Publications by authors named "Lawrence Tychsen"

52 Publications

Decorrelation of cerebral visual inputs as the sufficient cause of infantile esotropia.

Am Orthopt J 2008 ;58:60-9

From the Departments of Ophthalmology and Visual Sciences.

Background And Purpose: Human infants at greatest risk for esotropia are those who suffer cerebral insults that could decorrelate signals from the two eyes during an early critical period of binocular, visuomotor development. The authors reared normal infant monkeys under conditions of binocular decorrelation to determine if this alone was sufficient to cause esotropia, and associated behavioral as well as neuroanatomic deficits.

Methods: Binocular decorrelation was imposed using prism-goggles for durations of 3-24 weeks (control monkeys wore plano goggles), emulating unrepaired strabismus of durations 3 months to 2 years in human infants. Behavioral recordings were obtained, followed by neuroanatomic analysis of ocular dominance columns and binocular, horizontal connections in the striate visual cortex (area V1).

Results: Concomitant, constant esotropia developed in each monkey exposed to decorrelation for a duration of 6-24 weeks. The severity of ocular motor signs (esotropia angle; dissociated vertical deviation; latent nystagmus; pursuit / optokinetic tracking asymmetry; fusional vergence deficits), and the loss of V1 binocular connections increased as a function of decorrelation duration. Stereopsis was deficient and motion visually evoked potentials were asymmetric. Monkeys exposed to decorrelation for 3 weeks showed transient esotropia, but regained normal alignment, visuomotor behaviors, and binocular V1 connections.

Conclusions: Binocular decorrelation is a sufficient cause of infantile esotropia when imposed during a critical period of visuomotor development. The systematic relationship between severity of visuomotor signs and severity of V1 connectivity deficits provides a neuroanatomic mechanism for these signs. Restoration of binocular fusion and V1 connections after short durations of decorrelation helps explain the benefits of early strabismus repair in humans.
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http://dx.doi.org/10.3368/aoj.58.1.60DOI Listing
October 2012

X-linked idiopathic infantile nystagmus associated with a missense mutation in FRMD7.

Mol Vis 2007 Nov 29;13:2233-41. Epub 2007 Nov 29.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.

Purpose: Infantile nystagmus is a clinically and genetically heterogeneous eye movement disorder. Here we map and identify the genetic mutation underlying X-linked idiopathic infantile nystagmus (XL-IIN) segregating in two Caucasian-American families.

Methods: Eye movements were recorded using binocular infrared digital video-oculography. Genomic DNA was prepared from blood or buccal-cells, and linkage analysis was performed using short tandem repeat (STR) and single nucleotide polymorphism (SNP) markers. Pedigree and haplotype data were managed using Cyrillic, and LOD scores calculated using MLINK. Mutation profiling of PCR-amplified exons was performed by dye-terminator cycle-sequencing and analyzed by automated capillary electrophoresis.

Results: Video-oculography of affected males recorded conjugate, horizontal, pendular nystagmus with increasing-velocity waveforms in primary gaze converting to jerk nystagmus in eccentric gaze. Linkage analysis detected significantly positive two-point LOD scores (Z) at markers DXS8078 (Z=4.82, recombination fraction [theta]=0) and DXS1047 (Z=3.87, theta=0). Haplotyping indicated that the IIN locus mapped to the physical interval DXS8057-(11.59 Mb)-rs6528335 on Xq25-q26. Sequencing of positional-candidate genes detected a c.425T>G transversion in exon-6 of the gene for FERM domain containing-7 (FRMD7) that cosegregated with affected and carrier status. In addition, the same change was found to cosegregate with IIN in a genetically unrelated family but was not detected in 192 control individuals.

Conclusions: The c.425T>G change is predicted to result in the missense substitution of the phylogenetically conserved leucine at codon 142 for an arginine (p.L142R), and supports a causative role for FRMD7 mutations in the pathogenesis of XL-IIN.
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November 2007

Horizontal rectus muscle anatomy in naturally and artificially strabismic monkeys.

Invest Ophthalmol Vis Sci 2007 Jun;48(6):2576-88

Department of Ophthalmology, University of California, Los Angeles, CA, USA.

Purpose: Structural abnormalities of extraocular muscles (EOMs) or their pulleys are associated with some forms of human strabismus. This experiment was conducted to investigate whether such abnormalities are associated with artificial or naturally occurring strabismus in monkeys.

