Lawrence Tychsen

Nasotemporal asymmetries in V1: Ocular dominance columns of infant, adult, and strabismic macaque monkeys

To quantify asymmetries of input from the two eyes into each cerebral hemisphere, we measured ocular dominance column (ODC) widths and areas in the striate visual cortex (area V1) of macaque monkeys. Ocular dominance stripes in layer 4C were labeled by using transneuronal transport of intraocularly injected wheat germ agglutinin‐horseradish peroxidase (WGA‐HRP) or cytochrome oxidase (CO) histochemistry, after deafferentation of one eye or even by leaving afferent input intact.

Frequency and Severity of Visual Sensory and Motor Deficits in Children with Cerebral Palsy: Gross Motor Function Classification Scale

PURPOSE Cerebral palsy (CP) is a permanent, nonprogressive disorder of movement and posture due to a lesion of the fetal or infant brain. The goal was to determine whether children with different severities of CP, as defined using the Gross Motor Function Classification System (GMFCS), had different degrees or types of visual dysfunction. METHODS An observational, cross-sectional-design study was conducted by using neurologic and masked ophthalmic measurements on a representative cohort of 50 children with CP. Mean age was 5.6 years (range, 2-19.5 years); mean gestational age was 31 weeks. RESULTS The likelihood of debilitating visual deficits was greater in children with higher GMFCS scores, independent of gestational age. Children with level 5 disease (most severe) were at greatest risk for high myopia, absence of binocular fusion, dyskinetic strabismus, severe gaze dysfunction, and optic neuropathy or cerebral visual impairment (CVI). These deficits were rare or absent in children with the mildest disease, level 1. When categorized by anatomic or physiologic CP subtype, diplegic and spastic children were more often hyperopic and esotropic, but had the highest prevalence of fusion and stereopsis. In contrast, children with quadriplegic and mixed CP (dyskinetic, athetoid, hypotonic, and ataxic) more often had high myopia, CVI, dyskinetic strabismus, and gaze dysfunction. CONCLUSIONS Visual deficits differ in children who have mild versus severe CP. Children with GMFCS level 1 to 2 have sensorimotor deficits resembling those of neurologically normal children with strabismus and amblyopia; children at level 3 to 5 have more severe deficits, not observed in neurologically normal children.

Neuroanatomic abnormalities of primary visual cortex in macaque monkeys with infantile esotropia: preliminary results.

To explore the structural basis for visuomotor deficits in infantile esotropia, we examined binocular connections and metabolic activity in the primary visual cortex of two strabismic macaque monkeys. The animals were documented to have onset of natural esotropia in early infancy. Behavioral testing showed that the animals had normal visual acuity in both eyes and the ocular motor deficits that characterize strabismus with onset in infancy. The neuronal tracer substance biotinylated-dextran-amine was injected into ocular dominance columns (ODC) in area V-1 (striate cortex), revealing a paucity of binocular connections between right-eye and left-eye ODCs. The metabolic label cytochrome-oxidase was used to stain neighboring right-eye and left-eye ODCs, revealing inequalities in metabolic activity compatible with interocular suppression. These results show that infantile esotropes have abnormalities of visual cortex structure that correlate with abnormalities in binocular behaviors.

Spectrum of Pediatric Dacryocystitis: Medical and Surgical Management of 54 Cases

BACKGROUND Dacryocystitis in infants and older children is a serious complication of congenital or acquired nasolacrimal duct obstruction. To define the modes of presentation and treatment strategies of this disorder better, we reviewed the clinical courses of 54 children treated for dacryocystitis at St Louis Childrens Hospital. METHODS Clinical, neuroradiologic, and laboratory data were collated for all cases of dacryocystitis treated from 1990 to 1995. Average follow up of the children in this consecutive series was 1.75 years (range, 4 months to 5 years). RESULTS Of the 54 patients, 36 (67%) had chronic low-grade dacryocystitis, which was treated with nasolacrimal duct probing on an outpatient basis. The remaining 18 patients (33%) had acute dacryocystitis, which was treated with a combined medical/surgical strategy. Medical treatment consisted of hospital admission for administration of intravenous antibiotics followed by inpatient surgery, which varied according to the age of the patient and the clinical history: 1) Acute dacryocystitis in neonates was treated surgically by nasolacrimal duct probing and nasal endoscopy for excision of intranasal duct cyst; 2) Acute dacryocystitis with periorbital cellulitis was treated surgically by nasolacrimal duct probing; 3) Acute dacryocystitis due to facial trauma was treated surgically by dacryocystorhinostomy and stent placement; and 4) Acute dacryocystitis complicated by orbital abscess was treated by inferior orbitotomy for orbital abscess drainage, simultaneous nasolacrimal duct probing, and stent placement. CONCLUSION Dacryocystitis in the pediatric population may present in either chronic or acute forms. An effective and safe treatment for acute dacryocystitis is hospital admission, both for administering intravenous antibiotics and monitoring to rule out orbital cellulitis or abscess formation. Intravenous antibiotic therapy is followed within a day or two by surgery tailored to the clinical history. In the majority of both chronic and acute cases, nasolacrimal duct probing appears to be an effective treatment strategy.

