed on the fifth day which resolved over the next 15 days.
Approximately 80 days after the injection she developed a recurrent right esotropia of 60 prism diopters. Forced duction test showed no limitation of right adduction. She underwent a repeat injection of 6.25 x 10 -5sub micrograms of botulinum toxin into the right medial rectus muscle. She once again achieved orthotropia within 15 days and has remained so for over eight weeks to date. Ptosis did not follow the repeat injection.
| Essential blepharospasm|| |
Nine patients with essential blepharospasm were treated with botulinum toxin [Table - 2]. Blepharospasm was graded both subjectively and objectively. Ail nine patients had severe grade of essential blepharospasm [Table - 3].
One vial of the botulinum toxin was diluted with 10 ml of normal saline to provide a concentration of 5 ng/ml. One nanogram of the toxin (0.2 ml) was injected into each of the five sites in both the orbicularis oculi muscles and three sites in the procerus muscle. For the orbicularis oculi, the injection was given at the junction of the preseptal and orbital parts, using a 24-gauge needle. In the upper eyelid, the injections were directed away from the centre of the eyelid to avoid the levator muscle (Figure 2).
The details of the patients are shown in [Table - 2]. An illustrative case is described below.
| Case report|| |
A 56-year-old man with incapacitating essential blepharospasm of six years' duration [Figure - 3]a and b had been earlier treated unsuccessfully with various drugs including antidepressants, antipsychotics, and even psychotherapy. On examination, the patient had grade 3 essential blepharospasm. He was injected with botulinum toxin according to the described protocol. Seven days later, the patient improved dramatically. He had no difficulty in opening his eyes, but was not able to forcibly close his eyes. The effect lasted for about 12 weeks with no complications. Six months later, the patient presented again with a slow recurrence of the symptoms which necessitated retreatment with the same dose of toxin.
This injection also produced similar beneficial results that lasted 16 weeks, again with no complications. The patient was given one more injection which was again efficacious. However, he developed a mild ptosis in one eye which lasted two weeks and thereafter resolved completely.
| Discussion|| |
Botulinum toxin type A is a sterile, lyophilized, purified form of the exotoxin of Clostridium botulinum type A. Following injection into a muscle, the toxin binds to receptor sites on motor nerve terminals. The toxin is then internalised, remaining in the nerve terminal for several weeks where it interferes with the release of acetylcholine causing a temporary muscle paralysis. 
In paralytic strabismus, the botulinum-induced paralysis of the antagonistic muscle prevents or reduces its contracture during spontaneous recovery of the paretic muscle. Also, as the initial overcorrection resulting from the infection slowly resolves and the eyes approach the primary position, fusion may "lock on" resulting in orthotropia. 
The advantages of botulinum toxin therapy for strabismus are: (1) it can be performed on an outpatient basis; (2) carries minimal risk; (3) leaves no scar; (4) can be used for postoperative residual strabismus; and (5) can be used when surgery is inappropriate. It has been shown in paralytic strabismus that eyes treated with botulinum toxin have better chance of recovery than those that have not been treated, 
Two of our patients (one with lateral rectus palsy and the other with inferior rectus palsy) have recovered completely. In the patient with lateral rectus palsy, we seem to have prevented contracture of the antagonist medial rectus muscle, and this should make subsequent elective surgery easier.
The reported disadvantages of both linum toxin therapy for strabismus are: (1) more than one infection is often needed to determine the optimum dose to obtain maximal benefit; (2) alignment changes are not as stable as with surgery; and (3) transient partial ptosis and vertical strabismus frequently occur.
The only complication that we encountered was temporary ptosis, which occurred in all cases. Presumably, this high incidence could partly be explained by the learning curve and with increasing experience should decrease.
Essential blepharospasm is a variably progressive, bilateral, involuntary focal cranial dyskinesia of unknown etiology. It is characterized by spasmodic, forceful, involuntary contractions of the orbicularis. It results in prolonged eyelid closure causing severe visual disability. Suggested medical treatments include tranquilisers, antidepressants, antipsychotics, biofeedback, acupuncture, psychotherapy, and hypnosis.  Surgical treatments, on the other hand, include orbicularis resection and selective facial neurectomy.  But unfortunately, both medical and surgical treatments have had limited success. Botulinum toxin is currently accepted as the treatment of choice in this otherwise intractable condition.,
Our patients exhibited dramatic relief of symptoms following treatment with botulinum toxin. All patients had previously been unsuccessfully treated with various medical treatments, for example, one patient had undergone a facial nerve block. Several satisfied patients returned seeking another dose of toxin. Ptosis, usually partial, has been the only significant complication following seven out of 15 injections. It was bilateral and complete in only one patient. Taping the upper eyelid to the forehead helped to tide over the period till recovery. In all the patients the ptosis resolved within four weeks.
The other reported complications of botulinum therapy are: (1) scleral perforation; (2) retrobulbar hemorrhages; (3) diplopia; (4) pupillary dilatation; (5) ecchymosis; (6) corneal exposure; (7) ptosis; (8) ectropion; (9) lagophthalmos; and (10) chemosis. , However, the only complication we encountered in both groups of strabismus and blepharospasm was ptosis. While the prospect of systemic toxicity is alarming, the clinical doses were well below 40 units/kg of body weight which is the estimated systemic toxic dose, 
It is our experience that botulinum toxin is indeed the treatment of choice for essential blepharospasm. While it is curative in some cases of paralytic strabismus, in others it prevents contracture of the antagonist and should therefore make subsequent surgery simpler. A major constrain in the therapeutic use of botulinum toxin, particularly in our country, is its prohibitive cost.
Acknowledgment : The botulinum toxin was obtained from Public Health Laboratory Services, Porton Down, England, for use on a named-patient basis.
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[Figure - 1], [Figure - 2], [Figure - 3]
[Table - 1], [Table - 2], [Table - 3]