Methods: Binocular alignment and grating visual acuities were determined in 10 monkeys representing various species using search coil recording and direct observations. Four animals were orthotropic, two had naturally occurring "A"-pattern esotropia, two had concomitant and one had "V"-pattern esotropia artificially induced by alternating or unilateral occlusion in infancy, and one had "A"-pattern exotropia artificially induced by prism wear. After euthanasia, 16 orbits were examined by high-resolution magnetic resonance imaging (MRI) in the quasi-coronal plane. Paths and sizes of horizontal rectus EOMs were analyzed quantitatively in a standardized coordinate system. Whole orbits were then serially sectioned en bloc in the quasi-coronal plane, stained for connective tissue, and compared with MRI. Nerve and EOM features were analyzed quantitatively.

Results: Quantitative analysis of MRI revealed no significant differences in horizontal rectus EOM sizes or paths among orthotropic or naturally or artificially strabismic monkeys. Histologic examination demonstrated no differences in EOM size, structure, or innervation among the three groups, and no differences in connective tissues in the pulley system. The accessory lateral rectus (ALR) EOM was present in all specimens, but was small, inconsistently located, and sparsely innervated. Characteristics of the ALR did not correlate with strabismus.

Conclusions: Major structural abnormalities of horizontal rectus EOMs and associated pulleys are unrelated to natural or artificial horizontal strabismus in the monkeys studied. The ALR is unlikely to contribute to horizontal strabismus in primates. However, these findings do not exclude a possible role of pulley abnormalities in disorders such as cyclovertical strabismus.
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http://dx.doi.org/10.1167/iovs.06-0662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1975407PMC
June 2007

Unilateral lens extraction for high anisometropic myopia in children and adolescents.

J AAPOS 2007 Apr 30;11(2):153-8. Epub 2006 Nov 30.

Department of Ophthalmology and Visual Sciences, St. Louis Children's Hospital at Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Introduction: A subpopulation of children with anisometropic myopia, amblyopia, and neurobehavioral disorders is noncompliant with spectacle wear and ill-suited to correction using contact lenses. We report the results of refractive surgery in a series of these children treated using lensectomy alone (clear lens extraction) or lensectomy with simultaneous implantation of an intraocular lens (refractive lens exchange).

Methods: Clinical course and outcome data were collated retrospectively in a group of 7 children and adolescents (mean age, 9.1 years; range, 4-20 years) with neurobehavioral disorders and noncompliance with spectacle wear for anisometropic myopia. Myopia in the 7 eyes ranged -11.9 to -24.5 D (mean, -16.7 D). Goal refraction was 0 to + 4 D. Correction was achieved by lensectomy in 5 eyes and lensectomy with intraocular lens implantation in 2 eyes. Primary posterior capsulectomy/subtotal vitrectomy was performed during the primary procedure in 5 eyes (71%). Mean follow-up was 3.8 years (range, 0.5-5.4 years).

Results: Myopia correction averaged 17.3 D. A total of 86% (6 eyes) were corrected within +/- 3 D of the goal refraction and the remaining 14% to within +/- 4 D. Uncorrected visual acuity improved postoperatively in all 7 eyes, albeit modestly (average gain 0.14 Snellen fraction; gain from a mean 20/2550 to a mean 20/130). Myopic regression averaged approximately 0.43 D/year. Capsular opacification necessitated YAG-laser membranectomy in the 2 eyes that had preservation of the posterior capsule at the primary procedure. Retinal detachment has not occurred in any of the eyes during the follow-up period.

Conclusions: Refractive myopic lensectomy reduced high anisometropia and improved functional vision in children who have high myopia beyond the range of excimer laser correction and who will not wear glasses. Further study is indicated to determine the long-term safety of this procedure in similar pediatric populations.
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http://dx.doi.org/10.1016/j.jaapos.2006.09.004DOI Listing
April 2007

Refractive surgery for high bilateral myopia in children with neurobehavioral disorders: 2. Laser-assisted subepithelial keratectomy (LASEK).

J AAPOS 2006 Aug;10(4):364-70

Department of Ophthalmology and Visual Sciences, St. Louis Children's Hospital at Washington University School of Medicine, University Medical Center, One Children's Place, St. Louis, MO 63110, USA.

