Incomitant Strabismus Does Extraocular Muscle Form Denote Function?
ABSTRACT The paradigm that an "underacting" extraocular muscle is always atrophic or hypoplastic and that an overacting extraocular muscle should always be enlarged leads to inconsistencies with clinical observations. These include findings of "overacting" inferior oblique muscles, superior rectus muscle overaction or contracture syndrome, and normal extraocular muscle diameters in patients with apparent superior oblique muscle palsy, among other clinical entities. These inconsistencies can be reconciled if one accepts the possibility that extraocular muscle contractile activity may reflect a change in neural input to an anatomically normal muscle or that muscle contractile activity may be altered by shifts in fiber type and distribution within a normal-sized muscle. This remodeling may result from vergence adaptation or from any change in neural stimulus to the muscle. There is substantial evidence to suggest that both of these theoretical possibilities may likely occur.
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ABSTRACT: Idiopathic superior oblique muscle palsy presents, as quantitative phenotypes, vertical deviation and cyclodeviation in eye alignment on clinical testing, and superior oblique muscle hypoplasia on imaging. We determined ARIX and PHOX2B polymorphisms as genotypes, and analyzed phenotype-phenotype and genotype-phenotype correlations in 37 patients with idiopathic superior oblique muscle palsy. Vertical deviations were measured at upright position of the head and head tilt for 30° to either side, and angles of objective excyclodeviations were determined by image analysis on fundus photographs. Cross-sectional areas of the superior oblique muscle near the eye globe-optic nerve junction were measured by image analysis on coronal sections of magnetic resonance imaging to calculate the paretic-side/normal-side ratios. Among the phenotypes, the increase in vertical deviations elicited by head tilt to the paretic side, the decrease in vertical deviations elicited by head tilt to the normal side and the difference of angles of objective excyclodeviations between the paretic side and normal side were significantly correlated inversely with the paretic-side/normal-side ratios of the cross-sectional areas of the muscle (r=-0.43 with P=0.0084, r=-0.34 with P=0.038, and r=-0.43 with P=0.009, respectively, n=37, Pearson's correlation test). Fifteen patients with ARIX and/or PHOX2B polymorphisms had significantly greater paretic-side/normal-side ratios of the muscle compared with 20 patients without the polymorphisms (P=0.017, n=35, Mann-Whitney U-test). The patients with ARIX and/or PHOX2B polymorphisms had less hypoplastic superior oblique muscles.Journal of Human Genetics 12/2011; 57(2):122-9. DOI:10.1038/jhg.2011.138 · 2.53 Impact Factor
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ABSTRACT: Strabismic extraocular muscles (EOMs) differ from normal EOMs in structural and functional properties, but the gene expression profile of these two types of EOM has not been examined. Differences in gene expression may inform about causes and effects of the strabismic condition in humans. EOM samples were obtained during corrective surgery from patients with horizontal strabismus and from deceased organ donors with normal EOMs. Microarrays and quantitative PCR identified significantly up- and down-regulated genes in EOM samples. Analysis was performed on probe sets with more than 3-fold differential expression between normal and strabismic samples, with an adjusted P value of ≤ 0.05. Microarray analysis showed that 604 genes in these samples had significantly different expression. Expression predominantly was upregulated in genes involved in extracellular matrix structure, and down-regulated in genes related to contractility. Expression of genes associated with signaling, calcium handling, mitochondria function and biogenesis, and energy homeostasis also was significantly different between normal and strabismic EOM. Skeletal muscle PCR array identified 22 (25%) of 87 muscle-specific genes that were significantly down-regulated in strabismic EOMs; none was significantly upregulated. Differences in gene expression between strabismic and normal human EOMs point to a relevant contribution of the peripheral oculomotor system to the strabismic condition. Decreases in expression of contractility genes and increases of extracellular matrix-associated genes indicate imbalances in EOM structure. We conclude that gene regulation of proteins fundamental to contractile mechanics and extracellular matrix structure is involved in pathogenesis and/or consequences of strabismus, suggesting potential novel therapeutic targets.Investigative ophthalmology & visual science 07/2012; 53(9):5168-77. DOI:10.1167/iovs.12-9785 · 3.66 Impact Factor
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ABSTRACT: We explored multiple quantitative measures of horizontal rectus extraocular muscle (EOM) morphology to determine the magnetic resonance imaging (MRI) measure best correlating with duction and thus contractility. Surface coil coronal MRI was obtained in target-controlled central gaze and multiple positions of adduction and abduction in 26 orbits of 15 normal volunteers. Duction angles were determined by position changes of the globe-optic nerve junction. Cross-sectional areas, partial volumes, and location of peak cross-sections of the horizontal rectus EOMs were computed in contiguous image planes 2-mm thick spanning the EOM origins to the globe equator. All measures correlated significantly with duction angle (P < 0.0001). The best measures obtainable in single image planes were the maximum change in the cross-sectional area between equivalent image planes, with coefficients of determination R(2) = 0.92 for medial rectus (MR) and 0.91 for lateral rectus (LR), and percentage change in maximum cross-section with R(2) = 0.79 for MR and 0.78 for LR. The best partial volume measure of contractility was the change in partial volumes in four contiguous posterior planes (R(2) = 0.86 MR and for 0.89 LR), particularly when combined with the corresponding change in partial volume for the antagonist EOM (R(2) = 0.95 for MR and LR). EOM morphologic changes are highly correlated with degrees of duction and thus contractility. Both changes in single-plane maximum cross-sectional areas and posterior partial volumes provide accurate, quantitative measures of EOM contractility.Investigative ophthalmology & visual science 09/2012; 53(11):7375-9. DOI:10.1167/iovs.12-9730 · 3.66 Impact Factor