Journal of Pediatric Ophthalmology and Strabismus

CONTROVERSIES 

Botulinum Injections for Strabismus

Eugene M Helveston, MD

Abstract

A time-honored and well-tested practice in the treatment of strabismus is that a so-called overacting, tight, or restricted muscle is weakened to improve ocular alignment in comitant or incomitant strabismus. A corollary to this is that a normally acting muscle, which is the antagonist of a paralyzed or paretic muscle, may be weakened to improve ocular alignment. In most cases, extraocular muscles are weakened by measured recession with attachment to sclera. Other techniques include adjustable recession, which is being used more frequently since the technique was reintroduced by Jampolsky et al.; socalled "hang-loose" recession; and marginal myotomy or tenotomy. Each of these procedures requires exposure of the muscle through a conjunctival incision followed by some type of surgical manipulation on the muscle itself. The relative success of these weakening procedures is evidenced by the fact that these techniques have been carried out for the past 200 years with only minor modifications in principle.

Recently, Alan B. Scott, M. D. proposed a new, revolutionary technique for weakening an extraocular muscle.1 This technique employs the use of attenuated botulinum A toxin. The toxin which is diluted to a dose in a range of billionths of grams is injected in the area of the motor end plate of the extraocular muscle to be weakened. For extraocular muscle weakening, this injection is guided by means of electromyography monitoring. Other facial muscles, especially the orbicularis oculi, can be injected with or without such monitoring.

Dr. Scott's work with botulinum is a natural, but highly innovative, extension of previous work by other authors which employed injections of local anesthestics and even alcohol to weaken an extraocular muscle. In these earlier techniques, the results were either effective for too short a time, or, as with alcohol, were permanent and therefore unsatisfactory. Botulinum A toxin was selected with the expectation that this agent would effectively weaken an extraocular muscle, and that the weakening would have long-term and beneficial therapeutic effects. This effect could occur as a result of cumulative weakening of the agonist or by allowing the antagonist to regain strength while opposed by a temporarily weakened antagonist.

At the outset, Dr. Scott had some difficulty convincing others that this technique could be safe and effective. After having the toxin prepared, with persistence he later obtained approval for clinical investigation under the auspices of the FDA. With this governmental permission granted, Dr. Scott proceeded along a carefully planned and well-executed course. He personally trained more than 40 investigators in the use of botulinum A toxin. He currently provides the toxin at a minimal cost, and he supplies modified needles and electromyography devices at a very reasonable price.

At the time of introduction of Oculinum (botulinum A toxin), several newspaper accounts of the use of botulinum A toxin implied that this was a special treatment that would virtually eliminate the need for strabismus surgery. These accounts also implied that onjy "special" doctors were qualified to use this technique, Dr. Scott has never taken this position, and has attempted to keep indications for oculinum use in the proper perspective.

We have used Oculinum on a regular basis since January 1983. We have given more than 120 injections on 100 patients. The results range from excellent to nil. Even though some patients have had unsatisfactory results, our enthusiasm for this treatment remains high. Oculinum is in a period of clinical trial, and, at the same time, the person injecting the toxin is in a period of clinical trial. Like other ophthalmologists who are using Oculinum, we are learning.

Part of the reason for the wide variation in results may be on…

A time-honored and well-tested practice in the treatment of strabismus is that a so-called overacting, tight, or restricted muscle is weakened to improve ocular alignment in comitant or incomitant strabismus. A corollary to this is that a normally acting muscle, which is the antagonist of a paralyzed or paretic muscle, may be weakened to improve ocular alignment. In most cases, extraocular muscles are weakened by measured recession with attachment to sclera. Other techniques include adjustable recession, which is being used more frequently since the technique was reintroduced by Jampolsky et al.; socalled "hang-loose" recession; and marginal myotomy or tenotomy. Each of these procedures requires exposure of the muscle through a conjunctival incision followed by some type of surgical manipulation on the muscle itself. The relative success of these weakening procedures is evidenced by the fact that these techniques have been carried out for the past 200 years with only minor modifications in principle.