Introduction: A subpopulation of children with high myopia and neurobehavioral disorders is noncompliant with spectacle wear and ill-suited to correction using contact lenses. We report the results of refractive surgery in a series of these children treated bilaterally using excimer laser technology.

Methods: Clinical course and outcome data were collated prospectively in a group of 9 children (mean age, 10.2 years; range, 3-16 years) with neurobehavioral disorders exacerbated by chronic noncompliance with spectacle wear, causing profoundly low functional vision. Myopia in the 18 eyes ranged from -3.75 to -11.5 D (mean -16.6 D) and the desired refraction was approximately +1D. Correction was achieved by bilateral laser-assisted subepithelial keratectomy (ie, LASEK) performed under brief general anesthesia. Mean follow-up was 17 months (range, 6-36 months).

Results: Myopia correction averaged 7.9 D. Eighty-nine percent (16/18 eyes) were corrected to within +/-1 D of goal refraction. Uncorrected acuity improved postoperatively in all 18 eyes, with commensurate gains in behavior and environmental visual interaction in 88% (15/17 children). Myopic regression averaged approximately 0.8 d/year. the only complication encountered was mild (1+) corneal haze in 35% of treated eyes.

Discussion/conclusions: Bilateral excimer laser surgery is effective for improving functional vision substantially in highly myopic, neurobehaviorally impaired children who have difficulties wearing glasses. Myopic regression is common. Further study is indicated to determine the long-term safety of these and alternative refractive procedures in similar pediatric populations.
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http://dx.doi.org/10.1016/j.jaapos.2006.04.004DOI Listing
August 2006

Refractive surgery for high bilateral myopia in children with neurobehavioral disorders: 1. Clear lens extraction and refractive lens exchange.

J AAPOS 2006 Aug;10(4):357-63

Department of Ophthalmology and Visual Sciences, St. Louis Children's Hospital at Washington University School of Medicine, University Medical Center, One Children's Place, St. Louis, MO 63110, USA.

Introduction: A subpopulation of children with high myopia and neurobehavioral disorders is noncompliant with spectacle wear and ill-suited to correction using contact lenses. We report the results of refractive surgery in a series of these children treated using lensectomy alone (clear lens extraction), or lensectomy with simultaneous implantation of an intraocular lens (refractive lens exchange).

Methods: Clinical course and outcome data were collated prospectively in a group of 13 children (mean age 10.4 years, range 1 to 18 years) with neurobehavioral disorders exacerbated by chronic noncompliance with spectacle wear, causing profoundly low functional vision. Myopia in the 26 eyes ranged from -14.25 to -26.00 D (mean -19.1 D). Goal refraction was approximately +1 D. Correction was achieved by lensectomy alone in 10 eyes, and lensectomy with intraocular lens implantation in 16 eyes. Primary posterior capsulectomy/subtotal vitrectomy was performed during the primary procedure in 11 eyes (42%). Mean follow-up was 4.5 years (range 1.3 to 7.5 years).

Results: Myopia correction averaged 19.9 D. Eighty-one percent (21 eyes) were corrected to within +/-2 D of goal refraction and the remaining 19% (5 eyes) to within +/-4 D. Uncorrected acuity improved substantially (ie, an average 2 log units) in all 26 eyes, with commensurate gains in behavior and environmental visual interaction in 85% [corrected] of children (11/13) [corrected] Myopic regression averaged -0.16 D/year. Capsular regrowth and/or opacification necessitated vitrector or YAG-laser membranectomy in 13 [corrected] eyes (50%) [corrected] Focal retinal detachment (successfully repaired) occurred after eye contusion in one eye (4%) with cicatricial retinopathy of prematurity.

Conclusions: Bilateral refractive lensectomy is effective for improving functional vision in neurobehaviorally impaired children who have high myopia (beyond the range of excimer laser correction: see companion publication) and difficulties wearing glasses. Posterior capsule regrowth/opacification is common, necessitating secondary membranectomy. Further study is indicated to determine the long-term safety of this procedure in similar pediatric populations.
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http://dx.doi.org/10.1016/j.jaapos.2006.04.003DOI Listing
August 2006

Aicardi-like chorioretinitis and maldevelopment of the corpus callosum in congenital lymphocytic choriomeningitis virus.

J AAPOS 2006 Feb;10(1):58-60

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

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http://dx.doi.org/10.1016/j.jaapos.2005.09.009DOI Listing
February 2006

Can ophthalmologists repair the brain in infantile esotropia? Early surgery, stereopsis, monofixation syndrome, and the legacy of Marshall Parks.

