Treatment of Acquired Nystagmus With Botulinum A Toxin Eugene M. H e l v e s t o n , M . D . , and Alexander E. Pogrebniak, M . D . We injected botulinum A toxin into the retrobulbar space of one eye each in two patients who had acquired nystagmus with oscillopsia and decreased vision. After injection of 25 units of botulinum A toxin, visual acuity improved from 20/80 to 20/30 in one patient, and both patients were able to read and watch television. Improved vision lasted from five to 13 weeks. No adverse side effects were observed after a total of five injections in each patient. BOTULINUM A TOXIN is injected directly into the extraocular muscles for treatment of se­ lected types of strabismus. 1,2 It is also injected into the orbicularis muscle and facial muscles for treatment of blepharospasm and Meige's disease. 3 Both of these uses for botulinum A toxin offer an alternative to orthoptic, prismat­ ic, surgical, or medical treatments. We injected botulinum A toxin into the retrobulbar space for the treatment of vertical, horizontal, and rotary pendular nystagmus after brainstem stroke producing oscillopsia, a rare but dis­ abling condition that has no other apparent alternative treatment. Case Reports Case 1 A 53-year-old woman had bilateral vertical, horizontal, and rotary pendular nystagmus, which produced oscillopsia with decreased vi­ sion. She had had a brainstem infarction 18 months previously that had produced lower extremity weakness, restricting her to a wheel­ chair. Best-corrected visual acuity was R.E.: Accepted for publication July 5, 1988. From the Section of Pediatrie Ophthalmology, Depart­ ment of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana. Reprint requests to Eugene M. Helveston, M.D., 702 Rotary Circle, Indianapolis, IN 46223. 584 20/120 and L.E.: 20/160. The patient sought relief from the oscillopsia so that she could read and watch television. As an initial trial, 3 units of botulinum A toxin were injected at the myoneural junction of the four recti muscles of the left eye under electromyographic control. The patient reported no subjective improvement in vision. One month later, she received a retro­ bulbar injection of 25 units of botulinum A toxin delivered through a 25-gauge, 38.1-mm needle inserted through the temporal aspect of the lower eyelid just inside the orbital rim and directed into the intraconal retrobulbar space. The patient reported by telephone that she had marked improvement in vision starting be­ tween three and four days posttreatment. She noted that she was able to read and watch television. The nystagmus gradually returned between three and six weeks after the injection. During this time, the patient noted decreasing vision. On examination two months later, the severity of her nystagmus had returned to its preinjection level. Retrobulbar injection of 25 units of botulinum A toxin was repeated on this occasion and at two additional visits, for a total of four treatments. After each treatment, the patient reported significant improvement in her vision. Visual acuity was not confirmed by examination because of travel difficulties for the patient. For additional treatment, the patient was referred to an ophthalmologist nearer her home. She subsequently received three addi­ tional injections of 25 units of botulinum A toxin in the retrobulbar space of the right eye. Preinjection visual acuity was 20/200 in both eyes. Postinjection visual acuity was R.E.: 20/60 and L.E.: 20/200; R.E.: 20/70 and L.E.: 20/200; and R.E.: 20/60 and L.E.: 20/200, respectively. Case 2 A 55-year-old woman had bilateral horizon­ tal, vertical, and rotary nystagmus producing oscillopsia. She also had left sixth and seventh nerve palsy and corneal scarring of the left eye ©AMERICAN JOURNAL OF OPHTHALMOLOGY 106:584-586, NOVEMBER, 1988 Vol. 106, No. 5 Botulinum A Toxin and Nystagmus secondary to eyelid lag and decreased blinking, with resulting poor vision of the left eye. She had had a left brainstem infarction three years earlier (Figure). Best-corrected visual acuity was R.E.: 20/80 and L.E.: 20/800. The patient was unable to read or watch television because of the oscillopsia. After obtaining informed consent, 25 units of botulinum A toxin were injected into the retrobulbar space of the right orbit. Within four days, a marked subjective improvement was noted by the patient. Using her +5.00diopter reading add spectacles, she was able to read the newspaper for the first time since the development of her nystagmus. Best-corrected visual acuity was R.E.: 20/40 one week after the injection; no change was noted in the left eye. The nystagmus of the right eye was minimal. She has since received three repeat injections, given five, 18, and 33 weeks after the initial injection. Three weeks after the third injection, visual acuity was R.E.: 20/30. No nystagmus was observed in the primary position, al­ though it did develop on attempted version movements. Ductions of the right eye were moderately reduced. A minimum right upper eyelid blepharoptosis was noted during the first week after injection. The eyelid returned to normal in two weeks. Videotapes obtained before and after treatment confirmed dampen­ ing of the nystagmus. The periodicity of the nystagmus was approximately 2 Hz and re­ mained unchanged after treatment. However, the nystagmus amplitude of approximately 20 to 25 degrees before treatment variably de­ creased to 6 to 10 degrees after treatment, with a corresponding decrease in duction move- Figure (Helveston and Pogrebniak). Case 2. Note left facial palsy and corneal leukoma in the left eye which has had a tarsorrhaphy. ments. Electro-oculography formed. 