Botulinum toxin management of childhood intermittent exotropia.

OBJECTIVE: Intermittent exotropia is a common form of childhood strabismus that has a late onset and presents a difficult and frustrating management dilemma. Surgical treatments have a high recurrence rate, and multiple surgeries often are required to achieve a desirable motor outcome. This study presents long-term observations on the use of botulinum toxin for the treatment of intermittent exotropia in children. DESIGN: This study is a nonrandomized, case-controlled study of consecutive pediatric patients who had intermittent exotropia. PARTICIPANTS: Thirty-two neurologically normal children ranging from 3 to 144 months in age were diagnosed with intermittent exotropia with a minimum distance deviation of 15 prism diopters (PD). INTERVENTION: Simultaneous bilateral injections of 2.5 units botulinum toxin type A were made into the lateral rectus muscles with the patient receiving nitrous oxide-ethrane inhalation anesthesia. Patients were observed for 12 to 44 months after the initial injection. MAIN OUTCOME MEASURES: A satisfactory outcome was considered to be stable binocular alignment of the eyes to an orthophoric range of +/-10 PD. RESULTS: Bilateral lateral rectus muscle injections of botulinum toxin were effective in reducing the mean preinjection deviation of -29 PD to an average exotropic angle of -6 PD. Stable orthophoria (+/-10 PD) was achieved in 22 patients (69%). Overall, male patients required significantly fewer injections than did female patients. All patients between 24 and 56 months of age, irrespective of gender, required only a single bilateral injection to achieve a favorable motor outcome. CONCLUSIONS: Botulinum toxin is at least as effective as surgical outcomes reported previously for the treatment of intermittent exotropia in children. This treatment method is particularly effective in children between 2 and 4.5 years of age irrespective of the initial strabismic angle and is not associated with any secondary abnormalities.

Botulinum toxin management of essential infantile esotropia in children.

BACKGROUND: Infantile esotropia has an onset during early infancy when visual cortical connections are established for binocular fusion and stereopsis. The goal of early treatment is to achieve normal binocular alignment and a favorable sensory outcome. OBJECTIVE: To determine the long-term effects of the use of botulinum toxin for the management of infantile esotropia in children. PATIENTS: Seventy-six neurologically normal children ranging from 4 to 48 months of age were entered consecutively into the study after being given the initial diagnosis of infantile esotropia with a mean strabismic angle of 33 prism diopters. INTERVENTIONS: Simultaneous bilateral injections of 2.5 U of botulinum toxin type A were made into the medial rectus muscles under nitrous oxide and ethrane anesthesia. Patients were followed up for 12 to 95 months after the last injection. Forty patients required 1 bilateral injection and 36 patients required multiple bilateral injections to achieve a favorable motor outcome. RESULTS: Bilateral medial rectus muscle injections of botulinum toxin were effective in reducing the mean preinjection deviation of 33 PD to an average esotropic angle of 2 PD. Binocular alignment (+/- 10 PD) was achieved in 68 patients (89%). Boys required significantly fewer injections than did girls. The secondary incidence of overacting inferior oblique muscles was significantly greater in boys, while girls had a significantly greater incidence of late-onset refractive errors. CONCLUSION: Botulinum toxin is an effective treatment modality for the management of infantile esotropia in infants and children, producing binocular alignment of the visual axes.

Observations on bilateral simultaneous botulinum toxin injection in infantile esotropia.

Botulinum toxin (BoTX) is an effective pharmacological alternative to the surgical management of strabismus in adults. In a previous study, we found that concurrent bilateral medial rectus muscle BoTX injections for infantile esotropia could produce stable ocular realignment without significant risk. No other investigators have used bilateral simultaneous BoTX injection. We report the results of bilateral simultaneous medial rectus BoTX injection in 57 infantile esotropia patients followed for a minimum of 12 months. The esotropic angle in 27 infantile esotropia patients under 12 months of age was reduced from 43 +/- 12 to 1 +/- 2 prism diopters. The esotropic angle in 30 infantile esotropia patients at a mean age of 24 months was reduced from 31 +/- 12 to 2 +/- 3 delta. Other variables including late onset of hyperopic refractive errors, dissociated vertical deviations, overacting oblique muscles, and consecutive exodeviations are evaluated. We regard BoTX as reliable therapy in infantile esotropia.