Authors:
Lawrence Tychsen

J AAPOS 2005 Dec;9(6):510-21

Department of Ophthalmology and Visual Sciences, Anatomy and Neurobiology, and Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Can ophthalmologists repair defects of visual cortex circuitry in infants who have esotropia? The answer to this question encompasses both sensory and motor behaviors because the clinical hallmarks of the disorder are stereoblindness and absence of motor fusion, which manifests as convergently deviated eyes. Functional recovery of sensory and motor fusion in infantile esotropia was a consuming interest, if not career-defining passion, of Marshall Parks. The purpose of this work is to pay tribute to Parks' legacy by showing how human and animal studies, conducted largely during the last 25 years, support both his clinical insights and treatment philosophy.
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http://dx.doi.org/10.1016/j.jaapos.2005.06.007DOI Listing
December 2005

Correction of large amblyopiogenic refractive errors in children using the excimer laser.

J AAPOS 2005 Jun;9(3):224-33

Department of Ophthalmology and Visual Sciences, St. Louis Children's Hospital at Washington University School of Medicine, Missouri 63110, USA.

Purpose: We sought to determine whether laser subepithelial keratomileusis (LASEK) and photorefractive keratectomy (PRK) are effective methods for correcting amblyopiogenic refractive errors in children.

Methods: Thirty-six eyes in 35 amblyopic children, who ranged in age from 4 to 16 years (mean, 8.4 years), received treatment for large magnitude ametropia. Seventy-two percent (25/35) of the children had a neurobehavioral disorder and/or were noncompliant with spectacle or contact lens wear. Myopia ranged from -3.25 to -24.25 D (mean, -11.48 D); one patient had hyperopia of +5.87 D. Correction was tailored to match the refractive error of the nonamblyopic eye. VISX Star S2/S3 excimer lasers were used in manual or auto-tracking modes, and corneal centration was achieved using brief, general anesthesia. Mean follow-up was 29.2 months (range, 4-42 months).

Results: Myopia correction averaged -8.95 +/- 2.89 D (range, -3.25 to -15.50). Eighty-nine percent (31 children) were corrected to within +/- 1.00 D of goal refraction and the remaining 11% to within 2.0 D of the goal (most were undercorrected). Acuity improved postoperatively in 97%; by 1 optotype line in 37% and by 2 or more in 60%. No child lost acuity. Binocularity improved in 69% (24/35) and remained the same in 31%. Corneal haze measured grade 0-1 in 78%, grade 2 in 14%, and grade 3-4 in 8%. Myopic regression exceeding congruent with 1.0 D/year (0.08 D/month) occurred in 50% (18/36) of eyes treated. No substantial differences were observed in PRK- (n = 18) versus LASEK- (n = 17) treated children.

Conclusions: Laser refractive surgery is effective for correcting anisometropic myopia in amblyopic children. Recurrence of myopia is common. Further study is indicated to determine long-term stability and safety of the procedure in this population.
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http://dx.doi.org/10.1016/j.jaapos.2005.01.006DOI Listing
June 2005

Suppression of metabolic activity caused by infantile strabismus and strabismic amblyopia in striate visual cortex of macaque monkeys.

J AAPOS 2005 Feb;9(1):37-47

Department of Ophthalmology and Visual Sciences,Washington University School of Medicine, St. Louis, MO, USA.

Introduction: Suppression is a major sensorial abnormality in humans and monkeys with infantile strabismus. We previously reported evidence of metabolic suppression in the visual cortex of strabismic macaques, using the mitochondrial enzyme cytochrome oxidase as an anatomic label. The purpose of this study was to further elucidate alterations in cortical metabolic activity, with or without amblyopia.

Materials And Methods: Six macaque monkeys were used in the experiments (four strabismic and two control). Three of the strabismic monkeys had naturally occurring, infantile strabismus (two esotropic, one exotropic). The fourth strabismic monkey had infantile microesotropia induced by alternating monocular occlusion in the first months of life. Ocular motor behaviors and visual acuity were tested after infancy in each animal, and development of stereopsis was recorded during infancy in one strabismic and one control monkey. Ocular dominance columns (ODCs) of the striate visual cortex (area V1) were labeled using cytochrome oxidase (CO) histochemistry alone, or CO in conjunction with an anterograde tracer ([H 3 ]proline or WGA-HRP) injected into one eye.

