Keith W. McNeer

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.

Extraocular muscles light microscopy and ultrastructural features

SummaryThirty 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 μm 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 μm 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 EOMs, 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.

Incidence of stereopsis after treatment of infantile esotropia with botulinum toxin A.

PURPOSE: The incidence of stereoscopic vision following surgery for infantile esotropia has been reported, but not from patients treated with simultaneous bimedial injection of botulinum toxin A. We previously reported other findings from 41 patients treated with botulinum toxin A before the age of 12 months. The purpose of this study was to report the incidence of stereopsis in these patients after long-term follow-up. PATIENTS AND METHODS: Data were acquired by recording the response to subjective stereoscopic testing during the postinjection follow-up period when reliable subjective responses could be obtained. At least 5 years had passed following injection, and the mean age of the patients was 8 years. RESULTS: Of the 41 patients, 11 were lost to follow-up, 10 had no stereopsis, 9 had gross stereopsis (according to Titmus fly tests), 1 had 800 seconds of stereoscopic vision, 2 had 400 seconds, 2 had 200 seconds, 1 had 60 seconds, and 5 had 40 seconds. CONCLUSIONS: In this study, two-thirds of the patients acquired stereopsis following simultaneous bimedial injection of botulinum toxin A for infantile esotropia. Stereopsis acquisition following injection of botulinum toxin A had a success rate comparable with that reported for surgically corrected infantile esotropia. Bimedial injection of botulinum toxin A accompanied by alternate patching prior to injection and diligent attention at ages ranging from 4 to 12 months is a simple and efficacious method for the management of infantile esotropia.

Extraocular muscles: Morphogenetic study in humans light microscopy and ultrastructural features

SummaryThe development of human extraocular muscles (EOM) was studied in a series of fetal specimens (12–24 weeks gestation). EOM were evaluated by enzyme histochemistry (EZ) (NADH and ATPase), by differential phase contrast microscopy (DPC) and electron microscopy (EM). In the early fetus (14 weeks), there was no clear-cut sub-division into fibre types. A uniform histochemical reaction was seen with NADH while ATPase showed light and dark myotubes. Myotubes contained large central nuclei, prominent eccentric nucleoli, abundant glycogen granules, free ribosomes, numerous mitochondria, and dense and looser bundles of myofilaments. Mesenchymal cells undergoing mitosis and fibroblasts with prominent stacks of rough endoplasmic reticulum were scattered within endomysium. Mast cells with well formed cytoplasmic granules were found as early as 18–24 weeks. The same specimens by DPC showed differentiation into at least 4 different fibre types at 12 weeks. All the intramuscular nerves at 12–16 weeks were composed of unmyelinated fibres. At 18 weeks, myelinated axons were present. Morphologically immature end-plates devoid of junctional folds were found at 12 weeks. The motor innervation of some EOM appears to be derived from more than one axon (multiple innervated fibres). At 18 weeks gestational age, differentiation into fibre types became apparent by enzyme histochemistry. These histochemical and morphological findings suggest that morphologically mature endplates are not prerequisites for differentiation into muscle fibre types.

Morphology of the Extraocular Muscles in Relation to the Clinical Manifestation of Strabismus

Strabismus is a congenital or acquired disorder of ocular motility that is characterized by misalignment of the eyes either in the primary position and/or during conjugate movements in specific directions. The etiology of acquired non-commitant or commitant forms of strabismus can be traced in some instances to a central lesion affecting either the motor nerve or areas of the brainstem involving the extraocular motor nuclei or the premotor structures and pathways related to oculomotor control (see papers by Lennerstrand and Harcourt in this volume). Congenital forms of strabismus, on the other hand, might be attributable to developmental abnormalities that affect the extraocular muscles, their motor innervation, or the central connections of the oculomotor system (see paper by Baker in this volume).

The Histopathology of Botulinum Toxin Injection into Extraocular Muscles

Extraocular muscle (EOM) structure and microanatomy has been rarely reviewed in clinical manuscripts and thus is vaguely understood by many clinicians. For example, the ordinary conception held my many is the now archaic identification of ‘Felderstuktur’ and ‘Fibrillenstruktur’, based on the obsolete concept of each representing slow and fast fiber function in EOM. Although these early obervations contributed much to our understanding of EOM originally, more recent investigations have demonstrated the structure and function of EOM to be considerably more complex and not so neatly correlated (Spencer and Porter, 1988). Earlier descriptions of EOM gross anatomy were generally correct as far as length and appearance but omitted reference to changes occuring with different lengths and positions that are normal to eye movement. It required the electrophysiologists to emphasize that contour alteration as well as length and position change were necessary for EOM to function effectively as elastic force generators (Collins, 1971, Robinson, 1975). Advances in histological techniques permitted further definition of EOM (Martinez et al, 1976, McNeer, 1982, Spencer and Porter, 1988), forever changing traditional interpretations.