Botulinum treatment of childhood strabismus.

Four hundred thirteen children ranging in age from 2 months to 12 years were treated for strabismus by botulinum injection of extraocular muscles. An average of 1.7 injections per patient was given. Follow-up at an average of 26 months after the last injection (minimum, 6 months) was available on 362 children (88%). The frequency of correction of 10 prism diopters (PD) or less in various groups of strabismus cases was: all 362 cases, 61%; all esotropia, 66%; infantile esotropia, 65%; and exotropia, 45%. Smaller deviations (10-20 PD) were more frequently corrected (73%) than were larger deviations (20-110 PD, 54%). The frequency of correction to 10 PD or less of previously operated cases was not different from that of unoperated cases. There was no globe perforation, amblyopia, or visual loss produced by the injection treatment in this series.

An investigation of the clinical use of botulinum toxin A as a postoperative adjustment procedure in the therapy of strabismus.

Attempts to circumvent multiple surgical procedures are an integral part of the history of investigations in strabismus. In 1973, Botulinum toxin A (Oculinum) injections into human EOM was proposed as an alternate method to surgery for strabismus and has since proved to be effective. This article reports the results from a retrospective investigation of EOM Oculinum injection used in the postoperative period as an alternate to additional surgery. It is difficult to establish whether Oculinum altered the time span of the clinical course in these patients, but when it was effective, it provided unprecedented convenience.

Botulinum toxin injection into the superior rectus muscle of the non-dominant eye for dissociated vertical deviation.

A variety of surgical procedures on the superior rectus muscles have been proposed as a remedy for Dissociated Vertical Deviation (DVD); Botulinum toxin (Oculinum) has been one such suggestion as a surgical alternative. We selected five older patients with DVD whose age placed them beyond a risk of amblyopia to evaluate Oculinum injection into the superior rectus muscle as therapy for DVD. The patients achieved a reduction from the mean value of 20 prism diopters to the mean value of less than 5 pd hypertropia at 172 weeks following injection. Our study suggests that Oculinum is effective in treating DVD, but caution should be exercised because transient ptosis invariably accompanies injection.

Botulinum toxin paralysis of adult monkey extraocular muscle. Structural alterations in orbital, singly innervated muscle fibers.

Botulinum toxin was injected into the medial rectus muscles of adult rhesus monkeys, with postinjection survival periods of three to 56 days. Light and electron microscopic changes were most apparent in the orbital, singly innervated muscle fibers, which during the acute stage (seven to 28 days), exhibited denervationlike hypertrophy with dispersion of the central mitochondria toward the periphery of the fibers. Withdrawal of the capillary network on which this fiber type normally is dependent for oxidative function was a secondary adaptive response to the disuse resulting from botulinum toxin paralysis of neuromuscular transmission. Neuromuscular junctions still were present on all muscle fiber types, although evidence of sprouting was apparent. In the long term (following return of function at 42 to 56 days), the muscle fibers appeared normal and the vasculature recovered in proportion to the decreased cross-sectional area of the muscle fibers.

Myectomy of the inferior oblique muscle.

The current surgical procedures usually selected to weaken clinically overactive inferior oblique muscles are recession, disinsertion, or myectomy. A review of published reports revealed that each technique appeared to produce the intended result but that investigators differed in their choices for reasons of simplicity, quickness, and complications. Our experience indicated distal myectomy to be simple, quick, predictable, and devoid of significant complications. To affirm our impressions, 130 myectomies performed in 81 patients were reviewed. The procedure was satisfactory, although 5% had a postoperative residual overaction, and 3% had a residual underaction. No significant complications, such as the "adherence syndrome," were observed.