Results: Each of the strabismic monkeys showed inequalities of metabolic activity in ODCs of opposite ocularity, visible as rows of lighter CO staining, corresponding to ODCs of lower metabolic activity, alternating with rows of darker CO staining, corresponding to ODCs of higher metabolic activity. In monkeys who had infantile strabismus and unilateral amblyopia, lower metabolic activity was found in (suppressed) ODCs driven by the nondominant eye in each hemisphere. In monkeys who had infantile esotropia and alternating fixation (no amblyopia), metabolic activity was lower in ODCs driven by the ipsilateral eye in each hemisphere. The suppression included a monocular core zone at the center of ODCs and binocular border zones at the boundaries of ODCs. This suppression was not evident in the monocular lamina of the LGN, indicating an intracortical rather than subcortical mechanism.

Conclusion: Suppression of metabolic activity in ODCs of V1 differs depending upon whether infantile strabismus is alternating or occurs in conjunction with unilateral amblyopia. Our findings reinforce the principle that unrepaired strabismus promotes abnormal competition in V1, observable as interocular suppression of ODCs.
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http://dx.doi.org/10.1016/j.jaapos.2004.09.004DOI Listing
February 2005

Paucity of horizontal connections for binocular vision in V1 of naturally strabismic macaques: Cytochrome oxidase compartment specificity.

J Comp Neurol 2004 Jun;474(2):261-75

Departments of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

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.
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http://dx.doi.org/10.1002/cne.20113DOI Listing
June 2004

Early versus delayed repair of infantile strabismus in macaque monkeys: II. Effects on motion visually evoked responses.

Invest Ophthalmol Vis Sci 2004 Mar;45(3):821-7

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Purpose: Infantile strabismus in humans and the monkey is associated with maldevelopment of visual motion responsiveness, one manifestation of which is directionally asymmetric motion visual evoked potentials (motion VEPs). Early repair of strabismus in infant monkeys has been shown to restore normal development of motion responsiveness for pursuit and optokinetic eye movements (optokinetic nystagmus [OKN]). The purpose of this study was to determine how early versus delayed repair of strabismus influences the development or maldevelopment of motion VEPs.

Methods: Optical strabismus was created in infant macaques by fitting them with prism goggles on day 1 of life. The Early Repair group wore the goggles for a period of 3 weeks (the equivalent of 3 months before surgical repair in humans), whereas the Delayed Repair group wore the goggles for a period of 3 to 6 months (the equivalent of 12-24 months before surgical repair in humans). Several months after the removal of the goggles, motion VEPs to horizontally oscillating grating stimuli were recorded during monocular viewing. An asymmetry index (AI) was measured for each animal by extracting an asymmetric (F1) and symmetric (F2) frequency component from the motion VEP. The AIs of the infant monkeys with Early versus Delayed Repair were also compared with that of a group of adult monkeys, who had unrepaired, natural strabismus.

Results: When tested with a 1-cyc/deg, 6-Hz stimulus, both control and Early Repair monkeys exhibited symmetric motion VEPs (AI < 0.25). Mean AI was 0.15 +/- 0.09 in control and 0.16 +/- 0.13 in Early Repair monkeys. In contrast, both Delayed Repair and naturally strabismic monkeys had asymmetric motion VEP responses: AI = 0.57 +/- 0.22 in the Delayed Repair and 0.49 +/- 0.17 in the naturally strabismic monkeys (P < 0.01). Delayed Repair and naturally strabismic monkeys also had motion VEP asymmetries of equivalent magnitude when tested using stimuli at higher (3 cyc/deg/11 Hz) spatial-temporal frequencies. The concordance between motion VEP symmetry and normal fusional vergence was significant (P < 0.01).

Conclusions: Early repair of optical strabismus in primates restores normal development of visual motion pathways in the cerebral cortex, measured as symmetric motion VEPs. Delayed repair causes permanent motion VEP maldevelopment. These results provide additional evidence that early strabismus repair is beneficial for brain development in infant primates.
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http://dx.doi.org/10.1167/iovs.03-0564DOI Listing
March 2004

Infantile glaucoma and punctal atresia in a child with caudal regression syndrome.

J AAPOS 2003 Aug;7(4):298-9

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.