Early versus delayed repair of infantile strabismus in macaque monkeys: I. ocular motor effects

INTRODUCTION The appropriate age for surgical correction of esotropic strabismus in human infants is controversial; some clinicians advocate surgery before age 6 months, and others recommend observation and surgery at older ages. Infantile (congenital) esotropia in humans and monkeys is known to be accompanied by a constellation of eye movement abnormalities caused by maldevelopment of cerebral visual motor pathways. The purpose of this study was to determine how early versus delayed correction of strabismus influences development and/or maldevelopment of these eye movement pathways. METHODS Optical strabismus was created in infant macaques by fitting them with prism goggles on day 1 of life. The early correction group (2 experimental and 1 control) wore the goggles for a period of 3 weeks (the equivalent of 3 months before surgical repair in humans). The delayed correction group (3 experimental and 1 control) wore the goggles for a period of 3 or 6 months (the equivalent of 12 or 24 months before surgical repair in humans). Several months after the goggles were removed, the monkeys were trained to perform visual fixation, smooth pursuit, and optokinetic nystagmus (OKN) tasks for a juice reward. Eye movements were recorded using binocular search coils. The performance of the early versus delayed infant monkey groups was also compared with that of a group of adult monkeys who had unrepaired, naturally occurring infantile esotropia. RESULTS Early correction monkeys developed normal eye movements and exhibited ocular motor behaviors that were indistinguishable from normal control animals. They regained normal binocular eye alignment and showed stable fixation (no latent nystagmus). Monocular horizontal smooth pursuit and large field OKN were symmetric. In contrast, delayed correction monkeys showed persistent esotropia, latent fixation nystagmus, dissociated vertical deviation, and pursuit/OKN asymmetry. Animals who had the longest delay in correction of the optical strabismus exhibited eye movement abnormalities as severe as those of adult animals with uncorrected, natural esotropia. CONCLUSIONS Early correction of strabismus in primates prevents maldevelopment of eye movements driven by cerebral motor pathways. Our results provide additional evidence that early strabismus correction may be beneficial for brain development in human infants.

Intramuscular Innervation of Primate Extraocular Muscles: Unique Compartmentalization in Horizontal Recti

PURPOSE It has been proposed that the lateral rectus (LR), like many skeletal and craniofacial muscles, comprises multiple neuromuscular compartments subserving different physiological functions. To explore the anatomic potential of compartmentalization in all four rectus extraocular muscles (EOMs), evidence was sought of possible regional selectivity in intramuscular innervation of all rectus EOMs. METHODS Whole orbits of two humans and one macaque monkey were serially sectioned at 10 μm thickness and stained with Massons trichrome. Three-dimensional reconstruction was performed of the intramuscular courses of motor nerves from the deep orbit to the anterior extents of their arborizations within all four rectus EOMs in each orbit. RESULTS Findings concorded in monkey and human orbits. Externally to the global surface of the lateral (LR) and medial rectus (MR) EOMs, motor nerve trunks bifurcated into approximately equal-sized branches before entering the global layer and observing a segregation of subsequent arborization into superior zones that exhibited minimal overlap along the length of the LR and only modest overlap for MR. In contrast, intramuscular branches of the superior and the nasal portion of the inferior rectus were highly mixed. CONCLUSIONS Consistent segregation of intramuscular motor nerve arborization suggests functionally distinct superior and inferior zones within the horizontal rectus EOMs in both humans and monkeys. Reduced or absent compartmentalization in vertical rectus EOMs supports a potential functional role for differential innervation in horizontal rectus zones that could mediate previously unrecognized vertical oculorotary actions.