Recently, Alan B. Scott, M. D. proposed a new, revolutionary technique for weakening an extraocular muscle.1 This technique employs the use of attenuated botulinum A toxin. The toxin which is diluted to a dose in a range of billionths of grams is injected in the area of the motor end plate of the extraocular muscle to be weakened. For extraocular muscle weakening, this injection is guided by means of electromyography monitoring. Other facial muscles, especially the orbicularis oculi, can be injected with or without such monitoring.

Dr. Scott's work with botulinum is a natural, but highly innovative, extension of previous work by other authors which employed injections of local anesthestics and even alcohol to weaken an extraocular muscle. In these earlier techniques, the results were either effective for too short a time, or, as with alcohol, were permanent and therefore unsatisfactory. Botulinum A toxin was selected with the expectation that this agent would effectively weaken an extraocular muscle, and that the weakening would have long-term and beneficial therapeutic effects. This effect could occur as a result of cumulative weakening of the agonist or by allowing the antagonist to regain strength while opposed by a temporarily weakened antagonist.

At the outset, Dr. Scott had some difficulty convincing others that this technique could be safe and effective. After having the toxin prepared, with persistence he later obtained approval for clinical investigation under the auspices of the FDA. With this governmental permission granted, Dr. Scott proceeded along a carefully planned and well-executed course. He personally trained more than 40 investigators in the use of botulinum A toxin. He currently provides the toxin at a minimal cost, and he supplies modified needles and electromyography devices at a very reasonable price.

At the time of introduction of Oculinum (botulinum A toxin), several newspaper accounts of the use of botulinum A toxin implied that this was a special treatment that would virtually eliminate the need for strabismus surgery. These accounts also implied that onjy "special" doctors were qualified to use this technique, Dr. Scott has never taken this position, and has attempted to keep indications for oculinum use in the proper perspective.

We have used Oculinum on a regular basis since January 1983. We have given more than 120 injections on 100 patients. The results range from excellent to nil. Even though some patients have had unsatisfactory results, our enthusiasm for this treatment remains high. Oculinum is in a period of clinical trial, and, at the same time, the person injecting the toxin is in a period of clinical trial. Like other ophthalmologists who are using Oculinum, we are learning.

Part of the reason for the wide variation in results may be on the basis of patient selection. In our clinic, we have chosen strabismus patients for injection who may represent a poor risk for a good result even after the most carefully planned and expertly conducted surgery. Our criteria for selection of strabismus patients for Oculinum injection is as follows:

1. Sub acute and chronic thyroid ophthalmopathy with or without prior surgery when Ocutinum injection rather than surgery is selected by the patient or by us. A patient with restriction who is in a more acute phase of the disease with vascular congestion may be a better candidate for Oculinum because of the higher risks of surgical complications.

2. Persistent strabismus after one or more extraocular muscle surgical procedures in a patient who does not wish to have further surgery but prefers Oculiimm injection. This includes patients with either free or restricted passive ductions.

3. An intermittent deviation causing significant symptoms in a patient who rejects surgery.

4. Patients with "essential" blepharospasm or other types of periocular or facial muscle myokymia or spasm.

5. Acute and chronic muscle palsy.

It is obvious that patients who have the greatest likelihood of obtaining successful results from surgery, except for blepharospasm, are excluded from our series. The reason we adhere to these criteria now is that we feel strabismus surgery offers a better opportunity for successful treatment than does Oculinum injection in selected patients at this time. Perhaps in the future our criteria may change. An example of why we follow our conservative program of patient selection is presented by the patient with congenital esotropia. Using our usual surgical procedure for congenital esotropia, augmented or enbloc bimedial rectus recession, an infant may be treated as an outpatient, requiring a general anesthetic lasting no more than 30 to 40 minutes. Cosmetically straight eyes are produced in more than 80% of infants with one procedure, and only 10% require early reoperation.2 This compares with Oculinum injection, which may require ketamine anesthesia in this age group administered by an anesthesiologist in a hospital setting and which may require two, three, or four return visits for injection. However, some investigators have injected infants in an outpatient setting with topical anesthetic alone. Since traditional surgery offers cosmetically straight eyes after one procedure in most cases of congenital-infantile esotropia treated by us, we feel that surgery is the best treatment choice for this type of case at this time.