585 was not per­ Discussion Both of our patients had intractable oscillopsia of sufficient duration to suggest that the condition would not resolve spontaneously. Treatment options for such patients in the past have been limited. Optical dampening of the oscillopsia with spectacles and contact lenses has been suggested. 4 Surgical treatment of nys­ tagmus has been mainly limited to congenital nystagmus, not acquired nystagmus. 5 For con­ genital null-point nystagmus, a KestenbaumAnderson operation may be used to relieve head turn, and the esotropia of nystagmus compensation syndrome may be treated with bilateral medial rectus muscle recession or fadenoperation. We previously treated sympto­ matic horizontal nystagmus with oscillopsia by recessing all four horizontal recti muscles be­ yond the limits of usual recession with some success. This limited success was probably be­ cause the fundamental contractability of the muscles causing the nystagmus was not changed, and perhaps because the recessions were not large enough. Because of the vertical, horizontal, and rotary components of the nys­ tagmus in these patients, it seemed necessary to dampen the effect of all of the recti muscles. We did not see a good effect from injection of botulinum A toxin directly into all four recti muscles, as reported by Crone, de Jong, and Notermans. 6 We believe that the patients de­ scribed here received a beneficial effect from retrobulbar botulinum A toxin because it pro­ duced paresis of all of the extraocular muscles, which in turn produced reduced ocular move­ ment and subjective improvement in the oscil­ lopsia. Both of our patients were offered repeat in­ jections with the expectation of achieving im­ provement similar to the previous injection. In the first case, the subjective improvement in vision had been substantial enough in the pa­ tient's mind to warrant repeat injection. It is unlikely that the beneficial subjective response was solely a placebo effect. In the second pa­ tient we observed objective improvement in the nystagmus and recorded improvement in visu­ al acuity. The primary reason for resorting to the un­ conventional use of botulinum A toxin was that 586 November, 1988 AMERICAN JOURNAL OF OPHTHALMOLOGY it allowed these patients who were unable to read or watch television before treatment to resume these activities in three to four days after treatment. In each case, because of gener­ al physical disability, sedentary activities were the principal avenues of diversion and enjoy­ ment available. The dose of 25 units was se­ lected because it has been administered repeat­ edly to patients with benign essential blepharospasm without adverse effect. No complications occurred after any of the nine retrobulbar injections given to our two patients. Significant blepharoptosis was not produced, perhaps because the intraconal in­ jection is more likely to spare the levator mus­ cle than the intramuscular (extraconal) injec­ tion near the superior rectus muscle or upper eyelid. In contrast to retrobulbar anesthesia, which causes a transient blepharoptosis, botulinum toxin acts on the motor endplates and not on the nerve axons. Intravascular injec­ tions of botulinum toxin should not pose a systemic risk, as the dosage is well below the amount necessary to cause systemic toxicity and the molecule is too large to pass through the blood-brain barrier. 5 The low toxicity of botulinum A toxin has been demonstrated by unchanged electroretinographic and visualevoked potential responses after intravitreal injection in the rabbit. 7,8 A major disadvantage of retrobulbar botu­ linum toxin injection is the necessity for repeat injections. The visual improvement in our two patients lasted from four to 20 weeks before vision returned to near preinjection levels. The risk of retrobulbar hemorrhage with each injec­ tion must also be weighed against the thera­ peutic effects perceived by the patients. We believe that retrobulbar injection of botulinum A toxin did not differ significantly from injec­ tion at the myoneural junction; therefore, no additional permission for use of the drug was sought. Despite these drawbacks, retrobulbar botulinum A toxin injection represents a useful therapeutic approach to an acquired nystagmus that produces disabling reduction in vision. This type of treatment to one eye may be considered in a patient who demonstrates re­ duced vision from nystagmus, with vision im­ proved by stabilizing one eye; understanding of the informed consent; no contraindication to receiving retrobulbar injection; and a health risk ruling out surgical intervention. ACKNOWLEDGMENT David Mittelman, M.D., provided additional information about Patient 1. References 1. Scott, A. B.: Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology 87:1044, 1980. 2. Scott, A.: Botulinum toxin. Injection of eye muscles to correct strabismus. Trans. Am. Ophthalmol. Soc. 79:735, 1981. 3. Freuh, B., and Musch D.: Treatment of facial spasm with botulinum toxin. Ophthalmology 93:917, 1986. 4. Rushton, D., and Rushton, R.: An optical meth­ od for approximate stabilization of vision of the real world. Proceedings of the Physiological Society. J. Physiol. 20-21, July 1984, p. 337. 5. Lee, J. P.: Surgical management of nystagmus. Eye 2:44, 1988. 6. Crone, R. A., de Jong, P. J., and Notermans, G.: Behandlung des nystagmus durch Injektion von Botulinustoxin in die augenmuskeln. Klin. Monatsbl. Augenheilkd. 184:216, 1984. 7. Wienkers, K., Helveston, E. M., Ellis, F. D., and Cadera, W.: Botulinum toxin injection into rab­ bit vitreous. Ophthalmic Surg. 15:310, 1984. 8. Hoffman, R. O., Archer, S. M., Zirkelbach, S. L., and Helveston, E. M : The effect of intravitreal botulinum toxin on rabbit visual evoked potential. Ophthalmic Surg. 18:118, 1987.