Paucity of Horizontal Connections for Binocular Vision in V1 of Naturally Strabismic Macaques: Cytochrome Oxidase Compartment Specificity

To describe the structural basis for lack of binocular fusion in strabismic primates, we investigated intrinsic horizontal connections within striate cortex (area V1) of normal and strabismic, adult macaque monkeys. The strabismic animals had early‐onset natural esotropia (the visual axes deviated nasally), normal visual acuity in each eye, and the constellation of ocular motor deficits that typify human infantile strabismus. Horizontal patchy connections and synaptic boutons were labeled by injections of the neuronal tracer biotinylated dextran amine. Ocular dominance columns (ODCs), and blob vs. interblob compartments, were revealed by using cytochrome oxidase (CO). In layers 2/3 and 4B of the strabismic monkeys, patchy projections and boutons terminated much more frequently in same‐eye (73%) as opposed to opposite‐eye (27%) ODCs (normal monkeys 58% and 42%, respectively). The deficiency of binocular connections in the strabismic cortex was evident qualitatively as a “skip” pattern, in which every other row of ODCs had labeled patches. Analysis of V1 in normal monkeys revealed that the deficits in strabismic V1 were due mainly to a loss of binocular connections between neurons in CO‐interblob compartments. In both normal and strabismic monkeys: (1) CO‐blob compartment neurons showed a more pronounced bias for monocular connectivity, and (2) commitment of connections to the same CO‐compartment as the injection site (blob‐to‐blob, or interblob‐to‐interblob) was moderately strong (64%) but far from absolute. These findings help elucidate the relative roles of visual experience vs. innate mechanisms in the development of axonal connections between ocular dominance domains and compartments within macaque V1. They also provide the first detailed description of the V1 maldevelopments associated with unrepaired natural, infantile‐onset strabismus in primates. J. Comp. Neurol. 474:261–275, 2004.

Compartmentalized Innervation of Primate Lateral Rectus Muscle

PURPOSE Skeletal and craniofacial muscles are frequently composed of multiple neuromuscular compartments that serve different physiological functions. Evidence of possible regional selectivity in LR intramuscular innervation was sought in a study of the anatomic potential of lateral rectus (LR) muscle compartmentalization. METHODS Whole orbits of two humans and five macaque monkeys were serially sectioned at 10-microm thickness and stained with Masson trichrome. The abducens nerve (CN6) was traced anteriorly from the deep orbit as it branched to enter the LR and arborized among extraocular muscle (EOM) fibers. Three-dimensional reconstruction was performed in human and monkey orbits. RESULTS Findings were in concordance in the monkey and human orbits. External to the LR global surface, CN6 bifurcated into approximately equal-sized trunks before entering the global layer. Subsequent arborization showed a systematic topography, entering a well-defined inferior zone 0.4 to 2.5 mm more posteriorly than branches entering the largely nonoverlapping superior zone. Zonal innervation remained segregated anteriorly and laterally within the LR. CONCLUSIONS Consistent segregation of intramuscular CN6 arborization in humans and monkeys suggests functionally distinct superior and inferior zones for the LR. Since the LR is shaped as a broad vertical strap, segregated control of the two zones could activate them separately, potentially mediating previously unappreciated but substantial torsional and vertical oculorotary LR actions.

Anomalous retinal correspondence: Neuroanatomic mechanism in strabismic monkeys and clinical findings in strabismic children