The only strabismus patients who we are injecting routinely with Oculinum as a primary procedure are those with an acute palsy of one or more extraocular muscles. The "sound" antagonist is injected in an effort to eliminate or reduce the likelihood of contraction of this muscle. In long-standing cases of extraocular muscle palsy where recovery has not occurred after four to six months, and who have not had prior treatment, ductions are usually restricted by contracture of the sound antagonist. In this type of case, we have carried out full tendon extraocular muscle transfer either at the time of injection of Oculinum into the sound antagonist or up to a week or ten days later. No controls have been applied to these cases. However, in comparison with past experience, we feel that this use of Oculinum is effective in eliminating the need for recession of the sound antagonist, thus eliminating the need for a Jensen type procedure and reducing the risk of anterior segment ischemia.

Several patients who had injection of the extraocular muscle for the reasons listed above have obtained excellent postoperative results, although most have required repeat injection. The follow-up of our cases is too brief to allow us to confidently state that the strabismus has been "cured" by Oculinum injection, but we suspect that in several cases it has.

Case Report

A 16-year-old boy sustained severe head trauma in an automobile accident one year prior to examination. At the initial examination by us, 15 prism diopters XT and 14 prism diopters left hypertropia were present in the primary position. Ductions were full and unrestricted in each eye. Prism and cover testing in the diagnostic position revealed only small variations in the deviation. The Bielschowsky head tilt teat was negative and no torsion was demonstrable. Fusion was obtained at the objective angle but this was fleeting and no fusional amplitudes couid be measured. The diagnosis was central disruption of fusion, skew deviation, or comitant strabismus after extraocular muscle palsy.

Two months after the initial visit, the patient underwent the following surgery: recession of the left superior rectus 4.0 mm, and recession of the left lateral rectus 6.0 mm. Four months after surgery only a "flick" of LHT remained, but the XT was 10 prism diopters and diplopia persisted.

Six months after surgery, measurements were the same and diplopia remained bothersome. Botulinum A toxin was injected into the right lateral rectus in a dose of 5 ? 10 micrograms. The XT reduced to 5 prism diopters, but diplopia persisted. Seven weeks later, approximately eight months after surgery, the left lateral rectus was injected with a similar dose of botulinum A toxin. Two months after the second injection, the patient has no strabismus measurable in the primary position and is now diplopia free 90% of the time.

The use of botulinum A toxin in this case may represent "fine tuning" of strabismus surgery in a difficult case.

Perhaps the best indication for the use of Oculinum is in cases of blepharospasm. Benign essential blepharospasm is a condition that was seen in our clinic only rarely, prior to January 1983. However, since Oculinum became available we have seen more than 50 patients afflicted with this condition. Use of Oculinum injected into the upper and lower pre-tarsal orbicularis oculi muscles of both eyes provides prompt and dramatic relief for most patients, This treatment appears to be superior to the surgical procedures which have been offered heretofore. Although most blepharospasm patients require more than one injection of Oculinum, the early indications are that the treatment will be extremely successful. Several patients have experienced minimal corneal drying and lagophthalmos after orbicularis injection. The condition seems to be transient, not disabling, and amenable to typical therapy.

In view of our clinical experience, it is difficult to be controversial in discussing use of Oculinum. The concept of injecting a "weakening" agent into what is customarily referred to as an overacting extraocular muscle (absolute or relative overaction) is a good one. The course of investigation that Dr. Scott has followed is scientifically accurate, clinically logical, and ethically impeccable. Clinical trials are being supervised carefully. Attempts by some at inappropriate publicity are being dealt with properly. The role which Oculinum will ultimately play in the therapeutic armamentarium of the strabismus surgeon is not known at this time. It has been estimated by Dr. Scott that Oculinum may be effective in treating about 15% of strabismus (Personal communication with Dr. Scott, November 1983). Only time will tell us how accurate this estimate is, and how well Oculinum treatment can serve the strabismic patient.

References

1. Scott AB: Botulinum toxin injection of eye muscles to correct strabismus. Tr Am Ophthalmol Soc 1981 ; 79:735-770.

2. Helveston EM, Ellia FD, Schott J, et al: Surgical treatment of congenital esotropia. Am J Ophthalmol 1983; 96:218-228.

10.3928/0191-3913-19840901-11

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