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http://dx.doi.org/10.1016/s1091-8531(03)00109-5DOI Listing
August 2003

Trochleitis and migraine headache.

Authors:
Lawrence Tychsen

Neurology 2003 Aug;61(3):425; author reply 425

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http://dx.doi.org/10.1212/wnl.61.3.425-aDOI Listing
August 2003

Maldevelopment of convergence eye movements in macaque monkeys with small- and large-angle infantile esotropia.

Invest Ophthalmol Vis Sci 2003 Aug;44(8):3358-68

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.

Purpose: To describe symmetric convergence eye movements evoked by disparity and/or accommodative cues in esotropic macaque monkeys, with the goal of determining whether these animals have the vergence deficits found in humans with esotropia.

Methods: Physical far and near targets were used to evoke large (approximately 8 degrees) symmetric convergence eye movements in four adult macaque monkeys (two with strabismus, two normal), using positive-feedback rewards. One strabismic monkey had infantile-onset, small-angle esotropia (small-eso approximately 2 degrees) induced by alternating occlusion from birth to age 9 months. The other strabismic monkey had naturally occurring, large-angle (approximately 25 degrees) infantile-onset esotropia (large-eso). Visual acuity was normal in each eye as measured by spatial sweep visually evoked potentials (VEPs). Eye movements were recorded using magnetic search coils.

Results: When viewing binocularly, both normal monkeys exhibited accurate, stereotyped symmetric convergence movements that achieved 87% to 96% of the required change in vergence angle by the end of the initial movement. In contrast, the small-eso monkey's convergence response when viewing binocularly was variable, strikingly asymmetric, usually accompanied by a disjunctive saccade, and subnormal, achieving only 56% of required vergence. The convergence response of the large-eso monkey was also asymmetric and weak, achieving 18% of the required vergence and employing conjugate saccades to refixate the near target. Monocular viewing (i.e., accommodative vergence) caused substantial reductions in both convergence amplitudes and velocities in the normal monkeys, but had a minor effect on the vergence behavior of the strabismic animals.

Conclusions: Monkeys with small- and large-angle infantile esotropia have striking maldevelopments of binocular (disparity-driven) convergence and use accommodative vergence and saccades to refixate near targets. Their vergence behavior resembles that in esotropic humans. The maldevelopment may be explained in large part by the paucity of binocular connections recently described in the visual cortex of esotropic macaques.
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http://dx.doi.org/10.1167/iovs.02-0698DOI Listing
August 2003

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

J AAPOS 2003 Jun;7(3):200-9

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.

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.
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http://dx.doi.org/10.1016/s1091-8531(03)00014-4DOI Listing
June 2003

Cone-rod retinal dystrophy and Duane retraction syndrome in a patient with achondroplasia.

J AAPOS 2002 Dec;6(6):400-1

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, Missouri, USA.

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http://dx.doi.org/10.1067/mpa.2002.129561DOI Listing
December 2002

The effect of an eyelid speculum on intraocular pressure measurement in children.

Am J Ophthalmol 2002 Dec;134(6):926-7

Department of Ophthalmology, St. Louis Children's Hospital at Washington University Medical Center, St. Louis, Missouri 63110, USA.

Purpose: To assess the effect of a pediatric eyelid speculum on the measurement of intraocular pressure (IOP) in children.

Design: Observational case series.

Methods: Intraocular pressure measurements were performed during examination under anesthesia immediately after induction. The measurements were made with and without a pediatric eyelid speculum in place.

Results: Intraocular pressure measurements were made in 77 eyes of 45 consecutive children. The mean IOP without the speculum was 16.33 mm Hg in the right eye and 16.55 mm Hg in the left eye. With the lid speculum in place the mean IOP was 20.26 mm Hg in the right eye and 20.05 mm Hg in the left eye (P <.05).

Conclusions: The presence of an eyelid speculum raised IOP an average of 4 mm Hg. This effect should be considered when interpreting IOP measurements in children.
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http://dx.doi.org/10.1016/s0002-9394(02)01793-2DOI Listing
December 2002

Eye movement training and recording in alert macaque monkeys: 1. Operant visual conditioning; 2. Magnetic search coil and head restraint surgical implantation; 3. Calibration and recording.

Strabismus 2002 Mar;10(1):5-22

Departments of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.