BACKGROUND Anomalous retinal correspondence (ARC) is a neural adaptation to eye misalignment in which non-corresponding retinal points are linked in the visual cortex to provide binocular fusion. ARC within the striate cortex would require that horizontal neurons link right-eye and left-eye ocular dominance columns (ODCs) separated by a distance in the cortex proportional to the angle of strabismus. Two hypothetical mechanisms are possible: (1) The ODCs can be linked by axons of horizontal neurons that project monosynaptically from a right-eye to a left-eye ODC. The further apart the ODCs, the longer the axons; hence, axon length should be greater in subjects with strabismus than in healthy subjects (elongated axon, monosynaptic hypothesis). In this case, the clinical probability of developing ARC should be independent of the angle of strabismus, until an upper-limit angle of strabismus is reached equally to the maximal length of axons available to link nonadjacent ODCs, at which point an abrupt decline of ARC probability should be evident. (2) Alternatively, ODCs can be linked by a chain of horizontal neurons, the number of which increases as the distance among ODCs increases; axon length in subjects with strabismus would be expected to be the same as in healthy subjects (normal axon, polysynaptic hypothesis). In this case, the greater the angle of strabismus, the more horizontal neurons and synapses required for linkage, and the greater the probability of signal degradation. Thus, the clinical probability of developing ARC through a polysynaptic mechanism should be inversely proportional to the angle of strabismus. The purpose of this study was to test these 2 hypotheses neuroanatomically in primates and clinically in children. METHODS For the neuroanatomic portion of the study, biotinylated dextran amine was injected into ODCs of area V1 to label individual neurons. The length of the horizontal axons from these neurons was then compared in strabismic and normal monkeys. In the clinical portion of the study, the medical records of 192 children with strabismus were reviewed retrospectively. The angle of strabismus (prism cover test) and the presence of ARC (Bagolini striated lenses, Worth/Polaroid 4-dot) were recorded. Plots of the presence of ARC as a function of the angle of strabismus were obtained. RESULTS There was no significant difference in axon length between healthy (7. 02 +/- 0. 83 mm) and strabismic monkeys (6. 60 +/- 1. 07 mm) (P =.16). In children with strabismus, ARC decreased as the angle of strabismus increased (P <. 05). ARC was more prevalent in children who had primary or postsurgical deviations of </=4 degrees to 5 degrees (8-10 PD), corresponding to </=2 horizontal axon lengths in the foveal striate visual cortex. CONCLUSIONS The visual cortex adapts to strabismus by combining information from paired ODCs of opposite ocularity that, because of the eye misalignment, are nonadjacent and separated by abnormally long distances across the striate cortex. The cortex appears to achieve the linkage, not by elongating neuronal axons, but by using chains of neurons that have normal-length axons. The visual cortex is most successful stochastically at achieving this linkage (ie, developing ARC) when the gap that must be bridged is no greater than 4 degrees to 5 degrees (8-10 PD), or the retinotopic distance in the foveal visual field is spanned by 2 normal V1 neurons.

Spectrum of infantile esotropia in primates: Behavior, brains, and orbits.

INTRODUCTION Recent studies of human infants have described a spectrum of early-onset esotropia, from small angle to large heterotropias. We report here a similar spectrum of early-onset esotropia in infant monkeys, with emphasis on the relationship between visuomotor deficits, central nervous system circuitry, and orbital anatomy. METHODS Eye movements were recorded in macaque monkeys with natural, infantile-onset esotropia (n = 7) and in control monkeys (n = 2) to assess alignment, latent nystagmus, dissociated vertical deviation (DVD), and pursuit/optokinetic nystagmus (OKN) asymmetries. Acuity was measured by preferential-looking technique or spatial sweep visual-evoked potentials. Geniculo-striate pathways were then analyzed with neuroanatomic tracers and ocular dominance column labels. Extraocular muscles were examined by high-resolution magnetic resonance imaging (MRI) and anatomic sectioning of whole orbits. RESULTS Esotropia ranged from 4 to 13.5 degrees (7-24(Delta)) with fixation preference (if any) varying idiosyncratically (as in human). Severity of ocular motor dysfunction (ie, nystagmus velocity, DVD amplitude, pursuit-OKN nasal bias index) increased as the magnitude of esotropia angle. Animals with greater ocular motor deficits tended to have greater visual area V1 (striate cortex) neuroanatomic deficits, evident as fewer binocular horizontal connections in V1. Orbital MRI/anatomic analysis showed no difference in horizontal rectus cross-sectional areas, muscle paths, innervation densities, or cytoarchitecture compared with normal animals. CONCLUSIONS The infantile esotropia spectrum in nonhuman primates is remarkably similar to that reported in human infants. Concomitant esotropia in these primates cannot be ascribed to abnormalities of the extraocular muscles or orbit. These findings, combined with epidemiologic studies of humans, suggest that perturbations of cerebral binocular pathways in early development are the primary cause of the infantile esotropia syndrome.