Adjustable sutures of the vertical recti.

Fifty patients were operated for vertical strabismus problems using the adjustable suture technique. Eighty-two vertical recti muscles were either adjustably recessed or resected. the surgical decisions and muscle placement placed emphasis on the cover test plus evaluation of muscle stiffness rather than the traditional prism diopter-millimeter correlations. It was necessary to adjust 26% of the muscles postoperatively.

Astigmatism in visually immature child with strabismus.

Astigmatic refractive errors may develop late in the visual maturity period of strabismic children. Seventeen strabismic children who had surgery and ten strabismic children who did not have surgery are discussed; none had astigmatic error at the initial refraction. Significant astigmatism developed in both groups at age 4 years and two years after the initial refraction. The ophthalmologist should be aware that late-developing astigmatism can cause a recurrence or deterioration of strabismus. The best response is serial refractions and appropriate correction of all strabismus patients during the visual maturity period.

Structural alterations in overacting inferior oblique muscles.

Primary and secondary overacting inferior oblique muscles were examined by light and electron microscopy and compared to normal inferior oblique muscles. The most conspicuous light microscopic difference between primary overacting and normal muscles was the presence of granular fibers in overacting muscles that contained sarcoplasmic masses. Some primary and secondary overacting muscles also contained fibers displaying increased vacuolization and atrophy. Other secondary overacting muscles showed only numerous fibers at various stages of atrophy. The affected fibers were distributed throughout the central and global regions of the posterior portion of the muscle. Electron microscopic examination showed aggregations of mitochondria and degenerating mitochondrial profiles. Longitudinal fiber splitting and activated satellite cells were associated with fibers displaying increased vacuolization. The results suggest that the primary overacting inferior oblique muscle is the result of a bilateral paresis of the superior oblique muscle.

Extraocular muscles: light microscopy and ultrastructural features.

Thirty extraocular muscles (EOM) from 20 patients were evaluated by light microscopy (LM), electron microscopy (EM), and enzyme histochemistry (EZH). Twenty-one EOM were obtained from 13 patients with strabismus, 9 EOM from 4 patients undergoing eye surgery for other reasons and from 3 autopsy cases. One mum thick sections revealed marked variation in muscle fibre shape and size and in myofibrillar structure; also noted were small, hypertrophied, whorled, and ringbinden fibres. Dense and granular material in the central portion of some fibres and sarcomere disruption in 2--3 mum sections was observed. EZH revealed the absence of the classical mosaic pattern usually found in skeletal muscles. ATPase studies were inconsistent and did not correlate with the expected reciprocal activity of NAD-H diaphorase, particularly on the large fibres. Ultrastructural features consisted of vacuoles within myofilament bundles, "smearing" of Z bands, and "nemaline rods". Occasional myelin figures and lipid-like droplets were observed in subsarcolemmal spaces, associated with scattered clusters of glycogen granules. Abnormal mitochondria and subsarcolemmal inclusions of dense and granular material were conspicuous. "Leptomeric" profiles, "Zebra bodies", or "striated bodies" were noted in 8 EOM's, and an Hirano body was found in 1. The intramuscular nerves contained structures resembling "Luse bodies" in 7 cases. These observations suggest that EOM from individuals with and without strabismus possess unique structural characteristics suggestive of developmental and morphological disarrangement of contractile elements. Some of these changes might play a role in the pathogenesis of strabismus and in the development of clinical symptoms. These features are significantly different from striated skeletal muscle. Therefore the criteria used in the pathological evaluation and diagnosis of skeletal muscle disorders cannot be unequivocally applied to EOM investigations. These data establish the necessity to determine histological norms, ultrastructural patterns, and develop new enzyme histochemistry criteria for the evaluation of EOM. Only then can an acceptable comparison of EOM and skeletal muscle be made.