Purpose: To describe current methodology used to: a) train alert adult macaque monkeys to perform visual fixation tasks, b) implant binocular magnetic scleral search coils and attach a head restraint, and c) precisely record their fixation and pursuit eye movements.

Methods: Animals are trained to sit in a primate chair and manipulate a lever. The animal turns on a laser spot (< 1 degree of arc) by pulling the lever. The spot dims after a variable, randomized period of time (luminance decrement 30-80%) and if the monkey releases the lever within 150-500 msec of dimming, a small bolus of juice is squirted via a servo into the monkey's mouth as a reward. The small size of the spot, the difficulty of detecting the dimming, and the short reaction time required for reward act in concert to assure attentive foveal fixation. After training, a search coil is implanted subconjunctivally in each eye and a polycarbonate head restraint device is attached to the skull. With the animal at the center of magnetic field coils, eye position is then calibrated precisely by requiring the animal to perform the dimming task at known positions of gaze. Fixation, vergence and pursuit eye movements are recorded by rewarding the animal for positioning the fovea of the eye within a small fixation 'window' encompassing the position of a stationary or moving target. A cover test of binocular eye alignment is performed by having the animal view through liquid crystal shutters that can be switched instantaneously from transparent to opaque. These methods have been used to train and to record eye movements in over 20 monkeys, and a representative sample of our experience in eight animals is reported in the Results.

Results: Normal monkeys, and monkeys who had strabismus or amblyopia, required an average of 53 days to learn to fixate steadily for a minimum of 5 sec with a dimming-detection performance of at least 75% correct. Implanted coils provided good signals for durations ranging from 4 months to longer than 3 years (average greater than 1 year) before signs of breakage or extrusion. Head restraints under daily use have lasted an average of 11 months (range 5 months to greater than 2 years) before spontaneous detachment.

Conclusion: The training and surgical techniques described provide an efficient, straightforward method for recording precise binocular eye movements in awake monkeys.
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http://dx.doi.org/10.1076/stra.10.1.5.8154DOI Listing
March 2002

Congenital restrictive external ophthalmoplegia and gustatory epiphora associated with fetal isotretinoin toxicity.

Arch Ophthalmol 2002 Aug;120(8):1094-5

St Louis Children's Hospital, One Children's Place, St Louis, MO 63110, USA.

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August 2002

Effects of extraocular muscle tenotomy on congenital nystagmus in macaque monkeys.

J AAPOS 2002 Apr;6(2):100-7

Department of Ophthalmology and Visual Sciences, St Louis Children's Hospital at Washington University School of Medicine, St Louis, MO 63110, USA.

Introduction: Extraocular muscle tenotomy has been reported to damp congenital nystagmus in an achiasmatic sheepdog. We performed extraocular muscle tenotomy to evaluate its effects on congenital nystagmus in primates.

Methods: Magnetic search coil eye movement recordings were used to document the presence of horizontal congenital nystagmus in 2 adult macaque monkeys that also had naturally occurring infantile strabismus. Extraocular muscle tenotomy was performed by operating on all 4 horizontal recti, surgically detaching the muscles from the globe and suturing them back to their original insertions without resection or recession. Eye movement recordings were repeated 4 months after the procedure, comparing the waveform, amplitude, retinal slip velocity, and intensity (frequency x amplitude) of the nystagmus before and after tenotomy. Visual acuity was also measured before and after surgery in 1 animal.

Results: Preoperatively, a disconjugate, pendular nystagmus was evident in 1 monkey, and the other had a conjugate pendular-jerk nystagmus damped by convergence. After tenotomy, nystagmus mean amplitude decreased 18% to 52% in 1 monkey but increased 14% in the other (t test, P <.002). Retinal slip velocity and nystagmus intensity increased in both monkeys. After tenotomy, mean velocity increased 22% to 218%, while mean intensity increased 40% to 208% (t test, P <.002). Visual acuity measured after tenotomy decreased an average of 20% ( approximately 2.0 cycles per degree) in each eye. Tenotomy had no noteworthy effects on eye alignment or other aspects of visual behavior other than the congenital nystagmus.

Conclusion: Nystagmus velocity and intensity increased after extraocular muscle tenotomy in 2 monkeys. Further studies are required to establish the clinical value of this procedure as a treatment for various subtypes of congenital nystagmus in humans.
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http://dx.doi.org/10.1067/mpa.2002.122060DOI Listing
April 2002
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